Genentech sinks SHP2 pact, leaving Relay to race thinning field

Genentech sinks SHP2 pact, leaving Relay to race thinning field

Roche’s Genentech has scuttled its SHP2 inhibitor pact, returning the rights to Relay Therapeutics after plowing more than $120 million into the alliance. The action is the latest in a series of terminations of SHP2 deals.

In 2021, Genentech paid $75 million upfront to license Relay’s SHP2 inhibitor, a molecule variously called RLY-1971, migoprotafib or GDC-1971. The outlay reflected the company’s belief in the promise of pairing the molecule with its KRAS G12C inhibitor GDC-6036.

Several years and $45 million in milestones later, Genentech has decided to terminate the R&D alliance without cause, depriving Relay of the chance to pocket another $675 million in success-based paydays.

The termination of the deal is part of a broader softening of Big Pharma interest in SHP2. Sanofi began the exodus by axing its Revolution Medicines pact in 2022. AbbVie was the next to rethink its interest in SHP2, culling a deal with Jacobio in 2023, and Bristol Myers Squibb extended the trend by terminating its agreement with BridgeBio Pharma earlier this year. Amid that activity, Erasca axed its SHP2 program.

Some companies have kept the faith as the wider sector has soured on SHP2. Merck & Co. entered into a SHP2 pact with Taiho and Astex in 2021 and is now enrolling patients in a phase 1 trial related to the target. Novartis is evaluating a SHP2 inhibitor, TNO155, in combination with a KRAS G12C candidate in a phase 1/2 trial. A clutch of smaller companies are still in the race too.

Genentech tested GDC-1971 in four phase 1 clinical trials, three of which are currently recruiting. The active trials are assessing the SHP2 inhibitor in patients with advanced solid tumors including colorectal and non-small cell lung cancer. Depending on the setting, Genentech has paired GDC-1971 with Erbitux, Tagrisso, Tecentriq and its KRAS G12C inhibitor GDC-6036.

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