GenVec, Inc. (“GenVec,” “we,” “our,” or the “Company”) is a biopharmaceutical company developing novel gene-based therapeutic drugs and vaccines. Our lead product candidate, TNFerade ä biologic (TNFerade), is being developed for use in the treatment of cancer. TNFerade is currently the subject of a randomized, controlled, Phase II/III pivotal trial, known as PACT, for first-line treatment of inoperable, locally-advanced pancreatic cancer. We completed enrollment in the Phase II portion of PACT in 2006 and interim data supporting a survival advantage in the TNFerade group were disclosed. Based on data available from the first 51 patients, survival at one year was 70.5 percent in the TNFerade plus standard of care group versus 28 percent in the standard of care group. Enrollment in the Phase III portion of the trial is ongoing.
TNFerade is also being evaluated for possible use in the treatment of other types of cancer. Clinical trials are in progress in head and neck cancer, metastatic melanoma and rectal cancer. Encouraging results have previously been reported in studies for esophageal cancer and in soft tissue sarcomas. Using the Company’s core adenovector technology, TNFerade, stimulates the production of tumor necrosis factor alpha (TNF a ), a known anti-tumor protein, in cells of the tumor.
We, in partnership with our collaborators, also have multiple vaccines in development. All of these funded programs utilize our core adenovector technology. We have a collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) to develop a HIV vaccine, a program with the U.S. Naval Medical Research Center and the PATH Malaria Vaccine Initiative to develop vaccines for malaria and vaccine development efforts for foot-and-mouth disease (FMD) with the U.S. Department of Homeland Security and the U.S. Department of Agriculture.
Our research and development activities have yielded additional novel product candidates that utilize our technology platform and we believe they represent potential commercial opportunities. We have conducted initial clinical testing of AdPEDF for the treatment of wet age-related macular degeneration (AMD), a leading cause of vision loss in people over 50. In the fields of hearing and balance disorders, preclinical research was recently published demonstrating that delivery of the atonal gene using a GenVec adenovector can re-establish sensory cells in the inner ear and restore both hearing and balance. There are currently no effective treatments available for patients who have lost all balance function, and hearing loss remains a major unmet medical problem.
Our core technology has the key advantage of localizing protein delivery in the body. This is accomplished by using our adenovector platform to locally deliver genes to cells, which then direct production of the desired protein. In the case of TNFerade, for example, this approach reduces the side effects caused by systemic delivery of the TNF a protein. For vaccines, the goal is to induce a broad immune response against a target protein or antigen. This is accomplished by using the adenovector to deliver a gene that causes production of antigen, which then stimulates the desired immune reaction by the body.
As a biopharmaceutical company, our business and our ability to execute our strategy to achieve our corporate goals are subject to numerous risks and uncertainties. Material risks and uncertainties relating to our business and our industry are described in Item 1A of this Form 10-K. The description of our business in this Form 10-K should be read in conjunction with the information in Item 1A.
OUR STRATEGY
Our primary objective is to develop and commercialize products with significant medical benefit. We plan to achieve this objective through the following strategies:
Develop and initially commercialize our lead product candidate, TNFerade, for the treatment of cancer. We intend to seek marketing approval for TNFerade for the treatment of locally advanced pancreatic cancer. We intend to commercialize TNFerade in the United States and build the commercial value of TNFerade by expanding its clinical use in a variety of cancers.
We will seek to retain significant commercial rights to TNFerade in North America and secure strategic partnerships to support TNFerade registration and commercialization efforts in Europe, Asia, and other world markets. Based on the survival data obtained to date, we believe the use of TNFerade in locally advanced pancreatic cancer represents a feasible path to commercialization.
Utilize our technology platform and early-stage product portfolio to take advantage of commercial opportunities. Our research and development efforts have generated additional product candidates for vision loss and hearing and balance disorders including:
• New approaches to improve the treatment of AMD based on our proprietary PEDF gene delivery technology.
• Treatments of hearing and balance disorders based on our proprietary Atoh1 gene which has the potential to address poorly met medical needs.
