Keros Therapeutics, Inc. · NASDAQ:KROS

Keros Therapeutics — Technical Presentation (March 2021)

13 slides from Keros Therapeutics's technical presentation, March 2021

  1. Slide 1: KER-050 induces red blood cell production by promoting multiple stages of erythroid differentiation

    KER-050, a novel inhibitor of TGFβ superfamily signaling, induces red blood cell production by promoting multiple stages of erythroid differentiation Marina Feigenson, Remya Nathan, Chris M Materna, Alana Gudelsky, Evan Lema, Claire C Tseng, ffolliott M7Fisher, March 2021| JasbirCONFIDENTIAL Seehra,

  2. Slide 2: Disclosures of Commercial Support

    DISCLOSURES OF COMMERCIAL SUPPORT Name of Research Employee Consultant Stockholder Speaker’s Scientific Other Company support Bureau Advisory Board Keros Therapeutics Marina Feigenson Keros Therapeutics Remya Nathan Keros Therapeutics Chris M Materna Keros Therapeutics Alana Gudelsky Keros Therapeut

  3. Slide 3: Introduction

    Introduction • Diseases such as myelodysplastic syndrome (MDS) and myelofibrosis (MF) are characterized by ineffective hematopoiesis, which can result in one or multiple cytopenias. • Current treatment options to address anemia in these diseases target discreet stages in erythropoiesis, whereas defe

  4. Slide 4: Methods

    Methods • Eleven-week-old mice were treated with a single intraperitoneal injection of 10 mg/kg dose of the research form of KER-050 (RKER-050). • Changes in hematological parameters in peripheral blood and in erythroid progenitors in bone marrow were measured at multiple time points from 12 hours t

  5. Slide 5: A single dose of RKER-050 resulted in rapid and sustained increases in hematological parameters

    A single dose of RKER-050 resulted in rapid and sustained increases in hematological parameters 12 hours post-dose Day 7 post-dose Day 14 post-dose Reticulocyte Red Blood Cells Hemoglobin Reticulocytes Red Blood Cells Hemoglobin Reticulocytes Red Blood Cells Hemoglobin ✱ ✱ ns ✱✱ ✱✱ 15 ✱✱ ✱✱ 500 15 ✱

  6. Slide 6: RKER-050 accelerated maturation of late-stage erythrocyte precursors and outflux of reticulocytes

    RKER-050 accelerated maturation of late-stage erythrocyte precursors and outflux of reticulocytes into circulation EryC A B Nucleated cells ✱✱ ✱✱✱✱ 10 1.5 Treatment with RKER-050: % DRAQ5 positive cells A) Led to increases in late orthochromatic (of live cells) % of live cells 1.0 8 erythroblasts (E

  7. Slide 7: RKER-050 increased early-stage precursors and numbers of cells progressing through erythropoiesis

    RKER-050 increased early-stage precursors and numbers of cells progressing through erythropoiesis CFU-E Day 2 – RKER-050 increased early-stage progenitor cells Day 2 CFU-E Day 4 Day 7 CFU-E CFU-E 500 400 500 400 300 400 BFU-E CFU-E Pro-E Baso-E Poly-E Ortho-E RET RBCs #colonies # colonies 300 # colo

  8. Slide 8: Erythropoietic tone is upregulated days after a single RKER-050 injection

    Erythropoietic tone is upregulated 14 days after a single RKER-050 injection BFU-E CFU-E ProE EryA EryB EryC ✱✱✱ ✱✱ ✱✱✱✱ ✱ ✱ 80 600 4 1.5 15 1.0 0.8 % of Live Cells % of Live Cells % of Live Cells % of Live Cells 70 3 # colonies # colonies 400 1.0 10 0.6 60 2 0.4 200 0.5 5 50 1 0.2 40 0 0 0.0 0 0.0

  9. Slide 9: RKER-050 treatment resulted in increase in circulating erythropoietin levels

    RKER-050 treatment resulted in increase in circulating erythropoietin levels even in the context of increased RBCs EPO RBC 15 15 15 • RKER-050-treated mice exhibited increases in RBCs RBC[% change compared to vehicle] [fold change compared to vehicle] and EPO levels increased by 2-fold starting at d

  10. Slide 10: A single dose of RKER-050 resulted in a long-lasting effect on erythropoiesis

    A single dose of RKER-050 resulted in a long-lasting effect on erythropoiesis Erythropoietin Red Blood Cells Hemoglobin 6 15 15 RBC[% change compared to vehicle] HGB [ % change compared to vehicle] [fold change compared to vehicle] 10 4 10 Erythropoietin 5 1.5 2 5 1.0 0.5 0.0 0 0 0 5 10 15 30 40 50

  11. Slide 11: Conclusions

    Conclusions • Our results suggest that the combination of RKER-050 effects on erythropoiesis potentially contributes to a rapid increase in RBCs and a continuous supply of progenitors that allows for sustained upregulation of erythropoiesis. • The ability of KER-050 to potentially target multiple st

  12. Slide 12: KER-050 exhibited robust effect on erythropoiesis in healthy human volunteers

    KER-050 exhibited robust effect on erythropoiesis in healthy human volunteers Reticulocytes Red Blood Cells Hemoglobin Mean Change from Baseline Mean Change from Baseline Mean Change from Baseline Reticulocytes (109/L) RBCs cells (109/L) HGB(g/dL) • Rapid increase in reticulocytes potentially indica

  13. Slide 13: KER-050 is currently in Phase 2 clinical trial in MDS, Phase 2 in MF to start in 2021

    KER-050 is currently in Phase 2 clinical trial in MDS, and Phase 2 trial in MF is scheduled to start in 2021

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