Dipeptidyl Peptidase 3 (DPP3) Cause of Acute Myocardial Depression. Sphingotec Launches First IVD Test For DPP3 on Nexus IB10 Point-of-Care Platform

DPP3 is at the core of a novel disease mechanism presented by Prof. Alexandre Mebazaa (Hôpital Lariboisière, Paris) today at ESC Congress 2019 (organised by the European Society of Cardiology ESC, Paris) and was described in detail in two high-ranking peer-reviewed publications by Prof. Mebazaa and co-workers also published today^1,2.Results from independent clinical studies provide evidence that outcomes of patients with cardiogenic shock are associated with DPP3 blood concentrations. The scientists hypothesize that DPP3 is released from cells into the bloodstream upon cell death and degrades central mediators of cardiovascular function, angiotensin II as well as kidney function mediator enkephalin.

In blood samples from patients with cardiogenic shock enrolled in the OptimaCC³(N=57) and the CardShock⁴ (174 patients) studies, sustained high or increasing DPP3 plasma levels were associated with a significantly reduced cardiac left ventricular ejection fraction, impaired kidney function, and a markedly increased risk of mortality while decreasing levels of DPP3 were associated with higher survival. The causal role of DPP3 was further substantiated by studies in pre-clinical models in which injection of DPP3 impaired heart and kidney function. All these effects were immediately reversed in vivo following administration of the pre-clinical stage anti-DPP3 antibody Procizumab in a severe acute heart failure model. Procizumab is developed by the biopharmaceutical company 4TEEN4 Pharmaceuticals GmbH (“4TEEN4”). 4TEEN4 has recently licensed DPP3 rights to sphingotec for diagnostic purposes.

“DPP3 represents a unique biomarker at the core of a novel disease mechanism with high potential utility in diagnosing organ dysfunction and predicting outcome in cardiogenic shock as well as in a range of other acute care indications”, said Prof. Mebazaa.

Dr. Andreas Bergmann, CEO and founder of sphingotec commented: “The new disease mechanism investigated by Prof Mebazaa has huge potential to provide novel diagnostic and therapeutic options in a range of acute care settings with high unmet clinical need. To better understand clinical utility of DPP3 in the management of acute care patients, we invite the critical care community to collaborate with us in the further evaluation of this promising biomarker with our fully automated DPP3 point-of-care test in laboratory and near-patient settings.”

1. Takagi (2019) Circulating dipeptidyl-peptidase 3 and alteration in hemodynamics in cardiogenic shock: Results from the OptimaCC Trial, European Journal of Heart Failure
2. Deniau (2019) Circulating dipeptidyl peptidase-3 is a myocardial depressant factor: DPP3 inhibition rapidly and sustainably improves hemodynamics, European Journal of Heart Failure
3. clinicaltrial.gov NCT 01367743
4. clinicaltrial.gov NCT 1374867

About Acute Heart Failure

Heart failure is a state of reduced cardiac output, in which the heart cannot pump blood through the body effectively. When symptoms appear suddenly, or a person experiences rapid worsening of existing symptoms of heart failure, this is called acute heart failure (AHF) or acute decompensated heart failure (ADHF). This condition can be life threatening and should be urgently evaluated by a physician, as outcomes can be affected by early and appropriate treatment. Heart failure is a common condition affecting more than 30 million people world-wide. Typical symptoms of acute heart failure include shortness of breath, tiredness and swelling of the feet and legs (congestion). Treatment typically involves supporting breathing and adjusting the blood pressure and, where necessary, removing excess fluid from the body by diuretic treatment. There is no cure, but long-term treatment involving medications and rehabilitation can improve the heart’s function.

About Cardiogenic Shock

Cardiogenic shock is an emergency with mortality rates up to 50 %. Most cases of cardiogenic shock occur after myocardial infarction and are defined by persistent low cardiac output state resulting in arterial hypotension, shortness of breath, reduced organ perfusion. Refractory cardiogenic shock presents as persistent organ hypoperfusion despite the administration of vasoactive treatments. Early initiation of mechanical circulatory support, early percutaneous coronary intervention, inotropes, and heart transplantation may improve outcomes for patients with cardiogenic shock.

About DPP3

Human Dipeptidyl Peptidase 3 (DPP3) is an ubiquitously expressed and highly conserved enzyme. DPP3 cleaves various bioactive peptides, such as such as angiotensin II, enkephalins. The most prominent substrate of DPP3 is angiotensin II, the central effector of the renin-angiotensin system (RAS), implicating extracellular DPP3 in the regulation of the RAS. RAS is activated in cardiovascular diseases, sepsis and septic shock and angiotensin II, in particular, has been shown to modulate many cardiovascular functions including the control of blood pressure and cardiac remodelling.

About Nexus Dx Inc. and the IB10 Platform

Nexus Dx Inc., a wholly owned subsidiary of sphingotec,headquartered in San Diego, CA, USA, is a global provider of a near patient testing system and advanced diagnostic solution. The company is improving patient care by providing the medical community with rapid and reliable testing at the point of care (POC), delivering patient information when and where it is needed most. The company has invested over $160m to develop and market the IB10 analyser system which, without the need for sample preparation, automatically separates plasma from whole blood with subsequent reliable and quantitative detection of biomarkers in the plasma by means of antibodies. With a hands-on-time of less than 3 minutes the easy-to-use system provides in only 20 minutes test results for biomarkers that are crucial in the management of critical care patients such as Procalcitonin, Troponin I, CK-MB, Myoglobin, NT-proBNP, and D-Dimer. sphingotecs proprietary test sphingotest(R) DPP3, an assay for Dipeptidyl Peptidase 3, a unique biomarker for signalling pathway disruptions leading to acute organ dysfunction was recently launched on Nexus IB10. Near-term product launches on Nexus IB10 will include: IB10 sphingotest(R) bio-ADM(R), an assay for bioactive Adrenomedullin, a unique biomarker for real-time assessment of vascular integrity, and IB10 sphingotest(R) penKid(R), an assay for Proenkephalin, a unique biomarker for real-time assessment of kidney function.

About sphingotec

SphingoTec GmbH (“sphingotec”; Hennigsdorf by Berlin, Germany) develops and markets innovativein vitro diagnostic IVD tests for novel and proprietarybiomarkers for the diagnosis, prediction and monitoring of acute medical conditions, such as acute heart failure, circulatory shock, and acute kidney injury in order to support patient management and provide guidance for treatment strategies. sphingotec’s assay portfolio includes sphingotest(R) bio-ADM(R) the assay for bioactive adrenomedullin, a unique biomarker for real-time assessment of vascular integrity in conditions like sepsis or congestive heart failure, sphingotest(R) penKid(R), the assay for proenkephalin, a unique biomarker for real-time assessment of kidney function and sphingotest(R) DPP3, an assay for Dipeptidyl Peptidase 3, a unique biomarker for signalling pathway disruptions leading to acute organ dysfunction.Along with the Nexus IB10 POC platform by its subsidiary Nexus Dx Inc. (San Diego, CA, USA) acquired from Samsung in 2018, sphingotec markets a standard marker portfolio for acute care. In addition, sphingotec developed a portfolio of novel biomarkers, which predict the risks of obesity, breast cancer and cardiovascular diseases.

CONTACT:

Deborah Bergmann
Head of Marketing
+ 49 3302 20565 0
d.bergmann@sphingotec.de

Ruxandra Lenz
PR and Market Communications Manager
+ 49 3302 20565 0
lenz@sphingotec.de
www.sphingotec.de