Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (January 2024)
49 slides from Keros Therapeutics's investor presentation, Jan 3, 2024
Slide 1: January 2024 Corporate Presentation
January 2024 Corporate Presentation
Slide 2: Forward-looking statements
Corporate Presentation 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," "intends," “
Slide 3: Focused on Transforming the Lives of Patients with Dysfunctional TGF-β Signaling
KER-065 therapeutic protein P R E C L I N I C A L Corporate Presentation 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 benefits of
Slide 4: Hematology Franchise
B Hematology Franchise Corporate Presentation 4
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 (elritercept) in Myelodysplastic Syndromes
B KER-050 (elritercept) 6 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 Corporate Presentation
Slide 7: Myelodysplastic Syndromes (MDS)
BCorporate Presentation 7 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 leu
Slide 8: Current Treatment Landscape for Anemia in Lower-Risk MDS
Corporate Presentation 8 Current Treatment Landscape for Treatment of Anemia in Lower- Risk MDS 1. Femaix P, et al. New Eng J Med 2020; 382:140-151; 2. Lspatercept FDA review document Page 11 4/3/2020. Red Blood Cell (RBC) Transfusions ▸ ESAs are currently first line treatment of choice but response
Slide 9: Ongoing Phase 2 Trial of KER-050 in MDS
BCorporate Presentation 9 Data are presented as of a data cutoff date of September 1, 2023. *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
Slide 10: KER-050 was Generally Well-tolerated
B 10Corporate Presentation 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) 3 treatme
Slide 11: Hematologic Responses Observed in Broad Array of Patients
B 11Corporate Presentation 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 (30) T
Slide 12: Higher Response Rates in Patients with Baseline EPO <500 U/L
B 12Corporate Presentation 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 acro
Slide 13: Observed Rates of TI for ≥24 Weeks Support Durability
B TI ≥ 8 wks TI ≥ 12 w ks TI ≥ 16 w ks TI ≥ 24 w ks TI ≥ 8 wks TI ≥ 12 w ks TI ≥ 16 w ks TI ≥ 24 w ks 0 10 20 30 40 50 39 35 31 27 45 40 37 34 Pe rc en t o f P ar tic ip an ts 13Corporate Presentation Observed Rates of TI for ≥24 Weeks Support Durability of Response with KER-050 Treatment TI ≥ 8 wks
Slide 14: Durable TI Responses Observed with KER-050
B 14Corporate Presentation 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 ba bi lit y of M ai nt ai ni ng T I Duration of TI Response Number at Risk 18 18 18 15 14 13 13 9 7 7 7 6 6 6
Slide 15: Improvements in FACIT-Fatigue Scores in TI Responders
B 15Corporate Presentation 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 FA CI T- F T ot al S co re C ha ng e (m ea n ± SE M ) TI ≥ 24 weeks Responder Non Responder 0 4 8 12 16 20 24 -10 -5 0 5
Slide 16: 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 17: Summary of KER-050 in MDS
B 17Corporate Presentation 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 profile
Slide 18: KER-050 (elritercept) in Myelofibrosis
B KER-050 (elritercept) 18 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 Participants with Myelofibrosis Corporate
Slide 19: Myelofibrosis (MF)
Corporate Presentation 19 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 20: Ongoing Phase 2 Trial of KER-050 in MF
B 20Corporate Presentation Ongoing Phase 2 Clinical Trial to Evaluate KER-050 as Monotherapy or in Combination with Ruxolitinib in Patients with MF RESTORE Baseline Demographics RESTORE Baseline Biomarkers of Erythropoiesis Data are presented as of a data cutoff date of September 14, 2023. Following
Slide 21: KER-050 Generally Well-Tolerated in Patients with Significant Disease Burden
B 21Corporate Presentation 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 dose Level
Slide 22: Preliminary Data Address Multiple Aspects of MF
B 22Corporate Presentation 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 • Maintenance or
Slide 23: Pulmonary & Cardiovascular Franchise
Pulmonary & Cardiovascular Franchise Corporate Presentation 23
Slide 24: KER-012 in Pulmonary Arterial Hypertension and Cardiovascular Disorders
KER-012 Corporate Presentation 24 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 KER-012 in Combination with Background Therapy in
Slide 25: KER-012 Modified Activin Receptor IIB Ligand Trap
Corporate Presentation 25 KER-012 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 26: 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 KER-012 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 Pulmonary A
Slide 27: PAH Preclinical and Phase 1 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 28: KER-012 Altered Expression of Serum Proteins and Lowered NT-proBNP
