Annexon, Inc. · NASDAQ:ANNX
Annexon — ASRS 2021
12 slides from Annexon's conference presentation, October 2021
Slide 1: Role of C1q Inhibition in the Treatment of Geographic Atrophy Secondary to AMD
Role of C1q Inhibition in the Treatment of Geographic Atrophy Secondary to Age-related Macular Degeneration Nancy Holekamp, MD Pepose Vision Institute Saint Louis, MO
Slide 2: Disclosures
Disclosures • Nancy M. Holekamp, MD – Consulting fee: Adverum, Allergan, Annexon, Apellis, Bayer, Lineage Cell Therapeutics, Clearside Biosciences, Gemini, Genentech, Gyroscope, Katalyst Surgical, Nacuity, Notal Vision, Novartis, Polyactiva, Regeneron, Stealth Biosciences – Speakers Bureau: Allergan
Slide 3: C1q and Classical Complement Pathway
C1q and Classical Complement Pathway Selective inhibition of C1q shuts down all tissue-damaging components of classical pathway (C4, C3, C5, C9) while allowing immune functions of lectin and alternative complement pathways to continue without disruption Katsche et al. Scientific Reports 2018 Law and
Slide 4: C1q and Classical Cascade are Key Drivers in Geographic Atrophy
C1q and Classical Cascade are Key Drivers in Geographic Atrophy • High local expression of C1q in the retina by infiltrating macrophages – Macrophages in OPL, POS, RPE, choroid express high levels of C1q • C1q activators present in all layers of the outer retina • C1q and downstream activated comple
Slide 5: C1q Accumulates with Age in Geographic Atrophy
C1q Accumulates with Age in Geographic Atrophy C1q accumulation on photoreceptor cell synapses C1q accumulation on drusen in mouse retina in human retina with GA IPL 3-month old 24-month old INL C1q OPL Drusen ONL Data on File, Annexon Biosciences Synapses C1q Nuclei Human retinal micrograph: Jiao,
Slide 6: ANX007 is Designed to Inhibit C1q
ANX007 is Designed to Inhibit C1q • Recombinant humanized antigen binding fragment (Fab) of a monoclonal antibody • Composed of one VH and CH1 segment of an IgG1 heavy chain covalently linked to one kappa light chain • Molecular weight - ~48 kDa • Binds to the complement protein C1q via its antigen
Slide 7: ANX007 Reduces C1q Levels in Retina of Non-Human Primates
ANX007 Reduces C1q Levels in Retina of Non-Human Primates Free ANX007 Free C1q • Optic Nerve • Choroid • Retina • Vitreous Humor • Aqueous Humor Two doses of 5 mg ANX007 administered IVT 28 days apart in cynomolgus monkeys • Day 44 = 15 days post-last dose • Day 59 = 30 days post-last dose Grover A,
Slide 8: Phase 1 Studies in Glaucoma
Phase 1 Studies in Glaucoma Phase 1a 5 mg (Single Injection) (n=3) 100ul IVT SUMMARY 2.5 mg (n=3) 50ul IVT • Repeat doses, in patients with Primary Open- Angle Glaucoma (n=17) 1 mg (n=3) 20ul IVT • Well-tolerated at all dose levels Follow-up through 8 weeks • No SAEs or severe TEAEs • All AEs were m
Slide 9: ANX007 Effectively Inhibits C1q
ANX007 Effectively Inhibits C1qFree C1q in Aq humor (% Day 1 levels) Sham 2.5 mg 5 mg 150 C1q in Aqueous Humor (%Pre-dose levels) 100 50 D1 = Day 1 (before ANX007 dosing) D29 = Day 29 (post-1st dose) 0 D1 D29 D1 D29 D1 D29 Single intravitreal injection inhibited C1q in aqueous humor for at least 29
Slide 10: C1q Inhibition in Vitreous Projected to be Maintained for at Least 2 Months
C1q Inhibition in Vitreous Projected to be Maintained for at Least 2 Months Projected ANX007 PK in human vitreous following a 5 mg dose based on observed data from cynomolgus monkey 10 7 Projected Human 5 mg / eye Vitreous ANX007 (ng/mL) 10 6 Observed Cyno 5 mg / eye Observed Cyno 1 mg / eye 10 5 10
Slide 11: The ARCHER Study: Ongoing Phase 2 Study Evaluating Effect of ANX007
The ARCHER Study: Ongoing Phase 2 Study Evaluating Effect of ANX007 ANX007 5.0 mg Monthly (n=~80) Randomization ANX007 5.0 mg q2 Months (n=~80) Off-treatment follow-up 2:2:1:1 for 6 months Sham Monthly (n=~40) n=~240 Sham q2 Months (n=~40) BSL Treatment Period 12 Months Primary Endpoint Mean change
Slide 12: Summary
Summary • C1q, the initiating molecule of the classical complement cascade, has been implicated in neurodegenerative diseases, including GA • ANX007 is designed to inhibit C1q while allowing immune functions of lectin and alternative complement pathways to continue • IVT ANX007 was well- tolerated i