Annexon, Inc. · NASDAQ:ANNX
Annexon — Investor Presentation (January 2021)
33 slides from Annexon's investor presentation, Jan 11, 2021
Slide 1: Stopping Classical Complement at the Start
Exhibit 99.1 STOPPING CLASSICAL COMPLEMENT AT THE START TREATING DISEASES OF THE BODY, BRAIN AND EYE COMPANY PRESENTATION JANUARY 11, 2021Exhibit 99.1 STOPPING CLASSICAL COMPLEMENT AT THE START TREATING DISEASES OF THE BODY, BRAIN AND EYE COMPANY PRESENTATION JANUARY 11, 2021
Slide 2: Disclaimer
Disclaimer This presentation contains “forward‐looking” statements about Annexon, Inc. and our industry that involve substantial risks a nd uncertainties. All statements other than statements of historical facts, including statements regarding our clinical and preclinical programs, timing and commen
Slide 3: Pioneering Classical Complement Therapies to Treat Autoimmune, Neurodegenerative and Ophthalmic Diseases
Annexon: Pioneering Classical Complement Therapies to Treat Autoimmune, Neurodegenerative and Ophthalmic Diseases • Blocking upstream complement to stop disease processes at the start • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic d
Slide 4: Demonstrated Leadership Advancing Transformative Therapies
Demonstrated Leadership Advancing Transformative Therapies Doug Love, Esq. Ted Yednock, Ph.D. President & CEO Chief Scientific Officer Genentech, Amgen, Elan Elan, Prothena, Athena Jennifer Lew Sanjay Keswani, M.D. Michael Overdorf Chief Financial Officer Chief Medical Officer Chief Business Officer
Slide 5: Building a Leading Multi-Faceted Complement Company
Building a Leading Multi-Faceted Complement Company 2020: A Foundational Year ü $100M Series D in June and $263M Nasdaq IPO in July ü Robust ANX005 and ANX007 patient data demonstrating tolerability, full target engagement, biomarker/clinical data 0 ü Rapidly advancing into multiple Ph2 autoimmune,
Slide 6: Robust Clinical Pipeline of C1q Inhibitors for Body, Brain & Eye
Robust Clinical Pipeline of C1q Inhibitors for Body, Brain & Eye Multiple clinical stage drug candidates with diverse routes of administration INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 2/3 CURRENT STATUS ANX005 (IV) Guillain-Barré Syndrome (GBS) Ph 2/3 Ongoing Warm Autoimmune Hemolytic Ph 2 Initi
Slide 7: Significant Catalysts in 2021 and Beyond
Significant Catalysts in 2021 and Beyond Sufficient cash-runway to achieve these milestones INDICATION 1H 2021 2H 2021 2022 2023 ANX005 (IV) Guillain-Barré Syndrome (GBS) DDI data Ph2/3 data Warm Autoimmune Hemolytic Ph2 data Anemia (wAIHA) Ph2 initial data Huntington’s Disease (HD) Amyotrophic Late
Slide 8: Why C1q and the Classical Complement Pathway?
Why C1q and the Classical Complement Pathway? C1q is key driver of disease processes for indications Annexon has targeted C1q directly binds to tissue, initiating and anchoring complement in diseases of the body, brain and eye GBS HEMOLYTIC ANEMIA HUNTINGTON’S GEOGRAPHIC ATROPHY C1q C1q C1q C1q C1q
Slide 9: Inhibiting C1q Shuts Down Entire Classical Complement Pathway
Inhibiting C1q Shuts Down Entire Classical Complement Pathway Blocks C1q binding to tissues and downstream activation of C4, C3, C5 and C9 Lectin pathway C6-C8 C2 FD,FB Classical C1r C1s C1q C4 C3 C5 C9 Pathway Alternative pathway Potential Efficacy Advantages Potential Safety Advantages 1 ü Anti-C1
Slide 10: Leveraging Biomarkers to Increase Probability of Clinical Success
Leveraging Biomarkers to Increase Probability of Clinical Success Measuring objective classical complement and disease markers in patients Right Indication and Optimal Dose and Objective Measures Patient Selection Dosing Regimen of Treatment Effect Target population for initial study – 25% of lupus
Slide 11: Improving Patient Outcomes in Autoimmune Diseases
IMPROVING PATIENT OUTCOMES IN AUTOIMMUNE DISEASES • G u i l l a i n-Barré Syndrome • Warm Autoimmune Hemolytic Anemia 11IMPROVING PATIENT OUTCOMES IN AUTOIMMUNE DISEASES • G u i l l a i n-Barré Syndrome • Warm Autoimmune Hemolytic Anemia 11
Slide 12: GBS, a Destructive Neuromuscular Autoimmune Disease
