Roche reminds the markets that it’s a Kras player

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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
Project Company Comment
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.

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