Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 99

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 99
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 increased density of blood vessels. Newborn mice were treated on postnatal day 1 and 3, and on day 8, retinas were dissected and stained to visualize the vasculature and measure vascular plexus. Administration of 10 mpk of ALK1-Fc (a potent inhibitor of BMP9 (which is required for normal vascular remodeling) and BMP10) significantly reduced retinal neovascularization. Additionally, administration of 20 mpk of a research form of sotatercept, RAP-011, which bound BMP9 with higher affinity than RKER-012, showed a dose-related inhibition of retinal vessel outgrowth. However, administration of 10 mpk and 20 mpk of RKER-012 did not inhibit retinal neovascularization. This lack of observed perturbation of retinal blood vessels of newborn mice treated with RKER-012 supports the potential for reduced bleeding risk with cibotercept.

9

Quantification of Vascular Outgrowth

**P value <0.01; ***P value <0.001; ****P value <0.0001; ns = not significant

Treatment with RKER-012 prevented cardiac dysfunction and remodeling in a mouse PAB model 

We used mechanical restriction of the pulmonary artery in mice to increase pressure in the right ventricular of the heart. In this model, increased ventricular pressure resulted in cardiac dysfunction, as demonstrated by increased end systolic pressure-volume relationship, or ESPVR, and increased myocardial performance index, or MPI. The increased ventricular pressure also results in cardiac remodeling, as evidenced by an increase in the Fulton index, an increase in the right ventricular free wall thickness, or RVFWT, and increased fibrosis in the heart. Treatment with twice weekly subcutaneous 10 mg/kg dosing of RKER-012 was observed to protect against both the PAB-related cardiac dysfunction and remodeling, which we believe demonstrates that cibotercept has the potential to have a cardioprotective effect that could potentially provide benefit in diseases such as PAH and other cardiovascular diseases in patients.

10

ESPVR, MPI, Fulton Index, RVFWT and Cardiac Fibrosis in a Mouse PAB Model

*** P value <0.001; **** P value <0.0001 vs. Sham; ## P value <0.01, #### P value <0.0001 vs. Vehicle

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KER-065

KER-065 is