A presentation by Labros Digonis

1. A disruptor to Precision Medicine & Nutrition through
biomarkers’ discovery
Labros Digonis, Co-Founder & CEO
Dr. Konstantinos Theofilatos, Co-Founder and CTO

2. If severely ill, what are the chances he survives if his life
depends on drug under trial?
52%
of clinical trials fail due
to drug efficacy and
wrong targeting of
patients!
Source: IMS
6.7%
of hospitalized patients
have adverse drug
reaction (ADR) and
0.32% die
Source: FDA
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3. Drug development is a long, expensive process
Source: The Tribune
Average $2.9B and 8 years to get drug to market

4. The History of Waiting and its deadly track record
4
Drug Indicated disease Clinical Delay Result
Eloxatin Colorectal cancer 3 years 40,000 Americans died
waiting
Erbitux Colorectal and head and
neck cancer
2 years 179,000 people died
waiting
Revlimid MDS, Multiple Myeloma,
MCL
2.5 years 74,000 patients died
without getting drug
Tarceva Lung cancer, Pancreatic
cancer
3 years 633,000 patients died
waiting
Tykerb Breast cancer 3 years 28,000 women died
waiting
Velcade Multiple Myeloma 1 year 2,600 patients died
waiting

5. Drug efficacy results are negatively affected because
people respond to treatments differently
+
+
=
=
BiDil approved for use only in
patients of African descent
• Two medications combined.
Indicated for cardiovascular
disease, heart failure diabetes
• Only a subgroup of people
received a benefit during trials
Example:

6. Molecular biomarkers can be used to predict
responses to drugs or food
Molecular Biomarker
Something that can be measured which
points to the presence of a disease or
differentiation in response to a treatment
or drug
Specific to: different -omics technologies
Molecular Biomarker Example
A combination of overexpressed
genes, or mutations to diagnose
tumors

7. Molecular biomarkers can be used to predict
responses to drugs or food
Molecular Biomarker
Something that can be measured which
points to the presence of a disease or
differentiation in response to a treatment
or drug
Specific to: different -omics technologies
Benefits of Finding Biomarkers
• Minimizes the risks for failed trials
• Patient Stratification: Enables the optimal
selection of participants to clinical trials
• Interpretation of the cause of diseases
• Allows precision medicine: provide the
more suitable drug to each patient in a
personalized manner.
Molecular Biomarker Example
A combination of overexpressed
genes, or mutations to diagnose
tumors

8. Biomarker discovery is a fragmented Data-driven process
Biological
Experiments Data
Preprocessing &
Visualization
Meta-Analysis
Biomarker
extraction
Diagnostic &
Clinical Trials
Applications
• DNA & RNA sequences
• Microarrays
• NGS
• Mass Spectrometry.
• Proteins
• Biological networks
• Associated sequences,
mRNA, non-coding
RNA, SNPs)
• Holistic/Systemic
approach to Research
& Clinical deduction
• Integrated biomarkers
of high confidence
• Biological
interpretation with
affected pathways &
side-effects prediction.
• Diagnosis, prognosis
• Drug Response/Toxicity
prediction
• Disease progression
• Therapeutic response.
Biomarker ID takes time, money and expertise

9. Biomarker discovery is a fragmented Data-driven process
Biological
Experiments Data
Preprocessing &
Visualization
Meta-Analysis
Biomarker
extraction
Diagnostic &
Clinical Trials
Applications
• DNA & RNA sequences
• Microarrays
• NGS
• Mass Spectrometry.
• Proteins
• Biological networks
• Associated sequences,
mRNA, non-coding
RNA, SNPs)
• Holistic/Systemic
approach to Research
& Clinical deduction
• Integrated biomarkers
of high confidence
• Biological
interpretation with
affected pathways &
side-effects prediction.
• Diagnosis, prognosis
• Drug Response/Toxicity
prediction
• Disease progression
• Therapeutic response.
Existing platforms are performing only part of the analysis

