Ocera Therapeutics Announces Publication of Promising Preclinical Data in Support of Its Ammonia Scavenger OCR-002 in the Journal of Hepatology

PALO ALTO, Calif. and RESEARCH TRIANGLE PARK, N.C., April 11, 2016 -- Ocera Therapeutics, Inc. (NASDAQ:OCRX), a clinical stage biopharmaceutical company focused on acute and chronic orphan liver diseases, today announced the publication of promising preclinical data related to the Company’s investigational drug candidate ornithine phenylacetate, OCR-002. The paper, entitled “Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension” is published in the April 2016 issue of the Journal of Hepatology (http://www.journal-of-hepatology.eu/article/S0168-8278(15)00777-1/abstract).

In this investigator-sponsored preclinical study, the authors investigated the role of ammonia in modulating human hepatic stellate cell (hHSC) activation in vitro and in vivo, and the ability of OCR-002 to lower ammonia and thus reduce resultant portal hypertension in bile duct ligated (BDL) rats, a model of cirrhosis. Portal hypertension, a complication of cirrhosis, is an increase in the blood pressure within a system of veins called the portal venous system.

Researchers subjected hHSCs to an ammonia challenge and results showed that pathophysiologic ammonia concentrations in vitro induced significant alterations in cellular morphology and caused significant and reversible changes in cell proliferation, metabolic activity, pro-inflammatory gene expression and activation markers. During the in vivo phase of the study, ammonia levels and portal pressure were compared in BDL rats vs. sham-operated controls prior to and after 5 days of treatment with OCR-002. Ammonia concentrations were significantly elevated in plasma in BDL rats compared to sham-operated rats (182 vs. 62.5μM, P < .0001), which decreased significantly following treatment with OCR-002 (83.8μM, P < .0001). These significant changes in plasma ammonia were correlated with alterations in portal pressure, which were significantly higher in BDL rats compared to sham (14 vs. 5.5mmHg, P < .0001). Ammonia lowering following administration of OCR-002 resulted in a significant reduction in portal pressure compared to BDL saline-treated rats (11mmHg, P < .01).

“The data clearly showed that increasing concentrations of ammonia were associated with marked structural and functional changes of hHSCs and that these effects were reversible when ammonia was removed from the medium and cells were allowed to recover,” said lead author Professor Rajiv Jalan, M.B.B.S, M.D. Ph.D., from the University College London. “Further, the reduction in ammonia concentration using OCR-002 resulted in a downregulation of HSCs activation markers that coincided with a significant reduction in portal pressure, providing a potential novel strategy to treat portal hypertension.”

“We are very encouraged by the study’s further findings supporting the ammonia-lowering properties of OCR-002 and its potential as a new therapy for hyperammonemic-implicated indications where current treatments are limited and or lack efficacy,” said Stan Bukofzer, M.D., Ocera’s Chief Medical Officer. “While Ocera remains focused on developing OCR-002 to potentially treat hepatic encephalopathy in patients with liver cirrhosis and acute liver failure, we believe that portal hypertension may, in the future, provide an additional clinical development opportunity for OCR-002 based on these early results.”

About Portal Hypertension

Portal hypertension, a complication of liver cirrhosis, is an increase in the blood pressure within a system of veins called the portal venous system. Veins coming from the stomach, intestine, spleen, and pancreas merge into the portal vein, which then branches into smaller vessels and travels through the liver. If the vessels in the liver are blocked due to liver damage, blood cannot flow properly through the liver. As a result, high pressure in the portal system develops. This increased pressure in the portal vein may lead to the development of large, swollen veins (varices) within the esophagus, stomach, rectum, or umbilical area (belly button). Varices can rupture and bleed, resulting in potentially life-threatening complications.

About Hepatic Encephalopathy

Hepatic encephalopathy is a debilitating and progressive complication of liver cirrhosis or liver failure, marked by mental changes including confusion, impaired motor skills, disorientation, and in its more severe form, stupor, coma and even death.

About Ocera

Ocera Therapeutics, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of OCR-002 (ornithine phenylacetate) in both intravenous and oral formulations. OCR-002 is an ammonia scavenger and has been granted orphan drug designation and Fast Track status by the U.S. Food and Drug Administration (FDA) for the treatment of hyperammonemia and resultant hepatic encephalopathy (HE) in patients with acute liver failure and acute-on-chronic liver disease.

Ocera's HE clinical development efforts include an ongoing Phase 2b clinical trial, STOP-HE, which is evaluating the safety and efficacy of intravenously-administered OCR-002 in resolving neurocognitive symptoms of acute HE in hospitalized patients with elevated ammonia, and a Phase 1 program evaluating the safety, tolerability and pharmacokinetics of orally-available OCR-002 for the prevention of HE. The Company expects to complete enrollment in the STOP-HE trial in the fourth quarter of 2016 with top-line data to be published soon thereafter. An additional Phase 1 study of oral OCR-002 will commence later this year after further formulation optimization. For additional information, please see www.ocerainc.com.

Forward-Looking Statements

This press release contains "forward-looking" statements, including, without limitation, all statements related to the OCR-002 clinical development program, including but not limited to the potential benefits of OCR-002 to help patients with hepatic encephalopathy, the potential benefits of OCR-002 to help patients with portal hypertension, the timing of clinical and enrollment milestones, and the timing of study data. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believe," "expected," "hope," "plan," "potential," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Ocera's current expectations. Forward-looking statements involve risks and uncertainties and Ocera's actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, including those risks and uncertainties discussed under the heading "Risk Factors" in Ocera's Annual Report on Form 10-K for the year ended December 31, 2015 and subsequent filings with the SEC. All information in this press release is as of the date of the release, and Ocera undertakes no duty to update this information unless required by law.

OCRX-G

Susan Sharpe
Ocera Therapeutics, Inc.
[email protected]
919-328-1109