- Cannabis use disorder (CUD) affects over 14 million
individuals in the US
- Despite the urgent need, there are no FDA-approved
medications to treat CUD; behavioral treatments have shown limited
benefit
- AEF0117 is the first of a new pharmacologic class, type 1
cannabinoid receptor signaling-specific inhibitors (CB1-SSi), with
a unique mechanism of action and greater safety and efficacy than
prior generations of CB1 inhibitors
- In a phase 2a clinical study in volunteers with CUD, AEF0117
produced statistically significant reductions in the positive
subjective and reinforcing effects of smoked cannabis
Regulatory News:
Aelis Farma (ISIN: FR0014007ZB4 – Ticker: AELIS), a
clinical-stage biopharmaceutical company focused on developing
treatments for brain diseases, today announced publication of a
series of studies describing a new pharmacological class,
cannabinoid receptor 1 signaling-specific inhibitors (CB1-SSi), and
its first drug candidate, AEF0117, for the treatment of cannabis
use disorder (CUD).
The report, “Signaling-specific inhibition of the CB1 receptor
for cannabis use disorder: phase 1 and phase 2a randomized trials,”
was published online by the journal Nature Medicine.
AEF0117 is the first compound that selectively inhibits the CB1
receptor signaling pathway responsible for the addictive effects of
cannabis, without interfering with the receptor's fundamental
physiological and behavioral functions. This breakthrough approach
differs from previous CB1 receptor antagonists that, due to their
broad blockade of all CB1 receptor activity, caused significant
adverse effects preventing their clinical use.
AEF0117, discovered and developed by Aelis Farma, is the first
of the new pharmacologic class, CB1-SSi, which is based on a
natural brain mechanism that combats CB1 receptor hyperactivity.
This mechanism was discovered by the research group of Aelis Farma
Chief Executive Officer Pier Vincenzo Piazza, MD, PhD, when he was
the director of the Neurocentre Magendie of the French National
Institute of Health and Medical Research (INSERM) in Bordeaux.1
This unique mechanism of action enables CB1-SSi to inhibit only the
cellular signals involved in CUD – without disrupting the
receptor’s physiological activity. The CB1-SSi class and AEF0117
represent a breakthrough in CB1 pharmacology.
“This landmark article culminates more than a decade of
research, from discovery of this natural brain mechanism to our
proof-of-concept clinical trial,” said Dr. Piazza. “We are
delighted to contribute to the field of neuropharmacology with a
class of drugs never tested in humans before. Now, we at Aelis are
sponsoring a large, placebo-controlled phase 2b study in
collaboration with Columbia University Irving Medical Center,
enrolling 330 participants with CUD to evaluate three dose levels
of AEF0117 in treating cannabis addiction. Results should be
available by mid-2024.”
Because of its unique mechanism of action, AEF0117 significantly
reduced phase 2a study participants’ self-reported ratings of the
positive subjective effects of cannabis, the primary outcome
measure, by a mean of 38% (p<0.04), while also reducing cannabis
use as measured by self-administration (p<0.05), the key
secondary endpoint. AEF0117 produced no treatment-related serious
adverse events or treatment-emergent adverse events distinct from
placebo. These reductions in cannabis effects occurred without
precipitating cannabis withdrawal, even for volunteers who smoked
several grams of cannabis per day.
“No other medication has been shown to safely reduce the direct
effects of smoked cannabis in daily cannabis smokers,” said
Margaret (Meg) Haney, PhD, supervisor of the phase 1 studies
and principal investigator of the 2a proof-of-concept study, and
Professor of Neurobiology in the Department of Psychiatry at
Columbia University Irving Medical Center, where she is the
Director of the Cannabis Research Laboratory and Co-Director of the
Substance Use Research Center. “These novel findings clearly
suggest that AEF0117 may be an effective approach for patients
seeking treatment for CUD.”
Aelis Farma thanks the volunteer study participants, Dr. Haney
and her team at Columbia, the National Institute of Drug Abuse, and
all the participating study centers and staff for their
assistance.
About Cannabis Use Disorder Cannabis use is widespread
and often leads to CUD, the current definition of problematic
cannabis use, which encompasses addiction.2 CUD affects about 14.2
million individuals in the U.S,3 and its prevalence is increasing
worldwide.4 Currently, CUD is treated using evidence-based
behavioral treatments, which often have poor adherence and limited
success.5 No medications are approved by the FDA to treat CUD.
