Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (November 2020)
27 slides from Keros Therapeutics's investor presentation, Nov 10, 2020
Slide 1: Corporate Presentation November 2020
Corporate Presentation November 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 marketed products, Infuse (BMP2) for spinal fusion and Reblozyl® (modified activin receptor IIB) for treatment o
Slide 4: Keros is 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* Initiated Phase 2 Initial data: Myelodysplastic syndromes (MDS) clinical trial mid-2021 KER-050 (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 MDS patients in U.S.* • 15,000-20,000 newly diagnosed MDS patients in U.S.
Slide 7: 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 of precursor cells • 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
Slide 8: Treatment with RKER-050 Increased Erythropoiesis in Mice
Treatment with RKER-50 Increased Erythropoiesis by Potentially Promoting Maturation at Multiple Stages and Increased Serum Erythropoietin • In a preclinical study conducted in mice, a single, subcutaneous 10 mg/kg dose of a mouse version of KER-050 (RKER-050) resulted in: • Rapid increase in RBCs •
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 to evaluate changes in PD (hematology and bone biomarkers) • Observed that KER-050 drug levels were dose proportional in Part 1 of th
Slide 10: KER-050 Phase 1 Clinical Trial Recapitulated Learnings from Preclinical Studies
KER-050 Phase 1 Clinical Trial Recapitulated Learnings from Preclinical Studies • Single, subcutaneous administration of KER-050 in healthy volunteers • Observed rapid increase in red blood cell parameters is supportive of acceleration of maturation of late-stage precursors • Reticulocytes, red bloo
Slide 11: KER-050 Treatment Led 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 cells/L 40 9 30 x 109 cells/L SEM) 20 20 x 109 cells/L ± 0 (Mean (Mean Placebo 0.05 mg/kg -20 0.5 mg/kg Change in Platelets 10 X in
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: Initiated a Phase 2 Trial of KER-050 in MDS
Initiated a Phase 2 Trial of KER-050 in MDS 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 2 • 12-week treatme
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 resulting from iron imbalance • Iron deficiency anemia • IRIDA • 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 homeostasis • Excessive ALK2 signaling results in high hepcidin and a shortage of iron availability for RBC production • ALK2 signaling requires BMP ligand and the co
Slide 18: Keros ALK2 Inhibitors Shown to Resolve Anemia in the Mouse Model of IRIDA
Keros ALK2 Inhibitors Shown to Resolve Anemia in the Mouse Model of IRIDA Mouse IRIDA Model Protocol Timeline • TMPRSS6 encodes MT-2, the protease that suppresses ALK2 signaling • MT-2/TMPRSS6 deficiency results in IRIDA • siRNA knockdown of TMPRSS6 in mice mimics changes seen in human IRIDA Mouse I
Slide 19: KER-047: Expanded Phase 1 Clinical Trial Recapitulated Preclinical Observations
KER-047: Expanded Phase 1 Clinical Trial Recapitulated the Observations from Preclinical Studies • All single ascending and multiple ascending dose cohorts evaluated (including additional cohort) (“expanded trial”) • The objective of the Phase 1 clinical trial was to evaluate the safety, tolerabilit
Slide 20: Phase 2 Trials to Provide Proof-of-Concept for Anemia from Iron Imbalance
Phase 2 Trials to Provide Proof-of-Concept for Treatment of Anemia Resulting from Iron Imbalance, Including IDA and IRIDA Iron Deficiency Anemia IRIDA • KER-047 is designed to re-establish normal iron • KER-047 is designed to normalize high hepcidin homeostasis by mobilizing iron out of tissues, lev
Slide 21: 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 mutat
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 • ActRII program (KER-050) is in a
Slide 26: Anticipated Key Milestones
Anticipated Key Milestones* KER-050 • Present additional preclinical data on mechanism Q4 2020 (ASH 2020) • Announce initial data for Phase 2 trial in MDS Mid-2021 • Initiate Phase 2 trial in myelofibrosis 2021 KER-047 • Present Phase 1 healthy volunteer data Q4 2020 (ASH 2020) • Initiate Phase 2 tr
Slide 27: Thank You
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