#1X 23andMe 23andMe Therapeutics 23andMe Therapeutics January 2024#2Forward-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 23andMe's strategy, financial position, funding for continued operations, cash reserves, projected costs, plans, database growth, future collaborations, future development of therapeutic programs or products and objectives of management, are forward-looking statements. The words "believes," "anticipates," "estimates," "plans," "expects," "intends," "may," "could," "should," "potential," "likely," "projects," "continue," "will," "schedule," and "would" or, in each case, their negative or other variations or comparable terminology, are intended to identify forward- looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMe's current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMe's forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company's filings with the Securities and Exchange Commission, including under Item 1A, "Risk Factors" in the Company's most recent Annual Report on Form 10-K, as filed with the Securities and Exchange Commission, and as revised and updated by our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward- looking statements. Investors are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Except as required by law, 23andMe does not undertake any obligation to update or revise any forward-looking statements whether as a result of new information, future events, or otherwise. Copyright © 2024 23and Me, Inc. 23and Me 2#3GENETICS 23andMe Therapeutics: Genetics Reimagining R&D Our Value Proposition Our credo: Every Day Matters Higher probability of success in the clinic Forward-thinking expert team • Current focus: Oncology Development, Immunology Discovery • Fast timelines and early kill decisions from discovery through clinical development to approval • Indication selection informed by lifetime genetic risk based on world's largest human genotypic & phenotypic data platform • Genetics (e.g. GWAS, PRS) and biomarkers to optimize target- indication-patient clusters • Experienced, innovative genetics researchers and clinical development team with track record for innovative approvals Genetics and clinical development scientists to identify higher success programs to bring into the clinic Copyright © 2024 23and Me, Inc. 23andMe 3#4Using Human Genetics to Create Meaningful Therapeutics for Diseases with High Unmet Need in Oncology and Immunology SPEED Antibody and protein engineering Pleiotropy informs clinical development and safety NEED Creative use of pleiotropy Translational assays to address unmet medical needs Patients POWER Largest human genetics-based discovery platform 1000+ traits World's largest pleiotropy map Copyright © 2024 23and Me, Inc. 23and Me 4#5The Power of Our Approach#6Leaders in Data 23andMe Has the Largest Recontactable Genetic Database for Target Discovery in the World Largest, most diverse recontactable database of genotyped + phenotyped individuals 23and Me REGENERON MILLION VETERAN PROGRAM UK BIOBANK DECODE GENETICS FINNGEN ALL OF US GENOMICS ENGLAND ¹ As of September 30, 2023. -2M+ 900,000+ 500,000 500,000 473,000+ 413,000+ 100,000 *Publications supporting human genetic evidence for approved drug indications Nelson et al., 2015 (Nature Genetics); King et al., 2019 (PLOS Genetics) ~80% consent to research 14M¹ Pharma partnerships leverage the database for research and recruitment Target discovery Target validation Patient selection Clinical trial recruitment GSK Janssen Drugs with human genetic support are 2x - 3x Copyright © 2024 23and Me, Inc. more likely to succeed* Genentech Pfizer 23andMe 