Diagnosis of early stages of pancreatic cancer Laura Chirica, PhD - - PowerPoint PPT Presentation

Diagnosis of early stages of pancreatic cancer

Laura Chirica, PhD Immunovia, 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 Overview
• 3. IMMray™ PanCan-d Pancreatic Cancer Test
• 4. Clinical Use
• 5. Conclusions and current status
• 6. 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 detection

Source: US NCI

5-yr survival can be ~50%

If detected early

Source: 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 , 2016

By 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 1 016 1 050 1 173 1 249 1 284 1 536 1 572 1 543 1 548 1 582 1 703 1 675 1 792 1 812 200 400 600 800 1 000 1 200 1 400 1 600 1 800 2 000 2007 2008 2009 2010 2011 2012 2013 2014 2015

Pancreatic Cancer

M&K Diagnosticerade M&K Döda

Diagnosed Deceased

Pancreatic Cancer is the most deadly cancer

Ref: Diagnosed and deceased cancer registry, Sweden, 2017

6 025 6 017 6 180 6 226 6 308 6 118 6 199 6 300 6 511 2 647 2 675 2 631 2 597 2 707 2 695 2 763 2 771 2 780 1 000 2 000 3 000 4 000 5 000 6 000 7 000 2007 2008 2009 2010 2011 2012 2013 2014 2015

Colorectal Cancer

DIAGNOSED DECEASED

7 088 7 346 7 415 7 950 8 427 7 560 7 864 8 064 7 426

1 495 1 522 1 396 1 401 1 420 1 465 1 480 1 404 1 430

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

Breast Cancer

Resectable Resectable/ Borderline resectable Unresectable

4.6 MONTHS MEDIAN SURVIVAL FOR SOMEONE DIAGNOSED WITH PANCREATIC CANCER IN EUROPE

Unresectable

LATE DIAGNOSIS TODAY

Early diagnosis in pancreatic cancer is the only hope

RESEARCH AND DEVELOPMENT >15 years PRODUCT DEVELOPMENT IMMRAYTM PANCAN-D MARKET INTROD Ø World renowned Translational Cancer Center Ø 75+ researchers. Ø 30 MEUR research grants Ø IP-rights for IMMrayTM platform tests transfered to Immunovia 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 MEUR NASDAQ 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 scFv antibodies in library ü Inhouse production of antibodies

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 blood sample

üStandard serum sample, <100 µl üBiotinylation pretreatment of serum ü Apply serum to Array Slide

Slide Scanning

ü Array Slide scanned with fluorescent scanner ü Signal intensity from each spot corresponds to protein concentration

Analysis & Test Result

ü Immunovia Advanced Bioinformatics Algorithm translate scanned image to a 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

Antibody Slide Antibody Array

• 3. IMMray™ PanCan-d pancreatic cancer test

extremely encouraging results so far

DISCOVERY

Define signature

PRE-VALIDATION

Verify and refine signature

VALIDATION Confirm signature

6 large clinical studies, 2500 blood samples PDAC stages I-IV and matched controls

Training Training Training Test Test Test

• 1. Ingvarsson J et al. Proteomics 2008

8(11):2211-9

• 2. Wingren et al. Cancer Res. 2012

15;72(10):2481-90

• 3. Gerdtsson et al. Int Journal of

Proteomics 2015;2015:587250

• 4. Gerdtsson et al. J Mol Oncol, 2016.

10, 1305-1316. American samples cohort in collaboration with OHSU Knight Cancer Institute and Brenden- Colcon Center for Pancreatic Cancer, Portland, Oregon, USA, 362 blood samples st I-IV and matched controls Manuscript submitted Febr 10, 2017, South Scandinavian study in collaboration with Herlev og Gentofte Hospital, Copenhagen, Denmark 1331 blood samples stages I-IV, and matched controls

ü 98 % accuracy

STAGE I STAGE II

ü96 % accuracy

IM IMMray™ PanCan-d can detect retrospectively 96% of the asymptomatic patients

Scandinavian & North American patient cohorts in 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 666 controls, 111 Stage I+II Test set 222 controls, 37 Stage I+II

98% accuracy for Pancreatic cancer stage I to IV

Healthy controls PDAC

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 SYMPTOMS PATIENTS ELIGIBLE FOR EARLY DETECTION Patients with symptoms No symptoms

CLINICAL USE 1

HEREDITARY High risk groups

• Familiar autosomal

stratified ≥ 2 close fam members

• Familiar non-

autosomal ≥ 3 close fam members

• BRCA1/2 Hereditary

PanCan/Breast/Ovaria n

• 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 5-8 Risk of developing pancreas cancer 1-3 year after diagnosis

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

• 4. IMMray™ PanCan-d Pancreatic Cancer Test clinical uses

CLINICAL USE 1

HEREDITARY High risk groups

• Familiar autosomal

stratified ≥ 2 close fam members

• Familiar non-autosomal ≥

3 close fam members

• BRCA1/2 Hereditary

PanCan/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 clinical study PanFAM-1 Retrospective &Prospective Studies planning Ongoing Prospective Studies planning

• ngoing

To start at a later stage

• 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 Study 1000 familiar pancreatic cancer high risk individuals 3 years Study Start Dec 2016 CLINICAL USE 1 HEREDITARY High risk groups

• Familiar autosomal stratified

≥ 2 close fam members

• Familiar non-autosomal ≥ 3

close fam members

• BRCA1/2 Hereditary

PanCan/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 analysed

with 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 detection national 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.com www.immunovia.com