Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 103

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 103
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 initial data from this trial in the first quarter of 2025. We believe this trial has the potential to inform the development of KER-065 in neuromuscular indications, such as DMD. 

Preclinical Data

We have generated preclinical data that we believe demonstrated proof-of-mechanism of KER-065 for the treatment of neuromuscular diseases, such as DMD. Specifically, in preclinical studies:

•KER-065 showed high affinity for and potent inhibition of ligands involved in the regulation of muscle and bone homeostasis;

•RKER-065 increased utrophin expression and muscle strength in a mouse model of DMD;

•Co-treatment with prednisolone and RKER-065 increased both muscle mass and strength and trabecular bone and strength;

•RKER-065 increased satellite cells in skeletal muscle; and

•Co-treatment with phosphorodiamidate morpholino oligomer, or PMO, therapy and RKER-065 improved grip strength and the efficiency of exon skipping.

KER-065 targeted ligands that signal through ActRIIA and ActRIIB to increase skeletal muscle and bone in preclinical studies

KER-065 is a modified ActRII ligand trap that contains sequences from both wild-type ActRIIB and wild-type ActRIIA. In preclinical studies, KER-065 bound to and inhibited multiple ligands that signal through these cell surface receptors, including activin A and myostatin (GDF8). These ligands are key negative regulators of muscle and bone growth. Consequently, we believe KER-065 has the potential to increase skeletal muscle and bone mass, increase fat metabolism and reduce fibrosis.

Treatment with RKER-065 increased utrophin expression and muscle strength in a mouse model of DMD

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In preclinical studies conducted in the MDX mouse model of DMD, twice weekly, intraperitoneal 10 mg/kg dosing of RKER-065 increased expression of utrophin in muscle fibers, potentially contributing to the observed increased strength.

Evoked Force Maximum Gastrocnemius

***P value <0.001

Co-treatment with prednisolone and RKER-065 increased both muscle mass and strength and trabecular bone and strength

MDX mice were treated with vehicle or 2-prednisolone, or co-treated with 10 mg/kg of prednisolone and RKER-065 twice weekly. Prednisolone-treated MDX