Annexon, Inc. · NASDAQ:ANNX
Annexon — Investor Day (March 2024)
56 slides from Annexon's investor day presentation, Mar 4, 2024
Slide 1: Virtual R&D Day | March 1, 2024
Exhibit 99.1 Virtual R&D Day | March 1, 2024 Nasdaq: ANNX
Slide 2: Guillain-Barré Syndrome: A Focus on its Serious Unmet Need and Annexon's Novel Therapeutic Approach
Guillain-Barré Syndrome: A Focus on its Serious Unmet Need and Annexon’s Novel Therapeutic Approach Douglas Love, President & CEO Annexon Biosciences 2
Slide 3: Forward-Looking Statements
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, ti
Slide 4: Agenda
Agenda TOPIC PRESENTER TIME (ET) Douglas Love Annexon: Overview and Commitment to GBS 10:00-10:05am President & CEO Lisa Butler GBS Patient Voice 10:05-10:15am Executive Director, GBS | CIDP Foundation Intl. Hugh J. Willison, MBBS, PhD GBS Disease Overview and Treatment Landscape 10:15-10:35am Profe
Slide 5: Late-stage Clinical Platform for Classical Complement-mediated Neuroinflammatory Diseases
ANNEXON: Late-stage Clinical Platform for Classical Complement- mediated Neuroinflammatory Diseases of the Body, Brain and Eye Large market opportunities supported by clinical proof-of-concept First-in-kind approach, data in multiple indications wholly owned pipeline Near-term registrational 2Q 2024
Slide 6: Only Complement Pipeline for Diseases of the Body, Brain & Eye
Only Complement-Pipeline for Diseases of the Body, Brain & Eye Potential to treat >8 MILLION patients worldwide Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Worldwide Rights FLAGSHIP PROGRAMS Phase 3 data ANX005 Autoimmune Guillain-Barré Syndrome (GBS) 2Q 2024 Phase 3 Ophthalmology ANX007 Geog
Slide 7: Annexon Has a Deep-Rooted History and Commitment to GBS
Annexon Has a Deep-Rooted History and Commitment to GBS Aligned With Our Mission Strong Scientific Rationale High Unmet Need to treat diseases driven by classical ANX005 is designed for rapid Well-characterized, underserved complement activation inhibition with a single dose disease afflicting thous
Slide 8: ANX005: Potential to be First FDA-approved Therapy for GBS
ANX005: Potential to be First FDA-approved Therapy for GBS Pursuing a monotherapy label in GBS Demonstrated POC across several clinically-meaningful measures Granted US FDA Fast Track & Orphan Drug Designations Granted EMA Orphan Drug Designation based on potential for benefit over available therapi
Slide 9: GBS Patient Voice
GBS Patient Voice Lisa Butler Executive Director of the GBS|CIDP Foundation 9
Slide 10: GBS|CIDP Foundation International
lll GBS|CIDP il Foundation International SUPPORT * EDUCATION + RESEARCH * ADVOCACY ARANK YOU * | ie gif STUART _ 2001, age 5
Slide 11: GBS|CIDP Foundation International
Mi GBS|CIDP | | Foundation International 2024, age 27
Slide 12: In The Voice of GBS Patients
In The Voice of GBS Patients “I was terrified, there was so much chaos around me as I “Went to ER, turned away for fatigue, dehydration was put in the ICU and told my body was paralyzed by and stress. The next day could not stand, legs this disease I had never heard of and that I would likely buckle
Slide 13: The Foundation
The Foundation 1980 2024 • 1980: First Meeting• 30,000 patients in database • 8 people• 20 members of Global Medical Advisory Board • 1 Doctor, 2 residents• 57 Global Centers of Excellence • 0 employees, 2 volunteers in Pennsylvania• 200 volunteers in 47 countries • 18 FTE, 13 Members of Board of Di
Slide 14: Support and Education
SUPPORT AND EDUCATION Support: • Approximately 100 patient inquiries monthly • Chapter support group meetings • 357 registered community members • Coffee Chats • 681 registered community members • Speaker Series • 2,218 registered community members Education: • 17 symposiums and 7,000+ attendees • W
Slide 15: Global Medical Advisory Board
Global Medical Advisory Board GMAB Members: Doctor-to-Doctor Consultations: Centers of Excellence: • United States: 12 2023 United States: 38 COEs • Barcelona: 1• 2 CIDP consultations International: 22 COEs • Denmark: 1• 1 IVIG Dosage consultation • United Kingdom: 1 • Brussels: 1 • Netherlands: 1 •
Slide 16: Research
