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Alnylam Provides Timing for New Pipeline Programs, Inks Two Deals for Biotherapeutics Initiative


By Doug Macron

Officials from Alnylam Pharmaceuticals last week presented additional details on the company's pipeline, which underwent a makeover of sorts last month with the unveiling of a new product-development strategy, and said that the firm remains on track to have five products in “advanced” clinical development by 2015.

They also indicated that Alnylam is making progress with its biotherapeutics initiative, having signed two deals to help undisclosed partners use its RNAi technology to improve biologics manufacturing.

“We've now learned we can deliver RNAi therapeutics safely in man and that RNAi therapeutics are biologically active in man,” Alnylam CEO John Maraganore said, citing recently phase I data released from the company's liver cancer program (GSN 1/6/2011).

Speaking during a conference call held to discuss Alnylam's fourth-quarter financial results, he said “we've never been in a stronger position to advance these therapeutic products, and we are extremely confident in our ability to pioneer this effort and … to do so all alone if necessary.”

Alluding to the departures of several high-profile companies from the RNAi drugs space, such as Pfizer and Roche, he added that “the increasing scarcity of what we do presents itself as a rare opportunity since it only creates more value for us and our partners that remain committed.”

Maraganore also emphasized the importance of clinical data driving Alnylam forward, noting that it is “the one and only thing that counts.” In line with this thinking, the company in January presented its so-called Alnylam 5x15 strategy, saying it focuses resources on "genetically defined target and disease … [with the] potential to have a major impact in a high unmet need population” (GSN 1/6/2011). Notably, Alnylam expects to commercialize these drugs in the US on its own, it said at the time.

Under the initiative, Alnylam has moved three programs to the forefront. The first is the transthyretin-mediated amyloidosis treatment ALN-TTR01, which entered phase I testing in mid-2010 (GSN 7/8/2010). The drug is designed to treat TTR amyloidosis, a hereditary, systemic disease caused by a mutation in the transthyretin gene, by inhibiting both its mutant and wild-type forms.

According to Alnylam, the phase I study is expected to wrap up in the first half of this year, with human proof-of-concept data becoming available in the third quarter. Phase II work is slated to begin next year.

At the same time, Alnylam is also working on a follow-on transthyretin-mediated amyloidosis drug called ALN-TTR02, “which takes advantage of the … achievements we've made in delivery using our second-generation delivery technology,” Akshay Vaishnaw, senior vice president of clinical research, said during the call.

Alnylam plans to file an investigational new drug application for the newer compound in the second half of this year and begin phase I testing in 2012.

Also on deck under the 5x15 program is ALN-PCS, a potential treatment for severe hypercholesterolemia that targets proprotein convertase subtilisn/kexin type 9. The firm expects to file an IND for the candidate in the first half of 2011 and launch phase I data before the end of the year.

Last on the short list is ALN-HPN, a new addition to the pipeline, which is designed to treat refractory anemia by blocking hepcidin, a gene related to iron homeostasis. An IND is scheduled for 2012.

The two remaining programs under the initiative will be announced later this year.

Plans for Alnylam three other programs — ALN-RSV01 for respiratory syncytial virus, ALN-VSP for liver cancer, and ALN-HTT for Huntington's disease — remain unchanged since the disclosure of the 5x15 initiative. Partner Cubist Pharmaceuticals still holds the opt-in rights to the RSV drug; the cancer program proceeds although Alnylam is aiming to find a partner before phase II development will begin; and an IND for a Huntington's disease therapy, already partnered with Medtronic, is slated for 2012.

Elsewhere at Alnylam, the company's biotherapeutics initiative appears to be gaining traction. Formally launched in late 2009, the project focuses on using RNAi to “improve the quantity and quality of biologics manufacturing processes using mammalian cell culture, such as Chinese hamster ovary cells” (GSN 11/19/2009).

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“Over the past year, we have formed two collaborations with leading biotechnology and pharmaceutical companies, generating approximately $2 million in payments to the company,” Alnylam President and COO Barry Greene said during last week's conference call. He did not name the companies.

“It turns out that both of these collaborations relate to the use of our technology on currently marketed biologic products, so we're gaining confidence in the potential opportunities that this technology effort can deliver in the near term,” he added.

Maraganore noted that the $2 million represents “just the initial amount” received as upfront and research and development payments, and said that the biotherapeutics effort is expected to “deliver positive cash flow for the company for the future.”

Alnylam has said that it intends to ink additional biotherapeutics collaborations this year, which it said would benefit from the data being generated in the two ongoing alliances. The company has already reported data showing that siRNAs designed to target a virus known to infect CHO cells can inhibit infection and viral replication (GSN 11/18/2010).

However, “the fact that we now have ... two collaborations in actual commercial cell lines establishes a set of data that is very powerful as we talk to other potential collaborators, and starts to improve the kind of deal and deal economics,” Greene noted.


For the three-month period ended Dec. 31, Alnylam's net loss dropped to $6.9 million, or $0.16 per share, from a year-ago loss of $7.8 million, or $0.19 per share.

Revenues in the quarter dipped to $21.2 million from $26.6 million, while R&D spending increased to $26.1 million from $21.6 million. The jump reflects “increased preclinical and clinical trial costs to support the company's product platform and expanding product pipeline,” Alnylam said.

Meantime, general and administrative costs sank to $7.5 million in the fourth quarter from $13.1 million in the same period the year before.

At the end of 2010, Alnylam had $349.9 million in cash, cash equivalents, and marketable securities.

Looking ahead, Alnylam said that it expects to finish 2011 with more than $275 million in cash, cash equivalents, and marketable securities.

Have topics you'd like to see covered in Gene Silencing News? Contact the editor
at dmacron [at] genomeweb [.] com.

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