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Unlocking a new era of care for neuroinflammatory diseases. Investor Call November 3, 2026 Nasdaq: ANNX
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Forward-Looking Statements Forward-Looking Statements This presentation contains “forward -looking” statements about Annexon, Inc. and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts, including statements regarding our clinical and preclinical programs, timing and commencement of future nonclinical studies and clinical trials and research and development programs, timing of clinical results, anticipated timing of submission of a Biologics Lic ensing Application, strategic plans for our business and product candidates, including additional indications which we may pursue, our financial position, runway and ant icipated milestones, are forward -looking statements. In some cases, you can identify forward -looking statements by terminology such as “aim,” “anticipate,” “assume,” “be lieve,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “focus,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: our history of net oper ating losses; our ability to obtain necessary capital to fund our clinical programs; the early stages of clinical development of our product candidates; the effects of COV ID-19 or other public health crises on our clinical programs and business operations; our ability to obtain regulatory approval of and successfully commercialize our pr oduct candidates; any undesirable side effects or other properties of our product candidates; our reliance on third -party suppliers and manufacturers; the outcomes of any future collaboration agreements; and our ability to adequately maintain intellectual property rights for our product candidates. These and other risks are des cribed in greater detail under the section titled “Risk Factors” contained in our Annual Report on Form 10 -K filed with the Securities Exchange Commission (SEC) on August 12, 2026 and our other filings with the SEC from time to time. All forward -looking statements in this presentation speak only as of the date of this presentation. Excep t as required by law , we undertake no obligation to publicly update any forward -looking statements, whether as a result of new information, future events or otherwise . This presentation concerns drug candidates that are under clinical investigation, and which have not yet been approved for ma rketing by the U.S. Food and Drug Administration (FDA). These are currently limited by federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates or statistical data. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. 2
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Introduction 3 ©2025 Annexon, Inc3 Doug Love President & CEO W Lloyd Clark, MD SVP of Ophthalmology Roger Goldberg, MD, MBA Retina and Vitreous Diseases · Bay Area Retina Associates Ted Yednock, PhD Chief Innovation Officer
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Agenda 4 TIME (ET) TOPIC PRESENTER 11:00-11:05am Introduction & Overview Douglas Love, Esq President & CEO 11:05-11:15am Clinical Insights in Dry AMD with Geographic Atrophy Roger Goldberg, MD Retina and Vitreous Diseases · Bay Area Retina Associates 11:15-11:35am Vonaprument Vision Protection in P2 Trial and P3 Clinical Program Lloyd Clark, MD SVP , Ophthalmology Strategy & Innovation 11:35-11:45am Summary & Takeaways Douglas Love, Esq President & CEO 11:45am-12:15pm Q&A Presenters and Ted Yednock, PhD Chief Innovation Officer
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5 The future of medicine isn't simply extending life. It's ... Protecting the ability to live life. Annexon is pioneering a new class of targeted therapies designed to stop inflammation at its source in the body, brain, and eye before damage becomes irreversible. Protecting function for patients with devastating neuroinflammatory diseases OUR FOCUS:
