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Alnylam

Capella

Alnylam welcomes you to Capella, the destination for updates on our progress in translating the science of RNAi toward innovative medicines.

July 7, 2014

Summer RNAi Roundtable Series

We plan to host a series of online “RNAi Roundtables” during July and August, at which Alnylam scientists and key clinical collaborators will review recent progress from several “Alnylam 5×15” programs and discuss the related disease areas.

Patisiran and ALN-TTRsc for the treatment of Transthyretin-Mediated Amyloidosis (ATTR)
Tuesday, July 15: 12:30 – 2:00 p.m. ET

  • Jared Gollob, M.D., Vice President, Clinical Research
  • Moderator: John Maraganore, Ph.D., Chief Executive Officer
  • Guest Speaker: Philip N. Hawkins, M.B., B.S., Ph.D., FRCP, Professor of Medicine, National Amyloidosis Centre, University College London Medical School

To register and access the webcast for this event, please click here.

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Pre-Clinical Data with ALN-CC5 for Treatment of Complement-Mediated Diseases

June 9, 2014

Pre-Clinical Data with ALN-CC5 for Treatment of Complement-Mediated Diseases

We presented pre-clinical data with our Development Candidate for ALN-CC5, a subcutaneously administered investigational RNAi therapeutic targeting complement component C5 in development for the treatment of complement-mediated diseases, at the 7th International Conference on Complement Therapeutics, held June 6 – 11, 2014, in Olympia, Greece.  These data demonstrate that ALN-CC5 led to an up to 98.7% knockdown of serum C5 and an up to 96.8% inhibition of complement activity in non-human primates (NHP) with weekly subcutaneous dose administration.



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Pre-Clinical Results with RNAi Therapeutics Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) Published in Proceedings of the National Academy of Sciences (PNAS)

May 21, 2014

Pre-Clinical Results with RNAi Therapeutics Targeting Aminolevulinic Acid Synthase-1 (ALAS-1) Published in Proceedings of the National Academy of Sciences (PNAS)

We have published pre-clinical results with RNAi therapeutics targeting aminolevulinic acid synthase-1 (ALAS-1) for the treatment of hepatic porphyrias in the Proceedings of the National Academy of Sciences (PNAS). The new paper highlights work that was done in collaboration with researchers at the Icahn School of Medicine at Mount Sinai in New York City. Data from studies performed in a mouse model of acute intermittent porphyria (AIP) demonstrate that RNAi therapeutics targeting ALAS-1 can achieve potent, rapid, and durable suppression of aminolevulinic acid (ALA) and porphobilinogen (PBG), the toxic heme biosynthesis intermediates that cause the symptoms and disease pathology of AIP.



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Positive Top-Line Data from Phase 1 Clinical Trial with ALN-AT3 for Treatment of Hemophilia and Rare Bleeding Disorders

May 13, 2014

Positive Top-Line Data from Phase 1 Clinical Trial with ALN-AT3 for Treatment of Hemophilia and Rare Bleeding Disorders

We presented positive top-line data from our Phase 1 clinical trial with ALN-AT3, an RNAi therapeutic targeting antithrombin (AT) in development for the treatment of hemophilia and rare bleeding disorders (RBD). In “Part A” of the Phase 1 study, we gave a single dose of drug to healthy volunteers to evaluate the drug’s safety and tolerability. Importantly, we had a dose escalation stopping rule at a maximum of 40% AT knockdown. Initial results, presented at the World Federation of Hemophilia (WFH) 2014 World Congress held May 11 – 15, 2014 in Melbourne, Australia, show that a single, low subcutaneous dose of ALN-AT3 at 0.03 mg/kg resulted in an up to 28-32% knockdown of AT at nadir relative to placebo (p <0.01 by ANOVA) and a temporally associated increase in peak thrombin generation (p <0.01). ALN-AT3 was found to be well tolerated with no significant adverse events reported.  With these results in hand, we have now proceeded to “Part B” of the Phase 1 study.



