Genecure LLC

Genecure wants to take the lessons learned in gene therapy, vector development, and vaccine research and apply them to AIDS therapy.

Adding to the gene transfer toolkit

• 24 Peachtree Center Ave.

• Suite 525

• Atlanta, GA 30303

• Phone: [phone]

• Fax: [phone]

• E-mail: [email protected]

• Web site: www.genecure.com

• Contact: Frank Y.T. Tung, PhD

• Industry Segment: Biotechnology

• Business: Gene Therapy; Vaccines

• Founded: November 1998

• Founder: Frank Tung

• Employees: 5

• Financing to date: $1 million

Genecure LLC wants to take the lessons learned in gene therapy, vector development, and vaccine research and apply them to AIDS therapy. The company has developed a platform technology for gene transfer based on a primate lentivirus, which it believes will enable the safe transfer of genes into primary human cells. It is also developing a vaccine against HIV.

Ideally, gene therapy vectors used for in vivo therapy must carry the desired segment of the gene to be inserted, transfer it into a sufficient number of target cells, and enable the gene to persist in the host cell. Lentiviral vectors, which are derived from the family of retroviruses including HIV and non-human immunodeficiency viruses (among them feline, bovine, and simian immunodeficiency viruses), have appeal as in vivogene delivery vehicles because of their ability to insert genetic material directly into the genome of non-dividing cells, such as bone marrow stem cells, heart muscle, liver cells, or brain tissue.

Other vectors have limitations: naked DNA, liposomes, and adenoviral vectors do not integrate DNA into the genome, resulting in shorter-duration gene expression and less production of the desired protein; adeno-associated viral vectors often cause inflammation and are difficult to manufacture; and retroviruses other than lentiviruses generally insert their DNA only into dividing cells.

The downside of using an HIV-related viral vector, of course, is that developers must be able demonstrate that replication-competent retroviruses won't form during manufacture. To eliminate the possibility of random recombination, vectors are designed such that different parts of the genome are segregated onto different constructs. To prevent viral contamination, retroviral packaging sequences of the viral genome essential for viral replication are removed or crippled.

Genecure's approach to gene therapy is based on use of a non-HIV lentiviral vector, derived from a primate virus. To avoid recombination and ensure safety, it splits the virus into two constructs, each with different helper functions; use of a non-HIV envelope protein prevents the risk of contamination with infectious viruses. The company is currently in preclinical studies using gene therapy to treat HIV-infected individuals by delivering antiviral genes to lymphocytes. However, applications of Genecure's lentiviral gene delivery system are broader, potentially including the treatment of cancer, viral diseases, genetic diseases, and cardiovascular disease.

Genecure is using a similar strategy to develop a novel live attenuated vaccine that can stimulate both cellular and antibody immune responses against HIV. Live attenuated vaccines, in general, pose risks to immunocompromised patients and neonates. Genecure therefore uses a replication-defective HIV virus where the polymerase gene of HIV has been truncated and only undergoes a single round of replication, which maintains the immunogenicity of the vaccine while ensuring safety. Although the efficacy of HIV vaccines generally is difficult to evaluate owing to the lack of readily accessible animal models, preclinical results using Genecure's vaccine show that the vaccine can infect rhesus monkeys and company CEO Frank Tung, PhD, describes them as promising. Using this model, the protective immunity conferred by the vaccine can be evaluated after challenge with an SIV/HIV chimeric virus.

Now Genecure needs to advance its vaccine into human testing. "The timetable for human clinical trials of our AIDS vaccine is complicated," Tung suggests, because of financing and ethical considerations. The company is talking to the major vaccine centers in the US, and Tung says he expects to initiate Phase I clinical trials in the US within a year in collaboration with a major center, for which Genecure will supply clinical batches of the vaccine. The company is also talking to private foundations with an interest in new approaches to AIDS therapy for financial support.

To date, Genecure has raised over $1 million in angel money from private investors. It currently is seeking another $2 million from federal grants and private investors to complete preclinical studies of its vaccine and gene therapy against HIV, and to further develop its research programs. It will then seek clinical development agreements from pharmaceutical companies for Phase I/II trials.

Genecure is not alone in the lentiviral vector field. Cell Genesys Inc. , for example, has a long-standing interest in retroviral vector systems, and claims broad intellectual property covering lentiviral vectors, which it obtained from the Salk Institute for Biological Sciences[See Deal].

Two years ago, Genetix believed it was a year away from clinical trials using its lentiviral vector technology. But development of gene therapy techniques has generally been slower than anticipated (and was further slowed by the controversy surrounding the death of a patient in a Phase I trial using adenoviral vector last year). But despite the fact that the safety of lentiviral vectors still awaits confirmation in human studies, according to Genetix's VP, Ron Dorazio, MD, encouraging work in CD34+ bone marrow stem cells has shown that they offer significant improvements over other retroviral vectors. Developers have created unique ways of making them safe, he says. "People have convinced themselves that it works."

Genecure recently moved from Pennsylvania to an incubator facility in the Atlanta area, to be closer to the research facility at Emory University , where its preclinical work is ongoing. Frank Tung has spent the last 15 years working on lentiviral vectors. He was assistant professor in the Department of Infectious Diseases and Microbiology of the University of Pittsburgh until 1999, when Genecure began operations. From 1990-94 he was an assistant professor in the Department of Pathology, University of Florida College of Medicine.—MLR