Dipeptidyl Peptidase 3 (DPP3) cause of acute myocardial depression: sphingotec launches first IVD test for DPP3 on Nexus IB10 Point-of-Care platform
- sphingotec launched the very first CE-marked IVD assay for Dipeptidyl Peptidase 3 (DPP3), a novel biomarker able to assess outcomes in patients with cardiogenic shock at admission for further clinical validation through the critical care community
- IB10 sphingotest® DPP3 is now available on sphingotec’s proprietary automated Nexus IB10 point-of-care platform and quantitatively measures levels of circulating DPP3 in whole blood and plasma samples
- Data presented by Prof. Alexandre Mebazaa at ESC Congress 2019 in Paris provide evidence for a novel disease mechanism in which circulating DPP3 has a causal role in cardiac and renal dysfunction
- Further results presented by Prof. Mebazaa demonstrate that effects of pathological concentrations of DPP3 were immediately reversed in pre-clinical disease models upon injection of Procizumab, an anti-DPP3-antibody in preclinical development by 4TEEN4 Pharmaceuticals
- sphingotec has in-licensed global rights to distribute DPP3 on Nexus IB10 from 4TEEN4 Pharmaceuticals GmbH for diagnostic purposes in multiple indications
- The novel DPP3 test complements sphingotec’s portfolio of IVD tests for acute care biomarkers, including vascular function marker bio-ADM®and kidney function marker penKid®,designed to support decision making at ICUs and EDs
Paris, France, and Hennigsdorf/Berlin, Germany, August 31, 2019
- Diagnostics company SphingoTec GmbH (“sphingotec”, Hennigsdorf near Berlin, Germany) today launched IB10 sphingotest® DPP3, the first CE-IVD-marked point-of-care biomarker test able to quantify DPP3 blood-plasma levels, a novel and unique biomarker predicting outcomes in patients with cardiogenic shock at admission to intensive care units (ICUs). The DPP3 biomarker indicates angiotensin II and enkephalin signaling pathway disruptions leading to acute, short-term organ dysfunction. sphingotec will make the test initially available to the critical care community for further assessment of the clinical utility of the DPP3biomarkerin critical care settings. The assay is designed and validated for use with sphingotec’s fully automated Nexus IB10 whole blood point-of-care platform for rapid testing in laboratories, emergency departments and intensive care units together with a menu of standard critical care tests also available on the Nexus IB10 instrument.
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 today1,2.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.”
Takagi (2019) Circulating dipeptidyl-peptidase 3 and alteration in hemodynamics in cardiogenic shock: Results from the OptimaCC Trial, European Journal of Heart Failure
Deniau (2019) Circulating dipeptidyl peptidase-3 is a myocardial depressant factor: DPP3 inhibition rapidly and sustainably improves hemodynamics, European Journal of Heart Failure
gov NCT 01367743
gov NCT 1374867
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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® 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® bio-ADM®, an assay for bioactive Adrenomedullin, a unique biomarker for real-time assessment of vascular integrity, and IB10 sphingotest® penKid®, 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® bio-ADM® the assay for bioactive adrenomedullin, a unique biomarker for real-time assessment of vascular integrity in conditions like sepsis or congestive heart failure, sphingotest® penKid®, the assay for proenkephalin, a unique biomarker for real-time assessment of kidney function and sphingotest® 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.
