Slide 1: PIVOT-HD Extension Study 24-Month Topline Interim Analysis Results
PTC Therapeutics PIVOT -HD LTE 24 -Month Interim Analysis Results PTC Therapeutics PIVOT -HD LTE 24 -Month Interim Analysis Results PIVOT -HD Extension Study 24 -Month Topline Interim Analysis Results 1 Matthew B. Klein, MD CEO April 2026 Patient living with HD
Slide 2: Forward-looking statements
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 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
Slide 3: PIVOT-HD Study Design
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results PIVOT-HD Study Design 3 *Placebo participants randomized 1:1 to 5 mg or 10 mg for LTE and all participants remain blinded to initial treatment assignment Primary Endpoint: Reduction in Blood HTT protein (Week 12) 12 Weeks Placebo-Contro
Slide 4: PIVOT-HD Met Primary Endpoint of Blood HTT Lowering
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results PIVOT-HD Met Primary Endpoint of Blood HTT Lowering with Dose-Dependent Lowering Maintained at Month 12 4 Favorable safety and tolerability profile with no treatment-related NfL increases Favorable and dose-dependent trends on clinical
Slide 5: 24-Month Interim Analysis Results
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 5 PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 24-Month Interim Analysis Results
Slide 6: 24-Month Interim Analysis Overview
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 24-Month Interim Analysis Overview 6 Explore blood-based and other disease associated biomarkers Assess long-term safety and tolerability profile of votoplam Evaluate long-term clinical efficacy of votoplam versus a propensity score–mat
Slide 7: Baseline Characteristics of 24-month Analysis Population
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results Baseline Characteristics of 24-month Analysis Population 7 Baseline Characteristic Stage 2 Stage 3 Votoplam 5 mg (N=21) Votoplam 10 mg (N=24) Votoplam 5 mg (N=22) Votoplam 10 mg (N=24) Age (years) Mean 45.6 46.7 53.2 49.2 Gender, n (%)
Slide 8: ENROLL-HD Registry Propensity Weighted Natural History Comparator Group
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results ENROLL-HD Registry Propensity Weighted Natural History Comparator Group 8 ENROLL-HD is a large (>30,000 patient records), global, prospective, longitudinal observational registry for Huntington’s disease designed to systematically colle
Slide 9: Natural History Cohort Well Matched to Votoplam Treated Population
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results Natural History Cohort Well Matched to Votoplam Treated Population 9 Demographics and Baseline Disease Characteristics Stage 2 Stage 3 Votoplam 5 mg (N=21) Votoplam 10 mg (N=24) NH Cohort (N=73) Votoplam 5 mg (N=22) Votoplam 10 mg (N=
Slide 10: Dose-dependent Slowing of Disease Progression on cUHDRS at 24 months in Stage 2
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results Dose-dependent Slowing of Disease Progression on cUHDRS at 24 months in Stage 2 Participants 10 Worsening Results based on observed data Baseline 12 Month 24 Month Mean (+/-SE) Change from Baseline of Composite UHDRS 0 -0.5 -1.0 -1.5 NH
Slide 11: Evidence of Treatment Benefit Across cUHDRS Subscales for Stage 2 Participants
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results -4 -3 -2 -1 0 1 2 Evidence of Treatment Benefit Across cUHDRS Subscales for Stage 2 Participants 11 -1.2 -1 -0.8 -0.6 -0.4 -0.2 0 Baseline 12 Month 24 Month Mean Change from Baseline (+/-SE) TFC Subscale Baseline 12 Month 24 Month Mean
Slide 12: No Evidence of Treatment-related NfL Spikes at Month 24
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results No Evidence of Treatment-related NfL Spikes at Month 24, with Mean Levels Below Baseline 12 -15% -10% -5% 0% 5% Mean % Change from Baseline (SE) in plasma NfL -4.1% -2.4% Votoplam 5 mg Votoplam 10 mg Plasma NfL reported to increase over
Slide 13: Benefit Signals Observed at Month 24 in Stage 3 Participants
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results Benefit Signals Observed at Month 24 in Stage 3 Participants 13 -2.5 -2 -1.5 -1 -0.5 0 Baseline 12 Month 24 Month cUHDRS Worsening -2 -1.5 -1 -0.5 0 Mean Change from Baseline (+/-SE) Baseline 12 Month 24 Month Mean Change from Baseline
Slide 14: Votoplam Treatment Continues to Show Favorable Safety Profile at Month 24
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results Safety profile consistent for both dose levels and stages No new AE signals identified at 24 months Votoplam safety profile remains favorable after 24 months of treatment Votoplam Treatment Continues to Show Favorable Safety Profile at
Slide 15: Votoplam Treatment Showed Favorable Safety Profile at Month 24
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 15 AE Category PIVOT-HD Long-Term Extension* Placebo N (%) Votoplam 5 mg N (%) Votoplam 10 mg N (%) Votoplam 5 mg N (%) Votoplam 10 mg N (%) Any TEAEs 46 (86.8) 43 (82.7) 49 (90.7) 38 (86.4) 45 (91.8) Any TESAEs 4 (7.5) 1 (1.9) 2 (3.7)
Slide 16: INVEST-HD Global Phase 3 Trial Initiated by Novartis
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results INVEST-HD Global Phase 3 Trial Initiated by Novartis 16 INVEST-HD* Global Phase 3 Study Overview • Individuals with early symptomatic disease • 3:2 randomization of votoplam 10mg: placebo • Target enrollment: ~770 participants in >30 co
Slide 17: Summary and Next Steps
PTC Therapeutics PIVOT-HD LTE 24-Month Interim Analysis Results 17 Align with partner Novartis on plans for potential regulatory interactions to discuss data Continued evidence of favorable safety profile with no new AE signals identified Evidence of dose-dependent disease slowing on cUHDRS in Stage
Slide 18: PTC)
PTC) / THERAPEUTICS 4 ..