By Frances Bishopp

Eukarion Inc. and Glaxo Wellcome plc will collaborate on the research and development of products for the treatment of chronic diseases. The agreement is the first major collaboration for the Bedford, Mass., company and focuses on developing Eukarion's synthetic catalytic scavenger (SCS) technology.

Eukarion, a privately held company founded in 1991, is developing proprietary therapeutic products using two approaches to inactivate intracellular targets associated with diseases. The first, which targets ubiquitous, toxic reactive oxygen species using novel synthetic molecules, Synthetic Catalytic Scavengers (SCS), is the subject of the agreement between the two companies.

Eukarion's second approach, a protein modification program, is directed at blocking the function of intracellular disease-associated targets using modified antibodies. The modification enables their passage across blood vessel walls and cellular membranes and, thus, their entry into cells to block their selected target.

Bernard Malfroy, president, CEO and co-founder of Eukarion, told BioWorld Today that during the course of the agreement, Eukarion will receive research funding, license fees and milestone payments from Glaxo Wellcome, of Middlesex, U.K., in addition to royalty payments on any products resulting from the collaborations.

Malfroy would not disclose financial details of the collaboration except to say the funds would "allow Eukarion to operate at break-even financial levels for the foreseeable future."

Malfroy said Eukarion has some compounds that are ready to be considered for development, but, at this point, is not ready to discuss them.

Eukarion's SCSs are small synthetic compounds that target reactive oxygen intermediates (ROI), toxic chemical byproducts of tissue stress. ROIs have been implicated in the irreversible damage that occurs in patients suffering from many chronic disorders, including asthma, atherosclerosis, lupus, multiple sclerosis, neurodegenerative diseases of the central nervous system, ischemia-induced organ damage, allergy and adult respiratory distress syndrome.

The SCSs work in animal models of such diseases by catalytically eliminating the toxic oxygen reactive species, including oxygen radicals and hydrogen peroxide.

These seemingly diverse conditions appear to have ROI involvement as a common link, creating the potential for a small number of SCS compounds to address huge unmet medical needs.

We are developing a class of synthetic, low molecular-weight compounds that are catalytic scavengers of reactive oxygen intermediates, explained Susan Doctrow, vice president of research at Eukarion.

These compounds exhibit superoxide dismutase activity, as evidenced by their ability to neutralize superoxide. Furthermore, they exhibit catalase activity, as evidenced by their ability to convert hydrogen peroxide to oxygen, she said.

These SCSs have displayed efficacy in a number of disease models, in broad categories that include inflammation, cardiovascular disease, acute critical illness, autoimmune disease and CNS disorders, Doctrow said.

For example, they protect cardiac function in animal models for myocardial ischemia. They also preserve neurons in animal models for stroke and Parkinson's disease. These compounds represent a new class of experimental therapeutic agents with potential utility in the broad range of diseases in which oxidative stress has been implicated, Doctrow said.

"Our SCSs, as combined SOD and catalase mimics, have a unique mechanism of action in two ways. First, they inactivate multiple ROIs. Second, they do this catalytically. As a result, very low doses are sufficient for efficacy in vivo. The opportunity for us to join forces with Glaxo Wellcome's scientists is, of course, a tremendous one for us. It should enable us, in synergy with our partners at Glaxo, to advance the SCS program rapidly and effectively toward its full clinical potential," Doctrow said.

Eukarion's SCS technology currently is protected by one issued patent and four pending patent applications.

Eukarion, which operated as a "virtual" corporation during its first several years, currently has six employees and its own laboratory. The company considers itself a fully integrated research and development company, with one of its major strengths being its extended organization, including academic and corporate relationships. *