PAION Conference Call. Dr. Wolfgang Söhngen, CEO 15 February 2016

Transcription

1 PAION Conference Call Dr. Wolfgang Söhngen, CEO 15 February 2016

2 Disclaimer It is important to note that this information contains forward-looking statements which are based on the currently held beliefs and assumptions of the management of PAION AG, which are expressed in good faith and, in its opinion, reasonable. Forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause the actual results, financial condition, performance, or achievements of PAION AG, or industry results, to differ materially from the results, financial condition, performance or achievements expressed or implied by such forward-looking statements. Given these risks, uncertainties and other factors, recipients of this information are cautioned not to place undue reliance on these forward-looking statements. PAION AG disclaims any obligation to update these forward-looking statements to reflect future events or developments. This presentation constitutes neither an offer to sell nor a solicitation to buy any securities of PAION AG (the Securities ) in Germany, the United States of America, the United Kingdom or any other jurisdiction. Neither this presentation nor anything contained herein shall form the basis of, or be relied on in connection with, any offer or commitment whatsoever. The Securities have not been and will not be registered under the U.S. Securities Act of 1933, as amended (the Securities Act ). The Securities may not be offered or sold in the United States absent registration or an exemption from registration under the Securities Act. 2

3 Agenda 1. Remimazolam EU Program Stop of Cardiac Surgery Study Outlook for potential new study U.S. Program Colonoscopy trial Bronchoscopy trial Japan/Asia Status Quo 3

4 Remimazolam 4

5 PAION s lead product Remimazolam Product Ultra-short-acting anesthetic/ sedative Trials More than 1,000 volunteers/ patients have received Remimazolam in trials Current focus is conducting Phase III trials Market Market exclusivity expected until at least 2027 (2031 in the U.S.) Attractive peak sales potential of ~US$ 500m worldwide per year in each indication 5

6 Remimazolam Extensive efficacy and safety database Completed Studies with more than 1,000 volunteers/patients on drug Ongoing/planned studies Procedural Sedation General Anesthesia Procedural Sedation General Anesthesia 4 Phase I/II trials in the U.S. 3 Phase I/II trials in Japan (Ono) Phase III program in the U.S. Phase III program in the EU 2 Phase III trials in Japan (Ono) 1 Hepatic impairment study in the U.S. (Ono) 1 Phase II trial in Germany Phase III in colonoscopy started in March 2015 Phase III in bronchoscopy started in June Phase I studies ongoing ASA III/IV patients started in Dec 2015) Discontinued More than 2,000 patients on drug 6

7 About Remimazolam Member of the benzodiazepine family Rapidly metabolized by tissue esterases Ultra-short-acting intravenous sedative/anesthetic Can be reversed with flumazenil if required Results to date indicate: Efficacy and safety in studied populations Rapid onset and offset of action Appropriate depth of sedation Hemodynamic stability Procedural sedation Standards of care: midazolam and propofol US Phase III program vs. midazolam General Anesthesia Standards of care: propofol and volatile gases EU Phase III program vs. propofol Japan Phase III program vs. propofol 7

8 Remimazolam EU Program 8

9 Remimazolam EU program discontinued EU Phase III General Anesthesia discontinued Phase III Trial in cardiac surgery patients discontinued due to insufficient recruitment No drug related serious adverse events have been observed or any other unexpected conditions The EU observations have no impact on the U.S. and Japanese program Despite a positive feasibility study (EU Phase II) and an intensive effort to enhance study recruitment the complex study design difficult to implement in practice PAION decided to discontinue the trial in order to avoid a long and expensive study with the existing design. 9

10 Basis for EU Phase III design in General Anesthesia Japanese Phase III Study confirms efficacy and safety of Remimazolam compared to propofol PAION Phase II Study confirms efficacy and safety of Remimazolam compared to propofol/sevoflurane Multicenter, randomized, parallel-group study in 375 patients undergoing surgery requiring general anesthesia Success rate of 100 %, met all endpoints The incidence rates of decrease in blood pressure were 35 % (Remimazolam group) vs. 60 % (propofol group) Remimazolam was well tolerated Randomized, parallel-group study in 90 patients undergoing cardiac surgery using a heart-lung machine Success rate of 98 % Improved hemodynamic stability profile as significantly less vasopressor therapy was needed Remimazolam was well tolerated Remimazolam has the potential to substitute propofol due to comparable efficacy and lower rates of decrease in blood pressure Dose regimen of Japanese trial confirmed Remimazolam has the potential to substitute propofol due to comparable efficacy and improved hemodynamic stability 10 Remimazolam has shown improved hemodynamic stability over propofol in two independent trials in two different patient populations

11 Our Mission in General Anesthesia: Reducing the detrimental effects of Hypotension Need for Vasopressors Too deep sedation Patients with APM < 60 mm Hg First hour after intubation Share of Patients with any vasopressor entire study Share of patients with BIS score below 40 until 1 h after intubation 80% 70% 80% 70% 70,7% NNT=3.4 64,0% 60% NNT=4.2 70% 73,3% NNT=3.1 60% 50% 40% -41% 41,3% 41,3% 50% 40% 30% -37% 40,0% 42,7% 60% 50% 40% -44% 40,7% 45,3% 30% 30% 20% 20% 20% 10% 10% 10% 0% Propofol Remi 6mg Remi 12mg 0% n=75 n=150 n=150 Propofol Remi 6mg Remi 12mg 0% Propofol Remi 6mg Remi 12mg 11

