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Alnylam Demonstrates Continued Commitment to Transthyretin-Mediated Amyloidosis Patients with Advancement of ALN-TTRsc02, an Investigational RNAi Therapeutic with Potential for Low Volume, Once Quarterly, Subcutaneous Dose Regimen


Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced today that it presented key pre-clinical data and provided program guidance for ALN-TTRsc02, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis). The new data were presented at the 11th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS), held October 11 – 14, 2015, in Leiden, Netherlands. In pre-clinical studies, including those in non-human primates (NHPs), ALN-TTRsc02 achieved potent and highly durable knockdown of serum TTR of up to 99% with multi-month durability achieved after just a single dose, supportive of a potentially once quarterly dose regimen. Based on these pre-clinical data, ALN-TTRsc02 is the most potent and durable investigational RNAi therapeutic discovered at Alnylam to date. The company is currently conducting Investigational New Drug (IND)-enabling studies and plans to file an IND or IND-equivalent in early 2016 with initial data in late 2016. Assuming positive clinical results, Alnylam expects to initiate a Phase 3 study for ALN-TTRsc02 in 2017.

“Alnylam is fully committed to improving the lives of patients with ATTR amyloidosis, and we believe that our investigational ALN-TTRsc02 program, if successful, has the potential to provide an important therapeutic option for the management of their disease. ALN-TTRsc02 is a logical extension of our overall TTR program, as we’re deploying our second generation ‘ESC’ GalNAc conjugate technology to achieve a best-in-class profile with the potential for a low volume, once quarterly subcutaneous dose regimen,” said Eric Green, Vice President, General Manager, TTR Program. “We continue to make excellent progress with patisiran and revusiran, both of which are in Phase 3 studies for the treatment of ATTR amyloidosis, and we now plan to work closely with regulatory authorities to diligently bring ALN-TTRsc02 to patients and the market as an additional option in the future.”

ALN-TTRsc02 utilizes the company’s Enhanced Stabilization Chemistry (ESC)-GalNAc-siRNA conjugate delivery platform, which enables high potency and durability with a very wide therapeutic index. Clinical data from other RNAi therapeutic programs in Alnylam’s pipeline that utilize ESC-GalNAc technology have demonstrated robust efficacy and the potential for a dosing regimen that is monthly, quarterly, or possibly, in certain cases, bi-annually.

In a presentation titled, “Enhanced Pharmacologic Activity and Durability Demonstrated with an ESC GalNAc-siRNA Targeting Transthyretin,” Alnylam scientists presented data characterizing the development of ALN-TTRsc02. First, a series of ESC-GalNAc-siRNAs targeting TTR were screened for knockdown activity in transgenic mice and NHPs. These and other data led to selection of the Development Candidate (DC) for ALN-TTRsc02. In pharmacodynamic studies, ALN-TTRsc02 achieved potent and durable knockdown of serum TTR in transgenic mice and NHPs. In NHPs, a single subcutaneous dose at 1 mg/kg led to TTR knockdown of up to 99% with sustained knockdown of more than 50% for greater than 84 days. Monthly subcutaneous dosing at 1 mg/kg achieved sustained TTR knockdown of up to 99% with mean maximal effects greater than 95%. Data were also shown comparing TTR knockdown activity of ALN-TTRsc02 to that of revusiran, a late-stage, investigational RNAi therapeutic targeting TTR that utilizes Alnylam’s first generation Standard Template Chemistry (STC)-GalNAc-siRNA conjugate technology. The results showed that ALN-TTRsc02 has a markedly superior TTR knockdown profile compared to revusiran. Finally, in initial rat toxicology studies, ALN-TTRsc02 was found to be generally well...