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Tekmira Official Defends apoB as Cholesterol Target, Touts RNAi Rx Over Isis Antisense Candidate


By Doug Macron

Tekmira Pharmaceuticals President and CEO Mark Murray this week defended his company's selection of apolipoprotein B as the target in its phase I hypercholesterolemia program, calling it "well validated" in light of clinical data generated by Isis Pharmaceuticals with its apoB-targeting antisense drug.

At the same time, he said that he viewed Tekmira's RNAi approach to knocking down apoB as more robust than an antisense one, offering greater potency and a more-rapid and extended duration of action.

Murray's comments come about three months after Alnylam Pharmaceuticals CEO John Maraganore called the target for his company's own hypercholesterolemia program, proprotein convertase subtilisn/kexin type 9, "more compelling" than apoB (see RNAi News, 5/14/2009).

Alnylam and Tekmira have long been close allies: Alnylam is using Tekmira's stable nucleic acid-lipid particle delivery technology in a number of its drug candidates, for instance, and the two firms just announced they will both participate in a drug-delivery technology-research deal with AlCana Technologies, an independent company founded by former Tekmira employees (see RNAi News, 8/6/2009).

Nonetheless, during Alnylam's first-quarter financials conference call in May, Maraganore said that his company passed on pursuing apoB itself, noting that "based on the very clear-cut human genetic data corroborated by lots of other data … PCSK9 is, in fact, the preferred target."

Then, in June, Alnylam Vice President of Drug Discovery Muthiah Manoharan indicated that the decision to go after PCSK9 rather than apoB was, at least in part, due to safety concerns, namely the incidence of fatty liver disease observed when apoB was knocked down (see RNAi News, 6/11/2009).

Speaking during a conference call held to discuss Tekmira's second-quarter financial results, Murray said that the phase I trial of its cholesterol drug, dubbed ApoB SNALP, will "be looking at all kinds of safety parameters, and classic liver markers of safety will be monitored carefully."

At the same time, he said that data on Isis' phase III cholesterol drug mipomersen, which, like ApoB SNALP, is designed to inhibit apoB and reduce low-density lipoprotein levels. Last year, Genzyme acquired the exclusive, worldwide rights to mipomersen.

"We've selected apoB … because it is a very well-validated biological target, but one that the pharmaceutical industry has thus far failed to be able to drug," Murray said. "We also believe and recognize that it has now been validated in the clinic by Isis, where they demonstrated that knockdown [of the target] led to LDL lowering."

When it comes to differentiating ApoB SNALP from mipomersen, Murray called Tekmira's siRNA drug "a very interesting molecular alternative to Isis' program. Isis has done a very nice job of validating apoB in the clinic, but we believe that our product will have better potency, better durability, [and the ability to] knock down apoB and LDL more rapidly."

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When asked by a financial analyst to compare apoB with PCSK9 as a hypercholesterolemia target, Murray struck a diplomatic note, stating that "we haven't seen very much data from [Alnylam on PCSK9], but we believe very strongly in apoB."

Q2 Financials

For the three-month period ended June 30, Tekmira's net loss dropped to C$2.3 million ($2.1 million), or C$0.04 per share, from C$4.8 million, or C$0.14 per share.

Revenues in the quarter rose to C$3.8 million from C$2.5 million in the same period a year earlier, which reflects C$2.2 million received through manufacturing and research agreements with Alnylam. This money included a C$500,000 milestone payment to Tekmira triggered by Alnylam's start of a phase I clinical trial of its liver cancer drug ALN-VSP, which incorporates the SNALP technology (see RNAi News, 4/9/2009).

Also contributing to the revenue increase was the expansion of an alliance with Roche (see RNAi News, 5/14/2009).

"Under this agreement, Roche will pay us up to C$17.6 million for staff, materials, and third-party costs to support the advancement of two product candidates through to the filing of [investigational new drug] applications," Tekmira CFO Ian Mortimer said during the call. He noted that the first IND is expected to be filed by Roche in 2010.

During the second quarter, Tekmira received C$1.1 million from Roche for the provision of staff and external costs incurred in relation to their alliance, as well as C$800,000 for SNALP-formulation work carried out during the first half of the year.

Tekmira's research and development spending fell to C$4.4 million from C$5.7 million during the second quarter, partly due to a reduction in R&D staff to 66 from 77 in the second quarter of last year. The job cuts were made in October last year as part of an integration process following the merger of Tekmira and Protiva Biotherapeutics (see RNAi News, 4/3/2008).

"We do expect our R&D expenses to increase for the remainder of the year, as we incur ApoB SNALP clinical costs, as well as increased preclinical costs for our PLK1 SNALP [cancer] program that is now entering [good laboratory practice] toxicology studies" and is slated to enter human trials next year, Mortimer said.

Murray added that Tekmira still expects to select its third clinical candidate before year-end.

General and administrative costs in the quarter, meanwhile, dropped to C$1.1 million from C$1.8 million.

As of June 30, Tekmira had cash, cash equivalents, and short-term investments totaling C$24.8 million. The company confirmed previous guidance that it has enough resources to fund its operations until mid-2011.

"As in previous quarters, if we are able to generate partner revenue greater than what is contractually committed, then we may be able to extend our cash even further," Mortimer noted.

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