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Diagnosis of early stages of pancreatic cancer
Laura Chirica, PhDImmunovia, Lund, Sweden
Oslo Life Science 15-17 February, 2017
This presentation is dedicated to Prof. Hans Rosling
Contents
1. Why pancreatic cancer?2. Company and Technology Overview3. IMMray™ PanCan-d Pancreatic Cancer Test4. Clinical Use5. Conclusions and current status6. Next steps
3rd
<5%
~50%
3:rd most common cancer by survival More deaths than from breast cancer (2015)Source: American Cancer Society
5-yr survival is <5%Due to late detectionSource: US NCI
5-yr survival can be ~50%If detected earlySource: Pancreatic Cancer Registry in Japan - 20 Years of Experience, 2004
Lung and bronchus
Colorectum
Pancreas
Breast
Liver and intraheptic …
Prostate
Leukemia
Non-Hodgkin lymphoma
Urinary bladder
Brain and other …
ESTIMATED DEATHS , 2016By cancer type, both sexes combined
158,080
49,190
41,780
40,890
27,170
26,120
24,400
20,150
16,390
16,050
Source: SEER Stat Fact Sheets: Pancreas Cancer 2016
Pancreatic Cancer by numbers
865
797 878 966 1016
1050
1173
1249
12841 536 1 572 1 543 1 548 1 582
1 703 1 6751 792 1 812
0
200
400
600
800
1 000
1 200
1 400
1 600
1 800
2 000
2007 2008 2009 2010 2011 2012 2013 2014 2015
PancreaticCancer
M&KDiagnosticerade M&KDödaDiagnosed Deceased
Pancreatic Cancer is the most deadly cancer
Ref:Diagnosed anddeceased cancerregistry,Sweden,2017
6 025 6 017 6 180 6 226 6 308 6 118 6 199 6 300 6 511
2647
2675
2631
2597
2707
2695
2763
2771
2780
0
1 000
2 000
3 000
4 000
5 000
6 000
7 000
2007 2008 2009 2010 2011 2012 2013 2014 2015
ColorectalCancer
DIAGNOSED
DECEASED
7 088 7 346 7 4157 950
8 427
7 560 7 864 8 0647 426
1495
1522
1396
1401
1420
1465
1480
1404
1430
0
1 000
2 000
3 000
4 000
5 000
6 000
7 000
8 000
9 000
2007 2008 2009 2010 2011 2012 2013 2014 2015
BreastCancer
Resectable
Resectable/
Borderlineresectable Unresectable
4.6MONTHSMEDIANSURVIVALFORSOMEONEDIAGNOSEDWITHPANCREATICCANCERINEUROPE
Unresectable
LATEDIAGNOSISTODAY
Early diagnosis in pancreatic cancer is the only hope
RESEARCH AND DEVELOPMENT>15 years PRODUCT DEVELOPMENT IMMRAYTM PANCAN-D
MARKET INTROD
Ø World renownedTranslational Cancer Center
Ø 75+ researchers.Ø 30 MEUR research grants Ø IP-rights for IMMrayTM
platform tests transfered toImmunovia AB.
IMMrayTM PanCan-d PANCREAS CANCER TEST
IMMUNOVIA LABORATORY SERVICES
PARTNER REFERENCE LABORATORIES
SLE (Lupus)
Prostate cancer
Breast cancer
2. Immunovia Overview
Horizon 2020 EU grant 4.2 MEURNASDAQ First North Introduction 1 Dec 2015
22 MEUR emission Oct 19, 2016
First test IMMrayTM PanCan-d
Hypothesis:Blood contains enough information to decipher complex disease, such as PDAC
Aim:To target high risk PDAC patients for detecting disease in asymptomatic individuals
Disease fingerprint = Biomarker signature
IMMrayTM
The tumor - stromal cell interaction - a window for clinical proteomics
Bíomarker signatures consist of - cytokines, immunregulatory factors, enzymes, complement proteins, innate factors, cancer associated antigens
Antibody library
ü Optimized for array surface
ü 1010 scFvantibodies in library
ü Inhouseproduction ofantibodies
Robot Spotter
üAntibodies spotted on the microarray
üFully automated
üOne antibody per spot
ü Up to 2000 antibodies/cm2
Array Slide
ü Industry Standard format
ü Discovery >400 Abs
ü Commercial 10-30 Abs
Patient bloodsample
üStandard serum sample, <100 µl
üBiotinylationpretreatment ofserum
ü Apply serum to Array Slide
Slide Scanning
ü Array Slidescanned withfluorescent scanner
ü Signal intensityfrom each spot correspondsto protein concentration
Analysis &Test Result
ü ImmunoviaAdvanced Bioinformatics Algorithm translate scanned image toa snapsot of the patients immune response
ü yes/no answer about the patient status
üActionable result for clinician,
PRODUCTION LABORATORY
IMMrayTM Platform
IMMrayTM PanCan-d product format
Layout:• 14 arrays/slide • 36 x 34 spots/array• 1224 data points/array• 17 136 data points/slide
AntibodySlide
AntibodyArray
3. IMMray™ PanCan-d pancreatic cancer testextremely encouraging results so far
DISCOVERYDefine signature PRE-VALIDATION
Verify andrefinesignature
VALIDATIONConfirm signature
6 large clinical studies, 2500 blood samples PDAC stages I-IV and matched controls
Training TrainingTraining
Test TestTest
1.Ingvarsson Jetal.Proteomics 20088(11):2211-92.Wingrenetal.CancerRes.201215;72(10):2481-903.Gerdtsson etal.Int JournalofProteomics 2015;2015:5872504.Gerdtsson etal.JMolOncol,2016.10,1305-1316.
