Geneva, Switzerland, 15 June 2010 - Allosteric modulation company Addex Pharmaceuticals Ltd (SIX:ADXN) today presented encouraging data from preclinical studies demonstrating the anti-Parkinson’s effects of ADX48621, a novel drug candidate that has completed three Phase I clinical trials. 

Addex presented preclinical data at the 14th International Congress of Parkinson’s Disease and Movement Disorders held in Buenos Aires, Argentina showing that ADX48621 was effective in two well-established models of PD: the MPTP monkey model of Parkinson’s disease levodopa induced dyskinesia (PD-LID) and the rat haloperidol induced catalepsy (HIC) model of PD symptoms. Addex previously disclosed that ADX48621, a negative allosteric modulator (NAM) of the metabotropic glutamate receptor 5 (mGluR5), was effective in these models and had achieved satisfactory pharmacokinetics, safety and tolerability in three separate Phase I clinical trials in a total of 130 healthy volunteers, including older subjects.

PD-LID develops in most PD patients after receiving levodopa for several years. It is a complication caused by dopamine replacement therapy (i.e. levodopa). The two main components of LID are chorea and dystonia. Chorea is manifest as sudden rapid uncontrolled movements (e.g. jerking). Dystonia is manifest as slow writhing type movements and sustained muscle contractions, which can be painful.

In the MPTP model of PD-LID, ADX48621 (30 mg/kg) statistically and significantly inhibited LID. At this dose, ADX48621 almost abolished chorea and dystonia, the two major components of LID, without affecting the beneficial effects of levodopa as determined by disability scores. 

In the rat HIC model of PD, ADX48621 decreased catalepsy time dose dependently, by 19% 43%, 53%, and 65% at 1, 3, 10 and 30 mg/kg, respectively, compared to vehicle control. There was a trend to efficacy at 3mg/kg, with statistical significance at 10 (p < 0.01) and 30 mg/kg (p<0.001). These data show that the minimal effective dose of ADX48621 was 10 mg/kg, with a corresponding plasma concentration of about 1700 ng/ml. 

“We are very encouraged by these data, particularly the effect of ADX48621 on dystonia, a debilitating movement disorder in PD and also in other patients who do not have PD. To our knowledge, no other drug on the market or in development has demonstrated this level of activity in this primate model. Furthermore, the data from the HIC model indicate that, in the long-run, ADX48621 also could be tested as a treatment for the general symptoms of PD, potentially as a complementary drug that would allow doctors to optimize levodopa dosing,” noted Charlotte Keywood, chief medical officer at Addex. “There is currently no treatment approved for PD-LID and with the condition affecting so many people. We look forward to starting Phase II testing of ADX48621 in PD-LID and dystonia patients around the end of this year.” 

Parkinson’s disease is a degenerative disease of the brain that often impairs motor skills, speech, and other functions. It is estimated that 60,000 new cases are diagnosed each year in the U.S., where more than 1.5 million people currently have PD. While the condition usually develops after the age of 65, 15% of those diagnosed are under 50. PD affects both men and women in almost equal numbers. Over time, generally several years, most PD patients treated with levodopa develop PD-LID.

mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate. Marketed blockbuster drugs treat multiple indications by targeting other types of neurotransmitter signaling, including selecitive serotonin reuptake inhibitors (SSRIs) used to treat depression and dopamine receptor inhibitors used to treat schizophrenia. The rationale for using mGluR5 inhibition in PD is that the loss of dopamine producing cells leads to excess glutamatergic stimulation in the brain’s “striatopallidal pathway”. mGluR5 are found abundantly in the striatum and are implicated in the excess glutamate activity in Parkinson’s Disease. Research shows that inhibition of glutamate stimulation in this pathway has generated anti-Parkinsonian effects in animal models of PD and PD-LID and in humans with PD-LID. 

Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric modulators for human health and is focused on validated therapeutic targets for diseases of the central nervous system, metabolic disorders and inflammation. Subject to the completion of Phase I testing and regulatory approvals, Phase II clinical trials are expected to start in 2010 in four indications for two lead products: ADX48621, an mGluR5 negative allosteric modulator (NAM), in dystonia and Parkinson’s disease levodopa-induced dyskinesia (PD-LID); and ADX71149, an mGluR2 positive allosteric modulator (PAM), in schizophrenia and anxiety. ADX71149 is licensed to Ortho-McNeil-Janssen Pharmaceuticals Inc. A third product, ADX71943, GABA-B receptor PAM with potential for chronic pain, is scheduled to enter Phase I testing around the end of 2010. In addition, Merck & Co., Inc. has licensed rights to two preclinical products: mGluR4 PAM for Parkinson's disease and mGluR5 PAM for schizophrenia. Additional preclinical discovery stage programs include: mGluR2 NAM, GLP1R PAM, IL1R1 NAM and TNFR1 NAM. Roche Venture Fund and SR-One, corporate venture arm of GlaxoSmithKline, are investors in Addex.

Chris Maggos
Investor Relations & Communications
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos(at)addexpharma.com


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.