Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — 65th Annual Congress of the American Society of Hematology 2023
33 slides from Keros Therapeutics's conference presentation, Dec 11, 2023
Slide 1: Hematology Franchise: Update at 65th Annual Congress of the American Society of Hematology
Hematology Franchise: Update at 65th Annual Congress of the American Society of Hematology December 2023
Slide 2: Forward-Looking Statements
Hematology Franchise Update 2 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," "intend
Slide 3: Focused on Transforming the Lives of Patients with Disorders Linked to Dysfunctional TGF-β Signaling
KER-065 therapeutic protein P R E C L I N I C A L Hematology Franchise Update 3 Focused on Transforming the Lives of a Wide Range of Patients with Disorders Linked to Dysfunctional TGF-β Superfamily Signaling We believe our product candidates have the potential to unlock the full therapeutic benefit
Slide 4: Clinical and Preclinical Presentations at ASH
B 4Hematology Franchise Update Clinical Presentations • “Durable Clinical Benefit with KER-050 treatment: Findings From an Ongoing Phase 2 Study in participants with Lower-Risk MDS” – Publication Number: 196 • “KER-050 Treatment Reduced Iron Overload and Increased Bone Specific Alkaline Phosphatase
Slide 5: Imbalanced TGF-β Signaling in Bone Marrow Results in Ineffective Hematopoiesis
B Imbalanced TGF-β Signaling in Bone Marrow Results in Ineffective Hematopoiesis and Poor Outcomes in Both MDS and MF1,2,3 Inhibition of Activin A may restore effective hematopoiesis and improve outcomes Poor Outcomes 1. Verma A, et al. J Clin Inv 2020; 2. Portale F, et al., Haematologica. 2019, 3.
Slide 6: KER-050 Designed to Target Bone Marrow Disorders of Ineffective Hematopoiesis
KER-050 is Designed to Target Bone Marrow Disorders of Ineffective Hematopoiesis Including MDS and MF Domain Effect Erythropoiesis ALL stages of differentiation and maturation Thrombopoiesis ALL stages of differentiation and maturation Bone Increased bone formation Iron Metabolism Improved iron util
Slide 7: KER-050 (Elritercept) in Myelodysplastic Syndromes
B KER-050 (Elritercept) 7 Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelodysplastic Syndromes Ongoing Phase 2 Clinical Trial of KER-050 for the Treatment of Anemia in Patients with Very Low-, Low- or Intermediate-Risk Myelodysplastic Syndromes Hematology Franchise Up
Slide 8: Myelodysplastic Syndromes (MDS)
BHematology Franchise Update 8 MDS MDS is a collection of bone marrow disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Clinical Consequences The clinical consequences of MDS include anemia, bleeding, iron overload, cardiovascular disease and progression to acute myeloi
Slide 9: Current Treatment Landscape for Anemia in Lower Risk MDS
Hematology Franchise Update 9 Current Treatment Landscape for Treatment of Anemia in Lower Risk MDS 1. Femaix P, et al. New Eng J Med 2020; 382:140-151 RBC Transfusions • ESAs are currently first line treatment of choice but response is limited in patients with endogenous erythropoietin levels (>200
Slide 10: Ongoing Phase 2 Clinical Trial of KER-050 in MDS
BHematology Franchise Update 10 Data are presented as of a data cutoff date of September 1, 2023. RP2D = Recommended Part 2 Dose; CMML: chronic myelomonocytic leukemia; high transfusion burden (HTB): ≥4 units of RBC/8 weeks for hemoglobin (Hgb) ≤9 g/dL; low transfusion burden (LTB): 1-3 units of RBC
Slide 11: Trial Enrolled Hard-to-Treat Patients with High Disease Burden
B 11Hematology Franchise Update Trial Enrolled Hard-to-Treat Patients with High Disease Burden Data are presented as of a data cutoff date of September 1, 2023. *9 RP2D patients had missing baseline EPO; **Excludes 22 RP2D participants with unknown dysplasia category EPO= erythropoietin, SLD = singl
