PTC Therapeutics, Inc. · NASDAQ:PTCT
PTC Therapeutics — Technical Presentation (June 2022)
36 slides from PTC Therapeutics's technical presentation, Jun 21, 2022
Slide 1: Translarna (Ataluren) Study 041 Topline Results
Translarna™ (Ataluren) Study 041 Topline Results 21st June 2022
Slide 2: Forward looking statements
Forward looking statements This 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 reg
Slide 3: Agenda
Agenda 1 Overview of DMD and Translarna 2 STRIDE Registry 3 Study 041 Topline Results 3
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
PTC has pioneered development of therapies for DMD patients for 25 years1 Translarna indication Translarna EU conditional expansion approved Readthrough approval for nmDMD by CHMP program initiated and Translarna discovery First ever DMD Emflaza approved Emflaza FDA label Initial natural drug trial
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 adulthood 1 in every 3,500-5,000 live male births with ~13% caused by nonsense mutations1-7 Caused by the lack of dystrophin protein due to mutations that prevent its productio
Slide 7: DMD follows well-established clinical progression
DMD follows well-established clinical progression Patient age: 10 years 15 years 20 years Impaired ability to hop, run, jump, rise Loss of ambulation Loss of upper limb function Pulmonary failure Cardiac failure 7
Slide 8: DMD pathology results from lack of full-length dystrophin
DMD pathology results from lack of full-length dystrophin • Dystrophin connects the cytoskeleton to extracellular matrix and is critical during muscle contractions • Muscles lacking dystrophin are more susceptible to damage • Damaged dystrophin is replaced by fatty and connective tissue • Dystrophin
Slide 9: Translarna enables the production of full-length, functional dystrophin
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. 9
Slide 10: Translarna enables the production of full-length, functional dystrophin
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. 10
Slide 11: Translarna enables the production of full-length, functional dystrophin
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. 11
Slide 12: Translarna demonstrated consistent treatment effect across multiple clinical endpoints in previous trials
Translarna demonstrated consistent treatment effect across multiple clinical endpoints in previous trials1 Decline Improvement Meters, mean and 95% CI Meta-analysis LS mean difference (SEM) -100 -75 -50 -25 0 25 50 75 100 6MWT2 17.2 m 10-m walk/run3 ‒1.1 s Meta-analysis (007, 020) (N=342) Study 020
Slide 13: STRIDE Registry
STRIDE Registry 13
Slide 14: STRIDE registry captures real-world evidence of Translarna benefit
STRIDE registry captures real-world evidence of Translarna benefit • Patient registry collecting Aims to understand: • STRIDE includes data from:1,2 long-term real-world • the safety profile of evidence Translarna over a long • 13 countries period of time • Collecting information on • 64 sites the c
Slide 15: STRIDE registry demonstrates Translarna treatment significantly preserves ambulation
STRIDE registry demonstrates Translarna treatment significantly preserves ambulation CINRG Duchenne Natural History Study STRIDE Registry 12.5 years old 17.9 years old 5.4 years longer of being able to walk and move independently1 aThe median (95% CI) ages at loss of ambulation were: 17.9 (14.4, NA)
Slide 16: STRIDE registry demonstrates Translarna treatment significantly preserves pulmonary function
STRIDE registry demonstrates Translarna treatment significantly preserves pulmonary function CINRG Duchenne Natural History Study STRIDE Registry 15.8 years old 17.6 years old 1.8-year delay in decline in lung function, prolonging quality of life1 aThe median (95% CI) ages at predicted FVC < 60% wer
Slide 17: Translarna protects against loss of pulmonary function
Translarna protects against loss of pulmonary function predicted FVC above 30% (%) Proportion of patients with < 30% FVC predicts mortality in DMD patients within 2-3 years Age (years) -- PTC Therapeutics, data on file 17
Slide 18: EMA regulatory history continues to support the positive risk-benefit of Translarna
EMA regulatory history continues to support the positive risk-benefit of Translarna STRIDE initiation Label change enabling physicians Study 041 Label expansion to continue patients placebo-controlled to include who become confirmatory EMA trial data readout marketing 2–5-year olds non-ambulatory au
Slide 19: Study 041: Overview and study design
Study 041: Overview and study design Eligibility Criteria Key Outcome Measures • Age ≥5 years old • Primary endpoint: 6MWT • 6MWD ≥150 meters • Secondary endpoints: Northstar Ambulatory • Stable steroid regimen Assessment (NSAA), Timed Function Tests (TFTs) Placebo 1:1 Placebo-controlled treatment O
Slide 20: Study 041: Intent-to-Treat (ITT) population
Study 041: Intent-to-Treat (ITT) population Baseline Characteristic Translarna (N=183) Placebo (N=176) Overall (N=359) Mean age at enrollment, yrs 8.1 [5.0, 14.0] 8.2 [5.0, 14.0] 8.1 [5.0, 14.0] [min, max] Baseline 6MWD, n (%) <300m 21 (11.5) 21 (11.9) 42 (11.7) 300 to <350m 40 (21.9) 37 (21.0) 77 (
Slide 21: Study 041: Subject disposition
Study 041: Subject disposition ITT population Translarna (N=183) Placebo (N=176) ITT Population 183 176 Completed placebo 179 (97.8) 172 (97.7) controlled portion (%) Early termination (%) 4 (2.2) 4 (2.3) Adverse event 0 0 COVID 0 0 Loss to follow-up 1 (0.5) 0 Withdrew consent 0 3 (1.7) Protocol non
Slide 22: Translarna treatment resulted in significant benefit across key endpoints in ITT population
Translarna treatment resulted in significant benefit across key endpoints in ITT population Endpoint Assessment Translarna Placebo Difference (Change from baseline) (N=183) (N=176) 6MWD (m) -53.0 -67.4 14.4 (p=0.0248) Rate of change (m/wk) -0.74 -0.94 0.20 (p=0.0248) Loss of ambulation, N (%) 12 (6.
