APEPTICO publishes significant scientific results of its development compound AP301

APEPTICO, a privately-held biotechnology company developing peptide drugs, today announced that significant scientific results of its development compound AP301 have been published in Molecular Pharmacology and The Journal of Clinical Pharmacology, summarising the mode of action of AP301 in activating the amiloride-sensitive epithelial sodium ion channel (ENaC) and presenting the results of APEPTICO’s first-in-man clinical study of orally inhaled AP301.

APEPTICO develops the AP301 peptide compound for the activation of pulmonary oedema clearance in intensive care patients with life-threatening oedematous respiratory failure and acute respiratory distress syndrome.

The December volume of Molecular Pharmacology publishes the original research article “Mechanism of action of novel lung edema therapeutic AP301 by activation of the epithelial sodium channel” (http://molpharm.aspetjournals.org/content/84/6/899.abstract) resulting from APEPTICO’s scientific collaboration with the Department of Pharmacology and Toxicology of the University of Vienna. The mode of action of AP301 peptide in activating the amiloride-sensitive epithelial sodium ion channel (ENaC) was studied in A549 lung epithelial cells as well as in human embryonic kidney cells and chinese hamster ovary cells heterologously expressing human ENaC subunits α, β, γ, and δ. The data suggest that AP301 specifically targets endogenously and heterologously expressed ENaC, activates proteolytically processed ENaC in a reversible manner, requires the pore-forming α- or δ-subunit co-expressed with βγ-subunits for maximal activity, and requires glycosylated extracellular domains of ENaC to enable binding of AP301 to the ion channel.

In collaboration with the Department of Clinical Pharmacology of the Medical University of Vienna, safety and tolerability of orally inhaled AP301 peptide was assessed in a FIM (first-in-man) clinical study at the Vienna General Hospital. The results of this study are summarised as “A FIM study to assess safety and exposure of inhaled single-doses of AP301–A specific ENaC channel activator for the treatment of acute lung injury” in the December volume of The Journal of Clinical Pharmacology (http://onlinelibrary.wiley.com/doi/10.1002/jcph.203/abstract). In the phase I clinical study 48 subjects received treatment, and completed the study as per protocol. No serious or local adverse events were noted. None of the assessments indicated notable dose or time-related alterations of safety outcomes. Inhaled AP301 single doses up to 120 mg were safe and well tolerated by study subjects. Distribution of inhaled AP301 was largely confined to the lung, as indicated by very low AP301 systemic exposure levels.

Dr. Bernhard Fischer, CEO of APEPTICO, commented: “2013 was another very productive year in the research & development programme of APEPTICO, illustrating that the Company’s strategy of investigating the mode of action and clinical use of its lead compound AP301 through a network of research collaborations, is paying off.” “AP301 has successfully completed a phase I clinical study and is currently undergoing two different phase II clinical trials in patients with life-threatening lung oedema and primary graft dysfunction following lung transplantation, respectively. We are looking forward reviewing the clinical data from both studies in just a few weeks from today” Dr. Fischer added.

About APEPTICO GmbH (www.apeptico.com)
APEPTICO is a privately-held biotechnology company based in Austria, developing peptide-based products targeting chronic and life-threatening diseases. The peptide molecules correspond to validated, pharmacodynamic active structures and domains of well-known proteins and biopharmaceuticals. By concentrating on synthetically produced protein structures APEPTICO avoids general risks associated with gene- and cell-technologies. APEPTICO makes use of its technology platforms PEPBASE(TM) and PEPSCREEN(TM) to significantly reduce cost and to shorten time to market.

About the AP301 peptide family
AP301 and derived peptides are synthetic molecules whose structures are based on the lectin-like domain of human Tumour Necrosis Factor alpha. AP301 peptides are water soluble and can be administered into the lung by oral inhalation. Formulated AP301 is easily nebulised and the resulting aerosol is composed of peptide/water droplets of diameter 4 μm or less. AP301 and derived peptides are designed for activation of the pulmonary epithelial sodium channel (ENaC). Activation of ENaC by AP301 results an accelerated lung oedema clearance in the airspace. Comprehensive research and development conducted by APEPTICO has demonstrated that AP301 peptides are effective in animal models of various forms of pulmonary oedema, including high altitude pulmonary oedema, acute lung injury / acute respiratory distress syndrome, pneumonia, influenza virus lung infection, and lung transplantation. Currently, AP301 is subject to two Phase IIa clinical studies for the treatment of patients suffering from life-threatening oedematous respiratory failure and primary graft dysfunction following lung transplantation, respectively.

About oedematous respiratory failure
Respiratory failure occurs when the respiratory system fails in oxygenation and/or carbon dioxide elimination. Oedematous Respiratory Failure is caused by a massive and life-threatening pulmonary oedema. Pulmonary oedema occurs when fluid leaks from the pulmonary capillary network into the lung interstitium and alveoli. There are many possible causes of lung oedema, such as inhaling high concentrations of smoke, toxins, or oxygen; severe burns; blood infections; lung infections; or trauma to other parts of the body. Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) are catastrophic forms of lung oedema. Lungs contain alveoli, which are tiny air sacs where the oxygen is passed into the blood. During lung oedema, blood and fluid begin to leak into the alveoli. When this happens, oxygen cannot enter the alveoli, which means oxygen no longer passes into the blood. Because the lungs are inflamed and filled with fluid, the patient finds it increasingly difficult to breathe. The mortality rate of patients with pulmonary oedema in ALI/ARDS is 30% to 60% within two to four weeks. Currently, no specific drug treatment exists for patients suffering from hyper-permeability-caused lung oedema.

About Primary Graft Dysfunction
Primary Graft Dysfunction (PGD) (Ischemia Reperfusion Injury, IRI) is characterized by poor oxygenation as the main criterion for the condition and is also characterized by low pulmonary compliance, interstitial/alveolar oedema, pulmonary infiltrates on chest radiographs, increased pulmonary vascular resistance, intrapulmonary shunt and acute alveolar injury, as revealed by diffuse alveolar damage (DAD) on pathology. PGD occurs in approximately 20% of lung transplant recipients and patients face prolonged ventilation, prolonged stays in the ICU and the hospital overall, increased medical costs, and increased risk of morbidity and mortality. Currently, no specific drug treatment exists for patients suffering primary graft dysfunction following lung transplantation.

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