Washington Editor

Isis Pharmaceuticals Inc. on Wednesday said it signed another major drug company to use its GeneTrove division’s antisense inhibitors for target validation studies.

This time, Isis, of Carlsbad, Calif., struck a deal with Peapack, N.J.-based Pharmacia Corp. to use both target validation services and the intellectual property-licensing program.

Richard Brown, president of GeneTrove, wouldn’t release financial terms of the agreement, but did tell BioWorld Today that Isis retains rights to develop antisense drugs to the genes.

Isis’ stock (NASDAQ:ISIS) closed Wednesday at $16.51, down 37 cents.

The collaboration calls for GeneTrove to develop antisense inhibitors to gene targets provided by Pharmacia. In turn, Pharmacia will use the antisense inhibitors in phenotypic assays in its own therapeutic areas.

“What it will be looking at is, what’s the biological effect, in some phenotypic experiment, of inhibiting a particular gene?” Brown said.

Brown wouldn’t discuss the number of genes or indications Pharmacia expressed interest in, but did say, “we would expect that some of these genes will be looked at in single therapeutic areas and others will cut across therapeutic areas.

“That’s a theme we’re seeing these days. If there’s a particular gene of interest then you’re interested in not only what it does in your particular phenotypic area, but what it might do in other areas,” Brown said. “This is looking for both beneficial effects and potential side effects and, of course, you can evaluate all of that by running multiple experiments inhibiting the same gene in a number of different types of experiments.”

The licensing side of the agreement allows Pharmacia to work on its own internal antisense target-validation programs independent of GeneTrove, and Brown said this part of the agreement is similar to deals signed late last year with Thousand Oaks, Calif.-based Amgen Inc. and Emeryville, Calif.-based Chiron Corp. (See BioWorld Today, Dec. 14, 2001.)

But the aforementioned companies are not the only ones that GeneTrove caught the attention of in the last year or so. Brown mentioned deals with Merck & Co. Inc., of Whitehouse Station, N.J.; Celera Genomics, of Rockville, Md.; and Eli Lilly and Co., of Indianapolis.

In addition to target validations and the patent-licensing program, GeneTrove also offers a Human Gene Function Database and Antisense Inhibitor Library.

While Isis set up GeneTrove about two years ago, Brown said the company last year built up both staff and infrastructure and “now we are really seeing the business flow in.

“From our vantage, the last six to 12 months have been a pretty exciting time, given the overall momentum [in the industry] toward using antisense for target validation and a lot of momentum toward partnering with GeneTrove,” he said.

Brown attributes much of GeneTrove’s success to awareness in the scientific community. “In scientific literature, there’s been a flood of publications on how antisense is successfully being used to basically turn off the function of genes and evaluate the effect of it,” he said. “That’s one aspect of our success; the other is that here at Isis, we’ve given this part of our business a much stronger focus by [turning GeneTrove into divisions] and going out and seeking collaborations.”

Antisense drugs work at the genetic level to interrupt the process by which disease-causing proteins are produced.

Isis recently said it initiated a second Phase II trial of ISIS 104838, an antisense inhibitor of tumor necrosis factor-alpha, in rheumatoid arthritis (RA). The trial evaluates the product when administered by subcutaneous injection for three months. The double-masked, placebo-controlled, randomized trial is expected to enroll 160 RA patients at 25 sites in the U.S. and Canada.

And, Isis and Elan Corp. plc, of Dublin, Ireland, recently said that their joint venture, HepaSense Ltd., initiated a Phase II trial of ISIS 14803 (an antisense drug) in patients with chronic hepatitis C.