Annexon, Inc. · NASDAQ:ANNX

Annexon — 2021 Peripheral Nerve Society (PNS) Annual Meeting

17 slides from Annexon's conference presentation, September 2021

  1. Slide 1: 2021 PNS Annual Meeting

    2021 PNS ANNUAL MEETING Virtually Anywhere

  2. Slide 2: Intravenous Administration of ANX005 Reduced CSF Antibody-Driven Complement Activity in GBS

    Intravenous Administration of ANX005, an Anti-C1q Therapy, Reduced CSF Antibody-Driven Complement Activity in Early-Stage Guillain-Barré Syndrome Poojan Suri, Sethu Sankaranarayanan, Ellen Cahir-McFarland, Henk-André Kroon, Zhahirul Islam and Ted Yednock

  3. Slide 3: Forward-Looking Statements

    Forward-Looking Statements This presentation and accompanying oral presentation contain “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 the res

  4. Slide 4: Guillain-Barré Syndrome (GBS)

    Guillain-Barré Syndrome (GBS) Intact nerve GM1-ganglioside • Acute antibody-mediated autoimmune disease myelin to muscle • Rapidly progressive muscle weakness, impaired axon mobility, respiratory distress Nerve impulse • Autoantibodies (IgM, IgG, IgA) target an array of GBS C1q gangliosides on perip

  5. Slide 5: Increased Blood-CSF Permeability in GBS Associated with Increased IgG and IgM in CSF

    Increased Blood-CSF Permeability in GBS Associated with Increased IgG and IgM Antibody Levels in the CSF Average Albumin Quotient = 60 36x increase in IgG 96x increase in IgM CSF IgG CSF IgM Albumin Quotient p=0.06 10000 p=0.02 1000 1000 p=0.006 Albumin ratio (x1000) CSF IgG(ug/mL) CSF IgM (ug/mL) 1

  6. Slide 6: Annexon Phase 1b Study Design

    Annexon Phase 1b Study Design Annexon GBS Phase 1b study (top-line results presented 2020 PNS meeting) • 38 patients treated with ANX005 (anti-C1q) • 12 placebo patients DAY 0 DAY 1 DAY 2 DAY 3 DAY 4 DAY 5 DAY 6 DAY 7 DAY 8 Single dose ANX005 or placebo 2nd CSF sample (post treatment) Between days 5

  7. Slide 7: Significant Elevation of Complement Proteins & Activation Fragments in CSF of GBS Patients

    Significant Elevation of 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 ug/mL ug/mL 1 0.1 0.1 BS 0.01 Control GBS 0.01 Control GBS Was found to correlate with blood-CSF barrier C3 C3a permeability 100

  8. Slide 8: GBS Patients Had Elevated Levels of IgM and IgG Anti-GM1 Antibodies in CSF

    GBS Patients Had Elevated Levels of Both IgM and IgG Anti-GM1* Antibodies in Their CSF Results consistent with published serum results from lipid arrays CSF Antibodies against GM1 IgG1/IgG3 IgM 50 50 GM1 specific antibodies 11/50 (22%) patients Signal fold increase Signal fold increase 40 40 (3 IgG,

  9. Slide 9: Ability of Anti-GM1 Antibodies in CSF to Activate Complement in Ex Vivo Assay

    Evaluated Ability of Anti-GM1 Antibodies within CSF to Activate Complement in an Ex Vivo Assay (Endogenous / No Additional Complement) Focused on the 11 patients with GM1 reactivity C4 and C3 specific activation ratios: Diluted CSF sample added to GM1 coated plate Positive signal / signal with class

  10. Slide 10: CSF Anti-GM1 Mediated Complement Activation Not Observed in Controls or Antibody-Negative Patients

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

  11. Slide 11: All Anti-GM1+ CSF Samples Showed Complement Deposition

    All Anti-GM1+ CSF Samples Showed Complement Deposition 100 Pre-treatment samples C4 deposition 10 1 0.1 0.25 1 4 16 64 C3 deposition 11

  12. Slide 12: Complement Deposition was Lowered in Patients Treated with ANX005

    Complement Deposition was Lowered in Patients Treated with ANX005 100 Pre-treatment samples C4 deposition 10 1 Samples after ANX005 dosing 0.1 0.25 1 4 16 64 C3 deposition 12

  13. Slide 13: Inhibition of Complement Activity Consistent with Full C1q Target Engagement 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 13

  14. Slide 14: Patients with Anti-GM1 IgG & IgM Have Most Robust C3 and C4 Deposition

    Patients with a Combination of Anti-GM1 IgG & IgM Have the Most Robust C3 and C4 Deposition 100 IgG C4 deposition 10 IgM IgG & IgM 1 0.1 0.25 1 4 16 64 C3 deposition 14

  15. Slide 15: Patients with Anti-GM1 Antibodies in CSF Also Had GM1-Specific Antibodies in Plasma

    Patients with Anti-GM1 Antibodies in Their CSF also Had GM1-Specific Antibodies in Their Plasma* 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

  16. Slide 16: 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 • CSF from these patients triggered complement deposition specifically on GM1-coated plates – highest in those with both IgM and IgG

  17. Slide 17: Thank You

    Thank You 2021 PNS ANNUAL MEETING

Annexon — 2021 Peripheral Nerve Society (PNS) Annual Meeting on 6ix