6#7POWER: Combining Our "I" and "O" Phenotypes Gives Us Broad Statistical Power to Drive Unique Immunological Insights for Oncology Development 10 phenotypes of interest (examples) "I" Immune phenotypes Vitiligo "O" Oncology phenotypes BCC Bladder Brain Breast Colorectal Endometrial Esophageal Head and Neck Kidney' Leukemia Liver Lung Melanoma Myeloma NH lymphoma Ovarian Pancreatic Prostate SCC Stomach Thyroid Cases 410,104 15,663 4,586 118,632 25,398 17,912 1,134 8,596 14,934 13,763 3,077 12,367 125,364 7,127 17,643 13,044 2,910 71,616 218,805 3,508 27,25al: 1,133,442 Alopecia areata Hashimoto's IBD Atopic dermatitis Poison oak rash Allergy Food allergy Asthma Tonsillectomy Toenail Fungus Psoriasis Hidradenitis suppurativa Lupus Cases 60,701 56,233 186,069 116,788 716,447 783,604 2,053,011 213,185 1,128,292 270,499 276,405 277,525 31,008 58,414 Biological processes of interest captured in "I" phenotypes, not targeted in the clinic yet Autoimmunity Immune Polarization Atopy Inflammation Chronic Infection Tissue Repair Copyright © 2024 23and Me, Inc. 23and Me 7#8POWER: 23andMe Database Contains >150 Immune Disease Phenotypes With Up To 100s of Novel Genetic Insights Per Disease for Immunology Discovery Drugs with human genetic support are 2x-3x more likely to succeed¹ Nelson et al., 2015 (Nature Genetics); King et al., 2019 (PLOS Genetics) Disease Asthma COPD Atopic dermatitis 23andMe GWAS Psoriasis Severe acne Urticaria Hidradenitis Rosacea 1.1M 83k 716k 278k 535k 461k 31k 352k Alopecia areata 56k 61k Vitiligo IBD 117k ¹23andMe multi-ancestry meta-analysis GWAS as of October 2023 cases Public GWAS cases 65k 36k 84k 19k 34k 41k 1.6k 73k 3k 4.7k 60k Skin 23andMe hits beyond largest public GWAS Copyright © 2024 23and Me, Inc. 716 171 399 319 735 386 148 421 67 75 54 Respiratory 23and Me Bowel 8#9GWAS: The Initial Foundation for Genome Analysis >>> >>> Single Nucleotide Polymorphism (SNP) GGCCAGCTGGACGAGG GGCCAGCTGGAT GAGG Cases Controls On GWAS = Genome-Wide Association Study SNPs associated with disease found at different frequencies in case vs controls Extensive know-how required to get from association to therapeutic target -log10 (pvalue) 200 100 50- 20- 10 5 2 3 4 9022 5 6 7 8 9 10 11 MEA 110.2 Copyright © 2024 23and Me, Inc. FEMINISTADEL 14 16 18 20 22 X T SNPs are tested across the genome and disease associations mapped to specific regions 23and Me 9#10PheWAS: Breadth of Phenotyping Elucidates Critical Disease Drivers 23andMe runs GWAS in >1,000 phenotypes PheWAS (Phenome-Wide Association Study) captures pleiotropic effects of genetic variants and points to possible unwanted toxicities or potential indication expansions OR [95% CI] 0.650.725 0.8 0.8750.95 1 eosinophilic_esophagitis any_asthma rhinitis TSLP PheWAS - - + eczema psoriasis crohns ulcerative colitis multiple sclerosis - LE psoriatic_arthritis hashimotos T1D ● ● ● We observe a clear genetic signal linking TSLP to asthma We do not observe signals in phenotypes that would point to safety issues Amgen clinical trials of anti-TSLP mAb as eczema target failed. We do not observe a statistically significant genetic signal linking TSLP to eczema We observe a strong genetic signal linking TSLP to eosinophilic esophagitis → potential indication expansion in a rare disease Copyright © 2024 23and Me, Inc. 23andMe 10#11POWER: Immune Genetics Implemented as an IO Clinical Biomarker Germline genetic score (PRS) for hypothyroidism risk separates survival probability Phase 3 trial failure → Withdrawal of triple-negative breast cancer indication Atezolizumab+Nab-Paclitaxel 181/451 Placebo+Nab-Paclitaxel 208/451 Percentage of Patients