Aptevo Therapeutics Inc. recently announced the publication of preclinical data in Frontiers in Immunology highlighting the activity of APVO210 as a potent and selective immunosuppressive agent with potential utility in the treatment of multiple autoimmune and inflammatory conditions, such as psoriasis, inflammatory bowel disease, rheumatoid arthritis, graft-versus-host disease, lupus, as well as other diseases where there is antigen-driven activation of T lymphocyte-mediated disease.
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 Jane Gross, PhD, Chief Scientific Officer for Aptevo. “Our data highlight the unique attributes of this molecule, demonstrating its ability in vitro to selectively target antigen-presenting cells without triggering IL-10R signaling in T or B cells. If these results are confirmed in the clinic, APVO210 could represent an improved version of IL-10 by maintaining its suppressive properties while reducing the stimulatory properties observed with other investigational IL-10 therapies. Most importantly, our data demonstrate that APVO210 induces tolerogenic dendritic cells and antigen-specific T regulatory cells, which may also act to suppress autoimmune and inflammatory disease processes.”
“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,” added Marvin L. White, President and Chief Executive Officer of Aptevo. “We have submitted our pre-IND package to the FDA and have received their feedback. Based on this, we are pleased to reaffirm our previous guidance that we anticipate filing an IND for APVO210 in the fourth quarter of 2018.”
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.
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 the US, are estimated to affect more than 23.5 million people while globally, autoimmune diseases are estimated to affect between 350-550 million people.
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 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 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 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, visit www.aptevotherapeutics.com
