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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 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 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]

Alnylam and The Medicines Company reported positive initial results from the ongoing Phase 1 clinical trial with ALN-PCSsc, an investigational RNAi therapeutic targeting PCSK9 for the treatment of hypercholesterolemia.  Subcutaneous administration of ALN-PCSsc resulted in an up to 83% lowering of LDL-C, with an up to 64 ± 5% mean maximum reduction, comparable to published results for anti-PCSK9 monoclonal antibodies (Zhang XL., et al., BMC Med, 2015).  Similar reductions in LDL-C were seen in patients on and off concomitant statin therapy.  The effects of ALN-PCSsc were highly durable, with clinically significant and clamped reductions in LDL-C maintained for over 140 days, supportive of a once-quarterly and possibly bi-annual subcutaneous dose regimen. Maximal lowering effects on LDL-C were consistently achieved at a dose of 300 mg associated with a low injection volume of 1.5 mL. Importantly, ALN-PCSsc was generally well tolerated with no clinically significant adverse events to date. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=929318" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-PCSsc-Phase-1_Poster_08302015.pdf" type="(0.4 MB PDF)"]View the poster[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-PCSsc-Phase-1_Presentation_08302015.pdf" type="(1.7 MB PDF)"]View the presentation[/spotlight-link]

We presented positive interim clinical data from our ongoing Phase 1 study for ALN-AT3, a subcutaneously administered, investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Data were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2015 Congress held June 20 – 25, 2015. New clinical results from 12 subjects with severe hemophilia show that subcutaneous administration of ALN-AT3 achieved potent and dose-dependent knockdown of AT of up to 86%. AT knockdown was highly durable, with effects lasting over two months after the last dose, supporting further evaluation of a once-monthly subcutaneous dose regimen. In addition, AT knockdown was associated with statistically significant increases in thrombin generation with a mean increase of up to 350% and marked improvements in whole blood clotting; these results demonstrate a re-balancing of hemostasis in severe hemophilia subjects. Furthermore, in an exploratory post-hoc analysis, a reduced frequency of bleeding was observed at higher AT knockdown levels with a maximum bleed-free interval of 114 days. Very importantly, ALN-AT3 continues to be generally well tolerated. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=919144" type=" "]Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/2015-ISTH-AT3-Phase1-Data.pdf" type="(614 KB PDF)"]View our Phase 1 data presentation[/spotlight-link]

We reported positive initial clinical results from our Phase 1/2 trial of ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases. The new clinical data are being presented at the 20th Congress of the European Hematology Association (EHA) held June 11 – 14, 2015. Initial study results from 12 healthy volunteer subjects showed that subcutaneous administration of a single dose of ALN-CC5 resulted in potent, dose-dependent, durable, and statistically significant knockdown of serum C5 of up to 96%. In addition, single dose administration of ALN-CC5 achieved inhibition of serum complement activity of up to 92%, including an up to 61% inhibition of serum hemolytic activity. Further, ALN-CC5 has been found to be generally well tolerated to date. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=917666" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-CC5-EHA2015_FINAL.pdf" type="(677 KB PDF)"] View our presentation[/spotlight-link]

We presented pre-clinical data on ALN-AAT, an investigational RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease. New data, presented at the Digestive Disease Week (DDW) meeting, held May 16 – 19, 2015, showed a robust knockdown of serum AAT of up to 93% in non-human primates (NHPs) with monthly subcutaneous dosing. This level of knockdown was highly durable, lasting for greater than 30 days following the final dose. Further, ALN-AAT was found to have a wide therapeutic index based on results from GLP toxicology studies. In addition, study results were reported from a transgenic mouse model of alpha-1 liver disease, where mice overexpress the human Z-AAT protein. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=913507" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AAT_DDW_051715.pdf" type="(7 MB PDF)"] View the presentation [/spotlight-link]

We presented initial 12-month clinical data from our ongoing Phase 2 open-label extension (OLE) study with patisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin (TTR)-mediated amyloidosis in patients with familial amyloidotic polyneuropathy (FAP). Study results, presented at the 67th Annual Meeting of the American Academy of Neurology (AAN) being held April 18 – 25, showed a mean 2.5 point decrease in modified Neuropathy Impairment Score (mNIS+7) at 12 months in patients who had reached the 12-month endpoint (N=20) at the time of data cutoff. This decrease in neuropathy progression compares favorably to the 13 to 18 point increase in mNIS+7 at 12 months that can be estimated from the literature in untreated FAP patients with similar baseline characteristics. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=907541" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/PATISIRAN-12MONTHOLE-AAN-FINAL_Capella.pdf" type="(497 KB PDF)"] View our presentation[/spotlight-link]

We presented results from a retrospective natural history study evaluating disease progression in transthyretin (TTR)-mediated amyloidosis (ATTR amyloidosis) patients with familial amyloidotic cardiomyopathy (FAC). These results were presented at a meeting with members of the Association of Black Cardiologists (ABC) at the American College of Cardiology (ACC) Annual Scientific Session, held March 14 – 16, 2015. Amongst other findings, study results showed a mean decline of 140 meters in 6-minute walk distance (6-MWD) over an 18-month period in FAC patients with mild-to-moderate heart failure. Also at the ACC meeting, we presented complete results from our Phase 2 clinical trial with revusiran, an investigational RNAi therapeutic for the treatment of FAC. Consistent with preliminary results presented last year, revusiran achieved an up to 98.2% knockdown of serum TTR – the disease-causing protein – and was found to be generally well tolerated. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=901611" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/FAC-NH-Presentation-for-ABC-meeting_15Mar20151.pdf" type="(2 MB PDF)"]View the FAC Natural History Study presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/Revusiran-ACC-15Mar2015.pdf" type="(406 KB PDF)"]View the complete revusiran Phase 2 results[/spotlight-link]

We announced updated clinical results from the ongoing Phase 1 study of ALN-AT3, a subcutaneously administered, investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders (RBD).  New results were presented at the 2015 Goring Coagulation Conference in London.  Specifically, data were presented from the study’s second dose cohort in hemophilia subjects (n=3), where subcutaneous administration of ALN-AT3 resulted in an up to 70% knockdown of AT.  New results provide initial evidence for potential correction of the hemophilia phenotype associated with ALN-AT3 administration and AT knockdown.  Specifically, ALN-AT3 administration resulted in an increase in thrombin generation of up to 334% and a marked improvement in whole blood clotting.  In addition, the most advanced severe hemophilia A subject in the cohort has remained bleed free for 47 days without replacement factor prophylaxis as of the January 6, 2015 data cut-off date. In addition, ALN-AT3 administration remains generally well tolerated. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=890625" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/2015-Goring-meeting-Akinc_Jan2015.pdf" type="(1.6 MB PDF)"] View our presentation[/spotlight-link]

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