September 30, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Cambridge, Massachusetts – Alnylam Pharmaceuticals recently presented 10 posters and oral presentations showing the progress of its GalNAc platform and its clinical translation at the 12th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in Montreal, Quebec. Included in the presentations was a bit of a bomb—in its Phase I/II study of ALN-AAT to treat AAT deficiency-associated liver disease (alpha-1 liver disease), three patients showed asymptomatic, transient increased liver enzymes. As a result, it has halted.
Alnylam took a drop as a result. Shares traded for a high of $78.09 on September 27 and are currently trading for $68.88.
Gena Wang, an analyst with Jefferies, maintained a “Buy” rating with a target price of $86. In a September 28 note, Wang wrote that “reported increases in liver enzymes are likely specific to the ATT siRNA and we see limited read-through to other clinical programs with the ESC-GaINAc chemistry.”
Janney Montgomery Scott began coverage of Alnylam on Wednesday, September 29, issuing a “neutral” rating and a price target of $74.
AAT, alpha-1 antitrypsin is a serine proteinase inhibitor that protects the lungs from neutrophil elastase and other irritants that can cause inflammation. Approximately 95 percent of people with AAT deficiency carry two copies of the abnormal Z allele (PiZ) that expresses the Z-AAT protein. As a result, in the liver, the misfolding of the mutant protein isn’t normally released into the blood, instead accumulating in liver cells. There it can cause damage to the liver, fibrosis, cirrhosis, and hepatocellular carcinoma.
New clinical data was also presented that evaluated ALN-AAT’s safety and efficacy. The Company noted in a statement, “Since the target patient population for ALN-AAT has established liver disease, Alnylam plans to advance a follow-on molecule targeting a different sequence for further development. Specifically, the Company is finalizing selection of a new Development Candidate—ALN-AAT02—and plans to rapidly advance this compound towards the clinic, with a planned CTA filing in 2017.”
Several other posters were presented that showed advances in optimizing the company’s Enhanced Stabilization Chemistry (ESC)-GaINAc platform. This proprietary platform is designed for targeted delivery of RNAi therapeutics to liver cells by way of uptake by the asialoglycoprotein receptors. The bottom line is it allows subcutaneous dosing with increased potency and durability.
In 2014, Alnylam created an alliance with Sanofi Genzyme to accelerate and broaden the development of RNAi therapeutics. It is described as a “multi-product geographic alliance in the field of rare diseases.” Alnylam holds products rights in North America and Western Europe. Sanofi Genzyme picked up the right to access specific programs in Alnylam’s current and future Genetic Medicines pipeline, including ALN-AAT in the rest of the world through the end of 2019.
Alnylam has a fairly broad pipeline focused on three strategic therapeutic areas, including Genetic Medicines, Cardio-Metabolic Diseases, and Hepatic Infectious Diseases. The focus is on RNAi as a new class of therapeutics. RNAi is a natural mechanism of gene silencing found in plants and animals. In short, the compounds are being used to stop a gene from manufacturing specific proteins, in essence, turning off the protein manufacturing at its source.
