Keros Therapeutics has announced promising topline results from its Phase 1 clinical trial of KER-065 in healthy volunteers, meeting key objectives for safety, tolerability, pharmacokinetics, and pharmacodynamics. The company plans to advance the investigational therapy into Phase 2 trials for Duchenne muscular dystrophy (DMD), pending regulatory discussions.
The randomized, double-blind, placebo-controlled trial evaluated KER-065 through multiple ascending dose treatment periods up to Day 85. According to data collected through February 6, 2025, the therapy was generally well-tolerated with no major safety signals, serious adverse events, or dose-limiting toxicities reported.
"We are pleased to report topline results that met the key objectives of the Phase 1 clinical trial and provided important insights to inform the development of KER-065 for patients with DMD," said Jasbir S. Seehra, Ph.D., Chair and Chief Executive Officer of Keros. "Considering the limitations of currently available therapies, the need for additional treatments in DMD remains high."
Mechanism of Action and Biomarker Evidence
KER-065 is a novel ligand trap designed to inhibit the biological effects of myostatin and activin A, two ligands that signal through activin receptors. The therapy aims to increase skeletal muscle regeneration, muscle size and strength, reduce body fat, decrease skeletal muscle fibrosis, and increase bone strength.
The Phase 1 results showed evidence of activin inhibition across tissues of interest, with KER-065 eliciting:
- Increases in bone specific alkaline phosphate (BSAP), a biomarker of bone formation
- Decreases in C-Terminal Telopeptide (CTX), a biomarker of bone resorption
- Increases in adiponectin, a biomarker of fat mobilization
- Decreases in leptin, a biomarker of fat mass
- Changes in body composition, including increases in bone mineral density and muscle mass and decreases in fat mass
"We observed evidence of activin inhibition based on multiple biomarkers and body composition data. These data, coupled with preclinical and mechanistic insights on the pivotal role of the activin pathway in neuromuscular pathobiology, demonstrate the exciting therapeutic potential of KER-065 in DMD and other neuromuscular disorders," said Yung H. Chyung, M.D., Chief Medical Officer.
Addressing Unmet Needs in DMD
DMD is the most common form of muscular dystrophy, affecting approximately one in every 3,500 male births worldwide. The disease results from the lack of functional dystrophin protein caused by a gene mutation, leading to progressive muscle degeneration and premature death.
The absence of dystrophin in muscle cells causes increased susceptibility to damage, progressive muscle cell death, and replacement of muscle with fibrotic and fatty tissue. This leads to loss of muscle strength and function, immobility, and respiratory and cardiac complications. Heart failure due to cardiomyopathy is currently the leading cause of death among DMD patients.
Current treatment options for DMD have significant limitations, highlighting the need for novel approaches that can address multiple aspects of the disease pathology. KER-065's mechanism targeting the TGF-β family of proteins offers potential advantages by addressing several disease components simultaneously.
Development Timeline and Next Steps
Keros plans to engage with regulatory authorities beginning in the third quarter of 2025. Subject to positive regulatory interactions, the company expects to initiate a Phase 2 clinical trial of KER-065 in patients with DMD in the first quarter of 2026.
"Our strong financial foundation enables us to continue advancing our promising pipeline of novel therapeutics," added Dr. Seehra, highlighting the company's commitment to developing KER-065 for DMD and potentially other neuromuscular indications.
About Keros Therapeutics
Keros Therapeutics is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics for disorders linked to dysfunctional signaling of the transforming growth factor-beta (TGF-β) family of proteins. The company's pipeline includes cibotercept (KER-012) for pulmonary arterial hypertension and cardiovascular disorders, KER-065 for neuromuscular diseases, and elritercept (KER-050) for cytopenias in myelodysplastic syndrome and myelofibrosis.
The company positions itself as a leader in understanding the role of the TGF-β family of proteins, which are master regulators of the growth, repair, and maintenance of various tissues, including blood, bone, skeletal muscle, adipose, and heart tissue.
