Tekmira Pharmaceuticals this week announced that it has pushed back the expected start date for a phase I study of its siRNA-based cancer therapy PLK1 SNALP to some time in 2010 as it works to incorporate improvements in its drug-delivery technology into the program.
Meanwhile, the company continues to find success on the partnering front, announcing today that Bristol-Myers Squibb has exercised an option to extend its research collaboration with Tekmira through 2009.
Additionally, Tekmira President and CEO Mark Murray said during a conference call held this week to discuss the company's fourth-quarter financial results that he expects Roche to expand its ongoing arrangement with the RNAi shop before the end of the year.
Last July, Tekmira said that it would launch human trials of its two drug candidates this year (see RNAi News, 7/24/2008). And while the company's most advanced agent, the hypercholesterolemia treatment ApoB SNALP, remains on track to enter the clinic during the first half of this year, PLK1 SNALP has taken a slight detour.
According to Tekmira President and CEO Mark Murray, the delay will give the firm "the opportunity to incorporate formulation improvements … into PLK1 SNALP, but will push out the start of our [investigational new drug application]-enabling studies to the second half of 2009."
As a result, Tekmira expects to file an IND for the cancer drug next year, most likely in the first or second quarter.
"Although we would prefer not to delay our filing, we believe in advancing product candidates based on rigorous scientific evaluation and developing the strongest product candidates possible," he said during the call. "The improvements in PLK1 SNALP are significant [enough] to warrant the delay."
In addition to improving PLK1 SNALP's therapeutic index, the formulation improvements are expected to improve siRNA delivery in a variety of organs and "provide greater opportunity to go after oncology indications outside the liver," Murray said.
As such, the additional formulation work will also likely play a role in Tekmira's selection of a third drug candidate later this year, he added.
"We continue to evaluate potential new targets we believe are well-suited for our technology … and for which there is a strong commercial rationale," Murray said, noting that although Tekmira's lead drug candidate focuses on a liver-based target, apolipoprotein B, the company is "certainly not going to limit [itself] to the liver."
Tekmira has long been a key collaborator for companies developing RNAi-based therapeutics, largely because of its core SNALP, or stable nucleic acid-lipid particle, delivery technology.
The company's list of disclosed partners include Johnson & Johnson Pharmaceutical Research & Development, which has been using SNALPs to deliver siRNAs against targets in the liver; and Alnylam Pharmaceuticals, which recently confirmed that it would use SNALPs in its liver cancer program (see RNAi News, 11/13/2008).
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The company had also been working with Sirna Therapeutics prior to its acquisition by Merck, although that relationship mostly soured as a result of a legal dispute between the big pharma and Tekmira predecessor Protiva Biotherapeutics (see RNAi News, 10/18/2007).
Last August, Tekmira added Bristol-Myers Squibb to its list of collaborators, inking a deal to research the delivery of siRNAs to specific organs and tissues outside the liver (see RNAi News, 8/4/2008). Now that arrangement has been extended for about nine more months, according to Tekmira.
Tekmira has also been working with Roche, which has become one of the most prominent big pharma players in RNAi through a sweeping alliance with Alnylam (see RNAi News, 7/12/2007) and the $125 million acquisition of Mirus Bio about a year later (see RNAi News, 7/24/2008). About a year ago, Roche paid $5 million for access to the SNALP technology, as well as a roughly 4 percent stake in Tekmira (see RNAi News, 4/3/2008).
In conjunction with its investment in Tekmira, Roche also began a six-month evaluation of the SNALP technology, which expired late last year (see RNAi News, 11/20/2008). At the time, Murray said that the future of that relationship was unclear.
During this week's conference call, however, Murray was more optimistic, indicating that the two companies have continued to collaborate. He added that Tekmira anticipates that the arrangement with Roche is probably going to be "converted this year to something more significant … focused around product development and manufacturing relationships."
Plans for the Clinic
During the conference call, Murray and Tekmira Vice President and CFO Ian Mortimer also provided a few details on the planned design of the ApoB SNALP phase I study.
The drug is an siRNA targeting apolipoprotein B, a protein involved in cholesterol metabolism. According to Murray, the dose-escalating trial is expected to enroll around 30 patients with elevated low-density lipoprotein, and will examine the effects of a single administration of the drug on levels of the cholesterol. Mortimer added that patients in the study will be divided into four cohorts, three of which will receive treatment.
Murray cautioned that "the trial is not designed and not powered to give us statistical proof of efficacy," but noted that the data may give some indication of the drug's activity.
The Fourth Quarter
For the three months ended Dec. 31, Tekmira reported a drop in revenues to C$11.7 million ($9.5 million) from C$15.8 million in the same period a year earlier. The Vancouver-based company noted that the 2007 revenues included payments stemming from a non-RNAi partnership from before a corporate reorganization.
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The company's net loss in the period rocketed to C$14.3 million, or C$0.35 per share, from a year-ago loss of C$2.6 million, or Cdn$0.11 per share.
Contributing to the higher losses was a jump in fourth-quarter research and development spending to C$16.1 million from C$8.3 million the year before, primarily as a result of preclinical toxicology work and manufacturing materials related to the ApoB SNALP program. General and administrative costs were essentially flat at C$4.4 million
As of the end of 2008, Tekmira had cash, cash equivalents, and short-term investments totaling C$31.9 million.
During the conference call, Mortimer noted that while Tekmira had previously said that its cash position would enable the company to continue operations until the first half of next year based on an average monthly burn rate of C$1.5 million, "we have consistently managed our burn rate lower than this guidance based on increased revenue from our partners and carefully managing our expenses."
As such, "we've extended our cash runway to the second half of 2010," he said.
"We expect our 2009 net monthly burn rate to be less than [C]$1.5 million … based on projected expenses and contractually committed revenue from our partners," he added. "However, as in previous quarters, if we are able to generate partner revenue greater than what is contractually committed, we may be able to extend our cash even further."