Academic, Government & Foundation Collaborations

Alnylam's Collaborations with Medical Research Foundations, the U.S. Government, and Academic Research Institutions

Alnylam has established relationships with leading medical research foundations, the federal government and many academic research institutions with a commitment to develop RNAi therapeutics for diseases with unmet medical needs. Among many such agreements, including license agreements related to key intellectual property from academic institutions, a select group of agreements are highlighted below.

Cancer Research Technology Limited (CRT)

In July 2003, Alnylam exclusively licensed the Glover patent (EP 1230375) from CRT. The Glover patent is one of several fundamental patents in Alnylam's broad intellectual property estate for RNAi therapeutics. CRT is a specialized commercialization and development company, which aims to develop new discoveries in cancer research for the benefit of cancer patients. CRT is wholly owned by Cancer Research UK, the largest independent funder of cancer research in the world.

CHDI Foundation

ALN-HTT is the drug under development as part of a drug-device combination therapy for the treatment of Huntington's disease being advanced in collaboration with Medtronic, Inc. and CHDI Foundation, Inc. As part of its alignment of resources on its ATTR and hemophilia programs, Alnylam has elected to exercise its option under its agreement with Medtronic to opt-out of the 50-50 expense/profit share arrangement of the ALN-HTT program. If Medtronic decides to continue the ALN-HTT program, Alnylam would continue to supply ALN-HTT drug product for the program and would be entitled to receive milestones and royalty payments on future annual net sales.

Cold Spring Harbor Laboratory (CSHL)

In January 2004, Alnylam licensed intellectual property related to the induction of gene silencing in mammalian cells through RNAi from Cold Spring Harbor Laboratory. Under the terms of the agreement, Alnylam receives a non-exclusive license from Cold Spring Harbor Laboratory to therapeutic uses of patent applications and related technology stemming from RNAi research conducted by Dr. Gregory Hannon and colleagues at Cold Spring Harbor Laboratory. This intellectual property encompasses certain aspects of gene silencing in mammalian cells by siRNAs. therapeutics.

Cystic Fibrosis Foundation Therapeutics

In March 2005, the Cystic Fibrosis Foundation Therapeutics (CFFT) and Alnylam initiated a collaborative program to discover RNAi therapeutics for the treatment of cystic fibrosis (CF). The goal of the collaborative program is to develop siRNAs that target host genes involved in the trafficking of protein known as the cystic fibrosis transmembrane conductance regulator (CFTR) whose mutation is involved in the cause of CF.

Defense Advanced Research Projects Agency (DARPA)

In December 2005, Alnylam received initial government funding for the its pandemic flu program from the Department of Defense's 'Defense Advanced Research Projects Agency' (DARPA).

Immune Disease Institute

In May 2006, Alnylam obtained rights to RNAi delivery technology developed in the laboratory of Professor Judy Lieberman from the Immune Disease Institute (formerly the CBR Institute for Biomedical Research), a Harvard Medical School Affiliate. The in-licensed technology, which was highlighted in an article published in the journal Nature Biotechnology in 2005, represents another potential approach for delivery of RNAi therapeutics with systemic administration.

Massachusetts Institute of Technology (MIT)

In May 2007, Alnylam announced a major research collaboration with the David H. Koch Institute for Integrative Cancer Research at MIT and the laboratories of Drs. Daniel Anderson and Robert Langer, two world leaders in innovations on the delivery of biopharmaceuticals. As part of this collaboration, Alnylam is sponsoring a five-year research program focused on the delivery of RNAi therapeutics with the exclusive option to license future RNAi technology resulting from the research sponsorship.

MIT has been a collaborator of Alnylam's for several years. In 2006, we exclusively licensed a portfolio of patent applications that cover a wide variety of drug delivery techniques for nucleic acid compounds. These patent applications are based on research programs of Dr. Robert Langer at MIT, whose discoveries in drug delivery can be applied to delivery of RNAi-based therapeutics.

Our relationship with MIT dates back to the earliest days of Alnylam's history. In February 2003, Alnylam completed the in-licensing of a series of fundamental patents, the so-called "Tuschl I" and "Tuschl II" patents, in the then emerging field of RNA interference. MIT joined the Max Planck Institute and the Whitehead Institute as part of that licensing agreement.

Max Planck Institute

In August 2008, Alnylam formed an exclusive research agreement with the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, to investigate and characterize the molecular mechanisms underlying intracellular transport of siRNA. Alnylam scientists will work closely with the laboratory of Marino Zerial, PhD, whose team is internationally recognized as being at the forefront of the intracellular trafficking field and have the needed expertise and capabilities to investigate cellular uptake pathways in a robust and high-throughput manner. Alnylam will have an option on any intellectual property that results from this agreement.

