ANNX Annexon Inc

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Exhibit 99.1

 

Annexon Announces Positive Topline Results from Pivotal Phase 3 Trial for First-in-Class C1q Blocking Antibody ANX005 in Guillain-Barré Syndrome

Single Infusion of ANX005 30 mg/kg Met Primary Endpoint, Delivering a Highly Statistically Significant and Clinically Meaningful 2.4-fold Improvement in GBS-DS vs. Placebo at Week 8, p=0.0058

ANX005 Demonstrated Early and Sustained Improvements in Key Secondary Endpoints Including Muscle Strength, Nerve Damage and Ventilation

ANX005 Displayed Rapid Target Engagement and was Generally Well-Tolerated Across Doses

Real-World Evidence (RWE) Comparability Data Expected in First Half 2025

Conference call and webcast today at 8:30 a.m. ET

BRISBANE, Calif., June 4, 2024 - Annexon, Inc. (Nasdaq: ANNX), a biopharmaceutical company advancing a late-stage platform of novel therapies for people living with devastating classical complement-mediated neuroinflammatory diseases of the body, brain, and eye, today announced positive topline results from its randomized placebo-controlled pivotal Phase 3 trial in patients with Guillain-Barré syndrome (GBS). The Phase 3 trial met its primary endpoint, with ANX005 30 mg/kg achieving a highly statistically significant 2.4-fold improvement on the GBS-disability scale (GBS-DS) at week 8 (proportional odds analysis, p = 0.0058).

ANX005 30 mg/kg treatment also demonstrated improvements versus placebo on key secondary endpoints, including early gains in muscle strength by Medical Research Council (MRC) sum score at day 8 (p <0.0001*) and at week 8 (p = 0.0351*), and a median of 28 fewer days on artificial ventilation through week 26 (p = 0.0356*). Additionally, ANX005 30 mg/kg demonstrated a 31-day reduction in the median time to walk independently versus placebo (p = 0.0211*) in a prespecified analysis. ANX005 30 mg/kg treated patients got better sooner on each of these assessments, presenting important clinical care outcomes for patients and the healthcare community. ANX005 also provided an early reduction in the prespecified analysis of serum levels of neurofilament light chain (NfL), a biomarker of nerve damage (11.2% reduction relative to placebo between weeks 2–4, p = 0.03*). (* nominal)

GBS is a rapid and acute neurological disease with a narrow therapeutic window that results in the hospitalization of over 22,000 people annually in the U.S. and Europe. The significant and long-term disease burden associated with GBS on patients, caregivers, hospitals and payers has led to a multi-billion-dollar annual economic cost to the U.S. healthcare system. Currently, there are no approved treatments for GBS by the U.S. Food and Drug Administration (FDA).

“These data represent an important moment for the GBS community and Annexon,” said Douglas Love, president and chief executive officer of Annexon. “With the potential to be the first targeted treatment for GBS in the U.S., ANX005 demonstrated consistent improvement and functional benefits on key primary and secondary endpoints. Additionally, we observed in our Phase 3 trial that early treatment with ANX005 resulted in rapid neuroprotection that stopped the advancement of disease and helped GBS patients get better sooner. These results reinforce

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Annexon’s founding thesis that C1q inhibition is a powerful mechanism of action to stop the progression of neuroinflammation and underscore the potential of ANX005 and our classical complement platform to treat GBS and a host of other diseases of the body, brain and eye.”

The randomized, placebo-controlled Phase 3 trial which enrolled 241 subjects in Bangladesh and the Philippines evaluated two doses of ANX005, 30 mg/kg and 75 mg/kg, which both delivered rapid and complete suppression of complement activity but differed in duration of C1q inhibition. The 30 mg/kg dose suppression lasted one week and the 75 mg/kg dose suppression lasted two to three weeks. ANX005 75 mg/kg outperformed placebo on multiple endpoints, however, it was not statistically significant on the primary endpoint of GBS-DS at week 8 (p = 0.5548). The two dose levels were evaluated based on findings in the earlier Phase 1b proof-of-concept study, which showed efficacy in pooled analysis of both shorter and longer duration of ANX005 C1q inhibition. Because classical complement drives tissue damage in the early phase of disease, while facilitating nerve repair after acute nerve injury, the strong positive Phase 3 results with the 30 mg/kg dose resulting in one week of C1q inhibition appeared to define the optimal treatment window.

Hugh Willison, MBBS, PhD, Professor Emeritus of Neurology, University of Glasgow said, “In the first placebo-controlled pivotal study in GBS in approximately 40 years, ANX005 demonstrated robust and immediate neuroprotection by inhibiting C1q and suppressing downstream complement components with a single dose during the critical progressive phase of the disease. By directly targeting complement-mediated inflammation, ANX005 has the potential to act early to prevent nerve damage in this acute neurological emergency. The outcomes of this study represent an important breakthrough in effectively tackling GBS and support the potential of ANX005 to address the significant unmet need in this vulnerable patient population.”

