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44TH ANNUAL J.P . MORGAN HEALTHCARE CONFERENCE JANUARY 2026 Nasdaq: ANNX ©2025 Annexon, Inc. All rights reserved STOPPING NEUROINFLAMMATION AT ITS SOURCE
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Forward-Looking Statements 2 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, which are subject to the “safe harbor” created by those sections. All statements other than statements of historical facts contained in this presentation are forward‐looking statements. These forward looking statements include, but are not limited to statements regarding the potential therapeutic benefits of our product candidates; 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 and results of regulatory interactions related to our product candidates, including the timing of our planned biologics license application (BLA) submission to the U.S. Food and Drug Administration (FDA); our ability to achieve regulatory approval for our product candidates; the potential for vonaprument to be the first drug approved for dry AMD with GA; the potential for vonaprument and tanruprubart to reset the standard of care; strategic plans for our business and product candidates, including additional indications which we may pursue, our ability to commercialize our product candidates, if approved; the potential for us to deliver significant value for patients and our stakeholders; our financial position, runway and anticipated milestones. In some cases, you can identify forward‐looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “focus,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and the negative of these terms or other similar expressions that are predictions of or indicate future events and future trends. 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 operating losses; our ability to obtain necessary capital to fund our clinical programs; the potential for delays in our clinical trials; the potential for our product candidates to not receive regulatory approval, including if the FDA and comparable foreign regulatory authorities determine that our submission package is not sufficient or require us to provide additional data in patients that are not feasible to obtain; the early stages of certain of clinical development of our product candidates; the effects of public health crises on our clinical programs and business operations; our ability to obtain regulatory approval of and successfully commercialize our product 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 described in greater detail under the section titled “Risk Factors” and in the other cautionary statements contained in our Annual Report on Form 10‐K for year ended December 31, 2024, our subsequent Quarterly Reports on Form 10‐Q and our other filings with the Securities Exchange Commission. Any forward‐looking statements that we make in this presentation are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and represent our management’s beliefs and assumptions only as of the date of this presentation. Except 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 marketing by the 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.
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Unlocking a New Era of Care for Neuroinflammatory Diseases 3 Tanruprubart (ANX005) MAA submitted Two Blockbuster Registrational Opportunities ~10M Patients and >$10B Global Market1 Dry AMD with Geographic Atrophy A leading cause of blindness in the elderly Guillain-Barré Syndrome Most common cause of acute neuromuscular paralysis Vonaprument (ANX007) Ph 3 registrational trial 1 Company market research reports, analysis of global market opportunity for Annexon’s pipeline of late‐stage assets
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2026: A Pivotal Year of PotentialSignificant Value Creation 4 Next gen targeted immunotherapies to halt neuroinflammation at the source in diseases with limited or no approved therapies Diversified pipeline of drug candidates for C1q‐mediated neuroinflammatory diseases Vonaprument (ANX007) Ph3 pivotal data Tanruprubart (ANX005) EMA/FDA submissions ANX1502 proof-of-concept for first oral C1 inhibitor Cash to fund anticipated key milestones into late 2027 Accelerating US medical education / pre‐launch efforts / potential partnering activities Driving Value From Multiple Late-Stage Assets Clinically Validated C1q Platform Multiple Catalysts in 2026 Well-positioned for Market Development
