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 2014, Alnylam and Genzyme formed a transformational alliance with Genzyme for the development and commercialization of RNAi therapeutics as genetic medicines. This new alliance will allow for the accelerated and expanded development and commercialization of RNAi therapeutics across the world. Under the terms of this alliance, Alnylam retains broad product rights in North America and Western Europe, while Genzyme obtains the rights to Alnylam’s genetic medicines pipeline in the rest of the world plus co-development and co-commercialization rights or global rights to three programs. In addition, Genzyme will make a $700 million equity investment in Alnylam. Importantly, this new partnership significantly expands our balance sheet to over $1 billion in cash to increase our investment in new RNAi therapeutic programs, while securing a cash runway that we believe will allow us to develop and launch multiple products as breakthrough medicines for patients in need.
In January 2014, we entered an agreement with Merck, whereby we are acquiring Merck’s wholly owned subsidiary Sirna Therapeutics, Inc. This acquisition provides us with intellectual property and RNAi assets including pre-clinical therapeutic candidates, chemistry, siRNA-conjugate and other delivery technologies. We believe the acquisition of Sirna Therapeutics will complement and extend our own progress and continued focus on RNAi therapeutics, including siRNA-conjugate technologies. The RNAi assets and intellectual property that we are acquiring from Merck will strengthen our efforts to build a new class of medicines, advancing them to patients in need.
We announced a new program, ALN-AGT, an RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertensive disorders of pregnancy (HDP), including preeclampsia. Pre-clinical data were presented at the American Heart Association’s High Blood Pressure Research 2014 Scientific Sessions, held September 9 – 12, 2014, in San Francisco. Data from experiments in an established rat model of preeclampsia demonstrated that an RNAi therapeutic targeting AGT ameliorates the clinical sequelae of preeclampsia and improves outcomes for the fetus. This treatment approach has the potential for selective delivery to the pregnant mother without fetal drug exposure, as our study confirmed undetectable siRNA levels in the fetus.
We hosted a series of online “RNAi Roundtables” during July and August, at which Alnylam scientists and key clinical collaborators reviewed recent progress from several “Alnylam 5×15” programs and discussed the related disease areas.
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.
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.