Capella

We reported data from our ongoing Phase 2 open-label extension (OLE) studies with patisiran and revusiran, investigational RNAi therapeutics targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis). [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=939975" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Patisiran-Ph-2-OLE-18-Month_EC-ATTR_110315.pdf" type="(720 KB PDF)"]View the initial 18-month patisiran Phase 2 OLE data presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Revusiran-Ph-2-OLE-6-Month_EC-ATTR_110315.pdf" type="(550 KB PDF)"]View the initial 6-month revusiran Phase 2 OLE data presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/DISCOVERY_EC-ATTR_110215.pdf" type="(350 KB PDF)"]View the DISCOVERY screening study presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/SSA-NH_EC-ATTR_110215.pdf" type="(670 KB PDF)"]View the SSA Natural History study presentation[/spotlight-link]

We presented pre-clinical data with ALN-TTRsc02, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis).  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. Results from studies comparing TTR knockdown activity of ALN-TTRsc02 to that of revusiran showed that ALN-TTRsc02 has a markedly superior TTR knockdown profile.  Further, in initial rat toxicology studies, ALN-TTRsc02 was found to be generally well tolerated with no significant adverse events at doses as high as 100 mg/kg. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=936518" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-TTRsc02_OTS_101415.pdf" type="(1.1 MB PDF)"]View the presentation[/spotlight-link]

We announced advancement of innovations in RNAi therapeutics with presentation of scientific data on two new platform technologies: Bis-RNAiTM and ReversirTM.  The Bis-RNAi platform enables simultaneous knockdown of two distinct disease genes using a single, subcutaneously administered molecular entity consisting of two linked siRNAs conjugated to a GalNAc moiety. The Reversir platform enables tailored control of RNAi pharmacology with rapid reversal of target gene silencing effects using GalNAc-conjugated, single-stranded oligonucleotide constructs that are designed to recognize and bind to the complimentary RISC-bound antisense strand of an siRNA. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=936348" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Bis-RNAi_OTS_101315.pdf" type="(1.0 MB PDF)"]View the Bis-RNAi poster[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Reversir_OTS_101315.pdf" type="(0.9 MB PDF)"]View the Reversir presentation[/spotlight-link]

We reported data from our ongoing Phase 2 open-label extension (OLE) study of patisiran, an investigational RNAi therapeutic targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR amyloidosis) patients with familial amyloidotic polyneuropathy (FAP). Alnylam scientists and collaborators from The Scripps Research Institute and Misfolding Diagnostics, Inc. were able to measure the effects of patisiran on pathogenic, misfolded TTR monomers and oligomers in FAP patients. Results showed a rapid and sustained reduction in serum non-native conformations of TTR (NNTTR) of approximately 90%. Since NNTTR is pathogenic in ATTR amyloidosis and the level of NNTTR reduction correlated with total TTR knockdown, these results provide direct mechanistic evidence supporting the therapeutic hypothesis that TTR knockdown has the potential to result in clinical benefit. Furthermore, complete 12-month data from all 27 patients that enrolled in the patisiran Phase 2 OLE study showed sustained mean maximum reductions in total serum TTR of 91% for over 18 months and a mean 3.1-point decrease in mNIS+7 at 12 months, which compares favorably to an estimated increase in mNIS+7 of 13 to 18 points at 12 months based upon analysis of historical data sets in untreated FAP patients with similar baseline characteristics. Importantly, patisiran administration continues to be generally well tolerated out to 21 months of treatment. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=933351" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Patisiran-Ph-2-OLE_Poster_ANA_09282015.pdf" type="(480 KB PDF)"]View the non-native TTR poster[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Patisiran-Complete-12mo-Ph-2-OLE_ANA_09282015.pdf" type="(620 KB PDF)"]View the complete 12-month patisiran Phase 2 OLE data presentation[/spotlight-link]

We hosted a series of online “RNAi Roundtables” in July, August and September, at which Alnylam scientists and key clinical collaborators reviewed recent progress in many of the company’s development-stage pipeline programs and discussed the related disease areas. Click on any of the RNAi Roundtables below to listen to the webcasts and view presentations from these events.

We reported positive initial results from our ongoing Phase 1 clinical trial with ALN-AS1, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias. Study results showed that single subcutaneous doses of ALN-AS1 resulted in an up to 82% lowering of ALA and an up to 93% lowering of PBG in asymptomatic “high excreter” (ASHE) patients, who carry the genetic mutation of acute intermittent porphyria (AIP) and have elevated levels of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme intermediates that mediate porphyria attacks. Furthermore, analysis of exosomal mRNA preparations from serum and urine revealed that treatment resulted in potent, dose-dependent, and durable silencing of liver ALAS1 mRNA.  Importantly, ALN-AS1 was found to be generally well tolerated with no clinically significant drug-related adverse events to date. These data provide human proof-of-concept for ALN-AS1 as a potential therapy for AIP and other acute hepatic porphyrias. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=931607" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AS1_ICPP_Interim-Ph1_09152015.pdf" type="(420 KB PDF)"]View the ALN-AS1 Phase 1 clinical data presentation[/spotlight-link]

We presented data on DMPK and safety of GalNAc-siRNA conjugates at the DIA/FDA Oligonucleotide-Based Therapeutic Conference, held September 9 – 11, 2015, in Washington, D.C.   [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/DIA_DMPK_09092015.pdf" type="(2.1 MB PDF)"]View the DMPK presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/DIA_Safety_09092015.pdf" type="(2.1 MB PDF)"]View the Toxicology/Safety presentation[/spotlight-link]  

We presented new pre-clinical data supporting the selection of a Development Candidate (DC) for ALN-GO1, an investigational RNAi therapeutic targeting glycolate oxidase (GO), also referred to as hydroxyacid oxidase 1 (HAO1), for the treatment of primary hyperoxaluria type 1 (PH1).  These data were presented at the 48th European Society of Paediatric Nephrology (ESPN) Annual meeting – held September 3 – 5, 2015, in Brussels – showing up to 99% silencing of the HAO1 mRNA and up to 98% mean reduction of urinary oxalate in animal models of PH1. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=930422" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-GO1-ESPN_Presentation_09052015.pdf" type="(1.4 MB PDF)"]View the presentation[/spotlight-link]

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