Elvira Berlingieri Email: berlingieri@projectipsilon.com Europe: +31 (0)6-1347-1876

1. Project Ipsilon B.V., 2023. All rights reserved.
Project Ipsilon B.V.
Novel cognitive screening and monitoring system

2. Routine pre-screening as
self-care
(digital marker)
Biomarkers for formal
evaluation
Intervention strategy
Extend the healthcare pathway with a focus on prevention
Enable at-home self-screening to help reduce GHG emissions 2
The mission
“Screen preclinical dementia with music-gamification
to help people actively prevent it without stigma, and
to support clinicians with quantified and repeatedly usable assessment solution
for timely intervention”
assessment assessment

3. Problem: Limits of cognitive tests: MoCA1
3
Administered only by clinicians Learning effects limit its use Paper and pencil-based
≤4 /year
Sensitive for moderate
dementia, not for early
detection
(1) MoCA: Montreal Cognitive Assessment test, one of the gold standard tests for dementia
(2) WHO, 2022
55Million people with Dementia2

4. Piano teachers and cognitive assessment
• Most experienced piano teachers are
very sensitive to student’s cognitive
abnormalities
• Piano teachers observe and profile how
the student learns and can project their
learning trajectory
4

5. Ipsilon System: early cognitive decline screening
5
Gamified for self-care
Repeatedly usable Securely cloud-based
Eye-hand coordination via music =
early dementia risk detection
WHAT HOW

6. Playing the Ipsilon game
Simplified music notes function as spatial
instructions.
Red indicates your right hand and the
corresponding field on the right, blue with left
hand and corresponding field on the left.
Collecting time-stamped finger
tapping response and its accuracy,
generates several parameters to
compile index scores and
assessment
Takes 3-5
minutes
6
It may include confidential information and prohibited to share beyond the addressed

7. Recommended uses according to user profiles
7
User over 55-years old
with no identified risks
User over 55-years old with
comorbidities and
neurodegenerative diseases
• Monthly use
• Cognitive baseline development
• Generate referential data between
checkups
• Weekly use
• Cognitive baseline development
• Abnormality detection for timely
intervention strategy
Diabetes, cardiovascular issues
Family history of neurological disorders

8. Ipsilon
Index
Assessment
IPS -3 to -1 Suspected mild cognitive impairment (MCI)
IPS 0 to 3
Subjective cognitive decline (SCD, earliest
cognitive decline phase)
IPS 4 to 5 Cognitively Healthy (HC)
Ipsilon Index: simple cognitive status index
• Comprehensive, simple cognitive status index system
• High correlation to MoCA
• Better sensitivity for precursors of dementia detection
• Phenotyping
• Diagnostic aid in workflow
• Accurate and reliable
• Early off mode tendency detection for Parkinson’s
8
Validated with (total N=48):

9. ROC analysis with Baycrest dataset (healthy cohort)
9
Validation with raw data (N=21 with full data logs, N=23 registered), to detect healthy subjects as positive, MCI as negative
TP=12 FN=4 16
FP = 1 TN = 4 5
13 8 21
Confusion matrix (N=21)
Sensitivity: 0.75
Precision: 0.92
Acuracy: 0.76
Specificity: 0.8
F1 score: 0.83
ROC analysis hypothesis:
TN when MoCA is equal to or below 86% and IPS is equal to or below 78%
FN when MoCA is equal to or above 86% and IPS is equal to or below 78%
TP when MoCA is equal to or above 86% and IPS is equal to or above 78%
FP when MoCA is equal to or below 86% and IPS is equal to or above 78%
N.B. MoCA MCI threshold is 26 points (87%) and IPS scores for cognitively healthy range are IPS 5 and IPS 4
with its lowest ratio is at 78%.

10. Phenotyping cohorts by data ranges
10
Healthy Cohort:
IPS: 4 to 5
Correlation Coefficient: -1
Accumulative accuracy: ≥80%
L9 reached in: 9≤15 attempts
Subjective Cognitive Decline:
IPS: 0 to 3
Correlation Coefficient: 1
Accumulative accuracy: 57%≤79%
L9 reached in: 15<30 attempts
Suspected Mild Cognitive Impairment:
IPS: -3 to 0
Correlation Coefficient: 1
Accumulative accuracy: ≤56%
L9: ≥30 attempts and/or not reached
IPS: Ipsilon index score L9: level 9 of Ipsilon System data collection app, highest level with random selections from all learnt patterns
[Subgroups – HC to SCD]
Super Cognitively Healthy: Age-relevant Healthy: Borderline Healthy-SCD:
IPS:5 IPS: 4 IPS: 2 to 3
Correlation Coefficient: -1 Correlation Coefficient: -1 Correlation Coefficient: -1 and/or 1
Accumulative accuracy: ≥90% Accumulative accuracy: 80%≤89% Accumulative accuracy: 70%≤79%
L9 reached in: 9≤11 attempts L9 reached in: 11≤13 attempts L9 reached in: 13≤15 attempts

