Aptevo Therapeutics’ Novel Bispecific Antibody Therapeutic APVO436 Shows Broad Activity in Primary Human AML Samples
New APVO436 Preclinical Data Show Robust T-Cell Engagement and Cytotoxicity in AML Patient Specimens
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.
“CD123 is an attractive target for bispecific antibody-based therapies in AML due to its prevalence on AML myeloblasts and leukemic stem cells. With an extended half-life, enhanced potency, and desirable manufacturing properties, APVO436 holds promise as a novel immunotherapeutic molecule in the treatment of AML,” said
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). The latest data presented at the ASH annual meeting build on these earlier findings, showing that APVO436 has broad immunotherapeutic activity against primary human AML cells in vitro, suggesting its utility as a potent and selective immunotherapeutic candidate in the treatment of AML.
In a series of experiments sponsored by Aptevo and conducted in collaboration with scientists at the
- Broadly induce AML cytotoxicity in a dose-dependent and effector:target-dependent manner;
- Induce cytotoxicity across a range of blast CD123-expression levels, including in specimens with very limited CD123 expression, suggesting that APVO436 is highly potent
- Promote endogenous T-cell activation and proliferation accompanied by CD123+ cell depletion in both normal and AML subject samples.
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 peripheral T-cell lymphoma (PTCL). A previous Phase 2 clinical study evaluating otlertuzumab for the treatment of chronic lymphocytic leukemia (CLL) showed that 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 initiate killing of tumor cells. Aptevo intends to file an IND and begin clinical development of APVO436 in 2018.
- 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 5T4, a tumor antigen widely overexpressed in a number of different types of cancer. 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. Aptevo intends to file an IND for APVO210 in 2018.
- 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.
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Senior Director, Investor Relations and Corporate Communications
Source: Aptevo Therapeutics Inc.