Stepping into the biotech spotlight, cancer drug developer Threshold Pharmaceuticals Inc. raised $41 million in a second round of financing that attracted new and existing investors.

Founded in 2001, the South San Francisco-based company's drug development activities focus on targeting the metabolic properties of tumors. Its investigational therapeutics are designed to selectively destroy malignant cancer cells based upon low oxygen concentration, or hypoxia, within solid tumors. Its drugs are being developed to treat not only rapidly dividing cells, but also oxygen-starved cells within tumors that generally evade traditional therapies and ultimately contribute to relapse.

From that approach, the company already has moved two compounds into clinical development.

"We are the first company with the first technology to really target an entire tumor," Threshold Founder and President George Tidmarsh told BioWorld Today. "It does so by addressing the hypoxic core, as well as the remaining proliferating area of the tumor that currently is addressed with chemotherapy."

The privately held firm has raised $50 million including the Series B, and expects the latest funding to last through 2005, CEO Harold Selick told BioWorld Today. Threshold plans to use the proceeds to support clinical trials, fund ongoing internal research, expand its clinical development staff, pursue the in-licensing of additional products and begin to establish sales and marketing capabilities.

Its glufosfamide compound has demonstrated Phase II efficacy in five cancers, while a 2-deoxyglucose compound is entering Phase I for non-small-cell lung cancer.

"We have been able to transform this novel, first-in-class technology very rapidly to the clinic," Tidmarsh said. "A portion of the funds will be used to drive the glufosfamide program forward to pivotal clinical trials for registration. We're initially targeting pancreatic cancer, and the compound has utility in a variety of solid tumors, as our technology would suggest."

He labeled tissue oxygen concentration a fundamental property of all solid tumors, addressing 90 percent of all types of cancer, and, as such, glufosfamide could prove useful in treating breast and colorectal cancer as well. The 2-deoxyglucose compound also will be evaluated in treating a variety of solid tumors.

Threshold plans to develop its compounds internally, which Tidmarsh called a manageable expectation in cancer drug development. He added that the company would look to in-license other compounds that fit with the hypoxia technology to ensure complete remission.

The approach's underlying fundamental is bolstered by positron emission tomography (PET), a tumor imaging procedure that better identifies residual pockets of hypoxic tumor cells than traditional CT scanning. Tidmarsh pointed to a growing list of tumors - lymphoma, non-small-cell lung and colon cancers - managed with PET scanning, which relies on hypoxia and increased glucose consumption of tumors.

As for its longer-term success, Threshold's engine is being driven by its vice president of discovery, Mark Matteucci. The research program aims to develop highly selective tumor drugs.

"In spite of the fact that the company is relatively small, with 20 or 21 employees," Selick said, "we do have a fully integrated discovery capability in order to build a pipeline of follow-on candidates to fuel our clinical development going forward."

And Tidmarsh said the company is positioned for such growth.

"The combination of a first-in-class ability to address the entire tumor to prevent relapse, as well as the speed with which we've been able to move that forward, is a tribute to our management team," he said. "That's the other major reason that the investors have ponied up so much money. Our management has brought six drugs to the clinic, combined sales of almost half a billion dollars, and we've been involved in many of the major biotechnology companies in the Bay Area. So we really have the track record to put that money to work and execute the plan."

Led by Cleveland-based Morgenthaler Ventures, the financing also included two other new investors - Pequot Ventures, of New York, and CHL Medical Partners, of Stamford, Conn. Returning investors included Three Arch Partners, of Portola Valley, Calif.; Sofinnova Ventures, of San Francisco; Sutter Hill Ventures, of Palo Alto, Calif.; and ProQuest Investments, of Princeton, N.J.

Concurrent with the financing, Threshold expanded its board with two new members - Morgenthaler's Ralph Christoffersen and Pequot's Patrick Enright.

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