GENEVA, SWITZERLAND, Nov 03, 2009 (MARKETWIRE via COMTEX) -- Addex
Pharmaceuticals (SWISS: ADXN), the allosteric modulation company, presented
results today from studies of its lead clinical candidate, ADX10059, in animal
models of Parkinson's disease levodopa induced dyskinesia (PD-LID) at the
Discovery on Target GPCR-based Drug Discovery conference in Boston. Addex
disclosed for the first time that in a non-human primate model of PD-LID,
ADX10059 had a statistically significant impact on dystonia, a neurological
movement disorder seen in Parkinson's disease and other conditions, including
generalized dystonia, tardive dyskinesia, levodopa non responsive PD syndrome
and multiple system atrophy. There is no approved treatment available for
PD-LID.
ADX10059 is the first-in-class negative allosteric modulator (NAM) of
metabotropic glutamate receptor 5 (mGluR5), a mechanism that is being tested in
multiple indications by Addex and competitors. ADX10059 is currently being
evaluated in Phase IIb clinical trials for the treatment of gastroesophageal
reflux disease (GERD) and to prevent migraine. Separate announcements of data
from the two ongoing GERD trials are expected before year-end and early in 2010.
The migraine study will report data early in the second quarter of 2010.
Addex disclosed earlier this year that ADX10059 demonstrated significant
efficacy in well-established preclinical models of PD and PD-LID. Importantly,
these effects in PD and PD-LID were seen at doses and plasma concentrations that
have shown efficacy in both clinical and preclinical studies with the compound
in other indications. The effects on dystonia announced today differentiate the
Addex mGluR5 inhibitor within the PD indication but also present potential
development opportunities for treatment of other types of dystonia.
The oral slide presentation today will show that in the non-human primate MPTP
model of PD-LID, all doses of ADX10059 abolished LID during the first hour
following L-DOPA administration and a dose response was observed during the
second hour, reaching statistical significance for the two higher doses tested.
Statistically significant reductions were seen for both chorea and dystonia in a
dose dependent fashion. Similar effects on dystonia have not previously been
reported in this model with drug-like molecules either in development or on the
market.
When tested in the rat model, oral administration of ADX10059 dose-dependently
reversed the catalepsy induced by haloperidol in three independent experiments.
Dystonia is a neurologic movement disorder characterized by sustained muscle
contractions that frequently cause twisting or repetitive movements and
abnormal, sometimes painful, postures or positions. Dystonia may affect any part
of the body including the arms, legs, trunk, neck, head, or face.
PD-LID develops in most PD patients after receiving levodopa for several years.
It is a complication caused by dopamine replacement therapy (i.e. levodopa). The
two main components of LID are chorea and dystonia. Chorea is manifest as
abnormal involuntary movements. Currently there are an estimated 1.2 million
patients with PD-LID in the U.S.
PD is a degenerative disease of the brain that often impairs motor skills,
speech, and other functions. It is estimated that 60,000 new cases are diagnosed
each year in the U.S., where more than 1.5 million people currently have PD.
While the condition usually develops after the age of 65, 15% of those diagnosed
are under 50. PD affects both men and women in almost equal numbers.
mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate.
Marketed blockbuster drugs treat multiple indications by targeting other types
of neurotransmitter signaling, including selective serotonin reuptake inhibitors
(SSRIs) used to treat depression and dopamine receptor inhibitors used to treat
schizophrenia. The rationale for using mGluR5 inhibition in PD is that the loss
of dopamine producing cells leads to excess glutamatergic stimulation in the
brain's "striatopallidal pathway". mGluR5 are found abundantly in the striatum
and are implicated in the excess glutamate activity in Parkinson's Disease.
Research shows that inhibition of glutamate stimulation in this pathway has
generated anti-Parkinsonian effects in animal models of PD and PD-LID, and in
humans with PD-LID.
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric
modulators for human health. Allosteric modulators are a different kind of
orally available small molecule therapeutic agent, which we believe will offer a
competitive advantage over classical drugs. Our lead allosteric modulator
product, ADX10059, has achieved clinical proof of concept and is in Phase IIb
testing for the treatment of GERD and, separately, migraine headache. ADX10059
is a first-in-class mGluR5 inhibitor, a therapeutic strategy that also is being
pursued in multiple indications by large pharma competitors.
Our products and technology already have proven their value through our
relationships with four of the top 10 pharmaceutical companies in the world.
Specifically, under an agreement with Ortho-McNeil-Janssen Inc., a Johnson &
Johnson company, ADX71149, a positive allosteric modulator (PAM) of mGluR2, is
undergoing Phase I clinical testing and has potential for treatment of
schizophrenia and anxiety. Under two separate agreements with Merck & Co., Inc.,
we are developing PAMs of mGluR4 and mGluR5 as drugs to treat Parkinson's
disease and schizophrenia, respectively. In addition, GlaxoSmithKline and Roche
have made equity investments in Addex.
Disclaimer: The foregoing release contains 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
Pharmaceuticals Ltd, 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
Pharmaceuticals Ltd regarding future events, and involve known and unknown
risks, uncertainties and other factors that may cause actual results with
allosteric modulators of mGluR4, mGluR2, mGluR5 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 mGluR4, mGluR2 or mGluR5 will be approved for sale in
any market or by any regulatory authority. Nor can there be any guarantee that
allosteric modulators of mGluR4, mGluR2, mGluR5 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 mGluR4,
mGluR2, mGluR5 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 Pharmaceuticals 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.
Chris Maggos
Investor Relations & Communications
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos@addexpharma.com
SOURCE: Addex Pharmaceuticals
CONTACT: mailto:chris.maggos@addexpharma.com