liquid biopsy rna biomarkers
TRANSCRIPT
© 2017 Biogazelle. All rights reserved. 1
Liquid biopsy RNA biomarkersJan Hellemans, Biogazelle CEO
Nordic Life Science days
Stockholm, Norway, September 14, 2016
© 2017 Biogazelle. All rights reserved. 2
Biogazelle is a biotechnology companydeploying the power of RNA as source of
next generation diagnostics and therapeuticswith primary focus on oncology.
© 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
© 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
© 2017 Biogazelle. All rights reserved. 5
In 2015, 28% of NNDs approved by FDA were precision medicines
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1985 1990 1995 2000 2005 2010 2015 2020 2025
Tria
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biom
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measured
projected
Source: Amplion
© 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
© 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)mRNA21000
miRNA2500
lncRNA63000
mRNA pond total RNA pond
© 2017 Biogazelle. All rights reserved. 8
Deploying the transcriptomeUsing different validated RNA sequencing workflows
100 ng total RNA or 200 µl biofluid
Workflows currently under development in the frame of Research Agreement with
© 2017 Biogazelle. All rights reserved. 9
Biogazelle’s RNA biomarker discovery program
7 steps in 3 phases
feasibilitystudy
discoverydata
generation
signature establishment
technology switch
signature optimization
generation validation
data
signature validation
biomarker discovery biomarker validationqPCR test development
RNA seq @ NextSeq 500
© 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
© 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
© 2017 Biogazelle. All rights reserved. 12
Biogazelle’s expertise in RNA biomarker discovery and diagnostics Indication D TR S Biomarker
discoveryBiomarker 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)
© 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
feasibilitystudy
discoverydata
generation
signature establishment
technology switch
signature optimization
generation validation
data
signature validation
biomarker discovery biomarker validationqPCR test development
