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Jefferies 2016 Healthcare Conference
Greg Weinhoff, Chief Financial Officer
CONFIDENTIAL
Forward-Looking Statements
Statements made in this presentation contain forward-looking statements, including: statements regarding Axovant’s
expectations about timing of the results for the Phase 3 MINDSET study of intepirdine in patients with Alzheimer's
disease, the Phase 2b HEADWAY-DLB study of intepirdine in patients with dementia with Lewy bodies, the Phase 2
study of nelotanserin in patients with DLB or PDD suffering from visual hallucinations, the Phase 2 study of nelotanserin
in patients with DLB suffering from RBD and other elements of its clinical development and regulatory strategy; and
statements regarding the size of the market opportunity for one or both drug candidates. Forward-looking statements
can be identified by the words such as “believe,” “anticipate,” “continue”, “estimate”, “project,” “expect,” “plan,”
“potential,” “intends,” “may,” “will,” “would”, “could”, “should” or the negative or plural of these words or other
similar expressions that are predictions or indicate future events, trends or prospects. Forward-looking statements are
subject to risks and uncertainties that could cause actual results and the timing of certain events to differ materially
and reported results should not be considered as an indication of future performance. These risks and uncertainties
include, but are not limited to: risks associated with the success, cost and timing of our product development activities
and clinical trials; the approval and commercialization of our product candidates intepirdine and nelotanserin; and
increased regulatory requirements. These statements are subject to the risk that clinical trial data are subject to
differing interpretations, and regulatory agencies, medical and scientific experts and others may not share Axovant’s
views of the clinical study data. There can be no assurance that the clinical programs for intepirdine or nelotanserin will
be successful in demonstrating safety and/or efficacy, that we will not encounter problems or delays in clinical
development, or that any of our product candidates will ever receive regulatory approval or be successfully
commercialized. For a further description of the risks and uncertainties that could cause actual results to differ from
those expressed in these forward-looking statements, as well as risks relating to Axovant’s business in general, see the
“Risk Factors” section of our annual report on Form 10-K to be filed with the Securities and Exchange Commission on
June 6, 2016, and other filings that Axovant makes with the SEC from time to time. These forward-looking statements
are based on information available to Axovant as of the date of this presentation and speak only as of the date of this
presentation. Axovant disclaims any obligation to update these forward-looking statements, except as may be required
by law.
June 2016
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Axovant Sciences – The Dementia Solutions Company
Vision: Dementia Solutions
• Become the leading company focused on the treatment of dementia by
addressing all forms and aspects of the condition
Mission: Create Value for Patients and Shareholders
• Build a late-stage pipeline of CNS drugs in a capital-efficient manner to
deliver value to patients and shareholders
Lead Drug in Phase 3 for Alzheimer’s Disease
• Intepirdine (RVT-101) is one successful pivotal phase 3 study away from
approval by FDA and EMA in Alzheimer’s disease
Global Leader in Lewy Body Dementia
• Intepirdine and nelotanserin could potentially be first two drugs approved
by FDA and EMA in Dementia with Lewy Bodies
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Strong Leadership Team
Management and Directors
Vivek Ramaswamy*
Chief Executive Officer
Lawrence Olanoff,
M.D., Ph.D.
Director
Mark Altmeyer*
President & Chief
Commercial Officer
Atul Pande,
M.D.
Director
Lawrence Friedhoff,
M.D., Ph.D.*
Chief Development
Officer
Ilise Lombardo,
M.D.
Vice President,
Clinical Research
Greg Weinhoff,
M.D.*
Chief Financial Officer
Axovant team includes developers of both Aricept (Dr. Friedhoff) and Namenda (Dr. Olanoff)
*Employee and officer of Axovant Sciences, Inc., a wholly-owned subsidiary of Axovant Sciences Ltd.