David Cornblath, MD, Professor Emeritus of Neurology, Johns Hopkins University School of Medicine said, “This well designed, rigorous Phase 3 study demonstrated that acute and early intervention with ANX005 can deliver clinical benefits across the entire GBS disease spectrum. These data are consistent with the earlier Phase 1b findings, which showed improvements across multiple supportive functional and prognostic measures important to aid patient recovery. Among other outcomes in the Phase 3 trial, patients dosed with 30 mg/kg were able to walk independently one month earlier and removed off a ventilator one month sooner, which are paramount to getting patients back to normal activities of daily living and represent a potentially transformative advancement for the treatment landscape. I am excited by the potential of ANX005 to be the first FDA approved therapy to treat GBS.”

The clinical safety and tolerability findings of ANX005 at both doses in the Phase 3 study support a generally well-tolerated profile with no new safety signals. The majority of adverse events were mild Grade 1 to moderate Grade 2 events. The most common treatment-related adverse events were infusion related reactions (30.4%) that were mostly mild transient rashes. There were no autoimmune related adverse events, and no drug-related deaths or serious infections were observed.

The GBS Phase 3 study was conducted in Bangladesh and Philippines due to the high prevalence of GBS and limited access to standard of care intravenous immunoglobulin (IVIg). Based on feedback from the FDA, Annexon has initiated a real-world evidence (RWE) protocol with

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International Guillain-Barré Syndrome Outcomes Study (IGOS) to establish comparability between Phase 3 participants and Western patients. IGOS is a global, prospective, observational, multicenter cohort study that has enrolled 2,000 patients who were followed for one to three years. Approximately 50% of all Western IGOS patients met the entry criteria for the Annexon GBS Phase 3 trial and, importantly, ANX005 30 mg/kg achieved a robust treatment effect on GBS-DS at week 8 in patients with Western characteristics and milder GBS. In a prespecified subgroup analysis of patients with baseline MRC sum score ≥20, ANX005 30 mg/kg treated patients were three times more likely to be in a better state of health compared to placebo on GBS-DS at week 8 (p = 0.0102*). (* nominal)

RWE data and BLA submission are expected in the first half of 2025. Annexon plans to present Phase 3 data at the 2024 Peripheral Nerve Society Annual Meeting on June 25, 2024.

ANX005 has been granted Fast Track and Orphan Drug Designations from the FDA. ANX005 has also been granted Orphan Drug Designation by the European Medicines Agency (EMA) based on a meta-analysis of past studies with ANX005 and IVIg demonstrating notable, early improvement in muscle strength with ANX005 that translated into observable gains in health status, including a reduction in the need of mechanical ventilation.

Conference Call and Webcast Information

Annexon management will hold a conference call and webcast today at 8:30 a.m. ET to discuss topline results from its Phase 3 trial evaluating ANX005 for patients with GBS. The dial-in number for the conference call is 1-877-407-0784 (U.S./Canada) or 1-201-689-8560 (international). The conference ID for all callers is 13747058. The live webcast and replay may be accessed by visiting Annexon’s website at https://ir.annexonbio.com/events-and-presentations/events.

Call me^™: Click here. Participants can use guest dial-in numbers above and be answered by an operator or they can click the Call me^™ link for instant telephone access to the event (dial-out). The Call me^™ link will be made active 15 minutes prior to scheduled start time.

About Guillain-Barré Syndrome (GBS)

GBS is a severe disease resulting from an acute autoantibody attack on peripheral nerves that generally occurs post-infection in otherwise healthy persons following activation of C1q and the classical complement cascade. It is a rapid and acute neurological disease with a narrow therapeutic window that results in hospitalization of over 22,000 people annually in the U.S. and Europe. The peripheral nerve damage progresses rapidly, causing acute neuromuscular paralysis, and may lead to significant morbidity, disability and mortality. Currently, there are no approved treatments for GBS in the U.S. The long-term disease burden associated with GBS has led to a multi-billion-dollar annual economic cost to the U.S. healthcare system alone.

About Annexon

Annexon Biosciences (Nasdaq: ANNX) is a biopharmaceutical company advancing a late-stage clinical platform of novel therapies for people living with devastating classical complement-mediated neuroinflammatory diseases of the body, brain, and eye. Annexon’s novel scientific approach targets upstream C1q to block the classical complement inflammatory cascade before it starts, and its therapeutic candidates are designed to provide meaningful benefits across multiple

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autoimmune, neurodegenerative and ophthalmic diseases. With proof-of concept data in Guillain-Barré syndrome, Huntington’s disease and geographic atrophy, Annexon is rigorously advancing its mid-to late-stage clinical trials to bring their potential treatments to patients as quickly as possible. To learn more visit annexonbio.com.

