Addex Presents ADX10059 PD-LID Data at GPCR Drug Discovery Conference
Geneva, Switzerland, 3 November 2009 – Addex Pharmaceuticals (SWX:ADXN), the allosteric modulation company, presented results today from studies of its lead clinical candidate, ADX10059, in animal models of Parkinson’s disease levodopa induced dyskinesia (PD-LID) at the Discovery on Target GPCR-based Drug Discovery conference in Boston. Addex disclosed for the first time that in a non-human primate model of PD-LID, ADX10059 had a statistically significant impact on dystonia, a neurological movement disorder seen in Parkinson’s disease and other conditions, including generalized dystonia, tardive dyskinesia, levodopa non responsive PD syndrome and multiple system atrophy. There is no approved treatment available for PD-LID.
ADX10059 is the first-in-class negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), a mechanism that is being tested in multiple indications by Addex and competitors. ADX10059 is currently being evaluated in Phase IIb clinical trials for the treatment of gastroesophageal reflux disease (GERD) and to prevent migraine. Separate announcements of data from the two ongoing GERD trials are expected before year-end and early in 2010. The migraine study will report data early in the second quarter of 2010.
Addex disclosed earlier this year that ADX10059 demonstrated significant efficacy in well-established preclinical models of PD and PD-LID. Importantly, these effects in PD and PD-LID were seen at doses and plasma concentrations that have shown efficacy in both clinical and preclinical studies with the compound in other indications. The effects on dystonia announced today differentiate the Addex mGluR5 inhibitor within the PD indication but also present potential development opportunities for treatment of other types of dystonia.
The oral slide presentation today will show that in the non-human primate MPTP model of PD-LID, all doses of ADX10059 abolished LID during the first hour following L-DOPA administration and a dose response was observed during the second hour, reaching statistical significance for the two higher doses tested. Statistically significant reductions were seen for both chorea and dystonia in a dose dependent fashion. Similar effects on dystonia have not previously been reported in this model with drug-like molecules either in development or on the market.
When tested in the rat model, oral administration of ADX10059 dose-dependently reversed the catalepsy induced by haloperidol in three independent experiments.
Dystonia is a neurologic movement disorder characterized by sustained muscle contractions that frequently cause twisting or repetitive movements and abnormal, sometimes painful, postures or positions. Dystonia may affect any part of the body including the arms, legs, trunk, neck, head, or face.
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 abnormal involuntary movements. Currently there are an estimated 1.2 million patients with PD-LID in the U.S.
PD 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.
mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate. Marketed blockbuster drugs treat multiple indications by targeting other types of neurotransmitter signaling, including selective 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. Allosteric modulators are a different kind of orally available small molecule therapeutic agent, which we believe will offer a competitive advantage over classical drugs. Our lead allosteric modulator product, ADX10059, has achieved clinical proof of concept and is in Phase IIb testing for the treatment of GERD and, separately, migraine headache. ADX10059 is a first-in-class mGluR5 inhibitor, a therapeutic strategy that also is being pursued in multiple indications by large pharma competitors.
Our products and technology already have proven their value through our relationships with four of the top 10 pharmaceutical companies in the world. Specifically, under an agreement with Ortho-McNeil-Janssen Inc., a Johnson & Johnson company, ADX71149, a positive allosteric modulator (PAM) of mGluR2, is undergoing Phase I clinical testing and has potential for treatment of schizophrenia and anxiety. Under two separate agreements with Merck & Co., Inc., we are developing PAMs of mGluR4 and mGluR5 as drugs to treat Parkinson's disease and schizophrenia, respectively. In addition, GlaxoSmithKline and Roche have made equity investments in Addex.
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Disclaimer: The foregoing release contains 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, and involve known and unknown risks, uncertainties and other factors that may cause actual results with allosteric modulators of mGluR4, mGluR2, mGluR5 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 mGluR4, mGluR2 or mGluR5 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR4, mGluR2, mGluR5 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 mGluR4, mGluR2, mGluR5 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 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.