PTC Therapeutics Jefferies Virtual Healthcare Conference Stuart W. Peltz, Ph.D., CEO - PTC ...
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PTC Therapeutics Jefferies Virtual Healthcare Conference Stuart W. Peltz, Ph.D., CEO
Forward looking statement
Th i s p re s e n t a t i o n c o n t a i n s f o rwa rd -l o o k i n g s t a t e me n t s wi t h i n t h e m e a n i n g o f Th e P r i v a t e S ec uri ti es Li ti gati on Ref orm A c t o f 1 9 9 5 . A l l s tate ments c ont ai n ed i n th i s
p re s e n t a t i o n , o t h e r t h a n s t a t e me n t s o f h i s t o ri c f a c t , a re f o rwa rd -l o o k i n g s t a t e me n t s , i n c l u d i n g s t a t e me n t s wi t h re s p e c t t o f u t u re re ve n u e a n d s t a t e me n t s re g a rd i n g : t h e
f u t u re e x p e c t a t i o n s , p l a n s a n d p ro s p e c t s f o r P TC, i n c l u d i n g wi t h re s p e c t t o t h e e x p e c t e d t i mi n g o f c l i n i c a l t ri a l s a n d s t u d i e s , a va i l a b i l i t y o f d a t a , re g u l a t o r y s u b mi s s i o n s a n d
re s p o n s e s a n d o t h e r m a t t e rs ; e x p e c t a t i o n s wi t h re s p e c t t o P T C 's g e n e t h e ra p y p l a t f o rm , i n c l u d i n g a n y p o t e n t i a l r e g u l a t o r y s u b mi s s i o n s a n d ma n u f a c t u ri n g c a p a b i l i t i e s ;
a d va n c e me n t o f P TC 's jo i n t c o l l a b o ra t i o n p ro g ra m i n S MA , i n c l u d i n g a n y p o t e n t i a l re g u l a t o ry s u b mi s s i o n s , c o m me rc i a l i z a t i o n o r r o y a l t y o r mi l e s t o n e p a y me n t s ; P TC 's
e x p e c t a t i o n s wi t h re s p e c t t o t h e l i c e n s i n g , re g u l a t o r y s u b mi s s i o n s a n d c o m me rc i a l i za t i o n o f i t s p ro d u c t s a n d p ro d u c t c a n d i d a t e s ; P TC 's s t ra t e g y, f u t u re o p e ra t i o n s , f u t u r e
f i n a n c i a l p o s i t i o n , f u t u r e re ve n u e s , p ro je c t e d c o s t s ; a n d t h e o b je c t i ve s o f ma n a g e me n t. Ot h e r f o rwa rd -l o o k i n g s t a t e me n t s ma y b e i d e n t i f i e d b y t h e w o rd s "g u i d a n c e ", "p l a n , "
" a n t i c i p a t e , " "b e l i e ve , " " e s t i ma t e , " " e x p e c t , " "i n t e n d , " "ma y, " "t a rg e t , " "p o t e n t i a l , " "wi l l , " "wo u l d , " "c o u l d , " "s h o u l d , " "c o n t i n u e , " a n d s i mi l a r e x p re s s i o n s .
