Targeting endothelial barrier function in critically ill COVID-19 patients: Adrecizumab shows beneficial effects

- Adrecizumab (HAM8101) showed a favourable outcome in a case series of eight COVID‐19 patients with life-threatening organ failure in ICU

- At publication, this represented the first data evaluating an experimental therapy in such late-stage COVID-19 patients

- Adrecizumab targets Adrenomedullin to restore endothelial barrier function and impaired vascular integrity

Hennigsdorf/Berlin (Germany), August 24, 2020 - Adrenomed AG, the vascular integrity company, announced today the publication of data from eight extreme-critically ill COVID-19 patients treated with Adrecizumab (HAM8101) in the peer-reviewed journal . The treatment with Adrecizumab showed an encouraging outcome in this limited data set, seven out of eight patients survived the observation period. To date, this represents the first data assessing an experimental therapy targeting loss of vascular integrity in COVID‐19 patients who were extreme‐critically ill and under invasive mechanical ventilation with no other treatment option.

Adrenomed's lead candidate Adrecizumab is a first-in-class, monoclonal antibody under clinical development in septic shock. Adrecizumab targets the vasoprotective peptide Adrenomedullin to restore and maintain the endothelial barrier function. Loss of endothelial barrier function is a major cause of mortality in sepsis.

Sepsis is characterized by an overreaction of the body's immune system to fight a bacterial or viral infection, like SARS-CoV-2, leading to vascular leakage, severe organ dysfunction and eventually death. Varga et al. demonstrated the endothelial cell involvement in a series of patients with COVID-19, thus proposing the stabilization of the endothelium as a therapeutic approach in treating the condition. Furthermore, addressing Adrenomedullin, a key player in promoting endothelial stability and integrity following severe infection, was described as a promising target.

The patients were treated at the Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf. In contrast to other case series reported recently, all patients (n = 8) suffered from extensive pre‐existing conditions, such as hypertension, Type-2 diabetes mellitus, and obesity. At the time of treatment, all patients received invasive mechanical ventilation due to severe Acute Respiratory Distress Syndrome (ARDS) and required vasopressors due to shock. Six patients suffered from acute renal failure at baseline. The median Sequential Organ Failure Assessment (SOFA) score was 12.5, reflecting the very critical health status and high risk of mortality. At time of treatment, all patients showed elevated blood levels of Adrenomedullin (bio-ADM) indicating impaired endothelial barrier function. Patients received a single-dose of Adrecizumab (4 or 8 mg/kg b.w.) between one and three days after initiation of mechanical ventilation.

In this case series, seven out of eight patients survived the observation period. In five out of these seven patients, treatment with Adrecizumab resulted in a rapid improvement of organ function (indicated by SOFA Score) and subsequent reduction in the disease severity within 12 days after administration. One patient died at day 4 due to a non-treatment related fulminant pulmonary embolism. During the follow-up period, which ranged between 13 to 27 days, four patients were in stable condition in ICU and three were transferred to normal wards. Adrecizumab was well tolerated in all patients and, again, showed a favorable safety profile.

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 (HAM8101) is a first-in-class monoclonal antibody. Adrecizumab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Adrecizumab has completed a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial with 301 patients suffering from septic shock ().^,

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^[3] Lancet 2020; 395: 1417-18.
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^[6] JAMA 2001; 286: 1754-58.
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^[8] /article-in-bioworld-shock-away-adrenomeds-adrecizumab-hits-phase-ii-endpoint-in-septic-shock/.