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

Erik BUNTINX, MD-Psychiatrist

Founding CEO erik.buntinx@aneurotech.com

www.aneurotech.com

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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

ANT01 in the Prevention of Alzheimer

EXECUTIVE SUMMARY

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Founding CEO In Inventor Chair ir Scie ientific Advis isory ry Board

ANT’ KEY TEAM

Charles B. Nemeroff, M.D., Ph.D., Dell Med, UT,

Austin(US), Mulva Clinic for the Neurosciences.

▪ President of the Anxiety and Depression Association of America (ADAA). ▪ Co-editor in chief (with Alan F. Schatzberg, M.D.)

• f the Textbook of Psychopharmacology

▪ Co-editor in chief of Personalized Medicine in Psychiatry.

Erik Buntinx, M.D.,

Founding CEO Medical Center Anima & Anima Research Center, Alken (BE)

▪ Experienced Chief Executive Officer with a demonstrated history of working in the pharmaceuticals industry. ▪ Inventor of multiple worldwide granted patents in the field of neurosciences ▪ Veteran Principle Investigator in key CNS programs

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CURRENT ALZHEIMERS’ OUTLOOK:

IN PRECLINCAL STAGE OF AD ANY KNOWN POC STUDY ADRESSING COGNITIVE ENHANCEMENT

ANT01 in the Prevention of Alzheimer

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UNIQUE DIFFRERENTIATING POSITION FROM COMPETITORS IN AD:

AN ESTABLISCHED PHASE II, SYSTEM-REDUCING SMALL MOLECULE IN PRECLINICAL STAGE OF AD

ANT01 in the Prevention of Alzheimer

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))*

*Liew et al. Alzheimer’s Research & Therapy (2019) 11: 170 & Simona et al, Journal of Alzheimer’s Disease 66 (2018) 483-495

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

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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

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)

Relative gamma power (abs. values) MMSE (Total Score)

0.0 0.5 1.0 1.5 5 10 15 20 25 30

Alzheimer Patient

MMSE Total Score

3 months 3 weeks

pre-AD Stage

AD Stage

pre-Rx post-Rx

rel gamma (abs. values)

Relative gamma power (abs. values) MMSE (Total Score)

0.0 0.5 1.0 1.5 5 10 15 20 25 30

pre-Rx

At Risk Patient 1

>6 months

post-Rx

3 weeks

rel gamma (abs. values) MMSE Total Score

Relative gamma power (abs. values) MMSE (Total Score)

0.0 0.5 1.0 1.5 5 10 15 20 25 30

At Risk Patient 2

>6 months 3 weeks

pre-Rx

post-Rx

rel gamma (abs. values) MMSE Total Score

ANT01 induces – in contrast with AD patients – Sustained Enhanced Cognitive Performance over 6 months in defined AD at risk patients

accompagnied by enhanced REM Sleep Associated Frontal Gamma Frequency

ANT01 in the Prevention of Alzheimer:

A Potential +10 B Drug

*Alzheimer’s Association (2018) Alzheimer’s Disease Facts and Figures. Alzheimers Dement 14: 367

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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