Grail, Inc. · NASDAQ:GRAL
Grail — Technical Presentation (September 2022)
22 slides from Grail's technical presentation, Sep 11, 2022
Slide 1: PATHFINDER: A Prospective Study of a Multi-Cancer Early Detection Blood Test
PATHFINDER: A Prospective Study of a Multi-Cancer Early Detection Blood Test Deb Schrag, MD, MPH Tomasz M. Beer, MD Lincoln Nadauld, MD, PhD Christina A. Dilaveri, MD Robert Reid, MD Eric A. Klein, MD Karen C. Chung, PharmD Catherine R. Marinac, PhD Margarita Lopatin, MS Charles H. McDonnell, MD Eri
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Deb Schrag, MD, MPH Chair, Department of Medicine, Memorial Sloan Kettering Cancer Center New York, NY USA Study was funded by GRAIL, LLC, a subsidiary of Illumina, Inc.* Presenting Author Disclosures: Uncompensated advisory role (GRAIL, LLC*); research funding (GRAIL, LLC*
Slide 3: Background: Multi-Cancer Early Detection (MCED) Blood Assays
Background: Multi-Cancer Early Detection (MCED) Blood Assays MCED testing uses a targeted methylation, next-generation sequencing (NGS)-based assay to: • Detect and analyze cfDNA in the bloodstream • Deploy machine learning to detect a cancer signal • Predict the likely cancer signal origin (CSO) Ca
Slide 4: PATHFINDER: A Prospective Cohort Study to Return the Results of MCED Tests to Participants
PATHFINDER: A Prospective Cohort Study to Return the Results of MCED Tests to Participants Day 1 Day 15 Adults ≥50 years enrolled MCED test ordered Questionnaire Blood drawn and Test report from 7 US sites into 2 cohorts: for Participantsb shipped generated witha and without additional risk Cancer S
Slide 5: Study Motivation
Study Motivation Understand the Clinical Experience of MCED Testing • Understand the diagnostic evaluations precipitated by receipt of a “signal detected” MCED test • Evaluate MCED test performance characteristics • Understand levels of participant anxiety and distress associated with MCED testing P
Slide 6: PATHFINDER Study Objectives
PATHFINDER Study Objectives Primary Objective Secondary Objectives • Assess extent of diagnostic testing required • Evaluate test performance to achieve diagnostic resolution following a o Specificity “signal detected” test result o Positive Predictive Value (PPV) o Time to diagnostic resolution o N
Slide 7: PATHFINDER Eligibility Criteria
PATHFINDER Eligibility Criteria Inclusion: Exclusion: • Adults ≥50 years who were eligible for either: • Clinical suspicion of malignancy o With Additional Risk Cohort • Undergoing diagnostic evaluation for o Without Additional Risk Cohort malignancy • History of invasive or hematologic • Eligibilit
Slide 8: Participant Characteristics
Participant Characteristics With Additional Without Additional Total Riska Risk N = 6,621 n = 3,681 n = 2,940 Ageb, in years, mean (SD) 64.7 (8.7) 61.6 (8.1) 63.4 (8.6) Female 65% 62% 63% White, Non-Hispanic 93% 89% 92% College Degree or Higher 59% 71% 65% Up to Date With Standard Cancer Screening P
Slide 9: Cancer Signal Detection
Cancer Signal Detection Enrolled With Without N=6,662 Additional Additional Total Riska Risk N = 6,621 Analyzable n = 3,681 n = 2,940 n=6,621 Signal 1.5% 1.2% 1.4% Detected Cancer Signal No Cancer Detected Signal Detected No Signal 98.5% 98.8% 98.6% n=92 n=6,529 Detected aPrevious history of cancer,
Slide 10: Primary Objective: Time to Achieve Diagnostic Resolution
Primary Objective: Time to Achieve Diagnostic Resolution Time to Diagnostic Resolution for Participants with MCED Signal Detected % of Participants with (N=90; not calculable for 2 participants who began Diagnostic Resolution in <3 months diagnostic evaluation before test results returned) 73% TP FP
Slide 11: Primary Objective: Extent of Diagnostic Evaluation
Primary Objective: Extent of Diagnostic Evaluation Extent and Types of Diagnostic Evaluation for Participants with MCED Signal Detected (N=90) TP FP Total % of participants N=33a N=57b N=90a Any imaging procedure, % 91 93 92 Any advanced imaging 88 89 89 (CT, PET, MRI) Any invasive procedure, % 82 3
