APEPTICO Announces Successful Completion of Phase I Trial

PRESS RELEASE APEPTICO Announces Successful Completion of Phase I Trial with AP301 in Oedematous Respiratory Failure Vienna, Austria, 25 th October, 2011 - APEPTICO GmbH , a biotechnology company developing peptide drugs based on its PEPBASE™ discovery techn ology, today announced completion of a Phase I clinical trial for its pulmonary sodium ion channel activator AP301. The orally inhaled drug candidate was safe and well-tolerated by all study participants. AP301 is being developed for the prevention and treatment of oedematous respiratory failure in patients suffering from lung infection, lung injury and lung transplantation. The Phase I single-center clinical trial evaluated the safety, tolerability and pharmacokinetic profil e of AP301 in an orally inhaled, double-blind, random ized, placebo-controlled, dose escalation study in 48 healthy male volunteers. AP301 was shown to b e safe at all doses investigated, with no reports of serious adverse side effects. AP301 is the first compound against respiratory fai lure caused by pulmonary oedema that activates lung oedema reabsorption and thus differs from the currently used anti-inflammatory treatment that often fails in patients with acute lung injury. The synthetic peptide AP301 activates alveolar liquid clearance (ALC) and prevents both endothelial and epithelial lung tissue from hyper-permeability as a result of microbial and viral lung infections. AP 301 also prevents ischaemia reperfusion injury following lung transplantation in the lower respiratory tract. "The successful completion of our Phase I trial is an important step for APEPTICO’s drug development program" said Dr. Bernhard Fischer, CEO of APEPTICO. “We look forward to starting the Phase IIa trial with the aerosol formu lation of AP301 in 2012, and are committed to building on our success with peptide drugs.” About AP301 AP301 is a fully synthetic peptide molecule whose s tructure is based on the lectin-like domain of human Tumour Necrosis Factor alpha. The AP301 pepti de is water soluble and can be administered into the lung by oral inhalation. AP301 is designed to activate the pulmonary epithelial sodium channel (ENaC) which results in an accelerated oede ma clearance in the airspace. Comprehensive research and development conducted by APEPTICO has demonstrated that the AP301 peptide is effective to clear lung water in animal models of p ulmonary permeability oedema, pneumonia, influenza virus lung infection, acute lung injury a nd lung transplantation. AP301 has received Orphan Drug Designation by the EMA and by the FDA for various indications. About oedematous respiratory failure Respiratory failure occurs when the respiratory sys tem fails in oxygenation and/or carbon dioxide elimination. Oedematous respiratory failure is caus ed by a massive and life-threatening pulmonary oedema. Pulmonary oedema occurs when fluid leaks fr om the pulmonary capillary network into the lung interstitium and alveoli. When this happens, o xygen cannot enter the alveoli, which means oxygen no longer passes into the blood. There are m any possible causes of lung oedema, such as inhaling high concentrations of smoke, toxins, or o xygen, severe burns, blood infections, lung infections, or trauma to other parts of the body. A cute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are catastrophic forms of lung oedema. The mortality rate of patients with pulmonary oedema in ALI/ARDS is 30% to 60% wit hin 2 to 4 weeks. Currently, no specific drug treatment exists for patients suffering from hyper-permeability-caused lung oedema. About APEPTICO GmbH APEPTICO is a privately-held biotechnology company based in Austria, developing peptide-based products targeting chronic and life-threatening dis eases. The peptide molecules correspond to validated, pharmacodynamic active structures and do mains of well-known proteins and biopharmaceuticals. By concentrating on synthetical ly produced protein structures APEPTICO avoids any risk of transmitting microbial and viral infections. Development cost and time to market are significantly reduced if compared to the recomb inant development process of biomolecules. APEPTICO’s development platform PEPBASETM combines structural, functional and clinical data from relevant biopharmaceuticals and well-character ised proteins. Based on preclinical and clinical data, including adverse reactions, risk factors and contraindications to be circumvented and supported by structural, biochemical and physicoche mical data, for each relevant protein a specific profile is established that links biological & functional properties with discrete structural elements. Contact Univ.