Tobira Announces Interim 12-week Results from the ORION Study

"ORION was designed to evaluate whether CVC's anti-inflammatory mechanism may indirectly, by blocking CCR2/5, have a favorable effect on insulin sensitivity. Preliminary findings from the pre-planned 12-week interim analysis show that CVC treatment was associated with improvements in multiple glucose parameters. In addition to the previously known anti-inflammatory and anti-fibrotic effects, these preliminary data on improved insulin sensitivity are encouraging and further support the therapeutic potential for CVC in NASH," said Eric Lefebvre, M.D., chief medical officer of Tobira. "Additionally, CVC was observed to be safe and well tolerated in obese patients with fatty liver disease.  Drug related adverse events were infrequent and comparable to placebo."

ORION is a randomized, double-blind, placebo-controlled study exploring the metabolic effects of CVC in obese adults (BMI ≥ 30 kg/m2) with prediabetes or type 2 diabetes and suspected non-alcoholic fatty liver disease (NAFLD). The pre-planned week-12 analysis was designed to evaluate the safety and the 'time-to-effect' of CVC in advance of the full week-24 analysis. The study was not powered for statistical significance.

The interim data analysis of this mechanistic study was based on 35 subjects, with a mean baseline fasting plasma glucose level of 122.31 mg/dL (SD; 33.73) and HbA1c of 6.25 (SD; 0.80). Over 50% of subjects were diagnosed with NASH. Over the 12-week treatment period, pre-defined as the interim analysis period, effects in exploratory efficacy endpoints were observed in multiple insulin resistance-related parameters compared to placebo (change at week 12 compared to baseline; placebo-subtracted difference [95% CI]), including a reduction in fasting plasma glucose of -11.52 mg/dL (CI; -28.35, 5.31) and HbA1c of -0.36 (CI; -0.74, 0.01).  CVC treatment was also associated with a reduction of serum free fatty acid levels (AUC-2h) following a 75 gram oral glucose tolerance test of -4.9 mmol/L (CI; -11.4, 1.6) compared to placebo. CVC treatment was observed to be safe and well-tolerated with adverse events being comparable to placebo.

The study will continue as planned and the primary analysis will be based on 24-week data from all 45 subjects enrolled and will include, in addition to insulin sensitivity parameters: inflammation biomarkers, effects on adipose tissue, changes in liver histology in the subset of subjects with NASH, and changes in liver magnetic resonance based imaging by LiverMultiScan at selected sites.

"Being able to better regulate the metabolic drivers that promote fat storage in the liver is a significant development in liver disease research," said Stephen A. Harrison, M.D., chief of hepatology, division of gastroenterology, Brooke Army Medical Center. "A large amount of data has been generated demonstrating CVC is a potent anti-inflammatory and anti-fibrotic agent. These new data in obese patients with NAFLD or NASH suggest that CVC can address metabolic abnormalities as well. This is important, as this early population is reflective of patients who are at risk of progression, and these interim results suggest that CVC has the potential to impact NASH."

The company plans to submit the full comprehensive data set from the ORION study, including insulin sensitivity parameters and inflammation biomarkers for presentation at a future medical meeting. The company also anticipates announcing topline data from CENTAUR, a phase 2b study in patients with NASH and fibrosis in the third quarter of 2016.

Details about ORION can be found at www.clinicaltrials.gov using identifier NCT02330549. 

About Cenicriviroc (CVC) 

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). 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. To date, approximately 600 subjects have been dosed with CVC in Phase 1 and Phase 2b clinical studies, including 115 HIV infected subjects on treatment for up to 48 weeks.  CVC is also being evaluated in the PERSEUS study (identifier NCT02653625), a Phase 2 proof-of-concept study of CVC in patients with primary sclerosing cholangitis, a rare inflammatory liver disease.

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), primary sclerosing cholangitis (PSC) and as an adjunctive therapy to standard of care in HIV.  Tobira's pipeline also includes evogliptin, a selective DPP-4 inhibitor, which it plans to develop for NASH in combination with CVC. Learn more about Tobira at www.tobiratx.com.

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) and evogliptin (EVO); the potential benefits of CVC; any predictions of future clinical trial success, the potential timing and outcomes of clinical studies of Tobira's product candidates 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 the company's 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 other filings with the Securities and Exchange Commission.