Conatus Pharmaceuticals Announces Three Accepted Abstracts for AASLD Annual Meeting

Conatus Pharmaceuticals Announces Three Accepted Abstracts for AASLD Annual Meeting

SAN DIEGO, Oct. 02, 2018 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (NASDAQ: CNAT) announced today that two abstracts – one addressing clinical results with the company’s pan-caspase inhibitor, emricasan, and one addressing preclinical results with the company’s pan-caspase inhibitor, IDN-7314 – have been accepted for oral presentations; and one abstract addressing preclinical results with emricasan has been accepted for a poster presentation at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in San FranciscoNovember 9-13, 2018. Accepted abstracts were published yesterday on the Hepatology website1.

Abstracts accepted for oral presentations included:
“Multicenter, double-blind, randomized trial of emricasan in subjects post liver transplantation (LT) with recurrent hepatitis C virus (HCV) and liver fibrosis or cirrhosis despite achieving sustained virologic response (SVR),” (abstract #1226, originally accepted as poster, later accepted as oral presentation); and

“Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis,” (abstract #25);
and abstracts accepted for posters included:

“Molecular mechanisms underlying the effects of emricasan in portal hypertension and chronic liver disease: the hepato-sinusoidal cross-talk matters,” (abstract #1344).

Abstract #25 is an AASLD Foundation Abstract Award Recipient and was accepted for presentation in the Presidential Plenary Session on Translational Science and Genomics.

“As we advance toward releasing top-line results over the next 15 months from our three ENCORE Phase 2b clinical trials in patients with nonalcoholic steatohepatitis (NASH), the body of preclinical and clinical data documenting the activity and effects of pan-caspase inhibitors continues to grow,” said Conatus co-founder, President and Chief Executive Officer Steven J. Mento, Ph.D. “Thanks to the work of our principal investigators and our scientific collaborators, we have an ever-deepening understanding of the multiple mechanistic effects of caspase inhibitors on liver structure and function, as well as their disease-modifying potential. We are pleased with the recognition afforded to these latest developments at the upcoming AASLD meeting.”

About Conatus Pharmaceuticals
Conatus is a biotechnology company focused on the development of novel medicines to treat liver disease. In collaboration with Novartis, 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 inhibitor designed to reduce the activity of enzymes that mediate inflammation and apoptosis. Conatus believes that by reducing the activity of these enzymes, caspase inhibitors have the potential to interrupt the progression of a variety of diseases. 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 are forward-looking statements, including statements regarding: the timeline for results from the ENCORE trials; and caspase inhibitors’ potential to modify disease and interrupt the progression of a variety of diseases. 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: the risk that the preclinical results may not be predictive of future clinical trial results; and those risks described in the company’s prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in the company’s 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, the company 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.

1 Hepatology 68:S1 (October 2018) https://aasldpubs.onlinelibrary.wiley.com/journal/15273350.

Emricasan Development - A potential treatment for fibrotic liver disease

Why Conatus Pharmaceuticals May Have the Answer to Liver Disease

Steven Mento, PhD on Advanced Therapy for Liver Disease

Video Source - The Doctor's Channel 

Emricasan Development

• We have designed a comprehensive clinical program to demonstrate the therapeutic benefit of emricasan across the spectrum of fibrotic liver disease. We plan to study emricasan in patients with rapidly progressing fibrosis (HCV-POLT) as well as in patients with established liver cirrhosis and decompensated disease (ACLF and CLF). 
• Current clinical focus is on patients with chronic liver disease to:
  • Improve and/or stabilize liver function during acute and chronic liver failure
  • Delay progression of fibrosis to cirrhosis due to Hepatitis C Virus (HCV) recurrence

HCV-POLT - post-orthotopic liver transplant due to Hepatitis C virus infection
ACLF- acute-on-chronic liver failure
CLF - chronic liver failure
Emricasan, also known as IDN 6556 and  PF 03491390

Overview
Conatus Pharmaceuticals is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. We are developing our lead compound, emricasan, for the treatment of patients in orphan populations with chronic liver disease and acute exacerbations of chronic liver disease. Emricasan is a first-in-class, orally active caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or apoptosis. We believe that by reducing the activity of these enzymes, emricasan has the potential to interrupt the progression of liver disease. We have observed compelling preclinical and clinical trial results that suggest emricasan may have clinical utility in slowing progression of liver diseases regardless of the original cause of the disease

To date, emricasan has been studied in over 500 subjects in ten clinical trials. In a randomized Phase 2b clinical trial in patients with liver disease, emricasan demonstrated a statistically significant, consistent, rapid and sustained reduction in elevated levels of two key biomarkers of inflammation and cell death, alanine aminotransferase, or ALT, and cleaved Cytokeratin 18, or cCK18, respectively, both of which are implicated in the severity and progression of liver disease. Emricasan has been generally well-tolerated in all of the clinical studies. Our initial development strategy targets indications for emricasan with high unmet clinical need in orphan patient populations, such as patients with acute-on-chronic liver failure, or ACLF, chronic liver failure, or CLF, and patients who have developed liver fibrosis post-orthotopic liver transplant due to Hepatitis C virus infection, or HCV-POLT.

