PARTNERSHIP PROGRAMS
We have entered into various arrangements with corporate, academic, and government collaborators, licensors, licensees, and others. In addition to the agreements summarized below, we conduct ongoing discussions with potential collaborators, licensors and licensees.
Corporate Partners - Outlicensing
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Corporate Partners - Inlicensing
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Academic Research Institutions
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Corporate Partners - Outlicensing
AnGes MG
In 2005, we granted an exclusive worldwide license to AnGes for use of our core DNA delivery technology in the development and commercialization of DNA-based products encoding Hepatocyte Growth Factor (HGF) for cardiovascular applications.
AnGes is developing DNA-based delivery of HGF for indications related to PAD and ischemic heart disease, or IHD, which affects blood supply to the heart muscle. AnGes initiated Phase 2 trials in the United States and Phase 3 trials in Japan in 2003 and 2004, respectively, with DNA-based HGF for PAD. AnGes also initiated Phase 1 trials in the United States for IHD in 2004. AnGes has partnered with Daiichi Pharmaceutical Co., Ltd. for worldwide development and commercialization of DNA-based HGF for PAD and IHD.
AnGes stopped its Phase 3 trial in June 2007 after an interim analysis on the first 41 patients showed that the primary efficacy endpoint in the trial had been achieved with statistical significance and that there were no major safety concerns related to treatment. On the basis of these data, AnGes is preparing to file for marketing approval in Japan.
In May 2006, Vical and AnGes entered into a collaborative agreement for Vical's Allovectin-7® cancer immunotherapeutic. Under the agreement, AnGes will provide up to $100 million in ongoing clinical trial funding and future sales-based milestones as Allovectin-7® is successfully commercialized. Vical retains exclusive marketing rights for Allovectin-7® in the United States and the rest of the world outside of specified Asian countries, for which AnGes has exclusive rights.
We announced in October 2008 that AnGes has signed a non-binding letter of intent with us indicating its mutual interest to license the development and marketing rights for our pandemic influenza DNA vaccines in Japan. AnGes plans to conduct due diligence on the pandemic influenza DNA vaccines, and both parties intend to negotiate terms and conditions potentially leading to a license.
For program status, see the Product Development table.
Sanofi-aventis Group
In 2000, sanofi-aventis licensed the rights to our core DNA delivery technology for cardiovascular applications using FGF-1, an angiogenic growth factor. Initial development is for patients with peripheral arterial disease, or PAD, a severe condition caused by blockage of arteries feeding the foot and lower leg. Published interim results from a Phase 1 clinical trial indicated that the FGF-1 plasmid-based therapeutic was well-tolerated, with no serious adverse events related to the treatment, and demonstrated reduction in pain and evidence of newly visible blood vessels three months after treatment. Sanofi-aventis has completed double-blind, placebo-controlled Phase 2 trials of its FGF-1 plasmid-based therapeutic in the United States and Europe and released data demonstrating improvement in amputation-free survival compared with placebo. Sanofi-aventis started a 500-patient Phase 3 trial in late 2007 and expects to file for marketing approval in 2010.
For program status, see the Product Development table.
Merck & Co., Inc
In 1991, we entered into an agreement with Merck, which was subsequently amended, providing Merck with certain exclusive rights to develop and commercialize vaccines using our core DNA delivery technology for specified human diseases. Under the agreement, as amended, Merck licensed preventive and therapeutic human infectious disease vaccines using our core DNA delivery technology.
In 2003, we amended the agreement, providing Merck options for rights to use our core DNA delivery technology for three cancer targets. The two disclosed targets were human epidermal growth factor receptor 2, or HER-2 and carcinoembryonic antigen, or CEA. In addition, Merck returned rights to us for certain infectious disease vaccines. Merck has retained rights to use the licensed technology for HIV, hepatitis C virus, and hepatitis B virus.
In 2005, Merck exercised the options related to three cancer targets that were granted under the 2003 amendment. We also amended the agreement with Merck to grant renewable options for additional cancer targets. In exchange, we obtained non-exclusive, sublicenseable rights to use the licensed technology for vaccines against HIV. Merck also obtained a fixed-term option to exclusively sublicense from us electroporation-enhanced delivery technology for use with HIV vaccines, on terms to be negotiated.
In 2005, Merck initiated a Phase 1 clinical trial of a DNA cancer vaccine based on our DNA gene delivery technology that uses pDNA encoding HER-2 and CEA. The Phase 1 trial will evaluate the safety, tolerability and immunogenicity of the vaccine.
In 2005, Merck initiated two Phase 2 trials of an investigational HIV vaccine based on a weakened version of a common virus (adenovirus type 5) as a delivery vector for three synthetically produced HIV genes known as gag, pol and nef. DNA technology licensed from Vical was not involved in these trials.