PMID: 30345906; PMID: 34099659 100- 90- 80- 70- 60- 50- 40- 30- 20- 10- 0- 0 T 3 No. of Events/ No. of Patients -6 9 12 Median Overall Survival (95% CI) mo 21.3 (17.3-23.4) 17.6 (15.9-20.0) 15 Stratified hazard ratio for death, 0.84 (95% CI, 0.69-1.02) P=0.08 N~900 HR~0.84 18 Months 21 Atezolizumab+nab-paclitaxel 2-Yr Rate of Overall Survival (95% CI) % Placebo+nab-paclitaxel 24 42.1 (34.3-49.9) 39.7 (33.2-46.3) 27 30 33 36 N~150 HR~0.62 Survival probability 1.0 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 Number at risk 737 Atezo (PD-L1) + Chemotherapy ~15 months 266 #5 60 ~26 months 20 14 10 900 580 Copyright © 2024 23and Me, Inc. 1000 1100 1200 1300 1400 5 10 14 13 23andMe 11#12POWER: Combining Extensive Pleiotropy in the 23andMe Database and Computational Biology for Target Discovery Genetic insights GWAS signals / pleiotropy (one variant affecting multiple traits) disease 1 disease 2 disease 3 disease 4 signal 1 signal 2 signal 3 signal 4 signal 5 signal 6 Computational Biology ML / AI QTL-based and custom ML models for gene mapping and target hypothesis prioritization Interpretation of GWAS signals making extensive use of pleiotropy and allelic series and to increase reliability of biological conclusions Analysis of bulk/single cell/differential gene expression Biological insights genes, mechanisms, pathways and cell types Copyright © 2024 23and Me, Inc. JAK/STAT Th1/Th2 dif Recept int Th17 diff 23andMe 12#13Utilizing the World's Largest Human Pleiotropy Map to Address Unmet Medical Need#14NEED: Our Unique Approach to De-risk Development: Leveraging Pleiotropy to Characterize Novel Cancer Targets 23andMe "IO Signature" Type 1 diabetes thyroid diseases celiac RA psoriasis SCC BCC Melanoma Variant 1 Variant 2 CTLA4 gene increased risk signed log(p) 10 5 -5 -10 decreased risk 23ME-00610 Lead Asset (currently in Ph2a*) CD200R1 Basal cell carcinoma Hypothyroidism Hashimoto's DOK2 Basal cell carcinoma Mosquito bite itch/size Eczema Any asthma Any allergy Juvenile asthma Any animal allergy *Currently in Phase 2a portion of Phase 1/2a Cancer Immune 10 5 -5 -10 -Log(P value) Investigator-assessed irAEs Genomic data successfully predicted '610 AE Profile 1400 mg- 600 mg 200 mg- 60 mg 20 mg 6 mg 2 mg 8 5 10 15 20 % of Phase 1 Participants Hypothyrodism Pruritus Rash/Rash maculo-papular Copyright © 2024 23andMe, Inc. 25 23andMe 30 14#15NEED: Our FXG Efforts Leverage Pleiotropy to Identify Targets in Defined Areas of Medical Need in Asthma 23andMe genetics 23andMe Asthma & COPD GWAS Eczema GWAS Bulk and single-cell RNA-seq In vitro functional genomics Gene Editing 32 days NHBE cells ALI culture Arrayed Library Disease-relevant readouts Barrier function Cell composition & mucin production Log10FU Negative Copyright © 2024 23andMe, Inc. CD63 STATE Positive STA FOX NO MUCS Validated targets with pharmacologically meaningful effects in disease relevant assays hom 23and Me 15#16Progression of Therapeutics at Speed#17SPEED: Our In-House Expertise in Antibody and Protein Engineering Enables Rapid Therapeutic Generation Experienced Antibody and Protein Engineering group • Deep experience in protein engineering, biochemistry, structural biology, enabling diverse approaches to antibody discovery, antibody engineering, and automation ● hCD200R1 610 Fab Protein engineering and biochemistry NGS/Automation M13 Phage Antibody discovery and optimization YAHY Antibody formats and Fc engineering Copyright © 2024 23andMe, Inc. 23andMe 17#18SPEED: Our lead IO program progressed from discovery to the clinic in 5 years 23andMe "IO Signature" Type 1 diabetes thyroid diseases celiac RA psoriasis SCC BCC