Tempus Ai, Inc. · NASDAQ:TEM
Tempus Ai — Technical Presentation (2023)
22 slides from Tempus Ai's technical presentation, 2023
Slide 1: Germline Alterations In Patients With Lung Cancer
Germline Alterations In Patients With Lung Cancer Ramaswamy Govindan1, Katie Navo2, Minxuan Huang2, Calvin Chao2, Sumithra Sankararaman1, Kelly Bolton1, Yin Cao1 1Washington University School of Medicine, Saint Louis, MO, 2Tempus Labs Inc, Chicago, IL Presented by: Ramaswamy Govindan, MD Anheuser Bu
Slide 2: Germline alterations are prevalent at 8% across all cancers
Germline alterations are prevalent at 8% across all cancers Prevalence in lung cancer specifically? Background Huang K-L et al, Cell (2018) PRESENTED BY: Ramaswamy Govindan, MD
Slide 3: Pathogenic Germline Variants In 10,389 Adult Cancers (33 Cancer Types)
Pathogenic Germline Variants In 10,389 Adult Cancers (33 Cancer Types) TCGA Germline variants identified, annotated and classified by CharGer pipeline (Characterization of Germline variants) Scott A D et al, Bioinformatics (2019) Cancer Number of % Age at samples Females diagnosis LUAD Lung 518 (5%)
Slide 4: Germline Variants in TCGA
Germline Variants in TCGA ATM BAP1 Lung Adenocarcinoma (LUAD) BRCA1 BRIP1 CHEK2 EXT2 % carriers in LUAD FANCE Pathogenic 3.5% (n=18) FANCG Likely Pathogenic 2.9% (n=15) MLH1 34 Germline variants MSH2 59% are in TSGs and NF1 Oncogenes PALB2 POLE RAD51C RET TP53 VHL Background WRN Huang K-L et al, Cel
Slide 5: Germline Variants in TCGA
Germline Variants in TCGA Lung Squamous Carcinoma (LUSC) ATR BLM BRCA1 BRCA2 % carriers in LUSC Pathogenic 2.6% (n=13) 28 Germline variants BRIP1 Likely Pathogenic 2.8% (n=14) 75% in TSGs and BUB1B Oncogenes CDH1 CHEK2 FANCC PALB2 PMS2 POLD1 RET Background Huang K-L et al, Cell (2018) PRESENTED BY:
Slide 6: Germline Analysis From Never Smokers
Germline Analysis From Never Smokers CharGer classification of germline variants from 160 Never-Smokers and 299 Smokers Enriched in Smokers Enriched in Never Smokers (Suggestive/Significant) (Suggestive/Significant) CDKN1B FANCG FANCF TMEM127 FANCI MUTYH SRY STAT3 Pathogenic and likely pathogenic ge
Slide 7: Primary Objectives Of This Study
7 Primary Objectives Of This Study Ø To explore the association between presence of pathogenic and likely pathogenic germline alterations, as defined by ACMG criteria, in lung cancer patients Ø To compare the frequency of these germline alterations between smokers and never smokers, EGFR mutated vs.
Slide 8: 46 Genes (germline) Explored Within The UK Biobank And Tempus Data Analyses
8 46 Genes (germline) Explored Within The UK Biobank And Tempus Data Analyses APC ATM AXIN2 BMPR1A BRCA1 BRCA2 BRIP1 CDH1 CDKN2A CEBPA CHEK2 EGFR EPCAM ETV6 FH FLCN GATA2 MEN1 MLH1 MSH2 MSH3 MSH6 MUTYH NBN NF2 PALB2 PMS2 POLD1 POLE PTEN RAD1C RAD1D RB1 RET RUNX1 SDHAF2 SDHB SDHC SDHD SMAD4 STK11 TP5
Slide 9: Tempus Tumor-Normal Matching And Multimodal Database
9 Tempus Tumor-Normal Matching And Multimodal Database Tumor-Normal Matching • Sequencing of tumor tissue and a normal sample parallelly • Normal match sequencing allows for identification of incidental germline variants filtered from somatic findings Multimodal database • It contains over 70 petaby
Slide 10: Germline Profiling Methods
10 Germline Profiling Methods Tempus xT Tumor N = 11,740 Normal Match assay Germline Race + Selected for retrospective analysis alteration Histology (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq) Prevalence of pathogenic/likely pathogenic (P/LP) germline alterations as defined b
Slide 11: Germline Variants in 46 genes
Germline Variants in 46 genes UKBB Lung Cancer Samples UKBB 200K WES release (Dec 2020) Exclusion (~8 Million SNVs and 370,000 indels) • Variants/samples with missingness >= 10% • Variants which violate Hardy-Weinberg equilibrium • Samples with low coverage • Samples with low VAF Inclusion • Variant
