Every day matters

Every life matters

February 2019

© 2019 Axovant Gene Therapies. All Rights Reserved. NASDAQ: AXON

Forward looking statements
This presentation contains forward-looking statements for the purposes of the safe harbor provisions under The Private
Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as “may,” “might,” “will,”
“expect,” “plan,” “anticipate,” “believe,” “estimate,” “intend,” “future,” “potential,” “continue” and other similar expressions are
intended to identify forward-looking statements. For example, statements Axovant makes regarding the initiation, timing,
progress, and reporting of results of its preclinical programs, clinical trials, and research and development programs; its ability
to advance its product candidates into and successfully initiate, enroll, and complete clinical trials; the potential clinical utility of
its product candidates; its ability to develop and manufacture its products and successfully transition manufacturing
processes; its ability to perform under existing collaborations with, among others, Oxford BioMedica, Benitec, and the
University of Massachusetts Medical School, and to add new programs to its pipeline; its ability to enter into new partnerships
and collaborations for new or existing product candidates; its ability to retain and successfully integrate its leadership and
personnel; and the timing or likelihood of its regulatory filings and approvals, are forward-looking. 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 product candidates discussed are investigational and not approved
and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that
Axovant will not encounter problems or delays in clinical development, or that any of Axovant's product candidates will ever
receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and
assumptions by Axovant’s management that, although Axovant believes to be reasonable, are inherently uncertain. All
forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those
that Axovant expected. Such risks and uncertainties include, among others, the initiation and conduct of preclinical studies
and clinical trials; the availability of data from clinical trials; the expectations for regulatory submissions and approvals; the
continued development of Axovant’s product candidates and platforms; Axovant’s scientific approach and general
development progress; and the availability and commercial potential of Axovant’s product candidates including the size of
potentially addressable markets. These statements are also subject to a number of material risks and uncertainties that are
described in Axovant’s periodic and other reports filed with the Securities and Exchange Commission (SEC), including the risk
factors detailed in the Company’s most recent Quarterly Report on Form 10-Q filed with the SEC on November 7, 2018, as
updated by its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was
made. Axovant undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of
new information, future events or otherwise.

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Emerging, potentially best-in-class
pipeline in partnership with world-
renowned organizations

Leadership team with extensive gene

therapy development expertise

Integrated capabilities from

manufacturing to commercial launch
 Multiple clinical-stage programs in 2019

PROGRAM GENE INDICATION RESEARCH PRE-CLINICAL CLINICAL STATUS

First patient to be Initial data H2

AXO-AAV-GM1 GLB1 GM1 gangliosidosis dosed in H1 2019 2019

GM2 gangliosidosis
First patient dosed Initial data Q1
AXO-AAV-GM2 HEXA/HEXB (Tay-Sachs and Nov 2018 2019
Sandhoff diseases)

Two patients Initial data

AXO-LENTI-PD AADC/TH/CH1 Parkinson’s disease dosed in 2018 March 2019

Clinical
Oculopharyngeal
AXO-AAV-OPMD PABPN1 program to
muscular dystrophy begin H2 2019

Amyotrophic lateral
AXO-AAV-ALS C9orf72
sclerosis

Frontotemporal
AXO-AAV-FTD C9orf72
dementia

Additional research collaboration programs utilizing silence and replace platform.

4
Recent team additions with decades of gene therapy experience

Experienced Scientific Advisory Board

Michael Hayden, MB ChB, PhD, FRSC: Former Chief

Scientific Officer and President of Global R&D at Teva

Beverly Davidson, PhD: Scientific Co-Founder at Spark

Therapeutics, Chief Scientific and Strategy Officer at
Children’s Hospital of Philadelphia
Fraser Wright, PhD Parag Meswani, PharmD Greg MacMichael, PhD
Chief Technology Officer, Senior Vice President, Senior Vice President,
Gene Therapies Commercial Strategy & Operations Technical Operations R. Jude Samulski, PhD: Scientific Founder at Bamboo
Therapeutics, UNC Gene Therapy Center Director