- Doz. Dr. Bernhard Fischer Chief Executive Officer APEPTICO Forschung und Entwicklung GmbH Mariahilferstraße 136 A-1150 Vienna, Austria T: +43-664-1432919 [email protected] PRESS RELEASE The 2011 Annual Conference of the European Respiratory Society has been a major success for APEPTICO Forschung und Entwicklung GmbH 29th September, 2011, Vienna, Austria: APEPTICO Forschu ng und Entwicklung GmbH, a biotechnology company developing novel peptide-base d drugs for the treatment of life threatening lung diseases today announced that the 2011 Annual Conference of the European Respiratory Society has been a major success for the company. At the 2011 Annual Congress of the European Respira tory Society (ERS) in Amsterdam (The Netherlands, September 24 th to 28 th 2011), APEPTICO has presented significant research results of its clinical stage development compound AP301. The beneficial effects of APEPTICO’s development compound AP301, also known as “TIP-peptide”, have been subject of three presentations at this prestigious congress. Professor Dr. Rudolf Lucas (Georgia Health Sciences University, Augusta, USA) reported that the AP301 TIP-peptide reduces lung dysfunction in experimenta l influenza A virus infection in vitro and in vivo . Dr. Susan Tzotzos reported on characterisation of TNF-a lpha lectin-like domain derived AP301 TIP-peptides associated with improved alveolar fluid clearance i n pulmonary oedema. The potential synergism of AP30 1 and anti-viral drugs, such as oseltamivir and zanamiviral, was reported in by Dr. Hendrik Fischer. The AP301 peptide is being developed by APEPTICO for inhalation therapy for prevention and treatment of Oedematous Respiratory Failure. AP301 activates the pulmonary epithelial sodium ion channel (ENaC) and prevents Protein Kinase C activation in lung tissue s. It thus accelerates pulmonary oedema reabsorptio n and stabilises endothelial-epithelial barrier function in life-threatening conditions resulting from hyper - permeability of lung micro-capillaries. Currently, AP301 is subject to a Phase I clinical study in the Vienna General Hospital. Extracts from presentations Prof. Dr. R. Lucas: “The AP301 “TIP-peptide” which reduces PLY-induced oedema, can blunt influenza A virus (IAV) induced Alveolar Liquid Clearance dysfu nction and combined IAV/PLY-induced barrier dysfunction. The TIP peptide represents a therapeut ic candidate for the treatment of IAV-associated lu ng dysfunction, since it interferes with both IAV infe ction-associated ALC and barrier dysfunction, upon reducing PKC-α activation.” Dr. S. Tzotzos: “Our data suggest that TIP-peptides with charge distribution and interatomic distances most closely resembling the 3D structure of the native l ectin-like domain of TNF-alpha, are those with grea ter ability to enhance activation of sodium current thr ough ENaC. No standard therapy exists for pulmonary oedema, thus these TIP-peptides represent promising therapeutic agents for activating sodium uptake fr om the alveolar fluid through ENaC and improving clinical outcome in this condition.” Dr. H. Fischer: “Influenza A is a serious public he alth problem that causes severe illnesses and death s for higher risk populations. Antiviral drugs like oselt amivir and zanamivir block increase and spreading o f the virus in the body, however already existing virus p articles will not be affected. 2/3 of patients show pulmonary oedema that can deteriorate to ALI/ARDS. Current experiments suggest a benefit of combining anti-viral drugs (neuraminidase inhibitors) and AP301 a substance with alveolar liquid clearing activity.” - - - - - ENDS - - - - - Notes to Editors: About APEPTICO GmbH 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 b iopharmaceuticals. By concentrating on syntheticall y produced protein structures APEPTICO avoids any risk of tran smitting microbial and viral infections. Developmen t cost and time to market are significantly reduced if compared to the recombinant development process of biomolecules. APEPTICO’s development platform PEPBASE TM combines structural, functional and clinical data from relevant biopharmaceuticals and well-characterised proteins. Based on preclinic al and clinical data, including adverse reactions, risk factors and contraindications to be circumvented and supported by structural, biochemical and physicochemical data , for each relevant protein a specific profile is established that links biological & functional properties with discrete structural elements. About the AP301 peptide family AP301 and derived peptides are synthetic molecules whose structures are based on the lectin-like domai n of human Tumour Necrosis Factor alpha. AP301 peptides are wa ter soluble and can be administered into the lung b y oral inhalation. Formulated AP301 is easily nebulised an d the