Keros Therapeutics Doses First Patient in Phase 2 Rinvatercept Trial in Duchenne Muscular Dystrophy
核心洞察
Keros Therapeutics dosed the first patient in a Phase 2 trial of rinvatercept (搜索) in Duchenne muscular dystrophy (搜索), an open-label, multi-cohort basket study registered as NCT07704099.
The trial's primary objective is safety and tolerability in late-ambulatory and early non-ambulatory DMD patients, with pharmacokinetics and functional measures as key secondary objectives.
Rinvatercept (搜索) is a ligand trap designed to block myostatin (搜索) and activin A, negative regulators of muscle and bone mass, and is also in development for ALS.
Keros Therapeutics announced on September 28, 2026 that the first patient has been dosed in its Phase 2 clinical trial of rinvatercept (搜索) in patients with Duchenne muscular dystrophy (搜索) (DMD). The Lexington, Massachusetts-based clinical-stage biopharmaceutical company said the open-label, multi-cohort basket trial (NCT07704099) is designed to assess the safety and tolerability of the ligand trap in late-ambulatory and early non-ambulatory patients.
"Dosing the first patient in our Phase 2 clinical trial of rinvatercept (搜索) represents an important step in advancing our neuromuscular development strategy, and reflects the progress of our team as we continue to advance Keros' clinical pipeline," said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. "Rinvatercept is designed to modulate key regulators of muscle and bone biology, and we look forward to generating clinical data to inform its potential to treat patients with DMD."
Trial Design and Endpoints
The primary objective of the Phase 2 study is safety and tolerability. Key secondary objectives are pharmacokinetics, anti-drug antibodies, body composition and comprehensive functional improvements spanning skeletal muscle, motor, cardiac and pulmonary measures.
The basket design allows Keros to enroll patients across different disease stages or background therapy profiles simultaneously, generating safety signals and early efficacy reads across subgroups without running separate sequential trials. Early cohort data could inform dose decisions for later cohorts while enrollment continues, an efficiency relevant in a rare disease where patient numbers are limited.
Mechanism of Action
Rinvatercept (搜索) is a novel ligand trap comprised of a modified ligand-binding domain derived from activin receptor type IIA (搜索) and activin receptor type IIB (搜索) fused to the Fc domain of a human antibody. It is designed to inhibit the biological effects of myostatin (搜索) and activin A, negative regulators of muscle and bone mass and strength, to improve skeletal muscle regeneration, increase muscle size and strength, inhibit and reduce fibrosis, inhibit inflammation, reduce fat accumulation and improve bone health through bone anabolic mechanisms.
Keros is developing rinvatercept (搜索) for DMD and for amyotrophic lateral sclerosis (搜索) (ALS). The company's most advanced product candidate, elritercept, is being developed for cytopenias, including anemia (搜索) and thrombocytopenia (搜索), in patients with myelodysplastic syndromes (搜索) and myelofibrosis (搜索).
Unmet Need in DMD
Gina O'Grady, B.H.B., MBChB, Ph.D., a pediatric neurologist at Starship Children's Hospital (搜索), said the mechanism established in preclinical studies provides a rationale for clinical evaluation in DMD. "DMD, despite advances in treatment, continues to place a significant burden on patients and their families, and the need for additional options remains high," she said. "This trial represents an important opportunity to assess its potential impact across both ambulatory and non-ambulatory patients with DMD."
The approved DMD treatment landscape has expanded considerably, from exon-skipping agents to the 2023 gene therapy Elevidys. None of those approaches directly address the fibrosis and muscle wasting driven by myostatin (搜索) and activin A signaling, the pathway rinvatercept (搜索) targets. Whether blocking myostatin and activin A translates into functional gains in DMD patients, whose disease biology differs from the myeloproliferative conditions where rinvatercept has existing data, is the question the study is intended to answer.
What to Watch
The near-term readout is the safety data from the first cohort. A clean tolerability profile in DMD patients would support expanding dosing and collecting the functional outcome data needed to justify a pivotal program. A signal of muscle benefit on top of existing standard-of-care therapy would be the result that changes the program's trajectory.