Jan 06, 2011 Press Release for Alnylam

Alnylam Launches "Alnylam 5x15" Product Strategy and Provides Guidance and Goals for 2011

Jan 06, 2011

CAMBRIDGE, Mass., Jan 06, 2011 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, today announced that it has launched its "Alnylam 5x15" product strategy focused on the development of innovative RNAi therapeutics for genetically defined diseases addressing major unmet medical needs. The company expects to progress five RNAi therapeutic programs into advanced clinical development by 2015, with the potential for early commercialization opportunities. Alnylam also announced additional product and business goals for 2011 and increased its guidance for its 2010 year-end cash position.

"We believe that now is the time for a transformation in our business, with major advances in RNAi delivery ready for clinical advancement and potential product commercialization," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "The company is stronger than ever due to our scientific achievements and clinical progress. Indeed, as evidenced earlier this week, we have achieved yet another important clinical milestone with proof of RNAi mechanism in man with systemic delivery. Our 'Alnylam 5x15' strategy actualizes this progress and is focused on genetically defined molecular targets and diseases where we believe there is a rapid and clear path for clinical advancement and commercialization of medicines that really matter. All told, we look forward to an exciting year ahead, with more human proof-of-concept data expected from our clinical programs, execution on our 5x15 strategy, and the advancement of additional partner-based development and clinical programs."

"Alnylam 5x15" Strategy and Key Goals

The "Alnylam 5x15" strategy establishes a path for development and commercialization of novel RNAi therapeutics to address genetically defined diseases with high unmet medical need. Products arising from this initiative share several key characteristics including: a genetically defined target and disease; the potential to have a major impact in a high unmet need population; the ability to leverage the existing Alnylam delivery platform; the opportunity to monitor an early biomarker in Phase I trials for human proof of concept; and the existence of clinically relevant endpoints for the filing of a new drug application (NDA) with a focused patient database and possible accelerated paths for commercialization. This strategy leverages Alnylam's clinical progress on siRNA delivery, including recent human proof-of-concept data for systemic delivery.

By 2015, the company expects to have five RNAi therapeutic programs in advanced clinical development. These include ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and two additional programs from the company's ongoing discovery efforts that will be named and advanced into development later in 2011. Alnylam intends to commercialize the products arising under the "Alnylam 5x15" strategy itself in the United States and potentially certain other territories; the company will seek development and commercial partners in other global territories.

"As part of our 'Alnylam 5x15' strategy, we have made portfolio decisions to focus our investments in our highest value activities and on programs with exciting potential for addressing major unmet medical needs," said Barry Greene, President and Chief Operating Officer of Alnylam. "Our ALN-TTR program represents a major opportunity for a disease-modifying therapy in ATTR. In addition, our ALN-PCS program represents an opportunity in severe hypercholesterolemia for a novel therapeutic strategy that phenocopies human genetics, and our new program targeting hepcidin creates an opportunity for RNAi therapeutics in the treatment of refractory anemias. We also expect to start development of two additional RNAi therapeutics targeting genetically defined diseases by the end of 2011."

Specific goals for "Alnylam 5x15" include:

