Revolution Medicines Inc. has divulged son of sevenless homolog 1 (SOS1) inhibitors reported to be useful for the treatment of cancer, neurofibromatosis type 1, cardiofaciocutaneous, Noonan, Costello and Legius syndrome (neurofibromatosis type 1-like syndrome), among others.
Researchers from Revolution Medicines Inc. presented the discovery and preclinical characterization of RMC-5127, a novel noncovalent, tri-complex inhibitor of GTPase KRAS (G12V mutant), or KRAS G12V(ON).
Revolution Medicines Inc. is acquiring Eqrx Inc. in an all-stock transaction designed to add more than $1 billion in net cash for Revolution so it can forge ahead with its RAS pathway programs. Serial biotech entrepreneur and investor Alexis Borisy co-founded Eqrx in 2020 to deliver new medicines for cancer and other conditions at "radically lower prices." Borisy also co-founded Revolution, where he remains as executive chairman.
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.
