Download Remimazolam

PAION
Conference Call
Dr. Wolfgang Söhngen, CEO
15 February 2016
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.
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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
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Remimazolam
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PAION‘s lead product Remimazolam
Product
 Ultra-short-acting anesthetic/
sedative
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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
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)
 Phase III in colonoscopy
started in March 2015
 1 Hepatic impairment
study in the U.S. (Ono)
 Phase III in bronchoscopy
started in June 2015
 1 Phase II trial in Germany
 Discontinued
 3 Phase I studies ongoing
 ASA III/IV patients started
in Dec 2015)
More than 2,000 patients on drug planned @filing
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About Remimazolam
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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:
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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
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General Anesthesia
 Standards of care: propofol and volatile gases
 EU Phase III program vs. propofol
 Japan Phase III program vs. propofol
Remimazolam – EU Program
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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.
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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  Randomized, parallel-group study in 90 patients
patients undergoing surgery requiring general
undergoing cardiac surgery using a heart-lung
anesthesia
machine
 Success rate of 100 %, met all endpoints
 Success rate of 98 %
 The incidence rates of decrease in blood
 Improved hemodynamic stability profile as
pressure were 35 % (Remimazolam group) vs.
significantly less vasopressor therapy was
60 % (propofol group)
needed
 Remimazolam was well tolerated
 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
Remimazolam has shown improved hemodynamic stability over propofol in two
independent trials in two different patient populations
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Our Mission in General Anesthesia:
Reducing the detrimental effects of
Hypotension
Patients with APM
< 60 mm Hg
First hour after intubation
80%
70%
Share of patients with BIS
score below 40 until 1 h after
intubation
Share of Patients with any
vasopressor
entire study
70%
70,7%
60%
Too deep sedation
Need for Vasopressors
NNT=3.4
60%
-41%
50%
80%
64,0%
NNT=4.2
70%
73,3%
60%
-37%
50%
-44%
50%
40%
40%
41,3%
40,0%
NNT=3.1
42,7%
45,3%
40%
41,3%
40,7%
30%
30%
30%
20%
20%
20%
10%
10%
10%
n=75
0%
n=150
n=150
0%
Propofol
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Remi 6mg
Remi 12mg
0%
Propofol
Remi 6mg
Remi 12mg
Propofol
Remi 6mg
Remi 12mg
EU Phase III study design in cardiac surgery
Weaning with
Remimazolam
Induction with
Maintenance with
Remimazolam
Remimazolam
6.0 mg/kg/hr
1.0 – 3.0 mg/kg/hr
0.1 mg/kg/hr
ICU Sedation with
Remimazolam
0.25 – 1.0 mg/kg/hr
Surgery incl.
HLM
Randomization
Weaning with
Propofol
Induction with
Propofol
Maintenance with
Propofol
ICU Sedation with
Propofol
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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
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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.
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Remimazolam – U.S. Strategy
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U.S. – Launch indication targets growing outpatient
colonoscopy screening market
Hospital
Out-Patient
Remimazolam
ICU
Sedation
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Surgical General
Anesthesia
Procedural
Sedation
(eg. day cases)
Procedural
Sedation
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
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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.
Remimazolam – U.S. program procedural sedation
Pivotal Studies
Colonoscopy: Remimazolam (n=300) vs.
placebo (n=60) and midazolam (n=100)
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Started in March 2015 – Completion expected in
Q1 2016
 Bronchoscopy: Remimazolam (n=300) vs. placebo
(n=60) and midazolam (n=100)
Started in June 2015 – Completion expected in
2016/2017
Pediatric Study
 After filing
Pediatric Plan agreed with FDA
Labeling comparable to
midazolam
Safety Studies
 primary goal
 Colonoscopy ASA III/IV patients
(Remimazolam n=30 vs. midazolam n=30 vs.
placebo n=15)
Filing scheduled in 2017
Started in December 2015 – Completion expected in
2016
 Phase I Studies
Thorough QT Study, Renal Impairment,
Abuse Liability
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Next Steps - U.S. program procedural sedation
 Colonosocopy
 Recruitment completion expected in Q1 2016
 Bronchoscopy
 Patient recruitment in the Phase III bronchoscopy trial remains moderate which
could possibly extend the completion into 2017
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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 2017
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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
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Remimazolam – Strategy Japan / Asia
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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)
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Summary
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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 Q1 2016
 All other regions:
 Continuation of development activities by cooperation partners
(Yichang Humanwell, Hana Pharm, R-Pharm, TR-Pharm, Pendopharm)
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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.
2016
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Pre-NDA Meeting in Japan
Q &A
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Thank you very much
for your attention!
Contact:
PAION AG
Martinstrasse 10–12
52062 Aachen – Germany
Phone +49 241 44 53-0
[email protected]
www.paion.com
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