By Debbie Strickland

In a deal worth approximately $50 million plus royalties, Vion Pharmaceuticals Inc. has secured Boehringer Ingelheim GmbH as the worldwide marketing partner for its lead anticancer product, Promycin (porfiromycin), now in pivotal Phase III studies in the U.S. and Europe.

Vion has exclusive North American copromotion rights, and plans to develop a small U.S. marketing force to sell the drug, designed for use in combination with radiation therapy. Boehringer Ingelheim gains exclusive worldwide rights to market and sell the drug outside North America.

Vion will receive up-front fees and milestones, plus royalties on sales outside North America. In addition, the companies will share worldwide development costs, and Boehringer Ingelheim will make a $3 million equity investment in Vion "at a premium to current market price." Vion will manufacture and supply Promycin for all territories.

The up-front fee and equity investment total $7 million, a substantial cash boost for the small New Haven, Conn.-based firm, which, as of Sept. 30, had $5.4 million in cash, following a net loss of $2.7 million in the third quarter.

"It's our first major corporate deal," said John Spears, Vion's president and CEO. This validates us as a company, and it validates the product."

Vion was formed in April 1995 with the merger of two virtual companies — OncoRx Inc. and MelaRx Pharmaceuticals Inc. — which were both founded to commercialize technology developed at Yale University.

The company conducted an initial public offering in August 1995, and has since ramped up quickly to the Phase III level, with additional candidates nearing the clinic.

The Promycin Phase III program will likely wrap in 1999, with a new drug application filing to come "possibly in late 1999 but more likely in 2000," Spears said.

In a Phase I/II clinical trial, the combination of Promycin and radiation therapy produced in patients with head and neck cancer a 33 percent disease-free survival rate at five years, which is considered a cure.

Tumor Cell Destroyer

Promycin is a small-molecule bioreductive alkylating agent that destroys hypoxic, or oxygen-depleted, tumor cells. Resistant to radiation therapy and most chemotherapeutic agents, hypoxic cells result from the lack of proper blood vessel development, thereby limiting blood flow and oxygen to tumor tissue.

"Radiation needs oxygen to work," said Spears. "Radiation does a great job on oxygenated cells; it kills anywhere from 85 to 99 percent of cancers, but 1 to 15 percent of cells are left viable . . . Promycin sops up, or destroys, the remaining hypoxic cells."

In addition to head and neck cancer, plans to evaluate Promycin in other tumor types, such as cervical cancer, a likely second target, are in the works.

The Vion product most likely to enter the clinic next is an anticancer ribonucleotide reductase inhibitor, which blocks conversion of RNA to DNA, thus arresting cancer cell growth. The company plans to submit an investigational new drug (IND) application by the end of the year.

Spears said his young company's "most exciting technology" is TAPET (Tumor Amplified Protein Expression Therapy), which uses highly attenuated, tumor-targeting Salmonella bacteria that contain genes to express various cancer-attacking proteins.

"They find the tumors anywhere in the body and selectively replicate in them," said David Bermudes, one of the inventors of TAPET and Vion's associate director of biology.

In preclinical studies, the Salmonella vector showed potential to effectively target cancerous tumors, replicate within them and inhibit tumor growth.

Spears said an initial IND for this project could come in the second half of 1998.

In a fourth cancer project, Vion is developing alkylating agent pro-drug candidates. Alkylating agents are highly reactive and typically cause a number of side effects.

What Vion and its Yale collaborators have done is to add reactivity-blocking pro-drug components that separate upon contact with enzymes found predominantly in and around tumors. At the tumor site, the separation restores the alkylating component's reactivity — and hence its cytotoxicity.

Vion also is working on antiviral nucleoside analogues, with the lead agent geared toward fighting the hepatitis Bvirus and HIV.

The company's shares (NASDAQ:VION) closed Tuesday at $5, up $0.125. *

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