KRAS Q61H mutation has been found in pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC) among other solid tumors. In healthy cells, RAS proteins switch between ON and OFF states during signal transduction, but in cancer, mutations in RAS genes or regulators install RAS proteins in ON state permanently.
Targeted oncology firm Revolution Medicines Inc. is seeking $300 million through a public offering as it prepares to say farewell to Sanofi SA, partner for its most advanced RAS program, and with it the prospect of earning more than $500 million in developmental and regulatory milestone payments and tiered royalties on annual net sales.
To target mutant RAS in the GTP-bound RAS(ON) state for cancer treatment, Revolution Medicines Inc. has developed a platform in which binding and inhibition occur through small molecule-driven formation of a high-affinity ternary complex (tri-complex) between the target protein, a small molecule and a chaperone such as cyclophilin A.
Though Revolution Medicines Inc.’s SHP2 inhibitor, RMC-4630, fell short of internally set benchmarks in a pair of phase I combo trials, the prospect remains alive, as the company has been “very publicly moving towards combining the companion inhibitors that we have, which include RMC-4630 with RAS inhibitor therapies that we and others make,” said Steve Kelsey, president of R&D.
Although, the appetite for biopharma IPOs in the U.S. slowed during the meltdown of the financial markets in March, the flow of new offerings has been steady this year, according to BioWorld, with 11 companies graduating to the public stage and listing on U.S. exchanges by the end of April, collectively raising $1.774 billion along the way. This amount is 9.5% higher than the $1.62 billion raised from 15 U.S. biopharma IPOs completed in the same period last year.
Revolution Medicines Inc. (NASDAQ:RVMD) shares closed at $28.90, a 70% jump above the $17 price in its upsized IPO of 14 million shares, which raised $238 million, showing further confidence in the Redwood City, Calif.-based company’s bid to blast cancer targets once deemed “undruggable.”
Amgen Inc. and Revolution Medicines Inc. will collaborate on a clinical trial evaluating the combination of RMC-4630, Revolution's SHP2 inhibitor, and Amgen's AMG-510, a KRAS-G12C inhibitor. Amgen will conduct the phase Ib trial to treat patients with advanced solid tumors harboring the KRAS G12C mutation and Revolution will provide Amgen with RMC-4630.
Revolution Medicines Inc., a California-based company developing a small-molecule inhibitor of SHP2 in partnership with Sanofi SA and other programs targeting mutant forms of the key signaling protein RAS, has raised a $100 million series C equity financing led by Boxer Capital LLC, an investment firm funded by British businessman Joe Lewis' Tavistock Group, which has backed financings of companies including G1 Therapeutics Inc., Kura Oncology Inc. and, more recently, Encoded Therapeutics Inc.