Seek collaborative partnerships that will leverage our technology. We will continue to seek to enhance our gene delivery capabilities through internal research as well as external collaborations and possibly acquisitions. We have received funding from research and development collaborations to develop preventative vaccine candidates against HIV, malaria and other infectious diseases, an anti-viral and vaccine to prevent the spread of foot-and-mouth disease and a second-generation TNFerade product candidate. We have received peer-reviewed external funding from the U.S. Government and from non-profit foundations to improve our technology platform for vaccine and gene delivery applications. We intend to further strengthen our technologies relating to process development, formulation, and manufacturing through our existing and future relationships.
THERAPEUTIC PRODUCT DEVELOPMENT PROGRAMS
TNFerade, our most advanced product candidate, is a novel approach to treating cancer. Administered directly into tumors, TNFerade is an adenovector, or DNA carrier, which contains the gene for tumor necrosis factor-alpha (TNF a ), a potent immune system protein with well-documented anti-cancer effects. TNFerade works by causing cells in the tumor to produce and secrete TNF a . TNF a binds to cells in the tumor, leading to the death of cells in the tumor. We are developing TNFerade for use in combination with radiation and/or chemotherapy for the treatment of various cancers. Emerging clinical data suggest that TNFerade may prolong the survival of patients with locally advanced pancreatic cancer when TNFerade is combined with front-line therapy. Clinical data also suggest that TNFerade has activity against a variety of different types of cancer.
In two separate Phase I trials (solid tumors and soft tissue sarcomas), TNFerade demonstrated, in conjunction with standard radiation therapy, that it was generally well tolerated, and tumor size reduction of 25 percent or greater was observed in more than 70 percent of patients in 12 different tumor types, including pancreatic, melanoma, rectal, small cell lung, breast, and sarcoma. Results from the Phase I trial in solid tumors were published in the February 15, 2004 issue of the Journal of Clinical Oncology . The Phase I study of 14 patients with soft tissue sarcoma, published in the September 1, 2004 issue of Clinical Cancer Research , demonstrated 95 percent pathologic complete response, with TNFerade activity confirmed in a similar indication for which the TNF a protein has been approved for use in Europe. In January 2006, we presented long-term survival data from a Phase II study of TNFerade in 17 patients with locally advanced esophageal cancer at the ASCO Gastroenterological Symposium demonstrating two-year survival of 71 percent, for all dosage levels of TNFerade, compared to an average two-year survival of 33 percent based on five comparable studies.
Based on the results of our Phase I studies, we initiated a Phase II dose-escalation study in 50 patients with locally-advanced, inoperable pancreatic cancer to determine the best therapeutic dose for use of TNFerade in combination with standard chemoradiation. Results from this study suggested a dose-dependent improvement in tumor response, rates of surgical resection, time to disease progression, and survival. Based on these data, we initiated a randomized, controlled Phase II study of 74 patients. In consultation with the FDA, this Phase II study was amended in March 2006 to become a pivotal Phase II/III 330-patient trial (PACT) that would support registration of TNFerade for this indication. The primary endpoint for the PACT trial is 12-month survival. We completed interim safety and efficacy analyses of the Phase II/III trial in the fourth quarter of 2006, and in December 2006, we reported the preliminary analysis of safety data based on the first 40 patients treated, and survival data on the first 51 patients treated.
Results showed that one-year survival was 70.5 percent in the TNFerade plus standard of care group versus 28 percent in the standard of care group. The Phase III portion of this multi-site trial is ongoing in the United States.
New treatments for pancreatic cancer are urgently needed. According to the American Cancer Society, pancreatic cancer is the fourth leading cause of cancer deaths in the United States, and the number of cases being diagnosed has been increasing year to year. Approximately 37,000 new cases of pancreatic cancer will be diagnosed this year in the United States, and nearly all of these patients will probably die of their disease.
Additional Indications: TNFerade is being evaluated for its potential use in the treatment of several other cancers:
• Head and Neck Cancer. According to the American Cancer Society, approximately 34,000 new cases of head and neck cancer will be diagnosed in the United States this year. We are sponsoring two separate Phase I/II studies at the University of Chicago to explore the use of TNFerade as a component of standard of care treatment for head and neck cancer, a disease where local control is crucial for effective treatment and considered an accepted regulatory endpoint for this indication. The two studies were initiated in January 2007 and are being funded, in part, by the National Cancer Institute. The first study will enroll up to 70 patients and examine TNFerade as a second-line treatment for inoperable, recurrent tumors. The second study will enroll up to 60 elderly or frail patients with new onset, locally advanced disease. Investigators will first determine the best dose in each indication, and will assess safety and the ability of TNFerade to control the local spread of the cancer following treatment.
