Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — ASBMR 2022
16 slides from Keros Therapeutics's conference presentation, 2022
Slide 1: KER-012 Administered to Healthy Postmenopausal Women Was Generally Well Tolerated
KER-012, A Modified ActRIIB Ligand Trap, Administered to Healthy Postmenopausal Women Was Generally Well Tolerated and Increased Biomarkers of Bone Formation, Supportive of A Bone Anabolic Mechanism (P1053) Harveen Natarajan1, Sylvain Bedard1, Richard Friend2, Ying Jiang1, Jennifer Lachey1, Jasbir S
Slide 2: Disclosures
Disclosures • Harveen Natarajan, Ying Jiang, Jennifer Lachey, Jasbir Seehra, Enrikas Vainorius and Simon Cooper are employees of and security holders in Keros Therapeutics, Inc. • Sylvain Bedard is engaged as an independent contractor for Keros Therapeutics, Inc. • Richard Friend - no disclosures 2
Slide 3: Dysregulated TGF-b Superfamily Signaling Underlies Bone Loss Associated With Multiple Disease States
Dysregulated TGF-b Superfamily Signaling Underlies Bone Loss Associated With Multiple Disease States • Transforming growth factor-beta (TGF-b) TGF-b GDFs Activins BMPs superfamily ligands regulate bone remodeling and growth • Activins: promote osteoclasts, inhibit osteoblast formation and mineraliza
Slide 4: Proof of Concept Established for Targeting TGF-b Superfamily in Diseases Characterized by Bone Loss
Proof of Concept Established for Targeting TGF-b Superfamily in Diseases Characterized by Bone Loss • Pharmacologic inhibition of activin signaling has been shown to reverse bone loss in multiple myeloma1 and neuromuscular diseases2 • Investigational activin receptor (ActR) ligand traps have been sh
Slide 5: KER-012: A Novel, Investigational Activin Receptor Type IIB Ligand Trap
KER-012: A Novel, Investigational Activin Receptor Type IIB Ligand Trap KER-012 Structure • Designed to inhibit TGF-b superfamily ligands with specificity for activins to: Activins Modified ActRIIB • Maximally inhibit SMAD 2/3 signaling via Extracellular Domain activins • Permit SMAD 1/5/9 signaling
Slide 6: KER-012 Not Only Prevented, But Reversed Bone Loss in Multiple Preclinical Models
KER-012 Not Only Prevented, But Reversed Bone Loss in Multiple Preclinical Models of Bone Dysfunction Preventive: Sugen—hypoxia rat (PAH)1 Trabecular Number Trabecular Bone Micro-CT Scans KER-012 administration increased trabecular Volume Fraction bone in multiple preclinical models of bone loss: Hy
Slide 7: Phase 1 Trial of KER-012 in Healthy Postmenopausal Women
Phase 1 Trial of KER-012 in Healthy Postmenopausal Women Part 1: Single Ascending Dose Part 2: Multiple Ascending Dose (Double-blinded) (Double-blinded) 0.75 mg/kg 0.75 mg/kg Key Inclusion: n=8 n=8 Placebo n=2 Placebo n=2 Postmenopausal females* 1.5 mg/kg 1.5 mg/kg • 45 to 70 years (inclusive) n=8 •
Slide 8: Demographics and Disposition (Part 1 SAD)
Demographics and Disposition (Part 1 SAD) PBO 0.75 mg/kg 1.5 mg/kg 3.0 mg/kg 5.0 mg/kg All Subjects (N=8) (N=8) (N=8) (N=8) (N=8) (N=40) Age, years 56.0 58.3 54.9 57.8 59.3 57.2 mean (range) (48 – 60) (52 -70) (50 - 59) (50 - 66) (53 - 68) (48 - 70) Race, n (%) White 8 (100) 8 (100) 8 (100) 7 (87.5)
