GENOMICS

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Precision Medicine Prevention, Diagnosis and Treatment

DNA: We are all different !

Although we share a large amount of our DNA, we all have differences in our genomes

On average, a person's genome sequence is ~99.6% identical to a reference human genome sequence; that person's set of genomic variants accounts for the ~0.4% difference

Our DNA Could Change the Future of Health

Precision medicine focuses on identifying optimal care based on a unique personal profile and constitutes a world class shift in HealthCare

Industry evolution

Genetic Testing Market

Booming market
Health &Wellness-
- Predisposition/Risk/Tendency is the fastest growing segment

The company

1. Structure
2. iDNA Laboratories: Medical company, Licensed Diagnostic Laboratory
3. iDNA Genomics: Commercial company
1. Fully integrated company, from concept to product
2. Unique certified in vitro Diagnostics (IVD) DNA tests available
3. New DNA tests development expertise
1. Advanced Science
2. Combined Genetic & Epigenetics concepts
3. Own algorithms
4. Bioinformatics platform
1. Regulatory clearance
2. CE IVD Status
3. IS0 9001:2015, ISO 13485:2016, ISO 27001:2013
1. Competitive Pricing
1. Team
2. Successful track record & expertise, int'l know how
3. Opinion leaders on board

Industry challenges & our solutions

We meet the needs

* Phenotype is defined as any observable trait such as blood pressure, body weight etc., that can be affected by lifestyle

Our Products

Medical Genomics

1. Pharmacogenetics - iDNA PGx CNS DEPRESSION

2. Genetic Predisposition - iDNA Cardio Health CARDIOVASCULAR DISEASES

3. Personalized Nutrigenetic Analysis - iDNA NutriGenetix OBESITY

• 322 million people suffer from Depression

• 523 million suffer from CVD

• 650 million people are obese

Our Products

Scientific Wellness Genomics

3 in 1 holistic genetic report on :

Nutrition
Vitamins & minerals
Exercise

47% of people are overwhelmed by conflicting advice on health & wellness.

What is our process

From saliva DNA to personalized Health report

What is our process

From saliva DNA to personalized Health report

[Header] GSGT Version Num SNPs / Total SNPs		2.0.4 730059 730059	Processing Date 9/7/2023 7:27 AM		Content GSAMD-24V3- & EA_20034606_A2.bpm
Num Samples
Total Samples		92
	File
[Data]
Sample ID												RsID Score Cluster Sep SIP IIN Strand Top Genomic Sequence Plus/Ninus Strand
												Top Allele2 - Top Allele1 - Plus Allele1 - Forward Allele2 - Forward		Allele1 - Design			Allele2 - Design
	Theta		X			X Raw Y Raw B Allele Freq Log R Ratio					CNV Value		CNV Confidence
	WL008951				0.8339 1:103380393		1	구	ML008951			0		102914837			0.8123 0.9535 T/C		BOT
	TOP			ഫ്രാമ്മ		G	G	G	G		G	ﮟ	ﮟ		0.974 00.816 0.032 00.783			327	1978
	1.0000	0.0721
WL008951		rs577315876			0.8355 1:106737318		2	ਜ	WL008951			0	ਜ	106194696		0.8133	0.5527 A/C A/C		TOP
	BOT			A		ব	C	T	G T		G	A	C		0.416 0.491	0.278	0.213	1540	563
	0.5330	-0.0192
WL008951		rs755970517			0.4783 1:109439680		ന	1	WL008951			0	1	108897058		0.8776	1.0000	[A/G]	TOP
	TOP =		+		A A A A A		র্ব	(	A A		ব	A	র্ব	0.042 0 0.690		0.647	0.042	3160	142
		0.0037 -0.1924
					WL008951		ব	1	WL008951			0	ਜ	109685814		0.5536	0.3024 [A/G]		TOP
	BOT			ഫ്ര		ତ	G	C	C		C	G	G	0.815 0.277		0.064	0.213	494	୧୫୫
	1.0000 0.1866
	WL008951				0.2214 1:110228505 CNV GSTM1		ഗ	1	WL008951			0	ਜ	109685883		0.5798	0.2299	A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/C A/ C/ A/ C/ A/ C/	TOP
	TOP		+	A	ഫ്ര	র	C	র্ব	C A		C	A	C		0.622 0.092	0.037	0.055	337 -	206
		0.6634 -1.0783
					WL008951		6	1	ML008951			0	1	109685993		0.8614 0.9994		T/C	BOT
	BOT		+	A	ব	A A	ব	T	T		T	T	T	0.073 00.426		0.382	0.044	2180	195
		0.0260 -0.7740
WL008951						rs1419817467 0.3448 1:110228695 CNV GSTM1		7 - 1		WL008951			0		109686073		0.7621 0.5021
		T /C \ CONT = " = " = " = " = " = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =											C	C	Carola 701
Ln 1, Col 1		126,348,820 characters												100%