• Metastatic Melanoma. According to the American Cancer Society, approximately 62,000 new cases of melanoma will be diagnosed in the United States this year, and approximately 16 percent or 10,000 of these cases will be diagnosed as metastatic. In the Phase I study of TNFerade, all three patients with metastatic melanoma showed objective responses, and two of the three patients showed disease-free survival greater than three years. Based on these data, a Phase II trial in metastatic melanoma was initiated to evaluate anti-tumor activity, time to disease progression, survival and safety. Patients will receive TNFerade in combination with radiation therapy. Evaluation of the first 10 patients treated in this protocol is required before enrolling additional patients.
• Rectal Cancer. According to the American Cancer Society, approximately 41,000 new cases of rectal cancer will be diagnosed in the United States this year. A Phase II trial is in progress to assess the ability of TNFerade to improve tumor responses in conjunction with standard chemoradiation. This single-site study is being done in collaboration with the National Cancer Institute and is designed to compare TNFerade plus standard of care therapy versus standard of care therapy in the treatment of patients with biopsy-proven rectal cancer. One objective of this study is to achieve better surgical outcomes in these patients, such as avoidance of colostomy.
The following table summarizes key information regarding our ongoing TNFerade clinical studies:
| TARGETED # OF | ||||||
| DISEASE INDICATION | DEVELOPMENT STAGE | PATIENTS | ||||
Pancreatic Cancer
|
Phase II/III — Randomized, Controlled | 330 | ||||
Melanoma
|
Phase II — Proof of Concept | 29 | ||||
Rectal Cancer
|
Phase II — Dose Escalation | 10 | ||||
Head and Neck Cancer
|
Phase I/II — Dose Escalation/Recurrent Tumors | 70 | ||||
Head and Neck Cancer
|
Phase I/II — First-line Treatment/Elderly | 60 | ||||
Additional Therapeutic Programs
• AdPEDF is being developed for patients with wet age-related macular degeneration (AMD), the leading cause of blindness in people over the age of 50. AMD is a progressive eye disease characterized by the growth of abnormal blood vessels in the macula, the area of the eye that controls central vision and visual acuity. Approximately 200,000 new cases of wet age-related macular degeneration are diagnosed each year in the United States and there are an estimated 500,000 cases diagnosed worldwide.
We have completed a dose-escalation Phase I clinical trial of AdPEDF in patients with severe AMD. Data from this trial demonstrated that AdPEDF was generally well tolerated and showed evidence of slowing disease progression for six to twelve months after a single intravitreal injection of AdPEDF. Results from this study were published in the February 2006 issue of Human Gene Therapy . We expanded the Phase I clinical testing of AdPEDF in AMD patients with less severe disease and, in March 2006, announced the completion of enrollment of this 22-patient trial. Data from this study are currently being collected for analysis. AdPEDF uses our proprietary adenovector to deliver the pigment epithelium-derived factor (PEDF) gene to produce PEDF protein in the treated eye. PEDF is naturally produced in the eye and serves two important functions. It regulates blood vessel growth and is also a neuro-protective agent of the photoreceptors (the vision-sensing cells of the eye) responsible for sight. PEDF differs from other therapies in its potential to protect the retina from damage caused by fragile, leaky, abnormal blood vessels. Preclinical studies have demonstrated that AdPEDF can rapidly elevate intraocular PEDF protein levels in the eye, inhibit growth of unwanted blood vessels in the eye, cause selective regression of established abnormal blood vessels, and protect the retina from further damage. We believe that PEDF holds the promise to stabilize or improve vision in patients suffering from AMD.
• TherAtoh is our adenovector for delivering the human atonal gene to trigger the production of therapeutic proteins by cells in the inner ear. The Company has a research program focused on the restoration of hearing or balance function through the regeneration of critical cells of the inner ear. Hearing and balance require specialized cells of the inner ear called sensory hair cells. During embryonic development, a gene termed atonal (Atoh1) induces the generation of these cells. We have demonstrated in multiple animal models that the production of the Atoh1 protein results in the formation of new inner ear sensory hair cells, and the restoration of hearing and balance function. There are currently no marketed drug therapies in the U.S. to treat hearing loss or balance disorders.
• BIOBYPASS â . As a result of our previously announced decision in May 2006 to focus our resources on the clinical development of TNFerade, the Company ceased further patient enrollment in our BIOBYPASS â clinical trial for the treatment of severe coronary artery disease. In agreement with our collaborator, Cordis Corporation, patients enrolled in the Phase II study will complete follow-up under the study protocol, and data will be collected and analyzed in accordance with the research agreement between GenVec and Cordis. We retain exclusive development rights to BIOBYPASS â and will explore alternative commercialization strategies as data and circumstances warrant.
VACCINES DEVELOPMENT PROGRAM
In addition to our internal product development programs, we are working with collaborators to develop new applications for our technology, such as preventative vaccines to treat HIV, malaria and other infectious diseases, and veterinary vaccines for foot-and-mouth disease. We describe the collaborations for these vaccine development programs in the section below entitled “Partnerships and Collaborative Relationships.”
• Global HIV Vaccine – With our collaborators, we are developing and providing adenovector-based vaccine candidates targeted against the major strains of HIV present in the world. The Vaccine Research Center (VRC) has completed multiple Phase I clinical trials and is currently conducting multiple Phase IIa clinical trials involving this vaccine candidate, including an international 480-subject study. In addition, this vaccine candidate is being tested as a therapeutic vaccine in a 15 subject, Phase I study with the objective to determine safety and collect evidence of efficacy as measured by immunogenicity and reduction in viral load. GenVec has manufactured late-stage clinical supplies for a proof-of-concept efficacy trial where approximately 8,000 individuals will be enrolled in a Phase IIb international study. This study is to be conducted and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and its collaborators and is expected to commence in 2007.
• Malaria – With our collaborators, we are generating vaccine candidates for the prevention of malaria. We have produced clinical supplies of a multi-antigen vaccine candidate and, under the auspices of the U.S. Naval Medical Research Center (NMRC), a Phase I/II clinical study was initiated in January 2007. There are currently over 300 million cases of malaria in the world each year resulting in 1.5 to 3.0 million deaths annually, mostly among children.
• Foot-and-mouth disease (FMD) – FMD is a highly contagious viral disease affecting cows and other animals with cloven hoofs. With our collaborators, we are developing vaccine and anti-viral candidates for the prevention and containment of FMD outbreaks in the United States. Initial testing with a vaccine against a single type of FMD showed that inoculated cattle challenged with the virus that causes foot-and-mouth disease did not develop symptoms.
• Seasonal and pandemic influenza – We have a collaboration with the VRC to develop and supply potential vaccine candidates for seasonal and pandemic flu. Initial candidates are in preclinical testing.
PARTNERSHIPS AND COLLABORATIVE RELATIONSHIPS
We have entered into various arrangements with corporate, academic, and government collaborators that help to offset our development costs, enhance our technology and product development efforts, and reduce the risks associated with product commercialization. For example, we are currently working with selected U.S. government institutions to develop new applications, such as vaccines, for our proprietary technology. Potential partnership and collaborations are evaluated according to strategic, operational, and financial criteria.
We have received governmental funding to advance the clinical development of our product candidates, and to develop vaccines against HIV, malaria and other infectious diseases and veterinarian vaccines against foot-and-mouth disease. These collaborations include:
National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). In December 2001, the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health selected GenVec to collaborate in the development of worldwide preventative HIV vaccine candidates. This collaboration was expanded to include the development of a SARS vaccine candidate (April 2003) and an influenza vaccine candidate (February 2006). The collaboration includes a Cooperative Research and Development Agreement (CRADA) and a cost-plus subcontract, which is managed for the VRC through SAIC-Frederick, Inc., with potential total revenue to GenVec under the contract of approximately $53 million. Under the subcontract, the Company is responsible for constructing and producing adenovector-based vaccine candidates utilizing our proprietary cell line and second-generation adenovector technology. The subcontract will extend through the end of fiscal year 2008 if annual renewals are exercised. Revenue recognized under this program amounted to $13.9 million in 2006, $18.8 million in 2005, $7.2 million in 2004, and $7.2 million in 2003. In October 2006, GenVec entered into an additional contract directly with NIAID, providing up to $52 million in revenue to GenVec with the exercise of annual renewal options, to support the transfer of our manufacturing and purification processes to the Dale and Betty Bumpers Vaccine Research Center’s Vaccine Pilot Plant in Frederick, Maryland. The Vaccine Pilot Plant is part of NIAID and produces materials for clinical research. This contract will further clinical development of an HIV vaccine, and facilitate the development of a larger-scale manufacturing and product-release process necessary for further vaccine production. This new contract also provides the VRC with a non-exclusive research license to GenVec’s proprietary adenovector, production cell line, manufacturing process, and formulation technologies for HIV vaccines, which will allow the production of next-generation HIV vaccines.
Department of Homeland Security (DHS). In February 2007, we signed a new three-year contract with the DHS to further support the development and manufacture of novel adenovector-based vaccines against FMD. Under the new agreement, we will receive up to $6 million in program funding the first year and up to a total of $15 million over three years if DHS exercises its annual renewal options under the contract. GenVec will be responsible for the development, production, and regulatory approval of the vaccine while the DHS will be responsible for conducting animal studies at the Plum Island Animal Disease Center. The vaccines under development will utilize our proprietary adenovector technology and a novel cell line capable of producing antigens that would normally inhibit production.
U.S. Department of Agriculture (USDA). In September 2004, the Company entered into a collaboration with the Agricultural Research Services (ARS), a branch of the USDA, which included a CRADA and $0.3 million in funding through a Specific Cooperative Agreement for the development, production and evaluation of anti-virals to prevent the spread of FMD in cattle. In March 2006, the Company announced the amendment of this agreement to include up to an additional $1.7 million for the construction of vaccines against FMD. Under the agreement, the Company will be responsible for constructing adenovector-based vaccine candidates using its proprietary cell line and second-generation adenovector technology. As part of the cooperative efforts, ARS will provide the Company with optimized FMD antigens and anti-viral genes to be used in the development of the adenovector-based vaccines and anti-virals as well as provide evaluation of the vaccine candidates in animals.
U.S. Naval Medical Research Center (NMRC). In January 2003, we entered into a collaboration with the NMRC, which included a CRADA and a two-year, $1.9 million contract to develop and construct vaccines against malaria and dengue virus using our proprietary adenovector technologies and production cell line. Under the CRADA, NMRC will provide the Company with optimized malaria genes to be used in the development of the adenovector-based vaccines as well as provide preclinical evaluation of the vaccine candidates. In January 2005, we signed a one-year, $1.6 million fixed price contract for the production of malaria vaccines under current Good Manufacturing Practices (cGMP) standards. The NMRC tested the vaccine candidates in preclinical and animal models to assess safety and effectiveness. In conjunction with the preclinical evaluation of the vaccine, we provided regulatory support to NMRC for an Investigational New Drug application (IND) with the FDA. A Phase I/II clinical trial being conducted and funded by NMRC was initiated in January 2007.
PATH’s Malaria Vaccine Initiative (MVI). In March 2004, we signed a two-year, $2.6 million contract with MVI for the development, production and evaluation of vaccines against malaria. Under the contract, the Company will be responsible for optimizing and constructing multi-valent, multi-antigen adenovector-based vaccine candidates using our proprietary cell line and second-generation adenovector technology, and testing these vaccine candidates in preclinical animal models. This agreement has been amended to increase the total contract value of approximately $3.1 million and extend the term through August 2007.
Fuso Pharmaceuticals Industries, Ltd (FUSO). Funding under a three-year $4.5 million funded research agreement with FUSO ended on December 31, 2006. This collaboration focused on potential targeted cancer therapy product candidates for development in Japan by FUSO. FUSO has elected not to develop product candidates for the Japanese market at this time.
Sponsored Research. We sponsor research at leading academic institutions to enhance our ability to discover, evaluate, and develop new product candidates. Our academic collaborations currently include an agreement with the University of Chicago (TNFerade).
DRUG DISCOVERY AND DEVELOPMENT PLATFORM
We focus on developing differentiated gene delivery technology based on molecularly modified adenovectors. Our technology enables us to:
• Rapidly put genes or antigens into vectors to evaluate function and usefulness in therapy;
• Deliver our product candidates to specific organs or cell types to avoid systemic exposure;
• Achieve efficient delivery of gene or antigen to, and stimulate protein expressions in, target cells;
• Control the amount and duration of therapeutic protein production to allow flexibility in treating different diseases; and
• Scale our manufacturing process for commercial production.
Our product candidates combine a gene with a vector. Our vectors are derived from a naturally occurring virus, called an adenovirus. In humans, adenoviruses reproduce in certain tissues, spread, and can cause a form of the common cold. We design our vectors so that they cannot reproduce themselves or cause a cold. This limits toxicity, including unwanted effects on target cells and the surrounding tissues. We have multiple versions of vectors to suit different applications in therapeutic and vaccine products.
When administered to tissues, our vectors enter target cells, which cause them to produce the protein encoded by the inserted gene. In addition, adenovectors can be re-engineered to alter their performance characteristics, potentially including their ability to selectively deliver genes to targeted tissue.
We believe that adenoviruses are an excellent starting point for generating vectors because they efficiently deliver genes, can be readily modified, and have the following safety characteristics:
• Adenoviruses do not integrate into the DNA of the target cell, thereby minimizing the potential for mutations that can occur with other vector systems.
• Adenoviruses are naturally eliminated from cells and tissues.
• Vectors derived from adenoviruses have been generally well tolerated in clinical testing when administered locally. Thousands of patients have been treated with adenovectors with very few serious adverse events related to these vectors.
TECHNOLOGY FOR LOCAL DELIVERY AND EXPRESSION OF GENES
Use of delivery devices. To achieve local production of proteins, we administer our product candidates directly to the site of disease using standard medical devices, such as injection catheters or syringes. Direct administration of our product candidates into diseased tissue allows us to increase effectiveness by achieving high concentrations of the protein at disease sites while improving safety by avoiding exposure throughout the body. For example, we have used percutaneous injection to administer TNFerade directly to tumors and intravitreous injection to administer AdPEDF directly into diseased areas of the eye.
Delivering genes to cells. We believe that we are a leader in understanding and modifying the molecular interactions that specify how vectors derived from adenoviruses bind to cells. Adenoviruses enter cells by binding to receptors on the surface of the cell.
We have developed vectors that enable us to create product candidates that deliver genes only to specific cells. In order to achieve selective delivery to target cells, we first disable the normal binding of vectors to cell surface receptors. We then insert new binding sites into the vector that bind to specific receptors found on the surfaces of target cells. We have a broad proprietary position covering such vectors. This technology is being used to develop second-generation oncology and vaccine candidates.
New Adenovector Platforms. As part of our vaccine collaborations, we have generated vectors based on different serotypes of adenovirus. We do this by our production cell line 293-ORF6, which supports the growth of all virus and vector serotypes tested to date. These vectors have the potential to improve vaccine potency and to generate mucosal immune responses. In addition, new serotypes of adenovirus vectors are being explored as second-generation TNFerade products.
Control of gene expression. Our technology also allows us to modify the location, duration and rate of therapeutic gene expression. We alter gene expression by inserting a sequence of DNA, called a promoter, into our vectors adjacent to the therapeutic gene. For some diseases, long-term expression of the therapeutic gene is required to achieve a clinical benefit. In TNFerade, local production of the TNF-alpha protein in cancerous tissue subject to radiation treatment and chemotherapy is regulated by inserting a specific proprietary promoter that increases protein production after radiation or chemotherapy.
LICENSES FOR THERAPEUTIC GENES
To create our product candidates, we combine our vectors with genes intended to produce proteins with therapeutic potential. We have secured licenses to applicable genes for this purpose. We often seek to obtain exclusivity, consistent with our business needs, when securing such licenses. In return for the rights we receive under our gene licenses, we typically are required to pay royalties based on any commercial sales of the applicable product during a specified time period, as well as provide additional compensation, including up-front license fees and product development-related milestone payments. Our gene licenses for our lead product candidates include:
| SOURCE | GENE | NATURE OF LICENSE | ||
Scios, Inc.
|
VEGF121 | Worldwide, exclusive for gene therapy applications | ||
Northwestern University
|
PEDF | Worldwide, exclusive for ocular gene therapy applications | ||
Baylor College of
Medicine
|
Atoh1 | Worldwide, exclusive for gene therapy applications |
Any of our licenses may be terminated by the licensor if we are in breach of a term or condition of the license agreement, or if we become insolvent. In addition, some of our licenses require us to achieve specific milestones.
