AXOVANT SCIENCES LTD. JEFFERIES HEALTHCARE CONFERENCE JUNE 7, 2017
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 mild-to-moderate Alzheimer s disease on a stable background of donepezil therapy, the Phase 2b HEADWAY-DLB study of intepirdine in patients with DLB, 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, the Phase 2 study of the effects of intepirdine on a background of cholinesterase inhibitor therapy on gait and balance in patients with Alzheimer s disease, DLB and PDD, the clinical studies of RVT-103 and RVT-104 and the licensed technology related to a combination of cholinesterase inhibitors and peripheral muscarinic receptor antagonists, and other elements of its clinical development and regulatory strategy. Forward-looking statements can be identified by the words believe, anticipate, continue, estimate, project, expect, plan, potential, intend, 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 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, nelotanserin, RVT-103 and RVT-104; 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. In addition, promising interim results or other preliminary analyses do not in any way ensure that later or final results in a clinical trial or in related or similar clinical trials will replicate those interim results. The drug candidates discussed are investigational and not approved and there can be no assurance that the clinical programs including the programs for intepirdine, nelotanserin, RVT-103, or RVT-104 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 quarterly report on Form 10-Q filed with the Securities and Exchange Commission on February 14, 2017, 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. 2
A X O VA N T C O M PA N Y O V E R V I E W AXOVANT: THE NEUROLOGY SOLUTIONS COMPANY Vision: Neurology Solutions Become the leading company focused on the treatment of dementia by broadly addressing multiple forms of the condition Lead Drug in Phase 3 for Alzheimer s Disease If the results of the MINDSET study are favorable, we plan to seek regulatory approval and commercialize intepirdine Global Leader in Lewy Body Dementia Phase 2b HEADWAY-DLB study of intepirdine ongoing Two Phase 2 studies of nelotanserin ongoing in patients with visual hallucinations and REM sleep behavior disorder Long-Range Plan Reinvest any potential profits from intepirdine and nelotanserin launches into developing disease-reversing therapies for Alzheimer s disease and Lewy body dementia, as well as other neurological diseases of significant unmet patient need 3
A X O VA N T S C I E N C E S, I N C. C O M PA N Y O V E R V I E W STRONG AND EXPERIENCED LEADERSHIP TEAM David Hung, M.D. Chief Executive Officer Marion McCourt President & Chief Operating Officer Lawrence Friedhoff, M.D., Ph.D. Chief Development Officer Greg Weinhoff, M.D. Chief Financial Officer Mark Altmeyer* Chief Commercial Officer Ilise Lombardo, M.D. Senior Vice President, Clinical Research * President of Axovant Sciences GmbH All trademarks are property of their respective owners. 4
A X O VA N T S C I E N C E S, I N C. C O M PA N Y O V E R V I E W RECENT KEY MANAGEMENT ADDITIONS Stephen Mohr General Counsel Eric Floyd, Ph.D. Senior Vice President, Regulatory Affairs Thomas Templeman, Ph.D. Senior Vice President, Pharmaceutical Operations and Quality Assurance Mark Wadley Senior Vice President, U.S. Business All trademarks are property of their respective owners. 5
