This is an enormous amount of work and it shows. Building the whole history as a ladder of increasing specificity, from Mustargen killing anything that divides through to Gleevec targeting one fusion protein, is what makes the last section land rather than read as hype.
Your line about intismeran being precision oncology taken to its logical extreme is the sharpest thing here, and the CAR-T comparison is what proves it. Every rung below it, CAR-T included, is one molecule or one construct given to a population. Intismeran isn't. Which makes it a different kind of object to evaluate. What INTerpath-001 is testing isn't a drug's effect, it's how reliably a pipeline (sequencing, neoantigen selection, manufacturing) produces a good product for every single patient in that arm. The hazard ratio is a statement about process consistency as much as biology.
That's probably why the missing numbers in the August release bothered people more than usual, and why the mature KEYNOTE-942 curves you pulled in do more work than the topline ever could.
Thank you for the kind words! Yes, I was worried that intismeran's advancement of precision oncology got buried in all of the noise that Moderna tends to attract, but you got it. We'll see the Phase 3 KM curves at a medical conference in short order.
Looking forward to those. If the pipeline-consistency reading holds, the curve shape may end up more informative than the hazard ratio.
A platform that makes a good product for nearly everyone should shift the whole treatment arm. One that works beautifully for some and poorly for others would separate into two populations while producing a similar HR. The Phase 2b TCR repertoire data you flagged is probably the best hint we have of which it will be.
Good read with good overview of the landscape. Since you ended on intismeran wanted to get your thoughts on whether you think the industry will move towards more precision and personalized therapies or do you think that more off-the-shelf therapies (ie. in vivo CAR-T) will be the standard? Or perhaps both? Just curious about your thoughts.
Thanks Paul! For now, it seems like Moderna has the only viable personalized cancer vaccine. Especially with BioNTech (also of COVID-19 mRNA vaccine fame) recently terminating a Phase 2 trial in colorectal cancer after a futility analysis by the DSMB (see link below). The ability to personalize like Moderna can is more of a luxury enjoyed by that specific company, rather than a secular trend that others can quickly catch up to, although I’m sure many will try. In the meantime, the rest of the industry will likely be forced to compete in the CAR-T-TCE space.
This is an enormous amount of work and it shows. Building the whole history as a ladder of increasing specificity, from Mustargen killing anything that divides through to Gleevec targeting one fusion protein, is what makes the last section land rather than read as hype.
Your line about intismeran being precision oncology taken to its logical extreme is the sharpest thing here, and the CAR-T comparison is what proves it. Every rung below it, CAR-T included, is one molecule or one construct given to a population. Intismeran isn't. Which makes it a different kind of object to evaluate. What INTerpath-001 is testing isn't a drug's effect, it's how reliably a pipeline (sequencing, neoantigen selection, manufacturing) produces a good product for every single patient in that arm. The hazard ratio is a statement about process consistency as much as biology.
That's probably why the missing numbers in the August release bothered people more than usual, and why the mature KEYNOTE-942 curves you pulled in do more work than the topline ever could.
Thank you for the kind words! Yes, I was worried that intismeran's advancement of precision oncology got buried in all of the noise that Moderna tends to attract, but you got it. We'll see the Phase 3 KM curves at a medical conference in short order.
Looking forward to those. If the pipeline-consistency reading holds, the curve shape may end up more informative than the hazard ratio.
A platform that makes a good product for nearly everyone should shift the whole treatment arm. One that works beautifully for some and poorly for others would separate into two populations while producing a similar HR. The Phase 2b TCR repertoire data you flagged is probably the best hint we have of which it will be.
Good read with good overview of the landscape. Since you ended on intismeran wanted to get your thoughts on whether you think the industry will move towards more precision and personalized therapies or do you think that more off-the-shelf therapies (ie. in vivo CAR-T) will be the standard? Or perhaps both? Just curious about your thoughts.
Thanks Paul! For now, it seems like Moderna has the only viable personalized cancer vaccine. Especially with BioNTech (also of COVID-19 mRNA vaccine fame) recently terminating a Phase 2 trial in colorectal cancer after a futility analysis by the DSMB (see link below). The ability to personalize like Moderna can is more of a luxury enjoyed by that specific company, rather than a secular trend that others can quickly catch up to, although I’m sure many will try. In the meantime, the rest of the industry will likely be forced to compete in the CAR-T-TCE space.
https://www.biontech.com/int/en/home/mediaroom/news/statements/2026/08/BioNTech-Provides-Update-on-Phase-2-Clinical-Trial-of-Autogene-Cevumeran-in-Resected-Colorectal-Cancer.html