Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Corporate Update (May 2022)
25 slides from Keros Therapeutics's corporate update, May 18, 2022
Slide 1: Corporate Update May 2022
vse IKKEROS OSG THERAPEUTICS Corporate Update May 2022
Slide 2: Disclaimer
Disclaimer 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," “plans,” “poten
Slide 3: Introductions
Introductions • Jasbir Seehra, President and Chief Executive Officer • Keith Regnante, Chief Financial Officer • Simon Cooper, Chief Medical Officer • Jenn Lachey, Chief Scientific Officer • Christopher Rovaldi, Chief Operating Officer 3
Slide 4: 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 5: Keros is Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders
Keros is Developing Differentiated Clinical Assets in Hematological and Musculoskeletal Disorders 5*Anticipated clinical milestone are subject to the impact of COVID-19 on our business.
Slide 6: KER-012
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Slide 7: 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 8: Role of TGF-β in Pulmonary Arterial Hypertension
Role of TGF-β in Pulmonary Arterial Hypertension Pulmonary arterial hypertension (PAH) is a debilitating disorder characterized by elevated pulmonary vascular resistance, resulting in diminished oxygenation, impaired cardiac output, and right ventricle (RV) overload PAH is associated with imbalanced
Slide 9: 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 10: 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 11: Phase 1 Clinical Trial of KER-012 in Healthy Post Menopausal Women
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
Slide 12: Phase 1 Clinical Trial Design
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 13: 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 14: Demographics and Disposition (Part SAD)
Demographics and Disposition (Part 1 SAD) PBO (N=8) 0.75 mg/kg (N=8) 1.5 mg/kg (N=8) 3.0 mg/kg (N=8) 5.0 mg/kg (N=8) All Subjects (N=40) Age, years mean (range) 56.0 (48 – 60) 58.3 (52 -70) 54.9 (50 - 59) 57.8 (50 - 66) 59.3 (53 - 68) 57.2 (48 - 70) Race, n (%) White Multiple* 8 (100) 0 8 (100) 0 8
Slide 15: Safety, Tolerability and PK (Part 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 16: 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 em o
Slide 17: 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 18: 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 19: 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 SA P (% c ha ng e, m ea n ± S EM ) 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 dose o
Slide 20: KER-012 Part 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 21: KER-012 Elicited Maximum Increases in Bone-Specific Alkaline Phosphatase (BSAP)
0 10 20 30 40 50 KER012 SAD: Mean Maximum Percent Change from Baseline in BSAP BS AP m ea n m ax im um % c ha ng e ± SE M 0.75mg/kg 1.5 mg/kg 3.0 mg/kg 5.0 mg/kg Placebo KER-012 Elicited Maximum Increases in Bone-Specific Alkaline Phosphatase (BSAP) • Increasing doses of KER-012 was observed to elic
Slide 22: Sotatercept Increased BSAP Concurrently with Increases in Hemoglobin in Third-Party Phase 1 Trial
Sotatercept Increased BSAP Concurrently with Observed Increases in Hemoglobin in a Third-Party Phase 1 Clinical Trial* 0 10 20 30 40 50 Sotatercept: Mean Maximum Percent Change from Baseline in BSAP B SA P m ea n m ax im um % c ha ng e ± SE M 3 mg/kg IV 1 mg/kg IV 0.3 mg/kg IV Placebo *All data on t
Slide 23: KER-012: Next Steps
KER-012: Next Steps • Part 2 of this trial (multiple ascending dose) is ongoing; expected to report data in H2 2022 • Expect to confirm SAD biomarkers and include changes in bone mineral density by dual- energy x-ray absorptiometry • Keros expects to initiate a Phase 2 clinical trial of KER-012 in P
Slide 24: Anticipated Key Milestones
Anticipated Key Milestones* KER-050 • Announce additional data from Phase 2 trial in MDS Mid-2022 (EHA 2022) • Announce initial data from Phase 2 trial in myelofibrosis End of 2022 KER-047 • Initiate Phase 2 trial in IDA H1 2022 (initial data end of 2022) • Initiate Phase 2 trial in IRIDA H1 2022 (i
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