PAION CLOSES ENROLLMENT IN EU PHASE III TRIAL WITH REMIMAZOLAM IN GENERAL ANESTHESIA

DGAP-News: PAION AG / Key word(s): Research Update
02.04.2020 / 13:00
The issuer is solely responsible for the content of this announcement.

PAION CLOSES ENROLLMENT IN EU PHASE III TRIAL WITH REMIMAZOLAM IN GENERAL ANESTHESIA

- 424 patients have been enrolled representing a sufficient number to conduct the planned statistical analyses

- Data monitoring committee has agreed to close the trial with the current number of patients

- Topline study results expected in H2 2020, timeline for MAA submission confirmed

Aachen (Germany), 02 April 2020 - The Specialty Pharma Company PAION AG (ISIN DE000A0B65S3; Frankfurt Stock Exchange Prime Standard: PA8) today announces the close of patient recruitment in the EU Phase III trial with remimazolam, an ultra-short-acting benzodiazepine sedative/anesthetic, for the induction and maintenance of general anesthesia.

The randomized, single-blind, propofol-controlled, confirmatory Phase III trial was expected to enroll approximately 500 ASA III/IV patients (American Society of Anesthesiologists classification III to IV) undergoing planned surgery at more than 20 European sites. Due to the coronavirus pandemic, patient recruitment was completed at 424 patients agreed to by the Data Monitoring Committee.

PAION believes that these data will provide sufficient statistical power to conduct analyses of the primary and secondary endpoints of the trial. Data from Phase III trials conducted by our licensees in South Korea and Russia will provide additional safety data in the general anesthesia indication.

Topline data are expected in the second half of 2020 and the timeline for preparing regulatory submission following the anticipated approval of remimazolam in procedural sedation in the EU remains unchanged.

The primary objective of the trial is to demonstrate the non-inferiority of remimazolam compared to propofol for the induction and maintenance of general anesthesia during elective surgery. The key secondary objective is to show improved hemodynamic stability (avoidance of intraoperative drop of blood pressure and vasopressor usage) compared to propofol.

Based on Scientific Advice obtained from the European Medicines Agency (EMA) in January 2018, PAION expects that a positive Phase III trial in combination with previously completed clinical studies in Europe, South Korea, Russia and Japan should be sufficient for market approval in the indication of general anesthesia in the EU.

Assuming approval of the Marketing Authorization Application (MAA) in procedural sedation and positive results in this Phase III trial in general anesthesia, PAION plans to submit an extension of the marketing authorization application for remimazolam for general anesthesia. The review process for an extension is generally faster than for an MAA. The complete data from the EU Phase III study in general anesthesia, which are required for the submission of an extension of marketing authorization application, are expected to be available at the time of the regulatory decision on the MAA in procedural sedation. PAION is allowed to submit an extension for general anesthesia after the EMA's decision on the MAA in procedural sedation at the earliest.

Dr. Jim Phillips, CEO of PAION AG, commented: "Following discussion with the Data Monitoring Committee and a careful assessment of the current situation, given the ongoing coronavirus pandemic, we believe it is the right decision to stop recruitment in the remimazolam Phase III trial in general anesthesia now.

The statistical powering of the study means that we are confident that we can report both primary and secondary endpoints in the analysis. We look forward to obtaining topline data in the second half of 2020 and, if all goes as expected, preparing for a regulatory submission following the anticipated approval of remimazolam in procedural sedation in the EU.

We would like to thank all of the hospitals participating in the Phase III study for their work with our trial and we give thanks to all our healthcare colleagues & centres for their work now to combat the Covid-19 pandemic."

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About remimazolam
Remimazolam is an ultra-short-acting intravenous benzodiazepine sedative/anesthetic. In the human body, remimazolam is rapidly metabolized to an inactive metabolite by tissue esterases and is not metabolized by cytochrome-dependent hepatic pathways. Like other benzodiazepines, remimazolam can be reversed with flumazenil to rapidly terminate sedation or anesthesia if necessary. In clinical studies, remimazolam demonstrated efficacy and safety in around 2,500 volunteers and patients. Data so far indicate that remimazolam has a rapid onset and offset of action combined with a favorable cardio-respiratory safety profile.

In Japan, licensee Mundipharma received market approval in general anesthesia in January 2020. In the U.S., licensee Cosmo Pharmaceuticals submitted a New Drug Application for procedural sedation in April 2019, with a PDUFA decision date of 05 July 2020. In China, licensee Yichang Humanwell filed for market approval in procedural sedation in November 2018. In South Korea, licensee Hana Pharm filed for market approval in general anesthesia in December 2019. In Europe, PAION submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in procedural sedation in November 2019 and results of an EU Phase III trial in general anesthesia are expected in the second half of 2020.

In addition to procedural sedation and general anesthesia, based on positive Phase II study results, ICU sedation is another possible indication for remimazolam.

Remimazolam is partnered in the U.S. (Cosmo Pharmaceuticals, sublicensed to Acacia Pharma), Japan (Mundipharma), China (Yichang Humanwell), Canada (Pharmascience), Russia/CIS, Turkey and the MENA region
(R-Pharm) as well as South Korea and Southeast Asia (Hana Pharm). For all other markets including parts of the EU, remimazolam is available for licensing.

About PAION
PAION AG is a publicly listed specialty pharmaceutical company developing and aiming to commercialize innovative drugs for out-patient and hospital-based sedation, anesthesia and critical care services. PAION's lead compound is remimazolam, an intravenous, ultra-short-acting and controllable benzodiazepine sedative/anesthetic. Remimazolam is partnered in multiple territories outside of Europe. In Japan, remimazolam was approved for general anesthesia in January 2020. In the U.S., a New Drug Application (NDA) for procedural sedation is under review, with a PDUFA date of 5 July 2020. In China, licensee Yichang Humanwell filed for market approval for remimazolam in procedural sedation in November 2018 and in South Korea, licensee Hana Pharm filed for market approval for remimazolam in general anesthesia in December 2019.

In Europe, PAION is seeking approval of remimazolam for general anesthesia and for procedural sedation. PAION submitted a Marketing Authorization Application (MAA) for procedural sedation in November 2019. Results of a Phase III trial in general anesthesia are expected in the second half of 2020.

PAION's mission is to be a leading specialty pharmaceutical company in the fields of anesthesia & critical care by bringing novel products to market to benefit patients, doctors & stakeholders in healthcare.

PAION is headquartered in Aachen (Germany) with an additional site in Cambridge (United Kingdom).

Contact
Ralf Penner
Vice President 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 the Company'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.

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