CanAssist-Breast: New test for prediction of risk of recurrence in ER+/Her2- early stage breast cancer patients Manjiri Bakre, Ph.D.

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1 CanAssist-Breast: New test for prediction of risk of recurrence in ER+/Her2- early stage breast cancer patients Manjiri Bakre, Ph.D. Founder and CEO OncoStem Diagnostics Pvt. Ltd.

2 Treatment Decision: HR+/HER2- patients Which early stage ER+/PR+/HER2- patients need Chemotherapy? Multigene tests: Have helped breast cancer patients 8 th Edition of AJCC Staging System Anatomic Stage Group -Purely TNM based Prognostic stage Group - TNM stage + (tumor grade, HER2, ER, PR status; and multigene panel) OncoStem Diagnostics Pvt Ltd Confidential 2

3 Unmet Need: Our goal A test : Developed & validated in Asian patients: Younger at onset Biomarkers beyond proliferation: CT benefit Uses machine learning based Statistical algorithm Cost-effective and simple CanAssist-Breast ER+, HER2- patients in Stage 1 and 2 OncoStem Diagnostics Pvt Ltd Confidential 3

4 CanAssist-Breast: Morphometric IHC test IHC: 5 Biomarkers Strong Science based, Signaling pathways in tumor recurrence At OncoStem Proprietary Machine Learning Statistical Algorithm CanAssist-Breast Risk Score Morphometric Analysis: 3 Clinical Parameters: Tumor Size, Grade & Node status From hospital Low Risk For Recurrence High Risk OncoStem Diagnostics Pvt Ltd Confidential 4

5 Role of CanAssist-Breast Biomarkers Steps in cancer progression 5 CAB Biomarkers CD44 ABCC4 / ABCC11 Cancer in duct Epithelial-mesenchymal transition (EMT) Loss of cell-cell adhesion, dissociation 1) CD44 RhoA / ROC / RAS Signaling domain / lipid raft Invasion Extravasation /Mesenchymal epithelial transition (MET) Chemotherapy resistance Distant metastasis 2) N-Cadherin 3) Pan Cadherin 4) ABCC 4 5) ABCC 11 RAF MEK MAPK Cadherins PI3K AKT FAK Self renewal, loss of cell adhesion, migration, invasion, drug resistance, EMT/MET lead to METASTASIS OncoStem Diagnostics Pvt Ltd Confidential 5

6 CanAssist-Breast Development: Training Set Patient Cohort: 298 samples Age > T1 41 Tumor Size T2 230 T3 27 N0 122 Node Status N1 107 N2 69 Grade Well differentiated 22 Moderately Differentiated 150 Poorly Differentiated 126 ER+/PR+ 227 Hormone Receptor Status ER+/PR- 49 ER-/PR+ 22 Median 5.8 Years Follow up Maximum 10.6 Years Minimum 5 Years OncoStem Diagnostics Pvt Ltd Confidential 6

7 EGAPP Guidelines For Laboratory Developed Test (LDT) Evaluation of Genomic Applications in Practice and Prevention Analytical Validity Clinical Validity Clinical Utility CAB is reproducible and repeatable High concordance on: Inter-operator, Inter-run, Intra-run, Inter-observer, Intra-observer Inter-lot Clinical validation on 850+ patients CAB is Prognostic and predictive Further validation is ongoing CAB used on 250+ patients to prognose risk of recurrence Prospective study planned OncoStem Diagnostics Pvt Ltd Confidential 7

8 Clinical Validation Cohort Age Tumor Size Node Status Grade Hormone Receptor Status Ki67 Follow up Chemotherapy details Patient Cohort: 857 samples < > T1 240 T2 560 T3+T4 57 N0 486 N1 277 N2/N3 94 Well differentiated 80 Moderately Differentiated 450 Poorly Differentiated 327 ER+/PR+ 689 ER+/PR- 155 ER-/PR+ 13 Ki 67 < 14% 433 Ki 67 > 14% 424 No info 1 Median 5.5 Years Maximum 8.5 Years Minimum 5 Years Chemotherapy naive 195 Chemotherapy treated 662 OncoStem Diagnostics Pvt Ltd Confidential 8

9 Risk Stratification Using CanAssist-Breast Total validation cohort HT alone cohort % D M F S C A B L o w -R is k C A B H ig h -R is k n = 8 5 7, P < % 84% % D M F S C A B L o w -R is k C A B H ig h -R is k n = 1 9 5, P = % 80% T im e in m o n t h s T im e in m o n t h s # at risk # at risk CanAssist-Breast: No intermediate zone. HT=Hormone Therapy OncoStem Diagnostics Pvt Ltd Confidential 9

