Addex Partners with Viva Biotech to Advance Allosteric Modulators Targeting Adenosine 2A Receptor

Addex Partners with Viva Biotech to Advance Allosteric Modulators Targeting 
Adenosine 2A Receptor 
GENEVA, SWITZERLAND -- (Marketwire) -- 03/04/13 --  Addex
Therapeutics / Addex Partners with Viva Biotech to Advance Allosteric
Modulators Targeting Adenosine 2A Receptor 
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solely responsible for the content of this announcement. 
Partnership to demonstrate the potential to accelerate the
development of allosteric modulator-based therapeutics against GPCRs
by integrating proprietary
functional and structural biology
approaches 
Geneva,  Switzerland, 4 March 2013 -  Addex Therapeutics (ADXN: SIX),
a leading
company  pioneering allosteric modulation-based  drug
discovery and development,
and Viva Biotech Ltd., a leading company
in structure-based drug discovery based
in  Shanghai, China,  today
announced  they have  entered into  a partnership to accelerate  the
advancement of oral  small molecule adenosine 2A receptor
(A2AR)
positive  allosteric modulators (PAMs)  by leveraging the 
relative expertise of each  company.   The  A2AR  natural  ligand,
extracellular adenosine, is locally
produced  at the sites of
inflammation and has been characterized for decades as a  "brake for 
inflammation."  An  oral small  molecule compound  targeting
A2AR
activation,   which   selectively   enhances   the   effect  of 
high adenosine
concentration  only within inflamed tissues and not in
other tissues, may have a profound  therapeutic  effect  in  any 
number  of  inflammatory-based diseases
including rare diseases such
as sickle cell and Huntington's diseases. 
"We  are delighted  to initiate  this collaboration  with Viva 
Biotech, a world
leader  in structural  biology of  GPCRs," said 
Graham Dixon,  Chief Scientific
Officer  at Addex Therapeutics. 
"Structural biology  is a key complement to our proprietary 
allosteric modulation  capability and  increases the  chances of us
successfully  developing  novel,  allosteric  modulators for
membrane-associated receptors.   The combination of  our industry
leading allosteric modulator drug discovery  platform  with  Viva's 
cutting-edge  structural biology expertise is expected  to facilitate
 the development  of a  selective and  potent oral small
molecule 
for the activation  of A2AR, a  compelling new mechanism  of action
to address   multiple   inflammatory   diseases,  including  certain 
rare disease
indications with significant unmet medical needs." 
Under  the terms of the agreement,  Viva Biotech will provide a
fully-integrated structural biology discovery service to Addex to
deliver high resolution crystal structures  of A2AR in  complex with
positive  allosteric modulators (PAMs) that
were  identified  using 
Addex  proprietary  HTS  technologies.  Based  on this
structural
information, Addex scientists will then be able to rationally
develop
novel A2AR PAMs in a structure-guided lead optimization
program. To date, Addex'
A2AR PAMs constitute the first examples of
chemically tractable, selective, oral
small molecule compounds with
functional activity on this important GPCR target. 
"We  are very pleased to be collaborating with Addex on this
important program,"
said  Cheney Mao, Chief Executive Officer of Viva
Biotech.  "Viva works with our collaborators  to advance novel drug
targets from the ideas to identifying novel
drug candidates to the
clinics, utilizing our broad experience in drug discovery
and  deep
expertise in G2P,  G2S, GPCRs and SBDD/FBDD.   With Addex, Viva
brings
unique  structural  biology  expertise  and  capability  to
the partnership.  We believe   the   combination  of  our  capability 
with  Addex' state-of-the-art allosteric  modulator  platform  will 
accelerate  the delivery  of  a clinical candidate against this
important GPCR drug target." 
About Addex' novel A2AR PAMs 
Addex  has  developed  proprietary  HTS  technologies  specifically
designed to respond  to  the  challenges  of  detecting  and
optimizing allosteric modulator
drugs.  Using this  technology, Addex
 has been  able to  identify structurally-independent  novel chemical
series with drug-like properties and with functional activity  at the
human A2AR in recombinant cell  lines as well as in a cell
line
endogenously expressing A2AR. In addition, these compounds have
been shown to be active  in industry-standard assays  (such as cAMP 
HTRF and GTP-gamma-S assays)
and  do not  compete with  radioactive
orthosteric  ligand binding, exemplifying
their  allosteric mechanism
of action.  These  novel compounds are selective for A2AR,  do  not 
demonstrate  any  agonist  activity  and  are only active in the
presence of adenosine binding to the active site of A2AR. 
About allosteric modulators 
Allosteric  modulators are an emerging class  of orally available
small molecule
therapeutic  agents that may offer a competitive
advantage over classical drugs.
