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Alnylam Presents Data from its Phase I Extension Study with ALN-VSP, an RNAi Therapeutic for the Treatment of Liver Cancers, at American Society of Clinical Oncology (ASCO) Meeting

– Complete Response Achieved in Endometrial Cancer Patient with Multiple Liver Metastases –

– Results Provide Additional Safety Data on Longer Term Dosing with RNAi Therapeutics Delivered with Lipid Nanoparticles (LNPs) –

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 4, 2012-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, announced results today from its Phase I extension study with ALN-VSP, a systemically delivered RNAi therapeutic for the treatment of advanced solid tumors with liver involvement. The data are being presented in a poster titled “Open-Label Extension Study of the RNAi Therapeutic ALN-VSP02 in Cancer Patients Responding to Therapy,” in the Development Therapeutics – Experimental Therapeutics poster session being held Monday, June 4, 2012 from 8:00 a.m. to 12:00 p.m. CDT. Overall, the results demonstrated 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. In this study, chronic dosing of up to 23 months with ALN-VSP was found to be generally safe and well tolerated.

“We are very encouraged with the continued positive data from our ALN-VSP Phase I clinical trial and extension study. These data include safety and tolerability of multiple doses of ALN-VSP, as well as evidence for anti-tumor activity in this very advanced, heavily pre-treated cancer patient population. We have seen multiple patients achieve stable disease or better, including a patient with endometrial cancer metastatic to the liver who has achieved a complete response,” said Jared Gollob, M.D., Senior Director of Clinical Research at Alnylam. “Results from the extension study also give us increased confidence in long-term chronic dosing with RNAi therapeutics delivered via LNPs, as patients have received drug twice a month for up to nearly two years, and approximately 11 months on average. We look forward to partnering this program to further advance the clinical development of ALN-VSP as we believe the evidence of anti-tumor activity warrants Phase II testing.”

The extension study included patients enrolled in the ALN-VSP Phase I trial who achieved stable disease (SD) or better after four months of treatment; patients were eligible to continue on the extension study until disease progression. Main objectives included continued evaluation of safety and tolerability and assessment of disease response. Seven of 37 patients (18.9%) evaluable for response went onto the extension study. These included 1 of 7 (14.2%) at 0.4 mg/kg, 2 of 5 (40%) at 0.7 mg/kg, and 4 of 11 (36.3%) at 1.0 mg/kg. At the time of enrollment, six patients had SD and one had an unconfirmed partial response. For these patients treated on both the Phase I trial and extension study, the average length of time on treatment was 10.5 months, with a range of five to 23 months. As of today, two patients remain on the extension study, including an endometrial cancer patient on study for 23 months who achieved a CR after 20 months of treatment at 0.7 mg/kg and one patient with pancreatic neuroendocrine tumor (PNET) with continued SD after 14.5 months of treatment at 1.0 mg/kg. A PNET patient and a renal cell carcinoma patient who achieved SD at 1.0 mg/kg came off the study after 5.5 and 8.5 months, respectively, for adverse events that included grade 3 elevated alkaline phosphatase or grade 2 fatigue deemed possibly related to study drug.

“Both primary liver cancer and metastatic disease of the liver are associated with poor prognosis for patients, and new therapies are clearly needed,” said Josep Tabernero, M.D., Chairman of the Medical Oncology Department and Phase I Program at Vall d'Hebron University Hospital in Barcelona, Spain. “This Phase I trial and extension study with ALN-VSP currently represents, to our knowledge, one of the most comprehensive clinical trials of a systemically delivered RNAi therapeutic and also one of the most extensive experiences with RNAi therapeutics in cancer. The safety data and anti-tumor activity with ALN-VSP, including a complete response in a patient with multiple liver metastases who had failed multiple prior therapies, are very encouraging and I look forward to the further development of this promising agent.”

Results from the extension study showed that chronic bi-weekly dosing with ALN-VSP up to 1.0 mg/kg was generally safe and well tolerated in this setting. No new toxicities were reported among the seven patients enrolled onto the extension study. A decrease in spleen volume, likely an on-target anti-kinesin spindle protein (KSP) effect based on pre-clinical findings and not associated with any adverse events, occurred to a greater degree on the extension study than in the Phase I trial and was most pronounced in patients receiving 12 or more doses.


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 company plans to partner its ALN-VSP program prior to initiating a Phase II clinical study.

About ALN-VSP Phase I Trial and Extension Study Designs

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. Primary liver cancer, or hepatocellular carcinoma (HCC), is one of the most common cancers worldwide, with more than 600,000 people diagnosed each year. Secondary liver cancer, also known as metastatic liver cancer, is cancer that spreads to the liver from another part of the body due to other common cancers like colon, lung, or breast cancer. Worldwide, more than 500,000 people are diagnosed with secondary liver cancer each year.

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-APC 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, 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. 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™ 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 www.alnylam.com.

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, including ALN-VSP, its expectations with respect partnering the ALN-VSP program, and Alnylam’s expectations regarding 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, successfully demonstrate the efficacy and safety of its drug candidates, including ALN-VSP, the pre-clinical and clinical results for these product candidates, 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.

Source: Alnylam Pharmaceuticals, Inc.

Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Vice President, Investor Relations and
Corporate Communications
Amanda Sellers (Media), 202-955-6222 x2597

"Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release regarding Alnylam Pharmaceuticals's business which are not historical facts are "forward-looking statements" that involve risks and uncertainties. For a discussion of such risks and uncertainties, which could cause actual results to differ from those contained in the forward-looking statements, see "Risk Factors" in the Company's Annual Report or Form 10-K for the most recently ended fiscal year.