Revolution Medicines has filed to raise $100 million in an IPO. The anticipated fundraising haul will bankroll development of a pipeline of RAS programs up to the completion of IND-enabling studies.
Amgen and Mirati Therapeutics have generated clinical data to suggest KRAS, the target of several of Revolution’s assets, no longer deserves to be seen as undruggable. The data have turned KRAS into one of the hottest areas of oncology R&D, driving shares in Mirati up more than 200% last year in the process.
Now, Revolution, a 2015 Fierce 15 company, is set to add to the list of public companies targeting KRAS. If all goes to plan, the Sanofi-partnered biotech will raise money to support preclinical work on drugs against KRAS-G12C, KRAS-G13C, KRAS-G12D and NRAS-G12C.
Revolution is trailing the KRAS leaders—it is due to nominate its first candidate this year—but it is operating in a slightly different space. Specifically, Revolution is working on inhibitors of the active, GTP-bound form of RAS, also known as RAS(ON). AMG 510, the Amgen drug that showed KRAS can be drugged, is a KRAS-G12C(OFF) inhibitor.
The leaders at Revolution think they have the first potent, selective, cell-active inhibitors of RAS(ON). Revolution explained why that may be significant for its prospects in its IPO filing.
“In some cells harboring a KRAS-G12C mutation, 80% or more of cellular KRAS-G12C is in the GTP-bound state (RAS(ON)), representing a >15-fold increase compared to wild-type KRAS. As a general principle, RAS-dependent cancer cells exploit a high level of RAS(ON) for continued survival and growth,” the company wrote in its S-1.
Work on KRAS features prominently in the S-1, topping the list of uses for the money Revolution aims to raise. However, Revolution got into the field through a cut-price deal, paying $69 million to acquire Warp Drive Bio. Warp Drive began life with big plans and a high-profile $125 million investment from Third Rock Ventures and Sanofi, but, as the S-1 shows, ended with a whimper.
At Revolution, Warp Drive’s KRAS assets will advance in parallel to a 4EBP1/mTORC1 program that is also in preclinical. Revolution made its name with SHP2 inhibitor RMC-4630, but, under the terms of its deal with Sanofi, it’s now on the hook for just a fraction of the R&D costs of that asset. The drug remains important to Revolution, though, in part because of the potential to combine it with KRAS inhibitors.