Our Approach

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="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=846985" type=" "] Read the press release[/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/ALNY-ESC-GalNAc-siRNA-TIDES-May2014-Capella.pdf" 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="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=814802" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/Files/Presentations/ALNY-12thUS-Japan%20Symp-on%20DDS-131220.pdf" 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="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=795424" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/ALNY-ALN-AS1update-OTS2013.pdf" type="(1.1 MB PDF)"] View our ALN-AS1 presentation [/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/ALNY-ConjugateUpdate-OTS2013.pdf" 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="https://www.alnylam.com/web/assets/ALN-TTRsc-PhaseI-Results-HFSA-Sept2013.pdf" type="(1.8 MB PDF)"] View our presentation [/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/ALN-TTRsc-PhI-HFSA-Poster-Sep2013.pdf" type="(0.7 MB PDF)"] View our poster [/spotlight-link] [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=792320" type=" "] Read our press release[/spotlight-link]

On July 11, we hosted an R&D Day in New York City. Alnylam scientists and management reviewed progress with our Alnylam 5x15 pipeline for the development and commercialization of RNAi therapeutics. The event featured presentations by experts in the following disease areas: TTR-Mediated Amyloidosis, Hemophilia and Rare Bleeding Disorders, and Acute Intermittent Porphyria. [spotlight-link icon="podcast" href="http://investors.alnylam.com/eventdetail.cfm?eventid=131417" type=" "] Listen to the webcast replay[/spotlight-link] [spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/Alnylam-RDDayPres-Capella-July2013.pdf" type="(3.4 MB PDF)"] View the complete presentation[/spotlight-link] TTR-Mediated Amyloidosis [spotlight-link icon="podcast" href="https://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-ATTRAmyloidosisOverview-July2013.mp3" type="(24.7 MP3)"] Listen to Dr. Philip Hawkins discuss TTR-Mediated Amyloidosis[/spotlight-link][spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-ATTRAmyloidosisOverview-July2013.pdf" type="(1.8 MB PDF)"] View the presentation[/spotlight-link][spotlight-link icon="podcast" href="https://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-ALN-TTR-ProgramOverview-July2013.mp3" type="(25.4 MP3)"] Listen to the ALN-TTR program overview[/spotlight-link][spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-ALN-TTR-ProgramOverview-July2013.pdf" type="(0.6 MB PDF)"] View the presentation[/spotlight-link] Hemophilia and Rare Bleeding Disorders (RBD) [spotlight-link icon="podcast" href="https://www.alnylam.com/web/assets/RDday-2013/alnylam_podcast_RDDay-HemophiliaAndRDBsOverview-July2013.mp3" type="(28.6 MP3)"] Listen to Dr. Craig Kessler discuss Hemophilia and RBDs[/spotlight-link][spotlight-link icon="presentation" href="https://www.alnylam.com/web/assets/RDday-2013/Alnylam-RDDay-HemophiliaAndRDBsOverview-July2013.pdf" type="(0.8 MB PDF)"] View the presentation[/spotlight-link]

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