Journal of Critical Care publishes positive results from prespecified, biomarker-guided subgroup analysis of AdrenoMed’s Phase II AdrenOSS-2 trial in septic shock

Press Release

Journal of Critical Care publishes positive results from prespecified, biomarker-guided subgroup analysis of AdrenoMed’s Phase II AdrenOSS-2 trial in septic shock

• Precision medicine approach: Targeted treatment using two biomarkers (bio-ADM and DPP3) identifies septic shock patients most likely to benefit from enibarcimab treatment
• Promising clinical results: Peer-reviewed data show enibarcimab improves organ function and reduces 28-day mortality in targeted patient groups
• Future clinical development: Phase IIb/III BOOST trial will build on this targeted strategy to maximize enibarcimab’s effectiveness by addressing the root cause of septic shock

Hennigsdorf / Berlin (Germany), May 20, 2025 – AdrenoMed AG, the vascular integrity company, announced today that positive results from a prespecified subgroup analysis of its biomarker-guided, double-blind, placebo-controlled Phase II trial AdrenOSS-2 were published in a peer-reviewed Letter in the Journal of Critical Care.[1] This prespecified subgroup analysis from the AdrenOSS-2 trial revealed the strong signal of AdrenoMed’s drug candidate enibarcimab in reducing mortality in septic shock patients who were identified with the precision medicine approach utilizing two biomarkers, one for inclusion of patients (adrenomedullin, ADM) and one for exclusion of patients (dipeptidyl peptidase 3, DPP3).

Increasingly, sepsis is understood not as a single disease, but as a multifactorial syndrome with a complex underlying pathophysiology, involving different pathways that may lead to the development and progression of septic shock. Two major disease pathways can be characterized by the independent biomarkers ADM and DPP3. While elevated bio-ADM levels reflect endothelial barrier dysfunction and may be susceptible to treatment with the antibody, patients with elevated levels of DPP3 suffer from a different septic shock pathology that cannot be addressed by treatment with the ADM-antibody enibarcimab.[2] Correspondingly, the prespecified subgroup analysis included patients with elevated bio-ADM and excluded patients with high DPP3 levels for the efficacy endpoints of 28-day all-cause mortality and SOFA score before unblinding. In patients with high bio-ADM (>70 pg/mL) and low DPP3 levels (<70 ng/mL) (n=128), treatment with enibarcimab led to a pronounced improvement in organ function and a reduction in mortality compared to placebo (n=141). Specifically, the Sequential Organ Failure Assessment (SOFA) score improved over seven days, with a between-group difference of 1.33 points (p=0.006) in favor of enibarcimab. Moreover, the 28-day mortality rate was 18% in the enibarcimab group compared to 26% in the placebo group, corresponding to a hazard ratio of 0.65.

Corresponding author Prof. Dr. Peter Pickkers, Professor of Experimental Intensive Care Medicine at Radboud University Nijmegen Medical Centre, commented: “For too long, sepsis treatment has relied on a one-size-fits-all approach, failing to account for the complexity of this multifactorial condition. This prespecified subgroup analysis from the AdrenOSS-2 trial demonstrates that combining biomarkers results in pronounced enrichment as it identifies the patients in septic shock who will likely experience the best treatment efficacy of enibarcimab. These highly promising findings warrant advancing this drug candidate to a pivotal trial, with the goal of ultimately delivering a much-needed therapy that targets the underlying pathophysiology of this devastating disease.”

Dr. Stephan Witte, Chief Medical Officer of AdrenoMed, remarked: “These results highlight the critical value of a biomarker-guided precision medicine approach in sepsis. By stratifying patients based on both bio-ADM and DPP3 levels, we can more effectively target those most likely to benefit from our causal therapy. These data form a strong foundation for our ongoing clinical development, and I’m pleased to see them now published in the Journal of Critical Care. We are looking forward to initiating our confirmatory BOOST trial, that aims to validate the observed reduction in septic shock mortality as the basis for a future marketing authorization application.”

Additional exploratory analyses further support the link between biomarker levels and enibarcimab efficacy. Based on the combined findings from the AdrenOSS-2 Phase II trial, AdrenoMed has designed the confirmatory BOOST clinical trial, applying a precision medicine approach to obtain efficacy data to support a future marketing authorization application. Even with best standard of care, the mortality rate for septic shock patients is still 30-50%. Enibarcimab holds the potential to significantly improve this outcome.
 

About enibarcimab

Enibarcimab (formerly known as Adrecizumab) is a humanized, non-neutralizing monoclonal antibody targeting adrenomedullin (ADM), a key regulator of vascular integrity. By binding to ADM, enibarcimab increases plasma levels of bioactive ADM, enhancing its beneficial effects on endothelial function and counteracting sepsis-induced vascular leakage. Designed as a first-in-class therapy, enibarcimab aims to restore vascular integrity in patients with septic shock, addressing one of the critical pathophysiological mechanisms contributing to organ failure and mortality. Enibarcimab is being developed with a precision medicine approach, guided by biomarker-based patient selection strategies.

About AdrenOSS-2

AdrenOSS-2 was a Phase II, double-blind, placebo-controlled, randomized, multicenter clinical trial (n=301) designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of enibarcimab in patients with early septic shock. The study incorporated a biomarker-guided enrichment strategy, selecting patients based on elevated concentrations of bioactive adrenomedullin (bio-ADM), a marker of endothelial dysfunction. A prespecified subgroup analysis further stratified patients by introducing dipeptidyl peptidase 3 (DPP3) as a second biomarker to exclude individuals unlikely to respond to enibarcimab treatment. DPP3 is a cytosolic enzyme involved in the degradation of various cardiovascular and endorphin mediators, with elevated levels indicating a high risk of organ dysfunction and mortality. This pathological pathway is mechanistically distinct from the loss of vascular integrity — the primary driver of mortality in septic shock — which is reflected by elevated plasma levels of bio-ADM (>70 pg/mL).

About AdrenoMed

AdrenoMed 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.

^[1]  Knothe C, Witte S, Bergmann A, Mebazaa A, Laterre PF, Pickkers P. Enibarcimab for the treatment of septic shock in patients selected by a combination of the biomarkers bio-ADM and DPP3: A prespecified subgroup analysis of the AdrenOSS-2 trial. J Crit Care 2025; Apr 10:88:155077. https://doi.org/10.1016/j.jcrc.2025.155077

^[2]  Kim H, Hur M, Struck J, Bergmann A, Di Somma S. Circulating biologically active Adrenomedullin predicts organ failure and mortality in Sepsis. Ann Lab Med 2019; 39(5):454–63. DOI: 10.3343/alm.2019.39.5.454