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C1q Inhibition Platform Creates Competitive Advantage Transformative therapeutic approach halting neuroinflammation at its source to minimize damage Proprietary anti-C1q approach yields enhanced efficacy and safety by blocking all classical cascade neuroinflammation Improved inhibition of neuroinflammation vs. first generation C3 & C5 inhibitors Differentiated clinical outcomes across multiple diseases (e.g., GBS, GA, ALS) Classical Complement Cascade AMPLIFYING INFLAMMATION 5
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PRECLINICAL PHASE 1 PHASE 2 PHASE 3 FLAGSHIP PROGRAMS Autoimmune Tanruprubart Guillain‐Barré Syndrome (GBS) Ophthalmology Vonaprument Dry age‐related macular degeneration (AMD) with geographic atrophy (GA) Autoimmune ANX1502 First oral C1 inhibitor for Autoimmune Indications NEXT WAVE PROGRAMS Neurodegenerative Tanruprubart Huntington’s Disease Amyotrophic Lateral Sclerosis (ALS) Autoimmune ANX009 Lupus Nephritis Late-Stage Pipeline with Multiple Blockbuster Opportunities 6 Diverse and informed drug candidates addressing neuroinflammatory diseases for ~10 million patients
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Annexon Poised to Capture Asymmetric Value Opportunity 1https://www.astrazeneca.com/media‐centre/press‐releases/2020/astrazeneca‐to‐acquire‐alexion.html# 2https://investors.ivericbio.com/news‐releases/news‐release‐details/astellas‐enters‐definitive‐agreement‐acquire‐iveric‐bio 3Yahoo Finance APLS as of 1/8/2026 4Based on 191M fully diluted shares outstanding, including 149M common shares and 42M prefunded warrants at $4.85 per share, the last 30‐day average closing price of the company’s stock on 1/8/2026. Comparisons to complement companies are purely for illustrative purposes only. Actual results for the Company will vary and nothing in this presentation should be regarded as a representation by any person that similar results will be achieved. 7 Positioned to unlock significant value with multiple late-stage assets Pioneered C5 inhibition Acquired by AstraZeneca $39B1 $5.9B2 Pioneered C5 inhibition in GA Acquired by Astellas ~$3B3 Pioneered C3 inhibition in GA Next Generation C1q Inhibition ~$900M4 Pioneering C1q Inhibition in several diseasesFirst Generation C5 Inhibition Second Generation C3 Inhibition
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Established Leadership with Drug Development through Commercial Depth Doug Love President & CEO Jennifer Lew Chief Financial Officer Jamie Dananberg, MD Chief Medical Officer Michael Overdorf, MBA Chief Business Officer Shikhar Agarwal Head of Commercial Ted Yednock, PhD Chief Innovation Officer Rick Artis, PhD Chief Scientific Officer 8
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Shifting Treatment Paradigm in 2026 Vonaprument: First Potential Treatment to Preserve Vision for Dry AMD with Geographic Atrophy
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Geographic Atrophy Remains a Significant Unmet Need 10 • Avg. Age of GA Patient: 79 years • GA greatly impacts quality of life, interfering with reading, driving, recognizing faces • Incidence projected to increase due to aging population GA SEVERELY LIMITS INDEPENDENCE AND IS A LEADING CAUSE OF BLINDNESS IN THE ELDERLY No approved treatments demonstrating vision preservation WORLDWIDE 8M+ patients affected by GA1 US ~1.5M patients affected by GA2 EU ~2.5M patients affected by GA3 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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Vonaprument Designed to Stop Vision Loss Prior to Lesion Growth Targeting C1q, the locus of disease vs. lagging indicator addressed by first generation C3 and C5 inhibitors Photoreceptorcell synapses (OPL) Photoreceptor cells (ONL) Retinal Pigmented Epithelium (RPE) 200 mm IPL INL OPL ONL RPE FAFLesion (no RPE) Average12 month GA lesiongrowth4 Intact photoreceptors,synapses and RPE furthest from lesion Gradient of synapse loss in OPL above intact RPE nearing lesion edge (on right) Synapses (red dots w/ white arrows) = functional connections1 GA retinal tissue Section Image: Annexon, data on file Representative FAF image from Fleckenstein et al., 2017, to illustrate position of retinal cross section (yellow bar) relative to lesion 200 µm Vonaprument Protects Eye Structure: Photoreceptor Cells, Synapses & Function (Vision) Lost Prior to RPE in GA (picture of human GA eye) 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 4:89911
