DGAP-News: PAION REPORTS POSITIVE PHASE II RESULTS OF ITS

DGAP-News: PAION AG / Key word(s): Research Update PAION REPORTS POSITIVE PHASE II RESULTS OF ITS SHORT ACTING ANAESTHETIC REMIMAZOLAM IN MAJOR CARDIAC SURGERY 28.05.2014 / 18:46 --------------------------------------------------------------------- PAION REPORTS POSITIVE PHASE II RESULTS OF ITS SHORT ACTING ANAESTHETIC REMIMAZOLAM IN MAJOR CARDIAC SURGERY - Excellent cardiovascular stability confirmed in major cardiac surgery - Primary Endpoint met - Outstanding safety profile of Remimazolam confirmed Aachen (Germany), 28 May 2014 - PAION AG (ISIN DE000A0B65S3; Frankfurt Stock Exchange Prime Standard: PA8), a specialty pharma company, today announced positive headline data from the Phase II clinical trial in Germany with the short-acting anaesthetic/sedative Remimazolam in the EU lead indication "general anaesthesia" in patients undergoing major cardiac surgery with extracorporeal circulation. The primary efficacy endpoint of effectiveness as a general anaesthetic (defined as successful anaesthesia not requiring rescue therapy) was achieved in 98% of patients in the two Remimazolam dose groups and 96% in the Propofol/Sevoflurane group. Therefore, an excellent efficacy rate across all treatment groups was shown. As expected, the onset and offset of action profile was comparable between all treatment groups, showing that Remimazolam indeed shares the fast-acting sedative profile of Propofol. The safety profile was generally very good in all treatment groups. One of the key targets of this trial was to assess the cardiostability during cardiac surgery with Remimazolam when compared to Propofol/Sevoflurane, both of which are known to cause cardiac depression. The study evaluated a substantial number of parameters to analyse these effects. Remimazolam already had shown excellent cardiostability in the ONO Phase III study. During cardiac surgery norepinephrine is routinely used to maintain blood pressure in the normal range and counteract pronounced blood pressure decreases. Norepinephrine and other adrenergic substances however are known to impair the microcirculation in vital organs and thus have a negative effect on short, mid and long-term outcomes. Therefore lowering the norepinephrine dose is of high medical relevance. The amount of norepinephrine required to counteract the cardio-depressive effects (e.g., drop in blood pressure) is a direct measure of the cardio-depressive effects in each group: a higher amount of norepinephrine would be used to counteract higher cardio-depressive effects. The use of norepinephrine was 36.7% lower in Remimazolam treated patients when compared to the Propofol/Sevoflurane group which can be regarded as a clinically meaningful differentiation. Dr Wolfgang Söhngen, CEO of PAION, commented: "This trial was designed to bridge the European anaesthesia program to the Japanese data set which has been successfully achieved. Within the next months, this will be complemented by the PK data, which is still work in progress. We are currently in advanced stages of preparing the EU Phase III program including the EMA advice meeting to fine-tune the development program on the basis of the scientific advice meeting with the BfArM in 2013. The study team in Leipzig as well as our internal and external teams have done a tremendous job, for which we are very grateful." Dr Stefan Probst, principal investigator from the Heart Centre Leipzig, commented: "The observations we made when performing the trial have been verified by the data set. With the high recruitment rate that we achieved, we showed that the usability of Remimazolam in routine procedures was excellent. We are looking forward to the Phase III study in which we will cooperate with selected high profile EU cardiac surgery sites and will share our experience and findings with our peers." Notes to Editor About the Phase II study The Phase II study was a randomized, Propofol and Sevoflurane (standard treatment) controlled Phase II study to evaluate the efficacy, tolerability and pharmacokinetics of Remimazolam during general anaesthesia in patients undergoing cardiac surgery using a heart-lung machine. After surgery, a follow-up sedation in the recovery room or in the intensive care unit (ICU) could be continued for up to 24 h. A total of 90 patients have been treated. The study was carried out at the Heart Centre Leipzig - University Hospital and was designed to provide detailed information about the cardiovascular safety profile of Remimazolam as an anaesthetic during general anaesthesia for cardiac surgery. Moreover, it is expected to deliver further insights on titration of sedation in the postoperative phase. Two doses of Remimazolam (6 mg/kg/h and 12 mg/kg/h) have been evaluated head to head and against Propofol during induction of general anaesthesia. In the maintenance phase of anaesthesia, Remimazolam was tested against the standard combination of Propofol and Sevoflurane. Furthermore, data in the postoperative sedation phase in the postoperative care unit or ICU against Propofol were obtained and can be used for further exploration of the ICU sedation indication. The study was designed such that the data can complement the anaesthesia study results conducted by Ono in Japan and could then be used together with the Japanese studies for filing for regulatory approval. ### About Remimazolam Remimazolam is an innovative short-acting general anaesthetic/sedative. Due to its short duration of action and good controllability, it has a preferable efficacy and safety profile relative to other currently marketed anaesthesia compounds. The rapid offset of Remimazolam's effect is due to its metabolism by tissue esterase enzymes that are widely distributed throughout the body. Remimazolam has potential in three indications: - Procedural sedation - General anaesthesia - ICU sedation Remimazolam is available for licensing outside Japan, China, Russia (CIS) and Turkey, as well as South Korea, where the compound is partnered with Ono Pharmaceutical, Yichang Humanwell, R-Pharm and Hana Pharm. About PAION PAION AG is a publicly-listed specialty pharma company headquartered in Aachen, Germany with a second site in Cambridge, UK. The company has a track record in developing hospital-based treatments for which there is substantial unmet medical need. PAION AG is transforming its business model from a pure development company to a specialty pharmaceutical company with a focus on anaesthesia products to take advantage of the unique profile of its main compound, Remimazolam. Contact Ralf Penner Director Investor Relations / Public Relations PAION AG Martinstrasse 10-12 52062 Aachen - Germany Phone: +49 241 4453-152 E-mail: r.penner@paion.com www.paion.com Disclaimer: This release contains certain forward-looking statements concerning the future business of PAION AG. These forward-looking statements contained herein are based on the current expectations, estimates and projections of PAION AG's management as of the date of this release. They are subject to a number of assumptions and involve known and unknown risks, uncertainties and other factors. Should actual conditions differ from PAION AG's assumptions, actual results and actions may differ materially from any future results and developments expressed or implied by such forward-looking statements. Considering the risks, uncertainties and other factors involved, recipients should not rely unreasonably upon these forward-looking statements. PAION AG has no obligation to periodically update any such forward-looking statements to reflect future events or developments. End of Corporate News --------------------------------------------------------------------- 28.05.2014 Dissemination of a Corporate News, transmitted by DGAP - a company of EQS Group AG. The issuer is solely responsible for the content of this announcement. DGAP's Distribution Services include Regulatory Announcements, Financial/Corporate News and Press Releases. Media archive at www.dgap-medientreff.de and www.dgap.de --------------------------------------------------------------------- Language: English Company: PAION AG Martinstr. 10-12 52062 Aachen Germany Phone: +49 (0)241-4453-0 Fax: +49 (0)241-4453-100 E-mail: info@paion.com Internet: www.paion.com ISIN: DE000A0B65S3 WKN: A0B65S Listed: Regulierter Markt in Frankfurt (Prime Standard); Freiverkehr in Berlin, Düsseldorf, Hamburg, München, Stuttgart End of News DGAP News-Service --------------------------------------------------------------------- 271195 28.05.2014