Viridian Therapeutics, Inc. · NASDAQ:VRDN

Viridian Therapeutics — Technical Presentation (July 2023)

12 slides from Viridian Therapeutics's technical presentation, July 2023

  1. Slide 1: END#?07?4

    END#?07?4

  2. Slide 2: VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor in Development for TED

    VRDN-001, a Full Antagonist Antibody to IGF-1 Receptor in Development for Thyroid Eye Disease (TED), Binds to a Distinct Epitope from Teprotumumab Vahe Bedian, Jordan Tsai, Rachel Newell, Yang Zhao OR26-02 Viridian Therapeutics Inc., Waltham, MA

  3. Slide 3: Disclosures

    Disclosures • This study was sponsored by Viridian Therapeutics Inc. VRDN-001 is an investigational therapy not approved in any country. All authors met the ICMJE authorship criteria and had full access to relevant data. • The authors would like to thank the study investigators and research teams wh

  4. Slide 4: TED: Stimulation of TSHR/IGF-1R signaling complex results in inflammation and tissue expansion

    TED: Stimulation of TSHR/IGF -1R signaling complex results in inflammation and tissue expansion in the fixed bony orbit

  5. Slide 5: Study rationale

    Study rationale • VRDN-001 and teprotumumab are both high-affinity, IGF-1R antagonist antibodies • Teprotumumab is FDA-approved for the treatment of TED; VRDN- 001 is in clinical development for the treatment of TED. • VRDN-001 and teprotumumab have overlapping epitopes by surface plasmon resonance

  6. Slide 6: Epitope analysis

    Epitope analysis Human IGF-1R ECD • To assess differences in binding, 3 N- L1 terminal truncations (L1, L1+CR, CR L1+CR+L2) and 40 point mutants of human IGF-1R were generated: alpha L2 − All residues at or near the IGF-1 binding site and all human/rodent differences were included in mutated sites •

  7. Slide 7: Teprotumumab and VRDN-001 are sensitive to the same IGF-1R domain deletions

    Teprotumumab and VRDN-001 are sensitive to the same IGF-1R domain deletions Impact on VRDN-001 binding Impact on teprotumumab binding CR IGF-1 I285 CR IGF-1 For both antibodies, L286 deletion of L1 domain L1 L1 (pink) reduced binding, CR’ CR’ while deletion of both L1 L1’ L1’ domain and CR domain PD

  8. Slide 8: Teprotumumab and VRDN-001 have distinct receptor interactions

    Teprotumumab and VRDN-001 have distinct receptor interactions • Mutation in 2 adjacent residues involved 0.6 Teprotumumab WT (Binding strength) I285A 0.4 L286A in teprotumumab binding: Δλ (nm) − I285A reduced binding (lower association and 0.2 faster dissociation) 0 − L286A abrogated binding 0 100 2

  9. Slide 9: Analysis of antagonist properties

    Analysis of antagonist properties Three assays were used to assess antagonist properties: 1. Inhibition of ligand binding to IGF-1R on FreeStyle™ 293-F Cells 2. Inhibition of IGF-1 mediated IGF-1R phosphorylation in human ocular choroidal fibroblasts (HOCFs) 3. Inhibition of IGF-1 mediated AKT phosp

  10. Slide 10: Inhibition of ligand binding

    Inhibition of ligand binding 30 nM biotinylated IGF-1 binding to FreeStyle™ 293-F Cells 30 nM Biotin-huIGF-1 • VRDN-001 gives near 50000 complete inhibition of IGF-1 Mean Fluorescence Intensity VRDN-001 40000 binding at ≥50 nM. Teprotumumab No Ab 30000 • Teprotumumab inhibition 20000 does not exceed

  11. Slide 11: Functional antagonism

    Functional antagonism Inhibition of IGF-1R Phosphorylation Inhibition of AKT Phosphorylation (proximal signaling) (distal signaling) • VRDN-001 provides more complete inhibition of IGF-1–induced IGF-1R and AKT phosphorylation in the dose range tested.

  12. Slide 12: Conclusions

    Conclusions • VRDN-001 and teprotumumab have overlapping but distinct epitopes. • Differences in binding correlate with differences in antagonist characteristics. − VRDN-001 inhibits ligand binding and IGF-1 mediated signaling more completely than teprotumumab in the dose ranges tested • VRDN-001’s

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