Zedoresertib

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. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

Preliminary clinical results of the MYTHIC study will be presented, revealing for the first time data of the combination of WEE1 and PKMYT1 inhibition (zedoresertib and lunresertib) for the treatment of solid tumors with specific genetic alterations Additional research posters on zedoresertib (Debio 0123) and novel dual payload MLINK Duo ADC technology, AI-driven virtual biomarkers, and multiplexed spatial profiling for HER3 therapeutic strategies will also be presented LAUSANNE, Switzerland--(BUSINESS WIRE)-- #AACR2026 --Debiopharm ( ), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard of care to cure cancer and infectious diseases, will release groundbreaking new data at the 2026 Annual American Association for Cancer Research (AACR) meeting in San Diego, California. A major highlight of this year’s conference participation is the first clinical data disclosure from the MYTHIC Study ( NCT04855656 ), a Phase I trial evaluating the combination of Debiopharm’s WEE1 inhibitor, zedoresertib (Debio 0123), with the PKMYT1 inhibitor lunresertib (Debio 2513) in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations. The oral presentation on April 19 th 2026 will be given by Dr. Timothy A. Yap, a Medical Oncologist and Physician-Scientist based at the University of Texas MD Anderson Cancer Center and Principal Investigator of the MYTHIC study. Comprehensive pre-clinical results will also be presented for the MultiLINK™ ADC Technology Suite, showcasing the potential of novel dual payload antibody drug conjugates (ADCs) to enhance therapeutic efficacy. Two translational research posters will also be featured: the first highlighting the development of a Deep Learning-based “virtual” Cyclin E1 biomarker to predict protein overexpression in gynecological malignancies from H&E slides; the second unveiling how multiplexed spatial profiling and 3D cluster analysis are being used to reconcile RNASeq, mass spectrometry, and IHC data to refine therapeutic strategies for HER3 bispecific antibody and ADC programs. “The first clinical results of the MYTHIC study mark an important milestone for the program. Early data readouts suggest strong synergistic activity between zedoresertib and lunresertib, with tumor regressions observed in patients,” explained Esteban Rodrigo Imedio, Executive Medical Director, Oncology, Debiopharm “Dual payload ADC technology has the potential to be a game changer for cancer patients. As patients need innovative solutions for hard-to-treat cancers, we hope that our dual payload research using MLINK Duo ADC linker technology will help us reshape how complex cancers are targeted and treated,” expressed Antoine Attinger, Director, Translational Pharmacology, Debiopharm. SESSION DETAILS Session Type: Clinical Trials Plenary Session AACR 2026 Oral Presentation Debiopharm Compound Title Presenter - Sun, April 19 - Time: 2:00 PM - Hall H zedoresertib (Debio 0123) & lunresertib (Debio 2513) First data disclosure of the Phase I trial of the first-in-class combination of WEE1 inhibitor zedoresertib with PKMYT1 inhibitor lunresertib in patients with advanced solid tumors harboring CCNE1, FBXW7, or PPP2R1A genomic alterations Dr. Timothy A. Yap, Medical Oncologist, University of Texas MD Anderson Cancer Center, Houston, TX Session Title: Antibody Drug Conjugates and Linker Engineering 1 AACR 2026 Poster Presentation Debiopharm Technology Title Author - Mon, April 20 - Display: 9:00 AM – 12:00 PM - Poster #: 1683 - Section: 12 MLINK Duo Enhancing therapeutic efficacy and overcoming resistance with a novel dual payload antibody drug conjugate technology Antoine Attinger et al., Translational Medicine, Debiopharm International SA, Lausanne Session Title: Digital Pathology 3 AACR 2026 Poster Presentation Debiopharm Program Title Author - Tue, April 21 - Display: 9:00 AM – 12:00 PM - Poster #: 4155 - Section: 3 zedoresertib (Debio 0123) Development of a virtual Cyclin E1 biomarker using Deep Learning from H&E slides for predicting Cyclin E1 overexpression in gynecological malignancy Jeannette Fuchs et al., Translational Medicine, Debiopharm International SA, Lausanne Session Title: Molecular Targets 2 AACR 2026 Poster Presentation Debiopharm Program Title Author - Tue, April 21 - Display: 2:00 PM – 5:00 PM - Poster #: 5738 - Section: 13 HER3 ADCs Beyond bulk: Resolving RNASeq/mass spectrometry/IHC discrepancies with multiplexed spatial profiling and 3D cluster analysis to refine HER3 (bs)Ab and (bs)ADC therapeutic strategies Jeannette Fuchs et al., Translational Medicine, Debiopharm International SA, Lausanne ABOUT DNA DAMAGE REPAIR (DDR) When cells have damaged DNA, they must undergo a repair process known as DDR to survive. Cancer cells rely heavily on DDR as they divide and grow uncontrollably. Inhibition of DDR, particularly in combination with other anticancer agents, prevents cancer cells from repairing their DNA, ultimately activating a programmed cell death process. DDR inhibitors such as zedoresertib (Debio 0123), Debiopharm’s WEE1 inhibitor, are currently being investigated in clinical and preclinical studies. ABOUT PKMYT1 INHIBITION Lunresertib (Debio 2513) is a first-in-class, oral PKMYT1 inhibitor designed to exploit specific genetic vulnerabilities in solid tumors, such as CCNE1 amplification. By targeting PKMYT1, the drug induces synthetic lethality, preventing cancer cells from repairing DNA damage and forcing them into programmed cell death. As the most advanced PKMYT1 inhibitor in clinical development, lunresertib has shown encouraging proof-of-concept results both as monotherapy and in combination therapies within the ongoing MYTHIC trial. DEBIOPHARM’S ADC PORTFOLIO We are developing fit-for-purpose antibody drug conjugates through a tailored “Trifecta” approach: strategic target selection, innovative MultiLINK™ linker technology and smart payload choices. Our broad and balanced portfolio of 1st-in-class and best-in-class ADCs includes Debio 0633 (undisclosed target), Debio 1562M, a CD37-targeted ADC for the treatment of acute myeloid leukemia (AML) and Myelodysplastic syndromes (MDS), as well as other ADCs with undisclosed targets including bispecific ADCs. To allow both high DAR and high stability, our ADCs are designed utilizing our innovative proprietary MultiLINK™ linker technology suite, a comprehensive toolbox of options allowing linker optimization for specific antibody, payload and clinical contexts. We are leveraging key collaborations and our in-house capabilities including ADC conjugation, optimization, PK/PD, toxicology, translational medicine, clinical development and supply chain to produce novel ADCs that respond to the high unmet needs of cancer patients. DEBIOPHARM’S COMMITMENT TO CANCER PATIENTS Debiopharm develops innovative therapies that target high unmet medical needs in oncology and infectious diseases. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high potential assets and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select pharmaceutical commercialization partners to maximize patient access globally. Learn more about the MYTHIC trial: Solid Tumors - Debiopharm - Patients Visit us: and Follow us: Contacts Debiopharm Contact Dawn Bonine Head of Communications dawn.bonine@debiopharm.com Tel: +41 (0)21 321 01 11