Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (June 2020)
27 slides from Keros Therapeutics's investor presentation, Jun 2, 2020
Slide 1: Corporate Presentation June 2020
Corporate Presentation June 2020
Slide 2: Disclaimer
Disclaimer Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as "anticipates," "believes," "expects," "intends," “plans,” “poten
Slide 3: Harnessing the Powerful Biology of the TGF-β Superfamily
Harnessing the Powerful Biology of the TGF-β Superfamily Clinical-stage biopharmaceutical company developing novel therapeutics that target the TGF-β superfamily Approach validated by FDA-approved third-party products derived from native amino acid sequences • Infuse (BMP2) for spinal fusion (Geneti
Slide 4: Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders
Keros is Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders Phase of Development Next Program Asset Preclinical Phase 1 Phase 2 Phase 3 Status Milestones* Initiate Phase 2 Myelodysplastic Syndrome (MDS) clinical trial: KER-050 Completed Phase H2 2020 (therapeuti
Slide 5: KER-050
KER-050 A novel treatment designed to address diseases arising from ineffective hematopoiesis • Myelodysplastic syndromes • Myelofibrosis 5
Slide 6: Myelodysplastic Syndromes (MDS) Overview
Myelodysplastic Syndromes (MDS) Overview Hematologic malignancy predominantly affecting the elderly, resulting in multiple cytopenias (anemia, thrombocytopenia, neutropenia) due to ineffective hematopoiesis 60,000-170,000 Prevalence of MDS patients in US* 15,000-20,000 New MDS patients diagnosed eac
Slide 7: KER-050 Designed to Fill Treatment Gap for Cytopenias in MDS
KER-050 Designed to Fill Treatment Gap for Cytopenias in MDS Anemia treatments Red Blood Cell (RBC) Transfusion • Risk of infection and iron overload ESAs • Low proportion of responders in Aranesp® Phase 3 clinical trials • Benefit limited to patients with low transfusion burden and low endogenous E
Slide 8: KER-050 is a Modified ActRII Fusion Protein
KER-050 is a Modified ActRII Fusion Protein • Activin receptors are expressed on hematopoietic cells and modulate differentiation • KER-050 is a ligand trap composed of a modified extracellular domain of activin receptor IIA (ActRIIA) fused to the Fc region of human IgG • KER-050 is designed to bind
Slide 9: KER-050 Completed First-in-human Trial
KER-050 Completed First-in-human Trial • First-in-human trial was designed to explore the safety, tolerability and PK in healthy volunteers with a secondary objective of changes in PD (hematology and bone biomarkers) • Observed to be well tolerated at dose levels up to 4.5 mg/kg, the highest dose le
Slide 10: KER-050 Leads to Increases in Reticulocytes, Hemoglobin and RBCs after a Single Dose
KER-050 Treatment was Observed to Lead to Robust and Sustained Increases in Reticulocytes, Hemoglobin and RBCs after a Single Dose RETICULOCYTES HEMOGLOBIN RED BLOOD CELLS Mean Change from Baseline Mean Change from Baseline Mean Change from Baseline 3 100 900 /L) 9 75 2 600 Placebo cells/L) 9 0.05 m
Slide 11: KER-050 Leads to Clinically Meaningful Changes in Platelets
KER-050 Treatment was Observed to Lead to Clinically Meaningful Changes in Platelets after a Single Dose Mean Change from Baseline in Platelets at Each Dose 60 cells/L 40 9 30 x 109 cells/L SEM) 20 20 x 109 cells/L ± 0 (Mean Placebo 0.05 mg/kg -20 0.5 mg/kg Change Change in X 10 Platelets 1.5 mg/kg
Slide 12: KER-050 has a Potentially Differentiated Mechanism of Action
KER-050 has a Potentially Differentiated Mechanism of Action • Robust and sustained increases observed in RBCs, hemoglobin and reticulocytes support the potential for administration of monthly or less frequent dosing • Observed sustained response potentially supports the dual mechanism of promoting
Slide 13: Expect to Commence a Phase 2 Trial of KER-050 in MDS
Expect to Commence a Phase 2 Trial of KER-050 in MDS (H2 2020) Part 1: Dose Escalation Part 2: Dose Confirmation • Open label Phase 2 trial in two parts to explore (Open Label) (Open Label) changes in hematology with treatment in patients with MDS Dose 1 • Red blood cell parameters • Platelets Dose
