This story has been updated to include comments from Alnylam officials and details about the company’s respiratory syncytial virus program.
By Doug Macron
Alnylam Pharmaceuticals said last week that it may not reach its previously stated goal of forging two or more new “major” industry partnerships before the end of the year despite continued interest from potential biotech and pharmaceutical allies.
Alnylam had been predicting it would forge these deals since at least the beginning of the year, and “there remains significant interest across the industry for new alliances in RNAi therapeutics based on Alnylam’s capabilities … technology and … intellectual property,” Alnylam CEO John Maraganore said during a conference call held to discuss the company’s third-quarter financial results.
“However … while multiple partnerships remain ongoing with potential biotech and pharmaceutical partners, we now believe that the timing for achievement of this goal could extend beyond year end,” he said.
Maraganore stressed during the call that the possible delay was not the result of decreased interest in RNAi or a drop-off in the quality or scope of potential deals, but rather a “timing issue, [and] it’s not a question of if; it’s simply a question of when.
“At this time, late in the year, it is more appropriate to reflect on the potential that [partnership discussions] could go into next year,” he said.
Meanwhile, Alnylam said that there has been a slight change within its ongoing collaboration with Cubist Pharmaceuticals to develop an RNAi-based treatment for respiratory syncytial virus, with Cubist deciding to focus its attention on a second-generation molecule rather than the program’s original drug candidate.
In January, Alnylam announced that Cubist had licensed the rights to its phase II RSV drug ALN-RSV01 in all markets outside of Asia as part of a 50/50 joint-development and profit-sharing deal (see RNAi News, 1/19/2009). The arrangement called for Cubist to handle the drug’s development in exchange for milestones of up to $82.5 million and double-digit royalties to Alnylam.
By July, Alnylam wrapped up a modestly sized phase II study of ALN-RSV01 in adult lung-transplant patients naturally infected with the virus and disclosed that the drug had meet the trial’s primary endpoint of safety and tolerability (see RNAi News, 7/23/2009).
The trial data also suggested efficacy, but Alnylam cautioned that these findings were “exploratory” at best given the size of the study with just 24 patients. At the time, Alnylam and Cubist said they would further analyze the data to determine “the optimal development strategy and specific plans for all RSV indications."
As it turns out, Cubist has decided to pull back from ALN-RSV01 in favor of a follow-on molecule ALN-RSV02 for use in pediatric RSV patients, Alnylam said last week.
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“After evaluating the clinical data for ALN-RSV01, we and our partner Cubist agreed to develop ALN-RSV01 in the adult lung-transplant setting in parallel with the development of a second-generation compound, ALN-RSV02, which will be focused on the pediatric population,” Alnylam Senior Vice President of Clinical Research Akshay Vaishnaw said during last week’s conference call.
Alnylam will advance ALN-RSV01 on its own into a phase IIb trial in RSV-infected adult lung-transplant patients in order to “repeat and extend the clinical results observed in the original phase II study,” he said, adding that the trial is expected to start enrolling patients in early 2010.
Maraganore declined to provide specific details about the new study’s protocols, noting that these would be made public next year, but said that it would be “quite a bit larger” than the first phase II trial.
Cubist will now have an opt-in right to the ALN-RSV01 for the adult lung-transplant patient indication, but Alnylam will be responsible for funding and overseeing the drug’s further development, Vaishnaw noted. Going forward in the collaboration, “Cubist will take the lead in advancing the ALN-RSV02 molecule towards the pediatric setting in continued collaboration and 50/50 funding with Alnylam.”
According to Maraganore, “Cubist … [has] always been primarily focused on the pediatric opportunity in [RSV]. … And while they fully support and are absolutely on board with our advancement of [ALN-RSV01] in the lung-transplant setting, their primarily interest is in the pediatric market and the pediatric segment.”
As for the decision to develop ALN-RSV01 for adult RSV patients and ALN-RSV02 for pediatric patients, Maraganore said that in light of “the differences in size and dosing levels required, it is impossible to think about a single product that would go into both [adult and pediatric] segments. Ultimately, to get the most value out of this opportunity, one has to think about differentiation of the product profiles consistent with the one market versus the other.”
Company officials did not provide specific details on the differences between the molecules, but Vaishnaw noted that the second-generation agent includes chemical modifications that improve stability and safety while retaining ALN-RSV01’s potency.
In the third quarter, Alnylam’s net loss jumped to $9.2 million, or $0.22 per share, from a year-ago loss of $2.9 million, or $0.07 per share.
Third-quarter revenues fell slightly to $24.2 million from $25.7 million. Meanwhile, research and development spending climbed to $23.2 million from $22.1 million, while general and administrative costs rose to $10.7 million from $6.9 million in the same period a year earlier.
“The increase in G&A expenses this quarter [was related] primarily to higher professional-service fees in association with business activities,” primarily legal activities tied to the company’s ongoing litigation over the rights to certain RNAi-related IP (see RNAi News, 9/17/2009), Patricia Allen, vice president of finance and treasurer at Alnylam, said during the conference call.
Looking ahead, she said that Alnylam expects its G&A expenses to continue to rise in the fourth quarter on the costs of that litigation. The company has also amended its year-end cash guidance to greater than $430 million from greater than $435 million amid “an increase in legal expenses … we are incurring as we prepare for our trial date in February 2010.”