American samples cohort incollaboration with OHSUKnightCancerInstitute andBrenden-Colcon CenterforPancreaticCancer,Portland,Oregon,USA,362blood samples st I-IVandmatched controls
Manuscript submitted Febr 10,2017,SouthScandinavianstudy incollaboration with Herlev og GentofteHospital,Copenhagen,Denmark1331blood samples stages I-IV,andmatched controls
ü 98 % accuracy
STAGE I STAGE II
ü96 % accuracy
IMMray™ PanCan-d can detect retrospectively 96% of the asymptomatic patients
Scandinavian & North American patient cohortsin retrospective studies
Healthy – Training Set
PDAC Stage I and II – Training Set
Healthy vs. Pancreatic cancer stage I and II
Training data set
Healthy vs. Pancreatic cancer stage I and II
Healthy – Training Set
Healthy – Test Set
PDAC Stage I & II – Training Set
PDAC Stage I & II – Test Set
Training & Test data set
96% accuracy for Pancreatic cancer stage I and II
1.0
Specificity
Sensitivity
0.8 0.6 0.4 0.2 0.0
1.0
0.8
0.6
0.4
0.2
0.0
AUC = 0.96
Training set 666controls,111Stage I+IITestset 222controls,37Stage I+II
98% accuracy for Pancreatic cancer stage I to IV
Healthy controlsPDAC
EUS
CT/MRI
CT PANCREAS
ERCP
RESULTS TREATMENT MEDIAN SURVIVAL
Inoperable (85 %)Chemotherapy 6 - 7 months
Untreated 3 - 4 months
Operable (15 %) Adjuvant chemotherapy
20 months
PDAC SYMPTOMSPATIENTS ELIGIBLE FOR EARLY DETECTION
Patients with symptomsNo symptoms
CLINICALUSE1
HEREDITARYHigh risk groups- Familiar autosomal
stratified ≥ 2 closefam members
- Familiar non-autosomal ≥ 3 closefam members
- BRCA1/2 HereditaryPanCan/Breast/Ovarian
- FAMMM p16, CDKN2A
- Peutz Jeghers- Lynch Syndrome with
PC history (HNPCC)- Hereditary
pancreatitis
CLINICALUSE2
NEW ONSET DIABETES TYPE II AFTER 50 YRS OF
AGE5-8 Risk of developing pancreas cancer 1-3 year after diagnosis
VAGUESYMPTOMS- Depression- Indigestion- Jaundice- Midback pain- Upper abdominal
pain- Painoneating- Fatigue- Unexplained weight
loss- Diabetes
CLINICALUSE3 CLINICALUSE4CONFIRMATORYDIAGNOSIS
4. IMMray™ PanCan-d Pancreatic Cancer Test clinical uses
CLINICAL USE 1
HEREDITARYHigh risk groups- Familiar autosomal
stratified ≥ 2 close fammembers
- Familiar non-autosomal ≥ 3 close fam members
- BRCA1/2 HereditaryPanCan/Breast/Ovarian
- FAMMM p16, CDKN2A- Peutz Jeghers- Lynch Syndrome with PC
history (HNPCC)- Hereditary pancreatitis
CLINICAL USE 2
NEW ONSET DIABETES TYPE II AFTER 50 YRS OF
AGE
VAGUE SYMPTOMS- Depression- Indigestion- Jaundice- Midback pain- Upper abdominal pain- Pain on eating- Fatigue- Unexplained weight
loss- Diabetes
CLINICAL USE 3 CLINICAL USE 4
CONFIRMATORY DIAGNOSIS/MONITORING
Prospective(longitudinal) validation clinicalstudyPanFAM-1
Retrospective&ProspectiveStudies planningOngoing
ProspectiveStudies planningongoing
Tostartatalaterstage
3. IMMray™ PanCan-d Pancreatic Cancer Test status
Diagnostic assessment studies for IPMNs (pre-cancer lesions) & different pancreatic diseases
IMMray™ PanCan-d early diagnosis through high risk surveillance of familiar pancreatic cancer
PANFAM-1 Global Multicenter Prospective Validation Study1000 familiar pancreatic cancer high risk individuals3 yearsStudy Start Dec 2016
CLINICAL USE 1HEREDITARY
High risk groups- Familiar autosomal stratified≥ 2 close fam members
- Familiar non-autosomal ≥ 3 close fam members
- BRCA1/2 HereditaryPanCan/Breast/Ovarian
- FAMMM p16, CDKN2A- Peutz Jeghers- Lynch Syndrome with PC
history (HNPCC)- Hereditary pancreatitis
PATIENTS ELIGIBLE FOR EARLY DETECTION
No symptoms
✓ IMMray™ PanCan-d detects with 98% accuracy PDAC stages I-IV in retrospective studies of 1750 blood samples and matched controls
✓ In total 2650 patients (Q4 2016) have been retrospectively analysedwith IMMray™ PanCan-d
✓ Validated in an US cohort 2016 with 96% accuracy for stages I-II
✓ Started multicentric prospective validation study
✓ Agreements in place, and discussions with most existing high risk surveillance programs
✓ Immunovia Laboratory Services Quality Assurance Management System verification and validation: processes, instruments, protocols, for both chip and software.
5. Conclusions and current status
ü New onset diabetes type II after 50 yrs- clinical studies with IMMray™PanCan-d
ü Vague symptoms for pancreatic cancer-clinical studies with IMMray™ PanCan-d
ü Collaborations with early detectionnational programs in USA and Europe
ü IMMray™ PanCan-d CE mark
ü Global Accreditation Immunovia Lab Services Lund Sweden and KDL,Portland, USA
ü Initiate regulatory approval process
6. Next steps – 2017/2018
A Kumar and Robert Berman, Editorial, Journal of Antibody Drug Conjugates. March 2016
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