In October 2004, Alnylam formed a co-exclusive agreement with the Max Planck Institute to in-license the therapeutic rights for the "Tuschl III" patent. During his research efforts at the Max Planck Institute, Dr. Tuschl discovered more than 120 naturally occurring microRNAs that are present in mammalian cells. These microRNAs have the potential to be new drug targets or therapeutic products and are the subject of the licensed patent applications. The Tuschl III patent series, which Alnylam and Isis both co-exclusively licensed for all therapeutic applications, now forms part of Regulus' exclusive patent position in this space. The first US patent in the Tuschl III series issued on June 19, 2007 as US Patent No. 7,232,806.

Our relationship with the Max Planck Institute dates back to the early days of the company's history. In February, 2003, Alnylam announced the licensing of a series of patents in the emerging field of RNA interference. Garching Innovation, the Munich based Technology Transfer Organization of the Max-Planck Society, led the negotiations on behalf of Max-Planck and the other co-owners of the licensed patents of Alnylam's founders. By entering into this transaction Alnylam has solidified its rights to develop therapeutics under the strongest intellectual property estate in the burgeoning field of RNA interference.

Mayo Clinic

In October 2003, Alnylam formed a research collaboration with the Mayo Clinic to apply its RNAi technology to silence alpha-synuclein involved in the causal pathway of Parkinson's disease.

The Michael J. Fox Foundation for Parkinson's Research

In August 2005, the Michael J. Fox Foundation awarded Alnylam a grant under the Foundation's Drug Discovery and Development program aimed at addressing obstacles that currently impede progress in bringing new Parkinson's disease therapies to market. Alnylam and scientific collaborators at Mayo Clinic are applying RNAi technology toward the development of a therapeutic for treatment of Parkinson's disease.

In January 2008, the Michael J. Fox Foundation awarded Alnylam and collaborators a second grant to further develop an RNAi therapeutic for the treatment of Parkinson's disease. The four-year grant, part of the Foundation's LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson's Institute and Clinical Center of Sunnyvale, California.

National Institute of Allergy and Infectious Diseases (NIAID)

Funded by the National Institute of Allergy and Infectious Diseases

In September 2006, NIAID, a division of the National Institutes of Health (NIH) awarded Alnylam a Small Business Innovation Research (SBIR) grant to advance the development of RNAi therapeutics for pandemic influenza.

Additionally, in September 2006, Alnylam was awarded a $23M contract to develop a RNAi anti-viral therapeutic against the Ebola virus. With this program, Alnylam is working with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). This contract fully supports all activities from program initiation through filing IND.

The Rockefeller University

In October 2005, scientist from Alnylam and Rockefeller University announced apublication that studied novel approach to regulate gene expression through the silencing of microRNAs. The publication described the rational design of a potential new class of chemically modified RNA-based drugs, called 'antagomirs', that specifically silence microRNAs across multiple tissue types following therapeutically relevant administration in animals. Alnylam has taken an exclusive license to all of The Rockefeller University's interest in antagomir technology and the basis of this research led to the formation of Regulus Therapeutics, the the joint venture with Isis Pharmaceuticals.

Salk Institute for Biological Studies

In August 2008, Alnylam completed an exclusive license agreement with the Salk Institute for Intellectual Property for RNAa activation, or RNAa, a new biological discovery for the activation of gene expression. RNAa is an emerging biological discovery involving double-stranded RNAs that target promoter regions in chromosomal DNA resulting in transcriptional activation of genes which may have applications in many human diseases, including certain genetic disorders and cancer. Studies on RNAa have been performed by the Gage lab at the Salk Institute (Kuwabara et al. Cell. 2004 Mar 19;116(6):779-93).

Stanford University

In May 2008, Regulus Therapeutics exclusively licensed from Stanford University rights to worldwide patent applications covering methods and compositions for antagonizing miR-181a to regulate immune responses. Changes in miR-181a levels have been shown to modify the response of immune cells and its antagonism could lead to a new way to treat inflammatory diseases.

Regulus is also the exclusive licensee of the patent portfolio that originated from Stanford University's discovery by Dr. Peter Sarnow that antagonism of miR-122 affects HCV replication. This patent portfolio has yielded US Patent No. 7,307,067, issued December 11, 2007, which claims methods of inhibiting HCV replication in a cell with an oligonucleotide antagonist targeted to miR-122.

