Annexon, Inc. · NASDAQ:ANNX
Annexon — Investor Presentation (July 2022)
41 slides from Annexon's investor presentation, Jul 8, 2022
Slide 1: Investor Presentation July 2022
Investor Presentation July 2022 Exhibit 99.2
Slide 2: 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 3: Pioneering a Powerful Approach to Classical Complement Inhibition
Pioneering a Powerful Approach to Classical Complement Inhibition Complement inhibition is a validated clinical and commercial approach Annexon’s next-generation approach blocks both upstream & downstream complement for enhanced outcomes Advancing 5 fit-for-purpose drug candidates for complement-med
Slide 4: C1q: A Key Driver of Complement-Mediated Disease
Initiator of aberrant or excess complement activity in autoimmune and neurodegenerative diseases C1q: A Key Driver of Complement-Mediated Disease C1q is initiating molecule in classical complement cascade C1q binds tissue surfaces to anchor and amplify complement activation and drive disease C1q mar
Slide 5: Upstream Classical Complement Inhibition Associated with Clinical Benefit
Upstream Classical Complement Inhibition Associated with Clinical Benefit Guillain-Barré Syndrome Patients achieving ≥3 point improvement in 8 weeks ANX005 28% Placebo 0% Huntington’s Disease 75% of patients with high baseline complement activity maintained improvement at week 36 ANX005 75% GBS Disa
Slide 6: Advancing Pipeline of 'Fit for Purpose' Drug Candidates
Advancing Pipeline of ‘Fit for Purpose’ Drug Candidates Across Multiple Complement-Targeted Diseases CANDIDATE DESIGN FRANCHISE INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 2/3 ANX005 IV mAb Guillain-Barré Syndrome (GBS) Warm Autoimmune Hemolytic Anemia (wAIHA) Huntington’s Disease (HD) Amyotrophic
Slide 7: Lead Candidates Demonstrated Robust Target Engagement in Body, Brain and Eye
Lead Candidates Demonstrated Robust Target Engagement in Body, Brain and Eye in Clinical Trials Weeks Ophthalmology Autoimmune Neuro C1q Body Inhibition ANX005 Full C1q Inhibition in Serum C1q Brain Inhibition ANX005 Full C1q Inhibition in CSF C1q Eye Inhibition ANX007 Full C1q Inhibition in Aqueous
Slide 8: Multiple Value-Creating Opportunities in 2022 and 2023
Multiple Value-Creating Opportunities in 2022 and 2023 CANDIDATE INDICATION FRANCHISE 1H 2022 2H 2022 2023 ANX005 Guillain-Barré Syndrome Warm Autoimmune Hemolytic Anemia Huntington’s Disease Amyotrophic Lateral Sclerosis (ALS) ANX007 Geographic Atrophy (GA) ANX009 Lupus Nephritis ANX105 Neuro / Aut
Slide 9: ANX005 for Autoimmune & Neurodegenerative Disease
ANX005 for Autoimmune & Neurodegenerative Disease Guillain-Barré Syndrome (GBS) Warm Autoimmune Hemolytic Anemia (wAIHA) Huntington’s Disease (HD) Amyotrophic Lateral Sclerosis (ALS)
Slide 10: ANX005: Designed to Fully Inhibit C1q and the Entire Classical Complement Pathway
ANX005: Designed to Fully Inhibit C1q and the Entire Classical Complement Pathway ANX005 ANX005 Key Attributes Full-length monoclonal antibody formulated for intravenous administration Fully inhibits C1q in the body and brain, with complete target engagement in blood and CSF Well-tolerated in clinic
Slide 11: ANX005 for GBS: Inhibiting Upstream to Stop Downstream Neuroinflammation
C1q binds autoantibodies on nerves and amplifies complement cascade Inhibiting C1q with ANX005 stops downstream activation of tissue-damaging components in GBS In POC trial, ANX005 was well-tolerated, achieved full target engagement, early reduction in neuronal death and improvement in muscle streng
Slide 12: Placebo-Controlled Phase 2/3 GBS Trial Ongoing with Data Anticipated in 2023
Placebo-Controlled Phase 2/3 GBS Trial Ongoing with Data Anticipated in 2023 Placebo (n=~60) ANX005 30 mg/kg (n=~60) ANX005 75 mg/kg (n=~60) Single-Dose Treatment Specifications Randomized, double-blind trial (N=180) Primary endpoint: GBS Disability Scale Patients stratified for baseline muscle stre
Slide 13: ANX005 for wAIHA: Inhibiting Upstream to Stop Complement-Mediated Disease
C1q binds to red blood cells on autoantibody coated surface causing anemia IgG and IgM antibodies C1q and complement activation amplify RBC destruction in ~25-50% of patients Complement levels correlate with level of hemolysis Selecting patients with high baseline complement activity who have a simi
Slide 14: Ex Vivo Blockade of C4 Deposition on RBC in wAIHA Patient Sera with ANX005
Ex Vivo Blockade of C4 Deposition on RBC in wAIHA Patient Sera with ANX005 ANX005 Blocks Complement Activity in wAIHA Patient Sera Autoimmune
Slide 15: ANX005 Phase 2 Trial for wAIHA Underway; Clinical Data Anticipated in 2H 2022