About AEF0117 AEF0117 is the first drug candidate of the
new pharmacological class of CB1-SSi, a rationally designed analog
of pregnenolone, the naturally occurring steroid hormone that binds
to a specific site on the CB1 receptor. Pregnenolone and AEF0117 do
not modify the binding of agonists to the CB1 but only block
certain signaling pathways activated by cannabinoid agonists, such
as THC, on the CB1. Through this selective mechanism of action,
AEF0117 potently inhibits THC’s behavioral effects without altering
normal behavior. Unlike pregnenolone, AEF0117, is highly
bioavailable when taken orally, exhibits favorable pharmacokinetic
properties for once-daily administration, and is not converted into
other steroids. AEF0117 has a 13,000-fold therapeutic index (i.e.,
the ratio between the toxic and active dose).
The clinical investigation of AEF0117 to date consists of two
phase 1 safety studies (NCT03325595, NCT03443895) and one phase 2a
proof-of-concept study (NCT03717272). The phase 1 single ascending
dose and multiple ascending dose studies, performed in healthy
volunteers, demonstrate that AEF0117 is safe, well tolerated and
produces no behavioral changes relative to placebo. AEF0117 has
favorable pharmacokinetic characteristics, allowing for once daily
dosing, which facilitates medication compliance. The phase 2a
study, conducted in 29 randomized participants with CUD who smoked
cannabis daily (averaging 2-3 grams/day), demonstrated that AEF0117
significantly decreased both the positive subjective effects of
cannabis (the main study endpoint) and the frequency of cannabis
use (key secondary objective) without precipitating withdrawal,
which has tended to limit the acceptability of inhibitors for
addiction treatment.
The development of AEF0117 was made possible by a broad
multinational collaboration with the Aelis Farma team. Several
research groups of the Neurocentre Magendie of INSERM in Bordeaux
contributed to the early preclinical development of AEF0117. The
U.S. intramural program of the National Institute of Drug Abuse
(NIDA) performed some of the preclinical experiments. Columbia
University Irving Medical Center played a seminal role in the
coordination and execution of the clinical studies. AEF0117
development has been supported by two NIDA grants, a first grant of
$3.3 million and a second one of $4.5 million. AEF0117, is
protected by a patent owned by INSERM and University of Bordeaux.
Aelis Farma holds an exclusive worldwide license to AEF0117.
Development of AEF0117 as a treatment for cannabis addiction is
currently ongoing. A phase 2b U.S. multi-center study, sponsored by
Aelis Farma and coordinated by Professor Frances Levin of Columbia
University, which will include 330 participants with CUD, is
comparing the efficacy of three AEF0117 doses with placebo. Initial
results are expected mid-2024. Aelis Farma and Columbia University
are also conducting a complementary series of clinical
pharmacokinetic studies and nonclinical regulatory studies to
prepare AEF0117 for the Phase 3 program.
In summary, AEF0117 is the first drug candidate in the new
pharmacological class of CB1-SSi, which exhibits high specificity,
signaling selectivity, and affinity for the CB1 receptor at a
distinct site from where cannabinoid agonists such as THC bind.
Because of this selective molecular mechanism of action, AEF0117
potently inhibits the intoxicating effects produced by cannabis and
reduces cannabis use without the behavioral side effects of the
past generation of CB1 receptor antagonists that prevented their
use in humans. This profile suggests that AEF0117 has the potential
to be a safe and novel treatment for CUD, supporting continued
confirmatory investigations in phase 2b and phase 3 clinical
trials.
About Nature Medicine The description of AEF0117
development in Nature Medicine is unique as it describes the
complete development of this new pharmacological class by Aelis
Farma, including the chemical design and characterization of the
signaling-specific inhibitors of the CB1 receptor (CB1-SSi) in
collaboration with INSERM; the discovery and development of AEF0117
by Aelis Farma; as well as the clinical investigation with the
contributions of Columbia University Irving Medical Center.
Nature Medicine is a monthly journal publishing original
peer-reviewed research in all areas of medicine based on its
originality, timeliness, interdisciplinary interest, and impact on
improving human health. Nature Medicine also publishes commissioned
content, including News, Reviews and Perspectives, aimed at
contextualizing the latest advances in translational and clinical
research to reach a wide audience of M.D. and Ph.D. readers. All
editorial decisions are made by a team of full-time professional
editors. Nature Medicine’s 2-year Impact Factor (2021): 87.241
Collaboration with Indivior Aelis Farma, in June 2021,
signed an exclusive option license agreement with Indivior PLC
("Indivior"), a global pharmaceutical company working to help
change patient’s lives by developing medicines to treat substance
use disorders and serious mental illnesses, for the development and
commercialization of AEF0117 as a treatment for disorders related
to excessive cannabis use. As part of this collaboration, Aelis
Farma has received $30 million (option payment) and is eligible to
receive, if the option is exercised by Indivior after the current
phase 2b, a $100 million license fee (potentially by the end of
2024) and supplementary payments, up to $340 million, in
development, regulatory and commercial milestones, as well as
royalties in the mid-teen percentage range on global net sales. The
option gives Indivior the right to assume all development and
commercialization activities for AEF0117 upon successful completion
of the phase 2b study. Phase 3 studies and commercialization would
then be at Indivior’s direction and expenses, while Aelis Farma
funds and manages the current Phase 2b.
