Keros Therapeutics Presents Preclinical and Clinical Data from its KER-012 Program at the American Thoracic Society International Conference - Seite 2

The following data from the subjects enrolled in the highest dose cohort (4.5 mg/kg) from Part 2 of this trial were presented at ATS 2023:

• Serum proteins associated with inflammation and structural remodeling pathways were altered following one dose of 4.5 mg/kg of KER-012 versus placebo, which Keros believes is consistent with the predicted mechanism of action of KER-012:
  • Decreases in markers of fibrosis, as indicated by changes in matrix metalloproteinases (MMP-7 and 10) and collagen fragments, were observed;
  • Reductions in pro-inflammatory cytokines (IL-6 and IL-11) were observed; and
  • Increases in anti-inflammatory cytokines (IL-4 and IL-35) and markers of macrophage polarization (MARCO and sCD163) were also observed.
• Sustained reductions in a biomarker of cardiac dysfunction (serum N-terminal pro-brain natriuretic peptide) were observed in subjects administered 4.5 mg/kg of KER-012 versus placebo.

Preclinical Presentations

• RKER-012, a Novel Modified ActRII Ligand Trap, Attenuated Cardiac Remodeling and Fibrosis in a Transverse Aortic Constriction Model of Heart Failure
  

Keros used a transverse aortic constriction (“TAC”) model of left ventricle overload to evaluate whether RKER-012 could prevent or treat cardiac remodeling and fibrosis in mice.

Mice either underwent sham or TAC surgery. Following these procedures, sham mice received vehicle and TAC mice received either vehicle (“TAC-vehicle”) or 10 mg/kg of RKER-012 (“TAC-RKER-012”) twice weekly, starting from the first day (“TAC-RKER-012 Group 1”) or fourteenth day (“TAC-RKER-012 Group 2”) after surgery. Eight weeks post-surgery, mice were assessed for associated cardiac pathologies. Relative to sham mice, TAC-vehicle mice had increased heart weight, left ventricular posterior wall thickness, interventricular septal end diastole, left ventricular fibrosis and elevated tissue remodeling markers, indicating that the TAC surgery worked as intended.

TAC-RKER-012 Group 1 mice had significantly reduced heart weight, left ventricular posterior wall thickness, interventricular septal end diastole and left ventricular fibrosis compared to TAC-vehicle mice. TAC-RKER-012 Group 2 mice had significantly reduced left ventricular posterior wall thickness and interventricular septal end diastole compared to TAC-vehicle mice, while heart weight and left ventricular fibrosis trended towards a decrease.