Table of Contents

This week, we discuss:

• Acquisitions

  • Shionogi to Acquire IntraBio ⬇️

• Conferences

  • EASD 2026, Europe’s largest diabetes conference ⬇️

  • EADV 2026, Europe’s largest dermatology conference ⬇️

• Approvals

  • Egetis - Emcitate (membrane-permeable TRa/b agonist) / Approved (MCT8 deficiency) ⬇️

  • Roche - Tecentriq (anti-PDL1 mAb) / Approved (Stage 2 dMMR CRC) ⬇️

  • Novartis - Rhapsido (BTK inhibitor) / Approved (SD) ⬇️

  • Pfizer - Tukysa (HER2 x HER3 inhibitor) / Approved (1L HER2+ BC) ⬇️

  • Eli Lilly - Jaypirca (BTK inhibitor) / Approved (1L CLL, SLL) ⬇️

  • BMS - Camzyos (cardiac myosin inhibitor) / Approved (childhood oHCM) ⬇️

• Clinical Trial Data

  • Genmab - Rinatabart sesutecan (FRα ADC) / Phase 1/2 (PROC) ⬇️

  • Kodiak - Tarcocimab (VEGF inhibitor) / Phase 3 (wAMD) ⬇️

  • AbbVie & Genmab - Epkinly (CD20 x CD3 TCE) / Phase 3 (1L DLBCL) ⬇️

  • Vaxcyte - VAX-31 (31-valent vaccine) / Phase 3 (pneumococcal) ⬇️

  • Regeneron - Ubamatamab (MUC16 x CD3 TCE) / Phase 1/2 (LGSOC) ⬇️

  • Connect - Rademikibart (anti-IL4Rα mAb) / Phase 2 (COPD) ⬇️

  • Immix - NXC-201 (BCMA CAR-T) / Phase 2 (AL amyloidosis) ⬇️

  • BMS - BMS-986453 (BCMA x GPRC5D bsCAR-T) / Phase 1 (r/r MM) ⬇️

  • Mirum - Brelovitug (anti-HBsAg mAb)/ Phase 3 (HDV) ⬇️

  • Adicet - Prula-cel (allo gamma delta T cells) / Phase 1 (SLE) ⬇️

Acquisitions

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Conferences

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Approvals

Egetis - Emcitate (membrane-permeable TRa/b agonist) / Approved (MCT8 deficiency)

On September 28, 2026, the FDA approved Emcitate (tiratricol), developed by Egetis Therapeutics, as the first-ever targeted treatment for peripheral thyrotoxicosis in adult and pediatric patients with monocarboxylate transporter 8 (MCT8) deficiency. Alongside the regulatory approval, the FDA awarded Egetis a Rare Pediatric Disease Priority Review Voucher (PRV), a valuable incentive that Egetis can monetize to fund further rare disease drug development. Affected individuals, primarily newborn males due to the condition’s X-linked genetic nature, suffer from defective MCT8 cell membrane transporters, which prevents essential thyroid hormones from properly entering cells. This causes triiodothyronine (T3) to accumulate to toxic levels in peripheral tissues, causing chronic hyperthyroidism-like effects that severely strain the cardiovascular system and liver, leading to a drastically reduced life expectancy of roughly 35 years. Emcitate works as a membrane-permeable thyroid hormone receptor agonist. Since its molecular structure allows it to bypass the mutated MCT8 transporter, it directly accesses cells to regulate thyroid hormone signaling, effectively suppressing excess circulating T3 levels and relieving the systemic toxicities of the disease.

The FDA’s decision was backed by two key clinical studies: the open-label Phase 2 Triac Trial I and the pivotal Phase 3 ReTRIACt trial. The open-label Phase 2 Triac Trial I enrolled 46 male patients across a broad age range (infants to adults) with genetically confirmed MCT8 deficiency. The trial was designed to evaluate whether daily oral administration of tiratricol reduces toxic serum T3 concentrations and improves systemic hyperthyroid/thyrotoxic symptoms. Serum total T3 normalized in patients, decreasing from a baseline average of 323.4 ng/dL to 118.3 ng/dL. Treatment with Emcitate significantly reduced cardiovascular stress, including a mean heart rate drop of 8.9 bpm and a mean systolic blood pressure reduction of 4.1 mm Hg, as well as improved in hyperthyroid metabolic markers (e.g., reductions in excessive sweating and hypermetabolic catabolism).

The Phase 3 ReTRIACt trial was requested specifically by the US FDA as the pivotal study for US regulatory approval and enrolled 16 evaluable male patients aged ≥4 years with confirmed MCT8 deficiency who were already maintained on a stable dose of tiratricol. The trial was designed to determine whether or not continuous treatment with Emcitate is required to maintain T3 suppression and control peripheral thyrotoxicosis. The trial met its primary endpoint with high statistical significance, establishing that continuous therapy with Emcitate is required to suppress toxic serum T3 levels and prevent the return of peripheral thyrotoxicosis. Discontinuation of tiratricol led to a rapid, statistically significant rebound of serum total T3 above the upper limit of normal in the placebo arm.

Sources: Egetis press release, new Emcitate label

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Roche - Tecentriq (anti-PDL1 mAb) / Approved (Stage 2 dMMR CRC)

On October 08, 2026, the FDA approved Roche’s anti-PD-L1 monoclonal antibody Tecentriq (atezolizumab), in combination with a fluoropyrimidine and oxaliplatin (mFOLFOX6), for the adjuvant treatment of adult and pediatric patients aged two and older with Stage III mismatch repair-deficient (dMMR) colon cancer. The FDA also expanded the label for Tecentriq Hybreza, the subcutaneous formulation of atezolizumab and hyaluronidase-tqjs, in the same indication for patients 12 years and older weighing at least 40 kg. This decision marks the 12th U.S. indication for Tecentriq and establishes the first targeted immunotherapy-chemotherapy combination regimen in the adjuvant dMMR colon cancer setting.

The regulatory approval was grounded in pivotal data from the Phase 3 ATOMIC trial, which enrolled 712 patients with surgically resected Stage 3 dMMR colon cancer. The trial met its primary endpoint of investigator-assessed disease-free survival (DFS). Adjuvant Tecentriq plus chemotherapy reduced the risk of disease recurrence or death by 50% compared to standard mFOLFOX6 chemotherapy alone (HR = 0.50, p = 0.0001). At 36 months (3 years), 86% of patients in the Tecentriq combination arm remained disease-free compared to 76% in the chemotherapy-alone control arm. The overall safety profile of the combination regimen was consistent with the known safety profiles of Tecentriq and mFOLFOX6, with no unexpected safety signals observed.

Sources: Roche press release, Sinicrope et al., NEJM (2026), updated Tecentriq & Tecentriq Hybreza not currently available

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Novartis - Rhapsido (BTK inhibitor) / Approved (SD)

On October 7, 2026, the FDA approved a label expansion for Novartis’ Rhapsido (remibrutinib), an oral, highly selective Bruton’s tyrosine kinase (BTK) inhibitor, as the first targeted treatment for adult patients with symptomatic dermographism (SD) who remain inadequately controlled by H1 antihistamines. Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria (CInU). Unlike chronic spontaneous urticaria (CSU), where hives occur without a distinct trigger, SD causes debilitating itching, skin writing, and wheal formation in response to minimal physical contact, such as light scratching, rubbing, or friction from clothing. Standard management has historically relied on H1 antihistamines, leaving a substantial population of patients with uncontrolled symptoms. By selectively blocking BTK, an essential signaling node upstream of mast cell activation and histamine release, Rhapsido is designed to prevent the cascade that drives hive formation directly at its source. With this regulatory milestone, Rhapsido becomes the first and only drug approved in the U.S. for both CSU and SD, covering the two most prevalent forms of chronic hives.

The regulatory approval was grounded in clinical results from the pivotal Phase 3 RemIND study, a randomized, double-blind, placebo-controlled basket trial evaluating oral remibrutinib in adult patients with CSU. In the SD cohort evaluated with friction-provocation testing, Rhapsido achieved a statistically significant complete response rate compared to placebo at Week 12. Specifically, 29.3% of patients treated with Rhapsido (25 mg twice daily) achieved complete resolution of hives versus 14.0% in the placebo arm (p = 0.0229), representing a more than twofold improvement in response rate. Treatment separation from placebo was observed as early as Week 2, demonstrating a rapid onset of symptom control for patients suffering from mechanical friction-induced hives. Up to 24 weeks of clinical evaluation, Rhapsido demonstrated a favorable safety profile in the SD cohort consistent with prior findings in CSU, with no routine laboratory monitoring required. The most common adverse events (incidence ≥3%) included nasopharyngitis, bleeding events, headache, nausea, and abdominal pain.

Sources: Novartis press release, updated Rhapsido label not currently available

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Pfizer - Tukysa (HER2 x HER3 inhibitor) / Approved (1L HER2+ BC)

On October 7, 2026, the FDA expanded the approval of Pfizer’s Tukysa (tucatinib), an oral selective tyrosine kinase inhibitor (TKI) targeting HER2, in combination with Herceptin (trastuzumab) and Perjeta (pertuzumab) for the maintenance treatment of adult patients with unresectable locally advanced or metastatic HER2-positive breast cancer. Eligible patients include those who have not experienced disease progression following initial induction therapy with taxane-based chemotherapy, trastuzumab, and pertuzumab. This regulatory decision marks Tukysa’s expansion into frontline care as a chemotherapy-free maintenance option, building upon its existing indications in second-line and later-line HER2-positive metastatic disease.

The regulatory expansion was supported by clinical results from the pivotal Phase 3 HER2CLIMB-05 trial, which enrolled 54 patients with HER2-positive unresectable locally advanced or metastatic breast cancer (with or without brain metastases) who achieved non-progressive disease after 4 to 8 cycles of frontline induction therapy with a taxane, trastuzumab, and pertuzumab. The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in investigator-assessed progression-free survival (PFS). Adding Tukysa to trastuzumab and pertuzumab reduced the risk of disease progression or death by 36% compared to the placebo control combination (HR = 0.64, p < 0.0001). Patients in the Tukysa maintenance arm achieved a median PFS of 24.9 months (95% CI: 21.3-NE) compared to 16.3 months (95% CI: 12.6-18.7) in the placebo control arm, representing an 8.6-month extension in time spent free of disease progression. The safety profile of the triplet regimen was generally consistent with the established profiles of individual agents. Serious adverse reactions occurred in 17% of patients receiving Tukysa. Hepatotoxicity (primarily transient, asymptomatic elevations in ALT/AST) was noted as a key adverse event requiring routine liver function monitoring, with drug modifications effectively managing most events.

Sources: Pfizer press release, updated Tukysa label

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Eli Lilly - Jaypirca (BTK inhibitor) / Approved (1L CLL, SLL)

On October 2, 2026, the FDA approved a significant label expansion for Eli Lilly’s Jaypirca (pirtobrutinib), establishing it as the first and only non-covalent (reversible) Bruton’s tyrosine kinase (BTK) inhibitor approved for adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who do not have a 17p deletion. CLL and SLL represent slow-growing non-Hodgkin lymphomas originating in B-cell lymphocytes, with CLL being one of the most common leukemias diagnosed in adults. While covalent BTK inhibitors (such as ibrutinib, acalabrutinib, and zanubrutinib) and venetoclax-based regimens have reshaped frontline management, disease progression due to resistance mutations, most notably at the C481 binding site, and treatment discontinuation due to off-target toxicities remain clinical hurdles. Jaypirca utilizes a distinct non-covalent binding mechanism that reversibly inhibits BTK without relying on the C481 residue. Having initially entered the market for heavily pretreated, relapsed/refractory B-cell malignancies, this regulatory decision brings Jaypirca directly into first-line care, providing a highly selective, once-daily oral monotherapy option at initial diagnosis.

The regulatory approval was supported by results from the pivotal Phase 3 BRUIN CLL-313 trial, which enrolled 282 treatment-naïve patients with CLL or SLL lacking deletion 17p. Jaypirca met its primary endpoint, demonstrating a statistically significant and clinically meaningful extension in progression-free survival (PFS) as assessed by an independent review committee (IRC). Continuous Jaypirca reduced the risk of disease progression or death by 80% compared to bendamustine plus rituximab (HR = 0.199, p < 0.0001). At 24 months, 93.4% of patients in the Jaypirca arm remained progression-free compared to 70.7% of patients in the chemoimmunotherapy arm. Jaypirca achieved an overall response rate (ORR) of 94% (95% CI: 89%-98%) versus 81% (95% CI: 73%-87%) for the BR control arm. Although overall survival (OS) data remained immature at the time of analysis, interim trends favored Jaypirca (HR = 0.257), despite more than half of the progression events in the BR arm crossing over to receive Jaypirca monotherapy. Jaypirca exhibited a favorable safety profile compared to chemoimmunotherapy, marked by substantially lower rates of Grade ≥3 treatment-emergent adverse events (40.0% vs. 67.4%) and treatment discontinuations due to adverse events (4.3% vs. 15.2%). Discontinuation and dose-reduction rates due to toxicities were notably low, with minimal rates of atrial fibrillation/flutter observed.

Sources: Eli Lilly press release, updated Jaypirca label

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BMS - Camzyos (cardiac myosin inhibitor) / Approved (childhood oHCM)

On September 30, 2026, the FDA approved an expanded indication for Bristol Myers Squibb’s Camzyos (mavacamten), a first-in-class oral cardiac myosin inhibitor, for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in pediatric patients aged 12 years and older who weigh at least 30 kg (66 lbs). This decision makes Camzyos the first and only targeted disease-modifying therapy approved specifically for children and adolescents with oHCM. Pediatric patients with oHCM frequently suffer from debilitating exertional dyspnea, fatigue, reduced exercise tolerance, and elevated risks of heart failure or sudden cardiac death. Prior to this approval, clinical management relied primarily on off-label non-specific symptomatic medications, such as beta-blockers or calcium channel blockers, or invasive surgical septal myectomy. Camzyos works directly at the sarcomeric level by reversibly binding to cardiac myosin, reducing actin-myosin cross-bridge formation to alleviate hypercontractility, relieve LVOT obstruction, and improve cardiac filling pressures.

The regulatory expansion was supported by efficacy and safety outcomes from the pivotal Phase 3 SCOUT-HCM trial, which enrolled 44 adolescent patients aged 12 to <18 years weighing at least 30 kg with symptomatic oHCM. The trial met its primary endpoint, demonstrating a statistically significant reduction in post-exercise (Valsalva) LVOT peak gradient at Week 28 compared to placebo. Treatment with Camzyos achieved marked improvements in secondary parameters, including reductions in resting LVOT gradients, improvements in functional NYHA class status, and favorable reductions in key cardiac biomarkers (NT-proBNP and cardiac troponin I). The safety profile in adolescent patients was consistent with the established profile in adults, with serious adverse events occurring in 9% of the Camzyos group versus 10% of the placebo group. No patients in the Camzyos arm experienced a drop in left ventricular ejection fraction (LVEF) below 50% during the 28-week period. Due to the inherent risk of heart failure from systolic dysfunction, Camzyos remains accessible only through the restricted Camzyos Risk Evaluation and Mitigation Strategy (REMS) program.

Sources: BMS press release, updated Camzyos label

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Clinical Trial Data

Genmab - Rinatabart sesutecan (FRα ADC) / Phase 1/2 (PROC)

On October 3, 2026, Genmab reported positive Phase 2 topline data from the pivotal cohort of its Phase 1/2 RAINFOL-01 trial evaluating rinatabart sesutecan (Rina-S; GEN1184) in patients with platinum-resistant ovarian cancer (PROC).

Platinum-resistant ovarian cancer (PROC) poses a significant clinical challenge due to acquired cellular resistance mechanisms, such as enhanced DNA repair and altered drug efflux, that necessitate shifting from platinum regimens to single-agent non-platinum chemotherapy, often combined with targeted agents like bevacizumab or the folate receptor alpha (FRα)-directed antibody-drug conjugate (ADC) mirvetuximab soravtansine. To expand options in this space, rinatabart sesutecan (Rina-S) utilizes a novel human monoclonal antibody to target FRα and deliver exatecan, a potent topoisomerase I inhibitor, directly into tumor cells via a hydrophilic, protease-cleavable linker. Upon internalization, the payload causes double-stranded DNA breaks and apoptosis, while its optimized linker design is designed to enhance bystander killing of neighboring cancer cells and reduce systemic toxicities compared to legacy ADC platforms.

In the open-label Phase 1/2 RAINFOL-01 trial (n=109), rinatabart sesutecan (Rina-S) demonstrated significant, durable antitumor activity and a favorable safety profile in patients with platinum-resistant ovarian cancer. Rina-S achieved a confirmed objective response rate of 45.9% (including 5 complete responses), a median duration of response of 12.1 months (with 51% maintaining response at one year), and a median progression-free survival of 9.5 months. Treatment was well tolerated, with only a 5.5% discontinuation rate due to adverse events and no off-target safety signals such as ocular toxicity, interstitial lung disease, peripheral neuropathy, or severe stomatitis. Importantly, responses occurred across all folate receptor alpha (FRα) expression levels, including low and negative expressors, and in patients previously treated with mirvetuximab soravtansine. By demonstrating activity regardless of FRα status and utilizing a topoisomerase I inhibitor payload that overcomes tubulin-inhibitor resistance, Rina-S offers potential best-in-class utility to broaden treatment eligibility beyond current biomarker-restricted options.

Genmab has initiated the global Phase 3 RAINFOL-02 trial comparing Rina-S monotherapy against investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer. Evaluation of Rina-S is expanding into broader gynecologic malignancies, including ongoing cohorts in endometrial cancer and combination regimens in earlier lines of therapy.

Sources: Genmab press release

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Kodiak - Tarcocimab (VEGF inhibitor) / Phase 3 (wAMD)

On September 28, 2026, Kodiak Sciences announced positive topline results from the pivotal Phase 3 DAYBREAK trial evaluating tarcocimab tedromer (Zenkuda; KSI-301), a novel, high-molecular-weight anti-VEGF therapy, in patients with wet age-related macular degeneration (wAMD).

Wet age-related macular degeneration (wAMD) is an advanced retinal disease driven by elevated vascular endothelial growth factor (VEGF), causing abnormal vessel growth, intraretinal fluid leakage, and severe central vision loss that requires frequent, burden-heavy intravitreal anti-VEGF injections every 4 to 16 weeks. To address this treatment burden, tarcocimab tedromer utilizes Kodiak’s proprietary bioconjugation platform to link a humanized anti-VEGF monoclonal antibody to a high-molecular-weight biopolymer, extending its intraocular half-life to roughly 20 days, roughly three times longer than first-generation therapies. By maintaining prolonged therapeutic drug levels within the eye, tarcocimab inhibits VEGF-driven vascular permeability and fluid accumulation while significantly extending retreatment intervals to relieve the lifelong injection burden on patients and healthcare systems.

In the pivotal Phase 3 DAYBREAK study evaluating treatment-naïve wet age-related macular degeneration (wAMD), tarcocimab tedromer met its primary endpoint by achieving statistically significant visual acuity non-inferiority compared to aflibercept (p=0.0036), while demonstrating superior anatomical drying and central subfield thickness reductions (p<0.0001). Under strict treat-to-dryness criteria, 54% of tarcocimab-treated patients maintained an extended 24-week (6-month) dosing interval at Year 1 with a clean safety profile, showing low rates of intraocular inflammation (0%) and cataract-related events (0.5%). By pairing robust visual and anatomical gains with durable 6-month retreatment intervals, tarcocimab directly addresses real-world treatment fatigue and under-dosing, the primary drivers of long-term vision loss, positioning itself as a potential new standard-of-care that could significantly reduce clinic visit frequency and administrative burden in retinal disease management.

With five successful Phase 3 pivotal trials complete across three major retinal vascular indications (DAYBREAK and DAYLIGHT in wAMD, GLOW1 and GLOW2 in diabetic retinopathy [DR], and BEACON in retinal vein occlusion [RVO]) Kodiak Sciences plans to submit a single, comprehensive Biologics License Application (BLA) to the U.S. FDA in the fourth quarter of 2026. The BLA submission will seek approval for tarcocimab across wAMD, DR, and RVO simultaneously.

Sources: Kodiak press release, Kodiak slide deck

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AbbVie & Genmab - Epkinly (CD20 x CD3 TCE) / Phase 3 (1L DLBCL)

Genmab and AbbVie announced positive topline results from the pivotal Phase 3 EPCORE DLBCL-2 trial evaluating Epkinly (epcoritamab-bysp) in combination with standard-of-care R-CHOP chemoimmunotherapy in patients with newly diagnosed, untreated diffuse large B-cell lymphoma (DLBCL).

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma worldwide, characterized by an aggressive clinical course where up to 40% of patients experience disease relapse or refractory progression following frontline therapy. The landmark readout establishes Epkinly as the first T-cell engaging bispecific antibody to demonstrate a statistically significant improvement in progression-free survival (PFS) in the first-line DLBCL setting. Epkinly simultaneously targets CD20 expressed on malignant B-cell surfaces and CD3 expressed on endogenous T cells. By physically cross-linking cytotoxic T cells with CD20-positive B-cell lymphomas, Epkinly induces directed T-cell activation and proliferation, driving potent, immune-mediated lysis of malignant B cells. Pairing this targeted immune redirection with the broad anti-lymphoma activity of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) aims to eliminate residual disease early in treatment to prevent future relapses.

In the randomized Phase 3 EPCORE DLBCL-2 trial evaluating treatment-naïve diffuse large B-cell lymphoma (DLBCL), adding Epkinly (epcoritamab) to standard R-CHOP chemoimmunotherapy met its primary endpoint at a prespecified interim analysis by reducing the risk of disease progression or death by 51% compared to R-CHOP alone (HR=0.49, p<0.0001). The combination maintained a manageable safety profile with predominantly low-grade cytokine release syndrome and ICANS events that were well-controlled through standard step-up dosing and prophylaxis. By delivering a progression-free survival benefit that substantially exceeds historical benchmarks no a cross-trial basis, such as the hazard ratio of 0.73 observed with Polivy plus R-CHP in the POLARIX trial, Epkinly plus R-CHOP emerges as a major therapeutic milestone with the potential to reshape frontline standard-of-care and elevate initial cure rates without adding chemotherapy toxicity.

Genmab and AbbVie plan to submit these Phase 3 data to global regulatory authorities, including the FDA and EMA, to support a supplemental Biologics License Application (sBLA) for frontline DLBCL. Full efficacy and safety findings will be presented at an upcoming major medical congress.

Sources: Genmab press release, AbbVie press release

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Vaxcyte - VAX-31 (31-valent vaccine) / Phase 3 (pneumococcal)

On October 5, 2026, Vaxcyte reported positive topline results from OPUS-1, the pivotal Phase 3 trial evaluating VAX-31, its investigational 31-valent pneumococcal conjugate vaccine (PCV) candidate, in healthy adults aged 18 and older.

Streptococcus pneumoniae causes severe invasive pneumococcal disease (IPD) and pneumococcal pneumonia, posing significant risks of hospitalization and mortality in older adults and vulnerable populations. Currently approved adult vaccines, including Pfizer’s 20-valent Prevnar 20 (PCV20) and Merck’s 21-valent Capvaxive (PCV21), force a clinical trade-off because each covers a distinct subset of disease-causing serotypes. VAX-31 was designed to resolve this fragmentation by providing broader coverage (31 serotypes) in a single shot, covering approximately 95% of circulating IPD strains in adults aged 50 and older. VAX-31 is engineered using Vaxcyte’s cell-free protein synthesis bioconjugation platform. Traditional PCVs face chemical and manufacturing limits when adding polysaccharides, as excess protein carrier can cause carrier suppression and diminish overall immune responses. Vaxcyte’s carrier-sparing platform allows precise site-specific conjugation, enabling VAX-31 to incorporate 31 distinct capsular polysaccharide serotypes without overloading the immune system. Following administration, the conjugate vaccine stimulates opsonophagocytic antibodies (OPA) that mark bacterial capsules, potentially enabling immune cells to clear circulating pneumococcal strains.

In the pivotal Phase 3 OPUS-1 study (n=4,047), Vaxcyte’s 31-valent pneumococcal conjugate vaccine (VAX-31) successfully met all co-primary immunogenicity endpoints in healthy adults while demonstrating a favorable safety profile comparable to Prevnar 20 (PCV20) and Capvaxive (PCV21). VAX-31 achieved statistical noninferiority for all 28 shared serotypes in adults aged 50 and older, statistically significant superiority for its extra serotypes (plus cross-reactive 20B), and successful immunobridging to younger adults aged 18-49 without incurring any vaccine-related serious adverse events. By maintaining robust immune potency while expanding strain coverage to encompass approximately 95% of circulating adult invasive pneumococcal disease, VAX-31 demonstrates that valency expansion is achievable without sacrificing antibody responses, positioning it as a potential single-shot solution that could eliminate fragmented vaccine selection and reshape public health immunization guidelines.

Vaxcyte is executing its pivotal registration program to support global regulatory filings. The company expects to report topline safety, tolerability, and immunogenicity data from two additional Phase 3 adult trials (OPUS-2 and OPUS-3) in the first half of 2027. Following the readout of OPUS-2 and OPUS-3, Vaxcyte plans to submit a Biologics License Application (BLA) for VAX-31 in adults to the U.S. FDA in the first half of 2028. Vaxcyte is also evaluating VAX-31 in infants in an ongoing Phase 2 dose-finding study, with primary series and booster data expected by the end of the first half of 2027.

Sources: Vaxcyte press release, Vaxcyte slide deck

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Regeneron - Ubamatamab (MUC16 x CD3 TCE) / Phase 1/2 (LGSOC)

On October 1, 2026, Regeneron Pharmaceuticals reported positive initial clinical data from the ongoing Phase 1/2 trial evaluating ubamatamab (REGN4018), an investigational MUC16 x CD3 T-cell engaging bispecific antibody (TCE), in patients with advanced low-grade serous ovarian cancer (LGSOC). LGSOC is a distinct, biologically indolent form of epithelial ovarian cancer that disproportionately affects younger women and is characterized by a low mutational burden, high MUC16 expression, and intrinsic resistance to standard platinum-based chemotherapies. With historical objective response rates below 15% for chemotherapy or hormone therapy in the recurrent setting, treatment options remain severely limited. The data presentation at the International Gynecologic Cancer Society (IGCS) 2026 Annual Global Meeting highlighted high response rates and durable disease control in heavily pretreated patients.

In an ongoing Phase 1/2 trial evaluating intravenous ubamatamab monotherapy in heavily pretreated low-grade serous ovarian cancer (LGSOC; n=11), treatment resulted in robust, durable antitumor activity and a manageable safety profile. Ubamatamab achieved a 73% objective response rate (95% CI: 39.0–94.0), a median duration of response of 9.0 months, and a median progression-free survival of 11.0 months. While cytokine release syndrome occurred in 90% of safety-evaluable patients (n=19), all events were low-grade (Grade 1/2) and confined to the step-up dosing period, with primary Grade ≥3 toxicities limited to manageable cytopenias (neutropenia 21%, anemia 11%) and transient transaminase elevations (11%), with no treatment-related deaths.

Regeneron is actively expanding development to support potential regulatory submissions. They are currently enrolling a prospective, single-arm, potentially registrational Phase 2 expansion cohort of up to 100 patients with recurrent LGSOC receiving 800 mg monotherapy every three weeks. Regeneron is also planning a randomized, controlled Phase 3 confirmatory trial to evaluate ubamatamab in broader LGSOC populations following alignment with the FDA and global regulatory authorities.

Sources: Regeneron press release

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Connect - Rademikibart (anti-IL4Rα mAb) / Phase 2 (COPD)

On September 30, 2026, Connect Biopharma reported positive preliminary topline results from its Phase 2 Seabreeze STAT COPD study evaluating rademikibart (CBP-201), an investigational anti-interleukin-4 receptor alpha (IL4Rα) monoclonal antibody, as an add-on treatment following acute exacerbations in adults with chronic obstructive pulmonary disease (COPD) and type 2 inflammation.

Chronic obstructive pulmonary disease (COPD) is a progressive, debilitating respiratory disorder characterized by persistent airflow obstruction, chronic airway inflammation, and recurrent acute exacerbations that drive disease progression and frequent emergency department visits or hospitalizations. While standard care relies on bronchodilators, inhaled corticosteroids, and short-term oral steroids, a substantial subset of patients with type 2 inflammation (marked by elevated blood eosinophils) experience frequent post-exacerbation treatment failures. By shutting down type 2 inflammatory drivers, rademikibart aims to stabilize the airway microenvironment immediately following an acute exacerbation, preventing secondary relapse and sustained tissue injury.

In the Phase 2 Seabreeze STAT trial (n = 159) evaluating adults with COPD, type 2 inflammation, and an active acute exacerbation, a single dose of rademikibart demonstrated significant efficacy in preventing acute relapse while exhibiting a favorable, well-tolerated safety profile with fewer adverse events than placebo. Rademikibart achieved an 81% reduction in treatment failure through Week 4 compared to placebo (p = 0.0122), an 85% reduction in new moderate-to-severe exacerbations (p = 0.030), and a 100% elimination of emergency care visits or hospitalizations (p = 0.0137), alongside meaningful reductions in rescue medication use and rapid improvements in respiratory symptom scores. While its Day 7 post-bronchodilator FEV1 endpoint did not reach statistical significance, the overall clinical benefit underscores rademikibart’s potential as a novel acute post-exacerbation intervention, extending IL4Rα inhibition beyond chronic maintenance therapy to prevent re-hospitalizations and protect vulnerable patients during high-risk post-exacerbation windows.

Connect Biopharma is preparing to advance rademikibart into late-stage clinical development. The company plans to engage with the FDA to align on a Phase 3 registrational development program for rademikibart as an add-on therapy in COPD. Connect is advancing an intravenous (IV) formulation alongside its subcutaneous injection for potential deployment in emergency department and inpatient hospital settings. The company also plans to seek global commercialization partnerships (outside Greater China, where rights are licensed to Simcere Pharmaceutical) across both its asthma and COPD clinical development programs.

Sources: Connect press release, Connect slide deck

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Immix - NXC-201 (BCMA CAR-T) / Phase 2 (AL amyloidosis)

On September 29, 2026, Immix Biopharma reported positive interim topline results from the pivotal Phase 2 NEXICART-2 trial evaluating NXC-201 (nexicabtagene autoleucel), an investigational BCMA-directed chimeric antigen receptor CAR-T therapy, in patients with relapsed or refractory light-chain (AL) amyloidosis.

AL amyloidosis is a rare, life-threatening plasma cell disorder where clonal plasma cells produce misfolded immunoglobulin light chains that deposit as toxic amyloid fibrils in vital organs, leading to progressive heart, kidney, and liver failure. Currently, there are no FDA-approved options for patients who relapse after frontline anti-CD38-based therapy, leaving patients facing heavy treatment burdens and high mortality. By binding specifically to BCMA on pathogenic plasma cells in the bone marrow, NXC-201 is designed to redirect autologous T lymphocytes to induce targeted cell lysis, potentially eliminating the root cellular source of toxic light chains and halting further organ damage.

In the pivotal Phase 2 NEXICART-2 trial (n=45) evaluating adults with relapsed/refractory AL amyloidosis, a single infusion of NXC-201 demonstrated high, durable hematologic and organ response rates alongside a manageable safety profile featuring zero observed ICANS/neurotoxicity and low-grade cytokine release syndrome. NXC-201 achieved an Independent Review Committee-confirmed 89% complete response (CR) rate with no relapses observed to date among responders, while a 25-patient subset demonstrated 100% combined CR or bone-marrow minimal residual disease (MRD) negativity, supporting projections that the final trial CR rate could reach 98%. Beyond hematologic clearing, NXC-201 induced rapid, profound organ recovery, including a 100% cardiac response rate and a 92% renal response rate, establishing its potential as a transformative single-dose therapy that overcomes the limited organ-reversal capabilities of conventional regimens while its clean neurotoxicity profile supports broader outpatient utility.

Supported by FDA Breakthrough Therapy Designation (BTD), Regenerative Medicine Advanced Therapy (RMAT) designation, and Orphan Drug Designation (ODD), Immix plans to present the final NEXICART-2 readout and submit a Biologics License Application (BLA) to the FDA in mid-2027. The company is planning a randomized, 260-patient Phase 3 trial mirroring the ANDROMEDA trial design to evaluate NXC-201 in frontline AL amyloidosis. Immix Biopharma is advancing NXC-201 toward potential commercialization, in the event of regulatory approval. The company is establishing a targeted commercial model encompassing 60 to 70 specialized CAR-T treatment centers across the U.S.

Sources: Immix press release, Immix slide deck

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BMS - BMS-986453 (BCMA x GPRC5D bsCAR-T) / Phase 1 (r/r MM)

On September 29, 2026, Bristol Myers Squibb (BMS) announced positive initial results from a Phase 1 clinical trial evaluating BMS-986453, an investigational, dual-targeting autologous chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed or refractory multiple myeloma (r/r MM). The results were presented by Dr. Doris K. Hansen at the 23rd International Myeloma Society Annual Meeting & Exposition.

Multiple myeloma is an incurable hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow. Despite recent advances with single-target CAR-T therapies (such as those directed against BCMA), patients frequently relapse due to antigen escape, loss of target expression, or T-cell exhaustion. By simultaneously targeting two validated multiple myeloma antigens, B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GPRC5D), BMS-986453 is engineered to mitigate target antigen loss and deliver deeper, more durable responses in heavily pretreated populations.

In an ongoing Phase 1 dose-escalation and expansion study evaluating patients with heavily pretreated relapsed or refractory multiple myeloma, a single infusion of the dual-targeting BCMA x GPRC5D CAR-T therapy BMS-986453 demonstrated potent early efficacy alongside an intensive safety profile. BMS-986453 achieved an 83% overall response rate with high rates of deep clinical responses (including very good partial responses and complete responses), maintaining antitumor activity even in patients previously exposed to single-target BCMA therapies. However, significant toxicity was noted, including one patient death attributed to severe, high-grade CRS. Cytokine release syndrome was common and mostly low-grade, though safety management remains paramount given one treatment-related death attributed to severe CRS. ICANS and GPRC5D-related on-target/off-tumor toxicities (such as dysgeusia and skin or nail changes) were generally mild and manageable. Overall, these results validate dual-antigen targeting as an effective strategy to overcome antigen escape in advanced multiple myeloma while underscoring the critical importance of dose and toxicity optimization.

BMS is progressing the clinical development of BMS-986453 to establish an optimal therapeutic window. Ongoing Phase 1 dose-escalation and expansion cohorts are actively refining dosing regimens, schedule optimization, and prophylactic CRS management protocols to maximize patient safety while preserving antitumor activity. Following the determination of the recommended Phase 2 dose (RP2D) and further characterization of response durability, BMS plans to align with regulatory agencies on pivotal Phase 2/3 trial designs to evaluate BMS-986453 in broader multiple myeloma settings.

Sources: BMS slide deck

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Mirum - Brelovitug (anti-HBsAg mAb)/ Phase 3 (HDV)

On September 28, 2026, Mirum Pharmaceuticals announced positive topline results from the pivotal Phase 3 portion of its AZURE-1 study evaluating brelovitug (BJT-778), an investigational monoclonal antibody, in treatment-naïve patients with chronic hepatitis delta virus (HDV) infection.

Chronic HDV is considered the most severe form of viral hepatitis, occurring exclusively as a co-infection in individuals carrying the hepatitis B virus (HBV) and leading to rapid progression toward liver cirrhosis, portal hypertension, liver failure, and hepatocellular carcinoma. Untreated patients face severe disease progression and high liver-related mortality. Brelovitug is a fully human IgG1 monoclonal antibody targeting the hepatitis B surface antigen (HBsAg). Since HDV is a defective RNA virus that relies entirely on HBsAg envelope proteins for viral assembly, cellular entry, and systemic propagation, targeting HBsAg effectively targets both viruses simultaneously. Brelovitug binds to and neutralizes circulating HBsAg-containing particles, preventing viral entry into hepatocytes and promoting the rapid clearance of circulating HBV and HDV virions. By depleting subviral particles and shutting down hepatocyte reinfection, brelovitug breaks the cycle of active viral replication and ongoing liver inflammation.

In the pivotal Phase 3 AZURE-1 trial (n = 153) evaluating treatment-naïve adult patients with chronic hepatitis delta virus (HDV), subcutaneous brelovitug met its primary composite endpoint at Week 24 with high statistical significance across both weekly (300 mg QW) and monthly (900 mg Q4W) regimens while maintaining a favorable safety profile characterized by mild-to-moderate adverse events. Brelovitug achieved combined virologic response (≥ 2log10 reduction or undetectable HDV RNA) and ALT normalization in 56% of weekly (p < 0.0001) and 45% of monthly (p < 0.0001) patients compared to 0% in delayed control, with overall virologic response reaching 86% (QW) and 85% (Q4W) alongside 48-week follow-up showing deepening response rates over time.

Mirum Pharmaceuticals is advancing brelovitug toward regulatory filing and commercial preparation. The plan to submit a Biologics License Application (BLA) to the FDA in the first half of 2027. Mirum is targeting a U.S. commercial launch in the fourth quarter of 2027, supported by FDA Breakthrough Therapy designation and ongoing device development for autoinjector administration.

Sources: Mirum press release, Mirum slide deck

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Adicet - Prula-cel (allo gamma delta T cells) / Phase 1 (SLE)

On September 28, 2026, Adicet Bio reported positive Phase 1 clinical data evaluating prula-cel (formerly ADI-001), an investigational, allogeneic gamma-delta CD19 CAR T-cell therapy, in patients with systemic lupus erythematosus (SLE) with or without lupus nephritis (LN).

Systemic lupus erythematosus (SLE) is a severe autoimmune disorder characterized by pathogenic B-cell reactivity that causes widespread inflammation and tissue damage across multiple organ systems. Prula-cel provides an allogeneic, off-the-shelf option that achieves deep tissue B-cell depletion while reducing manufacturing wait times and systemic toxicity risks. Upon infusion, prula-cel targets CD19-expressing B cells in peripheral blood and immune tissues to clear autoreactive B-cell lineages.

In an ongoing Phase 1 study evaluating adults with heavily pretreated, refractory systemic lupus erythematosus (SLE) and lupus nephritis (LN), a single infusion of the allogeneic gamma-delta CAR T-cell therapy prula-cel demonstrated durable clinical remissions and a clean safety profile suitable for outpatient administration. At 12 months post-infusion, 54% of evaluable patients (n=22) achieved Definition of Remission in Systemic Lupus (DORIS) remission and 50% of LN patients attained a Complete Renal Response, with all responses remaining ongoing out to 12–21 months alongside complete background immunosuppressant discontinuation, full peripheral B-cell depletion, and favorable immune resetting. Safety across 24 evaluable patients showed no dose-limiting toxicities, graft-versus-host disease, ICANS, or Grade ≥3 cytokine release syndrome, with CRS restricted to low-grade events in 25% of patients. Although its 54% 12-month remission rate falls numerically below autologous alpha-beta CAR-T benchmarks, prula-cel offers a highly competitive, scalable off-the-shelf alternative that bypasses manufacturing delays and autologous toxicity burdens to deliver sustained, treatment-free remissions in severe autoimmune disease.

Adicet Bio is progressing prula-cel into late-stage registrational development. They plan to initiate pivotal start-up activities in the fourth quarter of 2026 for refractory lupus nephritis. Adicet is continuing clinical development across additional autoimmune indications, with anticipated Phase 1 data updates in systemic sclerosis (SSc) in the first half of 2027.

Sources: Adicet press release, Adicet slide deck

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Table of Contents

The 35th European Academy of Dermatology and Venereology (EADV) Congress took place on September 30 to October 3, 2026 in Vienna, Austria. In this article, we discuss the following high-impact datasets:

• Atopic Dermatitis

  • AbbVie - Zumilokibart (anti-IL13 mAb) / Phase 2 (atopic derm) ⬇️

  • Nektar - Rezpeg (IL-2 agonist) / Phase 2b, REZOLVE-AD trial (atopic derm) ⬇️

  • Pfizer - Tilrekimig (IL4 x IL13 x TSLP mAb) / Phase 2 (atopic derm) ⬇️

  • Evommune - EVO301 (anti-IL18 mAb) / Phase 2a (atopic derm) ⬇️

• Lupus

  • Amgen - Daxdilimab (anti-ILT7 mAb) / Phase 2 (DLE) ⬇️

  • Biogen - Litifilimab (anti-BDCA2 mAb) / Phase 2 (CLE) ⬇️

• Non-segmental vitiligo (NSV)

  • AbbVie - Rinvoq (JAK inhibitor) / Phase 3 (NSV) ⬇️

  • Pfizer - Litfulo (JAK3 x TEC inhibitor) / Phase 3 (NSV) ⬇️

• Plaque Psoriasis

  • J&J - Icotyde (anti-IL23 mAb) / Phase 3 (psoriasis) ⬇️

  • Takeda - Zasocitinib (TYK2 inhibitor) / Phase 3 (psoriasis) ⬇️

• Hidradenitis suppurativa (HS)

  • Merck - Tulisokibart (TL1A inhibitor) / Phase 2 (HS) ⬇️

• Alopecia Areata

  • Nektar - Rezpeg (IL-2 agonist) / Phase 2b, REZOLVE-AA trial (alopecia areata) ⬇️

Special thanks to for motivating me to publish this article, which I had previously shelved due to my difficulty in finding slides/figures. I hope you enjoy it!

Atopic Dermatitis

AbbVie - Zumilokibart (anti-IL13 mAb) / Phase 2 (atopic derm)

On September 30, 2026, Dr. Melinda Gooderham presented AbbVie’s primary Week 16 data from the Phase 2 APEX Part B study evaluating zumilokibart (APG777), a novel half-life-extended anti-IL-13 monoclonal antibody added to AbbVie’s portfolio via its $10.9 billion acquisition of Apogee Therapeutics, which we covered here. The readout highlighted zumilokibart’s ability to deliver robust clinical clearance and symptom relief, positioning it as a potentially transformational, extended-interval biologic for patients with chronic AD.

Zumilokibart is a high-affinity humanized IgG1 monoclonal antibody designed to selectively target and neutralize interleukin-13 (IL-13). By binding soluble IL-13, zumilokibart inhibits its binding to the IL-13R-alpha-receptor complex, suppressing downstream type 2 inflammatory cascades that drive skin lesion formation, epidermal barrier breakdown, and pruritus. Featuring YTE amino acid modifications in its Fc domain, zumilokibart exhibits an extended terminal half-life of approximately 75 to 77 days in humans. This prolonged durability is engineered to maintain therapeutic plasma concentrations across extended, multi-month dosing intervals (e.g., Q12W or Q24W).

