Slide 1: Topline Results from Phase 3 Study of ANX005 in Guillain-Barré Syndrome
Exhibit 99.2 Topline Results from Phase 3 Study of ANX005 in Guillain-Barré Syndrome 1
Slide 2: Forward-Looking Statements
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,
Slide 3: Pursuing an Intentional and Rigorous Approach to Tackling Classical Complement-Mediated Diseases
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 Neuroin
Slide 4: ANX005 Achieved a Breakthrough Phase 3 Win for GBS Patients Worldwide
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-f
Slide 5: GBS: Neurological Emergency with Long-Term Disability
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,
Slide 6: Well Designed & Executed Pivotal Trial Showed Clear Results
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 an
Slide 7: Baseline Characteristics Generally Well Balanced Across Treatment Groups
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
Slide 8: ANX005 30mg/kg Treated Patients Had Significant, Rapid and Sustained Improvement
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
Slide 9: Overview of Primary Endpoint: GBS-DS at Week 8
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‐ grad
Slide 10: ANX005 30mg/kg Showed Highly Significant Treatment Effect on GBS-DS at Week 8
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 Toplin
Slide 11: Pre-Specified GBS-DS Responder Analysis at Week 8
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
Slide 12: Getting Better Sooner: Increased Muscle Strength Earlier Relative to Placebo
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
Slide 13: ANX005 75mg/kg Did Not Meet the Primary Endpoint
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 Place
Slide 14: Getting Better Sooner: Significant Early Improvement in Motor Disability on ONLS
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
Slide 15: Consistently Showed Faster Recovery Across Clinically Important Measures
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 Ventil
Slide 16: Through Week 26, ANX005 30mg/kg-Treated Patients had Better Outcomes
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
Slide 17: GBS Phase 3 Results are Highly Relevant to Western Populations
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/Eur
Slide 18: ANX005 Generally Safe and Well-Tolerated
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
Slide 19: GBS Pathophysiology and the Targeted MOA of ANX005
GBS Pathophysiology and the Targeted MOA of ANX005 19
Slide 20: GBS is a Neurological Emergency Requiring Urgent Intervention
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
Slide 21: GBS Time Course: Complement-Mediated Nerve Damage Followed by Repair
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-
Slide 22: ANX005: Expected Pharmacokinetic and Dynamic Response for Both Doses
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 inhibit
Slide 23: ANX005 Rapidly Shuts Down Activation of the Entire Classical Complement Cascade
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 byp
Slide 24: ANX005 GBS Phase 3 Trial Summary and Path Forward
ANX005 GBS Phase 3 Trial Summary and Path Forward Douglas Love, President & CEO Annexon Biosciences 24
Slide 25: Real-World Evidence to Support Planned Regulatory Submission
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
Slide 26: GBS is an Untapped Commercial Opportunity
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 pati
Slide 27: ANX005 GBS Phase 3 Summary of Key Results
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 he
Slide 28: Acknowledgments to patients, caregivers and teams
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
Slide 29: Thank You! Q&A
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
Slide 30: Appendix
ANNEXON biosciences Appendix
Slide 31: ANX005 30mg/kg Demonstrated Significant Early Reduction in Neurofilament Light Chain
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
Slide 32: Complement is Pivotal Force in Driving Nerve Damage in GBS
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 pathw
Slide 33: Phase 3 Comparison of Eculizumab vs. ANX005
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
Slide 34: ANX005 Has Demonstrated Characteristics Required to Combat GBS
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, rec
Slide 35: The Phase 3 Study Embodies a Smart, Data-Driven, Patient-Centric Design
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 engage