Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (January 2025)
38 slides from Keros Therapeutics's investor presentation, Jan 10, 2025
Slide 1: January 2025 Corporate Presentation
January 2025 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: Cibotercept (KER-012) Investigational Treatment for 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 5: Cibotercept is an investigational modified activin receptor IIB ligand trap
Corporate Presentation Cibotercept is an investigational 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 (acti
Slide 6: TROPOS Trial: Global Phase 2 Clinical Trial of Cibotercept in Patients with PAH
Corporate Presentation TROPOS Trial: Global Phase 2 Clinical Trial of Cibotercept in Patients with PAH 6 • On December 12, 2024, Keros announced that it voluntarily halted dosing in the 3.0 mg/kg and 4.5 mg/kg treatment arms in the ongoing TROPOS trial, based on a safety review due to the unanticipa
Slide 7: Anticipated TROPOS Readout
Corporate Presentation Anticipated TROPOS Readout: Opportunity for Meaningful Insights to Inform Next Steps in Development Program 7 • Robust set of endpoints, including: • Pulmonary vascular resistance (PVR) • 6-minute walk distance (6MWD) • WHO Functional Class • Safety • Pharmacokinetics • Pharma
Slide 8: Dose Selection for Phase 2 Trial Based on Phase 1 Results
Corporate Presentation 8 • Preclinical safety studies established NOAEL of 50 mg/kg dosed every two weeks1 • Keros completed a Phase 1 randomized, double-blind, placebo-controlled, two-part clinical trial to evaluate single and multiple ascending doses of cibotercept in healthy volunteers. The prima
Slide 9: Cibotercept Designed To Have Reduced BMP Binding
Corporate Presentation 9 Cibotercept Designed To Have Reduced BMP Binding Activin/GDF Ligand Binding BMP Ligand Binding ActRIIA-Fc Cibotercept (Modified ActRIIB-Fc) ActRIIA-Fc Cibotercept (Modified ActRIIB-Fc) Activin A Strong Strong BMP-2 Semi-Weak Weak Activin B Strong Strong BMP-3 Weak Weak Activ
Slide 10: Lack of Observed Perturbation of Retinal Blood Vessels in Newborn Mice
Corporate Presentation Lack of Observed Perturbation of Retinal Blood Vessels of Newborn Mice Treated with RKER-012 Supports Potential for Reduced Bleeding Risk with Cibotercept 10 Healthy mice pups were randomly assigned to one of six groups. Treatments were administered on postnatal day 1 and 3. O
Slide 11: Cibotercept Designed to Lack Effect on Erythropoiesis
Corporate Presentation Cibotercept Designed to Lack Effect on Erythropoiesis 11 • In the Phase 1 healthy volunteer clinical trial, multiple doses of cibotercept did not elicit changes in hemoglobin or red blood cells (RBCs) • The lack of observed effect on erythropoiesis in humans was consistent wit
Slide 12: RKER-012 Reduced Pulmonary Arterial Pressure and Cardiac Fibrosis 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 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 Pulmonary Artery Pressure sP AP (m m Hg ) -27.5% -44.5% ✱ ✱ ✱ ✱ ns ✱ ✱ ns On
Slide 13: KER-065: Neuromuscular Diseases
Corporate Presentation KER-065: Neuromuscular Diseases 13
Slide 14: KER-065: Novel Activin Receptor Ligand Trap for Neuromuscular Disorders
Corporate Presentation KER-065: Novel Activin Receptor Ligand Trap for the Treatment of Neuromuscular Disorders KER-065 is an investigational modified activin receptor IIA (ActRIIA) and activin receptor IIB (ActRIIB) ligand trap ▸ ~50% amino acids derived from each activin receptor KER-065 is design
Slide 15: Chronic degenerative muscle diseases and DMD
Corporate Presentation 15 • Chronic degenerative muscle diseases eventually lead to a collapse in the ability of muscle to regenerate and eventual loss of function • DMD manifests as subtle motor defects postnatally leading to loss of ambulation and eventually death1,2 • In young boys with DMD, musc
Slide 16: Glucocorticoids Increased Negative Regulators of Skeletal Muscle and Bone
Corporate Presentation 16 MDX mice (mouse model of DMD) were treated with vehicle (Veh) or 2-prednisolone (Pred), or cotreated with prednisolone and RKER-065 (Pred-065) (10 mg/kg, twice weekly). The changes in body weight, body composition (NMR), grip strength, skeletal muscle gene expression, and b
Slide 17: RKER-065 Reduced Inflammatory Profile of Muscle Macrophages
Corporate Presentation 17 RKER-065 Reduced the Inflammatory Profile of Muscle Resident Macrophages and Shifted Towards Muscle Repairing Flow Cytometry DBA2J-Veh D2.MDX + Veh D2.MDX + 065 Data is shown as average ± SEM. 2-way ANOVA with repeat measures and Sidak post test. * P≤0.05, ** P<0.01, *** P<
Slide 18: RKER-065 Reduced Fibroblast and Fat Precursor Cells in Dystrophic Mice
Corporate Presentation 18 RKER-065 Reduced the Fibroblast and Fat Precursor Cells in Muscle of Dystrophic Mice DBA2J-Veh D2.MDX + Veh D2.MDX + 065 Data is shown as average ± SEM. 2-way ANOVA with repeat measures and Sidak post test. * P≤0.05, ** P<0.01, *** P<0.001, and **** P< 0.0001. TA = tibialis