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1st significant vision- sparing data in Phase 2 evaluating vision 1st Phase 3 trial evaluating vision - Mo 15 primary outcome Q4 2026 Potential Groundbreaking Lead Therapies for Patientsin Large Underserved Global Markets 6 First potential targeted rapid-acting therapy Tanruprubart for GBS Pipeline expansion opportunities including 1storal inhibitor of classical complement in the clinic (ANX1502), and 1st demonstration of inhibition of C1q inflammation in CNS for an array of diseases (e.g., HD, TBI) Comprehensive EU MAA filed Positive FORWARD study data to support planned US BLA First potential vision-preserving treatment Vonaprument for GA
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Takeaways for Today ©2025 Annexon, Inc7 Highlighting Key Aspects of ARCHER II Phase 3 Trial What vision protection means to patients and physicians Designed to replicate vision protection in targeted patient population Larger, longer, well-powered pivotal trial with multiple ways to win On track for 15-month primary analysis in Q4 2026 1 2 3 4
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Roger Goldberg, MD, MBA Vision is what Matters to Patients and Physicians in GA
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Geographic Atrophy Remains a Significant Unmet Need Geographic Atrophy Remains a Significant Unmet Need 9 GA IS A LEADING CAUSE OF BLINDNESS IN THE ELDERLY No approved treatments demonstrating vision preservation GA severely limits independence and greatly impacts quality of life Incidence projected to increase due to aging population Avg. Age of GA Patient: 79 years
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Vision Loss from GA Meaningfully Impacts Patients' Daily Lives 10 Recent survey results in patients with GA and their caregivers From the Voice of the Patient Report; Dry Age-Related Macular Degeneration (AMD) Externally-Led Patient Focused Drug Development Meeting (EL-PFDD) Meeting; Report date: May 17, 2024 ACTIVITIES GA PATIENTS ARE NOT ABLE TO DO, OR STRUGGLE WITH WHAT WORRIES GA PATIENTS MOST ABOUT THEIR CONDITION IN THE FUTURE
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GA is a Significant and Rapidly Growing Unmet Need Worldwide 11 1 in 100 Americans over age 50 have Advanced AMD WORLDWIDE 8M+ patients affected by GA1 US ~1.5M patients affected by GA2 EU ~2.5M patients affected by GA3 GA WORLDWIDE PREVALENCE IMPACTS MILLIONS INCIDENCE PROJECTED TO INCREASE WITH AGING POPULATION 1Keenan et al, Ophthalmology. 2018 Jul 27;125(12):1913–1928; 2Tufail A, et al. Presented at the 15th EURETINA Congress, Nice, France, September 17-20, 2015. Accessed November 21, 2019; 3Based on Colijin JM, et al., 2016; Wong WL,et al., 2014; Rudnicka AR,et al., 2014; Korb CA,et al., 2014; Piermarocchi S,et al., 2011; Fernandez-Arias C, et al., 2011; Augood CA,et al., 2006; 4Rudnicka AR et al., Ophthalmology. 2012;119(3):571-80. doi:10.1016/j.ophtha.2011.09.027
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ARCHER II Phase 3 Endpoint – BCVA 15 Letter Loss – is the Gold Standard Visual Acuity Endpoint in Retina Space 12 PRODUCT FUNCTIONAL PRIMARY ENDPOINT Wet AMD Lucentis Proportion losing <15 letters BCVA Eylea Mean BCVA change Vabysmo Mean BCVA change DME Lucentis BCVA ≥15 letter Eylea Mean BCVA change Vabysmo Mean BCVA change GA Syfovre N/A Izervay N/A BCVA 15 Letter Loss • Represents 3 lines of letter loss • Loss of independence (e.g., inability to read, drive) • Impact on independent living Clinically relevant, stable endpoint when confirmed at two consecutive visits
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13 CURRENT PARADIGM Establishing a new standard of care <10% of US patients being treated today1 Vonaprument HIGHLY DIFFERENTIATED PRODUCT PROFILE Enhanced benefit-risk enables full activation of global market opportunity Vonaprument Represents Potential Paradigm Shift for GA Patients Vision protection is what matters to patients, physicians and payers. Lesion Growth Slowing Medicines (no vision protection) 25 microliter dose Fab antibody Non-pegylated, low viscosity Well-tolerated 1 Derived from current publicly stated data that 10-15-% of US patients already diagnosed with GA have received treatment. But only about half (800,000 of 1.5m) of patients who are thought to have GA are actually diagnosed. Using 1.5m as a denominator, less than 10% have received treatment.