P TC 's a c t u a l re s u l t s , p e rf o rma n c e o r a c h i e ve me n t s c o u l d d i f f e r ma t e ri a l l y f ro m t h o s e e x p re s s e d o r i mp l i e d b y f o rw a rd -l o o k i n g s t a t e me n t s i t ma k e s a s a re s u l t o f a va ri e t y o f
ri s k s a n d u n c e rt a i n t i e s , i n c l u d i n g t h o s e re l a t e d t o : t h e o u t c o me o f p r i c i n g , c o ve ra g e a n d re i mb u rs e m e n t n e g o t i a t i o n s wi t h t h i rd p a r t y p a y o rs f o r P T C 's p ro d u c t s o r p ro d u c t
c a n d i d a t e s t h a t P T C c o m me rc i a l i z e s o r ma y c o m me rc i a l i ze i n t h e f u t u re ; e x p e c t a t i o n s wi t h re s p e c t t o P T C 's g e n e t h e ra p y p l a t f o rm , i n c l u d i n g a n y p o t e n t i a l r e g u l a t o r y
s u b mi s s i o n s a n d p o t e n t i a l a p p r o v a l s , ma n u f a c t u ri n g c a p a b i l i t i e s a n d t h e p o t e n t i a l f i n a n c i a l i mp a c t a n d b e n e f i t s o f i t s l e a s e d b i o l o g i c s ma n u f a c t u ri n g f a c i l i t y a n d t h e
p o t e n t i a l a c h i e ve me n t o f d e ve l o p me n t , re g u l a t o r y a n d s a l e s mi l e s t o n e s a n d c o n t i n g e n t p a y me n t s t h a t P TC ma y b e o b l i g a t e d t o ma k e ; t h e e n ro l l me n t , c o n d u c t , a n d re s u l t s
o f s t u d i e s u n d e r t h e S MA c o l l a b o ra t i o n a n d e ve n t s d u ri n g , o r a s a r e s u l t o f , t h e s t u d i e s t h a t c o u l d d e l a y o r p r e v e n t f u rt h e r d e ve l o p m e n t u n d e r t h e p ro g r a m, i n c l u d i n g a n y
p o t e n t i a l r e g u l a t o ry s u b mi s s i o n s a n d p o t e n t i a l c o m me rc i a l i za t i o n w i t h re g a rd s t o ri s d i p l a m; P T C 's a b i l i t y t o c o mp l e t e a d ys t r o p h i n s t u d y n e c e s s a r y t o s u p p o rt a r e -
s u b mi s s i o n o f i t s T ra n s l a rn a N D A f o r t h e t re a t me n t o f n o n s e n s e mu t a t i o n D u c h e n n e mu s c u l a r d ys t ro p h y (n m D M D ) t o t h e FD A , a n d P TC 's a b i l i t y t o p e rf o r m a n y n e c e s s a ry
a d d i t i o n a l c l i n i c a l t ri a l s , n o n -c l i n i c a l s t u d i e s , a n d C MC a s s e s s me n t s o r a n a l ys e s a t s i g n i f i c a n t c o s t ; P T C 's a b i l i t y t o ma i n t a i n i t s ma rk e t i n g a u t h o ri za t i o n o f Tra n s l a rn a f o r
t h e t re a t me n t o f n m D M D i n t h e E u ro p e a n E c o n o mi c A re a (E E A ) , i n c l u d i n g w h e t h e r t h e E u r o p e a n Me d i c i n e s A g e n c y (E MA ) d e t e r mi n e s i n f u t u re a n n u a l re n e wa l c yc l e s t h a t
t h e b e n e f i t-ri s k b a l a n c e o f Tra n s l a rn a a u t h o ri z a t i o n s u p p o r t s re n e wa l o f s u c h a u t h o ri za t i o n ; P TC 's a b i l i t y t o e n ro l l , f u n d , c o mp l e t e a n d t i m e l y s u b mi t t o t h e E MA t h e re s u l t s
o f S t u d y 0 4 1 , a ra n d o m i ze d , 1 8 - mo n t h , p l a c e b o -c o n t ro l l e d c l i n i c a l t ri a l o f Tra n s l a rn a f o r t h e t re a t me n t o f n mD M D f o l l o we d b y a n 1 8 - mo n t h o p e n -l a b e l e x t e n s i o n , wh i c h i s a
