Aelis Farma, a clinical-stage biopharmaceutical company specializing in the development of treatments for brain diseases, announced the favorable results of the phase 1 clinical study program in healthy volunteers with AEF0217, a drug candidate specifically developed for the treatment of cognitive deficits caused by hyperactivity of the CB1 receptor, and as a first indication those associated with trisomy 21 (Down syndrome). Acute and chronic administration of AEF0217, up to 30 times the anticipated therapeutic range, is well tolerated and has favorable safety and plasma exposure profiles for further clinical development.
AEF0217 is the second representative of the new class of drugs developed by Aelis Farma: specific inhibitors of CB1 receptor signaling (CB1-SSi). CB1 is the main receptor of the cerebral endocannabinoid system responsible for regulating several physiological and cognitive processes. Recent studies have shown that cognitive disorders linked to trisomy 21 involve hyperactivation of the CB1 receptor. AEF0217 is positioned as the first treatment for cognitive deficits caused by hyperactivity of the CB1 receptor. AEF0217 aims to capitalize on the specificity of CB1-SSi residing in their ability to inhibit the hyperactivity of the CB1 receptor without altering normal physiological functions and without inducing significant side effects, two particularly important criteria for fragile populations such as those carrying the Down syndrome.
Pier Vincenzo Piazza, Chief Executive Officer of Aelis Farma, declares: “The very favorable results of the phase 1 program obtained with AEF0217 constitute an important step in the development of this drug candidate intended for the treatment of cognitive deficits and in particular those related to trisomy 21, also called Down syndrome. It is also a strong signal for the therapeutic class developed by Aelis Farma, CB1-SSi, which confirms that it has an excellent safety profile as well as advantageous pharmacokinetic characteristics. AEF0217 can now be evaluated in phase 1/2 in subjects with trisomy 21. This important advance in the development of AEF0217 allows us to quickly approach the confirmation of its therapeutic potential to improve the management of cognitive deficits in people carriers of trisomy 21 for which there is no effective therapeutic solution to date. »
The phase 1 clinical study program combined three clinical studies authorized by the Spanish health authority (AEMPS) in September 2021: a single ascending dose study, a multiple (7-day) ascending dose study, and a pharmacokinetics analyzing the impact of food intake on drug absorption. This global clinical program aimed to evaluate the safety, tolerance and absorption of AEF0217, compared to placebo, in a range between 0.2 mg and 6 mg in a total of 68 healthy volunteers, aged 18 to 55 years. .
The results obtained showed that all doses of AEF0217 were well tolerated by healthy volunteers and no serious or serious adverse effects were detected. Only 3 AEF0217-related adverse effects were observed during the full program, manifesting as mild diarrhea. No clinically relevant changes in routine laboratory tests, electrocardiograms or vital signs were observed. Psychometric tests assessing the main psychological dimensions, such as depression, anxiety, psychosis and suicidal tendencies were also carried out and no significant difference was observed between AEF0217 and placebo. The pharmacokinetic profile of AEF0117 was also found to be favorable and is characterized by very good absorption, linearity between doses and a long half-life as expected.
“These positive results of AEF0217 are all the more encouraging since the safety of the compound is a particularly important criterion for the treatment of the Down syndrome population and for the acceptance by families of a treatment for the cognitive deficits of these fragile people. We are delighted to be part of this revolutionary project and enthusiastic to continue the evaluation of this drug candidate which represents real hope for many people with Down syndrome and their loved ones,” concludes Prof. Rafael de la Torre Fornell, principal investigator of the clinical studies and coordinator of the ICOD project.
It is thanks to these positive data that the AEMPS has authorized the first clinical trial in participants with trisomy 21. The main objective of this phase 1/2 study will be to demonstrate the safety, tolerance and pharmacokinetic profile of AEF0217 in people with Down syndrome and could also provide the first evidence of the activities of this drug candidate. The first inclusions are expected before the end of 2022 and the first clinical results should be available in mid-2023.
About the clinical program of AEF0217 for the treatment of trisomy 21 cognitive impairment: the European ICOD project.
The phase 1 program of AEF0217 is part of the European project H2020 ICOD (Improving COgnition in Down syndrome, Grant N° 899986), and is carried out in collaboration with the Hospital del Mar Institute of Medical Research (IMIM) of Barcelona (Spain). ) and Prof. Rafael de la Torre Fornell, project coordinator and principal investigator of the study. In February 2021, the ICOD project received €6 million in funding from the European Commission to fund the clinical development of AEF0217 for the treatment of cognitive deficits related to Down syndrome.
Source: Aelis Farma