Adrecizumab(AdrenoMed AG)

Patient population benefitting most from enibarcimab treatment in septic shock can clearly be defined by two biomarkers, as shown by data presented todayIn the AdrenOSS-2 trial, the respective patient subgroup had a statistically significant >60% relative reduction in 28-day mortality vs. placebo. Adrenomed is preparing a confirmatory trialEnibarcimab is targeting loss of vascular integrity, a previously unaddressed pathophysiological mechanism1Adrenomed presenting on individualized precision medicine treatment at the World Sepsis Day Event, Berlin, September 122 HENNIGSDORF, Germany and BERLIN, Sept. 08, 2023 (GLOBE NEWSWIRE) -- Adrenomed AG, the vascular integrity company, today announced new findings on the biomarker-guided treatment of septic shock with enibarcimab. New data analyses of the phase II clinical trial AdrenOSS-2 validate the precision medicine approach applied by Adrenomed in the development of its non-neutralizing antibody enibarcimab for the treatment of septic shock. It shows that the patient population benefitting most from enibarcimab can clearly be identified by the biomarkers Adrenomedullin (ADM) with elevated levels, and low levels of circulating dipeptidyl peptidase 3 (cDPP3). During the 11th Weimar Sepsis Update3, the data were presented in a scientific talk4 given today by Prof. Matthijs Kox, Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands, and in a poster presentation5 from the working group of critical care physician Prof. Peter Pickkers, Nijmegen. In preparation of a confirmatory clinical trial, the double-blind, randomized, placebo-controlled, biomarker-guided phase II trial AdrenOSS-2 (n = 301) included a prespecified analysis of the role of cDPP3 as a second biomarker (next to ADM) to exclude patients who are unlikely to respond to enibarcimab treatment. DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators. High levels of circulating DPP3 (cDPP3) indicate a high risk of organ dysfunction and mortality.6 This pathway is mechanistically independent from the loss of vascular integrity, which is known to be the main driver of mortality in septic shock and is indicated by elevated plasma levels of ADM (>70 pg/mL). Consequently, the aim of additional analyses was to investigate the impact of different cDPP3 levels on the treatment effect (28-day all-cause mortality) and to identify a suitable cut-off level. It was shown that the effect of enibarcimab on mortality improves with lower cDPP3 values and that the patients with elevated ADM, but non-elevated baseline cDPP3 (below the upper normal range, ≤ 30-50 ng/mL), benefitted the most from enibarcimab treatment.7 At 28 days, this patient subgroup had a statistically significant >60% relative reduction in mortality compared to placebo.8 Adrenomed’s CMO Dr. Stephan Witte commented: “We are very pleased with these findings. They underpin Adrenomed’s hypothesis that there is an interplay between baseline DPP3 levels and treatment effects of enibarcimab in patients with septic shock. After many failures with other potential treatments in development, the use of biomarkers for the identification of patients most likely to respond to treatment is the appropriate way towards an effective treatment. It is therefore a great confirmation of Adrenomed’s efforts to bring precision medicine – which has been long established in other disease areas like oncology – also to intensive care units to reduce patient heterogeneity and develop effective treatments.” Dr. Richard Jones, CEO of Adrenomed, added: “These compelling clinical data results, presented at this very important sepsis congress strongly enhance our belief that enibarcimab can make a real difference to saving or improving the lives of the many patients suffering from septic shock. The AdrenOSS-2 trial has marked an important step forward in bringing our precision medicine approach to patients. Adrenomed is now using these findings for the confirmatory development trial and subsequent marketing authorization of enibarcimab.” Adrenomed’s participation in further meetings: In addition to the Sepsis Update meeting in Weimar Adrenomed’s representatives can be met at the following events: (1) Dr. Joachim Struck, Head of Research & Development, Adrenomed AG, will talk about ”Precision Medicine in New Therapies for Septic Shock” at the World Sepsis Day Event which will be held on September 12, 2023, in Berlin and virtually.9 (2) David Germonpré, Chief Financial Officer of Adrenomed, will attend the 23rd Annual Biotech in Europe Forum (Sachs Conference) on September 20-21, 2023, in Basel, Switzerland. About AdrenomedAdrenomed AG is a German privately financed, clinical-stage biopharmaceutical company. Adrenomed’s mission is to rescue vascular integrity in order to save the lives of critically ill patients with limited treatment options. Founded in 2009 by a management team with decades of in-depth experience in sepsis and deep knowledge in diagnostics and drug development, the company’s lead product candidate enibarcimab (formerly adrecizumab) is a first-in-class non-blocking monoclonal antibody. Enibarcimab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Enibarcimab has successfully completed a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial with 301 patients suffering from septic shock. For further information, please visit www.adrenomed.com and follow us on LinkedIn and Twitter. Contact Adrenomed AGMartina Kalle-Brune, Ph.D.phone: +49 (0)3302 207780bd@adrenomed.com Media Inquiries MC Services AGEva Bauer / Julia von Hummelphone: +49 (0)89 2102280adrenomed@mc-services.eu _________________ References: 1 Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. Shah FA et al. Am J Respir Crit Care Med. 2021 Oct 15;204(8):891-901.2 World Sepsis Day Event 2023, Sept. 12, 2023, 18:00 h: “Precision medicine in new therapies for septic shock”, Joachim Struck, Adrenomed, Germany.3 11th Weimar Sepsis Update of the German Sepsis Society (GSS), Weimar (Germany), Sept. 6-8, 2023.4 11th Weimar Sepsis Update, Session 10 Immunmodulation – advances and adaptions 3, Lecture “Non-neutralizing adrenomedullin antibody”, Matthijs Kox, Nijmegen, Netherlands.5 11th Weimar Sepsis Update, Poster Session 2: Clinical Sepsis / COVID-19 Research – Therapy, Poster “Biomarker-guided treatment of septic shock with enibarcimab – cut-off selection to overcome patient heterogenicity”.6 https://doi.org/10.1186/s13054-021-03471-2.7 https://doi.org/10.3389/fmed.2022.1058235.8 Van Lier D., Knothe C., Struck J., Witte S., Pickkers P. “Biomarker-guided treatment of septic shock with enibarcimab – cut-off selection to overcome patient heterogenicity”, 11th Weimar Sepsis Update, Poster Session 2023.9 WSD Event 2023 — World Sepsis Day – September 13 (attendance is free of charge, sign-up here).

