Genentech Ends SHP2 Inhibitor Collaboration with Relay Therapeutics

Genentech, a member of the Roche Group, has decided to terminate its SHP2 inhibitor collaboration with Relay Therapeutics, returning the rights after investing over $120 million into the alliance. This decision marks another instance of the growing trend of major pharmaceutical companies withdrawing from SHP2 inhibitor deals.

In 2021, Genentech made an initial payment of $75 million to license Relay’s SHP2 inhibitor, known as RLY-1971, migoprotafib, or GDC-1971. The investment was driven by the potential of combining this molecule with Genentech's KRAS G12C inhibitor, GDC-6036. Over subsequent years, Genentech added $45 million in milestone payments to the investment. However, the termination of the research and development partnership means Relay will miss out on up to $675 million in potential success-based payments.

This move is part of a broader retreat by major pharmaceutical companies from SHP2 inhibitors. Sanofi initiated this trend by ending its partnership with Revolution Medicines in 2022. Following this, AbbVie discontinued its deal with Jacobio in 2023, and earlier this year, Bristol Myers Squibb terminated its agreement with BridgeBio Pharma. In addition, Erasca decided to halt its SHP2 program.

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Despite the widespread pullback, some companies remain committed to exploring the potential of SHP2 inhibitors. Merck & Co. has an ongoing partnership with Taiho and Astex, enrolling patients in a phase 1 trial targeting SHP2. Novartis is conducting a phase 1/2 trial of its SHP2 inhibitor, TNO155, in combination with a KRAS G12C candidate. Additionally, several smaller companies continue to investigate SHP2 inhibitors.

Genentech's decision to terminate the pact comes after testing GDC-1971 in four phase 1 clinical trials, with three trials still actively recruiting. These trials focus on advanced solid tumors, including colorectal and non-small cell lung cancer. In these studies, Genentech has explored combinations of GDC-1971 with Erbitux, Tagrisso, Tecentriq, and GDC-6036.

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