Genentech ends SHP2 deal, Relay faces fewer competitors

Roche’s Genentech has abandoned its SHP2 inhibitor collaboration, returning the rights to Relay Therapeutics after investing over $120 million in the partnership. This move is part of a growing trend of pharmaceutical companies reconsidering their involvement in SHP2 inhibitor projects.

In 2021, Genentech initially paid $75 million upfront to license Relay's SHP2 inhibitor, known as RLY-1971, migoprotafib, or GDC-1971. The investment was driven by the company's optimism about combining this molecule with its KRAS G12C inhibitor, GDC-6036. Despite several years of research and an additional $45 million in milestone payments, Genentech has now chosen to end the R&D collaboration without cause. This decision means Relay will miss out on potentially earning another $675 million in success-based payments.

The termination of this deal is indicative of a broader decline in Big Pharma's interest in SHP2 inhibitors. Sanofi led the way in 2022 by ending its agreement with Revolution Medicines. Following that, AbbVie discontinued its partnership with Jacobio in 2023, and Bristol Myers Squibb recently terminated its agreement with BridgeBio Pharma. In a related move, Erasca also halted its SHP2 program.

Despite the dwindling interest from major pharmaceutical companies, some firms remain committed to SHP2 research. Merck & Co., for instance, entered a SHP2 collaboration with Taiho and Astex in 2021 and is currently enrolling patients in a phase 1 trial targeting SHP2. Similarly, Novartis is investigating a SHP2 inhibitor, TNO155, in combination with a KRAS G12C candidate in a phase 1/2 trial. Additionally, several smaller companies continue to pursue SHP2 inhibitor programs.

Genentech has conducted four phase 1 clinical trials for GDC-1971, three of which are still actively recruiting participants. These trials are focused on evaluating the SHP2 inhibitor in patients with advanced solid tumors, including colorectal and non-small cell lung cancer. Depending on the specific trial setting, GDC-1971 has been paired with Erbitux, Tagrisso, Tecentriq, and Genentech's KRAS G12C inhibitor, GDC-6036.

This ongoing research activity highlights that while the overall enthusiasm for SHP2 inhibitors may be waning among some large pharmaceutical companies, the scientific and clinical exploration of this target continues. Researchers and smaller entities remain invested in uncovering the potential benefits of SHP2 inhibitors, particularly in combination therapies for difficult-to-treat cancers.