CymaBay Therapeutics Announces Plans To Initiate Its Next Phase 2 Study Of MBX-8025 In Primary Biliary Cholangitis

Newark, CA (GLOBE NEWSWIRE) - CymaBay Therapeutics, Inc. (NASDAQ:CBAY), a clinical-stage biopharmaceutical company focused on developing therapies to treat metabolic diseases with high unmet medical need, today announced that after receiving input from the U.S. Food and Drug Administration (FDA), it has determined the next step in the development of MBX-8025 in subjects with primary biliary cholangitis (PBC).  MBX-8025 is an orally administered potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist.

An initial Phase 2 study of MBX-8025 in subjects with primary biliary cholangitis was terminated earlier this year when proof-of-concept was demonstrated by marked improvements in biochemical markers of cholestasis, including alkaline phosphatase (ALP), a surrogate biomarker that has been linked to clinical outcomes in PBC. The study also identified a treatment emergent signal of transaminase elevations. The magnitude of the ALP reductions in the study suggested that lower doses may retain ALP reductions while avoiding transaminase elevations. After discussions with regulatory authorities, the company will be initiating a second Phase 2 study that will investigate lower doses of MBX-8025 in subjects with PBC to optimize the response. Initiation of the study is expected by year end 2016.

“We are very pleased that the next steps in the development of MBX-8025 for PBC are now clearly defined,” said Harold Van Wart, Ph.D., President and Chief Executive Officer of CymaBay Therapeutics. “Having established clinical proof-of-concept, we can now focus on dose selection to optimize the response in the next study.  Based on the magnitude of the ALP lowering observed in our earlier Phase 2 study and the fact that MBX-8025 does not appear to cause pruritus, we are eager to explore a lower dose range.”

About MBX-8025

MBX-8025 is a potent and selective agonist of PPARδ, a nuclear receptor important for lipid transport, storage and metabolism in liver and muscle. In a Phase 2 study in subjects with mixed dyslipidemia, MBX-8025 decreased LDL-C, triglycerides and high sensitivity CRP, a biomarker of inflammation. MBX-8025 also decreased alkaline phosphatase and gamma glutamyl transferase, two key markers of cholestasis. In a recently completed Phase 2 study in subjects with primary biliary cholangitis (PBC), MBX-8025 decreased markers of cholestasis and inflammation without appearing to cause pruritus while also lowering LDL-C. CymaBay has also completed a pilot Phase 2 clinical study showing that MBX-8025 lowers LDL-C in patients with homozygous familial hypercholesterolemia (HoFH).  The U.S. Food and Drug Administration (FDA) has granted CymaBay orphan drug designation for MBX-8025 as a treatment for HoFH and Fredrickson types I and V hyperlipoproteinemia.

About PBC

Primary biliary cholangitis (PBC), formerly known as primary biliary cholestasis, is a serious and potentially life threatening autoimmune disease of the liver characterized by impaired bile flow (cholestasis) and accumulation of toxic bile acids. There is an accompanying inflammation and destruction of the intrahepatic bile ducts which can progress to fibrosis, cirrhosis and liver failure. Other clinical symptoms of PBC include fatigue and pruritus, which can be quite disabling in some patients. PBC is primarily a disease of women, afflicting approximately one in 1,000 over the age of 40.

About CymaBay

CymaBay Therapeutics, Inc. (CBAY) is a clinical-stage biopharmaceutical company focused on developing therapies to treat metabolic diseases with high unmet medical need, including serious rare and orphan disorders. MBX-8025 is a potent, selective, orally active PPARδ agonist. A Phase 2 study of MBX-8025 in patients with mixed dyslipidemia established that it has an anti-atherogenic lipid profile. CymaBay has completed Phase 2 studies for MBX-8025 in subjects with primary biliary cholangitis and homozygous familial hypercholesterolemia, establishing proof-of-concept in both indications. Arhalofenate, CymaBay’s other product candidate, is a potential Urate-Lowering Anti-Flare Therapy that has completed five Phase 2 studies in subjects with gout. Arhalofenate has been found to reduce painful flares in joints while at the same time lowering serum uric acid by promoting excretion of uric acid by the kidney. This dual action addresses both the signs and symptoms of gout while managing the underlying pathophysiology of hyperuricemia.

Cautionary Statements

The statements in this press release regarding the expected timing of the initiation of CymaBay’s Phase 2 study of MBX-8025 in patients with PBC and the potential future performance of CymaBay's product candidates, are forward looking statements that are subject to risks and uncertainties. Actual results and the timing of events regarding the further development of CymaBay’s product candidates could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties, which include, without limitation, risks related to: the success, cost and timing of any of CymaBay's product development activities, including clinical trials of MBX-8025 and arhalofenate; effects observed in trials to date which may not be repeated in the future; any delays or inability to obtain or maintain regulatory approval of CymaBay's product candidates in the United States or worldwide; and the ability of CymaBay to obtain sufficient financing to complete development, regulatory approval and commercialization of its product candidates in the United States and worldwide. Additional risks relating to CymaBay are contained in CymaBay's filings with the Securities and Exchange Commission, including without limitation its most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q and other documents subsequently filed with or furnished to the Securities and Exchange Commission. CymaBay disclaims any obligation to update these forward-looking statements except as required by law.

For additional information about CymaBay visit www.cymabay.com.

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