Addex Presents Data on Allosteric Modulators of GPCRs at the Discovery on Target Conference
Geneva, Switzerland, 2 November 2011 – Addex Pharmaceuticals (SIX:ADXN), a leading biopharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that its scientists will present data on several key positive allosteric modulators (PAM), or activators, at the Discovery on Target conference (November 2-4, 2011) in Boston, USA. Data will be presented in oral presentations on the following programs:
Oral GLP1 Receptor Positive Allosteric Modulators
Addex discovered a series of orally available glucagon like peptide-1 receptor (GLP1R) PAM that are in the lead generation stage of development for type II diabetes. While there are marketed injectable peptide drugs targeting GLP1R, a GLP1R PAM from this series could become the first orally available small molecule therapeutic agent against this target and has the potential to change the treatment paradigm for type II diabetes and co-morbid obesity. In addition, the allosteric mechanism may offer a superior side effect profile compared to injectable peptide drugs.
The presentation shows that orally available GLP1R PAM from Addex increased insulin secretion and decreased glycemia in response to glucose in well-known preclinical models of diabetes. In the preclinical “db/db” model, in which the insulin response to oral glucose (sugar) is muted, oral GLP1R PAM facilitated an insulin response and better control over blood glucose than vehicle or a marketed drug to treat type II diabetes, sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor.
Oral Metabotropic Glutamate Receptor 4 Positive Allosteric Modulators
The metabotropic glutamate receptor 4 (mGluR4) PAM is one of the most highly sought after potential therapeutic approaches for Parkinson’s disease today. At the conference, Addex will disclose a novel oral mGluR4 PAM chemical scaffold with a pharmacophore and structure activity relationship that is completely different from existing molecules in the field. Data will also be presented on a lead mGluR4 PAM candidate that has demonstrated efficacy in preclinical models of Parkinson’s disease and anxiety after oral administration. Addex is currently advancing first-in-class brain-penetrant orally bioavailable mGluR4 PAM and expects to select a clinical candidate in the first half of 2012.
Oral GABA-B Receptor Positive Allosteric Modulators
GABA-B receptor (GABA-BR) agonism (activation) has been validated as a potentially effective treatment in a number of indications including pain and overactive bladder (OAB). However, use of the marketed generic GABA-BR agonist, baclofen, is severely limited by its poor tolerability profile. In contrast, because of the inherent differences in the mechanisms of positive allosteric modulators and agonists, GABA-BR PAMs are expected to have a superior side effect profile compared to baclofen. As a result, GABA-BR PAM could provide a much needed alternative to opioids for pain and anti-muscarinic drugs for OAB, both of which are associated with use limiting side effects. At the conference, Addex will present data that has demonstrated that Addex’ GABA-BR PAMs have in vivo efficacy and superior tolerability in preclinical models of anxiety, inflammatory pain and osteoarthritis pain. Addex GABA-BR PAMs are in the final stages of lead optimization and a clinical candidate is expected to be selected by the end of 2011.
11:10 Discovery and Characterization of a Novel Chemical Class of GABA-BR Allosteric Potentiators
Geraldine Parenty, Ph.D., Senior Scientist, in vitro Pharmacology, Addex Pharmaceuticals
4:30 A GLP1 Positive Allosteric Modulators Approach for the Treatment of Type-2 Diabetes
Guillaume Duvey, Ph.D., Group Leader, Medicinal Chemistry, Addex Pharmaceuticals
11:25 Antiparkinsonian and Anxiolytic Effects of a Novel Chemical Class of Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4
Sylvain Celanire, Ph.D., Group Leader, Medicinal Chemistry, Addex Pharmaceuticals
Addex Pharmaceuticals discovers and develops an emerging class of small molecule drugs, called allosteric modulators, which have the potential to be more specific and confer significant therapeutic advantages over conventional “orthosteric” small molecule or biological drugs. The Company uses its proprietary discovery platform to address receptors and other proteins that are recognized as attractive targets for modulation of important diseases with unmet medical needs. The Company’s two lead products are being investigated in Phase IIa clinical testing: dipraglurant (ADX48621, an mGluR5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson’s disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive allosteric modulator or PAM) is being developed by our partner Janssen Pharmaceuticals Inc. to treat schizophrenia. Addex also is advancing several preclinical programs including: GABA-BR PAM for pain, overactive bladder and other disorders; mGluR4 PAM for Parkinson's, anxiety and other diseases; GLP1R PAM for type 2 diabetes; mGluR2 NAM for treating Alzheimer's disease and depression; and FSHR/LHR NAM for sex hormone dependent tumors & reproductive system disorders. In addition, Addex has discovery programs to identify allosteric modulators of: receptor tyrosine kinase (RTK) superfamily, including TrkB PAM for treating neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s and Huntington’s diseases); and TNF receptor superfamily, including TNFR1 NAM for inflammation (e.g. rheumatoid arthritis) and other diseases.
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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, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB 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, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB or other therapeutics targets 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, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB 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, GABABR, FSHR/LHR, GLP1R, TNFR1, RTK, TrkB 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.