RAS Oral Inhibitors

KRAS is one of the most highly mutated genes of human cancers. KRAS alteration increases the KRAS oncoprotein activity by promoting the RAS (ON) state and leading to uncontrolled signaling that drives tumor cell proliferation. RAS-addicted cancers with KRAS activating mutations include non-small cell lung cancer, colorectal cancer, and pancreatic cancer, although these KRAS mutations are also observed in many cancer types.

RAS signaling and pathway alterations are frequent mechanisms for tumor resistance to prior therapies. Secondary mutations in KRAS as well as KRAS, NRAS, HRAS uncoupled overexpression are well-established tumor resistance mechanisms, associated with poor therapeutic outcomes and cancer progression.

280Bio is advancing several programs with a broader spectrum of activity against RAS signaling to address the unmet need of tumor resistance. Our agents are targeting RAS-addicted cancers and are anticipated to provide clinical benefit in patient populations stratified with the RAS signaling alterations.

Our RAS discovery engine is expanding the arsenal of additional RAS-directed oral inhibitors by combining our lead optimization, medicinal chemistry and pharmacology capabilities.