Revolution Medicines Inc. followed the results offered last month with zoldonrasib (RMC-9805), a RAS G12D (ON) inhibitor, with plenty more about pipeline progress – “an embarrassment of riches,” CEO Mark Goldsmith said – during the firm’s first-quarter update. Shares of the firm (NASDAQ:RVMD) closed May 8 at $41.91, up $4.25, or 11%.
Revolution Medicines Inc. has disclosed macrocyclic compounds acting as GTPase KRAS (G12V mutant) inhibitors reported to be useful for the treatment of cancer.
Early phase I data for Revolution Medicines Inc.’s RAS(ON) G12D-selective inhibitor zoldonrasib encouraged both the company and the analysts. Initial study data produced a 61% objective response rate in 11 solid tumor patients receiving the 1,200-mg dose once a day. The disease control rate for 16 patients came in at 89%.
RAS G12D is one of the most frequent mutations in RAS, and when it occurs, it leaves RAS in a permanently active state, causing the cell to proliferate uncontrollably. Examples of the so-called RAS-addicted cancers are colorectal cancer or pancreatic ductal adenocarcinoma.
Revolution Medicines Inc. has synthesized macrocyclic compounds acting as GTPase KRAS, NRAS, HRAS and their mutant inhibitors reported to be useful for the treatment of cancer.
The effective targeting of RAS-mutant acute myeloid leukemia (AML) still remains a challenge; RAS mutations are tied to relapse to targeted therapy, such as resistance to FLT3 inhibitors due to the RAS/MAPK pathway, for example.
The development of covalent KRAS G12C inhibitors has represented a significant advance for non-small-cell lung cancer treatment, but other mutations such as KRAS G13C/D still lack effective treatments.
The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable.
The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.
Aethon Therapeutics Inc. has entered into a collaboration agreement with Revolution Medicines Inc. under which Aethon will use its Hapimmune platform to discover novel bispecific antibodies to mount an immune attack directed towards cancer cells hit by Revolution Medicines’ RAS(ON) inhibitors.