Slide 23: NSAA results confirm Translarna treatment preserves functional abilities in ITT population
NSAA results confirm Translarna treatment preserves functional abilities in ITT population Placebo Translarna Climb box step - right Gets to sitting Climb box step - left Walk (10m) Stand Hop left Lifts head Run (10m) Hop right Descend box step - right Stand on one leg - left Descend box step - left
Slide 24: Translarna demonstrated consistent treatment effect across multiple clinical endpoints in previous trials
Translarna demonstrated consistent treatment effect across multiple clinical endpoints in previous trials1 Decline Improvement Meters, mean and 95% CI Meta-analysis LS mean difference (SEM) -100 -75 -50 -25 0 25 50 75 100 6MWT2 17.2 m 10-m walk/run3 ‒1.1 s Meta-analysis (007, 020) (N=342) Study 020
Slide 25: Translarna demonstrated greatest effects in patients with baseline 6MWD of 300-400 meters
Translarna demonstrated greatest effects in patients with baseline 6MWD of 300-400 meters in previous trials1 Decline Improvement 6MWT, Meters, mean and 95% CI Meta-analysis LS mean difference (SEM) -100 -75 -50 -25 0 25 50 75 100 6MWT2 43.9 10-m walk/run3 -2.1 s Meta-analysis (007, 020) (N=342) Stu
Slide 26: Clinically meaningful, 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 ≥300m 6MWD, <400m 6MWD ≥300m 6MWD, ≥5s stand from supine 0 0 C h a n g e in 6 M W D , M e a n ( m ) C h
Slide 27: Study 041: Subgroup analyses
Study 041: Subgroup analyses 6MWD 300-400m 6MWD ≥300m and ≥5 sec supine to stand* Baseline Characteristic Translarna Placebo Translarna Placebo (N=86) (N=83) (N=92) (N=93) Mean age at enrollment (yrs) [min, max] 8.1 [5, 14] 8.5 [5, 14] 8.9 [7, 14] 8.9 [6, 14] Baseline 6MWD, n (%) <300m 0 (0) 0 (0) 0
Slide 28: Translarna treatment resulted in significant benefit in 300-400m subgroup
Translarna treatment resulted in significant benefit in 300-400m subgroup 6MWD 300m – 400m 6MWD 300m and ≥5 sec supine to stand* Endpoint Assessment Translarna Placebo Difference Translarna Placebo Difference (N=86) (N=83) (N=92) (N=93) 6MWD (m) Change from baseline -55.8 -80.0 24.2 (p=0.0310) -81.8
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 population Study 007, 020 and 041 Translarna (N=354) Placebo (N=347) 6MWD -28.1 -47.4 (48 weeks) 19.3 (p=0.0002) NSAA* Total Score 1.01 (p=0.002) Linear Score 2.28 (p=0.005) TFTs 10m walk -1.30
Slide 30: Study 041: Safety summary
Study 041: Safety summary Translarna well tolerated without any drug-related serious adverse events No adverse events leading to drug discontinuation No difference in adverse event frequency between Translarna and placebo 30
Slide 31: Study 041 confirms Translarna treatment benefit in nmDMD patients
Study 041 confirms Translarna treatment benefit in nmDMD patients First disease modifying Totality of evidence Translarna demonstrates treatment for DMD to across multiple DMD a favorable safety profile show a statistically clinical studies and real- with more than 3000 significant treatment world d
Slide 32: Alternative analysis method (ANCOVA)
Alternative analysis method (ANCOVA) 32
Slide 33: Translarna treatment demonstrated benefit across key endpoints in ITT population
Translarna treatment demonstrated benefit across key endpoints in ITT population Endpoint Assessment Difference - MMRM Difference - ANCOVA (Change from baseline) (p value) (p value) 6MWD (m) 14.4 (p=0.0248) 15.3 (p=0.0805) Rate of change (m/wk) 0.20 (p=0.0248) 0.21 (p=0.0805) NSAA Total score 0.9 (p
Slide 34: Pooled analysis from three placebo-controlled trials confirms significant treatment benefit
Pooled analysis from three placebo-controlled trials confirms significant treatment benefit Overall study population Study 007, 020 and 041 Translarna (N=354) Placebo (N=347) 6MWD -28.1 -47.4 (48 weeks) 19.3 (p=0.0002) NSAA* Total Score 1.01 (p=0.002) Linear Score 2.28 (p=0.005) TFTs 10m walk -1.30
Slide 35: Study 041 confirms Translarna treatment benefit in nmDMD patients
Study 041 confirms Translarna treatment benefit in nmDMD patients First disease modifying Study 041 adds to existing Submit results confirming Utilize 041 results to align treatment for DMD to evidence of clinical benefit favorable Translarna with the FDA on NDA show a statistically from STRIDE real
Slide 36: Questions?
Questions? 36
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