A X O VA N T C O M PA N Y O V E R V I E W MARKET LEADING DEMENTIA PIPELINE Compound Indication Phase 1 Phase 2 Phase 3 Mild-to-moderate Alzheimer s disease Intepirdine (RVT-101) 5HT 6 receptor antagonist Dementia with Lewy bodies Gait and balance impairments in dementia Nelotanserin (RVT-102) 5HT 2A receptor inverse agonist REM sleep behavior disorder in Lewy body dementia Visual hallucinations in Lewy body dementia RVT-103 Glycopyrrolate + Donepezil RVT-104 Glycopyrrolate + High Dose Rivastigmine Alzheimer s disease Alzheimer s disease/ Lewy body dementia These are investigational drugs subject to FDA approval 6
A X O VA N T C O M PA N Y O V E R V I E W CATALYSTS IN 2017 Catalyst Expected Timing Intepirdine MINDSET Phase 3 Study Results Mild-to-moderate Alzheimer s disease Late September 2017 Intepirdine HEADWAY-DLB Study Results Dementia with Lewy bodies Q4 2017 Intepirdine Phase 2 Study Results Gait and balance impairments in dementia 2017 Nelotanserin Phase 2 Study Full Results Visual hallucinations in Lewy body dementia 2H 2017 Nelotanserin Phase 2 Study Results REM sleep behavior disorder in Lewy body dementia 2H 2017 RVT-103 Proof-of-Concept Study Results 1H 2017 7
INTEPIRDINE - I N TEPIRDINE: ALZHEIMER S DISEASE - I N TEPIRDINE: G AIT AND BALANCE I N AD, DLB, AND PDD
I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E INTEPIRDINE INCREASES ACETYLCHOLINE BY A DIFFERENT MECHANISM OF ACTION THAN DONEPEZIL Donepezil reduces acetylcholine breakdown in the synapse Intepirdine increases acetylcholine release into the synapse Intepirdine Acetylcholine level in the brain Donepezil Baseline Donepezil alone Intepirdine + donepezil Vehicle Intepirdine (1.0 mg/kg) Donepezil (0.3 mg/kg) Donepezil + intepirdine Donepezil (1.0 mg/kg) Donepezil + intepirdine Microdialysis studies in rats demonstrate increased acetylcholine levels over donepezil alone 1 1 Dawson, Intl. Review of Neurobiology, Vol. 96 9
I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E KEY HIGHLIGHTS OF INTEPIRDINE Validated Target (Acetylcholine) But New MOA (5HT6) Cholinesterase inhibitors improve cognition and function in dementia 5HT 6 receptor antagonists observed to promote the release of acetylcholine and other neurotransmitters 1 Strong Clinical Results of 5HT6 Inhibition in Phase 2 Lundbeck s idalopirdine with statistically significant effects on ADAS-cog in Phase 2 (n = 278) at 90mg/day Axovant s intepirdine with statistically significant effects on ADAS-cog and ADCS-ADL in Phase 2 at 35 mg/day Phase 3 MINDSET Study Design Mirrors Successful Phase 2 Study Phase 2 study: 684 patients, 15 and 35 mg/day, achieved statistical significance on endpoints ADAS-cog and ADCS-ADL at the 35 mg/day dose Phase 3 MINDSET study: 1,315 patients, 35 mg/day, primary endpoints are ADAS-cog and ADCS-ADL Strong Intellectual Property Position Composition of matter IP protection through 2029 (including anticipated PTE) Pending applications may extend patent life through 2036 1 Upton et al., Neurotherapeutics 2008, Vol. 5:3, 458-469 10