• Accelerated Clinical Development of ALN-TTR Program for ATTR. ALN-TTR01 is a systemically delivered RNAi therapeutic being developed for the treatment of ATTR, including familial amyloidotic polyneuropathy (FAP) and familial amyloidotic cardiomyopathy (FAC). Alnylam continues to enroll patients in a randomized, placebo-controlled, dose escalation Phase I study to evaluate the safety and tolerability of ALN-TTR01 in patients with ATTR. Alnylam expects to complete this Phase I study in the first half of 2011 and report data in the third quarter of 2011. In parallel, Alnylam is also advancing ALN-TTR02, which utilizes second-generation delivery technology. The ALN-TTR02 program is on track for an investigational new drug (IND) application filing in the second half of 2011 that supports a multi-dose treatment regimen. In 2012, following results from both ALN-TTR01 and ALN-TTR02 studies, Alnylam expects to advance this program into Phase II clinical studies.
• Advance ALN-PCS Program for Severe Hypercholesterolemia into Clinical Studies. ALN-PCS is a systemically delivered RNAi therapeutic targeting intracellular and extracellular PCSK9, which is involved in regulation of LDL receptor (LDLR) levels on hepatocytes and the metabolism of LDL ("bad") cholesterol (LDLc). Pre-clinical studies with ALN-PCS have demonstrated a greater than 50% reduction in levels of LDLc, which is rapid and durable after a single dose. Alnylam expects to file an IND application for its ALN-PCS program in the first half of 2011, and has a goal of initiating a Phase I clinical trial in the second half of 2011 with initial data by the end of 2011.
• Expand "Alnylam 5x15" Pipeline with ALN-HPN for the Treatment of Refractory Anemia. ALN-HPN is a new development program, comprising a systemic RNAi therapeutic targeting hepcidin, a genetically defined gene in iron homeostasis, for the treatment of refractory anemia. Anemia of chronic disease (ACD) occurs in patients with end-stage renal disease, cancer, and chronic inflammatory disease. ACD patients who are refractory to erythropoietin and intravenous iron define a condition of refractory anemia for which there is substantial unmet need. Pre-clinical studies with a candidate ALN-HPN siRNA have demonstrated the ability to silence the hepcidin gene and increase serum iron levels. The company intends to advance this program toward the clinic in 2011 with an IND expected to be filed in 2012.

2011 Partner Program Goals

While focusing its core efforts on executing its "Alnylam 5x15" strategy, the company will continue to advance its additional pipeline programs through existing or future partnerships.

• Continue Clinical Development of ALN-RSV01 for the Treatment of Respiratory Syncytial Virus (RSV). Alnylam continues to enroll patients in a Phase IIb clinical trial in RSV-infected lung transplant patients, and expects to present data from this study in 2012. Alnylam and its partner for this program, Cubist Pharmaceuticals, Inc., have jointly made a portfolio decision to put the development of ALN-RSV02 for the pediatric population on hold; Cubist maintains its opt-in right for ALN-RSV01 in the lung transplant indication. Kyowa Hakko Kirin maintains its opt-in rights in Asia for ALN-RSV01.
• Complete Phase I study of ALN-VSP for Liver Cancer, with Additional Data in Second Quarter of 2011 and Form Partnership for Advancement into Phase II Studies. ALN-VSP is a promising RNAi therapeutic for the treatment of advanced malignancies with liver involvement, and comprises two siRNAs targeting KSP and VEGF in a first generation lipid nanoparticle (LNP) formulation. Earlier this week, Alnylam presented human proof-of-concept data with ALN-VSP and, earlier in 2010, reported additional clinical results regarding the drug's safety, pharmacokinetics, and preliminary evidence for clinical activity. Alnylam expects to partner its ALN-VSP program prior to initiating a Phase II clinical study.
• Advance ALN-HTT for the Treatment of Huntington's Disease towards the Clinic. Alnylam also expects to advance its ALN-HTT program, in collaboration with Medtronic, Inc. and CHDI Foundation, Inc., towards the clinic and plans on filing an IND in 2012. ALN-HTT, which targets production of the huntingtin gene, is a drug-device combination being developed as a disease-modifying therapy for the treatment of Huntington's disease.

Overall Development and Clinical Pipeline Goals

The table below highlights key Alnylam pipeline goals for the period from January 2011 through year-end 2012.

Specifically by the end of 2011, Alnylam expects to advance two additional programs in clinical development with IND filings for ALN-PCS and ALN-TTR02, as well as achieve additional human proof-of-concept results in its RNAi therapeutic clinical programs. This is in addition to the new human proof-of-concept data reported earlier this week regarding evidence for RNAi activity in human biopsy samples from the company's ALN-VSP Phase I study and potentially includes additional results from the ongoing ALN-VSP Phase I study, analysis of results from the ongoing ALN-TTR01 Phase I study, and results from the planned Phase I study of ALN-PCS.

