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|
|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.