s p e c i f i c o b l i g a t i o n t o c o n t i n u e d ma rk e t i n g a u t h o ri z a t i o n i n t h e E E A ; e x p e c t a t i o n s wi t h re s pec t t o t h e c omme rc i a l i zati on o f Tegs edi an d W ayl i v ra ; s i gni f i c ant bus i nes s
e f f e c t s , i n c l u d i n g t h e e f f e c t s o f i n d u s t ry, ma rk e t , e c o n o mi c , p o l i t i c a l o r re g u l a t o r y c o n d i t i o n s ; c h a n g e s i n t a x a n d o t h e r l a ws , re g u l a t i o n s , ra t e s a n d p o l i c i e s ; t h e e l i g i b l e
p a t i e n t b a s e a n d c o m m e rc i a l p o t e n t i a l o f P TC ' s p ro d u c t s a n d p r o d u c t c a n d i d a t e s ; P T C 's s c i e n t i f i c a p p ro a c h a n d g e n e ra l d e ve l o p m e n t p ro g re s s ; P TC 's a b i l i t y t o s a t i s f y i t s
o b l i g a t i o n s u n d e r t h e t e rms o f t h e l e a s e a g re e me n t f o r i t s l e a s e d b i o l o g i c s ma n u f a c t u ri n g f a c i l i t y ; P T C 's a b i l i t y t o s a t i s f y i t s o b l i g a t i o n s u n d e r t h e t e r ms o f t h e s e n i o r
s e c u re d t e r m l o a n f a c i l i t y w i t h Mi d C a p Fi n a n c i a l ; t h e s u f f i c i e n c y o f P TC 's c a s h re s o u rc e s a n d i t s a b i l i t y t o o b t a i n a d e q u a t e f i n a n c i n g i n t h e f u t u re f o r i t s f o re s e e a b l e a n d
u n f o re s e e a b l e o p e ra t i n g e x p e n s e s a n d c a p i t a l e x p e n d i t u r e s ; a n d t h e f a c t o rs d i s c u s s e d i n t h e " Ri s k Fa c t o rs " s e c t i o n o f P T C's mo s t re c e n t Qu a rt e rl y Re p o rt o n F o rm 1 0 - Q
a n d A n n u a l Re p o rt o n F o rm 1 0 - K , a s w e l l a s a n y u p d a t e s t o t h e s e r i s k f a c t o rs f i l e d f ro m t i me t o t i me i n P T C 's o t h e r f i l i n g s wi t h t h e S E C . Y o u a re u rg e d t o c a re f u l l y c o n s i d e r
a l l s u c h f a c t o rs .
A s w i t h a n y p h a r ma c e u t i c a l u n d e r d e ve l o p m e n t , t h e re a re s i g n i f i c a n t ri s k s i n t h e d e v e l o p me n t , r e g u l a t o r y a p p ro va l a n d c o m me rc i a l i za t i o n o f n e w p ro d u c t s . Th e r e a re n o
g u a ra n t e e s t h a t a n y p r o d u c t w i l l re c e i v e o r ma i n t a i n re g u l a t o r y a p p ro v a l i n a n y t e r ri t o r y , o r p ro ve t o b e c o m m e rc i a l l y s u c c e s s f u l , i n c l u d i n g Tra n s l a rn a , E mf l a za , P T C -
A A D C , Te g s e d i , W a yl i vra o r ri s d i p l a m .
Th e f o rwa rd -l o o k i n g s t a t e me n t s c o n t a i n e d h e re i n re p re s e n t P T C 's vi e ws o n l y a s o f t h e d a t e o f t h i s p re s e n t a t i o n a n d P TC d o e s n o t u n d e rt a k e o r p l a n t o u p d a t e o r r e vi s e a n y
s u c h f o rwa r d -l o o k i n g s t a t e me n t s t o re f l e c t a c t u a l re s u l t s o r c h a n g e s i n p l a n s , p ro s p e c t s , a s s u mp t i o n s , e s t i m a t e s o r p ro je c t i o n s , o r o t h e r c i rc u ms t a n c e s o c c u rri n g a f t e r t h e
d a t e o f t h i s p re s e n t a t i o n e x c e p t a s re q u i re d b y l a w .
