Since its discovery in 1993, the vasoactive peptide hormone Adrenomedullin (ADM) has attracted a great deal of interest as a multifunctional regulator of the vascular system, i.a. regulating angiogenesis and cardiovascular homeostasis . Adrenomedullin is mainly expressed and secreted by vascular endothelial cells and is best known for its vasodilatory activity . In addition, Adrenomedullin has been extensively described as key determinant of vascular integrity [4,5,6].
Molecular Mechanism of Action
Adrenonomedullin exerts its molecular action mainly via the stimulation of cAMP formation. ADM binds the G protein–coupled receptor CRLR (calcitonin receptor-like receptor) that is expressed both on vascular smooth muscle and vascular endothelial cells. CRLR is associated with one of three different accessory single-pass transmembrane proteins called RAMP1-3 . ADM only interacts with CRLR receptors that are accompanied by either RAMP2 or RAMP3 . Binding of Adrenomedullin to CRLR/RAMP2 or CRLR/RAMP3 on endothelial cells triggers downstream signaling pathways that affect endothelial barrier function and blood vessel permeability .
Adrecizumab is a humanized murine monoclonalIgG1 antibody specifically binding the N-terminal region of human Adrenomedullin. It will be a first-in-class drug that targets and balances an essential reagulator of vascular activity.
Adrecizumab has shown to improve all clinically relevant end points in several resuscitated animal models of vascular integrity (mouse, rat, pig). It reduces vascular leakage, stabilizes the circulation, by restoring blood pressure and reducing vasopressor demand, improves renal function and reduces mortality from septic shock by 50%.
Adrecizumab restores blood pressure Blood pressure [in mmHg] of healthy rats (Healthy) and of rats after sepsis induction (CLP model), either treated with Adrecizumab or an unspecific control antibody (control). Adapted from Blet et al. Intensive Care Med Exp 2015, 3(Suppl 1):A618.
|Adrecizumab reduces mortality by 50% Survival rate of rats after sepsis induction (CLP model), either treated with Adrecizumab or an unspecific control antibody. Adapted from Struck et al. Intensive Care Medicine Experimental 2013, 1:3.For further results and details please see our publication list or contact Dr. Frauke Hein|
Adrecizumab restores blood pressure
Blood pressure [in mmHg] of healthy rats (Healthy) and of rats after sepsis induction (CLP model), either treated with Adrecizumab or an unspecific control antibody (control). Adapted from Blet et al. Intensive Care Med Exp 2015, 3(Suppl 1):A618.
Adrecizumab reduces mortality by 50%
Survival rate of rats after sepsis induction (CLP model), either treated with Adrecizumab or an unspecific control antibody. Adapted from Struck et al. Intensive Care Medicine Experimental 2013, 1:3.
Adrenomed AG is a privately-financed biopharmaceutical company with a clear mission: to improve vascular integrity in order to improve survival. Adrenomed was established in 2009 by Dr. Bernd Wegener and Dr. Andreas Bergmann, co-founders & former executive managers of BRAHMS AG. They changed the standard of care in sepsis by developing Procalcitonin (B.R.A.H.M.S. PCTTM), the diagnostic gold standard sepsis biomarker.
We are focusing on the discovery and development of monoclonal antibody therapies that target the vasoactive Adrenomedullin system as a new strategy for causative and safe treatment of acute circulatory failure, e.g. septic shock. Our lead product is the first-in-class drug candidate Adrecizumab, a humanized monoclonal Adrenomedullin-specific antibody . Adrenomedullin is a vasoactive peptide hormone released by vascular endothelial cells. During sepsis, the impairment of the endothelial barrier leads to collapse of blood pressure (septic shock) which frequently results in multiple organ failure and death. Adrenomedullin is a key regulator of vascular integrity and plays a pivotal role in the development of septic shock. Adrecizumab has an innovative mode of action that spatially controls Adrenomedullin activity, thereby reducing vascular leakage, stabilizing the circulation and lowering mortality.
Dr. Gerald Moeller | Chief Executive Officer (CEO)
Dr. Andreas Bergmann | Chief Scientific Officer (CSO)
The virtual nature of the company leads to a very lean personnel structure that mainly focusses on project management. The key competences for planning and evaluation of the preclinical and clinical study program as well as CMC development are in-house capabilities; all operational resources are third party based capacities. The experienced sepsis research for decades resulted in an extensive network with key opinion leaders worldwide in cardiovascular disease and sepsis that support Adrenomed’s clinical research.
Dr. Jens Zimmermann | Chief Medical Officer (CMO)
Dr. Frauke Hein | Chief Business Officer (CBO)
Dr. Joachim Struck | Head of Research & Development
Granzer Regulatory Consulting & Services
Renke Lührs (Chairman) | Corporate Lawyer & Partner of Buse Heberer Fromm Rechtsanwälte Steuerberater Partnerschaftsgesellschaft in Berlin
Dr. Bernd Wegener | Co-founder of Adrenomed with over 35 years of Management Experience in the Diagnostic and Pharmaceutical Industry
Dr. Metod Miklus | CEO of ExpoCapital GmbH and Co-founder of BRAHMS