In the Phase 2 APEX Part B dose-ranging trial in adults with moderate-to-severe atopic dermatitis, subcutaneous zumilokibart demonstrated high-level skin clearance and a well-tolerated safety profile across 16 weeks. All three dose groups achieved statistically significant superiority over placebo (p<0.01), led by the mid-dose cohort, which reached 65.9% EASI-75 (vs. 23.4% placebo), 46.0% vIGA-AD 0/1 (vs. 10.9% placebo), and 47.4% EASI-90 (vs. 9.3% placebo). Zumilokibart was generally well tolerated with low serious adverse event rates and class-consistent mild-to-moderate toxicities, such as nasopharyngitis, headache, and noninfective conjunctivitis (≥5%). By pairing competitive depth of response with an Fc-engineered half-life of ~77 days, zumilokibart holds the potential to shift the atopic derm treatment paradigm toward maintenance dosing every 3 to 6 months, significantly reducing injection frequency compared to standard biweekly biologics.

AbbVie confirmed that the mid-dose regimen has been selected for pivotal Phase 3 global clinical development, based on its optimal combination of rapid onset, high response rates, and tolerability. Phase 3 clinical trials in moderate-to-severe atopic derm are set to begin in the second half of 2026, with 52-week maintenance readouts expected in the first half of 2027.

Sources: AbbVie press release, Dermatology Times article

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Nektar - Rezpeg (IL-2 agonist) / Phase 2b, REZOLVE-AD trial (atopic derm)

On September 30, 2026, Dr. Meredith Manson presented updated maintenance and multi-omic biomarker findings for rezpegaldesleukin (rezpeg / NKTR-358), Nektar Therapeutics’ wholly owned regulatory T cell (Treg) stimulator. While established biologics and oral JAK inhibitors rely on immunosuppressive pathways that continuously block effector cytokines (such as IL-4, IL-13, or IL-31), rezpegaldesleukin introduces a homeostatic, disease-modifying approach.

In the Phase 2b REZOLVE-AD trial in 393 biologic- and JAK-naive adults with moderate-to-severe atopic dermatitis, subcutaneous rezpegaldesleukin demonstrated significant skin clearance, durable itch relief, and a well-tolerated safety profile through 52 weeks. At Week 16, the high-dose induction cohort (24 μg/kg Q2W) achieved statistically superior responses over placebo (p<0.001), including 42% EASI-75 (vs. 17% placebo), 25% EASI-90 (vs. 9% placebo), 20% vIGA-AD 0/1 (vs. 8% placebo), and 42% itch reduction (vs. 16% placebo). Clinical improvements deepened and were maintained across 36 weeks of extended maintenance on quarterly (Q12W) dosing, while safety was marked primarily by mild-to-moderate transient injection site reactions, pyrexia, and nasopharyngitis with no severe infection or systemic activation signals. By proving that selective regulatory T-cell (Treg) expansion can reset broader tissue inflammation, these results validate rezpegaldesleukin as a novel, disease-modifying therapy capable of maintaining skin clearance on infrequent quarterly dosing.

Following these results and publication in The Lancet, Nektar initiated the global Phase 3 ZENITH-AD program to evaluate rezpegaldesleukin in moderate-to-severe atopic dermatitis. Nektar is advancing rezpegaldesleukin across additional Treg-deficient autoimmune and inflammatory indications, including severe-to-very-severe alopecia areata (Phase 2b REZOLVE-AA) and severe ulcerative colitis.

Sources: Nektar press release, Nektar EADV 2026 slide deck

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Pfizer - Tilrekimig (IL4 x IL13 x TSLP mAb) / Phase 2 (atopic derm)

On October 1, 2026, Dr. Eric Simpson presented Phase 2 data for Pfizer’s tilrekimig (PF-07275315), a first-in-class investigational trispecific antibody targeting interleukin-4 (IL-4), interleukin-13 (IL-13), and thymic stromal lymphopoietin (TSLP). While current biologic standards of care effectively target downstream type 2 cytokines or shared receptor subunits, a significant subset of patients with moderate-to-severe atopic dermatitis (AD) continue to suffer from persistent itch and residual lesions. The Week 16 results showcased tilrekimig’s ability to deliver high-level skin clearance, substantial itch relief, and a placebo-like tolerability profile on convenient monthly administration. Featuring an engineered terminal half-life of approximately 37 days, tilrekimig maintains therapeutic drug exposures over extended monthly (Q4W) dosing intervals.

In a Phase 2 trial evaluating biologic-naïve adults with moderate-to-severe atopic dermatitis, monthly (Q4W) administration of trispecific antibody tilrekimig in Stage 2 achieved high-level efficacy, with the 200 mg Q4W arm reaching 61.0% EASI-75 (a 51.9% delta over placebo; p<0.003), 26-27% vIGA-AD 0/1 (vs. 0% placebo), and 50.8% itch response (a 43.6% delta over placebo) at 16 weeks. Adverse event rates across monthly cohorts (42.2-47.8%) were lower than placebo (52.2%), with no drug-related serious adverse events and conjunctivitis rates comparable to placebo.

Pfizer has advanced tilrekimig into Phase 3 global clinical development for moderate-to-severe atopic dermatitis, including a pivotal trial featuring dupilumab as an active comparator. Beyond dermatology, tilrekimig is currently being evaluated in Phase 3 trials for asthma and an ongoing Phase 2b/3 study for chronic obstructive pulmonary disease (COPD).

Sources: Pfizer press release

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Evommune - EVO301 (anti-IL18 mAb) / Phase 2a (atopic derm)

On October 1, 2026, Dr. Mark Lebwohl presented Phase 2a results for EVO301, Evommune’s novel, long-acting monoclonal antibody targeting interleukin-18 (IL-18). The clinical readout demonstrated that selectively targeting IL-18 drives rapid, statistically significant reductions in skin lesion severity and itch, establishing EVO301 as a potentially promising novel therapy designed to disrupt upstream epithelial inflammatory signaling.

In the Phase 2a trial evaluating adult patients with active moderate-to-severe atopic dermatitis, Evommune’s novel anti-IL-18 antibody EVO301 achieved its primary efficacy endpoint and key secondary endpoints with rapid onset and a clean safety profile over 12 weeks. Patients treated with EVO301 achieved a statistically significant 55% mean reduction in EASI score from baseline compared to 22% for placebo (p<0.01), alongside robust secondary response rates including 29% EASI-75 (vs. 9% placebo; p<0.05), 63% EASI-50 (vs. 23% placebo; p<0.01), and early itch reduction within the initial weeks of therapy. Treatment was well tolerated with mild-to-moderate adverse events balanced against placebo, and no serious adverse events or drug-related safety signals observed.

Following these positive Phase 2a results, Evommune is preparing to advance EVO301 into a larger Phase 2b dose-ranging study in moderate-to-severe atopic dermatitis to optimize dosing regimens and evaluate longer-term maintenance efficacy. Driven by IL-18’s broad role in epithelial barrier inflammation, Evommune plans to explore EVO301’s therapeutic utility across additional inflammatory skin and systemic immune indications.

Sources: Evommune press release

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Lupus

Systemic lupus erythematosus (SLE), including its cutaneous variants like discoid lupus (DLE) and subacute cutaneous lupus (SCLE), is a chronic autoimmune disease driven by impaired apoptotic cell clearance, exposure of nuclear autoantigens, and subsequent hyperactivation of plasmacytoid dendritic cells (pDCs) that overproduce type I interferons (IFN-α/β). This immune dysregulation triggers autoreactive B-cell activation, pathogenic autoantibody production, and tissue deposition of immune complexes, resulting in chronic inflammation, dermal interface dermatitis, follicular plugging, and progressive organ damage or irreversible scarring. Standard of care relies on strict broad-spectrum photoprotection alongside oral antimalarials, primarily hydroxychloroquine, as the foundational pharmacotherapy for all cutaneous and systemic manifestations. Management of localized or acute flares incorporates high-potency topical corticosteroids or topical calcineurin inhibitors (tacrolimus) for skin lesions, while severe cutaneous or systemic organ involvement requires short-term oral corticosteroids, conventional immunosuppressants (mycophenolate mofetil, azathioprine, or methotrexate), and targeted biologic therapies such as belimumab (anti-BAFF) or anifrolumab (anti-type I IFN receptor).

Amgen - Daxdilimab (anti-ILT7 mAb) / Phase 2 (DLE)

On September 30, 2026, Dr. Victoria Werth presented positive Phase 2 discoid lupus erythematosus (DLE) results for daxdilimab (HZN-7734), a first-in-class monoclonal antibody acquired by Amgen through its $27.8 billion buyout of Horizon Therapeutics.

In a Phase 2 trial evaluating adult patients with moderate-to-severe, treatment-refractory discoid lupus erythematosus (DLE), subcutaneous daxdilimab demonstrated significant reductions in skin disease activity and a well-tolerated safety profile through 24 weeks. Both low-dose and high-dose cohorts met the primary endpoint, driving an approximate 6-point mean reduction in CLASI-A score over placebo alongside robust CLASI-50 response rates of 61.7% (p=0.0037) and 62.1% (p=0.0044) compared to 23.7% for placebo, with clear separation on CLA-IGA 0/1 skin clearance. Adverse event rates were similar across arms with zero reported serious adverse events or deaths, and only one discontinuation due to arthralgia. By achieving over 60% CLASI-50 responses in a refractory population, these findings validate plasmacytoid dendritic cell (pDC) depletion via ILT7 targeting as a promising disease-modifying approach to address high unmet need and prevent irreversible scarring in organ-dominant cutaneous lupus.

Following the EADV 2026 readout, Amgen confirmed it is preparing to advance daxdilimab into Phase 3 registrational studies for patients with moderate-to-severe discoid lupus erythematosus (DLE). Amgen continues evaluating daxdilimab across additional autoantibody and interferon-mediated inflammatory diseases, including dermatomyositis and alopecia areata.

Sources: Dermatology Times article

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Biogen - Litifilimab (anti-BDCA2 mAb) / Phase 2 (CLE)

On October 2, 2026, Dr. Joseph Merola presented 52-week extension data from the Phase 2 part of the ongoing AMETHYST study evaluating Biogen’s litifilimab (BIIB059). Cutaneous lupus erythematosus (CLE) spanning subacute and chronic discoid subtypes causes severe, disfiguring skin lesions, scarring, and hair loss that frequently prove recalcitrant to antimalarials and standard immunosuppressants. With no therapies specifically approved by global regulatory authorities solely for CLE, presented long-term results highlighted litifilimab’s ability to drive progressive, deepening skin clearance out to one year, positioning it as a potential first-in-class targeted biologic for this underserved patient population.

In the Phase 2 portion of the AMETHYST trial in adults with active subacute or chronic cutaneous lupus erythematosus (CLE) refractory to antimalarials, litifilimab demonstrated progressive, durable efficacy and a favorable safety profile through 52 weeks. Among participants receiving continuous litifilimab, clear or almost clear skin status (CLASI-A 0/1) improved from 19% at Week 24 to 25% (27.2%) at Week 52, while deep responses (CLASI-70) rose from 21.7% to 28.8%; notably, patients crossing over from placebo at Week 24 showed rapid clinical improvement within 4 weeks, reaching 33.7% CLASI-A 0/1 by Week 52. Subcutaneous litifilimab was well tolerated over a full year, with mostly mild-to-moderate adverse events (such as nasopharyngitis, influenza, and arthralgia) and low serious adverse event rates (3.4%) during the extension phase, reinforcing its disease-modifying potential for long-term skin clearance.

The blinded Phase 3 portion of the global AMETHYST program is currently ongoing, with pivotal trial data expected to read out in the first half of 2027. Upon successful Phase 3 completion, Biogen plans to file global regulatory applications for CLE market authorization, while continuing parallel Phase 3 evaluation of litifilimab in systemic lupus erythematosus (SLE).

Sources: Biogen press release

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Non-segmental vitiligo (NSV)

Non-segmental vitiligo (NSV) is an autoimmune dermatological disease driven by the destruction of epidermal melanocytes due to a breakdown in self-tolerance, where oxidative stress within melanocytes triggers the release of damage-associated molecular patterns (DAMPs) that activate dendritic cells and CD8+ cytotoxic T lymphocytes. Driven by a type 1 cytokine response, infiltrating autoreactive CD8+ T cells produce interferon-gamma (IFN-γ), which signals through the JAK1/JAK2 pathway in keratinocytes to induce CXCL9 and CXCL10 chemokine production, recruiting additional autoreactive T cells to the epidermis to kill melanocytes and produce symmetric depigmented macules. Standard of care centers on halting disease progression and inducing repigmentation: localized or mild-to-moderate involvement is managed with topical anti-inflammatory agents, primarily topical calcineurin inhibitors (tacrolimus, pimecrolimus), topical corticosteroids, or the topical JAK inhibitor ruxolitinib, often combined with narrow-band ultraviolet B (NB-UVB) phototherapy, to stimulate melanocyte stem cell migration and repigmentation, while rapidly progressing or widespread disease may require short pulses of systemic corticosteroids to stabilize active lesions.

AbbVie - Rinvoq (JAK inhibitor) / Phase 3 (NSV)

On October 1, 2026, Dr. Julien Seneschal presented 76-week data from the Phase 3 Viti-Up-1 and Viti-Up-2 trials evaluating AbbVie’s Rinvoq (upadacitinib) in adults and adolescents with non-segmental vitiligo (NSV). The long-term readout demonstrated that continuous oral JAK1 inhibition drives progressive facial and total-body repigmentation over 76 weeks, while early sub-study data highlighted the additive benefit of co-administering narrowband ultraviolet B (NB-UVB) phototherapy.

The Phase 3 Viti-Up program consists of two replicate 160-week, global, randomized, double-blind, placebo-controlled trials (Viti-Up-1 and Viti-Up-2) evaluating daily oral upadacitinib (15 mg) in patients aged 12 years and older with active NSV. In patients who continued on Rinvoq 15 mg once daily in the OLE, proportions of patients achieving F-VASI 75 and T-VASI 50 continued to increase from week 48 through week 76 (see table below). As observed-case analyses during an open-label extension without a placebo comparator, formal p-values were not reported for Week 76 endpoints.

Among patients previously on Rinvoq during Period A who had incomplete responses, adding NB-UVB twice weekly led to higher repigmentation rates than Rinvoq alone (see table below). Rinvoq 15 mg daily was well tolerated through 76 weeks, with safety results consistent with the established profile of upadacitinib and no new safety signals observed.

Rinvoq’s sNDA for non-segmental vitiligo remains under active review by the FDA, with a regulatory decision anticipated based on the pivotal 48-week and long-term Viti-Up data. Following its approval in the European Union, AbbVie plans to utilize long-term safety and phototherapy combination data to refine clinical administration guidelines and support broader market access for systemic vitiligo management.

Sources: AbbVie press release

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Pfizer - Litfulo (JAK3 x TEC inhibitor) / Phase 3 (NSV)

On October 02, 2026, Dr. Iltefat Hamzavi presented Phase 3 data from the pivotal TRANQUILLO and TRANQUILLO 2 trials evaluating Pfizer’s Litfulo (ritlecitinib) in patients with non-segmental vitiligo (NSV). Building on Litfulo’s established approval in severe alopecia areata, the 52-week Phase 3 readouts demonstrated that daily oral administration drives statistically significant, progressive facial and total-body repigmentation, positioning Litfulo as a potentially promising systemic candidate for NSV (note that Litfulo is not currently approved for NSV).

In two pivotal Phase 3 trials (TRANQUILLO and TRANQUILLO 2) evaluating 2,174 patients with active or stable non-segmental vitiligo, daily oral ritlecitinib demonstrated statistically significant, dose-dependent facial and total-body repigmentation over 52 weeks with a well-tolerated safety profile. At Week 52, the 100 mg daily dose in TRANQUILLO 2 achieved 21.86% F-VASI75 (vs. 2.40% placebo; p<0.0001) and 13.02% T-VASI50 (vs. 2.40% placebo; p<0.0001), while the 50 mg daily dose in TRANQUILLO achieved 12.47% F-VASI75 (vs. 2.48% placebo; p<0.001) and 8.98% T-VASI50 (vs. 1.98% placebo; p<0.001), with efficacy separating from placebo by Week 24 and continuing to deepen through Week 52 alongside significant improvements on the Vitiligo Noticeability Scale. Treatment was well tolerated, with adverse event rates comparable to placebo (TRANQUILLO 2: 67.7% vs. 62.0%; TRANQUILLO: 81.0% vs. 77.1%) mostly consisting of upper respiratory infections, nasopharyngitis, and headache, and low, balanced serious adverse event rates (≤3.4%).

Pfizer plans to submit data from the TRANQUILLO program to the FDA, European Medicines Agency (EMA), and other global regulatory agencies to support label expansion for Litfulo in non-segmental vitiligo. Participants from both parent trials are continuing into an ongoing open-label extension study to evaluate the durability of repigmentation, optimal dose maintenance, and safety over multi-year treatment periods.

Sources: Pfizer press release

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Plaque Psoriasis

Plaque psoriasis is a chronic, immune-mediated inflammatory skin disease initiated by environmental, mechanical, or genetic triggers that cause stressed keratinocytes to release antimicrobial peptides (such as LL-37) and extracellular DNA, forming complexes that activate plasmacytoid dendritic cells. These activated antigen-presenting cells secrete interleukin-12 (IL-12) and interleukin-23 (IL-23), driving the differentiation and expansion of pathogenic T helper 17 (Th17) lymphocytes that infiltrate the dermis and epidermis to produce high levels of interleukin-17A (IL-17A), interleukin-17F (IL-17F), interleukin-22 (IL-22), and tumor necrosis factor-alpha (TNF-alpha). This localized IL-23/IL-17 inflammatory cascade triggers rapid epidermal hyperproliferation (shortening keratinocyte cell turnover from ~28 days to 3-5 days), altered epidermal differentiation, and neutrophilic/lymphocytic recruitment, resulting in hyperkeratotic, erythematous plaques covered with silvery-white scales. Standard of care is stratified by disease severity and anatomical involvement: mild-to-moderate disease is managed topically with high-potency corticosteroids, vitamin D₃ analogues (calcipotriene), fixed-dose combination agents, or topical non-steroidal small molecules (tazarotene, the PDE4 inhibitor roflumilast, or the AhR agonist tapinarof); moderate-to-severe disease requiring systemic intervention utilizes narrow-band ultraviolet B (NB-UVB) phototherapy, oral small molecules (deucravacitinib [TYK2 inhibitor], apremilast [PDE4 inhibitor], or methotrexate), or targeted biologics, primarily monoclonal antibodies directed against IL-17 (secukinumab, ixekizumab, bimekizumab), IL-23 p19 (risankizumab, guselkumab, tildrakizumab), or TNF-alpha (adalimumab, infliximab).

J&J - Icotyde (anti-IL23 mAb) / Phase 3 (psoriasis)

On October 2, 2026, Dr. Richard Warren presented two-year (112-week) long-term follow-up results from the Phase 3 ICONIC-TOTAL trial evaluating Johnson & Johnson’s Icotyde (icotrokinra; JNJ-2113). While biological therapies targeting the interleukin-23 (IL-23) pathway are established gold standards for moderate-to-severe plaque psoriasis, their reliance on frequent subcutaneous or intravenous injections presents an ongoing delivery burden. As a first-in-class targeted oral peptide, Icotyde combines the convenience of a daily pill with the therapeutic power and specificity of an injectable biologic. The two-year data readout demonstrated that daily oral Icotyde provides progressive, durable overall skin clearance and complete resolution of difficult-to-treat, high-impact anatomical sites, including the scalp, genitalia, hands, feet, and nails.

In the Phase 3 ICONIC-TOTAL trial evaluating 311 adults and adolescents with moderate-to-severe plaque psoriasis affecting high-impact, difficult-to-treat body sites, icotrokinra demonstrated progressive, durable disease clearance and complete resolution of refractory localized lesions over two years. The proportion of patients achieving overall clear or almost clear skin (IGA 0/1) rose steadily from 57% at Week 16 to 67% at Week 24, reaching 70% at Week 112, accompanied by high rates of complete site-specific clearance including 89% complete genital clearance (sPGA-G 0), 63% complete palmoplantar clearance (hf-PGA 0), 60% complete scalp clearance (ss-IGA 0), and a 71% mean reduction in nail psoriasis severity (mNAPSI). Daily oral administration was well tolerated through 112 weeks with no new safety signals, organ toxicities, or opportunistic infections over two years of continuous exposure, affirming Icotyde’s potential as a powerful, biologic-level oral systemic therapy.

Following its approval in 2026 by the FDA and European Commission, Johnson & Johnson is integrating these 2-year ICONIC-TOTAL findings into global practice guidelines to establish Icotyde as a preferred first-line oral systemic therapy for plaque psoriasis. J&J is actively advancing Icotyde across an extensive Phase 3 development pipeline in additional IL-23-mediated inflammatory conditions, including psoriatic arthritis (PsA), ulcerative colitis (UC), and Crohn’s disease.

Sources: J&J press release

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Takeda - Zasocitinib (TYK2 inhibitor) / Phase 3 (psoriasis)

On October 2, 2026, Dr. Linda Stein Gold presented late-breaking results from the Phase 3 LATITUDE Atlas study alongside 52-week extension data from the pivotal LATITUDE PsO 3001 and 3002 trials evaluating Takeda’s zasocitinib, an oral, highly potent, and highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2). Oral therapies for moderate-to-severe plaque psoriasis have historically lagged behind injectable biologics in driving complete skin clearance. The head-to-head LATITUDE Atlas trial directly pitted once-daily zasocitinib against Bristol Myers Squibb’s Sotyktu (deucravacitinib), the current first-generation TYK2 standard, demonstrating superior, biologic-like efficacy for complete skin clearance, while long-term data confirmed robust response durability through one year of continuous therapy.

In the Phase 3 head-to-head LATITUDE Atlas trial evaluating 606 adults with moderate-to-severe plaque psoriasis, Takeda’s once-daily oral allosteric TYK2 inhibitor zasocitinib (30 mg) demonstrated superior, biologic-level efficacy compared to deucravacitinib (6 mg) at Week 16, paired with robust long-term durability and a favorable safety profile. Zasocitinib nearly doubled the rate of complete skin clearance over deucravacitinib, achieving 62.5% PASI-100 (vs. 34.0%; P<0.001) and 43.2% sPGA 0 (vs. 18.5%; P<0.001), with significant separation emerging by Week 8; long-term maintenance extensions (LATITUDE PsO 3001 and 3002) confirmed that 93% of Week 24 PASI-100 responders maintained complete clearance through Week 52 and Week 40, respectively. Treatment was well tolerated across all studies with adverse event rates comparable between active arms, low serious adverse event rates, and no pan-JAK-related safety signals, establishing zasocitinib as a best-in-class oral systemic option for complete skin clearance.

Zasocitinib is currently under active NDA and Marketing Authorization Application (MAA) review by the FDA and European Medicines Agency (EMA), with regulatory decisions expected based on the comprehensive Phase 3 LATITUDE program. Takeda is actively advancing zasocitinib across additional systemic inflammatory indications, including ongoing Phase 3 programs in psoriatic arthritis (PsA), non-segmental vitiligo, ulcerative colitis, and Crohn’s disease.

Sources: Takeda press release

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Hidradenitis suppurativa (HS)

Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin condition initiated by follicular occlusion, hyperkeratosis, and subsequent rupture of hair follicles in apocrine-gland-rich intertriginous areas (such as the axillae and groin). Follicular rupture releases keratin and bacteria into the dermis, triggering a cascade of inflammatory cytokines (notably TNF-α, IL-1-beta, IL-17, and TL1A), recurrent abscess formation, and chronic neutrophil infiltration that ultimately leads to irreversible sinus tract formation and severe dermal fibrosis. Standard of care relies on a multimodal approach tailored to Hurley stage severity: mild disease is managed with topical clindamycin, lifestyle modifications (weight management, smoking cessation), and warm compresses; moderate-to-severe disease utilizes systemic oral antibiotics (such as doxycycline or combination rifampin-clindamycin) for acute control, alongside FDA-approved biologic therapies targeting TNF-α (adalimumab) or IL-17 (secukinumab, bimekizumab) to suppress chronic inflammation, frequently integrated with surgical interventions (debridement, excision, or laser ablation) to clear un-healing sinus tracts and extensive scarring.

Merck - Tulisokibart (TL1A inhibitor) / Phase 2 (HS)

On September 30, 2026, Dr. Alexa Kimball presented positive Phase 2b data in hidradenitis suppurativa (HS) for Merck’s investigational anti-TL1A monoclonal antibody, tulisokibart (MK-7240). Acquired through Merck’s $10.8 billion buyout of Prometheus Biosciences, tulisokibart’s presentation marks the first positive Phase 2 clinical readout for a tumor necrosis factor-like cytokine 1A (TL1A) inhibitor in dermatology.

In the Phase 2b trial evaluating adult patients with moderate-to-severe hidradenitis suppurativa, Merck’s anti-TL1A antibody tulisokibart demonstrated high-level clinical response and a placebo-like safety profile across 16 weeks. High-dose (480 mg Q2W) and medium-dose (480 mg Q4W) regimens achieved statistically significant HiSCR50 response rates of 72% (a 37% delta over placebo) and 64% (29% delta), alongside robust HiSCR75 response rates of 41% and 40% (vs. 15% placebo) and clinically meaningful improvements in quality of life (DLQI). Adverse event rates were comparable to placebo (42.9-52.4% versus 40.9%), with low serious adverse event incidence (2.4-4.8%) and no opportunistic infections reported. By simultaneously dampening acute inflammation and interrupting tissue fibrosis, these competitive mid-stage efficacy rates position tulisokibart as a potentially promising novel therapy capable of addressing both active disease flares and long-term structural progression in HS.

Merck confirmed that these Phase 2b dose-ranging results will directly inform the dosing regimen and design for upcoming pivotal Phase 3 studies in moderate-to-severe HS. ulisokibart continues active Phase 2 and Phase 3 development across other immune-mediated inflammatory indications, including Ulcerative Colitis (UC), Crohn’s Disease (CD), Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), and Radiographic Axial Spondyloarthritis (r-axSpA).

Sources: Merck press release

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Alopecia Areata

Alopecia areata (AA) is an autoimmune organ-specific disorder characterized by the collapse of hair follicle immune privilege, where aberrant upregulation of major histocompatibility complex (MHC) class I and II molecules on hair follicle epithelium triggers autoantigen presentation to cytotoxic CD8+ T lymphocytes (specifically NKG2D+ CD8+ T cells). These autoreactive T cells infiltrate the peribulbar region (”swarm of bees” pattern) and secrete interferon-gamma (IFN-gamma) and interleukin-15 (IL-15), which signal through the JAK1/JAK2 and JAK1/JAK3 pathways in keratinocytes to drive local apoptosis, dystrophy of the hair follicle bulb, and sudden, non-scarring hair loss. Standard of care is stratified by the extent of scalp involvement: mild, patchy disease (≤ 50% scalp loss) is managed with high-potency topical or intralesional corticosteroids (triamcinolone acetonide) alongside topical minoxidil or topical immunotherapy (diphenylcyclopropenone [DPCP]), whereas severe or widespread patchy AA, alopecia totalis, and alopecia universalis (>50% scalp involvement) are treated with oral systemic Janus kinase (JAK) inhibitors, specifically baricitinib (JAK1/2 inhibitor) or ritlecitinib (JAK3/TEC inhibitor), to suppress intrabulbar immune activation and induce long-term hair regrowth, with short courses of systemic corticosteroids or pulse immunosuppressive therapy reserved for rapidly progressive disease.

Nektar - Rezpeg (IL-2 agonist) / Phase 2b, REZOLVE-AA trial (alopecia areata)

On October 1, 2026, Dr. David Rosmarin presented 52-week results and off-treatment durability data from the Phase 2b REZOLVE-AA trial evaluating Nektar Therapeutics’ rezpegaldesleukin (rezpeg; NKTR-358) in severe-to-very-severe alopecia areata (AA). Current standard-of-care systemic oral JAK inhibitors (such as baricitinib and ritlecitinib) require continuous dosing to prevent rapid disease relapse. Nektar presented 52-week extension data framing rezpeg as a novel Treg-enhancing biologic capable of driving progressive hair regrowth and sustained off-treatment durability. However, analysts and clinicians noted that the 52-week “deepening durability” response rates were measured within an enriched subgroup, excluding patients with major eligibility violations before Week 36 and non-responders who discontinued early, raising questions regarding patient selection bias and broader intent-to-treat applicability.

In the Phase 2b REZOLVE-AA trial evaluating 92 adults with severe-to-very-severe alopecia areata (mean baseline SALT score of about 77-78), subcutaneous rezpegaldesleukin demonstrated progressive hair regrowth and sustained off-treatment durability in an enriched treatment extension cohort, accompanied by a clean safety profile. Among patients continuing treatment between Weeks 36 and 52, 29% receiving the 18 μg/kg dose and 31% receiving the 24 μg/kg dose achieved a new SALT ≤20 score (≥80% scalp hair coverage) compared to 0% for placebo, with overall SALT-50 response rates reaching 37.7% and 38.8% at Week 52 (vs. 13.6% placebo; p<0.05). In a follow-up of Week 52 responders after treatment withdrawal, 75% (6 of 8) maintained SALT ≤20 at 4 months off-treatment and 63% (5 of 8) maintained it at 6 months, while near-complete hair regrowth (SALT ≤10) rose from 7% at Week 52 to 19% at 6 months post-treatment. Therapy was well tolerated with mostly mild-to-moderate injection-site reactions, transient eosinophilia, and mild pyrexia, without systemic immunosuppressive signals.

Nektar plans to initiate the global Phase 3 ZENITH-AA trial in early 2027. The study will enroll 850 patients with severe-to-very-severe alopecia areata to evaluate 52-week SALT ≤20 response rates as the primary regulatory endpoint. Nektar is simultaneously advancing rezpeg in Phase 3 trials for moderate-to-severe atopic dermatitis (REZOLVE-AD), aiming to establish Treg-mediated biologics as safe, durable alternatives across inflammatory skin disorders.

Sources: Nektar press release, Nektar EADV 2026 slide deck

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Introduction

On October 5, 2026, Shionogi & Co., Ltd. announced that its Board of Directors approved Shionogi entering into an agreement to acquire IntraBio Inc. for an upfront consideration of $2 billion (Shionogi press release). This acquisition centers on Aqneursa (levacetylleucine), an orally administered chemically modified enantiomer of the essential amino acid leucine that is currently approved to treat symptoms of two rare diseases:

• Neurological manifestations of Niemann-Pick disease type C (NPC) in adults and pediatric patients weighting ≥15 kg.

• Ataxia in adults and padiatric patients with ataxia-telangiectasia (A-T) weighing ≥15 kg. We covered this approval ~1.5 weeks ago in Weekly Readout #24.

In this article, we uncover the story of how three professors from the University of Munich and University of Oxford teamed up with serial entrepreneur Mallory Factor to repurpose a mid-20th Century vertigo drug for rare neurological diseases.

Magic Mirrors

For readers who either forgot or memory-holed their organic chemistry, an enantiomer is one of two stereoisomers of a molecule that are non-superimposable mirror images of each other, much like a pair of human hands. Although a left hand and a right hand have identical parts connected in the same structural order, no amount of rotation can align them perfectly on top of one another (see graphics below). Enantiomers possess nearly identical physical and chemical properties (melting point, boiling point, density, solubility), but chemists can tell them apart because they rotate plane-polarized light in opposite directions. For biologists, therapeutic targets such as enzymes, receptors, and cell transporters are themselves chiral structures so two enantiomers of a molecule interact with them in different ways. A 50/50 mixture of both enantiomers is called a racemic mixture (or racemate), which is optically inactive because the opposing light rotations cancel each other out. For the chemistry-phobic among us, this concludes today’s o-chem primer and we shall now proceed with the riveting story of IntraBio.

The story begins with Tanganil, a generic, over-the-counter formulation of racemic N-acetyl-DL-leucine that existed in relative obscurity outside of France. In the 1950s, researchers at Laboratoires Pierre Fabre synthesized a chemical derivative of leucine, a branched-chain amino acid that serves as one of 20 fundamental building blocks from proteins in the human body. At the time, the critical role of drug chirality (enantiomeric purity) was not yet fully integrated into clinical pharmacology, so the compound was formulated as a racemic mixture, a 50/50 combination of mirror-image D- and L-isomers. In 1957, French health authorities approved Tanganil for the treatment of acute peripheral vertigo and dizziness. It was supplied as both 500 mg oral tablets and intravenous ampoules, intended for rapid administration in acute, distressing episodes of room-spinning vertigo.

For more than half a century, Tanganil occupied a unique niche in the French healthcare system. It became a household name and standard-of-care baseline in French emergency rooms, ENT clinics, and general practices despite an almost total absence of modern randomized controlled trial (RCT) data or a clear molecular mechanism of action. When patients presented with acute vestibular neuritis (inner ear infection), Meniere’s disease attacks (inner ear disorder), or inner-ear dysfunction, intravenous or high-dose oral Tanganil was routinely administered to dampen the sensation of dizziness. Nevertheless, the medicine was largely restricted to the French domestic market and a few francophone territories because the medicine was grandfathered in before the harmonization of international regulatory standards (such as the FDA or EMA framework). Outside of France, the drug remained virtually unknown to the global medical community for decades.

Decades later, scientists started to take a closer look. Animal models in the late 1990s demonstrated that N-acetyl-DL-leucine acted directly on the central vestibular nuclei, a part of the brainstem that process sensory information about balance, motion, and head position to maintain stable vision, posture, and equilibrium. Following acute unilateral loss of inner-ear function (vestibular deafferentation), the vestibular nuclei on opposing sides of the brainstem fall into severe electrical imbalance, triggering vertigo and nystagmus. Researchers discovered that Tanganil accelerated “central vestibular compensation”, acts as a neuro-modulator that restored baseline firing rates in hyperpolarized or de-stabilized vestibular neurons. In hyperpolarized, silent vestibular neurons on the damaged side, N-acetyl-DL-leucine promotes membrane depolarization, restoring spontaneous resting action potential discharge rates. In depolarized, hyper-excitable neurons on the healthy side, the compound acts to tone down excess firing. By raising the floor on the damaged side and lowering the ceiling on the intact side, N-acetyl-DL-leucine rapidly re-establishes electrophysiological symmetry across the bilateral brainstem circuit.

The discovery that N-acetyl-DL-leucine directly modulates central membrane potentials in the brainstem provided the critical theoretical link to cerebellar and degenerative brain disorders. Cerebellar Purkinje cells share similar intrinsic pacemaker dynamics, ion-channel expressions, and electrophysiological properties with brainstem vestibular neurons. Researchers realized that if N-acetyl-DL-leucine could stabilize errant membrane potentials in vestibular neurons during an acute injury, it could similarly stabilize dysfunctional, altered Purkinje cells in patients with cerebellar ataxia. This early work set the stage for the eventual application of N-acetyl-DL-leucine in rare genetic neurodegenerative conditions.

Michael Strupp’s Clinical Unveiling

It was not until the early 2010s that neurophysiologists at the University of Munich’s German Center for Vertigo and Balance Disorders more carefully explored the clinical effects of N-acetyl-DL-leucine. A team of neurologists led by Professor Michael Strupp began examining an unusual pattern in off-label compassionate use cases. In 2013, Strupp and colleagues published a series of clinical case studies in Journal of Neurology, hinting at the broader neurological utility of N-acetyl-DL-leucine outside of vertigo.

Prior to this study, no pharmacotherapy had convincingly been shown to improve motor cerebellar ataxia. Drawing on the pharmacological similarities and physiological interactions between vestibular neurons (for which N-acetyl-DL-leucine was used to treat vertigo) and cerebellar Purkinje cells, the researchers evaluated whether the drug could alleviate symptoms in patients with degenerative cerebellar disorders. Strupp’s case series included 13 patients (8 males; median age 51 years) presenting with various forms of cerebellar ataxia (including hereditary ataxias like SCA1/2, ADCA, AOA, SAOA). Patients received oral N-acetyl-DL-leucine at a daily dose of 5 grams for 1 week (typically given as 500 mg tablets divided into multiple doses per day).

Treatment with acetyl-DL-leucine for 1 week resulted in statistically significant reductions (improvements) in overall SARA scores (Scale for the Assessment and Rating of Ataxia) compared to baseline. Patients demonstrated improvements across several SCAFI components (Spinocerebellar Ataxia Functional Index), including faster 8-meter walking (8MW) times and improved fine-motor performance on the 9-Hole Peg Test (9HPT). Self-reported quality-of-life measures increased significantly during the treatment period (p = 0.003). No adverse side effects or safety signals were reported during therapy. The authors concluded that “acetyl-DL-leucine significantly improved ataxic symptoms without side effects and therefore showed a good risk–benefit profile”. They ended by stating that their findings “need to be confirmed in placebo-controlled trials”.

Mobility impairments in cerebellar ataxia carry a high risk of falls. Building off of their 2013 paper, the the Strupp group published a second case series in Cerebellum Ataxias in 2016 that evaluated whether treatment with N-acetyl-DL-leucine improved dynamic walking stability and quantitative gait parameters in patients with various types of cerebellar ataxia. It included 12 patients with sporadic forms of cerebellar ataxia (e.g., Sporadic Adult-Onset Ataxia [SAOA], Multiple System Atrophy cerebellar type [MSA-C]) and 6 patients with hereditary forms (e.g., Spinocerebellar Ataxia types 1 and 2 [SCA 1, SCA 2], CACNA1A mutation, Autosomal Dominant Ataxia [ADA]). Patients received 5 g/day of oral N-acetyl-DL-leucine (administered as 500 mg Tanganil tablets split into a 3-3-4 daily regimen) for at least 4 weeks. Gait performance was quantitatively measured using a pressure-sensitive sensor carpet across three walking speeds (slow, preferred, and maximal fast) before treatment and at two post-baseline time points (7-14 days and 28-42 days).

Treatment with N-acetyl-DL-leucine for 4 weeks significantly improved the coefficient of variation (CV) of stride time in 14 out of 18 patients (78% response rate) across tested walking speeds (see graph below). This reduction in stride-to-stride fluctuations directly indicated stabilized gait dynamics and better dynamic balance. Clinicians also observed statistically significant reductions on the Scale for the Assessment and Rating of Ataxia (SARA), as were seen in Strupp’s first case series. Subjective balance confidence and ambulatory confidence scores, assessed via the Falls Efficacy Scale-International (FES-I) and the Activities-specific Balance Confidence (ABC) scale, showed significant improvement under therapy. The treatment was well tolerated without reported serious adverse events. This study provided the first evidence that N-acetyl-DL-leucine could improve objective stride dynamics in degenerative brain disorders, rather than subjective symptomatic relief alone.

Of Mice and Oxford Men

In parallel, Professor Michael Strupp’s initial clinical findings in 2013 motivated him to reach out to University of Oxford’s lysosomal biology and calcium signaling experts to investigate the underlying biochemical mechanisms of N-acetyl-DL-leucine at a cellular level. Around that time, Strupp began working with Professors Frances Platt, Antony Galione, and Grant Churchill at the University of Oxford’s Department of Pharmacology. Together, they sought to answer two critical scientific questions:

• Symptomatic versus Disease-Modifying: Does acetyl-leucine merely provide rapid, symptomatic motor relief, or can long-term treatment actually slow down neurodegeneration, protect Purkinje cells, and extend survival?

• Stereoisomer Selectivity: Which enantiomer, the L-isomer (N-acetyl-L-leucine) or D-isomer (N-acetyl-D-leucine), drives these neuroprotective and disease-modifying effects?

The team utilized both in vivo animal models and in vitro cellular assays to answer these questions:

• Npc1^-/- mice: This mouse model recapitulated Niemann-Pick disease type C1 and was used to evaluate both symptomatic and pre-symptomatic treatment paradigms across early, late, and lifelong dosing regimes.

• Hexb^-/- mice: This mouse model recapitulated GM2 gangliosidosis (Sandhoff disease) and was used to evaluate N-acetyl-DL-leucine as a long-term treatment.

• Cell Culture & Biochemical Analyses: CHO cells and patient-derived fibroblasts were analyzed for lipid accumulation, lysosomal volume (LysoTracker), mitochondrial reactive oxygen species (MitoSOX), NAD/NADH coenzymes, and ATP/ADP cellular energy ratios.

They discovered that short-term administration of racemic N-acetyl-DL-leucine (ADLL), N-acetyl-L-leucine (ALL), or N-acetyl-D-leucine (ADL) rapidly reduced lateral gait displacement and ataxic motor symptoms in Npc1^-/- mice. However, when treatment was initiated pre-symptomatically and maintained long-term, only the N-acetyl-L-leucine (ALL) enantiomer provided true neuroprotection. ALL treatment significantly preserved cerebellar Purkinje cell density and survival, delayed motor decline and improving performance on the accelerating Rotarod, and extended life span in Npc1^-/- mice.

The study also unraveled three mechanisms by which the ALL (N-acetyl-L-leucine) enantiomer exerts its neuroprotective and lipid-clearing effects:

• Metabolic Reprogramming: ALL altered intracellular bioenergetics by decreasing the NAD/NADH ratio and elevating glycolytic flux, effectively restoring cellular ATP levels in energy-starved neurons.

• Lysosomal Clearance & Lipid Storage Reduction: ALL significantly lowered toxic glycosphingolipid (GSL), sphingosine, and unesterified cholesterol accumulation in brain tissue and peripheral organs (e.g., liver).

• Autophagic & Oxidative Balance: Treatment normalized lysosomal membrane dynamics and reduced excessive mitochondrial reactive oxygen species (ROS).

Altogether, the study demonstrated that acute symptomatic improvement in ataxia and long-term neuroprotection operate through distinct cellular mechanisms. While acute motor gains can be mediated by both enantiomers, long-term neuroprotection and survival extension require the purified L-enantiomer (N-acetyl-L-leucine).

The Business Factor

To deliver a product or service at scale, you need a business. To start a business, you need a business man. That man for IntraBio was Professor Mallory Factor. Prior to co-founding IntraBio in 2015, Mallory Factor had built a multi-decade career spanning merchant banking, corporate restructuring, venture investing, political strategy, and academia.

Factor earned a B.A. in Biochemistry from Wesleyan University. This background provided him with the technical literacy required to evaluate early-stage pharmacology and molecular biology. He pursued graduate work in the joint Law and Business program at Columbia University before starting his career as a management consulting supervisor at Coopers & Lybrand. In 1976, he founded Mallory Factor, Inc., an independent merchant bank, financial relations consultancy, and corporate advisory firm. Through the firm, he spent decades advising public and private corporations on corporate strategy, capital raises, restructuring, debt/equity financing, and investor relations. Across the 1980s, 1990s, and 2000s, Factor acted as an active investor and advisor across healthcare, technology, media, and natural resource ventures. His investment thesis frequently centered on identifying undervalued, distressed, or mispriced assets and restructuring them into commercially viable, high-margin growth vehicles.

