Aptevo Therapeutics Submits IND for APVO436 For Acute Myeloid Leukemia and Myelodysplastic Syndrome

Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, today announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to evaluate APVO46 in a Phase 1 clinical study for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Dr. Scott C. Stromatt, Chief Medical Officer for Aptevo, remarked, “There is a strong unmet medical need for novel targeted biological therapies to treat patients with relapsed or refractory AML or MDS. Chemotherapy, which is the standard of care for these patients, is generally poorly tolerated in the elderly and patients are still confronted with high relapse rates after treatment. In contrast, an immunotherapy such as APVO436, which recruits the patient’s own immune system to kill leukemic cells could offer a safer and more effective therapy.”

“We are very encouraged by recent preclinical data presented by Aptevo at the American Association for Cancer Research annual meeting, which support our assessment of APVO436 as a best-in-class CD123 x CD3 immunotherapeutic,” continued Dr. Stromatt. “We compared APVO436 to an Aptevo-generated version of Macrogenics’ CD123 x CD3 dual-affinity re-targeting (DART) molecule, MGD006, evaluating T-cell activation, proliferation, cytotoxicity and cytokine secretion. While both molecules showed potent T-cell activation, proliferation and cytotoxicity, APVO436 induced lower levels of several key T-cell cytokines, which are believed to be responsible for dosing toxicities observed in other companies' clinical studies, in particular, IFNg, IL-2, IL-6, TNFa. While these data would need to be confirmed in the clinic, it does suggest that APVO could have an enhanced safety profile at comparable or higher doses. The IND filing for APVO436 is an important milestone for our ADAPTIR platform as we advance APVO436, our first next generation ADAPTIR candidate towards clinical development.”

APVO436 is an optimized, next generation bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity to the tumor. APVO436 was built on Aptevo’s proprietary ADAPTIR protein therapeutic platform. Focused on generating novel, targeted bispecific antibody-based immunotherapies for cancer and autoimmune diseases, the ADAPTIR platform offers key advantages over other bispecific formats, derived in part from the flexible and modular nature of the ADAPTIR structure. These advantages include: (i) achieving potent biological activity and extended half-life while retaining desirable manufacturing characteristics; (ii) unique properties for redirecting T-cell cytotoxicity (RTCC) compared to other bispecific platforms, including a favorable cytokine release profile; (iii) ability to achieve target-dependent induction of RTCC at lower concentrations than other bispecific antibody formats; and (iv) flexibility to build ADAPTIR candidates with diverse mechanisms of action, including RTCC, and targeted cytokine release and others. Two ADAPTIR molecules are currently in clinical development, with several more ADAPTIR bispecific immunotherapies in preclinical development.

There are estimated to be approximately 100,000 new cases of AML diagnosed worldwide each year, while the American Cancer Society estimates that approximately 20,000 new cases of AML are diagnosed each year in the United States alone.

Myelodysplastic syndromes (MDS) are conditions associated with abnormalities in the blood-forming cells in the bone marrow. Approximately 1 in 3 patients with MDS will progress to have AML. The incidence of MDS in the six major world markets is estimated to be approximately 33,000 per year, while the American Cancer Society estimates that approximately 10,000 new cases of MDS are diagnosed each year in the United States alone.