Forward Looking Statements

This press release 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. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “suggest,” “target,” “on track,” “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. All statements other than statements of historical facts contained in this press release are forward-looking statements. These forward-looking statements include, but are not limited to, statements about: ability of ANX005 to stop C1q activity; the clinical and regulatory status of ANX005; the potential of ANX005 to be the first approved treatment for GBS; the potential of the 75mg dose of ANX005 to be used in patients with severe disease; the timing of completion of RWE study and potential submission of a BLA with the FDA; the potential therapeutic benefit of ANX005 or any other product candidates on GBS, Huntington’s disease or geographic atrophy; potential benefit of ANX005, if approved, compared to existing therapies; market size; the potential benefits from treatment with anti-C1q therapy; and Annexon’s ability to rigorously advance mid-to late-stage clinical trials and continue development of the company’s portfolio. 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: the potential for any final clinical trial results to differ from preliminary or topline results; the company’s history of net operating losses; the company’s ability to obtain necessary capital to fund its clinical programs; the early stages of clinical development of the company’s product candidates; the effects of public health crises on the company’s clinical programs and business operations; the company’s ability to obtain regulatory approval of and successfully commercialize its product candidates; any undesirable side effects or other properties of the company’s product candidates; the company’s reliance on third-party suppliers and manufacturers; the outcomes of any future collaboration agreements; and the company’s ability to adequately maintain intellectual property rights for its product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in the company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q and the company’s other filings with the SEC. Any forward-looking statements that the company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, the company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.

Investor Contact:

Joyce Allaire

LifeSci Advisors, LLC

jallaire@lifesciadvisors.com

Media Contact:

Sheryl Seapy

Real Chemistry

949-903-4750

sseapy@realchemistry.com

Exhibit 99.2 Topline Results from Phase 3 Study of ANX005 in Guillain-Barré Syndrome 1

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Forward-Looking Statements This presentation contains “forwardlo ‐ oking” 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 Licensing Application, strategic plans for our business and product candidates, including additional indications which we may pursue, our financial position, runway and anticipated 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 operating 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 COVID19 o ‐ r other 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 thirdp ‐ arty 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” contained in our Quarterly Report on Form 10Q ‐ filed with the Securities Exchange Commission (SEC) on May 13, 2024 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. 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 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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Pursuing an Intentional and Rigorous Approach to Tackling an Array of Classical Complement-Mediated Diseases Poised for a transformational 2024 and beyond Stopping the Start of Broad Therapeutic Potential Significant Near Term Classical Pathway of Late-Stage Clinical Value Creating Catalysts Neuroinflammation Platform ON A PATH TO HELPING PATIENTS GET THEIR LIVES BACK ü GBS pivotal Ph3 data readout (Q2) Well-supported MOA demonstrated Suite of fit-for-purpose drug differentiated functional outcomes candidates for diseases of the body, GA pivotal Ph3 initiation (mid-yr) Oral program POC data readout (2H) across GBS, GA, HD and ALS brain and eye GBS: Guillain‐ Barré Syndrome; HD: Huntington’s Disease; ALS: amyotrophic lateral sclerosis 3

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ANX005 Achieved a Breakthrough Phase 3 Win for GBS Patients Worldwide A single infusion demonstrated consistent benefit across multiple endpoints meaningful to patients Met Primary Endpoint Expedited Recovery Durable Treatment Effect Generally Well Tolerated P=0.0058 Patients Got Better Sooner 2.4-fold higher likelihood of Early, robust & clinically Maintained improvement over being in a better state of health meaningful benefit on multiple placebo at all timepoints across Safety data was similar to on GBS-DS at Week 8 outcome measures @ Week 8 multiple measures placebo ✓ FDA‐ agreed primary endpoint✓ Able to walk earlier vs placebo✓ Less time on ventilation ✓ Consistent, significant results ✓ Less overall disability ✓ No new safety signals ✓ Able to run earlier vs placebo from multiple pre‐ specified ✓ No increased infection rate ✓ Less nerve damage vs placebo analyses ✓ No difference in all‐ cause ✓ Larger effect in sub‐ group with mortality western baseline characteristics 4 Topline Results Subject to Change

