September 14, 2016 - Biogazelle’s CEO dr Jan Hellemans presented Biogazelle’s strategy and expertise to deploy RNA in liquid biopsies to further diagnostic applications and drug development at the “Nordic Life Science days 2016” (Stockholm, Sweden).

1. © 2017 Biogazelle. All rights reserved. 1
Liquid biopsy RNA
biomarkers
Jan Hellemans, Biogazelle CEO
Nordic Life Science days
Stockholm, Norway, September 14, 2016

2. © 2017 Biogazelle. All rights reserved. 2
Biogazelle is a biotechnology company
deploying the power of RNA as source of
next generation diagnostics and therapeutics
with primary focus on oncology.

3. © 2017 Biogazelle. All rights reserved. 3
Low clinical development success rate
63%
30%
57%
85%
9%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
phase 1 > phase 2 phase 2 > phase 3 phase 3 > NDA/BLA NDA/BLA >
approval
phase I > approval
Source: Amplion

4. © 2017 Biogazelle. All rights reserved. 4
Biomarkers increase likelihood of approval
3x
63%
29%
55%
84%
8%
77%
47%
77%
95%
26%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
phase 1 > phase 2 phase 2 > phase 3 phase 3 > NDA/BLA NDA/BLA >
approval
phase I > approval
without biomarker with selection biomarker
Source: Amplion

5. © 2017 Biogazelle. All rights reserved. 5
In 2015, 28% of NNDs approved by FDA were
precision medicines
0
500
1000
1500
2000
2500
1985 1990 1995 2000 2005 2010 2015 2020 2025
Trialswithbiomarkers
measured
projected
Source: Amplion

6. © 2017 Biogazelle. All rights reserved. 6
RNA biomarkers in body fluids
• RNA reflects dynamic changes in patient
• health vs. disease
• disease subtyping
• predict or monitor therapy response
• untapped potential of 80,000 candidate biomarkers
• clinically relevant fluids contain more cell-free RNA than DNA, enabling
non-invasive testing
• combination of multiple genes into robust and powerful biomarker
signature based on expression levels, fusions & mutations
• accurate, low cost clinical-grade testing

7. © 2017 Biogazelle. All rights reserved. 7
The power of non-coding RNAs
Non-coding RNAs (miRNA & lncRNA)
• more numerous then coding genes
• are master regulators of gene expression, in health and disease
• tissue and disease specific expression patterns
• growing evidence for their potential as excellent biomarkers
• attractive intellectual property landscape (FTO)
mRNA
21000
miRNA
2500
lncRNA
63000
mRNA pond total RNA pond

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Deploying the transcriptome
Using different validated RNA sequencing workflows
100 ng total RNA or 200 µl biofluid
Workflows currently under development in the frame of Research Agreement with

9. © 2017 Biogazelle. All rights reserved. 9
Biogazelle’s RNA biomarker discovery program
7 steps in 3 phases
feasibility
study
discovery
data
generation
signature
establishment
technology
switch
signature
optimization
generation
validation
data
signature
validation
biomarker discovery biomarker validationqPCR test development
RNA seq @ NextSeq 500

10. © 2017 Biogazelle. All rights reserved. 10
qPCR test development
• Assay design
• proprietary primerXL design engine
• used to design >250,000 assays (coding genes of 13 species), brought to the market
by Bio-Rad as PrimePCR assays
• Analytical assay validation
• empirical RUO validation of >75,000 PrimePCR assays
• full analytical (LDT-IUO-IVD) validation for a smaller set of assays
• Analyze biomarker candidates on discovery cohort using qPCR
• Optimize biomarker model

11. © 2017 Biogazelle. All rights reserved. 11
Biomarker validation
• Validate biomarker model on an independent cohort
• Run the biomarker in a clinical trial
• Run the biomarker as a diagnostic test
• +15 years expertise in gene expression, +15,000 citations
• GCLP compliant & ISO17025 accredited

12. © 2017 Biogazelle. All rights reserved. 12
Biogazelle’s expertise in RNA biomarker
discovery and diagnostics
Indication D TR S
Biomarker
discovery
Biomarker
validation
Clinical assay
development
Clinical trial
Arthritis
Heart disease
Endometriosis
Heart disease
Breast cancer
Arthritis
Colon cancer
T-cell lymphoma
Prostate cancer
Colon cancer
Inflammatory bowel disease
Arthritis
Arthritis
Multiple sclerosis
* D (diagnosis), TR (therapy response), S (stratification)

13. © 2017 Biogazelle. All rights reserved. 13
Summary
• Biomarkers may help increase the success rate of drug development
• (non-coding) RNA is a great source of biomarkers
• Biogazelle can assist in all stages of biomarker development
or run your biomarkers in a clinical trial or as a diagnostic test
feasibility
study
discovery
data
generation
signature
establishment
technology
switch
signature
optimization
generation
validation
data
signature
validation
biomarker discovery biomarker validationqPCR test development

14. © 2017 Biogazelle. All rights reserved. 14
email: jan.hellemans@biogazelle.com
www.biogazelle.com