Guardant Health, Inc. · NASDAQ:GH
Guardant Health — American Association for Cancer Research Annual Meeting 2019
12 slides from Guardant Health's conference presentation, Mar 31, 2019
Slide 1: Combined genomic and epigenomic assessment of ctDNA improves assay sensitivity in early stage CRC
Combined genomic and epigenomic assessment of cell-free circulating tumor DNA (ctDNA) improves assay sensitivity in early stage colorectal cancer (CRC) Seung-Tae Kim, MD PhD, Victoria M. Raymond MS, Joon Oh Park MD PhD, Elena Zotenko PhD, Young Suk Park MD PhD, Matthew Schultz PhD, Won Ki Kang MD Ph
Slide 2: Disclosures
Disclosures Employee, Director, and Shareholder of Guardant Health, Inc. Kim (Talasaz), 2019. American Association for Cancer Research Annual Meeting. Abstract #916. 2
Slide 3: ctDNA has the potential to identify early stage cancer, but accurate detection is challenging
ctDNA has the potential to identify patients with early stage cancer, but accurate detection is challenging Detection Challenges Genomic Sensitivity Signatures • Genomic signatures are limited to ~50% sensitivity for early cancer TUMOR + Specificity • Non-tumor sources of biological noise, such as C
Slide 4: Diverse sources of signal motivate multimodal analysis of ctDNA
Diverse sources of signal motivate multimodal analysis of ctDNA Genomic Alterations Epigenomic Alterations ACTACGTACCTG Genomic Alterations Methylation Nucleosomal Positioning & Fragmentomics • SNVs, InDels, • Aberrant methylation • ctDNA has differential fragment Fusions, and CNVs signals in tumor
Slide 5: ctDNA fragment genomic position provides biological information
ctDNA fragment genomic position provides biological information Nucleosomal (long) fragments Sub-Nucleosomal (short) fragments TSS: Transcription Start Site CTCF: a DNA binding protein that binds to tens of thousands of genomic sites, some tissue-specific and Snyder, et al. Cell 2016. others ultra-c
Slide 6: Integrated genomic and epigenomic analysis of ctDNA
Integrated genomic and epigenomic analysis of ctDNA Digital Sequencing Sequence Methylation & Signal Methylated Target Fragmentomics processing cfDNA capture ctDNA Non- detection Methylated Digital Sequencing Biological cfDNA Genomic Alterations Noise Filter 500kb Panel 80,000 low- ctDNA coverage WG
Slide 7: Multi-modal epigenomics approach integrating methylation and fragmentomics improves signal-to-noise
Multi-modal epigenomics approach integrating methylation and fragmentomics improves signal-to-noise Hyper-methylated fragments Relative number of cfDNA fragments All fragments Hypo-methylated fragments Relative Genomic Position Late stage cancer Early stage cancer Age-matched healthy donor Kim (Tala
Slide 8: Accurate testing cohort required age-matched cases and controls
Accurate testing cohort required age-matched cases and controls • 105 patients with a diagnosis of colorectal cancer had plasma collected prior to surgical resection • From three independent cohorts • Cancer-free controls were age-matched • Median age was 67 years, consistent with the median age at
Slide 9: Inferred tumor level correlates between epigenomic and genomic estimate
Inferred tumor level correlates between epigenomic and genomic estimate Kim (Talasaz), 2019. American Association for Cancer Research Annual Meeting. Abstract #916. 9
Slide 10: Promising ctDNA sensitivity and specificity for early stage CRC
Promising ctDNA sensitivity and specificity for early stage CRC 90% Target Specificity 95% Target Specificity 98% Target Specificity 90% 88% 79% 98% 89% 94% Sensitivity Specificity Sensitivity Specificity Sensitivity Specificity 100% 95% 100% 100% 90% 95% 87% 84% 82% 84% 75% 76% 75% 75% 64% 56% 56%
Slide 11: Summary and Next Steps
Summary and Next Steps • Utilizing a plasma-only sequencing assay incorporating somatic genomic and epigenomic analysis, and a bioinformatic classifier to filter non-tumor derived variants, ctDNA detection rate in early stage CRC (I-III) can far outperform the detection rate of somatic sequence vari
Slide 12: Acknowledgements
Acknowledgements • Patients and Providers who collaborated on this research • Investigators at Samsung Medical Center in South Korea Kim (Talasaz), 2019. American Association for Cancer Research Annual Meeting. Abstract #916. 12
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