Annexon, Inc. · NASDAQ:ANNX
Annexon — Technical Presentation (February 2024)
23 slides from Annexon's technical presentation, Feb 3, 2024
Slide 1: Efficacy and Safety of Intravitreal Injections of ANX007 in Geographic Atrophy: ARCHER Results
Efficacy and Safety of Intravitreal Injections of ANX007 in Patients With Geographic Atrophy: Results of the ARCHER Study Jeffrey Heier, Charles Wykoff, Glenn Jaffe, David Lally, Roger A. Goldberg, Allen Hu, Carl Regillo, David Boyer, Karl Csaky, Wendy Murahashi, Harman Hansra, Scott Borland, Lori T
Slide 2: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 3: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 4: Anti-C1q: A Unique Neuroprotective Mechanism
Anti-C1q: A Unique Neuroprotective Mechanism C1q initiates classical complement cascade to drive photoreceptor synapse & cell loss and neuroinflammation • C1q is a key driver of neurodegeneration1 C1q binds stressed photoreceptor synapses and activates the classical pathway • C1q anchors classical p
Slide 5: Photoreceptor Cells, Synapses & Function Are Lost Prior to RPE in GA
Photoreceptor Cells, Synapses & Function Are Lost Prior to RPE in GA Blocking C1q protects photoreceptor cells and function upstream of RPE loss Healthy Human Retina (top) • Uniform layer of photoreceptor synapses (red) and photoreceptor neurons (blue) GA Patient Retina (Bottom) Healthy Healthy huma
Slide 6: Anti-C1q Protected Photoreceptor Cells and Their Function in Damage Models
Anti-C1q Protected Photoreceptor Cells and Their Function in Models of Photoreceptor Damage C1q Deposition on Photoreceptor Cells Anti-C1q Protected Photoreceptors and Function and Synapses with Light-Induced Damage ANTI-C1Q PROTECTED 3 DAYS POST WHITE PHOTORECEPTOR CELLS/ PROTECTED RETINAL CONTROL
Slide 7: ANX007: Differentiated Inhibitor of C1q and Classical Complement to Treat GA
ANX007: Differentiated Inhibitor of C1q and Classical Complement to Treat GA Specificity • Full target engagement/inhibition Dosing of classical • 5 mg/100 microliter complement pathway • PK in patient aqueous • Lectin and alternative Profile pathways in place for humor supports • 50kD Fab antibody
Slide 8: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 9: ARCHER: Phase 2 Trial ANX007 in GA
ARCHER: Phase 2 Trial ANX007 in GA Randomized, double-masked Included foveal and non-foveal lesions Stratified for lesion location and lesion size 12 months (n=270) Sham ANX007 ANX007 monthly or every other month 5mg monthly (EM) 5mg every other month (EOM) (n=89) (n=89) (n=92) PRIMARY BIOMARKER E
Slide 10: ANX007 Did Not Significantly Reduce Lesion Area, a Surrogate Biomarker
ANX007 Did Not Significantly Reduce Lesion Area, a Surrogate Biomarker of Functional Change in GA GA LESION AREA CHANGE FROM BASELINE TO MONTH 12# 2.5 LS Mean （±SE）Change 2.0 GA Area Change from Baseline from Baseline, mm2 Sham (n=89) at 12 Months 1.5 ANX007 EM (n=89) Arm mm2 % p-value ANX007 EOM (n
Slide 11: ANX007 Effect on Lesion Growth Improves with Longer Treatment
ANX007 Effect on Lesion Growth Improves with Longer Treatment CHANGE IN LESION GROWTH OVER TIME# 5 +4.1% Growth Compared to Sham % Difference in Lesion 0 -1.0% EM (n=89) EOM (n=92) -5 -5.6% -10 -10.5% -15 0 to 6 Months 6 to 12 Months #The least-square (LS) mean and its standard error (SE) are based
Slide 12: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 13: ANX007 Demonstrated Statistically Significant Protection From Vision Loss by BCVA
