Alnylam and Ascletis Form Strategic Collaboration to Develop ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers

Alnylam and Ascletis Form Strategic Collaboration to Develop ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers
Partnership is Focused on Developing ALN-VSP for Hepatocellular Carcinoma (HCC) in China, with Alnylam Retaining Rest-of-World Rights

CAMBRIDGE, Mass. & HANGZHOU, China & RESEARCH TRIANGLE PARK, N.C., Jul 12, 2012 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc., a leading RNAi therapeutics company, and Ascletis Pharmaceuticals (Hangzhou) Co., Ltd.., a privately held US-China joint venture pharmaceutical company, announced today that they have formed a strategic collaboration for the development of ALN-VSP, a first-in-class, systemically delivered RNAi therapeutic for the treatment of liver cancers including hepatocellular carcinoma (HCC), a significant area of unmet need in China. This collaboration provides Ascletis with the exclusive rights to develop and commercialize ALN-VSP in China including Hong Kong, Macau, and Taiwan. Alnylam will retain all rights in the rest of the world, and is eligible to receive milestones and royalties based on product sales.

"We are excited to form this new partnership with Ascletis and have great confidence that they will be an excellent partner for the continued development of ALN-VSP in the Chinese market. Indeed, we believe Ascletis has the appropriate expertise in place to advance ALN-VSP through that region's clinical and regulatory system. As an organization, they aim to develop first-in-class medicines for the Chinese market and, given the encouraging clinical data seen to date with ALN-VSP, this represents a unique opportunity for them to make a significant impact," said Laurence Reid, Ph.D., Senior Vice President and Chief Business Officer of Alnylam. "With this collaboration, we are able to develop ALN-VSP globally through the product's advancement in a region where HCC is a particular challenge. As we retain all rights in the rest of the world, this partnering strategy provides multiple future opportunities for Alnylam to advance this novel therapeutic in other markets."

"Liver cancers, and specifically HCC, are a major unmet need in China, which has the highest incidence of this aggressive cancer in the world," said Jinzi J. Wu, Ph.D., President and Chief Executive Officer of Ascletis. "No effective therapies currently exist for this disease. Alnylam is a global leader in the development of innovative RNAi-based therapies, and we are pleased to be collaborating with them in the war on cancer. We are very encouraged by the clinical data that have emerged to date from their ALN-VSP program. We believe that their Phase I results in liver cancers - which included one patient who achieved a complete response and several others who have achieved prolonged stable disease -- clearly support further development of this novel medicine, and we look forward to bringing this first-in-class therapy to patients in need."

Per the terms of the agreement, Ascletis has received an exclusive license from Alnylam to develop and commercialize ALN-VSP in China including Hong Kong, Macau, and Taiwan. The initial focus will be on advancing ALN-VSP into a Phase II study for the treatment of HCC. Ascletis will diligently advance ALN-VSP, and as the program progresses, Ascletis will pay Alnylam development and commercial milestones and royalties on net sales in the Ascletis territory. Alnylam retains all rights to develop and commercialize the product in the rest of the world. Alnylam may use the data generated in China by Ascletis under this strategic collaboration for development of ALN-VSP in the rest of the world, and Ascletis may potentially receive sublicense payments based on any such future partnerships. No further financial details were disclosed.

ALN-VSP has completed a Phase I study in patients with advanced malignancy with liver involvement and patients that achieved stable disease or better have been enrolled into an extension study. Results of the Phase I study in 41 patients were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2011 and demonstrated proof of RNAi mechanism based on liver biopsy samples and disease control (stable disease or better after first two months) in 13/31 (42%) patients treated at doses greater than or equal to 0.4 mg/kg. Data were presented recently at ASCO Annual Meeting in 2012 from the ongoing extension study with ALN-VSP. Results showed disease control lasting more than six months in the majority of patients treated on the extension study, including a complete response (CR) in an endometrial cancer patient who had multiple liver metastases. Results also showed that chronic bi-weekly dosing with ALN-VSP, including a patient treated for 23 months, was generally safe and well tolerated.

About ALN-VSP, Phase I Trial and Extension Study Designs

ALN-VSP is a systemically delivered RNAi therapeutic comprising two siRNAs designed to target two genes critical for the growth and development of cancer cells: vascular endothelial growth factor (VEGF) and kinesin spindle protein (KSP), also known as eglin 5 (Eg5). The ALN-VSP Phase I trial was designed as a multi-center, open label, dose escalation study in patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective was to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP. Other secondary and exploratory objectives included: assessment of tumor response using Response Evaluation Criteria for Solid Tumors (RECIST), a set of published guidelines that define when cancer patients' disease improves, stabilizes or progresses during treatment; quantitation of change in tumor blood flow and vascular permeability as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); and, analysis of pharmacodynamic effects of ALN-VSP on tumors as measured in patients electing to proceed with voluntary pre- and post-treatment biopsies. The ALN-VSP extension study was designed to enable continued dosing with ALN-VSP in patients who had achieved stable disease or better after completing four months of treatment on the Phase I trial. Patients enrolling onto the extension study were permitted to receive bi-weekly ALN-VSP until disease progression or unacceptable toxicity. The primary objective was to collect long-term safety data. The secondary objective was to assess tumor response.

About Liver Cancers

Cancer affecting the liver, known as either primary or secondary liver cancer, is associated with one of the poorest survival rates in oncology and represents a major unmet medical need affecting a large number of patients worldwide. Hepatocellular carcinoma (HCC), or primary liver cancer, is one of the most common cancers worldwide, with more than 630,000 people diagnosed each year including approximately 350,000 in China.

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 the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, ALN-AT3 for the treatment of hemophilia, and ALN-TMP for the treatment of hemoglobinopathies. As part of its "Alnylam 5x15TM" strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a partner by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of 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, Cubist, and Ascletis. 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. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for applications in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam's VaxiRNA(TM) platform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. 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 .

About Ascletis Pharmaceuticals (Hangzhou) Co., Ltd.

Ascletis is a US-China joint venture pharmaceutical company, dedicated to discovering, developing and commercializing important new treatments for cancer and infectious diseases. Ascletis raised, in April, 2011, US$100 M in committed funding in Series A private equity financing, including a first tranche of US$50 M. It leverages U.S./European innovation and pharmaceutical/biotech strategic experience along with China's capital efficiency and market potential. Ascletis's goal is to establish a sustainable business and accelerated revenues through the in-licensing of clinical stage programs and commercialization of new medicines for the growing Chinese pharmaceutical marketplace. The company, at the same time, is building value through discovery, demonstration of clinical proof-of-concept, and global partnering of novel therapeutics for life-threatening diseases. Ascletis has assembled an entrepreneurial management and senior scientific team with a track record of successful pharmaceutical discovery and development at major global pharmaceutical and emerging biotechnology companies in the United States and Europe. For more information, please visit outside China or inside China.

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, statements regarding Alnylam's views with respect to the potential for RNAi therapeutics, its expectations regarding the continued development of ALN-VSP in China and the rest of the world, the possibility of Alnylam receiving future milestones and royalties from Ascletis based on the development and commercialization of ALN-VSP in China and Taiwan, and its "Alnylam 5x15" product strategy, 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, the pre-clinical and clinical results for these product candidates, including ALN-VSP, which may not support further development of such product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials for such product candidates, obtaining, maintaining and protecting intellectual property, obtaining regulatory approval for products, competition from others using technology similar to Alnylam's and others developing products for similar uses, and Alnylam's ability to establish and maintain strategic business alliances and new business initiatives, 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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        Jinzi J. Wu, Ph.D.
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