Luigi Naldini, MD, PhD: Scientific Director of the San

Raffaele Telethon Institute for Gene Therapy

Jeffrey Kordower, PhD: Director of the Research Center

for Brain Repair at Rush University Medical Center

Nicole Déglon, PhD: Research Director and Deputy

Director of MIRCen

Guy Rouleau, PhD: Director of the Montreal Neurological

Paul Korner, MD, MBA Greg Stewart, PhD Sean O’Bryan
Senior Vice President, Senior Vice President, Vice President, Institute and Hospital
Clinical Development Vector Delivery & Optimization Regulatory Affairs

5
 Multiple clinical milestones and data readouts expected in 2019

Q4 2018 H1 2019 H2 2019

First patient Interim data Interim data

dosed readout readout
AXO-AAV-GM1

First patient Interim data Interim data Interim data Interim data
dosed readout readout readout readout

AXO-AAV-GM2

First two Interim data Interim data Interim data

patients dosed readout readout readout

AXO-Lenti-PD

Cohort 2*

AXO-AAV-OPMD Start of clinical program

*Timing of initiation subject to Data Monitoring Committee review

6
 AXO-AAV-GM1 and AXO-AAV-GM2

First clinical gene therapies for GM1 gangliosidosis,

Tay-Sachs and Sandhoff diseases
GM1 gangliosidosis, Tay-Sachs and Sandhoff diseases: devastating
pediatric diseases

DESCRIPTION EPIDEMIOLOGY
Incidence of up to ~1 per 65,000 live
• Fatal, pediatric, neurological births worldwide for GM1 and Tay-Sachs/
lysosomal storage disorders Sandhoff disease1,2,4

• Characterized by rapidly
progressive neurological decline
resulting in intellectual UNMET NEED
disability, paralysis, and death
No current disease modifying
treatments2,3
• Life expectancy in the severe
form reduced to 2-4 years1,2

1: Fitterer, et al, Mol Genet Metab. 2014; 111(3):382-389.

2: Hayward, et al, Ann Transl Med. 2015 May; 3(Suppl 1): S28.
3: Cachon-Gonzalez, et al, Curr Gene Ther. 2018; 18(2):68-89.
4: Orpha.net

8
 Natural history of infantile GM1 gangliosidosis and Tay-Sachs and
Sandhoff diseases1,2
Clinical course illustrates rapidly progressive and uniformly fatal nature of both diseases
100%

90%

80%
~50% mortality by 3.5 years
70% Dysphagia
Requiring
60% Feeding Tube
Percent Survival

Lose Head
50%
Control ~75% mortality by 5 years
Lose Head Cannot Sit
40% Control Alone

30% Life expectancy curve derived from

Seizure Blindness Osteoporosis natural history study in GM2 patients
20% Onset

10%

0%
0 1 2 3 4 5 6 7 8
Age (years)
GM1 Gangliosidosis
1: Bley, et al, Pediatrics. 2011; 128(5):1233-1241.
2: Utz, et al, Mol Genet Metab. 2017; 121(2):170-179. Tay-Sachs/Sandhoff

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Incidence and prevalence is comparable to other well-known gene
therapy indications

Disease Incidence Prevalence

GM1 Gangliosidosis ~1/100,0001 ~450 in US+EU2

(90 births in US+EU)
600-800 patients
in US+EU
Tay-Sachs/Sandhoff Disease ~1/180,0003,4 ~250 in US+EU2
(50 births in US+EU)

SMA Type 1 ~1/20,0005 ~1000 in US+EU6

(450 births in US+EU)

Myotubular Myopathy ~1/100,0007,8 ~200 in US+EU9

(90 births in US+EU)

5: D’Amico, et al, Orphanet J Rare Dis. 2011;6:71.

