Addex mGlu2PAM Demonstrates Potential in Substance Use Disorder
24 Luglio 2023 - 7:00AM
Addex mGlu2PAM Demonstrates Potential in Substance Use Disorder
- Data
published in Neuropharmacology
shows mGlu2 PAMs
attenuate oxycodone use
and potential as a novel treatment
for opioid use
disorder
Ad Hoc Announcement Pursuant to
Art. 53 LR
Geneva, Switzerland,
July 24,
2023 - Addex
Therapeutics (SIX and Nasdaq: ADXN), a clinical-stage
pharmaceutical company pioneering allosteric modulation-based drug
discovery and development, today announced data showing that
administration of a metabotropic glutamate 2 (mGlu2) positive
allosteric modulator significantly reduces oxycodone
self-administration in preclinical models, supporting a potential
role in opioid use disorder. The data were published in
Neuropharmacology by Addex and The Scripps Research Institute.
“In the United States, opioid abuse and overdose
have reached epidemic proportions, with oxycodone being the most
abused prescription opioid. Research suggests that glutamate
release elicits drug-seeking behaviors, which suggests targeting
the glutamate system with novel pharmacotherapies could alleviate
these cravings,” said Dr. Rémi Martin-Fardon from The Scripps
Research Institute, the paper’s lead author. “Our research
demonstrates that using an mGlu2 PAM to decrease glutamate activity
can stop oxycodone self-administration and seeking in preclinical
models, which supports this approach as a future potential
treatment of prescription opioid use disorder.”
Study DetailsThe aim of the
study was to test whether the mGlu2 receptor positive allosteric
modulator ADX106772 could reduce oxycodone self-administration and
the conditioned reinstatement of oxycodone seeking without
affecting behaviors directed toward a highly palatable non-drug
reinforcer (sweetened condensed milk, SCM). Rats were trained to
self-administer oxycodone (0.15 mg/kg/infusion, i.v.,12 h/day) or
sweetened condensed milk for 13 days in the presence of a
contextual/discriminative stimulus (SD). Oxycodone, SCM, and the SD
were then withheld. Once oxycodone or SCM self-administration was
acquired and oxycodone dependence verified, the effect of ADX106772
(0.3, 1, 3, or 10 mg/kg, s.c.) was tested on oxycodone or SCM
self-administration. ADX106772 was found to reduce oxycodone
self-administration and conditioned reinstatement without affecting
SCM self-administration or conditioned reinstatement. ADX106772
reduced oxycodone taking and seeking but did not affect the
motivation for the palatable conventional reinforcer.
“The results of this study add to existing
research supporting targeting mGlu2 receptors with PAMs to counter
drug use and seeking. In previous research, this approach has
successfully been used in nicotine, cocaine and alcohol models,”
said Dr. Robert Lütjens, Head of Discovery – Biology at Addex.
“Demonstrating the wide potential of mGlu2 PAMs, an Addex
discovered drug candidate, ADX71149, is being evaluated in a phase
2 clinical study as a potential treatment for epilepsy by our
partner Janssen.”
About Addex Therapeutics:Addex
Therapeutics is a clinical-stage pharmaceutical company
focused on the development and commercialization of an emerging
class of novel orally available, small molecule drugs known as
allosteric modulators for neurological disorders. Allosteric
modulators offer several potential advantages over conventional,
non-allosteric molecules and may offer an improved therapeutic
approach to conventional "orthosteric" small molecule or biological
drugs. Addex's allosteric modulator drug discovery platform targets
receptors and other proteins that are recognized as essential for
therapeutic intervention. Addex's lead drug candidate, ADX71149
(mGlu2 positive allosteric modulator or PAM), developed in
collaboration with Janssen Pharmaceuticals, Inc., is in a Phase 2
clinical trial for the treatment of epilepsy. Addex's second
clinical program, dipraglurant (mGlu5 negative allosteric modulator
or NAM), is under evaluation for future development in a range of
indications. Indivior PLC has licensed Addex’s GABAB PAM program
for the development of drug candidates, with a focus on substance
use disorder. Addex is also advancing a broad preclinical pipeline,
which includes development of a range of GABAB PAMs for CMT1A,
chronic cough and several types of pain, mGlu7 NAM for stress
related disorders, mGlu2 NAM for mild neurocognitive disorders and
depression, M4 PAM for schizophrenia and other forms of
psychosis, as well as mGlu4 PAM and mGlu3 PAM. Addex shares are
listed on the SIX Swiss Exchange and American Depositary Shares
representing its shares are listed on the NASDAQ Capital Market,
and trade under the ticker symbol "ADXN" on each
exchange. About Scripps ResearchScripps
Research is an independent, nonprofit biomedical institute ranked
one of the most influential in the world for its impact on
innovation by Nature Index. We are advancing human health through
profound discoveries that address pressing medical concerns around
the globe. Our drug discovery and development division, Calibr,
works hand-in-hand with scientists across disciplines to bring new
medicines to patients as quickly and efficiently as possible, while
teams at Scripps Research Translational Institute harness genomics,
digital medicine and cutting-edge informatics to understand
individual health and render more effective healthcare. Scripps
Research also trains the next generation of leading scientists at
our Skaggs Graduate School, consistently named among the top 10 US
programs for chemistry and biological sciences. Learn more
at www.scripps.edu.
Contacts:
Tim DyerChief Executive OfficerTelephone: +41 22 884 15
55PR@addextherapeutics.com |
Mike SinclairPartner, Halsin Partners+44 (0)7968
022075msinclair@halsin.com |
Addex Forward Looking
Statements:This press release contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995, as amended, including statements about the
intended use of proceeds of the offering. The words “may,” “will,”
“could,” “would,” “should,” “expect,” “plan,” “anticipate,”
“intend,” “believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “target” and similar expressions are intended to
identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release, are based on
management's current expectations and beliefs and are subject to a
number of risks, uncertainties and important factors that may cause
actual events or results to differ materially from those expressed
or implied by any forward-looking statements contained in this
press release, including, without limitation, uncertainties related
to market conditions. These and other risks and uncertainties are
described in greater detail in the section entitled “Risk Factors”
in Addex Therapeutics’ Annual Report on Form 20-F for the year
ended December 31, 2022, as filed with the SEC on March 30, 2023,
the final prospectus supplement and accompanying prospectus and
other filings that Addex Therapeutics may make with the SEC in the
future. Any forward-looking statements contained in this press
release represent Addex Therapeutics’ views only as of the date
hereof and should not be relied upon as representing its views as
of any subsequent date. Addex Therapeutics explicitly disclaims any
obligation to update any forward-looking statements.
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