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Market Leading Dementia Pipeline
Compound
Indication
Phase 1
Mild-to-moderate
Alzheimer’s disease
Intepirdine
(RVT-101)
Dementia with
Lewy bodies (DLB)
Visual hallucinations in
Lewy body dementia
Nelotanserin
• DLB and Parkinson’s
disease dementia
(PDD)
REM behavior
disorder (RBD)
• DLB
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Phase 2
Phase 3
Key Highlights of Intepirdine in Mild-to-Moderate
Alzheimer’s Disease
Intepirdine May be One
Successful Trial from Approval
Favorable Safety and
Tolerability Profile
Immediate Benefit that is
Sustained over Time
• Confirmatory MINDSET Phase 3 trial started in October 2015
• Agreement with FDA on Special Protocol Assessment
• Data and potential NDA filing expected in 2017
• 16 clinical studies complete with > 1,300 human subjects exposed
• Three new studies completed by Axovant, including at 70 mg QD dose
• Dosing for 48 weeks with low dropout and adverse event rates
• Benefits compared to donepezil alone are above baseline at earliest time
points measured
• Benefits sustained for at least 48 weeks vs. donepezil alone
Ease of Use for Patients
• Once-daily oral dosing
• Potential for fixed-dose combination with donepezil at launch
• No requirement for PET imaging, MRI monitoring, or IV infusions
Strong Intellectual
Property Position
• Composition of matter IP protection through 2029 (including PTE)
• Pending applications may extend patent life through 2035
• Axovant owns global rights
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Proven Mechanism of Action with Donepezil
Mechanism Supports Potential Utility in Multiple Forms of Dementia
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48-Week Intepirdine Combination Trial
Adjunctive Therapy to Donepezil
• International, multi-center, double-blind, placebo-controlled trial in
subjects with mild-to-moderate Alzheimer’s disease (n = 684)
– Locations: U.S., Germany, Italy, Canada, Spain, Chile, Czech Republic, Argentina, Australia
%
completing
Intepirdine 35 mg
Once daily on top of
stable dose of
donepezil (n = 236)
684 subjects*
receiving
stable dose of
donepezil
Intepirdine 15 mg
Once daily on top of
stable dose of
donepezil (n = 221)
89%
86%
WEEK
24
Primary Endpoints
%
completing
210
subjects
Intepirdine 35 mg
Once daily on top of
stable dose of
donepezil (n = 194)
191
subjects
Intepirdine 15 mg
Once daily on top of
stable dose of
donepezil (n = 170)
198
subjects
Placebo
Once daily on top of
stable dose of
donepezil (n = 173)
89%
WEEK
48
Intepirdine 35 mg
Once daily on top of
stable dose of
donepezil (n = 172)
86%
Intepirdine 15 mg
Once daily on top of
stable dose of
donepezil (n = 147)
87%
Placebo
Once daily on top of
stable dose of
donepezil (n = 151)
* Two subjects did
not receive a dose
Randomization was
stratified to achieve:
MMSE 10-15: < 30% subjects
MMSE 16-20: < 60% subjects
MMSE 21-26: < 30% subjects
Placebo
Once daily on top of
stable dose of
donepezil (n = 225)
88%
Double-Blind Treatment: 48 Weeks
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Improvements on ADAS-cog and ADCS-ADL at 48 Weeks
Pre-Specified ITT Method of Analysis
Change from Baseline: ADAS-cog
-1.5
Change from Baseline: ADCS-ADL
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Donepezil Alone
15 mg Intepirdine Plus Donepezil
-0.5
Donepezil Alone
15 mg Intepirdine Plus Donepezil
1
35 mg Intepirdine Plus Donepezil
35 mg Intepirdine Plus Donepezil
0
0.5
-1
-2
1.5
-3
2.5
-4
-5
3.5
0
12
24
Weeks
36
-6
48
0
12
24
Weeks
36
48
Week
35 mg Intepirdine Difference
vs. Donepezil Alone
P- value
Week
35 mg Intepirdine Difference
vs. Donepezil Alone
P- value
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1.30
0.006
12
1.72
0.019
24
1.50
0.013
24
2.00
0.024
36
1.21
0.057
36
1.93
0.038
48
1.64
0.024
48
1.94
0.088
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Intepirdine Phase 3 Confirmatory MINDSET Trial
Initiated in October 2015
Clear Regulatory Guidance:
Designed to Replicate Success:
• FDA confirmed a single successful phase 3 trial may
be sufficient to support regulatory filing
• Co-primary endpoints: ADAS-cog and ADCS-ADL
 Gold standard measures of cognition and function
• Two arms: intepirdine 35 mg and placebo
 May reduce residual placebo response
• 500+ subjects per arm (>2x as many as prior trial)
 Added statistical power relative to prior trial
• Special Protocol Assessment (SPA) with FDA for
MINDSET phase 3 trial
Phase 3 MINDSET Design and Key Assessment Timeline
1,150 subjects
receiving stable
dose of donepezil
Intepirdine 35 mg
Once daily on top of
stable dose of
donepezil
Placebo
Once daily on top of
stable dose of
donepezil
WEEK 24
Primary
Endpoints
Double-Blind Treatment: 24 Weeks
10
Completing
Subjects
Eligible for
Open-Label
Extension
WEEK 76
Intepirdine 35 mg
Once daily on top of
any cholinesterase
inhibitor and/or
memantine
Safety and
Tolerability
Open-Label Extension: 52 Weeks
Lewy Body Dementia
CONFIDENTIAL
What is Lewy Body Dementia?