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Lloyd Clark, MD Unprecedented ARCHER Phase 2 Visual Acuity Outcomes ©2025 Annexon, Inc. All rights reserved
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Protected BCVA Gold Standard Ophthalmology Outcome Mechanistic Rationale for Functional Protection Vonaprument Overview Only GA Program toDemonstrate Significant Vision Protection 15 Protected Key Retinal Structure Required For Central Vision Anti-C1q stops inflammation & damage on vision-required photoreceptors Preserved functional photoreceptors followed by RPEs Dose dependent protection across multiple measures
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Anti-C1q is a Well-Researched & Differentiated Approach to Treating Neurodegeneration (protect synaptic / neuronal function) 1Stevens, et al., 2007 DOI 10.1016/j.cell.2007.10.036; Schafer et al., 2012 DOI 10.1016/j.neuron.2012.03.026; Hong, et al., 2016 doi: 10.1126/science.aad8373; Lui et al., 2016 doi.org/10.1016/j.cell.2016.04.001; 2Davies et al., 1987 J Neurological Sci 78:151; Terry, et al., 1991 Ann Neurol 30:572; 3Yoshiyama et al., 2007 DOI 10.1016/j.neuron.2007.01.010 C1q PLAYS KEY ROLE in NEURODEGENERATION PROCESS Normal role for synapse elimination in development Pathogenic role in neurodegenerative diseases Anti-C1q protects against synapse loss & neurodegeneration Ben Barres, M.D., Ph.D. Discovererof C1qTechnology ScientificCo-Founder,Annexon Anti-C1q Protective in Neurodegenerative Diseases, Including: Dry AMD (photoreceptor damage) Glaucoma Retinal ischemia Multiple Sclerosis/ Optic Neuritis Huntington’s disease Guillain-Barré syndrome Alzheimer’s disease Traumatic brain injury 16
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Photoreceptor cells (ONL) Photoreceptor cell synapses (OPL) Retinal Pigmented Epithelium (RPE) IPL INL Lesion loss of photoreceptors synapses and RPE Average 12 month GA lesion growth1 Intact photoreceptors synapses and cells furthest from lesion Declining photoreceptor synapses and cells dysregulated as approach lesion Annexon, data on file 200 m In GA Photoreceptorsand Synapses are Lost Before RPE Loss 1Selkoe, 2002 doi: 10.1126/science.1074069; Burger, et al., doi.org/10.1016/j.ydbio.2021.04.001; 2Bird et al., 2014 JAMA Ophthalmol doi:10.1001/jamaophthalmol.2013.5799; Li, et al., 2018 Retina 38:1937; Pfau, et al., 2020 10.1001/jamaophthalmol.2020.2914; Sarks, et al., 1988 Eye 2:552; 3Heier, et al., 2020 Ophthalmology Retina 4:673; 4Shen, et al., 2020 Ophthalmol Retina 4:899 Photoreceptor Health Functional retina Reduced function Lost function Photoreceptors responsible for visual acuity. Photoreceptor loss = vision loss 17
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ARCHER Phase 2: Greater Protection Against EZ Loss in Central Retina Necessary for Visual Acuity 18 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0 6 12 Sham (n = 22) Vonaprument pooled (n = 24) 0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0 6 12 Sham (n = 25) Vonaprument pooled (n = 36) 0 0.5 1 1.5 2 2.5 3 0 6 12 Sham (n = 67) Vonaprument pooled (n = 107) 27% decrease Nominal p-value^ PAN-MACULA Total EZ Loss LS Mean Change (± SE) from Baseline (mm2) Month Vonaprument Pooled vs Sham 0.0457 ^Nominal p-values from a linear mixed model for repeated measures model (slope) analysis; Heidelberg Spectralis OCT population with baseline OCT data, excludes patients with >98% atrophy/attenuation at baseline Month 48% decrease Vonaprument Pooled vs Sham 0.0218 CENTRAL 2.0 MM Vonaprument Pooled vs Sham 0.0319 CENTRAL 1.5 MM Month 59% decrease
