- The CB1-SSi AEF0217 successfully met the safety (primary),
pharmacokinetic (secondary) and efficacy (secondary and
exploratory) objectives of this phase 1/2 performed in young adults
with Down syndrome (Trisomy 21) for whom cognitive disorders are a
major unmet medical need.
- AEF0217 was well tolerated, and no safety concerns were
identified, confirming that the drug could be safely used even in
the more fragile population of young adults with Down
syndrome.
- After four weeks of treatment, AEF0217 significantly
improved important behavioral abilities in the communication, daily
living skills and social interactions domains, as measured by the
reference Vineland Adaptative Behavior Scale (VABS).
- These improvements were associated with a consistent trend
to increase in cognitive flexibility which was measured using the
NIH-Toolbox Cognitive Battery. Statistically significant changes in
EEG parameters indicating a decrease in the strain to perform a
working memory task and of target engagement were also
observed.
- On the basis of these results, Aelis Farma plans to initiate
around mid-2025 an international multicenter Phase 2 dose finding
study in participants with Down syndrome.
Regulatory News:
Two videoconferences will be held tomorrow,
on Tuesday November 19, 2024, the first in French at 10:00
am CET and the second in English at 4:00 pm CET / 10:00 am
ET.
To participate, please register
here:
Videoconference in French
Videoconference in English
Aelis Farma (ISIN: FR0014007ZB4 – Ticker: AELIS), a
clinical-stage biopharmaceutical company specializing in the
development of treatments for brain and peripheral diseases
involving the CB1 receptor, today announces the positive results of
a Phase 1/2 clinical study with AEF02171 in young adults with Down
syndrome.
This Phase 1/2 clinical trial with AEF0217 was a randomized,
double-blind, parallel study comparing one dose of AEF0217 (0.2mg
oral dose) to placebo after 28 days of treatment once a day in
young adults (between 18 and 35 years old) with Down syndrome. The
primary objective of the trial was to assess the safety and
tolerability of AEF0217, which is particularly relevant in the
fragile population with Down syndrome. The secondary and
exploratory objectives investigated the pharmacokinetic and the
efficacy of AEF0217 on the behavioral impairments of young adults
with Down syndrome. 29 young adults with Down syndrome with mild to
moderate intellectual disability were included in the study by the
teams of Prof. de la Torre Fornell at the Hospital del Mar Medical
Research Institute (HMRIB) in Barcelona (Spain), the principal
investigator, and Dr Real de Asua at the Hospital de la Princesa in
Madrid (Spain). The effects of a treatment with AEF0217 were also
studied as a function of the APOE4 genotype (APOE4-positive versus
APOE4-negative). This genetic marker has been shown to be related
to endocannabinoid physiology and to the susceptibility to develop
Alzheimer disease.
The study successfully met its safety (primary),
pharmacokinetics (secondary) and efficacy (secondary and
exploratory) objectives. AEF0217 was well tolerated, and no safety
concerns were observed. The adverse events were similar in the
placebo and AEF0217 groups. Most of the adverse events observed
were of mild severity and considered unrelated to treatment. No
serious or severe adverse events were observed nor was there any
discontinuations of the treatment due to adverse events. AEF0217
also showed a favorable pharmacokinetic profile with plasma
exposure on average slightly higher in young adult with down
syndrome than in healthy volunteers. These results are consistent
with previous Phase 1 clinical studies conducted in healthy
volunteers, in which AEF0217 also demonstrated a very favorable
safety and pharmacokinetic profile.
The effects of AEF0217 on the behavioral impairments of young
adults with Down syndrome were studied using two assessment tools.
The Vineland Adaptive Behavior Scale (VABS), which directly
measures the potential improvements in everyday life functioning of
people with Down syndrome and the NIH-Toolbox Cognitive Battery for
intellectual disabilities which directly measures different
cognitive functions. Of the nine behavioral skills investigated by
the VABS, AEF0217 improved five: (i) expression abilities
(P<0.002); daily living skills: (ii) of the personal sphere
(P<0.003), and (iii) in the community (P<0.03, in
APOE4-negative participants); (iv) interpersonal relationships
skills (P<0.01), and (v) a strong trend to an improvement in
writing abilities in APOE4-negative participants. It is noteworthy
that AEF0217 seemed to induce larger improvements in participants
with the greater impairments before starting the treatment (P<
between 0.04 and 0.003).