Umbrella term
for two related diagnoses with
similar pathology and clinical presentation
Dementia with Lewy
Bodies (DLB)
Parkinson’s Disease
Dementia (PDD)
Cognitive decline must occur
within one year of the onset of
movement disorder symptoms
Movement disorder symptoms
must precede cognitive decline
by more than one year
80% have visual hallucinations
65% have RBD
70% have visual hallucinations
30% have RBD
300,000 patients
1.1 million patients
Lewy Body Dementia has both cognitive and behavioral
aspects that have largely been unaddressed
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Intepirdine in Dementia with Lewy Bodies (DLB)
Potential First-in-Class Therapy
Significant Unmet
Need
Cholinergic Deficits
Cognition and
Function
Behavioral
Disturbances
• No drugs approved in the U.S. or EU
• Aricept was approved in Japan for the treatment of DLB in 2014
• A prominent feature of DLB
• Cholinergic neurotransmission is more dysfunctional in DLB than Alzheimer’s
disease
• Increasing acetylcholine improves cognition and function in DLB
• Intepirdine promotes the release of acetylcholine
• 5HT2A activity is a potential driver of visual hallucinations1
• In addition to 5HT6 activity, intepirdine is an antagonist of the 5HT2A receptor
 Evaluating 35mg and 70mg dose of intepirdine to increase 5HT2A receptor occupancy
1Ballanger
et al., Arch Neurol 2010. Vol. 67:4, 416-421.
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Intepirdine HEADWAY-DLB Program
Addressing Cognition and Function
Population:
Key Endpoints:
• 240 subjects with diagnosis of DLB
• MMSE score: 14 – 26 (inclusive)
• Stable background therapy will be allowed
240 subjects with
diagnosis of DLB
• Change from baseline on CIBIC+ and a
computerized cognitive battery
• Safety, tolerability, and change in behavioral
symptoms
Intepirdine 70 mg
WEEK 24
Intepirdine 35 mg
Primary
Endpoints
Placebo
Double-Blind Treatment: 24 Weeks
Completing
Subjects Eligible
for Active
Treatment
Extension
Active Treatment
Extension
Single successful study could serve as basis for approval of
intepirdine in DLB when combined with Alzheimer’s NDA filing
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Nelotanserin
CONFIDENTIAL
Nelotanserin: Potential Best-in-Class 5HT2A Inverse Agonist
Initial Focus on Behavioral Disturbances in Lewy Body Dementia
Strong Binding Affinity
Weak Binding Affinity
Drug Profile:
Atypical
Antipsychotics1
“1st Generation”
5HT2A Inverse Agonist
“Next Generation”
5HT2A Inverse Agonist
Pimavanserin2
Nelotanserin
5HT2A Antagonism
5HT2C Antagonism
MIXED
D2 Antagonism
Known risk of
motor symptoms?
YES
NO
NO
Known risk of
QTc prolongation?
MIXED
YES
NO
1Richtand
et al., Neuropsychopharmacology 2007. Vol. 32:8, 1715-1726.
et al., Int J Neuropsychopharm 2008. Vol. 11:2, 163-171.
