Bristol exits KRAS G12D

Although interest in KRAS G12D inhibition is swelling, one company no longer involved in this arena is Bristol Myers Squibb. The company confirmed to ApexOnco that it had canned MRTX1133, a G12D inhibitor gained via its $4.8bn purchase of Mirati. The acquisition primarily concerned the G12C inhibitor Krazati, with MRTX1133 seen as a bonus. However, data on the G12D project, once promised by Mirati in the first half of 2024, never materialised, and in January a phase 1/2 study was quietly terminated after completing phase 1, according to its clinicaltrials.gov listing. A Bristol spokesperson said no safety concerns had been identified, but that pharmacokinetics data were “highly variable and suboptimal”. The group “continues to believe” in KRAS, the spokesperson added – but Krazati sold just $118m in 2024. Bristol also gained a G12D project through its 2022 Turning Point takeover, but this hasn’t progressed, and is presumably no longer in development. The selective G12D inhibition leader is Revolution Medicines, whose zoldonrasib (RMC-9805) showed promise at last year’s Triple meeting. Meanwhile, Astellas’s degrader ASP3082 disappointed at ESMO; that asset is still in development, the company recently told ApexOnco, despite the group advancing another G12D degrader, ASP4396. KRAS G12D-selective inhibitors in industry-sponsored clinical trialsProjectCompanyDescriptionStatusZoldonrasib (RMC-9805)Revolution MedicinesInhibitorPh1 data at Triple meeting 2024; pivotal trials could start 2026ASP3082AstellasDegraderLacklustre ph1 data at ESMO 2024; proof-of-concept judgement due in H1 2025HRS-4642Luzsana (Jiangsu Hengrui)InhibitorLacklustre ph1 data at ESMO 2023GFH375Verastem/GenFleetInhibitorChinese ph1/2; data due H1 2025INCB161734IncyteInhibitorPh1; data due 2025AZD0022AstraZeneca (via Usynova)InhibitorPh1/2 Alafoss-01; data due >2026NT-112AstraZeneca (via Neogene)TCRPh1; data due 2026RNK08954Ranok TherapeuticsDegraderPh1/2TSN1611Tyligand BioscienceInhibitorPh1/2DN022150Jiangxi KeruiInhibitorChinese ph1/2ASP4396AstellasDegraderPh1INCB186748Incyte?Ph1LY3962673LillyInhibitorPh1PT0253PAQ TherapeuticsDegraderPh1QTX3046Quanta TherapeuticsInhibitorPh1RG6620RocheInhibitorPh1AST2169AllistInhibitorChinese ph1QLC1101Qilu PharmaceuticalInhibitorChinese ph1Source: OncologyPipeline.