Slide 14: Myelofibrosis (MF) is Characterized by Ineffective Hematopoiesis
Myelofibrosis (MF) is Characterized by Ineffective Hematopoiesis • Molecular abnormalities in JAK-STAT pathway result in expansion of RBC and platelet precursors and subsequent ineffective hematopoiesis 16,000-18,500 • Megakaryocyte accumulation/breakdown is implicated in the inducement of bone Prev
Slide 15: KER-047
KER-047 A novel treatment designed to address • Anemia arising from high hepcidin levels • Fibrodysplasia ossificans progressiva (FOP) 15
Slide 16: KER-047: A Potentially Potent and Selective ALK2 Inhibitor
KER-047: A Potentially Potent and Selective ALK2 Inhibitor • Small-molecule inhibitor of the activin receptor like kinase-2 KER-047 (ALK2) kinase domain • Potency: Low nanomolar IC50 • Selectivity: Highly selective over kinases outside of the TGF- superfamily as well as other, structurally similar
Slide 17: ALK2 Regulates Hepcidin and Iron Homeostasis
ALK2 Regulates Hepcidin and Iron Homeostasis • ALK2 signaling in the liver controls hepcidin expression, a hormone that controls iron transport • Excessive ALK2 signaling results in high hepcidin and a shortage of iron availability for RBC production • ALK2 signaling requires BMP ligand and the co-r
Slide 18: Keros ALK2 Inhibitors Observed to Resolve Anemia in TMPRSS6-Deficient Mice
Keros ALK2 Inhibitors Observed to Resolve Anemia in TMPRSS6- Deficient Mice • TMPRSS6 encodes MT-2, the protease Mouse IRIDA Model Protocol Timeline that suppresses ALK2 signaling • MT-2/TMPRSS6 deficiency results in IRIDA • siRNA knockdown of TMPRSS6 in mice copies human IRIDA patients Mouse IRIDA
Slide 19: ALK2 Mutation is a Driver of FOP
ALK2 Mutation is a Driver of FOP FOP is a rare genetic disease in which muscles and connective tissues transform into bone No cure or effective treatments • Most patients are confined to a wheelchair by third decade of life • Typical life expectancy – 40 years Caused by single amino acid mutations i
Slide 20: KER-047 Exhibited Dose-dependent Efficacy in FOP Mouse Model
KER-047 Exhibited Dose-dependent Efficacy in FOP Mouse Model KER-047 dose-dependently reduced heterotopic ossification in the genetic mouse model of FOP Preclinical studies conducted in young animals demonstrated that ALK2 inhibition did not result in growth plate ablation or synovial joint malforma
Slide 21: Two Phase 2 Trials to Provide Proof-of-Concept for Anemia and FOP
Two Phase 2 Trials to Provide Proof-of-Concept for Anemia Arising from High Hepcidin and FOP • We are conducting a Phase 1 clinical trial to evaluate single and multiple ascending doses of KER-047 in healthy volunteers • The primary objectives of this trial are to assess safety, tolerability and pha
Slide 22: KER-012
KER-012 A preclinical program designed to address • Bone loss disorders such as osteoporosis and osteogenesis imperfecta • Pulmonary arterial hypertension (PAH) 22
Slide 23: KER-012 (Preclinical Product Candidate)
KER-012 (Preclinical Product Candidate) • Proprietary selective activin receptor ligand trap in preclinical development for the treatment of pulmonary arterial hypertension (PAH) and bone disorders • In preclinical studies, KER-012: • Demonstrated high affinity for, and potent inhibition of, ligands
Slide 24: Keros Summary
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Slide 25: We Believe Keros is Positioned for Clinical and Commercial Success
We Believe Keros is Positioned for Clinical and Commercial Success • Keros is focused on the development of novel TGF- therapeutics • Robust biology that has been validated in the clinic • Keros is well-positioned to harness the potential of the TGF- superfamily • Multiple product candidates expec
Slide 26: Anticipated Key Milestones
Anticipated Key Milestones* KER-050 • Present Phase 1 and preclinical data supporting hematopoietic effects EHA25 (June 2020) • Initiate Phase 2 trial in MDS H2 2020 • Initiate Phase 2 trial in myelofibrosis 2021 KER-047 • Present preclinical data demonstrating potential to address anemia EHA25 (Jun
Slide 27: Thank You
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