Endothelial disruption: Rapid translation from bench to bedside
Hennigsdorf, Germany 25. January 2019 -
bio-ADM, the very first blood biomarker capable to diagnose when blood vessels become leaky (endothelial dysfunction), is set to make a rapid carrier at intensive care units (ICUs) and emergency departments (EDs) of hospitals. Data from pilot clinical routine testing presented at the 2nd Scientific Symposium on Endothelial Disruption (18. December 2018) in Berlin impressively confirmed results from previous tests on 30,000 patients with acute heart failure (AHF) and severe sepsis indicating that bio-ADM testing improves medical decision making to prevent mortality, organ damage and re-hospitalization. An automated point-of- care (POC) test measuring bio-ADM both as a biomarker and as a companion diagnostic to a therapeutic antibody (Adrecizumab) that repairs endothelial dysfunction, will be launched by H1/2019 by SphingoTec GmbH. However, bio- ADM is just the first representative of a full pipeline of diagnostic blood proteins reflecting disturbed signaling pathways underlying disorders of unmet medical need.
Late in 2017, key opinion leaders (KOLs) in the field of heart failure (AHF) and sepsis presented data supporting that elevated levels of the vasoactive peptide hormone Adrenomedullin (ADM) indicate when blood vessels become leaky and that such endothelial dysfunction precedes bad outcomes in congestive heart failure (AHF) and septic shock. New clinical data presented at the 2nd Scientific Symposium on Endothelial Disruption (18 December 2018, Berlin, Germany) demonstrated that the first diagnostic test measuring the biologically active form of Adrenomedullin (sphingotest® bio-ADM®, SphingoTec GmbH, Hennigsdorf, Germany) is on a good way to be translated to bedside very rapidly as key opinion leaders at the meeting confirmed actionable clinical utility of bio- ADM testing in sepsis and AHF.
From clinical trials to routine testing
New data on pilot routine testing of bio-ADM in patients with sepsis presented at the meeting in Berlin suggest that the new diagnostic concept could enter broader routine testing very soon. According to representative case studies, elevated blood levels of bio-ADM at admission, which remained high, were a strong predictor for mortality. Daily monitoring of bio-ADM levels identified the outcome and response to therapy in sepsis patients: if bio-ADM levels remained high or rose above the cut-off value of 70 pg/ml, patients died. When bio-ADM levels dropped below the cut-off, patients survived. Even when inflammation biomarkers such as PCT or CRP pointed to recovery, high bio-ADM levels were an independent predictor of bad outcome and non-response to therapy, the study leaders told European Biotechnology pointing to the need of those patients to receive immediate critical care. The medical interest was to generate data from clinical practice and translate them into therapy decisions, they said. Routine tests with more patients, even in AHF, are currently in planning.
Automated test to be launched in H1/2019
While the routine testing was conducted with a manual version of a bio-ADM sandwich immunoassay (see photo), confirmatory data may be generated with a fully automated test that runs on the established Nexus IB 10 point-of-care (POC) testing platform of German SphingoTec GmbH. The company announced at the meeting that it will launch such a fully automated bio-ADM test particularly suited to the needs of ICUs and EDs in H1/2019 latest. Nexus IB 10 is a market-established microfluidic POC testing platform currently used by over 1,000 hospitals including ICUs/EDs that allows measurement of a test panel of up to five acute care blood biomarkers.
Academic leaders in emergency medicine reported further progress regarding clinical utility with the biomarker of endothelial dysfunction. Several lectures in Berlin confirmed the diagnostic and therapeutic utility of bio-ADM monitoring of therapy response. “In septic shock patients, bio-ADM levels reflect the pathophysiological relaxation of vascular tone 1-2 days before clinical signs of shock appear”, stressed Prof. Dr. Salvatore Di Somma, Head of Emergency Medicine (ED) at University La Sapienza, Rome. According to Di Somma, data from a clinical multicenter study on approx. 1,000 sepsis patients (ALBIOS) admitted to the ED demonstrated that plasma bio-ADM levels increased with the severity of disease, correlated with the requirement for intensive care such as immediate vasopressor therapy and 28-day mortality rate. Di Somma confirmed that, “serial measurement of bio-ADM may add important information to levels measured at admission”. Almost 100% of sepsis patients with high bio-ADM levels at admission whose bio-ADM blood level dropped below 70 pg bio- ADM/ml blood 4 days post-admission survived.