Slide 12: KER-050 was Generally Well-tolerated
B 12Hematology Franchise Update KER-050 was Generally Well-tolerated • Most frequent TEAEs (≥ in 15% of patients) regardless of causality were: ▸Dyspnea or diarrhea (18; 22.8% each) ▸Fatigue (16; 20.3%) ▸Nausea (15; 19.0%) ▸Headache (12; 15.2%) • Most TEAEs were mild (Grade 1) to moderate (Grade 2)
Slide 13: KER-050 Treatment Led to Sustained Increases in Hemoglobin
B Data are presented as of a data cutoff date of September 1, 2023. Hgb=hemoglobin; sTfR=soluble transferrin receptor 13Hematology Franchise Update KER-050 Treatment Led to Sustained Increases in Hemoglobin Observed Change in HgB, sTfR, and Ferritin Number of Patients • Durable increases in hemoglob
Slide 14: KER-050 Led to Decreased Iron Overload Regardless of Transfusion Burden
B Data are presented as of a data cutoff date of September 1, 2023. Hgb=hemoglobin; sTfR=soluble transferrin receptor 14Hematology Franchise Update Treatment of KER-050 Led to Decreased Iron Overload Regardless of Transfusion Burden in Exploratory Analysis Observed Change in Serum Ferritin by Baseli
Slide 15: Potential of KER-050 to Restore Osteohematopoietic Environment
B Data are presented as of a data cutoff date of September 1, 2023. 1. Moses B, et al. ASH 2022; OHN=osteohematopoietic niche 15Hematology Franchise Update Potential of KER-050 to Restore Osteohematopoietic Environment in Exploratory Analysis • In MDS, disrupted crosstalk between hematopoietic stem
Slide 16: Hematologic Responses Observed in Broad Array of Patients
B 16Hematology Franchise Update Hematologic Responses Observed in Broad Array of Patients Treated with KER-050 Responders/N (%) mITT24 All (N=60) HTB (N=33) Overall Responsea,b 30/60 (50) 15/33 (45.5) Modified IWG 2006 HI-Ec 28/60 (47) 15/33 (45.5) RS+ 23/40 (58) 12/23 (52.2) non-RS 5/20 (25) 3/10 (
Slide 17: Higher Response Rates in Patients with Baseline EPO <500 U/L
B 17Hematology Franchise Update Higher Hematologic Response Rates Observed in Patients with Baseline EPO <500 U/L • Studies in mainly LR-MDS patients suggest that the majority (~90%) of patients have serum EPO levels < 500 U/L1 • EPO levels ≥500 U/L are associated with lower erythroid response rates
Slide 18: Observed Rates of TI for ≥24 Weeks Support Durability
B TI ≥ 8 w ks TI ≥ 1 2 w ks TI ≥ 1 6 w ks TI ≥ 2 4 w ks TI ≥ 8 w ks TI ≥ 1 2 w ks TI ≥ 1 6 w ks TI ≥ 2 4 w ks 0 10 20 30 40 50 39 35 31 27 45 40 37 34 P e rc e n t o f P a rt ic ip a n ts 18Hematology Franchise Update Observed Rates of TI for ≥24 Weeks Support Durability of Response with KER-050 Tre
Slide 19: Durable TI Responses Observed with KER-050 Treatment
B 19Hematology Franchise Update Durable TI Responses Observed with KER-050 Treatment 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96100 0.0 0.2 0.4 0.6 0.8 1.0 Weeks P ro b a b il it y o f M a in ta in in g T I Duration of TI Response Number at Risk 18 18 18 15 14 13 13 9 7 7
Slide 20: Improvements in FACIT-Fatigue Scores in TI Responders
B 20Hematology Franchise Update Durable and Clinically Meaningful Improvements in FACIT-Fatigue Scores were Observed in TI Responders to KER-050 0 4 8 12 16 20 24 -10 -5 0 5 10 15 Week F A C IT - F T o ta l S c o re C h a n g e ( m e a n ± S E M ) TI ≥ 24 weeks Responder Non Responder 0 4 8 12 16 20
Slide 21: Potential of KER-050 to Reduce Cardiac Stress
B Data are presented as of a data cutoff date of September 1, 2023. 1. Madry et al, Br J Haematol 2022; 2. Oliva E, et al. Am J Blood Res 2011; 3. Gatterman N Int J Hematol 2018; 4. Yndestad A J Appl Physiol. (2009) 106:1356–64; 5. Liu H et al Arteriosclerosis,Thrombosis, and Vascular Biology. 2023;
Slide 22: Summary of KER-050 in MDS
