SOUTH SAN FRANCISCO, Calif., Sept. 13, 2016 /PRNewswire/ -- Kezar Life Sciences, a company focused on the discovery and development of drugs targeting protein homeostasis, announced today the initiation of its Phase 1 randomized, double-blind clinical program for KZR-616, a selective inhibitor of the immunoproteasome. Since enrollment of the first cohort on August 9, Kezar has completed dosing of 24 subjects across three cohorts in the single ascending dose (SAD) portion of the Company's Phase 1a study, which includes both SAD and multiple ascending dose (MAD) portions. The study is expected to enroll a total of 64-80 subjects, with key endpoints including pharmacokinetics and biomarkers of target engagement, as well as safety and tolerability. In the Phase 1 program, KZR-616 is administered once-weekly as a subcutaneous injection.
Pending progress of the study, the Company anticipates that it will report topline pharmacokinetics, safety, and target engagement data by the end of 2016. Additionally, in the first half of 2017 the Company anticipates commencing a Phase 1b study of KZR-616, which is expected to enroll up to 40 patients with autoimmune disorders and include a cohort with a placebo control.
"We are proud to be the first company to move a selective inhibitor of the immunoproteasome into the clinic," said John Fowler, Kezar's Chief Executive Officer and Co-Founder. "The Kezar scientific team is unparalleled in its understanding of the unique biology and therapeutic potential of the immunoproteasome, and has done a tremendous job moving our lead program rapidly into the clinic. We look forward to demonstrating the safety profile and target engagement of KZR-616 in the coming months, and launching Phase 1b and 2 trials in patients in 2017."
Research using KZR-616 and its tool molecule, ONX 0914, has demonstrated the unique therapeutic potential of selective targeting of the immunoproteasome in preclinical in vivo models of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and other autoimmune diseases. Specifically, these compounds have been shown to block inflammatory cytokine production, downregulate inflammatory T cell activity, and deplete autoantibody-secreting plasma cells. Selective immunoproteasome inhibition has also been well-tolerated in these models and does not impair normal immune responses.
"Initiation of the KZR-616 clinical program represents an exciting milestone for our extensive research program to develop a first-in-class treatment that can address substantial unmet needs across many autoimmune disorders," said Christopher Kirk, Ph.D., President, Chief Scientific Officer & Co-Founder of Kezar. "We believe that the immunoproteasome is a profoundly untapped area of translational medicine. Our scientific research has shown that selective inhibitors of the immunoproteasome have the potential to reset normal immune function in patients with complex and difficult-to-treat autoimmune diseases. We look forward to the continued progress of the program."
About the Immunoproteasome
Protein degradation is a key process in the function and survival of all mammalian cells and is mediated by the ubiquitously expressed proteasome. Inhibitors of the proteasome, such as VELCADE™ and KYPROLIS™, are currently used to treat multiple myeloma, a plasma cell malignancy. In cells of the immune system, such as B- and T-cells, a unique form of the proteasome, termed the immunoproteasome, is expressed. The immunoproteasome regulates multiple aspects of immune responses and selective inhibitors, such as KZR-616, are well-tolerated and highly active in multiple mouse models of autoimmunity, including rheumatoid arthritis, multiple sclerosis, Crohn's disease, and lupus.
About Kezar Life Sciences
Kezar Life Sciences, a privately held company based in South San Francisco, was founded in 2015 to develop small molecule drugs to revolutionize the treatment of autoimmune disorders. Leveraging research begun in 2006 under the direction of co-founder Dr. Kirk at Proteolix and then Onyx Pharmaceuticals, Kezar will advance drugs that selectively target the immunoproteasome for the treatment of autoimmune disorders. In addition, Kezar will discover and develop drugs that target protein secretion and transmembrane protein expression. For more information, please visit http://kezarlifesciences.com/.
Ben Matone, Burns McClellan, Inc., on behalf of Kezar Life Sciences
Michael Wolfe, Director of Finance & Operations at Kezar Life Sciences
SOURCE Kezar Life Sciences