11. Potential MCI* risk marker (SCD**)
• Correlation coefficient returns -1 when:
• Accumulative accuracy is around ≥80%
• Level 9*** is reached within 15 attempts
• Ipsilon Index Score of ≥4 (3 is borderline)
• Distinguishing cognitively healthy to detect
subjects with earliest cognitive decline for timely
MCI-preventing therapies
• Validated as proof-of-concept with small sample
size (N=48)
• Fits perfectly with reinforcement learning AI model
*MCI: mild cognitive impairment, a precursor phase of dementia
**Subjective Cognitive Decline (SCD): earliest phase of cognitive decline
*** Level 9 is the highest level in the Ipsilon System, randomly selected patterns from all levels are presented as instructions
11

12. Kobe Model & Health Captains Club healthy aging
chapter**(Kobe-Bonn, under establishment as of Apr 2023)
• Complement to cognitive assessment
• Wholistic cognitive-emotional approach
• Distinguish the causes for MCI
• Cognitive origin
• Emotional origin (depression)
• better relay to tests & therapies
12
Central points of
care
Routine
preclinical
dementia
screening
Blood
biomarkers
Digital
therapeutics
solutions
City of Kobe
Dementia
prevention
organizer
Pharmacological
intervention
New chapter on
dementia
prevention/
healthy aging
Kobe Model: WHO dementia
prevention model city*
Collective project goal:
Prevent and delay the dementia
onset by early detection relaying
to early intervention
All companies mentioned are in discussion for partnerships and to be confirmed.
*| WHO Centre for Health Development
** new chapter with dementia prevention through digital health under establishment
Global application

13. Planned R&D activities
13
*MCI: mild cognitive impairment, a precursor to dementia
**Brain Health Quotient: https://www.bhq.co.jp/, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187137
Multiple Sclerosis music
as tool for care
(N=331; 2H 2023;
approval pending)
Tamba cohort MCI*
screening phase 1
to compare to
cognitive/psychological
batteries and MRI/
fMRI imaging
(N=70-100; 1H, 2023)
MCI screening study
Phase 1
to compare to
cognitive/psychological
batteries and MRI/
fMRI imaging
(N=70-100; 1H, 2023)
Ipsilon as Brain Health Quotient’s
connectivity (FM-BHQ**)
prescreening tool
Ipsilon’s MCI study phase 2, integrated clinical
studies on MCI
• compare against blood biomarker
• Validate early detection – early intervention
dementia care pathway
• Relay to digital therapy and pharmacological
therapy if dementia risk identified
(N=250-500, 2H 2023~)
Multi-institutional study; Ipsilon as
prescreening tool for blood
biomarkers
Companies in discussion
In early discussion,
to be confirmed

14. 14
Regulatory Certifications: AI/ML-based SaMD*
(computerized cognitive assessment aid)
*AI/ML-SaMD: Artificial intelligence and machine learning-based software as medical device
2024
MCI:
prescreening
tool for
biomarkers
1H, 2023~
Dementia
predictive
AI model
development
2024-2025
Multiple
Sclerosis
Japanese market:
PMDA certification
not needed for
current version as
diagnostic aid,
Launch expected
in June, 2023
IP: SSI Trademark
Smart Systems Integrated® is a Collective
European Union Trademark, according to
Council Regulation (EC) no. 207/2009

15. Market and business model
https://www.grandviewresearch.com/industry-analysis/mhealth-market
Total Addressable
Market (TAM)
45.7 B USD (2020)
Serviceable
Available
Market (SAM)
6 B USD
Serviceable
Obtainable
Market (SOM)
107 M USD
mHealth market: 45.7B USD (2020)
CAGR (2021-2028): 17.6%
• Private users (B2C) and institutions for healthy ageing
(B2B2C): monthly subscription model
• Pharmaceutical industry (stratification/ prescreening tool for
biomarkers, routine cognitive assessment data generation):
subscription model
• Online clinic services, remotely conducted research, clinical
trial companies: IP licensing with third-party branding
• Research institutions: de-identified and anonymized decision-
making datasets
15

16. • Sales channel establishments
• A subsidiary set-up in Kobe, Japan
Investment needed in 2023
• AI algorithms validation and training
• Clinical validation
• Software updates for clinical version
• Risk & quality managements
• Compliance (HIPAA, GDPR, Japan-equivalent)
• openEHR compatibility, CE mark application
Compliance &
Regulatory
R&D
€850k ($930k USD as of Apr 2023)
for 1-year runway
R&D
290K EUR
Compliance,
Regulatory
267K EUR
OPEX
293K EUR
Sales
channels,
scale-up 16

