In December 2016, Conatus announced an exclusive option, collaboration and license agreement with Novartis for the global development and commercialization of emricasan. In May 2017, Conatus announced that Novartis had exercised its license option following initiation of the Phase 2b ENCORE-LF clinical trial.
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. To date, emricasan has been administered to over 650 subjects in eight Phase 1 and eight Phase 2 clinical trials, and has been generally well-tolerated in both healthy volunteers and patients with liver disease. Emricasan has also been extensively profiled in in vitro tests and studied in many preclinical models of human disease.
We met with the FDA in May 2015 to discuss potential registration pathways for emricasan, including pathways based on validated surrogate endpoints published by the FDA in conjunction with AASLD that may be suitable for approval in cirrhosis, and received feedback on the proposed patient populations and methods of measuring and analyzing these endpoints. Based on communications with the FDA recommending single-etiology clinical trials, we plan to focus on advancing toward initial registration of emricasan for patients with cirrhosis due to NASH, with parallel development toward registration of emricasan for patients with NASH fibrosis.
In February 2016, we announced that the FDA granted Fast Track designation to the emricasan development program for the treatment of liver cirrhosis caused by NASH. The Fast Track program provides greater access to the FDA in order to expedite review of drugs that have demonstrated the potential to treat serious or life-threatening conditions.
We are pursuing a registration strategy with an initial focus in cirrhosis, with additional supportive long term safety data in patients with NASH fibrosis. Multiple parallel clinical trials, the EmricasaN, a Caspase inhibitOR, for Evaluation, or ENCORE trials, will evaluate a range of emricasan doses over various treatment durations in patients of different etiologies. We expect top-line results from these trials to be available periodically beginning in the first half of 2018:
We are conducting a comprehensive clinical program to demonstrate the therapeutic benefit of emricasan across the spectrum of liver disease. We currently have three active Phase 2b clinical trials:
- POLT-HCV-SVR: in post-orthotopic liver transplant (POLT) recipients with liver fibrosis or cirrhosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy;
- ENCORE-NF: in patients with non-alcoholic steatohepatitis (NASH) and liver fibrosis; and
- ENCORE-PH: in patients with compensated or early decompensated NASH cirrhosis and severe portal hypertension (baseline HVPG ≥12 mmHg);
and expect to initiate a fourth Phase 2b clinical trial in the second quarter of 2017:
- ENCORE-LF: in patients with decompensated NASH cirrhosis and baseline Model for End-stage Liver Disease (MELD) scores of ≥15.
We expect the next milestones from our clinical development programs to be as follows: