Washington Editor

Isis Pharmaceuticals Inc. on Monday said it reacquired full rights to its preclinical Type II diabetes antisense candidate, ISIS 113715, from partner Merck & Co. Inc.

In a conference call with investors, reporters and analysts, Stanley Crooke, chairman and CEO of Carlsbad, Calif.-based Isis, declined to disclose financial terms of the transaction, which ended the deal valued at $50 million signed in May 2001. (See BioWorld Today, May 24, 2001.)

He said Isis is disappointed that Merck has decided against further investment in 113715, but vowed to initiate human clinical trials in the first half of 2003.

"During the past year, we have compiled a strong preclinical package and are now planning the Phase I clinical trials," Crooke said in a prepared statement. "We believe this is a compound that can potentially offer distinct advantages over existing treatments and is a significant commercial opportunity for Isis."

Crooke said on the call that Isis had been disappointed with the progress Merck was making with 113715, adding that it should have been in the clinic some time ago.

ISIS 113715, a second-generation antisense inhibitor of PTP-1B, is designed to improve the regulation of blood sugar levels in Type II diabetes, Isis said.

It's too early to say whether Isis will seek another partner for 113715, Lynne Parshall, Isis' chief financial officer and executive vice president, told BioWorld Today. However, Crooke mentioned that prior to signing the deal with Merck, other companies had expressed an interest in the candidate.

While Isis conducted a majority of the preclinical studies, Crooke said Merck was responsible for some work that resulted in promising findings.

For one, Sanjay Bhanot, executive director of Isis' antisense drug discovery program, told conference call listeners that 113715 does not appear to cause weight gain in patients, which is advantageous because more than 50 percent of Type II patients are obese.

Indeed, the company intends to explore the drug as a potential therapy for chronic obesity.

The product also produced normalization of blood sugar levels in multiple rodent models, which are industry-accepted predictors of probable efficacy in humans, and improved glucose tolerance tests in normal and obese monkeys, the company said. Studies revealed that 113715, which may be a candidate for oral administration, can be given once a week or potentially up to once a month by subcutaneous injection.

And even when given at dose levels 20 times as high as the estimated clinical dose, 11317 did not produce hypoglycemia.

Even though the 113715 deal didn't come to fruition, Parshall said the two other collaborations between Isis and Merck are progressing well.

The companies in 1998 entered a partnership valued at $50 million to develop a hepatitis C drug. According to Parshall, in the last year Isis has reached two milestones in that collaboration. (See BioWorld Today, June 10, 1998.)

Meanwhile, in February, the companies formed a target validation collaboration to support Merck's internal research and discovery efforts. The deal calls for Isis' Gene-Trove division to provide Merck with antisense-based tools to discover the biological roles of genes selected by Merck before validating them as potential drug targets. (See BioWorld Today, Feb. 22, 2002.)

Isis' stock (NASDAQ:ISIS) closed Monday at $6.91, up 41 cents.