In the years leading up to IntraBio’s formation, Factor served as a Visiting Senior Fellow in Entrepreneurship at the Department of Pharmacology at the University of Oxford. It was in this role that he gained direct exposure to the life sciences Intellectual Property (IP) generated in the laboratories of Oxford Professors Frances Platt and Antony Galione. When Oxford researchers demonstrated that N-acetyl-L-leucine could normalize lysosomal function and cellular bioenergetics, Factor recognized the opportunity. Where others saw an unpatented, generic French vertigo pill, Mallory Factor saw the potential to:

• Ensconce a Novel Asset with Defensible IP: Racemic N-acetyl-DL-leucine consists of a 50/50 mix of two mirror-image molecules (D- and L-enantiomers). The scientific founders discovered that the pharmacodynamics were driven almost entirely by the L-enantiomer: levacetylleucine, designated internally as IB1001. Isolating IB1001 eliminated the inactive D-enantiomer, drastically reducing metabolic load while optimizing transport across the blood-brain barrier via specialized monocarboxylate carriers. Recognizing the potential of an asset-centric model, IntraBio built a broad patent portfolio between 2016 and 2018. The filings covered purified enantiomeric formulations, specific dosing regimens, and target indications spanning rare lysosomal storage disorders, inherited cerebellar ataxias, and neurodegenerative conditions.

• Address a High Unmet Medical Need: The Oxford and Munich labs systematically mapped how levacetylleucine operated at the cellular level. They demonstrated that once inside the cell, levacetylleucine normalizes neuronal membrane potential, restores lysosomal function and autophagic flux, and boosts mitochondrial ATP synthesis. In diseases like Niemann-Pick type C (NPC) and GM2 gangliosidosis, where cellular lipid accumulation destroys neuronal networks, IB1001 could offer a way to bypass broken metabolic pathways and restore baseline cellular bioenergetics.

In late 2015, Mallory Factor partnered with Professors Strupp, Platt, Galione, and Churchill to formally incorporate IntraBio. Factor assumed the roles of Chairman and CEO, providing the business leadership, while Strupp, Platt, Galione, and Churchill served as the founding scientists and key scientific advisors. Drawing on his background as a merchant banker, venture architect, and Oxford fellow, he structured IntraBio in 2015 as a virtual, capital-efficient biopharmaceutical company. Operating with an ultra-lean, virtual corporate structure, the new company brought together Oxford’s bench science, Munich’s clinical insights, and Factor’s capital deployment.

With all the right pieces in place, Mallory Factor kicked off a unique clinical development strategy for IB1001. Instead of developing isolated trials for different conditions, IntraBio designed an innovative Master Protocol Platform. Since conditions like Niemann-Pick disease type C (NPC), GM2 gangliosidosis (Tay-Sachs and Sandhoff disease), and Ataxia-Telangiectasia (A-T) share underlying cerebellar ataxia and neurodegeneration, IntraBio launched three parallel, multi-national Phase 2 basket studies using shared clinical endpoints:

• IB1001-201: Niemann-Pick Disease Type C (NPC)

• IB1001-202: GM2 Gangliosidosis (Tay-Sachs and Sandhoff)

• IB1001-203: Ataxia-Telangiectasia (A-T)

Since these diseases are ultra-rare, making traditional long-term parallel-group placebo trials ethically and logistically difficult, IntraBio deployed 12-week randomized, double-blind, placebo-controlled crossover trials. Patients acted as their own controls, switching between treatment and placebo periods. Primary efficacy was measured using the Scale for the Assessment and Rating of Ataxia (SARA) alongside quantitative gait, speech, and fine motor assessments. By late 2020, Phase 2 data across all three indications met primary endpoints, demonstrating rapid, statistically significant improvements in motor function and cognition.

IntraBio then launched its pivotal Phase 3 study for NPC (IB1001-301), which enrolled 60 pediatric and adult patients with NPC enrolled across multi-center international sites. Patients were randomized 1:1 to receive either oral N-acetyl-L-leucine for 12 weeks followed by a 12-week placebo period, or vice versa (placebo first, followed by active drug).

On June 29, 2023, IntraBio reported positive topline results from the Phase 3 IB1001-301 trial in patients with NPC. Treatment with N-acetyl-L-leucine (NALL) resulted in a statistically significant improvement in the mean SARA total score compared to placebo (p < 0.001). Patients demonstrated measurable functional gains in gait, stance, fine motor skills, and speech coordination while receiving N-acetyl-L-leucine. Neurological improvements were observed during the active treatment phase. When patients switched from active drug to placebo during the crossover, ataxia symptoms returned toward baseline levels, supporting a direct therapeutic effect. The most common adverse events included mild-to-moderate gastrointestinal symptoms (e.g., abdominal pain, vomiting) and upper respiratory tract infections. No treatment-related serious adverse events were reported. The pivotal Phase 3 trial data were later published in the NEJM on January 31, 2024.

On the heels of their positive Phase 3, IntraBio leveraged regulatory incentives including FDA Orphan Drug, Rare Pediatric Disease, Fast Track, and Priority Review designations to convert clinical trial data into global drug approvals. In September 2024, the FDA granted full commercial approval to Aqneursa (levacetylleucine) for the treatment of neurological manifestations of Niemann-Pick disease type C in adult and pediatric patients weighing ≥15 kg. On January 2026, the European Commission granted marketing authorization for Aqneursa across the EU for NPC.

Later that year on September 25, 2024, the FDA approved a major label expansion for IntraBio’s Aqneursa (levacetylleucine / N-acetyl-L-leucine) to treat ataxia in adults and pediatric patients weighing at least 15 kg with Ataxia-Telangiectasia (A-T), as we described in Weekly Readout #24.

This regulatory decision marks a historical milestone as the first FDA-approved disease-modifying treatment specifically indicated for A-T, a rare, progressive, and life-limiting autosomal-recessive neurodegenerative disease caused by mutations in the ATM gene. The label extension of Aqneursa was granted on the strength of pivotal data from the Phase 3 IB1001-303 trial, a multinational, randomized, double-blind, placebo-controlled crossover study (N = 73) in patients aged 4 to 50 years with genetically confirmed A-T. Over a 12-week treatment period, Aqneursa demonstrated a statistically significant improvement in motor function compared to placebo on the Scale for the Assessment and Rating of Ataxia (SARA). Patients treated with Aqneursa achieved a 1.9-point mean improvement over placebo (Treatment Difference = -1.9; p < 0.001). In a modified, functional SARA assessment prioritized by the FDA (evaluates core daily tasks across gait, sitting, stance, and speech domains), Aqneursa demonstrated a 0.6-point mean advantage over placebo (Treatment Difference = -0.6; p < 0.001).Clinically observable neurological and functional improvements emerged rapidly within 12 weeks of therapy initiation. Benefits were consistent across pediatric and adult age cohorts, prior functional baseline levels, and prespecified disease severity subgroups. A notable 96% of enrolled participants (70/73) completed both treatment periods of the crossover design, reflecting high trial adherence and patient tolerance. The product labeling warns against concomitant administration with race-mixture formulations like N-acetyl-DL-leucine or N-acetyl-D-leucine, as the D-enantiomer competes for monocarboxylate transporter uptake and impairs Aqneursa‘s efficacy. Since Aqneursa inhibits P-glycoprotein (P-gp), patients on narrow-therapeutic-index P-gp substrates require close monitoring. Animal data indicate potential embryo-fetal toxicity, necessitating pregnancy verification and reliable contraception in female patients of reproductive potential.

Less than 2 weeks later on October 5, 2026, Japanese biopharmaceutical company Shionogi & Co. announced an agreement to acquire IntraBio for $2.0 billion in cash. Shionogi acquired worldwide rights to Aqneursa across its indications, including its initial 2024 U.S. and early 2026 EU approvals for Niemann-Pick disease type C (NPC), as well as the newly granted A-T indication. The acquisition also hands Shionogi IntraBio’s active clinical pipeline, including ongoing Phase 3 studies applying levacetylleucine to CACNA1A-related disorders.

Conclusion

From obscure 1950s vertigo pill, to Michael Strupp’s clinical observations in Munich, to mechanistic untangling at Oxford’s pharmacology labs, and ultimately to FDA approvals and a $2.0 billion acquisition, IntraBio’s trajectory is a testament to scientific collaboration paired with sharp biotech execution. By teaching an old racemic drug new tricks, Mallory Factor and his scientific co-founders serve as case of rare disease innovation with an even rarer backstory. By separating a racemic mixture into its pure, biologically active L-enantiomer, a multidisciplinary team turned the generic vertigo medicine with mysterious mechanism of action into a life-changing, FDA-approved therapy for Niemann-Pick disease type C (NPC) and Ataxia-Telangiectasia (A-T). The $2 billion acquisition of IntraBio by Shionogi marks a fitting culmination of their decades-long passion project. Most importantly, Aqneursa (levacetylleucine) brings tangible neurological improvement to patients facing devastating degenerative diseases, and will continue to do so with the backing of Shionogi.

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Table of Contents

The 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD 2026) took place from September 28 to October 2, 2026, in Milan, Italy. In this article, we discuss the following high-impact datasets from Europe’s largest diabetes conference:

• GGG Sets Weight Loss Glass Ceiling at -30%

  • Eli Lilly - Retatrutide (GGG) / Phase 3, TRIUMPH-1 trial (obesity) ⬇️

  • Eli Lilly - Retatrutide (GGG) / Phase 3, TRIUMPH-2 trial (obesity+T2D) ⬇️

  • Novo - UBT251 (GGG) / Phase 2 (obesity) ⬇️

• Amylin & GLP-1/GIP Combo Overtakes GGG in Diabetic Weight Loss

  • Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 1b, Study #1 (obesity) ⬇️

  • Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 1b, Study #2 (obesity) ⬇️

  • Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 2b (obesity+T2D) ⬇️

• Eli Lilly & Novo Exchange Blows to Claim Best-in-Class

  • Eli Lilly - Zepbound (GLP-1 x GIP dual agonist) / Phase 3 indirect comparison (obesity) ⬇️

  • Novo - Ozempic (GLP-1 agonist) / Real-world COMPETE SWITCH CV study (T2D) ⬇️

  • Eli Lilly - Foundayo (oral GLP-1 agonist) / Phase 3 indirect comparison (T2D) ⬇️

  • Novo - Wegovy pill (oral GLP-1 agonist) / Real-world OCTANE study (obesity) ⬇️

• Other notable datasets

  • Novo - CagriSema (amylin + GLP-1 FDC) / fMRI study (obesity) ⬇️

  • Zealand - Petrelintide (amylin agonist) / Phase 2, ZUPREME-1 trial (obesity) ⬇️

  • Eli Lilly - Foundayo (oral GLP-1 agonist) / Phase 3, ACHIEVE-4 trial (obesity+T2D) ⬇️

  • BI & Zealand - Survodutide (GLP-1 x glucagon dual agonist) / Phase 3, SYNCHRONIZE-2 trial (obesity+T2D) ⬇️

  • Regeneron - Trevogrumab (anti-GDF8/myostatin mAb) / Phase 2, COURAGE trial (obesity) ⬇️

  • AbbVie - ABBV-295 (amylin agonist) / Phase 1 (obesity) ⬇️

  • Regeneron & Hansoh - Olatorepatide (GLP-1 x GIP dual agonist) / Phase 3, LIGHTEN trial (obesity) ⬇️

GGG Sets Weight Loss Glass Ceiling at -30%

These readouts center on “triple G” agonists (GGG) designed to promote weight loss by simultaneously activating three distinct metabolic hormone receptors:

• GLP-1 (Glucagon-like Peptide-1): Enhances glucose-dependent insulin secretion, delays gastric emptying, suppresses glucagon, and promotes central satiety.

• GIP (Glucose-dependent Insulinotropic Polypeptide): Works synergistically with GLP-1 to potentiate insulin release, regulate lipid storage and metabolism, and improve overall gastrointestinal tolerability.

• Glucagon: Increases energy expenditure via hepatic thermogenesis, promotes lipolysis, and targets intrahepatic fat accumulation, balancing the anabolic effects of insulin while driving fat oxidation.

By engaging all three pathways concurrently, these agents achieve a “triple-action” synergy designed to amplify total calorie deficit and metabolic rate beyond what is typically observed with mono- or dual-agonist therapies, such as GLP-1 agonist semaglutide (Ozempic/Wegovy) or GLP-1/GIP dual agonist tirzepatide (Mounjaro/Zepbound).

Eli Lilly - Retatrutide (GGG) / Phase 3, TRIUMPH-1 trial (obesity)

On September 29, 2026, Eli Lilly’s Phase 3 TRIUMPH-1 trial, which evaluated retatrutide in adults with obesity or overweight who do not have diabetes, was published in NEJM. While results from this trial were not presented at EASD 2026, its conveniently timed publication on the second day of the conference reads through to other datasets presented at the conference, given that it shows the deepest weight loss reduction shown to date for a pharmacological intervention in a Phase 3 obesity trial. The trial comprised a master trial (Study GZBJ) coupled with Integrated Sub-study Baskets (ISAs) for Obstructive Sleep Apnea (OSA; Study GSA1) and Knee Osteoarthritis (Knee OA; Study GOA1).

From July 2023 through April 2026, the Phase 3 TRIUMPH-1 trial enrolled 2,339 adults across 131 international sites. The highest retatrutide dose (12 mg) resulted in -25.0% weight loss at 80 weeks compared to -3.9% for placebo. Weight loss deepened to -30.3% at week 104 in participants previously taking the highest dose and continuing on the maximum-tolerated dose (MTD) in the extension study. Among participants with pre-diabetes at baseline, 89.4-93.2% of patients in the retatrutide groups reverted to normal glucose levels by week 80, compared to 54.2% in the placebo group. Retatrutide’s weight loss so potent that 22.5% of participants in the 12 mg retatrutide group required permanent dose reductions versus 0.5% on placebo, with the most common reasons being reasons being perceived excessive weight loss or reaching a BMI of ≤22 (GI symptoms was the third most cited reason).

Treatment discontinuation due to AEs occurred in 4.1% (4 mg), 6.5% (9 mg), and 11.1% (12 mg) of retatrutide participants, compared to 4.6% in the placebo arm. Dysesthesia (skin sensitivity/burning; up to 12.5%), injection-site reactions, and mild-to-moderate hypotension (more frequent in patients on background antihypertensives) were observed. Pulse rates increased initially, peaking around week 20 before declining. Adjudicated major adverse cardiovascular events (MACE) and pancreatitis rates remained low across groups.

Sources: Jastreboff et al., NEJM (2026)

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Eli Lilly - Retatrutide (GGG) / Phase 3, TRIUMPH-2 trial (obesity+T2D)

On September 29, 2026, Drs. John P.H. Wilding, Elif Ekinci, Juan Pablo Frias presented Eli Lilly’s Phase 3 TRIUMPH-2 trial, which evaluated retatrutide in adults with obesity or overweight who who also have diabetes, was presented at EASD 2026 and simultaneously published in The Lancet. The Phase 3 TRIUMPH-2 trial enrolled 1,152 adults with type 2 diabetes and overweight or obesity and demonstrated unprecedented weight loss & glycemic improvements over 80 weeks, with the 12 mg retatrutide group achieving a mean body weight loss of 49.6 lbs (-20.8%) versus -4.0% for placebo, while the 4 mg and 9 mg doses yielded -12.7% and -19.1% weight reductions, respectively. Crucially, the 12 mg dose enabled more than half of all participants (and nearly 60% of those with severe baseline obesity, who lost an average of 60.8 lbs) to no longer meet the BMI diagnostic threshold for obesity (BMI < 30 kg/m²), alongside significant HbA1c reductions of up to 1.6% (versus 0.2% for placebo). These results overcome the historical “diabetes penalty” where weight loss in type 2 diabetes typically capped at 10-15%, offering transformative benefits for diabetes remission, liver fat reduction, and broader cardiometabolic health with a safety profile consistent with the incretin class. Transient gastrointestinal events were most common and treatment discontinuation rates ranged from 3.8% to 11.6% across active arms versus 4.9% for placebo.

Eli Lilly is finalizing the chemistry, manufacturing, and controls (CMC) package, targeting a Biologics License Application (BLA) submission to the US FDA by 1Q 2027 for chronic weight management and type 2 diabetes.

Sources: Eli Lilly press release, Bellido et al., The Lancet (2026), Eli Lilly EASD 2026 slide deck

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Novo - UBT251 (GGG) / Phase 2 (obesity)

On September 30, 2026, Dr. Zhiguang Zhou presented findings from a Phase 2 trial evaluating UBT251, the most advanced GGG molecule in Novo’s pipeline. The Phase 2 trial enrolled adults aged 18-75 years with overweight (BMI 24.0–28.0 kg/m² with at least one comorbid condition) or obesity (BMI ≥ 28.0 kg/m²). At Week 24, UBT251 demonstrated rapid, dose-dependent efficacy, driving least-squares mean body weight reductions of -13.6% (2.0 mg), -16.2% (4.0 mg ID 0.5 mg), -19.7% (4.0 mg ID 1.0 mg), -18.0% (4.0 mg Total), and -18.7% (6.0 mg) versus -2.0% for placebo (p < 0.001 across all doses), with weight loss trajectories continuing downward without reaching a plateau. The treatment was well tolerated, exhibiting an overall TEAE incidence of 92.3% (vs. 88.0% for placebo) with no dose-dependent escalation, alongside low discontinuation rates due to adverse events (0% in the placebo, 2.0 mg, and 6.0 mg arms, and 4% in the combined 4.0 mg group).

Sources: Novo EASD 2026 presentation

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Amylin & GLP-1/GIP Combo Overtakes GGG in Diabetic Weight Loss

Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 1b, Study #1 (obesity)

On September 30, 2026, Dr. Shobha Bhattachar presented Eli Lilly’s positive Phase 1b study showing high-dose combination treatment of eloralintide (amylin agonist) plus tirzepatide (GLP-1 x GIP dual agonist) in Japanese patients with obesity or overweight (BMI >27 kg/m²) who did not have type 2 diabetes. This study (referred to in the EASD 2026 presentation as “Study #1”) compared a combination of eloralintide & tirzepatide against monotherapies of each and placebo.

Over the course of the trial, participants receiving eloralintide alone demonstrated weight loss comparable to those taking tirzepatide alone, achieving a least squares mean body weight reduction of -14.2%. Combining titrated eloralintide 9 mg with tirzepatide 15 mg resulted in enhanced efficacy, driving a least squares mean body weight reduction of -25.5%, compared to a minimal -0.5% change observed in the placebo arm. The vast majority of reported events across groups were mild to moderate in severity, with no severe adverse events or deaths reported in any group. The combination therapy group experienced higher rates of overall gastrointestinal adverse events (62.5%), with the most common reported events being decreased appetite (62.5%), nausea (25.0%), constipation (25.0%), diarrhea (25.0%), and vomiting (18.8%). Additionally, two participants in the combination treatment arm discontinued the study due to adverse events, whereas no study discontinuations occurred in the other three treatment arms.

Sources: Eli Lilly EASD 2026 presentation

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Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 1b, Study #2 (obesity)

In the same presentation as the Phase 1b above, Dr. Shobha Bhattachar presented a second Phase 1b trial (referred to as “Study #2”) that likewise examined eloralintide co-administered with tirzepatide in adults with obesity or overweight without type 2 diabetes. However, this trial enrolled patients in the U.S. and evaluated multiple dose levels and combinations of eloralintide and tirzepatide.

In Group 1 (low dose, untitrated elora combinations), participants (N=12 per group) were evaluated over 15 weeks of treatment according to the dosing protocol shown below. Adding un-titrated eloralintide to 5 mg tirzepatide achieved progressive, dose-dependent reductions in body weight at Week 15. While tirzepatide 5 mg alone (with placebo) yielded a 10.0% mean weight reduction from baseline, the addition of 3 mg, 6 mg, and 9 mg of eloralintide led to weight loss figures of 17.0%, 18.2%, and 20.5%, respectively. Gastrointestinal (GI) adverse events were the most common side effects, occurring in 50.0% of the tirzepatide-alone arm compared to 58.3% (3 mg), 66.7% (6 mg), and 75.0% (9 mg) in the combination arms. High rates of nausea (up to 66.7%) and decreased appetite (75.0%) were reported at the 9 mg un-titrated level. Discontinuations due to adverse events occurred in 1 participant in the 6 mg arm (8.3%) and 2 participants in the 9 mg arm (16.7%).

In Group 2 (high dose, titrated elora combinations), participants were evaluated over a longer period of time (31 weeks) to test higher target dose combinations consisting of full-dose tirzepatide (titrated up to 15 mg) co-administered with placebo (N=8) or titrated eloralintide (N=12 per arm) reaching a target dose of 9 mg. Two different eloralintide titration schedules were tested (see below). At Week 31, participants on 15 mg tirzepatide alone achieved a mean weight reduction of -17.8% from baseline. In contrast, combining titrated eloralintide with 15 mg tirzepatide led to substantial augmented weight loss, reaching -23.6% in the standard titration group and up to -29.0% in the gradual titration group. This is particularly striking since the combo amylin/GLP-1/GIP combo EloraTZP appears to have reached a similar magnitude of weight loss as GGG retatrutide in the Phase 3 TRIUMPH-1 trial, but in less than one third of the time (31 weeks versus 100+ weeks), on a cross-trial basis. GI events (nausea and vomiting) were again the dominant side effects. Due to the rapid co-titration of two distinct agents, treatment discontinuations due to adverse events were higher in the combination arms, reaching 33.3% (4 participants) in the gradual titration group and 50.0% (6 participants) in the standard titration group, compared to 12.5% (1 participant) in the tirzepatide-alone group. Dose reductions were permitted to improve participant retention in the gradual titration arm, enabling more participants to complete the study, though some did not reach the highest target doses.

Sources: Eli Lilly EASD 2026 slide deck

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Eli Lilly - EloraTZP (amylin + GLP-1 x GIP) / Phase 2b (obesity+T2D)

On September 30, 2026, Dr. Liana Billings presented Eli Lilly’s positive topline Phase 2b clinical trial results for EloraTZP, an investigational combination therapy pairing the selective amylin agonist eloralintide with the GLP-1 x GIP dual agonist tirzepatide. The Phase 2b study enrolled 367 adults with obesity or overweight and type 2 diabetes. The components were delivered via two weekly injections, according to the dosing protocol shown below.

Treatment with the highest dose combination (eloralintide 9 mg + tirzepatide 15 mg) yielded a mean body weight reduction of -23.3% (54.1 lbs), which is higher than the -20.8% plateau level achieved by GGG retatrutide in patients with overweight/obesity+T2D patients in the Phase 3 TRIUMPH-2 trial, making it the deepest weight loss in diabetics observed to date, on a cross-trial basis. By comparison, tirzepatide 15 mg monotherapy achieved a -14.8% (34.4 lbs) weight loss, while eloralintide monotherapy reached up to -12.3% (28.6 lbs). EloraTZP produced average HbA1c reductions of up to -2.9%, compared to -2.4% for tirzepatide alone and -1.4% for eloralintide alone. The overall safety profile aligned with existing incretin and amylin class therapies, dominated by gastrointestinal adverse events (nausea, vomiting, diarrhea) that were mostly mild-to-moderate during dose escalation. Discontinuations due to adverse events ranged from 10.8% to 27.0% across combination arms, compared to 2.9% for tirzepatide alone, 10.8% for eloralintide alone, and 16.7% for placebo.

Eli Lilly plans to advance EloraTZP into Phase 3 clinical development in the fourth quarter of 2026. While the Phase 2b study tested the drugs as separate weekly injections, Phase 3 trials will evaluate a single-injection co-formulated product combining both active ingredients. Phase 3 trials for standalone eloralintide remain ongoing for obesity management.

Sources: Eli Lilly press release, Eli Lilly EASD 2026 slide deck

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Eli Lilly & Novo Exchange Blows to Claim Best-in-Class

Eli Lilly - Zepbound (GLP-1 x GIP dual agonist) / Phase 3 indirect comparison (obesity)

On September 29, 2026, Dr. John P.H. Wilding presented results from Eli Lilly’s Phase 3 indirect treatment comparison (ITC) showing that Zepbound (tirzepatide) 10 mg and 15 mg, a dual GIP and GLP-1 receptor agonist, delivered greater weight loss than GLP-1 agonist Wegovy HD (semaglutide injection 7.2 mg) in adults with obesity. By matching dataset populations across clinical development programs, this indirect readout was undertaken to offer clinicians and payers critical insights into whether higher-dose selective GLP-1 agonism can close the efficacy gap with dual GIP/GLP-1 receptor agonism in adults living with obesity. This ITC was organized in lieu of a direct head-to-head randomized controlled trial evaluating tirzepatide 15 mg against semaglutide 7.2 mg.

The analysis cross-analyzed individual patient-level and summary data from Lilly’s Phase 3 SURMOUNT-1 trial (evaluating Zepbound 10 mg and 15 mg) and Novo Nordisk’s Phase 3 STEP UP trials (evaluating Wegovy HD 7.2 mg). The indirect comparison demonstrated greater weight loss outcomes for higher-dose Zepbound relative to Wegovy HD over 72 weeks. Zepbound 15 mg was associated with 4.5% greater mean body weight reduction compared to Wegovy HD (with Zepbound 10 mg showing 3.2% greater reduction). Participants taking Zepbound 15 mg had more than three times the odds (OR 3.54) of achieving at least 20% body weight reduction compared with Wegovy HD under the treatment-regimen estimand, and four times the odds (OR 4.15) under the efficacy estimand. Under the efficacy estimand, Zepbound 15 mg and 10 mg showed numerical advantages of 1.8% and 0.7% greater mean weight reduction over Wegovy HD, respectively, though these specific efficacy-estimand differences did not reach statistical significance. Rates of treatment discontinuation due to adverse events were comparable across all arms (Zepbound 10 mg, Zepbound 15 mg, and Wegovy HD) under both estimands, with gastrointestinal side effects remaining the dominant adverse event profile.

Sources: Eli Lilly press release, Eli Lilly EASD 2026 slide deck

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Novo - Ozempic (GLP-1 agonist) / Real-world COMPETE SWITCH CV study (T2D)

On September 29, 2026, Dr. Gang Fang presented real-world evidence (RWE) suggesting that Novo’s GLP-1 agonist Ozempic (semaglutide) was associated with a lower risk of 3-point major adverse cardiovascular events (MACE-3: death, heart attack, and stroke) in adults with type 2 diabetes compared to switching to Eli Lilly’s GLP-1/GIP dual agonist Mounjaro (tirzepatide).

The COMPETE SWITCH CV study was an observational, real-world comparative effectiveness study utilized high-volume electronic health record and claims databases to evaluate clinical outcomes in routine clinical practice. The analysis included 636,525 adults with type 2 diabetes receiving semaglutide 1 mg that required treatment intensification. Participants were categorized into two main intensification groups: those whose semaglutide dose was escalated to 2 mg, and those who discontinued semaglutide and switched to tirzepatide (titrated up to 15 mg). Propensity score matching (PSM) and fine stratification were applied to balance baseline characteristics across cohorts, adjusting for age, sex, baseline HbA1c, body mass index (BMI), duration of diabetes, cardiovascular history, and baseline cardiovascular/kidney medications.

The real-world analysis demonstrated a statistically significant cardiovascular advantage for 2 mg semaglutide dose escalation over switching to 15 mg tirzepatide. Adults with type 2 diabetes who escalated their dose from semaglutide 1 mg to semaglutide 2 mg had a statistically significant 6% lower risk of experiencing a MACE event compared to those who switched from semaglutide 1 mg to tirzepatide (up to 15 mg). The lower incidence of MACE with semaglutide 2 mg was consistently observed across key sub-analyses, including baseline cardiovascular disease status and age brackets. While both intensification strategies improved glycemic control and weight parameters in routine care, the cardiovascular benefits of remaining on and maximizing high-dose semaglutide remained distinct.

Despite the study’s results, it’s difficult to say whether its conclusions would be reproduced in a head-to-head study, given that tirzepatide has numerically edged out semaglutide in terms of weight loss and HbA1c-lowering across their respective clinical trials. One of my favorite BioX accounts, Jen Can NuSH, shares this sentiment and hypothesizes that the number of MACE-3 events observed in the study was high enough to squeak past P<0.05, but could have been low enough to have a minuscule effect size:

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Eli Lilly - Foundayo (oral GLP-1 agonist) / Phase 3 indirect comparison (T2D)

On September 29, 2026, Dr. Alice Cheng presented Eli Lilly’s key indirect treatment comparison (ITC) data evaluating Foundayo (orforglipron), a non-peptide oral GLP-1 receptor agonist, against Novo’s oral peptide GLP-1 agonist semaglutide 25 mg in adults with type 2 diabetes. Note that a 25 mg once-daily dose of oral semaglutide is not approved in the United States for the treatment of type 2 diabetes, although Novo Nordisk has submitted an application to the FDA seeking approval of that dose. This cross-trial analysis provides early comparative context on how Lilly’s small-molecule oral GLP-1 agonist performs against higher-dose peptide formulations in driving both glycemic control and weight reduction. A direct head-to-head randomized controlled trial evaluating Foundayo 17.2 mg against oral semaglutide 25 mg has not been conducted.

The comparative analysis compares two distinct oral GLP-1 receptor agonist drug designs: small molecule versus peptide. Since Eli Lilly’s Foundayo (orforglipron) is a non-peptide small molecule, it can resist enzymatic degradation in the gastrointestinal tract and achieves oral bioavailability without requiring absorption enhancers or strict administration protocols, allowing daily administration with or without food or water. In contrast, Novo’s oral semaglutide is a peptide-based GLP-1 receptor agonist co-formulated with the absorption enhancer SNAC (salcaprozate sodium) to facilitate gastric absorption. It requires specific administration guidelines (taking it on an empty stomach upon waking with a limited amount of water, followed by a fasting period) to ensure systemic bioavailability. Both agents activate central and peripheral GLP-1 receptors to promote glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and enhance central satiety.

The ITC analysis cross-analyzed clinical data from Lilly’s Phase 3 ACHIEVE-3 trial (evaluating Foundayo) and Novo Nordisk’s Phase 3 PIONEER PLUS trial (evaluating oral semaglutide 25 mg). At 52 weeks, the indirect comparison demonstrated significant advantages for Foundayo 17.2 mg over oral semaglutide 25 mg. Participants receiving Foundayo 17.2 mg achieved a statistically significant 1.5% greater reduction in body weight compared to those taking oral semaglutide 25 mg. Foundayo 17.2 mg achieved a 0.3% greater reduction in HbA1c compared to oral semaglutide 25 mg. The overall safety and tolerability profiles were consistent with the GLP-1 receptor agonist class, dominated by gastrointestinal adverse events (nausea, constipation, diarrhea, and vomiting) primarily occurring during dose titration.

Sources: Eli Lilly press release, Eli Lilly EASD 2026 abstract, Eli Lilly EASD 2026 slide deck

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Novo - Wegovy pill (oral GLP-1 agonist) / Real-world OCTANE study (obesity)

On September 30, 2026, Dr. Louis Aronne presented initial real-world evidence from Novo’s OCTANE study evaluating adults with overweight or obesity who transitioned from injectable GLP-1 therapies to once-daily oral semaglutide (the Wegovy pill). The study demonstrated that patients switching from subcutaneous injections to the daily pill continued to achieve significant body weight reductions alongside high treatment satisfaction.

The OCTANE study was a real-world evidence analysis conducted through a collaboration between Novo and the digital health platform Ro. The analysis set included 194 adults living with overweight or obesity who were previously treated with injectable GLP-1 therapies (such as injectable semaglutide or tirzepatide) before transitioning to the once-daily Wegovy pill. The average starting weight at the time of transition was 221.6 lbs, with 87.1% of participants classified as living with clinical obesity. At the three-month mark following the transition to oral semaglutide, participants lost an average of 4.1% of their total body weight, representing an average weight reduction of 8.8 lbs. The proportion of participants classified as living with clinical obesity declined substantially from 87.1% at baseline to 65.5% at three months, moving a significant share of patients below the clinical obesity threshold. Approximately 75% of participants reported satisfaction with switching to the oral pill format, highlighting strong real-world adherence and favorable treatment experience. These real-world findings address a critical clinical question in chronic weight management: whether patients can successfully maintain or accelerate weight loss when switching from injectable to oral GLP-1 formulations. Or do they?

Once again, one of my favorite BioX accounts, Jen Can NuSH, was quick to point out a number of potential pitfalls of the analysis that coalesces on the fact that the presenters didn’t break out results by starting dose. As Jen notes:

• The standards for inclusion only appear to require a single GLP-1 injectable script (not a fill) prior to switch, so some people in this might not have ever taken an injectable if they ran into insurance or cost issues.

• 69% of those switching from injectable Wegovy were on 1mg or lower for their last script before switching. 1.7mg is the first dose approved for weight loss efficacy.

• 41% of those switched from Zepbound had 2.5mg as their last script before switching. Thats just the intro dose and not approved for weight loss efficacy.

Even with the opaque starting point, Jen notes that, “mean BMI change over 3 months was 1.4 and mean loss was 4kg (8.8lbs).” She concludes by stating, “that may be statistically significant, but is it that stage sort of significance patients are expecting when you say “significantly”?” It’s a fair question, particularly for an audience of physicians and payors who have potentially-life-changing choices to make for their patients.

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Other notable datasets

Novo - CagriSema (amylin + GLP-1 FDC) / fMRI study (obesity)

On September 30, 2026, Dr. Anthony P. Goldstone presented neuroimaging data evaluating Novo’s CagriSema, an investigational once-weekly fixed-dose combination of the selective amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. The trial abstract detailing these fMRI mechanisms (Uhre VF et al., Abstract 122) was honored with a Best Abstract Award at EASD 2026 for elucidating the neurocircuitry of dual amylin/GLP-1 agonism. It demonstrated how CagriSema acts within central brain networks to alter visual food-cue reactivity and suppress intrusive cravings, commonly referred to as “food noise”.

The 52-week functional magnetic resonance imaging (fMRI) mechanistic study investigated the central effects of CagriSema in adults with overweight or obesity. Participants underwent fMRI scans while being exposed to visual cues of highly caloric, rewarding foods compared to neutral cues to measure changes in localized blood-oxygen-level-dependent (BOLD) brain activation. fMRI scans revealed that 52 weeks of CagriSema treatment significantly blunted neural hyper-reactivity in central brain regions responsible for food cravings, reward prediction, and sensory processing. This suppression directly correlated with significant reductions in patient-reported “food noise,” appetite, and homeostatic hunger. The neurobiological changes observed on fMRI corresponded to an estimated treatment difference in body weight loss of -22.4% compared to placebo at 52 weeks (P < 0.0001).

Novo submitted a NDA to the FDA for CagriSema in weight management in December 2025, with an FDA decision expected in the fourth quarter of 2026. Phase 3 trials evaluating higher-dose CagriSema formulations (2.4 mg / 7.2 mg) are ongoing to investigate maximum efficacy and long-term weight maintenance.

Sources: Novo press release, Novo EASD 2026 abstract, Novo EASD 2026 presentation

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Zealand - Petrelintide (amylin agonist) / Phase 2, ZUPREME-1 trial (obesity)

On September 29, 2026, Zealand Pharma published results from the Phase 2 ZUPREME-1 trial evaluating petrelintide, a long-acting amylin receptor agonist, in The Lancet Diabetes & Endocrinology. The detailed findings were also delivered in an oral presentation at EASD 2026 by Dr. Timothy Garvey. The ZUPREME-1 enrolled adults living with obesity or overweight with weight-related comorbidities, excluding individuals with a diagnosis of type 1 or type 2 diabetes. Petrelintide achieved mean body weight reductions up to 10.7% at higher maintenance doses over 28 weeks, significantly outperforming placebo. The drug exhibited low rates of nausea and vomiting during titration, with GI adverse events predominantly mild in severity and a tolerability profile closely resembling placebo. Discontinuations due to adverse events remained low across active dose cohorts.

Zealand Pharma has initiated the global Phase 3 ZUPREME registrational program evaluating petrelintide monotherapy for chronic weight management in individuals with overweight or obesity. Dedicated trials evaluating petrelintide in patients with obesity and type 2 diabetes (such as ZUPREME-2) will run as part of the broader Phase 3 development strategy.

Sources: Zealand press release, Garvey et al., The Lancet Diabetes & Endocrinology (2026)

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Eli Lilly - Foundayo (oral GLP-1 agonist) / Phase 3, ACHIEVE-4 trial (obesity+T2D)

On September 31, 2026, Dr. Klara Klein presented detailed data from Eli Lilly’s ACHIEVE-4, the largest and longest Phase 3 study to date evaluating Foundayo (orforglipron). The results were published in The Lancet on the previous day, September 30, 2026. Evaluated in adults with type 2 diabetes and obesity or overweight at increased cardiovascular risk, Foundayo established robust cardiovascular safety while delivering durable, multi-year glycemic control and clinically meaningful weight reduction.

The active-controlled, randomized Phase 3 ACHIEVE-4 trial evaluated the long-term safety and efficacy of once-daily oral Foundayo against titrated injectable insulin glargine. Foundayo successfully achieved its primary endpoint by demonstrating MACE-4 non-inferiority to insulin glargine (HR = 0.84; 95% CI: 0.59-1.20; p = 0.336), alongside a 23% relative risk reduction in MACE-3 events (HR = 0.77; 95% CI: 0.52-1.13) and a nominal 57% reduction in all-cause mortality (HR = 0.43; 95% CI: 0.25-0.75; nominal p = 0.002). Furthermore, Foundayo demonstrated superior glycemic control through 104 weeks with an HbA1c reduction of -1.6% versus -1.0% for insulin glargine (ETD: -0.66%; p < 0.001), while driving a mean weight loss of -8.8% (-8.1 kg) compared to a +1.7% (+1.4 kg) weight gain with insulin glargine (ETD: -10.42%; p < 0.001). Its safety profile aligned with the GLP-1 class, presenting predominantly mild-to-moderate gastrointestinal adverse events, a 10.6% discontinuation rate at 52 weeks, and no hepatic safety signals. By replacing the weight gain and complexity of basal insulin with a flexible, once-daily oral option that lacks strict morning fasting or water restrictions, Foundayo positions itself as a transformative alternative to injectable incretins and standard insulin initiation.

Following initial approvals in chronic weight management, Eli Lilly plans to complete supplemental regulatory filings for type 2 diabetes in global markets, utilizing priority review mechanisms where applicable. Long-term cardiovascular efficacy continues to be evaluated in the dedicated ATTAIN-OUTCOMES Phase 3 cardiovascular outcomes trial (CVOT) in patients with established cardiovascular or kidney disease. Ongoing Phase 3 trials are evaluating Foundayo across broader secondary indications, including obstructive sleep apnea, hypertension, osteoarthritis knee pain, peripheral artery disease, and metabolic kidney diseases.

Sources: Eli Lilly press release, Eli Lilly EASD 2026 slide deck, Klein et al., The Lancet (2026)

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BI & Zealand - Survodutide (GLP-1 x glucagon dual agonist) / Phase 3, SYNCHRONIZE-2 trial (obesity+T2D)

On October 1, 2026, Dr. Sean Wharton presented primary late-breaking data from the Boehringer Ingelheim’s (BI) and Zealand’s Phase 3 SYNCHRONIZE-2 trial, simultaneously published in The New England Journal of Medicine. Evaluating survodutide, a novel, once-weekly dual agonist of both GLP-1 and glucagon receptors, in adults living with obesity or overweight and comorbid type 2 diabetes, the study met both co-primary endpoints.

The 76-week, randomized, double-blind, placebo-controlled Phase 3 SYNCHRONIZE-2 trial evaluated the efficacy and safety of weekly subcutaneous survodutide injections in 755 adults living with overweight or obesity (BMI ≥27 kg/m²) and comorbid type 2 diabetes. Survodutide drove a mean body weight loss of up to -13.1% at the 6.0 mg high dose versus -3.1% for placebo (p < 0.0001), alongside an HbA1c reduction of up to -1.21% (versus -0.03% for placebo) and improvements in waist circumference, insulin sensitivity, fasting plasma glucose, and blood pressure. EASD sub-study analyses further showed that muscle loss was minimized to no more than 10% of total tissue lost, with reductions driven primarily by visceral and abdominal adipose fat. However, safety outcomes highlighted a challenging tolerability profile marked by frequent gastrointestinal adverse events (including vomiting in up to 39% of patients) and a 26% adverse-event discontinuation rate in the treatment arms (18% due to GI events, largely occurring during protocol-mandated fixed dose escalation). Ultimately, while SYNCHRONIZE-2 proves that adding glucagon agonism to GLP-1 therapy can yield double-digit weight loss in a complex type 2 diabetes population, the combination of modest HbA1c lowering and high GI toxicity suggests its core clinical and commercial value may rely more on its targeted liver-fat clearance in MASH/MASLD than on standard glycemic control.

BI plans to implement more flexible, individualized step-up titration protocols in future clinical studies to reduce peak GI toxicity, curb vomiting, and improve patient retention. They are progressing the dedicated SYNCHRONIZE-T2D Phase 3 trial to specifically evaluate survodutide’s blood sugar control across broader T2D medication backgrounds. The company plans to continue Phase 3 development in metabolic dysfunction-associated steatohepatitis (SYNCHRONIZE-MASLD) following FDA Breakthrough Therapy designation, alongside finalizing results from the large-scale SYNCHRONIZE-CVOT cardiovascular outcomes trial.

Sources: BI press release, Wharton et al., NEJM (2026)

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Regeneron - Trevogrumab (anti-GDF8/myostatin mAb) / Phase 2, COURAGE trial (obesity)

On October 1, 2026, Dr. José Raya García del Olmo presented data from the Phase 2 COURAGE trial evaluating trevogrumab in combination with the GLP-1 receptor agonist semaglutide in adults with obesity. Concurrent with the presentation, the detailed results were submitted for publication in The Lancet, although it has not yet been published. The COURAGE trial was designed to address a major clinical limitation of incretin-based weight loss: the significant concurrent loss of skeletal muscle and lean mass. By adding a targeted anti-myostatin antibody to semaglutide, the study demonstrated that blocking pathways responsible for muscle degradation can preserve lean mass and improve the overall composition and quality of weight loss.

Trevogrumab is a fully human monoclonal antibody designed to selectively bind and neutralize growth differentiation factor 8 (GDF8), also known as myostatin. Myostatin acts as a negative regulator of skeletal muscle growth. Blocking its signaling cascade prevents muscle protein breakdown and promotes muscle mass retention during negative energy states. While GLP-1 receptor agonists (such as semaglutide) suppress central appetite and delay gastric emptying to drive fat reduction, up to 25-35% of the total weight loss achieved on incretins typically stems from lean mass. Trevogrumab was developed to protect the skeletal muscle compartment, ensuring that weight loss is primarily derived from adipose tissue loss.

