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A unique mechanism of action for delivering IL-10
SEATTLE—Aptevo Therapeutics Inc., a biotechnology company focused on developing novel oncology and hematology therapeutics, recently announced the publication of preclinical data in Frontiers in Immunology. The data highlight 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 and 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 Dr. Jane Gross, 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 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 Marvin L. White, president and CEO 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.”