Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Technical Presentation (December 2020)
10 slides from Keros Therapeutics's technical presentation, December 2020
Slide 1: KER-050 induces red blood cell production by promoting multiple stages of erythroid differentiation
Abstract # 2736 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 M Fisher, Jasbir Seehra, Jennife
Slide 2: Disclosures
Disclosures All authors are employees of and shareholders of Keros Therapeutics, Inc
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
Slide 4: Methods
Methods • Eleven-week-old mice were treated with a 10mg/kg dose of the research form of KER-050 (RKER-050) by a single intraperitoneal injection. • Changes in hematological parameters in peripheral blood and in erythroid progenitors in bone marrow were measured at 12 hours, 2, 7, and 14 days after a
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 500 ✱ ✱ ns ✱✱ ✱✱ 15 ✱✱ ✱✱ 15 ✱
Slide 6: RKER-050 accelerated maturation of late-stage erythrocyte precursors and reticulocyte outflux
RKER-050 accelerated maturation of late-stage erythrocyte precursors and outflux of reticulocytes into circulation Treatment with RKER-050: A Nucleated cells B Immature Reticulocyte C EryC ✱✱ Fraction 0.025 ✱ A) Reduced the number of nucleated erythroid cells in the 10 ✱✱ bone marrow % DRAQ5 positiv
Slide 7: RKER-050 increased early-stage precursors and 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 Day 4 Day 7 500 400 500 400 300 400 BFU-E CFU-E Pro-E Baso-E Poly-E Ortho-E RET RBCs #colonies # colonies 300 # colonies 300 200 200 2
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 70 3 % of Live Cells % of Live Cells % of Live Cells % of Live Cells 400 1.0 10 # colonies # colonies 0.6 60 2 0.4 200 0.5 5 50 1 0.2 40 0 0 0.0 0 0.0
Slide 9: RKER-050 treatment increased circulating erythropoietin levels despite increased RBCs
RKER-050 treatment resulted in increase in circulating erythropoietin levels even in the context of increased RBCs Serum Erythropoietin and RBC Count Serum Erythropoietin and RBC Count 400 Serum Erythropoietin and RBC Count 20 400 20 400 Veh 20 • RKER-050-treated mice exhibited increases in RBCs and
Slide 10: Summary and Conclusions
Summary and Conclusions • Our studies demonstrate that RKER-050 potentially affects erythropoiesis at several stages: • Stimulated terminal maturation of late-stage erythroid precursors and increased the outflux of late-stage reticulocytes into circulation • Expanded the early-stage precursor popula
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