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GBS: Neurological Emergency with Long-Term Disability; Requires an Immediately Targeted and Effective Intervention • Following infection, complement‐ activating POST-INFECTIOUS autoantibodies attack nerves leading to COMPLEMENT- nerve damage & acute paralysis MEDIATED DISEASE • Can happen to anyone, anytime, anywhere • 22,000 patients hospitalized in US & Europe every year HIGH UNMET MEDICAL NEED • IVIg not FDA approved, unknown MOA, requires 5‐ day treatment • Notwithstanding IVIg treatment, GBS results in: • Severe weakness and paralysis SIGNIFICANT • Mechanical ventilation in 25% of patients MORBIDITY • Extensive nerve damage causing uncertain and incomplete recovery Weaned from mechanical ventilation MOA: mechanism of action 1) van Doorn, 2013; Willison et al., 2016 2(van den Berg et al., 2014) 3 Walgaard et al (2021) Lancet Neurology 20(4):275, 4AAN Guidelines “Immunotherapy for GBS”, 4Hund EF et al (1993) Crit Care Med 21:433, 5 454Fletcher D, et al. (2000) Neurology 27;54(12), 46, 5Van den Berg B, et al (2014) Nat Rev Neurol Aug;10(8), 6Stephan et al (2012) Neuroscience 35:369, 7Lansita et al (2017) Int. J. Toxicol. 36:449

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Well Designed & Executed Pivotal Trial Showed Clear Results ANX005 for GBS Granted FDA Fast Track and FDA / EMA Orphan Drug Designation STUDY DESIGN • Baseline GBS‐ DS score 3‐ 5 • GBS diagnosed <10 days from onset of weakness • Patients stratified for baseline prognostic factors: muscle strength and time from onset of weakness • Conducted in Bangladesh and Philippines given high prevalence of GBS of all types, scientific leadership in GBS, and limited access to IVIg KEY ENDPOINTS 1 • Primary Outcome Measure: GBS‐ DS at week 8: well‐ accepted regulatory endpoint assessing functional status • Secondary Endpoints: Muscle strength (MRC sumscore), Motor TWO DOSES SELECTED TO DETERMINE Disability (ONLS), Duration of Ventilation, and others MOST EFFECTIVE DURATION OF INHIBITION 1 Analyzed using a proportional odds model, a common statistical analysis method (van Leeuwen, et al., 2019, doi.org/10.1371/journal.pone.0211404) 6 Topline Results Subject to Change

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Baseline Characteristics Generally Well Balanced Across Treatment Groups Stratified by Key Prognostic Factors: MRC Sumscore and Time Since Onset of Weakness Placebo ANX005 30mg/kg ANX005 75mg/kg Baseline Characteristic (N=81) (N=79) (N=81) Age at Screening (years); mean (SD) 34.2 (12.59) 36.9 (14.88) 37.9 (15.29) Sex, n (%) Male 57 (70.4) 51 (64.6) 51 (63.0) Baseline GBS-DS Score, n (%) 3 Able to walk 10 meters across open space with help 7 (8.6) 12 (15.2) 10 (12.3) 64 (79.0) 56 (70.9) 60 (74.1) 4 Bedridden or chair bound 10 (12.3) 11 (13.9) 11 (13.6) 5 Requiring assisted ventilation for at least part of the day Baseline MRC Sumscore (range 0-60), n (%) 21‐ 60 Mild/moderate loss of muscle strength 42 (51.9) 41 (51.9) 44 (54.3) 0 ‐ 20 Severe loss of muscle strength 38 (46.9) 38 (48.1) 37 (45.7) Time since of onset of weakness to randomization 6.4 (1.7) 6.3 (1.9) 6.5 (2.0) Days, mean (SD) Time since of onset of weakness to treatment Days, mean (SD) 6.5 (1.7) 6.3 (1.9) 6.6 (2.0) Electrophysiology by Hadden criteria, n (%) 18 (22.2) 16 (20.3) 16 (19.8) Acute Inflammatory Demyelinating Polyneuropathy (AIDP) 49 (60.5) 50 (63.3) 50 (61.7) Acute Motor Axonal Neuropathy (AMAN) 14 (17.3) 13 (16.5) 15 (18.5) Other 7 Topline Results Subject to Change

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ANX005 30 mg/kg Treated Patients Had Significant, Rapid and Sustained Improvement Across Multiple GBS Measures Achieved Goal of Helping Patients GET BETTER SOONER 1 1 1 ü Rapid & Complete ü Statistically Significant ü Statistically Significant ü Statistically Significant ü Statistically Significant Vent wk 26 Inhibition of classical Early Reduction in NfL Higher Odds of Being Early & Sustained Less Time on Ventilator complement cascade Better at Week 8 Improvement in over entire study (Primary Endpoint) Muscle Strength period C1q NfL GBS-DS MRC Sumscore Ventilation 1 nominal p‐ value 8 Topline Results Subject to Change