B 22Hematology Franchise Update Summary of KER-050 in MDS • In the ongoing Phase 2 clinical trial of KER-050 in LR-MDS, the majority of patients enrolled had HTB or MLD indicating a difficult-to-treat trial population • KER-050 was generally well-tolerated as of the data cut-off date, with a safety
Slide 23: KER-050 (Elritercept) in Myelofibrosis
B KER-050 (Elritercept) 23 Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelofibrosis Ongoing Phase 2 Open-Label Clinical Trial to Evaluate the Safety and Efficacy of KER-050 as Monotherapy or in Combination with Ruxolitinib in patients with Myelofibrosis Hematology Fra
Slide 24: Myelofibrosis (MF)
Hematology Franchise Update 24 Myelofibrosis MF MF is a rare cancer of the bone marrow in which the marrow is replaced by scar tissue and is not able to produce healthy blood cells Current Treatments Currently, there are limited therapeutic options to address the MF-associated cytopenias. Patients n
Slide 25: Ongoing Phase 2 Trial of KER-050 in MF with or without Ruxolitinib
BHematology Franchise Update 25 Primary Objective: ▸ Part 1: Assess safety and tolerability of KER-050 ▸ Part 2: Confirm safety and tolerability of the dose(s) selected from Part 1 Secondary Endpoints include: ▸ Evaluate the pharmacokinetics, pharmacodynamics and efficacy of KER-050 administered wit
Slide 26: Baseline Characteristics RESTORE
B • Patients with high disease burden and severe erythropoietic dysfunction • Most receiving transfusions • 37% TD (IWG 2013 criteria; ≥6 RBC units/12 weeks) • Transfusions prevalent even among NTD (median: 3 RBC units/12 weeks) • Most had splenomegaly • Marked splenomegaly observed in the KER-050+R
Slide 27: KER-050 Generally Well-Tolerated in Patients with Significant Disease Burden
B 27Hematology Franchise Update KER-050 Was Generally Well-Tolerated in Patients with Significant Disease Burden • TEAEs mild to moderate • Treatment-related TEAEs relatively infrequent • Two had Grade 3 or higher worsening cytopenias • One Dose Limiting Toxicity in Part 1 • Increased Hgb ≥2 g/dL in
Slide 28: KER-050 Treatment Led to Sustained Increases in Hemoglobin
B 28Hematology Franchise Update KER-050 Treatment Led to Sustained Increases in Hemoglobin • Biomarkers of erythropoiesis assessed in NTD RESTORE patients • Sustained increases in Hgb observed over first 12 weeks of KER-050 treatment in both monotherapy and combination arms • Observed increases in s
Slide 29: Robust Increases in Hemoglobin and Reduction in Transfusion Burden in MF
B 29Hematology Franchise Update Treatment with KER-050 Led to Robust Increases in Hemoglobin and Reduction in Transfusion Burden in MF Patients • Hemoglobin assessed in NTD RESTORE patients: • Observed increases in Hgb in monotherapy arm suggests potential for KER-050 to address anemia due to underl
Slide 30: Preliminary Data Support Potential to Address Multiple Aspects of MF
B 30Hematology Franchise Update Preliminary Data Support Potential for KER-050 to Address Multiple Aspects of MF Hematopoiesis Spleen Size Symptoms • Observed increases in markers of erythropoiesis • Mean increases in hemoglobin and reduction in transfusion burden observed over 12 weeks • Maintenanc
Slide 31: Summary of KER-050 in Myelofibrosis
B 31Hematology Franchise Update Summary of KER-050 in Myelofibrosis • KER-050 was generally well-tolerated in RESTORE Part 1 as of the data cutoff date, including patients with high disease burden and complex comorbidities • Safety review committee approved RP2D of KER-050 consistent with dose selec
Slide 32: Summary and Next Steps
B •KER-050 is a novel ligand trap designed to inhibit select TGF-beta ligands, including Activin A, which has been associated with driving disease pathogenesis and progression •Data presented at ASH from the Phase 2 trials in MDS and MF support the potential of KER-050 to ameliorate ineffective hema
Slide 33: Q&A
Q&A
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