Slide 9: Demographics and Disposition (Part 2 MAD)
Demographics and Disposition (Part 2 MAD) PBO 0.75 mg/kg 1.5 mg/kg 4.5 mg/kg All Subjects (N=6) (N=8) (N=6) (N=6) (N=26) Age, years 59.5 59.1 55.7 61.2 58.9 mean (range) (51 – 68 ) (52 – 65 ) (52 – 59 ) (52 – 71 ) (51 – 71 ) Race, n (%) White 6 (100.0) 7 (87.5) 5 (83.3) 6 (100.0) 24 (92.3) Asian 0 1
Slide 10: KER-012 was Generally Well Tolerated after Single and Repeated Dosing
KER-012 was Generally Well Tolerated after Single and Repeated Dosing Part 1: Single Ascending Dose Part 2: Multiple Ascending Doses KER-012 Dose (mg/kg) KER-012 Dose (mg/kg) PBO 0.75 1.5 3.0 5.0 PBO 0.75 1.5 4.5 Adverse Event (N = 8) (N = 8) (N = 8) (N = 8) (N = 8) (N = 6) (N = 8) (N = 6) (N = 6) A
Slide 11: Multiple Doses of KER-012 Did Not Elicit Changes in Erythropoiesis
Multiple Doses of KER-012 Did Not Elicit Changes in Erythropoiesis Mean Hemoglobin Change Mean RBC Change Placebo (n=6) 1.5 mg/kg (n=6) Placebo (n=6) 1.5 mg/kg (n=6) 0.75 mg/kg (n=8) 4.5 mg/kg (n=6) 0.75 mg/kg (n=8) 4.5 mg/kg (n=6) 3 1.0 Hemoglobin Change (g/dL, ± SEM) RBC Change (x1012/L, ± SEM) 2
Slide 12: KER-012 Elicited Dose-Dependent Reductions in Serum FSH
KER-012 Elicited Dose-Dependent Reductions in Serum FSH Part 2 (MAD) • Follicle stimulating hormone (FSH) secretion by the pituitary is controlled through signaling by the activin receptor and Gonadotropin Releasing Hormone (GnRH) Placebo (n=6) 1.5 mg/kg (n=6) • Approximately 50% of the FSH secretio
Slide 13: Dose-Dependent Increases in Serum BSAP with Maximal Effects at Highest Doses
Dose-Dependent Increases in Serum BSAP with Maximal Effects Seen at Highest Doses of KER-012 Tested Part 1 (SAD) Part 2 (MAD) Mean Maximum Percent Change Mean Maximum Percent Change 75 75 from Baseline in BSAP from Baseline in BSAP# Placebo maximum % change (mean ± SEM) maximum % change (mean ± SEM)
Slide 14: Serum BSAP Increased After Administration of Each Dose of KER-012
Serum BSAP Increased After Administration of Each Dose of KER-012 Part 2: Multiple Ascending Doses Placebo (n=6) 1.5 mg/kg (n=6) 0.75 mg/kg (n=8) 4.5 mg/kg (n=6) 100 % change from baseline = KER-012 dose (mean ± SEM) 80 60 BSAP 40 20 0 -20 1 15 29 43 57 71 Study Day Administration of KER-012 at a
Slide 15: Robust Increases in Additional Markers of Bone Formation Were Elicited by a Single Dose
Robust Increases in Additional Markers of Bone Formation Were Elicited by a Single Dose of KER-012 (Part 1) Procollagen Type 1 N-Terminal Propeptide Osteocalcin 50 50 P1NP mean maximum % change ± SEM maximum % change (mean ± SEM) 40 40 Osteocalcin 30 30 20 20 10 10 0 0 PBO 0.75 1.5 3.0 5.0 PBO 0.75
Slide 16: Summary
Summary • KER-012 is a novel, investigational activin receptor type IIB ligand trap designed to correct SMAD 2/3 and SMAD 1/5/9 signaling imbalances in multiple degenerative disease states • Demonstrated ability to not only prevent, but reverse bone loss in multiple preclinical models of induced bon