#1.25 uBiome BIG DATA FROM BACTERIA Dr. Jessica Richman, PhD Co-Founder and CEO uBiome Harvard Precision Medicine June 20, 2017 CLIA Compliant CAP ACCREDITED ik#2Executive Team from Stanford, Harvard, Yale, UCSF, and Genomic Health VP R&D Dr. Audrey Goddard, PhD Genentech and VP Genomic Health, 25 years of experience In diagnostics uBiome Founder & CEO Dr. Jessica Richman, PhD PhD Oxford, Fulbright, McKinsey, Stanford Econ and Eng VP Data Dr. Daniel Almonacid, PhD PhD Cambridge, post-doc UCSF, Professor of Bioinformatics VP Product Nathaniel Walton Oberlin, VR Product at Brandwatch Founder & CTO Dr. Zachary Apte, PhD PhD UCSF in 2.5 years, serial inventor and entrepreneur General Counsel Fred Melendres, Esq. Yale, Latham & Watkins Quest Diagnostics CFO Eric Weisman MBA, CPA MBA Harvard, VP CAN Capital, Capital One Privileged and Confidential#3$350k INDIGOGO μBiome Quick Summary Top 15 on indiegogo Largest citizen science crowdfunding in history $350k in crowdfunding Largest microbiome dataset in the world 3k people - 6k samples 40+ countries#4Largest Microbiome Dataset in the World uBiome 500k 250k 50k 80+ COUNTRIES 2013 50,000+ Samples Jun 2014 500,000+ Samples 150,000+ Samples 2,500+ Samples May Dec 2017 2017 OVER 100 PATENT FILINGS 250,000+ Samples Dec 2018 LARGEST PRIVATE DATASET MANY DISEASES + HEALTHY STANDARDIZED METHODS Privileged and Confidential#5Understanding microbiome for better health SYSTEMIC CONDITIONS OBESITY DIABETES ANTIBIOTIC OVERUSE uBiome DEVELOPMENT INFANT TO ADOLESCENT HEALTH Human microbiome 1,000,000+ genes MENTAL HEALTH ANXIETY AUTISM DEPRESSION Human genome 23,000 genes REPRODUCTION FERTILITY PREGNANCY STIS DIGESTIVE HEALTH IBS CROHN'S C. DIFFICILE INFECTIONS PERSONAL CARE ACNE DANDRUFF#6Invention of Germ theory of yogurt, bread, beer disease (Pasteur) Pathogen prevention Health, intoxication Pre-history uBiome Expands Use of Microbiome for Human Health uBiome 1880s Discovery and use of penicillin Pathogen destruction 1920-1940s CRISPR Using bacterial DNA to rewrite genetic code 1990-2000s Microbiome Data Diagnosing and curing disease with microbes 2000-2010s Privileged and Confidential#7Dramatic growth in microbiome publications uBiome 3500 3000 2500 2000 1500 1000 500 0 Peer-reviewed Articles Patents 1996 1999 withi 2002 2005 2008 2011 120 100 80 60 40 20 20140#8Meaningful inferences require larger dataset HMP HUMAN MICROBIOME PROJECT Biome 242 individuals sampled Meta HIT So, how do we get more data? > 500 individuals sampled#9Biome Citizen Science#10Clinical Trials Product Co-Creation Quantified Self ↑ Patient-Centric Medicine Citizen Science Convergence Large Scale Studies Translational Medicine Digital Health Evidence-Based Medicine#11What is Citizen Science? Term created by ornithologists in the 1970s, in use in many fields. uBiome BIRD MIGRATION > 60 peer-reviewed papers Cornell Lab citizen-science data since 1997 OCEAN PLANKTON Continuous Plankton Recorder (CPR) identified 500 taxa since 1948 MORAL DECISIONS Crowd-sourced study on how machines should make moral decisions#12The Future: Science will be a crowdsourced, collaborative effort A world where there are 7 billion scientists, not 7 million#13uBiome IRB Doing Citizen Science right Privacy & security Making it foolproof (or trying) Listening to the participants Encouraging participation Collecting samples#14uBiome Lessons learned from Citizen Science What does the participant get out of it? Power to the patient = Need for empathy What are problems of success?#15uBiome Over 200 Research Partners HARVARD MEDICAL SCHOOL Yale University COLUMBIA UNIVERSITY THE UNIVERSITY EDINBURGH Tufts Penalitate ALABAMA WARWICK OXFORD UCSF School of Michir SYDNEY MONASHnenty UCDAVIS Ų Berkeley JOHNS HOPKINS TORONTO BROWN U UNIVERSITY UTAH SALEM COLLEGE KENT SINTE STANFORD UNIVERSITY Mit Duke MAYO CLINIC M Universität Zürich MARYLANIS MELBOURNE AM KU UNT UNIVERSITY OF NORTH TEXONE CU NY ETH zürich Children's Hispla NIH CDC St.Jade Childrens ANNE 500,000 samples committed through 2018 TAKE STEPS Takeda MERCK ISION Health eHeart#16• Academic Grants • Microbiome Impact Grant in conjunction with the Obama White House National Microbiome Initiative THE NATIONAL