In late 2007, Merck announced the discontinuation of these two Phase 2 trials because the vaccine was not effective.
For program status, see the Product Development table.
Merial Ltd.
In 2004, we granted an exclusive license to Merial, a joint venture combining the animal health businesses of Merck and sanofi-aventis, for use of our core DNA delivery technology in a vaccine to protect dogs against melanoma. Under the agreement, Merial is responsible for research and development activities.
The Merial canine melanoma vaccine received conditional approval from the United States Department of Agriculture, or USDA, in 2007.
For program status, see the Product Development table.
Aqua Health Ltd. (Novartis)
In 2003, we granted a non-exclusive license to Aqua Health for use in Canada of our core DNA delivery technology in a vaccine against a disease that affects both wild and farm-raised fish. In 2005, Aqua Health received notification of approval from the Canadian Food Inspection Agency to sell its proprietary product, Apex-IHN® , a DNA vaccine to protect farm-raised salmon against infectious hematopoietic necrosis virus. We believe this approval is an important step in the validation of our DNA delivery technology.
For program status, see the Product Development table.
Invitrogen Corporation
In 1991, we licensed the use of certain proprietary lipids for research products applications to Life Technologies, Inc., or Life Technologies, which was subsequently acquired by Invitrogen in 2000. Invitrogen manufactures and markets these lipid compounds, and pays royalties to us on the sales of the lipids.
Corporate Partners - Inlicensing
Bioject Medical Technologies, Inc.
In 2006, we entered into an agreement with Bioject Medical Technologies, Inc., or Bioject, giving us an option to obtain a worldwide, non-exclusive license to develop and commercialize Bioject’s proprietary needle-free delivery technology for use with certain vaccines. Bioject’s needle-free injection works by forcing medication at high speed through a tiny orifice held against the skin. This creates a fine stream of high-pressure fluid penetrating the skin and depositing medication in the underlying tissue.
CytRx Corporation
In 2001, we entered into an exclusive agreement with CytRx Corporation, or CytRx, which grants us rights to use or sublicense CytRx’s poloxamer technology to enhance viral or non-viral delivery of polynucleotides in all unexcluded preventive and therapeutic human and animal health applications, including CMV. The agreement excludes applications for prostate-specific membrane antigen and four infectious disease vaccine targets that had been licensed to Merck. In addition, the agreement permits our use of CytRx’s technology to enhance the delivery of proteins in prime-boost vaccine applications that involve the use of polynucleotides.
Government Collaborators
CRADAS
We have entered into several Collaborative Research and Development Agreements, or CRADAs, with the NIH, the Naval Medical Research Center, and the U.S. Army Medical Research Institute of Infectious Diseases to promote the development and use of our technologies in DNA vaccine candidates. Our general responsibility under each CRADA includes providing materials and/or expertise to the government agency in return for an option to obtain an exclusive license for rights to any intellectual property that result from the CRADA.
NIH Vaccine Research Center
The NIH through its Dale and Betty Bumpers Vaccine Research Center, or VRC, has clinical stage vaccine programs based on our technology for HIV and Ebola. The NIH has also completed Phase 1 studies based on our technology for WNV and SARS.
HIV. In 2007, the NIH released results from its Phase 2a HIV vaccine trial using a DNA prime-adenoviral vector boost approach. The results showed the vaccine regimen was safe and well-tolerated, and was effective in inducing T-cell immune responses in up to 70% of the vaccine recipients. The NIH planned to further test the DNA prime-adenoviral vector boost approach in a trial known as the PAVE 100 study, which was designed to enroll 8,500 volunteers. We manufactured the DNA prime component of the vaccine to be used in the PAVE 100 study. The study was to begin recruitment in October 2007, but was postponed following the NIH’s review of interim data from an unrelated Phase 2b trial known as the STEP study which utilized an adenoviral vector vaccine alone. The NIH concluded that the adenoviral vector vaccine failed to prevent HIV infection or reduce viral load, and the vaccinated group exhibited a higher incidence of infection than the placebo group. In July 2008, after soliciting and considering broad input from the scientific and HIV communities, the NIH determined that it would not conduct the Pave 100 study. However, the NIH believes the DNA prime-adenoviral vector boost approach is scientifically intriguing and sufficiently different from previously tested HIV vaccines to consider testing it in a smaller, more focused clinical study.
