1CONFIDENTIAL November 2015

Other Strategies for Different MutationsStuart Peltz, PhD, CEO PTC Therapeutics

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Stem cells

Exon skipping

Gene therapy

Treatment development focuses across all DMD Intervention points

Utrophin upregulation

DMD

Dystrophin restoration & replacement

Inflammation & fibrosis

Muscle growth &

regeneration

Cardiac & calcium

regulation

Ataluren

Ryanodine receptor

Serca2a

Traditional cardiac drugs

Steroids

Anti-fibrotics

mIGF1myostatin

3

PTC Therapeutics’ integrated approach to treat DMD

DMD

MuscleGrowth &

Regeneration

ReadthroughTherapy

Utrophin

mIGF1SERCA2a

ataluren

MembraneIntegrity

Exon skipping

preclinicalSmall

molecule

4

Development history of Ataluren in nmDMD

17 years of research & development

750+ healthy volunteers/patients exposed/treated and

~900 patient-years of treatment

Safety profile: Generally well tolerated

Phase 2a: Dystrophin expression demonstrated

Phase 2b: Clinically meaningful benefit in 6MWT/Natural History data

Phase 3: ACT DMD fully enrolled with data expected Q4 2015

EMA granted marketing authorisation approval for ambulatory nmDMD patients aged 5

years and older – July 2014

98–2003 2008 2009 2011 2012 2013201020072005

Phase 2a (004)38 nmDMD patients

Phase 2a (004)38 nmDMD patients

20062004

Phase 162 healthy

males

Phase 162 healthy

males

2014

Phase 2b (007)174 nmDMD patients

Phase 2b (007)174 nmDMD patients

EMA DMDdraft guidelines

Initial natural history

publications

ataluren discoveryataluren

discovery

EMA approval of ataluren

2015

Phase 3 (020)220 nmDMD patients

Phase 3 (020)220 nmDMD patients

5

As Proof of concept, ataluren treatment results in full-length functional dystrophin production

• ataluren partially restored dystrophin protein in different muscle groups, including diaphragm and heart, and improved muscle function1,2

• ataluren has also been found to enhance dystrophin expression in other preclinical models of nmDMD3,4

ataluren

Ataluren

Ataluren

mdx mouse

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During Phase 2a study, we demonstrated an increase in dystrophin expression in patients with nmDMD

Improvements in dystrophin were seen in ~60% of patients after 28 days of ataluren 16 mg/kg/day, 40 mg/kg/day or 80 mg/kg/day*

A mean change in dystrophin expression of 11% was observed after 28 days of treatment with ataluren (p = 0.008, paired t test)

No dose–response relationship was observed

Pretreatment End of treatment (day 28)

Immunohistochemistry of muscle cross-sections to visualize dystrophin expression in extensor digitorum brevis at baseline and after 28 days of treatment with ataluren 40 mg/kg/day

61% of patients showed an increase in dystrophin staining in 28 days of ataluren treatment

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Phase IIb (Study 007): Patients receiving ataluren 40 mg/kg/day showed a smaller decline in walking ability over 48 weeks than those given placebo1

*Adjusted p value from analysis of all data across three treatment arms with 80 mg/kg/day not different from placebo; 70% of placebo and ataluren patients respectively were receiving corticosteroids through study, as part of best standard of care. 6MWD, 6-minute walk distance; CI, confidence interval.1. Haas et al. Neuromuscul Disord 2015 (25):5–13. Graph taken from Bushby K et al. Muscle Nerve 2014;50:477–87, with data from Haas et al. 2015. For 31.7 m, 95% confidence interval: 5.1, 58.3.

Ataluren

Time function test results

1. Escolar DM et al. 2011 – the threshold for a clinically meaningful difference in timed function tests was defined as 0.4 log seconds, which was back-transformed to ~1.5 seconds; 2. ataluren EPAR EMA website; 3. Bushby K et al. Muscle Nerve 2014;50:477–87. TFT, timed function test. S, seconds. 70% of placebo and ataluren patients respectively were receiving corticosteroids through study, as part of best standard of care

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• A clinically meaningful difference of 1.5 seconds1 was reached in three of the four TFT tests2, 3

• No difference was seen for the stand from supine test, due to baseline demographics2, 3

Ataluren

2008ataluren ‘007

2010 drisapersen

2013tadalafil

2013ACT DMD

2015 eteplirsen

2015Anti-myostatin

Six minute walk test (6MWT) and time function tests are commonly used clinical endpoints utilized in ambulatory DMD trials

6MWD

Stair Climb

Primary Endpoint

Secondary Endpoints Time to 10% 6MWD Worsening

10-meter walk/run

Stair climb

Stair descend

PedsQL

Myometry

PODCI

North Star Ambulatory Assessment

Note: ataluren study conducted by PTC Therapeutics; drisapersen study conducted by GSK / Prosensa (Biomarin); tadalafil study conducted by Lilly; eteplirsen study conducted by Sarepta; anti-myostatin mAb study conducted by Pfizer. 7

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6MWD

450m

400m

300m

150m

Loss of riseFrom floor

Loss ofStair climb

Loss of ambulation

Optimal window for 1 year clinical trials

Timed Function Tests(10m walk, stair climb, stair

descend)

Ambulatory Function (6MWT)

Progressive loss of function highlights the complexities associated with conducting clinical studies in DMD

Data from Study 007 and ACT DMD of high performing DMD placebo patients (≥400m) show stable 6MWD over 48 weeks

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In peer reviewed literature Pane et al 2014 demonstrated slower decline in subjects with baseline 6MWD of >350m