resulting aerosol is composed of peptide/wate r 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 peptide s results an accelerated oedema clearance in the ai rspace. Comprehensive research and development conducted by APEPTICO has demonstrated that AP301 peptides are effective in animal models of pulmonary permeabilit y oedema, pneumonia, influenza virus lung infection , Acute Lung Injury / Acute Respiratory Distress Syndrome and lu ng transplantation. AP301 has received Orphan Drug Designation by the EMA and by the FDA for various indications. Currently, AP301 is subject to a Phase I clinical study in the General Hospital in Vienna. About Oedematous Respiratory Failure Respiratory failure occurs when the respiratory sys tem fails in oxygenation and/or carbon dioxide elim ination. Oedematous Respiratory Failure is caused by a massi ve and life-threatening pulmonary oedema. Pulmonary oedema occurs when fluid leaks from the pulmonary capillar y network into the lung interstitium and alveoli. T here are many possible causes of lung oedema, such as inhaling hi gh concentrations of smoke, toxins, or oxygen; seve re burns; blood infections; lung infections; or trauma to other par ts of the body. Acute Lung Injury (ALI) and Acute R espiratory Distress Syndrome (ARDS) are catastrophic forms of lung oedema. Lungs contain alveoli, which are tiny air sacs wher e 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 me ans 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 patient s with pulmonary oedema in ALI/ARDS is 30% to 60% w ithin 2 to 4 weeks. Currently, no specific drug treatment exists for patients suffering from hyper-permeability-caused lung oedema. About ERS Conference The ERS Conference is the largest international con ference specialising in pulmonary medicine. It prov ides a unique forum where scientists and medical professionals fr om around the world have the opportunity to meet an d exchange ideas and information in the field of respiratory m edicine. The scientific programme of the ERS Congre ss aims to provide a perfect balance between clinical educatio n and the latest scientific developments. The ERS C ongress highlights key issues in the diagnosis, management and treatment of respiratory diseases, giving clini cians and research scientists the opportunity to report the latest findings in basic, clinical and population research. Contact Univ.- Doz. Dr. Bernhard Fischer, Chief Executive Officer APEPTICO Forschung und Entwicklung GmbH Mariahilferstraße 136, A-1150 Vienna, Austria T: +43-664-1432919 F: +43-664-1477280 E-mail: [email protected] URL: www.apeptico.com PRESS RELEASE APEPTICO presents significant research results of its inhalation therapy for prevention and treatment of Oedematous Respiratory Failure at the 2011 Annual Congress of the European Respiratory Society 09 th September, 2011, Vienna, Austria: APEPTICO Forschu ng und Entwicklung GmbH, a biotechnology company developing novel peptide-base d drugs for the treatment of life threatening lung diseases today announced that it w ill present significant research results of its inhalation therapy for prevention and treatment of Oedematous Respiratory Failure at the 2011 Annual Congress of the European Respiratory Society. At the 2011 Annual Congress of the European Respira tory Society (ERS) in Amsterdam (The Netherlands, September 24 th to 28 th 2011), APEPTICO will present significant research results of its inhalation therapy for prevention and treatment of Oedematous Respiratory Failure to the scientific community. The scientific advisory board of the ERS has appointed in total three contributions of APEPTICO to be presented at this m ajor event. In the oral presentation entitled “Characterisation of TNF-alpha lectin-like domain d erived peptides associated with improved alveolar fluid clearance in pulmonary oedema” APEPT ICO’s strategy for design and pharmacodynamic assessment of state-of-the-art lung ENaC agonists will be presented. Professor Dr. Rudolf Lucas will give a talk entitled “The lec tin-like domain of TNF reduces lung dysfunction in experimental Influenza A virus infection” and re searchers of APEPTICO will present additional scientific findings in “Potential synergism of drugs with anti-viral and pulmonary oedema clearance activity may be advantageous for influenza patients”. APEPTICO develops synthetic peptide drugs, based on the structural motif of the lectin-like domain of human tumour necrosis factor alpha (TNF-alpha), which activate the pulmonary epithelial sodium ion channel (ENaC) and thus accelerate pulmo nary oedema reabsorption in life-threatening conditions such as pneumonia, influenza virus lung infection and Acute Lung Injury / Acute Respiratory Distress Syndrome. APEPTICO’s lead peptide