Targeted genetics presents promising data from cystic fibrosis clinical trial

June 04, 2000

Studies suggest that aerosolized tgAAV-CF is safe, well tolerated, and efficiently delivered to the lung

Seattle, WA-June 5, 2000-Targeted Genetics Corporation (Nasdaq: TGEN) presented data from its Phase I clinical trial of an aerosol formulation of tgAAV-CF, the Company's gene therapy product for the treatment of cystic fibrosis (CF). Dr. Thomas C. Reynolds, Vice President, Clinical Affairs at Targeted Genetics, presented the data in an abstract titled "A Phase I Study of Aerosolized Administration of tgAAV-CF to CF patients with Mild Lung Disease" this weekend at the American Society of Gene Therapy Third Annual Meeting in Denver, Colorado.

The Phase I dose-escalation study evaluated the safety and tolerability of tgAAV-CF delivered via nebulizer to 12 patients age 19-41 (median age 29) with mild CF lung disease. All patients in the study had FEV1 levels (a standard measure of lung function) at least 60% of normal. Doses of 1010, 1011, 1012 and 1013 DNAse Resistant Particles (DRP) were evaluated, with each cohort containing three patients. Patients received a single dose of tgAAV-CF and were followed for 90 days post treatment.

"The aerosolized formulation of tgAAV-CF, which we are developing in collaboration with Celltech Group, plc, is well-tolerated in this patient population," said Dr. Reynolds. "Our ability to achieve broad distribution of tgAAV-CF throughout the lungs of these patients validates the aerosol delivery approach we are taking in developing this product. We are on track to initiate a Phase II multi-dose study of aerosolized tgAAV-CF within the next several months. As with the Phase I study presented today, we are working closely with the Cystic Fibrosis Foundation's Therapeutics Development Network (CFF TDN) in designing and conducting the Phase II study. tgAAV-CF is the first gene therapy approach for CF to be selected by the TDN for collaboration and we are proud to be working with the leading physicians and opinion leaders in the CF community."

"The TDN has developed a productive collaborative relationship with Targeted Genetics and we look forward to initiating the upcoming Phase II trial," said Bonnie Ramsey M.D., Director of the CFF TDN. "We appreciate the commitment that Targeted Genetics has made to conduct gene therapy research for the future benefit of individuals with CF. The Company has paved the way for clinical trials using AAV-based products in CF, a promising approach for this pulmonary disease."

Data suggest that tgAAV-CF delivered via nebulizer was safe and well-tolerated at all doses evaluated. Efficient gene transfer was observed in all patients at the highest dose, as measured by examining tissue samples obtained by bronchoscopy at 14, 30, 60 and 90 days post treatment. These samples, taken from various regions of patients' lungs, indicate that tgAAV-CF was delivered efficiently throughout the upper airways of these patients, despite the presence of thickened mucus in their lungs. Maximum levels of 0.1-0.6 vector-delivered gene copies per cell were detected 14 days following administration of a single vector dose. Vector was still present in some patients up to 90 days after a single administration of aerosolized tgAAV-CF. Neutralizing antibodies were not detected in bronchial wash fluid, although they were detectable in serum from some patients. Serum antibodies are not expected to interfere with the product's activity in the lung. Sputum, stool and urine samples were analyzed for the presence of tgAAV-CF. The product was observed transiently in the sputum of some patients one day following administration, and was not detected in urine and stool samples.

"Although CF is one of the most common inherited single-gene defects in North America, there is still no cure for the disease," said H. Stewart Parker, President and Chief Executive Officer of Targeted Genetics. "We believe that the good safety profile and long-term gene expression properties of our AAV vectors make them a promising approach to treat a variety of chronic diseases such as CF, hemophilia and rheumatoid arthritis. Our strong intellectual property portfolio in the area of AAV vectors for delivering the CFTR gene combined with our proprietary, scalable AAV manufacturing process puts us in good position to develop the first gene therapy treatment for CF."

In March 1999, the Company presented data from a Phase I/II, placebo-controlled study of tgAAV-CF in a sinusitis model of CF lung disease in patients with mild disease. Data suggest that tgAAV-CF is safe and well-tolerated and is able to induce a reduction in the levels of IL-8, an inflammatory cytokine thought to play a role in the lung damage experienced by CF patients. Complete results from this study are expected to be published later this year.

Targeted Genetics was the first company to initiate clinical trials with AAV-based products. Clinical trials of AAV vectors in cystic fibrosis are in progress and additional preclinical data are being generated in the areas of hemophilia, arthritis, and AIDS prophylaxis. The Company has dealt with all regulatory issues to date concerning the human testing of AAV-based products, and has developed proprietary, efficient production methods that it believes can be scaled-up to supply large clinical trials and commercial needs in a cost-effective manner, meeting GMP requirements. The Company has treated nearly 60 patients with AAV vectors manufactured in this manner, and they appear to be well-tolerated with a good safety profile.
Background on CF
CF results from the loss of function of the CFTR gene. Normally, the protein encoded by this gene is found in the respiratory passageways, pancreas, salivary and sweat glands, where it helps to regulate the cellular concentration of chloride ions and water. In CF patients, the loss of this gene's function leads to the production and build-up in the lungs and sinuses of thick mucus, colonization by bacteria and the invasion of white blood cells, thus causing inflammation. These events produce scarring in the lung, which ultimately results in loss of respiratory function. It is estimated that 60,000 people worldwide have cystic fibrosis including approximately 24,000 people in the United States. The median age of survival for patients with CF is approximately 31 years.

Targeted Genetics Corporation develops gene therapy products for the treatment of acquired and inherited diseases. The company has lead clinical product development programs targeting cystic fibrosis and cancer, and a promising pre-clinical pipeline of product candidates focused on hemophilia A, arthritis, cancer and AIDS prophylaxis. The company has a broad platform of gene delivery technologies, as well as a promising body of technology for cellular therapy. For more information about Targeted Genetics Corporation please visit the Company's web site at

NOTE: This release contains forward-looking statements relating to the Company's products under development, technologies and future operating results that are subject to certain risks and uncertainties that could cause actual results to differ materially from those projected. The words "believes", "expects", "intends", "anticipates", variations of such words, and similar expressions identify forward-looking statements, but their absence does not mean that the statement is not forward-looking. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could affect the Company's actual results include the need for additional capital, the early stage of product development, uncertainties related to clinical trials, and uncertainties related to patent position. Reference is made to the Company's latest Quarterly Report on Form 10-Q filed with the SEC for a more detailed description of such factors. Readers are cautioned not to place an undue reliance on these forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date of this release or to reflect the occurrence of unanticipated events.

Targeted Genetics Corporation
Stephanie Seiler, Ph.D.
Director, Communications

Noonan/Russo Communications
Mary Claire Bice (investors)
212-696-4455, ext. 238

Noonan/Russo Communications

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