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Nov 29, 2021

Aelis Farma announces good results from its first administration in humans for AEF0217, its first drug candidate for the treatment of cognitive disorders in Down syndrome

• AEF0217 is the second most advanced drug candidate from the new pharmacological class developed by Aelis Farma: Signaling Specific inhibitors of the CB1 receptor (CB1-SSi).

• AEF0217 aims to be the first treatment for cognitive deficits caused by hyperactivity of the CB1 receptor, the first indication being those associated with Down syndrome, which currently present a significant unmet need.

• This single ascending dose study is designed to assess the safety, tolerability and the bioavailability of AEF0217 and is part of a wider phase 1 trial expected to include 68 healthy volunteers for which the full results are expected in the third quarter of 2022.

Bordeaux, November 2021 – AELIS FARMA, a biotechnology company specializing in the treatment of brain disorders, announces today that AEF0217 has been administered to the first cohort of healthy volunteers, as part of a phase 1 clinical study to assess the safety, tolerability and the pharmacokinetic characteristics of its second drug candidate.

The administration of AEF0217, using a dose in the expected therapeutic range, has good tolerability and demonstrates encouraging safety and plasma exposure characteristics for further clinical development.

AEF0217 is the second compound of the new class of drugs developed by Aelis Farma: the signaling specific inhibitors of the CB1 receptor (CB1-SSi). This new class of drugs is based on the discovery of a new brain regulatory mechanism by the research group of Dr. Pier Vincenzo Piazza, co-founder and CEO of Aelis Farma and former director of the Neurocenter Magendie of INSERM in Bordeaux, France. CB1-SSi have a unique mechanism of action that allow them to specifically target the activity of the CB1 mediating the pathological hyperactivity of the receptors, leaving basal physiological functions undisturbed. The CB1 receptor is the main receptor in the endocannabinoid system that is responsible for regulating several physiological and cognitive processes.

AEF0217 aims to be the first treatment for cognitive deficits caused by hyperactivity of the CB1 receptor, which is caused by a malfunctioning of the endogenous endocannabinoid system. Recent studies1 have shown that cognitive disorders linked to Down syndrome (Trisomy 21) involved the hyperactivation of the CB1 receptor.

Down syndrome is a genetic condition, the prevalence of which has been increasing because of the rise in maternal age, and the increase in life expectancy of people with Down syndrome. Today, it is estimated that approximately 0.8 million people live with Down syndrome in the main western economies and in Japan. There is currently no approved medical treatment for cognitive disorders associated with Down syndrome, which presents a significant unmet medical need in this population and a significant strain for individuals with Down syndrome, their families and healthcare systems.

CB1-SSi are unique because of their ability to inhibit hyperactivity of the CB1 receptor without altering normal physiological functions and without causing significant side effects, two particularly important criteria in the treatment of vulnerable patients such as those with Down syndrome.

“We are very happy to announce today the encouraging results from the first cohort of volunteers that have been given AEF0217 as part of our development program for this compound to treat cognitive deficits, in particular those linked to Down syndrome. The successful start of the clinical phase of our second drug candidate is an important strategic step in the development of Aelis Farma”, commented Dr. Pier Vincenzo Piazza, co-founder and CEO of Aelis Farma.

Dr. Pier Vincenzo Piazza added: “AEF0217 has strong therapeutic potential to improve care for Down syndrome patients suffering from cognitive deficits, for which there is currently no effective medical solution. We are equally delighted to collaborate with leading institutions and experts such as Prof. de la Torre Fornell from IMIM in Barcelona, Spain , whose contribution will be key to the development of this new therapy. We are eager to advance the clinical development of this very promising product.”

This single ascending dose study is the first of three phase 1 trials authorized by the Spanish Agency of Medicines and Medical Devices (AEMPS) in September 2021. These studies will assess the safety and tolerability of single and multiple doses of AEF0217 in a range between 0.2mg and 6mg, as well as the effects of food on the absorption of the drug in a total of 68 healthy volunteers, between 18 and 55 years old.

This phase 1 program is part of the European H2020 ICOD project (Improving COgnition in Down syndrome) which is led in collaboration with IMIM2 in Barcelona, (Spain) and Prof. Raphael de la Torre Fornell, coordinator of the project and the principal investigator of the study. In February 2021, the ICOD project received funding of €6m from the European Commission to finance the clinical development of AEF0217 for the treatment of cognitive deficits linked to Down syndrome.

“The positive results from the first cohort of healthy volunteers to be administered AEF0217 is a very important first step on the path to a promising therapy for cognitive deficits caused by Down syndrome. We are delighted to be part of this project, which represents real hope for many people affected by Down syndrome and their families”, added Prof. Rafael de la Torre Fornell, principal investigator of the clinical trials and coordinator of the ICOD project.

About AELIS FARMA Aelis Farma is a biotechnology company founded in 2013 that has developed a new class of drugs, the signaling specific inhibitors of the CB1 receptor (CB1-SSi), of which two compounds are at clinical stage. In recognition of the discovery of CB1-SSi by the team led by Dr. Pier Vincenzo Piazza, CEO of Aelis Farma, when he was director of the Neurocenter Magendie at INSERM in Bordeaux, France, he was awarded two of the most prestigious French awards for Medicine and Neurology, the Grand Prix of INSERM and the Grand Prix of Neurology from the French Academy of Science, respectively.

CB1-SSi, which target the main receptor of the endocannabinoid system, the CB1, have significant potential for the treatment of several brain diseases. Aelis Farma has already developed two “first-in-class” drug candidates, AEF0117 and AEF0217, and has a portfolio of innovative CB1-SSi for the treatment of other pathologies associated with disruption of the activity of the CB1 receptor.

AEF0117, which targets disorders linked to cannabis use (addiction and psychosis), has completed a phase 2a trial, which produced positive results in terms of therapeutic efficacy and will enter phase 2b in the United States in 2022. In June 2021, Aelis Farma announced an option license agreement with Indivior PLC, a pharmaceutical leader in addiction treatment, for the development and worldwide commercialization of AEF0117 for disorders linked to cannabis use. Under this agreement, Aelis Farma received an initial payment of $30m (for the option to license) and, if the option is exercised after the phase 2b, would receive up to $440m in milestone payments, as well as mid-teens royalties on sales of AEF0117.

AEF0217, which targets cognitive disorders such as those caused by Down syndrome, recently entered phase 1 clinical development. This compound underwent a comprehensive proof of concept using innovative and powerful predictive tests to assess cognitive functions. In this context AEF0217 showed that it is capable of completely reversing cognitive deficits in several experimental models of cognitive disorders: Down syndrome, Fragile X syndrome, as well as some age-related cognitive deficits. Aelis Farma has several CB1-SSi that are at an early preclinical stage. Over time, Aelis Farma has acquired unique knowledge and capability regarding the pharmacology of CB1-SSi and has broadened its portfolio of compounds and patents targeting treatments for several brain diseases.

Headquartered in Bordeaux, within the Neurocenter Magendie of INSERM, Aelis Farma employs 23 people and benefits from the financial support of the Nouvelle-Aquitaine region, the INSERM Transfert Initiative, Bpifrance, regional investment funds ACI and NACO and from IRDI Capital Investissement. To date, its various research programs have benefited from grants from the European Regional Development Fund (ERDF), BPI’s Deeptech program, the European Union’s H2020 program and from the “Strategic Alliance” program of America’s NIH-NIDA (National Institute of Health-National Institute on Drug Abuse).

1Navarro-Romero et al. Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome. Neurobiol Dis. 2019; 125:92-106.
2Hospital del Mar Medical Research Institute (IMIM).