RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension - Summary - MDSpire

RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension

  • By

  • R. Keith Babbs

  • Jeanne Ishimwe

  • Chris Materna

  • ffolliott M. Fisher

  • Tandicka Nurse

  • Cynthia Pinkus

  • Pritesh Jain

  • Kevin Dagbay

  • Rosa Grenha

  • Tyler Daman

  • Claire C. Tseng

  • Emily A. Ledoux

  • Evan Lema

  • Alana Gudelsky

  • Francis Wolenski

  • Harveen D. Natarajan

  • Lorena Lerner

  • Jennifer L. Lachey

  • Jasbir Seehra

  • Sachindra R. Joshi

  • June 24, 2026

  • 0 min

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Objective:

To evaluate the efficacy and safety of KER-012/RKER-012, a modified ActRIIB-Fc ligand trap, in targeting overactive activin/GDF signaling in pulmonary arterial hypertension (PAH).

Approach:
  • Development of KER-012/RKER-012: Engineered a modified ActRIIB-Fc ligand trap to minimize BMP binding while retaining binding to Activin/GDF ligands.
  • Comparative Analysis: Compared the BMP-sparing properties of RKER-012 with RAP-011 (murine analog of sotatercept) in various models.
  • Efficacy Evaluation: Assessed the effects of RKER-012 on pulmonary vasculopathy, RV dysfunction, and remodeling in a SuHx rat model of PAH.
  • Clinical Trial: Conducted a Phase 1 clinical trial to evaluate the safety and pharmacokinetics of KER-012 in healthy post-menopausal women.
Key Findings:
  • KER-012/RKER-012 did not induce erythrocytosis or thrombocytopenia, unlike sotatercept.
  • The modified ligand trap effectively reduced the risk of hyperviscosity syndrome and bleeding.
  • RKER-012 attenuated experimental PAH by targeting multiple pathobiological components.
Interpretation:

The study suggests that KER-012/RKER-012 may provide a safer alternative to existing therapies by preserving BMP signaling while effectively targeting overactive activin/GDF pathways in PAH.

Limitations:
  • The study primarily focuses on preclinical models, and clinical efficacy in humans remains to be fully established.
  • Potential long-term effects and safety of KER-012/RKER-012 in diverse populations are not yet known.
Conclusion:

KER-012/RKER-012 represents a novel approach to targeting PAH, focusing on minimizing adverse effects associated with current treatments.

Original Source(s)

RKER-012, a modified ActRIIB-Fc ligand trap with BMP sparing properties, attenuates pathological features of experimental pulmonary arterial hypertension

  • by R. Keith Babbs, Jeanne Ishimwe, Chris Materna, ffolliott M. Fisher, Tandicka Nurse, Cynthia Pinkus, Pritesh Jain, Kevin Dagbay, Rosa Grenha, Tyler Daman, Claire C. Tseng, Emily A. Ledoux, Evan Lema, Alana Gudelsky, Francis Wolenski, Harveen D. Natarajan, Lorena Lerner, Jennifer L. Lachey, Jasbir Seehra, Sachindra R. Joshi

  • June 24, 2026

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