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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Research Institutions
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Corporate Partners - Outlicensing
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.
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.
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.
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, an affiliate of the Swiss-based company Novartis Animal Health Inc., for use in Canada of our core DNA delivery technology in a vaccine against Infectious Haematopoietic Necrosis Virus, or IHNV, a disease that affects both wild and farm-raised fish. In July 2005, Aqua Health received approval from the Canadian Food Inspection Agency to sell its proprietary product, APEX-IHN, a DNA vaccine to protect farm-raised salmon against IHNV.
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
Inovio Biomedical Corporation
In 2003, we entered into an agreement with Inovio, giving us options to worldwide exclusive licenses to use Inovio's proprietary electroporation technology in combination with our DNA delivery technologies for undisclosed targets. In October 2004, we exercised options and we amended the agreement to include HIV. Our first application of the licensed technology is for enhanced delivery in solid tumors of the pDNA encoding IL-2. We began Phase 1 safety testing in 2005 of intralesional administration of IL-2 pDNA followed by local electroporation in certain patients with metastatic melanoma.
CytRx Corporation
In 2001, we entered into an exclusive agreement with CytRx which grants us rights to use or sublicense CytRx's poloxamer technology to enhance viral or non-viral delivery of polynucleotides in preventive and therapeutic human and animal health applications. 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.
Research Institutions
National Institutes of Health
In 2002, we entered into a subcontract agreement, which was subsequently amended, to manufacture HIV, Ebola, West Nile Virus, or WNV, and severe acute respiratory syndrome, or SARS, DNA vaccines for the VRC. In 2003, we entered into a separate subcontract agreement to manufacture bulk DNA vaccines for the VRC.
Using clinical supplies provided under these agreements, the VRC has conducted Phase 1 and Phase 2 trials of investigational DNA vaccines against HIV, and Phase 1 trials of investigational DNA vaccines against Ebola, severe acute respiratory sydrome, or SARS, and West Nile virus, or WNV.
A Phase 2 trial demonstrated that a “DNA prime-adenoviral vector boost” vaccine regimen against HIV was safe and well-tolerated, and was effective in inducing T-cell immune responses in up to 70% of the vaccine recipients.
A Phase 1 trial demonstrated that the Ebola vaccine candidate was safe and well-tolerated, and produced both antibody and T-cell responses specific to Ebola proteins in healthy volunteers who received the full three doses of vaccine.
A Phase 1 trial demonstrated that the WNV vaccine candidate was safe and well-tolerated, and produced WNV-specific neutralizing antibody responses in all healthy volunteers who returned for follow-up testing after completing the three-dose vaccination schedule in the study.
Results from a Phase 1 trial of the SARS vaccine candidate have not yet been released.
For program status, see the Product Development table.
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®.
Office of Naval Research
In 2003, we entered into an agreement with the Office of Naval Research, or ONR, under which the ONR agreed to provide funding to us for research and development work on a malaria vaccine. We do not plan to participate in development of a malaria vaccine.
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.