MICROBIOME uBiome uBiome grants INITIATIVE THE WHITE HOUSE WASHINGTON uBiome Announces Over $1 Million in Microbiome Grant Funding to Support National Microbiome Initiative uliome announces over 31 million in grant funding for microbiome retaach projects with great potential to advance tuman health SAN FRANCISCO CAPO) MAY A The Whouw Office of parenthe mabome field for Nacional Merobom tp://whehouse ge no 22 emenge connections Partea with MIT (MT)n for Co Biome ALADEMIC GRANT FINALISTS JANT TO ME, RENATO POLIMANTE PH D#17Research Studies with UCSF, Harvard, CDC, NIH, Stanford, and more CDC CENTERS FOR DISEASE CONAN Pwever Predisposing factors for hospital-acquired infections 4,000 samples Boston Children's Hospital Un every child is wall Preterm birth and the microbiome 2.000 samples uBiome 232 HARVARD TAS UNIVERSITY Genome + microbiome with Dr. George Church 1,000 samples Stanford MEDICINE The Snyderome: Longitudinal profiling of the microbiome 3.200 samples UCSF Health eHeart Largest study ever on cardiovascular health 100,000+ samples Yale University School of Medicine Smoking and the oral microbiome 1.000 samples 1.D THE UNIVERSITY of NORTH CAROLINA at CHAPEL HILL 17,000 person study on eating disorders 85,000 samples NIH National Institutes of Health Acute Myeloid Leukemia and the microbiome 1.500 samples#18Leading Presentations/ Publications • 16s rRNA Gene Sequencing as a Clinical Diagnostic Ald for Gastrointestinal-related Conditions, PLoS ONE, May 2017 • A gut check at the doctor, Industry Focus, Biochemist, Apr 2017 Phylogenomic Insight into Salinispora Species Designations, Scientific Reports, in press • Healthy ranges for clinically important microbial faxa in the human gut, Keystone Symposium, Poster, Jan 2017 • Friends for Life: Human Microbiota, Dutch Journal of Medical Microbiology, Dec 2016 • When Biology Meets Computers, Annual Meeting, Society of Biochemistry and Molecular Biology, Sep 2015 • Crowdsourcing the Microbiome, ICG8 Beijing Genomics Institute, Oct 2013 Citizen Science and the Microbiome, ASM Microbe, Jun 2013 uBiome Healthy ranges for clinically important microbial taxa in the human gut Introduction 16S rRNA Gene Sequencing as a Clinical Diagnostic Aid for Gastrointestinal-related Conditions Daniel E Almonac Jessica Richman, Friends for life: human microbiota 2 doi: https://doi.o This article is a pre Jan 17, 2017 Poted by julle Taylor Learning Research | Ocomments Abstract Abstract uBiome Accurate del a initiate the detect gut be that are ofter multiple targ Privileged and Confidential By E.M. Bk, Science Editor at uBiome Translated from Dutch. Read the original publication in the December 2016 issue of the Dutch Journal of Medical Microbiology (Nederlands Tijdschrift voor Medische Microbiologie) Abstract The human body is home to larg microbiome or microbiota, and immune systems. Recent innova resulting in a spectacular increas article gives a brief overview of t -until recently-invisible worl discussed asm microbe#19Biome SmartGut™M Made by you#20What is SmartGut? PATHOGEN IDENTIFICATION Examples: Clostridium difficile Salmonella enterica Campylobacter Escherichia-Shigella uBiome IBD vs. IBS Examples: Akkermansia muciniphila Bifidobacterium Lactobacillus DISEASE RISK FACTORS Examples: Type II Diabetes Obesity#21Developing a clinical test from big data uBiome IDENTIFY Review literature for desired commensal and pathogenic bacteria TARGET Replicate pathogen detection, develop healthy ranges, and mine data for risk factors VALIDATE Full clinical validation of data, sequencing, and target selection under CAP#22Mission: Targets to include in SmartGut Mission: Healthy ranges for sequences of commensal bacteria for the first time Mission: High sensitivity and specificity on all targets uBiome How To Make a Test from Data Use patent pending bioinformatics techniques developed on large dalasel to differentiate targets List all targets that can be differentiated with marker-based sequencing Examine 150,000 samples in dataset Clean up public database with knowledge gained from 150,000 samples Review literature extensively and find targets that are clinically relevant Select 897 healthy people and examine their gut bacteria Use patent pending bioinformatic techniques on cleaner database to get better resolution Create ranges for 26 commensal bacteria Test positive samples from existing PCR test for pathogens and incorporate healthy ranges for commensals - Result: Test with most bacterial targets in the world Result: Set new ranges that have never existed for these bacteria & publish in PLOS One Result: 99% specificity and sensitivity for targets Requires Biome data to achieve#23uBiome With uBiome's Data It's Possible to Test for Salmonella and Cholera with Just One Marker SPECIES Vibrio cholerae Salmonella enterica 16S GENE SENSITIVITY 6.93 2.74 Using uBiome data, we are able to detect these pathogens with high sensitivity From what is known in the literature we won't be able to detect these pathogens using the 165 gene UBIOME SENSITIVITY 98.84 98.98 Privileged and Confidential#24Analytic Specification Sensitivity Specificity Accuracy Intra-run Agreement (Precision) Inter-run Agreement (Precision) Reportable Range Reference Range Limit of Detection Cross-contamination uBiome Wet Lab Validation Samples 45 45 129 21 159 177 807 24 96 Sample types Stool samples which are positive and negative for pathogenic taxa Stool samples which are positive and negative for pathogenic taxa Stool samples which are positive and negative for pathogenic taxa. Standard stool sample spiked with sDNA Standard stool samples. Stool samples from 53 donors Stool samples from 55 donors plus 18 positive E. coli controls Samples from 807 self-reported healthy individuals SDNA mock communities of 28 targets at known abundance 19 samples with one sDNA each plus 77 blanks Validation Results 100.00% 100.00% 100.00% 100.00% genera, 100.00 % species 97.16% genera, 97.16% species Positive/Negative Low/Normal/High Negative or Normal 0.03% average abundance 75 reads per taxa Acceptance Criteria > 95.00% > 95.00% > 95.00% > 95.00%, > 95.00% > 95.00%, > 95.00% (Qualitative) N/A N/A N/A Status Pass Pass Pass Pass Pass Completed Completed Completed Completed Privileged and Confidential#25. Accessioning CAP Inspection Personnel Training Competency Equipment Maintenance Correlation Materials Management Assay Validations uBiome Quality Control Patient Reports Amended and Corrected Reports Laboratory Information System • Document Change Notices 5 . Occurrence and Nonconforming Events Corrective and Remedial Actions Assessments: Internal . Turn-Around Time . Proficiency Testing • Quarterly Laboratory Audit for Safety Annual SOP Matrix Review . Annual Internal Audits Report • Assessments: External . Continual Process Improvement . Communication / Client Services . Facility and Safety Privileged and Confidential#26Biome UMii uBiome Medical Informatics Initiative Contact: [email protected]#27Academic and Clinical collaborations For Collaborators ACCESS Largest microbiome dataset makes it easier to find controls and do comparisons PLATFORM Citizen science makes it easier to source populations or integrate medical records uBiome FREE Free microbiome sequencing from grants; vast experience with collaborations For uBiome PARTNER With leading researchers and clinicians DIVERSITY Directed populations balance heterogeneity and enable targeted studies BUILD Strong relationships to advance biomedical science globally#28Use Case: Regional Cancer Center Cancer and the Microbiome • Microbiome signature of subtypes • Use in early detection. • Medication metabolism uBiome#29Use Case: Network of Community Health Physicians Metabolic Disorder and the Microbiome • Medical record integration. • Links with environmental factors . and genetics uBiome#30uBiome Use Case: Allergies and Inflammatory Disease Hygiene Hypothesis and Immune Development Development of pediatric microbiome Relationships to gut, oral, and nasal microbiome#31uBiome Use Case: Women's Health Vaginal Microbiome and Women's Health Links with pre-term birth, fertility, and HIV infection Gut and vaginal microbiome correlations#32Clinical Trials Product Co-Creation Quantified Self Patient-Centric Medicine Citizen Science Convergence Precision Medicine Large Scale Studies Translational Medicine Digital Health Evidence-Based Medicine