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Overview of Primary Endpoint: GBS-DS at Week 8 FDA accepted endpoint with alignment on statistical methodology GBS-DS SCALE COLLAPSED INTO 3 CATEGORIES GBS-DS SCALE FOR PIVOTAL PHASE 3 Enhances Clinical Interpretability GBS-DS 3-point scale (trichotomy) Approach: Collapse 7‐ grade scale to a 3‐ grade scale 1 2 3 (trichotomy) Good State Severely Disabled of Health Disabled/Death • 0-1: Good State of Health 0 1 2 3 4 5 6 • 2-3: Disabled • 4-6: Severely Disabled/Death ANX005 Shift to Better Health Rationale: ü Enhances clinical interpretability by focusing on a subject’s actual health status at week 8 after receiving ANX005 or placebo ü Evaluates patients across all health states GBS Ph3 Study Population ü Most efficient statistical analysis approach GBS-DS Scores of 3-5 at Baseline 9 Topline Results Subject to Change

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ANX005 30 mg/kg Showed Highly Significant and Clinically Meaningful Treatment Effect on GBS-DS at Week 8 (Primary Endpoint) 2.41-fold higher likelihood of being in a better state of health relative to placebo Grotta Bar of GBS-DS at Week 8 ANX005 30mg/kg N=78 OR 2.41, p=0.0058 Placebo N=81 10 Topline Results Subject to Change

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Pre-Specified GBS-DS Responder Analysis at Week 8: ANX005 30 mg/kg Demonstrated a Significant ≥3-Point Improvement vs. Placebo Substantial treatment effect at week 8, further supporting primary analysis 1 1 nominal p‐ value 11 Topline Results Subject to Change

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Getting Better Sooner: ANX005 30 mg/kg Increased Muscle Strength Earlier Relative to Placebo, and the Advantage Grew Over Time Early muscle strength improvement maintained & increased through full 26-week study (p=0.001) ANX005 30mg/kg (n=79) 10-point improvement Placebo (n=81) over placebo p=0.0351 * 1 45.5 days p<0.0001 1 35 days *** Gain in time to recovery maintained throughout study 1 28 days Nominal p‐ values Modified Intent‐ to‐ Treat (N=241) 1 Approximate Time difference 12 Topline Results Subject to Change

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ANX005 75 mg/kg Did Not Meet the Primary Endpoint with Inhibition Beyond Active Disease Process 75mg/kg did improve muscle strength similar to 30 mg/kg at early timepoints to week 4 Grotta Bar of GBS-DS at Week 8 Change from Baseline MRC Score ANX005 30mg/kg (n=79) ANX005 75mg/kg (n=81) ANX005 Placebo (n=81) 75mg/kg N=81 Placebo N=81 OR 1.20, p=0.5548 Modified Intent‐ to‐ Treat (N=241) Nominal p‐ values 13 Topline Results Subject to Change

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Getting Better Sooner: ANX005 30 mg/kg Showed Significant Early * Improvement in Motor Disability vs. Placebo on the ONLS Scale Maintains ability to perform daily tasks through 26 weeks p=0.0063 2.1-point improvement over placebo, p<0.0001 *** Gain in time to recovery maintained throughout study * 1 20 days 1 18 days ***Week 1: p <0.0001 1 Week 8: p=0.0965 35 days Nominal p‐ values *Overall Neuropathy Limitation Scale 1 Approximate Time difference 14 Topline Results Subject to Change

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Getting Better Sooner: ANX005 30 mg/kg Consistently Showed Faster Recovery Across Clinically Important Measures Relative to Placebo Helping patients achieve their independence sooner 56 Days ANX005 30mg/kg: N=79 Walking Earlier 87 Days 31 days earlier, p=0.0211 Placebo N=81 20 Days ANX005 Off Ventilation Earlier 30mg/kg: N=15 48 Days 28 days earlier, p=0.0356 Placebo N=15 Nominal p‐ values 15 Topline Results Subject to Change

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Through Week 26, ANX005 30mg/kg-Treated Patients had Better Outcomes Relative to Placebo ANX005 treatment demonstrated better outcomes than placebo at all time points in the study GBS-DS: 1.49x more likely of being better Be in a better state of health p=0.012 Through Week 26, Patients Treated with MRC: 5.4 mean point improvement Have more muscle strength p=0.0010 ANX005 30mg/kg Were More Likely to: ONLS: 1.1 mean point improvement Perform daily tasks better p=0.0063 Nominal p‐ values 16 16 Topline Results Subject to Change

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GBS Phase 3 Results are Highly Relevant to Western Populations ANX005 30 mg/kg treatment effect more pronounced in Western World-type patients Western patients tend to have less severe disease ANX005 30 mg/kg impact on patients and an AIDP neurotype with these characteristics Disease Severity US/Europe Severe Disease 3.03x more likely to be in a better state (MRC 0‐ 20) 80% of US/European 20% of health at Week 8 patients have baseline p=0.0102 MRC of >20 points (47% of patients had milder disease) 80% Mild/Mod Disease (MRC 21‐ 60) Neurotype 5.31x more likely to be in a better state of health at Week 8 60% of US/European 40% AMAN + Other 60% patients have AIDP p=0.0130 (21% of patients had AIDP) AIDP Nominal p‐ values 17 Topline Results Subject to Change

