PTC Therapeutics : PIVOT-HD Long-Term Extension Study Topline Results Call – April 28, 2026

Published: 2026-04-28 17:54:50 ET PTCT

Published on 04/28/2026 at 05:54 pm EDT

Matthew B. Klein, MD CEO

April 2026

Patient living with HD

PTC Therapeutics

1 PIVOT-HD LTE 24-Month Interim Analysis Results

Placebo-Controlled Study

Votoplam 5 mg

Votoplam 10 mg

Placebo

12 Weeks

12 Months

Long-Term Extension Study*

Votoplam 5 mg

Votoplam 10 mg

Votoplam 5 mg

Votoplam 10 mg

48 Months

PIVOT-HD Study Design

Screening

Primary Endpoint: Reduction in Blood HTT protein (Week 12)

*Placebo participants randomized 1:1 to 5 mg or 10 mg for LTE and all participants remain blinded to initial treatment assignment

PIVOT-HD study met primary endpoint of blood HTT protein lowering at Week 12 with durable dose-dependent lowering at Month 12

Favorable and dose-dependent trends on clinical scales at Month 12

in Stage 2 subjects

Favorable safety

and tolerability profile with no treatment-related

NfL increases

PTC Therapeutics

5 PIVOT-HD LTE 24-Month Interim Analysis Results

24-Month Interim Analysis Overview

Evaluate long-term clinical efficacy of votoplam versus a propensity score-matched natural history cohort*

Assess long-term safety

and tolerability profile

of votoplam

Explore blood-based and other disease associated biomarkers

*Natural history comparison was prespecified in the long-term extension protocol

Baseline Characteristics of 24-month Analysis Population

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 (%) Male Female

11 (52.4%)

10 (47.6%)

11 (45.8%)

13 (54.2%)

12 (54.5%)

10 (45.5%)

14 (58.3%)

10 (41.7%)

CAG length Mean (SD) Min - Max

44.1 (2.28)

41 - 49

43.8 (2.66)

41 - 50

43.0 (2.31)

40 - 50

44.3 (3.03)

40 - 50

TFC (Total Functional Capacity) Score Mean

13.0

11.6

12.0

ENROLL-HD Registry Propensity Weighted Natural History Comparator Group

ENROLL-HD is a large (>30,000 patient records), global, prospective, longitudinal observational

registry for Huntington's disease designed to systematically collect standardized natural history data.

ENROLL-HD was used to create a comparator group based on key drivers of disease progression.

Variables Used for Identification of Natural History Cohort

Sex

Total Functional Capacity (TFC)

Age

Symbol Digit Modalities Test (SDMT)

CAG repeats

Stroop Word Reading Test (SWRT)

Independence Score (IS)

Total Motor Score (TMS)

Natural History Cohort Well Matched to Votoplam

Treated Population

Demographics and Baseline Disease Characteristics

Stage 2

Votoplam 5 mg (N=21)

Votoplam 10 mg (N=24)

NH Cohort (N=73)

Sex (% Male)

52.4%

45.8%

54.9%

Age

45.6

46.7

47.0

CAG repeats

44.1

43.8

cUHDRS

14.3

14.5

Total Functional Capacity (TFC)

13.0

SDMT

41.1

38.7

39.7

SWRT

80.0

86.4

84.4

Total Motor Score (TMS)

12.9

11.2

11.4

Independence Score (IS)

100.0

Stage 3

Votoplam 5 mg (N=22)

Votoplam 10 mg (N=24)

NH Cohort (N=67)

54.5%

58.3%

56.7%

53.2

49.2

51.2

43.0

44.3

43.6

11.6

11.9

11.4

11.6

11.9

11.6

31.1

31.4

30.7

70.3

72.6

69.9

22.0

22.3

24.4

89.8

91.0

88.7

Groups well matched based on Standardized Mean Difference (SMD) < 0.05 for all matching variables

Dose-dependent Slowing of Disease Progression on cUHDRS at 24 months in Stage 2 Participants