10 CanAssist-Breast: Independent predictor of prognosis Covariate Hazard ratio p-value 95% CI Age ER PR CT treatment CAB risk score 3.39 < CanAssist-Breast is an independent predictor of prognosis with significant Hazard Ratio OncoStem Diagnostics Pvt Ltd Confidential 10

11 % D M F S CanAssist-Breast: Chemotherapy benefit CAB Low-risk CAB High-risk % 94% 9 0 % D M F S T a m o n ly T a m + C T T a m o n ly T a m + C T 75% 5 0 n = 4 1 5, P = n = 7 1, P = # at risk T im e in m o n t h s # at risk T im e in m o n t h s Tam=Tamoxifen Chemotherapy benefit for High-Risk patients only OncoStem Diagnostics Pvt Ltd Confidential 11

12 % D M F S % D M F S CanAssist-Breast: Useful in < or > 45 years patients <45 years age cohort > 45 years age cohort C A B L o w ris k C A B H ig h ris k 5 0 n = 1 8 3, p = C A B L o w ris k C A B H ig h ris k n = 6 7 4, p < T im e in m o n th s T im e in m o n th s CanAssist-Breast is useful in younger or older patients. OncoStem Diagnostics Pvt Ltd Confidential 12

13 % D M F S CanAssist-Breast: Useful in N- or N+ patients Node negative cohort Node positive cohort C A B L o w -R is k C A B H ig h -R is k n = 4 8 6, P = % 88% % D M F S C A B L o w -R is k C A B H ig h -R is k n = 3 7 1, P = % 82% # at risk T im e in m o n t h s # at risk T im e in m o n t h s CanAssist-Breast is useful in node negative and positive patients OncoStem Diagnostics Pvt Ltd Confidential 13

14 Oncotype Dx Vs CanAssist-Breast Head to head study with Oncotype Dx 60% - low-risk by Oncotype Dx 82% - low-risk by CanAssist-Breast OncoStem Diagnostics Pvt Ltd Confidential 14

15 Oncotype Dx Vs. CanAssist-Breast Oncotype Dx and CanAssist-Breast have: 80% concordance on low-risk stratification 90% agreement on no-recurrence outcomes 85% of ODx intermediate-risk stratified as low-risk by CAB OncoStem Diagnostics Pvt Ltd Confidential 15

16 Regulatory Approvals for CanAssist-Breast CE Mark ISO NABL Under review for: 1) US-FDA 510 (k) for CanAssist-Breast 2) US- CAP for the laboratory OncoStem Diagnostics Pvt Ltd Confidential 16

17 Conference Presentations Molecular Biomarkers, Canada 2015 Controversies in breast cancer, Spain 2016 ICC, India 2017 ABSICON, India 2016 SABC, US 2017 OncoStem Diagnostics Pvt Ltd Confidential 17

18 Conference and Publications OncoStem Diagnostics Pvt Ltd Confidential 18

19 Summary of CanAssist-Breast Effective recurrence predictor in Stage I / II, node negative and positive diseased patients in younger patients as well. Test includes 3 clinical parameters + 5 biomarkers, & is globally validated. Will bring out targeted drugs in future. Has 80% concordance with Oncotype Dx Quick and cost effective option for Asia and Middle East. Will reduce overall cost of Breast Cancer management, Improve QOL. OncoStem Diagnostics Pvt Ltd Confidential 19

20 Thank you! OncoStem Diagnostics Pvt Ltd Confidential 20

21 Thank you

22 Clinical Advisory Board Dr. Mark Pegram, MD : Program Director, Breast Cancer Program, Stanford University Over 35 years of experience in cancer care Dr. Sudeep Gupta, DM : Professor of Medical Oncology, Tata Memorial Hospital, Deputy Director- ACTREC, Mumbai Over 20 years of experience in cancer care Dr. Harit Chaturvedi, M.Ch : Chairman Cancer Care, Director & Chief Consultant - Surgical Oncology Over 30 years of experience in cancer care OncoStem Diagnostics Pvt Ltd Confidential 22

23 Hospital Partners India: Bangalore: Manipal hospital, HCG, MSCC and BBH Ahmedabad -HCG Mumbai: Tata Memorial Hospital and Jaslok hospital Delhi: RGCI and Max hospital Apollo Hospitals: via Sapien Biosciences Coimbatore: GKNM Hospital International: USA Drexel University Medical Center, Philadelphia, USA Virtua Hospital, New Jersey, USA Stanford University, USA: In discussion Europe Vall D Hebron - Spain OncoStem Diagnostics Pvt Ltd Confidential 23