Slide 1: Translarna (Ataluren) Study 041 Topline Results
Translarna™(Ataluren)Study 041 Topline Results21stJune 2022
Slide 2: Forward looking statements
Forward looking statementsThis presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this presentation, other than statements of historic fact, are forward-looking statements, including statements rega
Slide 3: Agenda
Agenda 3 Study 041 Topline Results Overview of DMD and TranslarnaSTRIDE Registry123
Slide 4: Overview of DMD and Translarna
Overview of DMD and Translarna 4
Slide 5: PTC has pioneered development of therapies for DMD patients for 25 years
5PTC has pioneered development of therapies for DMD patients for 25 years1CHMP, Committee for Medicinal Products for Human Use; DMD, Duchenne muscular dystrophy; FDA, Food and Drug Administration; nmDMD, nonsense mutation Duchenne muscular dystrophy. 1. Data on file. PTC Therapeutics. South Plainfie
Slide 6: DMD is a relentlessly progressive, fatal, genetic disorder
DMD is a relentlessly progressive, fatal, genetic disorder Debilitating X-linked genetic disorder leading to death in early adulthood1 in every 3,500-5,000 live male births with ~13% caused by nonsense mutations1-7Caused by the lack of dystrophin protein due to mutations that prevent its production
Slide 7: DMD follows well-established clinical progression
DMD follows well-established clinical progression7 Patient age:10 years15years20years Loss of ambulation Loss of upper limb function Pulmonary failure Cardiac failure Impaired ability to hop, run, jump, rise
Slide 8: DMD pathology results from lack of full-length dystrophin
Goemans, Nathalie et al. “New Perspectives in the Management of Duchenne Muscular Dystrophy.” European neurological review 9 (2014): 78. DMD pathology results from lack of full-length dystrophin•Dystrophin connects the cytoskeleton to extracellular matrix and is critical during muscle contractions•M
Slide 9: Translarna enables the production of full-length, functional dystrophin
•mRNA, messenger ribonucleic acid. Peltz SW, et al. AnnuRev Med. 2013;64:407–425•Translarna, Summary of Product Characteristics. •Haas M et al. NeuromusculDisord. 2015;25:5–13.Translarnaenables the production of full-length, functional dystrophin9
Slide 10: Translarna enables the production of full-length, functional dystrophin
•mRNA, messenger ribonucleic acid. Peltz SW, et al. Annu Rev Med. 2013;64:407–425•Translarna, Summary of Product Characteristics. •Haas M et al. Neuromuscul Disord. 2015;25:5–13.Translarnaenables the production of full-length, functional dystrophin10
Slide 11: Translarna enables the production of full-length, functional dystrophin
•mRNA, messenger ribonucleic acid. Peltz SW, et al. Annu Rev Med. 2013;64:407–425•Translarna, Summary of Product Characteristics. •Haas M et al. Neuromuscul Disord. 2015;25:5–13.Translarnaenables the production of full-length, functional dystrophin11
Slide 12: Translarna demonstrated consistent treatment effect across multiple endpoints in previous trials
1. Campbell, et al. Journal of Comparative Effectiveness Research. 2020; 9(14), 973–984. Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy.2, Primary endpoint. 3, Secondary endpoint. 12Translarnademonstrated consistent treatment effect across mul
Slide 13: STRIDE Registry
STRIDE Registry PTC)
Slide 14: STRIDE registry captures real-world evidence of Translarna benefit
•STRIDE includes data from:1,2•13countries•64sites•288patients Aims to understand:•the safety profile of Translarnaover a long period of time•how effective long-term treatment is in preservingthe ability to walk, move independently, as well as lung and heart function •Patient registry collecting lon
