Alnylam is developing an entirely new class of medicines based on the breakthrough discovery in biology known as RNA interference, or RNAi. Alnylam believes that RNAi therapeutics are a promising approach to silence disease-causing genes, and represent an opportunity to transform the treatment of many diseases.
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 clinical programs – including 4 in late stages of development – across 3 Strategic Therapeutic Areas (STArs). Our 3 STArs include: Genetic Medicines, RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, RNAi therapeutics for the treatment of unmet needs in dyslipidemia, hypertension, diabetes, and non-alcoholic steatohepatitis (NASH); and Hepatic Infectious Disease, RNAi therapeutics for the treatment of infectious diseases with liver involvement. “Alnylam 2020” marks our expected transition from a late-stage clinical development company to a multi-product commercial-stage company with a robust and sustainable development pipeline – a profile that we believe has rarely been achieved in the biopharmaceutical industry.
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.
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.
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.
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.
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.