New Preclinical Data Show APVO436 Demonstrates Rapid and Significant Reduction in Skeletal Tumor Burden in Mice with Well-Established and Disseminated Tumors

SEATTLE, WA, USA I October 30, 2017 I Aptevo Therapeutics Inc. (Nasdaq:APVO), a biotechnology company focused on developing novel oncology and hematology therapeutics, today announced that new preclinical data on the Company’s next generation bispecific antibody candidate, APVO436, were presented at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics 2017 annual meeting. 

Aptevo is developing APVO436 for the treatment of acute myeloid leukemia (AML), a form of blood and bone marrow cancer that is characterized by rapid disease progression.  While treatments for AML are available, there remains a high unmet medical need for targeted immunotherapies like APVO436, that can potentially treat patients with relapsed or refractory disease, or patients who cannot tolerate traditional chemotherapy.

Aptevo has previously shown APVO436’s ability to induce tumor-specific immune responses and T-cell mediated cytotoxicity in vitro and in vivo through the simultaneous targeting of CD123 (a cell surface receptor highly expressed in several hematological malignancies) and CD3 (a T-cell co-receptor that promotes cytotoxicity.) 

Preclinical data presented at the AACR-NCI-EORTC meeting further demonstrate the highly-desirable attributes of APVO436 as a potent and selective immunotherapeutic candidate in the treatment of AML. These data show that APVO436:

  • Possesses low (nM) binding affinity; binds with high affinity to human and cynomolgus CD123-expressing cells with EC50 values in the low nanomolar range
  • Demonstrates potent, concentration-dependent, T-cell engagement against multiple CD123 expressing tumor cell lines at low effector to target ratios, accompanied by target-dependent primary T-cell activation and proliferation
  • Dose-dependently inhibits tumor growth and significantly prolongs survival compared to vehicle-treated animals in a preclinical in vivo xenograft model of human AML (data previously presented at AACR in April 2017)
  • Demonstrates a rapid and significant reduction in skeletal tumor burden in mice with well-established and disseminated tumors
  • Is well-tolerated by single intravenous injection in non-human primates at doses up to 1.0 mg/kg with no observable changes in body weight, food consumption or clinical chemistry
  • Has an antibody-like serum half-life of up to 3.5 days in non-human primates (NHP), and 12.5 days in mice, significantly longer than other bispecific candidates in development

“The accumulating preclinical data suggest a desirable target product profile for APVO436, which support its role as a targeted immunotherapeutic for the treatment of AML or other hematological malignancies,” said Jane Gross, Chief Scientific Officer for Aptevo. “Unlike other bispecific candidates targeting CD123, APVO436 has traditional antibody-like manufacturing characteristics, including a longer half-life that could potentially support a weekly dosing regimen.  We look forward to completing ongoing IND-enabling and CMC activities to advance APVO436 into the clinic next year.”

ADAPTIR Clinical and Preclinical Portfolio:

  • APVO414 – a bispecific ADAPTIR candidate, currently in Phase 1 development, targeting prostate specific membrane antigen (PSMA), an enzyme that is expressed on the surface of prostate cancer cells, and, CD3, a component of the T cell receptor complex expressed on all T cells.  APVO414 redirects T cells to specifically kill PSMA expressing tumors and is being developed for metastatic castration-resistant prostate cancer, which is advanced prostate cancer that has spread to other organs and no longer responds to hormone blocking therapies.
  • Otlertuzumab – a monospecific ADAPTIR candidate currently in Phase 2 development for the treatment of chronic lymphocytic leukemia (CLL).  Data from a Phase 2 clinical trial evaluating otlertuzumab in combination with bendamustine, compared to bendamustine alone, demonstrated a significant increase in median progression free survival for the combination, from approximately 10 to 16 months.
  • APVO436 – a bispecific ADAPTIR candidate currently in preclinical development targeting CD123, a cell surface receptor highly expressed on several hematological malignancies and CD3, a component of the T-cell receptor. APVO436 engages T cells to kill tumor cells.
  • ALG.APV-527 – a bispecific antibody candidate, partnered with Alligator Bioscience, featuring a novel mechanism of action designed to simultaneously target 4-1BB (CD137) and an undisclosed tumor antigen.  4-1BB, a costimulatory receptor on T cells, is known to enhance the immune response to cancer through activation of tumor-specific T cells and is believed to be a promising target for new immunotherapeutic approaches. ALG.APV-527 could potentially have utility in the treatment of a broad spectrum of cancers over-expressing the tumor antigen, including breast, cervical, non-small-cell-lung, prostate, renal, gastric, colorectal and bladder cancers.
  • APVO210 – a bispecific ADAPTIR preclinical candidate with a novel mechanism of action based on targeted cytokine delivery.  APVO210 is composed of a humanized anti-CD86 antibody fused with a modified form of IL-10 that specifically induces IL-10 signaling on antigen presenting cells, but not on lymphoid populations. APVO210 functions by suppressing immune responses and inducing certain tolerogenic responses and therefore may have potential benefit for the treatment of autoimmune and inflammatory diseases.
  • ROR1 Bispecific – a proof-of-concept bispecific candidate targeting ROR1, an antigen found on several solid tumors and hematologic, or blood-related malignancies.  Initial preclinical data demonstrate redirected T cell killing of tumors expressing ROR1 in vitro and in vivo in animal models.

About APVO436 and Aptevo’s ADAPTIR Platform

APVO436 is a bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity.  It was developed based on Aptevo’s proprietary next generation ADAPTIR 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) potent biological activity and extended half-life in preclinical studies; (ii) traditional antibody-like manufacturing processes with the potential for extended dosing regimens; (iii) unique properties for redirecting T-cell cytotoxicity (RTCC), including a favorable cytokine release profile and the ability to achieve target-dependent induction of RTCC at low drug concentrations.  If these data are confirmed in clinical studies, it could suggest the potential for enhanced safety and tolerability compared to other immuno-oncology approaches.

Two ADAPTIR molecules are currently undergoing clinical trials, with several more bispecific immunotherapies in preclinical development. The advantages of the ADAPTIR platform provides an opportunity for diverse therapeutic applications in the future. 

About Aptevo Therapeutics Inc.

Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on novel oncology and hematology therapeutics to meaningfully improve patients’ lives.  Aptevo has a commercial product, IXINITY® coagulation factor IX (recombinant), approved and marketed in the United States 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 or autoimmune diseases.  Aptevo has two ADAPTIR antibody candidates currently in clinical development and a broad pipeline of novel investigational-stage bispecific antibody candidates focused in immuno-oncology and autoimmune disease and inflammation. For more information, please visit

SOURCE: Aptevo Therapeutics