Oslo Life Science 15-17 February, 2017 Diagnosis of early stages of pancreatic cancer Laura Chirica, PhD Immunovia, Lund, Sweden
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
Pancreatic Cancer by numbers ESTIMATED DEATHS , 2016 By cancer type, both sexes combined 3:rd most common cancer by Lung and bronchus 158,080 3rd survival More deaths than from breast cancer (2015) Colorectum 49,190 Source: American Cancer Society Pancreas 41,780 Breast 40,890 5-yr survival is <5% Liver and intraheptic … <5% 27,170 Due to late detection Source: US NCI Prostate 26,120 Leukemia 24,400 Non-Hodgkin lymphoma 20,150 5-yr survival can be ~50% Urinary bladder ~50% If detected early 16,390 Source: Pancreatic Cancer Brain and other … Registry in Japan - 20 Years of Experience, 2004 16,050 Source: SEER Stat Fact Sheets: Pancreas Cancer 2016
Pancreatic Cancer is the most deadly cancer DIAGNOSED Breast Cancer Colorectal Cancer Pancreatic Cancer 8 427 9 000 7 000 8 064 6 511 2 000 7 950 7 864 1 812 6 308 6 300 1 792 6 226 6 180 6 199 7 560 6 118 6 025 6 017 7 415 7 426 8 000 1 703 7 346 1 675 1 800 7 088 1 582 6 000 1 572 1 543 1 548 1 536 7 000 1 600 1 284 1 249 1 173 5 000 1 400 6 000 1 050 1 016 1 200 966 5 000 4 000 878 865 2 780 2 763 2 771 2 707 2 695 2 675 2 647 2 631 1 000 2 597 797 4 000 3 000 800 3 000 600 1 522 1 495 1 480 1 420 1 465 1 430 1 396 1 401 1 404 2 000 2 000 400 1 000 200 1 000 0 0 0 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 Diagnosed Deceased M&K Diagnosticerade M&K Döda Ref: Diagnosed and deceased cancer registry, Sweden, 2017 DECEASED
Early diagnosis in pancreatic cancer is the only hope Resectable/ Borderline resectable Resectable Unresectable Unresectable LATE DIAGNOSIS TODAY 4.6 MONTHS MEDIAN SURVIVAL FOR SOMEONE DIAGNOSED WITH PANCREATIC CANCER IN EUROPE
2. Immunovia Overview IMMRAY TM PANCAN-D RESEARCH AND DEVELOPMENT PRODUCT DEVELOPMENT >15 years MARKET INTROD IMMray TM PanCan-d IMMUNOVIA LABORATORY SERVICES PANCREAS CANCER TEST PARTNER REFERENCE LABORATORIES SLE (Lupus) Ø World renowned Prostate cancer Translational Cancer Center Breast cancer Ø 75+ researchers. Ø 30 MEUR research grants Ø IP-rights for IMMray TM platform tests transfered to Immunovia AB. Horizon 2020 EU grant 4.2 MEUR NASDAQ First North Introduction 1 Dec 2015 22 MEUR emission Oct 19, 2016
First test IMMray TM 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 IMMray TM
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
IMMray TM Platform PRODUCTION LABORATORY Slide Scanning Antibody library Robot Spotter Array Slide Patient blood Analysis & sample Test Result ü Antibodies ü Array Slide ü Optimized for ü Industry Standard ü Standard serum ü Immunovia spotted on the scanned with array surface format sample, <100 µl Advanced microarray fluorescent scanner Bioinformatics 10 10 scFv ü ü Discovery ü Biotinylation Algorithm translate ü Fully automated ü Signal intensity antibodies in >400 Abs pretreatment of scanned image to from each spot library serum a snapsot of the ü One antibody per corresponds ü Commercial patients immune spot to protein ü Inhouse 10-30 Abs ü Apply serum to response concentration production of Array Slide ü Up to 2000 antibodies ü yes/no answer about antibodies/cm 2 the patient status ü Actionable result for clinician,
IMMray TM PanCan-d product format Antibody Slide Antibody Array Layout: • 14 arrays/slide • 36 x 34 spots/array • 1224 data points/array • 17 136 data points/slide
3. IMMray™ PanCan- d pancreatic cancer test extremely encouraging results so far