10. Biomarker discovery is a fragmented Data-driven process
Biological
Experiments Data
Preprocessing &
Visualization
Meta-Analysis
Biomarker
extraction
Diagnostic &
Clinical Trials
Applications
• DNA & RNA sequences
• Microarrays
• NGS
• Mass Spectrometry.
• Proteins
• Biological networks
• Associated sequences,
mRNA, non-coding
RNA, SNPs)
• Holistic/Systemic
approach to Research
& Clinical deduction
• Integrated biomarkers
of high confidence
• Biological
interpretation with
affected pathways &
side-effects prediction.
• Diagnosis, prognosis
• Drug Response/Toxicity
prediction
• Disease progression
• Therapeutic response.
InSyBio is first to
integrate the
process and
extract prioritized
and relevant
biomarkers from
raw data
Public
databases &
knowledge
InSyBio Suite is a proprietary, cloud platform for big biological data analysis

11. Biomarkers
Disease
Interpretation
Cause of
Disease
Mechanism
Genetic Mutations
Diagnostic tests
Prognosis/Predispositions
Novel Therapies
Improved efficiency
Personalized Medicine
AI-
Machine
Learning
Biological Experiments
Clinical Trials Hospital EHR Research Institutes Pharma
Disrupting Clinical trials
and Drug discovery
process
A model approach to Precision Medicine
& Nutrition through biomarkers’
discovery at a glance

12. Accurate, targeted, and highly reproducible
biomarkers with small sample size requirements
10
Case Studies Method
Number of
biomarkers
Accuracy
Early Stage
Parkinson’s
Diagnosis
State-of-the-art Method 834 ~96%
InSyBio solution 5 100%
Ischemic Stroke
Diagnosis
State-of-the-art Method ~3000 <70%
InSyBio solution 4 88%
Glioblastoma
Diagnosis
State-of-the-art Method 24 90.01%
InSyBio solution 13 94.45%

13. …extracted Fast and at a Low-cost thru a single user
friendly platform decreasing thus the need for many
validation experiments and outsourced bioinformatics
analysis
~ 6 months
~ 1/6 of time
$100,000 - $millions
Time to
extract
biomarkers
Relative Cost
to extract
biomarkers
1/8 cost
Fast
Cost
Effective

14. Our innovation lies in 4 main areas
One, end-to-end, integrated
process for biomarker discovery
Data (Vertical) Integration from many
sources with
patent-protected network-based
approach
Technology to locate
30%
more common proteins in
proteomics data
Rifle Approach
Fewer, relevant and accurate
biomarkers

15. Our technology has already demonstrated ability to
accelerate pharma & nutrition R&D tasks
Nutrition
Diet Selection/Effects of nutrition
products in health and patients
Pharma: Clinical Trials
Discovery of candidate-biomarkers for
effective patient recruitment
R&D resources efficiency
Shorten time-to-market
Pharma: Pre-clinical Drug
Design
Faster and more reliable detection of
drug targets
Minimization of risk for side effects
Diagnostic Companies and Labs
Diagnostic, prognostic and therapeutic
biomarker discovery
Less candidate biomarkers, higher
predictive accuracy
More than 400 active
users with applications
in:
• Parkinson’s
• Alzheimer’s
• Major Depression
• Melanoma
• Cancer radiotherapy

16. The incorporation of InSyBio’s Technology in Clinical
Trials can save thousands!
• ~25,000 new clinical trials per year
• Average success rate is being
increased by 16% with the use of
predictive biomarkers
• 40% of those trials already try to use
predictive biomarkers
• InSyBio technology can allow the
use of predictive biomarkers in the
remaining 60% ending up with on
average ~2400 more successful
clinical trials and drugs to market
annually
15
Sources: Clarivate Analytics Cortellis, Feb 2017; Quintiles IMS Institute, April 2017,
BiomedTracker for Pharma Intelligence, Informa, Clinical Development Success Rates 2006-2015

