Efficacy Data from Adrenomed's AdrenOSS-2 Phase II trial evaluating Adrecizumab (HAM8101) in Septic Shock presented at DIVI

DGAP-News: Adrenomed AG / Key word(s): Study results
02.12.2020 / 16:00
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Efficacy Data from Adrenomed's AdrenOSS-2 Phase II trial evaluating Adrecizumab (HAM8101) in Septic Shock presented at DIVI

- Treatment of septic shock patients with Adrecizumab resulted in significant and sustained mortality reduction most pronounced in early treated patients

- Adrecizumab, a product candidate for personalized treatment of septic shock, addresses loss of vascular integrity, a major driver of the highly dynamic condition

Hennigsdorf/Berlin (Germany), December 2, 2020 - Adrenomed AG, the vascular integrity company, announced that post-hoc analysis data from its AdrenOSS-2 trial was presented today during the Annual Congress of DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), December 2-4, 2020. The biomarker-guided Phase II clinical trial evaluated Adrecizumab (HAM8101) in 301 patients with septic shock suffering from loss of vascular integrity.

"Sepsis is a multifactorial clinical syndrome with an extremely dynamic clinical course and is very diverse with respect to potential treatment responses," explained Prof. Tobias Schürholz, MD, PhD, Lead of Perioperative Intensive Care at the University Hospital Rostock. "For this analysis, patient characteristics and biomarkers were used to stratify septic shock patients according to their individual condition and to identify the patients who benefited most from a tailored therapeutic intervention with Adrecizumab."

In the biomarker-guided post-hoc analysis, in particular early treatment with Adrecizumab after ICU admission resulted in a significant and fast improvement of mean fluid balance, a surrogate endpoint for vascular leakage. Within 24 hours, Adrecizumab led to a significant and sustained improvement of systemic organ function (SOFA score). Subsequently, the relative mortality was significantly reduced by more than 50% after day 28 which persisted over 90 days.

"These findings strongly support Adrecizumab's mode of action: By restoring and maintaining the endothelial barrier function, Adrecizumab prevents vascular leakage, and thereby supports organ function and improves survival. We are the first to treat endothelial dysfunction, a major disease pathway of sepsis and septic shock, in a targeted approach. A precision medicine concept is urgently needed for sepsis, a multicomplex condition with high unmet medical need. We are looking forward to further develop a personalized treatment with Adrecizumab in sepsis," said Dr. Andreas Bergmann, Chief Scientific Officer and co-founder of Adrenomed.

In AdrenOSS-2 topline data, Adrecizumab already has reported a favorable safety profile and a significant and fast improvement of organ function, plus a substantial reduction on short-term mortality.^[1] In the post-hoc analysis, data from the AdrenOSS-2 trial were analyzed in depth and scrutinized by patient treatment characteristics and stratification of biomarker data. To identify the individual disease pathways of the trial participants bioactive adrenomedullin (bio-ADM^(R)) was used as the biomarker for endothelial barrier dysfunction and dipeptidyl peptidase 3 (DPP3) was applied as the biomarker for cardiac depression. Adrecizumab specifically targets bio-ADM to restore and maintain vascular integrity and does not address the clinical course involving DPP3 and myocardial depression. ^[2],[3]

About AdrenOSS-2 study design & analysis
The biomarker-guided, randomized, multicenter, double-blind, placebo-controlled AdrenOSS-2 Phase II trial (NCT03085758^[4]) enrolled a total of 301 patients with early septic shock and elevated blood levels of Adrenomedullin (bio-ADM) throughout Belgium, France, Germany and The Netherlands.^[5] Patients received Adrecizumab or placebo in addition to standard of care. The primary endpoints were safety and tolerability of Adrecizumab over a 90-day period. The exploratory efficacy endpoints included amongst others mortality rate at day 28, change in Sequential Organ Failure Assessment (SOFA) Score and fluid balance.
In the sensitivity analysis, the biomarker dipeptidyl peptidase 3 (DPP3) was used to identify patients suffering from organ dysfunction by a mechanism that involves myocardial depression and is not addressed by Adrecizumab.^2,3

About Adrecizumab and Adrenomedullin^[6]

Adrenomedullin (ADM) is a free-circulating peptide that is mainly expressed and secreted by vascular endothelial cells. It shows vasoprotective activity inside blood vessels, where it closes the gaps between endothelial cells, subsequently preventing intravascular fluid and other compounds from uncontrolled leakage into the interstitium/extravascular space (= vascular leakage). In the interstitium, however, ADM has vasodilatory properties and causes hypotension when present in higher concentrations, which, in sepsis patients, leads to worsening and progression of the disease. Adrenomed's first-in-class drug candidate, Adrecizumab, targets bioactive Adrenomedullin (bio-ADM) to restore endothelial barrier function (= vascular integrity). Binding of the monoclonal antibody Adrecizumab to ADM in the blood traps and stabilizes the peptide-hormone, resulting in increased ADM concentrations within the blood vessels. The complex of ADM and Adrecizumab in the blood is still active. This way, Adrecizumab treatment boosts ADM's protective effects on the endothelial barrier.

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 Adrecizumab is a first-in-class monoclonal antibody. Adrecizumab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Adrecizumab 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.

^[1] https://adrenomed.com/positive-results-from-adrenomeds-adrenoss-2-phase-ii-trial-evaluating-adrecizumab-ham8101-in-septic-shock-presented-during-e-isicem/
^[2] Eur J Heart Fail, 2020:22(2):290-299
^[3] J Appl Lab Med, 2019:3(6):943-953
^[4] clinicaltrials.gov/ct2/show/NCT03085758?term=NCT03085758&rank=1
^[5] BMJ Open, 2019;9:e024475
^[6] Shock, 2018;50(6):648-654

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