-Data demonstrate chemosensitization and progress toward systemic delivery-
Seattle, WA, December 9, 1999ÐTargeted Genetics Corporation (Nasdaq: TGEN) today will present data on the Company's synthetic gene delivery technology platform at the Eighth International Conference on Gene Therapy of Cancer being held in San Diego. Dr. Pervin Anklesaria, Director of Research at Targeted Genetics, will discuss two key advances in the company's portfolio of synthetic gene delivery technologies. A presentation titled "tgDCC-E1A Therapy in Ovarian, Breast and Head and Neck Cancer" will discuss the ability of tgDCC-E1A, Targeted Genetics' lead cancer product, to sensitize tumor cells to standard chemotherapeutic agents. Additionally, Dr. Anklesaria will present data on the systemic delivery of therapeutic genes using Targeted Genetics' newest synthetic gene delivery system.
E1A Sensitizes Tumor Cells to Chemotherapy In a mouse model of human ovarian cancer expressing high levels of HER2/neu, the combination of tgDCC-E1A, paclitaxel and cisplatin provided an 80 percent decrease in tumor weight over paclitaxel/cisplatin (0.1 gram and 0.5 gram respectively, p<0.01) and a 75 percent decrease over tgDCC-E1A alone (0.1 gram and 0.4 gram respectively, p<0.01). Average tumor weight for untreated control animals was 2.4 grams. A similar model of cancer cells expressing normal levels of HER-2/neu showed that the combination of tgDCC-E1A with paclitaxel and cisplatin provided a 99 percent decrease in tumor weight over paclitaxel/cisplatin alone (0.006 gram and 0.8 gram respectively, p<0.001) and a 95 percent decrease over tgDCC-E1A alone (0.006 gram and 0.14 gram respectively, p<0.001).
"The data demonstrate that tgDCC-E1A has potent anti-tumor activity when used as a single agent and has the potential to sensitize tumor cells to standard chemotherapeutic agents," said Dr. Anklesaria. "Moreover, tgDCC-E1A elicits a response in cells over-expressing HER-2/neu as well as in cells with normal levels of HER-2/neu, increasing the types of cancers for which the product may provide efficacy. In our Phase I trials of tgDCC-E1A as a single agent therapy, 11 of 16 evaluable patients with head and neck or breast cancer exhibited tumor shrinkage or stable disease. The animal data presented today demonstrate that tgDCC-E1A improves the efficacy of standard chemotherapeutic agents. These results validate a combination regimen and support the rationale for initiating clinical trials using tgDCC-E1A in combination with paclitaxel and cisplatin. Combination regimens may provide therapeutic benefit to a larger population of patients whose disease does not respond to stand ard treatments. Targeted Genetics intends to initiate a Phase I trial of tgDCC-E1A in combination with paclitaxel and cisplatin for ovarian cancer by the end of 1999."
E1A is a tumor inhibitor gene. Previous laboratory and animal studies have demonstrated E1A's ability to suppress metastases, induce apoptosis (programmed cell death) and reverse the over-expression of HER-2/neu, a cancer-causing gene. In patients with cancer, over-expression of the HER-2/neu oncogene is correlated with poor prognoses, increased tumor formation and metastasis and resistance to chemotherapeutic agents.
Advances in Systemic Gene Delivery Technology Dr. Anklesaria also presented data on Targeted Genetics' newest synthetic gene delivery system, designated Lipid Polycation DNA (LPD). The LPD delivery system was used to deliver E1A systemically to mice transplanted with human breast cancer tumors. The study, done in collaboration with Dr. Mien-Chie Hung at M.D. Anderson Cancer Center, compared LPD-E1A to E1A plasmid alone, a control gene delivered with LPD, paclitaxel alone and a combination of LPD-E1A and paclitaxel. The LPD-E1A formulation inhibited tumor growth while the plasmid or the LPD-control gene did not. Further, the combination of LPD-E1A and paclitaxel inhibited tumor growth more efficiently than paclitaxel alone.
