Months after Amgen's landmark KRAS approval, Chris Varma bags a crossover round for next-gen candidate
For years, mutant, cancer-fueling KRAS proteins were considered “undruggable.” That all changed in May, when Amgen’s KRAS-blocking drug Lumakras snagged the FDA’s first approval in the field. And now a slate of investors are betting $88.5 million on a Bay Area startup’s next-generation candidate.
Frontier Medicines has closed a hefty Series B round, co-led by Woodline Partners and RA Capital Management, the company said on Monday. Deerfield Management, Deep Track Capital, ArrowMark Partners, Driehaus Capital Management, Sphera Healthcare, DCVC’s Bio fund, Droia Ventures and MPM Capital also chimed in. With the latest round, it’s possible CEO Chris Varma has an IPO on the mind.
Varma launched Frontier back in 2019 with $67 million in launch money and a mission to drug previously “undruggable” proteins. Since then, the 10-person team has grown to about 60 staffers. Varma — who has also co-founded Blueprint Medicines and built companies at Third Rock and Flagship — says the team is likely a couple years away from the clinic.
“We’re progressing rapidly to IND-enabling studies,” he told Endpoints News on Monday morning.
Back in December, AbbVie shelled out $55 million upfront to partner with Frontier on protein degradation work, promising to reimburse the startup for its preclinical R&D costs.
Meanwhile, the B round will be used to advance the company’s preclinical pipeline of precision medicines against drivers of cancer. Its lead program is focused on blocking active and inactive forms of KRAS G12C, the same mutation targeted by Amgen’s Lumakras for non-small cell lung cancer. What differentiates Frontier’s candidate is that it targets both active and inactive forms of the protein. A majority of patients who are treated with inhibitors targeting inactive forms of KRAS G12C don’t respond, Varma added.
“The ability to target both forms of KRASG12C, which includes the active and inactive states of the protein, with a small molecule therapy would be a long-awaited scientific breakthrough,” said Frank McCormick, a professor of the UCSF Helen Diller Family Comprehensive Cancer Center, in a statement.
“Importantly for patients, a drug with this dual inhibition may be more efficacious than a drug that targets just the inactive form of KRASG12C by addressing the large majority of patients who are non-responders to first generation single-form KRASG12C inhibitors, as well as those patients whose tumors become resistant to the first-generation molecules,” he continued.
At the core of Frontier’s platform is machine learning paired with something the company calls chemoproteomics, or finding new ways to bind targets by examining temporary pockets in proteins.
Upon the company’s launch back in 2019, Varma told Endpoints that “druggable” proteins are like coat hangers — they have corners that drugs can dock into. “Undruggable” proteins on the other hand appear — figuratively — more like a string.
“If you shake the string, you wiggle it, then you see that actually curves do form and within those curves are corners and you could imagine docking a small molecule drug into those,” he said.
Frontier is working on tech that would allow scientists to put a covalent bind there, creating a permanent lock in a transient corner.
A handful of other drugmakers are pursuing KRAS inhibitors, including Mirati, which snagged breakthrough therapy designation for its adagrasib in non-small cell lung cancer back in June. Eli Lilly jumped into the hunt back in March, and said it planned to put a new small molecule in Phase I later this year. And back in October 2019, Boehringer Ingelheim advanced its pan-KRAS inhibitor into the clinic.
In addition to the financing, Frontier has announced that it’s adding a new site in Boston to complement its South San Francisco headquarters, where it will “build its employee expertise across research and development, including discovery, pre-clinical development, translational medicine, and early clinical development.” The new site is expected to open before the end of the year, and will be home to about 60 or so more employees — and Varma added that he’s looking to hire.
*A correction has been made to note that DCVC’s investment came from their Bio fund.