NEW YORK (GenomeWeb) – Having earlier this month unveiled its plan to merge with hepatitis B therapeutics firm OnCore Biopharma, Tekmira Pharmaceuticals has provided a few details about its drug-development plans going forward in a recent filing with the US Securities and Exchange Commission.
Going forward, Tekmira aims to make its siRNA-based HBV therapy TKM-HBV the foundation of a treatment regimen that will also include one or two other drugs from OnCore's pipeline of preclinical candidates, it said in the SEC filing.
This combination strategy, Tekmira noted, is the same one behind the development of the highly effective hepatitis C therapy Harvoni, which combines the HCV drug sofosbuvir that was developed by OnCore founders while at Pharmasset and Gilead Sciences' ledipasvir. Gilead acquired Pharmasset for $11 billion in 2011.
As for Tekmira's other non-HBV RNAi programs, the company said it will continue clinical testing of TKM-Ebola and the cancer drug TKM-PLK1. The future for its other RNAi assets, however, is less clear, with Tekmira only stating in the filing that they will be advanced "in an appropriate way."
While its sole focus has long been the development of RNAi therapeutics based on its proprietary lipid nanoparticles (LNPs), Tekmira announced a few weeks ago that it had agreed to merge with pure-play HBV firm OnCore — a move that, while unexpected, was well-received. Indeed, Tekmira's stock has held onto the roughly 60 percent gain it saw at the time the deal was announced. In Monday afternoon trading, shares of Tekmira were trading at $25.50.
At the time, the companies' management highlighted the combination of TKM-HBV, which has been shown in preclinical studies to cut expression of both HBV surface antigen (s-antigen), a key indicator of active infection, and covalently closed circular DNA (cccDNA), which gives rise to immunosuppressive viral proteins and viral genomic materials; and OnCore's stable of preclinical agents including OCB-030, a second-generation cyclophilin inhibitor designed to suppress viral replication, as well as stimulate and reactive the body's immune response.
"Our goal is to deliver a cure for HBV," Tekmira said in its SEC filing last week. "We believe we can leverage the insights gained from our management’s successful HCV development track record combined with the aggregation of multiple relevant technologies within one company to more rapidly deliver an HBV cure, with potentially fewer intermediate steps in the process."
Specifically, the company aims to tackle uncontrolled HBV replication, the suppression of the host immune response by s-antigen and other antigens, and eliminate the cccDNA reservoir in infected liver cells.
To do so, Tekmira said it will test each of its drug candidates alone in Phase I studies to establish safety and initial proof of concept. As reported by GenomeWeb, TKM-HBV has just advanced into a Phase I trial where two formulations of the drug, one using a third-generation LNP technology and one using a fourth-generation version, will be examined in healthy adults.
"Assuming favorable outcomes, we intend to pursue an iterative testing process by progressing combinations into a rolling Phase II program similar to what was done … with sofosbuvir," Tekmira said. "Our plan is to advance the most promising regimens from these studies toward Phase III registration studies with the goal of confirming their effectiveness in the broader population, potentially gaining regulatory approval and introducing them to the market."
While TKM-HBV may not necessarily be part of any future approved HBV therapy, it will be post-merger Tekmira's most advanced HBV candidate, and the company said that it remains on track to move into a multi-dose trial in chronically infected HBV patients later this year.
Despite its transformation into an HBV company, Tekmira has not abandoned its efforts outside of the indication.
According to Tekmira, it intends to "continue to support the clinical development of TKM-PLK1 and TKM-Ebola," including a version of the Ebola drug, called TKM-Ebola-Guinea, that has been optimized for the strain of the disease behind the current outbreak in West Africa.
Notably, the Ebola program is being supported by a US Department of Defense (DoD) contract worth up to $140 million. Additionally, the DoD has recently asked Tekmira to manufacture 500 treatment courses of TKM-Ebola-Guinea, while the University of Oxford's International Severe Acute Respiratory and Emerging Infection Consortium is planning to test the drug in humans in West Africa later this year.
Questions remain, however, for Tekmira's other RNAi programs, which include ones in hypertriglyceridemia, glycogen storage disorder type IV, and alcohol use disorder. The company said in the SEC filing that it believes that "value resides" in these efforts, but did not explicitly state that it will push them forward as it did for its cancer and Ebola programs.
"We … plan to determine what we believe can be the best strategies for optimizing the value of the remaining assets," the company said, adding that it will continue to support those companies with which it has partnered, such as ag-bio firm Monsanto and RNAi drug developer Dicerna Pharmaceuticals.