Repare Therapeutics Inc. announced that it has entered into a clinical study and collaboration agreement with Debiopharm aiming to establish standards of care to cure cancer and infectious diseases. This clinical collaboration aims to explore the synergy between lunresertib, a first-in-class, selective and potent oral, small molecule inhibitor of PKMYT1 with demonstrated anticancer activity, and Debio 0123, a potential best-in-class, brain-penetrant and highly selective WEE1 inhibitor. Under the clinical study and collaboration agreement, the combination of lunresertib and Debio 0123 will be evaluated in a new arm of Repare?s ongoing global MYTHIC study (NCT04855656) under Repare?s sponsorship.

The Phase 1/1b clinical trial is anticipated to initiate in the first half of 2024. Repare and Debiopharm will collaborate on the design of the trial arm for the development of the combination and will share all costs equally. Repare and Debiopharm will each supply their respective drugs, and each retain all commercial rights to their respective compounds, including as monotherapy or as combination therapies.

Lunresertib (RP-6306) is a first-in-class, selective and potent oral small molecule inhibitor of PKMYT1, a cancer target Repare discovered and identified as synthetic lethal with CCNE1 amplification, FBXW7 and PPP2R1A alterations in solid tumors. Lunresertib is currently the sole PKMYT1 inhibitor known to be in clinical trials and is being evaluated alone and in combinations across several studies in the US, EU and Canada. Repare has presented positive initial Phase 1 data from its ongoing Phase 1 MYTHIC trial (NCT04855656) demonstrating proof of concept for lunresertib alone and in combination.

In addition to being well tolerated and having a compelling safety profile, Repare presented anti-tumor activity for lunresertib in combination with camonsertib, an ATR inhibitor developed by Repare and partnered with Roche, expanded clinical studies for which are ongoing. Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle.

WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cell cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers.