Mirati Therapeutics KRASG12C Inhibitor Adagrasib (MRTX849) Adagrasib is an investigational highly selective and potent oral small molecule therapy designed to treat some of the most complex and aggressive cancers. Mechanism of Action Mirati is developing the investigational drug candidate adagrasib, to target KRASG12C and maximize inhibition by irreversibly locking the mutant protein in its inactive state. Preclinical studies of adagrasib demonstrated key characteristics including: Potent Low nanomolar potency across multiple cellular models of KRASG12C10 Long half-life Only KRASG12C inhibitor with a ~ 24-hour half-life10 Highly selective 1,000+ fold selective for mutant KRASG12C vs wild-type KRAS and other protein cysteines10 Wide therapeutic index Preclinical projection of >10-fold safety margin10 Extensive tissue distribution Only KRAS inhibitor where projected human volume of distribution exceeds 10L/kg10 Sorry, your browser doesn't support embedded videos. Program Summary Adagrasib is being explored as a monotherapy as well as in combination with other anticancer drugs. The goal is to optimize efficacy and prevent treatment resistance, ensuring these potentially promising combination therapies can help patients throughout the course of their treatment journey. Extensive preclinical studies showed that combining adagrasib with a broad range of therapies, including PD-1, SHP2, Pan-EGFR, CDK 4/6, and SOS1 inhibitors, resulted in even more robust anti-tumor activity. Adagrasib (MRTX849) Combination Therapy Clinical Trials Adagrasib is being evaluated in a Phase 1/2 clinical trial treating patients with molecularly identified, KRASG12C-positive advanced solid tumors. In the first quarter of 2020, enrollment began in the registration-enabling monotherapy cohort, evaluating patients with non-small cell lung cancer and colorectal cancer. Initial results from the Phase 1/2 study demonstrating the potential of adagrasib as a potent and effective KRAS therapy were presented at the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics in October 2020. Learn More About Our Clinical Trials Mirati Therapeutics © Copyright 2021 - Mirati Therapeutics, Inc. 858.332.3410 info@mirati.com Terms of Use Privacy Cookies Expanded Access Community Guidelines