Ebola. The VRC began human testing of an investigational DNA vaccine against Ebola in 2003. In February 2006, the VRC presented data from its Phase 1, randomized, placebo-controlled, dose-escalation study, which was the first human trial for any Ebola vaccine. The DNA vaccine used in the Phase 1 trial incorporates genetic material encoding core and surface proteins from two strains of Ebola. The data indicated that the Ebola vaccine candidate administered using Vical’s proprietary DNA delivery technology was safe and well-tolerated, and produced both antibody and T-cell responses specific to Ebola proteins in six healthy volunteers who received the full three doses of vaccine in the study. We have secured a license from the NIH for the commercialization rights and the technology used in its Ebola vaccine.
Contract Manufacturing for the VRC. In 2002, we entered into a subcontract agreement, which was subsequently amended, to manufacture HIV, Ebola, WNV, and SARS DNA vaccines for the VRC for use in the studies discussed above. In 2003, we entered into a separate subcontract agreement to manufacture bulk DNA vaccines for the VRC. These subcontracts are issued and managed on behalf of the VRC by SAIC-Frederick, Inc. under the umbrella of a federally funded contract with the NIH. In 2007, we completed all production orders under our 2003 subcontract agreement with the VRC and this agreement expired in July 2007. We do not expect to receive future material orders for the manufacture of bulk DNA from the subcontractor as the subcontractor has built its own DNA vaccine manufacturing facility to meet the future manufacturing needs of the VRC.
Manufacturing Process Development. In 2005, we were awarded funding for a one-year, $0.5 million project for the Defense Advanced Research Projects Agency of the U.S. Department of Defense. The award funded feasibility studies of a new approach for rapidly manufacturing large quantities of DNA vaccines. Conventional vaccine development and manufacturing methods require prolonged effort after the emergence of a new pathogen for production of even a single dose for testing. Current DNA vaccine development and manufacturing processes allow initial production of vaccines in as little as three months after selection of a gene sequence associated with a pathogen, but quantities are limited by the batch-processing capacity of available manufacturing equipment.
In 2007, we were awarded funding for a three-year, $6.0 million grant from the NIAID for further development of a DNA vaccine manufacturing process with the potential to produce several million doses of vaccines in a matter of days. Our RapidResponse™ DNA vaccine manufacturing platform is intended to significantly reduce the time required to develop, manufacture and deploy vaccines against emerging diseases during the early stages of an infectious outbreak. By using a cell-free manufacturing process, we believe that the RapidResponse™ DNA platform can overcome the time, capacity and cost challenges of manufacturing conventional vaccines for diseases such as influenza, which use killed or disabled viruses grown in chicken eggs or via cell culture, requiring months of production time in large, dedicated facilities.
Academic Research Institutions
Wisconsin Alumni Research Foundation
Under a 1989 research agreement, scientists at the University of Wisconsin, Madison, and our scientists co-invented a core technology related to intramuscular DNA administration. In 1991, we licensed from the WARF its interest in that technology. We paid the WARF an initial license fee and agreed to pay the WARF a percentage of certain initial upfront monetary payments and a small percentage of some royalty payments received from third parties under sublicense agreements.
University of Michigan
In 1992, we licensed from the University of Michigan rights to various U.S. and international patents related to the injection of DNA-based therapeutics into tumors that, for example, provide additional protection for Allovectin-7®. In July 2005, we amended the agreement to exclude certain patents. In February 2006, we entered into an additional agreement with the University of Michigan which provides for rights to a lipid patent related to the injection of DNA-based therapeutics which we believe provides additional protection for Allovectin-7®.
University of Massachusetts
In 2006, we licensed from the University of Massachusetts certain intellectual property related to the use of DNA based vaccines with influenza.
The Wistar Institute
In 2008, we licensed from The Wistar Institute exclusive, worldwide rights to Wistar’s Towne strain of CMV and related technologies. The Towne strain is an attenuated, or weakened, form of human CMV which was developed for potential vaccine applications by vaccinologist Stanley Plotkin, M.D., a member of Wistar’s research faculty from 1960 to 1991 and co-author of the definitive medical text “Vaccines.”
Academic Licenses
We have granted non-exclusive, academic licenses to our DNA delivery technology patent estate to ten leading research institutions: Stanford University, Harvard University, Yale University, the Massachusetts Institute of Technology, Fred Hutchinson Cancer Research Center, Texas Tech University Health Sciences Center, University of Iowa, University of Notre Dame, University of Pittsburgh, and University of Washington. The academic licenses are intended to encourage widespread commercial use of our innovative DNA delivery technologies in the development of new antibodies, vaccines, therapeutic proteins, and diagnostics. The academic licenses allow university researchers to use our technology free of charge for educational and internal, non-commercial research purposes. In exchange, we have the option to exclusively license from the universities potential commercial applications stemming from their use of the technology on terms to be negotiated.