Debiopharm Highlights Clinical Momentum Across DDR Portfolio at ESMO 2026, Advancing WEE1-Based Therapies in Ovarian and Uterine Cancers and Glioblastoma

Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard of care to cure cancer and infectious diseases, today announced their upcoming Phase 1/Phase 2 clinical updates at the European Society for Medical Oncology (ESMO) Congress (Madrid, Spain, 23-27 October). During the event, Debiopharm will highlight clinical updates on its pipeline targeting the DNA Damage Response (DDR), featuring single-agent data on zedoresertib (Debio 0123) as well as rational combination strategies, with both temozolomide in glioblastoma and with lunresertib (Debio2513) in solid tumors.

Debiopharm’s planned activities at ESMO 2026 include:

• Rapid Oral Presentation (Debio 0123-GBM-105 / NCT05765812): Presenting dose escalation data evaluating zedoresertib in combination with temozolomide in patients with recurrent or progressive glioblastoma.

• Poster Presentation (Debio 0123-102 / NCT05109975): Presenting Phase 1 expansion data evaluating single-agent zedoresertib in advanced solid tumors, including uterine serous carcinoma and Cyclin E1-overexpressing high-grade ovarian cancer.

• Meet-the-Expert Event (MYTHIC Study): An invitation-only session alongside the congress during which leading international oncology experts will discuss emerging data from the MYTHIC clinical trial (Debio 0123-106 / NCT04855656), dual WEE1/PKMYT1 checkpoint inhibition, and precision biomarker selection.

“The data to be presented at ESMO 2026 reinforce our belief that zedoresertib has the potential to become a breakthrough therapy in oncology in combination with key agents across multiple tumor types,” expressed Esteban Rodrigo Imedio, Executive Medical Director, Oncology at Debiopharm. “From establishing single-agent disease control in solid tumors and confirming blood-brain barrier penetrance in glioblastoma to advancing dual WEE1/PKMYT1 targeting in the MYTHIC trial, we are committed to unlocking the benefits of synthetic lethality for patients battling hard-to-treat cancers.”

Clinical Progression: Monotherapy, Glioblastoma, and Combination Strategies

Zedoresertib (Debio 0123) is a potent, oral, brain-penetrant, and highly selective WEE1 kinase inhibitor. In the monotherapy expansion study (Debio 0123-102), continuous daily administration of zedoresertib at the recommended Phase 2 dose demonstrated a manageable safety profile alongside evidence of target engagement and signals of activity in heavily pretreated solid tumors, particularly uterine serous carcinoma and ovarian cancer. In parallel, the Debio 0123-GBM-105 clinical trial in recurrent glioblastoma confirmed early signals of antitumor activity, central nervous system penetration and a manageable safety profile in combination with temozolomide, supporting ongoing evaluation in randomized cohorts.

Supported by this favorable tolerability profile and single-agent foundation, Debiopharm has expanded zedoresertib’s clinical evaluation into rational combination regimens. The ongoing MYTHIC trial evaluates zedoresertib in combination with lunresertib, a first-in-class, selective oral PKMYT1 inhibitor, in patients with advanced solid tumors, particularly ovarian cancer.

Therapeutic Rationale: Exploiting Synthetic Lethality in DDR

The scientific rationale underlying Debiopharm’s DDR pipeline focuses on targeted cell-cycle checkpoint disruption. Combining WEE1 and PKMYT1 inhibition creates a dual-checkpoint blockade within the G2/M transition, preventing cancer cells from repairing DNA damage and inducing mitotic catastrophe. Early clinical data from the MYTHIC study indicate promising signs of synthetic lethality and tumor regression in biomarker-selected populations, notably patients harboring CCNE1 amplification as well as FBXW7 or PPP2R1A alterations. Clinical development continues to refine combination dosing and biomarker selection in the MYTHIC trial for solid tumors, while advancing randomized expansion cohorts to evaluate zedoresertib with temozolomide in glioblastoma.

ESMO 2026 Presentation Details

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 (Debio2513) is a first-in-class, oral PKMYT1 inhibitor designed to exploit specific genetic vulnerabilities in solid tumors, such as CCNE1 amplification. PKMYT1 acts as a key regulator at the G2/M checkpoint, and its inhibition reduces CDK1 activity, thereby preventing cancer cells from properly 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 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 Debio 0123-GBM-105 trial: Glioblastoma – Debiopharm – Patients

• The MYTHIC trial: Solid Tumors- Debiopharm- Patients

Visit us at https://www.debiopharm.com/our-expertise/ddr/

Follow us: https://www.linkedin.com/company/debiopharminternational/

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