Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Investor Presentation (August 2022)
47 slides from Keros Therapeutics's investor presentation, Aug 4, 2022
Slide 1: August 2022 Corporate Presentation
August 2022 Corporate Presentation
Slide 2: Disclaimer
Disclaimer Statements contained in this presentation by Keros Therapeutics, Inc. ("Keros", "we" or "our") 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 "anticipat
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 • Leveraging our extensive experience in TGF-β superfamily protein structure, function and protein engineering to generate a clinical pi
Slide 4: Keros is Developing Differentiated Clinical Assets in Hematological, Pulmonary, and Musculoskeletal Disorders
Keros is Developing Differentiated Clinical Assets in Hematological, Pulmonary, and Musculoskeletal Disorders 4 *Anticipated clinical milestones are subject to the impact of COVID-19 on our business. Program Asset Phase of Development Status Next Milestones*Preclinical Phase 1 Phase 2 Phase 3 Hemato
Slide 5: KER-050
KER-050 A novel product candidate designed to address diseases arising from ineffective hematopoiesis • Myelodysplastic syndromes • Myelofibrosis 5
Slide 6: KER-050: A Potential Treatment for Ineffective Hematopoiesis in MDS and MF
KER-050: A Potential Treatment for Ineffective Hematopoiesis in Myelodysplastic Syndromes (MDS) and Myelofibrosis (MF) MDS • Hematologic malignancy predominantly affecting the elderly, resulting in multiple cytopenias (anemia, thrombocytopenia, neutropenia) due to ineffective hematopoiesis • 60,000-
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: KER-050 Increased RBC Parameters and Platelets Following Single Doses in Phase 1
KER-050 Increased RBC Parameters and Platelets Following Single Doses in a Phase 1 Clinical Trial in Healthy Volunteers • Single doses of KER-050 observed to lead to clinically meaningful changes in platelets through day 29 • Maximum changes observed between 7-15 days post-dosing • Observed increase
Slide 9: KER-050 Preclinical Data Support Potential to Promote Multiple Stages of Erythropoiesis
KER-050 Preclinical Data Support Potential to Promote Multiple Stages of Erythropoiesis B as lin e 12 hr 24 hr 0 20 40 60 80 100 120 7d 14 d 28 d 35 d 42 d P e rc e n t o f B a s e li n e L a b e le d C e ll s Vehicle RKER-050 RKER-050 treatment did not alter RBC life span BFU-E CFU-E Pro-E Poly-EBa
Slide 10: RKER-050 Preclinical Data Support Potential to Promote Multiple Stages of Thrombopoiesis
RKER-050 Preclinical Data Support Potential to Promote Multiple Stages of Thrombopoiesis • Observed rapid onset of platelet increase in mouse models is consistent with terminal maturation of proplatelets • Observed increase in the number of CD41+ cells and the polyploid in mouse models is consistent
Slide 11: RKER-050 Increased Platelets Potentially Through Activin A Inhibition
RKER-050 Increased Platelets Potentially Through Activin A Inhibition • Treatment with Activin A inhibited differentiation of platelet production in a preclinical study in mice • Decreased number of polyploid CD41+ cells (megakaryocytes) • In contrast, inhibition of activin A through administration
Slide 12: KER-050 Summary
KER-050 Summary • KER-050 increased RBC parameters and platelets following single doses in a Phase 1 clinical trial in healthy volunteers • In preclinical studies, a research form of KER-050 (RKER-050) was observed to increase RBCs and platelets, potentially through promotion of multiple stages of e
Slide 13: KER050-MD-201 Phase 2 Clinical Trial in MDS
