GENEVA, SWITZERLAND--(Marketwire - October 02, 2012) - Grant to Further Characterize Allosteric
Modulators Against mGluR4 and mGluR7
Addex Therapeutics (SIX: ADXN), a leading
company pioneering allosteric modulation-based oral small molecule drug
discovery and development, announced today that it has been awarded a
CHF700,000
grant from the Swiss Commission for Technology and Innovation (CTI) to develop
allosteric modulator therapeutics for neurodegenerative and psychiatric
diseases. Addex will collaborate with the Center for Psychiatric Neuroscience
at
the University of Lausanne and at the Laboratory for the Study of
Neurodegenerative Diseases (LEN) at Ecole Polytechnique Fédérale de
Lausanne
(EPFL).
The objective of the project is the characterization and optimization of
potent
and selective allosteric modulators targeting Group III of metabotropic
glutamate receptors, mGluR4 and mGluR7. Drug candidates targeting mGluR4 will
be
assessed in animal models replicating human Parkinson's disease.
Electrophysiological studies will be carried out with allosteric modulators
targeting both mGluR4 and mGluR7 to investigate their role in modulating
synaptic transmission. Data from the project will contribute to the selection
of
the best candidate compounds for clinical development.
"We are thrilled by this opportunity to collaborate with Addex, a leader in
allosteric modulator discovery, and to help advance these two exciting
neuroscience programs" commented Dr Ron Stoop, Center for Psychiatric
Neuroscience at the University of Lausanne. "Testing Addex proprietary
compounds
in our models will bring essential understanding of the significant role
mGluR4
and mGluR7 may play in a number of important human diseases."
Addex is currently characterizing a number of novel, selective, orally
available
mGluR4 positive allosteric modulators (PAMs), which have demonstrated efficacy
in several different rodent models of Parkinson's disease, anxiety and most
recently in the industry standard neuroinflammation model of multiple
sclerosis,
the Relapsing-Remitting Experimental Allergic Encephalomyelitis (RR-EAE)
model.
Addex is currently advancing this lead series towards identification of a
clinical candidate compound. The Company's mGluR7 negative allosteric
modulator
(NAM) program is currently in lead optimization phase where compounds
representing multiple chemical series have been shown to be efficacious in
animal models of anxiety. There are currently no described mGluR7 NAM
compounds
and therefore Addex is uniquely positioned to potentially unravel the role of
this receptor in the brain.
"This grant will enable us to characterize further the role of mGluR4 and
mGluR7, believed to play an important role in several neurodegenerative and
psychiatric diseases," explained Dr. Robert Lütjens, Vice-President of
Biology
at Addex. "Allosteric modulators targeting mGluR4 and mGluR7 have the
potential
to offer a more precise way to regulate brain function in a number of large
unmet medical needs. Working with the world class academic labs of Doctors Ron
Stoop (UNIL) and Bernard Schneider (EPFL) will significantly improve our
scientific understanding of the mode of action of our compounds."
About mGluR4
The mGluR4 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
neurotransmitter release from presynaptic terminals. The mGluR4 is uniquely
distributed in key brain regions involved in multiple CNS disorders. In
particular, mGluR4 is abundant in striato-pallidal synapses within the basal
ganglia circuitry a key area implicated in movement disorders, like
Parkinson's
disease. In the immune system mGluR4 has been found on dendritic cells (DCs).
Emerging data implicate mGluR4 in multiple indications such as multiple
sclerosis, Parkinson's disease, anxiety, neuropathic and inflammatory pain,
schizophrenia and diabetes.
About mGluR7
The mGluR7 receptor is the most highly conserved of all mGluR subtypes,
exhibiting the widest distribution in the brain. It is localized pre-
synaptically at a broad range of glutamatergic and GABAergic synapses and is
thought to be one of the most important mGluR subtypes in regulating CNS
function. Preclinical data suggest that mGluR7 antagonism could alleviate
stress-related anxiety and depressive symptoms and deficits in amygdala-
dependent behaviors (fear response and conditioned taste aversion). These data
are consistent with the abundant localization of mGluR7 in brain regions
involved in the control of fear and emotion.
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: GABABR PAM for overactive bladder 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, GABABR 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 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 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 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#1645482]
