#1X 23andMe 23andMe R&D Day January 18, 2022#2Disclaimer Forward-Looking Statements This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the future performance of 23andMe's businesses in consumer genetics and therapeutics and the growth and potential of its proprietary research platform. All statements, other than statements of historical fact, included or incorporated in this presentation, including statements regarding 23and Me's strategy, financial position, funding for continued operations, cash reserves, projected costs, plans, and objectives of management, are forward-looking statements. 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Copyright © 2022 23andMe, Inc. 23andMe® 2#3Agenda Introduction -- Anne Wojcicki, CEO and Co-Founder 23andMe Therapeutics Therapeutics program overview - Kenneth Hillan, Head of Therapeutics Target discovery vision - Joe Arron, Chief Scientific Officer, Therapeutics Genetics-based target discovery - Adam Auton, VP of Human Genetics CD200R1 immuno-oncology program - Jennifer Low, Head of Therapeutics Development and Adrian Jubb, Sr. Clin. Dev. Fellow, Therapeutics CD96 immuno-oncology program - Jennifer Low, Head of Therapeutics Development Using genetics to inform clinical development - Jennifer Low, Head of Therapeutics Development Therapeutics program concluding remarks - Kenneth Hillan, Head of Therapeutics 23andMe Consumer Genetics-based primary care - Paul Johnson, VP, General Manager, Consumer The power of polygenic risk scores (PRS) for personalized health Geoff Benton, Director, Product R&D Delivering a genetic-based primary care service - Davis Liu, Chief Clinical Officer Concluding Remarks - Anne Wojcicki, CEO and Co-Founder Q&A Copyright © 2022 23andMe, Inc. 23andMe 3#4Introduction Anne Wojcicki CEO and Co-Founder Copyright © 2022 23andMe, Inc. 23andMe 4#5Today's News on 23andMe and GSK Collaboration • GSK has elected to extend the exclusive target discovery period of the collaboration for a fifth year • We will continue to discover and validate novel drug targets using 23andMe's proprietary genetic and health survey database o 23andMe will receive a one-time payment of $50 million • 23andMe elects for royalty option on collaboration program targeting CD96 o 23andMe will be eligible to earn tiered worldwide royalties up to the low double digits o The worldwide royalty option curtails 23and Me's future investment in this program and provides 23andMe with a potentially high value revenue stream if the program is successful Copyright © 2022 23andMe, Inc. 23andMe® 5#6FY2022 Highlights Advanced a wholly owned immuno-oncology program into Phase 1 study • Acquired Lemonaid Health to expand into Primary Care and Pharmacy Received FDA clearance for HOXB13 hereditary prostate cancer Released 14 new genetic health predisposition reports Reported on key genetic research findings on COVID-19, reproductive lifespan in women, depression, Parkinson's disease, and more ● ● ● Added a new ancestry analysis, including additional insights into some customers' indigenous genetic ancestry from North America and ancestral connections to 25 African ethnolinguistic groups Copyright © 2022 23andMe, Inc. 23andMe 6#7Our Mission is to Help People Access, Understand, and Benefit from the Human Genome 23andMe Welcome to you 1 As of September 30, 2021. saliva collection kit 23andMe REGENERON MILLION VETERAN PROGRAM UK BIOBANK DECODE GENETICS ALL OF US FINNGEN 1M 825,000 500,000 500,000 366,000 219,000 GENOMICS ENGLAND 100,000 Size and scale of 23andMe enables rapid, novel discoveries Copyright © 2022 23andMe, Inc. 11.9M¹ 23andMe® 7#8Consumer 11.9M Genotyped Customers¹ »>»>> Consumer Powered Healthcare Flywheel We run hundreds of billions of association tests per year that further our unique understanding of human biology Data >>> 80% Opt-In to Research Research اااه XXX Phenotypic Data Genetic Data Insights 1. As of September 30, 2021. 2. As of March 31, 2021. Programs include collaborated, 100% owned and royalty interest targets. 4B+ Phenotypic Data Points¹ Innovative Results Return Value to the Customer Therapeutics / Product Drug Discoveries 40+ Programs² Novel Consumer Products ≈ Copyright © 2022 23andMe, Inc. 23andMe 8#9What's Coming: • Next Generation Reports: Polygenic Risk Score reports that incorporate life- style factors to improve risk estimates Genetics-based Primary Care: Delivering personalized, prevention-oriented, genetics-based healthcare at scale by integrating Lemonaid Health's digital health platform with 23andMe's personal genetic services • Advancing Therapeutics Pipeline: Advancing a pipeline of multiple clinical and research stage investigational programs addressing targets validated by human genetics Copyright © 2022 23andMe, Inc. 23andMe® 9#10Therapeutics Program Overview Kenneth Hillan, M.B., Ch.B. Head of Therapeutics Copyright © 2022 23andMe, Inc. 23andMe 10#11Limited Use of Genetic Data and Lack of Patient Engagement Constrain Productivity 1. IND= Investigational New Drug Application. fdareview.org, "The Drug Development and Approval Process" (2020). 2. Probability of success for a drug to be approved is estimated to be <12%. 3. PhRMA, "Biopharmaceutical Research & Development: The Process Behind New Medicines" (2015). Drug Development is Inefficient 7 years average time-to-IND¹ $2.6B average cost of drug development³ ~90% failure rate2, 3 Copyright © 2022 23andMe, Inc. 23andMe® 11#12Pharmaceutical Industry 7 years average time-to-IND¹ ~90% failure rate² NATURE GENETICS PUBLICATION 23andMe ~4 years to IND with CD96 drug Targets with genetic evidence have historically had a higher Success rate³ The support of human genetic evidence for approved drug indications Nelson et. al 2015 ¹ IND = Investigational New Drug Application. fdareview.org, "The Drug Development and Approval Process" (2020). 2 Probability of success for a drug to be approved is estimated to be <12%. PhRMA, "Biopharmaceutical Research & Development: The Process Behind New Medicines" (2015). 