By Randall Osborne

SAN FRANCISCO - Idun Pharmaceuticals Inc., which focuses on regulating apoptosis, or programmed cell death, signed a $30 million deal with Abbott Laboratories to develop cancer treatments.

"We want to develop drugs that allow the existing oncologic signals to be transmitted, so the cells die on their own," said Steven Mento, president and CEO of La Jolla, Calif.-based Idun, in a presentation at the 17th annual Hambrecht & Quist Healthcare Conference here.

"The $30 million is real dollars," Mento told BioWorld Today. "We're at a three-year cash position now."

Under the terms of the deal, Idun will provide primary molecular assays against targets in the apoptosis pathway. Abbott will use the assays for high-throughput screening of compound libraries, and will analyze the compounds, which then will be taken up by Idun for secondary characterization through the company's biological assays.

Abbott, of Abbott Park, Ill., will provide an equity investment up front, as well as guaranteed research and development funding.

Technology Mix Improves Prospects

Targets in the deal are "very difficult," Mento said.

"The problem is that the natural antagonist is a 16-amino-acid peptide, not a small molecule," he said, adding that he expects Abbott's technology employed with Idun's to meet the challenge.

"We think it's a perfect mix," Mento said.

Idun also has a deal, signed in September 1995, with Basel, Switzerland-based Novartis AG (formerly Ciba-Geigy Ltd.). That collaboration aims at developing therapeutics for central nervous system disorders. (See BioWorld Today, Sept. 15, 1995, p. 1.)

The companies have been looking for small molecules to manipulate genes that can delay the death of neurons linked to Alzheimer's disease, Parkinson's disease and other degenerative disorders.

"We're currently in final stages of lead selection with Novartis, which we hope will take place in early 1999," Mento said. Novartis has responsibility for clinical trials, which are expected to begin at the end of this year or in early 2000, he added.

Idun also has an internal program working on treatment for alcoholic hepatitis.

"We were very careful in selecting the indication that we have," Mento said. "Endpoints are relatively straightforward and clean."

Idun, which plans to develop the hepatitis treatment without a partner, has selected a lead compound - the company's first - and expects to file an investigational new drug application late this year, Mento said.

Caspase, Bcl-2 Families Targeted

The apoptosis-controlling genes are cell-death effectors of the CED-3/ICE, or caspase, family, and cell-death inhibitors of the Bcl-2 family. Caspases encode a set of proteases responsible for carrying out the death process - proteases that normally are kept inactive by proteins encoded by the Bcl-2 family.

Idun is directing its research toward drugs that specifically modulate the caspase family or the Bcl-2 family, or that become active at other key points in the apoptotic pathway.

Promoting or thwarting cell death could be useful across many applications, Mento said.

"I think the interest in anti-angiogenesis [in cancer treatment] is great," he said. "Basically, there's a new target cell to try and kill, or try to stimulate, in the case of angiogenesis for chronic heart disease."

Idun has a cardiovascular program dealing with myocardial infarction. Mento said the company is conducting talks with prospective partners for that program, and for another research effort into inflammatory disorders.

"We've really focused a lot of our effort in the past year on closing a big pharma deal in cancer," Mento said. "Now, we'll move on to some of the smaller deals. Very few therapies don't touch either on preservation of cell survival or stimulation of cell death, and one of the things we're looking at in 1999, like everyone else, is whether there might be some in-licensing opportunities to fill the pipeline with later-stage products." n

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