Nucleosomics New blood based assays to characterize tumours. Clinical applications of cell free circulating nucleosome profiling

Transcription

1 Nucleosomics New blood based assays to characterize tumours Clinical applications of cell free circulating nucleosome profiling Dr Mark Eccleston III Simposio Biopsia líquida 2018

2 Vision Volition Clinical Focus Approach

3 Rethinking the approach to cancer Nucleosomics represents a powerful step change in detecting cancer Unique Nu.Q TM technology looks for very early nucleosomic markers of cancer A simple solution to a challenging problem Early cancer diagnosis These tests identify early stage cells before the cancer spreads Nu.Q TM uses an array of simple, cost-effective, and accurate blood based assays Just a drop of blood

4 Clincal Focus on Colorectal Cancer (CRC) 97% 5-year survival If diagnosed at stage I 5 yr survival rate for stage IV diagnosis falls to just 7% Globally 700,000 CRC deaths annually < 10% diagnosed at stage I CRC Product Pipeline Nu.Q CRC Screening Test Nu.Q CRC Triage Test Nu.Q CRC Symptomatic Test 3

5 Clinical demand Nucleosomics Technology Platform Example data

6 Blood based testing Improving Compliance Screening = Survival Mortality > 50,000 CRC deaths in the U.S. annually (USPSTF) CRC screen 50 to 75 yrs Screen 80% reduce deaths 33% Screening Participation 58% 30M in U.S. NOT up-to-date with CRC screening 200,000 deaths saved by

7 Recommended CRC Screening 432,000 New CRC cases in Europe p/a 148 million Screening population US recommendations EU mandated screening programs. Organized programs in 14 of 28 EU states, 10 states offering some form of public or privately accessible screening. Asian countries 6

8 Nu.Q - How it works The Nu.Q TM family currently consists of 29 Nu.Q TM blood biomarker assays that fall into 5 main families of double antibody ELISA biomarker assays: 1. Nu.Q TM -X specific DNA modifications 2. Nu.Q TM -V histone variants 3. Nu.Q TM -M histone modifications 4. Nu.Q TM -A nucleosome-protein adducts 5. Nu.Q TM -T total nucleosomes Each captures intact nucleosomes and labels a specific structural feature Capture Antibody HRP Reporter Profiling Antibody Nucleosome 7

9 Easy to implement, low cost ELISA platform Cutting-Edge Science that Leverages Robust, Affordable Test Methods Test Advantages 1. Ease of use 2. Existing instrumentation already in most labs 3. Established robust methodology allows for low cost per test, and easy to mass produce 4. Flexible to be run in any clinical setting - Manual ELISA - Automated ELISA - Point of Care 5. Small amount of blood required from patient 8

10 Nucleosomics - Adenoma Trial Blinded 530 patient retrospective study in colorectal adenomas and CRC Evaluated expanded 13 NuQ assay repertoire capability to: Improve precancerous polyp/adenoma detection. Improve early stage colorectal cancer detection Diagnosis No of patients Mean Age (range) Male:Female Adenoma (24.0 to 88.8) 133:113 High Risk Low Risk (24.0 to 88.5) 62.7 (27.2 to 88.8) 93:79 40:34 CRC (42.1 to 91.8) 51:47 Stage I (49.2 to 91.8) 27:22 Stage II (42.1 to 88.4) 24:24 No Evidence of Disease (21.0 to 91.3) 72:114 9

11 4 normalised NuQ assays in age-adjusted algorithm Box plot 1: Optimised for CRC vs No Evidence of Disease (Model 1). Box plot 2: Optimised for Adenomas vs No Evidence of Disease (Model 2). 10

12 Optimize for CRC or Adenoma Detection Linear models, based on weighted sum of 1 to 5 variables, were developed using Linear Discriminant Analysis (LDA) Diagnosis Model 1 Model 2 (CRC trained) (Adenoma trained) Adenoma High risk Low risk CRC Stage I Stage II Sensitivity at 80% specificity 11

13 Nucleosomics - CRC Prospectiove Trials Blinded 58 patient retrospective study in colorectal adenomas and CRC Evaluated 12 Nu.Q TM assay repertoire on: Patients with symptoms suggestive of CRC. High risk individuals. Diagnosis No. of patient Mean Age (range) Male:Female CRC (52-88) 16:7 stage 0-I 4 71 (62-84) 3:1 stage II 7 78 (70-84) 4:3 stage III 7 76 (52-88) 6:1 stage IV 4 80 (75-83) 3:1 Unknown :1 Adenoma (50-88) 10:6 hyperplastic 6 59 (50-68) 1:5 dysplastic (53-82) 9:1 No Evidence of Disease (50-71) 11:9 12

14 4 normalised NuQ assays in age-adjusted algorithm % sensitivity at 90% specificity CRC CEA 4 Nu.Q assays + age All stages Stage I 0 75 Stage II Stage III Stage IV % of high risk polyps Rahier et al Clinical Epigenetics :53 13

15 CRC Clinical trials Screening Triage Symptomatic Pancreatic

16 On going Clinical Trials 15

17 On going Clinical Trials 16

18 Screening Products Diagnostic RUO

19 Colorectal Cancer Pipeline Nu.Q CRC Screening Test EU Anticipated Launch Asia Anticipated Launch U.S. Anticipated Launch Nu.Q CRC Triage Test EU Anticipated Launch Asia Anticipated Launch Nu.Q CRC Symptomatic Test EU Anticipated Launch U.S. & Asia Anticipated Launch 18

20 New for Research Use Only HRP Reporter Nucleosomics Proprietary epigenetic immunoassay platform Determine total level of circulating cell free nucleosomes Profilng ant i body Chromosome DNA strand Nucleosome i DNA wrapped around histones Capture antibody Nu.Q and Nucleosomics are trademarks of Singapore,Volition Pte Limited. All rights reserved. Copyright 2017 VolitionRx Limited. Editeur responsable Gaetan Michel, CEO, Belgian Volition SPRL.Printed in Belgium. 19

21 Thank you Volition Belgian Volition SPRL Parc Scientifique Crealys 22 rue Phocas Lejeune 5032 Isnes Belgium