Slide 12: Safety
Safety • There were no serious, study-related adverse events reported as a result of MCED testing • There were no serious, study-related adverse events due to diagnostic workup prompted by receipt of a “signal detected” MCED test result Deb Schrag, MD, MPH Content of this presentation is copyright a
Slide 13: Secondary Objective: Accuracy of Predicted Cancer Origin
Secondary Objective: Accuracy of Predicted Cancer Origin Test Performance: Ability to Predict Origin of Malignancy TP FP Total Participants, n 35 57 92 Determinate predicted origin 34 53 87 Indeterminate predicted origin 1 4 5 Predicted Origin Accuracy a b First Predicted Origin, n 29/34 % (95% CI)
Slide 14: Cancers Diagnosed After a True Positive MCED Signal
Cancers Diagnosed After a True Positive MCED Signal 35 people were diagnosed 19 Solid Tumors with 36 cancers 17 Hematologic Cancers • 24 in high-risk cohort Plasma Cell Oropharyngeal (n=2) Myeloma/Disorders • 11 in not-high-risk cohort (n=1) Lung (n=1) Breast ♀ (n=5) Lymphoid Leukemia Pancreas (n=1)
Slide 15: Cancers Identified Within One Year of MCED Testing
Cancers Identified Within One Year of MCED Testing Participants with Cancers Detected by Either Screening or Clinical Findings 121 participants had a cancer diagnosis within 1 year 73 80 • 35/121 (29%) had cancer No. of Participants 60 35 MCED 48 diagnosed and positive MCED d 6 Incidental o 2/35 had
Slide 16: Secondary Objective: MCED Test Performance
Secondary Objective: MCED Test Performance Test Performance Metric Result Number Cancer Signal Detected 1.4% 92/6621 a Specificity 99.1% 6253/6290 Positive Predictive Value (PPV) 38.0% 35/92 a Negative Predictive Value (NPV) 98.6% 6235/6321 Number needed to screen to detect one cancer 189 6621/35 Yi
Slide 17: Secondary Objective: Performance of a Refined MCED Test
Secondary Objective: Performance of a Refined MCED Test • The banked specimens were re-analyzed using a refined version of the MCED assay • These results were not returned to participants or their physicians • The refined MCED assay was intended to: o Reduce false positives with hematologic predicti
Slide 18: Secondary Objective: Performance of a Refined MCED Test
Secondary Objective: Performance of a Refined MCED Test Refined Version of MCED Test MCED Test Test Performance Metric (Results Not Returned to Participants or Providers) Results Returned Cancer Signal Detected 0.9% 58/6578 1.4% a Specificity 99.5% 6216/6249 99.1% Positive Predictive Value PPV 43.1%
Slide 19: Conclusions
Conclusions • MCED screening was safely implemented for adults with and without additional cancer risk • 1.4% of participants had a cancer signal detected • 0.5% of participants were diagnosed with cancer due to MCED signal detection • Median time to diagnostic resolution was 79 days • High accuracy
Slide 20: Limitations and Caveats
Limitations and Caveats • It will be important for future clinical utility studies to evaluate whether MCED testing reduces mortality, the primary goal of all cancer screening • Study cohort had limited diversity • 12 month follow-up was incomplete for 3% of the cohort • Further work is needed to un
Slide 21: Future/Ongoing Work
Future/Ongoing Work • Evaluation of MCED screening in cohorts with greater socioeconomic, ethnic and racial diversity • Optimization of test performance characteristics • Ongoing PATHFINDER2 study is screening 20,000 individuals using the refined version of the MCED test • NHS-Galleri (ISRCTN 914315
Slide 22: Thank you to study participants
Thank you to study participants who were recruited from: • Dana Farber Cancer Institute • Sutter Health • OHSU Knight Cancer Institute • US Oncology • Intermountain Healthcare • Cleveland Clinic • Mayo Clinic European Society for Medical Oncology (ESMO) Via Ginevra 4, CH-6900 Lugano T. +41 (0)91 973