3 Nature Genetics Publication, "The support of human genetic evidence for approved drug indications" (2015). Potential to More Efficiently Develop Novel Therapeutics by "Power, Need, and Speed"#13DNA-based Target Discovery Playbook: How it works Survey & Genetic Data rs23423590 rs8712300 9999 Diabetes Asthma rs3454055 rs4597906 rs57565167 rs67565048 High Blood Pressure Hypertension Pollen Allergy Type 2 Diabetes Parkinson's SNP X GWAS PheWAS Target Identification by Phenotype Drug Discovery Clinical Trials Copyright © 2022 23andMe, Inc. Product Approval 23andMe® 13#14Our Scale Enables Real-Time Genetics Health Research¹ 1,876,573 High cholesterol 1,785,456 Depression 1,113,057 Asthma 634,734 Irritable Bowel 534,696 Arrhythmia 9,047 Systemic Sclerosis 358,275 Type 2 Diabetes 2,355,068 APOE e4 carriers (Alzheimer's risk) 667,019 Eczema 107,126 UC / Crohn's 159,135 Coronary Artery 7,334 Sarcoidosis 37,853 Type 1 Diabetes 85,604 Epilepsy 250,764 Psoriasis 64,800 Barrett's Esophagus 42,836 Pulmonary Embolism 4,528 Idiopathic Pulmonary Fibrosis ¹ As of August 2, 2021. 2 As of September 2021. 3 23andMe COVID-19 manuscript live on MedRXiv September 7, 2020. 1,287,060 COVID-19 study participants COVID-19 Research March 16 April 6 June 8 750K Consumers participated in the COVID-19 study in the first 90 days Sept. 7 (2020) Kicked Off Study Launched Study Preliminary Findings Posted Findings³ Re-contactable Customers Participate in Health Research#15We Have Generated a Research and Development Pipeline Covering Multiple Therapeutic Areas Immuno-oncology GSK'608 (CD96) EARLY-STAGE THERAPEUTIC AREAS (multiple programs in each area) Immuno-oncology Immunology 23ME'610 (CD200R1) Cardiovascular/ Metabolic Neurology Discovery Preclinical Phase 1 ¹40+ programs in the combined therapeutic areas. Programs include collaborated, 100% owned and royalty interest targets. Note: As of March 31, 2021 40+ programs¹ gsk 23andMe Phase 2 Next Milestone Phase 1 Data Phase 1 Data Copyright © 2022 23andMe, Inc. 23andMe 15#16Target Discovery Vision Joe Arron, M.D., Ph.D. Chief Scientific Officer, Therapeutics Copyright © 2022 23andMe, Inc. 23andMe 16#17My Background ● MD/PhD Cornell and Rockefeller • Postdoc Stanford • Genentech 2006-2021 o VP and Senior Fellow, Immunology Research ■ Led target discovery for inflammatory, fibrotic, & ophthalmic diseases across >20 laboratories o Developed forward & reverse translational strategies across multiple disease areas o Contributed to >25 clinical programs from discovery through postmarketing o Authored >75 peer-reviewed publications Copyright © 2022 23andMe, Inc. 23andMe® 17#18Human Genetics has the Potential to Double the Probability of Success in Drug Development Huw 000 Reasons for failure Wrong target • Hypothesized target not a critical node in disease pathogenesis • Safety issues associated with target Wrong drug Insufficient affinity/avidity; off-target effects • Poor PK/tissue penetration/inadequate dosing Wrong outcomes • Clinical outcome measure not related to biology of target • Clinical outcome measure not relevant in trial population Our rich database and translational focus has the potential to mitigate these and increase probability of success Wrong patients • Patients not properly stratified according to molecular, pathophysiological, or clinical heterogeneity • Trials underpowered to detect an effect in the right subset Copyright © 2022 23andMe, Inc. 23andMe 18#19Focusing on Translational Research to Link Targets and Outcomes VALUE TO PATIENTS meaningful benefit TARGET/MOA BENCH PATHOPHYSIOLOGY identify indications and develop outcome measures most relevant to biologically compelling targets develop targets that are most relevant to unmet needs in existing indications tettet ** unselected population N U biomarker level ok okok ·oK CLINICAL ENDPOINTS Townsend & Arron, Nat Rev Drug Discov 15:517 (2016) BEDSIDE biomarker-defined phenotype A pathway A' clinical manifestation A" biomarker-defined phenotype B pathway B' clinical manifestation B" Copyright © 2022 23andMe, Inc. 23andMe® 19#20>>> >>> >>> >>> Systematic, Scalable Research Platform Yields Novel Drug Targets Phenotypic Data Genetic Data 10,000s of Genome-Wide Association Study (GWAS) Hits Determine Disease Associated Genes and Directionality Translational Research to Understand Mechanism Identifying Druggable Targets Phenome-Wide Association Studies (PheWAS) Reveal Additional Indications and Potential Safety Concerns Assessment of Unmet Need and Competitive Landscape Best Drug Targets Wet lab validated targets progress through standard stages of research toward the selection of preclinical lead molecules and clinical development »>»> »>»> »»>> >>> 23andMe's database yields thousands of GWAS hits Advanced biology and medicinal chemistry guide design of optimal compounds from initial targets Phenotypic breadth provides unique ability to uncover potential safety issues or possible indication expansions Copyright © 2022 23andMe, Inc. 23andMeⓇ 20#21Leveraging our database: I/O signature implicates CD200R1 pathway CD200R1 pathway identified as a critical immune checkpoint with our I/O genetic signature I/O genetic signature shows opposing effects on autoimmune and cancer phenotypes CD200R1 Receptor Immune II Cancer Cancer CD200 Ligand Immune Immune Cancer DOK2 Protein -10 -5 0 5 10 Signed log(p) Implicates 3 components of the CD200R1 signaling pathway CD200:CD200R1 Signaling Tumor cell Reduced Anti-Tumor Immune Response CD200 Dok2 CD200R1 RasGAP ERK T-cell Ras We are applying similar approaches to many diseases that are well- represented in our database Copyright © 2022 23andMe, Inc. 23andMe® 21#2223ME'610 is an antibody against CD200R1 that can block CD200-mediated immune suppression CD200 is strongly expressed in a subset of human tumors CD200 immunohistochemistry (brown) shows expression on tumor cells Inhibiting CD200R1 signaling enhances anti- tumor immune responses 23ME'610 T APC Copyright © 2022 23and Me, Inc. 23and Me 22 22#23Consumer 11.9M Genotyped Customers¹ »>»>> Consumer Powered Healthcare Flywheel We run hundreds of billions of association tests per year that further our unique understanding of human biology Data >>> 80% Opt-In to Research Research اااه XXX Phenotypic Data Genetic Data Insights 1. As of September 30, 2021. 2. As of March 31, 2021. Programs include collaborated, 100% owned and royalty interest targets. 