Gyre Therapeutics, Inc. · NASDAQ:GYRE

Gyre Therapeutics — Technical Presentation (September 2021)

14 slides from Gyre Therapeutics's technical presentation, Sep 9, 2021

  1. Slide 1: Complement Factor I (CFI) as a protease medicine: engineered new therapeutics for complement-mediated disorders

    Complement Factor I (CFI) as a protease medicine: engineered new therapeutics for complement-mediated disorders Natacha Le Moan, Ph.D. | Executive Director 9 September 2021

  2. Slide 2: Forward-looking statements

    Forward-looking statements Certain information contained in this presentation and statements made orally during this presentation include forward-looking statements that involve substantial risks and uncertainties. All statements included in this presentation, other than statements of historical fac

  3. Slide 3: Catalyst discovery platform of proteases

    Catalyst discovery platform of proteases Unique design of optimized & differentiated protease candidates Natural Structure Guided Design – Molecular evolution protease Modulate biological activation or inactivation Pharmacokinetic Improvement Optimized protease candidate 3

  4. Slide 4: Therapeutic advantage of proteases in regulating biological cascades

    Therapeutic advantage of proteases in regulating biological cascades Protease Therapeutic neutralization of target Efficient regulation at low concentrations of therapeutic protease Antibodies Requires high concentrations in excess of the target Small molecules / peptides Requires high concentration

  5. Slide 5: C3b-C4b degraders – unique approach to complement regulation

    C3b-C4b degraders – unique approach to complement regulation Cascade initiation Cascade regulation Terminal complement C4b Degraders C3b Degraders degradation C2 CFI C1r Classical C4b C3a C1s C4 Immune response inflammation Lectin MASP C3 C5 C5a C3 Alternate FB FD C3b C5b (H2O) Membrane attack CFI c

  6. Slide 6: Dialing catalytic power & specificity into Complement Factor I (CFI)

    Dialing catalytic power & specificity into Complement Factor I (CFI) Engineering C3b & C4b degraders from CFI Complement Factor I Catalytic Activity Precision CFI Therapeutics Tunable potency to C3b/C4b control dysregulated Specificity complement Tunable specificity Desired Functionality toward C3b

  7. Slide 7: Using ProTUNE engineering platform to tune specificity

    Using ProTUNE™ engineering platform to tune C3b & C4b degraders Classical-Lectin pathway specific regulators Engineering specificity Dual regulators Fold change in activity against C4b Alternative pathway specific regulators ProTUNETM platform allows precision medicine Fold change in activity agains

  8. Slide 8: Screening strategy for complement therapeutics

    Screening strategy for complement therapeutics In vitro assays and in vivo models are used to evaluate C3b & C4b degraders ~1200 variants ~30 variants ~10 variants ongoing + In vitro cleavage of C3b & + Hemolysis + In vivo activity in + In vivo activity in C4b fragments by ELISA inhibition acute rod

  9. Slide 9: Using ProTUNE Platform to tune C3b & C4b cleaving capabilities

    Using ProTUNETM Platform to tune C3b & C4b cleaving capabilities Rational Design Dual degrader: High cleavage activity of C3b High cleavage activity of C4b Exclusive degrader: High cleavage activity of C4b CFI base scaffold 9

  10. Slide 10: Using ProTUNE Platform to tune C3b & C4b cleaving capabilities

    Using ProTUNETM Platform to tune C3b & C4b cleaving capabilities Reduction of hemolysis Rational Design EC50= 77 nM EC50= 41 nM EC50= 15 nM EC50= 5.8 nM EC50= 15.6 nM EC50= 1.8 nM 10

  11. Slide 11: Degraders significantly reduce inflammation in vivo

    C3b & C4b degraders significantly reduce inflammation in vivo Rat model of complement Inflammatory markers in Concomitant reduction of inflammatory activation IgA nephropathy markers and complement C3 cleavage % C3b formation IFNγ (pg/mL) % C3b formation TNF⍺ (pg/mL) Reduction of IFNγ, TNF⍺, & RANTE

  12. Slide 12: C3b & C4b degraders for IgA nephropathy patients

    C3b & C4b degraders for IgA nephropathy patients Dual targeting of alternate & lectin pathways Classical Lectin Alternate Differentiation pathway pathway pathway + Dual targeting mode of action: lectin & C1q MBL C3(H2O) alternate pathways C1r MASPs CFD CFB Rationale for IgA nephropathy C1s Clinicall

  13. Slide 13: C3b & C4b degraders for precision medicine in complement disorders

    C3b & C4b degraders for precision medicine in complement disorders Diseases in which classical, lectin and/or alternative pathways drive pathogenesis Classical / Specific inhibition of complement Alternative Lectin components at different sites of the complement cascade allows a personalized approac

  14. Slide 14: Acknowledgements

    Acknowledgements Catalyst Biosciences Aarhus University Newcastle University IPST Lauren Kelly Emil Oldenburg Thomas Hallam Camille Simard Shyam Rajan Iyer Agnieszka Jendroszek Kevin Marchbank Emilie Dupré Jim McGuire Christine R. Schar Grant E. Blouse Jan K. Jensen 14

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