GBS, a Destructive Neuromuscular Autoimmune Disease Severe disease that causes acute paralysis GUILLAIN-BARRÉ SYNDROME (GBS) Rare orphan disease: • 12K patients diagnosed annually in North America/Europe • No approved therapy in the U.S. Autoantibody attack on peripheral nerves, triggering complemen
Slide 13: ANX005 Well-Tolerated, Achieved Full Target Engagement, Reduced NfL in GBS Phase 1b
ANX005 Well-Tolerated, Achieved Full Target Engagement, Reduced NfL and Prevented Disability in GBS Phase 1b Dose-Ranging Trial Full Target Engagement in CSF Significant Early NfL Reduction 28% of High Dose Patients Improved by ≥ 3 pts on at Higher Doses (18-75 mg/kg) (Weeks 2 – 4) GBS-Disability Sc
Slide 14: Ongoing GBS Phase 2/3 Trial with ANX005
Ongoing GBS Phase 2/3 Trial with ANX005 Fast Track and Orphan Drug designations granted Placebo (n=~60) • Randomized, double-blind trial (N=~180) • Primary endpoint: GBS Disability Scale ANX005 30 mg/kg (n =~60) • Patients stratified for baseline muscle strength and time from symptom onset ANX005 75
Slide 15: Targeting Life Threatening RBC Autoantibody Attack in wAIHA
Targeting Life Threatening RBC Autoantibody Attack in wAIHA WARM AUTOIMMUNE HEMOLYTIC ANEMIA (wAIHA) Autoantibodies attack and destroy RBCs, resulting in anemia, can develop rapidly or gradually • ~30,000 patients globally • No approved therapy in U.S. Complement activation amplifies RBC destruction
Slide 16: Antibody-Mediated Complement Activation in wAIHA Patient Sera
Antibody-Mediated Complement Activation in wAIHA Patient Sera – Identifying an Enriched Patient Population ANX005 inhibits complement activation ACTIVITY FULLY INHIBITED BY ANX005 in wAIHA in vitro (n=1) • Detected complementa ‐ ctivating antibodies in 4 of 12 wAIHA patients (literature suggests 20
Slide 17: Planned Phase 2 wAIHA Trial with ANX005
Planned Phase 2 wAIHA Trial with ANX005 • Open label trial (n= up to 12) • Using Phase 0 ‘feeder’ study to identify/ select patients for Phase 2 ANX005 100 mg/kg 8 weeks Phase 0 at weeks 0 and 1 follow up • Objective endpoints: safety, PK/PD, (n= up to 12) hemolysis markers, improvement in hemoglobi
Slide 18: Tackling Blindness in Retinal Diseases
TACKLING BLINDNESS IN RETINAL DISEASES • Geographic Atrophy 18TACKLING BLINDNESS IN RETINAL DISEASES • Geographic Atrophy 18
Slide 19: Pioneering Treatment of Complement-Mediated Neurodegeneration
Pioneering Treatment of Complement-Mediated Neurodegeneration Well-researched role of C1q inhibition to protect against synapse loss and neurodegeneration Ben Barres, M.D., Ph.D. Discoverer of C1q Technology Scientific Co‐ Founder, Annexon • Synapse loss is a major driver of neurological disability
Slide 20: Differentiated Neuroprotective Approach for Geographic Atrophy
Differentiated Neuroprotective Approach for Geographic Atrophy Targeting up and downstream complement activity associated with retinal nerve loss GEOGRAPHIC ATROPHY (GA) Loss of vision due to loss of neurons (photoreceptors) • ~1 million U.S. patients; ~5 million worldwide • No approved therapies to
Slide 21: Intravitreal Anti-C1q Provides Neuroprotection in Mouse Model
Intravitreal Administration of Anti-C1q Provides Neuroprotection in a Mouse Model of Photoreceptor Cell Loss / Geographic Atrophy Intravitreal Administration of ANX007 Protects Photoreceptor Cells and Retinal Function Anti-C1q Protects Photoreceptor Protects Retinal Cells / Retinal Thickness Functio
Slide 22: Intravitreal ANX007 Effectively Inhibits C1q in Phase 1b Patients
Intravitreal ANX007 Effectively Inhibits C1q in Phase 1b Patients Full inhibition at low and high doses support monthly or less frequent dosing Free C1q Levels in Aqueous Humor ANX007 DATA SUMMARY • ANX007 well-tolerated at all dose levels • Single intravitreal injection inhibited C1q in aqueous hum
Slide 23: Initiating GA Phase 2 Trial with ANX007 in Q1 2021
Initiating GA Phase 2 Trial with ANX007 in Q1 2021 • Randomized, double-masked trial ANX007 5.0 mg/eye 1x monthly (n=~80) (N= ~240) Sham once monthly (n=~40) • Primary endpoint: change in area of 6 month geographic atrophy on FAF Off-treatment follow up • Leveraging experience from related ANX007 5.