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Pre-Clinical Data with ALN-HBV for the Treatment of Hepatitis B Virus (HBV) Infection

May 12, 2014

Pre-Clinical Data with ALN-HBV for the Treatment of Hepatitis B Virus (HBV) Infection

We presented pre-clinical data with ALN-HBV, an RNAi therapeutic targeting the hepatitis B virus (HBV) genome for the treatment of HBV infection, at the TIDES 2014 meeting held May 12 – 15 in Providence, Rhode Island. Specifically, we reported significant, multi-log reductions in HBV surface antigen (HBsAg) and HBV viral titers, and showed evidence for an immune-mediated therapeutic effect in chronically infected chimpanzees.



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Key Scientific Data on Enhanced Stabilization Chemistry (ESC)-GalNAc-Conjugate Technology

May 11, 2014

Key Scientific Data on Enhanced Stabilization Chemistry (ESC)-GalNAc-Conjugate Technology

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.



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Pre-Clinical Data on ALN-AAT for the Treatment of Alpha-1 Antitrypsin (AAT) Deficiency-Associated Liver Disease

May 6, 2014

Pre-Clinical Data on ALN-AAT for the Treatment of Alpha-1 Antitrypsin (AAT) Deficiency-Associated Liver Disease

We presented new pre-clinical data supporting the advancement of a Development Candidate (DC) for ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) for the treatment of AAT deficiency-associated liver disease. Data were presented in a Late-Breaking Abstract Session at Digestive Disease Week (DDW), held May 3 – 6, 2014 in Chicago. As previously presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD, “The Liver Meeting”) in November 2013 and as updated at DDW, studies were performed in transgenic mice overexpressing the human Z-AAT protein. Subcutaneous administration of a GalNAc-siRNA targeting AAT led to rapid, potent, dose-dependent, and durable knockdown of AAT of greater than 95%, as well as a significant reduction in fibrosis and the incidence of liver tumors.



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Pre-clinical Results with RNAi Therapeutics for Cardiovascular Metabolic Disease at ATVB 2014

May 1, 2014

Pre-clinical Results with RNAi Therapeutics for Cardiovascular Metabolic Disease at ATVB 2014

We have presented new pre-clinical data from our growing pipeline of RNAi therapeutics for the treatment of cardiovascular metabolic disease, including ALN-PCSsc targeting PCSK9 for the treatment of hypercholesterolemia, and a newly named program, ALN-AC3 targeting apolipoprotein C-III (apoCIII) for the treatment of hypertriglyceridemia.  The data were presented in an oral presentation at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) 2014 Scientific Sessions held May 1-3, 2014 in Toronto, Ontario.



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April 29, 2014

Pre-Clinical Data on RNAi Therapeutics Targeting Transthyretin (TTR)

We have presented pre-clinical data with RNAi therapeutics targeting TTR for the treatment of TTR-mediated amyloidosis (ATTR).  These data were presented at the International Symposium on Amyloidosis (ISA) held April 27 – May 1, 2014.  These data showed that the degree of TTR knockdown in a mouse disease model was highly correlated with regression of TTR tissue deposits.  Further, comparative studies performed with the TTR stabilizer tafamidis and a TTR-specific antisense oligonucleotide (ASO) showed RNAi therapeutics targeting TTR to have superior pharmacologic profiles.



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Positive Initial Data from Phase 2 Open-Label Extension (OLE) Study with Patisiran

April 28, 2014

Positive Initial Data from Phase 2 Open-Label Extension (OLE) Study with Patisiran

We have reported positive initial data from our Phase 2 open-label extension (OLE) study with patisiran (ALN-TTR02), an RNAi therapeutic targeting transthyretin (TTR) in development for the treatment of TTR-mediated amyloidosis (ATTR).  Data were presented at the International Symposium on Amyloidosis, held April 27 – May 1, 2014.  Preliminary results showed that multiple doses of patisiran achieved sustained knockdown of serum TTR protein levels at the approximately 80% target level through 168 days.  Moreover, OLE results showed a favorable tolerability profile with up to eight doses administered.  These data provide the first clinical evidence of sustained RNAi-mediated TTR knockdown in FAP patients beyond two doses of patisiran.




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