Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 98

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 98
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 suppress bone growth. BMP9 is a ligand capable of signaling through the ActRIIB and bone morphogenetic receptor II. Inhibition of BMP9 results in disruption of vascular remodeling, which can lead to the development of epistaxis and telangiectasias. Cibotercept did not bind BMP9 or inhibit BMP9 signaling in preclinical studies. Consequently, we believe cibotercept has the potential to avoid bleeding.

Treatment with cibotercept increased bone mineral density 

In preclinical studies conducted in wild-type mice, twice weekly intraperitoneal 20 mg/kg dosing of cibotercept increased bone mineral density compared to vehicle-treated mice 31 days post-treatment. Additionally, we observed that treatment with 

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cibotercept statistically significantly increased trabecular bone formation and mineral apposition rate, which we believe is consistent with an anabolic effect on bone. 

Bone Mineral Density in Mice and Representative Microct Scans

*** P value <0.001

In a separate preclinical study, we observed that treatment with cibotercept increased the ratio of osteoblasts, which are bone forming cells, to osteoclasts, which are bone resorbing cells, which further supports that cibotercept acts via an anabolic effect on bone. We also observed in preclinical studies conducted in mice with established osteoporosis that twice weekly intraperitoneal 20 mg/kg dosing of cibotercept increased bone mass compared to vehicle-treated mice 46 days post-treatment. 

Osteoblast-to-Osteoclast Ratio in Mice

** P value <0.01

Treatment with RKER-012 prevented bone loss from hypoxia in the rat model of PAH

In the rat model of PAH, chronic hypoxia induced a catabolic state that resulted in wasting of tissue, including bone and muscle. Treatment with a subcutaneous 10 mg/kg dose of RKER-012 was observed to prevent bone loss in the rat model of PAH. 

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Bone Volume Changes as a Result of Hypoxia in the Rat Model of PAH

* P value <0.05; ** P value <0.01

Treatment with RKER-012 did not inhibit retinal neovascularization in healthy newborn mice

In the mouse model of retinal vascularization, which is an established model to study vascular growth and remodeling during development and disease, inhibition of BMP signaling leads to premature termination and