Vion Demonstrates Readiness Of First Tumor-Targeting Salmonella For Human Testing Against Solid Tumors

April 11, 1999

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

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).

Kureczka/Martin Associates

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to