BioWorld International Correspondent

Addex Pharmaceuticals SA raised CHF40 million (US$31.9 million) in a Series C financing to fund Phase II trials of its lead compound, ADX10059, a negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), in three different indications.

Two big pharma-backed venture capital funds joined the Geneva-based company's roster of investors. SR One, of West Conshohocken, Penn., the venture capital arm of London-based GlaxoSmithKline plc, led the round, while the Roche Venture Fund, backed by F. Hoffmann-La Roche Ltd., of Basel, Switzerland, also participated. Existing investors Sofinnova Partners, Index Ventures, TVM Capital, PolyTechnos Venture-Partners, Bio*One Capital Pte. Ltd., Renaissance PME and Varuma AG also supported the round.

Addex, which was established in 2001, has raised more than CHF106 million to date and has enough cash, CEO Vincent Mutel told BioWorld International, to fund operations until the end of 2008. The company aims to take ADX10059 through clinical development, and it plans to participate in its commercialization.

"We believe it's the only way to maximize revenue," Mutel said.

The compound recently entered Phase II trials in acute migraine and gastro-esophageal reflux disease (GERD), and it is about to enter a Phase II study in acute anticipatory anxiety. The migraine trial, Mutel said, has a clearly defined endpoint and will not require complicated assessments. "You have to be free of pain after two hours, according to the guidelines," he said.

The migraine market is dominated by the triptan class of serotonin receptor agonists, which act by inducing vasoconstriction and relieving pain. However, the neuronal aspects of the condition are not affected by triptan therapy, Mutel said, and other symptoms of migraine, such as photophobia, phonophobia and debilitating nausea are not improved. While animal models of migraine are not well defined or highly predictive, he said, "the involvement of glutamate in migraine is very well recognized."

In GERD, Mutel said, Addex aims to correct the inappropriate opening of the esophageal sphincter. Current therapy involves the use of proton pump inhibitors, which reduce the acidity of the stomach.

Acute anticipatory anxiety, experienced by people with a fear of flying or going to a dentist, for example, remains the primary indication for which ADX10059 is being developed. The company will use a validated induced stress model in the upcoming Phase II trial.

While at Roche, Mutel and colleagues demonstrated that fenobam - a compound with known anti-anxiety or anxiolytic activity in man and in animals - acted via negative allosteric modulation of mGluR5. The compound, discovered in the 1980s, was never optimized as a pharmaceutical, he said, because its mechanism was then unknown, but the class has substantial potential in the field.

"In man they are anxiolytic, with rapid onset of action but without the effects of benzodiazepines," he said. Use of the latter is strictly controlled because they can induce addiction, have a sedative effect and interact with alcohol.

Addex also is seeking near-term revenue opportunities by out-licensing additional clinical and preclinical drug candidates that are targeted at larger indications, which are beyond its scope.

Those include ADX10061, a selective dopamine D1-selective antagonist, which will shortly enter a Phase IIa trial in smoking cessation in the U.S.

Its two other drug candidates are at the preclinical stage. ADX4862, another negative allosteric modulator of mGluR5, which has a different pharmacokinetic profile from ADX10059, is in development for generalized anxiety disorder and depression. ADX50938, which also acts on mGluR5, is in development for schizophrenia and Alzheimer's disease.

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