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Vonaprument Profoundly Protected Central Retinal Structure Responsible for Visual Acuity 12 Protection against loss of photoreceptors (neurons) in retina center, the locus of disease 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) Nominal p‐value^ Month Vonaprument Pooled vs Sham 0.0218 CENTRAL 2.0 MM 48% decrease 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) Vonaprument Pooled vs Sham 0.0319 CENTRAL 1.5 MM Month 59% decrease ARCHER Phase 2 ^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
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Vonaprument Demonstrated Robust Vision Protection on Multiple Measures of Visual Acuity 13 Consistent, dose dependent vision preservation ARCHER Phase 2 LLVA≥15-LETTER LOSS THROUGH MONTH 121 Nominal p-value vs sham2 -- 0.0497 0.0216 8/856/7916/79 1Patients with at least one post‐baseline LLVA measurement and two consecutive or last visit 15‐letter loss events 2Nominal p‐value from a Chi Square test; *p<0.05 Final data 1Confirmed for two consecutive visits through month 12 or at last study visit 2Nominal p‐value from a Chi‐square test in ITT population: * Nominal p < 0.05 Final data BCVA ≥15-LETTER LOSS THROUGH MONTH 121 Nominal p-value vs sham 2 -- 0.032 0.0021 Sham EOM EM 0 5 10 15 20 25% Patients 21.3% 5.6%9.8% 9/92 5/8919/89 * * Sham EOM EM 0 5 10 15 20 25% Patients 20.3% 7.6%9.4% 16/79 6/798/85 * *
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100% 95% 90% 85% 80% 75% 70% 65% Vonaprument Monthly Dosing Reduced Risk of Vision Loss by 73% at Month 12 HR, hazard ratio; Nominal log‐rank test (versus sham) p‐values are presented; 1 Confirmed BCVA 15‐LL at two consecutive visits including month 12 supported by ensuing (off‐treatment) visit Final data14 % Patients without ≥15 Letter BCVA Loss 50% Risk Reduction Vonaprument EOM HR (CI) = 0.504 (0.214 to 1.189); Nominal p = 0.1098 73% Risk Reduction Vonaprument EM HR (CI) = 0.272 (0.090 to 0.819); Nominal p = 0.0119 INCREASING VONAPRUMENT IMPACT OVER TIME Month 0 1 2 3 4 5 6 7 8 9 10 11 12 BCVA ≥15-LETTER LOSS CONFIRMED AT 2 CONSECUTIVE VISITS THROUGH MONTH 12 1 EM (n=89) EOM (n=92) Sham (n=89) ARCHER Phase 2
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Vonaprument Demonstrated Clear On vs. Off-Treatment Vision Protection 15 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 Sham Pooled (n=89) ANX007 EOM (n=92) ANX007 EM (n=89) Off Treatment PATIENTSWITH ANY BCVA ≥15-LETTER LOSS FROM BASELINE Sham pooled (n=89) Vonaprument EOM (n=92) Vonaprument EM (n=89) ARCHER Phase 2 Reinforces on- treatment drug effect and disease-modifying mechanism of action
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Vonaprument (ANX007) Monthly 5.0 mg/eye Sham Phase 3 Pivotal Study: Well-Informed Design and Powering 16 Leverages Phase 2 learnings and enriched for patients with higher risk of vision loss Treatment masked through 24 months Primary analysis: 15 months Sites: North America, Europe, AUS, NZ N=659 Randomized 2:1 PRIMARY ENDPOINT Proportion of patients who experience a BCVA ≥15‐Letter Loss confirmed at two consecutive visits SECONDARY ENDPOINT Safety, LLVA, EZ integrity GLOBAL REGISTRATION PATH Prime designation in EU Selected by EMA for PDC1 program FDA Fast Track designation ARCHER II Phase 3 1Product Development Coordinator
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Vonaprument Poised to Capture and Drive Immense GA Market 17 Vision- preservation medicines ~$1.5B Combined current sales1 Vonaprument Lesion-sparing medicines 1st generation IVT drugs have established patient demand, but lagged expectations due to benefit‐risk profile >$7B Global peak sales2 Vision preservation offers enhanced benefit-risk to tap full market Differentiated profile: Small, non‐pegylated, low viscosity, limited conversion to CNV Pursuing vision preservation to drive a fundamental shift in standard of care 1Analyst estimates 2ClearView Healthcare Partners analysis of 2037 worldwide sales
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Delivering for Patients in 2026 Tanruprubart: Potential First‐in‐Class Targeted Therapy for Guillain‐Barré Syndrome
