Swiss biopharmaceutical company Debiopharm has initiated dosing in the first-in-human clinical trial of Debio 1562M, a novel CD37-targeted antibody-drug conjugate (ADC) designed for patients with relapsed/refractory acute myeloid leukemia (AML). The Phase 1/2, multicenter, open-label trial (NCT06969430) will evaluate the safety, tolerability, and antileukemic activity of the first-in-class compound as monotherapy.
Addressing Critical Unmet Need in AML
AML represents one of oncology's most challenging therapeutic areas, particularly affecting older adults who comprise the majority of cases. Current treatment outcomes remain poor despite recent advances in understanding AML biology and the introduction of new therapies. The 5-year overall survival rate stands at just 32%, with median overall survival dropping to as low as 7 months in certain patient populations.
"It's time for AML research to advance with more precise therapeutic options," said Marianna Muller, Senior Medical Director, Oncology at Debiopharm. "This study will help us better understand the potential of Debio 1562M and how it could provide an effective new treatment while minimizing tolerability challenges for patients facing this very difficult disease with high unmet medical need."
The therapeutic gap is particularly pronounced for patients who are not candidates for intensive treatments such as traditional chemotherapy or stem cell transplantation. While intensive chemotherapy and targeted therapies are available, they have not substantially improved long-term outcomes across all patient populations, leaving thousands of patients without viable treatment options annually.
Novel CD37-Targeted Approach
Debio 1562M targets CD37, a cell-surface antigen that has emerged as a relevant ADC target in AML due to its broad expression on blasts and leukemic stem cells, along with efficient internalization. Research indicates that this increased expression is restricted to malignant cells compared to healthy hematopoietic stem cells and correlates with poor patient outcomes.
The compound was developed using Debiopharm's proprietary Trifecta approach, which optimizes three key components: naratuximab (an anti-CD37 monoclonal antibody), MultiLink™ proprietary linker technology, and a microtubule inhibitor as the cytotoxic payload. This design enables both high drug-to-antibody ratios and enhanced stability.
Promising Preclinical Results
In preclinical studies, Debio 1562M demonstrated anti-leukemic activity across all AML subtypes and showed superior activity compared to current standard-of-care and targeted therapies in AML models. The compound also exhibited promising antitumor activity and tolerability profiles in these hard-to-treat leukemia models.
"We recognize how critical the need is for AML patients and remain dedicated to addressing it through our ADC expertise," commented Bertrand Ducrey, CEO of Debiopharm. "As our pre-clinical results have shown promising antitumor activity and tolerability in this hard-to-treat leukemia, we're looking forward to seeing what this clinical stage research with Debio 1562M could reveal."
Comprehensive ADC Development Platform
Debiopharm has been developing targeted drug delivery solutions for more than a decade through its MultiLink™ ADC technology suite. The company's ADC portfolio includes multiple first-in-class or best-in-class candidates, including Debio 1562M for AML and myelodysplastic syndromes, and Debio 0532, an HER3-targeted ADC for solid tumors.
The Phase 1/2 trial will characterize the safety and tolerability profile of Debio 1562M, optimize dosing parameters, and define the product's therapeutic activity. This foundational study will establish the groundwork for further clinical development of this potentially transformative treatment for AML patients facing limited therapeutic options.