Medical utility in AHF patients
According to further data presented at the meeting, bio-ADM testing also cuts time to diagnosis and appropriate treatment in the medically underserved area of congestive acute heart failure (AHF). “Monitoring of this biomarker of endothelial dysfunction can inform clinical decision making in order to reduce patients’ mortality, in-hospital length of stay and re-hospitalization rate,” stressed Di Somma pointing to results of multi-center studies that proved that bio-ADM levels identified patients with residual congestion before discharge – a main cause of mortality, kidney damage, and re-hospitalization of AHF patients.
“The issue in heart failure is congestion and thus the identification of patients that require immediate diuretic therapy”, explained heart failure biomarker and critical care expert Prof. Dr. Alexandre Mebazaa (Head AP-HP, Hôpital Lariboisière Paris) pointing to data from a meta-analysis of studies on 3,000 patients with acute heart failure in which elevated bio-ADM levels at admission preceded development of life-threatening pulmonary edema and/or interstitial edema. Data from PD Dr. Hans-Dirk Duengen proved that elevated/rising bio- ADM levels identified high-risk patients with worsening heart failure requiring immediate diuretic therapy. He supported Di Somma’s view that bio-ADM monitoring might help to support discharge decisions in acute heart failure by diagnosing residual congestion.
Enhancing medical utility by therapeutic targeting of bio-ADM
Speaking in Berlin, Prof. Dr. Pierre François Laterre, St Luc Hospital, Brussels, told European Biotechnology that bio-ADM testing definitely provides an added value to sepsis patients, as the biomarker determines the amount of vasopressors needed by sepsis patients early in the process, and thus helps prevent bad outcomes. In AHF patients, bio-ADM was the first blood biomarker capable to diagnose residual congestion prior to discharge of AHF patients that did not sufficiently respond to diuretic therapy resulting in re-hospitalization, death and kidney damage, he said.
Laterre added that medical utility of diagnostic bio-ADM monitoring is set to improve in the future. A clinical Phase II trial assessing efficacy of Adrecizumab, a therapeutic antibody targeting bio-ADM, conducted by Laterre, will have Phase II read-out in sepsis patients this summer. The target is reduction of mortality in 300 sepsis patients with bad prognosis as identified by a bio-ADM level above 70 pg /ml at admission. This would qualify bio-ADM as companion diagnostic to targeted antibody therapy resolving endothelial dysfunction
According to data published in 2018, Adrecizumab binds Adrenomedullin at its C-terminus and does not affect receptor-binding and subsequent cAMP signaling, which had been previously shown to support vascular integrity and block vascular leakage. Adrecizumab thus repairs endothelial dysfunction, providing a targeted therapy to improve outcomes both in sepsis but also in AHF.
According to preclinical and Phase I data provided by Tobias Schürholz (University Rostock) and the group of Peter Pickkers (University Nijmegen), binding to Adrecizumab additionally protects bio-ADM from proteolytic degradation thus improving the half-life of the vasoactive peptide hormone in blood.
A Phase II trial will start enrollment of 300 AHF patients this year to evaluate the clinical safety and efficacy of Adrecizumab in patients with AHF.
Experts such as Dr. Allan Jaffe from Mayo Clinic in Rochester or Prof. Dr. Michael Bauer from University Jena, stressed that bio-ADM as a companion diagnostic would enable an optimal therapy choice both in sepsis as well as in patients with congestive heart failure.
