Castle Biosciences, Inc. · NASDAQ:CSTL
Castle Biosciences — Technical Presentation (2021)
37 slides from Castle Biosciences's technical presentation, 2021
Slide 1: TissueCypher Objectively Risk Stratifies Barrett's Esophagus Patients with Low-Grade Dysplasia
TissueCypher Objectively Risk Stratifies Barrett’s Esophagus Patients with Low-Grade Dysplasia N.F. Frei1, A.M. Khoshiwal1, K. Konté1, R.E. Pouw1, F. Ten Kate2, C.A. Seldenrijk3, J. Offerhaus2, J.R. Goldblum4, J.M. Davison5, E. Montgomery6, SURF study pathologists consortium, E. Bossart7, R. Critchl
Slide 2: Disclosures
Disclosures This study was partially funded by Cernostics EA Bossart: Ownership interest in Cernostics (stock options) RJ Critchley-Thorne: Ownership in Cernostics (stock, stock options and patents) DDW 2021
Slide 3: Risk stratification in Barrett's surveillance
Risk stratification in Barrett’s surveillance • Is based on histological review of surveillance biopsies by pathologists • Low-grade dysplasia (LGD) is the best predictor of malignant progression DDW 2021
Slide 4: Diagnosing LGD in Barrett's is challenging
Diagnosing LGD in Barrett’s is challenging • High inter-observer variability for the histological diagnosis of LGD • Guidelines: LGD biopsies should be reviewed by an expert pathologist • LGD is overdiagnosed in 50-75% of the community based diagnoses • Such overdiagnosed cases do not have an increa
Slide 5: Problems with pathology review of LGD cases
Problems with pathology review of LGD cases • It is unclear what defines an “expert pathologist” • Access to an expert pathologist is not widely available • Logistical challenges in transferring slides for such review DDW 2021
Slide 6: We need an objective and easily accessible tool
We need an objective and easily accessible tool • TissueCypher Barrett’s Esophagus Assay is a commercially available, objective precision medicine tool for patients with Barrett’s Esophagus (BE) • An automated assay of 4 standard histology slides • Automated labeling and imaging for multiple (9) imm
Slide 7: How does TissueCypher work?
How does TissueCypher work? DDW 2021
Slide 8: Four 5-micron sections from standard BE biopsies
Four 5-micron sections from standard BE biopsies 4 slides for immunofluorescence staining (4 biomarkers per slide, incl. controls) DDW 2021
Slide 9: Automated Multiplexed Whole Slide Immunofluorescence Scanning
Automated Multiplexed Whole Slide Immunofluorescence Fluorescence Scanning Labeling of 9 Biomarkers COURTESY OF C/ASTLE DDW 2021 BIOSCIENCES.
Slide 10: TissueCypher Image Analysis
Automated Multiplexed Whole Slide TissueCypher Immunofluorescence Fluorescence Scanning Image Analysis Labeling of 9 Biomarkers 15 Features automatically extracted by image analysis software COURTESY OF C/ASTLE DDW 2021 BIOSCIENCES
Slide 11: TissueCypher Risk Classifier and Risk Score
Automated Multiplexed Immunofluorescence Labeling of 9 Biomarkers Whole Slide Fluorescence Scanning TissueCypher Image Analysis 15 Features automatically extracted by TissueCypher Risk Classifier 15 Features Scaled & Weighted* v Risk Score* image analysis T Low Risk inter Risk High Risk software (0-
Slide 12: TissueCypher has been extensively studied
TissueCypher has been extensively studied • 5 peer-reviewed publications in high impact journals over the last 5 years • All showing that TissueCypher can predict malignant progression in BE biopsies • Case-control studies, not yet studied in a ‘true’ cohort study • Not yet specifically studied for
Slide 13: Aim
Aim • To evaluate the predictive value of TissueCypher in a cohort of 155 BE patients with a community-based diagnosis of LGD • To benchmark its performance against a panel of 12 pathologists from the Netherlands and the US • Including pathologists with a track record as “expert BE pathologist” DDW
Slide 14: A cohort of 155 BE patients with LGD
A cohort of 155 BE patients with LGD • Derived from the screening cohort of the SURF trial: a RCT comparing Surveillance versus RFA for confirmed LGD (Phoa et al. JAMA 2014). • All biopsies of the baseline LGD-endoscopy • 5-micron slides cut and assessed by TissueCypher • “Sandwich slides” (2 H&E sl
Slide 15: All biopsies reviewed by 12 pathologists
All biopsies reviewed by 12 pathologists • Six EXPERT pathologists (3 from the Netherlands, 3 from the US) • Special interest in the field of Barrett's esophagus for over 10 years • Minimum case load of 5-10 mainly dysplastic cases per week • Co-authored >10 peer-reviewed publications in the field o
Slide 16: 155 patients with a community-based diagnosis of LGD
155 patients with a community-based diagnosis of LGD • 79% males, median age 62 ± 10 years, median Barrett’s length C3M4 • Median follow-up of 7.0 years (IQR 4.4 - 9.7) • Mean number of 3 ± 2 endoscopies • 25 developed HGD/EAC within 5 years (progressors) • 130 did not progress to HGD/EAC within 5 y
Slide 17: How did our panel review the baseline biopsies?