I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E ADJUNCTIVE THERAPY STUDY International, multi-center, double-blind, placebo-controlled trial in subjects with mild-tomoderate Alzheimer s disease (n = 684) Locations: U.S., Germany, Italy, Canada, Spain, Chile, Czech Republic, Argentina, Australia % completing WEEK 24 Primary Endpoints % completing WEEK 48 Intepirdine 35 mg Once daily on top of stable dose of donepezil (n = 236) 89% 210 subjects Intepirdine 35 mg Once daily on top of stable dose of donepezil (n = 194) 89% Intepirdine 35 mg Once daily on top of stable dose of donepezil (n = 172) 684 subjects * receiving stable dose of donepezil Intepirdine 15 mg Once daily on top of stable dose of donepezil (n = 221) 86% 191 subjects Intepirdine 15 mg Once daily on top of stable dose of donepezil (n = 170) 86% Intepirdine 15 mg Once daily on top of stable dose of donepezil (n = 147) * 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% 198 subjects Placebo Once daily on top of stable dose of donepezil (n = 173) Double-Blind Treatment: 48 Weeks 87% Placebo Once daily on top of stable dose of donepezil (n = 151) 11
Change from Baseline ADAS-Cog I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E ADAS-COG BENEFIT OVER 48 WEEKS PRE-SPECIFIED ITT METHOD OF ANALYSIS* -1.5-0.5 0.5 Treatment Effect 35 mg Intepirdine Visit Week 12 Difference vs. Donepezil Alone P Value 1.30 0.006 1.5 Week 24 1.50 0.013 2.5 3.5 Donepezil Alone 15 mg Intepirdine Plus 15 Donepezil mg RVT-101 Plus Donepezil 35 mg Intepirdine Plus 35 mg RVT-101 Plus Donepezil Donepezil Week 36 Week 48 1.21 0.057 1.64 0.024 0 12 24 36 48 Weeks *Mixed Model Repeated Measure. Includes the following covariates: Baseline ADAS-cog Total Score, Baseline MMSE, Country Group, Visit, Time Since Diagnosis, Treatment, Baseline BMI, Baseline ADAS-cog Total Score by Visit, Baseline MMSE by Visit, Treatment by Visit 12
Change from Baseline in ADCS-ADL I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E ADCS-ADL BENEFIT OVER 48 WEEKS PRE-SPECIFIED ITT METHOD OF ANALYSIS* 1 0-1 -2 Treatment Effect 35 mg Intepirdine Visit Week 12 Difference vs. Donepezil Alone P Value 1.72 0.019-3 Week 24 2.00 0.024-4 -5-6 Donepezil Alone 15 mg Intepirdine Plus 15 Donepezil mg RVT-101 Plus Donepezil 35 mg Intepirdine Plus 35 mg RVT-101 Plus Donepezil Donepezil 0 12 24 36 48 Weeks Week 36 Week 48 1.93 0.038 1.94 0.088 *Mixed Model Repeated Measure. Includes the following covariates: Baseline ADCS-ADL Total Score, Baseline MMSE, Country Group, Visit, Time Since Diagnosis, Treatment, Baseline BMI, Baseline ADCS-ADL Total Score by Visit, Baseline MMSE by Visit, Treatment by Visit 13
I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E PHASE 3 MINDSET TRIAL Designed to Replicate Success: Co-primary endpoints: ADAS-cog and ADCS-ADL Gold standard measures of cognition and function Two arms: intepirdine 35 mg and placebo Designed to reduce residual placebo response 600+ subjects per arm (>2x as many as prior trial) Added statistical power relative to prior trial Similar subject inclusion/exclusion criteria ClinicalTrials.gov Identifier: NCT02585934 Attention to Execution: MINDSET is powered to detect the treatment effects observed in the prior trial on ADAS-cog and ADCS-ADL Multiple enhancements implemented to improve MINDSET study quality Phase 3 MINDSET Design and Key Assessment Timeline 1,315 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 Completing Subjects Eligible for Open-Label Extension Intepirdine 35 mg Once daily on top of any cholinesterase inhibitor and/or memantine WEEK 76 Safety and Tolerability Double-Blind Treatment: 24 Weeks Open-Label Extension: 52 Weeks 14
