Signaling Specific inhibitors
A New Pharmacological Class to treat CNS disorders
AELIS FARMA’S PROPRIETARY | March 2021 | 1 AELIS FARMA : a breakthrough in pharmacology
AELIS CB1-Signaling AEF0217 for FARMA Specific Cognitive at a Glance inhibitors Impairments
AEF0117 for Cannabis Related Disorders
AELIS FARMA The company at a glance
AELIS FARMA’S PROPRIETARY | March 2021 | 2 Aelis Farma Team
Management Three utmost dedicated founders
Pier Vincenzo . Scientist-Entrepreneur, Aelis is the third biotech founded by Piervi Piazza - Former director of the Neurocentre Magendie of INSERM (MD, PhD) CEO - Business savvy, cutting-edge vision on drug discovery and development (Grand Prix INSERM and French Academy of Science for CB1-SSi) .
Valérie . An associated director for 10 years at EY before founding Aelis Scappaticci (MBA) - Perfectly mastering business, tax and grant regulations. Instrumental in CFO securing record non dilutive financings for Aelis.
Stéphanie . A neuroscientist with a unique talent for R&D management Monlezun (PhD) - Never taking no for an answer. 360° knowledge of drug development, the driving COO force behind the record timeline of AEF0117 and AEF0217 developments.
Neurocentre Magendie INSERM Headquarters . One of the best Neuroscience institutes in Europe . State-of-the-art scientific infrastructure Bordeaux (France) . Access to cutting edge scientist and facilities
| March 2021 | AELIS FARMA’S PROPRIETARY 3 Scientific Advisory Board Board of Directors
& Board of Directors Anders Gersel Pedersen - Chairman of the Board - Former Exc. VP R&D Lundbeck
Scientific Advisory Board François Thomas - Board Member - CEO of Inserm Transfer Initiative (ITI) Robert Malenka investment Fund Professor and Deputy Director Neurosciences Institute - Chairman of the SAB Thibaut Richebois - Board Member - Director of Economic Development of Keith Humphrey the Nouvelle Aquitaine Region Professor and Section Director for Mental Health Policy Department of Alain Sainsot Psychiatry - Board Member - Former CEO of Amatsi Group
Daniele Piomelli Professor University of California Irvine Pier Vincenzo Piazza Former Director of Drug Discovery and - Board Member - Development IIT Former Director Magendie Neurocentre CEO AELIS FARMA
Markus Heilig Benedikt Timmerman Director, Center for Affective - Censor - Neuroscience Linköping University Venture Partner at IRDI SORIDEC (Sweden), Former Clinical Director Gestion NIAAA & NIDA
| March 2021 | AELIS FARMA’S PROPRIETARY 4 Overview of Aelis Farma Achievements
2014 From discovery to end of phase IIa in 6 years 2021
A Growing Pipeline of Signaling Specific inhibitors of the CB1 New A new pharmacological class of biased inhibitors CB1-SSi . Reversing disease states without behavioral side effects for multiple . Proven efficacy in model of addiction & cognitive impairments diseases . Provide pharmacologically differentiated new drug candidates
Cannabis Related Disorders: Addiction & Psychosis AEF0117 Exclusivity Clinical stage Phase IIb . Extensive preclinical POC & FDA IND up to 2039 . Phase IIa completed at Columbia Univ. (NY) in 2021 . Phase IIb will start in 2021
Cognitive Impairments: First target Down syndrome AEF0217 Will enter phase I in 2021 Phase I Exclusivity . Very positive preclinical POC up to 2039 . Very favorable ADMET characteristics in 2021 . Studies in Down syndrome subjects will start in 2022
| March 2021 | AELIS FARMA’S PROPRIETARY 5 AELIS FARMA : a breakthrough in pharmacology
AELIS CB1-Signaling AEF0217 for FARMA Specific Cognitive at a Glance inhibitors Impairments
AEF0117 for Cannabis Related Disorders
CB1-SSi The first biased inhibitors
| March 2021 | AELIS FARMA’S PROPRIETARY 6 CB1-SSi biased inhibition decreases side effects and increases efficacy
Available inhibitors Signaling Specific inhibitors - CB -SSi - CB1 - agonist 1
CB1 - agonist Antagonist
CB1 Receptor CB1-SSi
P-ERK P-ERK c-AMP β-Arrestin Biased inhibition Total block of activity GOOD TOLERABILITY c-AMP β-Arrestin ADVERSE EFFECTS Not modified
| March 2021 | AELIS FARMA’S PROPRIETARY 7 CB1-SSi allow to target a large spectrum of indications The CB1-Receptor is involved in several disease states
1 Exocannabinoids (Cannabis/THC) Related Disorders
THC • Cannabis addiction (CUD) • Cannabis induced Psychosis (CiP) AEF0117 • Cannabis Toxicity (hyperemesis…)
CB1 Receptor 2 Endocannabinoids (2AG, AEA) Related Disorders
2AG Cognitive Impairments • Down syndrome AEF0217 • Fragile X • Aging related impairments Psychiatric Diseases AEA • PTSD • ADHD New SSi • Schizophrenia We are opening )a) new frontier in pharmacology
| March 2021 | AELIS FARMA’S PROPRIETARY 8 AELIS FARMA : a breakthrough in pharmacology
AELIS CB1-Signaling AEF0217 for FARMA Specific Cognitive at a Glance inhibitors Impairments
AEF0117 for Cannabis Related Disorders