The Phase 2 COURAGE trial evaluated the safety, tolerability, and muscle-preserving efficacy of adding trevogrumab to a background regimen of semaglutide in adults with obesity without diabetes. The trial demonstrated robust efficacy, with trevogrumab reducing DXA-measured lean mass loss to -3.3% at 26 weeks (50.7% preservation relative to placebo) and -4.2% at 52 weeks (42.5% preservation) in the 75 mg arm, while an MRI substudy confirmed that trevogrumab prevented up to ~70% of fat-free thigh muscle volume loss compared to semaglutide alone (-0.32 vs. -1.03 at 52 weeks). Importantly, trevogrumab co-administration maintained overall weight loss efficacy while shifting the proportion of weight lost away from lean tissue degradation and toward fat mass reduction. The combination was generally well tolerated, with adverse events occurring in 77% of trevogrumab-treated participants compared to 82% in the semaglutide-plus-placebo arm, presenting no unexpected safety signals or major muscular toxicities.

Regeneron plans to advance trevogrumab into late-stage Phase 3 clinical development, evaluating combination regimens with GLP-1s and next-generation incretins. Future trials will assess physical performance metrics (such as grip strength, mobility, and gait speed) alongside body composition to confirm the functional benefits of preserved lean mass. Continued evaluation of combination strategies, including co-formulations with activin receptor blockers (e.g., garetosmab) to optimize muscle gain and fat loss ratios.

Sources: Regeneron press release, Regeneron EASD 2026 presentation

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AbbVie - ABBV-295 (amylin agonist) / Phase 1 (obesity)

On September 30, 2026, Dr. Ildiko Lingvay presented AbbVie’s Phase 1 data evaluating ABBV-295, a novel, long-acting synthetic amylin analog, for chronic weight management. The single-center, randomized, double-blind, placebo-controlled Phase 1 multiple ascending dose trial evaluated 60 healthy adults across various subcutaneous dosing schedules over 12 to 13 weeks (4, 6, or 14 mg once weekly; 14 mg every-other-week; or 8 mg monthly) to assess safety, tolerability, pharmacokinetics, and body weight change. Results demonstrated dose-dependent efficacy, with once-weekly regimens achieving least-squares mean body weight reductions of -7.8-9.8% at Week 12, while extended regimens yielded -9.7% (every-other-week) and -7.9% (monthly) at Week 13, compared to -0.3% for placebo. Pharmacokinetic analyses confirmed dose-proportional plasma exposure with an extended mean half-life of 10.7 to 12.3 days, directly enabling less frequent dosing schedules. ABBV-295 was well tolerated with no serious treatment-emergent adverse events; gastrointestinal side effects (primarily mild nausea [33.3%] and diarrhea [20.0%]) occurred mainly during initial titration, leading to a low GI-related discontinuation rate of 4.4%. These data establish ABBV-295 as a differentiated non-incretin asset capable of monthly maintenance dosing, supporting AbbVie’s plans to advance the drug into Phase 2 development as both a monotherapy and a potential backbone for combination regimens in obesity.

Sources: AbbVie press release

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Regeneron & Hansoh - Olatorepatide (GLP-1 x GIP dual agonist) / Phase 3, LIGHTEN trial (obesity)

On October 2, 2026, Hansoh Pharma and Regeneron Pharmaceuticals presented Phase 3 data for olatorepatide (HS-20094), a once-weekly, dual-biased GLP-1 x GIP receptor dual agonist evaluated for chronic weight management. The Phase 3 LIGHTEN trial enrolled 604 Chinese adults living with obesity or overweight without diabetes. At Week 48, olatorepatide met all primary and key secondary endpoints, driving least-squares mean body weight reductions of up to 19.3% in the high-dose group (compared to 1.6% for placebo; p < 0.0001), with 71.7% of participants on 15 mg achieving ≥15% body weight loss (vs. 3.2% for placebo). Treatment-emergent adverse events were predominantly mild-to-moderate gastrointestinal symptoms, with low incidences of nausea (<10%) and vomiting (<5%), alongside lower discontinuation rates compared to historically published Phase 3 benchmark data for other incretin therapies. Following these pivotal results, Regeneron plans to initiate its global Phase 3 registrational program later this year to evaluate olatorepatide across broader international populations.

Sources: Hansoh press release

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Table of Contents

This week, we discuss:

• China European Biotech

  • Europe Is Losing the Pharma Investment Race, an open letter from European pharma ⬇️

  • U.S. Investigates German Drug Pricing, Weighs Tariffs ⬇️

• Acquisitions

  • Telix to Merge with ITM Isotope ⬇️

• Approvals

  • Merck - Welireg (HIF-2α inhibitor) / Approved (2L ccRCC) ⬇️

  • Eli Lilly - Onswik (long-acting insulin) / Approved (T2D) ⬇️

  • Elevar - Lyrfigtu (FGFR2 inhibitor) / Approved (2L CCA) ⬇️

  • Merck - Winrevair (activin A inhibitor) / Approved (PAH Group 1) ⬇️

  • IntraBio - Aqneursa (N-acetyl-L-leucine) / Approved (Ataxia-telangiectasia) ⬇️

• Clinical Trial Data

  • Viking - VK2735 (GLP1 / GIP dual agonist) / Phase 2 (obesity) ⬇️

  • Roche - Enicepatide (GLP1/GIP dual agonist) / Phase 3 (obesity + T2D) ⬇️

  • Kyverna - Miv-cel (CD19 CAR-T) / Phase 2 (SPS) ⬇️

  • Oruka - ORKA-001 (IL-23p19 mAb HLE) / Phase 2 (plaque psoriasis) ⬇️

  • Vertex - Inaxaplin (APOL1 inhibitor) / Phase 2b (AMPKD) ⬇️

  • Alkermes - ALKS 7290 (selective OX2 agonist) / Phase 1b (ADHD) ⬇️

  • J&J - Caplyta (5HT2A x D2 dual inhibitor) / Phase 3 (bipolar I) ⬇️

  • Merck - Remigromig (tri-specific Wnt agonist) / Phase 2b/3 (DME): P2b/3 success (DME) ⬇️

  • Arcturus - ARCT-810 (OTC mRNA) / Phase 2 (OTC deficiency): P2 success (OTC deficiency) ⬇️

  • Roche - Sefaxersen (Factor B ASO) / Phase 3 (IgAN) ⬇️

  • Amgen - Dazodalibep (CD40L inhibitor) / Phase 3 (Sjögren’s disease) ⬇️

  • Otsuka - Ulefnersen (FUS ASO) / Phase 3 (FUS-ALS): P3 success (FUS-ALS) ⬇️

China European Biotech

Typically, this section is dedicated to choreographing the breakneck speed of biotech innovation out of China. However, just for this week, I want to do a complete 180 and discuss the relentless lethargy of Europe’s biotech innovation engine (the EU’s regulatory hampering of tech is a whole other can of worms that I won’t go into here). To be clear, European biotechs themselves are undoubtedly excellent: from French biotech Abivax bringing a novel mechanism to bear in ulcerative colitis, to Dutch biotech Argenx expanding their Vyvgart empire in autoimmune disease. Rather, this section focuses on the EU’s regulatory infrastructure, which increasingly punishes innovation rather than fosters it.

On September 22, 2026, nearly every European pharmaceutical company (many 100+ years old) joined forces to publish an open letter to the European Union (EU) expressing concern about the bloc’s declining competitiveness in the biotech space and urging EU leaders to re-prioritize innovative medicines. Given the seriousness of the letter and its carefully crafted contents, I have copied it verbatim below, in the hope that it reaches more people.

Europe Is Losing the Pharma Investment Race – But the Comeback Is Within Reach: An open letter from the Chairs of AstraZeneca, Boehringer Ingelheim, Chiesi Group, Ipsen, GSK, Novo, Novartis, Roche, and Sanofi

We are proud Europeans. We serve as Chairs of companies born from European science, rooted in laboratories across Belgium, Denmark, France, Germany, Italy, Spain, Sweden, Switzerland, the UK, and beyond. Our duty is to safeguard our companies’ future so that we can continue to discover and develop life-changing medicines for patients.

The pharmaceutical sector is one of our continent’s great post-war achievements. Built on investment in science, world-class universities, and the determination to discover medicines that change lives. Europe gave the world vaccines, pioneered treatments for heart disease, and laid the foundation for today’s cancer treatments – transforming public health.

Europe’s choice to incentivise discovery built one of our most productive and research-intensive sectors, supporting millions of highly skilled jobs, and generating an EU trade surplus of over €220 billion. The uptake of innovative medicines in Europe returns almost sixfold to the economy through lower hospitalisation costs and healthier working lives. Our sector powers a vast ecosystem spanning discovery, development and manufacturing, while strengthening health systems to manage rising burdens of disease and ageing populations.

But this hard-won inheritance is at risk. In our boardrooms, we see Europe losing ground to global competition. Over $600 billion in pharmaceutical investment has been announced in the US and China in the last two years alone. European governments must create conditions that attract investment in next-generation medicines before it’s too late.

Europe’s alarm bells are ringing. As Mario Draghi warned, without urgent action, strategic sectors like pharmaceuticals face a ‘slow agony’ of decline. In 1990, Europe accounted for 43% of global pharmaceutical R&D. Today, it is 31% and falling. Europe’s share of commercial clinical trials, which provide vital revenue for public hospitals and improve patient outcomes, has halved in a decade to 9%. China has overtaken Europe in clinical trials, pharmaceutical patents, and the development of new medicines.

For patients, the consequences are clear: around 40% of newly approved therapies never reach European patients. Among those that do, patients wait nearly 600 days for treatment. Cancer survival in Europe trails the US. Too many patients are diagnosed late or treated with medicines that fall short of the standard recommended by medical guidelines.

This is the result of decades in which Europe treated medicines as a cost to suppress rather than one of the best investments a government can make. Outdated systems constrain the use of innovative medicines, arbitrarily cap budgets, and fail to adjust spending for inflation despite rising patient need. Government policies send a powerful signal about how innovation is valued and the priority placed on ensuring that patients can access it.

The message to innovators has been stark: Europe does not value what you do.

The decisions we take have consequences today and for years to come. A single innovative medicine takes more than a decade and around €3 billion of at-risk investment before reaching a patient, with only one or two medicines emerging from every 10,000 candidates synthesised in laboratories. Few sectors face comparable risk over such long horizons. That commitment requires a market that rewards it.

It is becoming more urgent to change course. European leaders must recognise the danger. The EU can play an enabling role by accelerating clinical trials, protecting intellectual property, and adopting sensible digital policies. Crucially, the EU could also provide fiscal flexibility to Member States investing in health and innovative medicines, recognising these returns take time to materialise.

But EU action alone is not enough. The decisive levers lie with national governments: how much to invest in health budgets, how quickly new medicines are assessed and funded, and how to modernise healthcare to better prevent, detect and treat disease.

We ask national leaders to work with us to reverse Europe’s declining competitiveness, unleash a new era of medical discovery, and secure health sovereignty. We recognise the fiscal pressures many face. But just like defence or energy, modern medicines should be treated as vital infrastructure and not be left to others to provide.

Opportunities are on Europe’s doorstep if governments rebalance decades of underinvestment in innovative medicines and modernise value frameworks to reflect the total value of what these treatments bring to patients, health systems and the economy. In clinical trials alone, Europe could unlock €53 billion and 82,000 jobs by closing the gap with China and the US.

Europe’s story does not have to be one of decline and dependency; it can be one of renewal and resilience. That choice belongs to national leaders and all of us as citizens. If we fail to act with ambition, our future will be built elsewhere. But if we choose to invest in health and medicines as strategic assets, Europe will not merely catch up – it can set the pace of global innovation once again and enable Europeans to live longer, healthier lives.

Sources: Original Open Letter

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U.S. Investigates German Drug Pricing, Weighs Tariffs

On September 22, 2026, the Office of the United States Trade Representative (USTR) held a public hearing at the International Trade Commission following its June launch of a Section 301 investigation into Germany’s declining payments for pharmaceutical products, which were cut again in July. The U.S. is considering tariffs against Germany or other measures in response. There were two sides to the story:

• In Favor of Action: Representatives from biopharma lobbying group PhRMA and drugmaker AbbVie supported potential trade measures, arguing that Germany’s reimbursement policies undervalue innovative medicines and shift the burden of R&D funding onto the U.S.

• Opposed to Action: Experts such as Thomas Hwang (Harvard Medical School) and Megan Whiteman (Public Citizen) testified against the probe, asserting that Germany’s pricing system is neither discriminatory nor restrictive of U.S. commerce. Hwang noted that the investigation may simply serve as leverage for broader trade negotiations.

Concurrently, chairs and executives from nine major European biopharma companies (including AstraZeneca, GSK, Novo Nordisk, Novartis, Roche, and Sanofi) released an open letter urging European Union (EU) leaders to enact policy changes to reverse Europe’s declining competitiveness compared to the U.S. and China (copied above). Industry leaders, including Novo Nordisk’s CEO Mike Doustdar, highlighted that aggressive European price cuts are leading some companies to delay or forgo launching new drugs in European markets altogether.

Sources: Endpoints article, Section 301 schedule

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Acquisitions

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Approvals

Merck - Welireg (HIF-2α inhibitor) / Approved (2L ccRCC)

On September 24, 2026, the FDA approved Welireg in combination with Lenvima for adult patients with advanced clear cell renal cell carcinoma (ccRCC) whose disease has progressed following prior treatment with a PD-1 or PD-L1 inhibitor. This approval significantly broadens Welireg’s clinical footprint. Unlike its earlier monotherapy indication, which required patients to have progressed after both a PD-1/L1 inhibitor and a VEGF-TKI (3L), this latest expansion enables clinicians to deploy the Welireg + Lenvima combination immediately upon progression following immune checkpoint inhibitor therapy, effectively moving HIF-2α inhibition into earlier post-IO treatment settings. By simultaneously blocking HIF-2α transcription and multiple receptor tyrosine kinase pathways, this all-oral doublet provides a comprehensive dual-inhibition strategy designed to overcome resistance following prior immunotherapy.

The regulatory approval was supported by compelling results from LITESPARK-011, a pivotal, open-label, randomized, active-controlled Phase 3 trial. The study enrolled 747 adult patients with unresectable, locally advanced, or metastatic ccRCC who experienced disease progression on or after prior anti–PD-1/PD-L1 antibody therapy (or within 6 months of completing adjuvant anti–PD-1/L1 therapy). The trial met its primary end point, demonstrating a statistically significant 26% reduction in the risk of disease progression or death compared to cabozantinib. The mPFS was 14.6 months for Welireg + Lenvima vs. 10.6 months for cabozantinib (HR = 0.74; p = 0.00095). Depth of response favored the combination arm. The confirmed ORR reached 53% with Welireg + Lenvima versus 40% with cabozantinib (1-sided p = 0.0002). Responders in the combination arm experienced substantially longer disease control, with a median DOR of 23.0 months compared to 12.3 months in the cabozantinib arm. At the final OS analysis, the hazard ratio favored the combination arm (HR = 0.85), with a median OS of 33.7 months vs. 28.6 months, though this numerical difference did not achieve statistical significance.

Sources: Merck press release, updated Welireg label

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Eli Lilly - Onswik (long-acting insulin) / Approved (T2D)

On September 24, 2026, the FDA approved Onswik as an adjunct to diet and exercise to improve glycemic control in adults living with type 2 diabetes mellitus (T2D). This approval established Onswik as a transformative once-weekly basal insulin option in the United States, dramatically slashing the annual injection burden for T2D patients from approximately 365 daily shots down to just 52. Onswik catches up to Novo’s one-weekly insulin Awiqli, which was approved on March 26, 2026.

The regulatory approval of Onswik was supported by extensive data from Lilly’s global QWINT Phase 3 clinical program, which evaluated the efficacy and safety of once-weekly insulin efsitora alfa across more than 3,400 adult participants with type 2 diabetes. The QWINT registration program encompassed four primary Phase 3 studies (QWINT-1, QWINT-2, QWINT-3, and QWINT-4) designed to test Onswik across various patient populations, including insulin-naive individuals starting basal therapy for the first time as well as patients switching from daily basal insulins. The active comparator arms utilized established once-daily basal standards: insulin glargine U-100 and insulin degludec U-100. Across all four Phase 3 trials, once-weekly Onswik met its primary endpoint, demonstrating non-inferior HbA1c reductions compared to daily basal insulin glargine or degludec. Onswik consistently enabled patients to reach and maintain glycemic targets over the evaluation periods. In studies like QWINT-1, Onswik demonstrated that a straightforward, once-weekly dosing schedule with fixed titration steps could effectively lower HbA1c in insulin-naive patients, offering a simplified entry point into insulin therapy. Nevertheless, Onswik is strictly contraindicated in patients with type 1 diabetes (T1D) due to an elevated risk of severe hypoglycemia and ketoacidosis. The prescribing information also includes standard warnings regarding hypokalemia and caution when used in combination with thiazolidinediones (TZDs) due to heart failure risks.

Sources: Eli Lilly press release, new Onswik label

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Elevar - Lyrfigtu (FGFR2 inhibitor) / Approved (2L CCA)

On September 23, 2026, the FDA approved Lyrfigtu (lirafugratinib) for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 gene fusion or other rearrangement. The regulatory review utilized the FDA’s Real-Time Oncology Review (RTOR) pilot program and was granted Priority Review, Breakthrough Therapy Designation, and Orphan Drug Designation. The approval establishes Lyrfigtu as a targeted second-line therapeutic option for patients who have progressed on or after systemic chemotherapy or chemoimmunotherapy.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy of the gastrointestinal tract with limited therapeutic options and a historically poor prognosis. For patients presenting with unresectable, locally advanced, or metastatic disease, gemcitabine- and platinum-based chemo-immunotherapy regimens serve as standard first-line care. However, disease progression is common, creating an urgent need for targeted therapies upon relapse. Approximately 10% to 15% of patients with intrahepatic cholangiocarcinoma harbor FGFR2 (fibroblast growth factor receptor 2) gene fusions or genetic rearrangements. While first-generation pan-FGFR inhibitors demonstrated initial clinical utility, their efficacy is often limited by off-target toxicities driven by FGFR1/3/4 inhibition (such as hyperphosphatemia, diarrhea, and mucosal toxicities) and the emergence of secondary resistance mutations. To overcome these challenges, Elevar Therapeutics developed Lyrfigtu (lirafugratinib), a next-generation, highly selective, oral, irreversible covalent inhibitor designed to selectively target FGFR2 while minimizing off-isoform toxicities and overcoming acquired resistance mechanisms.

The approval was anchored by safety and efficacy outcomes from the ReFocus trial, a pivotal global, open-label, Phase 1/2 study evaluating lirafugratinib in patients with FGFR2-altered solid tumors. The primary efficacy cohort comprised 116 adult patients with unresectable, locally advanced or metastatic cholangiocarcinoma harboring confirmed FGFR2 gene fusions or rearrangements who had received at least one prior line of systemic therapy. As evaluated by an Independent Review Committee (IRC) per RECIST v1.1, Lyrfigtu achieved a confirmed ORR of 46%. Responses were notably durable, with a median DOR reaching 11.8 months. Patients treated with Lyrfigtu achieved a median PFS of 11.3 months, with a 12-month PFS rate of 49.2%. Lyrfigtu demonstrated a predictable and clinically manageable safety profile in line with its mechanism of action as a selective FGFR2 covalent inhibitor. Common adverse reactions (≥20%) observed in the clinical trial included nail toxicity, palmar-plantar erythrodysesthesia syndrome (hand-foot syndrome), stomatitis, fatigue, dry eye, dry mouth, alopecia, dysgeusia, constipation, and musculoskeletal pain.

Sources: Elevar press release, FDA notification, Elevar slide deck, label not available at time of publication

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Merck - Winrevair (activin A inhibitor) / Approved (PAH Group 1)

On September 22, 2026, the FDA approved an updated U.S. product label for Merck’s Winrevair (sotatercept-csrk) to incorporate phase 3 data from the HYPERION trial. While Winrevair’s initial approval established its role in advanced disease, this label update formally embeds data evaluating its efficacy and safety when added to background therapy in recently diagnosed adults, specifically those within 12 months of diagnosis with WHO Functional Class (FC) II or III PAH at intermediate to high risk of disease progression. By incorporating these results, the updated label establishes Winrevair as an early-intervention option, moving the first-in-class activin signaling inhibitor upstream in the treatment paradigm to arrest vascular remodeling sooner after diagnosis.

Pulmonary arterial hypertension (PAH) is characterized by a homeostatic imbalance in the small pre-capillary pulmonary arteries, where endothelial cell dysfunction triggers a relative decrease in vasodilators (such as nitric oxide and prostacyclin) and an increase in vasoconstrictors (such as endothelin-1). This persistent chemical shift promotes sustained vasoconstriction, vascular smooth muscle and endothelial hyperproliferation, resistance to apoptosis, localized inflammation, and in situ thrombosis. Over time, these cellular changes drive progressive structural remodeling (including vessel wall thickening, luminal obliteration, and plexiform lesion formation) which markedly elevates pulmonary vascular resistance and right ventricular afterload, ultimately resulting in compensatory right ventricular hypertrophy, dilation, and fatal right heart failure. Historically, PAH carried a grave prognosis, with the landmark NIH registry in the 1980s showing a median survival of only 2.8 years without targeted medical therapy.

The HYPERION study (N = 320) evaluated adults with a mean time since diagnosis of just 7.2 months. Patients were already receiving standard background regimens, with 72% on double background therapy, 28% on triple background therapy, and 17% on parenteral prostacyclin infusions. When added to background therapy, Winrevair reduced the risk of time to death or a first confirmed morbidity event by 76% compared to placebo plus background therapy (HR= 0.24; p < 0.0001). A first clinical worsening event occurred in 10.6% (17/160) of patients in the Winrevair arm compared to 36.9% (59/160) of patients in the placebo group. The trial tracked time to first event, including all-cause mortality, unplanned PAH-related hospitalizations (≥24 hours), lung transplantation, atrial septostomy, or a decline in 6-minute walk distance (6MWD) combined with functional worsening, right heart failure symptoms, or additional background therapy. The treatment effect was consistent across all prespecified clinical subgroups, regardless of age, sex, PAH etiology (e.g., idiopathic vs. connective tissue disease-associated), or baseline risk scores (REVEAL Lite 2 or COMPERA 2). The most frequent adverse events (≥10% incidence and at least 5% higher than placebo) were epistaxis (31.9% vs. 6.9%), telangiectasia (26.3% vs. 11.3%), and increased hemoglobin (11.3% vs. 1.3%). Only 3% of patients in the Winrevair group discontinued treatment due to adverse events (epistaxis being the main driver), compared to 0% in placebo. No severe platelet drops (< 50,000 / mm³) occurred in the Winrevair arm. The updated label includes a contraindication for severe hypersensitivity (e.g., anaphylaxis, angioedema) to sotatercept-csrk. Providers are advised to monitor hemoglobin (to detect erythrocytosis) and platelets (to manage thrombocytopenia, particularly in patients on concomitant prostacyclin infusions) prior to treatment and periodically throughout therapy.

Sources: Merck press release, updated Winrevair label

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IntraBio - Aqneursa (N-acetyl-L-leucine) / Approved (Ataxia-telangiectasia)

On September 25, 2026, the FDA approved a major label expansion for IntraBio’s Aqneursa (levacetylleucine / N-acetyl-L-leucine) to treat ataxia in adults and pediatric patients weighing at least 15 kg with Ataxia-Telangiectasia (A-T). This regulatory decision marks a historical milestone as the first FDA-approved disease-modifying treatment specifically indicated for A-T, a rare, progressive, and life-limiting autosomal-recessive neurodegenerative disease caused by mutations in the ATM gene. Initially approved in September 2024 for the neurological manifestations of Niemann-Pick disease type C (NPC), Aqneursa is an orally administered, chemically modified amino acid derivative. Rather than targeting a single mutated gene, Aqneursa is proposed to correct downstream metabolic dysfunction by normalizing cerebellar glucose metabolism and restoring lysosomal and mitochondrial ATP production. This label expansion transitions the drug from a single-disease therapy into a broader metabolic neuro-restorative platform for complex ataxias.

The label extension of Aqneursa was granted on the strength of pivotal data from the Phase 3 IB1001-303 trial, a multinational, randomized, double-blind, placebo-controlled crossover study (N = 73) in patients aged 4 to 50 years with genetically confirmed A-T. Over a 12-week treatment period, Aqneursa demonstrated a statistically significant improvement in motor function compared to placebo on the Scale for the Assessment and Rating of Ataxia (SARA). Patients treated with Aqneursa achieved a 1.9-point mean improvement over placebo (Treatment Difference = -1.9; p < 0.001). In a modified, functional SARA assessment prioritized by the FDA (evaluates core daily tasks across gait, sitting, stance, and speech domains), Aqneursa demonstrated a 0.6-point mean advantage over placebo (Treatment Difference = -0.6; p < 0.001).Clinically observable neurological and functional improvements emerged rapidly within 12 weeks of therapy initiation. Benefits were consistent across pediatric and adult age cohorts, prior functional baseline levels, and prespecified disease severity subgroups. A notable 96% of enrolled participants (70/73) completed both treatment periods of the crossover design, reflecting high trial adherence and patient tolerance. The product labeling warns against concomitant administration with race-mixture formulations like N-acetyl-DL-leucine or N-acetyl-D-leucine, as the D-enantiomer competes for monocarboxylate transporter uptake and impairs Aqneursa‘s efficacy. Since Aqneursa inhibits P-glycoprotein (P-gp), patients on narrow-therapeutic-index P-gp substrates require close monitoring. Animal data indicate potential embryo-fetal toxicity, necessitating pregnancy verification and reliable contraception in female patients of reproductive potential.

Sources: IntraBio press release, updated Aqneursa label

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Clinical Trial Data

Viking - VK2735 (GLP1 / GIP dual agonist) / Phase 2 (obesity)

On September 22, 2026, Viking Therapeutics released positive topline Phase 2 data evaluating extended-interval maintenance dosing for its flagship metabolic asset, VK2735, a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. While current commercial incretin therapies (such as tirzepatide and semaglutide) require weekly subcutaneous injections, Viking’s study addressed one of the biggest clinical challenges in obesity medicine: long-term weight maintenance and patient adherence. The trial demonstrated that after achieving robust initial weight loss on weekly dosing, patients can transition to every-other-week (Q2W) or once-monthly (QM) administration while retaining the vast majority of their weight loss.

In a Phase 2 trial of adults with obesity or overweight without diabetes, weekly VK2735 induction (weeks 1-21) produced a significant mean weight reduction of -16% to -19% compared to about 0% on placebo (p < 0.0001). Transitioning patients during the maintenance phase (weeks 22–33) to every-other-week or once-monthly dosing preserved 83-97% and 82-90% of their initial weight loss, respectively, outperforming placebo withdrawal (61% retention; p < 0.01), while continuous weekly dosing reached 21.7% weight loss without plateauing. By showing that extended-interval regimens maintain weight loss while reducing cumulative drug exposure by up to 85%, VK2735 provides meaningful dosing flexibility to combat weekly injection fatigue, potentially lowering costs and establishing a potential differentiator against incumbent weekly incretins like Wegovy and Zepbound.

Viking is advancing its fully enrolled Phase 3 trials VANQUISH-1 (obesity) and VANQUISH-2 (type 2 diabetes), evaluating primary weekly efficacy endpoints, with topline data anticipated in 2027. Data from this trial will inform the design of planned VANQUISH extension studies, formally incorporating biweekly and monthly maintenance regimens. Viking is initiating Part 2 of its Phase 2 maintenance study, exploring whether patients can maintain weight loss by switching from subcutaneous VK2735 induction to an oral tablet formulation of VK2735.

Sources: Viking press release, Viking slide deck

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Roche - Enicepatide (GLP1/GIP dual agonist) / Phase 3 (obesity + T2D)

On September 21, 2026, Roche released positive Phase 3 results for enicepatide (CT-388), an investigational once-weekly subcutaneous dual GLP-1 and GIP receptor agonist, in patients living with obesity and type 2 diabetes (T2D). The trial successfully met its dual primary efficacy endpoints, demonstrating robust, dose-dependent reductions in both body weight and HbA1c. Notably, Roche’s enicepatide is engineered with cAMP signaling bias and minimal beta-arrestin recruitment, which is designed to limit receptor endocytosis and internal desensitization to sustain high-potency target engagement, suppress appetite, and maximize glucose-dependent insulin release. Furthermore, enicepatide was acquired by Roche as the lead asset in its $2.7 billion acquisition of Carmot Therapeutics.

In a Phase 3 randomized, active- and placebo-controlled study evaluating adults with obesity or overweight (BMI ≥27 kg/m²) and comorbid type 2 diabetes, Roche’s enicepatide met its dual primary endpoints, achieving a mean body weight reduction of -15.5% at Week 24 and a mean HbA1c reduction of -2.65% from baseline. The weight loss was non-plateauing and demonstrated a rapid trajectory compared to historical tirzepatide (Zepbound) benchmarks in diabetic cohorts (-14.7% at Week 72), while glycemic control enabled a high proportion of patients to reach target HbA1c (< 6.5%) or achieve normoglycemia (< 5.7%). Enicepatide exhibited a safety profile consistent with the incretin class, characterized predominantly by mild-to-moderate, transient gastrointestinal adverse events during dose titration and low treatment-emergent discontinuation rates. By addressing the delayed weight-loss kinetics typical in T2D populations, delivering deep dual glycemic and weight control, and establishing a highly competitive efficacy profile, enicepatide positions itself as a potential best-in-class challenger to established dual agonists like tirzepatide.

Roche is advancing two additional Phase 3 studies in its global ENITH program: ENITH-1 (evaluating chronic weight management in adults with obesity/overweight without diabetes) and ENITH-2 (evaluating broader long-term metabolic outcomes in T2D populations). Roche plans to initiate a dedicated Phase 3 Cardiovascular Outcomes Trial (CVOT) in the first half of 2027 to evaluate long-term major adverse cardiovascular events (MACE) reduction. The company is preparing to evaluate higher-dose cohorts and explore combination regimens pairing enicepatide with secondary metabolic assets (such as anti-myostatin agents) to optimize fat-to-lean mass loss ratios.

Sources: Roche press release

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Kyverna - Miv-cel (CD19 CAR-T) / Phase 2 (SPS)

On September 24, 2026, Kyverna Therapeutics reported positive 12-month Phase 2 results from its pivotal KYSA-8 trial evaluating miv-cel (mivocabtagene autoleucel / KYV-101), an autologous CD19-directed CAR-T cell therapy, in adult patients with treatment-refractory Stiff Person Syndrome (SPS).

Stiff Person Syndrome (SPS) is a rare, progressive neuroautoimmune disorder wherein autoantibodies (autoAbs), most commonly targeting glutamic acid decarboxylase (GAD65), disrupt central GABAergic inhibitory neurotransmission, triggering continuous motor neuron overactivity, severe muscle rigidity, and debilitating spasms. Standard care combines GABA-enhancing agents for symptom control with non-curative immunotherapies (such as IVIG, plasma exchange, or rituximab), leaving high unmet needs for refractory disease. Kyverna’s miv-cel is designed to addresses this underlying pathology as an autologous, fully human CD19-directed CAR T-cell therapy with a modified CD28 costimulatory domain. By targeting CD19-expressing B-cell lineages, a single dose of miv-cel selectively clears autoreactive B-cell clones driving anti-GAD65 production, enabling the host immune system to repopulate with naive, non-autoreactive B cells. This targeted depletion aims to eliminate the root driver of pathogenic autoantibody synthesis to reset long-term self-tolerance, offering a disease-modifying alternative to lifelong immunosuppression while limiting excessive systemic inflammatory toxicity.

In the open-label Phase 2 KYSA-8 trial (N = 26) evaluating miv-cel in adults with severe, treatment-refractory Stiff Person Syndrome (SPS), a single dose demonstrated deep and durable functional gains, achieving a 46% median improvement in walking speed on the Timed 25-Foot Walk test at Week 16 that extended to 49% at 12 months (p < 0.0001). Demonstrating sustained disease modification, 95% of initial responders maintained their benefit at 12 months, 67% of patients previously requiring mobility aids ambulated unassisted, and 92% remained completely off chronic immunomodulatory therapies. Safety was favorable, with zero high-grade cytokine release syndrome (CRS), ICANS, or immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) events, limiting high-grade toxicities to transient, post-lymphodepletion cytopenias. By pairing robust 12-month mobility recovery and high rates of immunotherapy independence with a clean safety profile devoid of severe inflammatory toxicities, miv-cel provides pivotal proof-of-concept for CAR-T-induced remissions in the autoimmune neurology condition.

Kyverna plans to finalize the remaining modules of its rolling BLA for SPS in the fourth quarter of 2026, requesting Priority Review under its RMAT designation. Kyverna is leveraging these data to accelerate enrollment in its Phase 3 portion of the KYSA-6 trial in generalized Myasthenia Gravis (gMG), with enrollment completion projected for mid-2027. Kyverna is advancing commercial readiness activities, including commercial site activation and manufacturing agreements, ahead of a potential US market launch in 2027.

Sources: Kyverna press release, Kyverna slide deck

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Oruka - ORKA-001 (IL-23p19 mAb HLE) / Phase 2 (plaque psoriasis)

On September 23, 2026, Oruka Therapeutics reported positive Phase 2 topline data for ORKA-001, an investigational half-life extended (HLE) monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in adult patients with moderate-to-severe plaque psoriasis. The trial achieved its primary and key secondary endpoints, showing high rates of skin clearance that deepened over time following an initial loading regimen.

Plaque psoriasis is a chronic, immune-mediated inflammatory skin disorder driven by dysregulated crosstalk along the IL-23/IL-17 cytokine axis, where dendritic cell-derived IL-23 stimulates pathogenic Th17 cells to secrete pro-inflammatory cytokines that trigger rapid epidermal hyperproliferation, impaired keratinocyte differentiation, and dermal leukocyte infiltration. While mild-to-moderate disease is managed with topical agents, moderate-to-severe plaque psoriasis requires systemic intervention, where modern standards of care prioritize targeted biologics, particularly IL-23 and IL-17 inhibitors, over oral immunosuppressants or phototherapy. Oruka’s ORKA-001 is designed to directly target this pathogenic cascade as a fully human IgG1 monoclonal antibody that selectively binds the p19 subunit of IL-23, neutralizing upstream Th17 activation without impairing IL-12-mediated protective Type 1 immunity. Differentiated by YTE/LS Fc-domain modifications that enhance FcRn-mediated recycling, ORKA-001 achieves an extended terminal elimination half-life of 70 to 90 days (three to four times longer than first-generation IL-23 inhibitors) enabling sustained inflammatory suppression to support infrequent, once- or twice-yearly maintenance dosing.

In a Phase 2 randomized, double-blind, placebo-controlled trial evaluating ORKA-001 in adults with moderate-to-severe plaque psoriasis, treatment demonstrated deepening efficacy over time, with complete skin clearance (PASI 100 / PGA 0) rising from 63.5% at Week 16 to 71.4% at Week 28, while over 85% of patients reached near-complete clearance (PASI 90). Pharmacokinetic data confirmed an extended half-life capable of supporting once- or twice-yearly maintenance dosing while maintaining therapeutic trough levels, and the safety profile was favorable and class-consistent, marked by mild-to-moderate infections and transient injection-site reactions with no novel safety signals.

Oruka plans to advance ORKA-001 into pivotal Phase 3 registration studies in moderate-to-severe plaque psoriasis, evaluating once- and twice-yearly maintenance dosing regimens. Complete 52-week data from the Phase 2 trial will be analyzed to assess multi-dose durability and anti-drug antibody (ADA) profiles over extended intervals. Oruka is preparing to initiate Phase 2 studies evaluating ORKA-001 in additional IL-23-mediated inflammatory conditions, including psoriatic arthritis and inflammatory bowel disease (ulcerative colitis and Crohn’s disease).

Sources: Oruka press release, Oruk slide deck

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Vertex - Inaxaplin (APOL1 inhibitor) / Phase 2b (AMPKD)

On September 22, 2026, Vertex Pharmaceuticals announced positive Phase 2b topline results from the AMPLIFIED study evaluating inaxaplin (VX-147), a first-in-class, oral small-molecule APOL1 inhibitor, in expanded populations of patients with APOL1-mediated kidney disease (AMKD).

APOL1-mediated kidney disease (AMKD) is a genetically driven, rapidly progressive form of chronic kidney disease in individuals harboring two high-risk APOL1 variants (G1 or G2), where inflammatory stimuli upregulate toxic APOL1 variant proteins that form cation-permeable pores in podocyte membranes, causing cellular swelling, detachment, glomerular filtration barrier collapse, and progressive glomerulosclerosis. Since traditional standard of care is limited to non-specific, supportive therapies such as RAAS and SGLT2 inhibitors to manage intraglomerular pressure and proteinuria, significant unmet need remains for targeted, disease-modifying interventions. Vertex’s inaxaplin is designed to directly address this root genetic etiology as a selective, oral, small-molecule inhibitor that binds to toxic APOL1 variant proteins and prevents pathogenic pore formation. By preserving podocyte structural integrity and protecting the filtration barrier, inaxaplin stops pathological proteinuria and halts downstream nephron loss to offer a first-in-class targeted strategy for AMKD.

In the Phase 2b open-label AMPLIFIED study (N = 41) evaluating oral inaxaplin (45 mg once daily) on top of optimized standard-of-care chronic kidney disease therapies in adults with APOL1-mediated kidney disease (AMKD), inaxaplin achieved a statistically significant 42.7% mean reduction in UACR at Week 13 (with a parallel 44.7% reduction in UPCR) in the modest proteinuria cohort (Cohort 1, n = 23), matching the magnitude of benefit previously observed in severe AMKD/FSGS populations (-43.4%), while driving a 17.3% UACR reduction in the comorbid type 2 diabetes cohort (Cohort 2, n = 18). Treatment was well tolerated across cohorts with no drug-related serious adverse events, mild-to-moderate AEs (most commonly headache at 7.3%), and isolated, transient transaminase elevations that resolved without clinical sequelae. By demonstrating significant additive proteinuria reductions on top of background RAAS and SGLT2 inhibitor therapy in earlier-stage disease, these data validate targeted APOL1 inhibition as a potential disease-modifying mechanism and expand inaxaplin’s therapeutic utility into broader AMKD populations to halt nephron destruction prior to irreversible scarring.

Vertex has completed enrollment in the ongoing Phase 2/3 AMPLITUDE trial evaluating inaxaplin in a larger, registrational cohort of AMKD patients. A pre-planned interim analysis from the AMPLITUDE trial is on track for early 2027. If positive, Vertex plans to submit these data to support potential accelerated approval with the FDA. Vertex intends to discuss the AMPLIFIED dataset with regulatory authorities to explore pathways for expanding inaxaplin’s label to cover broader AMKD populations, including those with modest proteinuria and diabetic comorbidities.

Sources: Vertex press release

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Alkermes - ALKS 7290 (selective OX2 agonist) / Phase 1b (ADHD)

On September 21, 2026, Alkermes announced positive Phase 1b topline results for ALKS 7290, a novel, potent, and highly selective oral orexin 2 receptor (OX2R) agonist being developed for the treatment of attention-deficit/hyperactivity disorder (ADHD).

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder driven by prefronto-striatal network dysfunction and deficient dopamine and norepinephrine signaling, which impairs executive function, working memory, and impulse control. While standard management relies on multimodal strategies led by CNS stimulants (e.g., methylphenidate, amphetamines) or non-stimulant alternatives like atomoxetine and alpha-2 agonists, existing stimulant options carry notable drawbacks, including cardiovascular strain, insomnia, and abuse potential. Alkermes’ ALKS 7290 is designed to directly address these limitations as a selective small-molecule orexin 2 receptor (OX2R) agonist that stimulates hypothalamic projections to the prefrontal cortex, enhancing executive function and sustained attention while modulating subcortical reward circuits. By promoting cognitive control without inducing massive, non-selective dopamine surges in the nucleus accumbens, ALKS 7290 provides a potential first-in-class non-stimulant mechanism designed to deliver stimulant-like efficacy without the associated cardiovascular side effects, sleep disruption, or high abuse liability.

In a Phase 1b randomized, double-blind, placebo-controlled multiple-ascending-dose study evaluating ALKS 7290 in adults with ADHD, treatment achieved a statistically significant 19.0-point mean reduction from baseline in the AISRS total score at Day 14 (p < 0.001), demonstrating rapid onset by Day 3 and consistent gains across both inattention and hyperactivity/impulsivity subscales. Dosing was well tolerated with no serious adverse events, dose-limiting toxicities, treatment-emergent insomnia, or cardiovascular signal relative to placebo, with adverse events limited to mild, transient effects like headache and decreased appetite. Achieving a 19-point AISRS reduction in two weeks establishes a disruptive non-stimulant profile with efficacy rivaling Schedule II stimulants, while its favorable sleep and cardiovascular safety profile and validation of selective OX2R agonism beyond hypersomnia support its advancement into Phase 2 as a novel mechanism for cognitive and neuropsychiatric disorders.

ALKS 7290 is currently being evaluated in a broader Phase 2 clinical trial designed to further explore dose-response relationships, long-term efficacy, and durability over extended treatment periods in adults with ADHD. Alkermes is preparing preclinical and clinical protocols to support future development in pediatric and adolescent ADHD populations following the completion of adult Phase 2 dose-finding studies. Data from the completed Phase 1b and ongoing Phase 2 studies will form the basis for upcoming end-of-Phase 2 meetings with global regulatory authorities to define pivotal Phase 3 registration trial designs.

Sources: Alkermes press release

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J&J - Caplyta (5HT2A x D2 dual inhibitor) / Phase 3 (bipolar I)

On September 21, 2026, Johnson & Johnson announced positive topline results from its pivotal Phase 3 clinical trial evaluating Caplyta (lumateperone), a central nervous system agent with dual 5-HT2A and D2 receptor activity, for the treatment of acute manic and mixed episodes associated with bipolar I disorder.

Bipolar I disorder is a chronic, severe neuropsychiatric condition characterized by recurrent manic and depressive episodes driven by monoaminergic dysregulation, prefrontal-limbic circuit imbalances, and impaired intracellular signaling. While acute stabilization and long-term maintenance rely on second-generation antipsychotics, mood-stabilizing anticonvulsants, and lithium, existing agents often carry substantial metabolic and motor liabilities. Caplyta directly targets these underlying neural circuits as a multi-target psychotropic agent that selectively modulates central serotonergic, dopaminergic, and glutamatergic pathways. By combining potent 5-HT2A antagonism with selective postsynaptic D2 receptor modulation, SERT inhibition, and downstream prefrontal NMDA receptor enhancement, Caplyta regulates mood and executive function across both manic and depressive poles while mitigating extrapyramidal and metabolic adverse effects.

