By Randall Osborne
To push forward its lead drug for non-Hodgkin's lymphoma, Coulter Pharmaceutical Inc. has raised $42.625 million in a public offering of 2.75 million shares at $15.50 per share.
Coulter, of Palo Alto, Calif., has 13.1 million shares outstanding after the offering.
The company's monoclonal antibody, Bexxar, is conjugated with the iodine-131 isotope and works by attaching to a protein found on the surface of B cells at the stage when non-Hodgkin's lymphoma arises.
Bexxar, also known as B-1 therapy, is in pivotal Phase II/III trials. Subjects in the study are 60 low-grade and transformed low-grade non-Hodgkin's patients refractory to chemotherapy. A single-center Phase II trial in newly diagnosed non-Hodgkin's lymphoma patients also is ongoing. In the earlier Phase I/II clinical trial, 40 subjects were treated. Eighty-two percent showed an overall response and 45 percent showed a complete response.
Non-Hodgkin's lymphoma patients given chemotherapy often achieve remission, but typically relapse and die from the disease or from complications of treatment.
Coulter plans to file a new drug application for Bexxar with the FDA in the second half of next year. Meanwhile, under new guidelines adopted in May by the Nuclear Regulatory Commission, Coulter has begun providing outpatient treatment of Bexxar. The drug is administered in a two-step dosing regimen, replacing the need for patients to remain hospitalized, as is required after some radiotherapies.
Bexxar, the company has said, bears all the necessary attributes of an effective radioimmunotherapy for non-Hodgkin's lymphoma. It exploits an antigen specific to B cells; attacks with a therapeutically active monoclonal antibody; uses a radioisotope fitted to the disease profile; and is delivered by way of a fine-tuned protocol.
Coulter also is developing what the company calls tumor-activated peptide pro-drugs. These are chemically modified cytotoxic drugs triggered to action by enzymes or other chemicals produced by cancer cells.
Clinical trials of one such drug — doxorubicin for solid-tumor cancers, called Super-Leu-Dox — are expected to begin in early 1998. In vitro studies show the drug is 40 times more likely to be absorbed and chemically activated by tumor cells than by normal cells.
The company expects, by developing this program of drugs, it can broaden the scope of conventional chemotherapies.
In Europe, Coulter conducted two separate dose-escalation trials using 59 patients, who were given a leucine-doxorubicin conjugate as stand-alone treatment for solid tumors. The subjects in those trials safely tolerated doses well beyond the doses associated with unmodified doxorubicin.
Coulter plans to try for expedited approval of Bexxar, taking advantage of regulatory rules that allow quicker review of therapies for patients with limited treatment options, such as those afflicted with low-grade and transformed low-grade non-Hodgkin's lymphoma. At the same time, the company is pursuing clinical trials to prove the drug's effectiveness in other applications.
If approved, Bexxar would be the first radioimmunotherapy approved in the U.S. for cancer.
The public offering was managed by Hambrecht & Quist L.L.C., of New York; BT Alex. Brown Inc., of Baltimore; and Pacific Growth Equities Inc., of San Francisco. Coulter's initial public offering, by the same underwriters, was held in January and raised $30 million.
At the end of the second quarter, Coulter had $41.038 million in cash. For the six months ending June 30, the company reported a net loss of $8.8 million. Coulter's stock (NASDAQ:CLTR) closed Friday at $15.75, down $0.188. *