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Silence to Merge with Intradigm in Bid to Create Top RNAi Drug, Delivery Player

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This story has been updated from a version posted on Dec. 16 to include additional comments from Intradigm's CEO.

By Doug Macron

Silence Therapeutics and Intradigm this week announced that they have agreed to merge in a bid to create an RNAi therapeutics firm with multiple drug-development and -delivery technologies, as well as a pipeline of both clinical and preclinical candidates.

The companies touted the financial benefits of the transaction, which would give privately held Palo Alto, Calif.-based Intradigm access to the public markets through UK-based Silence's listing on the London Stock Exchange, and provide Silence with an even broader base of institutional investors.

But according to Intradigm CEO Philip Haworth, the establishment of a broad drug-delivery portfolio attractive to prospective big pharma and biotech partners was the primary driver of the deal.

"Although we're very pleased with what our delivery system can do, we know that it can never achieve all of the applications that the pharmaceutical industry requests of us," he told RNAi News.

"In theory, you could take your own time to build [a] diversity of [delivery] capabilities, but it's going to take so long and so much money that no one is going to care when you get there," he added. "So we thought to look around for technologies that were additive to our own."

"By bringing together a comprehensive platform of siRNA-delivery and -development technologies, we believe [the new company] will be a partner of choice for those seeking to develop RNAi therapeutics," Silence Chairman Iain Ross said in a statement.

Indeed, delivery has long beleaguered RNAi drug development. Notably, Alan Sachs, vice president of RNA therapeutics at Merck Research Laboratories, said during a keynote address at the second Drug Information Association Oligonucleotide-based Therapeutics Conference last year that although the RNAi field has made great strides, “I don’t think that we’re even close to finding a solution to [the delivery] problem" (see RNAi News, 9/25/2008).

And while early partnerships in the space were largely driven by intellectual property and expertise around RNAi molecule design and optimization, increasingly, big industry players are regarding effective delivery technologies as the key to such deals.

For example, in September, Silence forged a collaboration with Japanese drug firm Dainippon Sumitomo Pharma to demonstrate functional delivery of siRNAs using its AtuPlex liposomal delivery technology (see RNAi News, 9/3/2009).

In May, Tekmira Pharmaceuticals announced that it had signed a deal to help Roche move its first two RNAi therapeutics — both of which will incorporate Tekmira's proprietary stable nucleic acid-lipid particle delivery technology — into the clinic (see RNAi News, 5/14/2009). And in March, MDRNA announced that it had non-exclusively licensed its liposomal-based siRNA-delivery platform to Novartis (see RNAi News, 3/26/2009).

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Meanwhile, a growing number of RNAi companies are focused on delivery rather than RNAi agents themselves, such as Tekmira, Cequent Pharmaceuticals, and Calando Pharmaceuticals (see RNAi News, 5/7/2009).

By merging into a single company, Intradigm and Silence will share Silence's AtuPlex technology, which is being used with the company's phase I solid tumor drug Atu-027, and Intradigm's PolyTran peptide-based delivery polymers.

"We believe the next level of success will be through showing true systemic delivery in a way that is versatile," Haworth said. "We felt we needed to have the capability to say, 'If you want to go to the lung, we have these two methods to do it. If you want to go to cardiomyocytes, we have this [other] method.'

"We have payloads and interesting chemistries we think are valuable … but really the gap in the big picture is delivery," he noted. "Until we've solved that, we're not going to see the kind of product-development opportunities [with big pharma and biotech] that we'd like to see."

The Terms

Under the terms of the proposed merger, Silence will use roughly 79.6 million of its ordinary shares to acquire all shares of Intradigm. After the deal closes, Intradigm's shareholders and management will own about 36.6 percent of the new company, which will retain the Silence name.

According to Haworth, the new Silence will continue to trade its shares on the London Stock Exchange, and therefore will maintain a small corporate office in the UK. The company will also maintain Intradigm's California research and development operations, as well as Silence's R&D group in Berlin, which was acquired when the company — then known as SR Pharma — merged with Atugen in 2005 (see RNAi News, 7/29/2005).

Ross will remain chairman of the new company, while Haworth will become its CEO. Silence CSO Klaus Giese will retain his position in the merged firm. The transaction remains subject to approval by Silence shareholders at an extraordinary general meeting to be held on Jan. 4.

The merged company will have an eight-member board of directors, with five of the nominated members coming from Silence's existing board: Ross, Jerry Randall, Annette Clancy, David U'Prichard and Melvyn Davies. Nominees for the remaining seats — Haworth, James Topper, and David Mack — currently sit on Intradigm's board.

The companies also announced that in conjunction with the merger, Silence has raised ₤15 million ($24.5 million) through the placing and subscription of its shares at 23 pence per share. Contributing ₤5 million through the subscription are existing Intradigm shareholders, including Alta Partners, Frazier Healthcare, Lilly Ventures, Roche Finance, and Astellas Venture.

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