Slide 15: STRIDE registry demonstrates Translarna significantly preserves ambulation
5.4 years longer of being able to walk and move independently1STRIDE registrydemonstratesTranslarnatreatmentsignificantlypreservesambulation CINRG Duchenne Natural HistoryStudySTRIDE Registry 17.9 years old12.5 yearsoldaThemedian (95% CI) ages at loss of ambulation were: 17.9 (14.4, NA) years for ST
Slide 16: STRIDE registry demonstrates Translarna significantly preserves pulmonary function
1.8-year delay in decline in lung function, prolonging quality of life1 CINRG Duchenne Natural HistoryStudySTRIDE Registry 17.6 years old15.8 yearsoldaThemedian (95% CI) ages at predicted FVC < 60% were: 17.6 (16.2, NA) years for STRIDE and 15.8 (15.1, 16.5) years for the CINRG DNHS; p < 0.0051CINRG
Slide 17: Translarna protects against loss of pulmonary function
Translarnaprotects against loss of pulmonary function 17-- < 30% FVC predicts mortality in DMD patients within 2-3 years PTC Therapeutics, data on file Proportion of patients withpredicted FVC above 30% (%) Age (years)
Slide 18: EMA regulatory history supports positive risk-benefit of Translarna
2022 Study 041 placebo-controlled confirmatory trial data readout EMA marketingauthorizationLabel expansion to include 2–5-year olds EMA regulatory history continues to support the positive risk-benefit of Translarna Label change enabling physicians to continue patients who become non-ambulatory2014
Slide 19: Study 041: Overview and study design
Study 041: Overview and study design•Age ≥5 years old •6MWD ≥150 meters•Stable steroid regimenEligibility CriteriaKey Outcome Measures•Primary endpoint: 6MWT•Secondary endpoints: NorthstarAmbulatory Assessment (NSAA), Timed Function Tests (TFTs)Open-label treatment72 weeks Placebo 1:1Randomization T
Slide 20: Study 041: Intent-to-Treat (ITT) population
Study 041: Intent-to-Treat (ITT) population Baseline CharacteristicTranslarna (N=183)Placebo (N=176)Overall (N=359)Mean age at enrollment, yrs[min, max]8.1 [5.0, 14.0]8.2 [5.0, 14.0]8.1 [5.0, 14.0]Baseline 6MWD, n (%)<300m300 to <350m350 to <400m≥400m21 (11.5)40 (21.9)46 (25.1)76 (41.5)21 (11.9)37 (
Slide 21: Study 041: Subject disposition
Study 041: Subject disposition 21 ITT populationTranslarna(N=183)Placebo (N=176)ITT Population183176Completed placebo controlled portion (%)179 (97.8)172 (97.7)Early termination (%)Adverse eventCOVIDLoss to follow-upWithdrew consentProtocol noncomplianceOther4 (2.2)001 (0.5)02 (1.1) 1 (0.5)4 (2.3)00
Slide 22: Translarna treatment resulted in significant benefit across key endpoints in ITT population
Translarnatreatment resulted in significant benefit across key endpoints in ITT populationThe ITT population was not the primary analysis population22 Timed function tests10m walkStair ascendStair descend3.044.984.963.826.045.25-0.78 (p=0.0422)-1.06 (p=0.0293)-0.29 (p=0.5749) NSAA Total scoreLinear
Slide 23: NSAA results confirm Translarna preserves functional abilities in ITT population
-50-40-30-20-1001020304050Stand up from chairStand on heelsJumpRise from floorStand on one leg - rightDescend box step - leftStand on one leg - leftDescend box step - rightHop rightRun (10m)Lifts headHop leftStandWalk (10m)Climb box step - leftGets to sittingClimb box step - rightNSAA results confir
Slide 24: Translarna demonstrated consistent treatment effect in previous trials
24Translarnademonstrated consistent treatment effect across multiple clinical endpoints in previous trials1Meta-analysis LS mean difference (SEM)Meters, mean and 95% CITFTs, Seconds, mean and 95% CI Improvement Decline 75 100 50 25 0 -25 -50 -75 -100 8 6 4 2 0 -2 -4 -6 -86MWT210-m walk/run34-stair a
Slide 25: Greatest effects in patients with baseline 6MWD of 300-400 meters
