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

Thank You !

laura.chirica@immunovia.comwww.immunovia.com