Alnylam called a ‘looming knockout’

CAMBRIDGE, Mass.—In late January, Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, detailed its pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. The new strategy builds on the company's progress in the advancement of RNAi therapeutics, including its "Enhanced Stabilization Chemistry" (ESC)-GalNAc conjugate technology, as a modular and reproducible platform for discovery of innovative medicines. Alnylam's STArs will remain focused on liver-expressed and genetically validated or pathogen-derived disease targets, the company said in a statement, with biomarkers for assessment of clinical activity early in Phase 1 trials. In the January 2015 statement, the company said it expects to provide additional specific guidance on pipeline programs in its three STArs.

"Based on a wealth of growing pre-clinical and clinical data, we now believe that the breadth of Alnylam's opportunities for RNAi therapeutics extends beyond the original framework of our ‘Alnylam 5x15' strategy,´” said John Maraganore, Ph.D., CEO of Alnylam. “Accordingly, we are excited to announce an evolution in our growth strategy with a focus on development and commercialization of RNAi therapeutics in three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease,". "Across our three STArs, we believe that we can address major unmet needs in a wide range of diseases with high-impact, differentiated medicines, and continue to build what we believe to be one of the most robust pipelines in biotech. By executing on this strategy, we believe we have the potential to make a meaningful difference in the lives of patients, and maximize value for shareholders."

Alnylam is continuing to impress Wall Street with its “knockout” drug platform and solid performance, but it could still face risks as it bring products to the commercial stage, said Ritu Baral, an analyst with Cowen and Co. in a note to investors Friday.

“We think Alnylam is the undisputed leader in the field of RNAi therapeutics,” wrote Baral in her analysis of the company.

“The company has shrewdly built a strong IP position around both construct and delivery technology, and taken a modular, liver-targeted approach to drug development,” she said. “We view Alnylam's current clinical programs, particularly FAP and FAC, as extremely promising with a high probability of success. The company has established a strong development and commercialization partnership with Genzyme, the commercial force in orphan drug, for rare genetic diseases.”

ATTR, Transthyretin (TTR)-mediated amyloidosis (ATTR), is an inherited, progressively debilitating, and often fatal disease caused by mutations in the TTR gene and represents a major unmet medical need with significant morbidity and mortality. There are over 100 reported TTR mutations; the particular TTR mutation and the site of amyloid deposition determine the clinical manifestations of the disease which include two clinical syndromes: familial amyloidotic polyneuropathy (FAP) and familial amyloidotic cardiomyopathy (FAC).

Alnylam is currently pursuing RNAi based therapeutics for genetically defined targets of rare, cardiometabolic, and liver-based diseases. Their in-house technology is focused on suppressing endogenous protein using short, double stranded RNA to mediate the sequence-specific degradation of mRNA.

“This technology allows Alnylam's drugs to have mechanisms involving previously undruggable targets,” said Baral. The company’s most “clinically advanced” compounds, Patisiran and Revusiran, are in Phase 3 clinical trials.

“Alnylam also has an incredibly deep pipeline of four other compounds in the clinic, and one poised to enter the clinic shortly,” said Baral. “The company has a broad development and commercialization partnership with Genzyme for genetic rare diseases as well as a partnership with The Medicines Company for ALN-PCS, an RNAi PCSK9 knock-down therapy.”

Though optimistic, Baral stated the usual caveats. “Clinical track record is no guarantee of commercial success in a few years however. We note however, that while we expect ALNY to continue to successfully develop drugs in the clinic for the next few years, the company will face a whole new type of execution risk as lead drugs reach commercial stage,” wrote Baral. “Alnylam has carefully prepared for this by carefully building an experienced commercial force, many of which came from Orphan market leader Genzyme. While we believe ALNY will prove to be successful, we note this layer of risk to the forward story.”http://www.alnylam.com/