1: Hayward, et al, Ann Transl Med. 2015 May; 3(Suppl 1): S28. 6: Assumes 2 year average life expectancy (Avexis Corporate Presentation)
2: Assumes 5 year average life expectancy (McCurdy, et al, Gene Ther. 2015 Feb;22(2):181-9.) 7: Audentes Corporate Presentation
3: Bley, et al, Pediatrics. 2011 Nov; 128(5): e1233–e1241. 8: Assumes ~1:1 birth ratio between male and female (CIA World Factbook)
4: Fitterer, et al, Mol Genet Metab. 2014; 111(3):382-389. 9: Assumes 2 year average life expectancy (Will Cure Foundation)

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Attractive targets for gene therapy: well-understood neurobiology
underlying both diseases

HEXA Gene: HEXB Gene:

GLB1 Gene
Tay-Sachs disease Sandhoff disease

β-galactosidase β-Hexosaminidase A
(α-β heterodimer)
GM1 Ganglioside GM2 Ganglioside GM3 Ganglioside
GM1 Gangliosidosis GM2 Gangliosidosis

Well-defined, clinically
relevant biomarker threshold
Underlying neurobiology
CNS-wide targeting potential
supports the use of gene
Low levels of enzyme activity via one-time injection
therapy modality
(~5–10%) sufficient to convert
disease from severe to mild1,2

1: Gluszkiewicz, et al, Case Rep Clin Pract Rev, 2006; 7: 203-208.

2: Cachon-Gonzalez, et al, Curr Gene Ther. 2018; 18(2):68-89.

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 AXO-AAV-GM1 restored β-gal activity in GM1 mice

Adult GM1 mice given 5E12 vg/kg (LD) and 1.5E13 vg/kg (HD) at 6 weeks of age via intravenous injection

Rescue of β-gal activity in CNS and peripheral organs Treatment significantly reduces CNS GM1
gangliosides burden & astrogliosis (not shown)
Male Female

(nmol/hour/mg protein)
103 103 400
(nmol/hour/mg protein)

NS

(ng GM1/μg protein

β gal activity
NS
NS NS
β gal activity

102 102

GM1 Content
300

Improving Clearing
Enzyme 101 101 Disease 200
Activity Biomarkers
NS
100 100 100
NS

10-1 10-1 0
* *** ** **
** *** *** *** *** ** * *** * *
*** *** *
** ** *** ** ** *** * *

GM1 + AAV HD GM1 + AAV Male

GM1 + AAV LD GM1 + AAV Female
Wildtype Wildtype
GM1 + PBS GM1 + PBS

Figures from Weismann, et al, Hum Mol Genet. 2015;24(15):4353-4364.

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GM1 gene therapy efficacy is confirmed in a feline model1

GM1 felines treated with 1.5E13 vg/kg via intravenous injection at 5 weeks of age

Survival extension and stabilization of clinical Brain MRI revealed normal brain architecture
rating score of neuromuscular function at 2 years of age

Normal 8m Untreated GM1 8m GM1+AAV9 2yrs

Clinical Rating Score

Cortex
Normal
GM1+IV
GM1

Cerebellum
Age (months)

1: UMass Data on File

WPRE included in construct administered to felines

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AXO-AAV-GM2 corrects disease in mouse model1

Improvements in biochemical markers Dose-dependent extension of survival

800 Hex A activity in the brain
1.0
WT/High
Hex A activity

600
Dose

Survival Probability
0.8
400

0.6 Mid
200
Dose

0 0.4
WT Untreated PBS Low Dose Mid Dose High Dose

Low
200 GM2 levels in the brain 0.2 Dose

150 PBS Untreated

GM2 level

0.0
0 75 100 125
100
Days on Study

50

Low dose = 1.8E10 vg Mid dose = 3.5E10 vg High dose = 7.0E10 vg

0
WT Untreated PBS Low Dose Mid Dose High Dose

1. UMass data on file.

14
Multiple data readouts expected in 2019

Robust natural history study of GM1 and GM2 gangliosidoses could serve as comparator

Gangliosidosis-specific clinical MRI visualization of brain

Correlated CSF and serum
rating score and developmental architecture, atrophy, and
biomarkers
milestones myelination

Q4 2018 H1 2019 H2 2019

First patient Interim data Interim data

dosed readout readout
AXO-AAV-GM1

First patient Interim data Interim data Interim data Interim data
dosed readout readout readout readout

