Alnylam Files Clinical Trial Application (CTA) for ALN-GO1, an Investigational RNAi Therapeutic for the Treatment of Primary Hyperoxaluria Type 1 (PH1)

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Alnylam Pharmaceuticals, Inc. ALNY, the leading RNAi therapeutics company, today announced that it has filed a Clinical Trial Application (CTA) with the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) for ALN-GO1, a subcutaneously administered investigational RNAi therapeutic for the treatment of Primary Hyperoxaluria Type 1 (PH1). Upon approval of the CTA, the Company plans to initiate a Phase 1 study with ALN-GO1 in early 2016 and expects to report initial clinical data from the trial in late 2016.

PH1 is an ultra-rare orphan disease affecting approximately six to seven people per million worldwide. This devastating disease – which is often diagnosed in early childhood – is caused by failure to properly metabolize glyoxalate in the liver, leading to excessive oxalate production, kidney failure and further organ damage for some patients in infancy, and for most patients by their mid-twenties. There are no approved medical therapies for PH1, leaving combined liver-kidney transplant as the only effective treatment option. Left untreated, excessive oxalate overproduction can lead to severe illness and death. ALN-GO1 targets the gene for glycolate oxidase (GO), an enzyme upstream of the defect in PH1 patients, and is designed to starve the pathway of oxalate production and prevent its associated pathology.

"There is enormous unmet need for new therapeutic options for patients afflicted with PH1, a serious and debilitating disease of young children which can lead to kidney failure and damage to other organs," said Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D and Chief Medical Officer at Alnylam. "We are excited to advance ALN-GO1 toward clinical evaluation, and believe it represents an innovative approach for the treatment of PH1. ALN-GO1 now becomes the eighth program in our pipeline of investigational RNAi therapeutics to enter clinical stages. We look forward to providing updates as data from the Phase 1 study become available in late 2016."

ALN-GO1 Pre-clinical Data
Pre-clinical data were presented at the 48th European Society of Paediatric Nephrology (ESPN) Annual meeting, held September 3 – 5, 2015 in Brussels, showing that:

• ALN-GO1 demonstrated potent and durable silencing (up to 99%) of HAO1 mRNA (the mRNA encoding glycolate oxidase) across pre-clinical species and profound lowering of urinary oxalate (up to 98%) in animal models of PH1.
• In addition, pre-clinical durability data supports monthly, and potentially quarterly, subcutaneous dosing with ALN-GO1.

About Primary Hyperoxaluria Type 1 (PH1)
PH1 is an autosomal recessive disorder of glyoxylate metabolism, where hepatic detoxification of glyoxylate is impaired due to mutation of the AGXT gene – which encodes the liver peroxisomal alanine-glyoxylate aminotransferase (AGT) enzyme – resulting in excessive oxalate production. Excess oxalate in PH1 patients is unable to be fully excreted by the kidneys leading to the formation of recurrent kidney stones and the deposition of calcium oxalate crystals in the kidneys and urinary tract. Renal damage is caused by a combination of tubular toxicity from oxalate, calcium oxalate deposition in the kidneys, and renal obstruction by calcium oxalate stones. Compromised kidney function exacerbates the disease as oxalate is released into systemic circulation potentially resulting in subsequent accumulation and crystallization in bones, eyes, skin, heart, and the central nervous system, leading to severe illness and death. About 50% of patients will have kidney failure by age 15, and about 80% will have end stage renal disease by age 30. Current treatment options are very limited and although combined organ transplantation of liver and kidneys has been successful, it is a risky procedure and limited due to organ availability.

Genzyme Alliance
In January 2014, Alnylam and Genzyme, a Sanofi company, formed an alliance to accelerate and expand the development and commercialization of RNAi therapeutics across the world. The alliance is structured as a multi-product geographic alliance in the field of rare diseases. Alnylam retains product rights in North America and Western Europe, while Genzyme obtained the right to access certain programs in Alnylam's current and future Genetic Medicines pipeline, including ALN-GO1, in the rest of the world. In certain defined instances, Genzyme has co-development/co-commercialization and/or global product rights. Genzyme's rights are structured as an opt-in that is triggered upon achievement of human proof-of-principle.

About RNAi
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines. Alnylam's pipeline of investigational RNAi therapeutics is focused in 3 Strategic Therapeutic Areas (STArs): Genetic Medicines, with a broad pipeline of RNAi therapeutics for the treatment of rare diseases; Cardio-Metabolic Disease, with a pipeline of RNAi therapeutics toward genetically validated, liver-expressed disease targets for unmet needs in cardiovascular and metabolic diseases; and Hepatic Infectious Disease, with a pipeline of RNAi therapeutics that address the major global health challenges of hepatic infectious diseases. In early 2015, Alnylam launched its "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, Alnylam expects to achieve a company profile with 3 marketed products, 10 RNAi therapeutic clinical programs – including 4 in late stages of development – across its 3 STArs. The company's demonstrated commitment to RNAi therapeutics has enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen, Roche, Takeda, Kyowa Hakko Kirin, Cubist, GlaxoSmithKline, Ascletis, Monsanto, The Medicines Company, and Genzyme, a Sanofi company. In addition, Alnylam holds an equity position in Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 200 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, Cell, New England Journal of Medicine, and The Lancet. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information about Alnylam's pipeline of investigational RNAi therapeutics, please visit www.alnylam.com.

Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-GO1, expectations regarding the timing of its Phase 1 clinical trial with ALN-GO1 and the reporting of clinical data from that trial, its expectations regarding its STAr pipeline growth strategy, and its plans regarding commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates and delivery approaches, successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials, obtaining, maintaining and protecting intellectual property, Alnylam's ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, Alnylam's ability to manage operating expenses, Alnylam's ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and new business initiatives, Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products, the outcome of litigation, and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation to update any forward-looking statements.

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