Cheers, chills, and a standing ovation when RASolute 302 showed unprecedented survival on daraxonrasib for patients with progressive pancreatic cancer Seldom do you sense you’re witnessing a historic moment in cancer care but this feels like ras targeting has arrived #ASCO26

This April, we got a drug revolutionary in 3 ways: daraxonrasib roughly doubles survival in metastatic pancreatic cancer, cracked RAS, a protein deemed untreatable for decades & pioneered a drug class called molecular glues. Read more in my piece @WorksInProgMag worksinprogress.news/p/pancr… - Pancreatic cancer is a particularly tough cancer. - It's diagnosed late in its progression and it coats itself with tissue that block the immune system from attacking it. This makes immunotherapies, which have been revolutionary in other metastatic cancers (e.g. melanoma) ineffective against it. - 90% of pancreatic cancer have one mutated protein: RAS. This should make it easily targetable. But ... not so quick! - RAS has a property that has made it "undruggable" for decades: it largely lacks the pockets or grooves that most drugs depend on to bind and act upon their target. - Molecular glues sidestep the problem entirely. Instead of binding a pocket, daraxonrasib forces two proteins together — locking RAS in its inactive state by wedging a third protein in the way. - The result: median survival of 13.2 months vs ~6 on standard chemo. Not a cure, but a genuine doubling, delivered as a daily pill. - The implications go far beyond pancreatic cancer. RAS is mutated in lung, colorectal, and many other cancers. Molecular glues are now being developed against multiple other "undruggable" targets. The assumption that certain proteins are simply beyond reach has turned out, repeatedly, to be wrong. - The bad news is that most patients eventually develop resistance mutations that vary from patient to patient. In order to deliver a real cure, we need to rethink our regulatory system and make small-n, early stage bespoke trials much easier to run.