Tobira Therapeutics Announces Publication of CENTAUR Phase 2b Study Design and Rationale in Contemporary Clinical Trials

Print 09 March 2016

OUTH SAN FRANCISCO, Calif., March 9, 2016 /PRNewswire/ -- Tobira Therapeutics, Inc. (NASDAQ: TBRA), a biopharmaceutical company developing novel treatments for non-alcoholic steatohepatitis (NASH) and other serious immuno-inflammatory and fibrotic diseases, today announced that the description of the fully-enrolled CENTAUR Phase 2b clinical trial design has been accepted as a manuscript and published online in the journal Contemporary Clinical Trials. Available at:http://www.sciencedirect.com/science/article/pii/S155171441630026X.

"The treatment of NASH is a high unmet medical need as NASH is currently the second leading cause of liver transplant in the U.S. and is predicted to become the leading cause by 2020," said Scott Friedman, M.D., Chief, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai. "CENTAUR is the first large, well-controlled Phase 2b study in NASH that exclusively enrolled patients considered at higher risk of progression to liver cirrhosis and we are proud that CENTAUR's state-of-the-art study design was accepted for publication in the journal of Contemporary Clinical Trials."

Study Design
CENTAUR is a Phase 2b, randomized, double-blind, placebo-controlled, multinational study (NCT02217475). The study was planned to recruit 252 adults; due to high unmet need and investigator interest, a total of 289 adults were enrolled with:

• Histological evidence of NASH, as defined by a non-alcoholic fatty liver disease activity score (NAS) greater than or equal to 4, and
• Liver fibrosis (Stages 1–3 NASH Clinical Research Network scoring system [CRN]).

Subjects are also at an increased risk of progression to cirrhosis due to one or more of the following:

• Documented evidence of type 2 diabetes;
• High body mass index (BMI greater than 25 kg/m2) with at least one of the criterion of metabolic syndrome;
• Bridging fibrosis (NASH CRN stage 3) and/or NAS greater than or equal to 5.

Liver biopsy evaluation is performed at screening, Year 1 and Year 2 by a central pathologist.

The primary objective of CENTAUR is to assess hepatic histologic improvement in NAS after one year of cenicriviroc (CVC) treatment versus placebo relative to screening biopsy. This improvement is defined by a minimum 2-point improvement in NAS, with at least a 1-point improvement in more than one category, and no worsening of NASH CRN fibrosis stage. The key secondary objective of this study is to evaluate the complete resolution of NASH with no concurrent worsening of NASH CRN fibrosis stage. Other secondary objectives include evaluation of the proportion of subjects with improvement in fibrosis stage (NASH CRN and Ishak systems).

"The CENTAUR study was designed with guidance from pioneers in the field of fatty liver disease," said Eric Lefebvre, M.D., chief medical officer at Tobira. "We are in the midst of performing Year 1 liver biopsies, and we remain on track to report top-line Year 1 primary endpoint data in the third quarter of 2016. Our study includes two surrogate endpoints that have been identified as potentially approvable under accelerated approval, namely the complete resolution of NASH and improvement in fibrosis stage, which will inform Phase 3 development on the heels of the Year 1 primary analysis."

About Cenicriviroc (CVC) and Non-alcoholic Steatohepatitis (NASH)
CVC is an oral, once-daily, potent immunomodulator that blocks two chemokine receptors, CCR2 and CCR5, which are intricately involved in the inflammatory and fibrogenic pathways in NASH that cause liver damage and often lead to cirrhosis, liver cancer or liver failure. Tobira believes this novel approach will establish CVC as both a single-agent and as a cornerstone treatment in multi-therapy regimens for NASH, for which there is currently no approved drug.

CVC is currently being evaluated in Tobira's fully-enrolled global Phase 2b CENTAUR study (identifier NCT02217475) and the company expects to announce the study's primary endpoint in the third quarter of 2016. CENTAUR is comparing CVC to placebo in 289 patients with NASH and liver fibrosis. CVC has been granted Fast Track status in patients with NASH and liver fibrosis, the patient population at highest risk of progression to cirrhosis. The CENTAUR study includes surrogate endpoints identified as suitable for registrational studies in findings of an FDA-AASLD workshop reported in Hepatology and in use in current phase 3 studies. To date, approximately 600 subjects have been dosed in completed studies with CVC, including 115 HIV infected subjects on treatment for up to 48 weeks.

NASH is an emerging health crisis impacting 3% to 5% of the U.S. population and 2% to 4% globally. It is the fastest growing cause of liver cancer and liver transplant in the U.S. due to the rise in obesity. Additionally, this population is estimated to be three to five times larger than the size of the population with hepatitis C in the U.S.

About Tobira Therapeutics
Tobira is a clinical-stage biopharmaceutical company focused on the development and commercialization of therapies to treat liver disease, inflammation, fibrosis and HIV. The company's lead product candidate, cenicriviroc (CVC), is a first-in-class immunomodulator and dual inhibitor of CCR2 and CCR5 being evaluated for the treatment of non-alcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC). Learn more about Tobira at www.tobiratherapeutics.com.

Tobira® is a registered trademark owned by Tobira Therapeutics, Inc.

©2016 Tobira Therapeutics, Inc. All Rights Reserved.

Forward Looking Statements
This release contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the company's clinical development of cenicriviroc (CVC), the potential timing and outcomes of clinical studies of CVC undertaken now or in the future; the ability of the company to timely source adequate supply of its development products from third party manufacturers on whom the company depends; the company's limited cash reserves and its ability to obtain additional capital on acceptable terms, or at all; the company's ability to successfully progress, partner or complete further development of its programs; the uncertainties inherent in clinical testing; the timing, cost and uncertainty of obtaining regulatory approvals; the company's ability to protect its intellectual property; competition; changes in the regulatory landscape or the imposition of regulations that affect the company's products; and other factors listed under "Risk Factors" in the company's filings with the Securities and Exchange Commission.

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