PATENTS, LICENSES, AND PROPRIETARY RIGHTS
We generally seek patent protection for our technology and product candidates in the United States and abroad. We have submitted patent applications that are pending in the United States and other countries. The patent position of biotechnology firms generally is highly uncertain and involves complex legal and factual questions. Our success will depend, in part, on whether we can:
• Obtain patents to protect our own products;
• Obtain licenses to use the technologies of third parties, which may be protected by patents;
• Protect our trade secrets and know-how; and
• Operate without infringing the intellectual property and proprietary rights of others.
Patent rights and licenses. GenVec and its licensors have patents and continue to seek patent protection for technologies that relate to our product candidates, as well as technologies that may prove useful for future product candidates. As of February 28, 2007, GenVec holds or has licenses to 272 issued, allowed, or pending patents worldwide, 91 of which are issued or allowed in the U.S. These patents and patent applications pertain to genes that encode therapeutic proteins; expression control elements that regulate the production of the therapeutic proteins by such genes and targeting technology for enhanced target cell selectivity of our product candidates; cell lines used to manufacture our product candidates; methods of constructing, producing (including purification, quality control and assay techniques), storing, and shipping our product candidates; methods of administering our product candidates; and methods of treating disease using our product candidates.
TNFerade . We have issued patents and pending patent applications pertaining to the adenovectors, the expression control elements used in TNFerade to increase production of the TNF a protein by the TNF a gene upon exposure to radiation or chemotherapy, and methods of using TNFerade for treating disease. We have an exclusive worldwide license to issued U.S. patents expiring in 2020 and thereafter, pertaining to radiation-induced gene expression and a radiation-inducible promoter enabling controlled production of therapeutic proteins from gene therapy products, including TNFerade. We are aware, however, of issued patents and pending patent applications of third parties pertaining to the delivery of adenovectors and the treatment of cancer and tumors. It could be alleged that TNFerade conflicts with the issued patents as well as patents that may issue on these patent applications. AdPEDF therapy . We have issued patents and pending patent applications pertaining to particular adenovectors and methods of use thereof, utilized in conjunction with our AdPEDF product program. However, we are aware of issued patents and pending patent applications of third parties relating to various facets of gene therapy to the eye. It could be alleged that our AdPEDF product candidates conflict with such existing or future patents. Targeted vectors. We have issued patents, expiring in 2014 and thereafter, and pending patent applications covering our technology that allow for the delivery of genes in adenovectors to essentially all cell types, as well as our targeted vectors, which are designed for the purpose of creating product candidates that deliver genes in adenovectors only to selected cells. We are aware, however, of issued patents and pending patent applications of third parties relating to such vectors. It could be alleged that our targeted vectors conflict with such existing or future patents.
Production, purification, quality assessment, and formulation technology . We have issued patents, expiring in 2018 and thereafter, and pending patent applications pertaining to the production, purification, quality assessment and formulation of our product candidates. In particular, we have issued patents covering the process for manufacturing our product candidates, the purification of our product candidates applicable to both research and commercial scales, methods of assessing and confirming the quality and purity of our product candidates for clinical testing and commercialization and product formulations that improve the stability of product candidates and allow our product candidates to be conveniently stored, shipped and used. We are aware, however, of issued patents and pending patent applications of third parties relating to these and other aspects of production, purification, quality assessment and formulation technology. It could be alleged that our production, purification, quality assessment, and formulation technology conflicts with such existing or future patents.
We anticipate that we and our current and future licensors will continue to seek to improve existing technologies and to develop new technologies and, when possible, secure patent protection for such improvements and new technologies.
Certain patents pertaining to our product candidates may be eligible for Patent Term Extension under 35 U.S.C. § 156. The term of any patent which claims a human drug product (including human biological products), a method of using a drug product, or a method of manufacturing a drug product is eligible for an extension to “restore” that portion of the patent term that has been “lost” as a result of FDA review, which is, however, subject to certain limitations.