4B+ Phenotypic Data Points¹ Innovative Results Return Value to the Customer Therapeutics / Product Drug Discoveries 40+ Programs² Novel Consumer Products ≈ Copyright © 2022 23andMe, Inc. 23andMe 23#24Genetics-based Target Discovery Adam Auton, Ph.D. Vice President, Human Genetics Copyright © 2022 23andMe, Inc. 23andMe 24#25Genome-Wide Association Studies (GWAS) GWAS is a statistical analysis of Single Nucleotide Polymorphisms (SNPs), looking To identify differences in frequency between disease cases and controls. SNPs linked with disease will be found at different frequencies in cases versus controls. Association is represented by the level of statistical significance (p-value) of the SNP frequency difference. SNPs can be tested across the genome and mapped to specific regions. Single Nucleotide Polymorphism (SNP) GGCCAGCTGGACGAGG GGCCAGCTGGATGAGG - log10 (pvalue) 200 100- 50 8 20 10 5 2 1 2 3 4 10- 102.2 5 102.4 6 FL120079 7 AIR 102.6 8 9 LIRI AMAL 102.8 Cases 10 11 12 ns11123823 GALE SLOBAL LA 14 SLOBA 103.2 16 MESIDE THEMI 103.4 80 18 20 22 X Copyright © 2022 23andMe, Inc. Controls 23andMe® 25#26Example: Number of Osteoarthritis GWAS¹ hits dramatically increase as database grows 2016 2017 2021 log10(pvalue) - log10(pvalue) log10 (pvalue) 12- 10- 15 60 40- Size and Scale Accelerate Target Discovery 20 1 GWAS: Genome-Wide Association Study. 1 2 3 4 PT 5 ETSY 6 9 10 11 12 Chromosome 7 8 9 10 11 12 Chromosome 7 8 9 10 11 12 Chromosome 14 14 16 18 20 22 X 16 18 20 22 X 16 18 20 22 X Number of independent hits p<5e-8 New programs are identified through GWAS¹ hits, which increase as size of database grows 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 O 2015 2016 2017 2018 2019 Copyright © 2022 23andMe, Inc. 2020 23andMe® 26#27The Vast Majority of GWAS Discoveries Can be Made Without Large-scale Sequencing Nearby genetic variants are correlated with each other. Knowing the variants one position allows the nearby variants to be inferred. E.g. Fill in the blanks: The q***k brown f*x jumps ov*r the **zy dog. ● • The same principle applies in genetics. The process of filling in the gaps is known as 'genotype imputation'. Genotyped Samples 2 2 2? 2 0 1?2?2?011?? 2 0 1?2?1?1? 120??2?0 27272727121 27 0 12 12 12 13 ??? 2?0 022222220 21 22 2 1 27121 2 1 2 0 17070 2 1 0 Reference Genomes 0 0 1 0 1 1 1 0 0 1 1 1 1 1 1 0 1 1 1 1 1 1 1 0 0 1 0 0 1 1 1 0 1 1 1 1 1 0 1 0 0 1 0 0 0 1 0 1 0 000 1 1 0 0 1 1 1 1 1 1 0 1 1 1 0 1 1 0 0 1 1 1 0 1 1 1 0 0010111001 11110 1 1 1 1 1 0 1 0 0 1 0 0 0 1 0 1 11000 100 1 1 0 1 1 1 0 Imputation Process 0?1?1?1? 01 ? ? 1? 0 1?1?1?1? 011? ?1? 0 1?1?1?1? 010?? 1? 0 1?1?1?1? 1 1 1? ?1? 0 1?0?0?0?111? ?1? 0 0?1? 0?0? 1 1 1? ? 1 ? 0 Copyright © 2022 23andMe, Inc. Imputed Samples 1 2 0 1 2 200 2 1 112220011 2 0 11201110120122 0 22222120121122 0 1110121012212220 0121212002111211 2 2 111 101 121 0 0 2 2 2 0 022 2 1 22 0 23andMe® 27#28The Vast Majority of GWAS Discoveries Can be Made Without Large-scale Sequencing Nearby genetic variants are correlated with each other. Knowing the variants one position allows the nearby variants to be inferred. E.g. Fill in the blanks: The q***k brown f*x jumps ov*r the **zy dog. The same principle applies in genetics. The process of filling in the gaps is known as 'genotype imputation'. ● We type ~650,000 SNPs using our genotyping array, which allows accurate imputation for >35m SNPs in the genome. >> Genotype imputation is much more cost effective than large- scale sequencing. ● Whole-genome sequencing ~$1000 / sample. Exome sequencing -$400 / sample. Imputation < $0.01/ sample We do deploy sequencing in situations where there is a clear benefit over and above imputation (e.g. rare disease). Genotyped Samples 2 2 2? 2 0 1?2?2?011? ? 2 0 1?2?1?1? 120 ? ? 2?0 27272727121 27 0 12 12 12 11 ??? 2?0 02272222021? ? 2 1 2 2 1? 1 2 1 1 1?0?0 2 0 -logrolp-value) -logrolp-value) 20 15 10 0 20- 15 o 176.3 0 0 000 88% 176.4 O Reference Genomes 0 0 1 0 1 1 1 0 0 1 1 1 1 1 1 0 1 1 1 1 1 1 1 0 0 1 0 0 1 1 1 0 1 1 1 1 1 0 1 0 0 1 0 0 0 1 0 1 0 000 1 1 0 0 1 1 1 1 1 1 0 1 1 1 0 1 1 0 0 1 1 1 0 1 1 1 0 0010111001 11110 1 1 1 1 1 0 1 0 0 1 0 0 0 1 0 1 11000 100 1 1 0 1 1 1 0 Imputation Process 0?1?1?1? 01 ? ? 1? 0 1?1?1?1? 011? ?1? 0 rs2011077 176.5 1?1?1?1? 010?? 1? 0 1?1?1?1? 1 1 1? ?1? 0 1? 0?0?0?111 ??1? 0 0?1? 0?0? 1 1 1? ?1? 0 0080 o rs 1966265 *4 %0° DO O 176.6 176.7 Position on chr5 (Mb) 176.8 Copyright © 2022 23andMe, Inc. Imputed Samples 1 2 0 1 2 200 2 1 112220011 2 0 11201110120122 0 22222120121122 0 1110121012212220 0121212002111211 0 022 2 2 111 121 0 0 2 2 2 177 2 2 Before imputation After imputation 23andMe® 1 0 28#29Imputation and GWAS Enables Discovery of Vast Majority of Genes Identified via Exome Sequencing Genes identified via 23andMe Imputation + GWAS Genes identified via exome sequencing + burden test in UK BioBank¹ 1. List of genes identified via UKBB exome sequencing: Backman et al., Nature 2021. Exome sequencing and analysis of 454,787 UK Biobank participants Copyright © 2022 23and Me, Inc. 23andMe 29#30Hundreds of Distinct Clinical Phenotypes Across Major and Rare Diseases musculoskeletal Pretp Du care te waris foonwale fossctronice Satur, hand Four et hature major Potre pe true th Faure.n hamia hatal rem nourel hamiamb igbande sprain lobback pain frequency s labdisked shoulder abdupectacu preprog h cardiovascular Peritype artytina wybradyc www. eyes Pe esxgrane #ay dacor HP 1 ay hin patty iar chords ay sing or Orthopedic Cardiovascular İ Ophthalmology alldig See-New Lost aktail dis in d >>> Phenotype NAFLD (Non-Alcoholic Fatty Liver Disease) neurological ich hist gastrointestinal Phinchpa appendectamy appendectryppendola one conson circ ve ver call bladder removal PO gats mas Iesak type Type Ramel N y Ray kuendes obchoric cantipation metabolic Phenotype any ball supory d predp Neurology Cane Cre G.I. mm min -- Metabolic Disease Muse it hitach Shakes, add ka A la hakik didid Cases Controls 48048 2517644 immune autoimmune Phas alopecie ang php cortv.com cohortve cets d or th cons w Sibula coes.w.st gene capta HP e universalis peda bo polyca poes plaque prostat and artis ults and the alpha ormands sanctions www.a ulcerative col HP p infection Phiretype hosts Allergy Autoimmunity ---- HEI! Infectious Disease F Se-01-New Lat Hits New Lost 104 44 cancer colectal cancer dixer postve breast ca Terzoge HP to p toogmptonador topli po 40 dale blood Paytre www.pry wei prangetelny.htடிக ang and thrombos decan 28 rue desish HP deney cause noon populations mbayopen perus sete abert of Tom endocrine ا ... 