Merck & Co buys into Kras

A low-key research collaboration struck a year ago has led to Merck & Co today taking out an exclusive licence to an anticancer project targeting the Kras pathway. The work had originated at Otsuka, and focuses on inhibiting SHP2, an enzyme thought to play a role in cycling Kras between its “on” and “off” states. Though this is still preclinical, Merck has clearly seen enough to part with more cash; a year ago it had given Otsuka’s Taiho and Astex subsidiaries $50m to set up a research alliance into Kras, and today’s option for full rights involves a second payment, understood to amount to at least as much again. Direct inhibition of Kras is at present a battle between Amgen’s sotorasib and Mirati’s adagrasib, but other companies are working on indirect ways of hitting this target, which until recently had been thought to be undruggable. Such pathways include SOS1, under investigation at Bayer and Boehringer Ingelheim, as well as SHP2. The Merck programme’s most advanced competitors in this latter space are Novartis/Mirati’s TNO155 and Revolution/Sanofi's SAR442720.

Src homology phosphatase (SHP) 2 inhibitor pipeline
Project Company Comment
TNO155 Novartis/Mirati Ph1/2 (Krystal-2) study in Kras G12C mutants
RMC-4630 (SAR442720) Revolution Medicines/Sanofi Ph1/2 combo trial; deal signed Jul 2018
RLY-1971 Relay Therapeutics First-in-human ph1 started Feb 2020
BBP-398 (IACS-15509 / IACS-13909) Navire (Bridgebio Pharma) First-in-human ph1 started Aug 2020
ERAS-601 Erasca First-in-human ph1 (Flagshp-1) started Jan 2021
HBI-2376 Huya Bioscience/Suzhou Genhouse Preclinical; licensing deal Aug 2020
SHP2 programme Merck & Co/Otsuka Preclinical; licensing option exercised Jan 2021
SHP2 inhibitors Redx Pharma Earlier mentioned as a research project
Source: company announcements.

This story was updated to add the Erasca project.

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