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ANX005 Generally Safe and Well-Tolerated Placebo ANX005 30mg/kg ANX005 75mg/kg Majority of AEs were mild (Grade 1) to N=81 N=79 N=81 moderate (Grade 2) • Most common related events were All Grades Grade ≥ 3 All Grades Grade ≥ 3 All Grades Grade ≥ 3 infusion related reactions Number of Subjects 79 35 79 33 80 36 § Majority were mild transient rashes Reporting TEAEs, n (%) (97.5) (43.2) (100.0) (41.8) (98.8) (44.4) • No autoimmune related adverse events Number of Subjects with reported 4 (4.9) 1 (1.2) 24 (30.4) 4 (5.1) 32 (39.5) 7 (8.6) Infusion Related Reaction • Infection rates were comparable across dose groups and consistent with typical Rash (most common 2 (2.5) 0 20 (25.3) 1 (1.3) 25 (30.9) 2 (2.5) hospital acquired infections with IRR) • 3 patients had treatment Most Common TEAEs (non-IRR), n (%) discontinuations 44 (55.7) 14 (17.7) 35 (43.2) 12 (14.8) Blood CPK Increased 46 (56.8) 16 (19.8) § 1 in each dose group Deaths Musculoskeletal Pain 35 (43.2) 0 36 (45.6) 0 26 (32.1) 1 (1.2) • No difference observed in incidence of 21 (26.6) 2 (2.5) 23 (28.4) 6 (7.4) ALT Increased 23 (28.4) 6 (7.4) all-cause mortality - 3 deaths in each dose group Urinary Tract Infection 18 (22.2) 6 (7.4) 19 (24.1) 5 (6.3) 18 (22.2) 1 (1.2) • Mortality rate of 3.7% was consistent Hypokalemia 24 (29.6) 8 (9.9) 16 (20.3) 4 (5.1) 11 (13.6) 3 (3.7) with rates seen in US and EU Constipation 10 (12.3) 0 15 (19.0) 0 17 (21.0) 0 • Deaths occurred in older and more severe subjects 11(13.9) 1 (1.3) 17 (21.0) 3 (3.7) AST Increased 16 (19.8) 3 (3.7) 18 PROPRIETARY & CONFIDENTIAL Topline Results Subject to Change

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GBS Pathophysiology and the Targeted MOA of ANX005 19

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GBS is a Neurological Emergency Requiring Urgent Intervention Limited time window to stop the active disease process and achieve a therapeutic effect ACUTE ACTIVE PHASE RECOVERY PHASE ACUTE ACTIVE PHASE Active Disease Process • Rapidly progressive bilateral muscle weakness peaking by 1 – 2 weeks in most cases • Paralysis in legs, arms and potentially Paralysis breathing muscles • Extended periods of ventilation in ICU, and intensive supportive care RECOVERY PHASE Range of functional • Gradual muscle strength and functional recovery improvement over months to years as nerve Autoantibodies regeneration takes place • ~20% unable to walk or dead at 1 year and Infection additional 20% continue to experience symptoms ‐ 4 0 2 4 8 12+ Time from onset of weakness (weeks) 20 Adapted from van den Berg, et al. (2014) Nat Rev Neurol 10, 469–482

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GBS Time Course: Autoimmune Complement-Mediated Nerve Damage Followed by Normal Complement-Facilitated Repair Complement-mediated Complement-facilitated nerve nerve damage repair (debris clearance) IDENTIFY MOST EFFECTIVE Active Disease Process TREATMENT WINDOW Paralysis BLOCK AUTOIMMUNE COMPLEMENT- MEDIATED NERVE DAMAGE DURING Shorter duration of inhibition ACTIVE DISEASE Longer duration of inhibition Range of functional recovery Autoantibodies ALLOW NORMAL COMPLEMENT FACILITATED NERVE REPAIR DURING Infection RECOVERY PHASE ‐ 4 0 2 4 8 12+ Time from onset of weakness (weeks) 21 Adapted from van den Berg, et al. (2014) Nat Rev Neurol 10, 469–482

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ANX005: Expected Pharmacokinetic and Dynamic Response for Both Doses Duration of complement inhibition defines active treatment window • Rapid C1q engagement and functional inhibition (CH50 assay) § 30 mg/kg provided: ~1 week duration of inhibition § 75 mg/kg provided: 2‐ 3 weeks duration of inhibition ANX005 75 mg/kg ANX005 30 mg/kg C1q inhibition ~ 1 week C1q inhibition 2-3 weeks Active Disease Phase Recovery Phase Active Disease Phase Recovery Phase C1q Function C1q Function ANX005 ANX005 22 Topline Results Subject to Change