Προϊοντικός Σχεδιασμός

Ένα μοναδικό οικοσύστημα

Η ιδιόκτητη πλατφόρμα τεχνητής νοημοσύνης, χρησιμεύει ως βάση για το σχεδιασμό του προϊοντικού χαρτοφυλακίου μας και των παρεχόμενων υπηρεσιών.

Αποτελεί το unique selling proposition (USP) μας και βασίζεται σε στατιστική ανάλυση καθώς και σε artificial intelligence (AI), για τον υπολογισμό δεικτών που σχετίζονται με τη γενετική προδιάθεση ενός ατόμου.

Deal	Data quantity	Genomic data type	Price per unit (PPU)	Details
DECODE to Amgen for \$415M (2012)	300,000	Genotype	\$1,383	Company acquisition including genotyped data + medical records.
23andMe to Genentech for \$60M (2015)	3000	Whole genome sequence	\$20,000	Partnership including whole genome sequence data + self reported info from Parkinson's disease patients + ability to recontact.
FinnGen to group of pharmaceutical companies for \$75M (2017)	500,000	Genotype	\$150	7 international pharmaceutical companies funding a study to analyse 500,000 Finnish biobank blood samples. Genotype data + medical records + ability to re- contact.
UK Biobank to Regeneron group of 500,000 pharmaceutical companies (2018)		Exome	\$300	Regeneron group of pharmaceutical companies funding a study to sequence the exomes of 500,000 UK Biobank participants. Exome data + medical information + exclusive access period.
23andMe to GSK for \$300M (2018)	4,000,000	Genotype	\$75	Ownership stake in 23andMe with 4 year exclusive access to genotype + survey data.
Genomic Medicine Ireland to WuXi NextCODE for \$400M (2018)	400,000	Whole genome sequence	\$1000	Company acquisition including whole genome sequence data + medical records + ability to re- contact.
UK Biobank to group of pharmaceutical companies for \$200M (2019)	500 000	Whole genome sequence	\$400	4 international pharmaceutical companies funding a study to sequence the whole genomes of 500,000 UK Biobank participants. Whole genome sequence data + medical information + exclusive access period.

Pharmacogenetics of Central Nervous System Drugs

The problem

1/3 of patients with depression don't respond to selected drug treatment

Depression is no 1 cause of Suicide
322 million people suffer from Depression
35% of them don't respond even to the 2nd drug treatment
Doctors until today select an antidepressant by "Trial and Error "
Besides the social burden, there is a huge economic one for the Health Systems

The problem in Europe

7ΝA PGx CNS is an in vitro diagnostic (IVD) medical device bearing the CE mark

Through a simple saliva genetic test, the physician gets the genetic information needed to select the most appropriate medication for each patient:

Faster remission of symptoms
Less side effects
Increased compliance
Higher efficacy

Strong competitive advantage

The only in Europe with CE mark in vitro diagnostic medical device
Under reimbursement in Greece
3000 patients already
Pharmacogenetic analysis for 30 drugs