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0 5 10 15 20 25 ARCHER Phase 2: Dose-Dependent Vision Protection at Month 12 and Over Time 19 Month PROBABILITY OF CONFIRMED BCVA ≥15-LETTER LOSS THROUGH MONTH 12# Nominal p-value vs sham^ --- .0076.0994 PARTICIPANTSWITH CONFIRMED BCVA ≥15-LETTER LOSS THROUGH MONTH 12# Month 12 event confirmed at month 15 Sham % Participants Vonaprument EOM Vonaprument EM 73% Risk Reduction Vonaprument EM HR (CI) = 0.272 (0.090 to 0.819); Nominal p = .0119* 50% Risk ReductionVonaprumentEOM HR (CI) = 0.504 (0.214 to 1.189); Nominal p = .1098 Estimate of Kaplan-Meier Probability (%) of Participants without≥15 LetterBCVALoss 16.9% 8.7% 4.5% * 15/89 8/92 4/89 #Confirmed BCVA 15-LL at two consecutive visits including month 12 supported by ensuing (off- treatment) visit; visits were monthly through Month 12 and then at Months 15 and 18 ^Nominal p-value from a Chi-square test in ITT population: *Nominal p < .05 #Confirmed BCVA 15-LL at two consecutive visits including month 12 supported by ensuing (off-treatment) visit HR, hazard ratio; Nominal log-rank test (versus sham) p-values are presented; *Nominal p < 0.05 Von ap rumen t EM 88 87 (0) 85 (0) 83 (1) 81 (2) 80 (2) 79 (2) 77 (2) 74 (3) 73 (4) 72 (4) 70 (4) 39 (4) Von ap rumen t EOM 91 91 (0) 88 (1) 87 (1) 84 (4) 82 (5) 82 (5) 80 (5) 79 (6) 77 (7) 77 (7) 76 (7) 50 (7) Sham 89 87 (2) 86 (2) 85 (3) 83 (4) 82 (4) 81 (5) 77 (7) 74 (9) 73 (9) 71 (10) 68 (12) 41 (14)
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ARCHER Phase 2: Demonstrated Dose-Dependent Vision Protection in Participants with Foveal and Non-Foveal Lesions ©2025 Annexon, Inc20 Vonaprument treatment effect across the disease spectrum Review of Subgroup based on Structural Characteristics Participants with confirmed BCVA ≥15-letter loss through month 12# Nominal summary p- value vs. sham^ ANX007 EM 0.0019 ANX007 EOM 0.0254 0 10 20 30 NON-FOVEAL 25.0% 16.3% 5.9% 11/44 8/453/51 2/388/49 1/43 % Participants 17.8% 2.3% 5.3% 19.1% 12.5% Sham Vonaprument EOM Vonaprument EM Sham Vonaprument EOM Vonaprument EM FOVEAL #Confirmed for two consecutive visits at any time through month 12 or at last study visit ^Nominal p-value from a Cochran Mantel-Haenszel test (General Association) in ITT population Final data
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ARCHER Phase 2: Demonstrated Dose-Dependent Vision Protection in Both Healthier and Less Healthy Eyes 21 Broad treatment effect across severity of photoreceptor dysfunction 0 10 20 30 Sham Vonaprument EOM Vonaprument EM Sham Vonaprument EOM Vonaprument EM BSL LLVD < 30 (Healthier)1 16.9% 6.1% 0.0% 10/59 0/563/498/26 5/316/42 % Participants 30.8% 14.3% 16.1% 14.7% 16.9% BSL LLVD ≥ 30 (Less Healthy) Nominal summary p- value vs. sham^ ANX007 EM 0.0016 ANX007 EOM 0.0183 1LLVD <30 at baseline were designated as eyes with less advanced disease, based on mean baseline values in lampalizumab Phase 3 studies. Holz FG,et al. Efficacy and Safety of Lampalizumab for Geographic Atrophy Due to Age-Related Macular Degeneration:Chroma and Spectri Phase 3 Randomized Clinical Trials.JAMA Ophthalmol.2018;136(6):666–677. #Confirmed for two consecutive visits at any time through month 12 or at last study visit ^Nominal p-value from a Cochran Mantel-Haenszel test (General Association) in ITT population Final data Review of Subgroup based on Visual Acuity Measures Participants with confirmed BCVA ≥15-letter loss through month 12#
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ARCHER Phase 2: Demonstrated Dose-dependent, Disease- modifying Effect of Vonaprument 22 0 5 10 15 20 25 30 0 1 2 3 4 5 6 7 8 9 10 11 12 15 18 % Patients Study Month Off Treatment PATIENTSWITH ANY BCVA ≥15-LETTER LOSS FROM BASELINE Sham pooled (n=89) Vonaprument EOM (n=92) Vonaprument EM (n=89) Demonstration of treatment effect and disease-modifying mechanism of action Month 12 Month 15 Month 18 Sham 76 73 72 EOM 80 75 73 EM 72 73 72 Total Subjects
