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H.C. Wainwright 5th Annual Ophthalmology Virtual Conference Lloyd Clark, M.D., SVP , Ophthalmology Strategy & Innovation August 2025
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Forward-Looking Statements 2 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,” “believe,” “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 Quarterly Report on Form 10‐Q filed with the Securities Exchange Commission (SEC) on May 12, 2025 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 marke ting 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 the ir 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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A bold mission to enable MILLIONS of PATIENTS impacted by complement- mediated diseases of the body, brain and eye LIVE THEIR BEST LIVES
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BREAKTHROUGH 2025: Annexon Well-Positioned to Transform the Complement Landscape and Drive Immense Value 4 Clinically Validated Scientific Platform with broad potential across multiple therapeutic areas Only Geographic Atrophy (GA) Program to Demonstrate Vision Preservation in additional blockbuster opportunity Near-term Blockbuster Opportunity in Guillain-Barré Syndrome (GBS) poised to replace standard of care Disruptive Oral Classical Complement Inhibitor with potential to transform biologics-treated indications
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Pioneering Scientific Approach to Stop Complement-Driven Neuroinflammation Where it Starts 5 Broad applicability to millions of patients with autoimmune, neurodegenerative and ophthalmic diseases Blocking C1q to halt neuroinflammation in the body, brain and eye Deep understanding of C1q in neuroinflammatory diseases – 20 yrs of research Robust clinical data across flagship programs demonstrating differentiated functional outcomes Groundbreaking discoveries of Dr. Ben Barres unlocked the importance of inhibiting C1 family at the top of the classical complement pathway
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Leading Complement-Focused Pipeline with MULTIPLE WAYS TO WIN 6 Diverse late-stage clinical platform for classical complement-mediated neuroinflammatory diseases of the body, brain and eye PRECLINICAL PHASE 1 PHASE 2 PHASE 3 FLAGSHIP PROGRAMS Autoimmune Tanruprubart Guillain-Barré Syndrome (GBS) Ophthalmology Vonaprument (ANX007) Dry age-related macular degeneration (AMD) with geographic atrophy (GA) Autoimmune ANX1502 Autoimmune Indications NEXT WAVE PROGRAMS Neurodegenerative Tanruprubart Huntington’s Disease Amyotrophic Lateral Sclerosis (ALS) Autoimmune ANX009 Lupus Nephritis
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Global Pivotal Program with Potential Blockbuster Market Opportunity Vonaprument (formerly ANX007): Only Geographic Atrophy Program to Show Significant Vision Preservation
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Vonaprument: Unprecedented Clinical Outcomes in Phase 2 With Potential to Translate into Blockbuster Commercial Opportunity Global registration path established supporting potential first approval in both EU and US for dry AMD with GA; PRIME designation in EU Dry AMD with GA: >8M people worldwide with no vision-protecting therapies Clearly differentiated to disrupt dry AMD/GA landscape • Significant, consistent, dose‐ and time‐dependent vision preservation • Preservation of central photoreceptors necessary for visual acuity • Favorable safety profile • Results align with growing evidence that GA lesion area change is not a clinically meaningful biomarker ARCHER II P3 pivotal program completed enrollment July ’25, with topline data expected 2H’26 8
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Photoreceptor Synapse and Cell Loss Precede RPE Loss (GA Lesion)1 1Bird, 2014 JAMA Ophthalmol 132:338; Li, 2018 Retina 38:1937; Pfau, 2020 JAMA Ophthal 138:1026; Sarks, 1988 Eye 2:552; 2Selkoe, 2002 Science 298:789; Burger, 2021 Dev Biol 476:218; 3Shen, 2020 Ophthal Retina 4:899 RPE CELL PHOTORECEPTOR SYNAPSE PHOTORECEPTOR CELL NUCLEUS Retina from Healthy Donor Retina from Donor with GA Photoreceptor cells (ONL) Photoreceptor cell synapses (VGlut 1) Retinal Pigmented Epithelium (RPE65) IPL INL OPL ONL RPE FAF Lesion (no RPE) Intact photoreceptors, synapses and RPE furthest from lesion Gradient of synapse and photoreceptor loss above intact RPE nearing lesion edge 200 µm 200 FAF Lesion (no RPE) Average 12 month GA lesion growth3 Intact photoreceptors, synapses and RPE furthest from lesion Gradient of synapse and photoreceptor loss above intact RPE nearing lesion edge Photoreceptor cells (ONL) Photoreceptor cell synapses (VGlut 1) Retinal Pigmented Epithelium (RPE65) Loss of synapses = loss of function2 9
