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Data Published in the Journal Blood
Kadmon to Initiate Phase 2 Study of ROCK2 Inhibitor KD025 in cGVHD in 2016
NEW YORK, NY--(Marketwired - Mar 21, 2016) - Kadmon Corporation, LLC today announced the publication of preclinical data demonstrating that blocking the rho-associated coiled-coil kinase 2 (ROCK2) signaling pathway with KD025, the Company's Phase 2, highly selective ROCK2 inhibitor, effectively decreases the pathogenesis of chronic graft-versus-host disease (cGVHD) in murine and human models. The data are published online this week in the First Edition of Blood.
cGVHD is a common and often fatal complication following allogeneic stem cell transplantation in which transplanted immune cells attack recipient tissue, leading to fibrosis in the lung, liver and skin. Several studies have shown that IL-21 and IL-17, two pro-inflammatory cytokines regulated by the ROCK2 signaling pathway, play a key role in cGVHD pathogenesis. The new published data demonstrated that targeted ROCK2 inhibition with KD025 effectively ameliorated cGVHD in multiple models and had a major therapeutic effect on key cGVHD cytokines and signaling pathways involved in pathogenesis of the disease in both mice and humans.
KD025 treatment reversed the clinical and immunological symptoms of cGVHD in two murine models. Mice treated with KD025 showed improvements in pulmonary function and had a significant decrease in the cGVHD pathology in the lung, liver and spleen compared to vehicle-treated animals, while the graft-versus-leukemia effect and immune response to viral pathogens remained preserved. Importantly, in both animal models, KD025 treatment down-regulated phosphorylation of STAT3, a pro-inflammatory signaling pathway that plays a key role in the development of cGVHD. The therapeutic potential of ROCK2 inhibition was underscored by data from human cells demonstrating that KD025 inhibited the production of IL-21, IL-17 and IFN-γ, as well as decreased STAT3 activity. In both murine and human cells, ROCK2 inhibition with KD025 down-regulated STAT3 phosphorylation and simultaneously up-regulated STAT5 phosphorylation, which is responsible for regulatory cell function, reducing cGVHD progression in these models.
"These data demonstrate that ROCK2 inhibition decreases cGVHD manifestation in murine and human models, which correlates with a demonstrated effect on molecular signaling pathways responsible for cGVHD pathogenesis," said Bruce R. Blazar, M.D., a Regents Professor of Pediatrics, Division of Blood and Marrow Transplantation at the University of Minnesota and lead author of the manuscript. "The ROCK2 signaling pathway has been shown as a potential novel therapeutic for the treatment of cGVHD."
"These findings further support the importance of ROCK2 signaling in affecting key signaling pathways and disease pathogenesis to potentially treat cGVHD," said John L. Ryan, Ph.D., M.D., Executive Vice President, Chief Medical Officer at Kadmon. "Our IND has been accepted for our Phase 2 clinical trial of KD025 for the treatment of cGVHD and we look forward to initiating this study in mid-2016."
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 and genetic 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.