Melanoma Variant 1 Variant 2 CTLA4 gene increased risk signed log (p) 10 5 -10 decreased risk 23ME-00610 Lead Asset (currently in Ph2a of Phase 1/2a trial) Cance Immune CD200 Ligand ● DOK2 CD200R1 Protein Receptor Immune Cancer Immune || Cancer Hashimoto' S Hypothyroidism BCC Program initiated: 2016 • Lead molecule generated by 23andMe • First human dosed: 2021 Investigator-assessed irAEs Genomic data successfully predicted '610 AE Profile 1400 mg 600 mg 200 mg- 60 mg 20 mg 6 mg 2 mg Q 5 10 15 20 % of Phase 1 Participants Hypothyrodism Pruritus Rash/Rash maculo-papular Copyright © 2024 23andMe, Inc. 25 23andMe 30 18#1923andMe Therapeutics: Clinical Development#20Experienced Clinical Development Leadership Jennifer Low, MD, PhD Head of Development Genentech LOXO ONCOLOGY Erivedge (vismodegib) Vitrakvi (larotrectinib) Zelboraf (vemurafenib) Cotellic (cobimetinib) Maike Schmidt, PhD Sr Group Head, Translational Sciences Genentech FivePríme Avastin (bevacizumab) Tecentriq (atezolizumab) Dylan Glatt, PhD Sr Clinical Pharmacologist, 23ME-00610 PTL GILEAD Jyseleca (filgotinib) Copyright © 2024 23and Me, Inc. 23and Me 20#2123andMe Therapeutics IO Pipeline: First-in-Class Potential 23ME'610 anti-CD200R1 23ME'1473 anti-ULBP6 Target Discovery ● Lead Optimization Solid tumors, clinical stage, 10 effectorless mAb Solid tumors, IO effector-enhanced mAb 23ME'610/anti-CD200R1 Targets Innate and Adaptive Immunity Potent Ab with great PK/PD • Phase 1 monotx with on-target AEs • Ph2a data expected to be presented mid- 2024 Note: '610 is in Phase 1/2a as of January 2024. IND Enabling Phase 1 Phase 2 Phase 2a* 23ME'1473/anti-ULBP6 • Activator of tumor NK cells • Effector-enhanced Ab with dual NK- activating MOA Copyright © 2024 23and Me, Inc. 23and Me 21#2223ME-00610* Anti-CD200R1 Antibody for Hard-to-Treat Solid Tumors Phase 1/2a *Wholly owned; development ongoing in multiple relapsed/refractory solid tumors (including neuroendocrine and ovarian)#23Patients + Caregivers DESPERATELY seeking survival Targeted therapy Standard therapy Survival- 1 2 CD200R1 Basal cell carcinoma H Hypothyroidism Hashimoto's 30 Years after diagnosis CD200 CD200/R1 is a dominant immune checkpoint* Basal cell carcinoma Any allergy '610 Development Rationale Addressing Critical Unmet Need in Solid Tumors Allergic Asthma Juvenile Asthma Any asthma 1 DOK2 Immunotherapy Standard therapy Basal cell carcinoma Mosquito bite Itcn/size Eczema 2 Any asthma Any allergy Juvenile asthma Any animal allergy ©nature 10 Cancer Immune 10 5 Y 2 -5 3 -10 -Log(P value) CD200K (inhibitory cell surface receptor), CD200 (CD200R1 ligand), and DOK2 (involved in the CD200/CD200R1 signaling pathway). *PMIDS: 12960329, 23602662, 22264927, 19786546, 15557172, 22491458, 15220441, 34326171, 18081533, 24388216, 11099416 Potential activity in >60% of current patients not deriving efficacy from PD-(L)1 inhibitors Average Percent Change CD200 . Mean EASI Percent Change from Baseline by Treatment in Atopic Dermatitis* Targeted by samalizumab for CLL and MM, failed to achieve target saturation" Highly expressed on tumor, stromal, and endothelial cells 8 12 Week A Last dose Follow-up Period 16 20 24 CD200R1 ●CD200R Placebo Restricted immune expression: myeloid > T > B 23ME-00610 ('610) is first-in-class Lilly's Ucenprubart: Clinical POC for CD200/R1 agonism in immune disease *PMID: 31443741; https://investor.lilly.com/static-files/9efbede9-bd6a-4d7b-823e-2996b1c2d114 Copyright © 2024 23and Me, Inc. 23andMe 23#24'610 Primary Pharmacology* ● 23ME-00610 (¹610), a Fully Humanized, Effectorless IgG1, Inhibits Immunosuppressive Signaling via High Affinity Binding to