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ARCHER: Phase 2 Trial Of The C1q Inhibitor ANX007 (Vonaprument) in Patients with Dry AMD and GA 10 Randomized, double‐masked Included foveal and non-foveal lesions Stratified for lesion location and lesion size 12 months (n=270) Sham monthly or every other month (n=89) Vonaprument 5mg monthly (EM) (n=89) Vonaprument 5mg every other month (EOM) (n=92) PRIMARY ENDPOINT Rate of Change in GA lesion area as assessed by fundus autofluorescence at Month 12 PRESPECIFIED FUNCTIONAL ANALYSES Best Corrected Visual Acuity (BCVA) Low Luminance Visual Acuity (LLVA)& Deficit (LLVD) END OF STUDY Month 18 Off-treatment (6 months) ©2025 Annexon, Inc. All rights reserved
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0 5 10 15 20 25 30 0 1 2 3 4 5 6 7 8 9 10 11 12 15 18 Sham Pooled (n=89) ANX007 EOM (n=92) ANX007 EM (n=89) Off Treatment Vonaprument POC: Significant Time & Dose-Dependent Vision Preservation in GA Patients 11 FELLOW-EYE ANALYSIS: VISION PROTECTION IN STUDY EYE (SE) BUT NOT IN NON-TREATED FELLOW EYE (FE) Eyes with BCVA ≥15‐letter loss at month 12 in all patients with bilateral GA OFF TREATMENT ANALYSIS: ON-TREATMENT VISION PROTECTION WANES POST-TREATMENT % of patients with any BCVA ≥15‐letter loss from baseline SIGNIFICANT TIME AND DOSE-DEPENDENT VISION PROTECTION BCVA ≥15‐letter loss at 2 consecutive visits SIGNIFICANT VISION PROTECTION MEASURED BY BCVA ≥15-LETTER LOSS Patients with persistent BCVA ≥15‐letter loss through month 12+ HR, hazard ratio; Nominal log‐rank test (versus sham) p‐values are presented EM: monthly dosing; EOM: every other month dosing Nominal p‐value vs sham^ --- 0.0021 0.032 Sham EM EOM 0 5 10 15 20 % Patients 21.3% 5.6% 9.8% 9/925/89 19/89 * Vonaprument EOM 50% Risk Reduction HR (CI)= 0.504 (0.214to 1.190) p = 0.1181 Vonaprument EM 73% Risk Reduction HR (CI) = 0.272 (0.090 to 0.819) p = 0.0207 +Persistent for two consecutive visits including month 12 ^Nominal p‐value from a Chi‐square test in ITT population 4 % Patients Month EM (n=89) EOM (n=92) Sham (n=89) 100% 95% 90% 85% 80% 75% 70% 65% 0 1 2 3 4 5 6 7 8 9 10 Month 11 12 Sham Pooled (n=89) Vonaprument EOM (n=92) Vonaprument EM (n=89)
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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 12 ^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 Numerically Greater Photoreceptor Protection in Central Macula with Vonaprument Comparison of Vonaprument effect on Ellipsoid Zone (EZ) across macula and in central subdomains through 12 months ©2025 Annexon, Inc. All rights reserved Vonaprument, formerly ANX007
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13 ARCHER: Key Safety Data ADVERSE EVENTS OF SPECIAL INTEREST n (%) SHAM (N=89) VONAPRUMENT EM (N=89) VONAPRUMENT EOM (N=92) Choroidal Neovascularization 3 (3.4%) 4 (4.5%) 4 (4.3%) Endophthalmitis 0 1 (1.1%) 2 (2.2%) Retinal Vascular Occlusion 0 0 1^ (1.1%) Retinal Vasculitis 0 0 0 Intraocular Inflammation+ 0 2 (2.2%) 1 (1.1%) Ischemic Optic Neuropathy+ 0 0 0 INTRAOCULAR INFLAMMATION DETAILS* n Iritis – 1 Resolved with topical steroids in 2 days No Vasculitis Vitritis – 1 Resolved with topical steroids in 9 days No Vasculitis Vitreous Debris – 1 KP on endothelium, prior treatment with topical steroids No Vasculitis ^Isolated cilioretinal artery occlusion; no vasculitis confirmed by DSMC and reading center +Not AESI, included because of current interest *Event Verbatim term listed ©2025 Annexon, Inc. All rights reserved Vonaprument, formerly ANX007
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14 Treatment masked through 24 months Vonaprument (ANX007) Monthly 5.0 mg/eye Sham Primary analysis: At least 12 months from dosing initiation Sites: North America, Europe, AUS, NZ GLOBAL REGISTRATION PATH ESTABLISHED PRIMARY ENDPOINT Persistent* BCVA ≥15‐letter loss through primary analysis timepoint * ≥15-letter loss confirmed at two consecutive visits SECONDARY ENDPOINTS Safety, LLVA, EZ integrity N=~630 Randomized 2:1 PRIME designation from EMA ARCHER II Phase 3 Program – Now Fully Enrolled POPULATION FOR ARCHER II: Similar to ARCHER population, including foveal and non‐ foveal lesions and enriched for BCVA to exclude those with <45 ETDRS letters at baseline ©2025 Annexon, Inc. All rights reserved
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Vonaprument: A Novel Neuroprotective Agent Demonstrating Benefit on Visual Acuity and Photoreceptor Structure in GA 15 Common MOA across neurodegenerative diseasesBlocks C1q for Neuroprotection Consistent, dose‐ and time‐dependent protection of visionPreserved Visual Function Especially central photoreceptors, most closely associated with visionProtected Retinal Structure No CNV increase and no reported cases of vasculitisGenerally Well‐tolerated Topline Data expected in 2H’26 within existing cash runwayPhase 3 ARCHER II Enrollment Complete ©2025 Annexon, Inc. All rights reserved
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A bold mission to enable MILLIONS of PATIENTS impacted by complement- mediated diseases of the body, brain and eye LIVE THEIR BEST LIVES