International Opinion Leaders Align on Value of Adrenomedullin as Therapeutical Target and Biomarker in Sepsis and Acute Heart Failure

19. December 2018

  • For the second time, Adrenomed and sphingotec host international scientific symposium on vascular integrity in Berlin
  • Top-tier clinical scientists and key opinion leaders discuss potential of Adrenomedullin in diagnosis and treatment of acute heart failure and Sepsis

Hennigsdorf/Berlin (Germany), December 19, 2018 – The 2nd scientific symposium “Endothelial Dysfunction – Adrenomedullin as a diagnostic and therapeutic target” was hosted by Adrenomed AG, the vascular integrity company, and by sphingotec GmbH, a diagnostic company leading in innovative biomarkers, in Berlin on December 18, 2018. International top-tier clinical scientists and key opinion leaders aligned on the concept of vascular integrity, endothelial barrier dysfunction and the role of Adrenomedullin as a diagnostic and therapeutic target in life-threating conditions such as septic shock and acute congestive heart failure. Adrenomed and sphingotec aim to fulfill unmet medical needs in particular in ICU (intensive care unit) and ED (emergency department) patients.

Regulation of vascular integrity is a fundamental process for human physiology and pathology. Severe impairment of the endothelial barrier – presenting in porous, leaky blood vessels and resulting in tissue congestion and edema – drives conditions that are most threatening to life, such as septic shock and acute congestive heart failure.

The circulating hormone Adrenomedullin is the key regulator of vascular integrity. Adrenomedullin is mainly expressed and secreted by vascular endothelial cells and is known for its vasodilatory activity in the interstitium resulting in decreased blood pressure. In the circulation, Adreno­medullin has vasoprotective effects by directly tightening the gaps between endothelial cells, and subsequently preventing vascular leakage.[1]

“We validated Adrenomedullin as therapeutic target and biomarker in analyses of over 20,000 well-defined patient samples. Rising plasma levels of biologically active Adrenomedullin (bio-ADM®) clearly demonstrate a worsening of vascular integrity leading to shock or tissue congestion independent of any other comorbidity,” explained Dr. Joachim Struck, Vice President Medical Affairs of sphingotec GmbH and added “With the biomarker sphingotest® bio-ADM®, patients at risk of worsening conditions can be clearly identified and monitored during hospital stay.”[2], [3]

Subsequently, for rescuing vascular function, Adrenomed develops the monoclonal antibody Adrecizumab. Adrecizumab binds specifically to biologically active Adrenomedullin in the plasma, thereby stabilizing the molecule in the circulation and increasing the plasma levels of Adreno­medullin, while keeping its functionality. It has been recently published that Adrecizumab thereby improves vascular barrier function and survival in rodent models of systemic inflammation and septic shock.[4]

“With a biomarker-drug combination utilizing bioactive Adrenomedullin as target and biomarker for patient stratification, we are developing a unique solution to rescue vascular integrity in life-threatening conditions such as sepsis, septic shock and acute heart failure and are therefore responding to a very high unmet medical need,” said Dr. Andreas Bergmann, Chief Scientific Officer of Adrenomed AG and Chief Executive Officer of sphingotec GmbH.

Adrecizumab is currently under clinical evaluation in the AdrenOSS-2 trial, a biomarker-guided, double-blind, placebo-controlled, randomized, multicenter proof-of-concept Phase II trial in 300 septic shock patients preselected with high bio-ADM® levels.

Dr. Jens Zimmermann, Chief Medical Officer of Adrenomed AG, presented results from the randomized, double-blind, placebo-controlled Phase Ia and Phase Ib studies, that included a total of forty-eight healthy volunteers to evaluate escalating doses of Adrecizumab. Adrecizumab demonstrated an excellent safety profile in both studies. In addition, the Phase Ib study in systemic inflammation indicated dose-dependent beneficial effects of Adrecizumab on vascular integrity without affecting inflammatory parameters. Results of the Phase I trials were recently published in the British Journal of Clinical Pharmacology.[5]

To allow timely access to bio-ADM® values in daily practice, sphingotec is currently developing a point-of-care solution on the recently acquired Nexus IB10 platform. The test will deliver results within 20 minutes from whole blood without any preparation time. The fully-automated platform is already placed in more than 1,000 intensive care units, emergency departments and doctors’ offices in Europe and the Middle East and proved its applicability in routine. sphingotec’s biomarkers penKid® and bio-ADM® will complement the standard-of-care portfolio to offer an all-around solution for diagnosis of life-threatening conditions such as septic shock and congestion in acute heart failure. Furthermore, bio-ADM® is currently developed as a high-throughput solution on the automated VITROS® platform from Ortho Clinical Diagnostics.

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 is Adrecizumab, a clinical-stage, first-in-class monoclonal antibody. Adrecizumab targets the vasoprotective peptide Adrenomedullin, an essential regulator of vascular integrity. Adrecizumab is currently under clinical evaluation in a biomarker-guided, double-blinded, placebo-controlled, randomized, multicenter proof-of-concept Phase II study with 300 patients suffering septic shock. Excellent safety and tolerability were demonstrated in two Phase I trials.

About sphingotec
sphingotec GmbH (Hennigsdorf, Germany) is developing and marketing innovative biomarkers penKid® and bio-ADM® for prediction, diagnosis and therapy monitoring of AKI, congestive heart failure and septic shock, as well as the Nexus IB10 POC testing immunoassay platform acquired from Samsung-subsidiary Nexus Dx Inc. in May 2018. The company, founded by Dr. Andreas Bergmann in 2002, in addition is developing a pipeline of novel biomarkers which can predict the risks of obesity, breast cancer and cardiovascular diseases.

Contact
Adrenomed AG
Frauke Hein, Ph.D. (Chief Business Officer)
phone: +49 (0)3302 2077814
fhein@adrenomed.com

sphingotec GmbH
Deborah Bergmann (Vice President Marketing)
phone: +49 (0)3302 2056523
d.bergmann@sphingotec.de

Media Inquires
MC Services AG
Eva Bauer/Julia von Hummel
phone: +49 (0)89 21022880
adrenomed@mc-services.eu

References:
[1]    Geven C et al. Shock, 2018; 50(2):132–40.
[2]    Caironi P et al. Chest, 2017; 152(2):312–20.
[3]    Kremer D et al. Eur J Heart Fail, 2018; 20(9):1363–65.
[4]    Geven C et al. Shock, 2018; 50(6):648–54.
[5]    Geven C et al. Br J Clin Pharmacol, 2018; 84(9):2129–41.