Developing the therapeutic potential of the first Signaling Specific Inhibitors of the CB1 receptor (CB1-SSi). A new pharmacological class that appears to be able to treat brain diseases without side effects on normal behavior.
Signaling Specific inhibitors of the cannabinoid type 1 receptor (CB1-SSi) are a proprietary new pharmacological class never tested in humans before.

These new small molecules seem able to inhibit selectively the molecular changes involved in pathological hyperactivity of the CB1 receptor, while leaving undisturbed several other cellular activities of this target seemingly preserving normal physiological and behavioral functions of the brain.

As such, no behavioral side effects have been identified to date.
Molecular Target
The CB1 receptor is the molecular target of CB1-SSi
The CB1 is the principal receptor of the endocannabinoid system and one of the main neurotransmitter receptors of the brain.
The CB1 receptor has a very important role in the regulation of physiology and behavior and when dysregulated is involved in several disease states of the brain (see diagram below).
Aelis Farma’s CB1-SSi allow a wide range of disease states to be addressed and the development of a solid and diversified pipeline.
Physiological Functions and pathological states involving the CB1 receptor
Mechanism of Action
CB1-SSi have a unique mechanism of action
The previous generation of CB1 antagonists (left panel in the diagram) block not only a pathological hyperactivity but the entire activity of the CB1 receptor, because they prevent agonists reaching the receptors, inducing significant adverse effects that make, in most cases, their use in clinical practice unfeasible.
CB1-SSi are new molecular entities (NME) that mimic a natural defense mechanism of the brain which has been developed to counteract a hyperactivity of the CB1 receptor (Science, 2014).
CB1-SSi do not block all of the cellular activities of the CB1 (right panel in the diagram), but inhibit selectively a subset of the cellular activity of the CB1 leaving the others undisturbed.
Because of this unique mechanism of action, CB1-SSi appear not only efficacious but also well tolerated. This opens the way to develop new therapeutic tools for diseases caused by a hyperactivity of the CB1 receptor that are without treatment today because of the side effects of the previous generation of CB1 antagonists.
Illustration of the difference in the mechanism of action between Aelis Farma’s CB1-SSi and the previous generation of CB1 antagonists (antagonists).
Brain disorders targeted by Aelis Farma
Disorders linked to excessive cannabis use (AEF0117)
Aelis Farma is developing AEF0117, its first CB1-SSi, to fight Cannabis Related Disorders (CRD), a growing major global health and societal issue without available treatments today.
Excessive cannabis use can induce severe addiction and toxicity that can require visits to emergency rooms, of which cannabis-induced psychosis is the most serious manifestation.
The prevalence of these diseases is increasing in Western economies
There are an estimated 17.91 million daily or almost daily cannabis users in the main western economies (10 million in the US alone), of which 7.2 million have been diagnosed with Cannabis Use Disorders (CUD), the definition of cannabis addiction in the DSM-5 the major diagnostic manual of psychiatric disease.
In the US in 2014 there were 1.1 million visits to emergency room departments because of cannabis (double that in 2011). More recent data from individual states show a sharper increase in American states that have legalized cannabis (see the example of California in the diagram below).
Evolution in recent years of the number of cannabis users and emergency room admissions due to excessive cannabis use
1Data includes the European Union, the United States, Canada, and Australia.
Cognitive Deficits
(AEF0217)
Aelis Farma is developing AEF0217 to treat cognitive deficits, a major unsatisfied medical need of modern society.
The CB1 receptor is involved in several cognitive deficits, such as those associated with Down syndrome, Fragile X syndrome and also aging.
The first therapeutic target of AEF0217 is the treatment of cognitive deficits in Down syndrome (Trisomy 21) for which there is no available treatment.
Approximately 800,0002 individuals live today with Down Syndrome in the main western economies and Japan. The prevalence of this chromosomal abnormality has been steadily increasing because of two major factors: the increase in maternal age during pregnancy and the increase in life expectancy in Down syndrome people.
Cognitive deficits in Down Syndrome constitute the largest unmet medical need among neurodevelopmental disorders with a strong demand from families for a treatment able to increase the independence of their Down Syndrome offspring.
Evolution of the prevalence of Down syndrome and main causes
Aelis Farma aims to extend the indication of AEF0217 to other cognitive deficits such as those observed in Fragile X and aging.
2The European Union, the United States, Canada and Australia.