Debiopharm, a privately-owned biopharmaceutical company headquartered in Lausanne, Switzerland, announced that US FDA has granted Fast Track Designation to the combination of lunresertib (Debio 2513), an oral PKMYT1 inhibitor, and zedoresertib (Debio 0123), a WEE1 inhibitor, for adult patients with CCNE1-amplified or FBXW7/PPP2R1A-mutated platinum-resistant or refractory ovarian cancer. The announcement followed an oral presentation of Phase I data from the MYTHIC study at the American Association for Cancer Research (AACR) Annual Meeting on April 19, 2026.
Fast Track Designation enables more frequent FDA interactions during development and, if criteria are met, may support eligibility for Priority Review or Accelerated Approval at the time of a New Drug Application (NDA) submission. Both lunresertib and zedoresertib previously received FDA Orphan Drug Designation for ovarian cancer, and lunresertib also holds EMA Orphan Drug Designation for the same indication.
The MYTHIC study (NCT04855656) is a Phase I basket trial that has been evaluating lunresertib as monotherapy and in combination across several arms since April 2021. The lunresertib/zedoresertib arm targets the same genomic subgroups specified in the Fast Track indication. Phase I data presented at AACR 2026 by Dr. Timothy A. Yap of MD Anderson Cancer Center represented the first public clinical disclosure for this specific combination. Across 54 evaluable patients, the disease control rate (DCR) was 68.5%. Of 51 patients with measurable target lesions, 26 (51%) showed tumor shrinkage and 10 achieved a confirmed radiological response. Specific grade ≥3 adverse event rates were not publicly disclosed at this stage.
The mechanistic rationale centers on synthetic lethality within the DNA damage response (DDR) pathway. PKMYT1 and WEE1 are both kinases that regulate CDK1 activity at the G2/M cell cycle checkpoint. CCNE1 amplification drives replication stress and CDK2-dependent S-phase entry, creating dependence on PKMYT1 and WEE1 for mitotic fidelity. Simultaneously blocking both kinases forces tumor cells with these genomic vulnerabilities into aberrant mitosis and cell death. Preclinical support for the combination was published at AACR 2025, where Piggott et al. reported synergy between zedoresertib and lunresertib in ovarian and breast cancer models. A 2025 Nature Communications paper by Xu et al. further demonstrated that combined PKMYT1 and ATR inhibition targets CCNE1-amplified ovarian and endometrial cancers, reinforcing the biomarker-driven rationale across DDR combination strategies.
The MYTHIC trial is listed as recruiting with a planned primary completion date of December 2027. Debiopharm’s stated model is to develop assets through clinical proof-of-concept and then partner for commercialization.