BioWorld International Correspondent

Underlining Switzerland's current position as Europe's pre-eminent biotechnology IPO market, Addex Pharmaceuticals SA raised gross proceeds of CHF136.9 million (US$111.3 million) in an offering on the Swiss Stock Exchange in Zurich that was four times oversubscribed.

The company issued 1,875,000 new shares, priced at CHF73 per share, which was near the top of its previously published indicative price range of CHF58 to CHF75 per share. If exercised, an overallotment option comprising 281,250 additional shares would add another CHF20.5 million to the gross.

The stock, which is traded under the symbol 'ADXN', opened at CHF75 on the main segment of the Swiss Stock Exchange Tuesday morning, but dropped to a low of CHF68.40 within a couple of hours. By mid-afternoon it was back at CHF71.30.

Geneva-based Addex had raised more than CHF106 million prior to the IPO, including a CHF40 million Series C round, which it completed last fall. It plans to use the latest infusion of cash to progress development of its clinical and preclinical pipeline of allosteric modulators - compounds that alter the activity of a target by binding at a secondary site instead of the active, ligand-binding site. (See BioWorld International, Sept. 20, 2006).

"We believe we can go to 2010 with what we have, with a very aggressive development plan," CEO and co-founder Vincent Mutel told BioWorld International.

The company's lead product, ADX10059, an allosteric inhibitor of the metabotropic Glutamate Receptor 5 (mGluR5), has completed Phase IIa clinical trials in gastroesophageal reflux disease (GERD) and migraine and currently is undergoing a Phase IIa study in acute anxiety. It aims to commence Phase IIb clinical studies of the compound in GERD and in migraine by late this year or early in 2008. "We will complete the Phase IIb [trials], and then we will look for partners," Mutel said.

ADX10061, a selective inhibitor of the D1 Dopamine receptor - and the sole compound in Addex's pipeline that does not act via an allosteric mechanism - currently is undergoing a Phase IIa clinical trial in smoking cessation. The completion of that study is imminent, and the company aims to sign a partnering deal at this point.

Its third clinical stage project, ADX48621, is, like ADX10059, an allosteric inhibitor of mGluR5 but has a different pharmacokinetic profile and is in development for depression, generalized anxiety disorder, and inflammatory pain. It is undergoing a Phase I clinical trial and also is available for partnering.

In addition, two preclinical programs could enter the clinic within the next year. ADX63365 is in development for schizophrenia and cognitive impairment. The second program, involving allosteric activation of metabotropic glutamate receptor 2, already has been partnered with New Brunswick, N.J.-based Johnson & Johnson.

Addex has identified six more preclinical programs, including two that target indications outside of central or peripheral nervous system disorders. ADX2 acts on follicle-stimulating hormone (FSH) receptor, a validated G-protein coupled receptor (GPCR), and has potential application in contraception, breast cancer and osteoporosis. ADX4 is a positive allosteric modulator of glucagon-like peptide 1 (GLP-1) receptor and in development for Type II diabetes.

The latter has yielded drug leads that display activity in cell lines but those need further optimization before in vivo studies can commence, Mutel said. Extending the concept of allosteric modulation into areas such as metabolic disease will widen its scope, but it also poses additional challenges for Addex.

The company is collaborating with Bernard Thorens at the University of Lausanne, a well-known diabetes researcher. It is also hiring personnel with expertise in the area.