By Doug Macron
Alnylam Pharmaceuticals remains "confident" in RNAi as a therapeutic approach despite recent decisions by big pharma players to scale back their work with the gene-silencing technology, a senior company official said this week.
At the same time, the company has enough cash on hand to move its lead product candidates into "advanced development," Akshay Vaishnaw, Alnylam's senior vice president of clinical research, said during the Piper Jaffray Health Care Conference in New York.
For years, key pharmaceutical companies had been taking steps to establish footholds in the growing RNAi therapeutics space. The earliest deal came in 2003 when Merck and Alnylam struck an agreement to co-develop technologies based on RNAi (GSN 9/12/2003). That arrangement was later expanded to include a focus on ocular diseases.
Although the companies eventually parted ways on less-than-favorable terms (GSN 9/20/2007), the end of the relationship was in part due to Merck's decision to invest even more in RNAi through its $1.1 billion acquisition of Alnylam rival Sirna Therapeutics (GSN 9/2/2006).
Since that time, Alnylam continued to rack up major alliances with big pharmas. Among its biggest was a 2005 deal with Novartis, which gained access to Alnylam's technology and intellectual property (GSN 9/9/2005). Including the value of a 19.9 percent equity purchase, Alnylam realized $56.8 million upfront through that arrangement.
About two years later, Alnylam forged another significant alliance that gave Roche a non-exclusive license to use its fundamental RNAi intellectual property to develop therapeutics in oncology, respiratory diseases, metabolic diseases, and certain liver diseases (GSN 7/12/2007). The upfront value of the deal to Alnylam was $331 million.
Importantly, Roche also agreed to acquire Alnylam's German subsidiary.
While the Novartis deal proceeded smoothly, and was extended twice, the big pharma earlier this year decided against exercising an option to pick up broader rights to use Alnylam's IP and know-how — a transaction that would have triggered a $100 million payout to Alnylam (GSN 9/30/2010).
Although Novartis did select the maximum number of disease targets against which it would develop RNAi drugs on its own using Alnylam's technology, indicating that it plans to keep moving ahead with RNAi, the decision not to take the license was a blow to Alnylam, which slashed its workforce by 25 percent as a result.
Alnylam took another hit this month when Roche announced that it was shutting down its in-house RNAi-related research activities as part of a broader cost-savings initiative (GSN 11/18/2010). Alnylam stood to receive milestones and royalties from Roche on drugs developed using its technology.
Alnylam downplayed the impact of both situations, with company officials calling the end of the Novartis arrangement an opportunity to focus on its pipeline (GSN 11/11/2010) and expressing confidence in RNAi as a therapeutic modality despite Roche's decision.
At the Piper Jaffray conference, Vaishnaw echoed these sentiments.
Although he conceded that Alnylam "enjoyed very significant upfront payments in association with both the Roche and Novartis collaborations," going forward, the companies' actions don't "change our work in the slightest."
And Roche's vote of no confidence in RNAi "doesn't change our confidence in our technology and the progress we want to make," he said. "In the long run, I think that … Roche is missing out on a great opportunity."
Meanwhile, "the data that will come to light next year around [the company's phase I programs in liver cancer and TTR amyloidosis] will start showing everybody the power of RNAi in humans."
From a financial perspective, Vaishnaw said that Alnylam is "capable of running this business in a highly productive way, driving the pipeline, while having a significant cash reserve."
When it released its third-quarter financial guidance in early November, Alnylam said it expects to have cash, cash equivalents, and marketable securities exceeding $325 million at the end of 2010.
"We're quite confident that the reserves we have at the moment will allow us to exploit [our] pipeline … [to a point] that puts us in advanced development with our lead … products," Vaishnaw added.
Alnylam currently has three drugs in the clinic: a phase II treatment for respiratory syncytial virus called ALN-RSV01, the phase I liver cancer therapy ALN-VSP, and the phase I TTR amyloidosis drug ALN-TTR01.
It also anticipates moving its preclinical hypercholesterolemia drug ALN-PCS into human testing next year.
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