A novel inotropic/lusitropic peptide drug against decompensated chronic heart failure


Funded period

2018 – 2019

Granted budget

€ 475,566

Indication

heart failure

Therapeutic Principle

Drug

Principal Investigator

Patrick Most, Hugo Katus (University Hospital Heidelberg)

The objectives of this proposal are the preclinical development of a cardiac-targeted peptide drug with inotropic and lusitropic effects for the short-term intravenous treatment of decompensated chronic heart failure (CHF) and its clinical translation into a first-in-human clinical trial. The life-threatening complication of the clinical syndrome presents a significant unmet medical need given its high mortality and severe adverse effects of clinical drugs to reconstitute cardiac performance.

The proposed therapeutic innovation seeks to exploit a novel regulatory principle to improve cardiac contraction and relaxation by the molecular factor S100A1 and utilizes cell-permeable peptide technology that is derived from the molecule’s C-terminal domain. The translational research project originates from comprehensive preclinical data showing the ability of S100A1ct peptide for a reversible short-term improvement and protection of cardiac performance in vivo and in vitro. In its funded first developmental module, the project seeks to define the therapeutically effective dose-range of S100A1ct in clinically relevant large animal disease models as well as demonstration of toxicological and immunological safety to conclude regulatory steps on ultimate GMP/GLP pre-clinical and clinical development


Results

These studies were successful and qualified the peptide drug for subsequent preclinical tests funded by the BMBF. They also established a strategic development partnership with a global biopharmaceutical company to optimise the peptide drug for clinical trials. (Annual report 2019)