Grail, Inc. · NASDAQ:GRAL
Grail — Technical Presentation (April 2024)
19 slides from Grail's technical presentation, April 2024
Slide 1: A Targeted Methylation-Based MCED Blood Test Preferentially Detects High-Grade Prostate Cancer and Minimizes Overdiagnosis
A Targeted Methylation-Based MCED Brandon Mahal1; Matthew Margolis2; Earl Hubbell2; Cheng Chen2; Blood Test Preferentially Detects Jeffrey M. Venstrom2; John Abran2; High-Grade Prostate Cancer and Jordan J. Kartlitz2; Alexander W. Wyatt3; Eric A. Klein2 Minimizes Overdiagnosis 1Sylvester Comprehensi
Slide 2: Disclosure Information
Disclosure Information Eric A. Klein, MD I have the following relevant financial relationships to disclose: Employee of GRAIL, LLC, Menlo Park, CA
Slide 3: Overdiagnosis of Prostate Cancer
Overdiagnosis of Prostate Cancer Accounts for 23-42% of all screen-detected cases1 • Indolent disease typically defined as GG1-2, stage I-II Associated harms • Anxiety • Overtreatment • Unnecessary cost • Overuse of healthcare resources Imperative that new screening tests not exacerbate this problem
Slide 4: Multi-Cancer Early Detection (MCED) is a New Screening Paradigm
Multi-Cancer Early Detection (MCED) is a New Screening Paradigm MCED test as a complement to existing standard of care screening, including PSA for prostate Detect many lethal When used at cancers, including Identify signal population level, unscreened potential for: cancers, using origin to direct
Slide 5: Blood-Based MCED Using Targeted Methylation
Blood-Based MCED Using Targeted Methylation No cancer signal detected Cancer signal detected Tumor sheds Blood plasma Targeted Machine Cancer signal cfDNA isolated methylation learning origin predicted fragments into (contains analysis of cfDNAa classifier bloodstream cfDNA (sequencing, fragments) m
Slide 6: Age-Adjusted Prostate Cancer Incidence in the US Overlaps With the MCED Intended Use Population
Age-Adjusted Prostate Cancer Incidence in the US Overlaps With the MCED Intended Use Population MCED Intended Use Population Observed rate per 100,000 persons Age Observed SEER prostate cancer incidence rates by age at diagnosis, 2016-2020. Figure originally published by the National Cancer Institut
Slide 7: Study Objective
Study Objective Assess MCED test performance for detecting prostate cancer in 2 prospective clinical studies Substudy 3 of CCGA1 PATHFINDER2 NCT02889978 NCT04241796 Case-control, observational Prospective, return of results Refine and validate a cell-free DNA-based Evaluate clinical implemen
Slide 8: MCED Test Performance Characteristics
MCED Test Performance Characteristics Substudy 3 CCGA1 PATHFINDER2 Study design Case-control Prospective interventional Number of participants 4077a 6621b Specificity 99.5% 99.1% Overall test sensitivity 51.5%c – Cancer signal origin (CSO) prediction accuracy 88.7% 97% Positive predictive value (PPV
Slide 9: Prostate Cancer Cohorts
Prostate Cancer Cohorts Substudy 3 of CCGA1 PATHFINDER2 Prostate cancer cases 420 18 Age (median, IQR) 65 (59, 70) 65 (58, 70) White, non-Hispanic (%) 85% 89% PSA (median, IQR) 6.53 (4.8-11.2) Not collected CCGA, Circulating Cell-Free Genome Atlas Study; IQR, interquartile range; PSA, prostate-speci
Slide 10: Endpoints
Endpoints MCED test performance • Detectability of prostate cancer − Overall − By Gleason grade group (GG)1 − By clinical stage2 • CSO accuracy* Detectability as a function of Tumor Methylated Fraction (TMeF)* and PSA* Overall survival compared to SEER estimates adjusted for age, stage, and GG
Slide 11: Overall Prostate Cancer Detectability
Overall Prostate Cancer Detectability Substudy 3 of CCGA1 PATHFINDER2 n (%) n (%) Sensitivity 47/420 (11.2) 1/18 (5.6) CSO accuracy 43/47 (91.5) Not calculated CCGA, Circulating Cell-Free Genome Atlas Study; CSO, cancer signal origin. 1Klein et al. Ann Oncol. 2021;32(9):1167-1177. 2Schrag et al. The
Slide 12: Sensitivity of Prostate Cancer Detection By Grade
Sensitivity of Prostate Cancer Detection By Grade Substudy 3 of CCGA (N = 420) Gleason Grade Group Sensitivity (%) GG1 0 28/65 GG2 1.9 GG3 5.1 8/48 GG4 16.7 4/78 0/58 3/157 GG5 43.1 CCGA, Circulating Cell-Free Genome Atlas Study; CSD, cancer signal detected; GG, Gleason grade group.
Slide 13: Sensitivity of Prostate Cancer Detection By Stage
Sensitivity of Prostate Cancer Detection By Stage Substudy 3 of CCGA (N = 420) 22/27 Stage Sensitivity (%) I 3.2 II 4.7 III 14.9 7/47 IV 81.5 3/95 11/235 CCGA, Circulating Cell-Free Genome Atlas Study; CSD, cancer signal detected.
Slide 14: Relationship Between Cancer Detectability, TMeF, and PSA
Relationship Between Cancer Detectability, TMeF,1 and PSA Substudy 3 of CCGA (N = 420) Detected cases: • 34% had PSA < 10 ng/mL • 32% were ≥ GG3 & stage I-III Approximate limit of detection CCGA, Circulating Cell-Free Genome Atlas Study; GG, Gleason grade group; PSA, prostate-specific antigen; TMeF,
Slide 15: Observed Overall Survival of Prostate Cancer Cases Compared to SEER Expected Survival
Observed Overall Survival of Prostate Cancer Cases Compared to SEER Expected Survival SEER expected survival adjusted for age, cancer stage, and grade Substudy 3 of CCGA (N = 420) Not Detected vs SEER Detected vs SEER HR: 0.26 (95% CI 0.104 – 0.533) HR: 0.67 (95% CI 0.323 – 1.21) p-value < 0.05 p-va
Slide 16: Summary of Key Findings
Summary of Key Findings • Overall detection of prostate cancer low − 11.2% in substudy 3 of CCGA − 5.6% in PATHFINDER • CSO accuracy for prostate cancer high (> 90%) • Preferential detection of high-grade and -stage disease − No GG1 cases detected − Few GG2 cases detected (2.1%) − 33% of cases poten
Slide 17: Strengths and Limitations
Strengths and Limitations Strengths • Data from 2 independent clinical studies using the same MCED test classifiers • SEER reference data served as a synthetic control Limitations • Small number of prostate cancer cases and lack of PSA, TMeF, and OS data from PATHFINDER • GG and stage assignment fro
Slide 18: Conclusions
Conclusions A clinically validated targeted methylation-based MCED test preferentially detects high-grade and high-stage clinically significant prostate cancer A cancer signal detected test result with a prostate CSO prediction strongly suggests the presence of aggressive disease and warrants a
Slide 19: Acknowledgments
Acknowledgments Participants in CCGA and PATHFINDER Site investigators and study staff Co-authors for this analysis CCGA, Circulating Cell-Free Genome Atlas.