Slide 1: Essential3 Program Topline Results
Essential3 Program Topline Results October 16, 2025
Slide 2: Forward-looking statements
2 This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our business, operations, and financial conditions, including but not limited to express or implied statements regarding the current beliefs, expectatio
Slide 3: First positive Phase 3 program for a drug in Essential Tremor
3 First positive Phase 3 program for a drug in Essential Tremor Essential3 Program – Ulixacaltamide HCl Both studies in the Essential3 Program met their primary endpoints Generally well tolerated, with no drug-related SAEs Praxis has submitted a pre-NDA meeting request to the FDA
Slide 4: No specific drugs developed for ET currently approved
4 No specific drugs developed for ET currently approved An estimated 7 million people in the U.S. live with ET
Slide 5: Gratitude to people living with ET
5 With deep gratitude to the people living with ET who participated in our clinical studies, and to all the ET families and advocates who guide our work
Slide 6: Precision modulation of tremor circuits through T-type calcium channel modulation
6 Precision modulation of tremor circuits through T-type calcium channel modulation Targeting T-type Ca²⁺ channels offers circuit-level normalization Aberrant T-type calcium channel activity in the cerebello- thalamo-cortical circuit drives essential tremor Images from Matthews et al. Ann Clin Trans
Slide 7: Essential3 Program Topline Results
7 Essential3 Program Topline Results
Slide 8: Timeline of Essential3 Program
8 Timeline of Essential3 Program Essential1 Readout March 2023 Established endpoint and dose for registrational study End of Phase 2 FDA Meeting June – Sept 2023 Alignment on endpoint, dose and design of Phase 3 program Essential3 Initiated November 2023 Rapid and sustained interest by patients and
Slide 9: Essential3 is the First Successful Program in Essential Tremor
9 Essential3 is the First Successful Program in Essential Tremor Several important clinical questions answered Hypothesis 1 Study 1 Parallel-group design (PD) Hypothesis 2 Study 2 Blinded Stable-responder, randomized withdrawal design (RW) Hypothesis 3 Studies 1+2 Ulixa / Study 1 PBO Hypothesis 4 St
Slide 10: Essential3: An ambitious and innovative Phase 3 program
10 Essential3: An ambitious and innovative Phase 3 program Blinded randomization 2:1 (Study 1: Study 2) occurred following completion of screening Blinded randomization 1:1 (Ulixacaltamide: Placebo) for treatment arm allocation in Study 1 and for treatment arm allocation of Responders into the rando
Slide 11: Essential3 Study 1 – Parallel design
11 Essential3 Study 1 – Parallel design All efficacy analyses use the modified intent-to-treat (mITT) population defined as all randomized participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. Hypothesis 1 Study 1 Parallel-group design How
Slide 12: Study 1 Baseline demographics - mITT
12 Study 1 Baseline demographics - mITT ULIXACALTAMIDE (N = 199) PLACEBO (N = 233) Age, Mean (SD) 67.9 (9.1) 68.9 (8.1) Gender, Male/Female % 57.3% / 42.7% 56.7% / 43.3% Race, White/Other % 98.5% / 1.5% 95.7% / 4.3% Years since ET Onset, Mean (Median) 29.8 (26.0) 31.1 (27.0) ET symptoms worsened ove
Slide 13: Study 1 - Primary and all key secondary efficacy endpoints met
13 Study 1 - Primary and all key secondary efficacy endpoints met -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=199) PLACEBO (n=233) LS means for the mADL11 were estimated using a mixed model for repeated measures with treatment group, visit (categorical), treatment-by-visit interaction, randomization stra
Slide 14: Study 1 - Rapid and consistent response over weeks
14 Study 1 - Rapid and consistent response over 12 weeks
Slide 15: Study 1 efficacy – Robust response across subgroups
15 Study 1 efficacy – Robust response across subgroups
Slide 16: Essential3 Study 2 – Randomized Withdrawal design