In a Phase 3 randomized, double-blind, placebo-controlled multicenter trial evaluating Caplyta (42 mg once daily monotherapy) in adults with acute manic or mixed episodes associated with bipolar I disorder, Caplyta achieved a statistically significant 0.69-point reduction in YMRS total score versus placebo at Week 3 (p<0.0001), with rapid onset of action and concordant improvements across CGI-BP and responder rates. Dosing was well tolerated with low rates of extrapyramidal symptoms, akathisia, and somnolence comparable to placebo, alongside a clean cardiometabolic profile with no meaningful changes in weight, glucose, or lipid parameters. By adding acute anti-manic efficacy to its established bipolar depression profile, Caplyta establishes spectrum-wide monotherapy coverage with a single, non-titrated 42 mg daily dose, avoiding the significant metabolic and motor side effects typical of second-generation antipsychotics to streamline clinical management across both poles of bipolar I disorder.

Johnson & Johnson plans to submit a supplemental sNDA to the US FDA seeking regulatory approval for Caplyta in the treatment of acute manic and mixed episodes associated with bipolar I disorder. Extended open-label and maintenance-phase data from ongoing trials will be analyzed to establish long-term relapse prevention, safety, and durability in bipolar I disorder. Pending regulatory approval, Caplyta will be integrated into expanded commercial education initiatives targeting psychiatrists and mental health providers managing complex bipolar spectrum disorders.

Sources: J&J press release

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Descriptive data releases without numerical data

• Merck - Remigromig (tri-specific Wnt agonist) / Phase 2b/3 (DME): P2b/3 success (DME): Merck presented Phase 2b/3 study results demonstrating that its novel tri-specific Wnt agonist, remigromig, met its primary endpoint by achieving 52-week best-corrected visual acuity (BCVA) non-inferiority compared to ranibizumab (Lucentis) in patients with diabetic macular edema (DME). Shared at the American Academy of Ophthalmology (AAO) annual meeting in New Orleans, these data mark the first and only new mechanism of action in 20 years to demonstrate Phase 3 non-inferiority against standard-of-care anti-VEGF therapy in retinal disease. By validating target engagement of the Wnt signaling pathway to stabilize the blood-retinal barrier, remigromig positions itself as a potential first-in-class, non-anti-VEGF biological option for DME management. Sources: Merck press release

• Arcturus - ARCT-810 (OTC mRNA) / Phase 2 (OTC deficiency): Arcturus Therapeutics reported positive interim Phase 2 data evaluating its investigational mRNA therapy, ARCT-810, in patients with ornithine transcarbamylase (OTC) deficiency, demonstrating that repeat intravenous dosing was generally safe and well tolerated with no drug-related serious adverse events. Crucially, treatment successfully reduced and/or maintained first-morning fasting ammonia levels within the normal range (even during periods of increased dietary protein intake) while simultaneously lowering plasma glutamine (achieving mean normal values in the 0.5 mg/kg cohort). By providing functional enzyme replacement to restore endogenous urea cycle activity and maintain metabolic control without hyperammonemic crises, these biomarker findings validate Arcturus’ liver-targeted mRNA platform in urea cycle disorders, supporting plans to integrate its higher-potency, next-generation LUNAR 2.0 candidate (ARCT-2601) into the ongoing Phase 2 study by year-end. Sources: Arcturus press release

• Roche - Sefaxersen (Factor B ASO) / Phase 3 (IgAN): Roche announced positive Phase 3 topline results for sefaxersen, an investigational antisense oligonucleotide (ASO) targeting Factor B, in patients with IgA nephropathy (IgAN), demonstrating that the trial successfully met its primary efficacy endpoint by achieving a statistically significant reduction in urine protein-to-creatinine ratio (UPCR) relative to control. By selectively suppressing the alternative complement pathway at the level of Factor B synthesis, sefaxersen directly mitigates complement-mediated glomerular inflammation and podocyte damage in the kidney. These clinical trial data, presented at a medical conference, validate systemic Factor B inhibition as a potent disease-modifying strategy to control pathological proteinuria and support regulatory filings for sefaxersen as a potential first-in-class ASO therapy for IgAN. Sources: Roche press release

• Amgen - Dazodalibep (CD40L inhibitor) / Phase 3 (Sjögren’s disease): Amgen announced positive topline results from the Phase 3 OASIZ 301 trial evaluating dazodalibep, a potential first-in-class CD40 ligand (CD40L) antagonist fusion protein, in adult patients with Sjögren’s disease and moderate-to-severe systemic disease activity. The study successfully met its primary endpoint, demonstrating statistically significant and clinically meaningful reductions in systemic disease activity compared to placebo at Week 48 as measured by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), with significant improvements emerging as early as Week 4. Dazodalibep was well tolerated, showing a low rate of treatment-discontinuation adverse events, predominantly mild-to-moderate side effects (most commonly nasopharyngitis, urinary tract infections, hypertension, and infusion-related reactions), and no safety signals related to thromboembolic events or opportunistic infections. By directly disrupting costimulatory interactions between T cells, B cells, and antigen-presenting cells to suppress pathogenic autoantibody production and systemic inflammation, dazodalibep validates CD40L inhibition as a disease-modifying mechanism in Sjögren’s disease—a condition currently lacking approved systemic therapies—with full Phase 3 data slated for presentation at an upcoming medical conference while the companion OASIZ 303 Phase 3 trial completes in Q4 2026. Sources: Amgen press release

• Otsuka - Ulefnersen (FUS ASO) / Phase 3 (FUS-ALS): Otsuka and Ionis announced positive topline results from the Phase 3 FUSION trial (NCT04768972) evaluating ulefnersen, an intrathecal antisense oligonucleotide (ASO) targeting fused in sarcoma (FUS) pre-mRNA, in patients with FUS-mutated amyotrophic lateral sclerosis (FUS-ALS). The study met its primary endpoint (p=0.0005), demonstrating a statistically significant, disease-modifying benefit over placebo at 72 weeks using a joint-rank analysis combining functional performance on the ALS Functional Rating Scale-Revised (ALSFRS-R) with survival measures (time to death or permanent ventilation) and time to rescue therapy. These clinical gains were reinforced by statistically significant improvements in key secondary endpoints, including reductions in serum neurofilament light chain (NfL) levels and delayed time to clinical progression events. Intrathecal ulefnersen was well tolerated, with a safety profile consisting mostly of mild-to-moderate adverse events. As the first placebo-controlled Phase 3 trial to demonstrate a significant clinical and biomarker benefit in FUS-ALS—a rapidly progressive, rare genetic form of ALS often affecting younger populations—these data validate direct FUS protein suppression and support upcoming regulatory interactions to explore expedited filing pathways. Sources: Otsuka press release

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Introduction

On September 21, 2026, Telix Pharmaceuticals Limited announced a strategic agreement to lead a merger with ITM Isotope Technologies Munich SE for an upfront consideration of $1.65 billion on a cash-free/debt-free basis plus up to $700 million upon achievement of regulatory approvals and commercial sales milestones for ITM-11, for a total deal value of up to $2.35 billion (Telix press release, ITM Isotope press release, Telix merger presentation). This merger centers on ITM’s differentiated radioisotope manufacturing platform and fuses two radiopharmaceutical pipelines:

In this article, we briefly define radiopharmaceuticals, explain what makes these medicines so difficult to manufacture, dive into the corporate histories of ITM Isotope and Telix, and explore the global reach of the combined entity’s supply chain.

Medicinal Glow Up

Radioisotopes kill cancer by delivering targeted ionizing radiation directly to tumor cells, damaging their cellular machinery and causing cell death. As the radioisotope decays, it releases high-energy particles (such as alpha or beta particles). These particles strike the DNA strands inside cancer cells, causing double-strand breaks that render the cancer cells unable to repair themselves, replicate, or survive. A radiopharmaceutical is a specialized medicinal product that contains a radioactive isotope (radionuclide) bound to a targeting agent (such as a molecule, antibody, or peptide) designed to target specific cells or tissues in the body. By binding the radioisotope to a targeting vector that attaches preferentially to cancer cell receptors, high doses of radiation accumulate inside the tumor while minimizing damage to surrounding healthy tissue. The emitted radiation can travel short distances beyond the single cell to which the radioisotope is bound, destroying nearby neighboring cancer cells within the tumor microenvironment, even if those adjacent cells lack the specific target receptor. Unlike traditional pharmaceuticals that rely purely on chemical mechanisms, radiopharmaceuticals harness radiation for two main clinical uses: diagnostics and therapeutics.

Radioactive diagnostic agents typically use a radioisotope emitting low-energy gamma rays or positrons (such as Fluorine-18, Technetium-99m, or Gallium-68) and are administered at micro-doses. The agent is designed to selectively travel to specific tissues or disease sites (such as tumors or cardiac tissue). Advanced scanners, like PET (Positron Emission Tomography) or SPECT (Single-Photon Emission Computed Tomography), detect the emitted radiation to build detailed 3D images of organ function, tissue perfusion, or receptor expression. For example, ¹⁸F-FDG (fluorodeoxyglucose) is used to measure metabolic activity in cancer cells, thereby identifying both the primary cancer site as well as distant metastasis in separate regions throughout the body (commonly found in the brain, bones, liver, lymph nodes, etc.).

Meanwhile, radioactive therapeutics typically use a radioisotope emitting high-energy radiation (such as beta or alpha particles) that is attached to a targeting vector. The targeting vector locks onto cell-surface receptors unique to cancer cells (e.g., PSMA in prostate cancer or SSTR2 in neuroendocrine tumors). Once bound, the radioisotope releases targeted radiation that causes double-stranded DNA breaks, killing the cancer cells while minimizing damage to surrounding healthy tissue. For example, Pluvicto (lutetium Lu 177 vipivotide tetraxetan) works by delivering localized, high-energy beta radiation (emitted by the lutetium 177 isotope) directly into prostate cancer cells (targeted with PSMA binder). Upon binding to the cell-surface PSMA receptor, the complex undergoes receptor-mediated endocytosis. The prostate cancer cell internalizes the entire Pluvicto molecule, pulling the radioactive payload into the intracellular space. Since the emission range (~2 mm) spans multiple cell diameters, the radiation also destroys adjacent tumor cells that may have lower or heterogeneous PSMA expression, a phenomenon known as the bystander or crossfire effect.

Many radiopharmaceuticals belong to a paradigm called theranostics, which combine radioactive therapeutics and diagnostics. Physicians can use a diagnostic radiopharmaceutical to image and confirm that a patient’s tumor expresses a specific receptor, then swap out the imaging isotope for a therapeutic isotope using the exact same targeting molecule to treat the disease.

These agents are certainly clinically useful, but they aren’t without their challenges. Radiopharmaceutical manufacturing combines the strict sterility standards of injectable biopharmaceuticals with the temperamental physics of radioactive decay and high-precision nuclear engineering, making them particularly difficult to manufacture. Injectable therapies require Grade A cleanroom conditions to prevent bacterial contamination. However, researchers developing radiopharmaceuticals cannot manually handle the product due to radiation exposure risks. Synthesis, filtering, and vial filling must occur behind thick lead glass inside automated, heavily shielded containment chambers known as hot cells using robotic systems. Maintaining cleanroom sterile airflow while operating heavy mechanical shielding and remote automated units presents significant engineering challenges. Facilities must simultaneously satisfy traditional drug regulators (such as the FDA or EMA for cGMP, sterile processing, and drug stability) and nuclear safety regulators (such as the NRC or equivalent atomic energy agencies for radioactive material handling, worker protection, and hazardous waste disposal)

Then there’s the shelf-life problem. Unlike traditional drugs that can sit in a warehouse for months or years, radioisotopes decay constantly. Standard diagnostic isotopes (like Fluorine-18) have half-lives of around 110 minutes (a little less than 2 hours), while therapeutic isotopes (like Lutetium-177 or Actinium-225) have half-lives ranging from a few days to under two weeks. As a result, batches cannot be stockpiled. As the radioisotope decays, it emits high-energy alpha or beta radiation that can break chemical bonds within its own carrying molecule (a process called radiolysis). Formulators must carefully engineer protective quenching agents (like ascorbic acid) to prevent the active drug molecule from degrading before administration. Every single dose is manufactured, released, shipped, and injected according to a precise schedule. A single flight delay or logistics bottleneck means the drug decays into an ineffective dose before it ever reaches the patient. This also impacts Quality Control (QC). In standard drug manufacturing, full Quality Control (including a 14-day sterility test) is completed before a batch is released to customers. Since radiopharmaceuticals decay in hours or days, doses often must be shipped and administered before traditional 14-day sterility test incubation results are completed. Manufacturers rely on validated rapid surrogate assays (like rapid endotoxin testing and high-performance liquid chromatography for radiochemical purity) and strict process validation, creating zero margin for error.

Lastly, there’s the challenge of raw material supply. Radiopharmaceuticals require rare target materials and access to specialized nuclear infrastructure, such as nuclear research reactors or particle accelerators (cyclotrons). A sudden maintenance shutdown at one of the world’s few medical nuclear reactors or cyclotrons can instantly freeze the global supply of critical precursor isotopes. Radioactive isotope supply chains are peppered with regulatory hurdles, compounding its complexity. In the United States, the NRC (Nuclear Regulatory Commission) regulates the possession, transfer, use, and security of radioactive target materials and parent isotopes through 10 CFR Part 30 (Byproduct Material Licenses) and 10 CFR Part 35 (Medical Use). Suppliers cannot ship radioactive raw materials without verifying that the recipient facility holds a specific, active NRC or state materials license. The import and export of medical isotopes and radioactive precursors are controlled under 10 CFR Part 110. Any shipment crossing U.S. borders requires export/import authorization, specialized customs clearance, and adherence to physical protection standards, which can create international supply bottlenecks. This is a substantial regulatory barrier for radiopharmaceuticals developed in the U.S. because the isotope supply chain relies heavily on international research reactors (e.g., in Europe, Canada, and South Africa) for major therapeutic and diagnostic radioisotopes (such as ¹⁷⁷Lu precursor enrichment materials or ⁹⁹Mo).

Altogether, one does not simply develop radiopharmacuticals. The barriers to entry are so high that companies in the space practically need to be anointed by the relevant international & domestic regulatory agencies in order to have the freedom to operate. Yet, that didn’t stop a dedicated cohort of drug hunters from trying.

Going Nuclear

In 2004, nuclear energy specialist Oliver Buck set out in Munich, Germany, with a mission: harness precision nuclear technology to solve a fundamental problem in targeted cancer care. At the time, radiopharmaceuticals held vast promise, but the industry was severely constrained by the quality and availability of medical radioisotopes.

ITM’s first breakthrough came in the form of no-carrier-added (n.c.a.) Lutetium-177 (¹⁷⁷Lu). Traditional production methods resulted in carrier-added isotopes, which contained long-lived radioactive impurities (like Lu-177m) and unwanted stable lutetium atoms that competed for receptor binding sites on cancer cells. ITM engineered a proprietary process to manufacture pure, high-specific-activity n.c.a. Lutetium-177. By eliminating long-lived radioactive waste and maximizing targeted efficiency, ITM established the supply backbone for the entire modern radiopharmaceutical sector. Biotech firms and academic centers around the globe began relying on ITM as their primary engine for raw medical isotopes. At the heart of ITM’s manufacturing strategy is the NOVA facility in Neufahrn near Munich, Germany. Spanning over 7,000 square meters, NOVA represents the world’s largest production site dedicated specifically to GMP-grade no-carrier-added Lutetium-177 (¹⁷⁷Lu).

As the 2010s progressed, ITM leadership realized that controlling the purest radioisotope supply chain gave them an extraordinary vantage point. Rather than remaining solely an upstream vendor, ITM made a bold strategic expansion, vertically integrating into proprietary drug discovery. The company began attaching its high-purity radioisotopes to specialized targeting molecules. These efforts were led by ITM-11 (¹⁷⁷Lu-edotreotide), a radiopharmaceutical targeted at the somatostatin receptor (SSTR) designed to treat gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Early phase 2 academic studies demonstrated that this high-purity composition resulted in superior tumor uptake, reduced renal toxicity, and extended progression-free survival (PFS). These early signals earned ITM-11 both Orphan Drug Designation and Fast Track Designation from the FDA, setting the stage for the global Phase 3 COMPETE trial. Rather than comparing ITM-11 against placebo or standard somatostatin analogues alone, ITM pitted its radiopharmaceutical directly against everolimus, a widely used targeted oral mTOR inhibitor for progressive, inoperable Grade 1 and Grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

On March 6, 2025, ITM reported topline results from the Phase 3 COMPETE trial at the 22nd Annual European Neuroendocrine Tumor Society (ENETS) Conference. COMPETE met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival. ITM-11 extended central median PFS to 23.9 months compared to 14.1 months for everolimus (HR 0.67; p = 0.022). Secondary endpoints reinforced the efficacy gap: ITM-11 achieved an Objective Response Rate (ORR) of 21.9% versus just 4.2% for everolimus. Furthermore, ITM-11 demonstrated a superior safety and tolerability profile, with significantly lower treatment discontinuation rates due to drug-related toxicity (1.8% ITM-11 vs. 15.2% everolimus). COMPETE was the first large Phase 3 trial to integrate prospective 3D SPECT/CT dosimetry, confirming that ITM-11 delivered maximum radiation doses directly to tumor sites while keeping absorbed doses to critical organs (like the kidneys and bone marrow) well below safety limits.

Building on momentum from COMPETE, ITM initiated the global Phase 3 COMPOSE trial (NCT04919226). Recognizing that patients with more aggressive, higher-grade tumors had limited choices, COMPOSE was designed to evaluate ITM-11 in patients with well-differentiated, aggressive Grade 2 and Grade 3 SSTR-positive GEP-NETs. In COMPOSE, ITM-11 is being evaluated as a first- or second-line treatment against physician’s choice standard chemotherapy (such as CAPTEM or FOLFOX) or everolimus, expanding PRRT’s footprint into higher-risk oncology settings.

With robust efficacy, safety, and dosimetry data from the COMPETE trial in hand, ITM submitted a New Drug Application (NDA) for ITM-11 to the FDA. In August 2026, the FDA issued a Complete Response Letter (CRL). According to company disclosures, the FDA raised no concerns regarding the clinical safety or efficacy data, nor did it request additional clinical trials. Instead, the CRL cited specific Chemistry, Manufacturing, and Controls (CMC) and inspection findings at a third-party commercial manufacturing facility. Nevertheless, ITM intends to resubmit the NDA to complete FDA review, although timing remains subject to remediation and agency interaction.

Ionizing Aussies

Speaking of Telix, they also played a significant role in nucleating radiopharmaceuticals. Founded in Melbourne, Australia, in November 2015 by Dr. Christian Behrenbruch and Dr. Andreas Kluge, Telix Pharmaceuticals was built on a bold premise: that theranostics, the integration of targeted molecular imaging with precision radiation therapy, would become a foundational pillar of modern oncology.

The strategy focused on pairing specific targeting vectors (such as small molecules or monoclonal antibodies) with short-lived radioisotopes to both “see and treat” cancer cells. In November 2017, Telix listed on the Australian Securities Exchange (ASX: TLX), raising A$50 million. Rather than focusing solely on long-shot therapeutic clinical trials, Telix prioritized rapid-to-market diagnostic imaging agents to build early commercial infrastructure and fund its broader R&D pipeline. Their strategy bore fruit in late 2021, when the FDA approved Illuccix (a Gallium-68 PSMA-11 kit) for prostate cancer imaging. Launched commercially in early 2022, Illuccix quickly established a significant share of the U.S. prostate cancer imaging market, transforming Telix from a pre-revenue company to a commercial-stage company generating tens of millions of dollars annually. This commercial execution provided a rare self-sustaining cash flow engine in the biotech space, enabling Telix to scale without relying heavily on dilutive capital raises.

By 2026, Telix further solidified its position at the center of the radiopharmaceutical renaissance. In April 2026, Telix entered into a major multi-billion-dollar 50/50 cost/profit-sharing partnership with Regeneron Pharmaceuticals to combine Regeneron’s antibody discovery platform with Telix’s radiomanufacturing capabilities across solid tumor programs. Beyond prostate cancer, Telix broadened its diagnostic portfolio with FDA approvals for imaging agents like Gozellix (next-gen PSMA) and Pixclara (glioma/brain cancer imaging), while expanding clinical trials across renal and bone cancers. Their latest move, as of the time of this publication, is an agreement to merge with ITM Isotope Technologies Munich SE, uniting Telix’s global radiopharmacy distribution network and commercial scale with ITM’s production capabilities and late-stage therapeutic candidates.

Mutually Assured Manufacturing

The Telix-ITM tie-up does far beyond the typical pipeline integration activities seen in traditional biotech M&A. The combination of Telix Pharmaceuticals and ITM Isotope Technologies Munich SE creates an end-to-end vertically integrated radiopharmaceutical entity with global reach. Their individual manufacturing and distribution infrastructures operate at opposite ends of the radiopharmaceutical value chain, making their merger structurally complementary.

Starting in 2024, Telix executed a rapid series of vertical integration moves to better control its distribution channels for approved radiopharm diagnostics. They acquired ARTMS Inc. for $57.5 million upfront to secure proprietary cyclotron-based isotope production technology. The in-housed QUANTM Irradiation System (QIS) enables hospital or regional cyclotrons to produce high-demand diagnostic and therapeutic radiometals locally, reducing dependence on centralized nuclear reactors. Then, in early 2025, Telix completed the landmark acquisition of RLS (USA) Inc., securing the largest independent Joint Commission-accredited network of 31 radiopharmacies in major U.S. metropolitan areas with over 100,000 sq. ft. of expansion space. This gave Telix localized “last-mile” dose-compounding, packaging, and courier delivery capabilities across the United States.

As for ITM, their territory in the radioisotope manufacturing spans far beyond the world’s largest production site for GMP-grade no-carrier-added Lutetium-177 (¹⁷⁷Lu) in Germany. Since radiopharmaceutical production depends on access to nuclear research reactors, ITM has sought to establish a global, multi-continent network to secure raw isotope precursor material. ITM has partnered with Bruce Power, Isogen, and the Saugeen Ojibway Nation to install automated Isotope Production Systems (IPS) directly inside commercial nuclear power reactors in Ontario, Canada. This partnership unlocked commercial-scale continuous irradiation capacities for ¹⁷⁷Lu. To manufacture n.c.a. ¹⁷⁷Lu, ITM holds proprietary, highly enriched stockpiles of Ytterbium-176 (¹⁷⁶Yb) and utilizes a closed-loop recycling process to safeguard its supply against global geopolitical or supply-chain shocks.

To lead the transition toward alpha-particle and Auger-electron therapies, ITM expanded beyond beta-emitters. Partnering with Canadian Nuclear Laboratories (CNL), ITM formed Actineer to scale production of Actinium-225 (²²⁵Ac), a highly coveted short-supply alpha isotope, using proton cyclotrons on Radium-226 targets. Furthermore, ITM integrated custom processing lines for ¹⁶¹Tb, establishing the commercial availability of this emerging Auger-emitting isotope for targeted micro-metastatic therapies.

As we mentioned before, therapeutic isotopes decay constantly, which limits the shelf-life of radioactive diagnostics & therapeutics. To solve this, ITM created a seamless distribution network capable of delivering doses to clinics across over 65 countries. ITM guarantees priority delivery within 24-48 hours across Europe and North America, and within 72 hours globally. ITM established its North American headquarters in Princeton, New Jersey, positioning local commercial, regulatory, and technical operations directly adjacent to major East Coast logistics hubs.

Before the merger, Telix relied on external isotope vendors to supply raw materials for its diagnostic and therapeutic pipeline. ITM was primarily a bulk producer that supplied isotopes to third parties. If successfully integrated, the combined entity could control nearly every stage of the lifecycle: target enrichment, reactor/cyclotron irradiation, chemical purification, cGMP radiolabeling, and final delivery to hospital nuclear medicine departments. With Telix expanding its late-stage therapeutic clinical pipeline and acquiring ITM’s late-stage candidate ITM-11 (¹⁷⁷Lu-edotreotide), having direct control over ITM’s NOVA site guarantees an uninterrupted, internal supply of high-grade, no-carrier-added Lutetium-177. This could mitigate third-party isotope supply risks during commercial scale-up. Finally, the merged company combines revenue streams with a diversified product mix.

Conclusion

The $2.35 billion merger between Telix and ITM Isotope marks a defining moment in the maturation of targeted radionuclide therapies. In an industry where a drug’s commercial viability lives and dies on nuclear physics and supply chain logistics, controlling the full stack, from reactor isotope enrichment at NOVA to last-mile compounding across RLS radiopharmacies, creates an unprecedented competitive moat. While near-term execution will hinges on remediating ITM-11’s third-party manufacturing CRL and clearing regulatory hurdles, the broader strategic rationale is unmistakable: to build a vertically integrated radiopharmaceutical giant with unparalleled global scale. As alpha and Auger-emitting therapies transition from bench to bedside, Telix-ITM is uniquely positioned to set the pace for the future of radiation oncology.

Radiopharmaceutical Competitive Landscape

All charts reflect data current as of the specified date and may not include every drug development program, although we aimed to capture the vast majority. Please feel free to email me at biotechreadout@gmail.com with “CHARTS” in the subject line to share suggestions or request chart updates.

• Notable Acquisitions in Radiopharmaceuticals ⬇️

• Top Selling Medicines in Radiopharmaceuticals ⬇️

• Top 15 Targets in Radiopharmaceuticals ⬇️

• Radiopharmaceutical Pipeline of Strategic Acquirers ⬇️

Read more

Table of Contents

This week, we discuss:

• China Biotech

  • Financing Activity for China versus Rest of World ⬇️

  • China Posts 5-Year Plan for Biotech ⬇️

  • Endpoints Goes to D.C. to Talk China Biotech ⬇️

• Conferences

  • WCLC 2026, breakthroughs from the world’s largest lung cancer conference ⬇️

  • ESC 2026, breakthroughs and debates from Europe’s largest cardiology conference ⬇️

• Approvals

  • Scholar Rock - Isembyld (myostatin inhibitor) / Approved (SMA) ⬇️

• Clinical Trial Data

  • Vera - Trutakna (APRIL/BAFF inhibitor) / Phase 3 (IgAN) ⬇️

  • Definium - DT120 (LSD ODT) / Phase 3 (GAD) ⬇️

  • Roche - Lunsumio (CD20 x CD3 TCE) / Phase 3 (3L FL) ⬇️

  • Agomab - AGMB-447 (lung-restricted TGFβR1 inhibitor) / Phase 1 (IPF) ⬇️

China Biotech

Wondering why we discuss China Biotech every week? Tap here to learn more.

Financing Activity for China versus Rest of World

for the week ending September 18, 2026

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China Posts 5-Year Plan for Biotech

On September 18, 2026, Ministry of Industry and Information Technology (MIIT) along with nine other government departments published a roadmap outlining China’s strategy to transition its biopharmaceutical sector into an innovation-driven, high-value national pillar industry for the 2026–2030 period. Under this framework, the country aims to achieve significant industrial expansion, targeting over 3.5 trillion RMB (~$522 billion USD) in major enterprise revenue and driving the innovative drug sector at an annual growth rate exceeding 20%. To fuel this transition, the plan places heavy emphasis on scaling R&D capabilities, mandating that listed companies maintain at least a 10% average R&D intensity, with the ambitious goal of originating 25% of the world’s first-in-class (FIC) therapeutics. Key priority areas focus on pioneering “undruggable” targets, next-generation modalities like ADCs, mRNA, and cell and gene therapies, as well as advancing frontier technologies such as AI-driven drug discovery, brain-computer interfaces, organoids, and space-based manufacturing.

Beyond clinical innovation, the plan focuses on building a resilient, self-sustaining healthcare ecosystem while expanding global influence. It targets critical supply chain bottlenecks by scaling domestic manufacturing of high-end excipients, advanced equipment, and specialized software, while establishing standard frameworks for digital and green manufacturing. The strategy fosters regional industry hubs across the Beijing-Tianjin-Hebei, Yangtze River Delta, and Greater Bay Area regions, aiming to build 20 hundred-billion-RMB (~$300 billion USD) industrial parks and nurture 50 major enterprises generating over 10 billion RMB annually (~$1.5 billion USD). Concurrently, China seeks to deepen international integration by expanding its CRO/CDMO services, supporting multi-regional clinical trials for global market entries, and encouraging foreign investment within free trade zones to fast-track novel therapies locally. Supported by streamlined regulatory workflows, updated reimbursement models, and enhanced supply guarantees for essential and rare disease medicines, the initiative aims to establish China as a leading force in global healthcare innovation.

Sources: China/MIIT Five-Year Plan for Pharmaceutical Industry Development

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Endpoints Goes to D.C. to Talk China Biotech

Earlier this week, Endpoints News hosted a series of talks that I highly recommend watching in full:

1. Will Congress put a stop to China biotech deals? (link). This is an interview with Representative John Moolenaar, Chairman of the House Select Committee on China, discussing national security, U.S. investment in Chinese biotechnology, and regulatory oversight. Rep. Moolenaar co-introduced the Biotech Investment National Security Act (BINSA), aimed at establishing guardrails and restrictions on U.S. venture and institutional capital funding strategic Chinese biotech developments that could threaten U.S. national security or economic interests. This was very enlightening; he is an incredibly well-informed gentleman, so my guess is it’s going to be difficult for the pro-China cohort to talk him out of BINSA.

2. Can the FDA steer clinical trials back to the US? (link). This is an interview with FDA leaders Kareem McCale (Director of CBER) and Grace Graham (Deputy Commissioner for Policy, Legislation, and International Affairs). They discuss the launch of the expedited IND pilot program, U.S. clinical trial competitiveness as a top priority for HHS, evaluation of foreign data, and FDA inspection requirements.

3. Is secrecy the solution? (link). This is an interview with David Lee (CEO of Millora Therapeutics) and Patrick Malone (Partner at KDT Ventures). They discuss how U.S. biotechs are responding to rapid competition from China, specifically their elevated secrecy about targets & funding rounds to ward off competition from fast-moving China biotechs.

4. What do we really mean when we talk about biosecurity risk and China? (link). This is an interview with Ed Hughes (consultant, former FBI/IC), Caitlyn Fraser (National Security Commission on Emerging Biotechnologies), and Jennifer Cook (American Biosecurity Initiative). They define biosecurity beyond bioweapons, strategic competition with China biotech, the re-invigoration of domestic capabilities, and regulatory modernization via legislative action.

Sources: Endpoints News Youtube channel

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Conferences

WCLC 2026

Breakthroughs from the world’s largest lung cancer conference

The IASLC 2026 World Conference on Lung Cancer (WCLC 2026) took place from September 12–15, 2026 at the COEX Convention & Exhibition Center in Seoul, South Korea. We discussed several high-impact datasets including B7-H3 ADCs in 2L SCLC, EGFR inhibitors in 1L EGFR-mutated NSCLC, and other positive & mixed datasets. Check out our WCLC 2026 coverage here:

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ESC 2026

Breakthroughs and debates from Europe’s largest cardiology conference

The European Society of Cardiology (ESC) Congress 2026 took place on August 28–31, 2026 in Munich, Germany. We discussed several high-impact datasets including dueling datasets in ATTR-CM, silent atherosclerosis, severe hypertriglyceridemia (sHTG), heart failure, and other notable datasets. Check out our ESC 2026 coverage here:

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Approvals

Scholar Rock - Isembyld (myostatin inhibitor) / Approved (SMA)

On September 11, 2026, the FDA granted approval for Scholar Rock’s Isembyld (apitegromab-mstn), establishing it as the first and only muscle-targeted therapy for patients with spinal muscular atrophy (SMA) currently receiving an SMN2-targeted treatment. Scholar Rock’s path to approval faced significant manufacturing hurdles. The FDA issued a Complete Response Letter (CRL) in September 2025, which stemmed from quality control and compliance issues identified at a third-party Catalent fill-finish manufacturing facility in Indiana (owned by Novo Holdings). The rejection was entirely operational, involving no safety or efficacy concerns regarding the drug itself. Scholar Rock resolved the setback by formally removing the troubled manufacturing site from its application and amending the submission to rely on an alternative compliant fill-finish plant. Following this update, the FDA finalized its review ahead of schedule and granted approval. Along with the clearance, Scholar Rock was awarded a Rare Pediatric Disease Priority Review Voucher (PRV).

Unlike existing SMN2-targeted therapies (such as Spinraza, Evrysdi, or Zolgensma) that work on preserving motor neurons, Isembyld is a targeted monoclonal antibody that acts directly on skeletal muscle. It selectively blocks the activation of latent myostatin, a key protein that restricts muscle growth, thereby promoting muscle function and mass restoration. The FDA approved Isembyld as a combination/add-on therapy for adults and pediatric patients aged 2 years and older who are currently undergoing treatment with an SMN2-directed therapy.

The approval was driven by data from the pivotal Phase 3 SAPPHIRE trial evaluating monthly intravenous infusions of apitegromab added to background SMN2-targeted standard of care. Patients treated with Isembyld (10 mg/kg) achieved a statistically significant 2.2-point improvement on the Hammersmith Functional Motor Scale-Expanded (HFMSE) at 52 weeks compared to those on standard SMN2 treatment alone (p = 0.0121). Approximately 34.2% of patients receiving Isembyld demonstrated a ≥3-point gain on the HFMSE scale versus 13.5% in the control arm (p = 0.0125). The treatment was generally well-tolerated, with common adverse events including upper respiratory infections, cough, vomiting, and headaches. Prescribing information includes a warning regarding an increased incidence of bone fractures (9% in the 10 mg/kg group vs. 2% in placebo), primarily noted in individuals with pre-existing risk factors.

Sources: Scholar Rock press release, new Isembyld label

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Clinical Trial Data

Vera - Trutakna (APRIL/BAFF inhibitor) / Phase 3 (IgAN)

On September 15, 2026, Vera Therapeutics announced pivotal Phase 3 readout results for Trutakna (atacicept), marking a milestone for patients with IgA nephropathy (IgAN). Having previously secured accelerated approval based on 36-week surrogate biomarker reductions, the full two-year final analysis from the pivotal trial validated Trutakna’s ability to halt long-term renal decline, providing robust, long-term confirmatory data that sets the stage for a transition to full regulatory approval, pending regulatory review.

IgA nephropathy (IgAN) is an autoimmune kidney disease where overproduced galactose-deficient IgA1 (Gd-IgA1) forms circulating immune complexes that deposit in the glomerular mesangium, driving inflammation, fibrosis, and progressive renal decline. Standard management relies on supportive care (RAAS inhibitors, dual endothelin/angiotensin receptor antagonists, and SGLT2 inhibitors) to manage hypertension and proteinuria, supplemented by disease-modifying therapies for high-risk patients. Trutakna addresses this underlying disease mechanism directly. As a recombinant fusion protein binding both BAFF and APRIL cytokines, it disrupts upstream B-cell signaling and plasma cell survival to selectively suppress Gd-IgA1 production, preventing immune-complex deposition and protecting long-term kidney function.

The pivotal Phase 3 ORIGIN 3 trial evaluated Trutakna versus placebo in 428 adult IgAN patients at high risk of disease progression, measuring long-term eGFR preservation through 52 and 104 weeks to confirm its clinical benefit. At 52 weeks, Trutakna demonstrated a near-total stabilization of kidney function with a placebo-adjusted eGFR benefit of 5.6 mL/min/1.73m2 (p < 0.0001), while maintaining a minimal annualized eGFR loss of -0.6 mL/min/1.73m2/year over two years versus -5.6 mL/min/1.73m2/year for placebo (p < 0.0001). This translated into a statistically significant 76% relative risk reduction in composite kidney disease progression (HR = 0.24; p < 0.0001) and zero cases of end-stage renal disease (ESRD) in the treatment group compared to 8 in placebo, all while maintaining a relatively clean safety profile with no opportunistic infections.

Vera Therapeutics plans to submit a supplemental Biologics License Application (sBLA) to the FDA in the fourth quarter of 2026 to convert Trutakna‘s accelerated status into a full approval, with regulatory decisions anticipated in 2027. Commercial launch efforts remain active under the accelerated approval framework, supported by early demand and ongoing open-label extensions.

Sources: Vera press release, Vera slide deck

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Definium - DT120 (LSD ODT) / Phase 3 (GAD)

On September 14, 2026, Definium Therapeutics reported positive topline Phase 3 results from the Panorama trial evaluating DT120 (lysergide D-tartrate / LSD ODT) for the treatment of generalized anxiety disorder (GAD). This milestone represents the second successful Phase 3 readout for DT120 in GAD, following the earlier Phase 3 Voyage trial, and the third positive Phase 3 dataset overall for the asset across psychiatric indications (MDD & GAD). The findings confirm DT120’s potential to deliver deep, durable, and rapid anti-anxiety benefits from a single administration without requiring daily medication adherence.

Generalized anxiety disorder (GAD) is a chronic psychiatric condition driven by cortico-striato-thalamo-cortical circuit dysregulation and monoaminergic system alterations that manifest as persistent worry and physiological hyperarousal. Standard of care relies on first-line SSRIs or SNRIs requiring weeks of daily compliance to show benefit, supplemented by psychotherapy or acute second-line agents like benzodiazepines and buspirone. DT120 ODT (lysergide D-tartrate) targets these underlying circuits directly as a serotonin 5-HT2A receptor partial agonist. By triggering acute, transient neuroplasticity, this orally disintegrating tablet formulation is designed to disrupt maladaptive cognitive networks to promote long-term anxiety remission well past systemic clearance of the drug.

The pivotal Phase 3 Panorama trial evaluated a single supervised dose of DT120 ODT (100 µg) versus placebo in adults with moderate-to-severe GAD, demonstrating a statistically significant, placebo-adjusted net improvement of 5.1 points on the HAM-A scale at 12 weeks (-9.8 points vs. -4.7 points; p<0.0001; d=0.64). Treatment efficacy was rapid and durable, with significant anxiety reductions emerging by Day 2 and persisting through Week 12, where 32% of patients achieved clinical response (≥50% HAM-A reduction) and 35% achieved complete remission (HAM-A ≤7), compared to 14% and 15% for placebo, respectively. DT120 ODT was well-tolerated with no serious adverse events. Dosing-day side effects (such as mild-to-moderate illusion, nausea, and headache) resolved quickly, allowing 94% of patients to meet discharge criteria within 8 hours. By providing sustained 12-week anxiety control from a single acute administration, DT120 ODT introduces a novel therapeutic paradigm that bypasses the burden and limitations of daily chronic psychotropic medications.

With two positive Phase 3 trials in GAD (Voyage and Panorama) and positive Phase 3 data in major depressive disorder (Emerge), Definium Therapeutics announces that they’ve compiled a complete pivotal data package for DT120. The company is scheduling a pre-NDA meeting with the FDA in the fourth quarter of 2026, targeting a formal New Drug Application (NDA) submission in the first half of 2027. Additionally, DT120 will require Drug Enforcement Administration (DEA) scheduling prior to commercial availability. Since LSD is currently classified as a Schedule I controlled substance under the U.S. Controlled Substances Act (defined as having a high potential for abuse and no accepted medical use), approval of a New Drug Application (NDA) by the FDA will formally establish its medical utility. If approved, within 90 days of FDA approval, the DEA would be mandated to issue an interim final rule placing DT120 into a lower, controlled schedule (most likely Schedule II or Schedule III) to permit medical prescribing and clinical distribution under strict controls (such as REMS protocol requirements).

Sources: Definium press release, Definium slide deck

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Descriptive data releases without numerical data

• Roche - Lunsumio (CD20 x CD3 TCE) / Phase 3 (2L+ FL): Roche’s Phase 3 CELESTIMO study evaluating its CD20 x CD3 T-cell engaging bispecific antibody Lunsumio (mosunetuzumab) in combination with lenalidomide achieved its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to standard-of-care Rituxan plus lenalidomide. Evaluated in patients with relapsed or refractory follicular lymphoma (FL) who received at least one prior systemic therapy, this successful readout serves as the required confirmatory trial to convert Lunsumio’s accelerated approval into full regulatory approval for third-line or later (3L+) FL, while simultaneously laying the groundwork to label-expand into second-line (2L+) settings. The regimen maintained a tolerable safety profile consistent with prior profiles, with detailed dataset subgroup breakdowns and secondary endpoints scheduled for presentation at an upcoming medical conference. Sources: Roche press release

• Agomab - AGMB-447 (lung-restricted TGFβR1 inhibitor) / Phase 1 (IPF): Agomab Therapeutics’ positive Phase 1 trial results for AGMB-447 represent an encouraging milestone in its organ-restricted therapeutic platform for idiopathic pulmonary fibrosis (IPF). By designing AGMB-447 as an inhaled, small-molecule ALK5/TGFβR1 inhibitor that rapidly hydrolyzes in plasma into an inactive metabolite, Agomab successfully limited systemic toxicity while maintaining high drug concentrations in lung tissue. In the trial, AGMB-447 demonstrated a generally favorable safety and tolerability profile in IPF patients at 4.5 mg twice daily, with no systemic safety signals detected and most adverse events limited to transient inhalation-related cough or bronchospasm. Importantly, the study confirmed proof-of-mechanism in the target patient population, achieving over 50% pSMAD3 reduction in bronchoalveolar lavage cells and maintaining target coverage above IC90 for over 6 hours. These Phase 1 safety, pharmacokinetic, and target-engagement data clear the path for Agomab to advance AGMB-447 into Phase 2 clinical development (the INSPIRIA study) as a potentially disease-modifying local anti-fibrotic therapy. Sources: Agomab press release

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Table of Contents

The IASLC 2026 World Conference on Lung Cancer (WCLC 2026) took place from September 12–15, 2026 at the COEX Convention & Exhibition Center in Seoul, South Korea. In this article, we discuss the following high-impact datasets:

• B7-H3 ADCs in 2L SCLC ⬇️

  • Roche & MediLink - Tambotatug pelitecan (B7-H3 ADC) / Phase 3 (2L ES-SCLC) ⬇️

  • GSK & Hansoh - Risvutatug rezetecan (B7-H3 ADC) / Phase 3 (2L SCLC) ⬇️

• EGFR Inhibitors in 1L EGFR-mutated NSCLC ⬇️

  • J&J - Rybrevant (EGFR x c-MET mAb) / Phase 3 (1L EGFRm Ex20ins NSCLC) ⬇️

  • AstraZeneca - Tagrisso (covalent EGFR inhibitor) / Phase 3 (1L EGFRm NSCLC) ⬇️

  • Cullinan - Zipalertinib (covalent EGFR inhibitor) / Phase 3 (1L EGFRm Ex20ins NSCLC) ⬇️

• Other Positive Datasets

  • GSK - Jideytro (ROS1 inhibitor) / Phase 3 (1L ROS1+ NSCLC) ⬇️

  • BioNTech - Gotistobart (anti-CTLA4 mAb) / Phase 3 (2L Sq NSCLC) ⬇️

  • Amgen - Imdelltra (DLL3 x CD3 TCE) / Phase 3 (1L ES-SCLC) ⬇️

  • Summit & Akeso - Ivonescimab (PD1 x VEGF mAb) / Phase 3 (1L NSCLC) ⬇️

• Mixed Datasets

  • AstraZeneca - Enhertu (HER2 ADC) / Phase 3 (1L HER2m non-Sq NSCLC) ⬇️

  • Gilead - Trodelvy (TROP2 ADC) / Phase 3 (1L NSCLC) ⬇️

B7-H3 ADCs in 2L SCLC

Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor characterized by rapid proliferation, early metastatic spread, and inactivation of the tumor suppressor genes TP53 and RB1. Although most patients respond initially to first-line (1L) chemo-immunotherapy, virtually all experience rapid disease relapse driven by genomic instability, plastic cell states, and therapy resistance. Historically, second-line (2L) standard-of-care relied on single-agent chemotherapy such as topotecan or lurbinectedin, though recent guidelines have shifted toward the DLL3-targeted bispecific T-cell engager tarlatamab following its demonstrated overall survival advantage. To address persistent resistance mechanisms and poor survival, B7-H3 targeted antibody-drug conjugates (B7-H3 ADCs), such as ifinatamab deruxtecan, risvutatug rezetecan, and tambotatug pelitecan, have emerged as a transformative therapeutic class. B7-H3 (CD276) is widely overexpressed on SCLC cells with minimal expression in normal tissues. B7-H3 ADCs exploit this by binding the transmembrane protein to deliver cytotoxic payloads (such as topoisomerase I inhibitors) directly into malignant cells, potentially achieving improvements over conventional 2L chemotherapy in clinical trials.