Research • $8M total, $50k-$300k • Elevation Grant, Discover Grant, 3-year Benson Fellowship • Consortium based • Funding support for IGOS coordinating center’s research • NIH State of Science meeting: 2020 virtual meeting between NINDS and NIAID on state of GBS research 16
Slide 17: Advocacy
Advocacy • Dept of Defense Peer-Reviewed Medical Research Program (PRMRP): $6 million between 6 researchers since 2017 • Congressional Champion: John Garamendi • 2019: GBS patient listening session with FDA to increase awareness of the unmet need in GBS despite the current SoC • 2024: Hosting FDA Pa
Slide 18: Getting better slowly, Getting better sooner
Getting better slowly Getting better sooner 18
Slide 19: GBS Disease Overview and Treatment Landscape
GBS Disease Overview and Treatment Landscape Hugh J. Willison, MBBS, PhD Professor Emeritus of Neurology, University of Glasgow, Scotland 19
Slide 20: GBS: Neuro-Emergency Needing Urgent and Effective Intervention
GBS: Neuro-Emergency Needing Urgent and Effective Intervention Most common cause of acute paralytic inflammatory disease of the peripheral nervous system, known for its severity and rapid progression Frequently follows an infection that generates complement activating auto- antibodies that attack pe
Slide 21: GBS is a Neurological Emergency Requiring Urgent Intervention
GBS is a Neurological Emergency Requiring Urgent Intervention There is a limited time window in the acute illness phase to achieve a therapeutic effect PROGRESSION PLATEAU RECOVERY PROGRESSIVE PARALYTIC PHASE: rapidly progressive bilateral muscle weakness peaking by 1 week in most cases (ideal Antib
Slide 22: Auto-Antibodies Fix Complement to Peripheral Nerve Myelin & Axons
Auto-Antibodies Fix Complement to Peripheral Nerve Myelin & Axons COMPLEMENT – ACUTE NERVE DAMAGE BIOMARKER ELEVATED MEDIATED NERVE DAMAGE IN ALL GBS NEUROTYPES AIDP AMAN AMSAN Equivocal HC N=58 N=12 N=7 N=14 N=53 • Auto-antibody-mediated nerve damage affects both myelin • The gold standard biomarke
Slide 23: Complement is Pivotal Force in Driving Nerve Damage in GBS
Complement is Pivotal Force in Driving Nerve Damage in GBS C1q binds to IgG and IgM antibodies on nerve and activates the classical complement pathway leading to neuroinflammation, directs clearance of debris by macrophages (C3b) and inflicts direct membrane damage (C5b-9) causing sudden and prolong
Slide 24: ANX005 is a Targeted Immunotherapy Against Complement-Mediated Nerve Fiber Damage
ANX005 is a Targeted Immunotherapy Against Complement- Mediated Nerve Fiber Damage Immediate C1q inhibition with a single dose of ANX005 is designed to block all downstream complement components involved in acute or ongoing inflammation and nerve damage and allow nerve fiber recovery to start 24
Slide 25: Prognostic Factors of Functional Recovery
Prognostic Factors of Functional Recovery Used in clinical prognostic tools, critical in clinical trial design, essential to show comparability between populations Baseline factors have been identified from multiple, large, prospective and retrospective studies including IGOS that are highly prognos
Slide 26: Characteristics of an Effective Therapy to Combat GBS
Characteristics of an Effective Therapy to Combat GBS – Get Better Sooner Directly targets mechanism driving extensive nerve damage and paralysis 1 Treatment goal is to target complement-mediated acute nerve damage and inflammation to prevent paralysis, severe morbidity, disability and mortality Rap
Slide 27: ANX005 GBS Phase 1b POC Study
ANX005 GBS Phase 1b POC Study Randomized, double-blind trial, placebo-controlled Phase 1 trial; completed 2020 STUDY DESIGN KEY OBJECTIVES • Safety / Tolerability / PK KEY RESULTS • N=50 Adults with GBS in Bangladesh • C1q target engagement • SAD: ANX005 3 mg/kg to 100mg/kg ✓ No deaths • MAD: 2 x 75
Slide 28: ANX005 Phase 1b: Rapid and Complete Complement Inhibition
C1q function (% hemolytic activity) ANX005 Phase 1b: Rapid and Complete Complement Inhibition ANX005 DEMONSTRATED RAPID COMPLEMENT INHIBITION AT DAY 1 Serum PK/PD after Single 75 mg/kg Dose C1q activity not detectable when ANX005 was present in the circulation (Data from 75 mg/kg patient) • Single d
Slide 29: ANX005 Rapidly Inhibits Complement Alone or Following IVIg