Slide 19: Treatment with RKER-065 Increased Satellite Cells in Skeletal Muscle
Corporate Presentation 19 • Wild type mice were treated with a single dose of RKER-065 (10 mg/kg) or vehicle. Muscles were dissected and processed to obtain single cell suspensions on day 1, day 2, and day 4 (n=5, stained for markers of satellite cells (CD31, Sca.1, CD34, α7 integrin, and CD106) and
Slide 20: RKER-065 Increased Utrophin Expression and Muscle Strength in DMD Mouse Model
Corporate Presentation W T- ve h D 2. m dx -v eh D2 .m dx -0 65 Treatment with RKER-065 Increased Utrophin Expression and Muscle Strength 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’
Slide 21: RKER-065 Improved Efficiency of Exon Skipping
Corporate Presentation 21 • Treatment with PMO did not increase lean mass or muscle function • Co-treatment with PMO and RKER-065 improved lean mass and grip strength • RKER-065 treatment improved the efficiency of PMO driven exon skipping RKER-065 Treatment Improved Efficiency of Exon Skipping Lean
Slide 22: 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 is enrolling pat
Slide 23: 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 24: Elritercept (KER-050) Investigational Treatment for MDS and Myelofibrosis
B Elritercept (KER-050) Investigational Treatment for Anemia and Thrombocytopenia in Patients with Myelodysplastic Syndromes and in Patients with Myelofibrosis Corporate Presentation 24
Slide 25: Global License Agreement with Takeda Pharmaceuticals
BCorporate Presentation Global License Agreement with Takeda Pharmaceuticals* 25 On December 3, 2024, Keros announced it had entered into an exclusive license agreement with Takeda to develop, manufacture and commercialize elritercept globally, other than mainland China, Hong Kong, and Macau* Financ
Slide 26: 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 27: Disease Overviews: MDS and MF
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 28: Ongoing Phase 2 Trial of Elritercept in Anemia in MDS
BCorporate Presentation Data are presented as of a data cut-off date of August 30, 2024. *9 RP2D patients had missing baseline erythropoietin (EPO); RP2D = Recommended Part 2 Dose of 3.75 mg/kg with the ability to titrate to 5 mg/kg once every four weeks; CMML: chronic myelomonocytic leukemia; high
Slide 29: Elritercept was Generally Well-Tolerated
B 29Corporate Presentation Elritercept was Generally Well-Tolerated Treatment-related = considered to be related to the study treatment by the treating investigator. Data are presented as of a data cut-off date of August 30, 2024. AML = acute myeloid leukemia; COPD = chronic obstructive pulmonary di
Slide 30: Robust Responses Observed in a Broad Range of Patients
B 30Corporate 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 August 30, 2024. a. Includes data for weeks 0-24 in mITT24 patients; b. Includes data for Weeks 0-24 in mITT24 patients with
Slide 31: Durable TI Responses Observed with Elritercept Treatment
B 31Corporate Presentation Durable TI Responses Observed with Elritercept Treatment Data are presented as of a data cut-off date of August 30, 2024. *RBC transfusions for elective surgery and intercurrent disease (i.e. bleeding events) were recorded but were not counted towards baseline requirement
Slide 32: Sustained Improvements in FACIT-Fatigue Scores
B 32Corporate Presentation Sustained and Clinically Meaningful Improvements in FACIT-Fatigue Scores Observed with Elritercept Treatment Health-related quality of life (HRQOL) is negatively impacted by MDS1,2 with fatigue identified as a critically important domain to assess in patients with MDS3 •
Slide 33: Ongoing Phase 2 Trial of Elritercept in Myelofibrosis
BCorporate Presentation 33 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 34: Elritercept Generally Well-Tolerated in Patients with Significant Disease Burden
B 34Corporate Presentation Elritercept Was Generally Well-Tolerated in Patients with Significant Disease Burden Data are presented as of a data cut-off date of August 30, 2024 N/A= not applicable Category Monotherapy (N=29) Combination (N=44) Total (N=73) TEAEs, n (%) 29 (100) 40 (90.9) 69 (94.5) Mo
Slide 35: Data Support Potential for Elritercept to Address Multiple Aspects of MF
B 35Corporate Presentation Data Support Potential for Elritercept to Address Multiple Aspects of MF Hematopoiesis Spleen Size Symptoms • Increases in Hgb were observed in both monotherapy and combination arms • Reductions in transfusion burden observed in both arms further support potential to addre
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 Cibotercept ▸Announce topline data from Phase 2 TROPOS trial Q2 2025 ▸Regulatory interactions and development strategy H2 2025 KER-065 ▸Announce initial data from Phase 1 healthy volunteer trial Q1 2025 ▸Regulatory interactions and development strategy H2 2025 Elritercept ▸Com
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