• PenKid surpasses serum creatinine on Day 1 post-transplant in detecting delayed graft function (DGF), with an AUROC of 0.87 versus 0.56 for creatinine. • PenKid differentiates slow graft function (SGF) from DGF up to 8 days earlier than current methods, supporting more timely clinical decisions. • PenKid levels remain unaffected by kidney replacement therapy (KRT), allowing for more accurate assessment of kidney function. • Independent validation in transplant cohort from Australia confirms performance and broad applicability. Hennigsdorf/Berlin, Germany, July 1, 2025 - Diagnostic company SphingoTec GmbH (“SphingoTec”) announces a landmark study (1) published in Transplant International, led by Heidelberg University Hospital in Germany in collaboration with researchers from Sydney, Australia, which identifies Proenkephalin A 119-159 (penKid) as a reliable biomarker for early and precise assessment of graft function trajectories following kidney transplantation. The research demonstrates that PenKid not only identifies patients at risk for DGF significantly earlier than traditional markers but also distinguishes between slow and delayed graft function with remarkable accuracy, offering clinicians a valuable new tool for patient management. The study prospectively evaluated 159 consecutive kidney transplant recipients at Heidelberg University Hospital and validated findings in an independent cohort from Sydney. PenKid consistently outperformed serum creatinine (SCr) in predicting graft function trajectories, particularly in the critical early post-transplant period. Notably, PenKid’s ability to remain unaffected by KRT—a treatment for severe kidney dysfunction—further sets it apart from SCr, which can be influenced by non-renal factors and KRT itself, thereby enhancing the reliability of graft function assessment. Multivariate analysis confirmed PenKid as the strongest independent predictor of both short-term graft function and 30-day outcomes, underscoring its clinical utility for early risk stratification. The biomarker’s superior granularity allows for nuanced classification of DGF severity, supporting more informed decisions regarding the initiation of dialysis or biopsy and offering potential for individualized patient care. With these findings, penKid steps forward as a practical addition to the transplant clinician’s toolkit, promising to sharpen decision-making for optimal outcomes. Its adoption could help transplant teams act with greater confidence and precision, ultimately strengthening the standard of care in kidney transplantation. ## References 1. Benning L et al. (2025) Proenkephalin A 119-159 in Kidney Transplantation: A Novel Biomarker for Superior Tracking of Graft Function Trajectories. Transpl. Int. 38:14366. doi: 10.3389/ti.2025.14366 About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a biomarker company focusing on the out-licensing of innovative critical care solutions for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, commercially available on diagnostic platforms AFIAS and Nexus IB10 and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Discover more on www.sphingotec.com Contact : Ruxandra Lenz Marketing and Communication SphingoTec GmbH Phone +49-3302-20565-0 Email: press@sphingotec.com
• Boditech Med and SphingoTec announce the launch of the AFIAS sphingotest® penKid® assay, a diagnostic tool designed to aid in kidney function assessment for critically ill patients. • The IVDR-marked assay provides quantitative measurements of Proenkephalin A 119-159 (penKid), supporting clinical decision-making in acute and critical care. • This launch follows a licensing agreement granting Boditech the rights to develop and commercialize penKid-based assays, as well as a market development agreement between the two companies. Gangwon-do, Republic of Korea, and Hennigsdorf/Berlin, Germany, May 6, 2025 - Boditech Med Inc. (“Boditech”) and SphingoTec GmbH (“SphingoTec”) today announced the commercial launch of the AFIAS sphingotest® penKid® assay. The assay is designed to provide clinicians with a tool for assessing kidney function in critically ill patients by measuring Proenkephalin A 119-159 (penKid), a biomarker that reflects real-time kidney function independently of inflammation or comorbidities. The AFIAS sphingotest® penKid® assay is IVDR-marked for its intended use as an automated fluorescence immunoassay for the in vitro diagnostic quantitative determination of Proenkephalin A 119-159 in human whole blood/plasma, serving as an aid in the diagnosis of acute kidney injury (AKI) in adult patients with sepsis or septic shock. It provides additional information to support clinical decision-making in managing critically ill patients at risk of acute kidney injury (AKI). This