KRAS / RAS targeting: from platform to Phase 3
The floor also showed dual ON/OFF (VS-7375) and RM-055, built for amplification and daraxonrasib-resistant models.
The floor rewrote the question from “how long can G12C monotherapy last” to “who first makes first-line pancreatic cancer a standard.” daraxonrasib’s Phase 3 is still the only RAS-inhibitor overall-survival win.
Drug development is supposed to be linear.
Build the drug → use the drug → resistance shows up → then figure out what to do next.
Aaaand not what Revolution Medicines is doing. 🧬
At #AACR26 they disclosed RM-055, which honestly is a unique concept.
Before daraxonrasib is even fully in the world, they’re building around resistance.
How it works:
• Most mutant RAS proteins are relatively resistant to GAP-mediated hydrolysis
• That helps keep RAS in the active state
• They’ve found a way to enhance that hydrolysis with RM-055
RM-055 can:
• restore hydrolysis in mutant RAS
• flatten daraxonrasib-resistant models
• generate activity even in RAS-amplified settings 👀
That’s a very smart way to think about this space.
Not just “here’s our inhibitor.”
More like: we already know resistance to our drug is coming, so let’s start building now.
That’s how we cure cancer, not more me-toos (if I hear about another new PD1 program I’m going to cry).
@OncoAlert @TheGutOncLab @Onco_Nexus
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