2Nordstrom
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Rationale for Nelotanserin to Address
Visual Hallucinations in Lewy Body Dementia
5HT2A activity is a
potential driver
of visual
hallucinations
Underlying pathology
between PD and LBD
are very similar
Pimavanserin has
shown efficacy in
Parkinson’s disease
psychosis (PDP)
Broad Lewy body dementia population: Includes DLB and PDD patients
Pimavanserin Improvements on SAPS-PD
Phase 3 Parkinson’s disease psychosis trial
Ki Binding Affinity (nM)
Receptor
Nelotanserin
Pimavanserin
5HT2A
0.4
0.4
5HT2C
106
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Nelotanserin is selective only
for 5HT2A and has comparable
affinity to pimavanserin
Sources: Hacksell et al., Neurochem Res 2014; Al-Shamma et al., J Pharmacol Exp Ther 2010; Acadia Company Presentations; Ballanger et al., Arch Neurol 2010; Cummings et al., Lancet 2014
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Nelotanserin Phase 2 Pilot Study in Lewy Body Dementia
DLB and PDD Subjects Experiencing Frequent Visual Hallucinations
Population:
Key Endpoints:
• 20 subjects with diagnosis of DLB or PDD
• MMSE score ≥ 18
• Frequent visual hallucinations (occurring on most
days of the week)
20 subjects
with diagnosis
of LBD
(DLB or PDD)
• Change in frequency and severity of visual
hallucinations
• Safety and tolerability
• Exacerbation of motor symptoms
First Treatment Period
Second Treatment Period
Nelotanserin
Nelotanserin
Placebo
Placebo
28 Days
28 Days
Results to inform design of subsequent pivotal study
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Rationale for Nelotanserin in DLB Patients Experiencing
REM Behavior Disorder (RBD)
Overlap between visual
hallucinations and dream
content during REM behaviors
Arousals from sleep may
trigger disruptive REM
behaviors
In clinical studies, nelotanserin has shown robust
reductions in the number of arousals and
awakenings
Blocking the 5HT2A receptor reduces visual
hallucinations
Number of Arousals
Change from Screening
Positive Nelotanserin
Phase 2 Objective Sleep Study
•
n = 173 adult subjects with primary insomnia
Compared placebo to 10 mg and 40 mg nelotanserin
Subjects spent nights 1 and 2 and nights 6 and 7 combined in
a sleep laboratory
Both doses of nelotanserin showed robust benefits on wake
time after sleep onset, the primary endpoint (p < 0.0001)
Improvement
Number of Arousals
•
•
•
Nelotanserin produced statistically
significant improvements on
objective measures of sleep
maintenance and consolidation
Mean of:
Night 1 and 2
(Pre-Specified Modified ITT Population)
-9
Night 6 and 7
*
-7
*
-5
*
*
-3
-1
1
3
* = p < 0.0001
Sources: Rosenberg et al., SLEEP 2008; McKeith et al., Neuropsychopharmacology 2002.
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Placebo
10 mg
nelotanserin
40 mg
nelotanserin
Nelotanserin Phase 2 Study in REM Behavior Disorder
DLB Subjects Experiencing RBD
Population:
Key Endpoints:
• 60 subjects with diagnosis of DLB
• Frequent episodes of RBD (occurring on most days
of the week)
• Screening includes sleep lab evaluation
60 subjects with
diagnosis of DLB
experiencing RBD
• Change in frequency and severity of RBD
episodes as measured by objective sleep lab
assessments
• Safety and tolerability
Nelotanserin
Placebo
DAY 28
Primary
Endpoints
Double-Blind Treatment: 28 Days
Designed as potentially pivotal study
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Major Catalysts in 2016 and 2017
Catalyst
Expected Timing
Nelotanserin Phase 2 Study Results: LBD (Visual
Hallucinations)
H2 2016
Nelotanserin Phase 2 Study Results: RBD in DLB
2017
Intepirdine HEADWAY-DLB Study Results:
Dementia with Lewy Bodies
2017
Intepirdine MINDSET Study Results and potential
NDA Filing: Alzheimer’s Disease
2017
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Axovant Sciences – The Dementia Solutions Company
Axovant is Uniquely Positioned as the Leader in Dementia Solutions
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Jefferies 2016 Healthcare Conference
Greg Weinhoff, Chief Financial Officer
CONFIDENTIAL