ANX007 Demonstrated Statistically Significant Protection From Vision Loss as Measured by BCVA ≥15-Letter Loss PATIENTS WITH PERSISTENT BCVA ≥15-LETTER LOSS THROUGH MONTH 12# 25 21.3% 5.6% 10.9% 8.3% 20 • First known significant preservation of % Patients 15 vision in GA 10 * • Dose-dependent respons
Slide 14: Significant, Time-Dependent Protection From ≥15 Letter Vision Loss
Significant, Time-Dependent Protection From ≥15 Letter Vision Loss with ANX007 Monthly Treatment BCVA ≥15-LETTER LOSS AT 2 CONSECUTIVE VISITS THROUGH MONTH 12 OR LAST VISIT 100% % Patients without ≥15 Letter BCVA Loss 95% EM (n=89) 72% Risk Reduction ANX007 EM 90% HR (CI) = 0.28 (0.11 to 0.76) p = 0
Slide 15: BCVA ≥15-Letter Loss Accelerates After Cessation of Treatment
BCVA ≥15-Letter Loss Accelerates After Cessation of Treatment Visual Function Loss Parallels Sham in Off-Treatment Period % PATIENTS WITH ANY BCVA ≥15-LETTER LOSS FROM BASELINE 30 Off Treatment • Low frequency (<10% per Sham Pooled (n=89) timepoint) of single BCVA 25 ANX007 EOM (n=92) ANX007 EM (n=8
Slide 16: Prespecified Secondary Analyses: Protection on LLVA & LLVD
Prespecified Secondary Analyses: ANX007 Provided Consistent Protection from Vision Loss on Additional Measures—LLVA & LLVD LLVA ≥15-LETTER LOSS THROUGH MONTH 12# LLVD ≥15-LETTER WORSENING THROUGH MONTH 12# 25 30 20.3% 10.1% 11.8% 25.5% 9.4% 16.4% 20 20 % Patients % Patients 15 10 10 * 5 16/79 8/79 1
Slide 17: ANX007 Protection from Vision Loss Consistent Across Baseline Characteristics
ANX007 Protection from Vision Loss Consistent Across Baseline Characteristics HAZARD RATIO (ANX007 EM) HAZARD RATIO (ANX007 EOM) OVERALL adj. for baseline BCVA BCVA Baseline BCVA < 55 letters Baseline BCVA ≥ 55 letters adj. for baseline LLVD LLVD Baseline LLVD < 30 letters Baseline LLVD ≥ 30 letters
Slide 18: ANX007 BCVA Subgroup Analysis: Foveal and Non-Foveal Patients
ANX007 BCVA Subgroup Analysis: Protection from Vision Loss in Foveal and Non-Foveal Patients PATIENTS WITH PERSISTENT ≥15-LETTER LOSS THROUGH MONTH 12# 30 25.0% 5.9% 18.4% 17.8% 5.3% 2.3% Sham EM 20 EOM % Patients Nominal summary p- 10 value vs. sham^ EM 0.0019 11/44 3/51 9/49 8/45 2/38 1/43 EOM 0.0
Slide 19: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 20: ANX007 Generally Well-Tolerated
ANX007 Generally Well-Tolerated ADVERSE EVENTS OF SPECIAL INTEREST SHAM ANX007 EM ANX007 EOM n (%) (N=89) (N=89) (N=92) 3 4 4 Choroidal Neovascularization (3.4%) (4.5%) (4.3%) 1 2 Endophthalmitis 0 (1.1%) (2.2%) INTRAOCULAR INFLAMMATION DETAILS* n 1^ Iritis – 1 Retinal Vascular Occlusion 0 0 (1.1%)
Slide 21: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v
Slide 22: ANX007 Global GA Pivotal Program to begin Mid-2024
ANX007 Global GA Pivotal Program to begin Mid-2024 Replicate ARCHER and support global approvals PRIME Designation ARCHER II TRIAL Primary analysis: Treatment masked from EMA 12 months through 24 months** Sham Study* ANX007 Monthly (n = ~200) Sham (n = ~200) Primary Endpoint Persistent ≥15-Letter BC
Slide 23: Key Takeaways
Key Takeaways ANX007 has a unique neuroprotective mechanism of action targeting the C1q pathway In the Phase 2 ARCHER study, while the primary endpoint of GA reduction was not met, GA area reduction was trending over time Treatment with ANX007 resulted in consistent, dose dependent protection from v