17. The InSyBio team
Efficient & forward-looking with strong business and scientific background
Dr. Christos Alexakos
COO
Computer Engineer, MSc,
PhD in Computer Science
Labros Digonis
CEO
Entrepreneurial Manager,
Naval Architect & Marine Engineer, MBA
Dr. Konstantinos Theofilatos
CTO, Technical Sales Mgr.
Computer Engineer, MSc,
PhD in Bioinformatics
Christos Dimitrakopoulos
R&D Mgr.
Computer Engineer, MSc,
PhD Candidate in Computational Biology
Aigli Korfiati
Product Development Mgr.
Computer Engineer, MSc,
PhD Candidate
Dr. Seferina Mavroudi
CSO
Computer Engineer, MSc,
PhD in Bioinformatics
Prof. Georgios Georgiou
University of Texas
Prof. Nicholas Peppas
University of Texas,
Member of Chinese Academy
Prof. Konstantinos
Stathopoulos
University of Patras
Dr. Alexandros Georgakilas
National Technical University of
Athens
Co – Founders Team
Scientific Advisory
Committee
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18. Recent Publications and patents
• Theofilatos, K., Alexakos, C., Korfiati, A., Dimitrakopoulos, C. and Mavroudi, S., Theofilatos and Konstantinos, 2018. Generalized Computational
Framework And System For Integrative Prediction Of Biomarkers. U.S. Patent Application 15/837,407.
• Theofilatos, K., Dimitrakopoulos, C., Mavroudi, S., Korfiati, A. and Alexakos, C., InSyBio Ltd, 2017. Protein functional and sub-cellular
annotation in a proteome. U.S. Patent Application 15/361,461.
• J. Corthésy and K. Theofilatos, et al., An Adaptive Pipeline To Maximize Isobaric Tagging Data in Large-Scale MS-Based Proteomics,
Journal of Proteome Research 2018 17 (6), 2165-2173, DOI: 10.1021/acs.jproteome.8b00110
• A. Korfiati, K. Theofilatos, C. Alexakos and S. Mavroudi, InSyBio ncRNASeq: An efficient tool for analyzing non-coding RNAs, EMBnet.journal,
[S.l.], v. 23, p. e882, oct. 2017, DOI :https://doi.org/10.14806/ej.23.0.882.
• C. Dimitrakopoulos, K. Theofilatos, et al. (2016) InSyBio BioNets: A new tool for analyzing biological networks and its application to
biomarker discovery, EmbNet Journal, vol. 22, pp. e871, 2016, DOI: http://dx.doi.org/10.14806/ej.22.0.871.
• C. Dimitrakopoulos, K. Theofilatos, A. Pegkas, S. Likothanassis, S. Mavroudi, Predicting overlapping protein complexes from weighted
protein interaction graphs by gradually expanding dense neighborhoods, Artificial Intelligence in Medicine Journal, 2016, DOI:
http://dx.doi.org/10.1016/j.artmed.2016.05.006
• Nikitaki, Zacharenia, et al. "Systemic mechanisms and effects of ionizing radiation: A new ‘old’ paradigm of how the bystanders and
distant can become the players." Seminars in cancer biology. Academic Press, 2016, DOI: https://dx.doi.org/10.1016/j.semcancer.2016.02.002.
• K. Theofilatos, S. Likothanassis, S. Mavroudi (2015) Quo vadis* Computational Analysis of PPI data Or Why the Future isn’t Here
Yet, Frontiers in Genetics, vol. 6, pp. 289, DOI= https://dx.doi.org/10.3389/fgene.2015.00289
• Kleftogiannis, D., Theofilatos, K., Likothanassis, S., & Mavroudi, S. (2015). YamiPred: A novel evolutionary method for predicting pre-miRNAs
and selecting relevant features. IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB), 12(5), 1183-1192.
• Rapakoulia, T., Theofilatos, K., Kleftogiannis, D., Likothanasis, S., Tsakalidis, A., & Mavroudi, S. (2014). EnsembleGASVR: a novel ensemble
method for classifying missense single nucleotide polymorphisms. Bioinformatics, 30(16), 2324-2333.
• Theofilatos, K., Dimitrakopoulos, C., Likothanassis, S., Kleftogiannis, D., Moschopoulos, C., Alexakos, C., ... & Mavroudi, S. (2014). The Human
Interactome Knowledge Base (HINT-KB): an integrative human protein interaction database enriched with predicted protein–protein
interaction scores using a novel hybrid technique. Artificial Intelligence Review, 42(3), 427-443.
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19. Insybio Biomarkers
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20. Insybio Bionets
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21. Insybio Interact
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22. Find Us
url: http://www.insybio.com
demo: http://demo.insybio.com
evaluation: http://evaluation.insybio.com
Contact Us
info@insybio.com
Open Jobs
careers@insybio.com