12 EU Phase III study design in cardiac surgery Induction with Remimazolam 6.0 mg/kg/hr Maintenance with Remimazolam mg/kg/hr Weaning with Remimazolam 0.1 mg/kg/hr ICU Sedation with Remimazolam mg/kg/hr Randomization Surgery incl. HLM Weaning with Propofol Induction with Propofol Maintenance with Propofol ICU Sedation with Propofol 12

13 Practical implementation issues Use of Narcotrend monitoring instead of gold standard BIS. Reason: raw EEG recording Use of invasive blood pressure monitoring with arterial catheter and frequent need for calibration (PiCCO), method unknown to some sites Study drug requires high speed syringe pump Control arm proved difficult as TIVA is not standard of care in cardiac surgery Study nurse availability for real time documentation required over > 8 hours on the day of surgery Complex central lab works Need for daily delirium scoring 13

14 Remimazolam EU program next steps EU Phase III General Anesthesia discontinued New EU Phase III trial subject to further funding We will now develop a plan that allows to implement a clinical plan in Europe that builds on the insights we gained from the cardiac surgery trial New funding or partnering is necessary for a further trial Guidance We are currently updating our financial plans to reflect that we are focusing on the U.S. development Based on current assumptions and timelines we have sufficient funds to conduct the clinical development in the U.S. A new cash guidance will be given next month on 22 March 2016 when we publish FY 2015 earnings. 14

15 Remimazolam U.S. Strategy 15

16 U.S. Launch indication targets growing outpatient colonoscopy screening market Hospital Out-Patient Remimazolam ICU Sedation Surgical General Anesthesia Procedural Sedation (eg. day cases) Procedural Sedation 16

17 Market Opportunity: Primary focus Colonoscopy Rapidly growing market, big push for colorectal cancer screening: Colonoscopy = the only diagnostic proven to prevent cancer Regular and appropriate colorectal cancer screening is both recommended and covered by all major health plans including CMS More than 4 million patients turn 50 and are newly eligible each year, baby boomers are all of age for screening, i.e. > 50 years Millions more covered lives in the U.S. as a result of the Affordable Care Act U.S. Market Size Total U.S. market for procedural sedation = 33 million procedures National Health Statistics Report Number 11 Jan. 28, 2009 revised; procedure estimates from the NSAS National Survey of Ambulatory Surgery 20 million procedures were performed outside of hospitals and represent the most attractive segment for PAION 29 million unique procedure claims for colonoscopy and endoscopy in 2013 Colonoscopy/endoscopy procedures updated with 2013 CPT, ICD9, HCPCS procedure code data from Symphony Health Solutions. 17

18 Remimazolam U.S. program procedural sedation Pivotal Studies Colonoscopy: Remimazolam (n=300) vs. placebo (n=60) and midazolam (n=100) Started in March 2015 Completion expected in Q Bronchoscopy: Remimazolam (n=300) vs. placebo (n=60) and midazolam (n=100) Started in June 2015 Completion expected in 2016/2017 Safety Studies Colonoscopy ASA III/IV patients (Remimazolam n=30 vs. midazolam n=30 vs. placebo n=15) Started in December 2015 Completion expected in 2016 Phase I Studies Thorough QT Study, Renal Impairment, Abuse Liability Pediatric Study After filing Pediatric Plan agreed with FDA Labeling comparable to midazolam primary goal Filing scheduled in

19 Next Steps - U.S. program procedural sedation Colonosocopy Recruitment completion expected in Q Bronchoscopy Patient recruitment in the Phase III bronchoscopy trial remains moderate which could possibly extend the completion into 2017 Counter measures for the moderate recruitment of the bronchoscopy study include Initiation of additional study centers On site training of the study centers Focussing freed up resources from EU program to accelerate U.S. study completion U.S. Filing Conditional on successful implementation of ongoing counter measures, PAION expects filing for approval in

20 U.S.-Patent protection until 2031 Exclusive protection until 2031 in the U.S.market Grant strengthens the Remimazolam patent portfolio The subject matter of the patent relates to crystalline forms of the besylate salt of Remimazolam Selection of the besylate salt for patent protection was based on extensive screening data providing proof of its excellent stability profile Based on PAION's research and development activities, the besylate represents the most viable salt form both from a drug safety and commercial perspective 20

21 Remimazolam Strategy Japan / Asia 21

22 Remimazolam Japan Remimazolam rights for Japan returned from Ono to PAION in July 2015 Know-how transfer (ONO -> PAION) completed Data from six clinical trials (Phase I-III) and preclinical studies will now be integrated into PAION s database PAION has been contacted by parties interested in Japan Partnering process for a Remimazolam license for Japan ongoing KOLs confirmed that Remimazolam is regarded a needed innovation for the Japanese anesthesia market PMDA: PAION applied for a Pre-NDA meeting Positive PMDA feedback: Product produced in Europe can be used for commercialization in Japan Results of the Pre-NDA meeting will be published after the final meeting protocol is available (expected Q1 2016) 22

23 Summary 23

24 Outlook 2016 and strategy Remimazolam Focus on the Phase III program in the U.S. Partnering and commercialization: EU and U.S.: Evaluation of commercialization and partnering strategies Japan: Filing strategy to be decided after Pre-NDA meeting outcome in Q All other regions: Continuation of development activities by cooperation partners (Yichang Humanwell, Hana Pharm, R-Pharm, TR-Pharm, Pendopharm) 24

25 Upcoming milestones 2017 Potential filing in Japan (subject to and focus on partnering discussions) LPO Phase III Bronchoscopy U.S. Headline data Phase III Colonoscopy U.S. LPO Phase III Colonoscopy U.S Pre-NDA Meeting in Japan 25

26 Q &A 26

27 Thank you very much for your attention! Contact: PAION AG Martinstrasse Aachen Germany Phone