Capella

We have published pre-clinical results with ALN-AT3, an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia, in Nature Medicine. The paper documents a broad set of pre-clinical data supporting the clinical advancement of ALN-AT3. Among the many findings reported, subcutaneous administration of ALN-AT3 led to potent, dose-dependent, and durable knockdown of AT in wild-type mice, hemophilia A mice, and non-human primates (NHPs). In addition, ALN-AT3 treatment improved hemostasis in hemophilia mice and normalized thrombin generation in a non-human primate “inhibitor” model of hemophilia A (HA). Furthermore, long-term ALN-AT3 administration – even at highly exaggerated doses – was shown to be well tolerated in hemophilia mice, supporting a wide therapeutic index in the disease setting. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=906218" type=" "]Read the press release[/spotlight-link][spotlight-link icon="release" href="https://www.nature.com/nm/journal/v21/n5/full/nm.3847.html" type=" "]Read the abstract[/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]

In January 2015, we launched our “Alnylam 2020” guidance for the advancement and commercialization of RNAi therapeutics as a whole new class of innovative medicines. Specifically, by the end of 2020, we expect to achieve a company profile with 3 marketed products, 10 RNAi therapeutic...

In December 2014, we announced a pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. The strategy builds on our progress in the advancement of RNAi therapeutics, including our “Enhanced Stabilization Chemistry” (ESC)-GalNAc conjugate technology, as a modular and reproducible platform for discovery of innovative medicines. The three STArs will remain focused on liver-expressed and genetically validated or pathogen-derived disease targets, with biomarkers for assessment of clinical activity early in Phase 1 trials. Across our three STArs, we believe that we can address major unmet needs in a wide range of diseases with high-impact, differentiated medicines, and continue to build what we believe to be one of the most robust pipelines in biotech. By executing on this strategy, we believe we have the potential to make a meaningful difference in the lives of patients, and maximize value for shareholders. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=887405" type=" "]Read the press release[/spotlight-link][spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/RD-Day_Pipeline-Growth-Strategy.pdf" type="(2.0 MB PDF)"]View our Pipeline Growth Strategy presentation[/spotlight-link][spotlight-link icon="podcast" href="http://www.alnylam.com/web/assets/RD-Day_Pipeline-Growth-Strategy.pdf" type=""] Listen to our 2014 R&D Day webcast replay[/spotlight-link]

On December 12, we hosted an R&D Day in New York City. Alnylam management and key opinion leaders discussed the latest progress as well as plans for the future development of our RNAi therapeutics pipeline. At this event, we announced our pipeline growth strategy for development and commercialization of RNAi therapeutics across three Strategic Therapeutic Areas (STArs): Genetic Medicines, Cardio-metabolic Disease, and Hepatic Infectious Disease. [spotlight-link icon="podcast" href="http://edge.media-server.com/m/p/njherf95" type=" "] Listen to the webcast replay[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/MASTER-RD-DAY-DECK_Capella.pdf" type="(12.3 MB PDF)"] View the complete presentation[/spotlight-link]

We presented positive initial Phase 1 data for ALN-AT3, an investigational RNAi therapeutic targeting antithrombin (AT) for the treatment of hemophilia and rare bleeding disorders. Preliminary results, presented at the 56th Annual Meeting of the American Society of Hematology (ASH), showed that subcutaneous administration of ALN-AT3 given once weekly for three weeks at low doses of 15 (N=3) or 45 (N=1) micrograms/kg (mcg/kg) resulted in an up to 57% knockdown of AT in hemophilia subjects.  The effects of ALN-AT3 lasted for about 60 days after a single dose. ALN-AT3 was found to be well tolerated in both healthy volunteers and hemophilia subjects enrolled in the study.  These initial results show preliminary evidence for potency and durability of RNAi therapeutics at mcg/kg subcutaneous doses in human studies, and are the first clinical data to be reported for Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc conjugate technology. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=886691" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-AT3_Phase-1_ASH_120814.pdf" type="(1.1 MB PDF)"] View our ALN-AT3 Phase 1 presentation[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ASH_RNA_Symposium_Dec2014.pdf" type="(2.0 MB PDF)"] View our pre-clinical presentation[/spotlight-link]

We presented pre-clinical with ALN-CC5, an investigational RNAi therapeutic targeting complement component C5 for the treatment of complement-mediated diseases, at the American Society of Hematology (ASH) Meeting. Data showed an up to 99.2% knockdown of serum C5 and up to 96.2% inhibition of serum hemolytic activity in non-human primates (NHPs) with continued dosing for over seven months. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=886432" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/ALN-CC5_ASH_Dec2014_panel-by-panel.pdf" type="(0.9 MB PDF)"] View our poster[/spotlight-link]

We have published an article in the Journal of the American Chemical Society describing the discovery of GalNAc-conjugated siRNA as a novel strategy for delivery of RNAi therapeutics. This publication as a JACS "Communication" documents the landmark discovery by our scientists of GalNAc-conjugates as a potent and durable approach for subcutaneous administration of RNAi therapeutics with a wide therapeutic index. [spotlight-link icon="presentation" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=885342" type=""]Read our press release[/spotlight-link][spotlight-link icon="presentation" href="http://pubs.acs.org/doi/abs/10.1021/ja505986a" type=""]Read the abstract[/spotlight-link]

We presented pre-clinical data from our investigational RNAi therapeutic programs toward genetically validated targets in development for the treatment of cardiovascular metabolic diseases, including: ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia; ALN-AC3 targeting apolipoprotein C3 (apoC3) for the treatment of hypertriglyceridemia; and ALN-ANG targeting angiopoietin-like 3 (ANGPTL3) for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia.  The data, presented at the American Heart Association (AHA) Scientific Sessions 2014, included new pre-clinical multi-dose data in non-human primates (NHPs) with over six months of dosing for ALN-PCSsc, showing robust and clamped knockdown of PCSK9 of up to 92% and reductions in LDL-C of up to 77% with a once-monthly subcutaneous dosing regimen.  These studies confirm the potential for a once-monthly, and possibly once-quarterly, low volume subcutaneous dose regimen, thus highlighting the emerging profile of our ESC-GalNAc conjugate delivery technology. We believe that ALN-PCSsc represents an innovative, differentiated, and well-validated approach for the treatment of hypercholesterolemia. [spotlight-link icon="release" href="http://investors.alnylam.com/releasedetail.cfm?ReleaseID=883469" type=" "] Read our press release[/spotlight-link] [spotlight-link icon="presentation" href="http://www.alnylam.com/web/assets/CardioMetabolic_AHA_Poster_111714.pdf" type="(1.1 MB PDF)"] View our poster[/spotlight-link]

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