ANX005 Rapidly Inhibits Complement Alone or Following IVIg Complement levels measured by CH50 IVIg 400 • IVIg alone does not inhibit complement on Day 1 200 ANX005 • ANX005 alone or following IVIg results in complete inhibition 0 Day 1 Day 2 Post IVIg Post ANX005 First of 5 daily 400mg/kg infusions
Slide 30: ANX005 Phase 1b: Early Reduction in Nerve Damage
ANX005 Phase 1b: Early Reduction in Nerve Damage ANX005 PHASE 1b NfL RESULTS Statistically significant early NfL reduction RELEVANCE OF NfL (weeks 2-4) 90 • Neurofilament light chain increases proportionally 30 to the degree of axonal injury or degeneration 0 • Elevated NfL levels in serum are assoc
Slide 31: ANX005 Phase 1b: Early Improvement in Muscle Strength
ANX005 Phase 1b: Early Improvement in Muscle Strength MRC RESULTS PHASE 1b STUDY RELEVANCE OF MUSCLE STRENGTH Early Change in mean MRC Sumscore from Baseline • Loss of muscle strength is considered the primary clinical manifestation of GBS • Muscle strength is most important prognostic marker for ou
Slide 32: ANX005 Phase 1b: Consistent Shift to Better on Disability (GBS-DS)
ANX005 Phase 1b: Consistent Shift to Better on Disability (GBS-DS) Large shifts to better from baseline GBS-DS Grotta Bar: Consistent shifts to demonstrated on GBS-DS @ week 8 better in ANX005 groups vs. pbo @ week 8 Translated to Grotta Bar 28% of patients treated with ANX005 shifted to being in a
Slide 33: ANX005 Phase 1b: Consistent Demonstration of Getting Better Sooner
ANX005 Phase 1b: Consistent Demonstration of Getting Better Sooner Rapid target engagement, early nerve damage reduction and recovery of muscle strength precedes gain of function NEUROLOGICAL DISABILITY NEURAL DAMAGE MUSCLE WEAKNESS Rapid reduction in nerve fiber Early gain in muscle strength Improv
Slide 34: EMA Review of Ph1b Data Highlights Potential of ANX005
EMA Review of Ph1b Data Highlights Potential of ANX005 • ODD granted late 2023 based on potential of providing ‘significant benefit’ over approved SoC (IVIg) • EMA recognizes relevance of data from Bangladesh “…[the data] showed an increased response of ANX005 regarding DATA PACKAGE IN ODD APPLICATI
Slide 35: 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 36: Annexon GBS Clinical Program Overview
Annexon GBS Clinical Program Overview David Cornblath, MD Professor Emeritus, Johns Hopkins University 36
Slide 37: The Phase 3 Study Embodies Key Characteristics of 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 ✓ Data-driven by Ph1b, IGOS, and multiple external IVIg/PE datasets Use all available global data and ✓ Routinely engage
Slide 38: ANX005 Phase 3 Pivotal Trial On Track for Data Readout Q2 24
ANX005 Phase 3 Pivotal Trial On Track for Data Readout Q2 2024 Randomized, double-blind trial, placebo-controlled Phase 3 trial; enrollment completed in 2H 2023 STUDY DESIGN MONOTHERAPY SINGLE DOSE TREATMENT ENDPOINTS 1 • Patients diagnosed <10 days Primary Outcome Measure from onset of weakness GBS
Slide 39: Phase 3 GBS-DS Analysis Approach
Phase 3 GBS-DS Analysis Approach GBS-DS SCALE COLLAPSED INTO 3 CATEGORIES Enhances Clinical Interpretability GBS-DS SCALE FOR PIVOTAL PHASE 3 GBS-DS 3-point scale (trichotomy) Approach: Collapse 7-point scale to a 3-point scale (trichotomy) 1 2 3 • 0-1: Good State of Health Good State Severely Disab
Slide 40: Phase 3 Key Secondary Endpoints
Phase 3 Key Secondary Endpoints Designed to assess total clinical benefit and demonstrate durability of response with measures that are interpretable and relevant to patients and clinicians MUSCLE STRENGTH CHRONIC DISABILITY MORBIDITY AND MORTALITY MRC Sum Score GBS Disability Score Ventilation, Tim
Slide 41: Real-World Evidence in Support of Regulatory Submission
Real-World Evidence in Support of Regulatory Submission • FDA agreed that a single pivotal study would be Annexon + IGOS RWE Comparability Study sufficient for BLA assuming it demonstrates: ▪ Substantial evidence of ANX005’s treatment effect vs. placebo ▪ Comparability between Ph3 population & Weste
Slide 42: GBS Market Opportunity and Annexon's Commercial Approach
GBS Market Opportunity and Annexon’s Commercial Approach Michael Overdorf, Chief Business Officer Annexon Biosciences 42
Slide 43: GBS Market Opportunity and Annexon's Commercial Approach
