Alnylam Pharmaceuticals, Inc. (Nasdaq:ALNY), a leading RNAi therapeutics company, announced today that it is presenting key scientific data on its Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform. Specifically, the company will be presenting data showing that chemical modifications of siRNA that enhance in vitro stability result in higher liver exposure in vivo and lead to a significantly increased potency and durability of effect in pre-clinical studies. As compared with the “standard template chemistry” (STC)-GalNAc-conjugate approach used in ALN-TTRsc – a subcutaneously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR cardiac amyloidosis – ESC-GalNAc-siRNA conjugates demonstrated a 10-fold increased potency in non-human primate (NHP) studies, and a durability of effect that supports once-monthly or potentially even less frequent subcutaneous dosing regimens. The ESC-GalNAc-conjugate technology is being used in a wide range of Alnylam development programs, including ALN-AT3 – an RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders – which is currently in a Phase 1 clinical study.
“Our ESC-GalNAc-conjugate delivery platform enables subcutaneous dosing of RNAi therapeutics with increased potency and durability, and a wide therapeutic index. Importantly, we have demonstrated that increased siRNA stability is the key to realizing these potency and durability improvements. In addition, our data suggest that further improvements in potency and durability might be realized in human studies based on an attenuated nuclease environment. Accordingly, we believe that once-monthly and possibly less frequent subcutaneous dose regimens could be achieved in our clinical pipeline programs with this technology,” said Muthiah (Mano) Manoharan, Ph.D., Senior Vice President, Drug Discovery of Alnylam. “We look forward to sharing additional pre-clinical and clinical results in the weeks and months to come, where we expect to build on data sets that are defining what we believe will be a very attractive product profile for our RNAi therapeutics, including the ability to clamp down disease targets in a predictable, sustainable, and durable manner.”