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CombiMatrix Expands Antiviral Drug Discovery Collaboration with IrsiCaixa to Include Hepatitis C


CombiMatrix said this week that it has expanded an existing siRNA-based drug-discovery collaboration with Spanish non-profit research institute IrsiCaixa to include hepatitis C, marking the third viral disease area on which the company has focused its gene-silencing efforts.

Under the partnership, which was initiated in the area of HIV late last June , CombiMatrix designs and manufactures pooled siRNA compounds using its Express Track technology for testing at IrsiCaixa. CombiMatrix will own all compounds resulting from the arrangement.

Express Track designs siRNAs by using “a lot of the same rules that everyone else uses and are pretty much well-known in the industry,” according to CombiMatrix president and CEO Amit Kumar. The siRNAs “are about 20 to 22 mers, there are certain overhangs you want, and so forth.”

But on top of this, Kumar told RNAi News, the technology also incorporates proprietary techniques that allow the company to examine a viral genome and identify segments that would make good siRNA targets. “We take those segments and compare that to the human genome because we want as much orthogonality as possible,” he said. “If there’s a lot of homology — low orthogonality sequences — we toss those out and that gives us anywhere from a few thousand to 10,000 potential sequences that could be used.”

These sequences are then synthesized on CombiMatrix’s DNA arrays and shipped to IrsiCaixa for testing. Based on the results thus far, the company decided to expand the partnership to include hepatitis C.

The arrangement has yielded some positive in vitro data, Kumar said, and CombiMatrix expects the siRNAs against HIV will be ready for animal studies this year. An investigational new drug application permitting testing in humans could be ready for submission to US regulators in 2005, he added.

Kumar noted, however, that CombiMatrix isn’t in a position to bring a drug all the way onto the market alone. The company is experimenting with siRNA-based drug-delivery techniques, which Kumar said involve linking siRNA compounds with nanoparticles, but it is likely that a partner with expertise in this area will need to be found. Discussions with possible partners are ongoing, he noted.

Additionally, CombiMatrix expects to be on the lookout for a partner to help it with clinical development. “Our strength is in the discovery phase,” Kumar said. “We think we have the ability to find the best potent siRNAs and that’s what we’re shooting for.” After that, he said, the company expects to find a big biopharmaceutical player to either co-develop the RNAi drug or in-license the siRNAs for development on its own.

“Our plan is not to do it all ourselves. We would need a partner to go into the clinic,” he added. “It takes too long to build up all the expertise and it costs a lot — our focus is working with someone who already has that expertise.”

RNAi-based drug companies, such as Sirna Therapeutics and Alnylam Pharmaceuticals, are not partners that CombiMatrix expects to deal with, Kumar noted. “Alnylam and Sirna are good companies and I’ve talked to both of them,” he said. “But ultimately … you’re developing a drug and companies that do that the best are the big pharma companies.

“All of the … pure play siRNA companies are young — none has ever commercially developed a drug,” he added. As for these firms’ intellectual property estates, arguably the most valuable asset they could offer a partner, he said that he expects all fundamental RNAi IP will “get cross licensed everywhere” in the end.

Kumar said that CombiMatrix would prefer the kind of arrangement with a big pharma or biotech in which it had some role in developing the siRNA drugs, but that economics will ultimately determine whether the company settles for a straight out-licensing deal.

“We have a deal with Roche on a microarray product, and that’s the model that we’d love to use for other deals,” he said. Under that collaboration, Kumar said, Roche provided CombiMatrix upfront and milestone payments to conduct research, but handled manufacturing and marketing itself.

Aside from IrsiCaixa, CombiMatrix has an ongoing partnership with the US Army Medical Research Institute of Infectious Diseases to discovery siRNA compounds targeting the SARS virus. That arrangement, however, “is not in a very active mode right now,” Kumar said. CombiMatrix spokesman Bret Undem added that USAMRIID has been slow to return data to the company, moving the IrsiCaixa partnership to the top of the company’s list of priorities for its nascent siRNA operations.

Kumar said that CombiMatrix is currently in discussions with a number of other parties, mostly academic but some from industry, over additional siRNA partnerships. The company is looking to strike deals to use its technology to target a number of different viruses, including West Nile virus, human papillomavirus type 16, Kaposi’s sarcoma, smallpox, influenza virus A and B, and Leishmania RNA virus.

“One of the reasons we haven’t signed [these deals] as quickly as we’d like is because we’re still in negotiations about the economics,” he said. “We want to be sure that we own the compound and don’t give up economic interests.”


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