For Immediate Release     June 1, 2000

Contact: info@asgt.org

Gene Therapy Researchers Provide Insight to Genetic Disorders

DENVER (June 1, 2000) -Gene therapy researchers presented groundbreaking findings regarding genetic disorders at a press conference held today in conjunction with the American Society of Gene Therapy's 3^rd Annual Meeting in Denver, Colo. Gene therapy researchers from around the world have converged, making Denver the gene therapy capitol of the world for the next three days.

"The basic and scientific research and pre-clinical studies reported on here illustrate the rapid growth of the field of gene therapy and the magnitude of its promises for the future," said ASGT President, Savio L. C. Woo, PhD, Professor and Director of the Institute for Gene Therapy and Molecular Medicine at the Mount Sinai School of Medicine, NY. "The next wave could bring us treatments for genetic disorders, as well as more complicated diseases like cancer, diabetes, heart disease, and dementia."

Following are three abstracts of studies that show significant progress in efforts to combat genetic disorders using gene therapies.

---

"A Phase I Trial of AAV-Mediated Muscle-Directed Gene Therapy for Hemophilia B"

Presenter: Catherine Manno, The Children's Hospital of Philadelphia, University of Philadelphia School of Medicine

Hemophilia B, a blood clotting disorder, is the result of the insufficient levels of a protein known as Factor IX, one of many proteins involved in the biochemical cascade that leads to blood clotting. This is a particularly attractive disease for possible gene therapy for many reasons, not least of which is the difficult regimen patients must follow in injecting factor IX protein on a regular basis. Animal models (mice and dogs) of the disease have been effectively treated by transferring the gene for Factor IX into skeletal muscle using a form of a viral vector known as adeno-associated virus (AAV).

A collaboration between several different laboratories have undertaken a phase I clinical trial using AAV to transfer Factor IX into humans suffering from hemophilia B. Although still underway, the trial is showing encouraging signs that this approach will work in humans as it has in animals (i.e., even at the low doses tested so far, clinical signs of improvement have been seen in the few patients who have received the treatment). Although ongoing studies are required to further assess the safety of this approach, there is a real possibility that, even if not a cure, it will at least offer the possibility of making severe hemophilia B a milder form of the disease.

---

"Discontinuation of PEG-ADA in an ADA^- SCID Patient Undergoing PBL Gene Therapy"

Presenter: Claudio Bordignon, Telethon Institute for Gene Therapy, Scientific Institute H.S. Raffaele (HRS-TIGET)

The first gene therapy performed in humans was done in 1990 at the National Institutes of Health in a young girl suffering a rare form of immune disease known as adenosine deaminase (ADA) deficiency. Although the initial patients have continued to thrive, it has been difficult to determine if their positive outcome was related to the gene therapy itself or to the continued ADA replacement therapy, i.e., the administration of the protein itself. As the goal of gene therapy is to eliminate the need for other burdensome treatments, it is important to sort this out.

Thanks to advances in both gene delivery and in analysis methods following delivery, an international group of researchers have been able to remove one patient who received genetically modified blood cells from enzyme replacement therapy. The patient continues to thrive, suggesting that gene therapy for ADA deficiency is a viable alternative to continuous enzyme replacement. Nevertheless, the long-term success of this approach still needs to be determined.

---

"Regulated Delivery of Secreted Proteins: Preclinical Evaluation of Systems for Drug-Controlled Transcription and Secretion"

Presenter: Tim Clackson, ARIAD Gene Therapeutics Inc.

Technologies are being developed for enhancing the safety of gene therapies by allowing them to be controlled using small molecule drugs. In the application to bone marrow transplantation (BMT), a drug-controlled cell death (apoptosis) is used as a way to combat graft-versus-host disease (GvHD), the major toxicity of BMT. Before introducing cells into the body, they are equipped with ARIAD's suicide switch. If GvHD occurs, the cells can be eliminate by the patient taking ARIAD's drug to initiate T-cell death. This product has completed a phase 1 trial for safety of the drug, and two phase 2 trials are scheduled to begin later this year.

In another application, the orally active drugs are used to control the expression of genes, allowing the production of therapeutic proteins of interest to be regulated using a pill. For many proteins this will be an essential feature if gene therapy is to be used to deliver the proteins, since an unregulated product will be unsafe-- there is no way to control how much protein is delivered, or to turn off therapy if necessary.

For almost two years there has been regulation of the anemia protein therapeutic Epo in primates, and a phase 1 trial of this product is expected to start within one year.

---

The ASGT is the largest medical professional organization representing researchers and scientists dedicated to discovering new gene therapies. ASGT was established in 1996, and has grown to over 2,400 members. It is committed to promoting and fostering the exchange and dissemination of information and ideas related to gene therapy, encouraging the general field of research involving gene therapy and to promoting professional and public education in all areas of gene therapy.

# # #