Aptevo Therapeutics Introduces New Adaptir Bispecific Antibody Candidate

Aptevo Therapeutics Inc. recently introduced a new immuno-oncology candidate, APVO603, built on Aptevo’s proprietary ADAPTIR bispecific antibody platform.  Jane Gross, PhD, Chief Scientific Officer for Aptevo, presented preclinical data on APVO603 in an oral presentation at the 10^th Annual World Bispecific Summit in Waltham, MA.

APVO603 is a dual agonist bispecific antibody employing a novel mechanism of action to simultaneously target 4-1BB (CD137) and OX40 (CD134), both members of the TNF-receptor family. Dual targeting of 4-1BB and OX40 provides synergistic co-stimulation of T cells with the potential to amplify the cytotoxic function of activated T cells and NK cells, potentially leading to more robust anti-tumor responses.

“Aptevo continues to create new, innovative molecules based on our ADAPTIR platform technology and we are excited to introduce our newest bispecific antibody candidate, APVO603,” said Dr. Gross. “APVO603 demonstrates the versatility and flexibility of our ADAPTIR platform to generate multiple candidates with diverse mechanisms of action (T-cell engagers, T-cell co-stimulators and targeted cytokines) for the treatment of cancer and autoimmune diseases.  Importantly, this flexibility allows us to engineer novel molecules addressing both hematological cancers and solid tumors – a significant area of unmet medical need within the field of immuno-oncology therapeutics.”

“We believe that a targeted strategy combining activation of both the 4-1BB and OX40 TNF receptors represents an attractive approach in potentially overcoming the suppressive tumor microenvironment,” continued Dr. Gross. “The targeted co-stimulation of 4-1BB and OX40 has the potential to promote an important immunological cascade, enhancing T-cell activation, prolonging T-cell survival, and improving tumor killing. We look forward to furthering our preclinical work and advancing APVO603 towards clinical development.”
The potential advantages of APVO603 include:

Broad Utility – Unlike chimeric antigen receptor T-cell therapies (CAR-T) and bispecific CD3-based T-cell engagers, APVO603 does not target a specific tumor antigen, thus allowing for broad potential therapeutic use for a number of different types of solid tumors.

Reduced Toxicity – Since 4-1BB and OX40 are costimulatory receptors that are primarily expressed only on a limited number of T cells that have previously been exposed to tumor antigen, we believe APVO603 has the potential to cause less toxicity compared to traditional CD3-based T-cell engagers due to its selectivity.

Differentiation From 4-1BB Agonistic Monoclonal Antibodies – Because APVO603 contains an Fc that does not interact with Fc gamma receptors, it has the potential to be less toxic than monospecific 4-1BB antibodies.

Synergistic Activity – While the activation of either 4-1BB or OX40 alone stimulates anti-tumor T-cell responses, as a dual agonist bispecific antibody APVO603 has the potential to produce a synergistic or amplified response resulting in more robust T-cell responses.

“Bispecific antibodies are expected to be the cornerstone of the next generation of immuno-oncology products,” Dr. Gross continued.  “The key to success is having a technology and the necessary expertise to generate bispecifics with the desired activity, while maintaining excellent stability, half-life and manufacturing characteristics. Our demonstrated ability to create new molecules with novel function substantiates the power and versatility of the ADAPTIR platform.”

APVO603 is an optimized, next-generation bispecific antibody candidate designed to simultaneously target 4-1BB and OX40 to bolster activation of CD4 and CD8 T cells and Natural Killer cells to enhance anti-tumor immune responses to tumors.  APVO603 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: the potential to achieve potent biological activity; desirable manufacturability characteristics, and promote an extended half-life. In preclinical studies, ADAPTIR CD3-based T-cell engagers achieve potent T-cell tumor cytotoxicity with reduced T-cell cytokine release compared to other bispecific platforms. The flexible ADAPTIR platform allows Aptevo to build candidates with diverse mechanisms of action, including Redirected T-Cell Cytotoxicity (RTCC); T-cell co-stimulation, and targeted cytokine release. Two ADAPTIR molecules (APVO436 targeting CD123 and CD3 for treatment of AML and other hematologic diseases, and APVO210, a targeted cytokine therapeutic for treatment of multiple autoimmune diseases) are currently in clinical development. A third candidate, ALG.APV-527, (targeting 4-1BB and 5T4, a solid tumor antigen) and APVO603 (4-1BB and OX40) are in preclinical development.

Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel oncology, autoimmune, and hematology therapeutics to meaningfully improve patients’ lives. Aptevo has a commercial product, IXINITY coagulation factor IX (recombinant), approved and marketed in the US for the treatment of Hemophilia B, and a versatile core technology – the ADAPTIR modular protein technology platform capable of generating highly differentiated bispecific antibodies with unique mechanisms of action to treat cancer and autoimmune diseases. Aptevo has a broad pipeline of novel investigational-stage bispecific antibody candidates focused in immuno-oncology and autoimmune disease and inflammation. For more information, visit www.aptevotherapeutics.com.