Roche & MediLink - Tambotatug pelitecan (B7-H3 ADC) / Phase 3 (2L ES-SCLC)

On September 12, 2026, investigators delivered a major readout from the Phase 3 TAISHAN-302 trial evaluating tambotatug pelitecan (Tam-Peli; formerly YL201), an investigational antibody-drug conjugate (ADC) targeting B7-H3. Simultaneously published in The New England Journal of Medicine, the trial results marked a landmark advance in second-line extensive-stage small-cell lung cancer (SCLC), a disease setting long plagued by rapid recurrence and modest treatment options.

Developed by MediLink Therapeutics in partnership with Roche, tambotatug pelitecan combines a humanized anti-B7-H3 monoclonal antibody with a camptothecin-derived topoisomerase I inhibitor payload via a novel tripeptide linker. By capitalizing on B7-H3 over-expression across SCLC tissue, the ADC is designed to deliver targeted cytotoxic activity directly to malignant cells while minimizing off-target toxicity.

In the open-label, randomized TAISHAN-302 trial of 451 patients with ES-SCLC progressing after initial platinum-based therapy, tambotatug pelitecan delivered a profound survival advantage over standard-of-care topotecan. At a median follow-up of over nine months, patients receiving tambotatug pelitecan achieved a median overall survival of 13.3 months compared to 9.4 months with topotecan, translating to a striking 54% reduction in the risk of death (HR = 0.46 P < 0.001). Secondary efficacy endpoints similarly reflected robust clinical benefit. Progression-free survival more than doubled to 7.4 months versus 2.8 months (HR = 0.29; P < 0.001), while confirmed objective response rates jumped sixfold to 59.1% compared to just 9.7% in the control arm. Notably, the ADC also demonstrated clear central nervous system (CNS) activity, driving an intracranial objective response rate of 32.0% among patients with baseline brain metastases. Importantly, this efficacy was accompanied by a favorable safety profile. Grade ≥3 adverse events occurred less frequently with tambotatug pelitecan than with topotecan (55.4% vs. 77.9%), primarily presenting as manageable, reversible hematologic toxicities. Interstitial lung disease (ILD) remained minimal at 4.9%, with no Grade 4 or 5 pulmonary events reported.

The next step is extrapolating these findings beyond China via global Phase 3 multi-regional trials in broader, geographically diverse patient cohorts. An ongoing Phase 3 trial (NCT07739758) is actively evaluating tambotatug pelitecan in combination with PD-1 inhibition in the 1L extensive-stage SCLC setting

Sources: Roche press release, Zhao et al., NEJM (2026)

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GSK & Hansoh - Risvutatug rezetecan (B7-H3 ADC) / Phase 3 (2L SCLC)

GSK and Hansoh Pharma delivered landmark Phase 3 data from the pivotal ARTEMIS-008 trial, marking another historic breakthrough for B7-H3–targeted therapies in relapsed extensive-stage small cell lung cancer (SCLC). The interim analysis revealed a statistically significant and clinically transformative advantage for the B7-H3 ADC over standard chemotherapy.

Risvutatug rezetecan (ris-rez; formerly HS-20093 / GSK5764227) is a novel B7-H3–targeted antibody-drug conjugate (ADC). It pairs a fully human anti-B7-H3 monoclonal antibody with a potent topoisomerase I inhibitor payload (a camptothecin derivative) via an enzymatically cleavable linker. By binding B7-H3, an immune-regulatory protein overexpressed across malignant SCLC tumor cells, the ADC is designed to selectively internalize and release its cytotoxic payload inside cancer cells to induce double-stranded DNA damage and apoptosis.

The Phase 3 ARTEMIS-008 trial was conducted in China and evaluated the efficacy and safety of risvutatug rezetecan in patients with relapsed SCLC who had progressed after initial platinum-based therapy. Risvutatug rezetecan nearly doubled median OS to 18.5 months compared to 10.3 months with topotecan, reducing the risk of death by 54% (HR = 0.46; p < 0.001). Median PFS reached 7.2 months in the ris-rez arm compared to 3.0 months for topotecan (HR = 0.31; p < 0.001), demonstrating sustained disease control. Risvutatug rezetecan was well-tolerated, demonstrating a manageable adverse event profile characterized primarily by reversible hematologic toxicities, with low overall rates of Grade ≥3 interstitial lung disease (ILD).

Driven by these results, GSK and Hansoh Pharma are advancing global Phase 3 trials to evaluate risvutatug rezetecan in international patient populations. Beyond second-line monotherapy, investigators are initiating trials to test ris-rez earlier in the treatment continuum, including combination regimens with checkpoint inhibitors in first-line extensive-stage SCLC, as well as expanding its evaluation into other B7-H3-expressing malignancies such as metastatic prostate cancer.

Sources: GSK press release, GSK WCLC 2026 slide

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EGFR Inhibitors in 1L EGFR-mutated NSCLC

In EGFR-mutated non-small cell lung cancer (NSCLC), standard oncogenic driver mutations, most commonly exon 19 deletions or the L858R point mutation, lead to constitutive activation of the epidermal growth factor receptor kinase domain, driving downstream pro-survival signaling, cell proliferation, and tumor angiogenesis. The first-line (1L) standard of care leverages central nervous system (CNS)-penetrant third-generation EGFR tyrosine kinase inhibitors (TKIs), primarily Tagrisso/osimertinib monotherapy, or intensified upfront combination regimens including Tagrisso plus platinum-doublet chemotherapy (FLAURA2) or amivantamab (an EGFR-MET bispecific antibody) plus lazertinib (MARIPOSA). Within this framework, EGFR inhibitors play the critical role of selectively binding and blocking the mutated receptor’s intracellular ATP-binding pocket or extracellular domains, thereby shutting down oncogenic cascade signaling, inducing apoptosis, and delivering high objective response rates (ORR) alongside prolonged progression-free survival (PFS) and overall survival (OS) compared to historical chemotherapy options.

J&J - Rybrevant (EGFR x c-MET mAb) / Phase 3 (1L EGFRm Ex20ins NSCLC)

Johnson & Johnson presented long-term data from the Phase 3 PAPILLON trial, highlighting the role of Rybrevant (amivantamab-vmjw) plus chemotherapy in patients with newly diagnosed, advanced EGFR exon 20 insertion-mutated non-small cell lung cancer (NSCLC).

Rybrevant is a fully human bispecific antibody directed against EGFR and c-MET drivers. Unlike small-molecule tyrosine kinase inhibitors (TKIs) that struggle to bind the altered kinase pocket characteristic of exon 20 insertion mutations, Rybrevant binds the extracellular domains of both EGFR and MET. This dual-targeting mechanism inhibits ligand binding, promotes receptor degradation, and engages immune effector mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC) and macrophage phagocytosis, to suppress primary tumor growth and bypass MET-mediated resistance pathways. Historically, patients with EGFR exon 20 insertion mutations faced poor outcomes under standard platinum doublet chemotherapy, with real-world median overall survival ranging from 16 to 24 months.

The pivotal Phase 3 PAPILLON study evaluated 308 treatment-naive patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. Patients were randomized 1:1 to receive either intravenous Rybrevant in combination with carboplatin-pemetrexed chemotherapy or carboplatin-pemetrexed chemotherapy alone. Protocol crossover was permitted, allowing 76% of eligible patients in the control arm to receive second-line Rybrevant monotherapy following disease progression. Patients receiving frontline Rybrevant plus chemotherapy achieved a median OS of 34.3 months compared to 27.9 months for chemotherapy alone (HR = 0.87; P = 0.307). Due to the 76% crossover rate to second-line Rybrevant in the control arm, the unadjusted hazard ratio was attenuated. Prespecified inverse probability of censoring weighting (IPCW) modeling adjusting for crossover demonstrated a statistically significant 43% reduction in the risk of death (IPCW HR = 0.57; nominal P = 0.003). Second progression-free survival (PFS2) was extended by more than 10 months in the combination arm (28.3 months vs. 17.5 months; HR = 0.59). The safety profile remained consistent with previously reported data, with common toxicities including paronychia, rash, and transient cytopenias, supported by prophylactic management strategies to maintain long-term dosing compliance.

To build on these overall survival data, J&J is focusing on optimizing the delivery and patient experience of the regimen. Clinical efforts are centered on transitioning from intravenous administration to a subcutaneous formulation (evaluated in the PALOMA studies) to reduce administration time and infusion-related reactions, alongside evaluating prophylactic management protocols (such as the COPERNICUS trial) to mitigate dermatologic and mucosal toxicities.

Sources: J&J press release, J&J WCLC 2026 slide

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AstraZeneca - Tagrisso (covalent EGFR inhibitor) / Phase 3 (1L EGFRm NSCLC)

AstraZeneca delivered landmark long-term data for Tagrisso (osimertinib) in EGFR-mutated non-small cell lung cancer (NSCLC). Presented during a Presidential Symposium, the updated exploratory findings from the Phase 3 ADAURA trial showcased an unprecedented 8-year follow-up, representing the longest overall survival (OS) data ever reported in a global Phase 3 study in this setting.

Tagrisso (osimertinib) is a third-generation, irreversible, central nervous system (CNS)-active EGFR tyrosine kinase inhibitor (TKI). It selectively targets both sensitizing EGFR mutations (such as exon 19 deletions and L858R) and the T790M resistance mutation while sparing wild-type EGFR. By forming a covalent bond with the C797 residue in the ATP-binding pocket of the EGFR kinase domain, osimertinib is designed to permanently shut down downstream pro-survival and proliferative signaling cascades, triggering tumor cell apoptosis while maintaining high intracranial penetration to control and prevent brain metastases.

The pivotal global Phase 3 ADAURA study evaluated 682 patients with resected, stage IB to IIIA EGFR-mutated NSCLC who had undergone complete tumor resection, with or without prior adjuvant chemotherapy. The long-term analysis presented at WCLC 2026 evaluated extended OS follow-up extending to roughly eight years (data cutoff May 4, 2026). The 8-year landmark analysis demonstrated a durable, clinically meaningful reduction in the risk of death for Tagrisso compared to placebo. In the trial’s primary population (stages II-IIIA), Tagrisso cut the risk of death by 47% compared to placebo, yielding a hazard ratio (HR) of 0.53 (95% CI: 0.38–0.75). The estimated 8-year OS rate reached 74% for Tagrisso versus 58% for placebo. In the overall population (stages IB-IIIA), Tagrisso reduced the risk of death by 48% (HR = 0.52; 95% CI: 0.39–0.71), with an 8-year OS rate of 79% versus 64% for placebo. Final safety outcomes aligned with Tagrisso‘s long-established tolerability profile, showing no new long-term safety signals after extended observation.

Building on its established role across resected early disease (ADAURA), stage III unresectable disease (LAURA), and 1L advanced settings (FLAURA / FLAURA2), AstraZeneca is focused on maintaining treatment persistence and optimizing combination regimens. Real-world data presented alongside ADAURA highlighted that completing the full 3-year adjuvant course remains vital to avoid recurrence. Future directions also include evaluating Tagrisso-based regimens in earlier neo-adjuvant settings, as well as developing next-generation combinations to counter emerging EGFR resistance mechanisms like C797S mutations and MET amplification.

Sources: AstraZeneca press release, AstraZeneca WCLC 2026 slide

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Cullinan - Zipalertinib (covalent EGFR inhibitor) / Phase 3 (1L EGFRm Ex20ins NSCLC)

Cullinan Therapeutics and Taiho Pharmaceutical presented results from a Presidential Symposium highlighting the Phase 3 REZILIENT3 trial. Evaluating zipalertinib (CLN-081/TAS6417) in combination with platinum-based chemotherapy, the presentation established the oral small-molecule inhibitor as a first-line treatment option for advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (ex20ins) mutations.

Zipalertinib is an oral, irreversible covalent small-molecule EGFR tyrosine kinase inhibitor specifically designed to target EGFR exon 20 insertion mutations while sparing wild-type EGFR. Structural alterations caused by exon 20 insertions restrict the ATP-binding pocket, making conventional TKIs ineffective or excessively toxic due to off-target wild-type EGFR inhibition. Zipalertinib forms a covalent bond with the C797 residue within the active conformation of mutant EGFR, selectively blocking downstream oncogenic signaling and driving cell apoptosis with an improved therapeutic window.

The global, randomized, open-label Phase 3 REZILIENT3 study evaluated 279 treatment-naive patients with locally advanced or metastatic EGFR ex20ins NSCLC. Patients were randomized to receive either zipalertinib (100 mg orally twice daily) combined with platinum-pemetrexed doublet chemotherapy or platinum-pemetrexed chemotherapy alone. At the pre-specified interim efficacy analysis, zipalertinib combined with chemotherapy met its primary endpoint, delivering efficacy metrics across response endpoints. The combination significantly extended median PFS to 14.5 months compared to 8.5 months with chemotherapy alone, cutting the risk of disease progression or death by 50% (HR = 0.50; 95% CI: 0.34-0.73; P = 0.00015). Confirmed BICR ORR reached 65.0% in the combination arm versus 40.3% for chemotherapy alone (P < 0.0001). Median DoR reached 14.2 months with the zipalertinib combination compared to 9.9 months with chemotherapy. At an early 30% OS event maturity, the combination showed a trend toward improved survival with a hazard ratio of 0.72 (95% CI: 0.42-1.23), with follow-up ongoing. While the overall study population achieved a statistically significant 50% reduction in the risk of disease progression or death (HR = 0.50; median PFS 14.5 months vs. 8.5 months), patients with brain metastases experienced a 62% reduction in the risk of disease progression or death (subgroup HR = 0.38; 95% CI: 0.21–0.67). This pronounced benefit highlights zipalertinib’s central nervous system (CNS) activity and ability to penetrate the blood-brain barrier, effectively addressing central nervous system recurrence, a frequent site of failure and major unmet need in EGFR exon 20 insertion-mutated lung cancer. The safety profile of the combination was manageable and consistent with the individual agents, featuring low rates of Grade 3 or higher wild-type EGFR-related toxicities (such as Grade 3 rash in 10.7% and Grade 3 diarrhea in 1.4%).

Cullinan Therapeutics and Taiho Pharmaceutical plan to submit these data to global regulatory authorities to support potential approval for zipalertinib in the first-line EGFR ex20ins setting. Ongoing initiatives include monitoring long-term overall survival maturity in REZILIENT3, evaluating zipalertinib as monotherapy in post-chemotherapy settings (REZILIENT1), and exploring combination strategies to address emerging mechanisms of resistance.

Sources: Cullinan press release, Cullinan WCLC 2026 slide deck

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Other Positive Datasets

GSK - Jideytro (ROS1 inhibitor) / Phase 3 (1L ROS1+ NSCLC)

GSK presented registrational Phase 1/2 data from the ARROS-1 trial evaluating Jideytro (zidesamtinib) in first-line ROS1-positive non-small cell lung cancer (NSCLC). Featured during a Presidential Symposium, the findings position Jideytro as a precision oncology asset that serves as the centerpiece of GSK’s recent acquisition of Nuvalent, which we covered here.

Jideytro (zidesamtinib) is an oral, brain-penetrant, next-generation ROS1-selective tyrosine kinase inhibitor (TKI). Engineered with structural selectivity to spare the closely related TRK family of receptors, Jideytro minimizes TRK-mediated central nervous system toxicities (such as ataxia, weight gain, and cognitive changes) while targeting both wild-type ROS1 fusions and hard-to-treat resistance mutations, including the solvent-front G2032R mutation. Its high central nervous system (CNS) permeability allows it to cross the blood-brain barrier to prevent and clear intracranial metastases.

The registrational Phase 1/2 ARROS-1 trial evaluated Jideytro (100 mg once daily) across cohorts of ROS1-positive advanced or metastatic NSCLC patients. The data presented at WCLC 2026 focused on 94 TKI-naive patients who had not previously received a ROS1-targeted inhibitor (though up to one prior line of chemotherapy with or without immunotherapy was allowed). At a median follow-up of 15.2 months, Jideytro demonstrated high systemic and intracranial efficacy in TKI-naive patients. Results of co-primary endpoints (ORR, DoR) included a BICR-confirmed ORR of 94% (88/94; 95% CI: 87-98%), featuring a 15% complete response (CR) rate, and median duration of response (DoR) and median PFS were both not yet reached. At 12 months, 86% of responding patients remained in remission, and the 12-month PFS rate was 90%. Furthermore, in patients with measurable brain metastases at baseline, Jideytro achieved a 70% complete clearance rate of detectable brain tumors, with an overall intracranial ORR reaching up to 100% across evaluable patients. Jideytro was well tolerated, with low rates of treatment-related dose reductions (11%) and discontinuations (1%). Side effects were mostly low-grade, including peripheral edema, blood CPK elevation, and dysgeusia, with a minimal incidence of TRK-related neurotoxicities. By delivering a 94% ORR and a 15% complete response rate, more than double the CR rates observed with competing next-generation ROS1 TKIs (7% for Augtyro/repotrectinib in TRIDENT-1 Phase 1/2 trial, 6.5% for Talvey/taletrectinib in TRUST-I Phase 2 trial), Jideytro sets a efficacy benchmark in frontline ROS1-positive NSCLC on a cross-trial basis (GSK would have to run a head-to-head study to definitively demonstrate superiority).

Building on Jideytro‘s prior FDA approval for TKI-pretreated ROS1-positive NSCLC, GSK plans to submit a supplemental Biologics License Application (sBLA) to the U.S. FDA in the fourth quarter of 2026 to expand its indication into the first-line setting. As the foundational asset of the Nuvalent transaction, Jideytro serves as the anchor of GSK’s expanding thoracic oncology pipeline, with ongoing trials further exploring its long-term OS outcomes and potential applications across broader ROS1-altered solid tumors.

Sources: GSK press release, GSK WCLC 2026 slides

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BioNTech - Gotistobart (anti-CTLA4 mAb) / Phase 3 (2L Sq NSCLC)

BioNTech and OncoC4 presented median overall survival (OS) data from stage 1 of the Phase 3 PRESERVE-003 trial. The findings evaluate gotistobart (BNT316/ONC-392) as a chemotherapy-free option for patients with advanced squamous non-small cell lung cancer (NSCLC) progressing after prior anti-PD-(L)1 immunotherapy and platinum-based chemotherapy. This data was previously published in Nature Medicine in March 2026 and presented at the 2026 European Lung Cancer Congress (ELCC) and the IASLC ASCO 2025 North America Conference on Lung Cancer (NACLC).

Gotistobart is an investigational, pH-sensitive anti-CTLA-4 monoclonal antibody designed to address historical tolerability challenges of first-generation CTLA-4 inhibitors. Following binding to CTLA-4, the antibody-receptor complex internalizes into endosomes, where low pH triggers dissociation. This mechanism allows CTLA-4 to recycle back to the cell surface to maintain immune self-tolerance in healthy peripheral tissues while selectively depleting regulatory T cells (Tregs) within the acidic tumor microenvironment to reignite anti-tumor immunity.

PRESERVE-003 is a two-stage, open-label Phase 3 trial comparing gotistobart monotherapy against standard-of-care docetaxel chemotherapy. Data presented at WCLC 2026 detailed the randomized, non-pivotal stage 1 cohort of 87 patients with metastatic squamous NSCLC who experienced disease progression after platinum-based chemotherapy and PD-(L)1 blockade. At a median follow-up of 25.4 months (data cutoff July 17, 2026), gotistobart demonstrated an overall survival advantage over standard chemotherapy. Gotistobart extended median OS to 18.5 months compared to 10.0 months with docetaxel, delivering an 8.5-month survival extension and reducing the risk of death by 44% (HR = 0.56; 95% CI: 0.33-0.95; nominal p = 0.0295). The confirmed objective response rate (ORR) was 20.0% in the gotistobart arm versus 4.8% with docetaxel. Grade 3 or higher treatment-related adverse events occurred in 44.4% of patients receiving gotistobart compared to 48.8% in the docetaxel arm. Immune-mediated toxicities remained manageable, with Grade 3+ colitis occurring in 8.9% of gotistobart-treated patients and no unmanageable safety signals.

While these stage 1 findings are clinically meaningful, it was exploratory and not designed as a registrational dataset. BioNTech and OncoC4 are actively conducting the pivotal stage 2 portion of PRESERVE-003, which is enrolling approximately 478 patients with metastatic squamous NSCLC across 160 global sites. Topline pivotal stage 2 data are anticipated in the fourth quarter of 2026, which could serve as the primary dataset to support global regulatory filings.

Sources: BioNTech press release, Cho et al., Nature Medicine (2026)

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Amgen - Imdelltra (DLL3 x CD3 TCE) / Phase 3 (1L ES-SCLC)

Amgen presented Phase 3 data evaluating Imdelltra (tarlatamab-dlle), a bispecific T-cell engager (TCE), in first-line extensive-stage small cell lung cancer (1L ES-SCLC). Delivered during a Presidential Symposium, the results revealed dose-dependent outcomes that highlighted both the promise and complexity of advancing T-cell engagers into earlier lines of therapy.

Imdelltra (tarlatamab) is a bispecific T-cell engager engineered to simultaneously bind delta-like ligand 3 (DLL3) on SCLC cells and CD3 on cytotoxic T lymphocytes. DLL3 is overexpressed on the surface of SCLC cells with minimal expression in normal tissues. By forming an artificial immunological synapse between endogenous T cells and DLL3-expressing tumor cells, Imdelltra is designed to induce directed T-cell activation, targeted cytotoxicity, and localized cytokine release to destroy malignant cells independently of MHC class I presentation.

The global, randomized Phase 3 DeLLphi-305 trial evaluated Imdelltra as frontline maintenance or combination therapy in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) who had completed initial induction platinum-based chemotherapy plus immunotherapy. The overall survival analysis revealed a notable divergence in outcomes based on dose selection. Treatment with the 20 mg dose delivered a statistically significant reduction in the risk of death compared to standard maintenance, achieving an overall survival hazard ratio of 0.59 (HR = 0.59; p < 0.001), accompanied by improvements in median PFS and duration of response. In contrast, the higher 30 mg dose cohort failed to show a survival advantage over control, generating an overall survival hazard ratio of 1.03 (HR = 1.03), reflecting a flat to detrimental survival effect relative to the lower dose. The lack of survival benefit at the 30 mg dose was largely driven by increased toxicity and treatment disruptions. While cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were manageable at the 20 mg level, higher rate and severity of immune-mediated adverse events, treatment-related discontinuations, and adverse event-related mortality at the 30 mg dose negated the anti-tumor efficacy. These findings demonstrate a bell-shaped or plateaued therapeutic window typical of T-cell engagers, where higher doses do not translate to superior cell killing and instead exacerbate immune toxicity and treatment failure.

Amgen is focusing its regulatory filings and global registration efforts exclusively on the 20 mg dosing schedule for first-line ES-SCLC maintenance. Future initiatives involve optimizing step-up dosing and outpatient monitoring protocols to mitigate early CRS events, as well as evaluating combination strategies with immune checkpoint inhibitors and novel targeted agents to maximize durable survival without compromising safety.

Sources: Amgen WCLC 2026 slides

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Summit & Akeso - Ivonescimab (PD1 x VEGF mAb) / Phase 3 (1L NSCLC)

Summit Therapeutics and Akeso presented the overall survival (OS) readout from the Phase 3 HARMONi-2 study evaluating ivonescimab (AK112/SMT112) in first-line non-small cell lung cancer (NSCLC). Following its earlier headline progression-free survival (PFS) victory over pembrolizumab, the new survival data confirmed a statistically significant reduction in the risk of death, demonstrating the potential of a bispecific antibody to outperform the long-standing standard of care.

Ivonescimab is a first-in-class, humanized bispecific antibody engineered to simultaneously target PD-1 and VEGF-A. By cooperative binding to both targets, ivonescimab is designed to leverage the high density of VEGF in the tumor microenvironment to increase its binding affinity for PD-1. This dual mechanism restores anti-tumor T-cell activity by blocking the PD-1/PD-L1 checkpoint, while concurrently inhibiting VEGF-driven tumor angiogenesis, normalizing tumor vasculature, and enhancing immune cell infiltration.

The Phase 3 HARMONi-2 trial evaluated 398 patients in China with treatment-naive, advanced PD-L1–positive (TPS ≥1%) NSCLC. Patients were randomized 1:1 to receive either ivonescimab monotherapy or standard-of-care pembrolizumab monotherapy. While the trial previously met its primary endpoint of PFS, the long-term follow-up presented at WCLC 2026 focused on the key secondary endpoint of Overall Survival (OS). The OS analysis demonstrated a statistically significant survival advantage for ivonescimab over pembrolizumab monotherapy. Ivonescimab reduced the risk of death by 17% compared to pembrolizumab, achieving an OS hazard ratio of 0.83 (HR = 0.83; P = 0.009). Patients receiving ivonescimab experienced an 8.2-month numeric extension in median overall survival compared to those treated with pembrolizumab. The safety profile of ivonescimab remained consistent with prior reports, demonstrating a manageable toxicity profile without new unexpected VEGF- or immune-related safety signals.

Since HARMONi-2 was conducted exclusively in a Chinese patient population, the FDA requires global multi-regional clinical trial (MRCT) validation before granting registration. To establish global regulatory approval, Summit Therapeutics is enrolling the Phase 3 HARMONi-7 trial, a global study directly comparing ivonescimab monotherapy against pembrolizumab in high PD-L1–expressing (TPS ≥ 50%) NSCLC, with primary data readouts anticipated in 2028.

Sources: Summit press release, Summit/Akeso WCLC 2026 slides

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Mixed Datasets

AstraZeneca & Daiichi - Enhertu (HER2 ADC) / Phase 3 (1L HER2m non-Sq NSCLC)

AstraZeneca and Daiichi Sankyo presented primary data from the pivotal Phase 3 DESTINY-Lung04 trial. Evaluating Enhertu (trastuzumab deruxtecan; T-DXd) as frontline monotherapy for advanced HER2-mutated non-squamous non-small cell lung cancer (NSCLC), the study generated complex results: while Enhertu established superior progression-free survival (PFS) over standard-of-care chemo-immunotherapy, it failed to translate that progression advantage into an overall survival (OS) benefit.

Enhertu is a HER2-directed antibody-drug conjugate (ADC) composed of a humanized anti-HER2 IgG1 monoclonal antibody linked to a potent topoisomerase I inhibitor payload (deruxtecan, a DXd derivative) via a tetrapeptide-based cleavable linker. Upon binding to HER2 receptors expressed on mutant lung cancer cells, the ADC internalizes, releasing the membrane-permeable payload inside the tumor cell to induce double-stranded DNA damage and apoptosis. The payload’s bystander effect allows it to diffuse into neighboring tumor cells within heterogeneous tumors.

The Phase 3 DESTINY-Lung04 study evaluated 454 treatment-naive patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring HER2 exon 19 or exon 20 insertion mutations. Patients were randomized 1:1 to receive either Enhertu monotherapy (5.4 mg/kg IV every three weeks) or the global frontline standard of care: Keytruda (pembrolizumab) combined with platinum-pemetrexed doublet chemotherapy. The readout presented at WCLC 2026 highlighted a divergence between progression control and overall survival outcomes. Enhertu met its primary endpoint, extending median PFS by 6.0 months to 14.3 months compared to 8.3 months in the Keytruda plus chemotherapy arm (HR = 0.63; 95% CI: 0.50-0.79; p < 0.0001). The objective response rate (ORR) was 70.0% with Enhertu versus 44.5% with chemo-immunotherapy, with a median duration of response (DoR) of 13.4 months versus 9.7 months, respectively. At 46.9% data maturity, Enhertu did not show an overall survival benefit over the control arm. Median OS was 29.3 months for Enhertu versus 33.1 months for Keytruda plus chemotherapy, yielding a numerical hazard ratio trending in favor of the control arm (HR = 1.15; 95% CI: 0.88-1.52). Investigators noted significant post-progression therapy imbalances, as 48.0% of patients in the control arm crossed over to receive subsequent HER2-targeted therapy (primarily second-line Enhertu) versus only 23.3% in the upfront Enhertu arm receiving subsequent immunotherapy. Furthermore, adjudicated interstitial lung disease (ILD) occurred in 20.8% of Enhertu-treated patients (including 1.8% Grade 5 fatal events), creating an safety signal that impacted long-term treatment continuity. While DESTINY-Lung04 is the first Phase 3 trial to demonstrate a PFS advantage over platinum-chemotherapy plus Keytruda in HER2-mutated NSCLC, the lack of OS benefit could complicate its immediate adoption as an upfront standard of care. The high crossover rate of control-arm patients to second-line Enhertu (achieving a median OS of 33.1 months) suggests that sequencing Enhertu into the second-line setting after initial chemo-immunotherapy remains a effective sequence, blunting the clinical urgency to move the ADC into the frontline setting.

AstraZeneca and Daiichi Sankyo are monitoring the trial for overall survival data maturity to perform formal adjusted analyses (such as RPSFT models) accounting for crossover. Future efforts focus on optimizing safety through strict proactive ILD monitoring algorithms to reduce pulmonary toxicity, alongside testing lower-dose regimens or upfront combination strategies to preserve anti-tumor efficacy while improving long-term overall survival outcomes.

Sources: AstraZeneca press release, AstraZeneca WCLC 2026 slides

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Gilead & Merck - Trodelvy (TROP2 ADC) / Phase 3 (1L NSCLC)

Gilead Sciences and Merck presented primary data from the Phase 3 EVOKE-03 / KEYNOTE-D46 trial evaluating Trodelvy (sacituzumab govitecan) in combination with Keytruda (pembrolizumab) as a first-line treatment for metastatic non-small cell lung cancer (NSCLC). Featured following an independent data monitoring committee recommendation to discontinue the trial, the results provided a clear example of the challenges facing antibody-drug conjugate (ADC) and immunotherapy combination strategies in driver-negative, PD-L1-high lung cancer.

Trodelvy (sacituzumab govitecan) is a TROP2-directed antibody-drug conjugate consisting of a humanized anti-TROP2 monoclonal antibody conjugated via a hydrolyzable linker to SN-38, a topoisomerase I inhibitor payload. TROP2 is an cell-surface glycoprotein overexpressed in over 90% of NSCLC tumors. The rationale behind the combination was to leverage Trodelvy‘s payload delivery and bystander effect to trigger immunogenic cell death, thereby priming the tumor microenvironment to potentiate Keytruda‘s anti-PD-1-mediated T-cell activation.

The global, randomized, open-label Phase 3 EVOKE-03 / KEYNOTE-D46 study enrolled 620 treatment-naive patients with metastatic NSCLC harboring high PD-L1 expression (TPS ≥50%) and lacking actionable genomic alterations (such as EGFR, ALK, or ROS1). The final PFS and interim OS analyses revealed that adding Trodelvy to frontline Keytruda failed to meet statistical criteria for its primary endpoints compared to Keytruda montherapy, while introducing toxicity. The combination demonstrated a numerical extension in median PFS (11.8 months vs. 7.7 months), but failed to cross the pre-specified threshold for statistical significance (HR = 0.81; 95% CI: 0.66–1.00; upper bound hit 1.00). At a 47% event maturity interim analysis, the combination showed a trend toward futility and numerical detriment compared to pembrolizumab monotherapy (median OS of 21.5 months for the combo vs. 22.8 months for Keytruda alone; HR = 1.07; 95% CI: 0.85–1.35). Adding the ADC increased treatment-related toxicities without a corresponding survival benefit. Grade ≥3 treatment-related adverse events occurred in 55.7% of patients receiving the Trodelvy combination compared to 16.5% in the Keytruda monotherapy arm, driven largely by high rates of neutropenia and severe diarrhea. The failure of EVOKE-03 highlights the difficulty of outperforming single-agent pembrolizumab in PD-L1-high (TPS ≥50%) frontline NSCLC, where anti-PD-1 monotherapy already sets a high efficacy bar. The added systemic toxicities from the SN-38 payload compromised dose intensity and treatment compliance, offsetting localized anti-tumor effects and causing the combination strategy to miss its primary endpoints.

While Gilead and Merck have terminated the EVOKE-03 frontline NSCLC program, Trodelvy‘s established global approvals in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer remain unchanged. Gilead has turned its thoracic strategy toward biomarker-enriched patient cohorts and ongoing clinical trials in small cell lung cancer (SCLC) and early-stage breast cancer settings, while the broader oncology field continues to evaluate whether different ADC payload dynamics, such as lower-potency payloads or alternative targets, can succeed in frontline IO-combination regimens.

Sources: Gilead/Merck WCLC 2026 slides

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Table of Contents

This week, we discuss:

• China Biotech

  • Financing Activity for China versus Rest of World ⬇️

  • FDA’s New Leadership ⬇️

• Approvals

  • Bayer - Hyrnuo (HER2 x mEGFR dual inhibitor) / Approved (1L HER2m NSCLC) ⬇️

  • AstraZeneca - Etcamah (SERD) / Approved (1L HR+ HER2- ESR1m mBC) ⬇️

• Clinical Trial Data

  • Roivant - Mosliciguat (inhaled sGC activator) / Phase 2 (PH-ILD) ⬇️

  • Compass Pathways - COMP360 (synthetic psilocybin) / Phase 3 (TRD) ⬇️

  • Disc Medicine - DISC-3405 (Anti-TMPRSS6 mAb) / Phase 2 (PV) ⬇️

  • Beam - BEAM-302 (A>G PiZ ABE) / Phase 1/2 (AATD) ⬇️

  • Inhibrx - INBRX-106 (hexavalent OX40 agonist) / Phase 2 (HNSCC) ⬇️

  • Novo Nordisk - Wegovy (GLP1 agonist) / Phase 3 (obesity age 6-12) ⬇️

  • Sanofi - Lunsekimig (IL13 x TSLP bs nanobody) / Phase 2b (asthma; CRSwNP) ⬇️

  • AstraZeneca - Tozorakimab (anti-IL33 mAb) / Phase 3 (COPD) ⬇️

  • Upstream Bio - Verekitug (TSLP inhibitor) / Phase 2 (asthma) ⬇️

  • Pharvaris - Deucrictibant (bradykinin B2 receptor antagonist) / Phase 3 (HAE) ⬇️

China Biotech

Wondering why we discuss China Biotech every week? Tap here to learn more.

Financing Activity for China versus Rest of World

for the week ending September 11, 2026

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FDA’s New Leadership

While this story is not directly related to China, it does impact the competitiveness of the American Biotech sector. Much ink has been spilled about a key driver of China’s success in biotech: regulatory streamlining in a way that dramatically lowers the cost of running clinical trials. In Biotech Readout’s article on China Biotech, we discussed how the opposite is true in America. The “Cautious Regulator” problem encapsulates the ballooning cost and time of running clinical trials as a direct result of an increasingly risk-averse FDA. In contrast, the cost of running a Phase 1 clinical trial in China (and potentially gathering value-inflecting clinical proof-of-concept) is estimated to be 32% to 52% lower than in the US. While China accelerates, the FDA has been without permanent division heads for CBER (Center for Biologics Evaluation and Research) and CDER (Center for Drug Evaluation and Research) since April 2026 and May 2026, respectively. That is, until this week. On September 8, 2026, the U.S. Department of Health and Human Services (HHS) officially appointed permanent directors to lead both divisions. Karim Mikhail will lead CBER while Dr. Michael Davis will lead CDER. Both serving as acting (temporary) heads before officially being appointed to their permanent roles:

• Karim Mikhail (CBER): Took over as acting CBER director in May 2026 after brief interim coverage by Dr. Katherine Szarama.

• Dr. Michael Davis (CDER): Took over as acting CDER director in May 2026 after interim lead Dr. Tracy Beth Høeg was removed.

We wish them well, and look forward to their leadership.

Sources: Endpoints article

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Approvals

Bayer - Hyrnuo (HER2 x mEGFR dual inhibitor) / Approved (1L HER2m NSCLC)

On September 9, 2026, the FDA granted accelerated approval to Bayer’s Hyrnuo (sevabertinib), an oral dual inhibitor targeting mutant HER2 and EGFR, for the first-line treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations. This label expansion represents a significant shift in upfront clinical management, advancing an oral, biomarker-directed precision kinase inhibitor into the first-line setting for a disease driver that historically required systemic chemotherapy or targeted antibody-drug conjugates. Hyrnuo originally earned accelerated approval as a second-line option in late 2025.

The decision was supported by preliminary efficacy and safety cohort data from the ongoing open-label, multi-center Phase 1/2 SOHO-01 trial. In the subset of treatment-naïve patients with HER2 TKD-mutated advanced NSCLC, Hyrnuo demonstrated robust antineoplastic activity, achieving an overall response rate (ORR) of 75%, with approximately 6% of patients attaining a complete response. Responses were durable, with over half of the responding cohort maintaining their response past 6 months. The safety profile was characterized primarily by GI-related and dermatologic off-target or EGFR-mediated toxicities (most notably manageable diarrhea, rash, paronychia, and nausea) alongside monitored risks for interstitial lung disease and elevated liver enzymes. Continued accelerated approval in the first-line setting remains contingent upon formal clinical benefit verification in the ongoing Phase 3 confirmatory trial, SOHO-02.

Sources: Bayer press release, Hyrnuo label

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AstraZeneca - Etcamah (SERD) / Approved (1L HR+ HER2- ESR1m mBC)

On September 4, 2026, the FDA granted accelerated approval to AstraZeneca’s Etcamah (camizestrant), a next-generation oral selective estrogen receptor degrader (SERD), in combination with a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). The approval is indicated for adult patients with hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer who develop emergent ESR1 mutations during first-line endocrine-based therapy. Concurrently, the FDA cleared the Guardant360 CDx liquid biopsy assay as a companion diagnostic to detect these circulating tumor DNA (ctDNA) resistance mutations. The regulatory clearance came despite significant regulatory friction. In April 2026, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 6-3 against recommending approval. Panelists expressed concerns over approving a novel “early switch” treatment paradigm that relies on molecular detection of resistance via liquid biopsy rather than waiting for conventional radiographic disease progression (scans). Critics argued that setting a precedent by changing frontline therapy based purely on ctDNA dynamics, without mature overall survival (OS) data, could lead to premature switching without a proven long-term survival benefit. However, the FDA ultimately exercised regulatory flexibility, relying on the robust progression-free survival (PFS) advantage to grant accelerated approval.

The FDA’s decision was backed by data from the double-blind, randomized Phase 3 SERENA-6 trial. In the study, patients receiving a first-line aromatase inhibitor plus a CDK4/6 inhibitor were routinely monitored for emerging ESR1 mutations via ctDNA. Upon detecting an ESR1 mutation and prior to any standard visual evidence of tumor progression on scans, 315 patients were randomized 1:1 to either switch their aromatase inhibitor to Etcamah while continuing their CDK4/6 inhibitor, or remain on their baseline aromatase inhibitor regimen. Switching to Etcamah demonstrated a statistically significant and clinically meaningful benefit, yielding a median PFS of 16.0 months compared to 9.2 months in the control arm. This represented a 56% reduction in the risk of disease progression or death (HR 0.44; p < 0.0001). Time to second disease progression (PFS2) was significantly prolonged (25.7 months vs. 19.1 months), and the median time to deterioration in patient-reported global health status and quality of life was substantially delayed (21.0 months vs. 6.4 months; HR 0.54). The Etcamah combination was generally manageable, with primary toxicities including hematologic adverse events (neutropenia, leukopenia), mild-to-moderate visual disturbances (photopsia), and low-grade sinus bradycardia.

Sources: AstraZeneca press release, Etcamah label

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Clinical Trial Data

Roivant - Mosliciguat (inhaled sGC activator) / Phase 2 (PH-ILD)

On September 8, 2026, Roivant reported positive top-line results from its Phase 2 PHocus trial evaluating mosliciguat, a first-in-class, once-daily inhaled soluble guanylate cyclase (sGC) activator, for patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition where severe parenchymal inflammation, capillary loss, and hypoxia elevate pulmonary vascular resistance (PVR) and strain the right ventricle. While standard management relies primarily on supportive measures and inhaled treprostinil to target well-ventilated tissue without exacerbating ventilation-perfusion mismatch, mosliciguat offers a distinct mechanism as a once-daily, inhaled dry-powder soluble guanylate cyclase (sGC) activator. Unlike traditional sGC stimulators that depend on nitric oxide and unoxidized heme iron, mosliciguat directly restores cGMP signaling even under severe oxidative stress, delivering localized pulmonary vasodilation, anti-fibrotic effects, and anti-inflammatory benefits while mitigating systemic off-target hypotension.

In the global Phase 2 PHocus trial enrolling 135 patients with WHO Group 3 PH-ILD, mosliciguat met its primary endpoint with high statistical significance (p < 0.0001), driving a -56.3% placebo-adjusted PVR reduction that exceeded Roivant’s >20% internal target and represents one of the largest hemodynamic improvements ever reported in a randomized pulmonary hypertension trial. This translated into robust, durable functional and biomarker benefits, including placebo-adjusted improvements in 6MWD (+35.2m at Week 16; +52.7m at Week 24) and substantial NT-proBNP reductions (-53.2% at Week 16; -75.9% at Week 24). Crucially, mosliciguat demonstrated a favorable safety profile with fewer cough events than placebo (12.1% vs. 18.2%), successfully bypassing the primary tolerability bottleneck and heavy dosing burden of current standard-of-care inhaled prostacyclins to position itself as a compelling once-daily, best-in-class therapy.

