Strategic Center for Clinical Cancer Research Molecular Diagnostics for unmet clinical needs Deciphering the human proteome – delivering disease-specific biomarkers to the clinic
Strategic Center for Clinical Cancer Research Immunovia develop blood-based tests for SLE - Systemic Lupus Erythematosus Pancreatic cancer Breast cancer recurrence Clinicians are provided with actionable information and improved diagnosis, classiﬁcation, prognosis and treatment are enabled. The clinical impact of such tests for the patient and the healthcare system will be signiﬁcant.
Strategic Center for Clinical Cancer ResearchTechnology
Surveilling the Serum Proteome for Disease Strategic Center for Hypothesis: Clinical Cancer Research Each disease displays a unique serum (urine) protein ﬁngerprint The serum (urine) protein ﬁngerprint will be SLE ? a combination of the secretome & a systemic response against the diseaseRecombinant antibody arrays for high-throughput disease proteomics Technology Array platform development Disease proteomics
Core Technology Affinity Proteomics – Antibody Microarrays Strategic Center for Clinical Cancer Research Bioinfor- Detectio matics n Ø 120 µm Sample Recombinant antibody 1 proteomic map / sample Identiﬁcation of candidate microarray analysis biomarker signature Probes: Recombinant scFv antibodies Renewable source 2,000 ab / cm2 Microarray adapted by molecular design 1 µL serum/ array 1 cm2 ab array equivalent to ~21 ELISA plates!Wingren and Borrebaeck. Exp. Rew. Mol. Diag. 2007. 7, 673-686. Borrebaeck and Wingren. J Proteomics 2009, 72, 928-.Wingren and Borrebaeck, DDT, 2007, 12, 813-819. Borrebaeck and Wingren, Exp. Rew. Proteomics, 2009, 6, 11-13.
Core Technology Antibody Microarrays – Selected Features Strategic Center for Clinical Cancer • Content: 3 x 1010 recombinant scFv library Research microarray adapated by molecular design • Array density: 100 – 300 scFv /array • Array size: < 1 cm2 / array • Fabrication: non-contact printing • Support: Black Maxisorb slides (Nunc) • Sample: Non-fractionated proteomes (µL scale) Any proteome! (serum, plasma, cell lysate, urine • Array handling: Protein array Work station • Detection: Fluorescent based read-out system (pM to fM) • Reproducibility High! • Speciﬁcity High! • Bioinformatics Front-line! Wingren and Borrebaeck. Exp. Rew. Mol. Diag. 2007. 7, 673-686. Borrebaeck and Wingren. J Proteomics 2009, 72, 928-.Wingren and Borrebaeck, DDT, 2007, 12, 813-819. Borrebaeck and Wingren, Exp. Rew. Proteomics, 2009, 6, 11-13.
Biomarkers – Our Strategy Strategic Center High-throughput protein expression proﬁling for Clinical Cancer Research • Serum • Plasma i) Well-deﬁned clinical needs Clinical • Urine ii) From bed-to-bench and back again Sample • Tumour extracts • etc Validation using independent sample co-horts Affinity Candidate Pre-validated Validated Clinical Proteomics Biomarkers Biomarkers Biomarkers Implementation • Antibody Microarrays Validation using independent methodsWingren and Borrebaeck. Exp. Rew. Mol. Diag. 2007. 7, 673-686. Borrebaeck and Wingren. J Proteomics 2009, 72, 928-.Wingren and Borrebaeck, DDT, 2007, 12, 813-819. Borrebaeck and Wingren, Exp. Rew. Proteomics, 2009, 6, 11-13.
1. Biomarkers – SLE: premium features Strategic Center for Clinical Cancer Research Diagnosis Classiﬁcation Prognosis SLE vs. healthy controls Phenotype 1 vs. 2 vs. 3 Active vs. inactive SLE 0.80 0.79 0.81 AUC = 0.92 SLE1 SLE3 SLE2Candidate serum biomarker Candidate serum biomarker Candidate serum biomarkersignature for SLE diagnosis signature for SLE signature for prognosis classiﬁcation (disease activity monitoring) The antibody array data provides novel opportunities for diagnosis, classiﬁcation, and prognosis of SLE based on a blood sample
2. Biomarkers – Pancreatic Cancer: premium features DiagnosisPC vs. healthy controls PC vs. pancreatitis or PC vs. pancreatitis + controls pancreatitis + controls Pre-validation AUC = 0.85-0.99 AUC = 0.95 AUC = 0.88 Candidate serum biomarker signatures discriminating pancreatic cancer vs. healthy controls, pancreatitis as well as the combined cohort thereof. Well on the way to develop the ﬁrst blood-based diagnostic test for pancreatic adenocarcinoma
3. Biomarkers – Breast Cancer: premium features Metastasizing vs non-metastasizing breast cancer Analyte velocity 0 - 6 months (di/dt) Training set Predicting the risk for relapse SVM trained on all 135 antibodies, i.e. unﬁltered data 21-analyte condensed biomarker signature generated using a backward elimination algorithmTraining set38 patients ROC AUC=0.88 Heat map, illustrating the expression of the top 25 ROC curveTest set (p-value) analytes26 patients Test set Our biomarker signature plus conventional clinical parameters AUC=0.90 Classiﬁcation using the Clinically added value! 21-marker signature ROC AUC=0.85 AUC=0.66 Conventional clinical parameters
Conclusions Strategic Center for Clinical Cancer Research The ﬁrst blood- and urine-based tests for diagnosis, prognosis and classiﬁcation of SLE. The ﬁrst blood-based test for diagnosis of pancreatic cancer. The ﬁrst blood-based test for predicting breast cancer relapse. When conventional clinical parameters are at hand, the antibody microarray data performs signiﬁcantly better.