6 large clinical studies, 2500 blood samples PDAC stages I-IV and matched controls Test Training Test Training Test Training DISCOVERY Define signature PRE-VALIDATION VALIDATION Verify and refine signature Confirm signature 1. Ingvarsson J et al. Proteomics 2008 8(11):2211-9 Manuscript submitted Febr 10, 2017, 2. Wingren et al. Cancer Res. 2012 South Scandinavian study in 15;72(10):2481-90 American samples cohort in collaboration with Herlev og Gentofte 3. Gerdtsson et al. Int Journal of collaboration with OHSU Knight Hospital, Copenhagen, Denmark Proteomics 2015;2015:587250 Cancer Institute and Brenden- 1331 blood samples stages I-IV, and 4. Gerdtsson et al. J Mol Oncol, 2016. Colcon Center for Pancreatic matched controls 10, 1305-1316. Cancer, Portland, Oregon, USA, 362 blood samples st I-IV and matched controls
IM IMM ray™ PanCan- d can detect retrospectively 96% of the asymptomatic patients ü 98 % accuracy STAGE I STAGE II ü 96 % accuracy Scandinavian & North American patient cohorts in retrospective studies
Healthy vs. Pancreatic cancer stage I and II Training data set Healthy – Training Set PDAC Stage I and II – Training Set
Healthy vs. Pancreatic cancer stage I and II Training & Test data set Healthy – Training Set Healthy – Test Set PDAC Stage I & II – Training Set PDAC Stage I & II – Test Set
96% accuracy for Pancreatic cancer stage I and II AUC = 0.96 1.0 0.8 0.6 Sensitivity 0.4 0.2 0.0 0.8 0.6 0.4 0.2 0.0 1.0 Specificity 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
4. IMMray™ PanCan- d Pancreatic Cancer Test clinical uses PATIENTS ELIGIBLE FOR EARLY DETECTION PDAC SYMPTOMS No symptoms Patients with symptoms EUS CLINICAL USE 1 CLINICAL USE 2 CLINICAL USE 3 CLINICAL USE 4 CT/MRI CONFIRMATORY DIAGNOSIS VAGUE SYMPTOMS HEREDITARY NEW ONSET - Depression High risk groups DIABETES TYPE II CT PANCREAS - Indigestion - Familiar autosomal AFTER 50 YRS OF - Jaundice stratified ≥ 2 close AGE ERCP - Midback pain fam members 5-8 Risk of developing - Upper abdominal - Familiar non- pancreas cancer 1-3 pain autosomal ≥ 3 close year after diagnosis - Pain on eating fam members - Fatigue - BRCA1/2 Hereditary - Unexplained weight PanCan/Breast/Ovaria loss RESULTS TREATMENT MEDIAN SURVIVAL n - Diabetes - FAMMM p16, Chemotherapy 6 - 7 months CDKN2A Inoperable (85 %) - Peutz Jeghers Untreated 3 - 4 months - Lynch Syndrome with PC history (HNPCC) Adjuvant - Hereditary Operable (15 %) 20 months chemotherapy pancreatitis
3. IMMray™ PanCan- d Pancreatic Cancer Test status CLINICAL USE 1 CLINICAL USE 2 CLINICAL USE 4 CLINICAL USE 3 NEW ONSET HEREDITARY VAGUE SYMPTOMS CONFIRMATORY DIAGNOSIS/ DIABETES TYPE II High risk groups - Depression MONITORING - Familiar autosomal AFTER 50 YRS OF - Indigestion stratified ≥ 2 close fam AGE - Jaundice members - Midback pain - Familiar non-autosomal ≥ - Upper abdominal pain 3 close fam members - Pain on eating - BRCA1/2 Hereditary - Fatigue PanCan/Breast/Ovarian - Unexplained weight - FAMMM p16, CDKN2A loss - Peutz Jeghers - Diabetes - Lynch Syndrome with PC history (HNPCC) - Hereditary pancreatitis Prospective Retrospective Prospective To start at a later (longitudinal) &Prospective Studies planning stage validation clinical Studies planning ongoing study Ongoing PanFAM-1 Diagnostic assessment studies for IPMNs (pre-cancer lesions) & different pancreatic diseases
IMMray™ PanCan- d early diagnosis through high risk surveillance of familiar pancreatic cancer PATIENTS ELIGIBLE FOR EARLY DETECTION No symptoms CLINICAL USE 1 HEREDITARY High risk groups - Familiar autosomal stratified ≥ 2 close fam members PANFAM-1 Global Multicenter Prospective Validation Study - Familiar non-autosomal ≥ 3 1000 familiar pancreatic cancer high risk individuals close fam members 3 years - BRCA1/2 Hereditary Study Start Dec 2016 PanCan/Breast/Ovarian - FAMMM p16, CDKN2A - Peutz Jeghers - Lynch Syndrome with PC history (HNPCC) - Hereditary pancreatitis
5. Conclusions and current status ✓ 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.
Recommend
More recommend
