Keros Therapeutics, Inc. · NASDAQ:KROS
Keros Therapeutics — Corporate Update (March 2025)
30 slides from Keros Therapeutics's corporate update, Mar 31, 2025
Slide 1: KER-065 Update March 2025
KER-065 Update March 2025
Slide 2: Forward-Looking Statements
KER-065 Update 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,” “p
Slide 3: KER-065
KER-065 Update 3 KER-065 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 designed to bind and inhibit activin A and myostatin to: • Improve muscle regeneration to
Slide 4: Chronic degenerative muscle diseases and DMD
1. Parker, A. E., et al. (2005). QJM 98, 729–736. doi: 10.1093/qjmed/hci113; 2. Tabebordbar, M., et al. (2013). Annu. Rev. Pathol. 8, 441–475. doi: 10.1146/annurev-pathol-011811-132450; 3.Wallace, G. Q., and McNally, E. M. (2009). Annu. Rev. Physiol. 71, 37–57. doi:10.1146/annurev.physiol.010908.163
Slide 5: Current Treatment Landscape for DMD
HDAC Inhibitors • Modulate the deregulated activity of HDACs in dystrophic muscle • DuvyzatTM (givinostat) was approved by the FDA in patients aged 6+ • DuvyzatTM can cause dose-related thrombocytopenia and other signs of myelosuppression, including anemia and neutropenia KER-065 Update 5 Current Tr
Slide 6: Robust Preclinical Data Suggests Potential Benefits of KER-065
KER-065 Update 6 Robust Preclinical Data Suggests Potential Benefits of KER-065 Activin inhibition (but not myostatin inhibition) offers therapeutic potential Offer muscle, bone and fat benefits: Potential to increase muscle mass, decrease fat mass and improve BMD, based on preclinical data and pr
Slide 7: Phase 1 Clinical Trial Data
KER-065 Update KER-065: Phase 1 Clinical Trial Data 7
Slide 8: Encouraging Preclinical and Phase 1 Trial Data Support Rationale for Phase 2 Trial
KER-065 Update 8 Encouraging Preclinical and Phase 1 Trial Data Support Rationale for Phase 2 Trial Trial met key objectives for safety, tolerability, pharmacokinetics and pharmacodynamics • Pharmacokinetic profile generally consistent with that of a well-behaved biologic • Dose exposure levels su
Slide 9: KER-065 Phase 1 Trial Design
KER-065 Update 9 KER-065 Phase 1 Trial Design Part 1 Single Ascending Dose (SAD) (Double-blinded) Treatment period: 28 days Safety follow up: 28 days Single subcutaneous dose Part 2 Multiple Ascending Dose (MAD) (Double-blinded) Treatment period: 85 days Safety follow up: 56 days Three subcutaneous
Slide 10: Baseline Demographics Consistent with Desired Population to Enroll
KER-065 Update 10 Baseline Demographics Consistent with Desired Population to Enroll All participants in this trial were male and generally healthy Higher baseline weight, BMI and waist-to-hip ratio in MAD relative to SAD, further supporting evaluation of body composition parameters Wide range
Slide 11: Treatment with KER-065 Was Generally Well Tolerated
KER-065 Update 11 Treatment with KER-065 Was Generally Well Tolerated Most TEAEs were mild (Grade 1) to moderate (Grade 2) No dose-limiting toxicities or serious adverse events were observed No bleeding events / telangiectasias were observed One unrelated Grade 4 TEAE* was observed (transien
Slide 12: Most Commonly Reported TEAEs
KER-065 Update 12 Treatment with KER-065 Was Generally Well Tolerated Most Commonly Reported TEAEs (TEAE Preferred Term) SAD MAD KER-065 1.0 mg/kg (N=4) n (%) KER-065 3.0 mg/kg (N=4) n (%) KER-065 5.0 mg/kg (N=4) n (%) KER-065 Total (N=12) n (%) Placebo (N=6) n (%) KER-065 1.25 mg/kg (N=8) n (%) KER
Slide 13: Observed Mean Change in Hemoglobin From Baseline
KER-065 Update 13 Observed Mean Change in Hemoglobin From Baseline Dose of KER-065 Increases in hemoglobin were asymptomatic and reversible SAD: • Increases in hemoglobin were observed, most prominently in the highest dose MAD: • Hemoglobin increase observed, primarily following the initial do
Slide 14: Increases in BSAP and Decreases in CTX Observed
14 BSAP CTX Bone specific alkaline phosphatase (BSAP) is a biomarker of bone formation C-terminal telopeptide (CTX) is a biomarker of bone resorption Increases in BSAP and Decreases in CTX Observed Following KER-065 Administration KER-065 Update KER-065 treatment demonstrated the potential for b