Trade secrets. To a more limited extent, we rely on trade secret protection and confidentiality agreements to protect our interests. It is our policy to require our employees, consultants, contractors, manufacturers, collaborators, and other advisors to execute confidentiality agreements upon the commencement of employment, consulting, or collaborative relationships with us. We also require signed confidentiality agreements from any entity that is to receive confidential data. With respect to employees, consultants and contractors, the agreements generally provide that all inventions made by the individual while rendering services to us shall be assigned to us as our property.
COMPETITION
Competition in the discovery and development of new methods for treating disease is intense. We face, and will continue to face, intense competition from pharmaceutical and biotechnology companies, as well as academic and research institutions and government agencies both in the United States and abroad. We face significant competition from organizations that are pursuing the same or similar technologies used by us in our drug discovery efforts and from organizations that are developing pharmaceuticals that are competitive with our potential therapeutic and vaccine product candidates. Many of our competitors, either alone or together with their collaborative partners, have substantially greater financial resources and larger research and development staffs than we do. In addition, many of these organizations, either alone or together with their collaborators, have significantly greater experience than we do in developing products, undertaking preclinical testing and clinical trials, obtaining FDA and other regulatory approvals of products, and manufacturing and marketing products. Additional mergers and acquisitions in the pharmaceutical industry may result in even more resources being concentrated with our competitors. These companies, as well as academic institutions, governmental agencies, and private research organizations, also compete with us in recruiting and retaining highly qualified scientific personnel and consultants. Our ability to compete successfully with other companies in the pharmaceutical and biotechnology field will also depend to a considerable degree on the continuing availability of capital to us.
Future competition will likely come from existing competitors, including competitors with rights to proprietary forms of the genes or proteins expressed by the genes that we currently use in our product development programs and competitors with rights to gene delivery technologies, as well as other companies seeking to develop new treatments. Competitors or their collaborators may identify important new drug discovery, genes or gene delivery technologies before us, or develop gene-based therapies that are more effective than those developed by our corporate collaborators or us, or obtain regulatory approvals of their drugs more rapidly than us. We expect that competition in this field will intensify.
We are aware of products under development or manufactured by competitors that are used for the prevention or treatment of diseases we have targeted for product development. Various companies are developing biopharmaceutical products that potentially compete with our product candidates. These include, but are not limited to: Introgen Therapeutics, Inc. and Schering-Plough Corporation, which are developing adenoviral vectors to treat cancer. In addition, Alcon Laboratories, Inc., Allergan, Inc., Genaera Corp., Novartis Pharmaceuticals Division and Regeneron Pharmaceuticals, Inc. are developing inhibitors of blood vessel growth to treat macular degeneration. These product candidates are in the later stage of clinical development. Genentech, Inc. received FDA approval in June 2006 for Lucentis â , a new drug to treat age-related macular degeneration.
We believe that our competitive success will be based on the efficacy and safety of our products, our ability to create and maintain scientifically advanced technology, attract and retain skilled scientific and management personnel, obtain patents or other protection for our products and technology, obtain regulatory approvals and manufacture and successfully market our products either independently or through outside parties. We will rely on corporate collaborators for support of some product candidates and enabling technologies and intend to rely on corporate collaborators for the development, manufacturing, and marketing of some future product candidates. Generally, our strategic alliance agreements do not preclude the corporate collaborator from pursuing development efforts utilizing approaches distinct from that, which is the subject of the alliance. Our product candidates, therefore, may be subject to competition with a potential product under development by a corporate collaborator.
MANUFACTURING AND SUPPLY
Technology for Production, Purification, Quality Assessment and Formulation. We believe our proprietary production technology and know-how facilitates the production, purification, quality assessment and formulation of our product candidates. The structure of our vectors and the procedures for their production and purification enable us to minimize the presence of contaminants. We believe our proprietary positions in these areas provide a competitive advantage. We expect to use substantially similar methods to produce, purify, assay and formulate many of our adenovector products. This allows us to accelerate product development in a cost effective manner. We have developed production and quality assessment technologies suitable for late-stage clinical testing. We currently use third-party manufacturers for production of our product candidates for clinical purposes.
• Production and Scale Up . We produce our adenovectors using cell lines grown under standardized and controlled conditions. We have developed specialized cell lines for production of our vectors. We have designed our production processes to be scalable for commercial production and to reduce the potential for contamination.
