A low-key footnote to Roche’s first-quarter financials today revealed that the group had put RG6433, a Shp2 inhibitor, into a phase 1 trial. This pharmacology is becoming an important mechanism in targeting Kras-driven cancers, as the Shp2 enzyme is thought to play a role in cycling Kras between its “on” and “off” states. It appears that RG6433 is Roche’s new code for RLY-1971, a project the company licensed from Relay Therapeutics for $75m up front last December. Relay had started its own phase 1 study of RLY-1971 over a year ago, but no data are available. The most advanced Shp2 player is Novartis with TNO155, a project being combined with Mirati’s Kras G12C inhibitor adagrasib, while Merck & Co did an early Shp2 deal with Otsuka in January. Revolution Medicine/Sanofi’s RMC-4630, meanwhile, disappointed at an AACR late-breaker, at least as monotherapy. Mirroring the actions of Novartis/Mirati, Roche’s plan includes combining Shp2 inhibition with its early-stage Kras G12C inhibitor GDC-6036, which is separately in phase 1. Given the growing interest in Kras it seems unlikely that these assets will remain under the radar for long.
|Src homology phosphatase (Shp) 2 inhibitor pipeline|
|TNO155||Novartis||Ph1/2 studies in combo with in Kras G12C inhibitors adagrasib (Mirati) & JDQ443 (Novartis)|
|RMC-4630 (SAR442720)||Revolution Medicines/Sanofi||Ph1/2 combo trial; deal signed Jul 2018|
|JAB-3068||Abbvie/Jacobio||Ph1/2 ends Jul 2021; deal signed Jun 2020|
|JAB-3312||Abbvie/Jacobio||Ph1 ends imminently; deal signed Jun 2020|
|RG6433 (RLY-1971)||Roche/Relay Therapeutics||Ph1; deal signed Dec 2020|
|BBP-398 (IACS-15509 / IACS-13909)||Navire (Bridgebio Pharma)||Ph1 started Nov 2020|
|ERAS-601||Erasca||Ph1 (Flagshp-1) started Dec 2020|
|SH3809||Nanjing Sanhome||Ph1 started Apr 2021|
|HBI-2376||Huya Bioscience/Suzhou Genhouse||Preclinical; licensing deal Aug 2020|
|ETS-001||Shanghai Etern Biopharma||Preclinical data at AACR 2021.|
|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 has been updated to add the Shanghai Etern asset.