Strategic Center for Clinical Cancer ResearchMarket and Strategy
Target Groups Breast Cancer Pancreatic Lupus• Relapse risk prediction • Early, accurate detection • Early, accurate detection• Therapy monitoring • Risk group screening • Flare prognosis opportunity• Patient Beneﬁt: • Patient Beneﬁt: • Patient beneﬁt • Over and Under treatment • 90% high conﬁdence • Early treatment reduce avoided “Clean bill of health” severity of symptoms • Early information to • Increased Detection in • Previously misdiagnosed patients on effect of initial treatable state with SLE get proper treatment • Removing todays clinical management uncertainty in diagnosis accuracyCancer Type Breast Pancreatic Ovarian Non- Lupus HodgkinLife-time risk of contracting 12,7% 4,7% 1,6% 2,1% 0,1%diseaseNew Cases per year WW 1.300.000 250.000 204.000 280.000 >100.000New Cases per year US 192.370 42.470 21.500 65.980 >16.000Deaths per year US 40.170 35.240 14.600 19.500 1.000Death / New cases US 20,9% 83,0% 67,9% 29,6% 6,3%Five Year Survival rate 79,7% 1-3% 41,0% 65,0% 97,0%Source: American Cancer Society
The Importance of Early Detection Pancreatic cancer 5 Year Survival rate is 1-3%, 35.000 deaths per year in US No diagnostic only test for early detection of pancreatic cancer available A study* on the market demonstrated a 78% 4-year survival with asymptomatic patients with stage I adenocarcinomas;*Furukawa H, Okada S, Saisho H, Ariyama J, Karasawa E, Nakaizumi A, et al. Clinicopathologic features of smallpancreaticadenocarcinoma. A collective study. Cancer 1996; 78:986-90. [PMID8780535]
Clinical & Regulatory Development Breast cancer US • US registration time and cost intensive registration principal • Outsourcing to CRO focus Pancreatic cancer • Clinicals more rapid (24m) and less costly due to devastating product enable early nature of pancreatic cancer. Outsourcing to CRO revenues • Rapid market penetration possible, ﬁrst in Scandinavia and EU 24-48 Months 48-60 months0-12 Months 12-24 Months • Complete clinical • FDA • Launch • Establish Pancreatic disease studies, registration Clinical trial, speciﬁc KOL register and release Scandinavia network as Pancreatic. of Breast part of CE mark and product • Launch product Breast multisite Validation release Cancer Clinical trial, Studies • Complete US • First product clinical related studies • Launch breast cancer Lupus revenue Clinical trial, (Scandinavia) • Complete Scandinavia clinical studies Lupus. CE mark and release.
Key Selling ArgumentsDetection of difficult • No accurate tests exist today for Pancreatic cancer and Lupusto diagnose diseases Avoiding over- and • No Test to monitor breast patients after mastectomy exist today • Monitoring of disease progression under- treatment • Monitoring of therapy efficacy in individual patients Blood based • Less invasive, less patient stress compared to biopsies sampling • Suited for serial sampling Rapid turn around • Enable more rapid inclusion in patient treatment plans of test results
Market Introduction • Initially Pancreatic and Lupus initially in Scandinavia, using KOL network, followed by EU. Market • Breast Cancer clinical trials in US for US introduction Introduction • Distribution agreements for EU and NA • Pre Market Companion Diagnostics agreements possible • Penetration rate based on OncoType actuals ﬁrst 4 years Market • 2-3 tests per patient as opposed to one give hockey stick revenue penetration • With time additional tests at 12, 24 months can be added. • Price Point applicable for Service Lab Test Model Price-Point • Lower than Oncotype DX at $3820 per test, but several tests per patient at $2000 • Genomic Health has successfully developed the per test reimbursement environment for this type of diagnostics
Breast Cancer: Treatment tree Three Immunovia tests per patient over 24 month treatment period • High Risk • High Risk Group Group Determines High 12 Months monitors 24 Months monitors0 months, 6 Months, or Low relapse treatment treatment Sample0 Relapse Risk Metastasis Metastasis surgery risk, using • Low Risk • Low Risk Test Sample0 and 6) Test Test Group: Group: monitors monitors healthiness healthiness
Pancreatic cancer: Treatment tree Symptoms Blood analysis Ultra sound CT/MR CT Pancreas OP 15% ERCP InOP 85% Untreated Adjuvant chemo Chemo 3-4 months median survival 20 months median survival 6-7 months median survival Three Immunovia test situations • Hereditary Discriminates between Monitoring of Risk Group • Middle aged Treatment operable Screening diabetes onset Diagnosis pancreatic monitoring cancer and patients pancreatitis
Lupus: Clinical Decision Tree Clinical onset Several years > 1 year Three Immunova test situations SLE test solves issues of misdiagnosis / Flares test untreated for Classiﬁcation (disease activity) years test solves issue offer prediction Classiﬁcatio for timely Diagnosis n of non- Prognosis No other disease optimized symptom speciﬁc markers, therapy used treatment and nor blood or prevention urine based tests exist
Summary Immunovia has accurate MDx solutions to unmet clinical needs in breast cancer, pancreatic cancer and lupus Immunovia tests are applicable for diagnosis and for monitoring. Revenues therefore accumulative Immunovias platform is blood based and generically applicable in cancer and autoimmune areas. The pipeline of tests is strong.