OnCore marks milestones in mission to cure hepatitis B

DOYLESTOWN, Pa.—OnCore Biopharma has made a series of important steps toward its goal of developing a cure for chronic hepatitis B. During the last couple months, the biopharma firm has gained an exclusive worldwide license to a series of second-generation cyclophilin inhibitors for the treatment of hepatitis B and acquired a pharmaceutical company with two novel drug discovery programs that could prove crucial in the development of a treatment for the disease.

OnCore was founded in 2012 by a team of former executives from Pharmasset (acquired by Gilead Sciences in 2011) who were involved in developing the drug Sovaldi, a hepatitis C therapy that was approved by the FDA last December. The new company’s mission is to discover and develop an all-oral cure for hepatitis B.

Hepatitis B is a serious infection of the liver that is transmitted by exposure to infectious body fluids. It can lead to chronic liver disease, which increases a patient’s risk of death from liver cirrhosis and liver cancer. The World Health Organization estimates that more than 780,000 people die every year due to infection. The therapies that are currently available to treat the disease work by suppressing the hepatitis B virus (HBV), but do not lead to a cure in the vast majority of patients. Identifying a functional or complete cure remains a significant area of unmet medical need.

OnCore’s strategy to develop a treatment for hepatitis B involves developing an all-oral treatment that targets covalently closed circular DNA (cccDNA) in HBV-infected hepatocytes. cccDNA is a unique DNA structure that develops in the cell nucleus of some viruses as they propagate. The company believes this strategy of targeting cccDNA has the potential to result in a functional cure that lowers the risk of death from liver disease to the same level experienced by a person with a naturally resolved infection.

The company is working to develop a treatment that combines agents against cccDNA with other novel direct-acting antiviral mechanisms that engage immune response. OnCore anticipates that combination therapy will be required to completely eradicate HBV from patients’ livers.

OnCore gained rights to cyclophilin inhibitors that are central to this strategy through a licensing agreement with NeuroVive Pharmaceutical AB, a Swedish mitochondrial medicine company. The license agreement has a total value of up to $150 million, excluding royalty payments. OnCore will pay NeuroVive an initial upfront payment, development and sales milestones and royalties based on future sales.

NeuroVive’s cyclophilin inhibitors, known as sangamides, are based on a new and unique polyketide chemistry platform. The lead drug candidate in the company’s cyclophilin program, NVP018, has undergone extensive preclinical development. OnCore anticipates that NVP018 will be evaluated in clinical trials in 2015.

“NVP018 is a promising antiviral drug candidate and has tremendous clinical potential for oral use as a novel treatment for patients with chronic hepatitis B infection,” said Michael Sofia, OnCore’s chief scientific officer. “We believe that a curative therapy for HBV will likely contain an immunomodulatory agent, such as NPV018, combined with multiple antiviral agents with differing mechanisms of action.”

Jan Nilsson, NeruoVive CEO, said the OnCore management team’s experience developing a treatment for hepatitis C made the company an appealing partner. “OnCore stood out in negotiations, which included several leading pharmaceutical companies, because of its exclusive focus on hepatitis B and its plan to bring the drug candidate to market as quickly and efficiently as possible,” he said.

OnCore’s acquisition of Enantigen Therapeutics, a privately held pharmaceutical company, is also intended to support its goal of developing a hepatitis B cure. The acquisition will allow OnCore to assume development of Enantigen’s two novel discovery programs, one targeting inhibition of surface antigen secretion and one targeting capsid assembly inhibition.

“We are very proud of the discovery work that we have done in hepatitis B,” said Entanigen President and CEO Xiaodong Xu. “We believe that OnCore is in the best position to rapidly advance our programs into human clinical trials, and we look forward to joining the OnCore research team to help realize their vision.”

“Our plan is to combine Enantigen’s drug candidates with our existing all-oral portfolio of HBV compounds and advance multiple combination regimens into human clinical trials,” said OnCore CEO Patrick Higgins. “Enantigen programs, together with our lead cyclophilin inhibitor, NPV018, and our cccDNA formation and capsid assembly inhibition programs, give OnCore the most comprehensive platform of assets consolidated to target a cure for hepatitis B.”