AXO-AAV-GM2

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 AXO-Lenti-PD

Novel three-gene therapy for Parkinson’s disease

Parkinson’s disease: an area of significant unmet medical need
DESCRIPTION
Parkinson’s disease is a progressive
neurodegenerative disorder resulting in
the loss of dopamine in the striatum
Motor symptoms can include tremor,
rigidity, and bradykinesia
EPIDEMIOLOGY
PD affects approximately 1%
of adults over the age of 60, or
7–10 million patients worldwide
1. Evans et al. J Neurol Neurosurg Psychiatry
2011;82:1112-1118
UNMET NEED
Current standard of care is primarily
oral levodopa (L-dopa). However,
significant unmet need exists in
treated patients:
• Waning efficacy over time
• Fluctuations between ON
and OFF states
• Over 30% of patients
experience dyskinesias at
8 years after diagnosis1
Deep Brain Stimulation (DBS) is not
universally effective
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AXO-Lenti-PD: a novel gene therapy for Parkinson’s disease

AXO-Lenti-PD contains three genes that encode the critical enzymes required for endogenous
dopamine synthesis
• Tyrosine hydroxylase (TH) and Cyclohydrolase 1 (CH1): converts tyrosine to L-dopa
• Aromatic L-amino acid decarboxylase (AADC): converts L-dopa to dopamine

CH1

TH AADC

Restores steady, tonic levels of dopamine to reduce variability that leads to dyskinesia

Lentiviral vector system with large gene packaging capacity

• Permits delivery of multiple genes at once

One-time stereotactic delivery into the putamen

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Designed to address motor fluctuations in Parkinson’s disease

Oral L-dopa AXO-LENTI-PD*

Endogenous
Oral L-dopa
production
[Dopamine]

AXO-Lenti-PD’s novel 3-gene

therapy approach is designed to: Goals of therapy:

o Increase basal dopamine production o More ON time with fewer dyskinesias

o Reduce extreme dopamine variability o Reduced OFF score
o Minimize need for exogenous L-dopa

* Theoretical benefits based on postulated mechanism of action (not data from investigational studies)

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Lower rate of dyskinesia observed in non-human primate models with
ProSavin

Dyskinesia events with and without oral levodopa (“ON” and “OFF”)
120
*** ***
100
Dyskinesia score
(events/120 min)

80

60 *
**
*
40 **
20

OFF ON OFF ON OFF ON OFF ON

Normal MPTP-long term MPTP-Lenti-lacZ MPTP-ProSavin

* P<0.05 compared to normal

** P<0.05 compared to MPTP-ProSavin
*** P<0.05 compared to normal and MPTP-ProSavin

Figure adapted from Jarraya, et al, Sci Transl Med. 2009;1(2):2ra4.

20
Durable benefit in UPDRS Part III “OFF” scores seen with ProSavin

Mean UPDRS Part III (motor) “OFF” Score1

40
38
UPDRS III “OFF” Score

36
34
32
30
28 n=6
n=14 n=9
26 n=11 n=10
n=15
24 n=15
22
0
0 6 12 18 24 30 36 42 48 54 60 66 72
Months

• Prior sham-control arms in Parkinson’s disease gene therapy studies* showed change from baseline of
approximately -4.52 and -4.73
• UPDRS Part III (motor) “OFF” scores are expected to worsen by 3-4 points/year in this population4
• Mean Improvement in UPDRS Part III (motor) “OFF” score of 11.8 pts at 12 Months (p=0.0001)4
1: Palfi, et al, Hum Gene Ther Clin Dev. 2018;29(3):148-155. Mean UPDRS III (OFF) scores pooled across low, mid, and high dose
2: Olanow, et al, Ann Neurol. 2015;78(2):248-57. cohorts. Assessments post-deep brain stimulation (DBS) are excluded.
3: LeWitt, et al, Lancet Neurol. 2011;10(4):309-19. *Studies not conducted by either Oxford Biomedica or Axovant
4: Palfi, et al. The Lancet. 2014:383(9923):1138-1146