"We are making significant progress in our synthetic gene delivery programs," said Dr. Barrie J. Carter, Executive Vice President and Director of Research and Development at Targeted Genetics. "We have shown that LPD enables systemic delivery of therapeutic genes, an important step in the evolution of gene delivery technologies. LPD complexes have several advantages, namely they are compact, stable, efficient and resistant to blood components and thus best suited for intravenous delivery. Systemic delivery of E1A may provide a new approach to treating patients with metastatic disease as well as other cancers that are not amenable to treatment by direct injection. Moreover, the properties of LPD are such that they allow the addition of molecules that can target the complexes to specific tissues. Systemic, targeted delivery has been a long sought after approach to gene therapy and is the foundation of our joint venture with Elan plc (NYSE: ELN), Emerald Gene Systems."
In July 1999, Targeted Genetics and Elan plc established a joint venture, Emerald Gene Systems, to develop advanced gene delivery technologies. The joint venture combines the company's expertise in vector development and manufacturing with Elan's leadership in novel drug delivery technologies. The addition of Elan's targeting technologies to delivery vehicles such as LPD may provide targeted, systemic approaches for the delivery of therapeutic genes.
"These data provide further validation of Targeted Genetics' expertise in the development of gene delivery systems," said Michael Sember, Executive Vice President, Business Development, at Elan. "We believe that systemic gene delivery will catalyze the development of novel treatments for a broad array of significant diseases. Targeted Genetics' ability to develop novel and proprietary vectors, such as LPD, is one of the reasons we selected the company as our exclusive partner in gene delivery. Emerald Gene Systems will combine Elan's targeting technologies and Targeted Genetics' expertise in vector development and manufacturing to produce a new generation of therapeutics. We are pleased to be working with the leader in gene delivery and look forward to continuing our productive collaboration."
Background on LPD Targeted Genetics, in collaboration with Dr. Leaf Huang of the University of Pittsburgh, is developing a series of improved synthetic delivery systems based on various formulations of cationic lipids. In one of these systems, designated "LPD" for lipid-polycation-DNA, the DNA is condensed through the addition of a polycation to form small, degradation resistant cores encapsulated in a lipid shell. The resulting LPD formulation contains particles of defined size, which have enhanced stability and gene transfer efficiency. Pre-clinical experiments in non-tumor bearing mice have shown that the LPD system is able to deliver genes systemically through intravenous administration.
tgDCC-E1A Clinical Trial Background Targeted Genetics' Phase I trials of tgDCC-E1A in 36 breast, ovarian and head and neck cancer patients were completed in 1998. Dose-limiting toxicities were observed only in patients with ovarian cancer who received the highest doses of tgDCC-E1A by intraperitoneal infusion; however, subsequent changes to the procedure for making the final patient preparation are expected to reduce these toxicities in future trials. E1A gene transfer was detected in tumor samples from these patients in 15 of 15 patients tested. Eleven of 16 evaluable patients with head and neck cancer or breast cancer exhibited stable disease or some shrinkage of tumor. Reduced levels of HER-2/neu, a protein which is made by a cancer causing gene, was observed in the majority of patients that initially had elevated levels and could be evaluated again after treatment. Based on these data, a 40 patient Phase II clinical trial in head and neck cancer was initiated in September of 1998. The trial uses the highest dose of tgDCC-E1A evaluated in patients with head and neck cancer in the Phase I study. Initial data from the Phase II study are expected to be presented at a scientific conference in the first half of 2000.
Targeted Genetics Corporation develops gene and cell therapy products for the treatment of certain acquired and inherited diseases. The Company has four lead product development programs targeting cystic fibrosis, hemophilia A, cancer, and infectious disease, as well as an extensive technology platform.
NOTE: This release contains forward-looking statements relating to the Company's products under development, technologies, joint venture arrangements 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, uncertainties inherent in scientific collaborations, and uncertainties related to patent position. Reference is made to the Company's latest Annual Report on Form 10-K 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.