We expect to initiate a Phase 2b ACLF trial and a Phase 3 HCV-POLT trial (currently designated a Phase 3 registration study in the European Union and a Phase 2b study in the United States) in the second half of 2013 and a Phase 2b CLF trial in the second half of 2014.

Overview of Liver Disease
Liver disease can result from injury to the liver caused by a variety of insults, including Hepatitis C virus, or HCV, Hepatitis B virus, obesity, chronic excessive alcohol use or autoimmune diseases.

Regardless of the underlying cause of the disease, there are important similarities in the disease progression including increased inflammatory activity and excessive liver cell apoptosis, which if unresolved leads to fibrosis. Fibrosis, if allowed to progress, will lead to cirrhosis, or excessive scarring of the liver, which may result in reduced liver function. Some patients with liver cirrhosis have a partially functioning liver and may appear asymptomatic for long periods of time, which is referred to as compensated liver disease. When the liver is unable to perform its normal functions this is referred to as decompensated liver disease. ACLF occurs in patients who have compensated or decompensated cirrhosis but are in relatively stable condition until an acute event sets off a rapid worsening of liver function. Patients with CLF suffer from continual disease progression which may eventually lead them to require orthotopic liver transplantation. Patients with HCV who receive orthotopic liver transplants, in which the diseased liver is replaced by a donor liver, will have their HCV infections recur. Many of these HCV-POLT patients will experience accelerated development of fibrosis and progression to cirrhosis of the transplanted liver due to the recurrence of HCV.

The National Institutes of Health estimates that 5.5 million Americans have chronic liver disease or cirrhosis, and liver disease is the twelfth leading cause of death in the United States. According to the European Association for the Study of the Liver, 29 million Europeans have chronic liver disease and liver disease represents approximately two percent of deaths annually. In the United States, more than 5,000 liver transplants are performed in adults and more than 500 in children annually, with approximately 17,000 subjects still awaiting transplant. We are planning to study the effectiveness of emricasan in defined subsets of patients with liver disease. ACLF, CLF and HCV-POLT are potential orphan indications in both the United States and European Union, or EU. We estimate that the target populations for emricasan in these indications in the United States and the EU are approximately 150,000 ACLF patients, 10,000 CLF patients and 50,000 HCV-POLT patients.

Conatus Pharmaceuticals 

Related - Jan 13 2104
Fatty Liver Disease W-Advanced Fibrosis: Galectins Completes Enrollment For First Cohort Phase 1 Trial of GR-MD-02 

December 2013
Liver transplant therapy given orphan drug status
The FDA has granted orphan drug status to Conatus Pharmaceuticals for emricasan, a potential treatment for patients with chronic liver disease and acute exacerbations of chronic liver disease, according to a company news release.

The orally active caspase protease inhibitor is intended for liver transplant recipients with re-established fibrosis to delay the progression to cirrhosis and end-stage liver disease, the release said. It is designed to reduce activity of enzymes that mediate inflammation and apoptosis.
“The FDA’s orphan drug designation of emricasan … reinforces the critical need for alternatives to the only currently available treatment, which is a second transplant,” Conatus Co-Founder, President and CEO Stephen J. Mento, PhD, said in the release. “This designation is a significant step forward for Conatus' clinical development program for emricasan.”

The treatment has been studied in 10 clinical trials involving more than 500 patients, the release said, including a randomized phase 2b clinical trial in which it resulted in statistically significant, consistent, rapid and sustained reductions in key biomarkers related to the progression and severity of liver disease.

Another phase 2b trial involving emricasan and patients with acute-on-chronic liver failure is under way, as is a phase 2 trial involving patients with severe alcoholic hepatitis, the release said.
The FDA’s orphan drug program offers incentives to drug makers working on therapies for conditions affecting fewer than 200,000 people in the United States and for those affecting more than 200,000 people but not expected to allow for recovery of the costs of developing and marketing the treatment.

Source Healio