17. MCI = mild cognitive impairment; ADRD = Alzheimer’s disease related dementia; MS = multiple sclerosis TBI = traumatic brain injury
Altoida game Ipsilon System Linus Health
How long does the assessment
take?
10 min 3 to 5 min 10-40min
Monitoring, assessment and
intervention in one solution?
Yes Yes No
How does it fit into care pathway? digital marker and assessment Cognitive index, pre-screening tool for
early Alzheimer’s blood marker test and
MCI caused by connectivity
deterioration (MRI FLAIR/ DTI)
Digital marker and assessment
Operable by non-specialist and as
self-care at home?
Yes Yes Yes
Regulatory approval? In process, received Breakthrough
Device Designation from FDA
Filings in preparation Yes - FDA
Can function as preventive
solution?
Yes Yes Yes
Focus diseases MCI, Alzheimer’s, ADRD MCI, Alzheimer’s, ADRD, Parkinson’s,
MS
MCI, Alzheimer’s, ADRD
Amount raised: 24.7M USD (Series A) 161K USD (140K EUR; accelerator, FFF,
grants)
64.9M USD (Series B)
17

18. 18
Team
Yayoi Sakaki, MMus: Founder/ Director, Product designer.
Pianist, invented Ipsilon System and Ipsilon index. Neurology
and data science enthusiast. Passionate to bring music’s
potential to social and clinical wellnesses.
Hagen Wenzek, PhD.: Co-founder. Strategist, CTO. Former
strategist at IBM, former CTO at IPG MediaBrands. Also CEO
of GI Digital. PhD in electrical engineering with focus on AI.
Sought-after technology advisor in NY.
Elvira Berlingieri, LLM, Avvocato, MBA:
Business development.
Practices law, specialized in IP and personal
data laws.
Kanako Mori, GZ-Psycholoog: Product quality
and UX manager. Clinical Psychologist, licensed
to practice in Japan and The Netherlands.
Clinical & AI consultants
Prof. Claude Alain, PhD: dementia, geriatric cognition
Prof. Hisatomo Kowa, PhD, MD: dementia, Alzheimer’s disease
Prof. Aliza Ben-Zacharia, PhD, DNP: multiple sclerosis
Prof. Charalampos Tzoulis, PhD, MD: Parkinson’s disease
Assistant Prof. Mingbo Cai, PhD: AI and predictive model
Partners
Armengaud Innovate: project management, grant consulting
ITML: ML and AI solutions
Chino.io: data security and compliance management
Glorium Technologies: software development
Universitäts Klinikum Bonn: clinical partner
Nordic Proof: testing sites and partnership references in the Nordics
Eric Armengaud, PhD, MBA: Strategic support. CEO of
Armengaud Innovate, wealth of business knowledge on
innovative technology with strong strategic planning skills.
Advisors
Gita Subramaniam, MD. Klaus Niederlander

19. Company
19
Incorporated in
Rotterdam,
The Netherlands in
June, 2017
Completed HighTechXL
Accelerator’s
Autumn 2017 batch.
InnoLabs EU SME
phase 1 grant
awardee
2018-2019 cycle
https://www.cv-magazine.com/winners/project-ipsilon-bv/
“Best medical assessment
aid and training software,”
Technology Innovator
Awards 2020
by Corporate Vision magazine.
Research grant for
MCI/early dementia
detection and remote use
of Ipsilon System at
Baycrest
(Toronto, 2021)
Joint research agreement
on clinical version of Ipsilon
System as prescreening
tool for Alzheimer’s blood
biomarkers
(Kobe, 2022)
Sakaki, Y. “Clinical application of music playing: quantification of learning to train and monitor the cognitive functionality – a journey of a pianist.”
Medizinisch Wissenschaftlische Verlagsgesellschaft 2019. XPOMET©: Innovation in Medicine and Care. Ulrich H. Pieper and Alois G. Steidel, Eds.
Torrado JC, Husebo BS, Allore HG, Erdal A, Fæø SE, Reithe H, et al. (2022) Digital phenotyping by wearable-driven artificial intelligence in older
adults and people with Parkinson’s disease: Protocol of the mixed method, cyclic ActiveAgeing study. PLoS ONE 17(10): e0275747.
https://doi.org/10.1371/journal.pone.0275747
Publications

20. Contact
Director: Yayoi Sakaki
Email: sakakiyayoi@projectipsilon.com
Europe: +31 (0)6-1347-1876
Japan: +81 (0)80-5103-5450
Marconistraat 16, 11e verdieping
3029 AK Rotterdam
The Netherlands
20
Contact in Japanese
Contact in English