By Mary Welch

In a deal reportedly similar to one negotiated with Schering AG last year — and as lucrative — Ribozyme Pharmaceuticals Inc. (RPI) entered a research collaboration with Roche Bioscience focusing on the use of ribozymes to identify genetic therapeutic targets.

The estimated value of the deal is at least $25 million and may go as high as $60 million if all development milestones are met. Roche Bioscience, of Palo Alto, Calif., is a unit of Hoffmann-LaRoche AG, of Basel, Switzerland.

Neither Roche nor Boulder, Colo.-based RPI officials would confirm the financial arrangements.

RPI's stock (NASDAQ:RZYM) closed Wednesday at $5.625, up $0.062.

The collaboration will use ribozymes to discover critical genes in disease pathways and select new therapeutic agents based on those targets. RPI's CEO and president, Ralph Christoffersen, declined to name the diseases to be studied.

"This is important for us scientifically because it is the first time a partner is using us to discover new genes and not just validate which genes are important. It's a new direction," Christoffersen said.

RPI's ribozyme technology can identify critical genes by their phenotype without prior knowledge of their sequences. Ribozymes — RNA molecules that acts like enzymes — can inhibit gene expression and determine the level of that expression. Using RNA and other phenotypic in vitro and in vivo assays, the technique identifies those genes associated with disease and disease pathways.

RPI will use its expertise in ribozyme design, synthesis and delivery while Roche will provide in vivo models and clinical development. Roche has commercialization rights.

Roche Aiming To Speed Gene Identification

"We use ribozymes to inhibit any sequence, both in cell cultures and in animal models of the disease," Christoffersen said. "It is more important to go beyond determining the biological function of genes and find out which is a valid target. Our technology forms a natural and significant extension of genome sequencing efforts to target discovery and validation. Target discovery and validation are what's important."

Roche expects RPI's technology to reduce the time to identify genes. Christoffersen said the deal is important to the company in another way.

"When we started two years ago in target validation we said we wanted to add partners. In 1996, we partnered with Chiron, and last year we partnered with Schering and Parke-Davis. This year we wanted to add two partners and this is our first one. We're right on schedule. Adding partners is a way to create and nurture our business."

In a deal first inked in 1994 and expanded in 1996, RPI is collaborating with Chiron Corp., of Emeryville, Calif., for products targeted at viruses, cancer, restenosis and ocular diseases. In March 1997, the two began clinical trials with a gene therapy to make immune system cells resistant to the HIV infection. (See BioWorld Today, Oct. 20, 1997, p. 1.)

The agreement with Parke-Davis, a division of Morris Plains, N.J.-based Warner-Lambert Co., is not as lucrative as those with Schering, of Berlin, and Roche. (See BioWorld Today, March 23, 1998, p. 1)

The Schering pact, negotiated in April 1997, is worth a potential $60 million with, $25 million guaranteed. (See BioWorld Today, April 14, 1997, p. 1.)

The companies just finished a successful Phase I trial to down-regulate target gene sequences provided by Schering's U.S. subsidiary Berlex Laboratories Inc., of Wayne, N.J. The study showed a significant reduction in the expression of each of the target sequences in cell culture.

In the planned Phase II, RPI will design and synthesize GeneBloc reagents against additional target gene sequences, perform cell-line delivery optimization studies and carry out RNA and phenotypic assays in vitro. GeneBloc reagents are nucleic acid molecules that are capable of specifically down-regulating gene expression at the mRNA level. *