Addex Successfully Completes ADX48621 Phase I Program
GENEVA, Switzerland, 28 January 2009 - Addex Pharmaceuticals (SIX:ADXN) announced today the successful completion of two Phase I studies of a newly developed modified release formulation of ADX48621. The studies showed that ADX48621, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator (NAM) in development for Parkinson's disease levodopa induced dyskinesia (PD-LID), is safe and well-tolerated in healthy volunteers, including those over 50 years old.
Study ADX48621-102 consisted of two parts. Part One was a randomized, two-way crossover comparison in 12 healthy subjects of the pharmacokinetics, safety and tolerability of the original active pharmaceutical ingredient (API) in capsule with the modified release capsule. Part Two was a double-blind, placebo-controlled, multiple ascending, repeat dose study in 24 healthy subjects using three different doses of the modified release formulation. The study showed that the new formulation achieved satisfactory pharmacokinetics, safety and tolerability with single and repeat dose administration across the dose range planned to be used for the Phase IIa proof of concept study in PD-LID, which is expected to start later this year.
Study ADX48621-103 was a two-period crossover study that evaluated the safety, tolerability and pharmacokinetics of ADX48621 following single oral dosing in older healthy subjects (aged over 50 years) both fasting and following a high fat meal. ADX48621 was well tolerated by this group of older subjects and gave satisfactory drug exposure both in the fasted and fed states.
Chief Medical Officer Charlotte Keywood said: "The good safety and tolerability results for ADX48621 in older subjects are of particular interest because we plan to start Phase IIa proof of concept studies with the compound in Parkinson's disease dyskinesia later in the year."
mGluR5 inhibition has achieved clinical proof of concept in humans with PD-LID and separately in a primate model of PD-LID in studies with another company's mGluR5 inhibitor. Inhibition of mGluR5 has therapeutic potential in multiple indications because mGluR5 is involved in a variety of functions in the central and peripheral nervous systems*. In addition to PD-LID, mGluR5 inhibitors have achieved clinical proof of concept in separate studies in patients with gastroesophageal reflux disease (GERD), migraine and generalized anxiety disorder (GAD). Inhibition of mGluR5 also has potential in Fragile X syndrome. Our lead product, the mGluR5 inhibitor ADX10059, has been shown to have a superior effect to placebo in acute treatment of GERD and migraine headache in Phase IIa testing.
*mGluR5 antagonists: Discovery, characterization and drug development, Current Opinion in Drug Discovery & Development 2008 11(5):655-665
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 patients better results than 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. Both are important diseases for which existing products with limited efficacy have established multi-billion dollar markets despite sub-optimal efficacy. 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, in two separate agreements with Merck & Co., Inc., we are developing allosteric modulators as drugs to treat Parkinson's disease and schizophrenia. A third agreement, with Johnson & Johnson, is focused on development of allosteric modulators to treat anxiety and schizophrenia. Separately, the investment funds of Roche and GlaxoSmithKline have extended their validation of our technology, products and management by making significant investments in Addex.
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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.
Posted: January 2009