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Data Demonstrate the Potential of Selective ROCK2 Inhibition to Treat Autoimmune Disease
NEW YORK, NY--(Marketwired - Jan 11, 2016) - Kadmon Corporation, LLC today announced the presentation of preclinical data demonstrating that the rho-associated coiled-coil kinase 2 (ROCK2) signaling pathway plays an instrumental role in modulating immune response. The data demonstrated the mechanism by which selective ROCK2 inhibition down-regulates disease progression in an experimental model of lupus and effectively ameliorates lung pathology of experimental chronic graft-versus-host disease (cGVHD). The data will be summarized in a poster presentation today at the 2016 Keystone Symposia Conference taking place January 10-14, 2016 in Steamboat Springs, Colorado.
Recent studies have demonstrated that selective ROCK2 inhibition affects key cellular functions that control and restore balance to the immune system to effectively fight disease while avoiding auto-aggressive immune responses. Specifically, ROCK2 inhibition down-regulates STAT3, a regulator of the inflammatory pathway, and concurrently increases STAT5, a controller of regulatory cell function, helping to resolve inflammation with a minimal effect on the rest of the immune response.
New data demonstrated the molecular mechanism by which ROCK2 signaling regulates STAT3/STAT5 transcription activity to modulate gene expression during Th17-driven immune response. Selective ROCK2 inhibition concomitantly down-regulated STAT3 while increasing STAT5 binding to the same site of IL-21 and Bcl6 promoters, key controllers of the pro-inflammatory arm of T- cell immune response. Selective ROCK2 inhibition also increased STAT3 and STAT5 binding to the PRDM1 gene promoter, a gene that encodes Blimp1 protein, a key repressor of T follicular helper (Tfh) cell signature genes. ROCK2's role in regulating the balance of the immune response was further solidified by data demonstrating that targeted ROCK2 inhibition concurrently modulated STAT3/STAT5 activity in vivo, reducing disease progression in murine models of lupus and experimental cGVHD.
"These new findings demonstrate the critical role of ROCK2 in controlling the balance between pro-inflammatory (Th17/Tfh cells) and anti-inflammatory (Treg) T-cell responses via modulation of STAT3/STAT5 competitive antagonism," said Wei Chen, Ph.D., Associate Director, Immunology at Kadmon and first author of the study. "The molecular mechanism of targeted ROCK2 inhibition that was demonstrated both in vitro and in vivo underscores the therapeutic potential of ROCK2 inhibition for autoimmunity."
"Research at Kadmon has demonstrated the substantial therapeutic potential of selective ROCK2 inhibition to treat certain autoimmune and fibrotic diseases," said Harlan W. Waksal, M.D., President and CEO at Kadmon. "The new data provide further support for our ongoing and planned studies of selective ROCK2 inhibition for the treatment of multiple autoimmune and fibrotic diseases."
About Kadmon Corporation
Kadmon Corporation, LLC is a fully integrated biopharmaceutical company focused on developing innovative products for significant unmet medical needs. We have a diversified product pipeline in autoimmune and fibrotic diseases, oncology, genetic and metabolic diseases.
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.