2 Cancer Hematology Hulitindikalili ⠀⠀⠀⠀⠀⠀ Endocrine Copyright © 2022 23andMe, Inc. Case Cove ---- Jualcol un MATRIE stalas kamera med al X23andMe 30#31Breadth of Phenotyping Provides Deeper Genetic Understanding Across Multiple Diseases PheWAS = Phenotype Wide Association Study Every SNP in the genome can be interrogated at >1,000 medically related phenotypes Besides the role of a gene in a disease of interest, we can use genetics to learn potential indication expansions or possible unwanted effects Phenotypes associated with ABO blood type hemorrhoids- icp bruse easily thyroid removed- uker- hypocoagulation- cout- dvertcuts- high blood pressure- ignorovirus ever- icb.nose bleeds- igbwhooping cough- kichey stones- menorthagia- nosebleed after12- thyroid cancer_dk_or_fh- thyroid cancer- mumps- mesquito be more- idbinfluenza last 12m- any skin cancer- any_non_mellanoma_skin_cancer blood dets- arterial thrombosis_de_or_th any plant allergy- iqbstratch_marks- any_ashma- stroke- peripheral artery dis- hypothyroidism er positive breast cancer- Cumart_authra- antiphospholipid syndrome - anemia pregnancy healthy control- algic athra- anemia- heart failure- blood sugar mack- blood thinner meds- chap van thrombosis gallstories_or_gall bladder_removal heart attack high_chell- high_cholesterd broad- high Id- high pisems glucose- HP allergies hyperglycemia ibchildhood ear infections- icb galstores igb lipoma- icblow_hd- iqbuvaricose veins legs- juvenile asthma- juvenile asthme not current- myocardial infarction de or th pancreatic cancer_ds or fh- pulmeny e - pulmonary embolism_ck_or_fh- hints- stroke cke or th- superficial thrombophlebitis de or fh- t2d- 12d_bread- tonsillectomy perials any food allergy- migraine diagnosis any animal allergy- early onset heart attack- nafid- savere_aone- cach andoratrici- chronic_hives- transient ischemic attack_d_or_th- signed log(p) -105D5 10 maB176719G_GC Phenotypes with increased risk from having the 'O' blood type Phenotypes with decreased risk from having the 'O' blood type Color intensity indicates statistical significance of association. 23andMe® Copyright © 2022 23andMe, Inc. 31#32Using PheWAS to Identify Immuno-oncology Targets We have defined an 'immuno-oncology signature'; genetic evidence that a particular gene both activates the immune system and simultaneously reduces cancer risk. Immune and autoimmune phenotypes Cancer phenotypes Identified novel immuno-oncology signature around CTLA4. tonsillectomy anti_tnf_alpha_or_dmards t1d- signed log(p) juvenile_t1d- iqb.dry_skin_frequency - iodine treatment_ever- hypothyroidism - hyperthyroidism - hashimotos- graves - vitiligo - iqb.dandruff_frequency - celiac HLA_all- psoriasis rheumatoid arthritis - took_meds_anti_tnf_alpha- thyroid_removed - immunodeficiency- squamous_cell_carcinoma - basal cell carcinoma - actinic_keratosis non_melanoma_skin_cancer- any_skin_cancer- -10 -5 0 5 10 Genetic Variant in CTLA4 linked with multiple phenotypes in the 23andMe database Gene IO signature? 1 Use machine learning (ML) techniques to scan the genome and identify genes with similar signatures. X 2 X 3 ➡X 4 5 6 Similarity classifier 7 ➡X ➡X 8 ➡X 9 X Copyright © 2022 23andMe, Inc. 23andMe® 32#3323ME-00610 (P006): A Novel Immuno-oncology Antibody Targeting CD200R1 Jennifer Low, M.D., PhD Head of Therapeutics Development, and Adrian Jubb, M.B., Ch.B., Ph.D. Senior Clinical Development Fellow Copyright © 2022 23andMe, Inc. 23andMe 33#3423andMe Immune-Oncology (I/O) Signature Highlights Genetically-Driven Targets Large I/O market with over $41B expected in 2021 sales¹ 2021 projected sales of leading checkpoint inhibitors KEYTRUDA OPDIVO YERVOY $17.0B $7.9B $1.8B 1 Source: Evaluate Pharma historical and forecast estimates. Global Immuno-Oncology Drug Development Pipeline Published by Samik Upadhaya & Annie Yu on Sep 18, 2020 Sources: CRI, CRI Analytics, Clinicaltrials.gov, CRI-iAtlas, and GlobalData. Target CD19 TAA PD-L1 PD-1 BCMA HER2 4,720 agents and 504 targets in 2020. CD3 CTLA-4 CD47 HPV NY-ESO-1 4-1BB CD20 MUC1 CD22 STING STAT3 IFNAR1 IDO1 CSF1R neoantigens 0 53 50 49 48 46 44 41 41 39 39 38 37 37 136 87 132 CANCER The Anna-Maria Kellon RESEARCH Clinical INSTITUTE Accelerator 117 198 245 50 100 150 200 250 300 Number of active IO agents per target > 23andMe's I/O signature identifies targets that are genetically-driven ↓ ↓ X X 3 ↓ X 4 5 ↓ Similarity classifier ↓ ↓ ↓ X X Copyright © 2022 23andMe, Inc. 7 8 ↓↓ ↓ X ↓ X ↓ ↓ X 23andMe 34#35CD200R1 was Identified as a Promising Anti-Cancer Drug Target with 23andMe's Proprietary Immuno-oncology (I/O) Genetic Signature Immune and autoimmune phenotypes Cancer phenotypes Identified novel immuno-oncology signature around CTLA4. tonsillectomy - t1d- anti_tnf_alpha_or_dmards - juvenile_t1d- iqb.dry_skin_frequency - iodine treatment ever- hypothyroidism - hyperthyroidism - hashimotos - graves - vitiligo- iqb.dandruff frequency - celiac HLA all- signed log(p) psoriasis- rheumatoid arthritis - took meds_anti_tnf_alpha- thyroid_removed - immunodeficiency - squamous_cell_carcinoma - basal cell carcinoma - actinic_keratosis - _non_melanoma_skin_cancer - any_skin_cancer - -10 -5 0 5 10 Genetic Variant in CTLA4 linked with multiple phenotypes in the 23andMe database CD200R1 pathway identified as a critical immune checkpoint with our I/O genetic signature CD200R1 Receptor Immune I/O genetic signature shows opposing effects on autoimmune and cancer phenotypes Cancer Cancer Immune CD200 Ligand DOK2 Protein Immune Cancer signed log(p) -10 -5 0 5 10 We discovered that 3 components of the signaling pathway for CD200R1 have a similar genetic signature to other I/O drugs Copyright © 2022 23andMe, Inc. 23andMeⓇ 35#36CD200R1 is an Immune Checkpoint • CD200R1 is an inhibitory receptor expressed on T-cells and myeloid cells • CD200 is the only known ligand for CD200R1 in humans and is highly expressed