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Alnylam Provides Timelines for Drug Programs, Offers No Formal Guidance on Partnerships

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By Doug Macron

Officials from Alnylam Pharmaceuticals last week said that the company remains on track to meet the goals of its recently amended 5x15 drug-development initiative, which will see the company move five drug candidates into the clinic over the next three years.

Doing so will require that Alnylam find partners for three of the programs. While the officials said negotiations remain ongoing, they declined to provide any guidance on the timing of any such deals — a notable change from the past years when Alnylam readily offered timelines for when it would secure partnerships.

Alnylam also announced its fourth-quarter financial results, posting sharply higher losses amid increased spending on its various legal battles.

Alnylam unveiled the 5x15 effort in early 2011, promising that it will have five drug candidates for genetically defined diseases in “advanced clinical development” by 2015 (GSN 1/6/2011). The firm also said at the time that it intended to commercialize these products in the US itself.

A year later, however, Alnylam changed the terms of the 5x15 initiative, stating that that it would focus on bringing just two lead candidates to the market on its own — ALN-TTR02, a second-generation version of its phase I TTR amyloidosis treatment ALN-TTR01, and the preclinical hemophilia treatment ALN-APC (GSN 1/12/2012).

The other three molecules covered by the 5x15 project — ALN-HPN for refractory anemia and ALN-TMP for hemoglobinopathies, both of which are preclinical; and the phase I ALN-PCS for hypercholesterolemia — will now only advance through partnerships.

Alnylam, which made the pipeline disclosure around the time it announced the elimination of roughly one-third of its staff (GSN 1/26/2012), also quietly altered the timing of the 5x15 effort, stating that it now expects to have the five programs in any stage of clinical development by the end of 2015.

During a conference call held last week to discuss the quarterly results, Alnylam CEO John Maraganore said that he is “more confident than ever” that the company will meet its 5x15 goals. He added that with the recent downsizing, Alnylam has become “hyper-focused” on its TTR amyloidosis and hemophilia candidates, which now account for the lion's share of Alnylam's research and development spending.

Mike Mason, Alnylam's vice president of finance, noted during the call that “approximately two-thirds” of the company's 2012 R&D budget is allocated to ALN-TTR02 and ALN-APC, with most of the remaining one-third earmarked for the anemia, hemoglobinopathies, and hypercholesterolemia efforts.

Leading Alnylam's pipeline is ALN-TTR02, which was recently cleared for phase I testing by UK regulators. In that trial, 32 healthy volunteers will receive single, escalating doses of the drug as the company evaluates its safety and tolerability.

Secondary objectives of the study include pharmacokinetic characterization, and the preliminary determination of pharmacodynamics and clinical activity, Alnylam CMO Akshay Vaishnaw said during the call.

Alnylam expects to begin the phase I trial in the second half of the year, with data available in the third quarter. Assuming a positive outcome, a pivotal trial of ALN-TTR02 is slated for 2013. Meantime, Alnylam continues to advance a subcutaneously administered version of the drug called ALN-TTRsc, which is formulated as a GalNAc conjugate and expected to enter human trials in the first half of 2013, he said.

ALN-APC, meanwhile, is on track to enter phase I testing in the first half of 2013, with data expected in the second half of that year, according to Vaishnaw.

The other 5x15 programs are on hold pending partnership deals.

As for Alnylam's other drug candidates, its respiratory syncytial virus treatment ALN-RSV01 is nearing the end of a phase IIb trial, with data to be reported mid-year; an investigational new drug application for the Huntington's disease treatment ALN-HTT, which is partnered with Medtronic, is expected in the second half of 2012; and the phase I liver cancer drug ALN-VSP remains on the back burner until it is partnered.

Maraganore said that Alnylam expects to “do partnerships” during 2012, but fell short of making any solid promises, stating that “it would be premature to say when [a deal will be struck] and what phase we're at” in ongoing negotiations.

His caution follows missed partnership projections by Alnylam in recent years, including its so-called RNAi 2010 plan unveiled in 2008, which had required the company to secure at least three new alliances by 2010 (GSN 3/4/2010).

Despite its sharper focus on its lead programs, Maraganore said during the call that the company maintains its drug-discovery engine, with work in indications such as alpha 1-antitrypsin deficiency and acute intermittent porphyria.

He noted that Alnylam has certain goals for advancing new programs into formal in-house development, but declined to offer any specific details as it keeps its eye on near-term objectives with ALN-TTR02 and ALN-APC.

Q4

For the three-month period ended Dec. 31, Alnylam's net loss climbed to $14.3 million, or $0.33 per share, from a year-ago loss of $6.9 million, or $0.16 per share.

Revenues in the period fell slightly, to $20.5 million from $21.2 million in the same period a year earlier.

R&D costs in the quarter dipped to $23.4 million from $26.1 million, in part reflecting the termination of Alnylam's single-stranded RNAi collaboration with Isis Pharmaceuticals and the costs associated with a September 2010 restructuring.

General and administrative expenses climbed to $10.7 million from $7.5 million in the fourth quarter of 2010, a rise primarily due to the costs associated with ongoing litigation with Tekmira Pharmaceuticals (GSN 1/19/2012) and the University of Utah (GSN 12/8/2011).


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