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Addex And NIDA Enter Collaboration To Advance ADX71441 & ADX88178 In Drug Abuse And Addiction

GENEVA, Nov. 4, 2013 (GLOBE NEWSWIRE) --
Addex Therapeutics (SIX: ADXN), a leading
company pioneering allosteric modulation-based drug discovery and development
announced today entering a collaboration with the National Institute on Drug
Abuse (NIDA), a component of the National Institutes of Health (NIH) to evaluate
the pharmacology of ADX71441, a GABAB receptor positive allosteric modulator
(PAM), and ADX88178, an mGlu4 PAM in preclinical models of drug abuse and
addiction. The collaboration will evaluate Addex drug candidates, ADX71441 and
ADX88178 in a battery of preclinical models to study their potential as
treatments for nicotine and cocaine addiction.

"NIDA has made significant contributions to our understanding of the underlying
pathology of drug abuse and addiction and has coordinated development and
validation of a large battery of preclinical models which will provide Addex
with invaluable information for the further development of ADX71441 and
ADX88178," said Tim Dyer, CEO at Addex. "This is our first collaboration with
NIDA and another example of us executing our strategy to advance our pipeline
through collaborations with cutting edge academic and governmental research

Both pre-clinical and clinical data suggest that activation of GABAB receptors
offers a unique therapeutic opportunity to address the needs of drug abuse
patients by reducing drug intake, by maintaining abstinence, and by reducing
drug craving. Moreover treatment with a GABAB activator can alleviate many
physical signs (GI/urinary disturbances) and emotional symptoms (anxiety)
associated with withdrawal. Addex recently reported positive data with ADX71441
in two models of alcohol abuse in mice, the ethanol binge-like drinking,
drinking-in-the-dark (DID) and a model of long-term, excessive drinking,
intermittent access to alcohol (IAA). The data have been published online on
August 22 (L.S. Hwa et al. Psychopharmacology).

"Alcohol and nicotine addiction are often comorbid, and therefore the data from
this collaboration with NIDA will help us define the best clinical development
path for our lead programs," said Sonia Poli, VP translational science at Addex.
"We are also excited to learn more about the potential utility of both GABAB PAM
and mGlu4 PAM in further aspects of drug addiction"

About Drug Abuse and Drug Addiction
Scientific advances have revolutionized our understanding of addiction as a
chronic, relapsing disease and not a moral failure. Drug addiction is a complex
illness which is characterized by intense and, at times, uncontrollable drug
craving, along with compulsive drug seeking and use that persist even in the
face of devastating consequences. Addiction affects multiple brain circuits,
including those involved in reward and motivation, learning and memory, and
inhibitory control over behavior. While a person initially chooses to take
drugs, over time the effects of prolonged exposure on brain functioning
compromise that ability to choose, and seeking and consuming the drug become
compulsive, often eluding a person's self-control or willpower. Because drug
abuse and addiction have so many dimensions and disrupt so many aspects of an
individual's life, treatment is not simple. Addiction treatment must help the
individual stop using drugs, maintain a drug-free lifestyle, and achieve
productive functioning in the family, at work, and in society. Patients
typically require long-term or repeated episodes of care to achieve the ultimate
goal of sustained abstinence and recovery of their lives.

About GABAB Activation and ADX71441
Activation of gamma-aminobutyric acid subtype B (GABAB) receptor, a Family C
class of GPCR, is clinically & commercially validated. Generic GABAB receptor
agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and
used for overactive bladder (OAB), but is not commonly used due to variety of
side effects of the drug and rapid clearance. ADX71441 is a potent selective
positive allosteric modulator (PAM) which potentiates GABA responses at the
GABAB receptor. ADX71441 is a novel, first-in-class, oral, small molecules that
has demonstrated excellent preclinical efficacy and tolerability in several
rodent models of pain, anxiety, addiction and OAB and have also proven efficacy
in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A). ADX71441
differs from the generic drug baclofen in that it is a positive allosteric
modulator rather than an orthosteric agonist at the GABAB receptor. ADX71441
only acts when the natural ligand (GABA) activates the receptor, and therefore
respecting the physiological cycle of activation. It has been proposed that PAMs
produce less adverse effects and lead to less tolerance than direct agonists
(May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona et al.
2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al).

About mGlu4 Activation and ADX88178
The metabotropic glutamate receptor 4 (mGlu4) belongs to the Group III mGluRs
(Class C G-Protein Coupled Receptor) and is negatively coupled to adenylate
cyclase via activation of the Gai/o protein. It is expressed primarily on
presynaptic terminals, functioning as an autoreceptor or heteroceptor and its
activation leads to decreases in transmitter release from presynaptic terminals.
MGlu4 is currently receiving much attention based primarily upon its unique
distribution in key brain region involved in many CNS disorders. MGlu4 PAM is
emerging as a promising target for the treatment of motor and non motor symptoms
as well as a disease-modifying agent in Parkinson's disease through a non-
dopaminergic approach. Emerging data for other therapeutic indications such as
anxiety, multiple sclerosis, neuropathic and inflammatory pain, schizophrenia
and diabetes make mGlu4 a highly promising target for both CNS and non CNS
diseases. In particular, anxiety disorders are among the most prevalent
psychiatric disorders in the world. Addex has reported in 2010 that ADX88178
demonstrated oral efficacy in two preclinical rodent models of anxiety: the
marble burying test in mice and EPM in mice and rats. The mGlu4-mediated
specific effect has been also confirmed in knock-out mice. Therefore, mGlu4
activators may represent a new generation of anxiolytic therapeutics. More
recently, mGlu4 PAM PHCCC demonstrated efficacy in a neuroinflammation model,
the remitting-relapsing EAE model, by promoting regulatory T-cell (Treg)
formation and reverse pro-inflammatory T-cell release. Therefore, positive
modulation of mGlu4 could potentially stop the destruction of myelin in MS in a
robust and durable manner.

About Addex Therapeutics
Addex Therapeutics ( is a development stage company
focused on advancing innovative oral small molecules against rare diseases
utilizing its pioneering allosteric modulation-based drug discovery platform.
The Company's two lead products are being investigated in Phase 2 clinical
testing: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is being
developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-
LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric
modulator or PAM) is being developed in collaboration with Janssen
Pharmaceuticals, Inc., to treat both schizophrenia and anxiety as seen in
patients suffering from major depressive disorder. Addex also has several
preclinical programs including: GABAB receptor positive allosteric modulator
(PAM) for Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with
multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4
PAM for MS, Parkinson's disease, anxiety and other diseases. Allosteric
modulators are an emerging class of small molecule drugs 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 target receptors and other proteins that
are recognized as essential for the therapeutic modulation of important diseases
with unmet medical needs.

Tim Dyer
Chief Executive Officer
Addex Therapeutics
+41 22 884 1561

Disclaimer: The foregoing release may contain forward-looking statements that
can be identified by terminology such as "seek", "not pursue", "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, 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 factors may in particular cause actual results
with allosteric modulators of mGlu2, mGlu4, mGlu5, 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 Addex Therapeutics will complete the restructuring and reduction of its
liabilities or any financing nor that allosteric modulators of mGlu2, mGlu4,
mGlu5, 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 mGlu2, mGlu4, mGlu5, 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 mGlu2,
mGlu4, mGlu5, 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.


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