CD200R1 Subnanomolar affinity Kills tumor cells in vitro • Anti-tumor activity in vivo Potential for monotherapy o activity on huPBMCs that do not respond to PD-1 antibody Potential for combination * PMID: 37288324 ¹610 Activates T-cell Function by Blocking the CD200R1 Checkpoint Tumor cell Tumor cell CD200 +23ME-00610 DOO CD290R1 T cell ↓ IFNY +1-2 Antitumor cytotoxicity Tcell tIFNy t12 Antitumor cytotoxicity *CD200-expressing cell types include tumor, stroma and endothelial IFN, interferon; IL, interleukin '610 Clinical Development* Well tolerated up to 1400 mg • PK supports Q3W (or better) Promising therapeutic index, projected dose ≥ ~600 mg • Monotherapy dev ongoing O Further expansion in NE and OC for safety, PK, PD and dose selection Indication CDPs and TPPS * Rasco, et al., 2023, SITC Annual Meeting #619; Glatt, et al., 2023 SITC Annual Meeting #609 Copyright © 2024 23and Me, Inc. 23andMe 24#25'610 Phase 1 Results: Dose Escalation Duration of Treatment Stable disease rate across ALL Phase 1 patients is 52% with median duration of 18.6 weeks Merkel cell carcinoma. Chordoma Poorly differentiated pancreatic neuroendocrine Colorectal Pancreatic adenocarcinoma Myoepithelial carcinoma Squamous cell carcinoma TUMOR TYPE Osteosarcoma Papillary carcinoma Well differentiated pancreatic neuroendocrine Clear cell chondrosarcoma Colorectal Squamous cell carcinoma. Esophageal adenocarcinoma Colorectal Melanoma Colorectal Esophageal adenocarcinoma Prostate Neuroendocrine Sarcoma Endometrial adenocarcinoma Sarcoma Ampullary adenocarcinoma Melanoma Colorectal Pancreatic adenocarcinoma 10 A Rasco, D, et al., 2023, SITC Annual Meeting #619 2 A 3 Best Overall Response OSD+PD 4 5 8 Time from 23ME-00610 First Dose (Months) 60 mg 200 mg 6 20 mg 7 9 A First PD or death Treatment ongoing X Last non-PD Assessment 10 600 mg 2 mg 6 mg Note: Treatment Duration=lend of treatment date first dose date + 1)/38.437. If a participant remained on treatment at the time of data cut-off, the data cutoff date was used. Colored portions of the horizontal bars represent the dose level the participants received. Intra-patient dose escalation to the next cleared dose level was permitted for participants who did not experience a Grade 3 or above study-drug related AE 1400 mg 11 Copyright © 2024 23andMe, Inc. 12 May 15, 2023 data cut-off date. 23andMe 25#26'610 Preliminary Clinical Activity in Neuroendocrine Cancer Coches Baseline Baseline Liver Lesion Rasco, D, et al., 2023, SITC Annual Meeting #619 Week 24 Paratracheal Lymph Node Lesion Week 24 Week 40 Week 40 • 23ME-00610 treatment was well tolerated • 19% reduction in target lesions at Week 24 and Week 40 assessment • 58% size reduction in longest dimension of paratracheal lesion • Patient continues on study drug at Cycle 13 with stable disease at time of data cutoff (May 2023) Copyright © 2024 23and Me, Inc. 23andMe 26#27'610 Phase 2a Data: Estimated Timeline* 1400 mg Q1 CCRCC OV NE Q2 SCLC 2023 TMB-H/MSI-H Q3 Q4 -600 mg Q1^ Q2 Safety: N= ~55-60 pts Efficacy: N= ~25-30 pts OV NE First Efficacy Assess. First Efficacy Assess. ^Genotyping, tumor (archival) CD200/R1 IHC, tumor RNAseq, and pre/on-treatment tumor immunophenotyping exploratory analyses to identify potential correlates with activity 2024 First Efficacy Assess. Q3 Q4 Safety: N= ~90 pts Efficacy: N= ≤ ~60 pts 6-mo PFS/OS 6-mo PFS/OS First Efficacy Assess. First Efficacy Assess. N=15 in each cohort Enrolling Fully Enrolled 6-mo PFS/OS 12-mo PFS/OS 12-mo PFS/OS 6-mo PFS/OS 6-mo PFS/OS *Part of the Phase 1/2a clinical study of '610. Strictly estimated dates for discussion purposes only. Based on calendar year. Subject to change. Q1 Q2 Safety: N= ≤ ~100 pts Efficacy: N= ≤ ~75 pts 12-mo PFS/OS 12-mo PFS/OS 12-mo PFS/OS First Efficacy Assess. First Efficacy Assess = ie., Preliminary ORR, patients continue to be scanned First Efficacy Assess. 