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Alnylam Execs Foresee Partnerships in 2010, Provide Few Details as Pipeline Advances

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By Doug Macron

Alnylam Pharmaceuticals expects to forge new collaborations over 2010, but company officials last week declined to provide specific guidance on its partnering objectives after falling short of previous expectations.

At the same time, Alnylam's top official said that while the company is encouraged that it will be able to confirm efficacy data observed in a phase IIa trial of its respiratory syncytial virus treatment ALN-RSV01, he stressed that it may not be able to do so in a follow-up study initiated late last month.

Speaking during a conference call held to discuss Alnylam's fourth-quarter financial results, CEO John Maraganore said that "we were disappointed to not have met our goal of two or more partnerships … last year" on top of a development and commercialization deal with Cubist Pharmaceuticals for the company's respiratory syncytial virus drug ALN-RSV01 (see RNAi News, 1/15/2009).

Nonetheless, Alnylam expects to "form additional alliances in 2010," President and COO Barry Greene added during the call. Importantly, Alnylam is also hedging its bets by counting deals with Regulus Therapeutics, a microRNA drug joint venture with Isis Pharmaceuticals, and its Alnylam Biotherapeutics biologics manufacturing initiative.

Neither Greene nor Maraganore commented on the possible timing or number of such arrangements, but in a corporate update released in January Alnylam said it remains committed to its so-called RNAi 2010 plan (see RNAi News, 1/10/2008). Terms of this plan require the company to establish at least three new alliances during the year.

"Of course, we will do more partnerships," Maraganore said, citing as an example a collaboration between Regulus and GlaxoSmithKline unveiled late last month (see RNAi News, 2/25/2010).

Meanwhile, Alnylam continues to be "very excited about the potential" for ALN-RSV01, which last week moved into a phase IIb study in adult lung transplant patients (see RNAi News, 2/25/2010).

The latest trial, Maraganore noted, is "designed to repeat and extend the clinical results observed in the earlier study," namely a decrease in the incidence of new or progressive bronchiolitis obliterans syndrome, a non-reversible obstructive lung disease associated with RSV infection.

The first study, a phase IIa trial of 24 adult lung-transplant patients, met its primary objective of establishing safety and tolerability, and showed that multiple 0.6 mg/kg doses of the drug are "very well tolerated in this patient population in the context of acute RSV infection," Akshay Vaishnaw, senior vice president of clinical research at Alnylam, said during last week's call.

Data from the earlier study also showed "that the placebo-treated patients had a 50 percent incidence of new or progressive BOS and … the ALN-RSV01-treated patients showed a 7 percent incidence of new or progressive BOS," Maraganore added.

While these findings were encouraging, "because the initial phase IIa study was very small, it is important to bear in mind that we may not be able to repeat the encouraging effects we saw on certain clinical endpoints in this new phase IIb study," which is enrolling 76 patients, he cautioned. "However, if we do, we think this will be an important outcome for the advancement of ALN-RSV01."

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Also advancing in Alnylam's pipeline is ALN-TTR01, an siRNA-based treatment for TTR amyloidosis, which is a hereditary, systemic disease caused by a mutation in the transthyretin gene.

ALN-TTR01, which is delivered via partner Tekmira Pharmaceuticals' stable nucleic acid lipid particle delivery technology, is slated to enter phase I testing in the first half of 2011, according to Vaishnaw. Alnylam is also using the SNALP technology in its phase I liver cancer drug ALN-VSP.

Late last year, Alnylam released preclinical data showing that ALN-TTR01 could trigger dose-dependent reductions of liver TTR messenger RNA and serum TTR protein levels by more than 80 percent in transgenic mice and non-human primates.

Vaishnaw noted that the company is also developing a second TTR drug, ALN-TTR02, which uses a second-generation lipid nanoparticle delivery vehicle. He added that Alnylam also expects to move its hypercholesterolemia drug ALN-PCS, which targets proprotein convertase subtilisn/kexin type 9, into human testing in 2011.

The Financials

For the three-month period ended Dec. 31, 2009, Alnylam reported a net loss of $7.8 million, or $0.19 per share, versus a year-ago loss of $9.4 million, or $0.23 per share.

Revenues in the period rose to $26.6 million from $24.4 million, and included $15.2 million of collaboration revenue related to Alnylam's alliance with Roche, as well as $5.5 million in revenues from the company's alliance with Takeda Pharmaceuticals, which began in the second quarter of 2008, and $5.9 million of expense reimbursement and amortization revenues from Novartis, the National Institutes of Health, Cubist, and Biogen Idec.

Alnylam's research and development spending in the quarter shrank to $21.6 million from $24.9 million, primarily due to license fees incurred in the fourth quarter of 2008 related to intellectual property assets, and partially offset by an increase in clinical trial and manufacturing expenses.

General and administrative costs in the fourth quarter, meanwhile, jumped to $13.1 million from $7.3 million, in large part due to legal costs associated with the company's intellectual property lawsuit filed with the Max Planck Institute against the Whitehead Institute for Biomedical Research, the Massachusetts Institute of Technology, and the University of Massachusetts (see RNAi News, 7/9/2009).

At the end of the quarter, Alnylam had cash, cash equivalents, and marketable securities totaling $435.3 million.

Looking ahead, the company said it expects to end 2010 with more than $325 million in cash, cash equivalents, and marketable securities, excluding $100 million in payments from Novartis should that company decide to exercise an option to non-exclusively license Alnylam's RNAi technology pursuant to an agreement signed in 2005 (see RNAi News, 9/9/2005).

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