KER050-MD-201 A Phase 2 Clinical Trial Of KER-050 For The Treatment Of Anemia In Patients With Very Low, Low Or Intermediate Risk Myelodysplastic Syndromes (MDS) 13
Slide 14: Phase 2 Clinical Trial of KER-050 in MDS
Phase 2 Clinical Trial of KER-050 in MDS • Phase 2, multicenter, open-label clinical trial in very low-, low- and intermediate-risk MDS patients (LR- MDS) • KER-050 administered once every four weeks (Q4W) • Trial objectives: • Part 1 • Evaluate safety, tolerability and pharmacokinetics • Evaluate p
Slide 15: Phase 2 Clinical Trial of KER-050 in MDS: Key Eligibility Criteria
Phase 2 Clinical Trial of KER-050 in MDS Key Eligibility Criteria: • MDS with very low-, low-, or intermediate-risk disease, as classified by the International Prognostic Scoring System- Revised, including both patients that did not have ring sideroblasts (non-RS) and patients that have ring siderob
Slide 16: Trial Status and Baseline Characteristics
Trial Status and Baseline Characteristics • Data cut-off date: April 3, 2022 • Safety data from Cohorts 1 through 5 (0.75, 1.5, 2.5, 3.75 and 5.0 mg/kg, respectively) • 31 patients in Cohorts 1 through 5 received at least one dose of KER-050 as of the data cut-off date • Efficacy data from Cohorts 1
Slide 17: Safety Data as of the Data Cut-off Date (April 3, 2022)
Safety Data as of the Data Cut-off Date (April 3, 2022) • Safety Review Committee has reviewed data from 0.75 mg/kg (Cohort 1), 1.5 mg/kg (Cohort 2), 2.5 mg/kg (Cohort 3), Cohort 4 (3.75 mg/kg) and Cohort 5 (5.0 mg/kg) • Following recommendation by Safety Review Committee, dosing of participants in
Slide 18: Response Summary
Response Summary Response Rate, n/m (%) All evaluable patients HTB evaluable patients Overall Erythroid Response (HI-E or TI) 14/27 (51.9%) 11/16 (68.8%) IWG 2006 HI-E 12/26 (46.2%) 11/16 (68.8%) Transfusion independence (TI*) RS+ Non-RS 9/20 (45%) 6/12 (50%) 3/8 (37.5%) 7/16 (43.8%) 4/9 (44.4%) 3/7
Slide 19: Treatment with KER-050 Resulted in HI-E and TI in Transfusion-Dependent Patients
Treatment with KER-050 Resulted in HI-E and TI in Transfusion-Dependent Non-RS and RS+ MDS patients Post-Treatment -100 -50 0 T ra n s fu s io n R e d u c ti o n ( % ) Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 2 2 8 13 8 8 4 5 6 5 7 6 4 2 4 2 4 6 4 4 2 2 8 10 6 4 2 2 2 1 1 0 0 0 0 0
Slide 20: Sustained Increase in Platelets Observed in HTB Patients
Sustained Increase in Platelets Observed in HTB Patients Achieving HI-E or TI with KER-050 Treatment 1 15 29 43 57 71 85 99 -25 0 25 50 75 100 PLATELETS (HTB PATIENTS) Study Day C h a n g e f ro m B a s e li n e ( x 1 0 9 /L , ± S E M ) HI-E or TI (N=11) No HI-E or TI (N=5) April 3, 2022 data cutoff
Slide 21: Observed Changes in Hematologic and Ferrokinetic Biomarkers
Observed Changes in Hematologic and Ferrokinetic Biomarkers Support Induction of Erythropoiesis with KER-050 Treatment in all HTB Patients 1 29 57 85 -40 -20 0 20 40 60 SOLUBLE TRANSFERRIN RECEPTOR (sTfR) and FERRITIN (HTB patients) Study Day % c h a n g e f ro m b a s e li n e ( m e a n ± S E M ) F
Slide 22: Summary of KER-050 Phase 2 Clinical Trial
Summary of KER-050 Phase 2 Clinical Trial • LR-MDS patients enrolled in Part 1 of this Phase 2 clinical trial were primarily transfusion-dependent with multilineage dysplasia • 58% of patients were HTB patients with elevated serum ferritin • KER-050 was generally well-tolerated as of data cut-off da
Slide 23: Phase 2 Part 2 Dose Confirmation has been Initiated