Slide 12: Demographic Characteristics
12 Demographic Characteristics Tempus Cohort Gender Smoking Status Unknown = 1,321 Median Age Males = 5,871 68 years Non-smokers = 1,574 N = 11,740 N = 11,740 Females = 5,869 Smokers = 8,845 Histology Unknown = 1,030 SCLC = 595 NSCLC = 10,115 N = 11,740 N = 11,740 Race Somatic EGFR Status EGFR mut =
Slide 13: Germline Alterations in Patients with Lung Cancer Tempus Cohort
13 Germline Alterations in Patients with Lung Cancer Tempus Cohort Patients with Pathogenic/Likely Pathogenic Five most prevalent P/LP incidental (P/LP) incidental germline findings germline genes of the total population P/LP alterations (563, 4.8%) BRCA1 (28, CHEK2 0.2%) (40, 0.3%) MUTYH (148, 1.3%
Slide 14: Frequently Altered Genes In Smokers And Never Smokers With Lung Cancer (UKBB)
14 Frequently Altered Genes In Smokers And Never Smokers With Lung Cancer (UKBB) Never smokers with lung cancer (N=198) Smokers with lung cancer (N=1132) % with P/LP germline alterations Most commonly mutated genes in the 46 gene panel Never smokers 4.3% (n=49) Smokers 5.1% (n=10) Results PRESENTED
Slide 15: Germline Alterations in Patients with Lung Cancer: Smokers vs Non-smokers
15 Germline Alterations in Patients with Lung Cancer Smokers vs Non-smokers Tempus Smokers vs Never smokers Percentage patients UK BioBank (UKBB) Smokers vs Never smokers Note - EGFR discovered in smokers (<.1%) vs nonsmokers (0.4%) in Tempus data Results PRESENTED BY: Ramaswamy Govindan, MD
Slide 16: Germline Alterations in Never Smokers with Lung Cancer
16 Germline Alterations in Never Smokers with Lung Cancer EGFR Mutant vs EGFR Wild type Lung Adenocarcinoma Tempus Never smokers (N=1574) EGFR mutated vs EGFR WT Percentage patients Note - Germline EGFR was significant after Results FDR adjustment (q < 0.037) in this population PRESENTED BY: Ramaswa
Slide 17: Germline Alterations in Patients with Lung Cancer: NSCLC vs SCLC
17 Germline Alterations in Patients with Lung Cancer NSCLC vs SCLC Tempus Non-Small Cell Lung Cancer (NSCLC) vs Percentage patients Small Cell Lung Cancer (SCLC) Results PRESENTED BY: Ramaswamy Govindan, MD
Slide 18: Commonly Altered Germline Genes in Patients with EGFR mutant Lung Cancer
18 Commonly Altered Germline Genes in Patients with EGFR mutant Lung Cancer Tempus NSCLC (N=10115) EGFR mutated vs EGFR WT NSCLC Germline EGFR was significant after FDR adjustment (q < 0.001) Percentage patients Results PRESENTED BY: Ramaswamy Govindan, MD
Slide 19: Limitations To Be Addressed In Future
19 Limitations To Be Addressed In Future Ø This analysis included 46 genes of common hereditary genes, larger panels may enable the capture of more patients 46 hereditary gene panel in this study < Larger panel capturing more patients Ø This analysis lacked zygosity assessment of MUTYH Ø This analys
Slide 20: There Are No Current Guidelines For Those With Lung Cancer Or Germline EGFR Alterations
20 There Are No Current Guidelines For Those With Lung Cancer Or Germline EGFR Alterations Ø Identification of germline findings in lung cancer patients can transcend other cancer types and have clinical implications for both the patient and family Ø Germline EGFR alterations do not have screening g
Slide 21: Key Takeaways
21 Key Takeaways Germline Race 1. The largest analysis of germline alteration alterations in cancer-predisposing genes across histologies of lung cancer Histology Somatic 2. Germline alterations in cancer- predisposing genes occur in 5% of patients Germline with lung cancer Exclusive 3. EGFR germlin
Slide 22: Acknowledgments
22 Acknowledgments Washington University School of Medicine Sumithra Sankararaman Kelly Bolton Yin Cao Tempus Labs Katie Navo Minxuan Huang Calvin Chao Amrita A. Iyer PRESENTED BY: Ramaswamy Govindan, MD