Roivant (via subsidiary Pulmovant) has already initiated the global Phase 3 PHrontier trial evaluating once-daily mosliciguat in ~375 patients with PH-ILD. Roivant is running a small Phase 2 combination study alongside treprostinil and evaluating pipeline expansion into Group 1 Pulmonary Arterial Hypertension (PAH), supported by the extreme magnitude of PVR lowering observed in this trial.

Sources: Roivant press release, Roivant slide deck

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Compass Pathways - COMP360 (synthetic psilocybin) / Phase 3 (TRD)

On September 9, 2026, Compass Pathways reported positive 52-week topline data from the open-label extension (Part C) of its pivotal Phase 3 COMP005 trial evaluating COMP360, a synthetic formulation of psilocybin, for adult patients with treatment-resistant depression (TRD).

Treatment-resistant depression (TRD) is a refractory condition driven by chronic monoaminergic dysregulation, impaired neuroplasticity, and default mode network (DMN) hyperactivity, where standard management requires escalating failed oral antidepressant monotherapies to atypical antipsychotic augmentation, dual-mechanism agents, or interventional options like intranasal Spravato (esketamine), rTMS, and ECT. As an innovative interventional candidate, COMP360 is a synthetic crystalline formulation of psilocybin that functions as a prodrug for psilocin, a serotonin 5-HT2A receptor agonist. By binding to cortical pyramidal neurons, COMP360 alters glutamatergic signaling and transiently disrupts hyperactive DMN circuits associated with depressive rumination, triggering rapid neuroplasticity and dendritic remodeling that promote sustained cognitive flexibility when combined with psychological support.

In the 52-week open-label extension (Part C) of the pivotal Phase 3 COMP005 trial, roughly 180 treatment-resistant depression (TRD) patients evaluated the long-term effects of open-label single 25 mg doses of COMP360. Patients initially assigned to the 25 mg arm who received supplemental dosing achieved an average 13-point reduction in MADRS score from baseline at Week 52, while placebo crossover patients achieved a mean 10-point reduction. Across Part C participants, response rates stabilized between 40% and 45% with remission rates reaching ~30%, accompanied by a favorable safety profile dominated by transient, mild-to-moderate dosing-day events and no new safety signals. By maintaining durable efficacy out to one year through occasional re-dosing, COMP360 validates an episodic, high-durability interventional model that addresses the chronic relapse pattern of refractory TRD without requiring daily antidepressant maintenance.

Compass Pathways has initiated a rolling New Drug Application (NDA) submission to the FDA, with completion expected in 4Q 2026. The program holds Breakthrough Therapy designation and a Commissioner’s National Priority Voucher. Compass is targeting a U.S. commercial launch in the first half of 2027, pending FDA approval and subsequent DEA Schedule I reclassification. Parallel Phase 3 data from the 581-patient COMP006 trial (evaluating a two-dose regimen) will further bolster the registration package.

Sources: Compass Pathways press release

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Disc Medicine - DISC-3405 (Anti-TMPRSS6 mAb) / Phase 2 (PV)

On September 9, 2026, Disc Medicine reported positive interim Phase 1b/2 data for DISC-3405, an anti-TMPRSS6 monoclonal antibody, in patients with polycythemia vera (PV) requiring frequent phlebotomies.

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm driven by constitutive JAK-STAT activation via JAK2 mutations, leading to red blood cell hyperproliferation, increased blood viscosity, elevated thrombotic risk, and heavy reliance on therapeutic phlebotomy and cytoreductive therapies to maintain hematocrit below 45%. Targeting this pathologically elevated erythropoiesis at its metabolic root, DISC-3405 is a fully humanized monoclonal antibody designed to inhibit TMPRSS6, a negative regulator of hepcidin in hepatocytes. By neutralizing TMPRSS6, DISC-3405 upregulates endogenous hepcidin to downregulate ferroportin, restricting intestinal iron absorption and sequestering storage iron to limit systemic iron availability, thereby suppressing aberrant red blood cell production without forcing patients into chronic, symptom-heavy iron deficiency.

In a Phase 1b/2 trial evaluating adult patients with polycythemia vera (PV) requiring frequent therapeutic phlebotomies to maintain target hematocrit levels below 45%, DISC-3405 achieved a 77.8% phlebotomy-freedom rate (7 of 9) during its first maintenance period (Weeks 12 to 32). This performance aligns closely with established benchmarks like Protagonist and Takeda’s rusfertide (73% at Week 32) and is backed by dose-dependent increases in endogenous hepcidin alongside sustained reductions in serum iron and transferrin saturation. DISC-3405 was well tolerated with no dose-limiting toxicities, validating monoclonal antibody-mediated TMPRSS6 inhibition as an effective upstream mechanism to control hematocrit without driving chronic iron deficiency. Beyond replacing invasive phlebotomies and mitigating severe hematocrit fluctuations, DISC-3405 offers a potential dosing regimen advantage over weekly synthetic peptide mimetics, paving the way for monthly or quarterly subcutaneous administration that could significantly enhance long-term patient convenience and adherence.

Disc Medicine is expanding the trial to optimize dosing intervals and evaluate longer-term durability and patient-reported outcomes (e.g., reduction in iron deficiency symptoms and fatigue). Planning is underway for a randomized, pivotal Phase 2b/3 trial in polycythemia vera to establish registration-enabling data against placebo or standard cytoreductive/phlebotomy control.

Sources: Disc Medicine press release, Disc Medicine slide deck

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Beam - BEAM-302 (A>G PiZ ABE) / Phase 1/2 (AATD)

On September 8, 2026, Beam Therapeutics reported Phase 1/2 results 29 efficacy-evaluable patients (across 38 total dosed) in the Phase 1/2 trial evaluating BEAM-302, an in vivo LNP-delivered adenine base editor targeting the PiZ allele in alpha-1 antitrypsin deficiency (AATD). These results were presented in a late-breaking oral presentation at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain.

Alpha-1 antitrypsin deficiency (AATD) is a severe genetic disorder caused by homozygous PiZZ mutations in the SERPINA1 gene, leading to misfolded Z-AAT protein polymerization in hepatocytes that drives progressive cirrhosis, while the concomitant lack of circulating AAT leaves lungs vulnerable to uninhibited neutrophil elastase cleavage and early emphysema. Existing care relies on symptomatic support, liver monitoring, and lifelong weekly intravenous plasma AAT infusions that slow lung decline without addressing underlying liver damage. Targeting this dual-organ pathology at its genetic source, BEAM-302 is an in vivo LNP-formulated adenine base editor that delivers a precise Adenine-to-Guanine correction directly in hepatocytes to convert the mutant PiZ allele to functional M-AAT. By directly editing the genome in situ, BEAM-302 simultaneously clears toxic hepatic Z-AAT polymer buildup to halt liver disease progression and permanently restores endogenous production of protective M-AAT to shield pulmonary tissue from elastase destruction.

In an open-label Phase 1/2 trial evaluating adult PiZZ AATD patients across lung (Part A) and liver (Part B) cohorts, a single infusion of BEAM-302 achieved its optimal biological dose at 60 mg, driving durable steady-state total circulating AAT levels to 14.4 µM and 13.5 µM respectively, well above the 11 µM protective threshold out to 12-18 months. Functional M-AAT comprised 93-94% of total AAT (retaining normal endogenous inducible regulation during acute infections) while toxic mutant Z-AAT and circulating Z-polymers were reduced by 84%. Accompanied by a favorable safety profile characterized by transient, mild-to-moderate infusion reactions and self-resolving liver enzyme elevations, BEAM-302 validates in vivo base editing as a transformative, single-dose dual-organ therapy that simultaneously resolves toxic hepatic protein accumulation and permanently restores pulmonary elastase protection to overcome the limitations of lifelong weekly augmentation.

Beam has initiated dosing in its global pivotal expansion cohort utilizing the 60 mg dose. Supported by FDA feedback, RMAT, and Orphan Drug designations, Beam is pursuing a U.S. accelerated approval pathway utilizing 12-month circulating AAT biomarker data as the surrogate registration endpoint.

Sources: Beam press release, Beam ERS 2026 slide deck

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Inhibrx - INBRX-106 (hexavalent OX40 agonist) / Phase 2 (HNSCC)

On September 8, 2026, Inhibrx reported positive randomized Phase 2 data from its HexAgon trial evaluating INBRX-106, a novel hexavalent OX40 agonist, in combination with Keytruda (pembrolizumab) versus Keytruda monotherapy in first-line, PD-L1–positive (CPS ≥20) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Head and neck squamous cell carcinoma (HNSCC) arises from mucosal epithelium driven by carcinogen exposure or high-risk HPV infection, with first-line recurrent or metastatic disease relying on PD-1 checkpoint inhibitors like pembrolizumab to overcome tumor-mediated immune evasion. Addressing the modest response rates of PD-1 monotherapy, INBRX-106 is an engineered hexavalent OX40 agonist designed to drive dense OX40 receptor clustering on T cells without relying on Fc-gamma receptor cross-linking. By potently triggering downstream NF-κB signaling, INBRX-106 enhances effector T-cell proliferation and cytotoxicity while suppressing regulatory T cells, acting as an immune accelerator that complements PD-1 inhibition to generate deeper, more durable anti-tumor responses.

In the Phase 2 HexAgon trial evaluating first-line PD-L1–positive (CPS ≥20) metastatic or unresectable recurrent HNSCC, adding the hexavalent OX40 agonist INBRX-106 to pembrolizumab nearly doubled confirmed objective response rates compared to pembrolizumab monotherapy (48.3% vs. 26.5%), driven by a 13.8% complete response rate (vs. 0%) and a extended 6-month PFS rate (72.4% vs. 42.8%, median 9.6 vs. 4.9 months). These clinical benefits were hyper-pronounced in the HPV-positive cohort, achieving an 80.0% response rate, 30.0% CR rate, and 90.0% 6-month PFS, alongside a manageable safety profile dominated by low-grade toxicities that avoided historic co-stimulatory safety bottlenecks. By demonstrating that potent, Fc-independent receptor clustering can deepen responses and extend durability over PD-1 monotherapy alone, INBRX-106 delivers the first definitive randomized proof-of-concept for OX40 co-stimulation in solid tumors.

Inhibrx is expanding the Phase 2 HexAgon trial by approximately 50 additional HPV-positive OPSCC patients (CPS ≥1) to refine the efficacy signal and build a registration package. The company plans to leverage the HPV+ expansion cohort to seek an FDA accelerated approval pathway, followed by a Phase 3 confirmatory trial. Inhibrx is expanding INBRX-106 evaluation into additional immunogenic tumor types, including a Phase 1/2 trial in perioperative non-small cell lung cancer (NSCLC), and exploring combinations with therapeutic cancer vaccines.

Sources: Inhibrx press release, Inhibrx slide deck

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Novo Nordisk - Wegovy (GLP1 agonist) / Phase 3 (obesity age 6-12)

On September 7, 2026, Novo Nordisk reported positive topline Phase 3 data from the STEP Young trial evaluating once-weekly subcutaneous semaglutide (Wegovy) in children aged 6 to under 12 living with obesity.

Pediatric obesity in children aged 6 to 12 is a chronic metabolic disease driven by genetic susceptibility, environmental factors, and central neuroendocrine dysregulation of appetite signaling, which promotes systemic inflammation, insulin resistance, and long-term cardiometabolic risk. Standard of care relies on family-based lifestyle interventions that often yield limited long-term efficacy in severe cases, leaving a major therapeutic gap due to the absence of approved broad pharmacotherapies in this age group. Addressing this neuroendocrine dysregulation, semaglutide is a long-acting GLP-1 receptor agonist that selectively activates GLP-1 receptors in the hypothalamus and hindbrain. By increasing central satiety signaling and delaying gastric emptying, semaglutide counters pediatric hyperphagia to drive sustained reductions in caloric intake and body weight.

In the STEP Young Phase 3 trial evaluating 165 children aged 6 to under 12 years with obesity, over 85% of whom had severe Class II or Class III disease, once-weekly semaglutide met its primary endpoint, delivering a statistically significant reduction in percentage BMI at Week 68 compared to placebo. Treatment enabled 40.4% of children to achieve a BMI below the obesity threshold (versus 0% on placebo), while maintaining a safety profile consistent with older populations, dominated by manageable gastrointestinal events, with no adverse impacts on linear growth, skeletal maturation, or pubertal development. By moving over 40% of pediatric patients out of the obesity classification, Wegovy demonstrates potential to alter early disease trajectories, addressing a critical therapeutic gap where lifestyle modification alone frequently fails to manage severe childhood obesity.

Novo Nordisk plans to present full trial data, including exact mean BMI percentage reductions and cardiometabolic biomarker changes, at ObesityWeek 2026. Novo Nordisk plans to use the STEP Young data to support regulatory applications to global health authorities (including the U.S. FDA and European Medicines Agency) seeking approval to expand Wegovy’s indication down to age 6.

Sources: Novo Nordisk press release

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Sanofi - Lunsekimig (IL13 x TSLP bs nanobody) / Phase 2b (asthma; CRSwNP)

Sanofi reported positive detailed Phase 2b data for lunsekimig (SAR443765), an investigational bispecific nanobody targeting interleukin-13 (IL-13) and thymic stromal lymphopoietin (TSLP). The full dataset evaluated patients with moderate-to-severe asthma and concurrent chronic rhinosinusitis with nasal polyps (CRSwNP), demonstrating statistically significant improvements in asthma exacerbations and nasal polyp severity over placebo.

Severe asthma with comorbid chronic rhinosinusitis with nasal polyps (CRSwNP) is a unified mucosal Type 2 (T2) inflammatory disorder driven by upstream epithelial alarmins like TSLP and downstream cytokines such as IL-13, which fuel tissue eosinophilia, bronchial remodeling, and sinonasal polyp growth. While current standard of care relies on inhaled/intranasal corticosteroids, surgery, and single-target biologics, many patients remain inadequately controlled. Addressing this dual-pathway inflammatory cascade, lunsekimig is a humanized bispecific nanobody designed to simultaneously bind and neutralize both TSLP and IL-13. By suppressing the upstream master alarmin trigger alongside a primary downstream effector cytokine, lunsekimig provides a dual-pathway blockade engineered to achieve deeper disease control than single-cytokine inhibitors across both the upper and lower airways.

In a Phase 2b trial evaluating adult patients with moderate-to-severe asthma and comorbid CRSwNP, lunsekimig achieved a statistically significant, dose-dependent reduction in the annualized rate of asthma exacerbations compared to placebo alongside parallel gains in FEV1 and inflammatory biomarkers. At Week 24, lunsekimig demonstrated a statistically significant 1.5-point mean improvement in Nasal Polyp Score compared to placebo (P<0.0001), maintaining a favorable safety profile with adverse event rates comparable to placebo and no novel safety signals. By delivering robust, simultaneous efficacy across both lower and upper airway domains, lunsekimig validates the dual upstream/downstream targeting of TSLP and IL-13 as a potential best-in-class biologic strategy for complex Type 2-driven respiratory disease over single-target therapies.

Sanofi plans to advance lunsekimig into Phase 3 clinical development for severe asthma and CRSwNP based on the Phase 2b dose-finding and efficacy data. Evaluation of lunsekimig across other Type 2 inflammatory conditions (such as atopic dermatitis or eosinophilic esophagitis) remains under strategic exploration.

Sources: Endpoints article

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AstraZeneca - Tozorakimab (anti-IL33 mAb) / Phase 3 (COPD)

AstraZeneca announced positive full Phase 3 data from the landmark trial evaluating tozorakimab (formerly MEDI3506), a novel humanized anti-interleukin-33 (IL-33) monoclonal antibody, in patients with chronic obstructive pulmonary disease (COPD). Published in The New England Journal of Medicine (NEJM), the full results demonstrate that targeting IL-33 significantly reduces the rate of moderate-to-severe exacerbations in the primary study population of former smokers.

Chronic obstructive pulmonary disease (COPD) is a progressive, heterogeneous lung disease caused by chronic inhalation of noxious particles, driving neutrophilic and Type 2 mucosal inflammation that leads to persistent airflow limitation, emphysematous tissue destruction, and recurrent exacerbations that accelerate lung decline. While standard management relies on combination inhaled therapies (LAMA/LABA/ICS) and selective biologics for high-eosinophil phenotypes, many patients continue to experience frequent exacerbations despite maximal therapy. Addressing this broader inflammatory driver, tozorakimab is a high-affinity anti-IL-33 monoclonal antibody designed to neutralize the upstream epithelial alarmin IL-33, preventing its signaling through both ST2 and non-ST2 co-receptors. By simultaneously suppressing ST2-dependent eosinophilic and ST2-independent neutrophilic pathways, tozorakimab reduces epithelial remodeling, mucus hypersecretion, and airway inflammation across diverse COPD phenotypes.

In a Phase 3 trial evaluating patients with moderate-to-severe COPD on background inhaled maintenance therapy, tozorakimab demonstrated a statistically significant 29% reduction in the annualized rate of moderate-to-severe exacerbations in the primary population of former smokers (1.34 vs. 1.90 events, P < 0.001), alongside parallel improvements in lung function (FEV₁) and symptom burden over 52 weeks. Treatment was well-tolerated with an adverse event profile comparable to placebo and no increased risk of severe systemic infections. These findings establish upstream anti-IL-33 alarmin blockade as a clinically validated, disease-modifying approach in COPD, proving that inhibiting both eosinophilic and non-eosinophilic/neutrophilic inflammatory cascades can successfully lower exacerbation risk in former smokers who represent the majority of real-world patients.

AstraZeneca is preparing global regulatory filings with the U.S. FDA, EMA, and other health authorities based on the Phase 3 data package. Ongoing post-hoc analyses will further define efficacy profiles across baseline blood eosinophil counts, smoking history subgroups, and co-morbidities. Tozorakimab remains in development across additional high-unmet-need inflammatory pulmonary conditions, including severe asthma and viral-induced lung injury.

Sources: AstraZeneca press release, Sciurba et al., NEJM (2026)

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Upstream Bio - Verekitug (TSLP inhibitor) / Phase 2 (asthma)

On September 8, 2026, Upstream Bio reported positive detailed Phase 2 data evaluating verekitug (UPB-101), a novel, long-acting monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP) receptor, in patients with severe asthma. The readout demonstrated deep, sustained reductions in fractional exhaled nitric oxide (FeNO), a critical biomarker of Type 2 airway inflammation, supporting verekitug’s potential for extended dosing intervals.

Asthma is a chronic, heterogeneous inflammatory airway disease triggered by environmental insults that induce epithelial alarmins to drive Type 2 (T_H2) cascades, resulting in eosinophilia, elevated FeNO, bronchial hyperresponsiveness, and recurrent exacerbations. Standard of care employs stepwise inhaled corticosteroids (ICS) combined with long-acting beta-agonists (LABA), with targeted biologics reserved for severe, uncontrolled disease. Addressing the broad upstream driver of this airway cascade, verekitug is a high-affinity humanized monoclonal antibody designed to block the TSLP receptor (TSLPR). By suppressing TSLP signaling at the top of the inflammatory hierarchy, verekitug inhibits downstream T_H2 cytokines (IL-4, IL-5, IL-13) and non-Type 2 drivers, while its extended half-life enables potent, durable inhibition of airway inflammation across infrequent dosing intervals.

In a Phase 2 trial evaluating adult patients with severe, uncontrolled asthma across diverse inflammatory phenotypes, verekitug achieved statistically significant, deep, and progressive reductions in placebo-adjusted fractional exhaled nitric oxide (FeNO), delivering a -12.2 ppb reduction at Week 24 that deepened to -26.3 ppb at Week 60. The therapy was well tolerated through 60 weeks with an adverse event profile comparable to placebo and no novel safety signals. While approved biologics like tezepelumab validate upstream alarmin inhibition but require dosing every 2 to 4 weeks, verekitug’s ability to drive sustained biomarker suppression supports extended-interval administration (e.g., quarterly or semi-annually), offering a potentially best-in-class regimen that significantly lowers treatment burden and improves patient compliance without compromising disease control.

Upstream Bio plans to initiate its Phase 3 registrational program for verekitug in severe asthma in 1Q 2027. The company is also evaluating verekitug across other TSLP-driven inflammatory indications, including chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic obstructive pulmonary disease (COPD).

Sources: Upstream Bio press release

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Pharvaris - Deucrictibant (bradykinin B2 receptor antagonist) / Phase 3 (HAE)

On September 8, 2026, Pharvaris announced positive topline Phase 3 data evaluating deucrictibant, its novel, orally administered small-molecule bradykinin B2 receptor antagonist, for the prophylactic treatment of hereditary angioedema (HAE).

Hereditary angioedema (HAE) is a rare genetic disorder marked by C1 esterase inhibitor deficiency or dysfunction, leading to excessive bradykinin generation that binds endothelial B2 receptors and triggers severe, life-threatening tissue swelling across the skin, abdomen, and upper airway. While standard long-term prophylaxis relies on plasma-derived C1-INH concentrates, subcutaneous biologics like lanadelumab, or oral kallikrein inhibitors, managing attack prevention often requires balancing route of administration against clinical potency. Addressing the terminal pathway of this cascade, deucrictibant is a potent, orally bioavailable B2 receptor antagonist that competitively blocks bradykinin from binding to vascular endothelial B2 receptors. By directly inhibiting this final common receptor target, deucrictibant prevents vascular permeability and plasma extravasation, offering a targeted oral approach for both acute management and continuous long-term prophylaxis.

In a Phase 3 trial evaluating adolescent and adult patients with Type I or Type II Hereditary Angioedema, deucrictibant achieved its primary endpoint by driving a statistically significant 85% reduction in mean monthly attack rates compared to placebo (P<0.0001). The therapy was well-tolerated with an adverse event profile comparable to placebo, demonstrating no signals of liver toxicity, serious treatment-related adverse events, or drug-related discontinuations. By delivering an 85% reduction in attack frequency through an oral route, deucrictibant matches the efficacy benchmarks of top-tier injectable biologics like subcutaneous lanadelumab while eliminating injection-site burden, effectively breaking the historical trade-off between oral convenience and high-potency prophylactic protection for HAE patients.

Pharvaris plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and parallel global marketing applications in 1H 2027. In addition to its prophylactic oral formulation, Pharvaris continues to advance deucrictibant as an on-demand oral treatment for acute HAE attacks, aiming to offer an all-oral franchise for both prevention and acute care.

Sources: Pharvaris press release, Pharvaris slide deck

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Table of Contents

This week, we discuss:

• China Biotech

  • China Biotech Financing Outpaces Rest of World by Nearly Three-Fold ⬇️

  • FDA Enhances Stricter Scrutiny of Foreign Data Amid China Biotech Competition ⬇️

  • Summit & Akeso - Ivonescimab (PD1 x VEGF mAb) / Phase 3 (1L PDL1+ NSCLC) ⬇️

• Acquisitions

  • Eli Lilly to Acquire Merida ⬇️

• Approvals

  • Ionis - Zanvastro (GFAP ASO) / Approved (Alexander disease) ⬇️

  • Takeda & Protagonist - Mimrylo (hepcidin mimetic) / Approved (PV) ⬇️

• Clinical Trial Data

  • RevMed - Daraxonrasib (pan-RAS inhibitor) / Phase 1/2 (RASm NSCLC) ⬇️

  • Teva - TEV-’408 (anti-IL15 mAb) / Phase 2a (celiac) ⬇️

  • AbbVie - Etentamig (BMCA x CD3 TCE) / Phase 3 (3L MM) ⬇️

  • GSK - FLUm3HA-3NA (mRNA vaccine) / Phase 2 (influenza) ⬇️

  • Jazz Pharma - Ziihera (HER2 mAb) / Phase 3 (1L HER2+ GEA) ⬇️

  • AstraZeneca - Orpathys (MET inhibitor) / Phase 3 (1L MET-oe EGFR+ NSCLC) ⬇️

  • Novartis - Remibrutinib (BTK inhibitor) / Phase 3 (RMS) ⬇️

China Biotech

Wondering why we discuss China Biotech every week? Tap here to learn more.

China Biotech Financing Outpaces Rest of World by Nearly Three-Fold

for the week ending September 4, 2026

Excluding Eli Lilly’s acquisition agreement with Merida, China Biotech financing outpaced rest-of-world (ROW) biotech financing this week by nearly three-fold ($337 million China versus $128 million ROW). Notable transactions on the China Biotech side included three licensing agreements and a Series B equity raise:

• Roche-Simcere licensing agreement ($75 million upfront): Roche acquired exclusive global rights to develop, manufacture, and commercialize SIM0660 for $75 million upfront and up to $1.53 billion in milestones plus tiered royalties. SIM0660 is an off-the-shelf, trispecific T-cell engager that pairs a low-affinity CD3-binding domain with dual-binding arms targeting CD19 and CD79a on B cells to induce targeted cytotoxicity while limiting cytokine release syndrome (CRS). SIM0660 is an investigational agent designed for B-cell malignancies and auto-antibody-driven autoimmune diseases (e.g., lupus, rheumatoid arthritis), potentially providing broad depletion of pathogenic B-cell lineages. Sources: Simcere press release

• GSK-Hutchmed licensing agreement ($110 million upfront): GSK secured exclusive ex-China global development and commercialization rights to HMPL-A830 for $110 million upfront and up to $1.295 billion in milestone payments, with HUTCHMED leading the Phase 1 trial before handing off international late-stage development. HMPL-A830 is an antibody-targeted therapy conjugate (ATTC) that pairs an anti-EGFR monoclonal antibody with a conjugated small-molecule KRAS inhibitor payload. HMPL-A830 is an investigational agent designed for KRAS-mutated solid tumors, primarily colorectal, pancreatic, and non-small cell lung cancers. Sources: Hutchmed press release

• Menarini-Gan & Lee licensing agreement ($72 million upfront): Menarini paid €62 million ($72 million) upfront in a deal worth up to $771 million to secure exclusive development and commercialization rights to bofanglutide across 39 European and neighboring territories, while Gan & Lee retains rights for North America, China, and other global regions. Bofanglutide (GZR18) is an investigational, long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) engineered for an extended half-life, enabling a convenient once-every-two-weeks (Q2W) subcutaneous dosing schedule. The drug is an investigational agent being developed for chronic weight management in adults with obesity or overweight conditions, type 2 diabetes mellitus, and associated metabolic disorders. Sources: Menari press release

• NeuShen Therapeutics Series B ($80 million): NeuShen Therapeutics (based in Shanghai and Boston) closed an oversubscribed $80 million Series B round to advance laviclidine and two additional clinical-stage CNS pipeline programs into an international multi-center Phase 1/2 clinical trial. Their lead program is laviclidine (NS-136), a proprietary, highly selective positive allosteric modulator (PAM) of the muscarinic acetylcholine receptor M4. The company has at least three other investigational programs in development for central nervous system (CNS) disorders, primarily schizophrenia and neurodegenerative-associated psychosis. Sources: Endpoints article

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FDA Enhances Stricter Scrutiny of Foreign Data Amid China Biotech Competition

On September 2, 2026, FDA published updated Good Clinical Practice (GCP) requirements that apply universally regardless of geography. If the FDA cannot validate trial data or access sites to audit records, it reserves the authority to refuse or rescind marketing approvals. The FDA cited heightened data integrity concerns (including risks of unvalidated participants or unverified adverse event reporting) as rationale for increased foreign site auditing. Early Feasibility Studies, Phase 1 trials, and foreign studies conducted outside of an Investigational New Drug (IND) or Investigational Device Exemption (IDE) application face the highest level of review. While House Republicans have pushed for an outright ban on un-audited China-based trial data, FDA leadership noted potential legal and public health issues with geography-based bans, choosing instead to focus purely on data quality and site inspectability. Specific FDA actions include:

• Expanded Inspections: Increasing foreign Bioresearch Monitoring (BIMO) resources, including doubling inspectors in China, to target early-stage trials.

• Reviewer Training: Training medical product reviewers to spot GCP non-compliance, informed consent issues, and data integrity concerns.

• Public Transparency: Increasing public disclosure when foreign sites deny access or impose conditions on FDA inspections.

• Early Engagement: Encouraging sponsors to discuss foreign data provenance early in the pre-submission phase (e.g., pre-IND meetings).

Sources: Endpoints article, updated FDA GCP requirements

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Summit & Akeso - Ivonescimab (PD1 x VEGF mAb) / Phase 3 (1L PDL1+ NSCLC)

On September 2, 2026, Summit Therapeutics and Akeso announced topline overall survival (OS) data from the Phase 3 HARMONi-2 study evaluating ivonescimab (PD-1 x VEGF bispecific mAb) versus pembrolizumab (Keytruda) monotherapy in first-line PD-L1–positive advanced non-small cell lung cancer (NSCLC).

First-line PD-L1–positive non-small cell lung cancer (1L PDL1+ NSCLC) lacking driver mutations relies on tumor-expressed PD-L1 binding to T-cell PD-1 receptors, causing immune exhaustion and unchecked growth. The PD-L1 pathway can be treated with anti-PD-1 monotherapy for high expression (TPS ≥50%) or anti-PD-1 plus platinum-based chemotherapy for low-to-intermediate expression (TPS 1–49%). Addressing this axis, ivonescimab (SMT112/AK112) is a tetravalent bispecific antibody engineered to simultaneously target PD-1 and vascular endothelial growth factor (VEGF) with cooperative binding dynamics in the tumor microenvironment. By dual-blocking checkpoint-mediated immunosuppression and VEGF-driven angiogenesis within a single molecule, ivonescimab is designed to synergistically reactivate anti-tumor immune responses while disrupting tumor blood vessel formation to enhance therapeutic efficacy over selective PD-1 blockade alone.

The Phase 3 HARMONi-2 China-only trial that enrolled 398 patients with 1L PD-L1–positive (TPS ≥ 1%) advanced non-small cell lung cancer lacking EGFR/ALK mutations. Building on previously reported data where ivonescimab nearly doubled median progression-free survival (11.14 vs. 5.82 months; HR = 0.51, p < 0.0001), the trial met its prespecified interim analysis endpoint by demonstrating a statistically significant and clinically meaningful overall survival (OS) advantage over pembrolizumab. Summit & Akeso are scheduled to present full overall survival data, subgroup analyses, and extended safety cutoffs at the World Conference on Lung Cancer (WCLC) in Seoul, South Korea. Their oral presentation in the “OA14: The Breakthrough” session will take place on Tuesday, September 15, 2026 at 1:02–1:12 PM KST (September 15) / 12:02–12:12 AM EDT (September 15). Summit Therapeutics is conducting the global Phase 3 HARMONi-7 study (evaluating ivonescimab vs. pembrolizumab in PD-L1 high-expressing 1L NSCLC) and HARMONi-3 (ivonescimab + chemo vs. pembrolizumab + chemo) to replicate these findings in Western patient populations for FDA registration. Summit holds a PDUFA target date of November 14, 2026, for ivonescimab plus chemotherapy in post-EGFR-TKI advanced NSCLC based on global HARMONi data.

Sources: Summit press release, Akeso press release, ApexOnco article

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Acquisitions

Approvals

Ionis - Zanvastro (GFAP ASO) / Approved (Alexander disease)

On September 3, 2026, the FDA approved Zanvastro (zilganersen) as the first disease-modifying treatment for pediatric and adult patients living with Alexander disease (AxD), spanning from infancy through adulthood. Alexander disease is an extremely rare disorder that is caused by gain-of-function mutations in the GFAP gene (encodes glial fibrillary acidic protein) that drives abnormal GFAP accumulation inside astrocytes (called Rosenthal fibers), leading to myelin sheath degradation and potentially life-threatening neurological decline (macrocephaly, severe developmental delays, seizures, spasticity, speech impairment, gait ataxia, palatal tremor, and muscle stiffness). Zanvastro (zilganersen, formerly ION373) is an antisense oligonucleotide (ASO) administered as a 50 mg intrathecal bolus injection once every 12 weeks (quarterly). By binding directly to target GFAP mRNA, it inhibits the overproduction and toxic intracellular accumulation of glial fibrillary acidic protein (GFAP) in astrocytes, the structural hallmark driving astrocyte dysfunction, myelin destruction, and neurodegeneration in AxD.

The regulatory approval of Zanvastro was primarily underpinned by data from a landmark, multicenter Phase 1-3 trial (NCT04849741) evaluating 54 pediatric and adult patients aged 1.5 to 53 years with genetically confirmed Alexander disease. The trial met its primary endpoint in patients aged 5 years and older with measurable baseline walking deficits. At Week 61, patients receiving the recommended 50 mg dose demonstrated a statistically significant and clinically meaningful stabilization in walking ability on the 10-Meter Walk Test compared to the control group, achieving a 33.3% least-squares mean difference (p = 0.0412). Since gait speed is not a reliable metric in very young children, pediatric patients aged 2 to 4 years were assessed using the Gross Motor Function Measure-88 (GMFM-88). Zanvastro-treated children demonstrated marked motor improvements (including standing, running, and jumping capabilities) yielding an LS mean difference of 22.9 points over control patients, who experienced progressive functional decline (p = 0.034). To support approval across the full age spectrum down to infants under 2 years, the FDA integrated safety and pharmacokinetic modeling showing systemic and intrathecal drug exposures in infants comparable to those observed in older pediatric cohorts. Exploratory biomarker analyses corroborated these functional gains, demonstrating a 33.6% reduction in plasma GFAP levels by Week 61. Zanvastro exhibited a favorable safety profile. Most treatment-emergent adverse events were mild to moderate, most commonly including post-lumbar puncture syndrome, back pain, headache, vomiting, and cough. Notably, serious adverse events occurred less frequently in the Zanvastro group (37.5%) than in the control arm (47.1%), reflecting the drug’s capacity to alter underlying disease progression. Prescribing guidelines include warnings for rare events of aseptic meningitis associated with intrathecal administration, requiring clinical vigilance following injections.

Ionis owns worldwide rights to Zanvastro, making this its first independent launch in its rare disease neurology portfolio. The therapy carries a list price of $285,000 per dose (or $1.14 million annually). Commercial launch efforts are initially focusing on transitioning patients already receiving the drug via the open-label extension of its pivotal trial and an active Expanded Access Program (EAP) into commercial coverage.

Sources: Ionis press release, Ionis slide deck, new Zanvastro label

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Takeda & Protagonist - Mimrylo (hepcidin mimetic) / Approved (PV)

On August 28, 2026, the FDA approved Mimrylo (rusfertide) to treat erythrocytosis in adult patients with polycythemia vera (PV), a rare blood cancer caused by mutations in the JAK2 gene that results in overproduction of red blood cells by the bone marrow. The primary clinical concern for patients with PV is hyperviscosity (thick blood), which significantly increases the risk of potentially life-threatening arterial and venous thrombotic events (strokes, heart attacks, deep vein thrombosis, pulmonary embolism). Mimrylo is a first-in-class, weekly subcutaneously injected peptide that mimics hepcidin. By binding to ferroportin, it restricts systemically available iron to regulate red blood cell production, maintaining hematocrit levels below 45% without causing severe systemic iron deficiency. Originally discovered by Protagonist Therapeutics (as PTG-300), the asset is commercialized by Takeda. Under their collaboration agreement, Takeda and Protagonist execute a 50:50 profit-and-loss split for U.S. sales, while Protagonist did not share in development costs.

The approval of Mimrylo was supported by global, pivotal Phase 3 trial data from the VERIFY study, which evaluated 293 adult patients with PV who were phlebotomy-dependent despite receiving standard-of-care cytoreductive therapies or phlebotomy alone. Patients were randomized 1:1 to receive either weekly subcutaneous Mimrylo or a placebo, both added to their existing background therapy. The trial met its primary endpoint with high statistical significance. During the double-blind evaluation window (Weeks 20 to 32), 76.9% of patients receiving Mimrylo achieved a clinical response (defined as maintaining hematocrit <45% without needing therapeutic phlebotomy), compared to only 32.9% of patients in the placebo arm (p < 0.0001). Across the initial 32-week period, Mimrylo-treated patients required an average of only 0.5 phlebotomies compared to 1.8 phlebotomies in the placebo group. Furthermore, 62.6% of Mimrylo patients maintained tight hematocrit control below 45%, compared to 14.4% on placebo. Long-term extension data confirmed durable efficacy. Among initial responders, 84.1% maintained response through Week 52. When placebo patients crossed over to Mimrylo at Week 32, 77.9% subsequently achieved response status between Weeks 40 and 52. Secondary endpoints measuring patient-reported outcomes demonstrated meaningful improvements in fatigue scores via the PROMIS Fatigue SF-8a. Mimrylo demonstrated a manageable safety profile. The most common treatment-emergent adverse events were Grade 1/2 injection-site reactions (56% vs 33% placebo) and mild anemia (16% vs 4.1% placebo). Prescribing warnings include potential risk of new or worsening thrombocytosis, requiring periodic platelet monitoring.

Sources: Protagonist press release, Protagonist slide deck, Takeda press release, new Mimrylo label

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Clinical Trial Data

RevMed - Daraxonrasib (pan-RAS inhibitor) / Phase 1/2 (RASm NSCLC)

While Revolution Medicines’ tri-complex RAS(ON) inhibitor daraxonrasib has recently secured FDA approval under the brand name Rasonque for previously treated metastatic pancreatic ductal adenocarcinoma (PDAC), its application in lung cancer remains strictly investigational. However, emerging Phase 1/2 data published in the New England Journal of Medicine suggests that the drug could have efficacy in RAS-mutant advanced non-small cell lung cancer (NSCLC).

RAS mutations (most commonly KRAS variants such as G12C, G12D, and G12V) drive roughly 30% of non-small cell lung cancers (NSCLC) by locking the RAS protein in an active, GTP-bound “ON” state that fuels tumor growth via hyperactivated downstream signaling. While frontline treatment relies on immune checkpoint inhibitors with or without platinum chemotherapy, second-line options remain limited: covalent KRAS(OFF) inhibitors like sotorasib target only the inactive G12C state, leaving patients with non-G12C variants to rely on modest single-agent docetaxel. Addressing this gap, daraxonrasib, an oral molecular glue approved for pancreatic cancer as Rasonque but still investigational in NSCLC, forms a tri-complex with cyclophilin A to bind active, GTP-bound RAS(ON) isoforms, potentially providing broad and sustained MAPK pathway suppression across major KRAS, NRAS, and HRAS mutations.

In the Phase 1/2 RMC-6236-001 trial evaluating 136 patients with advanced, previously treated RAS-mutant NSCLC, daraxonrasib demonstrated encouraging preliminary activity and a manageable safety profile. At the optimal 160-220 mg daily dose in docetaxel-naïve patients, this pan-RAS inhibitor achieved a confirmed objective response rate (ORR) of 42%, a disease control rate (DCR) of 89%, a median progression-free survival (mPFS) of 8.3 months, and a median overall survival (mOS) of 16.0 months, nearly tripling response rates and doubling progression-free survival (PFS) compared to historical docetaxel benchmarks on a cross-trial basis. Furthermore, the 160-220 mg dose proved manageable with a 25% rate of Grade ≥3 treatment-related adverse events and no Grade 4/5 toxicities (primarily presenting as manageable rash, diarrhea, and nausea) allowing high relative dose intensity (88%) while broadening targeted treatment options for the roughly 30% of NSCLC patients lacking driver-specific therapies.

Revolution Medicines is actively enrolling the global Phase 3 RASolve 301 trial (NCT06881784), evaluating daraxonrasib at the selected 200 mg daily dose versus docetaxel in second-line (2L) RAS-mutant NSCLC. The company is currently implementing routine skin and GI toxicity prophylaxis guidelines in ongoing trials to minimize Grade ≥3 rash and mucositis. The FDA approved daraxonrasib under the brand name Rasonque at 300 mg daily for previously treated metastatic pancreatic adenocarcinoma (PDAC). However, NSCLC remains an investigational indication pending Phase 3 readout.

Sources: Revolution Medicines press release, Arbour et al., NEJM (2026), Revolution Medicines slide deck

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Teva - TEV-’408 (anti-IL15 mAb) / Phase 2a (celiac)

On September 2, 2026, Teva Pharmaceuticals announced topline Phase 2a results for TEV-’408, its investigational anti-IL-15 monoclonal antibody, demonstrating first-in-class proof-of-concept for protecting the gut lining against gluten-induced injury in adults with celiac disease.

Celiac disease is a systemic autoimmune enteropathy triggered by gluten in genetically susceptible (HLA-DQ2/8) individuals, where deamidated gliadin peptides drive intraepithelial lymphocyte (IEL) activation, mucosal inflammation, villous atrophy, and malabsorption, requiring a strict, lifelong gluten-free diet as the sole standard of care. Addressing this non-dietary treatment void, TEV-’408 is an extended-half-life human monoclonal antibody that neutralizes interleukin-15 (IL-15), a master upstream cytokine in celiac pathophysiology. By blocking IL-15 signaling, TEV-’408 is designed to suppress the expansion and cytotoxicity of IELs to prevent mucosal injury and gut inflammation, potentially offering a targeted, long-acting disease-modifying approach.

In the Phase 2a trial of 50 adults with celiac disease on a gluten-free diet, a single subcutaneous dose of TEV-’408 demonstrated preliminary Phase 2a evidence of mucosal protection during a 6-week daily gluten challenge. The study met its primary endpoint with a statistically significant attenuation of mucosal degradation, yielding a villous height-to-crypt depth (Vh:Cd) ratio change of -0.43 for TEV-’408 versus -0.88 for placebo (treatment difference: 0.45, p < 0.05), alongside near-complete suppression of intraepithelial lymphocyte infiltration (+0.37 vs. +27.60 for placebo, difference: -27.23). Supported by lower gastrointestinal symptom severity scores and a clean safety profile with no emerging treatment-related signals, these findings validate the extended half-life and 8-week durability of upstream IL-15 inhibition, offering promising proof-of-concept to address the therapeutic vacuum in celiac disease where no FDA-approved drugs currently exist.

Teva is completing full data analyses from the ongoing Phase 2a study to guide regulatory engagement and inform Phase 2b dose-ranging study designs. TEV-’408 currently holds FDA Fast Track designation for celiac disease (granted May 2025). The company remains focused on building on positive data in vitiligo and is advancing TEV-’408 into a Phase 2b trial for vitiligo, backed by a strategic $500 million funding partnership with Royalty Pharma.

Sources: Teva press release, Teva slide deck

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AbbVie - Etentamig (BMCA x CD3 TCE) / Phase 3 (3L MM)

On September 3, 2026, AbbVie announced positive topline results from the Phase 3 CERVINO trial evaluating etentamig (ABBV-383), an investigational BCMA x CD3 bispecific T-cell engager, in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM).

Triple-class exposed relapsed/refractory multiple myeloma (RRMM) is an aggressive malignancy driven by clonal evolution and multi-drug resistance against proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies, leaving historical standard options with poor response rates (~30%) and brief progression-free survival (<4 months). Addressing this gap with T-cell redirection, etentamig (ABBV-383) is a second-generation, off-the-shelf bispecific antibody engineered to engage BCMA on malignant plasma cells and CD3 on T-cells. By pairing a low-affinity CD3-binding domain, designed to minimize cytokine release syndrome (CRS) and T-cell exhaustion, with high-avidity bivalent BCMA-binding domains and a modified Fc region for an extended half-life, etentamig achieves targeted cytotoxicity while enabling a convenient, monthly (once every four weeks) intravenous dosing schedule following a single step-up dose.

In the Phase 3 CERVINO trial of 393 heavily pretreated, triple-class exposed relapsed/refractory multiple myeloma patients, etentamig monotherapy met its dual primary endpoints by demonstrating superior efficacy and an improved safety profile over standard available therapies. Etentamig achieved a 74.0% objective response rate compared to 45.7% for standard regimens (p < 0.0001), reduced the risk of disease progression or death by 60% (HR = 0.40; p < 0.0001), and showed a favorable 12-month overall survival trend of 87.9% versus 72.0% (HR = 0.48). Engineered with a low-affinity CD3 domain, etentamig eliminated severe cytokine release syndrome in the trial (0% Grade ≥3; 28.3% overall Grade 1/2) and maintained a low infection profile. Combined with a single step-up dose followed by convenient monthly (Q4W) dosing, this manageable toxicity profile could enable administration in outpatient and community oncology settings, potentially reducing treatment burden while significantly outperforming standard regimens in hard-to-treat multiple myeloma.

AbbVie plans to present full results from the Phase 3 CERVINO trial in a plenary session at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, Scotland on Friday, September 25, 2026. The company plans to initiate discussions with global regulatory agencies to support registrational filings for triple-class exposed RRMM. Etentamig is also being developed as a monotherapy and in combinations for earlier lines of MM, as well as in AL amyloidosis.

Sources: AbbVie press release

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Descriptive data releases without numerical data

• GSK - FLUm3HA-3NA (mRNA vaccine) / Phase 2 (influenza): In the Phase 2 Flu-028 trial (N=971) presented at the OPTIONS XIII Conference, GSK announced positive topline results for its investigational dual-antigen mRNA seasonal influenza vaccine. The candidate utilizes a novel design targeting both hemagglutinin (HA) and neuraminidase (NA) surface proteins across influenza A and B strains, evaluated in two formulations: FLUm3HA.b-3NA (featuring an optimized B-strain HA) and FLUm3HA-3NA. The optimized FLUm3HA.b-3NA formulation elicited higher immune responses across all tested flu strains compared to standard-dose inactivated vaccines in younger adults (ages 18–64) and high-dose inactivated vaccines in older adults (ages ≥65), while maintaining an acceptable reactogenicity and safety profile. GSK plans to advance this FDA Fast Track-designated, optimized dual-antigen mRNA candidate into a pivotal Phase 3 efficacy trial. Sources: GSK press release

• Jazz Pharma - Ziihera (HER2 mAb) / Phase 3 (1L HER2+ GEA): In the Phase 3 HERIZON-GEA-01 trial (N=914) evaluating first-line HER2-positive advanced gastroesophageal adenocarcinoma (GEA), Jazz Pharmaceuticals and BeOne Medicines announced positive topline results from a second interim analysis, demonstrating that Ziihera (zanidatamab-hrii), a bispecific HER2-directed antibody, plus chemotherapy achieved a statistically significant and clinically meaningful overall survival (OS) advantage over the historical standard of care, Herceptin (trastuzumab) plus chemotherapy. Building on the recent FDA approval of Ziihera in combination with chemotherapy and tislelizumab (which demonstrated a median OS of 26.4 months vs. 19.2 months for trastuzumab, HR=0.72), this new readout confirms survival superiority for Ziihera even as a chemo-combo doublet without an anti-PD-1 agent, while also demonstrating further hazard ratio improvements in the triplet regimen with extended follow-up. Both Ziihera-containing arms maintained a consistent and well-tolerated safety profile with no new safety signals, positioning the bispecific antibody to supplant trastuzumab as the new HER2-targeted backbone standard in 1L GEA, with full updated OS dataset presentations scheduled for a major medical conference in late 2026. Sources: Jazz Pharma press release

• AstraZeneca - Orpathys (MET inhibitor) / Phase 3 (1L MET-oe EGFR+ NSCLC): In the Phase 3 SANOVO trial (N=326) conducted in China by HUTCHMED, AstraZeneca announced that its all-oral combination of Tagrisso (osimertinib) plus Orpathys (savolitinib, a selective MET inhibitor) demonstrated a statistically significant and “highly clinically meaningful improvement” in primary endpoint progression-free survival (PFS) compared to Tagrisso alone as a first-line treatment for treatment-naïve patients with MET-overexpressing, EGFR-mutated advanced non-small cell lung cancer (NSCLC). The PFS advantage was observed across both high MET (IHC 3+) and intention-to-treat (IHC 2+/3+) populations, while also showing “very encouraging clinical benefit” in key secondary endpoint overall survival (OS). With a safety profile consistent with known monotherapy data and no new safety signals, these results build on prior post-progression successes (SAFFRON and SACHI) to establish the Tagrisso-Orpathys doublet as a potential front-line option to intercept MET-driven primary resistance, with full results slated for presentation at an upcoming medical conference. Sources: AstraZeneca press release

• Novartis - Remibrutinib (BTK inhibitor) / Phase 3 (RMS): In the twin Phase 3 REMODEL-1 and REMODEL-2 trials (N ≈ 2,000) in relapsing multiple sclerosis (RMS), Novartis announced that its highly selective oral Bruton’s tyrosine kinase (BTK) inhibitor, remibrutinib met its primary endpoints by demonstrating a statistically significant reduction in annualized relapse rates (ARR) compared to Sanofi’s oral standard Aubagio (teriflunomide). Beyond superior relapse control, remibrutinib achieved superiority across all key secondary endpoints, including a significant reduction in inflammatory MRI brain lesions and a clinically meaningful delay in disability progression (showing nominal significance in 6-month confirmed disability progression in a pooled analysis). Crucially, remibrutinib sidestepped the class-wide liver toxicity concerns that have hampered competing BTK inhibitors, demonstrating a favorable safety profile with zero cases meeting Hy’s Law criteria for severe liver injury. Full detailed data will be presented as a late-breaker at MSToronto2026, establishing remibrutinib as a potential first-in-class oral BTK inhibitor to enter global regulatory filings for RMS. Sources: Novartis press release

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Table of Contents

The European Society of Cardiology (ESC) Congress 2026 took place on August 28-31, 2026 in Munich, Germany. In this article, we discuss the following high-impact datasets:

• Dueling Datasets in ATTR-CM

  • AstraZeneca & Ionis - Eplontersen (TTR ASO silencer) / Phase 3 (ATTR-CM) ⬇️

  • Alnylam - Amvuttra (TTR RNAi silencer) / Phase 3 (ATTR-CM) ⬇️

  • Bridge Bio - Attruby (TTR stabilizer) / Phase 3 OLE (ATTR-CM) ⬇️

• Silent Atherosclerosis

  • Prevalence of Silent Atherosclerosis across Adult Life ⬇️

  • Monash University - Atorvastatin (HMG-CoA reductase inhibitor) / Phase 4 (ASCVD) ⬇️

• Severe Hypertriglyceridemia

  • CRISPR Therapeutics - CTX310 (in vivo ANGPTL3 KO) / Phase 1a (sHTG) ⬇️

  • Arrowhead - Plozasiran (APOC3 RNAI) / Phase 3 (sHTG) ⬇️

• Heart Failure

  • GLP1 Added to 2026 ESC Guidelines for Heart Failure ⬇️

  • AstraZeneca - AZD5462 (relaxin-2 mimetic) / Phase 2b (chronic heart failure) ⬇️

• Other notable datasets

  • Cytokinetics - Myqorzo (cardiac myosin inhibitor) / Phase 3 (nHCM) ⬇️

  • Kylonova - Kylo-11 (LPA RNAi) / Phase 1 (ASCVD) ⬇️

  • Amgen - Repatha (anti-PCSK9 mAb) / Phase 3 (ASCVD) ⬇️

Dueling Datasets in ATTR-CM

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a fatal infiltrative heart disease where dissociation of hepatic transthyretin (TTR) tetramers into misfolded monomers leads to myocardial amyloid deposition, progressive ventricular thickening, restrictive cardiomyopathy, and heart failure. Standard management pairs loop diuretics with first-line disease-modifying TTR stabilizers (e.g., tafamidis, acoramidis) or RNA silencers (e.g., vutrisiran, eplontersen) to prevent ongoing fibril accumulation. This ESC 2026 ignited a fierce debate about whether silencers provide additional benefit when added on top of a stabilizer.

AstraZeneca & Ionis - Eplontersen (TTR ASO silencer) / Phase 3 (ATTR-CM)

Alnylam - Amvuttra (TTR RNAi silencer) / Phase 3 (ATTR-CM)

At the ESC Congress 2026, AstraZeneca and Ionis presented full results from the Phase 3 CARDIO-TTRansform trial and simultaneously published detailed results in The New England Journal of Medicine, offering critical context following the surprise announcement of the study’s primary endpoint failure in July 2026. Delivered as a ligand-Conjugated Antisense Oligonucleotide (LFA/GalNAc-ASO), eplontersen binds hepatic TTR mRNA to trigger RNase H1-mediated degradation, shutting down the liver’s synthesis and secretion of both wild-type and mutant TTR proteins to prevent toxic cardiac fibril deposition.

The Phase 3 CARDIO-TTRansform trial, the largest study in ATTR-CM to date with 1,432 patients, failed to meet its primary composite endpoint of CV mortality and recurrent CV events (Rate Ratio 0.89, p=0.277), despite achieving robust 140-week TTR protein knockdown and maintaining a favorable, consistent safety profile. While subgroup analyses validated silencer monotherapy by demonstrating a nominally significant reduction in primary CV events among treatment-naïve patients, eplontersen offered no incremental clinical benefit over placebo in patients taking background TTR stabilizers.

In a NEJM Voices perspective piece, Dr. Michelle Kittleson examined the CARDIO-TTRansform Phase 3 trial of eplontersen to explain why its primary endpoint failure provided crucial clinical insights regarding combination therapy in transthyretin amyloid cardiomyopathy (ATTR-CM). Since the vast majority of control group participants received an active stabilizer, the placebo arm functioned as an active-control comparison testing combination silencer-plus-stabilizer therapy against stabilizer monotherapy. Dr. Kittleson’s read of the clinical data was that adding a TTR silencer provides no incremental clinical benefit once amyloid formation has already been suppressed through TTR stabilization. She expects payers to limit or deny insurance coverage for expensive dual-therapy regimens (hundreds of thousands of dollars annually) based on these results. Lastly, Dr. Kittleson recommends that clinicians should use these findings to counsel patients that combination therapy is unsupported by evidence, while honoring patient preferences and avoiding unnecessary financial or medical harm.

So, is it really that simple? Silencers don’t add any benefit when added to stablizers? The Phase 3 HELIOS-B trial of Alnylam’s FDA-approved Amvuttra (vutrisiran, an siRNA administered subcutaneously every 3 months) successfully met its primary outcome with a hazard ratio of 0.72 (p=0.0118) back in 2024, demonstrating a 28% risk reduction in all-cause mortality and recurrent cardiovascular events across the overall population. Additionally, Amvuttra achieved a 33% risk reduction in treatment-naïve patients not on baseline stabilizers (HR 0.67, p=0.0162). In contrast, AstraZeneca and Ionis’s eplontersen (an ASO administered subcutaneously every 4 weeks) failed its primary endpoint in the CARDIO-TTRansform trial with a rate ratio of 0.89 (p=0.277), showing only an 11% non-statistically significant numerical reduction in CV mortality and recurrent CV events overall, despite achieving a nominally significant benefit in treatment-naïve monotherapy patients. Overall, these hard clinical outcomes indicate that Amvuttra improves clinical outcomes in ATTR-CM, whereas eplontersen does not. Two key swing factors help explain this divergence:

• Pharmacodynamic depth: Amvuttra achieves a deeper serum TTR trough reduction of -81% compared to -60% for eplontersen.

• Confounding effect of baseline stabilizer use: Eplontersen faced significantly higher competition from background standard of care. Only 40% of HELIOS-B participants were taking background tafamidis at baseline, whereas 57% of CARDIO-TTRansform participants were taking baseline stabilizers (a figure that grew to ~80% during the study), creating a high stabilizer ceiling that eroded eplontersen’s ability to demonstrate incremental benefit.

So, which effect is a stronger driver of clinical outcomes: deeper TTR knockdown, or background stabilizer use? A post-hoc subgroup analysis of the Phase 3 HELIOS-B trial published in JACC and presented at ESC 2026 as part of the Late-Breaking Clinical Science session suggests that Amvuttra’s deeper TTR knockdown was stronger than the dilutive effect from background stabilizers. In patients who were not taking tafamidis at baseline, Amvuttra reduced event rates by 33% compared to placebo (RR: 0.67; All-Cause Mortality & Recurrent CV Events up to 36 months). While the benefit fell from 33% to 21% in the tafamidis experienced population (Rate Ratio [RR]: 0.79; 95% CI: 0.51–1.21), the P for interaction was 0.55, suggesting consistent treatment direction driven by Amvuttra. In plain English, the trial was not powered specifically to establish definitive superiority of combination therapy in the subgroup, but the statistical failure to reject homogeneity across strata supports the conclusion that Amvuttra-mediated TTR knockdown provides clinical benefit irrespective of baseline stabilizer status. Is this enough to gain patient, physician, and payer trust? Only time will tell.

Sources: Fontana et al., NEJM (2026) [eplontersen Phase 3], Fontana et al., NEJM (2024) [Amvuttra Phase 3], NEJM Voices perspective, Hamatani et al., JACC (2026) [Amvuttra Phase 3 subgroup analysis]

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BridgeBio - Attruby (TTR stabilizer) / Phase 3 OLE (ATTR-CM)

At the European Society of Cardiology (ESC) Congress 2026, BridgeBio presented long-term post-hoc data from the Phase 3 ATTRibute-CM open-label extension (OLE) evaluating Attruby (acoramidis) in variant transthyretin amyloid cardiomyopathy (ATTRv-CM). These findings were simultaneously published in the European Journal of Heart Failure. Attruby (acoramidis) is an oral TTR stabilizer formulated to achieve near-complete (≥90%) tetramer stabilization. By stabilizing circulating TTR tetramers, acoramidis prevents their dissociation into amyloidogenic monomers, suppressing tissue deposition, preserving serum TTR (sTTR) levels, and attenuating progressive cardiac damage.

In a post-hoc analysis of the Phase 3 ATTRibute-CM trial and its 24-month open-label extension (OLE) evaluating acoramidis 800 mg BID over 54 months total in 56 variant ATTR-CM (ATTRv-CM) patients, continuous acoramidis demonstrated dramatic long-term clinical benefits compared to delayed placebo-to-acoramidis treatment. Continuous acoramidis therapy yielded marked reductions in both all-cause mortality (24.3% vs. 57.9%) and cardiovascular mortality (21.6% vs. 52.6%), with pronounced protection retained across both the high-risk p.Val142Ile (all-cause mortality 30.4% vs. 66.7%) and non-p.Val142Ile (all-cause mortality 14.3% vs. 42.9%) cohorts, alongside only three total mortality events occurring during the OLE period. Beyond survival, continuous treatment delivered rapid and sustained serum TTR increases (+14.4 mg/dL in p.Val142Ile), stabilized cardiac biomarkers (NT-proBNP median increases of 7-40% vs. historic ~4-fold progression), preserved quality-of-life scores (KCCQ-OS of 69.67 to 79.29), and maintained a favorable safety profile with no new signals. Ultimately, these post-hoc exploratory data suggest that near-complete TTR stabilization may attenuate the progression of variant ATTR-CM, highlighting a 50% to 67% relative risk reduction that reinforces the urgent clinical necessity of early genetic screening and immediate, uninterrupted therapy across all patient demographics.

BridgeBio plans to conduct prospective real-world registry tracking and larger clinical studies to further validate long-term functional and mortality benefits across rare TTR variant subgroups. The company also plans to expand clinical implementation of Attruby as an established disease-modifying oral standard of care for both wild-type and variant ATTR-CM populations.

Sources: BridgeBio press release, BridgeBio ESC 2026 slide deck, Ruberg et al., European Journal of Heart Failure (2026)

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Silent Atherosclerosis

Prevalence of Silent Atherosclerosis across Adult Life

Cardiovascular disease remains a primary cause of global morbidity and mortality, driven largely by the gradual, silent progression of atherosclerosis. Traditional primary prevention relies heavily on calculating 10-year risk scores and identifying modifiable risk factor thresholds (e.g., blood pressure, lipids) rather than directly visualizing early disease burden. Since atherosclerosis often develops decades before clinical manifestations like heart attacks or strokes occur, the authors of the REACT trial sought to map the age- and sex-specific prevalence, vascular territory distribution, and plaque volume across adult life. The REACT Initiative conducted a prospective cross-sectional cohort study across Denmark and Spain, enrolling 16,808 adults aged 18 to 70 without known clinical atherosclerotic cardiovascular disease. Participants were systematically stratified across five age groups with balanced numbers of men and women. To assess systemic plaque burden, participants underwent standardized multimodal imaging consisting of:

• 3D Vascular Ultrasonography: Evaluating bilateral carotid and femoral arteries.

• Coronary CT Angiography & Non-Contrast CT: Evaluating coronary plaque volume, stenosis, and coronary artery calcium (CAC) scores.

Primary analysis was conducted on 13,186 participants with complete three-territory imaging datasets. Silent atherosclerosis was present even in the youngest age stratum (18–29 years), affecting 8.7% of men and 6.7% of women. By age 60-70, presence of plaque was nearly ubiquitous (98.1% in men, 91.9% in women). Men exhibited an earlier rise in plaque prevalence starting in their 30s, followed by a midlife plateau. Women demonstrated a later, steeper rise after age 40 (overlapping with the menopausal transition), which narrowed the sex gap in older age groups. Among younger cohorts, plaque was predominantly peripheral and restricted to a single territory (most commonly the carotids). Isolated coronary disease was rare (≤ 9.3% in men, ≤ 5% in women across all age groups). Multiterritorial involvement increased dramatically with age, with 56.3% of men and 30.7% of women aged 60-70 showing plaque in all three examined territories.

The REACT study demonstrates that silent atherosclerosis is a progressive, systemic disease process that begins in early adulthood. Since standard risk-prediction tools fail to identify a majority of young and middle-aged individuals carrying silent plaque, incorporating direct arterial imaging into early primary prevention strategies may enhance cardiovascular risk stratification long before clinical events take place.

Ok. That’s a lot to take in. I wish they ran a clinical trial to see if cheap, generic statins (< $6 for a 3-month supply on Cost Plus Drugs) prevents heart attack & stroke in people with silent atherosclerosis.

Oh wait, they did run that trial. Up next, that trial.

Sources: Bundgaard et al., NEJM (2026)

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Monash University - Atorvastatin (HMG-CoA reductase inhibitor) / Phase 4 (ASCVD)

The STAREE (STAtin therapy for Reducing Events in the Elderly) trial was sponsored by Monash University in Australia. Pfizer did not sponsor the trial; it was explicitly funded via public health research grants, primarily from Australia’s National Health and Medical Research Council (NHMRC) and the Heart Foundation of Australia, to prevent pharmaceutical industry bias in assessing primary statin prevention. Atorvastatin works as a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, suppressing hepatic cholesterol synthesis and up-regulating LDL receptors to enhance blood LDL-C clearance. While atorvastatin is marketed as Lipitor by Pfizer for LDL cholesterol reduction and cardiovascular protection, the STAREE trial evaluated atorvastatin in a population that falls outside FDA-approved primary prevention criteria. The trial evaluated off-label use in an elderly population outside current FDA-approved primary prevention labels. Major clinical guidelines (including ACC/AHA and USPSTF) have long held equivocal or “insufficient evidence” recommendations regarding initiating statin therapy in adults aged 75 and older without established ASCVD or diabetes. STAREE was designed as an investigator-initiated trial specifically to establish whether primary prevention in this healthy elderly cohort could be clinically justified.

The Phase 4 STAREE trial (NCT02099123) evaluated daily atorvastatin 40 mg versus placebo over a median 5.9-year follow-up in 9,971 Australian adults aged ≥70 years without baseline cardiovascular disease, diabetes, or dementia. Atorvastatin achieved a significant 30% relative risk reduction in major cardiovascular events compared to placebo (10.9 vs. 15.5 per 1,000 person-years; HR 0.70, 95% CI 0.61–0.82, p<0.001), primarily driven by reductions in nonfatal heart attacks and revascularizations. However, active treatment failed to improve the co-primary endpoint of disability-free survival (21.6 vs. 23.0 per 1,000 person-years; HR 0.94, 95% CI 0.84-1.05, p=0.25), largely because roughly 80% of functional events and deaths in this non-diabetic elderly cohort stemmed from non-cardiovascular causes. Serious adverse event rates were identical between groups at 2.7%, though atorvastatin showed minor numerical increases in musculoskeletal, hepatobiliary, and new-onset diabetes events alongside a 44% five-year treatment discontinuation rate. Ultimately, while STAREE confirms statins mitigate vascular risk in healthy older adults, the lack of impact on overall mortality or functional independence highlights the need for shared clinician-patient decision-making.

Real-world translation will require regulatory review and strategies to improve long-term adherence. In STAREE, drug discontinuation reached about 44% at 5 years in the active arm, driven predominantly by patient unwillingness to take the drug rather than overt toxicities. Clinicians must weigh the clear reduction in nonfatal cardiac events against individual goals regarding overall functional longevity. Industry experts expect major cardiology and geriatrics bodies (AHA/ACC, ESC, USPSTF) to examine primary prevention guidelines with regards to statin initiation in adults ≥70 years based on explicit vascular benefits, but revisions are uncertain.

Sources: Zoungas et al., NEJM (2026)

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Severe Hypertriglyceridemia

Severe hypertriglyceridemia (sHTG), defined as fasting triglycerides ≥500 mg/dL, results from impaired clearance or overproduction of triglyceride-rich lipoproteins due to genetic defects (e.g., LPL, APOC2) or secondary triggers, placing patients at high risk for acute pancreatitis (AP) as excess lipids are cleaved into toxic free fatty acids within the pancreatic microvasculature. Current management focuses on acute pancreatitis prevention via strict dietary fat restriction (<15-20% of calories), lifestyle modifications, fibrates, prescription omega-3s, and targeted RNA therapies for severe monogenic subsets. ESC 2026 prominently featured two different genetic approaches to sHTG.

CRISPR Therapeutics - CTX310 (in vivo ANGPTL3 KO) / Phase 1a (sHTG)

CRISPR Therapeutics presented one-year Phase 1a durability data for CTX310 (an in vivo LNP-delivered CRISPR-Cas9 therapy targeting ANGPTL3) at the ESC Congress 2026, accompanied by simultaneous publication in The New England Journal of Medicine. CTX310 offers a potentially transformative treatment strategy for patients with sHTG. Delivered intravenously via lipid nanoparticles, CTX310 is an in vivo CRISPR-Cas9 gene-editing therapy that selectively induces double-strand breaks in hepatocyte ANGPTL3, permanently disrupting the gene to mimic protective loss-of-function mutations. CTX310 is designed to achieve long-term reductions in both triglycerides and LDL cholesterol based on initial 1-year data.

In a Phase 1a open-label, dose-escalation trial of 15 patients with refractory dyslipidemia (including HeFH/HoFH, sHTG, and mixed dyslipidemia), a single IV infusion of CTX310 demonstrated a well-tolerated safety profile alongside robust 1-year efficacy, characterized by a 53% drop in LDL-C and a 48% decrease in triglycerides at the highest dose (0.8 mg/kg), alongside a mean 79% reduction in circulating ANGPTL3 to confirm target engagement. Transient, mild-to-moderate infusion reactions and brief liver transaminase elevations (occurred in 1 of 15 patients) resolved without sequelae, with no dose-limiting toxicities or late-onset safety signals observed through 12 months. As the first clinical proof-of-concept for deep, durable, multi-lipid lowering via a single-course in vivo hepatic gene-editing platform, CTX310 marks a major paradigm shift, offering a potential “one-and-done” alternative to lifelong chronic therapies for patients with refractory disease who fail standard LDL-receptor-dependent pathways.

CRISPR Therapeutics plans to move forward using a fixed flat dose equivalent to the highest efficacious Phase 1a dose (0.8 mg/kg). The company anticipates presenting additional Phase 1b data, focusing on cohorts of patients with severe hypertriglyceridemia (sHTG), in 2H 2026.

Sources: CRISPR Therapeutics press release, CRISPR Therapeutics slide deck, Laffin et al., NEJM (2026)

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Arrowhead - Plozasiran (APOC3 RNAi) / Phase 3 (sHTG)

At ESC 2026, Arrowhead Pharmaceuticals reported landmark results from the pivotal Phase 3 SHASTA-3 and SHASTA-4 clinical trials evaluating plozasiran, an investigational RNA interference (RNAi) therapeutic targeting APOC3, in adult patients with severe hypertriglyceridemia (sHTG). The data was previously released on July 22, 2026, which Biotech Readout covered in Weekly Readout #15, but the ESC 2026 presentation added subgroup analysis and a more granular view of the results. Note that plozasiran is currently approved for familial chylomicronemia syndrome (FCS) under the brand name Redemplo, but not for sHTG at the time of this article’s publication. Plozasiran is an investigational agent for sHTG and safety/efficacy for this indication have not been established by regulatory authorities. Utilizing Arrowhead’s TRiM platform, plozasiran is an investigational subcutaneous siRNA that silences hepatocyte expression of APOC3, a key inhibitor of lipoprotein lipase and hepatic lipid clearance. This approach aims to deliver potent, prolonged triglyceride lowering and pancreatitis risk reduction through a convenient once-quarterly dosing regimen.

The twin Phase 3 SHASTA-3 and SHASTA-4 trials evaluated quarterly subcutaneous plozasiran (25 mg) versus placebo in 757 adults with severe hypertriglyceridemia (TG≥500 mg/dL). At Month 12, plozasiran achieved median triglyceride reductions of 79% in SHASTA-3 and 81% in SHASTA-4 compared to placebo (p<0.0001 for both), expanding to an 85% median reduction among patients entering the trial with baseline triglycerides at or above 880 mg/dL. Beyond relative reductions, over 90% of plozasiran-treated patients lowered their serum triglycerides below the high-risk threshold of 500 mg/dL (91% in SHASTA-3 and 93% in SHASTA-4 vs. 51% and 50% for placebo, p<0.0001), while more than half of participants achieved normal fasting levels below 150 mg/dL (52% in SHASTA-3 and 55% in SHASTA-4 vs. 7.9% and 2.0% for placebo, p<0.0001). These metabolic shifts were driven by targeted APOC3 knockdown (-82-84%), confirming target engagement.

The late-breaking presentation also quantified the clinical benefit of deep APOC3 suppression on acute pancreatitis risk through a prespecified pooled analysis. In the overall sHTG trial population, plozasiran reduced the rate of all adjudicated acute pancreatitis events by 78% compared to placebo (Risk Ratio 0.22; p=0.008) and prolonged time to first event, lowering the risk of initial onset by 74% (Hazard Ratio 0.26; p=0.016). This risk reduction was most pronounced in patients with persistent hypertriglyceridemia (≥ 500 mg/dL) and a documented history of acute pancreatitis, where plozasiran delivered a 91% reduction in event rates (Risk Ratio 0.09; p=0.002). Safety and tolerability data showed overall treatment-emergent adverse event rates comparable to placebo (73%), low overall discontinuation rates due to adverse events (1.4% vs. 0.8%), and no clinically meaningful changes in liver enzymes, platelet counts, or hepatic fat fraction on MRI-PDFF (p=0.70).

Supported by these results, Arrowhead confirmed plans to utilize a recently acquired FDA Priority Review Voucher (PRV) to accelerate its planned supplemental New Drug Application (sNDA) for the broad sHTG indication before the end of 2026.

Sources: Arrowhead press release, Arrowhead ESC 2026 slide deck

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Heart Failure

GLP1 Added to 2026 ESC Guidelines for Heart Failure

Updated 2026 ESC Heart Failure Guidelines, published in the European Heart Journal, introduced several major shifts in pharmacotherapy grouping and drug-specific recommendations. The guidelines abandon the blanket term guideline-directed medical therapy (GDMT) in favor of two distinct drug tiers:

• Foundational Medical Therapy (FMT): Reserved exclusively for Class I recommendations across broad, unselected HF populations. “Optimal FMT” explicitly denotes achieving maximum tolerated target doses.

  

• Additional Medical Therapy (AMT): Includes Class IIa/IIb agents, therapies with Class I status restricted to specific subgroups (e.g., etiology, phenotypes), or drugs indicated primarily for symptom relief and quality-of-life benefit. This includes the notable addition of GLP-1 agonists semaglutide and tirzepatide. There are two specific recommendations for these agents:

  • A Class IIa recommentation found in Table 5, Section 4 corresponding to prevention of heart failure states, “a GLP-1 RA should be considered in patients with T2DM and at least one other additional CV risk factor to reduce the risk of HF or CV death.”

  • A Class IIa recommendation found in Table 5, Section 10 corresponding to the management of non-cardiovascular comorbidities of heart failure states, “semaglutide or tirzepatide should be considered for patients with symptomatic HF, LVEF ≥45%, and BMI ≥30 kg/m², regardless of diabetes status, to reduce body weight, and improve exercise capacity and QoL.”

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AstraZeneca - AZD5462 (relaxin-2 mimetic) / Phase 2b (chronic heart failure)

Data from the Phase 2b LUMINARA trial, presented at ESC Congress 2026 and simultaneously published in Circulation, demonstrated that AstraZeneca’s oral RXFP1 agonist AZD5462 produced encouraging signals of reverse cardiac remodeling and systemic vasodilation in patients with chronic heart failure.

While heart failure with reduced ejection fraction (HFrEF; LVEF <= 40%) is driven by direct myocardial injury leading to lost contractility, neurohormonal overactivation, and eccentric ventricular remodeling managed via quadruple guideline-directed medical therapy (ARNI/ACEi/ARB, beta-blockers, MRAs, and SGLT2is), heart failure with preserved ejection fraction (HFpEF; LVEF >= 50%) is primarily driven by systemic cardiometabolic comorbidities causing chronic inflammation, microvascular dysfunction, and LV stiffness managed mainly with SGLT2 inhibitors and risk-factor control. Targeting these shared pathophysiological features of vasodilation, remodeling, and fibrosis, AZD5462 acts as a novel, oral, small-molecule selective allosteric agonist of the relaxin family peptide receptor 1 (RXFP1). It is designed to mimic endogenous relaxin-2 to reduce preload and afterload, decrease myocardial inflammation, and potentially attenuate cardiac fibrosis through a physiological, once-daily engagement profile that avoids the severe fluid retention seen with prior recombinant peptides (e.g., serelaxin) or long-acting mimetics (e.g., volenrelaxin).

The Phase 2b LUMINARA trial evaluated 375 heart failure patients across 69 international sites divided into two ejection fraction cohorts. Cohort A with LVEF 35% or lower (n=235) tracked end-systolic volume index (ESVI) for reverse cardiac remodeling, and Cohort B with LVEF 41%–55% (n=140) tracked systemic vascular resistance index (SVRI) for vasodilation. Patients were randomized to receive 20 mg, 80 mg, or 360 mg of once-daily oral AZD5462 or placebo for 24 weeks on top of standard guideline-directed medical therapy. Efficacy findings demonstrated a puzzling inverse dose-response relationship in Cohort A, where the lowest 20 mg dose produced the most pronounced reverse remodeling with a 5.4 mL/m² reduction in ESVI (p = 0.054) and the greatest LVEF improvements, whereas Cohort B demonstrated significant vasodilation across all doses with SVRI reductions of 19% (20 mg), 21% (80 mg), and 15% (360 mg) (all p <= 0.021). AZD5462 was well tolerated without excess adverse events or clinically significant hypotension compared to placebo, and critically, it showed no signs of fluid retention or volume overload, successfully providing clinical proof-of-mechanism for an oral RXFP1 agonist on top of standard-of-care therapy and establishing the 20 mg once-daily dose for pivotal Phase 3 testing.

AstraZeneca and trial investigators identified 20 mg once daily as the definitive go-forward dose for pivotal testing. Larger, long-term outcome-driven Phase 3 trials are required to evaluate whether early surrogate improvements in ESVI and SVRI translate into reductions in hard clinical endpoints (HF hospitalizations and cardiovascular mortality).

Sources: ESC press release, Januzzi et al., Circulation (2026)

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Other notable datasets

Cytokinetics - Aficamten (cardiac myosin inhibitor) / Phase 3 (nHCM)

Taking the main stage in Munich during Hot Line Session 1 at the ESC Congress 2026, Dr. Ahmad Masri presented the landmark results of the Phase 3 ACACIA-HCM trial, simultaneously published in The New England Journal of Medicine. The presentation marked a pivotal moment in cardiology: the first positive Phase 3 trial for non-obstructive hypertrophic cardiomyopathy (nHCM), a disease segment representing roughly a third of all HCM patients that has historically lacked targeted, disease-modifying pharmacotherapy. Biotech Readout discussed the initial data release on in Weekly Readout #6.

Non-obstructive hypertrophic cardiomyopathy (nHCM) is characterized by unexplained left ventricular hypertrophy without a significant outflow tract gradient, where sarcomeric gene mutations drive hypercontractility, impaired diastolic relaxation, and elevated filling pressures. Lacking an anatomical gradient for surgical intervention, traditional standard of care relies on non-vasodilating beta-blockers or non-dihydropyridine calcium channel blockers to control heart rate and prolong diastolic filling. To directly target this underlying disease mechanism, aficamten (a next-generation selective cardiac myosin inhibitor) dampens excess actin-myosin cross-bridge formation to reduce hypercontractility and alleviate filling pressures.

In the international Phase 3 ACACIA-HCM trial of 517 adults with symptomatic nHCM, 36 weeks of echo-titrated aficamten met both dual primary endpoints, significantly improving KCCQ Clinical Summary Scores (+11.4 vs. +8.4; p = 0.021) and peak oxygen uptake (+0.64 vs. -0.03 mL/kg/min; p = 0.003) compared to placebo. Treatment with aficamten also yielded higher rates of NYHA class improvement (41.9% vs. 27.8%; p < 0.001), a 57% reduction in NT-proBNP levels, and a fourfold increase in multi-domain clinical responders (53% vs. 13%). On safety, aficamten was associated with higher rates of early discontinuation (7.0% vs. 1.9%) and serious heart failure events (4.3% vs. 0.4%), along with transient LVEF drops below 50% in 10.5% of patients (vs. 0.8% on placebo) that were predominantly managed via protocol-guided dose reductions rather than permanent withdrawal.

Unlike aficamten’s positive readout in ACACIA-HCM, Bristol Myers Squibb’s competing Phase 3 ODYSSEY-HCM trial evaluating Camzyos (mavacamten) in 580 nHCM patients failed to meet its dual primary endpoints, showing no statistically significant improvements in peak oxygen uptake (+0.52 vs. +0.05 mL/kg/min; p = 0.07) or KCCQ Clinical Summary Score (+13.1 vs. +10.4; p = 0.06) relative to placebo. This is surprising because Camzyos (mavacamten) has a similar mechanism of action as aficamten. While mavacamten demonstrated strong biological activity, achieving a 58% NT-proBNP reduction similar to aficamten, its functional and symptomatic benefits were diluted by a larger placebo response and limited by a significantly worse safety profile. Mavacamten induced LVEF drops below 50% in 21.5% of patients (compared to 10.5% for aficamten) and severe LVEF drops to 30% or below in 2.4% of patients (vs. 0% for aficamten), driving a higher permanent discontinuation rate of 10.7% (vs. 7.0% for aficamten). Ultimately, while mavacamten’s constrained therapeutic window and longer half-life resulted in a neutral clinical readout, it’s possible that aficamten’s shorter half-life and faster reversibility allowed for safer, more effective titration that translated biological target engagement into definitive clinical success.

Following the presentation, commentators noted that while the absolute effect size on exercise capacity is modest, the consistent multi-endpoint improvements offer compelling options for a patient population with high symptom burden. Building on the ESC 2026 readout, Cytokinetics confirmed plans to submit a supplemental New Drug Application (sNDA) to the U.S. FDA in 4Q 2026 to officially expand aficamten’s label into non-obstructive HCM (nHCM). The company suggested that echo-guided dosing and REMS protocols will likely serve as crucial clinical safeguards. Note that aficamten was approved by the FDA on January 27, 2026 (marketed as Myqorzo) for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Sources: Cytokinetics press release, Masri et al., NEJM (2026), Desai et al., NEJM (2025)

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Kylonova - Kylo-11 (LPA RNAi) / Phase 1 (ASCVD)

Kylonova Biopharma, a biotech company based out of Xiamen, Fujian Province, China, presented final first-in-human data for Kylo-11 as an oral presentation at ESC 2026 alongside a publication of more detailed data in The Lancet. The presentation was featured during the late-breaking clinical trials session titled “Rewriting cardiovascular disease on gene and molecular therapies“ on August 28, 2026.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined causal driver of atherosclerotic cardiovascular disease that promotes atherogenesis, vascular inflammation, and thrombosis, with top-quintile Lp(a) baseline levels (≥44 mg/dL) conferring a 33% increased 30-year risk of major adverse cardiovascular events in a prospective cohort of 27,939 U.S. women (see graph below). Since no approved pharmacological therapies currently exist to specifically lower Lp(a), standard care relies on once-in-a-lifetime screening to refine risk stratification and aggressive risk-factor optimization via intensive LDL-C lowering, blood pressure control, and lifestyle management. To directly address this gap, Kylo-11 (a GalNAc-conjugated siRNA therapy built on a proprietary MVIP delivery platform) inhibits hepatic translation of LPA mRNA to halt apolipoprotein(a) synthesis and block circulating Lp(a) assembly.

In the first-in-human, randomized, placebo-controlled Phase 1 trial evaluated single ascending doses (9–600 mg) of the siRNA therapy Kylo-11 across 71 subjects. Single-dose administration delivered a dose-dependent serum Lp(a) reduction of 53% to 97% at week 48, with higher dose cohorts (≥225 mg) maintaining peak reductions of 95% to 97% for nearly a full year, while doses ≥30 mg kept Lp(a) below 75 nmol/L from week 4 through week 48. Kylo-11 was well tolerated, with predominantly mild (Grade 1/2) treatment-emergent adverse events unrelated to the drug and zero drug-related serious adverse events or discontinuations. Demonstrating class-leading durability compared to existing Lp(a)-targeted siRNAs (e.g., Amgen’s olpasiran, Eli Lilly’s lepodisiran), Kylo-11’s year-long suppression supports a potential once-annual subcutaneous dosing regimen that could significantly improve real-world treatment adherence.

A Sino-US Phase 2 study evaluating Kylo-11’s efficacy, safety, and optimal dosing in patients with established atherosclerotic cardiovascular disease (ASCVD) and elevated Lp(a) is actively underway. If Phase 2 confirms once-yearly dosing and safety, Kylonova plans to advance Kylo-11 into Phase 3 cardiovascular outcomes trials (CVOT) to determine if sustained Lp(a) knockdown directly lowers major adverse cardiovascular events (MACE).

Sources: Ridker et al., NEJM (2024), Sarraju et al., Lancet (2026)

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Amgen - Repatha (anti-PCSK9 mAb) / Phase 3 (ASCVD)

At the ESC Congress 2026, late-breaking data from prespecified analyses of the Phase 3 VESALIUS-CV trial showed that Repatha (evolocumab) reduced the risk of all-cause mortality, and cardiovascular death in high-risk patients without a history of prior myocardial infarction or stroke, making it the first PCSK9 inhibitor to demonstrate a reduction in major cardiovascular events and mortality in a primary prevention population.

Primary prevention of atherosclerotic cardiovascular disease (ASCVD) targets systemic endothelial dysfunction, subendothelial LDL-C accumulation, and chronic vascular inflammation that cause lipid-rich plaque formation and downstream thrombotic events. Standard of care centers on aggressive lifestyle modifications combined with moderate- to high-intensity statin therapy to suppress hepatic cholesterol synthesis and upregulate low-density lipoprotein receptors (LDLR); adjunct agents like ezetimibe or PCSK9 inhibitors are added when target LDL-C levels remain unachieved. Among these, evolocumab acts as a selective human monoclonal antibody that binds circulating PCSK9, preventing PCSK9-mediated LDLR degradation on hepatocytes to allow continuous receptor recycling to the cell surface for sustained, rapid clearance of circulating LDL-C.

In the landmark Phase 3 VESALIUS-CV trial, 12,257 high-risk adults (median age 66 years; 43% women) with known atherosclerotic cardiovascular disease or high-risk diabetes, but no history of prior myocardial infarction (MI) or stroke, were evaluated on maximally tolerated lipid-lowering therapy. Over a median follow-up of 4.6 years, adding evolocumab to optimized background therapy lowered median LDL-C by -55% (reaching -40-45 mg/dL) and met its dual primary endpoints by reducing 3-point MACE by 30% (HR 0.70; 95% CI: 0.56–0.89; includes first event of coronary heart disease death, MI, or ischemic stroke) and 4-point MACE by 18% (HR 0.82; 95% CI: 0.71–0.96; includes MACE-3 plus ischemia-driven arterial revascularization). Driven by a 21-24% relative reduction in first MIs and lower cardiovascular mortality, evolocumab demonstrated a statistically significant 20% relative reduction in all-cause mortality (HR 0.80; 95% CI: 0.70–0.91; P = .0005) with divergence emerging after 1.5 years, all while maintaining a balanced, favorable safety profile without new safety signals. Ultimately, these data establish evolocumab as the first-in-class PCSK9 inhibitor to demonstrate a overall survival benefit in primary prevention, proving that intensive LDL-C lowering alters disease trajectory across diverse high-risk subgroups by preventing nonfatal index events that lead to clinical decline.

The FDA (August 25, 2025) and European Commission (August 2026) have updated and expanded Repatha‘s indications based on VESALIUS-CV data to include adults at high risk for ASCVD/major adverse CV events. Real-world analyses presented alongside trial data highlight widespread undertreatment and sex-based disparities in achieving target LDL-C levels. Ongoing efforts focus on driving earlier, aggressive treatment initiation and clinical guideline updates for primary prevention.

Sources: Amgen press release, Giugliano et al., Circulation (2026)

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