NEW YORK (GenomeWeb) – Amid increasing competition in the hepatitis B field among RNAi drug developers, Tekmira Pharmaceuticals remains on track to begin clinical testing of its HBV therapy early next year, the company's top official said last week.
Speaking during a conference call held to discuss Tekmira's first quarter financial results, President and CEO Mark Murray referred to the firm's HBV effort — unveiled only seven months ago — as its "most compelling program." He also indicated that Tekmira is setting the bar especially high for itself as rivals Arrowhead Research and Alnylam Pharmaceuticals make strides in the space.
Tekmira also last week provided some new clinical data on its cancer drug TKM-PLK, which offered hints of efficacy that could help the company pursue accelerated regulatory approval.
Tekmira's HBV drug, dubbed TKM-HBV, is designed to target several sites on the virus' genome and is delivered using a third-generation version of the company's lipid nanoparticles. Like Arrowhead, which has an HBV treatment in Phase II testing, Tekmira hopes it can cut levels of surface antigen (s-antigen) — a key indicator of active infection believed to be responsible for the immunosuppression that allows the virus to persist even when its replication has been halted.
Recently, Arrowhead officials said that they hope their company's drug, ARC-520, can achieve at least a one-log knockdown of s-antigen, which should be sufficient to effect a functional cure. But Murray hinted this week that Tekmira is aiming higher.
Although "we'd be happy" with a one-log s-antigen reduction, "I'm not sure that's where we want to be," he said during this week's call, highlighting the potency of Tekmira's latest LNP formulations.
Murray also pointed to non-human primate data generated by Merck with its HBV program, which showed that a single dose of siRNAs targeting one region of the HBV genome could produce an over 4 log10 reduction of circulating viral DNA and a 2.3 log10 reduction in s-antigen levels.
Having acquired Merck's HBV program as part of its deal for all of the big pharma's RNAi assets in January, Alnylam has officially added the HBV drug to its pipeline. It anticipates filing an investigational new drug application for the candidate in late 2015.
While Merck's data reinforce the overall potential for RNAi in HBV, Murray said, "we anticipate our HBV program, which will use newer generations of LNPs and a newly designed RNAi trigger cocktail, will exceed these results."
Murray did not provide further details about Tekmira's clinical goals for TKM-HBV, stating that the drug is currently "undergoing a comprehensive preclinical evaluation." It remains on schedule to enter clinical testing in early 2015.
Meanwhile, Tekmira continues to push ahead with a Phase I/II trial of TKM-PLK, which is testing the drug in patients with either metastatic adrenocortical carcinoma (ACC) or advanced gastrointestinal neuroendocrine tumors, also known as GI-NETs.
Although data from that study is slated for formal release mid-year, last week Murray disclosed promising results from the ACC arm.
Of the four ACC patients who have been evaluated, three have demonstrated a clinical benefit, he said, including one who has shown a partial response as measured by widely accepted criteria known as RECIST, or response evaluation criteria in solid tumors.
"This patient with a partial response has been on TKM-PLK for 12 months and has experienced a 42 percent reduction in their target tumor mass, which is located outside of the liver," Murray said. "Furthermore, this lesion is showing evidence of necrosis indicative of anti-tumor activity."
He said that Tekmira expects to kick off another Phase I/II trial of TKM-PLK, which will test the drug in ACC patients at multiple international sites, by the middle of this year. Should the company see strong patient responses, he added, there might be opportunities to take "accelerated approval paths" for the drug in both the ACC and GI-NET indications.
Q1 financials
For the three-month period ended March 31, 2014, Tekmira's net loss rose to $18 million, or $.91 a share, from a year-ago loss of $2.5 million, or $.18 per share. Contributing to the loss increase was a $13.6 million non-cash charge related to the revaluation of warrants. Exclusive of this charge, Tekmira's first quarter 2014 net loss was $6 million.
Research and development spending surged in the quarter, climbing to $8.2 million from $4 million, mostly due to work on newer product candidates including TKM-HBV, as well as the company's ongoing collaboration with Monsanto.
General and administrative costs in the quarter rose to $2.1 million from $900,000. Revenues, meantime, nearly doubled to $4.4 million as Tekmira realized $800,000 from Monsanto and $3.2 million from the US Department of Defense under a contract to develop an Ebola treatment.
At the end of the first quarter, Tekmira had cash and cash equivalents totaling $134.4 million.