How did our panel review the baseline biopsies? Dutch Dutch expert US expert US community- community-based pathologists pathologists based pathologists pathologists Downstaged to NDBE, (%) 60.0 (52.3 - 71.6) 76.8 (72.9 - 82.6) 59.4 (34.2 - 72.9) 44.3 (12.9 – 72.9) IND, (%) Confirmed LGD, (%) 23.0 (1
Slide 18: How did our panel review the baseline biopsies?
How did our panel review the baseline biopsies? Dutch Dutch expert US expert US community- community-based pathologists pathologists based pathologists pathologists Downstaged to NDBE, (%) 60.0 (52.3 - 71.6) 76.8 (72.9 - 82.6) 59.4 (34.2 - 72.9) 44.3 (12.9 – 72.9) IND, (%) Confirmed LGD, (%) 23.0 (1
Slide 19: How did our panel review the baseline biopsies?
How did our panel review the baseline biopsies? Dutch Dutch expert US expert US community- community-based pathologists pathologists based pathologists pathologists Downstaged to NDBE, (%) 60.0 (52.3 - 71.6) 76.8 (72.9 - 82.6) 59.4 (34.2 - 72.9) 44.3 (12.9 – 72.9) IND, (%) Confirmed LGD, (%) 23.0 (1
Slide 20: How did our panel review the baseline biopsies?
How did our panel review the baseline biopsies? Dutch Dutch expert US expert US community- community-based pathologists pathologists based pathologists pathologists Downstaged to NDBE, (%) 60.0 (52.3 - 71.6) 76.8 (72.9 - 82.6) 59.4 (34.2 - 72.9) 44.3 (12.9 – 72.9) IND, (%) 17.0 (11.6 -21.3) 5.8 (3.2
Slide 21: Do expert pathologists do a better job?
Do expert pathologists do a better job? Expert pathologists Community-based pathologists (n=6) (n=6) Downstaged to NDBE, (%) 68.4 (52.3 – 82.6) 47.6 (12.9 – 72.9) IND, (%) 11.4 (3.2 – 21.3) 25.8 (7.9 –74.2) Confirmed LGD, (%) 20.2 (14.2 – 29.7) 22.1 (10.5 - 40.6) Progression to HGD or cancer during
Slide 22: Do expert pathologists do a better job?
Do expert pathologists do a better job? Expert pathologists Community-based pathologists (n=6) (n=6) Downstaged to NDBE, (%) 68.4 (52.3 – 82.6) 47.6 (12.9 – 72.9) IND, (%) 11.4 (3.2 – 21.3) 25.8 (7.9 –74.2) Confirmed LGD, (%) 20.2 (14.2 – 29.7) 22.1 (10.5 - 40.6) Progression to HGD or cancer during
Slide 23: Do expert pathologists do a better job?
Do expert pathologists do a better job? Expert pathologists Community-based pathologists (n=6) (n=6) Downstaged to NDBE, (%) 68.4 (52.3 – 82.6) 47.6 (12.9 – 72.9) IND, (%) 11.4 (3.2 – 21.3) 25.8 (7.9 –74.2) Confirmed LGD, (%) 20.2 (14.2 – 29.7) 22.1 (10.5 - 40.6) Progression to HGD or cancer during
Slide 24: Do expert pathologists do a better job?
Do expert pathologists do a better job? Expert pathologists Community-based pathologists (n=6) (n=6) Downstaged to NDBE, (%) 68.4 (52.3 – 82.6) 47.6 (12.9 – 72.9) IND, (%) 11.4 (3.2 – 21.3) 25.8 (7.9 –74.2) Confirmed LGD, (%) 20.2 (14.2 – 29.7) 22.1 (10.5 - 40.6) Progression to HGD or cancer during
Slide 25: How did TissueCypher perform here?
