-FMC-376 is a highly selective, direct dual inhibitor designed to rapidly and completely block both the active and inactive forms of KRAS^G12C and overcome the limitations seen with single-acting inhibitors

-FMC-376 has demonstrated broad activity and efficacy, driving tumor regression across multiple KRAS^G12C mutant CDX and PDX models of non-small cell lung, pancreatic and colorectal cancers

-FMC-376 retains potency in the context of receptor tyrosine kinase activation, a known driver of treatment non-response and resistance—offering the potential for greater and more durable efficacy 

BOSTON and SOUTH SAN FRANCISCO, Calif. — Frontier Medicines Corporation, a precision medicine company seeking to unlock the proteome to advance breakthrough therapies against otherwise undruggable disease-causing targets, today unveiled new preclinical data on its KRAS^G12C inhibitor, FMC-376, demonstrating its uniquely differentiated mode of action. FMC-376 is the first product candidate discovered utilizing the Frontier™ Platform. The data were featured today in an oral presentation at the 2023 American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida (Abstract 1142).

“We are excited to share data showing how our novel dual inhibitor, FMC-376, is uniquely differentiated in its ability to rapidly and directly shut down both active and inactive KRAS^G12C,^” said Chris Varma, Ph.D., Frontier’s co-founder, chairman, and CEO. “FMC-376 was purposely designed to overcome treatment resistance for better outcomes for patients, and we look forward to further exploring its full potential in the clinic.” 

FMC-376: direct dual inhibition designed for better outcomes 
FMC-376 was developed utilizing the Frontier™ Platform to be highly proteome-selective and limit off-target toxicity, while directly engaging both active and inactive KRAS^G12C. Preclinical data demonstrate FMC-376 is >1,000-fold more effective at blocking key effector protein interactions (RAF1 and PI3Ka) compared to prior generation KRASG12C inhibitors. This approach translates into rapid and durable suppression of KRAS^G12C signaling. Additionally, FMC-376’s dual mechanism of action overcomes receptor tyrosine kinase driven resistance and demonstrates potent activity in models resistant to first-generation KRAS^G12C inhibitors. FMC-376’s differentiated dual mechanism of action offers the potential to overcome the lack of response and resistance seen with available treatments. 

FMC-376 has shown efficacy in vivo in multiple KRAS^G12C mutant CDX and PDX models, including in non-small cell lung, pancreatic and colorectal cancers. The company anticipates this will translate into substantial increases in objective response rate and duration of response. The Investigational New Drug (IND) filing for FMC-376 is planned for the second half of 2023. 

About Frontier Medicines
Frontier Medicines is a precision medicine company that has pioneered a powerful drug discovery engine, the Frontier™ Platform, designed to generate medicines against disease-causing proteins previously considered undruggable. The company is deploying its technologies in chemoproteomics, covalent drug discovery, and machine learning to develop potentially groundbreaking medicines for genetically-defined patient populations, starting in cancer. Frontier is advancing a deep pipeline of wholly-owned precision medicines against the most important drivers of cancer. The company’s lead candidate, FMC-376, is a dual inhibitor of active and inactive KRAS^G12C. By completely blocking both forms of the KRAS mutation, FMC-376 has the potential to overcome the non-response and resistance seen with single-acting KRAS^G12C inhibitors. For more information on how Frontier is boldly advancing science to defeat disease, visit www.frontiermeds.com and follow us on LinkedIn and Twitter.