NEW YORK – Repare Therapeutics on Thursday said it has reprioritized its pipeline around two newer Phase I drug candidates and paused the advancement of trials evaluating its PKMYT1 inhibitor lunresertib and ATR inhibitor camonsertib until it can secure partnerships for those programs.
In August 2024, Repare announced it was laying off about 25 percent of its workforce, largely from its preclinical group. According to the company, these pipeline changes combined with the planned cost and headcount reductions will extend its cash runway into mid-2027.
The Montreal-based company last month reported positive results from the MYTHIC Phase I trial investigating the combination of lunresertib with camonsertib in solid tumors. In an expansion cohort within the trial, investigators evaluated the drug combo in patients with endometrial cancer and platinum-resistant ovarian cancer harboring lunresertib-sensitizing biomarkers. Among 27 evaluable patients with endometrial cancer, the overall response rate was 25.9 percent and the clinical benefit rate was 48.1 percent. In the group of 24 evaluable ovarian cancer patients, the overall response rate was 37.5 percent and the clinical benefit rate was 79 percent.
Repare received positive feedback from regulatory agencies in the US and Europe and had hoped to begin a registrational Phase III trial in 2025.
"While [lunresertib plus camonsertib] demonstrated positive results from our Phase I clinical trial, after careful consideration, we have decided to progress this program into pivotal trials contingent on securing a strategic partner to fund further development," Repare CEO Lloyd Segal said in a statement.
Repare will also put other clinical development programs for lunresertib and camonsertib on hold until the company can secure a partnership, including a Phase I trial of lunresertib with FOLFIRI chemotherapy in patients with genomically defined solid tumors, the Phase I/II TRESR trial of camonsertib alone and with other agents in patients with advanced tumors bearing ATR sensitizing mutations, and the Phase I/Ib MYTHIC trial of lunresertib with the WEE1 kinase inhibitor Debio 0123 in patients with advanced tumors with targetable tumor biomarkers.
The company will now focus its resources on the PLK4 inhibitor RP-1664 and the Polθ ATPase inhibitor RP-3467, which Segal said, "have the potential to address significant unmet patient needs and deliver important catalysts in 2025."
Repare is evaluating RP-1664 in the Phase I LIONS trial in patients with TRIM37-high solid tumors and expects to begin a Phase I/II expansion trial of the drug in pediatric neuroblastoma. It has begun dosing patients in the Phase I POLAR trial of RP-3467 alone and with AstraZeneca's PARP inhibitor Lynparza (olaparib) in patients with advanced ovarian, breast, prostate, and pancreatic cancers and expects to report top-line data from the trial in the third quarter of 2025.