About AELIS FARMA Founded in Bordeaux in 2013, Aelis
Farma is a biopharmaceutical company that is developing a new class
of drugs, the Signaling-Specific inhibitors of the CB1 receptor of
the endocannabinoid system (CB1-SSi). CB1-SSi have been developed
by Aelis Farma based on the discovery of a natural brain defense
mechanism by the team led by Dr. Pier Vincenzo Piazza, the
Company’s CEO, when he was director of Neurocentre Magendie of the
INSERM in Bordeaux. By mimicking this natural mechanism, CB1-SSi
appear to selectively inhibit the disease-related activity of the
CB1 receptor without disrupting its normal physiological activity.
Thus CB1-SSi have significant potential for the treatment of
numerous brain diseases.
Aelis Farma is developing two first-in-class clinical-stage drug
candidates: AEF0117 for the treatment of CUD, currently being
tested in a phase 2b study in the United States; and AEF0217 for
cognitive disorders, including those of Down Syndrome (Trisomy 21),
currently in a phase 1/2 study in Spain. The Company also has a
portfolio of innovative CB1-SSi for the treatment of other
disorders associated with a dysregulation of the activity of the
CB1 receptor.
Aelis Farma draws on the talents of more than 20 highly
qualified employees.
For more information, visit www.aelisfarma.com and follow
us on LinkedIn and Twitter.
ISIN: FR0014007ZB4 Ticker: AELIS B Compartment
of Euronext Paris
Forward-looking statements Some information contained in
this press release are forward-looking statements, not historical
data. These forward-looking statements are based on current
beliefs, expectations, and assumptions, including, but not limited
to, assumptions about Aelis Farma's current and future strategy and
the environment in which Aelis Farma operates. They involve known
and unknown risks, uncertainties, and other factors, which may
cause actual results, performance, or achievements, or industry
results or other events, to differ materially from those described
or implied by such forward-looking statements. These risks and
uncertainties include those set out and described in detail in
Chapter 3 "Risk Factors" of Aelis Farma's registration document
approved by the Autorité des Marchés Financiers on January 14,
2022, under number I.22-003.
These forward-looking statements are made only as of the date of
this press release and Aelis Farma expressly disclaims any
obligation or undertaking to release any updates or corrections to
the forward-looking statements included in this press release to
reflect any change in expectations or events, conditions, or
circumstances on which any such forward-looking statement is based.
Forward-looking information and statements are not guarantees of
future performance and are subject to various risks and
uncertainties, many of which are difficult to predict and generally
beyond Aelis Farma's control. Actual results could differ
materially from those described in, or implied or projected by,
forward-looking information and statements.
References
1. Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone Can
Protect the Brain from Cannabis Intoxication. Science
2014;343(6166):94-98. DOI: doi:10.1126/science.1243985.
2. American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders - V: American Psychiatric Association,
2013.
3. Substance Abuse and Mental Health Service. Key substance use
and mental health indicators in the United States: Results from the
2020 National Survey on Drug Use and Health. Rockville, MD. 2021.
Accessed May 16, 2023
4. Reece AS, Hulse GK. Quadruple convergence – rising cannabis
prevalence, intensity, concentration and use disorder treatment.
The Lancet Regional Health - Europe 2021;10:100245. DOI:
https://doi.org/10.1016/j.lanepe.2021.100245.
5. Gates PJ, Sabioni P, Copeland J, Le Foll B, Gowing L.
Psychosocial interventions for cannabis use disorder. Cochrane
Database Syst Rev 2016;2016(5):Cd005336. (In eng). DOI:
10.1002/14651858.CD005336.pub4.
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version on businesswire.com: https://www.businesswire.com/news/home/20230608005533/en/
AELIS FARMA Pier Vincenzo Piazza, MD, PhD CEO
Corresponding author contact@aelisfarma.com
NewCap Dusan Oresansky/ Aurélie Manavarere Investor
Relations aelis@newcap.eu +33 1 44 71 94 92
NewCap Arthur Rouillé Media Relations aelis@newcap.fr +33
1 44 71 00 15
RXMD Charlotte Wray Media Relations cwray@rxmedyn.com +1
646 247 3405
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