Lead Clinical Candidate, APVO436, Recently Showed Clinical Activity and Acceptable Safety Profile in Adults with Myelodysplastic Syndrome (MDS)
Article outlines a new strategy to employ APVO436 for targeting both MDS clones and immunosuppressive myeloid-derived suppressor cells in high-risk adult MDS patients
SEATTLE, WA / ACCESSWIRE / September 28, 2021 / Aptevo Therapeutics Inc. ("Aptevo") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies, today announced that the prestigious medical journal Frontiers in Aging, published a peer-reviewed article by Fatih Uckun, M.D., Ph.D., Chief Clinical Advisor at Aptevo who is coordinating the APVO436 clinical development program.
The article discusses the clinical impact potential of bispecific antibodies (BiAB) capable of redirecting host T-cell cytotoxicity to malignant clones as well as immunosuppressive myeloid-derived suppressor cells (MDSC) as a new class of anti-MDS drug candidates.
The article, "CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk MDS Patients," has been published in Frontiers in Aging, section "Neoplastic Pathologies of Aging,"
and it is available online. To view the online publication, click here:
Citation Reference: Uckun FM and Watts J (2021) CD123-Directed Bispecific Antibodies for Targeting MDS Clones and Immunosuppressive Myeloid-Derived Suppressor Cells (MDSC) in High-Risk Adult MDS Patients. Front. Aging 2:757276. doi: 10.3389/fragi.2021.757276
Adult myelodysplastic syndrome (MDS), a heterogeneous group of clonal malignant hematologic disorders with an incidence rate of 4.5 per 100,000 persons per year, is characterized by an enhanced risk of transformation to acute myeloid leukemia (AML). There is no effective standard treatment that will prevent the leukemic transformation or result in sustained deep remissions in high-risk adult MDS patients.
The immunosuppressive bone marrow microenvironment (BMME) in adult MDS has been implicated in clonal evolution and disease progression. Expanded populations of myeloid-derived suppressor cells (MDSC) contribute to the immunosuppressive tumor microenvironment (TME) by inhibiting both memory and cytotoxic effector T-cell populations as well as natural killer (NK) cells, thereby promoting the immune evasion of MDS clones. The abundance of MDSC is associated with a higher risk of rapidly progressive disease and poor survival outcomes in adult MDS.
The expression of CD123 on MDSC as well as MDS clones provides a compelling rationale for targeting CD123 antigen on the malignant clones as well as the MDSC in the immunosuppressive BMME of adult MDS patients in an effort to delay disease progression and transformation to AML.
In a recently completed APTEVO study the results of which have been published in the respected oncology journal, Cancers, APVO436 induced bone marrow complete remissions in 3 of 6 evaluable high-risk MDS patients, providing the first proof of concept that APVO436 is a new candidate anti-MDS drug.
"There is an urgent need to identify effective strategies to prevent leukemic transformation and induce sustained deep remissions in adult high-risk myelodysplastic syndrome (MDS) patients," explained Fatih Uckun, M.D. Ph.D., the study's lead author. "T-cell engaging bispecific antibodies targeting the CD123 antigen like our lead drug candidate APVO436 may help delay disease progression in high-risk adult MDS and potentially reduce the risk of transformation to secondary AML."
"Emerging data that show APVO436 can sufficiently empower dysfunctional and exhausted T-cells to induce remissions in relapsed AML and MDS patients is the driving motivation behind our current clinical development plan for our lead clinical candidate," said Marvin White, CEO of Aptevo.
Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo's lead proprietary drug candidate, APVO436 is a bispecific ADAPTIR that targets CD123 x CD3 and is designed to redirect the immune system of the patient to destroy leukemia cells expressing the target CD123 molecule on their surface. This antibody-like recombinant protein therapeutic is designed to engage both leukemia cells and T-cells of the immune system and bring them closely together to trigger a rapid and complete destruction of leukemia cells. APVO436 has been engineered using Aptevo's proprietary and enabling bioengineering methods and is designed to reduce the likelihood and severity of an unintended and potentially harmful activation of the immune system. APVO436 has been engineered to stay in the blood circulation long enough to locate, bind with and destroy target leukemia cells. APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.
About Aptevo Therapeutics
Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel immunotherapies for the treatment of cancer. The Company's lead clinical candidate, APVO436, and preclinical candidates, ALG.APV-527 and APVO603, were developed based on the Company's versatile and robust ADAPTIR™ modular protein platform technology. APVO442 was developed based on the new ADAPTIR-FLEX™ platform technology. The ADAPTIR and ADAPTIR-FLEX platforms can generate highly differentiated bispecific and multi-specific antibodies with potentially unique mechanisms of action for the treatment of different types of cancer. Aptevo is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on difficult to treat forms of cancer. For more information, please visit www.aptevotherapeutics.com.
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SOURCE: Aptevo Therapeutics Inc.