25Translarnademonstrated greatest effects in patientswith baseline 6MWD of 300-400metersin previous trials16MWT, Meters, mean and 95% CITFTs, Seconds, mean and 95% CI 43.9 -2.1 s -3.4 s -4.3 sMeta-analysis LS mean difference (SEM) Improvement Decline 75 100 50 25 0 -25 -50 -75 -100 8 6 4 2 0 -2 -4 -
Slide 26: Significant treatment effects on 6MWT seen in subpopulations in previous trials
Clinically meaningful, significant treatment effects on 6MWT seen in subpopulations in previous trials•6MWD <400m (left panel) or stand from supine ≥5s (right panel) both exclude stable patients 81624324048 -120-100-80-60-40 -200 Placebo (N=67) Ataluren (N=72) BaselineTime (weeks)Change in 6MWD, Mea
Slide 27: Study 041: Subgroup analyses
*primary analysis population 6MWD ≥300m and ≥5 sec supine to stand*Translarna(N=92)Placebo (N=93)8.9 [7, 14]8.9 [6, 14]0 (0)29 (31.5)33 (35.9)30 (32.6)0 (0)32 (34.4)31 (33.3)30 (32.3)92 (100)41 (44.6)51 (55.4)93 (100)41 (44.1) 52 (55.9)092 (100)093 (100)Study 041:Subgroup analyses 27 6MWD 300-400mBa
Slide 28: Translarna treatment resulted in significant benefit in 300-400m subgroup
6MWD 300m and ≥5 sec supine to stand*Translarna(N=92)Placebo (N=93)Difference -81.8-1.14-90.1 -1.258.3 (p=0.3626)0.11 (p=0.3626)5 (5.4%)9 (9.7%)---5.2-11.4-6.1-14.00.9 (p=0.1258) 2.5 (p=0.0656)3.06 5.19 4.583.79 6.96 4.78-0.73 (p=0.1877)-1.76 (p=0.0155)-0.19 (p=0.7997)*primary analysis population Tr
Slide 29: Pooled analysis from three placebo-controlled trials confirms significant treatment benefit
Pooled analysis from three placebo-controlled trials confirms significant treatment benefit Overall study populationStudy 007, 020 and 041 Translarna (N=354)Placebo (N=347)6MWD (48 weeks)-28.1-47.419.3 (p=0.0002)NSAA*Total Score Linear Score1.01 (p=0.002) 2.28 (p=0.005)TFTs10m walkStair ascend Stair
Slide 30: Study 041: Safety summary
Study 041: Safety summaryNo difference in adverse event frequency between Translarnaand placebo 30 Translarnawell tolerated without any drug-related serious adverse eventsNo adverse events leading to drug discontinuation
Slide 31: Study confirms Translarna treatment benefit in nmDMD patients
Study 041 confirms Translarnatreatment benefit in nmDMDpatientsThe ITT population was not the primary analysis population31 Totality of evidence across multiple DMD clinical studies and real-world data demonstrate clinical benefitTranslarnademonstrates a favorable safety profile with more than 3000
Slide 32: Alternative analysis method (ANCOVA)
Alternative analysis method (ANCOVA) 32
Slide 33: Translarna treatment demonstrated benefit across key endpoints in ITT population
Translarnatreatment demonstrated benefit across key endpoints in ITT population Endpoint Assessment(Change from baseline)Difference -MMRM (p value)Difference -ANCOVA (p value)6MWD (m)Rate of change (m/wk)14.4 (p=0.0248)0.20 (p=0.0248)15.3 (p=0.0805)0.21 (p=0.0805)NSAATotal score Linear score0.9 (p=0
Slide 34: Supplemental analysis: pooled analysis from three placebo-controlled trials
Supplemental analysis34Pooled analysis from three placebo-controlled trials confirms significant treatment benefit Overall study populationStudy 007, 020 and 041 Translarna (N=354)Placebo (N=347)6MWD (48 weeks)-28.1-47.419.3 (p=0.0002)NSAA*Total Score Linear Score1.01 (p=0.002) 2.28 (p=0.005)TFTs10m
Slide 35: Study 041 confirms Translarna treatment benefit in nmDMD patients
First disease modifying treatment for DMD to show a statistically significant treatment benefit across the entire ITT population Study 041 confirms Translarnatreatment benefit in nmDMDpatientsThe ITT population was not the primary analysis population35 Study 041 adds to existing evidence of clinical
Slide 36: Questions?
Questions? PTC)