Of the five different cognitive functions investigated by the
NIH-Toolbox Cognitive Battery for intellectual disability, AEF0217
induced a clear trend to increase cognitive flexibility, an effect
close to statistical significance (P<0.09) in APOE4-negative
people with Down syndrome. Cognitive flexibility is a very
important cognitive function, impaired in Down syndrome. This
cognitive function is also improved by AEF0217 in genetic animal
models of down syndrome, confirming the translation of AEF0217
effects across species. AEF0217 also significantly (P<0.012)
decreased the Electro Encephalographic (EEG) activity associated
with a working memory task that is higher in young adults with Down
syndrome indicating a higher strain in performing this task
compared with neurotypical controls.
Finally, AEF0217 also showed clear indications of target
engagement, significantly modifying (P<0.05) a CB1 dependent EEG
parameter: the Gamma Intertrial Coherence (ITC) during Auditory
Steady State Response (ASSR) at 40 Hz (ITC-ASSR-40 HZ).
It is noteworthy that the results on adaptative behavior and
cognition were observed after only four weeks of treatment, whereas
it is generally believed by experts in the field that at least
several months of treatment are needed before a pharmacological
intervention is able to modify adaptative behavior and cognitive
performances in neurodevelopmental disabilities.
Prof. Rafael de la Torre Fornell, the trial’s principal
investigator, explains: “The promising and impressive results
of this study generate a real hope to develop an efficacious and
safe treatment for the cognitive disabilities of people with Down
syndrome. Particularly striking are the efficacy data, which
addresses crucial domains of adaptation, such as expression and
writing abilities as well as certain daily living skills and
societal interactions. These types of effects, especially because
obtained after only four weeks of treatment, are certainly a first
in the field of Down syndrome and represent a major step towards
the development of a treatment that could significantly improve the
autonomy and adaptation of people with Down syndrome. I would like
to take this occasion to also send my warmest thanks to the
participants, their families and family associations who supported
this innovative project and helped us to complete this pioneering
clinical trial.”
Pier Vincenzo Piazza, CEO of Aelis Farma, concludes: “I
would like to congratulate the teams of Prof. Rafael de la Torre
Fornell and Dr Diego Real de Asua, as well as the Aelis Farma team
for this major achievement in the development of AEF0217. I would
also like to extend my warmest thanks to all the participants,
their families and family associations, who have made this study
possible. We see this accomplishment as a milestone in the
development of a promising therapy that could significantly improve
the autonomy and quality of life of people with Down syndrome. It
is also, more generally, the first evidence of the positive impact
of AEF0217 on cognition, which could pave the way for the treatment
of other cognitive disorders. These results also provide a
supplementary validation of the safety and activity of the new
pharmacological class developed by Aelis Farma, the “Signaling
Specific inhibitors of the CB1 receptor (CB1-SSi)”. We believe that
the CB1-SSi represent a major innovation in pharmacology that will
allow to generate inhibitors not only efficacious but also safe and
well tolerated, opening the way to new treatments of conditions
without treatment today."
About AEF0217 and the Clinical Phase 1/2 Study
AEF0217 is Aelis Farma’s second drug candidate at the clinical
stage. It belongs to a new class of drugs discovered by the
company, the Signaling Specific inhibitors of the CB1 receptor of
the endocannabinoid system (CB1-SSi). A hyperactivity of the CB1 is
involved in many brain and peripheral disorders. AEF0217, like the
other CB1-SSi, is able to inhibit only certain components of CB1’s
activity. This molecular selectivity generates the first CB1
inhibitors that show beneficial pharmacodynamic effects but lack
the side effects characterizing the drugs of the previous
generation, the CB1 antagonists.
AEF0217 is developed as a new approach for the treatment of
cognitive impairments, a series of brain disorders which seems to
involve the CB1 receptor. The first indication targeted by AEF0217
is the behavioral impairment associated with Down syndrome.
The Phase 1/2 study in young adults with Down syndrome
(NCT05748405) is part of Aelis Farma clinical development program
of AEF0217. This was a randomized, double-blind, placebo-controlled
study (“Effect of AEF0217 in Young Adult Participants With Down
Syndrome (DS)”)1. Twenty-nine young adults (between 18 and 35 years
old) with Down syndrome (trisomy 21) were randomized across two
clinical centres in Spain (Barcelona and Madrid). Participants were
treated once a day for 4 weeks, with either an oral dose of AEF0217
(0.2mg) or placebo, followed by a four-week follow up period.
The primary objective was to assess the safety and tolerability
of AEF0217.
Secondary and exploratory endpoints measured pharmacokinetic and
pharmacodynamic parameters. Potential therapeutic effects of
AEF0217 were measured by two assessment tools.
