Debiopharm Reports First Clinical Data from MYTHIC Trial Combining WEE1 and PKMYT1 Inhibitors at AACR 2026
Key Insights
Debiopharm (search) will present first clinical data from the Phase I MYTHIC trial evaluating the combination of zedoresertib (search) (WEE1 (search) inhibitor) and lunresertib (PKMYT1 (search) inhibitor) in advanced solid tumors with specific genetic alterations.
Early data readouts suggest strong synergistic activity between the two DNA damage repair inhibitors, with tumor regressions observed in patients according to company executives.
The company will also showcase preclinical results for its MultiLINK dual payload antibody drug conjugate technology and AI-driven biomarker development at the 2026 AACR meeting.
Debiopharm (search) will unveil the first clinical results from its MYTHIC study at the 2026 Annual American Association for Cancer Research (AACR) meeting in San Diego, marking a significant milestone for the Swiss biopharmaceutical company's DNA damage repair inhibition program. The Phase I trial (NCT04855656) evaluates the combination of zedoresertib (search) (Debio 0123), a WEE1 (search) inhibitor, with lunresertib (Debio 2513), a PKMYT1 (search) inhibitor, in patients with advanced solid tumors harboring CCNE1 (search), FBXW7 (search), or PPP2R1A (search) genomic alterations.
Clinical Data Shows Promising Synergistic Activity
Dr. Timothy A. Yap, a Medical Oncologist and Physician-Scientist at the University of Texas MD Anderson Cancer Center and Principal Investigator of the MYTHIC study, will present the clinical data during an oral presentation on April 19th, 2026. According to Esteban Rodrigo Imedio, Executive Medical Director of Oncology at Debiopharm (search), "Early data readouts suggest strong synergistic activity between zedoresertib (search) and lunresertib, with tumor regressions observed in patients."
The combination approach targets cancer cells' reliance on DNA damage repair (DDR) mechanisms. When cells have damaged DNA, they must undergo DDR to survive, and cancer cells rely heavily on this process 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 programmed cell death.
First-in-Class PKMYT1 Inhibition
Lunresertib represents a first-in-class, oral PKMYT1 (search) inhibitor designed to exploit specific genetic vulnerabilities in solid tumors, such as CCNE1 (search) 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.
Dual Payload ADC Technology Advances
Beyond the MYTHIC study results, Debiopharm (search) will present comprehensive preclinical results for its MultiLINK ADC Technology Suite, showcasing the potential of novel dual payload antibody drug conjugates to enhance therapeutic efficacy. Antoine Attinger, Director of Translational Pharmacology at Debiopharm, emphasized the technology's potential: "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."
The company's ADC portfolio includes Debio 0633 (undisclosed target), Debio 1562M (search), a CD37 (search)-targeted ADC for treating acute myeloid leukemia and myelodysplastic syndromes, as well as other ADCs with undisclosed targets including bispecific ADCs. These ADCs utilize the proprietary MultiLINK linker technology suite, designed to allow both high drug-to-antibody ratio and high stability.
AI-Driven Biomarker Development
Two translational research posters will highlight innovative approaches to biomarker development and therapeutic strategy refinement. The first poster will showcase the development of a Deep Learning-based "virtual" Cyclin E1 biomarker to predict protein overexpression in gynecological malignancies from H&E slides. The second will unveil 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 (search) bispecific antibody and ADC programs.
The presentations will be featured across multiple sessions at AACR 2026, including Clinical Trials Plenary Sessions on Antibody Drug Conjugates and Linker Engineering, Digital Pathology, and Molecular Targets, reflecting the breadth of Debiopharm (search)'s research portfolio in addressing high unmet medical needs in oncology.