How did TissueCypher perform here? 25 patients progressed to 155 patients TissueCypher HGD/EAC within community-based LGD 5-yr follow-up Low-risk score (<5.5) 110 (71.0%) 8 (7.3%) Intermediate risk (5.5-6.4) 24 (15.5%) 7 (29.2%) High-risk (>6.4) 21 (13.5%) 10 (47.6%) • TissueCypher downstaged the ma
Slide 26: How did TissueCypher perform here?
How did TissueCypher perform here? 25 patients progressed to 155 patients TissueCypher HGD/EAC within community-based LGD 5-yr follow-up Low-risk score (<5.5) 110 (71.0%) 8 (7.3%) Intermediate risk (5.5-6.4) 24 (15.5%) 7 (29.2%) High-risk (>6.4) 21 (13.5%) 10 (47.6%) • TissueCypher downstaged the ma
Slide 27: How did TissueCypher perform here?
How did TissueCypher perform here? 25 patients progressed to 155 patients TissueCypher HGD/EAC within community-based LGD 5-yr follow-up Low-risk score (<5.5) 110 (71.0%) 8 (7.3%) Intermediate/high-risk (>5.5) 45 (29.0%) 17 (37.8%) • TissueCypher identified 17/25 progressors: sensitivity 68% • Tissu
Slide 28: How does TC compare to the 12 pathologists?
How does TC compare to the 12 pathologists? TissueCypher Pathologists Progression within 5 years Intermediate/high-risk LGD+IND vs. NDBE LGD vs. IND+NDBE vs. low risk score Sensitivity 68.0% 67.1% (52.0-84.0) 52.8% (40.0-68.0) Specificity 78.5% 65.4% (12.3-89.2) 85.1% (62.3-95.3) DDW 2021
Slide 29: How does TC compare to the 12 pathologists?
How does TC compare to the 12 pathologists? TissueCypher Pathologists Progression within 5 years Intermediate/high-risk LGD+IND vs. NDBE LGD vs. IND+NDBE vs. low risk score Sensitivity 68.0% 67.1% (52.0-84.0) 52.8% (40.0-68.0) Specificity 78.5% 65.4% (12.3-89.2) 85.1% (62.3-95.3) DDW 2021
Slide 30: How does TC compare to the 12 pathologists?
How does TC compare to the 12 pathologists? TissueCypher Pathologists Progression within 5 years Intermediate/high-risk LGD+IND vs. NDBE LGD vs. IND+NDBE vs. low risk score Sensitivity 68.0% 67.1% (52.0-84.0) 52.8% (40.0-68.0) Specificity 78.5% 65.4% (12.3-89.2) 85.1% (62.3-95.3) DDW 2021
Slide 31: TissueCypher vs. Expert vs. Community-based pathologist
TissueCypher vs. Expert vs. Community-based pathologist Perfect test
Slide 32: TissueCypher vs. Expert vs. Community-based pathologist
TissueCypher vs. Expert vs. Community-based pathologist LGD+INDvs. LGD+IND vs.NDBE NDBE LGD vs. IND+NDBE TissueCypher
Slide 33: TissueCypher vs. Expert vs. Community-based pathologist
TissueCypher vs. Expert vs. Community-based pathologist LGD+IND vs. NDBE LGD LGDvs. vs.IND+NDBE IND+NDBE TissueCypher TissueCypher
Slide 34: Risk prediction of LGD in Barrett's
Risk prediction of LGD in Barrett’s • Is mandatory for all cases with a community-based LGD diagnosis • Majority of cases will be down-staged to NDBE with low risk of progression • It identifies a subgroup with a high-risk of malignant progression DDW 2021
Slide 35: Risk prediction of LGD in Barrett's
Risk prediction of LGD in Barrett’s • Is mandatory for all cases with a community-based LGD diagnosis • Majority of cases will be down-staged to NDBE with low risk of progression • It identifies a subgroup with a high-risk of malignant progression • Conventional pathology review has significant limi
Slide 36: Risk prediction of LGD in Barrett's
Risk prediction of LGD in Barrett’s • Is mandatory for all cases with a community-based LGD diagnosis • Majority of cases will be down-staged to NDBE with low risk of progression • It identifies a subgroup with a high-risk of malignant progression • Conventional pathology review has significant limi
Slide 37: Thank you for your attention
Thank you for your attention DDW 2021