I N T E P I R D I N E : A L Z H E I M E R S D I S E A S E SIMILAR INCIDENCE OF ADVERSE EVENTS ACROSS TREATMENT AND PLACEBO ARMS Adverse Event Incidence of AEs occurring in 4% in any arm Week 48 Analysis: Safety Population Number (%) of Subjects Reporting Event Placebo + Donepezil (n = 225) Intepirdine 15 mg + Donepezil (n = 221) Intepirdine 35 mg + Donepezil (n = 236) Nasopharyngitis 17 (8) 19 (9) 18 (8) Urinary tract infection 16 (7) 11 (5) 13 (6) Diarrhea 9 (4) 12 (5) 11 (5) Fall 13 (6) 4 (2) 5 (2) Headache 6 (3) 8 (4) 7 (3) Bronchitis 3 (1) 4 (2) 9 (4) Nausea 8 (4) 4 (2) 4 (2) 15
I N T E P I R D I N E : G A I T A N D B A L A N C E I N A D, D L B, A N D P D D BOOSTING CHOLINERGIC FUNCTION HAS THE POTENTIAL TO REDUCE FALLS Prior Observations Incidence of Falls in Prior Studies of 5HT 6 Antagonists Intepirdine 866 Study (n = 684) Intepirdine + Donepezil: 2% Donepezil alone: 6% Idalopirdine LADDER Study (n = 278) Idalopirdine + Donepezil: 2% Donepezil alone: 6% In both trials of 5-HT6 receptor antagonists, the percentage of patients reporting falls was ~1/3 of the donepezil alone group 1 Henderson et al., Lancet Neurology (2016); Montero-Odasso et al., Journal of Alzheimer s Disease (2015); Li et al., European Neurology (2015); Mancini et al., BMC Neurology (2015). 16
I N T E P I R D I N E : G A I T A N D B A L A N C E I N A D, D L B, A N D P D D PHASE 2 GAIT AND BALANCE STUDY Description Population Double-blind, randomized, placebo-controlled, crossover study ClinicalTrials.gov Identifier: NCT02910102 ~40 subjects with diagnosis of Alzheimer s disease, DLB or PDD History of defined gait impairment On stable background therapy with acetylcholinesterase inhibitor Duration Two 14-day treatment periods 14-day washout period separates the two treatment periods Key Endpoints Changes in quantitative gait measurements (computerized assessment) Safety and tolerability ~40 subjects with diagnosis of AD, DLB, or PDD First Treatment Period Intepirdine 35 mg Placebo Second Treatment Period Intepirdine 35 mg Placebo 14 Days 14 Days Incidence of falls will also be captured in MINDSET and HEADWAY-DLB clinical studies 17
LEWY BODY DEMENTIA - LEWY BODY DEMENTIA BACKG ROUND - I N TEPIRDINE: DEMENTIA WITH LEWY BODIES
L E W Y B O D Y D E M E N T I A B A C KG R O U N D WHAT IS LEWY BODY DEMENTIA? Lewy Body Dementia (LBD) Approximately 1.4 million patients in the U.S. Dementia with Lewy Bodies (DLB) Parkinson s Disease Dementia (PDD) + Approximately 1.1 million patients in the U.S. Approximately 300,000 patients in the U.S. Distinctive Features of patients suffering from LBD include: Visual hallucinations, fluctuating cognition, attention and alertness, neuroleptic sensitivity, REM sleep behavior disorder (RBD), and movement disorder symptoms 19
L E W Y B O D Y D E M E N T I A B A C KG R O U N D CORE SYMPTOMS OF LEWY BODY DEMENTIA INTEPIRDINE COGNITIVE SYMPTOMS MOTOR SYMPTOMS NEUROPSYCHIATRIC SYMPTOMS REM SLEEP BEHAVIOR DISORDER 100% ~80% ~80% ~50-70% ~1.4 million LBD patients experience cognitive decline ~1.1 million LBD patients experience motor symptoms, including tremors and rigidity ~1.1 million LBD patients experience neuropsychiatric symptoms, including visual hallucinations ~700,000 to 1 million LBD patients experience REM sleep behavior disorder NELOTANSERIN Intepirdine and nelotanserin are investigational drugs subject to FDA approval 20
