Roche dumps Repare's synthetic lethal drug days after making $40M stitch in Tapistry trial

Roche has made a fast U-turn on Repare Therapeutics’ synthetic lethal drug candidate. Days after dosing a phase 2 patient and triggering a $40 million payment, Roche told the oncology biotech that it will hand back the asset following a review of its pipeline and “evolving external factors.”

On Jan. 25, Repare revealed it had earned a $40 million milestone payment because Roche had dosed the first patient with the ATR inhibitor camonsertib in the phase 2 TAPISTRY clinical trial. Thirteen days later, Roche told Repare it was exercising its right to terminate the agreement without cause with 90 days prior written notice. The biotech broke the news to investors after markets closed Tuesday.

The Big Pharma paid $125 million upfront for the asset in 2022. The deal gave Roche global rights to a molecule with the same mechanism of action as assets in development at AstraZeneca, Bayer, Merck KGaA and other companies. The drug developers had congregated around a target that regulates DNA replication and could improve outcomes in settings including cancers treated with chemotherapy and in combination with other synthetic lethal drugs.

Roche highlighted the candidate at its R&D day in September, when Chief Medical Officer Levi Garraway, M.D., Ph.D., told investors that “ongoing clinical data is showing monotherapy activity ... in several tumor contexts.” Back then, Roche was “in the process of stepping up combinations of camonsertib with PARP inhibitors” in light of the clinical data, “very strong preclinical data package” and evidence ATR is “a key component” of the DNA damage response pathway, Garraway said. 

While Roche is walking away from the asset, the candidate remains part of Repare’s plans. The deal with Roche allowed the biotech to test camonsertib in combination with its PKMYT1 inhibitor lunresertib. Repare posted phase 1 data in the combination in October. At an investor event the following month, Repare CEO Lloyd Segal called the data “really phenomenal” while noting the “very, very small numbers.”

Repare is continuing to study the combination and expects to report data from the expansion cohorts later this year. The biotech has seen activity in heavily pretreated gynecologic tumors at the preliminary recommended phase 2 dose, leading it to identify camonsertib as a potential best-in-class ATR inhibitor.

AstraZeneca is running a phase 3 trial of its own ATR inhibitor, ceralasertib, in non-small cell lung cancer and expects (PDF) to have data next year. Bayer has an ATR inhibitor but terminated a study it was running with GSK in December after seeing “no anticipated benefit” and now has no enrolling trials. Merck KGaA, which has a clutch of ATR inhibitors, is running multiple phase 1/2 studies of M1774.