A new way of personalized medicine
According to serial entrepreneur Dr. Andreas Bergmann, founder of sphingotec and Adrenomed, bio-ADM is just the first in a series of blood biomarkers/therapeutic targets set to improve outcomes in medically underserved conditions. “Our strategy is to identify protein biomarkers indicating severe medical disorders in the blood of patients. These biomarkers enable us to look for potential therapeutic targets and validate if these have an effect on humans following the blood biomarker read-out.” Bergmann, who co- founded and sold BRAHMS AG for €330M to Thermo Fisher Scientific, said his companies have the financial freedom to quit unsuccessful projects early and follow just the best approach that adds value to current medical standards. “We are thus delighted about the positive feedback from the scientific community on our bio-ADM approach”, commented Bergmann the outcome of the symposium.
Late in 2017, key opinion leaders (KOLs) in the field of heart failure (AHF) and sepsis presented data supporting that elevated levels of the vasoactive peptide hormone Adrenomedullin (ADM) indicate when blood vessels become leaky and that such endothelial dysfunction precedes bad outcomes in congestive heart failure (AHF) and septic shock. New clinical data presented at the 2nd Scientific Symposium on Endothelial Disruption (18 December 2018, Berlin, Germany) demonstrated that the first diagnostic test measuring the biologically active form of Adrenomedullin (sphingotest® bio-ADM®, SphingoTec GmbH, Hennigsdorf, Germany) is on a good way to be translated to bedside very rapidly as key opinion leaders at the meeting confirmed actionable clinical utility of bio- ADM testing in sepsis and AHF.
From clinical trials to routine testing
New data on pilot routine testing of bio-ADM in patients with sepsis presented at the meeting in Berlin suggest that the new diagnostic concept could enter broader routine testing very soon. According to representative case studies, elevated blood levels of bio-ADM at admission, which remained high, were a strong predictor for mortality. Daily monitoring of bio-ADM levels identified the outcome and response to therapy in sepsis patients: if bio-ADM levels remained high or rose above the cut-off value of 70 pg/ml, patients died. When bio-ADM levels dropped below the cut-off, patients survived. Even when inflammation biomarkers such as PCT or CRP pointed to recovery, high bio-ADM levels were an independent predictor of bad outcome and non-response to therapy, the study leaders told European Biotechnology pointing to the need of those patients to receive immediate critical care. The medical interest was to generate data from clinical practice and translate them into therapy decisions, they said. Routine tests with more patients, even in AHF, are currently in planning.
Automated test to be launched in H1/2019
While the routine testing was conducted with a manual version of a bio-ADM sandwich immunoassay (see photo), confirmatory data may be generated with a fully automated test that runs on the established Nexus IB 10 point-of-care (POC) testing platform of German SphingoTec GmbH. The company announced at the meeting that it will launch such a fully automated bio-ADM test particularly suited to the needs of ICUs and EDs in H1/2019 latest. Nexus IB 10 is a market-established microfluidic POC testing platform currently used by over 1,000 hospitals including ICUs/EDs that allows measurement of a test panel of up to five acute care blood biomarkers.
Academic leaders in emergency medicine reported further progress regarding clinical utility with the biomarker of endothelial dysfunction. Several lectures in Berlin confirmed the diagnostic and therapeutic utility of bio-ADM monitoring of therapy response. “In septic shock patients, bio-ADM levels reflect the pathophysiological relaxation of vascular tone 1-2 days before clinical signs of shock appear”, stressed Prof. Dr. Salvatore Di Somma, Head of Emergency Medicine (ED) at University La Sapienza, Rome. According to Di Somma, data from a clinical multicenter study on approx. 1,000 sepsis patients (ALBIOS) admitted to the ED demonstrated that plasma bio-ADM levels increased with the severity of disease, correlated with the requirement for intensive care such as immediate vasopressor therapy and 28-day mortality rate. Di Somma confirmed that, “serial measurement of bio-ADM may add important information to levels measured at admission”. Almost 100% of sepsis patients with high bio-ADM levels at admission whose bio-ADM blood level dropped below 70 pg bio- ADM/ml blood 4 days post-admission survived.