"On the business front, we expect to form additional partnerships based on platform, products, and broader applications of RNAi technologies and new ventures, such as our efforts in microRNA therapeutics with Regulus and biologics manufacturing with Alnylam Biotherapeutics," said Laurence Reid, Chief Business Officer of Alnylam. "Indeed, we see many opportunities for continued business leadership through formation of new partnerships and ventures across multiple dimensions of our platform, pipeline, and technology, providing both near-term funding and longer-term value creation."

2011 Business Goals

• Form Additional New Alliances. Alnylam expects to form additional new alliances, which could include platform and multi-target discovery alliances, such as the company's partnerships with Takeda and Novartis, or product alliances, such as those the company has formed with Medtronic, Cubist, and Kyowa Hakko Kirin. In addition, the company will continue to explore new alliances or business ventures related to RNAi technologies, such as Regulus Therapeutics, Inc., a leading microRNA therapeutics company, which has formed major collaborations with GlaxoSmithKline and sanofi-aventis, and Alnylam Biotherapeutics, regarding use of RNAi technologies for biologics manufacturing.
• Maintain Strong Financial Performance. Alnylam announced today that it now expects to achieve a 2010 year-end cash position of greater than $345 million, as compared with its previous 2010 year-end cash guidance of greater than $325 million. In 2011, the company aims to maintain a solid financial position, ending the year with greater than $275 million in cash.

"Alnylam continues to maintain strong financial performance and discipline, allowing us to increase our 2010 year-end cash guidance to greater than $345 million," said Patricia Allen, Vice President of Finance and Treasurer of Alnylam. "In addition, we believe we will finish 2011 with greater than $275 million in cash, excluding any significant new business development partnerships we may form. This financial profile provides us with a multi-year runway to execute on our pipeline goals, with a particular focus on 'Alnylam 5x15' programs."

About RNA Interference (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 RNAs (siRNAs), 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 with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for transthyretin-mediated amyloidosis (ATTR), ALN-PCS for severe hypercholesterolemia, and ALN-HPN for refractory anemia. As part of its "Alnylam 5x15^TM" strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for respiratory syncytial virus (RSV) infection, ALN-VSP for liver cancers, and ALN-HTT for Huntington's disease. The company's leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics, Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithkline and sanofi-aventis. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com.

Alnylam Forward-Looking Statement

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, Alnylam's expectations with respect to its "Alnylam 5x15" product strategy, Alnylam's views with respect to the potential for RNAi therapeutics, including ALN-TTR01 and ALN-TTR02, ALN-PCS, ALN-HPN, ALN-VSP, ALN-RSV01 and ALN-HTT, its expectations with respect to the timing and success of its clinical and pre-clinical trials, including its plan to initiate clinical trials for ALN-TTR02 and ALN-PCS, its expectations regarding human proof of concept data, the expected timing of regulatory filings, its expectations regarding the development of efficient delivery of RNAi therapeutics, the formation of new alliances and business ventures, its cash position at the end of 2010 and 2011, and its ability to continue to generate revenue through existing and new alliances, 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 risks related to: Alnylam's approach to discover and develop novel drugs, which is unproven and may never lead to marketable products; the pre-clinical and clinical results for its product candidates, which may not support further development of product candidates; actions of regulatory agencies, which may effect the timing and progress of clinical trials; obtaining, maintaining and protecting intellectual property; Alnylam's ability to enforce its patents against infringers and to defend its patent portfolio against challenges from third parties; Alnylam's ability to obtain additional funding to support its business activities; Alnylam's dependence on third parties for development, manufacture, marketing, sales and distribution of products; obtaining regulatory approval for products; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's dependence on current and future collaborators; and Alnylam's short operating history; as well as those risks more fully discussed in the "Risk Factors" section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. 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 does not assume any obligation to update any forward-looking statements.

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SOURCE: Alnylam Pharmaceuticals, Inc.

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