ANT01 in the Prevention of Alzheimer EXECUTIVE SUMMARY IN - PowerPoint PPT Presentation

Erik BUNTINX , MD-Psychiatrist Founding CEO erik.buntinx@aneurotech.com 1 www.aneurotech.com

ANT01 in the Prevention of Alzheimer EXECUTIVE SUMMARY IN PRECLINCAL STAGE OF ALZHEIMER DISEASE (AD), ANT01 IS AIMED TO INDUCE COGNITIVE ENHANCEMENT IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER ➢ Driven by ANT01’ unique selective modulation of 5 -HT2A and D4 receptors ➢ With Initial Clinical POP (Proof-Of-Principle) Bio-Marker Data in Targeted Patients, validated by the KoL of the UK Dementia Research Institute, Prof. Dr. Bart De Strooper ➢ Making ANT01 an unique opportunity in the competitive field of AD drug development and as such receiving from two of the top 5 global pharmaceutical companies (with a yearly revenue greater than 50 B USD) a formal request to review the positive proof-of-concept data once they are achieved. As a result, ANT is currently in the process of initiating its Proof of Concept Study RESTORE-COG 2

ANT’ KEY TEAM Founding CEO In Inventor Erik Buntinx , M.D. , Founding CEO Medical Chair ir Scie ientific Center Anima & Anima Research Center, Alken (BE) Advis isory ry Board Experienced Chief Executive ▪ Officer with a demonstrated Charles B. Nemeroff , M.D., Ph.D., Dell Med, UT, history of working in the Austin(US), Mulva Clinic for the Neurosciences. pharmaceuticals industry. Inventor of multiple President of the Anxiety and Depression Association of ▪ ▪ worldwide granted patents America (ADAA). in the field of neurosciences Co-editor in chief (with Alan F. Schatzberg, M.D.) ▪ Veteran Principle ▪ of the Textbook of Psychopharmacology Investigator in key CNS Co-editor in chief of Personalized Medicine in Psychiatry. ▪ programs

ANT01 in the Prevention of Alzheimer CURRENT ALZHEIMERS’ OUTLOOK: IN PRECLINCAL STAGE OF AD ANY KNOWN POC STUDY ADRESSING COGNITIVE ENHANCEMENT 4

ANT01 in the Prevention of Alzheimer UNIQUE DIFFRERENTIATING POSITION FROM COMPETITORS IN AD: AN ESTABLISCHED PHASE II, SYSTEM-REDUCING SMALL MOLECULE IN PRECLINICAL STAGE OF AD 5

ANT01 in the Prevention of Alzheimer RISK TO DEVELOP ALZHEIMER DISEASE (AD) Higly Correlated with co-morbidity DEPRESSION & SUBJECTIVE COGNITIVE DECLINE (SCD – Mean MMSE (SD): 27,5 (2,2))* ANT01 Phenotype Preclinical Alzheimer Disease Patients with Major Depressive Disorder Kaplan-Meier curve reflecting the risk of mild cognitivie impairment and dementia across the different combinations of presentation (n=13,462). MCI: Mild Cognitive Impairment; SCD: subjective cognitive decline * Liew et al. Alzheimer’s Research & Therapy (2019) 11: 170 & Simona et al, Journal of Alzheimer’s Disease 66 (2018) 483-495

ANT01 in the Prevention of Alzheimer ANT01 Endo-Phenotype in Alzheimer: HIPPOCAMPAL SYNAPSE LOSS, correlated with Increased tau-deposition and cognitive decline* * Van Laere Koen et al, KULeuven 7

ANT01 in the Prevention of Alzheimer ANT01 Endo-Phenotype in Alzheimer: MODULATION OF HIPPOCAMPAL SYNAPSES AD Target Brain Area Hippocampus where post-synaptic Dopamine 4 Receptor - Modulation entrains gamma frequency, attenuating amyloid load and modifying microglia - Activation suppresses long term potentiation which is impaired in AD Need for modulation of the negative impact of D4 receptor dependent dopaminergic activation of hippocampal synapses on cognitive performance * Iaccarino H.F. et al , Nature (2016) 540: 230 ** Andersson R.H. et al , PNAS (2012) 109: 13118

ANT01 Proof-of-Principle Bio-marker Study (n=3) ANT01 induces Alzheimer Patient – in contrast with AD patients – 3 weeks 3 months 1.5 30 rel gamma (abs. values) Relative gamma power 25 MMSE Total Score Sustained Enhanced Cognitive AD Stage (Total Score) (abs. values) 1.0 20 MMSE 15 Performance over 6 months 0.5 10 5 in defined AD at risk patients 0.0 0 pre-Rx post-Rx pre-AD Stage accompagnied by enhanced REM Sleep Associated Frontal Gamma Frequency At Risk Patient 1 At Risk Patient 2 >6 months 3 weeks >6 months 3 weeks 1.5 30 1.5 30 rel gamma (abs. values) Relative gamma power rel gamma (abs. values) Relative gamma power 25 MMSE Total Score 25 MMSE Total Score (Total Score) (abs. values) (Total Score) 1.0 20 (abs. values) 1.0 20 MMSE MMSE 15 15 0.5 10 0.5 10 5 5 0.0 0 0.0 0 pre-Rx post-Rx pre-Rx post-Rx

ANT01 in the Prevention of Alzheimer: A Potential +10 B Drug US POPULATION 2017 2017 325.700.000 MDD PREVALENTION 4% 13.028.000 MDD HISTORY + SUBJECTIVE COGNITIVE DECLINE 30% 3.908.400 WITH ACUTE Rx 50% 1.954.200 TOTAL PATIENTS TREATED PER YEAR WITH INITIAL RESPONSE 60% 1.172.520 AD PREVALENTION* 2030 8.400.000 TOTAL HEALTHCARE COST AD* 2030 $ 449.400.000.000 COST AD PATIENT PER YEAR* 2030 $ 53.500 NEW CASES PER YEAR* 2030 615.000 COST NEW CASES PER YEAR 2030 $ 32.902.500.000 PART NEW CASES AD IN TOTAL COST AD 2030 7,32% PROJECTED TOTAL COST AD +10 YEARS* 2040 $ 868.800.000.000 ADDITIONAL COST AD +10 YEARS 2040 $ 419.400.000.000 PART NEW CASES AD IN TOTAL COST AD +5 YEARS 2035 37% COST NEW CASES AD +5 YEARS 2035 $ 318.042.857.143 PREVENTION OF AD WITH ANT01 TOTAL OF NEW CASES AD PREVENTED WITH ANT01 PER YEAR 20% 234.504 SAVING HC COST AD +5 YEARS WITHOUT COST DRUG Rx 2035 $ 63.608.571.429 COST DRUG Rx PER YEAR 20% $ 12.721.714.286 TREATMENT COST PER MONTH PER PATIENT 12 $ 904 NET SAVING HEALTHCARE COST PER YEAR 2035 $ 50.886.857.143 *Alzheimer’s Association (2018) Alzheimer’s Disease Facts and Figures. Alzheimers Dement 14: 367 10