Gene-drug interactions

I rorgain actuality Πληροφορίες δείχματας Hungagayia monskinyaroo Husaounvia Filmana Къобской бабуратов - Baronde

Αποτελέσματα Φαρμακογονιδιωματικής Ανάλυσης Αντικαταθλιπτικά Φάρμακα

Ελάχιστη αλληλεπιδραση γονιδίου-φαρμάκου	Μέτρια αλληλεπιδραση γονιδίου-φαρμάκου		Σημαντική αλληλεπίδραση γονιδίου-φαρμακου
citalopram escitalopram	duloxetine fluoxetine fluvoxamine mirtazapine paroxetine sertraline venlafaxine vortioxetine	6.8 1,8 1,2 1,2,6,8 6.8 1,2,6 1,2,6,8 2	amitriptyline clomipramine	4,9 4,9

Κλινικές Συμβουλές

Ξεκινήστε τη θεραπεία με τη συνιστώμενη στο Φάλλο Οδηγιών Χρήσης αρχική δοσολογία και αναπροσορμόστε. 2. Εξετάστε μείωση της δοσολογίας και σταθμίστε τις ανεπιθύμητες ενέργειας.
Εξετάστε μείωση της δοσολογίας συντήρησης κατά 25%.
Εξετάστε μείωση της δοσολογίας κατά 50%, ή εναλλακτική θεραπεία.
Εξετάστε αλξηση της δοσολογίας και σταθμίστε τις ανεπιθύμητες ενέργειας, ή επιλέξτε εναλλακτική θεραπεία.
Αυξημένη πιθανότητα ανεπιθύμητων ενεργαών, ή μειωμένης αποτελεσματικότητας.
Αυξημένη πιθανότητα αύξησης βάρους.
Συμβουλευτείτε την ερμηνευτική ανάλυση και προσαρμόστε τη δοσολογία.
Αποφύγετε τη χρήση αυτής της κατηγορίας φαρμάκων. Εξετάστε εναλλακτικό φάρμακο.

Clinical Application

Before: One-dose-fits-all approach After: Personalised medicine (from genotype to phenotype)

100 mg

200 mg

100 mg

25 mg

The evidence

Key findings in >3000 Greek patients

Patient satisfaction (Gkouvas et al. 2022 and Ntoumou et al. 2022):
- o 96% of patients responded to their personalized treatment.
- o 83% reported no serious side-effects.
- o 90% reported a change in medication, including dosage adjustments or selection of alternative medication by their doctor.
- o 87% reported fewer visits and communications with their doctor.
Cost-effectiveness (Chatziandreou & Panagiotou 2022):
- o PGx-guided therapy was associated with 0.712 Quality-Adjusted Life Years (QALYs), while Treatment as Usual (TAU) was
- o associated with 0.651 QALYs.
- o PGx was found to be highly cost-effective with an Incremental Cost-Effectiveness Ratio (ICER) of 55 €/QALY.
- o Over a 5-year period, suicides to be reduced by approximately 25%.
Gene-drug interactions (Panagiotou et al. 2023 and Bothos et a.l 2021):
- o PGx guidance towards dosage adjustment benefits 38% and 60% of patients with altered CYP2D6 and CYP2C19 metabolism respectively, as well as 52% of patients with a reduced response phenotype related to FKBP5.
- o PGx guided therapy benefits over 70% of patients, where a moderate or significant gene-drug interaction was discovered.
Product Status
- o CE IVD
- o Under Reimbursement in MDD in Greece

The scientific publications

Depression

Figure 1: Comparison of standard of care and pharmacogenetic (PGx) guidance treatmen

A cost-effectiveness analysis was then conducted to compare the IDNA PGx CNS-guide

treatment to TAU (i.e., standard of care) for cases of Treatment Resistant Depression in the

Analysis (PSA), incorporating potential treatment options and probabilities of their clinic

outcomes, medication costs, healthcare costs, and QALYs, the iDNA PGx CNS-guidend care wa

found to be clinically superior to TAU. Specifically, the dispersion of the Incremental Cost