launch is the result of a strategic collaboration between Boditech and SphingoTec, including a licensing agreement granting Boditech the rights to develop and commercialize penKid-based assays on its diagnostic platforms, as well as a market development agreement aimed at accelerating global commercialization efforts. Eui-Yul Choi, CEO of Boditech Med, commented: “We are proud to introduce the AFIAS sphingotest® penKid® assay to clinicians worldwide. This launch reflects our commitment to delivering innovative diagnostic solutions that address critical needs in healthcare. Our collaboration with SphingoTec has been instrumental in bringing this important tool to market.” Deborah Bergmann, CEO of SphingoTec, added: “The launch of AFIAS sphingotest® penKid® demonstrates how partnerships can drive innovation and improve access to advanced diagnostics. By combining our biomarker expertise with Boditech’s diagnostic capabilities, we are reaching a new chapter in our collaboration. We are streamlining our processes to support the business of our license partners and further expand our global reach. This enables us to provide clinicians with essential tools to enhance patient care.” Scientific insights on penKid PenKid is a biomarker that enables real-time assessment of kidney function (1). Unlike traditional markers such as serum creatinine, penKid levels are not influenced by inflammation or other confounding factors like age or sex (1,2,3). Studies have shown that penKid allows earlier detection of acute kidney injury (AKI), predicting changes in serum creatinine up to 48 hours before conventional diagnostic criteria are met (1,3). This early detection capability is particularly valuable in critically ill patients, including those with sepsis or septic shock (1,3,4). Additionally, penKid has shown potential for monitoring renal recovery under dialysis and could help predict successful weaning from renal replacement therapy (5,6). ## References 1. Hollinger A, et.al. Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study. Kidney Int Rep. 2018 Aug 22;3(6):1424-1433. doi: 10.1016/j.ekir.2018.08.006. 2. Beunders et al. Assessing GFR With Proenkephalin, Kidney International Reports, 2023, DOI: https://doi.org/10.1016/j.ekir.2023.08.006 3. Caironi et al., Circulating proenkephalin, acute kidney injury, and its improvement in patients with severe sepsis or shock. Clin Chem (2018) DOI:10.1373/clinchem.2018.288068 4. Moledina DG. Penkid: A Novel Biomarker of Reduced GFR in Sepsis. Kidney Int Rep. 2018 Nov 15;4(1):17-19. doi: 10.1016/j.ekir.2018.11.002. 5. von Groote T et al. Proenkephalin A 119–159 predicts early and successful liberation from renal replacement therapy in critically ill patients with acute kidney injury: a post hoc analysis of the ELAIN trial. Crit Care 26, 333 (2022). doi.org/10.1186/s13054-022-04217-4 6. von Groote T, et al. Evaluation of Proenkephalin A 119-159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury. Crit Care. 2023 Jul 10;27(1):276. doi: 10.1186/s13054-023-04556-w. About Boditech Boditech Med (based in Chuncheon, Gangwon-do, Republic of Korea) is a leading company in the field of point-of-care diagnostics, which has accumulated 25 years of business expertise in the field. The company has more than 80 types of in vitro diagnostic products that detect biomarkers related to infectious diseases, diabetes, cardiovascular diseases, cancer, and hormone-related diseases with its immunofluorescence lateral flow technology, quantitative immunofluorescence technology and spectrophotometric technology. And the list continues to grow with new high-value-added products. With its instrument platform installed in more than 120 countries, the company also has a stable revenue model. The company is currently strengthening its value as a global company by expanding its manufacturing bases in the US, China, India, and Indonesia. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) is a diagnostic company focusing on the out-licensing of innovative critical care biomarkers for diagnosing, predicting, and monitoring acute medical conditions. SphingoTec develops its biomarkers to the commercial stage and partners with IVD companies to make them available on different IVD platforms. SphingoTec's proprietary biomarker portfolio includes Proenkephalin A 119-159 (penKid), a biomarker for the assessment of kidney function in critical diseases, commercially available on diagnostic platforms AFIAS and Nexus IB10 and bioactive Adrenomedullin 1-52 (bio-ADM), a biomarker for the assessment of endothelial function in conditions like sepsis. Discover more on www.sphingotec.com Contact: Ruxandra Lenz Head of Marketing and Communication SphingoTec GmbH Phone +49-3302-20565-0 Email: press@sphingotec.com