NEW HAVEN, CONN., NOVEMBER 18, 1999 -- VION PHARMACEUTICALS, INC. (NASDAQ NM: VION) presented preclinical data on two bioengineered ("armed") TAPET® vectors at the 1999 International Conference on Molecular Targets and Cancer Therapeutics in Washington, D.C. on November 17, 1999. This conference is sponsored by the American Association for Cancer Research (AACR), the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC). Vion's TAPET technology uses genetically altered Salmonella to colonize, multiply preferentially in solid tumors and produce cancer-fighting drugs within the tumors.
One abstract, titled "Tumor-Directed Delivery and Amplification of Tumor-Necrosis Factor-alpha (TNF) by Attenuated Salmonella Typhimurium" highlighted that in preclinical studies, using a colon tumor model, TAPET bacteria armed to express tumor-necrosis factor-alpha (TNF-alpha), a known anti-cancer agent, resulted in complete tumor regression in mice. Results from this preclinical study have been reproduced in three separate tests. The other abstract, titled "Activation of Cyclophosphamide by Tumor-Targeting Ability of Salmonella Typhimurium" explained that TAPET bacteria may be armed to express activators of cyclophosphamide, a widely used anti-cancer prodrug, and multiply preferentially within solid tumors. Stanley Lin, Ph.D., Senior Research Fellow and Michael F. Belcourt, Ph.D., Senior Scientist at Vion, attended poster presentations of their abstracts, which will be published in the November 1999 Supplement to Clinical Cancer Research. These presentations are two of three Vion abstracts presented at the conference, all focused on the TAPET development program.
In summary, abstract highlights include:
"Tumor-Directed Delivery and Amplification of Tumor-Necrosis Factor-alpha (TNF) by Attenuated Salmonella Typhimurium"
A genetically modified strain of Salmonella typhimurium was bioengineered ("armed") to express the TNF-alpha gene. Following a single intravenous injection into tumor-bearing mice, the vector:
- Accumulated preferentially in tumors as compared to other normal tissues;
- Expression of TNF-alpha did not enhance bacterial toxicity;
- A single inoculation caused complete tumor regression in colon (C38) tumor models.
These studies indicate that TAPET may be a useful vector for selectively delivering potent proteins that have previously had limited utility due to dose-limiting toxicity to tumors, and further enhance the antitumor efficacy of TAPET.
"Activation of Cyclophosphamide by Tumor-Targeting Ability of Salmonella Typhimurium"
A genetically modified strain of TAPET was armed to express the enzyme CYP2B1, which is capable of activating cyclophosphamide, a widely used anticancer prodrug (a compound that is converted within the body into an active form, with therapeutic effects). The results indicate that tumor-localized conversion of cyclophosphamide to a cytotoxic state may be achieved by TAPET organisms carrying the CYP2B1 gene and multiplying preferentially in tumors.
Alan Kessman, president and CEO of Vion, stated, "Preclinical studies of armed TAPET vectors further validate their ability to continuously deliver a variety of anticancer drugs directly to the tumor in a safe and effective manner, without the serious side effects associated with current cancer therapies. Scientists at Vion continue to focus their efforts on enhancing the clinical utility and safety profile of TAPET as a cancer therapy, particularly when armed to express certain potent anti-cancer agents. These results hold great promise for the future of our TAPET development program."
"Vion scientists are conducting several preclinical studies to validate TAPET's ability to deliver a wide variety of anti-cancer agents. It is important to note that while TNF-alpha is an extremely potent anti-cancer agent, it is also extremely toxic, and as such, cannot be delivered systemically. Because of TAPET's novel ability to selectively replicate within the tumor as compared to normal tissue and to express certain anti-cancer agents within the confines of the tumor, TAPET may prove to be an effective treatment in addressing the delivery and toxicity challenges associated with many current cancer treatments," concluded Mr. Kessman.
TAPET (Tumor Amplified Protein Expression Therapy), Vion's core platform technology, are bacterial vectors that replicate in solid tumors in preclinical tests. These TAPET vectors, based on highly attenuated Salmonella bacteria, have been engineered to colonize and multiply within the confines of a tumor, according to preclinical studies. The TAPET bacteria did not cause septic shock in preclinical septic shock models at the doses which showed anti-tumor effects, and remain susceptible to commonly used antibiotics. Vion plans to develop TAPET vectors to deliver a variety of anticancer agents, or prodrug converting enzymes to solid tumors. Preclinical studies have demonstrated the ability of the TAPET bacteria to inhibit the growth of tumors on their own and through the delivery of anticancer agents.
Vion Pharmaceuticals, Inc. is a biopharmaceutical company engaged in the research, development and commercialization of cancer treatment technologies. Vion's product portfolio consists of TAPET, a drug delivery platform, and three cancer therapeutics (Promycin®, Triapine® and Sulfonyl Hydrazine Prodrugs). TAPET has been shown in preclinical models to effectively deliver anticancer agents while having a minimal effect on healthy normal tissues. TAPET uses genetically altered strains of Salmonella as a bacterial vector, or vehicle, for delivering cancer fighting drugs preferentially to solid tumors. Promycin, which attacks oxygen depleted cancer cells, is currently being evaluated with radiation in a multicenter Phase III clinical trial for the treatment of head and neck cancer. Triapine, which is designed to prevent the replication of tumor cells by blocking a critical step in the synthesis of DNA, is currently being evaluated for its safety in a Phase I clinical trial. Sulfonyl Hydrazine Prodrugs, compounds that are designed to be converted to unique potent, alkylating agents, are currently being evaluated in preclinical studies.
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