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 28 KER-012 Altered Expression of Serum Proteins Associated with Inflammation and Ex
Slide 29: TROPOS Trial: Global Phase 2 Trial of KER-012 in PAH
Corporate Presentation 29 TROPOS Trial: Global Phase 2 Clinical Trial of KER-012 in Patients with PAH
Slide 30: Open-Label Biomarker Phase 2 Trial of KER-012
Corporate Presentation 30 Open-Label Biomarker Phase 2 Clinical Trial of KER-012 Ongoing open-label, exploratory Phase 2 clinical trial evaluating KER-012 in adult patients with chronic heart failure with preserved ejection fraction (HFpEF) or with reduced ejection fraction (HFrEF) The primary objec
Slide 31: Obesity & Neuromuscular Franchise
Obesity & Neuromuscular Franchise Corporate Presentation 31
Slide 32: KER-065, a Novel Activin Receptor Ligand Trap
Corporate Presentation 32 KER-065, a 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 mol
Slide 33: KER-065: Neuromuscular Diseases
Corporate Presentation 33 KER-065: Neuromuscular Diseases
Slide 34: Muscle Loss in Neuromuscular Disease and KER-065 Preclinical Data
Corporate Presentation 34 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, r
Slide 35: RKER-065 Led to Higher Utrophin Levels in Mouse Model of DMD
Corporate Presentation 35 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 Muscle lacking dystrophin is easily damaged during the process of contraction Many approaches have been utilized to stabilize the muscle and provide resistance
Slide 36: KER-065: Obesity
Corporate Presentation 36 ▸ We believe 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
Slide 37: Obesity is a Growing Public Health Crisis
Corporate Presentation 37 Obesity is a Growing Public Health Crisis Obesity is a global public health crisis, with over 1.9 billion overweight adults worldwide in 2016, 650 million of which were considered to be obese Obesity increases risk of hypertension, dyslipidemia, type 2 diabetes, certain can
Slide 38: Current GLP-1 RA Treatment Landscape for Obesity
Corporate Presentation 38 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 bett
Slide 39: Rationale for Targeting Activin and Myostatin Signaling in Obesity
Corporate Presentation 39 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
Slide 40: Inhibition of Both Activin A and Myostatin Maximally Increases Skeletal Muscle
Corporate Presentation 40 Inhibition of Both Activin A and Myostatin is 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). https://do
Slide 41: Equivalent Increase in Lean Mass in Obese Mice with RKER-034 and RKER-065
Corporate Presentation 41 Equivalent Increase in Lean Mass Observed in Obese Mice with RKER-034 and RKER-065 P value: *<0.05, **<0.01, *** <0.001, **** <0.0001 qNMR Veh icl e RKER-03 4 RKER-06 5 0 10 20 30 Change in Lean Mass from Baseline Pe rc en t C ha ng e fr om B as el in e (% ) ✱✱✱✱ ✱✱✱✱ ▸ RKE
Slide 42: RKER-034 Preserved Lean Mass in Obese Mice Treated with Semaglutide
Veh icl e / Veh icl e Sem a ( NN) / Veh icl e Sem a ( NN) / RKER-03 4 Veh icl e / RKER-03 4 -10 0 10 20 30 Change in Lean Mass from Baseline as a Percent of Vehicle Pe rc en t o f V eh ic le (% ) ✱✱✱✱ ✱✱✱✱ ✱✱✱✱ Corporate Presentation 42 RKER-034 Preserved Lean Mass in Obese Mice Treated with Semaglu
Slide 43: Treatment Enhanced Fat Loss with Semaglutide
Veh icl e / Veh icl e Sem a ( NN) / Veh icl e Sem a ( NN) / RKER-03 4 Veh icl e / RKER-03 4 -40 -30 -20 -10 0 10 Change in Fat Mass from Baseline as a Percent of Vehicle Pe rc en t o f V eh ic le (% ) ✱✱ Corporate Presentation 43 Treatment Enhanced Fat Loss with Semaglutide ▸ Obese mice on high calo
Slide 44: Summary of Preclinical Studies in Diet Induced Mouse Model of Obesity
Corporate Presentation 44 Summary of Preclinical Studies in the Diet Induced Mouse Model of Obesity Treatment with RKER-065 and RKER-034 showed similar increases in skeletal muscle As a single treatment, both RKER-065 and RKER-034 increased lean (muscle) mass and reduced fat mass Combination treatme
Slide 45: KER-065 Phase 1 Clinical Trial in Healthy Volunteers
Corporate Presentation 45 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 p
Slide 46: KER-065 Phase 1 Trial Design
Corporate Presentation 46 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 Objectiv
Slide 47: Proprietary Discovery Approach
Corporate Presentation 47 Proprietary Discovery Approach
Slide 48: Proprietary Discovery Approach
Corporate Presentation 48 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
Slide 49: Anticipated Key Milestones
Corporate Presentation 49 KER-050 ▸Engage with regulators on design of Phase 3 MDS trial H1 2024 ▸Announce additional data from Part 2 of Phase 2 MDS trial Q2 & Q4 2024 ▸Announce additional data from Phase 2 MF trial Q2 & Q4 2024 KER-012 ▸Provide update on enrollment of Phase 2 PAH TROPOS trial H1 2
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