Adrenomed presents new findings on its precision medicine treatment for septic shock with enibarcimab during Weimar Sepsis Update

• Patient population benefitting most from enibarcimab treatment in septic shock can clearly be defined by two biomarkers, as shown by data presented today
• In 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 trial
• Enibarcimab is targeting loss of vascular integrity, a previously unaddressed pathophysiological mechanism^[1]
• Adrenomed presenting on individualized precision medicine treatment at the World Sepsis Day Event, Berlin, September 12^[2]

Hennigsdorf/Berlin (Germany), September 8, 2023 – 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 11^th Weimar Sepsis Update^[3], the data were presented in a scientific talk^[4] given today by Prof. Matthijs Kox, Department of Intensive Care Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands, and in a poster presentation^[5] 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 23^rd Annual Biotech in Europe Forum (Sachs Conference) on September 20-21, 2023, in Basel, Switzerland.

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 and Twitter.

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]  11^th 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).}