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Tekmira Eyes mRNA Delivery as it Pushes Ahead with HBV, Other RNAi Candidates

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As it eyes new opportunities for its delivery technology, Tekmira Pharmaceuticals is exploring the potential of its lipid nanoparticles (LNPs) as carriers for messenger RNA therapeutics, the company's top official said last week.

Meanwhile, as it keeps it focus primarily on its core RNAi programs, Tekmira anticipates quickly moving a hepatitis B candidate into the clinic, with data available before the end of the year, President and CEO Mark Murray said during a conference call held last week to discuss Tekmira's financial results.

Interest in drugs based on mRNA, which are designed to trigger the production of a specific, therapeutic protein, has been increasing in recent years. One of the highest profile examples of this occurred in late 2013, when three-year-old mRNA drug firm Moderna Therapeutics closed a $110 million financing round just months after inking a partnership with AstraZeneca that included a $240 million upfront payment.

Yet challenges remain of this field, notably ones related to delivery given that "mRNA molecules are large, fragile, and easily degraded," Murray said during the call. "They do not readily cross membranes to enter target cells, so a delivery solution is required for many applications."

To that end, Tekmira has been adapting its LNPs, originally developed to carry siRNAs, for mRNA delivery, and last month presented details about this work, including data demonstrating the efficiency of its manufacturing process for mRNA encapsulation; delivery of mRNA in a range of tumor models including distal tumors and orthotopic liver tumors; and efficacy in mRNA delivery to the liver.

"By leveraging improvements in our LNP technology, we have made substantial improvements in mRNA delivery and performance, positioning us to enable the development of mRNA-based therapeutics," Murray said. "This clearly represents another business-development opportunity for Tekmira."

He added that Tekmira views its involvement in the mRNA drugs space as similar to its activity in RNAi. In its early days as Protiva Biotherapeutics, the company focused on optimizing its delivery technology for use by its partners, which handled actual drug development. It was only later on that Tekmira established its own drug pipeline.

"There are … companies out there that are quite interested in applying [our] delivery technology to mRNA right away," Murray noted during the call. But eventually "we … may be interested in developing products in this area ourselves."

Still, he cautioned that any internal mRNA drug work would likely occur "a little bit further in the distance."

Until then, Tekmira is pushing ahead with its stable of RNAi therapeutic candidates, including the cancer drug TKM-PLK1, which is currently in phase I/II testing with interim data expected midyear; TKM-Ebola, a phase I treatment for Ebola virus infection that is being developed under a US Department of Defense contract; and TKM-ALDH2, a preclinical agent for treating alcohol dependence expected to enter the clinic this year.

Late last year, Tekmira also unveiled a program in HBV, which aims to combine siRNAs against multiple targets on the virus's genome in order to suppress the surface antigen. Company officials said at the time that they expect the agent to allow HBV patients to seroconvert, developing antibodies against the virus and thereby resulting in a functional cure.

According to Murray, Tekmira is completing final screening of various HBV candidates in a "broad series of preclinical models" in order to select the appropriate combination of siRNAs, which will be based on the unlocked nucleobase analog technology licensed from Marina Biotech.

Tekmira expects to release preclinical data from the HBV program, as well as file an investigational new drug application for a final candidate, in the second half of 2014.

"We expect to have the most effective product in the field and to be in a position to report hepatitis B surface antigen suppression in chronically infected patients very early in development," Murray added.

Regardless of whatever success it has in HBV, however, Murray said that Tekmira does not anticipate entering the HCV market, which he called "currently well served by other drugs."

Indeed, recently approved oral drugs have proven highly effective in combating HCV — a development that many see as prompting GlaxoSmithKline as deciding not to pursue a microRNA-based HCV drug with Regulus Therapeutics and Santaris Pharma's failure to find a partner for its phase II miRNA-based HCV treatment miravirsen.

Before the end of the year, Tekmira is also planning on officially adding another program to its pipeline. Among the indications the company is evaluating are glycogen storage diseases and rare forms of hypertriglyceridemia.

Q4 financials

For the three-month period ended Dec. 31, 2013, Tekmira's revenues climbed to $7.6 million from $2.9 million the year before. Primarily driving up the revenues as a $5 million payment from Alnylam Pharmaceuticals tied to that company's initiation of a Phase III trial of patisiran, a transthyretin-mediated amyloidosis drug that uses Tekmira's LNPs.

Tekmira posted a net loss of $2.6 million, or $0.15 a share, in the fourth quarter, down from a loss of $5.9 million, or $0.41 a share, a year earlier.

R&D spending in the quarter dipped slightly, to $7 million from $7.2 million, despite an increase in clinical activities, reflecting non-recurring charges in the fourth quarter of 2012 linked to technology license deals.

At the end of 2013, Tekmira had cash and cash equivalents totaling $68.7 million — a figure that includes the roughly $32 million the company netted in a fourth-quarter public stock offering.

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