Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (August 2024)
38 slides from Keros Therapeutics's investor presentation, Aug 7, 2024
Slide 1: August 2024 Corporate Presentation
August 2024 Corporate Presentation
Slide 2: Forward-Looking Statements
Corporate Presentation 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," “pl
Slide 3: Focused on Transforming the Lives of Patients with Dysfunctional TGF-β Signaling
KER-065 P R E C L I N I C A L Corporate Presentation 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 benefits of modulating the TGF-β s
Slide 4: Elritercept (KER-050) in MDS
B Elritercept (KER-050) Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelodysplastic Syndromes Ongoing Phase 2 Clinical Trial of Elritercept for the Treatment of Anemia in Patients with Very Low-, Low- or Intermediate-Risk Myelodysplastic Syndromes Corporate Presentatio
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: Myelodysplastic Syndromes (MDS)
BCorporate Presentation 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 myeloid leuke
Slide 7: Current Landscape for Treatment of Anemia in Lower Risk MDS
Corporate Presentation 7 Current Landscape for Treatment of Anemia in Lower Risk MDS 1. Fenaux P, et al. New Eng J Med 2020; 382:140-151; 2. Luspatercept FDA Summary Basis of Approval Medical Review Page 11 4/3/2020. RBC Transfusions • ESAs are currently first line treatment of choice, but response
Slide 8: Phase 2 Trial of Elritercept in Lower Risk MDS
BCorporate Presentation Data are presented as of a data cut-off date of April 3, 2024. *9 RP2D patients had missing baseline erythropoietin (EPO); **Excludes 22 RP2D participants with unknown dysplasia category RP2D = Recommended Part 2 Dose of 3.75 mg/kg with the ability to titrate to 5 mg/kg once
Slide 9: Elritercept was Generally Well-Tolerated
B 9Corporate Presentation Elritercept was Generally Well-Tolerated • Most frequent TEAEs (≥ in 15% of patients) regardless of causality were: ▸Diarrhea (24; 27.6%) ▸Fatigue (22; 25.3%) ▸Dyspnea (18; 20.7%) ▸Dizziness (17; 19.5%) ▸COVID-19 & Nausea (16, 18.4%) ▸Anemia (15; 17.2%) • Majority of TEAEs
Slide 10: Robust Responses Observed in a Broad Range of Patients
B 10Corporate Presentation Robust Responses Observed in a Broad Range of Patients Including those with High Transfusion Burden Data are presented as of a data cut-off date of April 3, 2024. a. Includes data for weeks 0-24 in mITT24 patients; b. Includes data for Weeks 0-24 in mITT24 patients with ba
Slide 11: Durable TI Responses Observed with Elritercept Treatment
B 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 10 0 10 4 10 8 11 2 11 6 12 0 12 4 12 8 0.0 0.2 0.4 0.6 0.8 1.0 Longest TI interval in mITT24 participants who achieved TI ≥ 8 weeks from baseline through Week 24** TI Duration (Weeks) Pr ob ab ili ty o f M ai nt ai ni ng T I
Slide 12: Improvements in FACIT-Fatigue Score
B 0 4 8 12 16 20 24 -15 -10 -5 0 5 10 15 Change in FACIT-Fatigue Score in TI ≥24 Wk Responders and Non Responders Week TI ≥ 24 Wk Responders TI ≥24 Wk Non-Responders 16 46 13 40 9 20 14 31 13 31 12 25 FA C IT - F at ig ue T ot al S co re C ha ng e (m ea n ± SE M ) 12Corporate Presentation Transfusio
Slide 13: Phase 3 Registrational Trial in MDS
B 13Corporate Presentation Planned Endpoints • Primary Endpoint: TI at 8 weeks within the first 24 weeks • A key secondary outcome will be 24-week TI over 48 weeks Phase 3 Registrational Trial in MDS Received positive feedback from the U.S. Food and Drug Administration (FDA), which resulted in gener
Slide 14: Elritercept in Myelofibrosis
B Elritercept Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelofibrosis Ongoing Phase 2 Open-Label Clinical Trial to Evaluate the Safety and Efficacy of Elritercept as Monotherapy or in Combination with Ruxolitinib in Participants with Myelofibrosis Corporate Presentat
Slide 15: Myelofibrosis (MF)
Corporate Presentation 15 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 not on
