Revolution Medicines raised $100 million in series C financing to advance a stable of drugs aiming at what it calls “frontier targets” in cancer. These include a program targeting KRAS mutations, which were previously considered undruggable.
The new infusion comes nine months after Revolution snapped up Warp Drive Bio, folding in the latter’s SMART modality platform—small molecules that bind to intracellular receptor proteins and essentially create a biologic drug complex that operates within a cell—with its own work in undruggable targets.
“The merged R&D portfolio represents a rich pipeline of near- and long-term development opportunities for our R&D team to advance in support of our continuing commitment to translate frontier oncology targets on behalf of cancer patients,” said Revolution CEO Mark Goldsmith, M.D., Ph.D., at the time.
The California biotech’s lead asset is a molecule that blocks SHP2, a protein that plays a role in the RAS pathway, which is implicated in several cancers. The drug, RMC-4630, is in a phase 1/2 study in multiple tumor types and is also the focus of a global collaboration with Sanofi.
Revolution is also working on several preclinical programs targeting mutations in multiple RAS isoforms, which could include HRAS and NRAS, as well as the better-known KRAS. Its KRAS program is the most advanced—it is moving through lead optimization.
KRAS mutations turn up in up to one-quarter of all cancers, but patients with these mutations still don’t have targeted treatment, largely due to the lack of obvious binding sites on the KRAS protein. Amgen posted the first clinical data for a KRAS inhibitor at this year’s American Society of Clinical Oncology meeting, showing its drug AMG 510 stopped tumor growth in the majority of patients with non-small cell lung cancer and colorectal cancer.
“AMG 510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface,” said David Reese, M.D., Amgen’s R&D chief, at the time. “By irreversibly binding to cysteine 12 on the mutated KRAS protein, AMG 510 is designed to lock it into an inactive state.”
It took 30 years for researchers to crack KRAS, but Revolution reckons it can improve upon the likes of AMG 510. Amgen’s drug targets the inactive, or GDP-bound, state of mutant KRAS, while Revolution’s molecule is designed to bind to the active, GTP-bound state of mutant KRAS, which encourages tumor development.
“Preclinical evidence suggests that this mechanism of action confers a superior biological profile compared with first-generation inhibitors [like AMG 510] and thereby potentially offers significant competitive advantages,” Revolution said in the statement.
“This strong support comes at an exciting time for REVOLUTION Medicines as we advance novel programs addressing multiple frontier oncology targets within the resilient and adaptable RAS cancer pathway, including our clinical-stage inhibitor of SHP2,” Goldsmith said in a statement.
Revolution drew its financing from a marquee list of investors, including Boxer Capital of the Tavistock Group, Cormorant Capital, Deerfield Management, Fidelity, Vivo Capital and Biotechnology Value Fund. They were joined by Casdin Capital, The Column Group, Nextech Invest, Schroder Adveq and Third Rock Ventures—which all chipped into Revolution’s B round and came back for more.