2
A global, commercial,
diversified, biopharmaceutical company focused on
innovative therapies for rare genetic disorders
3
Global commercial capabilities & infrastructure
Offices in
20 countries
850+
employees
Footprint in
>50 countries
4
Strong Commercial Performance & Capital Position
$291M $68.2M +28% $596M
Total 2019 DMD Total 1Q20 Net 1Q20 YoY Total 1Q20 Ending
Franchise Product Net Product Cash Position
Revenue Revenue Revenue Growth
5
Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
6
Scientific platforms & strategic business development
drive sustainable innovation & continuous value creation
2023
DMD Franchise, risdiplam,
Tegsedi™, Waylivra® , PTC-AADC
2020
DMD Franchise, risdiplam, Beyond 2023
REVENUE Tegsedi™, Waylivra®
Nonsense Mutation
2019 Gene Therapy
DMD Franchise
Metabolic
2016 Emflaza® >$1.5B Splicing
Translarna™
2015 Bio-e
Translarna™
$291M
$34M
Angelman syndrome, FA,
Angelman syndrome, GBA-PD, HD, MEDS, PTC-FA,
HD, PTC-AADC, ataluren (US DMD), FA,
HD, PKU, undisclosed Bio-e, gene
PTC-FA, risdiplam, GBA-PD, HD, MEDS,
risdiplam risdiplam therapy, metabolic and splicing
Tegsedi™, Waylivra® PTC-FA, PKU
INNOVATION
7
Majority of pipeline not represented in >$1.5B revenue target
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
8
Multiple potential value driving events in 2020
4Q19 1Q20 2Q20 3Q20 4Q20
Risdiplam NDA filed SUNFISH Part 2 data FIREFISH Part 2 data Risdiplam PDUFA Initiate PTC518 HD Ph1 trial
Splicing
SUNFISH Part 2 topline FIREFISH Part 2 topline Risdiplam MAA filing Risdiplam US launch
AADC CHMP final opinion
Gene Therapy AADC MAA accepted PTC-FA IND filed*
AADC BLA filing
Initiate PTC743 MEDS trial
Bio-e Initiate PTC743 FA trial
Initiate PTC857 Ph1 trial
Nonsense US dystrophin data
Mutation
ANVISA approval hATTR launch
ANVISA filing
FCS sales through early access program
Clinical Regulatory Commercial
9 *PTC-FA IND filing delayed at least one quarter from 3Q20
Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
10Splicing is highly selective with broad applicability
Isoform plex Proprietary
RNA-targeted
small molecule
library
HTSpliceseq
Transcriptome
Exploiting U1-noncanonical exons mRNA isoform 2019 2020 and beyond
detection
platforms
SMA (risdiplam)
Alternative splicing SMN2 exon 7 inclusion
Familial dysautonomia
Exon skipping
ELP1 exon 20 inclusion
>5 additional
Stop exon inclusion Huntington disease undisclosed
Stop exon inclusion targets
11Risdiplam – Most competitive commercial profile across
broadest population
FIREFISH – Type 1 SMA
FIREFISH Part 2 85%
Results confirm
demonstrated statistically 29% 35 of 41 infants were
event-free at month 12 risdiplam’s clinically
significant improvement 12 of 41 infants were able meaningful efficacy in
in proportion of infants to sit for at least 5
seconds without support 95% infants with advanced
sitting for at least 5 at month 12; pRisdiplam – Most competitive commercial profile across
broadest population
Small Oral, at home- Full target Durably increases
Molecule with administration engagement - SMN2 SMN throughout
systemic mode of full-length , Δ7 CNS and periphery
action mRNA
PDUFA date:
Studied in type 1,2,3 Clinically meaningful Strong safety August 24,
patients from efficacy in real world profile 2020
newborns to 60 patient population
years of age
13Significant success-based revenue through remaining
risdiplam milestones and royalties
Total remaining regulatory
milestone-based payments
Potential 2020 risdiplam
milestone payments to PTC
Milestone Payment
$72.5M
MAA Filing with EMA $ 15,000,000
NDA Filing in Japan $ 7,500,000
$325M Up to
mid-teen
First US Commercial Sale $ 20,000,000 blended
Total $ 42,500,000
royalties
Total sales-threshold-based
payments
Annual, tiered potential
royalties-based on net sales
