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Positive Topline Data from Real-World Evidence in Guillain-Barré Syndrome December 16, 2024
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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, the adequacy and sufficiency of the RWE data to support marketing application, strategic plans for our business and product candidates, includ ing 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 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 November 14, 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 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 est imates 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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ANX005 Has the Potential to Be the First Targeted Therapy for Guillain-Barré Syndrome (GBS) • Anti‐C1q therapy rapidly blocks classical complement mediated neuroinflammation in a single dose to halt ongoing nerve damage • Annexon portfolio opens a new era of complement medicines to treat neuroinflammatory disease • Rapid and acute neurological disease with no FDA‐approved treatment • 22,000 patients hospitalized in US and Europe annually • Involves common underlying pathophysiology worldwide • Phase 3 trial demonstrated significant benefit with ANX005 over placebo • Real‐world evidence shows ANX005 benefit over IVIg/PE, strengthening body of evidence for ANX005 in GBS • Company plans to submit U.S. BLA in 1H 2025 ANX005 TARGETED IMMUNOTHERAPY GBS IS A SEVERE UNMET NEED ADVANCING ANX005 FOR GBS WORLDWIDE 3
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Phase 3 Demonstrated ANX005 30 mg/kg Single Dose Led to Rapid, Robust, and Consistent Benefit Across Multiple Endpoints • FDA‐agreed primary endpoint • Multiple sensitivity analyses of the primary endpoint show consistent improvements • Larger effect in sub‐group with western baseline characteristics • Less time on ventilation • Less overall disability • Higher proportion of patients returning to normal (GBS‐DS = 0) at week 26 vs. placebo • No new safety signals • No increased infection rate while not requiring vaccination or prophylactic antibiotics • No difference in all‐cause mortality MET PRIMARY ENDPOINT 2.4x more likely of being better on GBS-DS at Week 8 relative to placebo (p = 0.0058) DURABLE TREATMENT EFFECT Maintained improvement over placebo at all timepoints across multiple measures GENERALLY WELL TOLERATED Safety data was similar to placebo Topline Results Subject to Change 4
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Real-World Matched Cohort Study Showed Early and Greater Benefits of ANX005 30 mg/kg Single Dose over IVIg/PE 5 PH3 PATIENTS MATCHED WITH IGOS PATIENTS IMPROVED OUTCOMES OVER IVIG/PE RWE REINFORCES ANX005 EFFICACY ANX005 Phase 3 patients matched 1:1 with IGOS on prespecified criteria ✓ Propensity score matching based on key prognostic factors of muscle strength and GBS disability ✓ Matched cohorts demonstrate Phase 3 population is represented within global GBS patient spectrum Faster, more complete recovery with ANX005 vs IVIg/PE at multiple timepoints ✓ Rapid gain in muscle strength by week 1 (p <0.0001) ✓ Twice as likely to be in better state of health on GBS disability, including week 8 (p = 0.0459) ✓ Half as many patients required mechanical ventilation (p = 0.022) ✓ Trend toward fewer mechanical ventilation and ICU days (12 fewer days for each measure) Potential of ANX005 to be first targeted immunotherapy for GBS ✓ Study strengthens the body of evidence supporting ANX005 for treatment of GBS ✓ Study provides the first insights on how ANX005 may improve upon current standard of care Preliminary Topline Results Subject to Change
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Phase 3 ANX005 30mg/kg Patients Matched 1:1 with IGOS Patients Treated with IVIg/PE 6 1:1 Match to Compare ANX005 vs. IGOS IVIg/PE* 1Measured by Medical Research Council (MRC) sumscore and GBS‐Disability Scale (GBS‐DS); 2Walgaard 2011 * Caliper = 0.8; similar results in a subset cohort with caliper 0.2 Propensity score matching process blinded to outcomes Balanced cohorts based on prespecified key prognostic factors of muscle strength and GBS disability1 WIDELY ACCEPTED MATCHING METHODOLOGY APPLIED Literature2 and IGOS analysis indicate baseline MRC and GBS‐DS are most prognostic to disability outcomes ANX005 30mg/kg IGOS IVIg / PE N = 79 N = 79 Preliminary Topline Results Subject to Change
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At Week 1, ANX005 Treated Patients Improved in Muscle Strength While IVIg/PE Treated Patients Continued to Decline Consistent with Single Infusion and Rapid MOA 7 Muscle weakness is a hallmark of GBS MRC at week 1 is a sensitive measure of the ‘acute disease process’ of neuroinflammation, nerve damage and destruction2 Time is Nerve Early improvement in muscle strength is important for halting disease progression and highly prognostic of functional improvement on disability, ICU and ventilation MORE THAN A 10-POINT IMPROVEMENT IN MRC SUMSCORE1 OVER IVIG/PE 1MRC results are adjusted for Age, Onset, and Baseline MRC 2Walgaard, et al., 2011. Early recognition of poor prognosis in Guillain‐Barré syndrome. Neurology 76:968. MRC Sumscore ‐4 ‐2 0 2 4 6 8 10 ANX005 30mg/kg (N=79) IVIg/PE (N=79) p<0.0001 Change from baseline in LS mean MRC sumscore at week 1 Preliminary Topline Results Subject to Change
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ANX005 30mg/kg Patients Improved on Disability vs. IVIg/PE 8 1Odds Ratios (OR) – likelihood of being in a better state of health, adjusted for Age, Onset, and Baseline MRC 2.89x 1.86x 2.43x 1.84x WEEK 1 WEEK 4 WEEK 8 WEEK 26 (0.95, 8.79) p = 0.0623 (0.72, 4.80) p = 0.2001 (1.02, 5.81) p = 0.0459 (0.75, 4.52) p = 0.1828 ~2x more likely to be in a better state of health GBS‐DS Odds Ratios (OR) Primary Endpoint for Phase 3 Trial Preliminary Topline Results Subject to Change
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FEWER DAYS ON VENTILATION Median 12 fewer days, p = n.s. Fewer ANX005 Patients Required Ventilation and Trended to Less Ventilation Time and ICU: Measures of Decreased Burden of Care 20 Days 32 Days ANX005 30mg/kg N =15 IGOS IVIG/PE N = 32 25 Days 37 Days ANX005 30mg/kg N =18 IGOS IVIG/PE N = 36 19% 40.5% ANX005 30mg/kg N = 15 of 79 IGOS IVIG/PE N = 32 of 79 FEWER SUBJECTS VENTILATED Half as many patients, p = 0.022 FEWER DAYS IN ICU Median 12 fewer days, p = n.s. 9 Preliminary Topline Results Subject to Change
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Consistent, Robust Effects Across Phase 3 Trial and Real-World Study Strengthen Body of Evidence for ANX005 ANX005 HELPED PATIENTS WITH GBS GET BETTER SOONER Phase 3 results showed early and durable recovery with ANX005 vs. placebo • Rapidly suppressed neuroinflammation via C1q inhibition during the active phase of GBS • Statistically significant improvements across multiple endpoints and over multiple timepoints Real-world study showed consistent ANX005 benefit over IVIg/PE across multiple measures • Rapid week 1 gain in muscle strength • Twice as likely to be in better state of health on GBS disability scale • Half as many patients required mechanical ventilation Engaging with US and EU regulators in preparation for planned BLA Submission in 1H 2025 10 Preliminary Topline Results Subject to Change
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11 Closing Remarks & Q&A Session
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Participants in Q&A Discussion 12 Ken Gorson, MD Professor of Neurology Tufts University School of Medicine Hugh J. Willison, MBBS, PhD Professor Emeritus of Neurology University of Glasgow, Scotland
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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 13