By Doug Macron
Tekmira Pharmaceuticals' top official last week said that the company's research and development activities are on track, and that the firm expects by the end of the year to have an investigational new drug application for an Ebola infection treatment along with interim phase I data on its cancer therapy.
Speaking during Tekmira's second-quarter conference call, President and CEO Mark Murray also indicated that the firm is stiill developing its stalled hypercholesterolemia drug, and touched on efforts on the design of new lipid nanoparticle-delivery vehicles and their siRNA payloads.
Tekmira's most-developed pipeline candidate, the phase I oncology agent TKM-PLK1, targets polo-like kinase 1 and is delivered intravenously using the company's proprietary lipid nanoparticles. Earlier this month, the firm announced that it was cleared to begin a separate phase I study of the drug in collaboration with the National Cancer Institute, which will test its safety and tolerability when administered directly to liver tumors via hepatic-artery infusion (GSN 8/11/2011).
Tekmira has also used this collaboration to generate “promising preclinical data” related to the cancer targets WEE1 and CSN5, and is now “expanding” its preclinical work to evaluate an siRNA drug that can inhibit both targets, Murray said.
WEE1 is a tyrosine kinase involved in regulating cell-cycle progression and DNA-damage response, according to the company. CSN5 regulates protein turnover and other protein interactions that play a role in tumorigenesis.
“We are interested in WEE1 and CSN5 because both are key regulators in different cellular pathways controlling cancer cell division and death,” Murray said.
Tekmira holds a license to use technology developed by partner Alnylam Pharmaceuticals to design siRNAs against both targets, and said it is currently evaluating “a number of tumor-specific LNP formulations” before beginning the toxicology studies required for an IND filing.
Also moving through preclinical development is TKM-Ebola, which Tekmira is developing with funding from the US Department of Defense Chemical and Biological Defense Program. Preparing to file an IND for the drug before the end of 2011, the company has been enhancing its manufacturing capabilities and, as previously reported, has scaled up the manufacturing process from 10-gram batches to 1-kilogram batches of siRNA payload, Murray said.
“Importantly, the key LNP product specifications and characteristics are preserved and reproduced with this 100-fold increase in batch scale,” Murray said, adding that the company is working on “going to a higher scale.
“The next target would be to go to 5 kilograms,” he said.
Murray also noted that while the process of advancing TKM-Ebola to an IND filing and conducting an initial human-safety study is fairly straightforward, the development path that follows is “a bit different” than with drugs for other indications.
After phase I, “you follow what's called the animal rule,” he said, referring to US Food and Drug Administration regulations that can approve a drug based solely on animal data when human studies are not ethical or feasible.
Tekmira also continues to work on TKM-ApoB, an siRNA-based treatment for hypercholesterolemia and its first clinical candidate.
In early 2010, the company put a phase I study on hold after a patient experienced side effects consistent with immune stimulation triggered by the siRNA component (GSN 1/14/2010). Although the trial was expected to restart later that year, disappointing preclinical testing with different siRNAs led Tekmira to keep the program shelved indefinitely.
Murray said last week that TKM-ApoB remains in Tekmira's pipeline, but did not provide details on its status beyond stating that the company is “evaluating some primate work [that] has been done with some new formulations.
“We will be reporting on that when that data is completed and we've been able to digest it,” he said.
In addition to its product candidates, Tekmira has been advancing new LNP technologies, including nanoparticles that can be targeted to particular tissues with antibodies, and the development of nebulized LNPs through a collaboration focused on respiratory delivery of siRNAs with an undisclosed pharmaceutical company, Murray noted.
The company has also been exploring the design of novel RNAi molecules, he added, a notable effort given Tekmira's ongoing legal dispute with Alnylam, which has provided Tekmira with certain access to its siRNA technologies and know-how under their longstanding partnership.
As previously reported, Tekmira recently sued Alnylam for allegedly misusing its trade secrets to develop LNP technologies (GSN 8/18/2011).
Murray declined to comment on the litigation while on the conference call but said it is “progressing on the timeline we expected."
"We remain firm in our belief that this lawsuit was necessary in order for us to regain control of our technology and we are confident we are taking the appropriate steps to ensure that we can pursue this lawsuit without interruption to our core business activities,” he added.
The Second Quarter
For the three-month period ended June 30, Tekmira's net loss dropped to $6.6 million, or $0.63 per share, from a year-ago loss of $8.1 million, or $0.79 per share.
Contributing to the lower losses was a rise in revenue to $4.4 million in the quarter from $2.3 million a year earlier, in part reflecting $3.3 million received in the period from the US government related to the TKM-Ebola contract.
Research, development, collaboration, and contract expenses climbed to $6.2 million from $4.8 million, while general and administrative costs rose to $1.6 million from $1.1 million.
Tekmira had $9.7 million in cash and cash equivalents as of June 30.
At that date, "we had an unusually high level of cash in accounts receivable,” Tekmira CFO Ian Mortimer said during the conference call. “We also expect certain expenses to decrease in future periods. Therefore … we now expect that our cash and expected revenue will be sufficient to continue our product development into the second half of 2012.
He added that this is a revision from the company's 2010 annual report, when it forecast that it had sufficient cash and expected income to continue product development into the first quarter of 2012.
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