Frontier Medicines Raises $80M in Series C, Targets Amgen and BMS in KRAS

M&A deal_iStock, AmnajKhetsamtip

Pictured: Businessmen shaking hands after closing a deal/iStock, AmnajKhetsamtip

Frontier Medicines on Thursday closed its oversubscribed $80 million Series C funding round,  which it will use to advance its potentially first-in-class next-generation KRAS blocker FMC-376.

The financing brings Frontier’s total capital raised to $235.5 million since its founding, according to the announcement. The funding round was co-led by Deerfield Management Company and Droia Ventures. Galapagos NV, a Belgium-based pharmaceutical company, participated as a strategic investor, along with contributions from MPM Capital, RA Capital Management and DCVC Bio.

Frontier also announced on Thursday that it had dosed the first patient in the Phase I/II PROSPER trial, testing FMC-376 in patients with G12C-mutated KRAS cancers.

CEO Chris Varma in a statement called the development a major milestone for the company. “Frontier Medicines has amassed a robust data set that shows FMC-376 is expected to overcome the resistance seen with prior generating single-acting inhibitors, and we are excited to demonstrate this potential in the clinical setting.”

FMC-376 distinguishes itself from other KRAS inhibitors by directly engaging both the inactive and active forms of the G12C-mutated KRAS. This differentiated dual direct mechanism of action could help FMC-376 to potentially overcome the treatment resistance and suboptimal response observed in single-acting KRAS inhibitors.

In lab studies, FMC-376 showed activity against a wide range of KRAS G12C mutant cancer models, including non-small cell lung cancer (NSCLC), pancreatic cancer and colorectal cancer.

Frontier presented preclinical data for the candidate in April 2023 at the annual meeting of the American Association for Cancer Research, demonstrating that FMC-376 is more than 1,000-fold more effective at blocking the interactions of key effector proteins compared with prior-generation inhibitors. This blocking mechanism results in a “rapid and durable” inhibition of KRAS G12C signaling, according to the company.

With FMC-376, Frontier is looking to challenge Amgen and the recently BMS-acquired Mirati in the KRAS arena.

Amgen’s Lumakras (sotorasib) won the FDA’s accelerated approval in May 2021 for the treatment of NSCLC patients carrying the KRAS G12C mutation. To keep it on the market, Amgen ran the Phase III CodeBreaK 200 study as a confirmatory trial to verify Lumakras’ clinical benefit.

However, in October 2023, the FDA’s Oncologic Drugs Advisory Committee found that progression-free survival data from the study could not be reliably interpreted and voted 10–2 against Amgen. The FDA agreed with the advisory committee two months later, denying full approval for Lumakras and requesting an additional confirmatory trial due no later than February 2028.

Mirati’s Krazati (adagrasib) was granted accelerated approval in December 2022 for the same indication. The KRAS blocker then secured a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use in November 2023. BMS bought Mirati for $4.8 billion in October 2023, with Krazati as one of the acquisition’s prized assets.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

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