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Lloyd Clark, MD Strategically Designed ARCHER II Phase 3 Trial
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ARCHER II Phase 3: Designed and Executed for Success 24 Larger, Longer Study Global Regulatory Strategy • Over-enrolled (n=659), powered to >90% • Higher patient retention increased power to >90% • Two pre-defined, well-powered sub-studies for US filing • PRIME designation and Product Development Coordinator for EU filing KEY ATTRIBUTES DESIGNED TO INCREASE PROBABILITY OF SUCCESS Dual Endpoint Strategy to Show Vision Outcomes • Powered to show positive treatment effect at Month 15 or Month 24 • Alpha allocated between Month 15 (majority) and Month 24 for efficacy in label Controlled for Disease Heterogeneity • Enrolled patients at risk for vision loss but with enough vision to protect • Consistent treatment effect across broad spectrum of disease • Longer timepoints for more vision loss events and widening treatment delta
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Vonaprument (ANX007) Monthly 5.0 mg/eye Sham ARCHER II Phase 3: Designed and Powered to Confirm Vision Protection 25 Primary Analysis: 15 months Single Study (Q4’26) 2 Sub-studies (Q1’27) Sites: North America, Europe, AUS, NZ N=659 Randomized 2:1 DUAL PRIMARY ENDPOINTS Landmark analysis of proportion of patients with confirmed BCVA ≥15-Letter Loss at Month 15 or Month 24 GLOBAL REGISTRATION PATH EMA Prime and FDA Fast Track designations Single protocol for EU filing Single protocol analyzed as 2 sub-studies for US filing (powered at sub-study level) Primary Analysis: 24 months Single Study & 2 Sub-studies (Q3’27) Alpha Split
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ARCHER II Baseline Characteristics Well-Positioned to Successfully Replicate Phase 2 Vision Protection Outcomes 26 BASELINE VISUAL ACUITY MEASURES ARCHER P2 (N = 270) ARCHER II P3 (N = 659) Mean BCVA (SD) 58.4 (16.2) 65.8 (10.5) Baseline BCVA <45 Letters 23.3% 0.0%* Mean LLVA (SD) 33.0 (16.9) 38.3 (17.2) Mean LLVD (SD) 25.7 (16.9) 27.6 (15.6) LLVD < 30 Letters 62.4% 60.7% STRUCTURAL CHARACTERISTICS ARCHER P2 ARCHER II P3 GA Lesion Size (mm2), mean (SD) 7.36 (4.01) 7.23 (3.49) GA Lesion Location (% Subfoveal) 51.9% 54.8% Total EZ Loss, mm2 (% of Total Area Lost) 12.7 (35.3%) 12.3 (34.3%) PROPRIETARY & CONFIDENTIAL *Individuals with baseline BCVA <45 letters not enrolled in ARCHER II due to very low incidence of BCVA 15 -letter loss in ARCHER Excluded subjects VA<20/100, no vision loss events No 15-LL events (0/56) in P2 monthly arm 20% treatment delta in P2 ARCHER
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Illustration of Event Based Analysis Which Gets Stronger Over Time 27 Why we like month 15 as our base case and month 24 with growing treatment delta % Participants Linear Projection 15 and 24 Months Study Month ARCHER Phase 2 Through 12 Months Treatment delta grows over time ✓ Larger sample size (N=659; n~330/substudy) ✓ Prior GA trials1 informed masked event rate projections, which have held during study ✓ Linear progression of vision loss events in GA ✓ Longer timepoints to accumulate more sham events ✓ Result: Both 15 & 24 month primary endpoints de- risked with trial design and execution ARCHER II Key Features for Success 0 5 10 15 20 25 30 35 0 2 4 6 8 10 12 Sham Vonaprument EM 14 16 18 20 22 24 1Sunness et al (1999) Ophthalmology; Schmitz-Valckenberg (2016) Ophthalmologica; Anegondi at al (2025) Ophthalmology