Innovative biomarkers open new avenues for precision medicine approaches in treating acute and critical diseases that need differentiation of the underlying pathophysiology. Physicians from Europe, Canada, and the USA explore the role of biomarkers in the leap from a "one-fits-all"-treatment to a personalized approach based on the patient's characteristics. International medical leaders discuss ways to successfully implement biomarkers penKid, bio-ADM and DPP3 from research into routine clinical practice. HENNIGSDORF, GERMANY / ACCESSWIRE / August 8, 2022 / The diagnostics company SphingoTec GmbH (SphingoTec), announces that, during the 4th Scientific Symposium held near Potsdam, Germany, international medical experts discussed the latest developments in diagnostic and therapeutic innovations for advancing precision medicine in critically ill patients. The approach encompasses organ-specific biomarkers working hand in hand with drug candidates and existing therapies to improve the management of diseases such as sepsis and septic shock, acute kidney injury, COVID-19, and cardiogenic shock. The successful transition of the biomarkers from research to clinical routine is an important step that was addressed by current routine users. Biomarkers from research to clinical practice Acute kidney injury (AKI) affects 1 in 3 ICU patients. Since the therapeutical options are limited, the focus lies in managing the symptoms and avoiding the progression of AKI. However, current diagnostics are too late and insensitive, thus resulting in a limited intervention window. Prof. Peter Pickkers, Head of research in Intensive Care Medicine at Radboud University Nijmegen Medical Centre, explained "In AKI we need to bring the diagnostic clock before the current clinical clock to avoid further organ dysfunction. Proenkephalin A 119 - 159 (penKid) is a kidney function biomarker with more swift kinetics that strongly correlates with the actual glomerular filtration rate (GFR). It allows to detect a change in kidney function more than 24 hours earlier compared to the current diagnostic standard creatinine. We have confirmed these findings by developing a formula for estimating the GFR using penKid. After measuring penKid against complex and invasive reference diagnostics and comparing it to existing formulas for kidney function, we have seen a superior performance of the new penKid model." Notably, the biomarker penKid shows good kinetics in both adults and children (1,3). It is earlier than the current standard of care, and its property of not being influenced by muscle mass, inflammation and common comorbidities allows for monitoring the patient's condition, especially in critical care (2, 3). Scientists and routine users of penKid highlighted the potential to predict AKI development and recovery, as well as the need for renal replacement therapy (RRT) (3), which are unique features for a kidney biomarker (4, 5). Prof. Gernot Marx, Clinic Director of the University Hospital RWTH Aachen, comments: "We have made the first steps in translating scientific research into clinical practice. Measuring penKid in the morning routine required a change of our procedure and the alignment of all teams. Once established, we have seen immediate benefits in our daily practice that range from better risk stratification to early identification of worsening and improvement of renal function. The potential of this biomarker has not yet been fully exploited, therefore we are currently focused on better understanding the benefits for patients under RRT." Precision medicine relies on biomarkers for a targeted approach Not only diagnosing but also treating patients correctly can be a major challenge, especially if the underlying mechanisms of a disease vary and require different therapies. This is the case, for example, with sepsis, a disease that encompasses a very heterogeneous group of patients, making the discovery of new therapies very challenging. The biomarkers bioactive adrenomedullin (bio-ADM) and dipeptidyl peptidase 3 (DPP3) distinguish between two independent etiologies of septic shock (6). This facilitates the identification of separate homogenous groups of shock patients with the respective pathological mechanisms. Prof. Alexandre Mebazaa, Head of the Department of Anesthesia and Critical Care Medicine at Lariboisière, Paris stated "The biomarkers bio-ADM and DPP3 are biologically active. This means they can be both, biomarkers that point at different pathophysiologies of sepsis, but also biotargets for new drug candidates that modulate their activity, allowing specific treatment of respective disease mechanisms." Bio-ADM identifies patients with