Eright and lower right quadrants of the scatterpist, Indicating that the ma, mity of the
sinulations were sight of the scentryist, Indicating that the mey f

0.02 0.04 0.06 0.08 0.10 0.12

Incremental QALYs

ysis of IDNA PGx CNS-guid

reatment Resistant Depression in the Greek healthcare system. A. Thee diagram of potential treatment options and probabilities of their cilnical outcomes. B. Scatter plot of ICER.

s available to patients suffering from depression

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GREECE

SHI Jan Stone

V Personalized drue sele

V Tailored dose adjustment

iDNA PGx CNS: Pharmacogenetics-Empowered Precision Medicine Improves

Same treatment

· Standard dose

Treatment Outcomes in Major Depressive Disorder Nikolaos Panagiotou', Eleni Ntoumou', Alexis Sagonas', Effie Salata', Athanasios Fotis', Dimitris Roukas', Evi Chatziandreou

HDNA Genomics, Kifisia, Greece | 2417 Veterans Army Hospital NIMTS, Department of Psychiatry, Athens, Greece

Introduction

Background: Major Dearess ben Pfinonder (840)Db is = ne Background. Major Depressive Andress March (More Starts Childr. Throost Constrialse Marini Grammans
Do reamtial burden a Endresses and Series Childer, Marcos Check Checked C senefits of a PCx-guided approach, when compared to Treatment as Usual (TAU) (Figure 1 Airs: The purpose of this study was to define the extent to which patient genotypes co Alfer na partosan drag mestation approal in encars a contributes a contribut course course course course course course course
consector apara poscupion approv

Methods

The IDNA PGx CNS kIt was used to collect buccal swab samples from 1,387 patients. DNA wa Isolated and genotyped with Real-Time PCR, using OpenArray technology. The genotyping data underwent bloinformatics analysis to assign the associated phenotypes, along with gender and age. For the cost-effectiveness analysis, a tree diagram of all possible treatmy otions, where each path lieads to a dinical outcome and indicators such as Quality-Adjuste Life-Years (QALYs), was developed. The respective probabilities of occurrence, direct costs ( nospitalization, doctor visits, pharmacotherapy, and side effects, as well as patients' quality of ife were derived from the literature and according to a panel of psychiatry experts.

Rocults

Data were analyzed to study the distribution of CYP450 metabolizer status and FKBPS associated response efficacy in the population. Approximately 38% and 60% of patients had
altered CYP2C19 and CYP2C19 metabolism respectively, while approximately 52% of pati or related to their FKBP5 genotype (Figure 21

female and male patients. B. Percentage of age groups. C. Percentage of each CYP2D metabolizer genotype. D. Percentage of each CYP2C19 metabolizer genotype. E. Percentage of each FKBPS genotype.

The beneficial effects of IDNA PGx CNS-guided care in patients with MDD could -- because i

e scope and scale of the condition and its effects - have important ramifications for
tients and the healthcare system. Overall, this study highlights a paradigm shift in dopedia walliamin ministrative iders about the broader integration of pharmacogen
tely benefiting both patients and healthcare systems.

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գ առաջանում ուն ուսումներ
Բնակչության վրա նրա նրա նրա աստերոիդների մասնական կազմում էր 2000 թվականում էր 2000 թվականներ։
Ծանոթագրություններ Արտաքին դիմին մինչև 100 մարդ/կ

ISPOR Europe 2022 6-9 NOVEMBER 2022 | VIENNA | AUSTRIA

the International Society for Pharmacoeconomics and Outcomes Research

Prevention

Genetic Predisposition to Cardiovascular Diseases – Polygenic Risk Score (PRS)

The problem

No early detection of the risk

Source: 2023 World Heart Report, World Heart Federation

The problem

Risk underestimation

Source: American Heart Association

https://www.heart.org/en/healthy-living/healthy-lifestyle/lifes-essential-8

Polygenic Risk Score (Lots of genes)

Stroke : What is your Genetic Predisposition?

