Annexon, Inc. · NASDAQ:ANNX

Annexon — Technical Presentation (March 2022)

15 slides from Annexon's technical presentation, Mar 24, 2022

  1. Slide 1: Anti-C1q Therapy ANX005 Inhibits CSF Antibody-Driven Complement Activity in Early Stage GBS

    Anti-C1q Therapy ANX005 Inhibits CSF Antibody-Driven Complement Activity Elevated in Early Stage Guillain-Barré Syndrome Poojan Suri1, Sethu Sankaranarayanan1, Ellen Cahir-McFarland1, Henk-André Kroon1, Zhahirul Islam2, Ted Yednock1 1Annexon Biosciences, South San Francisco, CA, USA; 2International

  2. Slide 2: Guillain-Barré Syndrome (GBS)

    Guillain-Barré Syndrome (GBS) Intact nerve • Acute antibody-mediated autoimmune disease GM1-ganglioside • Rapidly progressive muscle weakness, myelin impaired mobility, respiratory distress axon to muscle nerve impulse • Auto-antibodies (IgM, IgG, IgA) target an array GBS of gangliosides on peripher

  3. Slide 3: Increased Blood-CSF Permeability in GBS Associated With Increased IgG and IgM Antibody Levels in CSF

    Increased Blood-CSF Permeability in GBS Associated With Increased IgG and IgM Antibody Levels in CSF Average Albumin Quotient = 60 36× increase in IgG 96× increase in IgM CSF IgG CSF IgM Albumin Quotient (x1000) p=0.06 10000 p=0.02 1000 1000 p=0.006 ratio (x1000) CSF IgM (µg/mL) CSF IgG (µg/mL) CSF

  4. Slide 4: Annexon Phase 1b Study Design

    Annexon Phase 1b Study Design Annexon GBS Phase 1b study • 38 patients treated with ANX005 (anti-C1q) • 12 placebo-treated patients DAY 0 DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DAY 8 Single dose of ANX005 or placebo 2nd CSF sample (post-treatment) Between days 5 - 8 1st CSF sample (pre-treatment)

  5. Slide 5: Significant Elevation in Complement Proteins & Activation Fragments in CSF of GBS Patients vs Controls

    Significant Elevation in Complement Proteins & Activation Fragments in CSF of GBS Patients vs Controls Annexon Phase 1b Study Free C1q Total C1q 09 100 0.11 10 0.003 10 1 µg/mL µg/mL ug/mL ug/mL 1 0.1 0.1 0.01 0.01 BS Control GBS Control GBS • Was found to correlate with blood-CSF barrier permeabili

  6. Slide 6: Patients with GBS Had Elevated Levels of Both IgM and IgG Anti-GM1a Antibodies in Their CSF

    Patients with GBS Had Elevated Levels of Both IgM and IgG Anti-GM1a Antibodies in Their CSF Findings consistent with published serum results from lipid arrays CSF Antibodies Against GM1 IgG1/IgG3 IgM 50 50 GM1-specific antibodies Signal fold increase Signal fold increase 40 40 • 11/50 (22%) patients

  7. Slide 7: Evaluated Ability of Anti-GM1 Antibodies Within CSF to Activate Complement on GM1-coated Plates

    Evaluated Ability of Anti-GM1 Antibodies Within CSF to Activate Complement on GM1-coated Plates in an Ex Vivo Assay Relies on endogenous complement components within CSF (no added complement) • Focused on the 11 patients with measurable anti-GM1 Complement antibodies in CSF Complement components act

  8. Slide 8: CSF Anti-GM1–Mediated Complement Activation Not Observed in Healthy Controls or Anti-GM1-negative Patients

    CSF Anti-GM1–Mediated Complement Activation is Not Observed in Healthy Controls or GBS Patients Lacking Anti-GM1 Autoantibodies 100 C4 deposition 10 Healthy Controls Anti-GM1–negative patients 1 0.1 0.25 1 4 16 64 C3 deposition

  9. Slide 9: All Anti-GM1+ CSF Samples Showed Complement Deposition

    All Anti-GM1+ CSF Samples Showed Complement Deposition 100 Pre-treatment C4 deposition samples 10 1 0.1 0.25 1 4 16 64 C3 deposition

  10. Slide 10: Complement Deposition was Lowered in Patients With Systemic ANX005 Treatment

    Complement Deposition was Lowered in Patients With Systemic ANX005 Treatment 100 Pre-treatment C4 deposition samples 10 1 Samples after ANX005 dosing 0.1 0.25 1 4 16 64 C3 deposition

  11. Slide 11: Inhibition of Complement Activity Consistent With Full C1q Target Engagement Observed in CSF

    Inhibition of Complement Activity Consistent With Full C1q Target Engagement Observed in CSF C1q fully inhibited with ANX005 treatment Levels of Free-C1q in CSF 10000 CSF C1q-Free (ng/mL) C1q fully engaged post- ANX005 treatment 1000 100 Predose Placebo ANX005 Post-treatment

  12. Slide 12: Patients With a Combination of Anti-GM1 IgG & IgM had the Most Robust C3 and C4 Deposition

    Patients With a Combination of Anti-GM1 IgG & IgM had the Most Robust C3 and C4 Deposition 100 IgG IgM IgG & IgM C4 deposition 10 1 0.1 0.25 1 4 16 64 C3 deposition

  13. Slide 13: Patients with Anti-GM1 Antibodies in Their CSF also had GM1-Specific Antibodies in Their Plasma

    Patients with Anti-GM1 Antibodies in Their CSF also had GM1-Specific Antibodies in Their Plasmaa Anti-GM1 IgM levels better reflect the time course of the disease, while anti-GM1 IgG levels persisted longer Anti-GM1 IgM measurements Anti-GM1 IgG measurements 1500000 2000000 700000 600000 1000000 Cou

  14. Slide 14: Conclusions

    Conclusions • IgM and/or IgG antibodies against GM1 were observed in the CSF of 22% of patients but not in controls – consistent with increased blood-CSF permeability • Note: This work focused on GM1 as a representative antigen in GBS – antibodies against other antigens will be present in this subse

  15. Slide 15: Thank You

    Thank You

Annexon — Technical Presentation (March 2022) on 6ix