The first tool was the Vineland Adaptive Behaviour Scale (VABS)
scale, which directly measures the potential improvements in
everyday life functioning of persons with Down syndrome by
analysing specific skills within three major domains of abilities:
(i) Communication: expressive, receptive and writing skills; (ii)
Daily living skills of the personal, domestic and community spheres
and (iii) Socialization: interpersonal relationships, play and
leisure time and coping skills.
The second tool was the NIH-Toolbox Cognitive Battery for
intellectual disabilities which measures five different cognitive
functions: Attention; Episodic Memory; Working Memory; Cognitive
flexibility and Processing speed. In particular, working memory and
cognitive flexibility are important functions impaired in Down
syndrome and in genetic animal models of this condition.
About the AEF0217 clinical program for the treatment of
cognitive disorders in Down syndrome: the European ICOD
project
The clinical development of AEF0217, the phase 1 program in
healthy volunteers, the phase 1/2 just completed and the next phase
2 in people with Down syndrome are part of the European H2020 ICOD
project (Improving COgnition in Down syndrome, Grant Agreement ID
899986). The ICOD project received €6 million of fundings from the
European Commission and involves partners in Spain, France and
Italy.
Based on the results of the Phase 1/2, Aelis Farma expects to
start an international multicenter Phase 2 dose finding study with
AEF0217, for the treatment of the behavioral impairments associated
with Down syndrome. This Phase 2 is planned to start around
mid-2025. As discussed with the European Medicines Agency (EMA),
and taking advantage of the knowledges generated by the Phase 1/2,
the Phase 2 study will focus on the improvement of the adaptative
behaviors measured by the VABS and on specific cognitive functions
measured by the NIH-Toolbox Cognitive Battery for intellectual
disabilities. It is noteworthy that an improvement in adaptative
behaviors as measured by the VABS is considered by regulatory
authorities as an endpoint that can be used to obtain approval.
Aelis Farma is also conducting additional preclinical studies to
better determine the range of potential indications of AEF0217 in
the broad field of cognitive deficits.
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 regulatory mechanism2 of CB1
hyperactivity made by the team led by Dr Pier Vincenzo Piazza, the
Company’s CEO, when he was the director of the Neurocentre Magendie
of 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.
CB1-SSi have consequently the potential to provide new safe
treatments for several brain and peripheral organ diseases.
Aelis Farma currently has two first-in-class clinical-stage drug
candidates. AEF01173 for the treatment of cannabis use disorders
(CUD), that has just completed a Phase 2B study in the United
States in CUD. AEF0217 for cognitive disorders, which has completed
a Phase 1/2 study in Spain in young adults with Down syndrome
(Trisomy 21). The Company also has a portfolio of new innovative
CB1-SSi for the treatment of other disorders associated with a
dysregulation of the activity of the CB1 receptor, including
diseases involving peripheral organs, such as obesity and related
metabolic conditions as well as fibrosis. The different drugs
developed by the company belong to the same general pharmacological
class, the CB1-SSi, but have distinct functional effects allowing
to target different types of dysregulations of the CB1 receptor and
guaranteeing that the different compounds are not substitutable one
with the others.
Aelis Farma draws on the talents of more than 30 highly
qualified employees. For more information, visit www.aelisfarma.com
and follow us on LinkedIn and Twitter.
References:
- Identifier: NCT05748405 -
https://clinicaltrials.gov/study/NCT05748405?intr=aef0217&rank=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.
- Haney M, Vallée M, Fabre S, Collins Reed S, Zanese M,
Campistron G, Arout CA, Foltin RW, Cooper ZD, Kearney-Ramos T,
Metna M, Justinova Z, Schindler C, Hebert-Chatelain E, Bellocchio
L, Cathala A, Bari A, Serrat R, Finlay DB, Caraci F, Redon B,
Martín-García E, Busquets-Garcia A, Matias I, Levin FR, Felpin FX,
Simon N, Cota D, Spampinato U, Maldonado R, Shaham Y, Glass M,
Thomsen LL, Mengel H, Marsicano G, Monlezun S, Revest JM, Piazza
PV. Signaling-specific inhibition of the CB1 receptor for cannabis
use disorder: phase 1 and phase 2a randomized trials. Nat Med. 2023
Jun;29(6):1487-1499.
https://doi.org/10.1038/s41591-023-02381-w
ISIN: FR0014007ZB4 Ticker: AELIS B Compartment
of Euronext Paris
Disclaimer
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 Universal Registration
Document approved by the Autorité des Marchés Financiers on April
24, 2024, under number R.24-004.
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.
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AELIS FARMA Arsène Guekam Chief Corporate Development
Officer 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.eu +33
1 44 71 00 15
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