in certain cancers Binding of CD200 to C200R1 decreases the ability of T-cells to recognize and kill cancer cells Several viruses, including HHV8 have co-opted CD200 analogues to suppress and evade the host immune response References: J Virol 2012;86:6246, J Virol 2004;78:7667, J Immunol 2005;175:4441, Structure 2013;21:820, JCI Insight 2018;3:e96836 CD200:CD200R1 Signaling Tumor cell CD200 Dok2 Reduced Anti-Tumor Immune Response CD200R1 RasGAP ERK T-cell Ras Copyright © 2022 23andMe, Inc. 23andMe® 36#3723ME-00610 (23ME'610) Binds with High Affinity to CD200R1 and Inhibits Immunosuppressive Signaling 23ME '610 is a fully humanized, effectorless, IgG1 antibody against human CD200R1 23ME '610 binds CD200R1 with high affinity (K, < 0.1 nM) 23ME '610 blocks CD200 ligand binding to CD200R1, resulting in inhibition of immunosuppressive signaling The restoration of T-cell activity by 23ME '610 was demonstrated using in vitro models of the tumor microenvironment No adverse effects of blocking CD200R1 have been observed in nonclinical toxicology studies 23ME'610 Activates T-cell Function by Blocking the CD200R1 Checkpoint Tumor Cell CD200 CD200R1 CD8+ T Cell + Suppressed T cell function Copyright © 2022 23andMe, Inc. Tumor Cell 23ME-00610 CD8+ T Cell + Activated T cell 23andMe 37#3823ME'610 Shows Broader Enhancement of Proinflammatory Cytokine Secretion than Anti-PD1 ● Mixed immune cell assay that stimulates T cells with MHCII binding bacterial super antigen SEB 23ME'610 ul Cancer patient-derived PBMCs PBMCs: Peripheral Blood Mononuclear Cell (T cells, B Cells, NK Cells, Monocytes) SEB: Staphylococcal Enterotoxin B (bacterial super antigen) 23ME'610 Increases Interferon-gamma Secretion from SEB-Stimulated Cancer Patient PBMCs to Control Fold Change Relative 1923 (Endometrial) 4195 (Ovarian) 9203 (Endometrial) Interferon-y 0824 (Lung) 7181 (Melanoma) 2019 (Pancreatic) 0818 (Prostate) 23ME '610 Isotype Control anti-PD-1 5011 (Endometrial) 0910 (Colorectal) Copyright © 2022 23andMe, Inc. *, p < 0.05 Interferon-gamma is a pro-inflammatory cytokine that is secreted by activated T cells 23ME '610 increases interferon-gamma secretion from SEB-stimulated cancer patient PBMCs compared to the isotype control antibody and anti-PD-1 in the majority of tumor samples tested 23andMeⓇ 38#39Phase 1 Study of 23ME'610 in Patients with Locally Advanced or Metastatic Solid Malignancies 1 Phase 1 Patients with locally advanced, unresectable or metastatic solid tumors that have progressed after or are inappropriate for standard therapy Study Design Y Openlabel Non- Randomized Part A (n = 26) Monotherapy Dose Escalation (IV Infusion Q3W) Accelerated Titration 3+3 Cohorts x RP2D / MTD Multi-center Part B (n = 75) Expansion Cohort Expansion Cohort Expansion Cohort Expansion Cohort Expansion Cohort Primary Objectives Part A: Safety (DLTS, AES) Part B: Efficacy (ORR) Secondary and Exploratory Efficacy (ORR [RECIST and iRECIST]), DOR, PFS, OS) and Safety Pharmacokinetics Pharmacodynamic biomarkers Abbreviations: AEs: Adverse Events; DLT: Dose limiting toxicity; DOR: duration of response; IV: intravenous; ORR: Objective Response Rate; OS: Overall Survival; PFS: Progression Free Survival; Q3W: every three weeks; RECIST: Response Evaluation Criteria in Solid Tumors; RP2D: Recommended Phase 2 Dose Copyright © 2022 23and Me, Inc. 23andMe® 39#40CD200R1 Ligand (CD200) is Highly Expressed in a Subset of Human Tumors CD200R1 and CD200 Protein are Co-expressed in Ovarian Cancer Source: 23andMe Data CD200R1 CD200R1 immunohistochemistry (brown) shows expression on immune cells within and around the tumor CD200 CD200 immunohistochemistry (brown) shows expression on tumor and stromal cells Copyright © 2022 23andMe, Inc. 23andMe® 40#41Why Target the Receptor (CD200R1) Instead of the Ligand? • CD200R1 expression is mainly expressed on immune cells o CD200 (ligand) is broadly expressed on many cell types • An anti-CD200 monoclonal antibody, samalizumab (ALXN 6000) did not saturate cell surface CD200¹ o evaluated in patients with CD200-expressing B-cell malignancies in a Phase 1 trial¹ • 23ME'610 is expected to saturate CD200R1 and fully block binding to CD200 Target distribution Antibody affinity (KD) 1 Journal for ImmunoTherapy of Cancer 2019;7:227 CD200R1 Immune cells 23ME'610 < 0.1 nM CD200 Expressed on a wide range of cells (B cells, endothelial cells, neuronal cells, etc) samalizumab ~10 nM Copyright © 2022 23andMe, Inc. 23andMe® 41#4223ME '610 Targeting CD200R1: A Genetically- Validated Approach to Anti-Cancer Therapy 23andMe's I/O signature highlights potential targets with genetic evidence of importance • CD200R1 is an immune checkpoint with a clearly defined I/O signature in three components of the pathway • CD200R1 ligand is highly expressed in a subset of human cancers • 23ME '610 is a potent monoclonal antibody against CD200R1 that has the potential to restore T-cell killing of cancer cells • The Phase 1 study of 23ME '610 in patients with advanced solid malignancies has been initiated and the first patient was dosed in January 2022 Copyright © 2022 23andMe, Inc. 23andMe® 42#43CD96 Program: First Clinical-stage Immuno-oncology Antibody Targeting CD96 Jennifer Low, M.D., Ph.D. Head of Therapeutics Development Strategic Collaboration with gsk Copyright © 2022 23andMe, Inc. 23andMe 43#44CD96 was Identified as a Promising Anti-Cancer Drug Target with 23andMe's Proprietary Immune-Oncology (I/O) Genetic Signature Immune and autoimmune phenotypes Cancer phenotypes Identified novel immuno-oncology signature around CTLA4 tonsillectomy - t1d- anti_tnf_alpha_or_dmards - juvenile_t1d- iqb.dry_skin_frequency - iodine treatment_ever- hypothyroidism - hyperthyroidism - hashimotos - graves- vitiligo- iqb.dandruff frequency - celiac HLA_all- signed log(p) psoriasis- rheumatoid arthritis - took meds_anti_tnf_alpha- thyroid_removed - immunodeficiency - squamous_cell_carcinoma - basal cell carcinoma - actinic_keratosis - _non_melanoma_skin_cancer- ny_sk cancer -10 -5 0 5 10 Genetic Variant in CTLA4 linked with multiple phenotypes in the 23andMe database CD96/CD226 pathway identified as a checkpoint with our I/O genetic signature I/O genetic signature shows opposing effects on autoimmune and cancer phenotypes CD226 pathway (includes CD96) signed log(p) Multiple Autoimmune Phenotypes Multiple Cancer Phenotypes -10 -5 0 5 10 Copyright © 2022 23andMe, Inc. 23andMe 44#45PD-1 is a Negative Regulator of the CD226 Axis Inhibition of CD96 and TIGIT may enhance PD-1 activity - Activating/co-stimulatory interaction - Inhibitory interaction CD112 PVRIG APC/Tumor TIGIT CD155 PD-L1 CD226 CD96 PD-1 T/NK cell ● CD226 activates NK/T-cells PD1 directly regulates CD226 activity TIGIT and CD96 indirectly suppress CD226 ● ● Combining inhibitors (anti- PD-1, anti-CD96, anti-TIGIT) may have more activity that anti-PD-1 alone Copyright © 2022 23andMe, Inc. 23andMe® 45#46Preclinical Data Supports Combining CD96 with PD-1 and TIGIT Inhibitors CD96, TIGIT and PD-1 Combination Suggests Synergy Mean tumor size (mm²) 200 150- 100- 50- 0 clg aCD96- BaPD1 A&TIGIT (G2a) e aCD96+ aTIGIT (G2a) aPD1+aCD96 aPD1+ aTIGIT (G2a) aPD1 + TIGIT (G2a) + aCD96 .**.**. 0 5 10 15 20 25 30 35 40 45 50 55 Days after CT26 tumor inoculation Cancer Immunol Res. 2019;7(4):559 Anti-CD96 + Anti-TIGIT + Anti-PD1 Combination CD226 pathway components owned by GSK Component Molecule PD-1 CD96 PVRIG TIGIT Dostarlimab GSK'608 SRF813 GSK4428859 (EOS448) Partner Acquired from Tesaro 23andMe In-license from Surface Oncology iTeos Copyright © 2022 23andMe, Inc. 23andMe® 46#47GSK6097608: Phase 1 Study Design https://www.clinical trials.gov/ct2/show/NCT04446351 Study Design 1 Phase 1 Study population: • Locally advanced, recurrent, or metastatic solid tumors Nonrandomized • Progressed after, intolerant of, or inappropriate for standard therapy Open label Sequential assignment Arm A (GSK6097608) Escalating doses of GSK6097608 Q3W 0₂ 000 L Escalating doses of GSK6097608 Q3W + fixed dose of dostarlimab Q3W Multicenter RP2D determined Enrollment in PK/PD cohort Enrollment in arm B begins once a dose of GSK6097608 from arm A has been identified based on safety and PK/PD data Arm B (GSK6097608 + dostarlimab) RP2D determined Enrollment in PK/PD cohort ADA, anti-drug antibodies; AEs, adverse events; ORR, objective response rate; PK, pharmacokinetics; PK/PD, pharmacokinetics/pharmacodynamics; Q3W, every 3 weeks; RP2D, recommended Phase 2 dose Study Endpoints Primary Secondary • Dose limiting toxicities • Adverse events • ORR per RECIST 1.1 •ADAS against GSK6097608 and dostarlimab • PK parameters of GSK6097608 and dostarlimab Strategic Collaboration with gsk Current Status The study is currently open and recruiting. . Serious adverse events . Clinically important changes in laboratory parameters, electrocardiograms, and vital signs • Dose reductions or delay • Withdrawal due to AEs Commenced in 2020; data expected 2022 A OPEN Copyright © 2022 23andMe, Inc. 23andMe® 47#48CD96 is Part of the Genetically-validated CD226 Axis and is Progressing in Clinical Development • The 23andMe immuno-oncology signature has highlighted the importance of the CD226 pathway which includes CD96 and TIGIT • Combining components of the CD226 pathway may be more efficacious than inhibiting single components, but will require complex clinical trials o GSK has the relevant agents to target the CD226 axis • The Phase 1 clinical trial with GSK'608 (anti-CD96) and dostarlimab is ongoing (conducted by GSK) o Data is expected in 2022 Copyright © 2022 23andMe, Inc. 23andMe® 48#49Using Genetics to Inform Clinical Development Jennifer Low, M.D., Ph.D. Head of Therapeutics Development Copyright © 2022 23andMe, Inc. 23andMe 49#50What if we could use genetics to predict immune function and immune response to I/O agents? Copyright © 2022 23and Me, Inc. 23andMe® 50#51Genetics-Based Drug Development Taking a different approach across our development pipeline Spit Genotyping Genetic Classification Clinically Informative Variants Detected Incidentally Exploratory Outcome Research Late-Onset Alzheimer's Disease Altheimer's disease is characterized by memory loss, cognitive decline and personality changes. Late onset Alzheimer's disease is the most common form of Alzheimer's disease, developing alter age 65. Marry factors, including genetics, can influence a person's chances of developing the condition. This test includes the most common ganetic variant associated with le-onset Alhairser's disease. Lois, you have one copy of the 24 variant we tested. People with variant have a slightly increased risk of developing lase-onset Alchema's diese Lifestyle, environment, and other factors can also affect your risk 1 variant detected in the APOE gene FDA-Authorized Report Copyright © 2022 23andMe, Inc. 23andMe 51#52PFS probability (%) Polygenic Scores for Hypothyroidism, Psoriasis Predicted Clinical Efficacy to Immune Checkpoint Blockade IMpassion131 Phase 3 (Breast Cancer) Placebo-paclitaxel (n=220) Atezolizumab-paclitaxel (n=431) 100 90 80- 70- 60 50 40 30 20 10- 0 Negative Phase 3 Studies 5.6 5.7 (95% CI 5.4-6.5) (95% CI 5.4-7.2) 6 9 Overall survival (%) Number at risk Atezolizumab Chemotherapy 100 IMvigor211 Phase 3 (Bladder Cancer) 80- 60- 40- 20- Stratified HR-0.86 (95% CI 0.70-1.05) Not formally tested 12 15 Time (months) Miles, et al. Ann Oncol 32:994, 2021. Overall survival 18 21 Events/ number of patients -Atezolizumab 72/116 Chemotherapy 88/118 24 12 month overall survival rate (95% CI) Median overall survival (months; 95% CI) 11-1 (8-6-15-5) 46-4% (37-3-55-6) 10-6 (8-4-12-2) 41-2% (32-2-50-3) Stratified HR 0-87, 95% CI 0-63-1-21: p-0-41 Leave 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 112 100 88 85 82 77 73 58 55 47 118 109 100 95 91 85 82 75 71 65 61 51 47 41 32 28 24 18 15 11 92821 27 Powles, et al. Lancet 391:748, 2018. Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade Zia Khan ¹, Christian Hammer¹, Jonathan Carroll, Flavia Di Nucci¹, Sergio Ley Acosta¹, Vidya Maiya', Tushar Bhangale¹, Julie Hunkapiller¹, Ira Mellman¹, Matthew L. Albert 1,3, Mark I. McCarthy ¹ & G. Scott Chandler 2 NATURE COMMUNICATIONS | (2021) 12:3355 | https://doi.org/10.1038/s41467-021-23661-4 | www.nature.com/naturecommunications Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer Zia Khan,¹, Flavia Di Nucci", Antonia Kwan", Christian Hammer", Sanjeev Mariathasan", Vincent Rouilly", Jonathan Carroll, Magnus Fontes, Sergio Ley Acosta, Ellie Guardino, Haiyin Chen-Harris, Tushar Bhangale", Ira Mellman ³¹, Jonathan Rosenberg, Thomas Powles, Julie Hunkapiller", G. Scott Chandler", and Matthew L. Albert1.2 PNAS June 2, 2020 117 (22) 12288-12294; first published May 19, 2020; https://doi.org/10.1073/pnas.1922867117 Survival probability 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Strata PRS(hypoT)-below median+ PRS(hypoT)-above median 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 1400 Time (days) impas130/ANabP Hazard Ratios for Atezolizumab Overall Survival Psoriasis PRSS Vitiligo PRSs Atopic Dermatitis PRS Tumor T-cell Effector • ● 0.6 0.7 0.8 0.9 1 1.25 1.5 1.75 HR per unit normalized PRS 95% CI; HR <1 high PRS better Copyright © 2022 23andMe, Inc. 23andMe® 52#53Polygenic Scores May Predict Safety and Efficacy 23andMe is incorporating clinical genotyping into our clinical trials • Use of polygenic scores could enable more efficient clinical development and improve the probability of success • Developing drugs in genetically-defined patient populations may differentiate products based on better outcomes and improved benefit-risk profiles Providing the right drugs to the right patients Copyright © 2022 23andMe, Inc. 23andMe 53#54Executive Summary - Therapeutics 23andMe has generated a research and development pipeline covering multiple therapeutic areas in indications of high unmet medical need • To date, more than 40 programs have been generated from the database as part of our collaboration with GSK GSK has extended their exclusive target discovery period of their collaboration with 23andMe for an additional fifth year • 23andMe advanced a novel immuno-oncology antibody targeting CD200R1, 23ME-00610, into the clinic • 23andMe has taken a royalty option on immuno-oncology antibody collaboration program targeting CD96 into later stages of development • Managing our therapeutic portfolio investments based on scientific data to optimize investment, mitigate risk and maximize potential future returns Copyright © 2022 23andMe, Inc. 23andMe 54#55Genetics-Based Primary Care Paul Johnson Vice President, General Manager, Consumer Copyright © 2022 23andMe, Inc. 23andMe 55#56Impact of Different Factors on Risk of Premature Death The NEW ENGLAND JOURNAL of MEDICINE SPECIAL ARTICLE SHATTUCK LECTURE - - Improving the Health of the American People We Can Do Better Steven A. Schroeder, M.D. Source: Schroeder, SA. (2007). We Can Do Better - Improving the Health of the American People. NEJM. 357:1221-8. Social & Environmental Factors 20% Health Care 10% Health and Well-being Individual Behavior 40% Genetics 30% Copyright © 2022 23andMe, Inc. 23andMe® 56#57Opportunity to Deliver Genetics-Based Primary Healthcare at Scale X 234 + 23andMe lemo émonaid 1 Health Affairs, "Views Of Primary Care Providers On Testing Patients For Genetic Risks For Common Chronic Diseases." (2018). Genetics-Based Primary Care Diagnostics Testing Pharmacy / E- Prescribing Telehealth Wellness Reports Medical Records Copyright © 2022 23andMe, Inc. 23andMe® 57#58What is Genetics-based Healthcare? Health Predispositions Targeted prevention, monitoring, and management Wellness Targeted to help you feel your best Carrier Status Understanding your potential risks Pharmacogenetics Therapeutics that work for you Copyright © 2022 23andMe, Inc. 23andMe® 58#59Personalized Healthcare at Scale Healthcare based on a patient's wellness, choices, and genetics Acquiring Lemonaid Health positions us to • Provide personalized healthcare at scale • Become a trusted holistic wellness and healthcare brand • Create a fully integrated offering across 23andMe with accessible, affordable healthcare, driving strategic differentiation Copyright © 2022 23andMe, Inc. 23andMe® 59#60The Power of Polygenic Risk Scores (PRS) for Personalized Healthcare Geoff Benton, Ph.D. Director, Product R&D Copyright © 2022 23andMe, Inc. 23andMe 60#61Consumer 11.9M Genotyped Customers¹ »>»>> Consumer Powered Healthcare Flywheel We run hundreds of billions of association tests per year that further our unique understanding of human biology Data >>> 80% Opt-In to Research Research اااه XXX Phenotypic Data Genetic Data Insights 1. As of September 30, 2021. 2. As of March 31, 2021. Programs include collaborated, 100% owned and royalty interest targets. 4B+ Phenotypic Data Points¹ Innovative Results Return Value to the Customer Therapeutics / Product Drug Discoveries 40+ Programs² Novel Consumer Products ≈ Copyright © 2022 23andMe, Inc. 23andMe 61#62Health Predispositions 30+ Including: Type 2 Diabetes (Powered by 23andMe Research) Coronary Artery Disease 23andMe+ Uterine Fibroids Migraine 23andMe+ MUTYH-Associated Polyposis BRCA1/BRCA2 (selected variants) HOXB13 (prostate cancer) Type 2 Diabetes Your genetics are associated with a typical likelihood. Based on your: DOC Genetics Age Our Health Service The First and Only Multi-Disease DTC Genetic Service That Includes FDA-Authorized Reports and Provides Personalized Genetic Insights and Tools 37% (4) Ethnicity 1 Wellness information does not require FDA Authorization. Wellness 1 10 Including: Muscle Composition Genetic Weight Alcohol Flush Reaction Saturated Fat and Weight Sleep Movement Dog & Cat Allergies 23andMe+ Genetic Weight YOUR RESULT Your genes predispose you to weigh about 7% less than average. Average 142 lbs Carrier Status 40+ Including: Cystic Fibrosis Sickle Cell Anemia Familial Hyperinsulinism (ABCC8-Related) Tay-Sachs Disease Glycogen Storage Disease (Type 1a) Chromosome 15 Tay-Sachs Disease YOUR RESULT You do not have the variants we tested. 