Repare Therapeutics Out-Licenses Discovery Platforms to DCx Biotherapeutics
Breakthrough Clinical Results
Repare Therapeutics announced it out-licensed its discovery platforms, including the SNIPRx platform and related intellectual property, to DCx Biotherapeutics for $4 million upfront and near-term payments, a 9.99% equity stake in DCx, and potential future milestone payments and royalties. This allows Repare to focus on its clinical portfolio and reduce costs while retaining an economic interest in the platforms. Approximately 20 Repare employees will transition to DCx, along with lease rights to certain lab facilities and equipment. Repare will also have a board nominee at DCx. DCx is a new Canadian biotech company developing next-generation precision drug conjugates.
Key Highlights
- Repare Therapeutics out-licensed its discovery platforms to DCx Biotherapeutics.
- The deal includes upfront and near-term payments totaling $4 million, equity in DCx, and potential milestone payments and royalties.
- Repare will focus on its clinical portfolio and reduce costs.
- DCx will retain some of Repare's preclinical research personnel and facilities.
Company drugs in pipeline
Repare Therapeutics Inc. has the following drugs in its pipeline:
- Camonsertib (RP-3500/RG6526): This is an ATR inhibitor being investigated for various solid tumors, including those with DNA damage response gene deficiencies. It is being evaluated as a monotherapy and in combination with other drugs like talazoparib, olaparib, niraparib, lunresertib, or gemcitabine. Clinical trials are exploring intermittent dosing schedules (e.g., 160 mg once daily, 3 days on/4 days off, or 2 weeks on/1 week off) to mitigate anemia, a common side effect.
- Lunresertib (RP-6306): This is a PKMYT1 inhibitor being investigated for certain types of DNA damage response cancers, particularly those with CCNE1 amplification. It is being explored in combination with camonsertib for ovarian and endometrial cancers with CCNE1 amplification, aiming to exploit synthetic lethality. Preclinical studies suggest synergistic activity between these two drugs in CCNE1-amplified cells.
It's important to note that these drugs are currently in clinical trials, and their efficacy and safety profiles are still being evaluated.
Company Mechanism of Action
Repare Therapeutics Inc. focuses on developing drugs that exploit vulnerabilities in DNA damage response (DDR) pathways within cancer cells. Specifically, they target proteins within these pathways that exhibit synthetic lethality relationships. This means that inhibiting the target protein becomes lethal only when another specific DDR protein is also deficient or mutated, a common occurrence in certain cancers.
One of their key drug candidates is camonsertib (RP-3500), an ATR inhibitor. ATR is a crucial kinase in the DDR pathway. Camonsertib was designed using a pharmacophore model to optimize a key hydrogen bond interaction, enhancing its potency and selectivity over related kinases like mTOR. Preclinical studies focused on mitigating camonsertib's myelosuppressive effects, leading to an intermittent dosing schedule (160 mg once daily, 3 days/week) to allow for erythroid recovery and reduce anemia.
Another area of focus for Repare Therapeutics is the combination of ATRi and PARP inhibitors. Preclinical research has shown that combining camonsertib with PARP inhibitors like talazoparib, olaparib, or niraparib leads to synergistic tumor cell killing by modulating complementary DNA repair pathways. However, this combination can cause hematological toxicities. To address this, research has explored intermittent dosing schedules and identified specific genetic alterations (e.g., RNase H2 deficiency, RAD51 paralog mutations) that hypersensitize cells to the ATRi-PARPi combination, allowing for lower, less toxic doses.
Repare Therapeutics also has a clinical candidate targeting PKMYT1, a regulator of CDK1 phosphorylation. This drug candidate exploits the synthetic lethal relationship between PKMYT1 and CCNE1 amplification, a common feature in certain cancers. While the specific mechanism of this PKMYT1 inhibitor is not detailed in the provided text, it is designed to inhibit PKMYT1 activity and thus selectively target CCNE1-amplified tumor cells.
