National Editor

Gearing up for a pivotal Phase III trial with its lead cancer drug, Threshold Pharmaceuticals Inc. filed for an initial public offering that would raise up to $86.25 million.

Threshold, of South San Francisco, did not specify the number of shares to be offered or estimate a price range.

The company's main areas of focus, according to a prospectus filed with the SEC, are cancer and benign prostatic hyperplasia. Threshold deploys what it calls Metabolic Targeting, described as a therapeutic approach that exploits "fundamental differences in energy metabolism between normal and certain diseased cells."

Glufosfamide, the lead candidate, has completed five Phase II trials and will be tested as a second-line treatment for pancreatic cancer. TH-070, the BPH drug, is in a Phase II trial. It is designed to work by inhibiting glycolysis (energy production by sugar breakdown) in prostate cells, and data are expected by the end of the year.

A third product in the pipeline, 2-deoxyglucose, or 2DG, is being studied in a Phase I trial as a combination therapy for solid tumors. 2DG is an orally administered small molecule that, like TH-070, inhibits glycolysis.

The alkylating agent glufosfamide also is being developed as a combination therapy, to be used with Gemzar (gemcitabine), from Indianapolis-based Eli Lilly and Co., for the first-line treatment of inoperable locally advanced or metastatic pancreatic cancer.

With 23 employees, Threshold has about $40.8 million in cash, cash equivalents and short-term investments, it said. Existing shareholders total about 34 million, with an average share price of $1.46. Incorporated in October 2001, Threshold has chalked up losses of $11 million through the end of last year, and from inception through that period, $8.5 million was spent on research and development.

Underwriting the IPO are Banc of America Securities, CIBC World Markets and Lazard Freres & Co. LLC, all of New York, along with Chicago-based William Blair & Co.