Alnylam Provides Update on RNAi Pipeline, Platform, and Technology at its R&D Day
ï€ Update on Pipeline Includes New Pre-clinical In Vivo Data Demonstrating that ALN-TTR Blocks Pathogenic Tissue Deposition of Mutant TTR Protein by Greater than 95% ï€
ï€ Update on Delivery Platform Includes Research on Discovery of Novel Lipid Nanoparticles with Improved Gene Silencing Potency at Doses Less than 30 Micrograms per Kilogram ï€
ï€ Update on Technology Efforts Includes New Data on Applications of RNAi in Biologics Manufacturing, Creating New Business Opportunity ï€
CAMBRIDGE, Mass., November 12, 2009 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, is providing an update on its RNAi pipeline, platform, and technology at its R&D Day being held in New York today. Alnylam scientists and management will be joined by two guest speakers: Professor Allan Glanville, Director of Thoracic Medicine and Medical Director Lung Transplantation, St. Vincent's Hospital, Sydney, will discuss respiratory syncytial virus (RSV) infection in the lung transplant patient population; and Professor Philip N. Hawkins, National Amyloidosis Centre, Division of Medicine, and University College London Medical School Royal Free Hospital, will discuss transthyretin (TTR)-mediated amyloidosis (ATTR). Alnylam is developing RNAi therapeutics for the treatment of both RSV infection and ATTR, amongst other pipeline programs.
"We are pleased to share the exciting progress we've made in harnessing RNAi to develop novel medicines," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "In addition to advancing our pipeline of RNAi therapeutics, we continue to make important progress with our platform and technology. In particular, we are making major strides in our delivery research efforts and are now on a trajectory to achieve single microgram/kilogram gene silencing potency. Also, while our focus remains on therapeutic applications of RNAi, technology advances in other areas of drug discovery, such as biologics manufacturing, exemplify the broad transformative potential of RNAi."
ALN-TTR Program
Alnylam is developing ALN-TTR, a systemically delivered RNAi therapeutic targeting the TTR gene for the treatment of ATTR, including familial amyloidotic cardiomyopathy (FAC) and familial amyloidotic polyneuropathy (FAP). ATTR is caused by mutations in the TTR gene, which is expressed in the liver, that result in the accumulation of toxic deposits of the mutant TTR protein in several tissues, including nerves, heart, and the gastrointestinal tract. There are more than 100 mutations that have been identified in the TTR gene; ALN-TTR targets a region of the gene common to wild-type and all known mutant forms of TTR, and therefore, has potential as a therapeutic for all patients with FAC and FAP.
New pre-clinical data demonstrate that ALN-TTR administration is associated with markedly reduced pathogenic deposition of mutant TTR in tissues. The new studies were performed in a transgenic mouse model where the human V30M mutated TTR is over-expressed, and were conducted by Alnylam scientists in collaboration with Dr. Maria Saraiva at the Institute for Molecular and Cell Biology in Portugal. Results showed that administration of ALN-TTR, as compared with control siRNA treatment, led to a marked and nearly complete reduction of mutant TTR protein accumulation by over 95% in peripheral tissues affected by disease. Specifically, ALN-TTR was found to block mutant TTR deposition in sciatic nerve, sensory ganglion, intestine, esophagus, and stomach - tissues that are associated with the sensory and autonomic neuropathy and the severe gastrointestinal dysfunction observed in patients with ATTR. The therapeutic efficacy for ALN-TTR was measured approximately one month after dosing.
Alnylam expects to file regulatory applications for ALN-TTR by the end of 2009 with a goal of initiating a Phase I clinical trial in early 2010. ALN-TTR is being advanced using stable nucleic acid-lipid particles (SNALP) delivery technology in collaboration with Tekmira Pharmaceuticals Corporation.
"Alnylam is advancing an important innovation in medicine to patients in need of new therapies. The progress we are making is reflected across our pipeline efforts, including our recent decision to advance ALN-RSV01 in a Phase IIb trial of adult lung transplant patients infected with RSV," said Akshay Vaishnaw, M.D., Ph.D., Senior Vice President, Clinical Research at Alnylam. "In addition, new data from our TTR program provide a clear validation of our RNAi therapeutics strategy in ATTR, where we block the production of TTR protein and its pathogenic deposition in tissues, thereby creating the potential to attenuate the cause of this devastating genetic disease. We certainly look forward to advancing this important program to patients."
Delivery
Alnylam also presented new data from its delivery research efforts showing the discovery of novel lipid materials that can be incorporated into lipid nanoparticles (LNPs) to achieve markedly improved in vivo potency for gene silencing with systemically delivered RNAi therapeutic. The improved potency of LNPs provides the opportunity to widen therapeutic index, decrease cost of goods, and broaden the number of tissues and cell types available for systemic RNAi. Alnylam showed new data on three distinct LNPs that derive from novel lipids discovered as part of the company's collaborations with Tekmira, AlCana Technologies, Inc., University of British Columbia, and Massachusetts Institute of Technology (MIT). In rodent and non-human primate studies, all three novel LNPs demonstrated marked improvements in in vivo potency as compared with current generation LNPs. Specifically, in non-human primate studies, novel LNPs containing an siRNA targeting TTR demonstrated ED50 values (the dose of drug required to achieve a 50% silencing effect in vivo) of less than 30 micrograms/kilogram.
Alnylam Biotherapeutics
Alnylam is also presenting today new data regarding the application of RNAi technology to improve the manufacturing processes for biologics, an approach that has the potential to create new business opportunities and which the company is advancing in an internal effort called "Alnylam Biotherapeutics." This initiative is focused on applying RNAi technologies to transform the $100 billion biologics marketplace, which is comprised of recombinant proteins, monoclonal antibodies, and vaccines.
In particular, Alnylam is advancing RNAi technologies to improve the quantity and quality of biologics manufacturing processes using mammalian cell culture, such as Chinese hamster ovary cells, or "CHO" cells. This RNAi technology can be applied to the improvement of manufacturing processes for existing marketed drugs, new drugs in development, and for the emerging biosimilars market. Alnylam has developed proprietary delivery lipids that enable the efficient transfection of siRNAs into CHO cells when grown in suspension culture. Studies have demonstrated that silencing certain target genes involved in certain CHO cell apoptotic and metabolic pathways resulted in 40 to 60% improved cell viability as compared with untreated cells.
As Alnylam Biotherapeutics advances the technology, it plans to seek partnerships with established biologic manufacturers, selling licenses, products, and services. Alnylam Biotherapeutics is comprised of a focused team of Alnylam employees and the company plans to retain complete ownership of this effort at the present time.
Alnylam's R&D Day is being held on Thursday, November 12, 2009 from 8:30 a.m. to 12:00 p.m. ET at the Loews Regency Hotel in New York City. A replay of the event will be available approximately three hours after the event on the Alnylam website at www.alnylam.com.
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 applying its therapeutic expertise in RNAi to address significant medical needs, many of which cannot effectively be addressed with small molecules or antibodies, the current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of innovative medicines with peer-reviewed research efforts published in the world's top scientific journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered with Cubist and Kyowa Hakko Kirin. In addition, the company is developing RNAi therapeutics for the treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia, Huntington's disease, and TTR amyloidosis. The company's leadership position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam established "RNAi 2010" in January 2008 which includes the company's plan to significantly expand the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint owner of Regulus Therapeutics, a joint venture focused on the discovery, development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit http://www.alnylam.com.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylam's future expectations, plans and prospects, 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 the company's ability to successfully research and develop products and to successfully prosecute and enforce its patents around the world, 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.