KRASG12C Inhibitor

Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective and potent oral small molecule therapy.

Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective and potent oral small molecule therapy.

Mechanism of Action

Mirati is developing adagrasib to target the KRASG12C mutation 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 KRASG12C11

Long half-life

Only KRASG12C inhibitor with a ~24-hour half-life11

Highly selective

Over 1,000-fold selective for mutant KRASG12C vs wild-type KRAS and other protein cysteines11

Wide therapeutic index

Preclinical projection of >10-fold safety8

Extensive tissue distribution

Only KRAS inhibitor where projected human volume of distribution exceeds 10 L/kg8

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Program Summary

Adagrasib is being explored as a single agent and in combination with other anticancer drugs.

Preclinical studies have shown 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. Our goal is to optimize efficacy and prevent treatment resistance, ensuring these potentially promising combination approaches can help patients throughout the course of their treatment journey.

Adagrasib (MRTX849) Combination Therapy