Trial Design Specifications ANX005 Phase 2 Trial for wAIHA Underway; Clinical Data Anticipated in 2H 2022 Open label trial (n= up to 12); on and off treatment assessments Using Phase 0 ‘feeder’ study to identify/select patients for Phase 2 Objective endpoints: safety, PK/PD, hemolysis markers, impro
Slide 16: ANX005 for Huntington's Disease (HD): Inhibiting Upstream to Protect Functioning Synapses
Inherited, fatal disease that causes progressive synapse damage and loss associated with neuroinflammation and loss of neurons Affects ~80K people globally, with ~300K at risk of inheriting the disease-causing HD gene1 Life expectancy after diagnosis estimated to be 15-20 years Progressive decline i
Slide 17: C1q's Role in Development and Neurodegenerative Disease
C1q’s Normal Role In Development C1q selectively recognizes, tags & drives removal of excess synapses Strong synapses remain to form appropriate circuits and normal brain health C1q C3b C4b C5b-9 C1q drives inappropriate synapse damage and loss C1q’s Role In Neurodegenerative Disease C1q recognizes,
Slide 18: Phase 2 Open-label Clinical Trial of ANX005 in Huntington's Disease
Phase 2 Open-label Clinical Trial of ANX005 in Patients With, or at Risk for, Manifest Huntington’s Disease Primary & Secondary Endpoints Safety and tolerability of ANX005 PK of ANX005 in serum & cerebrospinal fluid (CSF) PD as measured by C1q, NfL, and C4a serum and CSF concentrations 3-month follo
Slide 19: ANX005 Phase 2 Trial Patient Baseline Demographics
ANX005 Phase 2 Trial Patient Baseline Demographics * TRACK-HD, HD natural history study. For illustrative purposes only - differences exist between patient demographics, study designs, and other factors and caution should be exercised when comparing data across studies. NR=not reported Study Partici
Slide 20: ANX005 Demonstrated Complete & Durable C1q Inhibition in Blood and CSF
ANX005 Demonstrated Complete & Durable C1q Inhibition in Blood and CSF Full Target Engagement in CSF Full Target Engagement in Serum Target engagement 4-10 weeks in serum post last dose; may support less frequent dosing Off treatment CSF ANX005 CSF C1q Off treatment Serum C1q Serum ANX005 N = 23 Las
Slide 21: Drug Effects Continue into Off-treatment Period
C3a C3 Last Dose Drug Effects Continue into Off-treatment Period Off treatment Baseline levels Evidence of Reduced Downstream Complement Activation & Neuroinflammation Through Entire 9 Month Study 1Liddelow, Barres, 2017 Nature 541: 481–487 ANX005 showed: Reduction of downstream complement activatio
Slide 22: NfL Changes Stable and Consistent with Natural History
NfL Changes Stable and Consistent with Natural History Through Treatment and Follow-up Periods Results independent of baseline complement activity N = 23 Natural history Natural history1 Natural history2 Off treatment Off treatment Plasma NfL CSF NfL Neuro
Slide 23: cUHDRS and TFC Stable Over Months
cUHDRS Stable Over 9 Months TFC Stable Over 9 Months Off treatment Off treatment MMRM; LS means +/- 95% CI 1 Expected decline = interpolated natural history from Schobel 2017 (TRACK-HD) Expected decline1 Clinical Disease Progression Stable in Overall Patient Population Through Entire 9-month Study E
Slide 24: Patients with Higher Baseline Complement Activity May Be More Likely to Respond
Patients with higher baseline complement activity may be more likely to respond to anti-C1q therapy Complement Activation Correlates with Disease and Functional Decline in HD CSF C4a Activation Correlate with HD Functional Decline CSF C4a Elevated and Increase with HD Progression* p<0.001 CSF C4a Le
Slide 25: Rapid Benefit Maintained in Patients with High Baseline Complement Activity
*Comparing higher vs lower C4a/C4 groups at week 24 Benefit at All Time Points in High Complement Group (cUHDRS) Benefit at All Time Points in High Complement Group (TFC) Rapid Benefit Maintained in Patients with High Baseline Complement Activity Through Treatment and Follow-up Periods Off treatment
Slide 26: 75% of Patients with High Baseline Complement Levels Showed Improvement
Week 24 *p=0.032 75% patients with elevated baseline complement improved (9/12) vs. 36% with lower baseline complement (4/11) Week 24 cUHDRS Change from Baseline Week 36 *p=0.134 75% maintained during 3-month follow-up period Week 36 cUHDRS Change from Baseline Baseline Complement Activity (C4a/C4)
Slide 27: Chronic Dosing of ANX005 Generally Well-Tolerated in HD
Chronic Dosing of ANX005 Generally Well-Tolerated with Favorable Benefit-Risk Profile Demonstrated in HD No change in safety results from interim analysis IRR primarily first dose effect – none after 2nd dose No deaths and no serious infections observed Two treatment discontinuations unrelated to dr