-100

-80

-60

-40

-20

0

20

Ch

ang

e in

6M

WD

, Mea

n (

m)

ACT DMD Placebo Baseline 6MWD 400 m (N=41)

Study 007 Placebo Baseline 6MWD 400 m (N=22)

6 12 18 30 36 428 16 32 4024 480

1 m

-14 m

This is repetitive of precious one, I would delete

Emerging MRI data reinforce the view that patients with baseline 6MWD <300m are at higher risk of losing ambulation

Imaging data illustrate infiltration of muscle by fat and fibrous tissue

Data courtesy of H. Lee Sweeney, Ph.D.Myology Institute, University of Florida

6M

WD

300

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ACT DMD was designed to evaluate effect of ataluren on trial endpoints over 48 weeks in patients with nmDMD

Open-labelextension

Double-blindplacebo-controlled

study

PlaceboN=110

48 weeks

Ataluren 10, 10, 20 mg/kgN=110

R 1:1

Primary endpoint Change in 6MWD

Secondary endpoints 10% worsening in 6MWD Change in 10-m walk/run Change in 4-stair climb Change in 4-stair descend

Exploratory endpoints Change in NSAA Change in PODCI

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ACT DMD results demonstrate consistent benefit for Duchenne patients

cITT 300m - 400m ITT 300m - 400m0.0

10.0

20.0

30.0

40.0

50.0

60.0

32m (p=0.020)

49m (p=0.049)

15m (p=0.213)

47m (p=0.007)

6M

WD

Tre

atm

ent

Diff

ere

nce

vs.

Pla

cebo (

m)

Study 007 ACT DMD

(n=114) (n=44) (n=228) (n=99)

**

** pre-specifiedcITT: corrected ITT

ACT DMD study confirmed benefit for DMD patients previously observed in Study 007

49m (p=0.026)

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Pre-specified analysis of 300m-400m baseline 6MWD patients showed benefit across primary and secondary endpoints

Primary and secondary results consistent with Study 007 subgroup results

0.0

10.0

20.0

30.0

40.0

50.0

60.0

70.0

6M

WD

Tre

atm

ent

Diff

ere

nce

vs.

Pla

cebo (

m)

47m(p=0.007)

ACT DMD 300m – 400m Baseline 6MWD (n=99)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

-2.1s(p=0.066)

-3.6s(p=0.003)

TFT T

reatm

ent

Diff

ere

nce

vs.

Pla

cebo

(s)

-4.3s(p<0.001)

6MWT 10m Run/Walk 4-Stair Climb 4-Stair Descend

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A meta-analysis demonstrated a statistically significant benefit in favor of ataluren across primary and all TFT key secondary endpoints

0.0

10.0

20.0

30.0

40.0

50.06M

WD

Tre

atm

ent

Diff

ere

nce

vs.

Pla

cebo

(m)

22m(p=0.015*)

Meta Analysis: ACT DMD and Study 007 (n=291)

0.0

0.5

1.0

1.5

2.0

2.5

1.4s(p=0.025*)

1.6s(p=0.018*)

Change in T

FT T

reatm

ent

vs.

Pla

cebo (

s) 2.0s

(p=0.004*)

6MWT 10m Walk Stair Climb Stair Descend

* Statistically significant

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Loss of ambulation occurred more frequently in placebo patients with 300-400m baseline 6MWD across both ACT DMD and Study 007

Placebo Translarna Placebo Translarna

-14%

-12%

-10%

-8%

-6%

-4%

-2%

0%

9%(2 of 22)

0%(0 of 22)

8%(4 of 52)

Perc

enta

ge o

f P

ati

ents

Losin

g

Am

bula

tion (

%)

Study 007300m-400m Baseline 6MWD

ACT DMD300m-400m Baseline 6MWD

Six placebo patients with 300m-400m baseline 6MWD lost ambulation vs. no ataluren patients across both ACT DMD and Study 007

The NSAA is a comprehensive DMD specific instrument developed in Europe to measure global ambulatory status

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StandWalkSit to standSingle leg stand (right) Single leg stand (left)Climb step (right)Climb step (left)Descend step (right) Descend step (left) Lying to sittingRise from floorLift headStand on heelsJump Hop (right) Hop (left)Run

Lev

el o

f d

iffi

cult

y

17 different items with increasing level of difficulty

3 point scale from 0-2

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The NSAA demonstrated positive trend favoring ataluren in the ITT population and larger, statistically significant benefit (p=0.04) in the 300-400m baseline population

North Star Ambulatory Assessment

The NSAA complements the 6MWT by assessing a wide spectrum of functions important in everyday life [Mazzone 2013]

-9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9

Mean Difference

Baseline 6MWD300-400 m (N=99)

ITT (N=228)

p = 0.04

p = 0.27

Decline Improvement

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101 (87.8%) subjects had a treatment-emergent adverse event (TEAE) in placebo group compared to 103 (89.6%) in the ataluren-treated group

The majority of adverse events were mild or moderate

No life threatening AE were reported in ataluren treated patients

Only 8 patients (4 in each arm) experienced at least 1 serious adverse event

SAEs in ataluren-treated patients were pneumonia, bronchiolitis, post-traumatic pain, tendon disorder, adenoidal hypertrophy and nasal turbinate hypertrophy

2 patients (1 in each arm) discontinued due to adverse events

1 ataluren-treated patient D/C due to constipation considered possibly related to study drug

ACT DMD confirms favorable safety profile for ataluren

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These advances and successes have only been possible with the support of boys, young men, families, doctors and patient associations