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N=659 Randomized 2:1 ARCHER II: One Protocol Supporting Both EMA and FDA Filings 28 Phase 3 powered at Sub-study level EMA FDA Single Study 2 Sub-studies Vonaprument (ANX007) Monthly Sham Primary analysis: 15 months Primary analysis: 24 months Vonaprument (ANX007) Monthly Sham Primary analysis: 15 months Primary analysis: 24 months ARCHER II Vonaprument (ANX007) Monthly Sham Primary analysis: 15 months Primary analysis: 24 months ARCHER IIa ARCHER IIb N~330 Randomized 2:1 N~330 Randomized 2:1
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ARCHER II Phase 3: Potential Outcomes Scenarios & Expected Timing 29 PR: SINGLE STUDY HITS Primary Endpoint for EU at 15 mos (no p value) PR 1: TWO SUBSTUDIES HIT Primary Endpoint for US at 15 mos (no p value) PR: TOPLINE 24 MO DATA for Single Study & Substudies PR 2: TOPLINE 15 MO DATA for Single Study & Substudies SINGLE STUDY & SUBSTUDIES HIT 15 Mos Primary Analysis Q4’26 Q1’27 Q3’27 PR: SINGLE STUDY CONTINUES to 24 mos SINGLE STUDY CONTINUES to 24 Mos PR: TOPLINE 24 MO DATA for Single Study & Substudies PR: TWO SUBSTUDIES CONTINUE to 24 mos SINGLE STUDY HITS 15 Mos Primary Analysis SUBSTUDIES CONTINUE to 24 Mos PR: SINGLE STUDY HITS Primary Endpoint for EU at 15 mos (no p value) PR: TOPLINE 24 MO DATA for Single Study & Substudies *Futility – assessed by Data Monitoring Committee
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Douglas Love, Esq Summary of Vonaprument Program
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First in Class Vision Protection as New Standard of Care in GA ©2025 Annexon, Inc31 WORLDWIDE 8M+ patients affected by GA1 US ~1.5M patientsaffectedby GA2 EU ~2.5M patients affected by GA3 Less than 10% of US patients receive treatment4 1Keenan et al, Ophthalmology. 2018 Jul 27;125(12):1913–1928; 2Tufail A, et al. Presented at the 15th EURETINA Congress, Nice, France, September 17-20, 2015. Accessed November 21, 2019; 3Based on Colijin JM,et al., 2016; Wong WL,et al., 2014; Rudnicka AR,et al., 2014; Korb CA,et al., 2014; Piermarocchi S,et al., 2011; Fernandez-Arias C,et al., 2011; Augood CA,et al., 2006; 4Rudnicka AR et al., Ophthalmology. 2012;119(3):571-80. doi:10.1016/j.ophtha.2011.09.027 4 Derived from current publicly stated data that 10-15-% of US patients already diagnosed with GA have received treatment. But only about half (800,000 of 1.5m) of patients who are thought to have GA are actually diagnosed. Using 1.5m as a denominator, less than 10% have received treatment. Lack of clear functional benefit of current GA therapies Vonaprument poised to capture and drive immense GA market
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Building a Leading Ophthalmology Franchise 32 Recent organization enhancements with proven record of blockbuster commercialization in AMD space Clinical Development Donald Fong, MD SVP , Clinical Development - Ophthalmology Scientific Advisory Board Eleonora Lad, MD, PhD Vice Chair of Ophthalmology Clinical Research, Duke University Medical Center Board of Directors Commercialization Jake Schumacher, MBA SVP , Head of Ophthalmology Franchise Mark Blumenkranz, MD, MMS H.J. Smead Professor Emeritus in the Department of Ophthalmology Stanford University
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Vonaprument GA Program Designed & Executed for Success 33 Exceptional Pivotal Design & Execution Targeted Patient Population in Larger, Longer, Well-Powered Phase 3 Demonstrated Functional Outcomes Vision Protection in Phase 2 across Broad Patient Population First in Class Product for Vision Protection 8M+ patients with global unmet need