16 Essential3 Study 2 – Randomized Withdrawal design All efficacy analyses use the modified intent-to-treat (mITT) population defined as all randomized responders who received at least one dose of study drug during the randomized withdrawal phase and had at least one post-RW baseline efficacy assess
Slide 17: Study 2 – RW baseline demographics – stable-responders
17 Study 2 – RW baseline demographics – stable-responders BLINDED LEAD-IN ULIXACALTAMIDE ULIXACALTAMIDE STABLE RESPONDERS Age, Mean (SD) 67.9 ( 7.9) 67.3 (8.4) Gender, Male/Female % 51.8% / 48.2% 55.0% / 45.0% Race, White/Other % 96.3% / 3.7% 95.0% / 5.0% Years since ET Onset, Mean (Median) 28.7 (25
Slide 18: Study 2 efficacy - Primary and first secondary endpoint met
18 Study 2 efficacy - Primary and first secondary endpoint met 55% 33% p=0.037 ULIXACALTAMIDE (n=40) PLACEBO (n=40) OR=2.7 (1.06-6.92) For primary endpoint, odds ratio, 95% confidence interval, and p-value were obtained from a logistic regression model including treatment group as the main effect an
Slide 19: Hypothesis 3 – Day 56 Parallel-group combined efficacy analysis
19 Hypothesis 3– Day 56 Parallel-group combined efficacy analysis Studies 1 & 2 Ulixacaltamide: Study 1 Placebo Ulixacaltamide n=390 Placebo n= 233 Studies 1+2 Study 1 Hypothesis 3 Studies 1+2 Ulixa / Study 1 Placebo How does the combined group of patients receiving ulixacaltamide in both studies (P
Slide 20: Hypothesis 3 – Day 56 combined efficacy results
20 -4.3 -1.7 p < 0.0001 ULIXACALTAMIDE (n=390) PLACEBO (n=233) Primary Endpoint mADL11 CFB to Day 56 Hypothesis 3– Day 56 Parallel-group combined efficacy analysis
Slide 21: Hypothesis 4 – Day 56 Parallel-group combined efficacy analysis
21 Study 1 Placebo: Study 2 ulixacaltamide Ulixacaltamide n=191 Placebo n= 233 Hypothesis 4 Study 2 Ulixa / Study 1 PBO How do patients receiving ulixacaltamide in the RW study compare to placebo patients from the PD study after 56 days of intervention? Study 2 Study 1 Hypothesis 4– Day 56 Parallel-
Slide 22: Hypothesis 4 – Day 56 combined efficacy results
22 -4.2 -1.7 p < 0.0001 ULIXACALTAMIDE (n=191) PLACEBO (n=233) Primary Endpoint mADL11 CFB to Day 56 Hypothesis 4– Day 56 Parallel-group combined efficacy analysis
Slide 23: Safety across studies remains consistent
23 • No change in overall safety profile and no new signals identified • Most common TEAEs (≥10%) in participants treated with ulixacaltamide were constipation, dizziness, euphoric mood, brain fog, headache, paraesthesia and insomnia. • Discontinuations were primarily due to AEs, with most common du
Slide 24: Essential3 Program: Study 1 and Study 2 disposition
24 Essential3 Program: Study 1 and Study 2 disposition Study 1 Enrolled/ITT: All randomized participants Study 2 Enrolled: All randomized participants Safety: All participants who received at least one dose of study drug Study 1 mITT: All randomized participants who received at least one dose and ha
Slide 25: Safety population – Overview of AEs
25 Safety population – Overview of AEs OVERVIEW OF ADVERSE EVENTS STUDY 1 STUDY 2 ULIXACALTAMIDE (N = 233) PLACEBO (N = 234) ULIXACALTAMIDE (N = 231) Participants with any TEAE 221 (94.9%) 177 (75.6%) 209 (90.5%) Participants with: Mild TEAEs 98 (42.0%) 89 (38.0%) 87 (37.7%) Moderate TEAEs 109 (46.8
Slide 26: Safety population - Most common TEAEs
26 Safety population - Most common TEAEs TREATMENT EMERGENT ADVERSE EVENTS ≥10% OF PATIENTS STUDY 1 STUDY 2 Preferred Term ULIXACALTAMIDE (N = 233) PLACEBO (N = 234) ULIXACALTAMIDE (N = 231) Constipation 57 (24.5%) 16 (6.84%) 68 (29.4%) Dizziness 56 (24.0%) 27 (11.5%) 59 (25.5%) Euphoric mood 30 (12
Slide 27: One step closer to delivering life-altering treatments to ET patients
27 One step closer to delivering life-altering treatments to ET patients First positive Phase 3 program for a drug in Essential Tremor Praxis has submitted a pre-NDA meeting request to the FDA and, upon agreement with the agency, expect to file an NDA in early 2026 Will share additional data in upco
Slide 28: Slide 28