PRS: 82% relative to the population

The report provides PRS and PRS adjusted for 6 cardiovascular diseases. Next to PRS, PRS adjusted reflects the lifestyle impact on disease occurrence

Coronary Artery Disease
1. Cardiomyopathy Dilated
1. Cardiomyopathy Hypertrophic
1. Heart Failure
1. Arrhythmia Atrial fibrillation
1. Ischemic stroke

Phenotype + Polygenic Risk Score (PRS) = PRS adjusted

DELAY/AVOID Cardio disease

• The only in vitro diagnostic (IVD) medical device with CE mark

• The only one that combines the phenotypic with the genetic profile and comes up with the Adjusted PRS

5. Ισχαιμικό εγκεφαλικό επεισόδιο

Η βαθμολογία PRS είναι 93% επί του πληθυσμού. Αυτό σημαίνει ότι σε κάθε 100 άτομα, το εκτιμώμενο δικό σου PRS είναι υψηλότερο από 93 άτομα και ίδιο ή χαμηλότερο από τα υπόλοιπα 7 άτομα. Επομένως, το γενετικό σου υπόβαθρο σε θέτει σε αυξημένο ρίσκο εμφάνισης της πάθησης.

Β. Προσαρμοσμένη Βαθμολογία πολυγονιδιακού ρίσκου (Adjusted PRS): 31%

Για τον υπολογισμό του Προσαρμοσμένου PRS (Adjusted PRS), συνεκτιμάται:

Βαθμολογία PRS: 93% 1.
2.

Το Προσαρμοσμένο PRS (Adjusted PRS) εκτιμάται ότι είναι 31%, δηλαδή μειωμένο σε σχέση με την Βαθμολογία PRS και Βρίσκεται σε τυπικά επίπεδα ρίσκου σε σχέση με το γενικό πληθυσμό. Η τήρηση υγιεινών συνηθειών και η συμμόρφωση με τις οδηγίες του γιατρού σου, μπορεί να συμβάλουν στη Βέλτιστη καρδιαγγειακή υγεία και στην πρόληψη καρδιαγγειακών παθήσεων.

Ένα επεισόδιο συμβαίνει όταν διακόπτεται ή μειώνεται η παροχή αίματος σε μέρος του εγκεφάλου, εμποδίζοντας με αυτό τον τρόπο τον εγκεφαλικό ιστό να πάρει οξυγόνο και θρεπτικά. Αποτελεί μια επείχουσα ιατρική κατάσταση της οποίας έγκαιρη αντιμετώπιση είναι ζωτικής σημασίας.

(Πηγή: https://www.mayoclinic.org/diseases-conditions/stroke/symptoms-causes/syc-20350113)

Our scientific publications

Adjusted Polygenic Risk Score Enables Personalized Cardiovascular Disease Prevention and Clinical Manager Nikolaos Panagiotoul, Fragkiskos Bersimis?, Thanos Fotis, Eleni Ntoumou, Effie Salata', Evi Chatziandreou1

JDNA Genomics, Kiflsia, Greece

sugar / Hucose

We developed a nouel PBS to estimate, com

condions, comprising connery circe., citemic, circle, circlio.net, hypertrophic
cardiomypethy, trial finilation, ischemic, thank, family, spening may
design

rolined GWAS, il oetect the appropries SNPs by assessing Produe, beta combines with
rebio, and linksge disebuter

In=447). Finally, we employed the American Heart Association's Life's Simple 7 (LS7) lifestyle

(1-sphenotypic characterial seving system to season individual startic name and only messio
status. Using LS7 categorization were capable so genede and orguned PRS th

Our PRS stratification data suggest that we can identify a percentage of the population the

is at high risk and could thus benefit from lifestyle changes and a preventive mecicine
approach [3]. Nevertheless, to further improve risk prediction with the use of PPS, we

we employed the Lite's Smole 7 (LS7) [Figure 3] questionnaire and scoring austem to

