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ONCOLIPIDOMICSFOR EARLY DETECTION
OF CANCER
COMMERCIALIZATIONCONTACT
Karolina Kasparova,[email protected]
INVENTORS
Prof. Michal Holčapek
Dr. Robert Jirásko
Dr. Denise Wolrab
Dr. Eva Cífková
Epidemiology and medical need
2
Numbers of newly diagnosed patients in 2018 (selected diagnosis):
• prostate cancer 1,276,106• pancreatic cancer 458,918• kidney cancer 403,262• breast cancer 2,088,849
The increasing incidence also noted for preventable cancers.
The numbers of early diagnosed cases are still insufficient.
Comprehensive high-throughput blood test is NOT available.
Sources:GLOBOCAN 2018, doi: 10.3322/caac.21492Cancer Incidence and Mortality in the Czech Republic, Klin Onkol 2014; 27(6): 406-423. doi: 10.14735/amko2014406
OncoLipidomics / Intended use
3
• MS lipidomic profiling of human serum or plasma
• high-throughput screening for multiple cancers
• accurate supporting information to the clinicians
• improved overall prognosis of patients
OncoLipidomics test
4
The set of reagents
The protocol
The optimal MS setting for clinical use
will be performed as a multiple cancer screening test operated bythe accredited clinical lab.
The OncoLipidomics package consists of the following:
The confirmatory examination by the oncologist in case ofsample positivity using traditional techniques, inappropriate forhigh throughput screening.
Clinical Results: Retrospective & Multiple cancers
5
Discovery retrospective studies performed on a limited sample sets:
STUDY SAMPLES SAMPLEPancreatic cancer 372* serumKidney cancer 112** plasmaBreast cancer 103** plasmaProstate cancer 67** plasma
98 98
90
74
100
87 87
96 96100 100
91
100 10094 95
82
9299 99
9094
100
90 91 92 94
0
25
50
75
100
M F M F M F M M F
Pancreas Kidney Breast Prostate Pancreas
%
* 213 pancreatic cancer, 7 pancreatitis, 79 controls, 72 blinded;pancreatitis samples correctly determined as healthy;
** 112+103+67 multi-cancer samples, 180 healthy controls
SensitivitySpecificity
AccuracyKnown classifications Blinded
Clinical Results: Retrospective PDAC
6
Fig. 1 Prediction of blinded samples
Fig. 2 Receiver operating characteristic (ROC) and area under thecurve (AUC) values for blinded samples, a) UHPSFC/MS andb) Shotgun MS.
-15-10-50510
-5 -4 -3 -2 -1 0 1 2 3 41.01472 * tPS[1]
R2X[1] = 0.0477 R2X[XSide Comp. 1] = 0.406
HealthyT1T2T3T4Tx
Blinded
0.50 >0.751.06
75 *
toPS
[1]
AUC = 96.8%
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
ROC for males predictions
1- Specificity
Sens
itivi
ty
AUC = 99.6%
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
ROC for females predictions
1- Specificity
Sens
itivi
ty
AUC = 96.3%
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
ROC for males predictions
1- Specificity
Sens
itivi
ty
AUC = 93.1%
0.0 0.2 0.4 0.6 0.8 1.0
0.0
0.2
0.4
0.6
0.8
1.0
ROC for females predictions
1- Specificity
Sens
itivi
ty
<0.25
OPLS-DA prediction model for UHPSFC/MS measurements ofmale samples of all tumor stages. Predicted response valuesshow the probability of PDAC: >0.75 very likely PDAC, >0.5PDAC, ≤0.5 healthy, and <0.25 very likely healthy.
a)
b)
Development plans
7
The pilot clinical lab needs to be established to verify and optimize the OncoLipidomicspackage.Equipped with the optimal MS instrumentation, device for automated sample handling and operated by qualified personnel.
Prospective multi-site study to verify the clinical relevance on a larger sample set.approx. 2500 samples will be collected at the different sites including the healthy controls and newly diagnosed cancer patients(pancreatic, kidney, prostate and breast cancer ) of all stages.Clinical data required will be gender, age, body-mass-index, diabetes, inflammatory diseases, and further diagnosis influencing thelipid metabolism.
DISCOVERY
Define
VERIFICATION
Verify andoptimize
VALIDATION
Confirm in real clinicalsetting
✓
Project network
8
Project principal investigator:
prof. Michal Holčapek
Team:
Clinical collaborators:
Advisors:
Mass Spectrometry Group of prof. Michal Holčapek, http://holcapek.upce.cz/
University Hospital Olomouc, Department of Oncology Masaryk Memorial Cancer Institute (MMCI), Brno University Hospital Hradec Králové (Institute of Clinical Biochemistry
and Diagnostics, Department of Oncology and Radiology) University Hospital Prague, Institute of Endocrinology and Metabolism University Hospital Prague, Institute of Inherited Metabolic Diseases:
the nationwide newborn screening program using mass spectrometry
Lipidomics Standards Initiative i&i Prague – biotech hub in the Czech Republic
IP status
9
European Patent Application No. 18152687.2, filed 22. 1. 2018
European Patent Application No. 18174963.1, filed 29. 5. 2018
International application No. PCT/EP2018/082811, filed 28. 11. 2018
„OncoLipidomics“ EUTM No. 018006287, filed 5. 1. 2019
Challenges
the enrollment of the larger number of samples
the reduction of parameters (to approx. 20) while maintaining the testperformance
Competition analysis
10
IN PROTEOMICS & GENOMICS:
IMMray™ PanCan-d, Immunovia - proteomic-based screening; early detection ofpancreatic cancer.
GRAIL, a spin-off company of Illumina - the method based on the detection ofcirculating cell-free tumor DNA (cfDNA) in the blood.
CancerSEEK 10.1126/science.aar3247 - circulating proteins and mutations incell-free DNA, very low accuracy for early stages
IN LIPIDOMICS:
Zora Biosciences Oy - the product in an early stage of development, referred to as a Lipidomic Marker Testfor pancreatic cancer, lung cancer, and prostate cancer, the only source of information - GlobaData
The PanaSee, MED-LIFE DISCOVERIES LP, Canada - only risk assessment and monitoring; it is not astandalone diagnostic test.
Resources needed – 3 year estimate in EUR
11
Instrumentation300k€
Qualified personnel150k€
Consumables70k€
Study design and monitoring40k€
IP protection20k€
2019 2020 20212014 – 2018
MILESTONE 1
Pilot labStudy design
Sample collection
MILESTONE 1
Pilot labStudy design
Sample collection
DISCOVERYSTUDIES
Cell lines, tissues,mice models,retrospective
studies, EPs, PCTfiled
DISCOVERYSTUDIES
Cell lines, tissues,mice models,retrospective
studies, EPs, PCTfiled
MILESTONE 2
Study monitoringSample analysis
Sample collection
MILESTONE 2
Study monitoringSample analysis
Sample collection
MILESTONE 3
Study resultsData interpretation
Clinical performanceevaluation
MILESTONE 3
Study resultsData interpretation
Clinical performanceevaluation
OncoLipidomics packagefor licensing