4TEEN4's first-in-class therapeutic antibody Procizumab restores heart function in life-threatening cardiac depression induced by sepsis

September 16, 2020

Hennigsdorf/ Berlin, Germany, September 16, 2020 - 4TEEN4 Pharmaceuticals GmbH ("4TEEN4") announces data on the efficacy of its lead product, Procizumab, that promptly restored cardiac dysfunction in a preclinical sepsis model by inhibiting the cardiac depressant factor DPP3. The current findings indicate that DPP3 plays an important role in septic cardiomyopathy. Sepsis is a dysregulated host response to an infection that ultimately leads to organ dysfunction.

The study data (1) from the team lead by Prof. Alexandre Mebazaa have shown that high DPP3 blood values are associated with decreased heart function in a preclinical sepsis model. In this randomized, controlled study, the administration of Procizumab immediately and significantly improved heart function by increasing cardiac output, stroke volume, and left ventricular shortening fraction. Inactivation of the cardiac depressant factor DPP3 fully restored cardiac contraction and improved survival.

DPP3 is at the core of a recently discovered disease mechanism, which was previously demonstrated to be a leading cause of circulatory failure (2,3,4). The release of the cardiac depressant factor DPP3 into the bloodstream causes the inactivation of the heart-stimulating hormone, Angiotensin II, a process leading to cardiac depression, hemodynamic instability and shock.

"These findings demonstrate for the first time that DPP3 plays a role in sepsis. By inhibiting DPP3 with our antibody Procizumab, we are able to restore cardiac function in preclinical sepsis models. This paves the way for future investigations on the utility of Procizumab as a possible therapeutic option in patients with sepsis and septic shock" said Dr. Andreas Bergmann, CEO of 4TEEN4.

The antibody Procizumab offers a new approach for the treatment of life-threatening diseases related to acute circulatory failure. Preclinical safety and toxicity studies of the antibody as well as the initiation of the first-in-man studies are planned for 2021.

(1) Deniau (2020) Inhibition of circulating dipeptidyl-peptidase 3 restores cardiac function in a sepsis-induced model in rats: A proof of concept study, PLOS ONE, doi.org/10.1371/journal.pone.0238039

(2) Deniau (2019) Circulating dipeptidyl peptidase-3 is a myocardial depressant factor: DPP3 inhibition rapidly and sustainably improves hemodynamics, European Journal of Heart Failure, DOI: 10.1002/ejhf.1601

(3) Takagi (2019) Circulating dipeptidyl-peptidase 3 and alteration in hemodynamics in cardiogenic shock: Results from the OptimaCC Trial, European Journal of Heart Failure, doi: 10.1002/ejhf.1600

(4) Dépret (2020) Circulating dipeptidyl peptidase-3 at admission is associated with circulatory failure, acute kidney injury and death in severely ill burn patients, Critical Care, doi: 10.1186/s13054-020-02888-5

About 4TEEN4

4TEEN4 Pharmaceuticals GmbH is a biopharmaceutical company developing Procizumab, a humanized antibody targeting human Dipeptidyl Peptidase 3 (DPP3) for the treatment of acute cardiovascular diseases. 4TEEN4 licenses its proprietary biomarker DPP3 to make it available for diagnostic use in indications as acute heart failure, myocardial infarction, cardiogenic shock and septic shock. The company was established in 2013 in Hennigsdorf near Berlin, Germany, by Dr. Andreas Bergmann, CEO of 4TEEN4, as part of his Medicine4Future Initiative.

About Procizumab

Procizumab is a humanized monoclonal antibody in preclinical development specifically binding circulating Dipeptidyl Peptidase 3 (DPP3). It will be a first-in-class drug that targets and modulates DPP3 as an essential regulator of cardiovascular function. Procizumab has an innovative mode of action, relevant in acute diseases. Massive cell death and release of DPP3 into the bloodstream lead to degradation of its substrates, including angiotensin II and enkephalin, that are responsible for cardiac and renal function regulation. Procizumab inhibits the activity of DPP3, thereby reducing bioactive peptide degradation, stabilizing cardiovascular function and potentially increasing survival chances e.g. in acute heart failure and septic shock. Preclinical studies of Procizumab in models of cardiovascular failure showed instant efficacy.

About DPP3

Dipeptidyl Peptidase 3 (DPP3) is an active enzyme which, when released into the blood, inactivates angiotensin II, a hormone that is important for the heart function. This inactivation leads to cardiac depression and consequently hemodynamic instability and consequently cardiac depression. The DPP3 release is a newly identified disease mechanism explaining short-term organ failure in critically ill patients.

4TEEN4 Pharmaceuticals GmbH

Related Sepsis Articles from Brightsurf:

Hormone involved in obesity is a risk factor for sepsis
A group of scientists from Instituto Gulbenkian de Ciência (IGC), led by Luís Moita, discovered that a hormone that has been pointed out as a treatment for obesity reduces the resistance to infection caused by bacteria and is a risk factor for sepsis.

Antihypotensive agent disrupts the immune system in sepsis
Patients who go into shock caused by sepsis (septic shock) are treated with the antihypotensive agent norepinephrine.

Milestone for the early detection of sepsis
Researchers from Graz, Austria, are developing a ground-breaking method that uses biomarkers to detect sepsis 2 to 3 days before the first clinical symptoms appear.

Breast milk may help prevent sepsis in preemies
Researchers at Washington University School of Medicine in St. Louis and Mayo Clinic in Rochester, Minn., have found -- in newborn mice -- that a component of breast milk may help protect premature babies from developing life-threatening sepsis.

Finding a new way to fight late-stage sepsis
Researchers have developed a way to prop up a struggling immune system to enable its fight against sepsis, a deadly condition resulting from the body's extreme reaction to infection.

Study: Sepsis survivors require follow-up support
Survivors of sepsis -- a life-threatening response to an infection -- have expressed a need for advocacy and follow-up support, according to a study authored by professors at the University of Tennessee, Knoxville, and the University of Tennessee Health Science Center in Memphis, and published in Dimensions of Critical Care Nursing.

After decades of little progress, researchers may be catching up to sepsis
After decades of little or no progress, biomedical researchers are finally making some headway at detecting and treating sepsis, a deadly medical complication that sends a surge of pathogenic infection through the body and remains a major public health problem.

Study changes guidelines for sepsis management
University of Arizona Health Sciences researcher ends debate among physicians regarding sepsis management.

Improving outcomes for sepsis patients
More than 1 million sepsis survivors are discharged annually from acute care hospitals in the United States.

Genes linked to death from sepsis ID'd in mice
Bacteria in the bloodstream can trigger an overwhelming immune response that causes sepsis.

Read More: Sepsis News and Sepsis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.