Personalis, Inc. · NASDAQ:PSNL
Personalis — ESMO Congress 2023
15 slides from Personalis's conference presentation, Oct 21, 2023
Slide 1: Ultra-sensitive ctDNA assay provides novel pre-operative disease stratification in early stage lung cancer
An ultra-sensitive and specific ctDNA assay provides novel pre-operative disease stratification in early stage lung cancer TRACERx: NCT01888601 James R. M. Black M.D. PhD Postdoctoral Clinical Fellow, Francis Crick Institute Madrid, 21/10/2023
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Dr James Black: Data and analysis presented here was supported in part by funding from Personalis Inc. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Slide 3: Circulating tumour DNA
Circulating tumour DNA - Often comprises tiny fraction of cell-free DNA - Stratifies patients for outcome pre and post- operatively - Minimal residual disease can predict relapse prior to imaging ctDNA detection: requirements - High sensitivity - High specificity - Low input amounts - Applicable acr
Slide 4: ctDNA in TRACERx lung
ctDNA in TRACERx lung First generation tumour-informed ctDNA assays 16 variant personalised panel: LOD95* 50 variant personalised panel: LOD95* ~0.01% VAF (100 PPM) ~0.008% VAF (~80 PPM) OS in adenocarcinoma (LUAD) Presence of ctDNA within pre- operative plasma sample predicts poor OS in adenocarcin
Slide 5: NeXT Personal: ultra-sensitive ctDNA detection
NeXT Personal: ultra-sensitive ctDNA detection - Tracks ~1,800 mutations per patient - LOD95* of 3.76 PPM (0.00037% ctDNA fraction) - Simulations suggest LOD < 10 PPM (0.001% ctDNA fraction) with 1ng DNA input - Estimated specificity 99.98% *LOD95: Content of this presentation is copyright and respo
Slide 6: Cohort overview
Cohort overview - Early-stage NSCLC patients enrolled in TRACERx - Surgery with curative intent - 48% of patients received adjuvant treatment; nil neo- adjuvant treatment - Analysis of blood plasma collected at pre-operative timepoint - Median follow-up of 5 years
Slide 7: Pre-operative detection of ctDNA using NeXT Personal
Pre-operative detection of ctDNA using NeXT Personal LUAD Non-LUAD - ctDNA detected from 1.7 to 253,826 PPM - Pre-operative ctDNA detected in 81% of LUAD and 100% of non-LUAD patients - Includes 52% of pTNM stage I LUAD patients
Slide 8: Patient stratification with pre-operative ctDNA: adenocarcinomas
Patient stratification with pre-operative ctDNA: adenocarcinomas ctDNA status independently predicts RFS and OS 5-year 5-year RFS OS ctDNA negative 94% 100% Below-median 33.3% 59.8% ctDNA Above-median 31.7% 46.6% ctDNA ctDNA low: HR=13.7, 95% CI:1.8-105.8 ctDNA low: HR=9.1 95% CI:1.1-72.5 ctDNA high
Slide 9: Patient stratification with pre-operative ctDNA: non-adenocarcinomas
Patient stratification with pre-operative ctDNA: non-adenocarcinomas ctDNA status independently predicts RFS 5-year 5-year RFS OS ctDNA negative NA NA Below-median 64.1% 69.0% ctDNA Above-median 38.9% 50.3% ctDNA ctDNA high: HR=2.1, 95% CI: 1.0-4.4 ctDNA high: HR=2.0, 95% CI:0.98-4.2 HRs adjusted in
Slide 10: Adenocarcinoma with ultra-low pre-operative ctDNA levels
Adenocarcinoma with ultra-low pre-operative ctDNA levels Patients below 95LOD of assay used in Abbosh et al. 2023 (80 PPM ctDNA) stratified for RFS and OS by NeXT Personal NeXT Personal identifies ultra low-risk group of adenocarcinomas Abbosh et al., 2023, Nature Zhou et al., 2023, Mol Diagn Ther.
Slide 11: Future plans in TRACERx
Future plans in TRACERx Preliminary data from post-operative timepoints PPV NPV Sensitivity Specificity ctDNA PPM (IQR) - Planned analysis of ~450 TRACERx patients ongoing Landmark (n=123) 89% 69% 54% 94% 239 (21-1547) - Approximately 4200 plasma samples being analysed Landmark 90% 58% 46% 94% 159 (
Slide 12: NeXT Personal Landmark Performance
NeXT Personal Landmark Performance Surgery Recurrence on ❖ Best overall landmark performance to date in +/ - Adjuvant Imaging TRACERx cohort 331 days median lead time to recurrence(NeXT Personal) ❖ Landmark in NSCLC is challenging because of ultra-low ctDNA levels after surgery +/- adjuvant 228 days
Slide 13: NeXT Personal Longitudinal Performance
NeXT Personal Longitudinal Performance Surgery +/ - Adjuvant Recurrence on ❖ Exceptional lead time over imaging Imaging detection, with a median ~6 month lead time 173 days median lead time to recurrence(NeXT Personal) 119 days (Abbosh ‘23) ❖ NeXT Personal median lead time is ~2-3 70 days (Abbosh ‘1
Slide 14: Summary
Summary • Ultra-sensitive ctDNA detection identifies pre-operative ctDNA in 81% of patients with LUAD, including 52% of Stage I’s • High ctDNA level predicts poor OS and RFS in LUAD and RFS in non-LUADs • Added sensitivity is clinically meaningful: ultra-sensitive detection below 80 PPM (95LOD of ap
Slide 15: Acknowledgements
Acknowledgements Patients and families Swanton Lab McGranahan Lab Jamal-Hanjani Lab Chris Abbosh Personalis Charlie Swanton Nicky McGranahan Mariam Jamal-Hanjani Allan Hackshaw Richard O. Chen Alex Frankell Piotr Pawlik Wing Kin-Liu Jacqui Shaw Gabor Bartha Chris Bailey Kerstin Thol Charles Abbott M