div id="releaseBody">GENEVA, SWITZERLAND--(Marketwire - October 29, 2012) - Addex Therapeutics /
Addex Reports ADX71441 Reduces Alcohol Intake in a Preclinical Model of
Alcohol
Binge Drinking. Processed and transmitted by Thomson Reuters ONE.
The issuer is solely responsible for the content of this announcement.
* Data reinforces broad therapeutic potential of oral ADX71441
* Program on track for CTA filing before end of 2012
(SIX: ADXN), a leading company pioneering
allosteric modulation-based drug discovery and development, announced
today
positive preclinical data for its GABA-B receptor positive allosteric
modulator
(PAM) oral small molecule, ADX71441, in a validated rodent model of
alcohol
binge drinking. ADX71441 demonstrated robust, dose-dependent and
long-lasting
suppression of alcohol intake in animals compared to naltrexone, the
most-commonly prescribed treatment of alcoholism on the market.
"These data are extremely encouraging and superior to naltrexone in our
pre-clinical model, and warrant further exploration as a novel
treatment for
alcoholism," said Professor Klaus Miczek at Tufts University (USA) in
whose
laboratory the study was performed.
Both clinical and pre-clinical data suggest that activation of the
GABA-B
receptor offers a unique therapeutic opportunity to address largely unmet
needs
of patients with alcohol and drug abuse by (1) reducing the alcohol or
drug
intake; (2) alleviating many physical signs (pain,
Gastrointestinal/urinary
disturbances) and emotional symptoms (anxiety) associated with
withdrawal; and
(3) maintaining abstinence by reducing alcohol or drug craving.
ADX71441, which has potential for once daily dosing and selectively
activates
the GABA-B receptor, was evaluated in a mouse model of alcohol binge
drinking.
Acute, oral administration of ADX71441 (3, 10, 30 mg/kg) resulted in a
dose-dependent suppression of alcohol intake, achieving 80% reductions
at higher
doses (10, 30 mg/kg) in comparison to vehicle treatment. Reductions in
alcohol
consumption in response to ADX71441 treatment were present for the entire
4hour
alcohol access period. The effect of ADX71441 in this model was more
robust and
longer-lasting than that seen in mice treated with naltrexone, which was
used in
the study as a positive control. This is the first study showing efficacy
of a
GABA-B receptor PAM in a rodent model of alcohol binge drinking.
"Alcoholism is an important unmet medical need as current treatments
offer
marginal efficacy in reducing alcohol intake and are associated with
significant
side effects," noted Dr. Graham Dixon, CSO at Addex. "We are excited
by the
robustness of the data and look forward to the filing of a CTA for
ADX71441 by
the end of 2012 and initiating Phase 1 testing in Q1 2013."
Oral small molecule GABA-B receptor PAMs have potential in treating
multiple
indications and Addex has previously demonstrated positive proof of concept
in a
broad range of preclinical models, including those of pain, anxiety,
obsessive-compulsive disorder and overactive bladder (OAB). Addex is
positioning ADX71441
as a treatment for spasticity, with multiple sclerosis (MS) being an
initial
focus of the clinical development program.
"The advancement of ADX71441 towards the clinic clearly illustrates our
strategy
to bring forward innovative oral small molecule NCEs addressing
validated
targets with broad therapeutic potential," said Bharatt Chowrira, CEO at
Addex.
"GABA-B receptor is one such exciting target whose activation has been
validated
in a broad range of indications. We plan to initially focus on
evaluating
ADX71441 for the treatment of spasticity in MS patients who currently
are not
adequately treated for this debilitating disease."
About Alcoholism
Alcoholism is a broad term for problems with alcohol, and is
generally
indicative of compulsive and uncontrolled consumption of alcoholic
beverages. It
is medically considered a disease, specifically an addictive illness. The
World
Health Organization estimates that about 140 million people throughout the
world
suffer from alcohol dependence. Patients with alcoholism suffer major
changes to
the brain structure and chemistry. Excessive alcohol consumption damages
almost
every organ in the body and the cumulative toxic effects can cause both
medical
(cirrhosis of the liver, pancreatitis, heart disease, peptic ulcers,
sexual
dysfunction) and psychiatric (epilepsy, dementia, psychosis,
anxiety &
depression) problems. Treatment of alcoholism is complex with current
standard
of care typically being prescribed to patients with heavy drinking but
largely
being unable to prevent them from relapsing.
About GABA-B Receptor Activation
Activation of gamma-aminobutyric acid subtype B receptor (GABABR), a
Family C
class of GPCR, is clinically and commercially validated by a generic
GABA-BR
agonist, baclofen, which is marketed for spasticity in spinal cord
injury
patients. Baclofen has also shown clinical relevance in a number of
other
indications including overactive bladder, pain and is in early stage
clinical
development for alcohol dependence and autism. Despite baclofen's broad
clinical
validation, it is not commonly used due to multiple side effects,
rapid
clearance, development of tolerance to the drug, rebound and
withdrawal
syndromes. Orthosteric GABA-BR agonists have also shown clinical
validation in
gastroesophageal reflux disease (GERD). Addex' GABA-BR PAMs have shown
efficacy
in multiple preclinical models including: OAB, pain, osteoarthritis
pain,
anxiety and alcoholism.
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 and anxiety seen in
patients
suffering from major depressive disorder. Addex also is advancing
several
preclinical programs including: GABA-BR PAM for spasticity in MS, OAB and
other
disorders; mGluR4 PAM for Parkinson's, MS, anxiety and other
diseases. In
addition, Addex is applying its proprietary discovery platform to
identify
highly selective and potent allosteric modulators of a number of both
GPCR and
non-GPCR targets that are implicated in diseases of significant unmet
medical
need.
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, GABA-BR 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, GABA-BR 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, GABA-BR 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, GABA-BR 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
[HUG#1652941]
