Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 97

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 97
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 potentially promotes bone formation through a dual mechanism of activation and recruitment of bone forming osteoblasts and repression of osteoclasts, as demonstrated in our preclinical studies.

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In Part 2 of this trial, we observed increases in BSAP after each dose, which is supportive of activation of osteoblasts after each dose.

Part 2 of the Trial: BSAP Percent Change from Baseline

Multiple doses of cibotercept did not elicit changes in erythropoiesis

Administration of cibotercept did not elicit clinically meaningful changes in hemoglobin or red blood cells in this trial, and no changes in red blood cells were observed after the second or third dose.

Observed Mean Hemoglobin Change

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Observed Mean Red Blood Cell Change

The observed lack of effect on erythropoiesis in this trial is consistent with the lack of effect observed in our multiple preclinical models.

Preclinical Data

We have generated preclinical data that we believe demonstrated proof-of-mechanism of cibotercept for the treatment of PAH and for the treatment of cardiovascular disorders. Specifically, in preclinical studies, cibotercept:

•Demonstrated effects on bone, including:

◦Exhibited high affinity for, and potent inhibition of, ligands involved in the regulation of bone homeostasis;

◦Increased bone mineral density and trabecular bone volume in wild-type mice and mice with established osteoporosis; and

◦Rats receiving a rodent version of cibotercept, or RKER-012, were protected from hypoxia-associated bone loss.

•Demonstrated potential for reduced bleeding risk, including:

◦No inhibition of retinal neovascularization observed in healthy newborn mice.

•Demonstrated benefit in a model of cardiovascular disease, including:

◦In a mouse model of pulmonary arterial banding, or PAB, RKER-012 was observed to protect against both the PAB-related cardiac dysfunction and remodeling.

Cibotercept targeted ligands that signal through ActRIIA and ActRIIB in preclinical studies

Cibotercept is a modified ActRIIB ligand trap that contains sequences from both wild-type ActRIIB and wild-type ActRIIA. In preclinical studies, cibotercept bound to and inhibited multiple ligands that signal through these cell surface receptors, including activin A, activin B and growth differentiation factor 11. These ligands are key regulators of bone remodeling that act to