Stability, Safety and Efficacy Demonstrated for Novel Bacterial Anticancer Agent
NEW HAVEN, CT (April 12, 1999): Research by scientists at Vion Pharmaceuticals (Nasdaq: VION) and their Yale University collaborators demonstrates the suitability of the company's lead TAPETR vector, VNP20009, to enter human clinical testing. At the annual meeting of the American Association of Cancer Research (AACR) Vion scientists presented data demonstrating the genetically engineered Salmonella bacteria's overall safety profile and tumor targeting ability, including TAPET's safety when administered to non-human primates. In addition, they reported the ability of unarmed TAPET organisms (without "warheads") to inhibit both primary and metastatic tumors by more than 90% and to prolong survival in mouse xenograft models (human tumor tissue transplanted into mice) of several human cancers. In March, Vion announced that the company had filed an Investigational New Drug (IND) application to begin human safety testing with TAPET in the United States later this year. The U.S. filing is in addition to regulatory filings made by Vion in support of clinical trials of TAPET in Europe. Vion is developing TAPET organisms as vectors for the targeted, systemic delivery of anticancer agents to tumors throughout the body.
David Bermudes, Ph.D., associate director of biology at Vion, said, "VNP20009 possesses all of the properties required for its safe use in humans. These include attenuated virulence, a reduction in the potential of the bacterium to elicit septic shock, genetic stability in its safety-related mutations, and sensitivity to conventional antibiotics. At the same time, VNP20009 maintains TAPET's desirable anti-tumor properties, including the ability to selectively amplify in tumors at levels of at least 500:1 compared with normal tissues and to suppress tumor growth by more than 90%. Moreover, the VNP20009 TAPET strain is easily amenable to manufacture and pharmacological formulation, and we have successfully produced sufficient quantities for initial clinical trials."
Vion scientists Caroline Clairmont, Ph.D. and Li-mou Zheng, Ph.D. also reported new preclinical data showing the safety of VNP20009 in non-human primate models. Previous studies in mice have demonstrated that VNP20009 is more than 10,000 times less toxic than the wild-type Salmonella strain from which it is developed. Additionally, the studies showed that the TAPET bacteria were rapidly cleared from the blood to undetectable levels within 24 hours. New research reported at AACR showed that VNP20009 has no toxic effect when administered to cynomolgous monkeys at very high doses (109 cfu/monkey), which would be toxic using wild-type Salmonella. Moreover, the bacterium is not shed in the animals' feces or urine, and is rapidly cleared from the blood and from other tissues over extended periods of time.
A further report at AACR by Vion scientists showed VNP20009's ability to inhibit the growth of both primary tumors and metastases. VNP20009, injected intravenously into tumor-bearing mice, accumulated and proliferated within tumor tissue at a rate at least 500 times higher than it did in liver, the tissue of second greatest accumulation. This selectivity for tumors was observed in a variety of tumor types, including mouse melanoma, and human melanoma, colon, lung, prostate, and breast tumors transplanted into mice. In addition, the researchers demonstrated that VNP20009 inhibited the growth of lung metastases in models of metastatic melanoma and prolonged the life span of animals treated with the TAPET organisms.
"These new findings further support Vion's position that TAPET organisms should be safe for use in humans and offer considerable potential as a new approach to the treatment of cancer," said Dr. Ivan King, vice president of biology. "Our research has shown TAPET to have a wide ranging ability to inhibit a broad variety of both primarily and metastatic tumors when given systemically. This ability clearly and uniquely distinguishes TAPET from the numerous gene therapy approaches to cancer treatment, all of which require pre-detection of the tumor and local, direct administration of the agent, and thus do not allow for systemic therapy."
"We believe that TAPET vectors represent a novel and exciting approach to the treatment of cancer," said Alan Kessman, Vion chief executive officer. "These organisms, without "warheads", suppress tumor growth in a significant manner on their own, which enhances the even greater potential of using TAPET as a "guided missle" that can be engineered to selectively deliver a wide variety of anticancer agents (so-called "warheads") to solid tumors throughout the body."
Vion's TAPET vectors are Salmonella bacteria whose potential for virulence and the ability to cause septic shock are enormously reduced through the use of highly stable genetic modifications. Research reported in the January issue of Nature Biotechnology showed that the TAPET organisms' ability to trigger TNF-alpha and cause death in animal models was reduced by 10,000 fold. At the same time, the TAPET organisms retained their high selectivity for tumors over normal tissues. In addition, the TAPET organisms remained fully sensitive to a wide range of antibiotics, adding a further level of safety and control to their potential use as anticancer agents.
Vion Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to discovering, developing and commercializing novel products and technologies for the treatment of cancer and viral diseases. The Company has focused its research efforts in five principal areas: hypoxic cancer cell therapeutics, TAPET cancer therapy, alkylating agent prodrugs, ribonucleotide reductase inhibitors and nucleoside analogs. Vion's lead anti-cancer agent Promycin (porfiromycin) is currently in a Phase III clinical trial. For additional information on Vion and its research and product development programs, visit the Company's Internet web site at http://www.vionpharm.com
Statements included in this press release which are not historical in nature are forward-looking statements made pursuant to the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements regarding the Company's future business prospects, plans, objectives, expectations and intentions are subject to certain risks, uncertainties and other factors that could cause actual results to differ materially from those projected or suggested in the forward-looking statements, including, but not limited to those contained in the Company's Registration Statement filed on Form S-3 (file no. 333-37941).