- Dipeptidyl Peptidase 3 release is a fatal clinical pathway in severe COVID-19 patients resulting in organ dysfunction and short-term mortality
- New COVID-19 trial conducted by University Hospital Hamburg-Eppendorf is implementing a biomarker-guided therapy using DPP3 and bio-ADM for patient enrollment
- Targeted intervention for specific activated pathways in COVID-19 patients is crucial to ensure treatment success
HENNIGSDORF and BERLIN, GERMANY / ACCESSWIRE / April 11, 2022 / 4TEEN4 pharmaceuticals GmbH announces today that its biomarker DPP3 will be used in a biomarker-guided trial in severe COVID-19 as communicated by the University Hospital Hamburg-Eppendorf (UKE) and SphingoTec GmbH. The study will be using two biomarkers, bioactive adrenomedullin (bio-ADM) and dipeptidyl peptidase 3 (DPP3), for patient stratification and inclusion criteria for the use of Adrecizumab (1). This revolutionary approach could serve as a precision medicine strategy in patients with severe COVID 19 infection.
Similar to Sepsis, patients with severe COVID-19 infection undergo several life-threatening clinical pathways. Loss of endothelial function is a major pathway contributing to worsening lung function. Another concurrent pathway is the uncontrolled release of DPP3 due to cell injury resulting in loss of organ function and hemodynamic instability (1,2).
Both clinical pathways can be detected by specific biomarkers, bioactive Adrenomedullin (bio-ADM) for the loss of endothelial function and Dipeptidyl peptidase (DPP3) for the loss of heart function. A thorough understanding of the heterogeneity of COVID 19 will enable the administration of the right intervention and could potentially make a difference between life and death (1,2).
Adrecizumab, a new drug candidate to treat endothelial barrier dysfunction, is under development for the treatment of septic shock and it is currently investigated in hospitalized COVID-19 patients (3,4). The trial will follow a biomarker-guided therapy approach treating only patients with endothelial barrier dysfunction (bio-ADM positive). Patients with high DPP3 levels indicate the use of different therapeutic options and will not be enrolled (3,4).
DPP3 is a novel biomarker developed by 4TEEN4 pharmaceuticals and out-licensed to SphingoTec GmbH. It is available on a point of care platform for rapid testing. In several studies with critically ill patients such as septic shock, cardiogenic shock, burn shock, severe surgeries, and COVID-19, high DPP3 levels have been associated with reduced cardiac output, multiple organ failure, circulatory shock, and short-term mortality. DPP3 mediates the degradation of Angiotensin II, a hormone important for hemodynamic balance and cardiac function. This inactivation leads to hemodynamic instability, resulting in short-term organ dysfunction (4,5).
To treat patients with high DPP3 and circulatory failure, 4TEEN4 Pharmaceuticals develops an anti-DPP3 therapy that restores cardiac function, hemodynamic stability and improves survival. The drug candidate anti-DPP3 antibody, Procizumab, already demonstrated efficacy in preclinical models and will enter the first-in-human clinical trial by the end of 2022.
Dr. Andreas Bergmann, founder, and CEO of 4TEEN4 mentioned: "We are developing Procizumab as a targeted therapy to be available for critically-ill patients suffering from organ dysfunction due to high DPP3 levels and provide them with a treatment option for hard-to-treat diseases such as septic shock, cardiogenic shock, and COVID-19"
- Simon T-P et al. Prognostic Value of Bioactive Adrenomedullin in Critically Ill Patients with COVID-19 in Germany: An Observational Cohort Study. Journal of Clinical Medicine. 2021, 10, 1667. doi.org/10.3390/jcm10081667
- Laterre PF, et al. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med. 2021 Nov;47(11):1284-1294. doi: 10.1007/s00134-021-06537-5.
- Karakas, M et al. Targeting Endothelial Dysfunction in Eight Extreme-Critically Ill Patients with COVID-19 Using the Anti-Adrenomedullin Antibody Adrecizumab (HAM8101). Biomolecules 2020, 10, 1171. https://doi.org/10.3390/biom10081171
- van Lier et al 2020, Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3, J. Intern. Med., DOI: doi.org/10.1111/joim.13220
- Magliocca, A.; Omland, T.; Latini, R. Dipeptidyl peptidase 3, a biomarker in cardiogenic shock and hopefully much more. Eur. J. Heart Fail. 2020, 22, 300-302.
At 4TEEN4 we are dedicated to improving critically ill patient lives who suffer from hemodynamic instability, end-organ hypoperfusion, and multiple organ failure with our first-in-class humanized monoclonal antibody" Procizumab" targeting human dipeptidyl peptidase 3 (DPP3).
4TEEN4 licensed its novel biomarker DPP3 for diagnostic purposes in critical care conditions.
4TEEN4 Pharmaceuticals GmbH ("4TEEN4") was established in 2013 in Hennigsdorf near Berlin, Germany, by Dr. Andreas Bergmann, CEO of 4TEEN4, as part of his Medicine4Future Initiative.
For further information please visit www.4teen4.de
Dipeptidyl peptidase 3 is an active enzyme that, when released into the blood, inactivates angiotensin II, a hormone that is important for hemodynamic balance as well as cardiac function. This inactivation leads to hemodynamic instability and consequently to cardiac dysfunction. The DPP3 release is a newly identified disease mechanism explaining short-term organ failure in critically ill patients. Early identification of DPP3 release may allow better patient stratification and earlier therapy escalation to improve outcomes.
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 to acute diseases. Massive cell death and release of DPP3 into the bloodstream lead to degradation of its substrates, including angiotensin II and enkephalin, which are responsible for cardiac and renal function regulation. Procizumab inhibits the activity of DPP3, thereby reducing bioactive peptide degradation, stabilizing hemodynamics, cardiovascular function, and potentially increasing survival chances e.g., in cardiogenic and septic shock. Preclinical studies of Procizumab in models of cardiovascular failure showed instant efficacy.
Leen Alsaka Amini
Tel: +49 (0) 176 64322 193
Dr. Karine Bourgeois
Tel: +49 (0) 162 2145536
SOURCE: 4TEEN4 Pharmaceuticals GmbH