6-mo PFS/OS 6-mo PFS/OS 2025 Safety in Phase 2a Population Efficacy in Phase 2a Population Q3 Q4 Safety: N= ≤ ~110 pts Efficacy: N= ≤ ~90 pts CCRCC = clear cell renal cell carcinoma OV = ovarian cancer (predominantly non-clear cell histology) SCLC = small cell lung cancer (extensive stage) NE neuroendocrine Copyright © 2024 23andMe, Inc. 12-mo PFS/OS 12-m PFS/OS TMB-H/MSI-H = tumor mutational burden / microsatellite instability high tumors 2026 Q1 23and Me 27#28'610 Differentiation: Inhibition of CD200R1 Has the Potential to Address Resistance to Anti-PD1 Therapies IFNY fold change relative to isotype Y Blocking the CD200R1 pathway enhanced IFNy production from SEB-stimulated PBMCs compared to isotype control and anti-PD1 in the majority of samples tested Colorectal Endometrial 1 Endometrial 2 Endometrial 3 Lung Ovarian Melanoma Prostate Pancreatic Isotype 23ME-00610 Anti-PD-1 PBMC, peripheral blood mononuclear cell; PD-1, programmed death-1; SEB, staphylococcal enterotoxin B. PBMCs from each respective patient were incubated with 100 nM of 23ME-00610, anti-PD-1, or isotype control. Cells were stimulated with SEB. IFNy levels were determined by enzyme-linked immunosorbent assay. Mean biologic triplicates were normalized to isotype control. * p-value<=0.05 compared to control Copyright © 2024 23andMe, Inc. 23andMe 28#29● Primary Human T Cells CD200R1 '610 Differentiated Combo Potential: Anti-CD200R1 with Anti-PD-1 Potentially Enhances Immune Activation CD200 T Cell Activation TCR aCD3 CHO cells PD1 PDL1 +23ME-00610 + anti-PD-1 23ME-00610 CD200 2 ug/mL per antibody. Representative data from one of four donors tested. Statistics: Ordinary one- way ANOVA with Tukey's multiple comparisons test, **p<0.01, ****p<0.0001 T Cell Activation TCR IFN-Y. aCD3 CHO cells anti-PD-1 PDL1 IFNY (pg/mL) 3600- 3000- 2400- 1800- 1200- 600- 0 IFNY Secretion Isotype **** **** anti-PD-1 23ME-00610 Preliminary data from ex-vivo combination of anti-PD-1 and anti-CD200R1 blockade increased IFNY (interferon-gamma) secretion from primary human T-cells Ob Copyright © 2024 23and Me, Inc. 7 Combo *23andMe internal data 23andMe 29#30'610 Next Steps • Complete enrollment of Phase 2a Dose Expansion Cohorts Recently expanded Neuroendocrine, Ovarian cohorts o Initial Phase 2a data cohorts planned to be presented mid-2024 O o Clinical development planning for Fast-to-Market strategies o Potential clinical combinations with assets with complementary mechanisms, to support earlier line indications Seeking partnerships to expand Phase 2a and conduct randomized Phase 2b/3 clinical trials - multiple readouts expected in 2024 Copyright © 2024 23and Me, Inc. 23andMe 30#3123ME-01473 Genetically validated NK Cell Activator (Anti-ULBP6) Antibody for [Metastatic] Solid Tumors#32ULBP6 inhibition could benefit patients in broad range of tumor types with neoantigen loss Tumor type HNSC² CESC3 Additional tumor types under CDA 23andMe Tumor ULBP6 +++ 23ME'1473: Tumor Cell Killing-Enhanced Antibody Targets Major Resistance Mechanisms Hampering Immune Oncology Targeting NK cells and NKG2D shows clinical promise +++ +++ Soluble ULBP6 Under CDA Under CDA Under CDA 2HNSC, Head and Neck Squamous Cancer; 3CESC, Cervical Squamous Cell Cancer Loss of antigen presentation¹ ++ +++ +++ ¹Dhatchinamoorthy et al., Front Immunol 2021 Dual MOA achieves synergistic NK activation and tumor cell killing (Mean GFP expression