14 PTC Therapeutics Provides Corporate Update and Highlights Pipeline Progress at 2020 J.P. Morgan Healthcare ConferenceActivity of systemically distributed splicing drugs can be
measured in blood
SMN protein in blood of SMA patients and healthy subjects
before and after 4 weeks of treatment
8
SMN Protein (ng/ml)
6
4
2
0
Baseline Week 4
Firefish Sunfish =11yrs Jewelfish Healthy Volunteers
15Toxic HTT protein aggregates cause extensive neuronal cell
death
Healthy HD
16 Goh et al. Aus Psychiatry. 2018Splicing modifiers reduce HTT protein levels in Huntington
disease
Healthy HD
HD is a neurodegenerative disease caused by a toxic gain-of-function
triplet repeat (CAG) expansion in the huntingtin gene
(CAG)>35
Stop exon
Untreated Ex 1 Ex X Ex Y
Ex 1 Ex X Ex Y
Toxic HTT
protein
17Splicing modifiers reduce HTT protein levels in Huntington
disease
Healthy HD
HD is a neurodegenerative disease caused by a toxic gain-of-function
triplet repeat (CAG) expansion in the huntingtin gene
(CAG)>35 (CAG)>35
Stop exon Stop exon
Treatment
Untreated Ex 1 Ex X Ex Y Ex 1 Ex X Ex Y with splicing
modifier
R3
Stop exon
R1
Ex 1 Ex X Ex Y Ex 1 Ex X Ex Y
HET1 R2
Degraded through Ar
translation-linked
mRNA decay Splicing modifiers potentiate
stop exon inclusion
Toxic HTT Toxic HTT
protein protein
18HD splicing small molecules with broad tissue distribution
Dose dependent HTT lowering in the brain in BACHD mice
Ph1 trial planned for 4Q 2020
Brain • Oral, crosses BBB
% HTT Remaining 120
100 • Titratable
80
60 • IND toxicology studies ongoing
40
20 • Ability to measure mRNA and protein
0
Vehicle 1 3 7 21 63 in blood in healthy volunteers
Dose (mg/kg)
Measurements demonstrate uniform HTT lowering across brain regions with ~1:1 brain and blood concentrations*
Striatum Cortex Cerebellum Brain and blood HTT lowering
120
120 120 120
% HTT Remaining
% HTT Remaining
% HTT Remaining
100
100 100 100
% HTT Remaining
80 80 80 80
60 60 60 60
40 40 40 40
20 20 20 20
0 0 0 0
Vehicle Brain WBC
Vehicle 7 mg/kg Vehicle 7 mg/kg Vehicle 7 mg/kg
Treated
19 *Data on file from multiple studiesMultiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
20Treating rare monogenic disorders
with targeted gene therapy
Potential advantages of targeted therapy
• Local administration lowers systemic immunogenicity
and exposure
• Low turnover cells may lead to improved durability
• Micro-dosing lowers manufacturing and patient burden
Pipeline
• PTC-AADC MAA submitted
• PTC-AADC BLA expected in 2H20
• PTC-FA and Angelman syndrome IND enabling activities
progressing
• >5 nonclinical development candidates
21Internal gene therapy manufacturing capabilities
• GMP manufacturing of clinical material to
begin in early 2021
• 15-year lease on ~220,000 sq. ft. which
includes a state-of-the-art biologics
production facility with supporting research
and operations buildings in NJ
• Highly qualified staff in biologics
manufacturing joining PTC
• Facility to support gene therapy production
& continued development of investigational
medicines
22AADC deficiency – Rare disorder with significant unmet need
Normal AADC • Rare progressive childhood disease, affecting
approximately 5,000 patients globally
Head Position Up
3-4 months • Children with severe AADC deficiency never
achieve motor development milestones
• Profound development failure with shortened
Sitting life expectancy in severe forms (4 - 8 yrs)
6-9 months
• Patients identified in Asia, US, Europe and
LatAm
Standing • ~80 disease causing variants described in
10-12 months AADC deficiency
23 Wassenberg T et al. Orphanet J Rare Dis. 2017;12(1):12PTC-AADC patients make significant and sustainable progress
Untreated Post-Treatment
Age 2 Age 3 Age 4.5
24Adapting patient identification efforts due to COVID-19