0 variants detected in the HEXA gene Pharmacogenetics 3 Including: SLC01B1 Drug Transport CYP2C19 Drug Metabolism • e.g., citalopram and clopidogrel DPYD Drug Metabolism Pharmacogenetics Genetic variants may influence how you process medications. YOUR RESULTS CYP2C19 Drug Metabolism LIKELY NORMAL METABOLIZER DPYD Drug Metabolism LIKELY NORMAL METABOLIZER SLCO1B1 Drug Transport LIKELY NORMAL METABOLIZER Print summary 7 FDA Authorizations Copyright © 2022 23and Me, Inc. 23andMe+ 23andMeⓇ 62#63Genome-Wide Association Studies (GWAS) GWAS is a statistical analysis of Single Nucleotide Polymorphisms (SNPs), looking To identify differences in frequency between disease cases and controls. SNPs linked with disease will be found at different frequencies in cases versus controls. Association is represented by the level of statistical significance (p-value) of the SNP frequency difference. SNPs can be tested across the genome and mapped to specific regions. Single Nucleotide Polymorphism (SNP) GGCCAGCTGGACGAGG GGCCAGCTGGATGAGG - log10 (pvalue) 200 100- 50 8 20 10 5 2 1 2 3 4 10- 102.2 5 102.4 6 FL120079 7 AIR 102.6 8 9 LIRI AMAL 102.8 Cases 10 11 12 ns11123823 GALE SLOBAL LA 14 SLOBA 103.2 16 MESIDE THEMI 103.4 80 18 20 22 X Copyright © 2022 23andMe, Inc. Controls 23andMe 63#64GWAS GWAS: Genome-Wide Association Study Prediction with Polygenic Scores (PGS) Feature selection Modeling Personalized risk estimates Copyright © 2022 23andMe, Inc. 23andMe® 64#65Using Polygenic Risk Scores to Meaningfully Stratifying Actual Results Mean actual BMI 30 29 28 27 26 25 24 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Low predicted BMI High predicted BMI Genetic score Copyright © 2022 23andMe, Inc. 23andMe 65#66Personalized Risk Report Genetic Weight Your genes influence not just your weight, but also the impact of different healthy habits. Overview Scientific Details John, your genes predispose you to weigh about 8% more than average. This predisposition doesn't mean you will definitely weigh more than average. Keep in mind that your lifestyle and environment have a big impact on your weight. How did we calculate your result? We determined your result by looking at DNA variants associated with weight based on our research. Some variants have a stronger effect on weight than others, which our analysis took into account. Because of this, your proportion of higher to lower weight variants may not exactly align with your overall predisposition. Keep in mind What is average? } 179 lbs For a 41-year-old man who is 5'8" Copyright © 2022 23andMe, Inc. 23andMe 66#67FY'21 Releases Coronary Artery Disease, Atrial Fibrillation, High Blood Pressure, LDL Cholesterol Migraine Uterine Fibroids Obstructive Sleep Apnea Restless Legs Syndrome Gout Non-Alcoholic Fatty Liver Disease Kidney Stones Polycystic Ovary Syndrome Triglycerides FY'22 Releases Cat Allergy, Dog Allergy Eczema (Atopic Dermatitis) Low HDL Cholesterol Gallstones Gestational Diabetes Severe Acne ONearsightedness O Coming soon O Coming soon Coming soon Copyright © 2022 23andMe, Inc. 23andMe® 67#68It's Not Just About Genetics, It's About Prediction XX Genetics Lifestyle Environment Machine Learning Personalized Disease Risk Assessment Insight into potential trajectories • Potential impact of different interventions • Risk over time as behaviors, biometrics, and health change Copyright © 2022 23andMe, Inc. 23andMe® 68#69Using PGS to Predict Real-world Outcomes » Can use PGS to predict incident cases of Type 2 Diabetes (T2D) The 95th percentile of genetic risk has nearly 3x increase in risk for developing T2D Incidence Rate Cumulative Incidence Rate 0.03- 0.02 - 0.01 - 0.00 - I 20 40 Age onset 60 Copyright © 2022 23andMe, Inc. 80 95th percentile PGS Total Population 5th percentile PGS 23andMe® 69#70Bending the Curve with Lifestyle Combine PGS with lifestyle factors to improve prediction of incident cases of Type 2 Diabetes (T2D) Lifestyle factors allow for greater precision of risk estimates and better personalization of results for customers Incidence Rate 0.03 - Cumulative Incidence Rate 0.02 - 0.01 - 0.00 - 20 Age onset 60 Copyright © 2022 23andMe, Inc. I 80 High genetic risk Unhealthy lifestyle High genetic risk Healthy lifestyle 23andMe® 70#71Opportunity for Personalized Healthcare at Scale Practice of Medicine Today Reactive - no customization until symptomatic ¶¶¶¶¶ P 23andMe+ Proactive - truly individualized from the very beginning >>> >>> Copyright © 2022 23andMe, Inc. 23andMe® 71#72Delivering Genetics-based Primary Care Service Davis Liu, M.D. Chief Clinical Officer Copyright © 2022 23andMe, Inc. 23andMe 72#73Lemonaid Health is Fully Integrated with a Broad Service Offering Online doctor visits Cutting out the doctor waiting room - with fully integrated w-2 core clinical team Mail order pharmacy Cutting out the retail pharmacy - owned and controlled mail order pharmacy ← → Broad range of services Building the online healthcare brand with the biggest impact All connected using an algorithm-driven proprietary technology platform Copyright © 2022 23andMe, Inc. 23andMe® 73#74The Future: Primary Care Complete Will be matched with a doctor who is attuned to genetics, wellness goals, interests, and medical conditions. Previous What are your main health goals/interests? Select up to three. Get Healthy émonaid Sports Performance Eat Better Sleep Better Stay Healthy Log Build Muscle Quit Smoking Lose Weight Exercise More Reduce Stress Next Type 2 Diabetes Your genetics are associated with a typical likelihood. DDC 198 Age 37% (1) Genetic Weight Your genes predispose you to weigh about 7% less than average. Average 142 lbs Lemonaid Health clinician Copyright © 2022 23andMe, Inc. 23andMe® 74#75The Future: Primary Care Complete Initial video visit focused on overall health and well being - not just the 10% ● O Genetics O O O Individual Behavior Wellness Health Care Long-term relationship Leading to long, healthy, productive lives Just the beginning! Social & Environmental Factors 20% Health Care 10% Health and Well-being Individual Behavior 40% Genetics 30% Copyright © 2022 23andMe, Inc. 23andMe® 75#76Concluding Remarks Anne Wojcicki CEO and Co-Founder Copyright © 2022 23andMe, Inc. 23andMe 76#77Future of 23andMe • Continuing to be world leader in direct-to-consumer personal genetic health services, growing annually Pioneering a genetics-based primary care service that empowers individuals to be proactive with their health Developing a pipeline of over 40 clinical and research stage programs addressing targets validated by human genetics • Leveraging strong balance sheet to support investment in therapeutics portfolio and strategic initiatives in DTC personal health services Copyright © 2022 23andMe, Inc. 23andMe® 77#78Q&A Copyright © 2022 23andMe, Inc. 23andMe® 78