Mean (+/-SE) Change from Baseline of Composite UHDRS

-0.5

-1.0

-1.5

Baseline

Votoplam 10 mg

Mean difference in cUHDRS progression of 52% (10mg) and 28% (5mg)

at Month 24

Worsening

Votoplam 5 mg

NH Cohort

12 Month 24 Month

Treatment Group Mean (SE) Mean (SE)

Natural History (N=73) 5 mg (N=21)

10 mg (N=24)

-0.58 (0.15)

-0.42 (0.16)

-0.34 (0.21)

-1.20 (0.20)

-0.86 (0.24)

-0.57 (0.24)

Results based on observed data

Evidence of Treatment Benefit Across cUHDRS Subscales for Stage 2 Participants

Mean Change from

Baseline (+/-SE)

-0.2

-0.4

-0.6

-0.8

-1

-1.2

Mean Change from

Baseline (+/-SE)

-1

Baseline

TFC Subscale

Worsening

12 Month 24 Month

Worsening

TMS Subscale

12 Month 24 Month

Mean Change from

Baseline (+/-SE)

-1

-2

-3

-4

2.5

Mean Change from

Baseline (+/-SE)

-2.5

-5

-7.5

Baseline

SDMT Subscale

Worsening

12 Month 24 Month

Worsening

SWRT Subscale

12 Month 24 Month

Results based on observed data

NH Cohort Votoplam 5 mg Votoplam 10 mg

No Evidence of Treatment-related NfL Spikes at Month 24, with Mean Levels Below Baseline

5 mg

NfL-plasma (pg/mL)

Mean % Change from Baseline (SE) in plasma NfL

-5%

BL 12 24

10 mg

-10%

Votoplam

5 mg

-15%

-2.4%

-4.1%

12 PTC Therapeutics

PIVOT-HD LTE 24-Month Interim Analysis Results

*Parkin et al., 2024

Plasma NfL reported to

increase over time based on natural history*

Month

Votoplam

10 mg

Benefit Signals Observed at Month 24 in Stage 3 Participants

TFC Subscale

cUHDRS

Mean Change from Baseline (+/-SE)

-0.5

Worsening

-1

-1.5

-2

Baseline

12 Month 24 Month

-2.5

Baseline

12 Month 24 Month

NH Cohort

Votoplam 5 mg Votoplam 10 mg

Results based on observed data

Votoplam Treatment Continues to Show Favorable Safety Profile at Month 24 in Stage 2 and 3 Participants

Votoplam safety profile remains favorable after 24 months of treatment

No new AE signals identified at 24 months

Safety profile consistent for both dose levels and stages

Votoplam Treatment Showed Favorable Safety Profile at Month 24 in Stage 2 and 3 Participants

PIVOT-HD

Long-Term Extension*

AE Category

Placebo

Votoplam 5 mg

Votoplam 10 mg

Votoplam 5 mg

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)

3 (6.8)

3 (6.1)

Any TEAEs resulting

1 (1.9)

in death

Any TEAEs leading to

1 (1.9)

2 (3.7)

treatment discontinuation

TEAEs by maximum severity

27 (50.9)

15 (28.3)

2 (3.8)

1 (1.9)

23 (44.2)

18 (34.6)

1 (1.9)

20 (37.0)

24 (44.4)

5 (9.3)

20 (45.5)

16 (36.4)

2 (4.5)

23 (46.9)

18 (36.7)

3 (6.1)

1 (2.0)

Grade 1

Grade 2

Grade 3

Grade 4

Grade 5

*Grade 3 and 4 AEs not treatment related

INVEST-HD Global Phase 3 Trial Initiated by Novartis

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 countries

Primary endpoint: Change from baseline in cUHDRS

Treatment period up to 36 months

Interim analysis planned for efficacy and futility

*Study sponsored and funded by Novartis; NCT#: NCT07326709

Evidence of dose-dependent disease slowing on cUHDRS in Stage 2 participants

Continued evidence of favorable safety profile with no new AE signals identified

Align with partner Novartis on plans for potential regulatory interactions to discuss data

PTC Therapeutics

17 PIVOT-HD LTE 24-Month Interim Analysis Results

PIVOT-HD LTE 24-Month Interim Analysis Results

Disclaimer

PTC Therapeutics Inc. published this content on April 28, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 28, 2026 at 21:54 UTC.