During the annual meeting for the American Association for Cancer Research (AACR) meeting held April 25 – 30, 2025 in Chicago, Illinois, Swiss-based Debiopharm presented comprehensive preclinical results for Debio 1562M (see ADC Drugmap) a next-generation Antibody-Drug Conjugate (ADC) targeting the cell surface glycoprotein CD37 being developed to be a potential first in class therapy in Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS).
Increased expression of CD37, a trans-membrane protein exclusively expressed in hematopoietic tissues, has been measured on malignant B-cells and its relevance as an attractive therapeutic target has been confirmed in several clinical trials.[1]
In acute myeloid leukemia (AML), increased CD37 expression on blasts and leukemic stem cells (LSCs) has also been reported, both at protein and mRNA levels. Overall, increased expression is restricted to malignant cells compared to hematopoietic stem cells and generally correlated with poor patient outcome.[1]
Debio 1562M is constructed with naratuximab (K7153B[huCD37-3]), a humanized IgG1 anti-CD37 monoclonal antibody directed against CD37 and conjugated to a peptidic cleavable linker (Multilink™)* bearing a maytansinoid cytotoxic payload (DM1).
Debiopharm’s proprietary Multilink™, a linker chemistry which is selectively recognized and cleaved by the carboxydipeptidase activity of Cathepsin B, allows for high, homogeneous drug-to-antibody ratio (DAR~8), good solubility, high stability in systemic circulation and fast intracellular payload and catabolites release.
The investigational agent has shown good antitumor activity and tolerability in several in-vivo AML models and is expected to soon to undergo first-in-human evaluation.
ADC Portfolio
Debiopharm is developing 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) Myelodysplastic syndromes (MDS), Debio 0532, an HER3-targeted ADC for solid tumors, as well as other ADCs for undisclosed targets including a proprietary bispecific ADC.
Debio 0123
During the annual meeting, Debiopharm also presented preclinical data for Debio 0123, a selective WEE1 kinase inhibitor disrupting the DNA-damage response (DDR) of cancer cells.
The first data release shows how Debio 0123 can be used in combination with the first-in-class, oral small molecule PKMYT1 inhibitor lunresertib (RP-6306; Repare Therapeutics) as a promising therapeutic strategy in ovarian and breast cancer. PKMYT1 regulates the cell cycle and is part of DNA damage repair-related signaling.
Genlias showed its AI foundation model of cancer—the Genialis™ Supermodel—to predict how a patient will respond to a specific therapy.
Genlias large molecular model (LMM) has been trained on hundreds of thousands of RNA sequencing samples, defines a comprehensive landscape of cancer biology, learned from preclinical, single-cell, and globally diverse patient records. The LMM maps each new patient sample into this high-dimensional space, revealing its underlying biological states and processes. This helps explain how drugs work in the body and how the tumor learns to resist treatment, as well as propose potential new drug combinations to improve outcomes.
In the AACR presentations Genialis shared data on the company’s own work with KRASG12C NSCLC patient and its collaboration with Debiopharm on Debio 0123 WEE1 inhibitor in various cancer types. This last presentation showed how machine learning has the potential to enhance the ability to predict responders to Debio 0123, thus further advancing the understanding and application of WEE1 biology and response to inhibitors.[2]
AbYlink™ conjugation technology
Additionally, in the framework of a licensing agreement and a collaborative endeavor to support innovative research, Debiopharm and Oncodesign Services presented promising new data illustrating how AbYlink™ conjugation technology can facilitate the production of conjugates for use in preclinical research in cancer treatment[3]
In a joint poster Debiopharm and Oncodesign Services demonstrate the use of the non-invasive technology in Radioimmunotherapy, targeting animal models bearing HER2+ tumors.[3]
AbYlink™ is a versatile and rapid regio-selective chemical conjugation technology for use to prepare diagnostic or therapeutic conjugates. This one step method results in stable conjugation at defined and invariable sites on the Fc domain of an antibody or the like, with no impact on antigen-binding regions. The technology enables a seamless and reproducible conjugation of payloads (e.g. a chelator for radiolabeling, a fluorescent dye or a drug) to antibodies or ADCs. The universal applicability of the AbYlink™ technology has been demonstrated for various antibody isotypes and payloads.[3]
“The pre-clinical results are laying a solid foundation for future research,” explained Angela Zubel, Chief Development Officer, Debiopharm.
“The two drug research approaches of ADCs and DDR inhibition are harnessing novel modalities and targets with the potential to outsmart hard-to-treat liquid and solid tumors, revolutionizing patient outcomes. Our AbYlink™ technology demonstrates great potential in the context of antibody radio conjugates against cancer and shows promise for broader use and wider applications.”
Reference
[1] Ivanschitz L, Hue-Perron J, Monjardet A, Luong N, Artiga E, Larkin KT, Marx L.Debio 1562M, a 2ndgeneration ADC targeting CD37, shows high potency against AML and MDS and safe toxicological profile for future clinical development. In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr 1160
[2] Piggott L, Rocha Gomes DB, Martinez Sanz P, Serrs V. The WEE1 inhibitor Debio 0123 is synergistic with the PKMYT1 inhibitor lunresertib in preclinical models of ovarian and breast cancer. In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr 2914 / 21
[3] Mothes C, Provent P, Ruch M, Moreau M, Claron M, Helbling A, Postupalenko V, Marx L, Garrouste P, Koumarianou E. Pharmacological evaluation of bioconjugated trastuzumab using the AbYlinkTM regio-selective conjugation technology in gastric cancer expressing HER2+ In: Proceedings of the 116th Annual Meeting of the American Association for Cancer Research; 2025 April 25-30; Chicago, IL.: AACR; 2025. Abstract nr 1825 / 11
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This article was first published in ADC Review | Journal of Antibody-drug Conjugates on April 28, 2025
Featured image: Chicago. © 2016 – 2025. Sunvalley Communication. Used with Permission
DOI
 meeting held April 25 - 30, 2025 in Chicago, Illinois, Swiss-based Debiopharm presented comprehensive preclinical results for Debio 1562M (see ADC Drugmap) a next-generation Antibody-Drug Conjugate (ADC) targeting the cell surface glycoprotein CD37 being developed to be a potential first in class therapy in Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS).){kind=link}