Novel First-In-Class Immunotherapeutic APVO210 Features Unique Mechanism of Action Delivering IL-10
Suppresses Inflammation and Immune Activation Without Lymphocyte Stimulation
New Preclinical Data Published in ‘Frontiers in Immunology’ Show APVO210 Holds Promise in the Treatment of Autoimmune Diseases by Driving the Differentiation of Tolerogenic Dendritic Cells & Inducing Antigen-Specific T Regulatory Cells
APVO210 is a bispecific antibody candidate built on Aptevo’s ADAPTIR™ therapeutic protein platform. It is designed to modulate and suppress pathological immune activation without lymphocyte activation by selectively delivering a modified form of IL-10 to antigen presenting cells via CD86 without stimulating IL-10 responses on resting and activated lymphocytes.
Cytokines are pleiotropic and function by promoting or suppressing a variety of cellular functions, including inflammatory responses. Unregulated inflammation is believed to be responsible for a variety of chronic and acute inflammatory and autoimmune disorders. The cytokine IL-10 is known to play a key role in suppressing inflammation and, as a result, has been studied extensively by other companies in different clinical trials for autoimmune and inflammatory disorders. Unfortunately, the results of these studies have been disappointing. This may be due to the undesired stimulatory properties of IL-10, which exerts stimulatory effects on lymphocytes, promoting B-cell proliferation, immunoglobulin production and cytotoxic T-cell function, thus potentially reducing its overall therapeutic utility for immunosuppression.
Conversely, APVO210 is designed to deliver a modified form of IL-10 to suppress inflammation and immune activation without lymphocyte stimulation. Importantly, APVO210 also retains the ability to mediate the differentiation of tolerogenic dendritic cells and antigen specific T regulatory cells (Tr1)
“There is a growing body of data to support APVO210 as a novel, first-in-class targeted cytokine immunotherapy,” said
“We believe APVO210 represents a potentially groundbreaking new approach in immune suppressive therapy with implications for the treatment of a wide variety of IL-10-mediated diseases characterized by pathological immune activation and inflammation,” continued Dr. Gross. “The preclinical data published in Frontiers in Immunology demonstrate the potent immunomodulatory properties of APVO210, showing that it can selectively suppress antigen presenting function and T-cell activation and induce regulatory dendritic cell production without stimulating the function of naïve or activated B and T cells.”
“We are very encouraged by the mounting body of evidence for APVO210 supporting targeted cytokine delivery as a novel therapeutic approach for inflammatory and autoimmune diseases,” said
We believe that APVO210 improves the anti-inflammatory properties of IL-10 in two ways. First by specifically targeting cells expressing CD86, such as monocytes, macrophages, and dendritic cells, while eliminating the undesired stimulation of lymphocytes including resting and activated T and B lymphocytes expressing the IL-10 receptor. Aptevo believes that the absence of lymphocyte stimulation associated with APVO210 may reduce the toxicities previously observed in other companies’ clinical studies testing repeat administration of IL-10 in humans. If confirmed, this could potentially allow for improved dosing and enhanced efficacy. In addition, preclinical studies of APVO210 show that it has a longer half-life in non-human primates (approximately 40 hours) compared to IL-10, which is approximately 4 hours. An increased half-life should support an opportunity for improved dosing regimens.
About Autoimmune Diseases
More than 80 different types of autoimmune diseases have been identified. Some, such as Type 1 diabetes, multiple sclerosis and rheumatoid arthritis are well known. Others, however, are rare and difficult to diagnose. Collectively, autoimmune diseases are among the most prevalent diseases worldwide, and in
About APVO210 and the ADAPTIR Platform
APVO210 is a novel targeted cytokine therapeutic based on Aptevo’s ADAPTIR modular protein therapeutic platform. It targets a modified version of IL-10 to CD86+ cells, increasing its immunosuppressive properties without stimulating T and B lymphocytes.
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.
Aptevo Product Portfolio
- IXINITY (coagulation factor IX [recombinant]) – is a third-generation recombinant human coagulation factor IX approved in
the United Statesfor the control and prevention of bleeding episodes and for perioperative management in adults and children 12 years of age or older with Hemophilia B.
ADAPTIR Clinical and Preclinical Pipeline:
- Otlertuzumab – a monospecific ADAPTIR candidate currently in Phase 2 clinical 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.
- 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.
- 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 filed an IND in the second quarter of 2018 and plans to begin clinical development of APVO436 in the fourth quarter of 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.
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Senior Director, Investor Relations and Corporate Communications
Source: Aptevo Therapeutics Inc.