PLK4

“We acknowledge the extraordinary contributions and productivity of our discovery team,” Repare Therapeutics CEO Lloyd Segal said in the company's release. Repare Therapeutics is laying off a quarter of its workforce as the oncology biotech scales back its preclinical work to focus on more advanced candidates such as a synthetic lethal drug handed back by Roche earlier this year.The biotech had a number of synthetic lethal targets in advanced stages of preclinical development, according to the company’s website. But Repare has decided to “materially reduce the scale of its preclinical research and discovery activities,” the company said in a post-market release Aug. 28.This “strategic refocus” will see the company reduce its overall workforce by around 25%, with the biotech’s preclinical group bearing the brunt of the layoffs. Repare had 179 full-time employees as of February, of which 143 were primarily engaged in some form of R&D and 36 were focused on management or general and administrative activities. The redundancies outlined yesterday are expected to incur between $1.5 million and $2 million of costs in the third quarter before generating annual savings of $15 million.Repare ended June with $208.1 million in cash and equivalents, which it had estimated would fund its operations until at least mid-2026. The savings outlined in the Aug. 28 release are expected to pave a cash runway further into that year.“We acknowledge today the extraordinary contributions and productivity of our discovery team, who have enabled the development of our deep, innovative clinical portfolio,” Repare’s CEO Lloyd Segal said in the release.“In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Segal added.Those programs include a phase 1 dose expansion trial of a combination of the biotech’s lunresertib and camonsertib in patients with ovarian and endometrial cancers due to read out in the fourth quarter of 2024. Segal has previously touted phase 1 data of the PKMYT1 inhibitor lunresertib as “really phenomenal,” while the ATR inhibitor camonsertib made headlines in February when Roche walked away from a collaboration on the drug just days after the Big Pharma had dosed the first patient in a phase 2 trial. Undeterred by the rejection, Repare has hopes to launch a registrational trial of the lunresertib-camonsertib combo next year. The biotech is also assessing camonsertib as a monotherapy in a phase 2 trial in non-small cell lung cancer, which is due to read out next year.The company’s phase 1 pipeline also consists of a PLK4 inhibitor called RP-1664 that is in a study for patients with TRIM37-high solid tumors along with a Polθ ATPase inhibitor called RP-3467 that is set to enter human trials in the fourth quarter.

Repare Therapeutics is cutting its headcount by about 25%, with most of the layoffs concentrated in the company’s preclinical team, as part of what the company is calling a “strategic prioritization” of its R&D program. The move will allow Repare to focus on clinical-stage oncology candidates. That includes lunresertib and camonsertib, which are currently being evaluated together in a Phase 1 trial for patients with ovarian and endometrial cancers. The trial is now in the dose expansion phase, data are expected in the fourth quarter, and a registrational trial could begin as early as 2025. Camonsertib is also being investigated as a monotherapy in non-small cell lung cancer as part of a Phase 2 trial, with data expected in 2025. Roche had licensed camonsertib, an oral ATR inhibitor, back in 2022 but bowed out in February, shortly after paying $40 million for dosing the first patient with the drug in a different Phase 2 platform study. The deal originally carried up to $1.2 billion in milestones. The company also has RP-1664, an oral inhibitor of PLK4, in a Phase 1 trial in adult and adolescent patients with TRIM37-high solid tumors. Based on safety data, Repare said it will move the therapy into a Phase 1/2 study in pediatric patients with high risk, recurrent neuroblastoma, where prevalence of TRIM37-altered tumors is high. “In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Repare president and CEO Lloyd Segal wrote in a statement. The staff reduction will cost the company non-recurring cash payments of about $1.5 million to $2 million in the third quarter of this year — but it expects annual savings of around $15 million that will extend its cash runway into the second half of 2026. Stifel analysts wrote in a Wednesday note that “the reprioritization has a small positive impact,” and that “focusing resources on clinical efforts with near-term inflection points makes sense.”

In a bid to preserve cash and realign efforts towards advancement of its key clinical-stage oncology assets, Repare Therapeutics said it will curtail discovery and preclinical activities, and slash approximately 25% of its 179-member workforce, mainly within the preclinical research teams.As part of the overhaul, the company will focus on propelling four clinical programmes, comprising the oral small-molecule inhibitors lunresertib and camonsertib, alongside the oral PLK4 inhibitor RP-1664 and the Polθ ATPase inhibitor RP-3467. “We will more fully dedicate our resources to our most promising and advanced precision oncology programmes to maximise value for patients and for our shareholders,” commented Lloyd Segal, chief executive of Repare.The company is scheduled to release data from the MYTHIC dose-expansion trial of lunresertib plus camonsertib in ovarian and endometrial cancers in the fourth quarter, with the possibility of commencing a registrational trial next year. In June, Repare also shared positive initial data from the early-stage MINOTAUR study of lunresertib in combination with chemotherapy to treat advanced solid tumours. Earlier this year, the firm also partnered with Debiopharm to explore the combination of lunresertib with the latter’s brain-penetrant WEE1 inhibitor Debio 0123.Meanwhile, camonsertib is also being investigated as a monotherapy in the expansion position of the Phase II TRESR trial in non-small-cell lung cancer, with preliminary data expected in 2025. Additionally, the company is evaluating RP-1664 as a monotherapy in the Phase I LIONS study for TRIM37-high solid tumours and plans to initiate a dose-finding trial for RP-3467 later this year.Repare anticipates one-time costs of $1.5 million to $2 million in the third quarter to account for the job cuts, with annual savings of around $15 million — sufficient to extend its cash runway into late 2026.