In September 2003, we also completed a licensing agreement with Stanford University for intellectual property related to the method for inducing gene silencing through RNAi in adult mammals. The co-exclusive therapeutic license from Stanford for the RNA interference patent application and related technology which is based on the research of Dr. Mark Kay, Dr. Anton McCaffrey and colleagues at the Stanford University School of Medicine. This intellectual property encompasses the demonstration that delivery of synthetic si RNA molecules to an adult mammal can induce in vivo silencing of a specific target gene, thereby forming the basis for the systemic administration of RNAi-based therapies in mammals.

United States Defense Threat Reduction Agency (DTRA)

In August 2007, DTRA awarded Alnylam a $38M contract to develop a broad spectrum RNAi anti-viral therapeutic for the treatment of viral hemorrhagic fever. The goal of this research program is to develop a host targeted RNAi therapeutic for the treatment of hemorrhagic fever virus infection. This new contract fully supports all activities from program initiation through Phase I trials. Alnylam is working with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID).

University of California San Francisco (UCSF)

In August 2008, Alnylam completed an exclusive license agreement with UCSF for intellectual property for RNAa, a new biological discovery for the activation of gene expression. RNAa is an emerging biological discovery involving double-stranded RNAs that target promoter regions in chromosomal DNA resulting in transcriptional activation of genes which may have applications in many human diseases, including certain genetic disorders and cancer. Studies on RNAa have been performed by the Dahiya and the Li labs at UCSF (Li et al. PNAS. 2006 Nov 14;103(46):17337-42; Chen et al. Mol Cancer Ther. 2008 Mar;7(3):698-703; and Place et al. PNAS. 2008 Feb 5;105(5):1608-13).

The University of Georgia

In May 2005, Alnylam formed a research collaboration with scientists at the University of Georgia (UGA) to discover RNAi therapeutics for the treatment of pandemic flu, including the H5N1 avian flu.

University of Pennsylvania

In October 2009, it was announced that Alnylam will be participating in a $2.4 million research grant awarded to the University of Pennsylvania under the "American Recovery and Reinvestment Act of 2009", which will fund research over two years in the laboratories of Daniel Rader, M.D. of the University of Pennsylvania School of Medicine, Sekar Kathiresan, M.D. of Massachusetts General Hospital (MGH) and Harvard Medical School, and Alnylam. The goal of the initiative is to mechanistically evaluate the metabolic and molecular effects of 38 novel genes implicated by human genetic studies in prevention of cardiovascular disease and to discover and develop RNAi therapeutics towards these gene candidates. Alnylam will retain the rights to develop and commercialize RNAi therapeutics from the research effort.

University of Texas Southwestern Medical Center (UTSW)

In August 2008, Alnylam completed an exclusive license agreement with the UTSW for intellectual property for RNAa, a new biological discovery for the activation of gene expression. RNAa is an emerging biological discovery involving double-stranded RNAs that target promoter regions in chromosomal DNA resulting in transcriptional activation of genes which may have applications in many human diseases, including certain genetic disorders and cancer. The work by the Corey lab at UT Southwestern for the activation of the progesterone receptor was published last year (Janowski et al. Nat Chem Biol. 2007 Mar;3(3):166-73) and more recently Schwartz et al. Nat Struct Mol Biol. 2008 Aug;15(8):842-8.

In September 2007, Alnylam and UTSW were awarded a "Roadmap Grant" from the National Institutes of Health (NIH) for research on obesity. In the funded research, Alnylam is engaged in efforts to design, synthesize, and optimize RNAi therapeutic compounds toward disease targets involved in the cause or pathway of obesity discovered by UT Southwestern scientists. Alnylam retains the rights to develop and commercialize RNAi therapeutics from the research effort.

In June 2006, Alnylam entered into a collaboration with UTSW to evaluate new approaches for reducing LDL-cholesterol levels using RNAi therapeutics directed to a disease target called proprotein convertase subtilisn/kexin type 9, or PCSK9. PCSK9 is an important gene involved in the metabolism of LDL-cholesterol, or so-called "bad cholesterol." The normal role of the PCSK9 protein is to break down the LDL receptor (LDL-R); when there is less PCSK9 protein, there is more LDL-R on the cell surface. Research at UTSW has shown that reductions in humans in the levels of PCSK9 protein can lead to significant reductions of LDL in the blood, and also that mice lacking PCSK9 have significantly decreased cholesterol with no other adverse phenotype.