Ian humphrey smith innoiva presentation

www.immunovia.com

Strategic Center for Clinical Cancer Research

Molecular Diagnostics for unmet clinical needs

Deciphering the human proteome – delivering disease-specific biomarkers to the clinic


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.


Technology

Hypothesis: Each disease displays a unique serum (urine) protein fingerprint  The serum (urine) protein fingerprint will be a combination of the secretome & a systemic response against the disease

Surveilling the Serum Proteome for Disease

Technology Array platform development

Disease proteomics

Recombinant antibody arrays for high-throughput disease proteomics

SLE ?


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 Affinity Proteomics – Antibody Microarrays

Detection Sample

Recombinant antibody microarray analysis

1 proteomic map / sample Identification of candidate biomarker signature

Bioinfor-matics

2,000 ab / cm2

1 µL serum/ array

1 cm2 ab array equivalent to ~21 ELISA plates!

Ø 120 µm

Probes: Recombinant scFv antibodies   Renewable source   Microarray adapted by molecular design


Strategic Center for Clinical Cancer Research •  Content: 3 x 1010 recombinant scFv library

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!

Core Technology Antibody Microarrays – Selected Features


Biomarkers – Our Strategy

Validation using independent methods


High-throughput protein expression profiling

Clinical Implementation

Candidate Biomarkers

Clinical Sample

Pre-validated Biomarkers

Validated Biomarkers

•  Serum •  Plasma •  Urine •  Tumour extracts •  etc

•  Antibody Microarrays

Validation using independent sample co-horts

Affinity Proteomics

i) Well-defined clinical needs ii) From bed-to-bench and back again


1. Biomarkers – SLE: premium features Strategic Center for Clinical Cancer Research

The antibody array data provides novel opportunities for diagnosis, classification, and prognosis of SLE based on a blood sample

Diagnosis Classification Prognosis

SLE vs. healthy controls Phenotype 1 vs. 2 vs. 3 Active vs. inactive SLE

AUC = 0.92

0.79

0.80

0.81

SLE1

SLE3 SLE2

Candidate serum biomarker signature for SLE diagnosis

Candidate serum biomarker signature for SLE classification

Candidate serum biomarker signature for prognosis (disease activity monitoring)

2. Biomarkers – Pancreatic Cancer: premium features

AUC = 0.88

Candidate serum biomarker signatures discriminating pancreatic cancer vs. healthy controls, pancreatitis as well as the combined cohort thereof.

AUC = 0.95

Diagnosis

PC vs. healthy controls PC vs. pancreatitis or PC vs. pancreatitis + controls pancreatitis + controls Pre-validation

AUC = 0.85-0.99

Well on the way to develop the first blood-based diagnostic test for pancreatic adenocarcinoma

3. Biomarkers – Breast Cancer: premium features

Training set Predicting the risk for relapse SVM trained on all 135 antibodies, i.e. unfiltered data

ROC curve

21-analyte condensed biomarker signature generated using a backward elimination algorithm

Training set 38 patients

ROC AUC=0.88

Heat map, illustrating the expression of the top 25 (p-value) analytes

Metastasizing vs non-metastasizing breast cancer Analyte velocity 0 - 6 months (di/dt)

Test set

Test set 26 patients

Classification using the 21-marker signature ROC AUC=0.85 AUC=0.66

AUC=0.90

Conventional clinical parameters

Our biomarker signature plus conventional clinical parameters

Clinically added value!

  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.

Conclusions Strategic Center for Clinical Cancer Research


Market and Strategy

Target Groups

Cancer Type Breast Pancreatic Ovarian Non-Hodgkin

Lupus

Life-time risk of contracting disease

12,7% 4,7% 1,6% 2,1% 0,1%

New Cases per year WW 1.300.000 250.000 204.000 280.000 >100.000

New Cases per year US 192.370 42.470 21.500 65.980 >16.000

Deaths per year US 40.170 35.240 14.600 19.500 1.000

Death / 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%

Breast Cancer

• Relapse risk prediction • Therapy monitoring

• Patient Benefit: • Over and Under treatment

avoided • Early information to

patients on effect of initial treatment

Pancreatic

• Early, accurate detection • Risk group screening

opportunity

• Patient Benefit: • 90% high confidence “Clean bill of health” • Increased Detection in

