GENEVA--(Marketwire - November 05, 2012) - Addex Therapeutics /
Addex Reports Top-line Data from a Successful Phase 2a Clinical Study with
ADX71149 in Schizophrenia Patients. Processed and transmitted by Thomson
Reuters ONE.
The issuer is solely responsible for the content of this announcement.
* Key objectives achieved
* Safety and tolerability demonstrated
* Sub population identified for potential treatment with ADX71149
* ADX71149 dose with optimal benefit / risk identified
Addex Therapeutics (SIX: ADXN), a leading company pioneering
allosteric modulation-based drug discovery and development, announced today
top-line data from a successful Part B of the first-in-patient Phase 2a
clinical
study of ADX71149 in schizophrenia, that was conducted by Janssen Research
&
Development, LLC, on behalf of its affiliate Janssen Pharmaceuticals Inc.
The
data show that ADX71149 met the primary objectives of safety and
tolerability.
ADX71149 also demonstrated an effect in patients with residual negative
symptoms. The 50mg b.i.d. dose was identified as having the optimal
benefit/risk
ratio in this study.
ADX71149 is an oral, selective, small molecule, positive allosteric
modulator
(PAM) of the metabotropic glutamate receptor 2 (mGluR2), a Class C
G-Protein
Coupled Receptor (GPCR), with potential to be used in the
treatment of
schizophrenia and the treatment of anxiety in patients suffering from
major
depressive disorder.
This first-in-patient study is being conducted in the EU, to
determine the
safety and tolerability of ADX71149 and to explore the potential clinical
effect
of this mGluR2 PAM in patients with schizophrenia. The study has two
concurrent
parts (A and B) and is designed to identify the patient populations most
likely
to benefit from treatment with ADX71149.
Part A: Safety, tolerability and efficacy of ADX71149 as monotherapy
in the
treatment of patients with sub-acute psychosis. This is a 12 week
open-label
treatment in 15 patients not on antipsychotic medication. Dose range from
50 mg
b.i.d titrated up to 150 mg b.i.d. Part A is ongoing.
Part B: ADX71149 as adjunctive therapy to antipsychotics. This part of the
study
for which top-line data are being reported today, was a randomised
double-blind,
placebo-controlled trial designed to evaluate the safety,
tolerability and
exploratory efficacy of ADX71149, in 92 patients who were on stable
doses of
antipsychotic medication. The study population comprised 3 groups: patients
with
residual negative symptoms (n = 47); patients with residual positive
symptoms (n
= 25); and patients with insufficient response to clozapine treatment (n =
20).
For the first 4 weeks of treatment all patients were randomised to
receive
either ADX71149 50 mg b.i.d, ADX71149 150 mg b.i.d or placebo,
taken
concomitantly with their currently prescribed antipsychotic
medication
(randomized 2:2:1).
"I am delighted that the study achieved its objectives of demonstrating
good
safety and tolerability and identifying the population of schizophrenia
patients
most likely to benefit from adjunctive treatment with ADX71149,"
noted Dr.
Charlotte Keywood, CMO at Addex.
Negative symptoms (typically comprising apathy, social withdrawal,
loss of
emotional expression and sleep disorders) are common, and occur in up to
90% of
patients with schizophrenia. Currently available drugs do not always
provide
effective control and many patients remain with substantial disability
as a
result. Therefore, effective treatment of negative symptoms is a major
unmet
medical need in the management of schizophrenia.
"We are extremely proud of our partnership with Janssen and greatly
appreciate
their continued commitment towards advancing ADX71149 and our mGluR2 PAM
program
in these psychiatric indications with significant unmet medical need,"
said Dr.
Bharatt Chowrira, CEO at Addex. "These top-line results are a
significant
achievement for Addex and serve as further validation for our innovative
oral
small molecule allosteric modulation drug discovery technology platform."
The development of ADX71149 is part of a worldwide research
collaboration and
license agreement between Addex and Janssen Pharmaceuticals Inc. to
discover,
develop and commercialize novel mGluR2 PAM for the treatment of
anxiety,
schizophrenia and other undisclosed indications. Under the terms of
the
agreement, Addex is eligible for up to a total of EUR112 million in
milestone
payments upon potential development and regulatory achievements. In
addition,
Addex is eligible for low double-digit royalties on sales of
mGluR2 PAM
developed under the agreement.
About mGluR2PAM
Glutamate is a powerful transmitter in the brain and integral to the
normal
functioning of memory, learning and perception. Too much glutamate can
lead to
seizures and the death of brain cells. Too little glutamate can cause
psychosis,
coma and death. Glutamate exerts these effects by interacting with
many
receptors in the brain, especially NMDA and AMPA receptors. In addition to
these
primary receptors, glutamate triggers other receptors, termed
metabotropic
because they adjust the amount of glutamate that cells release rather
than
simply turning glutamate transmission on or off. In addition, there are
eight
types of metabotropic glutamate receptors (mGluR), each with
different
functions. Thus, these mGluRs, because of their ability to fine-tune
glutamate
signaling, appear to be attractive targets for drug treatment. Indeed,
industry
has been investing in mGluR research for about three decades and research
shows
that mGluR drugs have potential for the treatment of schizophrenia,
anxiety,
Parkinson's disease, fragile X syndrome, Alzheimer's disease,
depression and
post-traumatic stress disorder. The effects of positive allosteric
modulators of
mGluR2 are independent of dopamine receptors, indicating the
potential for
mGluR2 modulators to offer efficacy while avoiding the side effects
associated
with market leading antipsychotic drugs which appear to work
predominantly via
their effects on dopamine receptors. Furthermore, mGluR2 activation has
shown
efficacy in patients suffering from schizophrenia and, separately, anxiety.
About Schizophrenia
Schizophrenia is a chronic progressive highly disabling and distressing
disease
which affects the way patients perceive the world around them, and
profoundly
decreases their ability to function normally. Symptoms are divided into
three
categories, positive, negative and cognitive. Positive symptoms
reflect an
excess or distortion of normal functions (delusions, hallucinations,
thought
disorder and disorganized behavior. Negative symptoms refer to a
diminishment or
absence of characteristics of normal function, and may appear with or
without
positive symptoms. Negative symptoms include loss of interest in
everyday
activities, appearing to lack emotion, reduced ability to plan or
carry out
activities, neglect of personal hygiene, social withdrawal and
loss of
motivation. Cognitive symptoms involve problems with thought processes
and may
be the most disabling in schizophrenia because they interfere with the
ability
to perform routine daily tasks. As a result, schizophrenia patients
often
withdraw from society and are unable to support themselves. The
prevalence of
schizophrenia is estimated at about 1% of the population worldwide.
The
prevalence of negative symptoms in first-episode psychosis is high,
50-90%, and
20-40% of schizophrenia patients have persisting negative symptoms.
Estimates of
the costs to society from schizophrenia run at approximately $65
billion per
year in the United States, despite the use of antipsychotic
drugs.
Notwithstanding their over $15 billion in annual sales, not all of the
currently
marketed antipsychotic drugs fully address the negative
symptoms of
schizophrenia, such as anxiety, depression and cognitive
dysfunction. In
addition, marketed antipsychotic drugs may cause side effects,
including
sedation, extrapyramidal symptoms (impairment of control of movements),
hormonal
imbalances leading to hyperprolactinemia and weight gain.
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 in collaboration with
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.
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originality of the information contained therein.
Source: Addex Therapeutics via Thomson Reuters ONE
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