Implemented virtual education & patient finding initiatives
Conducted master class with >200 HCPs from >20 countries
Held multiple European AADC steering committee meetings
Virtual HCP meetings continue to support diagnosis of new patients in
cerebral palsy & epilepsy clinics
Early
diagnosis
Increased
awareness
300+ AADC patients by launch
Focused on education Launched social media
supporting early patient campaigns
diagnosis Leveraging expert videos
Rolled out ‘The Road Less focusing on symptoms and
Traveled’ program for finding a directing viewers to disease state
Genotyping websites
path towards early patient
diagnosis
25Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
26Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
27Bio-e Platform Overview
Platform capabilities: Novel approach: Validated target and Extensive pediatric Pipeline potential:
mechanism of safety and exposure
action: history:
Based on a family of Intersection of Lead compound PTC743 has been Large number of
oxidoreductase enzyme electron-transfer PTC743 targets the evaluated in over 500 oxidoreductase targets
targets critical to chemistry and biology enzyme 15- patients – mostly children with known biological
generation and lipoxygenase – a key – with duration of significance (>100), and
regulation of energy key enzyme hub that exposure up to 10 years, diverse redox small
to disease pathology regulates inflammation and has been safe and molecule library
and oxidative stress well-tolerated
28Initial target is 15-lipoxygenase — key regulator of
inflammation and oxidative stress pathways in CNS diseases
O
OH
Arachidonic acid
15-Lipoxygenase PTC743 & PTC857 15-lipoxygenase
OH Lipid
signaling
O O
molecule that
OH regulates
fundamental
15-OOH-Arachidonic acid 15(S)-HpETE*
disease
Glial Cell Alpha-synuclein Glutathione Oxidative Stress processes
Activation & Oxidation Oxidation & Mediated Glutathione
Inflammation & Aggregation Depletion Membrane GPX4
Damage Selenocysteine-
dependent active site
Glutathione
disulfide
HO O
OH
15-OH-Arachidonic acid
29Initiating Three Bio-e Clinical Trials in 2020
PTC743 PTC743 PTC857
Mitochondrial Epilepsy Trial Friedreich Ataxia Trial Phase 1 Trial
Trial Starting 3Q20 Trial Starting 4Q20 Trial Starting 3Q20
• Proof-of-concept established in • Mechanism linked to FA • Targeting GBA Parkinson’s
dozens of patients pathology disease as first indication
• Clinical trials demonstrated • >60 subjects treated; • Inhibits alpha-synuclein
reduction in hospitalizations and Improvement in FARS oxidation and aggregation in
mortality risk in mitochondrial compared to natural history preclinical studies
epilepsy patients
• Potentially complementary • Protects dopamine-related
• Enrolling patients with 4 most with FA gene therapy motor function in MPTP mouse
common sub-types of
mitochondrial epilepsy
5-6K 25K ~50 – 90K
patients in the US and EU patients WW patients in the US
30Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
31Diversifying and strengthening our rare disease portfolio
PTC923 Phase 3 Ready for Phenylketoneuria (PKU) Symptoms of PKU can be
managed well by maintaining
• High unmet need in PKU; 60-70% untreated low Phe levels in the body
• Significant commercial opportunity; ~58,000 PKU
patients globally
• Clearly defined market with newborn screening & Cognitive
Impairment
Seizures
established centers of specialists in place
• PTC923 differentiated relative to existing treatment
options
• Fits with both clinical development and commercial
Eczema Behavioral
expertise Abnormalities
32Differentiated mechanism of action leads to greater intracellular
bioavailability
COOH DHPR COOH
H2N CH BH4 BH2 H2N CH
CH2 CH2
H H
Phenylalanine PAH Tyrosine
H H
H H H H
Dietary protein Phenylketones Tissue protein Melanin
H Epinephrine Dopamine OH
