Three weeks after the RNAi-platform company Alnylam Pharmaceuticals Inc. signed a huge deal with Novartis AG, Sirna Therapeutics Inc. entered a potential $250 million collaboration with Allergan Inc. to develop drugs for ophthalmic diseases, starting with Sirna's early clinical candidate for age-related macular degeneration.

In its largest deal to date, San Francisco-based Sirna will combine its work in RNA biology and chemistry, specifically in short-interfering RNAs, with Allergan's delivery methods and ocular drug expertise.

"We create what I think is a very powerful force," Howard Robin, Sirna president and CEO, told BioWorld Today from New York, where he was presenting the company's development progress at the UBS Global Life Sciences Conference. "We're very proud of this deal, and we expect more to come."

Terms of the collaboration call for Sirna to receive an up-front payment of $5 million and development milestones of up to $245 million. On top of that, the company also stands to receive research funding and would get royalties on worldwide product sales. Allergan also has agreed to take over all development and commercialization costs for the AMD drug, Sirna-027, expected to begin Phase II trials next year.

A chemically modified siRNA, Sirna-027 targets vascular endothelial growth factor (VEGF), the same pinpointed by other AMD drugs, such as New York-based Eyetech Inc.'s Macugen and South San Francisco-based Genentech Inc.'s Lucentis. But, unlike those drugs, Sirna-027 is directed specifically at VEGF receptor-1, which is stimulated by both VEGF and placental growth factor. Sirna's drug is designed to shut down the angiogenesis activation of both growth factors.

"The data so far have demonstrated that [Sirna-027] is very effective in 100 percent of the patients with no side effects," Robin said.

Phase I results to date have shown that patients receiving a single dose of the drug all have exhibited stable or improved vision at eight weeks, and 23 percent of those have experienced improvements of three lines or more in visual acuity measurements. The drug also has been well tolerated, and there have been no cases of ocular inflammation.

In addition to AMD, the collaboration with Allergan also will focus on other drugs for ocular diseases, those that are "difficult to satisfy through traditional means, but that siRNA could potentially treat, Robin said.

Sirna will develop optimized lead compounds against gene targets identified by Allergan, and Allergan will handle all preclinical, clinical and commercialization activities. A joint steering committee will be established to oversee the alliance.

Sirna's deal follows on the heels of a collaboration by another RNAi company. Earlier this month, Cambridge, Mass.-based Alnylam signed a potential $700 million deal with Basel, Switzerland-based Novartis to provide its RNAi platform for drug development. (See BioWorld Today, Sept. 8, 2005.)

Competition in the AMD space has been growing, especially among drugs targeting the VEGF pathway, since Macugen's approval late last year. But Eyetech's stock was sent reeling in May following positive reports of top-line Phase III data of Lucentis, and several industry experts have suggested Lucentis will emerge as the market leader. Along with Sirna, several other companies are developing drugs for AMD, such as Tarrytown, N.Y.-based Regeneron Pharmaceuticals Inc., which has completed Phase I testing of its VEGF Trap, and Philadelphia-based Acuity Pharmaceuticals Inc., which is developing an RNAi-based drug, Cand5. However, the increasing competition has convinced Alnylam to delay development of its AMD drug, ALN-VEG01, a VEGF inhibitor, and focus resources on other products in its pipeline.

Robin said he is not surprised at the rising interest in RNAi therapeutics. Sirna, which demonstrated the first human data with a siRNA drug in AMD and has shown positive preclinical results with a systemic product against hepatitis B, already is in discussions with other companies looking at its siRNA technology.

"I believe that siRNAs are a true breakthrough in medicine, and you'll start to see them become an important part of large pharmaceutical companies' portfolios," he said. While the Allergan collaboration is "our first major deal, I would expect there to be more to come in other therapeutic areas."

Sirna is developing siRNA-based drugs to treat hepatitis C and hepatitis B, and has a dermatology program that "is moving along nicely," he said. Early programs focus on diseases such as Huntington's, asthma and diabetes, and the company has an oncology drug collaboration with Indianapolis-based Eli Lilly and Co.

The deal with Allergan also is expected to "free up revenues to accelerate other programs," Robin said.

Sirna completed its most recent financing in July, raising $28 million, part of which was supposed to have funded clinical trials of Sirna-027. But with Allergan taking over costs, some of that money could go toward other development efforts. Robin said he expects to end the year with between $40 million and $45 million in the bank.

"I think this is exactly what we wanted to have happen under our strategy," he said of the Allergan collaboration. "I think there will be many more products coming through the pipeline for Sirna."

For Allergan, of Irvine, Calif., it marks the second deal in recent months for an AMD drug. In July, the company entered an agreement to develop compounds for ocular disease from Princeton, N.J.-based Pharmacopeia Drug Discovery Inc. Those compounds target angiogenesis, but since they do not work by blocking VEGF, could provide an alternative therapy or possibly work in combination with VEGF inhibitors. In that deal, Allergan agreed to pay Pharmacopeia an up-front cash payment, milestones and royalties. (See BioWorld Today, July 13, 2005.)

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