SAN DIEGO, March 26, 2015 -- Conatus Pharmaceuticals Inc. (CNAT) today announced top-line results from the company's Phase 2 double-blind, placebo-controlled clinical trial of emricasan, a first-in-class, orally active pan-caspase protease inhibitor, in 38 patients with nonalcoholic fatty liver disease (NAFLD), including the subset of NAFLD patients with nonalcoholic steatohepatitis (NASH). The trial met its primary endpoint, showing a statistically significant (p<0.05) reduction in alanine amino transferase (ALT) in patients treated for 28 days with emricasan at 25 mg twice per day dosing compared to patients in the placebo control group. Reductions from baseline in ALT at Day 28 of approximately 39% in the emricasan treatment arm and approximately 14% in the placebo arm were similar to results observed in previous trials. Elevated baseline levels of three key serum biomarkers -- caspase-cleaved cytokeratin 18 (cCK18), full length cytokeratin 18, and caspase 3/7 -- also showed statistically significant reductions from baseline in emricasan-treated patients at Day 28. The baseline elevation in cCK18 confirmed that the underlying targets of emricasan's mechanism, apoptosis and inflammation, which are believed to drive liver disease progression, were engaged in the NAFLD/NASH patients in this trial. A reduction from baseline in cCK18 at Day 28 of approximately 30% in the emricasan treatment arm and an increase from baseline of approximately 4% in the placebo arm were similar to results observed in previous trials. The reduction in serum cCK18 levels demonstrated that emricasan can effectively reduce inflammation and elevated levels of apoptosis in NAFLD/NASH patients. These results were consistent with data obtained from the company's previous clinical trials in other liver disease patient populations.
Emricasan was safe and well tolerated in the NAFLD/NASH trial, with no dose-limiting toxicities and no drug-related serious adverse events. Treatment with emricasan also had no adverse effects on lipid levels or insulin sensitivity, important safety assessments in NAFLD/NASH patients who are at risk for cardiovascular disease. Detailed results from the NAFLD/NASH trial will be presented in a late-breaker poster at The International Liver Congress(TM) 2015, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria, April 22-26, 2015.
"With these results from the NAFLD/NASH trial, we have confirmed that the optimal dose of emricasan is consistent across different etiologies," said Conatus co-founder, President and Chief Executive Officer, Steven J. Mento, Ph.D., "and strengthened our belief that inhibiting excessive apoptosis and inflammation will be therapeutic in patients whose liver damage is associated with NASH."
"Our focus is on developing emricasan initially as a treatment in patients with liver cirrhosis," said David T. Hagerty, M.D., Executive Vice President of Clinical Development at Conatus. "The data from the NAFLD/NASH trial, along with the data from our three organ impairment dosing trials, support the conduct of efficacy trials in patients with liver cirrhosis due to NASH. In addition, the recently published proceedings of a 2013 NASH endpoints workshop sponsored by the American Association for the Study of Liver Diseases (AASLD) and U.S. Food and Drug Administration (FDA) provided important insights regarding validated surrogate clinical endpoints that could be useful for accelerated approval pathways in patients with NASH-driven liver cirrhosis. With this comprehensive information package, we are prepared for planned discussions with regulatory authorities to seek guidance on the appropriate use and analysis of these endpoints in registrational trials including patients with NASH cirrhosis."
About Emricasan Clinical Development
To date, emricasan has been studied in over 550 subjects in fourteen clinical trials across a broad range of liver disease etiologies and stages of progression. In multiple clinical trials, emricasan has demonstrated statistically significant, rapid and sustained reductions in elevated levels of key biomarkers of inflammation and apoptosis that are implicated in the severity and progression of liver disease. Importantly, these key biomarkers are known to be elevated and to have prognostic value in multiple hepatic indications that Conatus is currently pursuing.
About Conatus Pharmaceuticals
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease. Emricasan is a first-in-class, orally active pan-caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.
This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward looking statements, including statements regarding: the belief that inhibiting apoptosis and inflammation will be therapeutic in patients with NASH; the appropriateness of surrogate clinical endpoints for accelerated approval pathways; the company's ability to secure regulatory guidance on the appropriate use and analysis of surrogate clinical endpoints in registration trials including patients with NASH cirrhosis; and emricasan's therapeutic potential in patients with NASH cirrhosis and other forms of liver disease. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including: Conatus' ability to initiate and successfully complete current and future clinical trials; Conatus' dependence on its ability to obtain regulatory approval for, and then successfully commercialize emricasan, which is Conatus' only drug candidate; Conatus' reliance on third parties to conduct its clinical trials, enroll subjects, manufacture its preclinical and clinical drug supplies and manufacture commercial supplies of emricasan, if approved; the potential that earlier clinical trials may not be predictive of future results; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; results of future clinical trials of emricasan; the potential for competing products to limit the clinical trial enrollment opportunities for emricasan in certain indications; the uncertainty of the FDA's and other regulatory agencies' approval processes and other regulatory requirements; Conatus' ability to fully comply with numerous federal, state and local laws and regulatory requirements applicable to it; Conatus' limited operating history and its ability to operate successfully as a public company; Conatus' ability to obtain additional financing in order to complete the development and commercialization of emricasan; and those risks described in Conatus' prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in Conatus' forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, Conatus does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.