AP301 is currently subject to a Phase I clinical study in the Vienna General Hospital. The ERS Congress is the largest international confe rence specialising in pulmonary medicine. It provides a unique forum where scientists and medical professionals from around the world have the opportunity to meet and exchange ideas and informat ion in the field of respiratory medicine. The scientific programme of the ERS Congress aims to pr ovide a perfect balance between clinical education and the latest scientific developments. T he ERS Congress highlights key issues in the diagnosis, management and treatment of respiratory diseases, giving clinicians and research scientists the opportunity to report the latest findings in basic, clinical and population research. Dr. Bernhard Fischer, CEO of APEPTICO commented: “I am pleased that the scientific organising committee of the ERS Annual Congress is giving us t he opportunity to present the progress of our drug development programme - the development of new medicines for prevention and treatment of Oedematous Respiratory Failure. Today no specific drug treatment exists for patients suffering from hyper-permeability-caused lung oedema.” - - ENDS - - Notes to Editors: About APEPTICO GmbH 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 b iopharmaceuticals. By concentrating on syntheticall y produced protein structures APEPTICO avoids any risk of tran smitting microbial and viral infections. Developmen t cost and time to market are significantly reduced if compared to the recombinant development process of biomolecules. APEPTICO’s development platform PEPBASE TM combines structural, functional and clinical data from relevant biopharmaceuticals and well-characterised proteins. Based on preclinic al and clinical data, including adverse reactions, risk factors and contraindications to be circumvented and supported by structural, biochemical and physicochemical data , for each relevant protein a specific profile is established that links biological & functional properties with discrete structural elements. About the AP301 peptide family AP301 and derived peptides are synthetic molecules whose structures are based on the lectin-like domai n of human Tumour Necrosis Factor alpha. AP301 peptides are wa ter soluble and can be administered into the lung b y oral inhalation. Formulated AP301 is easily nebulised an d the resulting aerosol is composed of peptide/wate r 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 peptide s results an accelerated oedema clearance in the ai rspace. Comprehensive research and development conducted by APEPTICO has demonstrated that AP301 peptides are effective in animal models of pulmonary permeabilit y oedema, pneumonia, influenza virus lung infection , Acute Lung Injury / Acute Respiratory Distress Syndrome and lu ng transplantation. AP301 has received Orphan Drug Designation by the EMA and by the FDA for various indications. Currently, AP301 is subject to a Phase I clinical s tudy in the General Hospital in Vienna. Oedematous Respiratory Failure Respiratory failure occurs when the respiratory sys tem fails in oxygenation and/or carbon dioxide elim ination. Oedematous Respiratory Failure is caused by a massi ve and life-threatening pulmonary oedema. Pulmonary oedema occurs when fluid leaks from the pulmonary capillar y network into the lung interstitium and alveoli. T here are many possible causes of lung oedema, such as inhaling hi gh concentrations of smoke, toxins, or oxygen; seve re burns; blood infections; lung infections; or trauma to other par ts of the body. Acute Lung Injury (ALI) and Acute R espiratory Distress Syndrome (ARDS) are catastrophic forms of lung oedema. Lungs contain alveoli, which are tiny air sacs wher e 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 me ans 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 patient s with pulmonary oedema in ALI/ARDS is 30% to 60% w ithin 2 to 4 weeks. Currently, no specific drug treatment exists for patients suffering from hyper-permeability-caused lung oedema. Contact Univ.