Slide 16: Phase 2 Trial of Elritercept in MF
BCorporate Presentation 16 Ongoing Phase 2 Clinical Trial to Evaluate Elritercept as Monotherapy or in Combination with Ruxolitinib in Patients with MF Monotherapy: JAK inhibitor relapsed, refractory, intolerant or ineligible Combination with Ruxolitinib: Prior ruxolitinib treatment ≥ 8 weeks with s
Slide 17: Elritercept Generally Well-Tolerated in Patients with Significant Disease Burden
B 17Corporate Presentation Elritercept Was Generally Well-Tolerated in Patients with Significant Disease Burden Most frequent TEAEs (≥ 15% of patients in both arms) regardless of causality: • Thrombocytopenia (10, 18.5%) • Monotherapy: 7, 30.4% • Combination: 3, 9.7% • Diarrhea (9, 16.7%) • Monthe
Slide 18: Data Support Potential for Elritercept to Address Multiple Aspects of MF
B 18Corporate Presentation Data Support Potential for Elritercept to Address Multiple Aspects of MF Hematopoiesis Spleen Size Symptoms • Observed increases in markers of erythropoiesis were generally greater at higher doses • Increases in Hgb were observed in both monotherapy and combination arms •
Slide 19: Cibotercept (KER-012) in PAH
Cibotercept (KER-012) Corporate Presentation Investigational Treatment for Pulmonary Arterial Hypertension (PAH) and for Cardiovascular Disorders Ongoing Randomized, Phase 2, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Cibotercept in Combination with Backgr
Slide 20: Cibotercept is a Modified Activin Receptor IIB Ligand Trap
Corporate Presentation Cibotercept is a modified activin receptor IIB ligand trap: ▸Designed to rebalance TGF-β superfamily signaling ▸ Being developed for the treatment of pulmonary and cardiovascular disorders, including PAH ▸Designed to preferentially inhibit select ligands (activin A, activin B,
Slide 21: RKER-012 Reduced Pulmonary Arterial Pressure in Rodent PAH Models
1. K. Babbs, et al. Am J Respir Crit Care Med 2022;205:A5776; 2. Babbs K, et al. Am Heart Association Scientific Sessions 2021; RKER-012 = Research form of cibotercept fused with Fc region of murine IgG1 0.0 0.2 0.4 0.6 0.8 Fulton Index R V/ (L V+ S) -15.7% -28.0% ✱ ✱ ✱ ✱ ns ✱ ✱ ns 0 20 40 60 80 100
Slide 22: Cibotercept PAH Preclinical and Phase 2 Data
PAH Domain Preclinical Data Phase 1 Clinical Trial1,2 MOA & Ligand Specificity: • Strong activin/GDF binding observed • Observed to be BMP-sparing vs. ActRIIA-Fc • We believe PD data support potential for maximal target engagement with doses in Phase 2 Fibrosis & Inflammation: Inflammation Fibro
Slide 23: Cibotercept Altered Expression of Serum Proteins
Natarajan H, et al Am J Respir Crit Care Med 2023;207:A1187 Additional exploratory biomarker data demonstrated initial target engagement at 0.75 mg/kg and maximum target engagement at 4.5 mg/kg Corporate Presentation Cibotercept Altered Expression of Serum Proteins Associated with Inflammation and E
Slide 24: TROPOS Trial: Global Phase 2 Trial in PAH
Corporate Presentation TROPOS Trial: Global Phase 2 Clinical Trial of Cibotercept in Patients with PAH 24
Slide 25: KER-065: Obesity & Neuromuscular Diseases
Corporate Presentation ▸ Preclinical data suggests KER-065 has the potential to improve body composition by increasing muscle mass and decreasing fat mass alone or in combination with glucagon-like peptide-1 (GLP-1) receptor agonists ▸ By targeting activin A, KER-065 has the potential to directly re
Slide 26: KER-065: Novel Activin Receptor Ligand Trap
Corporate Presentation KER-065: Novel Activin Receptor Ligand Trap for the Treatment of Obesity and Neuromuscular Disorders Keros’ preclinical library of activin receptor ligand traps contains more than 40 distinct molecules containing sequences from ActRIIA and ActRIIB ▸ KER-065 is the 3rd molecule
Slide 27: Rationale for Targeting Activin and Myostatin Signaling
Corporate Presentation Well-Established Rationale for Targeting Activin and Myostatin Signaling as Treatment for Obesity and Associated Cardiometabolic Disease Muscle Tissue ▸ Inhibition of activin A and myostatin increase muscle hypertrophy and strength Adipose (Fat) Tissue ▸ Activin A, activin B,