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GBS: Sudden Neurological Emergency 19 No FDA‐approved therapies IVIg used off‐label WORLDWIDE ~150K cases per year1 INCIDENCE IN US ~8K cases per year3 INCIDENCE IN EUROPE ~15K cases per year SIGNIFICANT DISEASE BURDEN DESPITE IVIG TREATMENT1,2,3,4,5,6,7 ~75% in ICU require ventilation ~20% can't walk a year after treatment ~30% admitted to ICU 1ClearView Health Market Research (2024); 2Hughes et al. (2003). Neurology, 61, 736‐40; 3Hund et al. (1993). Crit Care Med, 21, 433‐46; 4Doets, et al. (2018). Brain, 141, 2866‐ 77; 5Van den Berg et al. (2014). Nat Rev Neurol, 10, 469‐82; 6Leonhard et al. (2019). Nat Rev Neurol, 15, 671‐83; 7Inflation‐ and population‐adjusted cost estimates from Frenzen (2008). Neurology, 71(1), 21‐7; 8Ongoing Annexon study submitted for AAN presentation • Most common cause of acute neuromuscular paralysis • Typically caused by infection, vaccine side effects, other therapies • >$7B annual burden associated with the disease 8
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GBS Provides a Compelling Market Opportunity 20 Tanruprubart is first targeted therapy designed to create a new standard of care in GBS BLOCKBUSTER MARKET OPPORTUNITY FOR GBS • Single infusion halts neuroinflammation • ~90% of treated patients improved by week 1 • Safety data comparable to placebo • Significant potential savings to U.S. healthcare system over IVIg/PE Tanruprubart Current treatments are slow and suboptimal Most patients suffer from incomplete benefit Targeted treatment offers faster, more complete recovery for patients to regain their independence Patients Treated Upon Diagnosis >90% >23K U.S./EU Patients Annually Top 50 U.S. Hospital Networks >50% of GBS Patients
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Distinct From IVIg or Placebo, Tanruprubart Significantly Reduced Key Markers of Neuroinflammation Within 1 Week 21 Phase 3 & IGOS Resulted in Rapid Muscle Strength and Motor Function Recovery REDUCTION OF ACUTE INFLAMMATORY BIOMARKERS WITHIN 1 WEEK
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86% OF PATIENTS TREATED WITH ANX005 IMPROVED IN WEEK 1 (10 PTS ON AVG) 2½ TIMES MORE TREATED PATIENTS FULLY RECOVER AT WEEK 26 (GBS-DS = 0) ~90% of Treated Patients Responded at Week 1, Translating to >2X Odds of Fully Recovering at Week 26 vs. Placebo 22 MRC Sumscore at Week 1 LS Mean Change From Baseline ± SEM Study Weeks % of Patients at GBS-DS 0 GBS-DS Through Week 26 Phase 3 10 8 6 4 2 0 ‐2 p<0.0001 ANNX005 30mg/kg (N=‐79) Placebo (N=81) 1Nominal
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Fewer days in ICU 7 fewer days4, p=ns Tanruprubart Demonstrated Profound Impact on Measures Most Important To Patients, HCPs and Payers 23 Tanruprubart 30mg/kg5: n=18 Placebo n=19 25 Days 32 Days Helped Patients Achieve Their Independence Sooner versus Placebo Phase 3 ICU, intensive care unit; ns, not significant. 1Based on first scheduled visit of recording; 2Nominal; 3Among patients ventilated; 4Among patients requiring ICU; 5Phase 3 data reported on the 30 mg/kg dose 20 Days 48 Days Tanruprubart 30mg/kg 5: n=15 Placebo n=15 56 Days 87 Days Tanruprubart 30mg/kg 5: n=79 Placebo n=81 Off ventilation earlier 28 days earlier3, p=0.03562 Walking independently earlier 31 days earlier1, p=0.02112
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Early Experience with Tanruprubart Treatment in EU & US Suggests Rapid and Consistent Effect Across Geographies 24 1Post tanruprubart treatment • Baseline: bed-bound, hospitalized • Treated with tanruprubart within 4 days from onset • Day 81: discharged from hospital, walking with assistance • Day 291: walking independently FORWARD STUDY Data anticipated in 2026 BLA planned in 2026 Example Patient: Moderate to severe FORWARD Study
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In Sum, 2026 is a Pivotal Year For Annexon to Unlock a New Era of Care for Neuroinflammatory Diseases and to Drive Immense Value 25 Establishing proof of concept for ANX1502, the first oral C1 inhibitor for neuroinflammatory autoimmune diseases Establishing the first potential vision-preserving treatment for GA WORLDWIDE 8M+ patients affected Vonaprument (ANX007) Establishing the first potential targeted rapid-acting treatment for GBS WORLDWIDE ~150K cases per year Tanruprubart (ANX005) • Topline Phase 3 data anticipated 2H 2026 • Established US/EU regulatory path • EU MAA filed • FORWARD study initial data anticipated 2026 • FDA BLA filing planned 2026
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helping millions of people impacted by devastating neuroinflammatory diseases to MISSION DRIVEN LIVE THEIR BEST LIVES