I N T E P I R D I N E : D E M E N T I A W I T H L E W Y B O D I E S POTENTIAL FIRST-IN-CLASS THERAPY FOR DLB 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 hallmark feature of DLB Cholinergic neurotransmission is MORE DYSFUNCTIONAL in DLB than Alzheimer s disease Increasing acetylcholine may improve cognition and function in DLB Intepirdine shown to promote the release of acetylcholine 5HT 2A activity is a potential driver of visual hallucinations * In addition to 5HT 6 activity, intepirdine is an antagonist of the 5HT 2A receptor HEADWAY-DLB includes both 35 mg and 70 mg doses of intepirdine to evaluate potential benefits of greater 5HT 2A receptor occupancy * Ballanger et al., Arch Neurol 2010. Vol. 67:4, 416-421. 21
I N T E P I R D I N E : D E M E N T I A W I T H L E W Y B O D I E S PHASE 2B HEADWAY-DLB PROGRAM ADDRESSING COGNITION AND FUNCTION Description IND has Fast Track designation from FDA Double-blind, randomized, placebo-controlled study ClinicalTrials.gov identifier: NCT02669433 Population 240 subjects with diagnosis of DLB; MMSE score: 14 26 (inclusive) Stable background therapy will be allowed Duration 24-week treatment period Active treatment extension following completion of treatment period Key Endpoints Change from baseline on CIBIC+ and a computerized cognitive battery Safety, tolerability, and change in behavioral symptoms 240 subjects with diagnosis of DLB Intepirdine 70 mg Intepirdine 35 mg Placebo WEEK 24 CIBIC+/CCB Primary Endpoints Double-Blind Treatment: 24 Weeks Completing Subjects Eligible for Active Treatment Extension Active Treatment Extension 22
NELOTANSERIN - VISUA L HALLUCINATIONS - MOTOR SYMPTOMS - REM SLEEP BEHAVIOR DISORDER
N E L O TA N S E R I N : R AT I O N A L E F O R L E W Y B O D Y D E M E N T I A D E V E L O P M E N T POTENTIAL BEST-IN-CLASS 5HT 2A INVERSE AGONIST Strong Binding Affinity Weak Binding Affinity Potential 1 st Generation 5HT 2A Inverse Agonist Potential Next Generation 5HT 2A Inverse Agonist Atypical Antipsychotics 1 Pimavanserin 2 Nelotanserin 3 5HT 2A Antagonism Ki binding affinity (nm) 0.4 0.4 5HT 2C Antagonism MIXED Ki binding affinity (nm) 16 106 D 2 Antagonism Initial Target Market Parkinson s Disease Psychosis Lewy Body Dementia 1 Richtand et al., Neuropsychopharmacology 2007. Vol. 32:8, 1715-1726. 2 Nordstrom et al., Int J Neuropsychopharm 2008. Vol. 11:2, 163-171. 3 Investigational Drug Product, subject to FDA approval 24
N E L O TA N S E R I N O V E R V I E W NELOTANSERIN PHASE 2 PILOT STUDY IN LBD D L B & PDD SUBJEC TS E X P E R I EN CING F R EQ U EN T V I S UA L H A L LU C I N ATIONS Description Double-blind, randomized, placebo-controlled, crossover study ClinicalTrials.gov Identifier: NCT02640729 Population 20+ subjects with diagnosis of DLB or PDD; MMSE score 18 Frequent visual hallucinations (occurring on most days of the week) Duration Two 28-day treatment periods 28-day washout period separates the two treatment periods Key Endpoints Safety and tolerability, UPDRS II+III SAPS subscales including SAPS-PD, SAPS-PD-H, SAPS-H; Caregiver Diary First Treatment Period Second Treatment Period 20+ subjects with diagnosis of LBD (DLB or PDD) Nelotanserin 40 mg 80 mg Placebo 28 Days Nelotanserin 40 mg 80 mg Placebo 28 Days Completing Subjects Eligible for Open-Label Extension Open-label Extension Results to inform design of subsequent pivotal study 25