Slide 28: Current GLP-1 RA Treatment Landscape for Obesity
Corporate Presentation Current GLP-1 RA Treatment Landscape for Obesity GLP-1 receptor agonists (GLP-1 RAs) have recently been approved for the treatment of obesity ▸ Treatment with GLP-1 RAs led to 15%-21% mean weight loss1,2, reductions in blood lipids, improvements in glycemic control and better
Slide 29: Inhibition of Both Activin A and Myostatin Required to Maximally Increase Muscle
Corporate Presentation Inhibition of Both Activin A and Myostatin Observed to be Required to Maximally Increase Skeletal Muscle in Mice and Monkeys 1. Latres, E., Mastaitis, J., Fury, W. et al. Activin A more prominently regulates muscle mass in primates than does GDF8. Nat Commun 8, 15153 (2017). h
Slide 30: RKER-065 Preserved Lean Mass in Obese Mice Treated with Semaglutide
Corporate Presentation RKER-065 Preserved Lean Mass and Enhanced Fat Loss in Obese Mice Treated with Semaglutide Veh /Veh Sem a/V eh Sem a/0 65 Veh /06 5 -30 -20 -10 0 10 20 Pe rc en t ( % ) ✱✱✱✱ ✱✱ ✱✱✱ Veh /Veh Sem a/V eh Sem a/0 65 Veh /06 5 -5 0 5 10 15 20 Pe rc en t ( % ) ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱✱ Ch
Slide 31: KER-065 Phase 1 Clinical Trial in Healthy Volunteers
Corporate Presentation KER-065 Phase 1 Clinical Trial in Healthy Volunteers Primary objectives of this Phase 1 clinical trial are to evaluate safety, tolerability and pharmacokinetics of single and multiple ascending doses of KER-065 The multiple ascending dose portion of this trial will enroll pati
Slide 32: KER-065 Phase 1 Trial Design
Corporate Presentation KER-065 Phase 1 Trial Design This trial has been designed to enable the evaluation of any treatment-related increases in skeletal muscle, decreases in fat and improvements in bone health. Primary Objective • Evaluate the tolerability and safety of KER-065 Secondary Objective •
Slide 33: KER-065 in Neuromuscular Disease
Corporate Presentation Muscle loss can occur as a consequence of many factors, including neuromuscular disease, disuse, aging and as a side effect of some therapies In neuromuscular diseases, muscle loss can result in muscle weakness and, with increased severity, can lead to loss of ambulation, reli
Slide 34: RKER-065 Led to Higher Utrophin Levels in Mouse Model of DMD
Corporate Presentation W T- ve h D2 .m dx -v eh D2 .m d- 06 5 Treatment with RKER-065 Led to Higher Utrophin Levels in Mouse Model of DMD 1. Nathan, R., et al. 28th International Annual Congress of the World Muscle Society; WT= wild type (control), D2.mdx = mouse model of DMD 34 0 50 100 150 0 50 10
Slide 35: PMO & RKER-065 Combined Treatment Increased Lean Mass and Muscle Function
Corporate Presentation PMO & RKER-065 Combined Treatment Demonstrated Significant Increase in Lean Mass, Muscle Function & Exon Skipping Efficiency 35 Lean Mass Percent Change 4 weeks 8 weeks -10 0 10 20 30 Le an M as s/ B as el in e (% ) ✱✱✱ ✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ Exon Skipping Efficiency
Slide 36: Proprietary Discovery Approach
Corporate Presentation Proprietary Discovery Approach 36
Slide 37: Proprietary Discovery Approach
Corporate Presentation We have developed a proprietary library of ActRII ligand traps by combining sequences from ActRIIA and ActRIIB ▸ We have engineered molecules that are designed to have the therapeutic properties of either or both parent molecules ▸ Our ActRII program has produced a broader pip
Slide 38: Anticipated Key Milestones
Corporate Presentation Elritercept ▸Announce additional data from Part 2 of Phase 2 MDS trial Q4 2024 ▸Announce additional data from Phase 2 MF trial Q4 2024 Cibotercept ▸Complete enrollment in Phase 2 TROPOS Trial Q4 2024 KER-065 ▸Announce data from Phase 1 healthy volunteer trial Q1 2025 Anticipat
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