GBS Market Opportunity and Annexon's Commercial Approach Significant commercial opportunity for ANX005 achieved through focused commercial footprint Significant Commercial Unique Commercial Focused Commercial Value-based Opportunity Dynamics Launch Benefits Indiscriminate and urgent Planning to targ
Slide 44: Increased GBS Incidence Numbers Reveal Full Magnitude of Disease and Commercial Opportunity
Increased GBS Incidence Numbers Reveal Full Magnitude of Disease and Commercial Opportunity • Completed first-ever analysis of 7 years of medical Annual US claims data to determine incidence of GBS GBS Incidence 7,000 • Updated GBS incidence: 7,000 in US and Hospitalized & Treated 1 15,000 for all E
Slide 45: Unique Commercial Dynamics
Unique Commercial Dynamics Unlike other rare diseases, indiscriminate and urgent nature of GBS drives low referrals Low Referral Rates Urgent, Acute Treatment Indiscriminate Disease Physicians are hesitant to refer GBS patients present at GBS is an acute, rapidly-developing patients given confidence
Slide 46: GBS Patients Geographically Concentrated Based on Population
GBS Patients Geographically Concentrated Based on Population Initial targeting of large metropolitan areas where GBS patients and treaters are concentrated NATIONAL POPULATION GBS PATIENTS Geographic Distribution Geographic Distribution (2016-2022) Source: 81qd claims data analysis and Census data 4
Slide 47: Planning Focused Launch Targeting Top Treatment Centers
Planning Focused Launch Targeting Top Treatment Centers Intend to target hospitals in three waves leveraging physician experience and endorsement Large Metropolitan and Academic hospitals (n~60) are initial launch targets since they treat the majority of GBS patients Top 15 hospitals treat ~15% of a
Slide 48: Planning Focused Commercial Footprint
Planning Focused Commercial Footprint Commercial team will provide education, support, and access to hospitals, neurologists, and care teams Key Account Managers Medical Science Liaisons Customer Support Reps Higher-level hospital engagement GBS education ANX005 education ANX005 promotion to label H
Slide 49: Commercial Teams Help Patients Achieve Goal of Getting Better Sooner
Commercial Teams Help Patients Achieve Goal of Getting Better Sooner Reinforce patient outcome benefits of ANX005 across care teams Neurologist Emergency PM&R & Intensive Team Care Team Key Account Medical Science Customer Managers Liaisons Support Reps Patient Getting Better Sooner 49
Slide 50: Potential ANX005 Value-Based Benefits
Potential ANX005 Value-Based Benefits 1,2,3,4,5,6,7 SIGNIFICANT DISEASE BURDEN DESPITE CURRENT TREATMENTS “I was put on my hands and knees, and I had to learn ~25% ~40% ~20% ~10% ~5% how to crawl just like a baby… require mechanical admitted to ICU can't walk at 1 year permanently disabled mortality
Slide 51: Closing Remarks & Q&A Session
Closing Remarks & Q&A Session Douglas Love, President & CEO Annexon Biosciences 51
Slide 52: Annexon GBS Program Key Takeaways and Next Steps
Annexon GBS Program Key Takeaways and Next Steps ANX005 potential to be the first FDA-approved treatment for GBS HIGH UNMET MEDICAL NEED WITH STANDARDS OF CARE • Devastating and rapid nerve disease afflicting over 20K in the US and Europe NEXT STEPS • No change in mortality rates in decades • Annexo
Slide 53: Thank You
THANK YOU Annexon Biosciences sincerely thanks all the patients, families, and study staff who are helping make the ANX005 Ph3 GBS study possible. 53
Slide 54: Powered By a Distinct Complement Approach Targeting C1q
Powered By a Distinct Complement Approach Targeting C1q to STOP the Inflammatory Cascade Where it STARTS Classical complement: common inflammatory pathway driving diseases of the body, brain & eye C1q STOPPING C1q AT THE START 1 Blocks All Classical Pathway Activity • Selectively stops upstream & do
Slide 55: Key IVIg Topics That Are Advantageous to ANX005
5 Key IVIg Topics That Are Advantageous to ANX005 1. IVIg’s MOAs in GBS remain largely unknown 2. In the era of targeted immunotherapy, IVIg is a dated approach 3. Full course of IVIg treatment takes 5 days allowing disease mechanisms to continue 4. IVIg does not significantly affect plasma CH50 in
Slide 56: 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