Addex Partner Starting Clinical Schizophrenia Trial

Addex Partner Starting Clinical Schizophrenia Trial

Geneva, Switzerland, March 28, 2011 – Allosteric modulation company Addex Pharmaceuticals (SIX:ADXN) announced today the start of a Phase IIa clinical trial of ADX71149 for the treatment of schizophrenia. ADX71149, a positive allosteric modulator (PAM) of metabotropic glutamate receptor 2 (mGluR2), is the result of a successful discovery collaboration and licensing deal announced in early 2005 between Addex and Ortho-McNeil-Janssen Pharmaceuticals, Inc. (OMJPI). Addex will receive a €2 million milestone payment from OMJPI.

“We believe that this mGluR2 PAM potentially offers one of the most exciting new and innovative ways to treat schizophrenia, anxiety and related indications,” said Dr Vincent Mutel, CEO of Addex. “Our partner has expertise and an interest in this indication that are of great value to Addex. This collaboration – which already is profitable for our young company – illustrates the great potential of our strategy to capitalize on our allosteric modulator discovery platform via carefully selected development partnerships like this one.”

The double-blind, placebo-controlled EU Phase IIa study will include about 105 schizophrenia patients in two parts:

  • Part A (monotherapy): 15 subjects with (sub)acute positive symptoms will be treated in an open-label design with a recommended starting dose of 50 mg bid. Then according to tolerability, as judged by the investigator, the dose may be increased stepwise to 100 mg bid up to the recommended target dose of 150 mg bid. In principle, the open-label treatment phase will last for maximally 12 weeks. Endpoints will examine tolerability, safety and efficacy.
  • Part B (add-on therapy): In 90 subjects with residual positive symptoms or predominant negative symptoms or in subjects with insufficient response to clozapine, ADX71149 will be administered in a double-blind, placebocontrolled, 2:1 (active drug : placebo) randomized design at 2 different dose levels, 50 mg bid up to maximally 150 mg bid, and this as adjunctive therapy to their currently prescribed antipsychotic. Endpoints will examine tolerability, safety and efficacy.

The development of ADX71149 is part of a worldwide research collaboration and license agreement between Addex and OMJPI to discover, develop and commercialize novel mGluR2 PAM for the treatment of anxiety, schizophrenia and undisclosed indications. Under the terms of the agreement, Addex is eligible for up to a total of €112 million in milestone payments upon potential development and regulatory achievements. In addition, Addex is eligible for low double-digit royalties on sales of mGluR2 PAM developed under the agreement.

Glutamate is a powerful transmitter in the brain and integral to the normal functioning of memory, learning and perception. Too much glutamate can lead to seizures and the death of brain cells. Too little glutamate can cause psychosis, coma and death. Glutamate exerts these effects by interacting with many receptors in the brain, especially NMDA and AMPA receptors. In addition to these primary receptors, glutamate triggers other receptors, termed metabotropic because they adjust the amount of glutamate that cells release rather than simply turning glutamate transmission on or off. In addition, there are eight types of mGluR, each with different functions. Thus, these metabotropic glutamate receptors (mGluR), because of their ability to fine-tune glutamate signaling, appear to be better targets for drug treatment. Indeed, industry has been investing in mGluR research for about three decades and research shows that mGluR drugs have potential for the treatment of schizophrenia, anxiety, Parkinson’s disease, fragile X syndrome, Alzheimer’s disease, depression and post-traumatic stress disorder.

The effects of positive allosteric modulators of mGluR2 are independent of dopamine receptors, indicating the potential for mGluR modulators to offer efficacy while avoiding the side effects associated with market leading antipsychotic drugs which appear to work predominantly via their effects on dopamine receptors.

Furthermore, mGluR2 activation has shown efficacy in patients suffering from schizophrenia and, separately, anxiety. A Phase II clinical study published in Nature Medicine* showed that activation of mGluR2 improved symptoms of schizophrenia with efficacy similar to that of one of the leading marketed drugs but did not cause weight gain or extrapyramidal symptoms, which are side effects that can be associated with the use of the leading marketed drugs. Another study showed that mGluR2 activation had a statistically significant benefit in patients suffering from generalized anxiety disorder**.

*Nature Medicine 13, 1102 - 1107 (2007)
**Neuropsychopharmacology 33, 1603-1610 (2008)

Addex Pharmaceuticals ( discovers and develops allosteric modulators for human health. The company is focused on using its proprietary discovery platform to discover allosteric modulators of cell surface receptors that are believed to have therapeutic potential for treating diseases of the central nervous system, metabolic disorders or inflammation. Subject to regulatory approvals, several Phase II clinical trials are expected to start soon for two lead products: ADX48621 and ADX71149. ADX71149 is undergoing Phase II testing for schizophrenia and may enter additional Phase II studies in anxiety and/or undisclosed indications. ADX48621 is an mGluR5 negative allosteric modulator (NAM), which will be tested in Parkinson’s disease levodopa-induced dyskinesia (PD-LID) and, separately, non-Parkinsonian patients suffering from dystonia, also a movement disorder. Other products nearing the clinic include: GABA-B receptor PAM with potential for chronic pain; follicle stimulating hormone receptor (FSHR) NAM, with potential for endometriosis and benign prostatic hyperplasia; and, mGluR2 NAM for Alzheimer’s disease. In addition, Merck & Co., Inc. has licensed rights to two preclinical programs: mGluR4 PAM for Parkinson's disease and mGluR5 PAM for schizophrenia. Preclinical discovery stage programs include: GLP1R PAM; IL1R1 NAM; and TNFR1 NAM.

Chris Maggos
Business Development & Communication
Addex Pharmaceuticals
+41 22 884 15 11

Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.