Debio 1562M

Potential 1st in class CD37 Antibody-Drug Conjugate

Debio 1562M is a next generation antibody-drug conjugate (ADC) directed against CD37 developed to be first in class therapy in Acute Myeloid Leukemia (AML) and Myelodysplastic syndrome (MDS). Debio 1562M is constructed with naratuximab, an anti-CD37 monoclonal antibody, Debiopharm proprietary linker (Multilink™) and a microtubule inhibitor as cytotoxic payload. The compound has shown good antitumor activity and tolerability in several in-vivo AML models.

Product Snapshot

Antibody-Drug Conjugate Targeting CD37

Selectively delivers cytotoxin to induce cell cycle arrest and promote apoptosis

Being researched in:

In short

Debio 1562M is conjugated to 8 molecules of a DM1 derivative, a highly potent anti tubulin binder inducing mitotic catastrophe and cell death via Multilink™, next gen linker allowing homogenous high drug-to-antibody ratio (DAR8), with high stability, and fast intracellular release of payloads

In preclinical setting, Debio 1562M has proven affinity and specificity to the target, successful internalization, antiproliferative activity in vitro and significant improvement of survival in multiple in vivo models

CD37: a relevant target in AML/MDS

The CD37 antigen is primarily expressed on hematopoietic tissues such as B cells, neutrophils and macrophages. However, increased expression of CD37 has been observed in various hematological cancers [1-4] and is associated with poor patient outcome in AML [5-6]. CD37 can be a suitable target in AML/MDS for an ADC approach as it is broadly expressed and efficiently internalized– to the same extent as in B cell diseases despite lower expression.

Acute Myeloid Leukemia (AML)

AML is a heterogenous group of fast progressing blood cancer that originates in the bone marrow where new blood cells are produced.[1] It primarily affects white blood cells but can also involve red blood cells and platelets. Normally, these cells would develop into mature blood cells, however, in AML, they remain immature and quickly escape into the blood stream.[1] It can sometimes spread to other parts of the body including the lymph nodes, liver, spleen and central nervous system. Despite intensive chemotherapy treatment options available for AML patients currently available on market, approximately half will experience relapse [3], and 10–40% will be refractory to initial first-line treatment. There have been significant changes in the AML space, however, there remains a large unmet need with 5-year Overall Survival at 32% (8).

Myelodysplastic Syndrome (MDS) patients today have only limited options

Similar to AML, MDS are a group of cancers characterized by immature blood cells in the bone marrow.[4] Patients suffering from MDS present similar symptoms to AML and about 1 in 3 patients might develop AML as a consequence of a process called “transformation”.[5-6] Depending on both their type of MDS and risk of developing AML, patients may require different kinds of treatment such as salvage chemotherapy, targeted agents, HMA alone, or enrolment in clinical trials.[5] Unmet need in higher risk MDS is equally as large as in AML.[7]

Sources

[1] PDQ® Adult Treatment Editorial Board. PDQ Acute Myeloid Leukemia Treatment. Bethesda, MD: National Cancer Institute. Updated <01/18/2023>. Available at: https://www.cancer.gov/types/leukemia/hp/adult-aml-treatment-pdq. Accessed <06/14/2023>. [PMID: 26389432]

[2] American Cancer Society: Cancer Facts and Figures 2023. American Cancer Society, 2023. Available2 online. Last accessed June 14, 2023

[3] Leukaemia care. Relapse in acute myeloid leukaemia. 1(2), 2–32 (2019).

https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf

[4] PDQ® Adult Treatment Editorial Board. PDQ Myelodysplastic Syndromes Treatment. Bethesda, MD: National Cancer Institute. Updated <03/31/2023>. Available at: https://www.cancer.gov/types/myeloproliferative/patient/myelodysplastic-treatment-pdq. Accessed <06/16/2023>. [PMID: 26389239]

[5] NHS. Myelodysplastic syndrome. Updated <03/11/2021>. Available at: https://www.nhs.uk/conditions/myelodysplasia/. Accessed <06/16/2023>

[6] American Cancer Society. What Are Myelodysplastic Syndromes? Updated <01/22/2018>. Available at: https://www.cancer.org/cancer/types/myelodysplastic-syndrome/about/what-is-mds.html. Accessed <06/19/2023>

[7] Deeg HJ, Storer B, Slattery JT, et al.: Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 100 (4): 1201-7, 2002

[8] SEER 2022 Statistics