ONCOLIPIDOMICSFOR EARLY DETECTION

OF CANCER

COMMERCIALIZATIONCONTACT

Karolina Kasparova,karolina.kasparova@upce.cz

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

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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

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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

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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

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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

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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

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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