BioWorld International Correspondent

Swiss start-up Addex Pharmaceuticals SA, which is developing new therapeutic approaches for treating addiction, attracted a string of European venture capital funds to its inaugural financing round, raising CHF15.75 million (US$10.9 million).

The financing was co-led by Sofinnova Partners, of Paris, and Index Ventures, of Geneva. Also participating were TVM, of Munich; BCV Initiative Capital, of Lausanne, Switzerland; and undisclosed private investors.

Although formally established May 16 and fresh as a company, Geneva-based Addex has been a year in the making. The firm is a spin-out of a scientific project at Glaxo Wellcome, now GlaxoSmithKline plc, of London. Addex CEO Francois Conquet, who headed Glaxo's department of experimental pathology in Lausanne, and Chief Scientific Officer Mark Epping-Jordan led a team who demonstrated that knockout mice lacking the gene encoding the mGluR5 glutamate receptor were impervious to the stimulatory and addictive effects of cocaine. That work was published in the September 2001 issue of Nature Neuroscience, in a paper titled "Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice."

The receptor itself is associated with primitive learning behaviors but plays no direct role in the metabolism of cocaine. Subsequent work has shown that the genetically engineered mouse strain also failed to become addicted to amphetamines, nicotine, morphine or alcohol. All of these drugs have different actions, mediated by specific processes. Yet all of them move toward a common outcome - dependency - leading the researchers to conclude that "something must be switched on to start off the process of dependence," Conquet told BioWorld International.

The mGluR5 receptor is his candidate for this task. Existing approaches to treating drug addiction are based on a "weaning strategy," Conquet said. Smokers use nicotine patches or nicotine gum, for example, while heroin addicts receive methadone in order to gradually reduce dependence on the drug. "So you don't break dependence," he said.

Modulators of the mGlu5R receptor potentially could tackle the problem of addiction by a different route. The target's druggability is enhanced by the observation that its absence does not appear to affect the primitive natural reward systems that stimulate the search for food, water, sex and opportunities for maternal behavior. If these are blocked, animals - and by extension, humans - would fail to survive.

"This mouse that we have engineered can no longer take cocaine but at the same time has a normal life," Conquet said. "We haven't touched the natural reward system."

Addex has generated lead compounds that affect its activity. One led to the disappearance of nicotine addiction in animal models just 1.5 hours after administration, he said. The company is seeking additional targets that also modulate drug addiction indirectly. It also is in negotiations to in-licence two therapeutic candidates that are already in clinical development.

This particular aspect of its model echoes another Swiss biotechnology firm - Actelion Ltd., of Allschwil, which is not a coincidence. Addex chairman Andre Mueller is a board member of Actelion and its acting chief financial officer, while Antoine Papiernik, of Sofinnova, who also has joined the Addex board, was an early investor in the same company.

Although it has secured a chunk of cash sufficient to fund the next two years of activity, Addex has embarked on a second round, seeking €30 million 18 months from now, Conquet said.