KRAS-driven Vulnerabilities

Targeting KRAS G12D — the most common variant in PDAC — with first-in-class degraders and RAS(ON) inhibitors.

Overview

KRAS mutations are present in more than 90% of pancreatic ductal adenocarcinomas. Our lab is at the forefront of targeting KRAS G12D — the most common substitution variant in pancreatic cancer, found in roughly 40% of patients.

First-in-class therapeutics

We led the first-in-human trial of setidegrasib (ASP3082), a first-in-class KRAS G12D targeted protein degrader, published in the New England Journal of Medicine (2026).

We also contributed to the phase 1–2 study of daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor that targets GTP-bound mutant and wild-type RAS, with encouraging activity in previously treated RAS-mutated PDAC.

Genomics of KRAS

Beyond drugging KRAS, we characterise how specific KRAS mutants and mutant dosage shape clinical outcomes and biology, informing which patients should receive which RAS-directed therapy.