well) NK cell T cell MOA 1 Shed ULBP60 Activating NKG2D receptor NKG2D ligand 60 Time lapsed (hour) 108 Tumor cell MOA 2 Effector enhanced Fc FcyR Surface ULBP6 NK cell MOA1 NKG2D activation MOA2 NKG2D activation + ADCC = 23ME-01473 Effector enhanced 23andMe developed major methodological improvements to targeting ULBP6 External clinical validation: Monotherapy activity observed in NKG2D pathway activator (related mechanism) with complete and partial responses at a tolerable dose in early phase clinical trial4 23andMe '1473 targets the highest affinity NKG2D ligand with a tumor cell killing-enhanced antibody 4Wang, et al., CLN-619 ASCO 2023 Copyright © 2024 23andMe, Inc. 32#33MOA 1 MOA 2 ¹1473 Dual MOA: Effector Enhanced Antibody Binds to Tumor Cell Surface ULBP6/2/5 to Bolster NK Cell Antitumor Activity via ADCC NK cell 23ME-01473 Activating receptor NKG2D NK cell FcyR Shed o Tumor ULBP6 O cell Surface MICA Surface ULBP2/5/6 Cytotoxic mediators Immune cells Tumor amount in the well (Mean GFP expression/ well) ADCC increases tumor cell killing 0 Green (GFP) Tumor Cells 20 40 60 80 Time elapsed (hour) 100 NKG2D activation 120 Isotype Effector enhanced CTRL anti-ULBP6 Effector attenuated MOA1 NKG2D activation + ADCC Copyright © 2024 23andMe, Inc. X 23ME-01473 Effector enhanced MOA1+2 23and Me 33#3423andMe Therapeutics: Target Discovery#35Bill Richards Head of Therapeutics Discovery AMGEN NURA BIO Insights from the 23andMe database Experienced Discovery Leadership Vladimir Vacic Research Fellow, Computational Biology NEW YORK GENOME CENTER Computational Biology Patrick Collins Director, Functional Genomics AMGEN Functional Genomics Antony Symons Senior Director Immunology & Inflammation AMGEN Immunology / Discovery Biology Germaine Fuh Senior Director Antibody & Protein Engineering Copyright © 2024 23andMe, Inc. Genentech Antibody Engineering Experienced team that delivered genetics-based targets from discovery to the clinic 23and Me 35#36Leveraging Pleiotropy to Expand Airway Target Space Hypothesis: loci associated with related phenotypes prioritize biologies not addressed by standard of care epithelial biology: screen mucociliary function in ALI culture genetic determinants of obstructive airway disease sensory neuron biology: screen in iPSC-derived neuron models genetic determinants of airway hyper-reactivity COPD > 200 loci + neuro- inflamm >500 loci asthma >600 loci eczema >500 loci + urticaria > 300 loci genetic determinants of allergy/T2 inflammation genetic determinants of mast cell pathology Pleiotropy + functional genomics = best targets T2 cytokine biology: deprioritize or develop SM/inhaled modality mast cell biology: screen in IgE dependent & independent assays Copyright © 2024 23and Me, Inc. 23andMe 36#37Strategic Sequencing Based on Polygenic Risk Scores Sequencing individuals from the tail ends of the polygenic risk score (PRS) distribution for whom the actual disease status does not match predictions low risk Polygenic Risk Score (PRS) Discovery of genes harboring rare variants of large effect high risk Copyright © 2024 23and Me, Inc. Legend: cases controls selected for sequencing 23andMe 37#38FxG in Respiratory Disease & Beyond Cell type Macrophage Mast cells Fibroblasts T cell Sensory Neurons Endothelial cells Airway Smooth Muscle Dendritic cell Keratinocytes Disease opportunities* Broad immune: skin, lung, GI Urticaria, allergy, RA, eczema Fibrosis, lung, skin, RA, IPF Broad immune: skin, lung, Gl Respiratory, IBD, eczema RA, sarcoidosis, IBD, PAH Asthma, COPD, PAH Broad autoimmune: T1D, Graves Skin Copyright © 2024 23andMe, Inc. 23and Me 38#398 23andMe Therapeutics