Addex Reports Positive Preclinical Data for GABA-BR PAM Oral Small Molecule in Overactive Bladder
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Addex Reports Positive Preclinical Data for GABA-BR PAM Oral Small Molecule in
Overactive Bladder
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* Program on track for IND filing before end of 2012
* GABA-BR PAM compounds have potential in several major Indications
Geneva, Switzerland, 16 April 2012 - Addex Therapeutics (SIX:ADXN), a leading
organization pioneering allosteric modulation-based drug discovery and
development, announced today positive data from studies of its lead GABA-B
receptor (GABA-BR) positive allosteric modulator (PAM) oral small molecule in
validated disease-relevant preclinical models of overactive bladder (OAB).
"Current treatments for OAB are associated with marginal efficacy and
significant side effects, which limits their use in treating the millions of
people suffering from this condition," noted Dr. Sonia Poli, Head of Non-
Clinical Development at Addex Therapeutics. "We believe that a well tolerated
and efficacious oral treatment would represent a major advance in OAB treatment.
We are delighted with the efficacy and safety profile of our GABA-B receptor PAM
oral small molecules and are rapidly advancing the lead candidate towards a
regulatory filing to initiate clinical trials by the end of 2012."
The Addex lead compound (ADX71441), an oral small molecule, with potential for
once daily dosing, selectively activating GABA-BR function, was evaluated in
female guinea pigs with bladder overactivity. ADX71441 (1 and 3 mg/kg, i.v.)
induced a strong increase in inter contraction interval (ICI), a validated
measure of bladder muscle control, in the first 15 min post-administration
compared to vehicle. The efficacy of ADX71441 was well correlated with its
pharmacokinetic properties. ADX71441 also significantly decreased micturition
(urination) frequency compared to vehicle at the 1 mg/kg dose.
In an independent mouse diuretic stress-induced model of overactive bladder,
administration of ADX71441 dose-dependently normalized urination latencies.
ADX71441 also dose-dependently reduced micturition frequency in furosemide-
treated animals. The magnitude of the effect in response to 10 mg/kg ADX71441
was similar to those observed in oxybutynin (a commonly prescribed anti-
cholinergic medication for OAB) - treated animals. At this dose, however, unlike
oxybutynin-treated animals, ADX71441 was well tolerated and had no marked
effects on body temperature, locomotor activity or motor coordination.
These data on ADX71441 will be presented at the American Urology Association
(AUA) Annual Meeting in Atlanta (May 19-23, 2012).
"We look forward to a regulatory filing for clinical testing for this molecule
at the end of this year as we drive forward our strategy of filing one IND per
year. These data along with our recent announcement of positive phase 2 data in
Parkinson's disease levodopa-induced dyskinesia demonstrate the strength of our
pipeline based on allosteric modulator oral small molecule platform and its
ability to generate multiple high value novel product opportunities" said
Bharatt Chowrira, President and CEO of Addex Therapeutics.
About Overactive Bladder
Approximately 11-16 million U.S. women suffer from overactive bladder, with some
estimates claiming an equal number of men suffer from the condition. Patients
with an overactive bladder feel a strong and sudden need to urinate, which is
usually associated with frequent nocturia (excessive trips to the bathroom in
the middle of the night). These symptoms arise due to involuntary contractions
of bladder muscle when filling with urine. Current standard of care is
inadequate due to limited efficacy and side effects, such as dry mouth, blurred
vision, tachycardia, CNS effects, ranging from cognitive impairment to episodes
of psychosis, which significantly limit their use.
About GABA-BR Activation
Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C
class of GPCR, is clinically & commercially validated. Generic GABA-B receptor
agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and
used for OAB, but is not commonly used due to severe CNS side effects of the
drug and rapid clearance. Orthosteric GABA-B receptor agonists have also shown
clinical validation in gastroesophageal reflux disease (GERD). Addex' GABA-B
receptor PAMs have shown efficacy in multiple preclinical models including: OAB,
pain, osteoarthritis pain and anxiety.
Addex Therapeutics (www.addextherapeutics.com) 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 2 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 overactive bladder, pain 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.
Tim Dyer
Chief Financial Officer
Addex Therapeutics
+41 22 884 15 61
PR(at)addextherapeutics.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
Therapeutics, formerly known as, Addex Pharmaceuticals, 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 Therapeutics 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 Therapeutics 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.
This announcement is distributed by Thomson Reuters on behalf of
Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Addex Therapeutics via Thomson Reuters ONE
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Datum: 16.04.2012 - 07:00 Uhr
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