Delivery of RNAi Therapeutics

We are presenting key scientific data on our Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform at the TIDES 2014 meeting held May 12 – 15, 2014 in Providence, Rhode Island. This technology enables subcutaneous dosing of RNAi therapeutics with increased potency and durability, and a wide therapeutic index.  Data show 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 our ALN-TTRsc program for the treatment of transthyretin (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 possibly even less frequent subcutaneous dosing regimens. [spotlight-link icon="release" href="" type=" "] Read the press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(1.3 MB PDF)"] View our presentation [/spotlight-link]

We presented new pre-clinical data on the pharmacology of GalNAc-siRNA conjugates at the 12th US-Japan Symposium on Drug Delivery Systems held December 16 – 20, 2013 in Lahaina, Maui, Hawaii. These new research findings describe the effects of long-term chronic dosing of GalNAc-siRNA conjugates on tissue drug levels and sustained target knockdown. [spotlight-link icon="release" href="" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(1.3 MB PDF)"]View our presentation[/spotlight-link]

We presented new pre-clinical data supporting the selection of the ALN-AS1 Development Candidate for the treatment of hepatic porphyrias, including acute intermittent porphyria (AIP). The new research, presented at the 9th Annual Meeting of the Oligonucleotide Therapeutics Society, held October 6 – 8, 2013 in Naples, Italy, showed that multi-dose administration of a GalNAc-siRNA targeting ALAS-1 led to rapid, dose-dependent, and long-lasting knockdown of the ALAS-1 mRNA in non-human primates, with an ED50 of approximately 1.25 mg/kg.  Further, in a rat model of AIP, ALN-AS1 administration at doses as low as 2.5 mg/kg resulted in a complete blunting of phenobarbital-induced over-production of PBG and ALA, the toxic heme intermediates in AIP. [spotlight-link icon="release" href="" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="" type="(1.1 MB PDF)"] View our ALN-AS1 presentation [/spotlight-link] [spotlight-link icon="presentation" href="" type="(1.3 MB PDF)"] View our GalNAc-siRNA conjugate presentation [/spotlight-link]

We have reported positive clinical results from our Phase I trial of ALN-TTRsc, a subcutaneously administered RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR). Data were presented at the Heart Failure Society of America 17th Annual Scientific Meeting being held September 22 – 25. These results demonstrated that ALN-TTRsc achieved robust, consistent, and statistically significant (p<0.01) knockdown of serum TTR protein levels of up to 94%. In addition, knockdown of TTR was found to be rapid, dose-dependent, and durable.  ALN-TTRsc was found to be generally safe and well tolerated in this study. [spotlight-link icon="presentation" href="" type="(1.8 MB PDF)"] View our presentation [/spotlight-link] [spotlight-link icon="presentation" href="" type="(0.7 MB PDF)"] View our poster [/spotlight-link] [spotlight-link icon="release" href="" type=" "] Read our press release[/spotlight-link]


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