Normal levels of apoptosis and caspase activity in healthy volunteers are not reduced by emricasan
Emricasan currently in Phase 2b study in acute-on-chronic liver failure and Phase 2 study in severe alcoholic hepatitis
SAN DIEGO, Nov. 2, 2013 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals (Nasdaq: CNAT ), a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease, today announced that data from the Phase 1 clinical trial of emricasan, a first-in class, orally active caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, are being presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) on November 4, 2013 in Washington, D.C. The Phase 1 clinical trial was conducted to understand the activity of emricasan on caspase activity in healthy subjects.
Emricasan is a potent inhibitor of pro-apoptotic and pro-inflammatory caspases, and in prior Phase 1 and Phase 2 clinical trials, has been shown to rapidly suppress apoptotic caspase activity as determined by a key biomarker of inflammation and cell death, caspase cleaved CK18 (cCK18), in hepatitis C virus (HCV) patients to within ranges typically reported for healthy volunteers. Caspase activity is known to be elevated in many liver diseases and is associated with disease severity and progression. In the Phase 1 clinical trial, physiologically normal levels of apoptosis and pro-apoptotic caspase activity in healthy volunteers remained unaffected following exposure to emricasan.
"This novel observation provides important new information regarding the effect of pan caspase inhibition in healthy volunteers and further insight regarding the overall safety profile of emricasan," said Alfred P. Spada, Ph.D., Senior Vice President, Research and Development and Chief Scientific Officer of Conatus. "We believe the results of this study demonstrate that emricasan does not interfere with the normal level of caspase-mediated apoptosis in humans, and taken together with our prior results in HCV patients, suggests that emricasan may be an effective therapeutic agent for the treatment of chronic and acute liver disease."
In the Phase 1 clinical trial, emricasan was administered to 15 healthy volunteers at a dose of either 25 mg single dose or 25 mg twice daily for 10 days as part of a 24 day drug-drug interaction study with cyclosporine. This dose was shown in prior clinical trials to provide near maximal reduction of elevated cCK18 and serum transaminases in HCV patients. In this trial, blood samples were taken on day 0 and on study days 1, 17- 20, 22 and 24-27. Serial blood samples were collected out to 12 hours post-dose on study days 1, 17 and 24. Both drug levels and cCK18 were measured at each time point. Emricasan had no effect on cCK18 levels in healthy volunteers at any time point in the trial. Drug exposure was consistent with previously reported blood levels.
Poster Presentation Details:
| Date/Time: | November 4, 2013, 8:00 a.m. – 5:30 p.m. ET |
| Presentation Title: | "Physiologically normal levels of apoptosis in healthy volunteers are not |
| reduced by the pan caspase inhibitor, emricasan" | |
| Location: | Poster Hall - Poster #1532 |
| Session Title: | Hepatotoxicity: Apoptosis and Necrosis |
About Emricasan Clinical Development
Conatus is developing its lead compound, emricasan, for the treatment of patients in orphan populations with chronic liver disease and acute exacerbations of chronic liver disease. To date, emricasan has been studied in over 500 subjects in ten clinical trials. In a randomized Phase 2b clinical trial, emricasan demonstrated a statistically significant, consistent, rapid and sustained reduction in elevated levels of two key biomarkers of inflammation and cell death that are implicated in the severity and progression of liver disease. Emricasan is currently in a Phase 2b clinical trial in patients with acute-on-chronic liver failure, as well as a Phase 2 clinical trial in severe alcoholic hepatitis.
About Conatus Pharmaceuticals Inc.
Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing emricasan as a first-in class, orally active caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the progression of liver disease. For additional information, please visit www.conatuspharma.com .
Forward-Looking Statements
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, including statements regarding the overall safety profile of emricasan, emricasan's lack of interference with the normal level of caspase-mediated apoptosis in humans, emricasan's effectiveness as a therapeutic agent for the treatment of chronic and acute liver disease and emricasan's potential to interrupt the progression of liver disease, are forward-looking statements. 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: potential adverse side effects or other safety risks associated with emricasan; results of future clinical trials of emricasan; the uncertainty of the FDA approval process and other regulatory requirements; and those described in Conatus' prior press releases and 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.
Paul Cox, Stern Investor Relations (212) 362-1200,