Figure 3: American Heart Associations (Aralie 7 (LS). Using the best available
evidence, the AHA developed the LS7, vich comprises the seven most important president health,

includes four modifiable behaviors (not smoking, healthy weight, eating healthy and being

physically active) and three biometric measures (blood pressure, total cholesterol and blood

Employing the LS7 methodology, individuals can also be categorized in three distinct
categories of cardiovascular health status: i] poor, ii) intermediate, and iii) ideal. He

following LS7 dasafication. PRS data can be dynamically adjusted, also dependine on chronological age, to depict a combined score of genetic iftestyle, and phone on
paraneters. Theretore, combined score of genetic iftestyle, and phone

ปี

Figure 4: Example of adjusted PRS estimation by combination of a high risk PRS (97%) with

an intermediate status of current cardiovascular health assessed following LS7

categorization criteria, for a 50-year-old individual.

produce a PRS that combines lifestyle and ghenotypic parameters [4], termed adjusted PRS

hensive risk for six common cardiovascular

rsity of Pineus, Department of Statistics and Insurance Science, Green

g the risk of cardiovascular disease is central to early detection, prevention, and chincel desister, litestyle, health parameters and temily history. Routine genetic testing common adult-onset disease risk. Novel genetic profiling methods have been developed to extinate the productions sist Score (PRS). That is a weighted sum of the number of the number of the number of the number of the number of the number of their measured effects as detected by Genome Wide Association Studies (GWAS). The aim of this study was to develop a PRS and an adjusted PRS, which estimates a combined risk by scopy was to Gevelop of Pro- and phenotypic characteristics, a combined Tractor
incorporating lifestyle and phenotypic characteristics, for use in medical practice

Results

Ve developed and employed a PRS methodology, termed IDNA Cardio Health, that allowed us to estimate and strativ genetic risk for a series of cardiovascular diseases, following
genotyping of DNA that was isolated from buccal swab samples. Based on publicand d | intermediate risk (PRS 20-80%), and iii) high risk (PRS > 80%) (Figure 1)

Figure 1: Example of Polygenic Risk Score (PRS) distribution in a population and high-rial ategorization (PRS > 80%) for coronary artery disease.

The PRS data that were calculated for a Greek population (n=447), were further analyaed,
and risk stratification was specifically examined for a senes of cardiovascular disea ding coronary artery disease, dilated cardiomyopathy, hypertrophic cardiomyopath atrial fibrillation, ischemic stroke, and heart failure (Figure 2).

Figure 2: Percentage of any population (n=47) Classified per Polygenic Rick Score (PRS)
category Low risk («20%), intermediate risk (20-80%), high nisches) ischenic troke, and heart failure

Preceinton as interline a mere isses casintersing e enter est merces anderente micere in micenty igniti histicale mi include in the include in the include in Firally or novel squate PS methoding, that its care encompares genetic risk, an iten to combined mith inis presidion metics to revolutions cardonascure risk.
detection, mon

References

I and clinical utility of polygenic rick scores. Nature Resident Genetice, 2018. 19(V); p. SM-500.
Iygenic scores for common diseases identify inchiduals with risk equivalent

ontinent program current bance. A circle connect con increar mant non taccades. Citados, 202. Aligno, 2007) L colors, 2007 Aligno, 2007 Aligno, 2002. Nijerja e 4041.
I Larin

Cost-Effectiveness Analysis of an Adjusted Polygenic Risk Score in

Cardiovascular Disease Prevention in Greece

Evi Chatziandreou¹, Nikolaos Panagiotis Rigopoulos², Isidoros Kougioumtzoglou³, Eleni Ntoumou³, Effie Salata³, Alexis Sagonas 3, Athanasios Fotis2, Foteini Maragkou2

DNA 4DNA Laboratories, Greece | ³Vianex S.A, Greece | ³Laboratory of Hygiene & Epidemiology, School of Public Health, University of West Attia | L A O R A T O R A T O R A T O R A