By Doug Macron
Alnylam Pharmaceuticals expects its biologics unit may soon secure industry deals centering around either drugs in development or ones already on the market, company officials said last week.
"We've really been very encouraged by the robust response to the [establishment] of this initiative," Stuart Pollard, Alnylam's vice president of scientific and business strategy, said during a conference call held last week to discuss the company's first-quarter financial results.
He added that the use of the company's RNAi technology for biotherapeutics manufacturing — a worldwide market he estimated to be $100 billion and growing — "could be quite near-term."
Expected to help drive this quick adoption, Alnylam CEO John Maraganore said during the call, is the technology's potential use in improving the manufacture of existing drugs, not just "products that are in the development stages within the biotherapeutics marketplace."
Doing so, he noted, would likely only require the filing of a supplemental biologics license application with the US Food and Drug Administration.
Pollard said that because the use of RNAi in the biotherapeutics manufacturing process involves the addition of siRNA to the media in which the drugs are produced, it follows a "clear precedent" set by other supplements such as protein agonists. As such, "for approved products, we believe a supplemental BLA … would be required."
Maraganore stressed that Alnylam has not yet had discussions on this matter with US regulators, but said that "we're very confident that this is an approach that is consistent with other types of strategies for biologics manufacturing that's typically supported by a supplemental BLA."
Alnylam first unveiled its so-called Alnylam Biotherapeutics initiative in November (RNAi News 11/19/2009). At the time, Pollard said that the company views its RNAi expertise as potentially useful in improving the efficiency and scope of biologics manufacture, while reducing costs and cycle time. “And beyond that … there are opportunities to create enhanced efficacy [and] reduced immunogenicity” of the drugs themselves, he said.
Last week, Alnylam released data showing that it was able to efficiently deliver siRNAs into Chinese hamster ovary cells, which are typically used in the production of biological drugs, grown in one-liter suspension culture (RNAi News 5/6/2010). The company also said it was able to achieve potent silencing of CHO host gene targets involved in both cellular apoptotic and metabolic pathways.
During this week's conference call, Pollard said that "there are many processes that are impactful on the successful manufacture of biologics, whether it's stress, apoptosis, secretion, metabolic processes. With the extraordinary power of RNAi, you can interrogate and modulate all of those pathways either singularly or in a multiplex manner."
To do so, siRNAs "would be used as a supplement into the media feed in a non-genetic manipulation of the cells," he explained. "That offers a completely new way … of interrogating these processes."
Currently, "you've only really got crude manipulations like temperature, pH, et cetera ... to alter the behavior of the cells," he added. "Here, we can use RNAi to do that at will and in a … potent manner."
Maraganore said during the call that the company sees "three categories of product offerings we believe emanate from the Alnylam Biotherapeutics effort."
The first relates to "products we believe are broadly applicable for general aspects of biologics manufacturing," he said. "These include products targeting apoptotic pathways or products targeting glycosylation pathways that are well understood to be … more generic aspects of challenges within the biotherapeutics industry."
Second are "specific agreements" Alnylam expects to strike potentially on a product-by-product basis for use of the firm's RNAi technology to address "idiosyncratic aspects of … biologics manufacturing," Maraganore continued. "This could be related to specific problems or challenges" a biologics firm is facing in producing its product, or "attributes they want to engender within their products."
Lastly, Alnylam Biotherapeutics could ink "flat-out license agreements … that are essentially broad and specific licenses to elements of our intellectual property and technology as it relates to the biotherapeutics marketplace," he said, noting that "there is quite a bit of interest across the industry with what we're doing here."
For the three-month period ended March 31, Alnylam posted a jump in its net loss to $12.3 million, or $0.29 per share, from a year-ago loss of $7.9 million, or $0.19 per share.
Contributing to the higher losses was a rise in general and administrative costs to $11.2 million in the quarter from $7.7 million in the same period a year earlier, in part reflecting Alnylam's expenses related to ongoing litigation over key RNAi intellectual property (RNAi News 1/28/2010).
Research and development spending, meanwhile, fell slightly in the quarter to $24.7 million from $25.3 million, primarily because of license fees and milestones in the first quarter last year related to Alnylam's respiratory syncytial virus collaboration with Cubist Pharmaceuticals (RNAi News 1/15/2009) and the initiation of a phase I study of the company's liver cancer drug ALN-VSP (RNAi News 1/29/2009).
Alnylam's revenues in the quarter slid to $24.6 million from $25.1 million, and included payments from partners including Roche, Takeda Pharmaceuticals, Novartis, Biogen Idec, and Cubist, among others.
At the end of the first quarter, Alnylam had cash, cash equivalents, and marketable securities totaling $419.3 million. The company said it expects to have greater than $325 million at the end of 2010.