21
AXO-Lenti-PD: a re-engineered gene therapy product to potentially
increase effect on motor symptoms

VECTOR CONFIGURATIONS

AXO-Lenti-PD is the ProSavin

product of multifactorial SIN LTR IRES IRES SIN LTR

experimentation to modify CMVp TH AADC CH1 WPRE

the payload configuration

of ProSavin to improve
dopamine production
AXO-Lenti-PD AXO-Lenti-PD achieves
SIN LTR IRES SIN LTR
up to 10-fold increases in
CMVp TH CH1 AADC WPRE
dopamine + L-dopa
production compared to
ProSavin1, without
impacting infusion volume
or rate of administration

1: Stewart, et al, Hum Gene Ther Clin Dev. 2016;27(3):100-110.

22
 AXO-Lenti-PD Increases Dopamine and L-Dopa Production Compared
to ProSavin1

Production of dopamine & L-dopa in

primary human neurons with ProSavin and AXO-Lenti-PD

4.5

Catecholamine production
3.5
Dopamine
3
L-dopa

(ng/mL)
2.5

1.5

0.5

0
ProSavin AXO-LENTI-PD

AXO-Lenti-PD achieved up to 10-fold increase in dopamine + L-dopa production

compared to ProSavin
1: Stewart, et al. Hum Gene Ther Clin Dev. 2016;27(3):100-10.

23
AXO-Lenti-PD shows increased AADC activity compared to ProSavin

Change in AADC activity (measured by 18F-FMT or Ki)

at 6 months in non-human primate model1
Baseline MPTP 3 months 6 months

MPTP) at 6MPI
200
200
EIAV-Null

Relative change in Ki
at 6MPI
150
150

in Ki (vs
ProSavin 100
100

(vs MPTP)
5050

Relative change
AXO-Lenti-PD Low Dose 00

-50
-50

n
l

D
LD
ul

vi
EIAV-Null

H
ProSavin AXO-Lenti-PD AXO-Lenti-PD

PD

PD
V-

oS
Low Dose High Dose

ti-

ti-
Pr
EI
AXO-Lenti-PD High Dose

en

en
-L

-L
xo

xo
A

A
Parametric images from 18F-FMT (Ki) PET scans showing commissural coronal. Images are
presented with scale bars for tracer binding intensity (red=highest; violet=lowest).

1: ProSavin®, a dopamine gene therapy for advanced Parkinson’s disease: 6 years phase I/II clinical update, ESGCT 2018 poster

24
Potentially best-in-class therapy for Parkinson’s disease

Characteristics of Gene Therapy AXO-Lenti-PD

Lentiviral vector allows for delivery of multiple genes in one construct

Restores end-to-end endogenous dopamine synthesis pathway

Delivery of TH and CH1 to convert tyrosine to L-dopa

Delivery of AADC to convert L-dopa to dopamine

Potential to lower dyskinesia rates by reducing dopamine pulsatility

Potential to increase motor function scores off-medication

Potential to reduce exogenous L-Dopa dose

One-time stereotactic delivery into the putamen, without the need for intraoperative MRI

25
SUNRISE-PD phase 2 clinical study design with initial data expected
March 2019
PART A: Dose Escalation PART B: Expansion Cohort vs Imitation Surgical Procedure

Dose Level 3
Treated
Dose Level 2 Optimal dose,
Advanced- Primary
expanded
stage Dose Level 1 endpoint at
patients, Imitation
patients 12 months
randomized surgical
procedure

STUDY DETAILS KEY ASSESSMENTS PROGRESS

• One-time MRI-guided • Safety and tolerability • Aligned with FDA on single

stereotactic delivery with
automatic pump
• Study will capture sham-
controlled data in Part B
• UPDRS scores and Hauser development program, proposed
patient diaries manufacturing and QC plan
• Biomarkers • FDA provided feedback on
clinical study design
UPDRS = Unified Parkinson’s Disease Rating Scale • First two patients dosed in 2018