N E L O TA N S E R I N O V E R V I E W : M O T O R F U N C T I O N PRELIMINARY DATA SUGGEST NELOTANSERIN MAY IMPROVE MOTOR FUNCTION AS MEASURED BY UPDRS 11 subjects with either DLB or PDD completed treatment in both 4-week crossover periods Axovant plans to expand patient recruitment to confirm the treatment benefits observed in this study 5 4 3 2 1.11 10 9 8 7 6 1 0 UPDRS Change from Baseline Relative to Placebo at Week 4 (N=11) 7.92 8.73 Part II Part III Part II+III Delta relative to Placebo * ** * p-value = 0.005 ** p-value = 0.012 UPDRS Part II measures activities of daily living UPDRS Part III measures motor function 26
Number of Arousals N E L O TA N S E R I N : R E M S L E E P B E H AV I O R D I S O R D E R NELOTANSERIN PHASE 2 STUDY DEMONSTRATED STATISTICALLY SIGNIFICANT IMPROVEMENT IN NUMBER OF AROUSALS FROM SLEEP Nelotanserin Phase 2 Objective Sleep Study n = 173 adult subjects with primary insomnia Nelotanserin showed statistically significant benefits on wake time after sleep onset, the primary endpoint Improvement -9 Number of Arousals Change from Screening (Pre-Specified Modified ITT Population) Night 1 and 2 Night 6 and 7-7 * = p < 0.0001-5 * * -3 * * -1 1 3 Placebo 10 mg nelotanserin 40 mg nelotanserin Sources: Rosenberg et al., SLEEP 2008; McKeith et al., Neuropsychopharmacology 2002. 27
N E L O TA N S E R I N : R E M S L E E P B E H AV I O R D I S O R D E R NELOTANSERIN PHASE 2 STUDY IN LBD SUBJECTS EXPERIENCING REM SLEEP BEHAVIOR DISORDER (RBD) Description Population Duration Key Endpoints Double-blind, randomized, placebo-controlled study Designed as potentially pivotal study ClinicalTrials.gov Identifier: NCT02708186 ~60 subjects with diagnosis of LBD Frequent episodes of RBD (occurring on most days of the week) 28-day treatment period Sleep lab assessment at baseline and at end of the treatment period All completing subjects will be eligible for an open-label extension Change in frequency and severity of RBD episodes as measured in sleep lab Safety and tolerability, UPDRS II + III ~60 subjects with diagnosis of LBD experiencing RBD Nelotanserin 80 mg Placebo Double-Blind Treatment: 28 Days DAY 28 Primary Endpoints Completing Subjects Eligible for Open-Label Extension Open-Label Extension 28
RVT-103 AND RVT-104 - RATIONALE
R AT I O N A L E : R V T - 1 0 3 A N D R V T - 1 0 4 P R O G R A M S RATIONALE TO COMBINE CHOLINESTERASE INHIBITORS WITH PERIPHERAL MUSCARINIC RECEPTOR ANTAGONISTS Cholinesterase inhibitors (AChEIs) are dose-limited by gastrointestinal (GI) tolerability profile which limits patient adoption and compliance Muscarinic receptor antagonists may reduce the GI side effects of AChEIs and could support greater efficacy Glycopyrrolate and Trospium, unlike some muscarinic receptor antagonists, are believed to have minimal-to-no CNS penetration Glycopyrrolate or Trospium in combination with AChEIs may be superior to competitors by avoiding anticholinergic CNS effects 30
A X O VA N T S C I E N C E S T H E N E U R O L O G Y S O L U T I O N S C O M PA N Y AXOVANT IS UNIQUELY POSITIONED TO BE A LEADER IN NEUROLOGY SOLUTIONS Intepirdine could be the first NCE in AD since 2003 and has significant potential Intepirdine and nelotanserin have the potential to be the first two NCEs ever approved in U.S. and EU for DLB Building a portfolio of drugs to broadly address multiple neurological conditions 31
AXOVANT SCIENCES LTD. JEFFERIES HEALTHCARE CONFERENCE JUNE 7, 2017