Medical utility in AHF patients
According to further data presented at the meeting, bio-ADM testing also cuts time to diagnosis and appropriate treatment in the medically underserved area of congestive acute heart failure (AHF). “Monitoring of this biomarker of endothelial dysfunction can inform clinical decision making in order to reduce patients’ mortality, in-hospital length of stay and re-hospitalization rate,” stressed Di Somma pointing to results of multi-center studies that proved that bio-ADM levels identified patients with residual congestion before discharge – a main cause of mortality, kidney damage, and re-hospitalization of AHF patients.
“The issue in heart failure is congestion and thus the identification of patients that require immediate diuretic therapy”, explained heart failure biomarker and critical care expert Prof. Dr. Alexandre Mebazaa (Head AP-HP, Hôpital Lariboisière Paris) pointing to data from a meta-analysis of studies on 3,000 patients with acute heart failure in which elevated bio-ADM levels at admission preceded development of life-threatening pulmonary edema and/or interstitial edema. Data from PD Dr. Hans-Dirk Duengen proved that elevated/rising bio- ADM levels identified high-risk patients with worsening heart failure requiring immediate diuretic therapy. He supported Di Somma’s view that bio-ADM monitoring might help to support discharge decisions in acute heart failure by diagnosing residual congestion.
Enhancing medical utility by therapeutic targeting of bio-ADM
Speaking in Berlin, Prof. Dr. Pierre François Laterre, St Luc Hospital, Brussels, told European Biotechnology that bio-ADM testing definitely provides an added value to sepsis patients, as the biomarker determines the amount of vasopressors needed by sepsis patients early in the process, and thus helps prevent bad outcomes. In AHF patients, bio-ADM was the first blood biomarker capable to diagnose residual congestion prior to discharge of AHF patients that did not sufficiently respond to diuretic therapy resulting in re-hospitalization, death and kidney damage, he said.
Laterre added that medical utility of diagnostic bio-ADM monitoring is set to improve in the future. A clinical Phase II trial assessing efficacy of Adrecizumab, a therapeutic antibody targeting bio-ADM, conducted by Laterre, will have Phase II read-out in sepsis patients this summer. The target is reduction of mortality in 300 sepsis patients with bad prognosis as identified by a bio-ADM level above 70 pg /ml at admission. This would qualify bio-ADM as companion diagnostic to targeted antibody therapy resolving endothelial dysfunction
According to data published in 2018, Adrecizumab binds Adrenomedullin at its C-terminus and does not affect receptor-binding and subsequent cAMP signaling, which had been previously shown to support vascular integrity and block vascular leakage. Adrecizumab thus repairs endothelial dysfunction, providing a targeted therapy to improve outcomes both in sepsis but also in AHF.
According to preclinical and Phase I data provided by Tobias Schürholz (University Rostock) and the group of Peter Pickkers (University Nijmegen), binding to Adrecizumab additionally protects bio-ADM from proteolytic degradation thus improving the half-life of the vasoactive peptide hormone in blood.
A Phase II trial will start enrollment of 300 AHF patients this year to evaluate the clinical safety and efficacy of Adrecizumab in patients with AHF.
Experts such as Dr. Allan Jaffe from Mayo Clinic in Rochester or Prof. Dr. Michael Bauer from University Jena, stressed that bio-ADM as a companion diagnostic would enable an optimal therapy choice both in sepsis as well as in patients with congestive heart failure.
A new way of personalized medicine
According to serial entrepreneur Dr. Andreas Bergmann, founder of sphingotec and Adrenomed, bio-ADM is just the first in a series of blood biomarkers/therapeutic targets set to improve outcomes in medically underserved conditions. “Our strategy is to identify protein biomarkers indicating severe medical disorders in the blood of patients. These biomarkers enable us to look for potential therapeutic targets and validate if these have an effect on humans following the blood biomarker read-out.” Bergmann, who co- founded and sold BRAHMS AG for €330M to Thermo Fisher Scientific, said his companies have the financial freedom to quit unsuccessful projects early and follow just the best approach that adds value to current medical standards. “We are thus delighted about the positive feedback from the scientific community on our bio-ADM approach”, commented Bergmann the outcome of the symposium.
• 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