By Randall Osborne

On the strength of its hairpin ribozyme technology for determining gene function in human cell lines, Immusol Inc. made its first genomics deal, a collaboration with Pfizer Inc. to validate therapeutic targets.

Under the terms of the agreement, New York-based Pfizer will provide candidate gene target sequence information to Immusol, for the design of specific ribozymes to each target. Immusol then will deliver ribozymes to mammalian cells, generating an in vivo model, to measure the loss of each selected target gene product and evaluate its disease function.

"As far as we know, no other company does it the way we do it," said Tsvi Goldenberg, chairman and CEO of San Diego-based Immusol.

Financial terms were not disclosed.

Ribozymes — RNA molecules that normally catalyze their own cleavage — can be engineered to cleave and inactivate other RNA molecules in a specific, sequence-dependent fashion. By cleaving target RNA, ribozymes inhibit the RNA's translation into a protein and thereby stop the expression of a specific gene.

Immusol's technologies use these chemically synthesized, structurally modified ribozymes with heightened catalytic activity, as well ribozymes that are introduced into cells through an optimized vector, allowing their continued synthesis inside the cell.

The company uses hairpin ribozymes, so named because of their shape. While smaller ribozymes may only assume a stable shape when bound to their substrates, hairpin ribozymes take their shape immediately after synthesis, thus remaining hardy and resistant to ribonucleases that might degrade them in the cell.

But the main feature of Immusol's technology is that it does target validation in human cell lines.

"Everybody has genes, and there's a bottleneck out there," he added. "Most companies put the gene into a nematode or a transgenic mouse, which takes a year to two years. We can do it in months, and we're about to finish the first batch [of genes from Pfizer]."

The deal is the second between Immusol and Pfizer.

In May 1995, the two entered a drug discovery collaboration related to an HIV therapy. That agreement was one of four made simultaneously by Pfizer, which collectively named the alliances Pfizergen. (See BioWorld Today, May 19, 1995, p. 1.)

Immusol's 1995 partnership — said to be worth up to $49 million, if it had lasted a full five years — will not be renewed, Goldenberg said, but the term of the new deal with Pfizer is indefinite.

"We get a batch of genes, we do them, and we get another one," he said.

Goldenberg declined to say how much was gained from the first Pfizer deal, but Immusol filed for an initial public offering (IPO) of 3 million shares in the fall of 1996, and did not complete it. (See BioWorld Today, Sept. 10, 1996, p. 1.)

"We decided we did not need the money at that time, and so we pulled back," Goldenberg said.

The IPO is not expected anytime soon, but a large Phase III trial of Restenase — Immusol's formulation of a specific ribozyme to prevent post-angioplastic restenosis — is on track for later this year, Goldenberg said. Restenase uses a ribozyme that has been engineered to cleave and inactivate a smooth-muscle cell target, sequence-dependently.

Meanwhile, Immusol is seeking more partners like Pfizer.

"That's going to be our model, to go to a pharmaceutical company and say, 'Let us have your genes of interest, and we'll put them through our model,'" Goldenberg said. "We believe we have a better mousetrap." *