- Doz. Dr. Bernhard Fischer, Chief Executive Officer APEPTICO Forschung und Entwicklung GmbH Mariahilferstraße 136, A-1150 Vienna, Austria T: +43-664-1432919 F: +43-664-1477280 E-mail: [email protected] URL: www.apeptico.com PRESS RELEASE APEPTICO Initiates Phase I Trial with AP301 in Pulmonary Oedema Vienna, Austria, April 07, 2011 - APEPTICO, a privately-held biotechnology company developing peptide drugs based on its PEPBASE™ discovery technology, t oday announced the initiation of a Phase I clinical trial with its lead product AP301 to assess the saf ety and tolerability of the orally inhaled peptide drug. AP301 is being developed for the treatment of oedem atous respiratory failure in patients suffering fro m lung infection, lung injury and lung transplantation. AP301 is the first compound against respiratory fai lure caused by pulmonary oedema that activates lung oedema reabsorption and thus differs from the curre ntly used anti-inflammatory treatment that often fa ils in patients with acute lung injury. The synthetic pept ide AP301 activates alveolar liquid clearance (ALC) and prevents both endothelial and epithelial lung tissu e from hyper-permeability as a result of microbial and viral lung infections. AP301 also prevents ischaemia repe rfusion injury following lung transplantation in th e lower respiratory tract. The randomized, double-blind, placebo-controlled, d ose escalating study is enrolled in Austria. Up to 48 patients will receive a single dose of AP301 or mat ching placebo converted into an aerosol by state-of -the- art nebuliser technology. "We are very pleased to expand the development of o ur lead molecule AP301 into clinical studies, particularly as we have faced widespread scepticism regarding the usefulness of peptide drugs in inhal ation therapy," said Bernhard Fischer, CEO of APEPTICO. “ Treatment of oedematous respiratory failure represents an unmet medical need as no specific the rapy or medicinal product has been approved so far for the prevention and treatment pulmonary oedema caused by hyper-permeability.” APEPTICO seeks partner in Influenza “Pulmonary oedema is the primary cause of death in patients with influenza. Due to our promising resul ts with AP301 in mice infected with influenza virus an d a porcine model of acute lung injury, we are very confident that we will soon find partners in the ph armaceutical industry for further development of AP 301,” said Bernhard Fischer. Treatment of influenza virus-infected mice with AP3 01 results in a significant reduction of oedema flu id accumulation in the air space and increased ALC. AP 301 acts synergistically with anti-viral neuraminid ase inhibitor, such as oseltamivir and zanamivir, in in fluenza virus-infected mice by reducing virus-media ted lung oedema and by prevention of endothelial/epithelial hyper-permeability. In a porcine model of acute lun g injury, inhalation of AP301 peptide results in a su stained improvement of the lung function according to the parameters oxygenation index, extravascular lung water (EVLWI) and pulmonary shunt fraction. About AP301 AP301 is a synthetic peptide that corresponds to a structural motif of the human tumour necrosis facto r alpha. It is water soluble and can be administered into the lung by instillation or by oral inhalation . Formulated AP301 can be nebulised and the resulting aerosol is composed of peptide/water droplets of diameter 3 µm or less. AP301 was originally designed for the tr eatment of acute lung injury and acute respiratory distress syndrome. Additional research demonstrated that AP301 has additional significant potential in related clinical indications, such as prevention and treatment of pulmonary permeability oedema, prevention of progression of acute hypoxemic respir atory failure due to bacterial/viral pneumonia and prevention of ischemia reperfusion injury. AP301 ac tivates lung oedema reabsorption and protects both endothelial and epithelial lung cells from virulenc e factor- and reactive oxygen species-induced hyper - permeability of lung capillaries. AP301 has receive d orphan drug designation by the EMA (European Community) for the treatment of acute lung injury a nd by the FDA (USA) for the prevention of ischemia reperfusion injury in the lung during lung transplantation. About APEPTICO GmbH - www.apeptico.com APEPTICO, a privately-held biotechnology company lo cated in Austria, develops peptide-based products targeting chronic and life-threatening diseases usi ng its PEPBASE™ discovery technology. PEPBASE TM combines structural, functional and clinical data o f relevant biopharmaceuticals and well-characterise d proteins to establish a specific profile for each p rotein that links biological & functional propertie s with discrete structural elements. Accordingly, APEPTICO ’s synthetic peptides correspond to validated, pharmacodynamic active structures and domains of pr oteins and biopharmaceuticals. By focusing on synthetically produced protein structures APEPTICO avoids any risk of transmitting microbial and viral infections. Development cost and time to market are significantly reduced compared to the recombinant development process of biomolecules. Contact Univ.-Doz. Dr. Bernhard Fischer Chief Executive Officer APEPTICO Forschung und Entwicklung GmbH Mariahilferstraße 136, Top 1.1.5 1150 Vienna, Austria T: +43-664-1432919 F: +43-664-1477280 E-mail: [email protected]

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