treatable state • Removing today's

uncertainty in diagnosis accuracy

Lupus

• Early, accurate detection • Flare prognosis

• Patient benefit • Early treatment reduce

severity of symptoms • Previously misdiagnosed

with SLE get proper clinical management

Source: American Cancer Society

The Importance of Early DetectionPancreatic cancer

5 Year Survival rate is 1-3%,

35.000 deaths per year in US

only

A study* 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 small pancreaticadenocarcinoma. A collective study. Cancer 1996; 78:986-90. [PMID8780535]

No diagnostic test for early detection of pancreatic cancer available on the market

Clinical & Regulatory Development

0-12 Months

• Launch Pancreatic Clinical trial, Scandinavia

• Launch Breast Cancer Clinical trial, US

• Launch Lupus Clinical trial, Scandinavia

12-24 Months

• Establish disease specific KOL network as part of multisite Validation Studies

• First product related revenue (Scandinavia)

24-48 Months

• Complete clinical studies, register Pancreatic. CE mark and product release

• Complete clinical studies breast cancer

• Complete clinical studies Lupus. CE mark and release.

48-60 months

• FDA registration and release of Breast product

• US registration time and cost intensive • Outsourcing to CRO

Breast cancer US registration principal

focus

• Clinicals more rapid (24m) and less costly due to devastating nature of pancreatic cancer. Outsourcing to CRO

• Rapid market penetration possible, first in Scandinavia and EU

Pancreatic cancer product enable early

revenues

Key Selling Arguments

• No accurate tests exist today for Pancreatic cancer and Lupus Detection of difficult to diagnose diseases

• No Test to monitor breast patients after mastectomy exist today • Monitoring of disease progression • Monitoring of therapy efficacy in individual patients

Avoiding over- and under- treatment

• Less invasive, less patient stress compared to biopsies • Suited for serial sampling

Blood based sampling

• Enable more rapid inclusion in patient treatment plans Rapid turn around of test results

Market Introduction

• Initially Pancreatic and Lupus initially in Scandinavia, using KOL network, followed by EU.

• Breast Cancer clinical trials in US for US introduction • Distribution agreements for EU and NA • Pre Market Companion Diagnostics agreements possible

Market Introduction

• Penetration rate based on OncoType actuals first 4 years • 2-3 tests per patient as opposed to one give hockey stick

revenue • With time additional tests at 12, 24 months can be added.

Market penetration

• Price Point applicable for Service Lab Test Model • Lower than Oncotype DX at $3820 per test, but several

tests per patient • Genomic Health has successfully developed the

reimbursement environment for this type of diagnostics

Price-Point at $2000 per test

Breast Cancer: Treatment tree

Sample0 0 months, surgery

Determines High or Low relapse

risk, using Sample0 and 6)

6 Months, Relapse Risk

Test

• High Risk Group monitors treatment

• Low Risk Group: monitors healthiness

12 Months Metastasis

Test

• High Risk Group monitors treatment

• Low Risk Group: monitors healthiness

24 Months Metastasis

Test

Three Immunovia tests per patient over 24 month treatment period

• Hereditary • Middle aged diabetes onset

Risk Group Screening

Discriminates between pancreatic cancer and pancreatitis

Diagnosis Monitoring of operable patients

Treatment monitoring

Pancreatic cancer: Treatment tree

Symptoms

Ultra sound

CT/MR

CT Pancreas

ERCP InOP 85%

Blood analysis

Adjuvant chemo

OP 15%

20 months median survival

Chemo

6-7 months median survival

Untreated

3-4 months median survival

Three Immunovia test situations

Lupus: Clinical Decision Tree

onset

Several years > 1 year

Clinical

SLE test solves issues of misdiagnosis / untreated for years No other disease specific markers, nor blood or urine based tests exist

Diagnosis

Classification test solves issue of non-optimized therapy used

Classification

Flares test (disease activity) offer prediction for timely symptom treatment and prevention

Prognosis

Three Immunova test situations

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.

Ian humphrey smith innoiva presentation

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