Slide 24: Tackling Patient Disability in Devastating Neurodegenerative Diseases
TACKLING PATIENT DISABILITY IN DEVASTATING NEURODEGENERATIVE DISEASES • Huntington’s Disease • ALS 24TACKLING PATIENT DISABILITY IN DEVASTATING NEURODEGENERATIVE DISEASES • Huntington’s Disease • ALS 24
Slide 25: Pioneering Classical Complement Approach in Huntington's Disease
Pioneering Classical Complement Approach in Huntington’s Disease Targeting synaptic loss and neuronal death to tackle neurodegeneration HUNTINGTON’S DISEASE (HD) Progressive movement disorder, dementia, psychosis • ~35,000 U.S. patients (Orphan) • Subjects have high and sustained NfL levels Aberrant
Slide 26: ANX005 Reduced Key Markers of Disease Activity in HD Mice
ANX005 Reduced Key Markers of Disease Activity in HD Mice Decreased Complement Activation on Synapses, CSF NfL and Synapse Loss Decreased Complement Decreased Levels of CSF NfL Protection Against Synapse Loss Activation on Synapses Fold-Change in Complement CSF NfL (pg/mL) Fold Change Synapse Number
Slide 27: Ongoing HD Phase 2 Trial with ANX005
Ongoing HD Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, C1q target 3 month engagement, and NfL reduction from 6mo Treatment Off-treatment baseline (n=~24) follow up • Develo
Slide 28: Targeting Downstream Neuronal Loss in ALS
Targeting Downstream Neuronal Loss in ALS Only upstream approach targeting both CNS and PNS aspects of the disease AMYTROPHIC LATERAL SCLEROSIS (ALS) Progressive weakness of limb and respiratory muscles • ~30,000 patients globally (Orphan) • Subjects have high baseline NfL levels Aberrant C1q activi
Slide 29: C1q Deposition Correlated with Muscle Weakness in ALS Mouse Model
C1q Deposition Correlated w/ Muscle Weakness in Mouse Model and Preceded Denervation in ALS Patients; NfL Elevated w/ Disease C1q Levels in NMJ of ALS Mouse C1q Deposition in NMJ of ALS Serum NfL Elevated in ALS Patients a Year Prior to Symptom Onset Model Correlate with Weakness Patients Prior to D
Slide 30: Planned ALS Phase 2 Trial with ANX005
Planned ALS Phase 2 Trial with ANX005 Leveraging biomarkers to inform next stage of development and future neuro indications • Open label trial (N= ~24) • Objective endpoints: Safety, PK/PD, C1q target engagement, and NfL reduction 3 month 3mo Treatment from baseline Off-treatment (n=~24) follow up
Slide 31: Potential to Expand Platform Across A Breadth of Diseases
Potential to Expand Platform Across A Breadth of Diseases Current indications and future opportunities in both orphan and large patient populations AUTOIMMUNE NEURODEGENERATION (warm Autoimmune wAIHA Hemolytic Anemia) HD (Huntington’s Disease) GBS (Guillain-Barré Syndrome) ALS (Amyotrophic Lateral S
Slide 32: Poised to Drive Value in 2021 and Beyond
Poised to Drive Value in 2021 and Beyond • Targeting aberrant C1q / classical pathway activation to treat devastating tissue damage in the diseases we’re pursuing • Broad platform potential in orphan and large patient populations in autoimmune, neurodegenerative and ophthalmic diseases • Great momen
Slide 33: Annexon Biosciences – Thank You
ANNEXON biosciences THANK YOU