As proof of concept builds for leading KRAS inhibitors in lung cancer and now other KRAS mutant tumors, the pipeline of KRAS inhibitors is growing, and they’re almost all unpartnered programs.
It's been a big year for the long undruggable target. The first inhibitor — Lumakras sotorasib from Amgen Inc. (NYSE:AMGN) — reached the market in May under the accelerated approval pathway for non-small cell lung cancer (NSCLC), and Amgen and Mirati both revealed strong proof of concept in colorectal cancer at this month’s European Society for Clinical Oncology (ESMO) Congress.
Amgen brought Lumakras to market without a partner, and Mirati Therapeutics Inc. (NASDAQ:MRTX) appears on track to do the same. Much of Mirati’s roughly $9 billion valuation is tied to KRAS inhibitor adagrasib, which it brought to the clinic alone, and for which it plans to submit an NDA next quarter to treat NSCLC.
Companies looking to enter the space through a licensing deal may need to go early, with preclinical programs offering the most opportunities.
Behind the Amgen and Mirati programs are six early stage clinical therapies, two of which belong to major pharmas. The third is in development by the Beijing-based mid-cap Jacobio Pharmaceutical Group Co. Ltd. (HKEX:1167), while the other three are at private biotechs:
Cambridge, Mass-based Elicio Therapeutics Inc. and China-based companies GenFleet Therapeutics (Shanghai) Co. Ltd. and Genhouse Bio Co. Ltd.
Like the leading KRAS inhibitors, the Jacobio, GenFleet and Genhouse programs are small molecules against G12C mutant KRAS; whereas Elicio’s program is a therapeutic vaccine that incorporates antigens from multiple mutant forms of KRAS.
The preclinical pipeline, by contrast, holds at least nine programs spanning four different therapeutic modalities and several KRAS mutations. Another nine programs are in discovery.
Companies that have already partnered up (not shown below) include Araxes Pharma LLC and Johnson & Johnson (NYSE:JNJ), Ionis Pharmaceuticals Inc. (NASDAQ:IONS) and AstraZeneca plc (LSE:AZN; NASDAQ:AZN), and Moderna Inc. (NASDAQ:MRNA) and Merck & Co. Inc. (NYSE:MRK).
Additionally, SEngine Precision Medicine Inc. and Atomwise Inc. have a discovery deal.