This  potential stems from their
ability to offer greater selectivity and better
modulatory  control 
at  disease  mediating  receptors. Most marketed drugs bind
receptors
 where the  body's own  natural molecular  activators (i.e.
endogenous
ligands)  bind, specifically to a  key part of each 
receptor called the "active
site". In short, most drugs must
out-compete endogenous ligands in order to bind
to  the  active 
site.  By  contrast,  allosteric modulators are non-competitive
because  they bind receptors at a different site and modify receptor
function in the  presence of endogenous ligand binding to  the active
site. Because of this,
allosteric  modulators  are  not  limited  to 
simply turning a receptor "on" or "off",  the  way  most 
conventional  drugs  are  designed.  Instead, allosteric
modulators
act more like a dimmer switch, offering control over the intensity of
activation  or  deactivation,  while  allowing  the  body  to retain
its natural
control over initiating receptor activation. One of the
most attractive features
of  receptor  activation  via  allosteric 
modulation  is  that  these positive
allosteric  modulators (PAMs)
activate the receptor  only in the presence of the natural ligand
binding to the target receptor.  In the absence of natural
ligand
these  PAMs do not activate the receptor.  This provides an
elegant regulate the receptor  activation  that  could  translate 
into  the  development  of a safer
therapeutic. 
Pharmacological advantages of PAMs for the activation of A2AR 
Beside  immune cells,  A2AR engagement  modulates the  activity of
numerous cell
types,  including  various  neuronal  populations, 
platelets, smooth muscle and endothelial  cells. Thus, systemic
engagement of A2AR with orthosteric agonists,
directed  at the
adenosine binding site, is  known to affect several tissues and
trigger  a  wide  range  of  side  effects  such as hypotension and
tachycardia.
Extracellular  adenosine is locally produced  within
inflamed or hypoxic tissues
and  is  highly  unstable  in  plasma. 
Therefore, in the course of inflammatory
reactions,  ligand
availability regulates adenosine receptors engagement both in space 
and time. Because it preserves  the natural spatial and temporal
controls
over  A2AR engagement, positive allosteric modulation
provides a uniquely suited
therapeutic  approach to  address the 
potential of  A2AR activation  in chronic
inflammatory  diseases. By
enhancing the  effect of high adenosine concentration
within 
inflamed  tissues,  A2AR  PAM  would  avoid  side effects that relate
to ectopic  or systemic  triggering of  A2AR and  could offer a
greater selectivity
over  other adenosine receptors.  In particular,
A2AR  PAMs are expected to show
reduced impact on hypotension and
tachycardia than straight agonists. 
About A2AR in inflammatory conditions 
Adenosine  2A receptor (A2AR or ADORA2A), a  Family A class of
G-protein coupled
receptor  (GPCR)  can,  among  other  things, 
negatively regulate over reactive
immune  cells, thereby  protecting
tissues  from collateral inflammatory damage,
The  A2AR's natural
ligand, extracellular adenosine,  is locally produced at the sites 
of inflammation and  has been characterized  for decades as  a "brake
for inflammation",  exerting  a  retro-control  over  inflammation.
Several lines of evidence  point to a broad anti-inflammatory  role of
A2AR in preclinical animal
models.  In leukocytes, A2AR is the most
abundantly expressed adenosine receptor
and  activating  this 
receptor  affects  a  range  of cellular functions across
different  
immune   cell   types  including  macrophage  cytokines
production,
neutrophil  migration, or T-lymphocyte activation.  A2AR
selective agonists show
anti-inflammatory  activity and reduce 
tissue damage in  vivo. Conversely, A2AR
selective  antagonists 
compromise  regulatory  T  cells  function  and prolong
inflammation 
following induction of an  inflammatory response. Similarly,
A2AR-deficient animals show enhanced and prolonged inflammatory
responses. 
Several   marketed   anti-inflammatory   drugs,   including  
methotrexate and
sulfasalazine,  mediate  some  of  their 
anti-inflammatory  effects   through  a mechanism that promotes
adenosine release and activation of A2AR. However, these
drugs  are 
non-specific  and  associated  with  significant  side effects.  In
addition, there is marked variability in the degree of efficacy and
side effects
observed  with these current drugs in the  clinic.  There
is a need for products
that  are selective, safe and truly 
disease-modifying. Therefore, an oral small
molecule  drug targeting
A2AR with a new mechanism of action such as an A2AR PAM that is
active only at the sites of inflammation, lacks any agonist activity
and preferably   is   peripheral,   could  revolutionize  and  offer 
an attractive
alternative to the existing therapeutic arsenal for the
treatment of a number of inflammatory  conditions, such as rheumatoid
arthritis (RA), Crohn's disease and psoriasis,  as  well  as  certain
 rare  diseases  such  as  ,  sickle cell and Huntington's disease. 
About Viva Biotech 
Viva  Biotech (www.vivabiotech.com) is  privately owned and  financed
by leading
investors  in  the  United  States.  It  is a
well-established contract research
organization  that provides
preclinical drug  discovery research services to the pharmaceutical
industry worldwide. The core capabilities of the company includes
its
 leading  expertise  in  protein  crystallography  and  structure
based drug
design,  a MS  based screening  technology with  a
proprietary fragment library,
GPCR target preparation and
crystallization, monoclonal antibody lead generation
and  other
preclinical drug discovery research capabilities such as DMPK,
animal
disease models for CNS and oncology. For additional
information on Viva Biotech,
please contact Dr. Zengquan Wang at:
Zengquan.wang@vivabiotech.com. 
About Addex Therapeutics 
Addex  Therapeutics (www.addextherapeutics.com)  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 (ADX48621, 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 is also
advancing
several  preclinical programs  including: GABA-BR  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. 
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 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 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 Thera
peutics 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
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[HUG#1682629] 
Tim Dyer
Chief Financial Officer
Addex Therapeutics
+41 22 884 15 61
PR@addextherapeutics.com
 
 
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