AEF0117 A First-in-class for Cannabis Related Disorders
| March 2021 | AELIS FARMA’S PROPRIETARY 9 Cannabis Related Disorders Growing opportunity: increased medical needs because of legalization
Cannabis Related Disorders Strong unmet medical needs Large Markets
12.4M patients with (CUD) worldwide Potential $2Bn turnover CUD: 9M patients in US, EU, CA, AU Cannabis Use Disorders per year for AEF0117 at Highest demand for treatment in addiction peak sales (Addiction in the DSM-5) clinics with no available therapy
40% of Schizophrenics abuse cannabis and become resistant to neuroleptics CiP: Potential $1Bn turnover 50% of European Emergency Room per year for AEF0117 at Cannabis induced entries for psychosis peak sales Psychosis Cannabis induced psychosis are resistant to neuroleptics
CiT: 0.5M ER entry in the US due to cannabis We are openingPotential a rapidnew Cannabis induced Recurring entries in ER after first visit with market approval frontier in pharmacology Toxicity significative health care costs
| March 2021 | AELIS FARMA’S PROPRIETARY 10 AEF0117: strong preclinical & clinical data package
Preclinical Phase I Phase II
Very favorable ADMET profile Developments in the US Phase IIa study in “Cannabis abusers” – FDA IND obtained in 2016 – University of Columbia Potent inhibition of THC effects – Cannabis subjective effects and self-administration – No relevant adverse Distinct pharmacological profile from events reported Phase I studies completed (US) CB antagonists – Study Completed 1 – Single and multiple ascending dose (SAD & MAD) Will enter phase IIb in 2021 – Excellent safety profile
✓ ✓ ✓
Good CMC characteristics and advanced development Three steps Final formulation Low costs of goods Administration via synthesis identified oral capsules
Supported by NIH (NIDA)
| March 2021 | AELIS FARMA’S PROPRIETARY 11 AELIS FARMA : a breakthrough in pharmacology
AELIS CB1-Signaling AEF0217 for FARMA Specific Cognitive at a Glance inhibitors Impairments
AEF0117 for Cannabis Related Disorders
AEF0217 A new approach to treat Cognitive Impairments
| March 2021 | AELIS FARMA’S PROPRIETARY 12 Cognitive Impairments in Down syndrome (DS) A major unmet medical need
Intellectual disability: Global market size the major unmet need in DS 7 Major Markets (in $ million) IQ < 70 in children and young adults
600 000 50% of DS subjects develop Alzheimer disease
550 000 after the age of 40 171,2 500 000 JP 944,94 132,96 450 000 High dependency, negative social and financial UK 160,09 885,14 400 000 impacts 104,03 ESP 123,53 350 000 98,83 300 000 IT 144,03 250 000 111,57 2018 2027 FR 200 000 150 000 DE 170,94 178,36
100 000 US 132,81 161,32 50 000 0 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 $1.7 Bn ~$2 Bn
No pharmacological treatment available Source: Down Syndrome Report Market Insights Epidemiology and Market Forecasts 2027 DELVEINSIGHT -- REPORT AND PERSPECTIVES
Strong demand for a treatment of cognitive impairments and low competition in the space
AELIS FARMA’S PROPRIETARY | March 2021 | 13 CB1 receptors inhibition: a new target for treating Cognitive Impairments
Inhibition of the CB1-receptors by antagonists reverses cognitive impairments in models of neurodevelopmental disorders
Targeting the endocannabinoids system Fragile X syndrome in the treatment of fragile X syndrome. Busquets-Garcia et al., 2013
Cannabinoid type-1 receptor blockade restores Down syndrome neurological phenotypes in two models for Down syndrome. Navarro-Romero et al. 2019
In animal models (Ts65Dn mice) and in Down syndrome subjects there seems to be a hyperactivity of the endocannabinoid system
| March 2021 | AELIS FARMA’S PROPRIETARY 14 AEF0217: strong preclinical package & ready for Phase I
Preclinical Phase I (2021-2022) Phase II (2022-2023)
Very favorable ADMET profile Healthy volunteers Phase II POC in Down syndrome Single ascending dose (SAD) – – Efficacy on cognitive impairments Very potent in reversing cognitive – Multiple ascending dose (MAD) in young adult Down syndrome impairments in trisomic (Ts65Dn) mice – Food effect (Single dose) subjects. Dose finding study
Distinct pharmacological profile from Down syndrome subjects Results expected in 2023 CB1 antagonists – MD for safety, absorption and biomarker of changes in plasticity
✓ ✓
Good CMC characteristics and advanced development Five steps synthesis Final formulation Low costs of goods Drinkable identified formulation
Supported by the H2020 program of the EU
| March 2021 | AELIS FARMA’S PROPRIETARY 15 AELIS FARMA : a breakthrough in pharmacology
AELIS CB1-Signaling AEF0217 for FARMA Specific Cognitive at a Glance inhibitors Impairments
AEF0117 for Cannabis Related Disorders
AELIS FARMA A paradigm shift in inhibitors pharmacology
| March 2021 | AELIS FARMA’S PROPRIETARY 16 Thank you !
AELIS FARMA’S PROPRIETARY | March 2021 | 17