Phase 2 Part 2 Dose Confirmation has been Initiated • Dose-related increases in reticulocytes and hemoglobin were observed in this primarily transfusion- dependent trial population • Following recommendation by the Safety Review Committee dosing for Part 2 was initiated in June • Part 2 starting dos
Slide 24: KER050-MF-301 Phase 2 Trial in Myelofibrosis
KER050-MF-301 A Phase 2 Clinical Trial to Evaluate KER- 050 as a Monotherapy or in Combination With Ruxolitinib in Myelofibrosis 24
Slide 25: Phase 2 Clinical Trial of KER-050 in Patients with Myelofibrosis-Associated Cytopenias
Phase 2 Clinical Trial of KER-050 in Patients with Myelofibrosis- Associated Cytopenias • Ongoing open label, two-part, multiple ascending dose Phase 2 clinical trial to evaluate KER-050 as a monotherapy and in combination with ruxolitinib in participants with myelofibrosis-associated cytopenias • P
Slide 26: KER-047
KER-047 A novel product candidate designed to address: • Anemia resulting from iron imbalance • Iron Refractory Iron Deficiency Anemia (IRIDA) • Iron deficiency anemia (IDA) 26
Slide 27: 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 28: Inhibition of ALK2 Demonstrated Activity in Rodent Models of Iron Imbalance
Inhibition of ALK2 Demonstrated Activity in Rodent Models of Iron Imbalance • ALK2 inhibition decreased hepcidin and increased serum iron in mice • In a mouse model of IRIDA, treatment with ALK2 inhibitors reduced hepcidin and ameliorated anemia • In a mouse model of chronic kidney disease, chronic
Slide 29: Phase 1: KER-047 Led to Reduced Hepcidin and Increased Reticulocyte Hemoglobin
• Consistent with ALK2 inhibition, decreases in serum hepcidin were observed in Cohorts 1 through 3 of Part 2 of the expanded trial • Treatment related decreases in hepcidin resulted in increased serum iron Phase 1 Clinical Trial: KER-047 Treatment Led to Reduced Hepcidin Levels and Increased Hemogl
Slide 30: Phase 2 Trials to Provide Proof-of-Concept for Anemia from Iron Imbalance
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 initiated a Phase 2 clinical trial in patients with IRIDA and expect to rep
Slide 31: KER-012
KER-012 A clinical program designed to address: • Pulmonary arterial hypertension (PAH) • Bone loss disorders such as osteoporosis and osteogenesis imperfecta 31
Slide 32: KER-012 is Designed to Address PAH and Bone Disorders
KER-012 is Designed to Address PAH and Bone Disorders • KER-012 is a proprietary, wholly-owned, investigational ligand trap • Modified ActRIIB fused to the Fc region of IgG1 • KER-012 is designed to bind and inhibit activins and SMAD 2/3 signaling • In preclinical studies, a research form of KER-012
Slide 33: RKER-012 Reduced Pulmonary Arterial Pressure and RV Hypertrophy in a Rat PAH Model
RKER-012 Reduced Pulmonary Arterial Pressure and Right Ventricle (RV) Hypertrophy in a Rat PAH Model • Hypoxic rats were dosed with vehicle, ActRIIA-Fc (10 mg/kg) or RKER-012 (10 mg/kg), twice weekly for three weeks • Normoxic rats were dosed with vehicle • Relative to vehicle-treated hypoxic rats,
Slide 34: RKER-012 Prevented Bone Loss in a Rat PAH Model
RKER-012 Prevented Bone Loss in a Rat PAH Model • In a separate preclinical study, RKER-012 demonstrated activity in improving bone mass in the Sugen/hypoxia rat model of PAH • Hypoxic rats were dosed with vehicle or RKER-012 (20 mg/kg), twice weekly for four weeks • Normoxic rats were dosed with ve
Slide 35: KER-012 Phase 1 Clinical Trial in Healthy Post-Menopausal Women
KER-012 Phase 1 Clinical Trial A Randomized, Double-Blind, Placebo Controlled, Two-Part, Dose-Escalation Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Effects of KER-012 in Healthy Post-Menopausal Women 35
