Scholar Rock Holding Corporation · NASDAQ:SRRK

Scholar Rock — Technical Presentation (September 2023)

9 slides from Scholar Rock's technical presentation, September 2023

  1. Slide 1: Discovery and Antifibrotic Activity of an Anti-LTBP-TGFβ1 Inhibitory Antibody

    Discovery and Antifibrotic Activity of an Anti-LTBP- TGFβ1 Inhibitory Antibody Poster #77 Justin Jackson Senior Scientist II, Antibody Discovery & Engineering

  2. Slide 2: Disclaimers

    Disclaimers Various statements in this presentation concerning the future expectations, plans and prospects of Scholar Rock, Inc. (“Scholar Rock”), including without limitation, Scholar Rock’s expectations regarding its strategy, its product candidate selection and development timing, including timi

  3. Slide 3: Revolutionary Approach to Regulating TGFβ Superfamily Implicated in Devastating Diseases

    Revolutionary Approach to Regulating TGFβ Superfamily Implicated in Devastating Diseases Scholar Rock’s Target TGFβ Superfamily: Highly Sought-After Targets Latent Growth Factor Recognized by the industry as Dysregulation plays a role in important targets given their devastating diseases that have a

  4. Slide 4: Latent TGFβ1 Forms Covalent, Large Latent Complexes with a Presenting Molecule

    Latent TGFβ1 Forms Covalent, Large Latent Complexes with a Presenting Molecule Matrix-associated TGFβ1 Non-matrix, Immune-associated TGFβ1 Latent TGFβ1 Latent TGFβ1 Latent TGFβ1 Extracellular matrix (ECM) Regulatory Macrophage T cell GARP LRRC33 Latent TGFβ-binding protein (LTBP) LTBP1 and LTBP3 pre

  5. Slide 5: Multiple Rounds of Affinity Maturation were Required to Attain Highly LTBP-TGFβ1 Selective Antibodies

    Multiple Rounds of Affinity Maturation were Required to Attain Highly LTBP- TGFβ1 Selective Antibodies • Poster #77 describes the affinity maturation campaign deployed to engineer LTBP-49247, a pM affinity antibody specific to LTBP complexes of TGFβ1 • Binding measured by a Meso Scale Discovery solu

  6. Slide 6: HDX Informs the Mechanism of LTBP-TGFβ1 Selectivity and Inhibitory Activity

    HDX Informs the Mechanism of LTBP-TGFβ1 Selectivity as Well as The Mechanism of Inhibitory Activity LTBP-49247 potently inhibits integrin-mediated Region 1 is most protected by activation of LTBP-TGFβ1 LTBP-49247 by HDX 125 100 % TGFβ1 activity 75 Parent Antibody 50 Cycle 1 Cycle 2 25 Cycle 3, LTBP-

  7. Slide 7: LTBP-49247 Reduces pSmad2 and Fibrosis in a Mouse Model of Alport Syndrome

    LTBP-49247 Reduces pSmad2 and Fibrosis in a Mouse Model of Alport Syndrome TGFβ Signaling (pSMAD2) Fibrosis (Collagen Content) 15 Het Col4a3 KO 1.0 Het Col4a3 KO %pSMAD2+ Positive Nuclei *** **** *** **** * * ** (% of total protein) Hydroxyproline 10 0.8 0.6 5 0.4 0 mg/kg 30 30 1 3 10 30 mg/kg 30 30

  8. Slide 8: Summary

    Summary • Scholar Rock’s approach of targeting latent growth factors has enabled unprecedented specificity in targeting the TGFβ superfamily • Extensive affinity maturation deployed to engineer LTBP-49247, an antibody that inhibits the activation of LTBP-TGFβ1 • Selective inhibition of matrix-associ

  9. Slide 9: Thank you!

    Thank you! Poster #77 Justin Jackson

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