endothelial dysfunction causing vascular leakage, which escalates into shock and organ dysfunction. The medical experts discussed the latest findings on Adrecizumab, a new promising clinical late-stage drug candidate developed by Adrenomed AG, that targets endothelial barrier dysfunction (7, 8). A separate disease mechanism, leading to hemodynamic instability and shock in sepsis, is the depletion of angiotensin II. DPP3, a biomarker that causes this depletion has been proposed to identify patients who may not be able to develop a positive treatment effect due to the different pathophysiology, thus excluding them from the respective clinical trials. Apart from the use of DPP3 as an enrichment tool for clinical trials, the modulation of DPP3 activity by the antibody Procizumab, a new drug candidate developed by 4TEEN4 Pharmaceuticals, has been discussed (9). Beyond sepsis and septic shock, the identified pathophysiologies could be of relevance in other distinct major mortality drivers such as COVID-19 (10) and cardiogenic shock (11). Dr. Andreas Bergmann, the founder of the three companies SphingoTec, Adrenomed, and 4TEEN4, summarizes: "During the symposium, we have shared the same vision with prestigious representatives of the critical care community: bringing personalized medicine in critical care to the same level the colleagues in oncology have succeeded. At the core of this endeavor are biomarkers that guide clinical decision making and support the development of new therapies. Now SphingoTec's biomarkers are well positioned for the adoption in clinical routine, laying a strong basis for "precision medicine"." References: 1. Hartman et al, Proenkephalin as a New Biomarker for Pediatric Acute Kidney Injury - Reference Values and Performance in Children Under One Year of Age, Clin Chem Lab Med, 2020; doi: 10.1515/cclm-2020-0381. 2. Kim et al. Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients with Sepsis. Ann Lab Med. 2020;40(6):466-73 3. Caironi P, Latini R, Struck J, Hartmann O, Bergmann A, Bellato V, Ferraris S, Tognoni G, Pesenti A, Gattinoni L, Masson S; ALBIOS Study Investigators. Circulating Proenkephalin, Acute Kidney Injury, and Its Improvement in Patients with Severe Sepsis or Shock. Clin Chem. 2018 Sep;64(9):1361-1369. 4. Khorashadi M, Beunders R, Pickkers P, Legrand M: Proenkephalin: A New Biomarker for Glomerular Filtration Rate and Acute Kidney Injury. Nephron 2020;144:655-661. Doi: 10.1159/000509352 5. Hollinger 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; doi: 10.1016/j.ekir.2018.08.006 6. van Lier (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 7. 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. 8. Geven et al, Effects of the Humanized Anti-Adrenomedullin Antibody Adrecizumab (HAM8101) on Vascular Barrier Function and Survival in Rodent Models of Systemic Inflammation and Sepsis. Shock. 2018 Dec;50(6):648-654. Doi: 10.1097/SHK.0000000000001102. 9. Deniau et al, Circulating dipeptidyl peptidase 3 is a myocardial depressant factor: dipeptidyl peptidase 3 inhibition rapidly and sustainably improves haemodynamics. Eur J Heart Fail, 2020; 22: 290-299. Doi: 10.1002/ejhf.1601 10. Clinicaltrials.gov/ct2/show/NCT05156671 11. Takagi K, Blet A, Levy B, Deniau B, Azibani F, Feliot E, Bergmann A, Santos K, Hartmann O, Gayat E, Mebazaa A, Kimmoun A. Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial. Eur J Heart Fail. 2020 Feb;22(2):279-286. About SphingoTec SphingoTec GmbH ("SphingoTec"; Hennigsdorf near Berlin, Germany) develops and markets innovative in vitro diagnostic (IVD) tests for novel and proprietary biomarkers for the diagnosis, prediction, and monitoring of critical medical conditions. SphingoTec's proprietary biomarker portfolio includes bioactive Adrenomedullin (bio-ADM), a biomarker for real-time assessment of endothelial function in conditions like sepsis, and Proenkephalin (penKid), a biomarker for real-time assessment of kidney function. Dipeptidyl Peptidase 3 (DPP3) is a biomarker for cardiac depression, in-licensed from 4TEEN4 Pharmaceuticals GmbH ( ). IVD tests for SphingoTec's biomarkers are made available as sphingotest® microtiter plate tests as well as point-of-care tests on the Nexus IB10 immunoassay platform by SphingoTec's subsidiary Nexus Dx Inc. (San Diego, CA, USA). The Nexus IB10 portfolio is complemented by established and commonly used biomarker tests for acute and critical care such as PCT, Troponin, NT-proBNP, D-Dimer, TSH and others. Media contact: Dr. Ulrike Glaubitz Senior Public Relations Specialist SphingoTec GmbH Neuendorfstr. 15 A 16761 Hennigsdorf Tel. +49-3302-20565-113 SOURCE: SphingoTec GmbH View source version on accesswire.com: