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Table of Contents
This week, we discuss:
China Biotech
Approvals
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
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
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
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
Clinical Trial Data
To address the elephant in the room: Yes, Novartis/Ionis’ Lp(a)-lowering ASO pelacarsen failed to show a statistically significant improvement in cardiovascular events in a Phase 3 trial. Since others have covered this so comprehensively, I won’t be covering it here. Instead, I’ll share my favorite article of the situation here. It is a very thoughtful piece penned by Eric Topol that also ties in the Phase 3 miss for ziltivekimab (anti-IL6 mAb).
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
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
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
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
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
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
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
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)
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 (TH2) 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 TH2 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
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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Disclaimers
Investigational Status Disclaimer
The therapeutic candidates discussed in this newsletter are currently in clinical development and have not been approved for commercial sale by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), or other global regulatory authorities. Their safety and efficacy have not been established. References to pipeline products and ongoing clinical trials involve significant risks and uncertainties. Statements regarding the potential safety, potency, or efficacy of investigational drugs reflect current hypotheses and are not a guarantee of future performance or regulatory clearance. The outcome of clinical trials is inherently unpredictable, and clinical results from earlier stages may not be predictive of results in later, larger-scale trials.
No Medical Advice Disclaimer
This newsletter is for informational and educational purposes only. The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this publication.
No Patient-Provider Relationship Disclaimer
The information provided in this newsletter is for educational and analytical purposes only. Receipt of this information, or any interaction with this content, does not create a physician-patient, pharmacist-patient, or any other professional-provider relationship between you and the authors or publishers. This newsletter should not be used as a substitute for a personal consultation with a qualified healthcare professional.
Forward-Looking Statements Disclaimer
This newsletter contains “forward-looking statements” regarding future events, including clinical trial timing, regulatory milestones, and projected market performance. These statements are based on current expectations and assumptions that are subject to significant risks and uncertainties. Actual results may differ materially from those expressed or implied. We undertake no obligation to update these statements as a result of new information or future developments.
Third-Party Links & Content Disclaimer
This newsletter contains links to third-party websites, including clinical trial registries and corporate presentations. Biotech Readout does not endorse, guarantee, or assume responsibility for the accuracy or reliability of any information offered by third-party providers.
Errors and Omissions Disclaimer
While we strive for technical accuracy, the information in this newsletter is provided on an “as is” basis with no guarantees of completeness, accuracy, or timeliness. Biotech Readout assumes no liability for any errors or omissions in the content of this publication.
Non-Endorsement Disclaimer
Any reference to specific commercial products, processes, or services by trade name, trademark, or manufacturer does not constitute or imply an endorsement or recommendation by the author. All trademarks are the property of their respective owners.
No Investment Advice Disclaimer
This newsletter is for informational purposes only and does not constitute financial, investment, or legal advice. The author is not a registered investment advisor. You should consult with a professional financial advisor before making any investment decisions. The biotechnology sector is highly volatile; past performance is not indicative of future results.
Conflict of Interest Disclaimer
The author of this newsletter maintains a position of independence. At the time of publication, the author holds no direct financial interest, equity, or options in any of the companies mentioned in this report. No compensation has been received from any third party to feature or analyze specific therapeutic candidates or corporate entities.