Genentech has struck a deal to license Relay Therapeutics' SHP2 inhibitor for $75 million upfront. The Roche subsidiary plans to combine the drug with its KRAS G12C inhibitor, reflecting evidence targeting SHP2 counters adaptive resistance to the red-hot approach to treating cancer.
Excitement about finally being able to design drugs that bind to frequently mutated oncogene KRAS has been tempered by early clinical data showing the limitations of the use of KRAS G12C inhibitors as single agents. The reactivation of the inhibited pathway, known as adaptive resistance, is one source of concern for KRAS drugs and other targeted therapies. Researchers at New York University School of Medicine found SHP2 inhibition may help by boosting G12C-I accessibility to mutant KRAS.
Relay has done its own assessments on the combination, reporting in its IPO paperwork earlier this year that it has shown the benefits of pairing a SHP2 inhibitor with a KRAS G12C agent in preclinical studies. The SHP2 inhibitor, RLY-1971, began phase 1 development in solid tumor patients earlier this year.
Genentech has seen enough promise in RLY-1971 and the broader assessment of the value of SHP2 inhibition to agree to pay Relay $75 million upfront, plus $25 million in near-term payments, for rights to the drug. Relay has the option to split profits and costs in the U.S. evenly with Genentech. If Relay takes up that option, milestones will top out at $410 million. Relay can earn up to $695 million in milestones if it leaves Genentech fully responsible for U.S. development and commercialization.
In disclosing the deal, Genentech specifically called out the potential to combine RLY-1971 with its KRAS G12C inhibitor GDC-6036. Genentech began a phase 1 clinical trial of the drug in July, putting it well behind the leader of the KRAS G12C race. Amgen plans to file for approval of its KRAS G12C inhibitor sotorasib by the end of the year.
Amgen is testing sotorasib in combination with 10 drugs, including a SHP2 inhibitor, in a phase 1 trial. Revolution Medicines is providing the SHP2 inhibitor for that trial. Mirati Therapeutics, developer of another experimental KRAS G12C inhibitor, has an agreement to use Novartis’ TNO155 in its trials. AbbVie also has a SHP2 inhibitor in its pipeline through an agreement with Jacobio Pharmaceuticals.