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ANX005 Rapidly Shuts Down Activation of the ENTIRE Classical Complement Cascade on the Nerve to Prevent Acute Injury Classical Complement Drives Harmful Inflammation and Tissue Destruction STOPPING AT THE START C1q • Blocks upstream and downstream inflammation & tissue damage • Before downstream bypass mechanisms (breakthrough) and Immune C4b C4 C4a pathway amplification cell attack • Differentiated functional outcomes C2 Immune cell shown in GBS, GA, HD and ALS recruitment DOWNSTREAM APPROACHES (C3/C5) • Do not block ongoing inflammatory pressure of upstream classical pathway C3a C3 C3b • More susceptible to complement bypass mechanisms / inflammatory breakthrough Membrane C5a C5b-9 C5 damage 23 23 GBS: Guillain‐ Barré Syndrome; GA: geographic atrophy; HD: Huntington’s Disease; ALS: amyotrophic lateral sclerosis

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ANX005 GBS Phase 3 Trial Summary and Path Forward Douglas Love, President & CEO Annexon Biosciences 24

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Real-World Evidence to Support Planned Regulatory Submission Interim RWE Data Support Comparability & Relevance of Phase 3 Findings to the West • FDA agreed that a single pivotal study would be Annexon + IGOS RWE sufficient for BLA assuming it demonstrates: Comparability Study § Substantial evidence of ANX005’s treatment effect vs. placebo § Comparability between Ph3 population & Western patients Global GBS Real-World Evidence Cohort • Annexon has developed a real-world evidence (RWE) comparability protocol with IGOS (ANX005-GBS-04) • IGOS data supports ongoing comparability study, including: Annexon Phase 3 Study § ~50% of all Western IGOS patients met the entry criteria for GBS Ph3 § Robust ANX005 impact on ‘Western World’ type Phase 3 patients § Preparing matched cohort for comparison with IVIg 25 Topline Results Subject to Change

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GBS is an Untapped Commercial Opportunity and Annexon is Pursuing a Tailored Approach Significant commercial opportunity for ANX005 achieved through focused commercial footprint ANX005 First-line, 22,000 monotherapy people in US treatment for & Europe GBS hospitalized with GBS ANX005 helped GBS patients Get Better Sooner every year ü Single infusion ü Faster recovery / independence 90% of GBS patients treated with off-label IVIg in US ü Potential for significant cost reductions for health care system ‐ Daily infusions over 5 days Robust HEOR plan to demonstrate reduced cost of care ‐ Non-specific approach to treating GBS Focused and targeted commercial launch plan >$2B annual cost burden on patients, caregivers, 1 Commercial manufacturing partnership with Lonza hospitals, and payers GBS a beachhead for mechanistically-related neuro and Majority of patients treated in major metro areas 2 and large community hospitals autoimmune indications 1 2 Frenzen, PD (2008) Neurology 71:21‐ 27 7, ClearView Health market research 26 26 Topline Results Subject to Change

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ANX005 GBS Phase 3 Summary of Key Results A profound moment for the GBS community – first targeted therapy to demonstrate positive outcomes Phase 3 Met Primary Endpoint, confirming earlier study 1 GBS-DS at Week 8: Patients treated with ANX005 were 2.4 times more likely to be in a better state of health compared to placebo, p=0.0058 ANX005 Helped Patients with GBS Get Better Sooner 2 Early, robust, and clinically meaningful benefit on multiple outcome measures by week 8 including ability to walk earlier and less nerve damage vs. placebo Durable Treatment Effects Across Full Course of 26-Week Study Maintained improvement over placebo at all timepoints across multiple measures including less time on 3 ventilation and less overall disability Generally Safe and Well Tolerated 4 Safety profile similar to placebo – no increased rate of infections, convenient single dose Clear Path to BLA Submission and Launch 5 Preparing to engage FDA later this year to support BLA submission 1H25 On-track to complete RWE study by 1H25 to support BLA timelines Preparing clear launch strategy with focused commercial team 27 27 Topline Results Subject to Change

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To the patients, families, caregivers, physicians and medical teams who participated in our trial, we are eternally grateful for your support and contributions! To our employees, collaborators and advisors, thank you for your WARRIOR SPIRIT AND ALL FOR ONE COMMITMENT! 28

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Thank You! Q&A Annexon Biosciences sincerely thanks all the patients, families, and study staff who are helping make the ANX005 Ph3 GBS study possible. 29