Slide 15: KER-065 Led to Increased Whole Body Bone Mineral Density
KER-065 Update 15 KER-065 Administration Led to Increased Whole Body Bone Mineral Density (BMD) Changes in bone biomarkers of increased bone formation and reduced bone resorption were consistent with tissue level changes, as demonstrated by observed increase in BMD Maximum increase data represented
Slide 16: Adiponectin Increased and Leptin Decreased
16 Adiponectin Leptin Adiponectin is a biomarker of fat mobilization Leptin is a biomarker of fat mass Adiponectin Increased and Leptin Decreased Following KER-065 Administration KER-065 Update Observed increase in adiponectin and reduction in leptin are supportive of fat mobilization Data repre
Slide 17: KER-065 Administration Led to Decreases in Fat Mass
-15 -10 -5 0 5 Day 85 Vi sc er al F at M ax im um % C ha ng e fr om b as el in e (M ea n ± S EM ) -10 -5 0 5 Day 85 W ho le B od y Fa t M as s M ax im um % In cr ea se fr om b as el in e (M ea n ± S EM ) DXA = dual-energy X-ray absorptiometry; MRI = magnetic resonance imaging KER-065 Update 17 KER-0
Slide 18: KER-065 Administration Led to Increases in Muscle Mass
KER-065 Update 18 KER-065 Administration Led to Increases in Muscle Mass Lean body mass (DXA) Thigh muscle volume (MRI) Observation of increased skeletal muscle, as demonstrated by increases in whole body lean mass (DXA) and thigh muscle volume (MRI) Data represented is baseline through day listed;
Slide 19: Encouraging Preclinical and Phase 1 Trial Data Support Rationale for Phase 2 Trial
KER-065 Update 19 Encouraging Preclinical and Phase 1 Trial Data Support Rationale for Phase 2 Trial Trial met key objectives for safety, tolerability, pharmacokinetics and pharmacodynamics • Pharmacokinetic profile generally consistent with that of a well-behaved biologic • Dose exposure levels s
Slide 20: Phase 1 Data Support Potential to Address Multiple Aspects of DMD
KER-065 Update 20 Phase 1 Data Support Potential for KER-065 to Address Multiple Aspects of DMD Bone Fat Muscle Reduced muscle strength, loss of ambulation and use of glucocorticoids in DMD contribute to the development of secondary osteoporosis KER-065 elicited: • Increases in BSAP demonstrating mo
Slide 21: Therapeutic Potential in a Broad Range of Neuromuscular Diseases
KER-065 Update 21 Therapeutic Potential in a Broad Range of Neuromuscular Diseases Created with BioRender Based on observed pharmacology in preclinical studies and the Phase 1 clinical trial, we believe KER-065 has potential in multiple, rare neuromuscular diseases with high unmet need BMD = Becker
Slide 22: Next Steps for KER-065
KER-065 Update 22 Next Steps for KER-065 We plan to engage regulators on the design of a Phase 2 clinical trial evaluating KER-065 in patients with DMD in the third quarter of 2025 Subject to regulatory feedback, we plan to initiate this Phase 2 clinical trial in the first quarter of 2026
Slide 23: Q&A
Q&A
Slide 24: Appendix
Appendix
Slide 25: Glucocorticoids Increased Expression of Negative Regulators of Skeletal Muscle and Bone
KER-065 Update 25 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 bone micr
Slide 26: RKER-065 Treatment Improved Efficiency of Exon Skipping
KER-065 Update 26 • 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 Mass Pe
Slide 27: RKER-065 Reduced the Inflammatory Profile of Muscle Resident Macrophages
KER-065 Update 27 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<0.001, a
Slide 28: RKER-065 Reduced Fibroblast and Fat Precursor Cells in Dystrophic Mice
KER-065 Update 28 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 anterio
Slide 29: Treatment with RKER-065 Increased Satellite Cells in Skeletal Muscle
KER-065 Update 29 • 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 analyze
Slide 30: RKER-065 Increased Utrophin Expression in Mouse Model of DMD
KER-065 Update 30 W T- ve h D 2. m dx -v eh D2 .m dx -0 65 1. Nathan, R., et al. 28th International Annual Congress of the World Muscle Society; WT= wild type (control), D2.mdx = mouse model of DMD’ *** P<0.001 30 0 50 100 150 0 50 100 150 200 250 Evoked Force Maximum Gastrocnemius Freq (Hz) m N DBA