Slide 36: Phase 1 Clinical Trial of KER-012 in Healthy Post-Menopausal Women
Phase 1 Clinical Trial of KER-012 in Healthy Post-Menopausal Women Part 1 endpoints: safety, pharmacokinetics (PK) and biomarkers Status: Completed; topline data shared in this presentation Part 2 endpoints: safety, PK, biomarkers and total body scan by dual-energy x-ray absorptiometry (DXA) Status:
Slide 37: Key Inclusion and Exclusion Criteria
Key Inclusion and Exclusion Criteria Inclusion: • Postmenopausal female aged 45 to 70 years (inclusive) at screening • NOTE: Postmenopausal is defined as ≥ 6 months of spontaneous amenorrhea OR 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy • Serum follicle-stimulating horm
Slide 38: Safety, Tolerability and PK (Part 1 SAD)
Safety, Tolerability and PK (Part 1 SAD) • KER-012 was generally well tolerated at doses up to 5 mg/kg when administered as a single dose • There were no serious adverse events observed in Part 1 • The majority of adverse events observed in Part 1 were mild in severity (CTCAE Grade 1) • No clinicall
Slide 39: No Clinically Meaningful Change in Hgb Observed with KER-012
No Clinically Meaningful Change in Hgb Observed with KER-012 Administration of up to 5 mg/kg • Single dose of KER-012 was not associated with clinically meaningful changes in Hgb at all doses in Part 1 of this trial -1.0 -0.5 0.0 0.5 1.0 Hemoglobin (g/dL) Mean Change from Baseline Through D29 H e m
Slide 40: KER-012 Administration Resulted in 40% Mean Decrease in FSH at 5 mg/kg Dose
KER-012 Administration Resulted in 40% Mean Decrease in FSH at 5 mg/kg Dose • As per the study protocol, only participants with baseline FSH >40 IU/L were included in the analysis for the changes in FSH with KER-012 treatment • Some of the participants that met the >40 IU/L criteria for FSH at scree
Slide 41: Robust Increase in Markers of Bone Formation Observed
Robust Increase in Markers of Bone Formation Observed • KER-012 is designed to inhibit activins and GDFs in the bone, which we believe potentially results in reduced SMAD 2/3 signaling and increased signaling of bone morphogenetic protein (BMP) pathway (SMAD1/5/8) • The increased BMP signaling poten
Slide 42: Observed Mean Maximal Increase in BSAP at Doses of 1.5 mg/kg and Higher
1 8 15 22 29 36 43 50 57 -10 0 10 20 30 40 50 Visit Day B S A P ( % c h a n g e , m e a n ± S E M ) 0.75mg/kg 1.5 mg/kg 3.0 mg/kg KER012 SAD: Mean BSAP % Change from Baseline at Each Visit 5.0 mg/kg Placebo Observed Mean Maximal Increase in BSAP at Doses of 1.5 mg/kg and Higher • A single 0.75 mg/kg
Slide 43: KER-012 Part 1 SAD Summary
KER-012 Part 1 SAD Summary • KER-012 was generally well tolerated at all doses up to 5 mg/kg when administered as a single dose in healthy postmenopausal women • KER-012 was associated with generally dose proportional exposure • Maximal target engagement was observed following a single 5 mg/kg dose
Slide 44: Keros Summary
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Slide 45: We Believe Keros is 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 46: Anticipated Key Milestones
Anticipated Key Milestones* KER-050 • Announce additional data from Phase 2 trial in MDS End of 2022 • Announce initial data from Phase 2 trial in myelofibrosis End of 2022 KER-047 • Announce initial data from Phase 2 in IRIDA End of 2022 • Initiate Phase 2 trial in IDA H2 2022; Initial data H1 2023
Slide 47: Thank You
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