Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (March 2021)
27 slides from Keros Therapeutics's investor presentation, Mar 25, 2021
Slide 1: March 2021 Corporate Presentation
March 2021 Corporate Presentation
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: Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders
Keros is Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders 4 * Anticipated clinical milestones are subject to the impact of COVID-19 on our business.
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 *MDS Foundation • 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
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: RKER-050 Increased Erythropoiesis and Serum Erythropoietin 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: Phase 1 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: Changes in Platelets after a Single Dose
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 -1 2 4 7 15 21 29 -40 -20 0 20 40 60 Days Post-Dose Placebo 0.05 mg/kg 0.5 mg/kg 1.5 mg/kg 4.5 mg/kg 30 x 109 cells/L 20 x 109 cells/L C h a n
Slide 12: KER-050 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 0.75 mg/kg 1.5 mg/kg Dose 3 Dose 4 Part 1: Dose Escalation (Open Label) Part 2: Dose Confirmation (Open Label) Treatment in Parts 1 and 2: 12 weeks Safety follow up: 12 weeks Dose TBD based on Part 1 • Open label Phase 2 trial in two parts to explore chang
Slide 14: Myelofibrosis (MF) is Characterized by Ineffective Hematopoiesis
Myelofibrosis (MF) is Characterized by Ineffective Hematopoiesis *Gangat 2011;**Srour 2016; ***Naymagon 2017 16,000-18,500 Prevalence of MF patients in US* >3,000 New MF patients diagnosed each year** ~100 % Nearly all MF patients will become transfusion- dependent*** 51% Anemia 38% Transfusion Depe
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 (ALK2) kinase domain • Potency: Low nanomolar IC50 • Selectivity: Highly selective over kinases outside of the TGF- superfamily as well as other, structurally similar TGF- re
Slide 17: 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-receptor hemojuvelin • Hepcidin expression i
Slide 18: ALK2 Inhibitors Resolve Anemia in the Mouse Model of IRIDA
Keros ALK2 Inhibitors Shown to Resolve Anemia in the Mouse Model of IRIDA • 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 patients • Increases hepcidin and reduces h
Slide 19: KER-047: Expanded Phase 1 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 in IDA and IRIDA
Phase 2 Trials to Provide Proof-of-Concept for Treatment of Anemia Resulting from Iron Imbalance, Including IDA and IRIDA • KER-047 is designed to normalize high hepcidin levels, restore serum iron and ameliorate anemia • We expect to initiate a Phase 2 clinical trial in patients with IRIDA in H2 20
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: 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 • Announce initial data from Part 1 of Phase 2 trial in MDS Mid-2021 • Initiate Phase 2 trial in myelofibrosis Mid-2021 (initial data 2022) KER-047 • Initiate Phase 2 trial in IDA H2 2021 (initial data 2022) • Initiate Phase 2 trial in IRIDA H2 2021 (initial data
Slide 27: Thank You
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