Slide 28: Promising ANX005 Phase 2 Results Support Continued Advancement in HD
Promising ANX005 Phase 2 Results Support Continued Advancement in Huntington’s Disease Full C1q target engagement in blood and CSF into follow-up period Stabilized disease progression in full cohort over 9-month study Rapid clinical improvement maintained in patients with higher baseline complement
Slide 29: ANX005 for ALS: Inhibiting Upstream to Stop Neuroinflammation & Synaptic Loss
A fatal neurodegenerative disorder, characterized by loss of upper (central) and lower (peripheral) motor neurons C1q binds to synapses, and amplifies complement-mediated synaptic loss and disability ANX005 demonstrated target engagement in central and peripheral nervous systems (HD & GBS) Amyotroph
Slide 30: ANX005 Phase 2a ALS Trial Ongoing; Data Anticipated in 2023
Trial Design Specifications ANX005 Phase 2a ALS Trial Ongoing; Data Anticipated in 2023 Open label trial (N= ~24) Target patients: Targeting all forms of ALS, onset of weakness within 3 years prior to enrollment, ALSFRS-R ≥ 30 Objective endpoints: Safety, PK, C1q target engagement, and NfL concentra
Slide 31: ANX007 for Ophthalmologic Diseases: Geographic Atrophy (GA)
ANX007 for Ophthalmologic Diseases Geographic Atrophy (GA)
Slide 32: ANX007 Designed to Fully Inhibit Complement Activation in Neurodegenerative Diseases of the Eye
ANX007 Designed to Fully Inhibit Complement Activation in Neurodegenerative Diseases of the Eye ANX007 ANX007 Therapeutic Approach Fab formulated for intravitreal administration Localized inhibition of C1q and the classical cascade in neurodegenerative diseases of the eye Administered to >200 patien
Slide 33: ANX007 for GA: C1q Inhibition Blocks All Downstream Tissue Damage
Data from ongoing Phase 2 trial anticipated in 1H 2023 ANX007 for GA C1q Inhibition Blocks All Downstream Tissue Damage ANX007 Therapeutic Approach GA is a leading cause of blindness1 Potential for enhanced efficacy by blocking upstream C1q and C4, and downstream C4, C3 and C5 activities that drive
Slide 34: ANX007 Phase 2 Trial in GA Ongoing; Data Anticipated in 1H 2023
ANX007 Phase 2 Trial in GA Ongoing; Data Anticipated in 1H 2023 OPTHAMOLOGY Sham once monthly (n=~45) ANX007 5.0 mg/eye once monthly (n=~90) 12-month Treatment Period Specifications Randomized, double-masked trial (N=~270) Primary endpoint: Change in area of geographic atrophy on fundus autofluoresc
Slide 35: ANX009 Subcutaneous for Autoimmune Diseases
ANX009 Subcutaneous for Autoimmune Diseases Lupus Nephritis (LN) and additional disorders
Slide 36: ANX009 Selectively Inhibits Complement Activation Only in Vascular Space
ANX009 Selectively Inhibits Complement Activation Only in Vascular Space ANX009 ANX009 Therapeutic Approach Subcutaneous formulation of an antigen-binding fragment (Fab) Selectively inhibits C1q in the vascular space Well-tolerated in Phase 1 trial, twice weekly dosing provided sustained C1q inhibit
Slide 37: ANX009 for Lupus Nephritis: Selectively Inhibiting C1q
ANX009 for Lupus Nephritis (LN) Selectively Inhibiting C1q to Stop Complement-Mediated Disease High baseline complement activity correlated with disease activity ANX009 Inhibits Serum C1q in Ph 1 Study Lupus Nephritis (LN) Overview1 Autoantibodies against C1q enhance its activity and uniquely amplif
Slide 38: ANX009 Phase 1b Trial in Lupus Nephritis Ongoing
Trial Design Specifications ANX009 Phase 1b Trial in Lupus Nephritis Ongoing; Initial Data Anticipated in 2H 2022 Target patients: Classical complement activity, smoldering disease, proteinuria, stable background therapy Objective endpoints: Safety and tolerability, complement PD markers, explorator
Slide 39: Looking Ahead: 2022 Priorities
LOOKING AHEAD 2022 Priorities
Slide 40: Robust Preclinical Pipeline with Two Named Candidates: ANX105 and ANX1502
ANX105 (IV) ANX1502 (oral) Whole antibody: Modified for enhanced systemic dosing Intravenous administration Chronic autoimmune and neurological disorders Small molecule: Novel oral inhibitor of classical cascade Oral administration Peripheral autoimmune indications Platform Wide range of additional
Slide 41: Five Key Clinical Priorities Driving Activities Through 2022
Engage with US and EU regulators to discuss well-controlled study of ANX005 in HD, leveraging precision medicine approach Expect to report Ph2 data from ANX005 trial in wAIHA in 2H22 Expect to report initial Ph1b data from ANX009 trial in LN in 2H22 Prepare for multiple 2023 clinical readouts in GA,