By Randall Osborne

West Coast Editor

Like squirrels tucking away nuts for the winter, biotech firms lately have proven notably fond of shelf registrations, and Ribozyme Pharmaceuticals Inc. (RPI) became the latest - filing to sell 3 million shares, which would raise $67.1 million at Monday's closing price of $22.375.

RPI, however, already has big plans for at least some of the proceeds, said Ralph Christoffersen, president and CEO of the Boulder, Colo.-based company, which is "embarking on a substantial expansion of our clinical programs," he said.

"We have eight different trials [starting] that have the potential to show efficacy by mid-2002," Christoffersen said.

With Emeryville, Calif.-based Chiron Corp., RPI is developing Angiozyme for solid tumors, a synthetic ribozyme that specifically inhibits synthesis of the vascular endothelial growth factor receptor, a key compound in the angiogenesis-blood growth pathway. Ribozymes, made up of a form of ribonucleic acid, can divide DNA, including messenger RNA, and thus selectively inhibit protein production.

"There will be five different Phase II trials, in non-small-cell lung cancer, colon cancer, breast cancer, renal cell carcinoma and melanoma," Christoffersen said. "At least some of these we hope to begin before the end of the year." Angiozyme recently finished a Phase I/II trial in cancer patients at the Cleveland Clinic.

On its own, RPI is developing Heptazyme, against hepatitis C. At the end of last month, at a meeting of the American Association for the Study of Liver Diseases in Dallas, RPI presented promising data from collaborative studies of the compound.

"We'll be starting the Phase II study, probably in the middle of next year," Christoffersen said. A Phase I/II study of Heptazyme finished in September.

With an affiliate of Dublin, Ireland-based Elan Corp. plc, RPI is developing Herzyme for the treatment of metastatic breast cancer in which the HER2 gene is overexpressed, and ovarian cancer.

"We'll be filing an [investigational new drug application] probably at the end of the first quarter" of next year, Christoffersen said.

RPI has anti-hepatitis B product candidates, too, which have shown activity in preclinical experiments. "The hepatitis B program is just getting started," Christoffersen said. "We'll be identifying a product candidate by the end of next year."

This spring, RPI sold 3.15 million shares at $18 each for gross proceeds of $56.7 million, reducing almost by half the amount it would have raised - $147 million - had the offering taken place when the registration was filed, and the stock was selling for $49.75. (See BioWorld Today, March 3, 2000; and June 7, 2000.)

"But, if you put it in context, at the time we did the offering, the closing price of the secondary offering was 80 percent higher than where we started the year," Christoffersen said.

In separate news Tuesday, the company revised its earlier statement of second-quarter results to show a $628,000 reduction of stock compensation expense for the three-month and six-month periods that ended June 30.

A review of the stock purchase plan led to the change, based on tax rules, and the loss per share went to 13 cents and 42 cents for the three-month and six-month periods, respectively, from 17 cents and 47 cents as first reported.

At the end of the second quarter, RPI had $59.53 million in cash, with a "$10 million to $12 million net burn" anticipated for the year, Christoffersen said. "Next year, it will jump for sure," he added. The company has not disclosed estimates of the jump, nor has it made any decisions on what portion of the shelf registration's potential 3 million shares might be sold, he said.

"We have sufficient funds to get [the trials] going," he added. RPI has 15.28 million shares outstanding.

Among the firms to file shelf registrations, or sell stock in conjunction with them, or both, in recent months are Alexion Pharmaceuticals Inc., of New Haven, Conn.; Aradigm Corp., of Hayward, Calif.; Avigen Inc., of Alameda, Calif.; CuraGen Corp., of New Haven, Conn.; and Human Genome Sciences Inc., of Rockville, Md.

RPI's stock (NASDAQ:RZYM) gained 37.5 cents Tuesday to close at $22.812.