26
 AXO-AAV-OPMD

Silence and replace gene therapy for OPMD

Overview of oculopharyngeal muscular dystrophy (OPMD)
DESCRIPTION
Defective polyA-binding protein
nuclear 1 (PABPN1) gene results
in misfolded proteins that form
insoluble nuclear inclusion bodies
Leading causes of death are
aspiration pneumonia and
malnutrition
1: Orpha.net
EPIDEMIOLOGY
Estimated to affect at least 11,000 individuals in
North America and Europe; concentrated in select
populations1
• Primarily autosomal dominant inheritance
with presentation in adulthood
UNMET NEED
No approved therapies available that
treat underlying cause of disease,
therefore limited treatment options
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AXO-AAV-OPMD: first application of Silence-and-Replace platform

AXO-AAV-OPMD program is the first gene therapy using Silence-and-Replace technology in a

single vector to enter the clinic
• Delivers a combination of DNA-directed RNA interference (Silence) along with a functional copy
of the gene (Replace)

ITR Muscle Specific Promoter Re-engineered functional PABPN1 PABPN1 shRNA-1 PABPN1 shRNA-2 ITR

REPLACE SILENCE
with functional copy of PABPN1 re- shRNA-mediated knockdown of
engineered to be resistant to PABPN1, including mutant form
knockdown
• Corrects the underlying genetic defect causing the disease and produces long-term restoration
of normal gene function

Single adeno-associated viral One-time administration under direct

vector delivering both silence and visualization into the cricopharyngeal
replace functions and pharyngeal muscles

29
AXO-AAV-OPMD clears intranuclear inclusions and restores muscle
force in mouse model1

Intranuclear inclusions measured 13 weeks after Normalized muscle force and weight to wild-type
administration levels at highest dose in mouse model
ns
ns
ns
ns
***
***
***
% nuclei containing INI

***
***
40 ***

Force (nM)
30
Clearing
20
intranuclear
inclusions 10

2e9 vg/muscle

4e8 vg/muscle
A17 — saline

Wildtype — saline

5e10 vg/muscle

1e10 vg/muscle
7.5e11 vg/muscle

2.5e11 vg/muscle

Dose

***P<0.001 Frequency (Hz)

Clinical program to initiate in second half of 2019

1: Benitec presentation, May 2018

30
Every day matters. Every life matters.
Scalable cGMP manufacturing capacity across gene therapy portfolio

Ongoing production at scale of GMP-grade material from

leading gene therapy manufacturing partners to support
clinical studies

• AXO-AAV-GM1 and AXO-AAV-GM2: cGMP vector

manufacturing ongoing to support the clinical programs.

• AXO-Lenti-PD: cGMP vector manufacturing ongoing at

Oxford Biomedica to support the clinical program.

• AXO-AAV-OPMD: Manufacturing process development and

scale-up performed, with plans for clinical vector to be
generated at 250L scale.

32
Emerging pipeline addresses both rare diseases and larger indications

Additional Patients with ALS,

Axovant is building its broad frontotemporal dementia and others
pipeline of best-in-class gene
therapies to address the unmet
needs of diverse patients with
serious neurological and
neuromuscular diseases. >500k
Advanced Parkinson’s Disease
Patients

~11,000
Oculopharyngeal Muscular Dystrophy (OPMD)
Patients

~600-800
Patients GM1/GM2 Gangliosidoses
1 Management estimate of addressable population in major reimbursable markets based on published incidence and prevalence
PD number represents estimate of the global prevalence; OPMD and GM1/GM2 numbers represent US/EU prevalence

33
 Multiple clinical milestones and data readouts expected in 2019

Q4 2018 H1 2019 H2 2019

First patient Interim data Interim data

dosed readout readout
AXO-AAV-GM1

First patient Interim data Interim data Interim data Interim data
dosed readout readout readout readout

AXO-AAV-GM2

First two Interim data Interim data Interim data

patients dosed readout readout readout

AXO-Lenti-PD

Cohort 2*

AXO-AAV-OPMD Start of clinical program

*Timing of initiation subject to Data Monitoring Committee review

34
Patients can’t wait,
neither will we

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