Kadmon Corporation Presents Preclinical Data on KD025 in Chronic Graft-Versus-Host-Disease at American Society of Hematology Annual Meeting
KD025 a Potential Novel Therapeutic Approach to Treating Chronic GVHD
(firmenpresse) - SAN FRANCISCO, CA -- (Marketwired) -- 12/08/14 -- Kadmon Corporation, LLC, today announced the presentation of preclinical data showing that KD025, the Company''s Phase 2, orally bioavailable, potent and highly selective inhibitor of ROCK2 (Rho-associated coiled-coiled kinase 2), effectively reverses chronic graft-versus-host disease (GVHD) in murine models. The data (Abstract #540) will be presented during an oral session titled, "Experimental Transplantation: Immune Function, GVHD and Graft-versus-Tumor Effects," taking place today from 2:45 p.m. - 4:15 p.m. at the 56th American Society of Hematology (ASH) Annual Meeting in San Francisco.
Chronic GVHD is a common and often fatal graft-mediated complication following allogeneic stem cell transplantation. It is a complex disorder with similarities to autoimmune disease and involves IL-21 and IL-17, two pro-inflammatory cytokines. The new data demonstrate that KD025 down-regulates STAT3 phosphorylation responsible for IL-21 and IL-17 production and concurrently up-regulates STAT5 phosphorylation responsible for the suppressive function of regulatory T cells (Tregs) in chronic GVHD animal models. Demonstration of the molecular mechanism of targeted ROCK2 inhibition in these preclinical models indicates the potential for KD025 in the treatment of chronic GVHD.
Specifically, KD025 administration significantly improved pulmonary function in an aggressive multi-organ system rodent model of fibrotic disease driven by IL-21 responses, showing a dose-dependent decrease in the development of pathogenic pulmonary function to levels comparable to non-GVHD controls. KD025 treatment also resulted in a two-fold decrease in collagen and antibody deposition in the lungs. In addition, KD025 decreased the number of germinal centers and percentage of T follicular helper cells in the spleens of mice, which contribute to the development of chronic GVHD. In a second rodent model, KD025 administration effectively blocked the progression of chronic sclerodermatous GVHD. Together, these data highlight the potential of KD025 for chronic GVHD therapy.
"These data emphasize that targeted inhibition of the ROCK2 pathway is highly effective in treating chronic GVHD in preclinical models," said Bruce R. Blazar, M.D., a Regents Professor of Pediatrics, Division of Blood and Marrow Transplantation at the University of Minnesota. "The data provide mechanistic insight into how KD025 resolves the immune response associated with chronic GVHD, and add to our understanding of how this novel ROCK2 inhibitor may be used in immunological and autoimmune diseases."
"By concurrently regulating STAT3/STAT5 phosphorylation, KD025 rebalances the immune system in a unique and very effective way," said Harlan W. Waksal, President and Chief Executive Officer at Kadmon. "We look forward to continuing our research on KD025 across multiple immunological and autoimmune indications, including clinical studies in chronic GVHD next year."
Kadmon Corporation, LLC, is a vertically integrated biopharmaceutical company focused on developing innovative products for significant unmet medical needs. We have a diversified product pipeline in oncology, autoimmune and fibrotic diseases, monogenic diseases and metabolic disease. For more information, visit .
This press release contains forward-looking statements. These forward-looking statements are based on management''s expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. The information contained in this press release is believed to be current as of the date of original issue. Kadmon expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
Ellen Tremaine
Investors
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David Pitts
Argot Partners
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Datum: 08.12.2014 - 16:45 Uhr
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