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Appendix 30

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ANX005 30 mg/kg Demonstrated Significant Early Reduction in Prespecified Analysis of Neurofilament Light Chain (NfL) Assessment of reduction of neuronal damage Change in Serum NfL Weeks 2 - 4 p=0.03 Key Takeaways p=0.027 Placebo (n=77) 30 mg/kg (n=76) • Prespecified assessment of NfL reduction 75 mg/kg (n=77) during weeks 2‐ 4 consistent with Ph1b • Captures transition from acute progressive to recovery phase of disease • ANX005 30 mg/kg achieved significant early reduction in NfL between weeks 2 – 4 vs. pbo 1 (31.3% vs. 20.1%, p=0.03 ) Weeks 1 Nominal p‐ value 31 Topline Results Subject to Change if found Serum NfL (ng/ml) ± 1 SEM

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Y Complement is Pivotal Force in Driving Nerve Damage in GBS ANX005 is a Targeted Immunotherapy which Rapidly Blocks Complement • C1q binds to autoantibodies on nerve surface • One dose of ANX005 rapidly blocks C1q • Activates classical complement pathway • Stops activation of entire classical pathway GBS ANX005 • Blocks nerve fiber damage during the active • Results in neuroinflammation, nerve disease phase damage, tissue debris and paralysis Peripheral Nerve Fiber Peripheral Nerve Fiber Under Attack in GBS in GBS with ANX005 • Classical complement activation C1q C1q Blocked ANX005 • Nerve fiber damage • Tissue debris Nerve fiber intact Pathogenic autoantibodies Hafer‐ Macko C et al., (1996) Ann Neurol 39 & 40 32

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Phase 3 Comparison of Eculizumab vs. ANX005 Eculizumab Ph3 GBS Trial ANX005 GBS Ph3 Trial Targets downstream complement (C5) Blocks entire classical complement MOA ‐ misses important upstream cascade complement drivers of nerve damage Mean time from onset of >7 days < 7 days* weakness to treatment N 57 241 Stratification by prognostic Not stratified leading to imbalance Stratified factors *Stratified for days since onset of weakness (<7 days, ≥7 days) 33

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ANX005 Has Demonstrated Characteristics Required to Combat GBS Directly targets mechanism driving extensive nerve damage and paralysis • Complement is an established target in GBS • C1q binds to autoantibodies on nerve components initiating local activation of complement leading to inflammation, recruitment of immune cells, and damage to nerves Rapid onset of action • ANX005 has demonstrated rapid target engagement in blood & CSF across multiple central and peripheral neurological disorders • A single dose of ANX005 inhibits classical complement pathway on day 1 • Prevents acute and ongoing nerve damage to promote nerve repair Provides clinical benefit across entire disease spectrum • Complement-mediated nerve destruction present in all neurotypes of GBS • ANX005 mechanism of action is agnostic to neurotype or disease severity • Early improvement in MRC seen across disease spectrum Minimal side-effects • ANX005 has been safely administered in > 250 patients with GBS • Generally well-tolerated • No drug-related deaths & no serious infections observed 34

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The Phase 3 Study Embodies Key Characteristics of a Smart, Data- Driven, & Patient-Centric Design HOW I WOULD DESIGN A PH3 GBS STUDY HOW ANNEXON DESIGNED THE PHASE 3 PIVOTAL STUDY ü Data-driven by Ph1b, IGOS, and multiple external IVIg/PE datasets Use all available global data and ü Routinely engaged with leading experts in GBS routinely seek expert input ü Proportional odds uses full GBS-DS scale, includes all patients, increases power Measures all meaningful outcomes ü Efficacy assessments cover all GBS symptoms & signs at all important timepoints through all phases of disease ü Patients stratified by baseline MRC and days since onset of GBS symptoms Control for disease heterogeneity ü Using MRC, time of onset of weakness, baseline NfL and age as covariates ü Streamlined time from onset to treatment increasing likelihood of better outcomes Rigorous execution ü Conducted at sites with internationally recognized GBS clinical experience 35

v3.24.1.1.u2

Document and Entity Information	Jun. 04, 2024
Cover [Abstract]
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Entity Central Index Key	0001528115
Document Type	8-K
Document Period End Date	Jun. 04, 2024
Entity Registrant Name	ANNEXON, INC.
Entity Incorporation State Country Code	DE
Entity File Number	001-39402
Entity Tax Identification Number	27-5414423
Entity Address, Address Line One	1400 Sierra Point Parkway
Entity Address, Address Line Two	Bldg C
Entity Address, Address Line Three	Suite 200
Entity Address, City or Town	Brisbane
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94005
City Area Code	(650)
Local Phone Number	822-5500
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Security 12b Title	Common Stock, par value $0.001 per share
Trading Symbol	ANNX
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	false

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