Aelis Farma Announces Positive Results of Non-clinical Studies Required by Regulatory Agencies to Enter Its First CB1-SSi, AEF0117, in Phase 3 Clinical Trial for the Treatment of Cannabis Use Disorder - Seite 2

To circumvent this problem, some companies have developed periphery restricted CB₁ antagonists, i.e. drugs that work like rimonabant but do not access the brain, such as the compound developed by Inversago, recently acquired by Novo Nordisk. While these drugs are likely safer than the previous generation of CB₁-antagonists, they only target peripheral diseases, and cannot be used for brain disorders.

Aelis Farma’s CB₁-SSi allow to address safely the entire spectrum of CB₁-related diseases as they reproduce a natural mechanism used by the brain to control the hyperactivity of the CB₁

CB₁-SSi are not antagonists, which block all the activity of the receptor, but they are able to selectively inhibit only some functional outputs (signalings) of the CB₁. Their name, Signaling Specific inhibitors (SSi), stems from this characteristic. In particular, CB₁-SSi seem able to selectively inhibit the signaling of the receptor linked to pathological states while preserving normal physiological activities. This characteristic confers them their very favorable safety profile. A striking aspect of their action is that they do not modify behavior per se, in animals or in humans, but are able to potently reverse the hyperactivation of the CB₁ induced by cannabis (AEF0117, Nature Medicine¹) or restore certain impaired cognitive functions (AEF0217).

CB₁-SSi can have this disease specific effect because instead of having an artificial mechanism of action like antagonists, they copy a natural inhibitory mechanism that the brain uses to control a hyperactivity of the CB₁. This mechanism, discovered by the CEO of Aelis Farma, Dr. Pier Vincenzo Piazza, has been fine-tuned by evolution and is mediated by the hormone pregnenolone. Pregnenolone can inhibit CB₁ activity in this signaling specific manner countering the overactive receptor while preserving its normal basal functioning (Science paper²). Unfortunately, pregnenolone cannot be used as a therapeutic drug. It has very low oral absorption, a very short half-life because is rapidly transformed in several active steroids (progesterone, testosterone etc..) that can potentially induce serious side effects. CB₁-SSi are new molecular entities that reproduce the signaling inhibition of the CB₁ by pregnenolone, but are well absorbed, stable and not transformed in steroids.