Tissue protein
GI Tract Plasma Intracellular (liver, brain, kidney)
Co-Factor Therapies
O O
Synthetic SP Rapid Cross-Membrane Active Transport
Sepiapterin HN
N
SP
(PTC923) Sepiapterin reductase
H2N N NH
OH
Inefficient Cross-
Cell membrane
Membrane Active O OH
Transport N
HN
BH2 7.8-Dihydrobiopterin
Dihydrofolate reductase OH
BH2
H2N N NH
Oxidation
O OH
Synthetic BH4 HN
HN
BH4 Tetrahydrobiopterin BH4
(Kuvan®) H2N N NH
OH
33Demonstrated statistically significant differences in reduction
of Phe relative to existing treatment options in Phase 2 study
• 60 mg/kg/day most effective
PTC923 PTC923
Kuvan 20mg/kg 60mg/kg dose
Least squares mean (LSM) changes (SE)
0
from baseline in blood Phe (μmol/L)
• 114.9 greater μmol/L
-50 reduction of Phe with
60 mg/kg/day PTC923
-100
p=0.0339 relative to Kuvan; p=0.0098
-150
p=0.010
• 50% increased responder
rate with PTC923 as
-200 compared to Kuvan (12/19
pMultiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
35Translarna™ demonstrates long-term
benefit in DMD patients
EU5 nmDMD patients treated with Translarna Compliance
STRIDE is a real-world, long-term registry of patients
receiving Translarna
Translarna treatment slowed disease progression in nmDMD
compared to matched natural history patients
3.5 years 3 years 2.2%
Delay in loss of Extension in ability to Translarna-treated pts
ambulation stand from supine in had an FVCStrong DMD franchise performance with continued growth
opportunities
Translarna
• Increased penetration in existing
territories
2019 net DMD
Translarna • Geographic expansion into new territories
Franchise revenue
• Increased awareness and earlier
diagnosis
$190M • Potential US NDA submission in 2020
$291M Emflaza
$101M
• Growth in 2-5 year olds from label expansion
Emflaza • Optimize dosing in both new and existing pts
• Publications showing the benefit of Emflaza
over prednisone
• Reduced payer restrictions
• Benefit of switching
37Ataluren US dystrophin trial data expected 3Q20
Open-label dystrophin study
Ataluren naïve patients Dystrophin levels measured
using ECL assay
Nonsense mutation DMD boys ranging in age • Validated with FDA
from 2-7
• More sensitive than western blot to
• Length: 40 weeks; N=20 patients the full-length dystrophin protein
• Biopsies taken at baseline and 40 weeks after treatment • Biopsies taken using less-invasive
needle biopsy
• Single site
• Biopsies taken from two muscles to
• All samples analyzed together at the end of the study improve sample quality
• Endpoint: % dystrophin change from baseline as measured by ECL
38Multiplatform approach builds diversified pipeline
SCIENTIFIC PLATFORMS & RESEARCH
Nonsense Gene
Deflazacort LatAm Commercial Splicing Bio-e Metabolic Oncology
Mutation Therapy
Commercial
SMA AADC
US Dystrophin PTC743 MEDS PTC923 PKU PTC596 DIPG
PTC743 FA PTC596 LMS
Clinical
PTC299 AML
PTC518 HD FA PTC857 GBA-PD
Undisclosed Angelman Undisclosed
IRDs
Research Cog Disorders
Potential registrational studies
39Leveraging our existing LatAm infrastructure
to commercialize Tegsedi & Waylivra
Best fit for Waylivra to utilize our patient support
Latin American hATTR market in Latin America
ANVISA approval granted in 2019 ANVISA submission expected in 2H20
First & only approved at-home therapy in Brazil Potential first FCS treatment
with slowing disease progression and QoL
Received EU conditional
indicated in label
marketing approval
hATTR most prevalent phenotype in Latin
America with ~6,000 patients
40 FCS = familial chylomicronemia-syndromePotential 2020 remaining milestones to generate value
PTC518
HD
US Translarna NDA
submission
Waylivra
ANVISA filing
PTC743
MEDS Risdiplam US
Launch
Tegsedi Brazil
Launch
PTC743
FA
AADC BLA filing
Risdiplam PTC857
PDUFA GBA-PD
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