Slide 1: Ulixacaltamide (PRAX-944) Essential1 Essential Tremor Topline Results
ULIXACALTAMIDE (PRAX-944) ESSENTIAL1 ESSENTIAL TREMOR TOPLINE RESULTS March 2023
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: Essential1 Design
3 ESSENTIAL1 DESIGN Essential1 Phase 2b Study Evaluating the Efficacy and Safety of Ulixacaltamide for Essential Tremor ADL = activities of daily living. ClinicalTrials.gov NCT05021991 10 m g 5 m g 10 m g 5 m g 20 m g 40 m g 20 m g 40 m g 60 m g 80 m g Screening Days -28 to -1 Day: 15–21 22–28 29–35
Slide 4: Topline Analysis: Essential1 Endpoints Measure Function and Quality of Life
4 Topline Analysis: Essential1 Endpoints Measure Function and Quality of Life Improvements that Matter Most to Patients ADL = activities of daily living; AE = adverse event; CUL = combined upper limb; PS = performance subscale; TETRAS = TRG Essential Tremor Rating Assessment Scale; UL = upper limb.
Slide 5: Essential1 Enrolled Adults with Moderate to Severe Essential Tremor
5 MODERATE TO SEVERE FUNCTIONAL IMPAIRMENT DETERMINED USING TETRAS AND CGI-S CLINICAL DIAGNOSIS OF ET OF ≥3 YEARS Essential1 Enrolled Adults with Moderate to Severe Essential Tremor NO PRIOR SURGICAL INTERVENTION OR FOCUSED ULTRASOUND FOR TREATMENT OF ET COULD CONTINUE PROPRANOLOL AT A STABLE DOSE
Slide 6: Essential1 Patient Disposition
6 Discontinued (n = 13) AE (9); Withdrew consent (2); Lack of Efficacy (2) Essential1 Patient Disposition RANDOMIZED & TREATED (n = 132) ulixacaltamide (n = 78) Placebo (n = 38) Discontinued (n = 4) AE (1); Lack of efficacy (1); Other (2) mITT ANALYSIS (n = 116) mITT ANALYSIS: Defined as all patient
Slide 7: Essential1 Demographics and Baseline Characteristics (mITT)
7 Essential1 Demographics and Baseline Characteristics (mITT) ULIXACALTAMIDE (n = 78) PLACEBO (n = 38) AGE, mean (min, max) 70.4 (32, 86) 67.7 (29, 88) GENDER (Male / Female, %) 59% / 41 % 58% / 42% FAMILY HISTORY OF ET 59 (76%) 23 (61%) PROPRANOLOL USE 27 (35%) 9 (24%) mADL SCORE, mean (min, max) 2
Slide 8: Ulixacaltamide was Generally Well-tolerated
8 Ulixacaltamide was Generally Well-tolerated *3 SAEs in 2 subjects, all deemed unrelated to treatment (exacerbation of COPD in 1 patient; esophageal obstruction & gastric adenocarcinoma in 1 patient) ULIXACALTAMIDE (n=91) PLACEBO (n=41) ANY TEAE 70 (76.9%) 21 (51.2%) TEAEs > 5% DIZZINESS 13 (14.3%)
Slide 9: Discontinuations – mITT Population
9 Discontinuations – mITT Population ULIXACALTAMIDE (n=78) PLACEBO (n=38) DISCONTINUATION 13 (17%) 4 (11%) DISCONTINUATION DUE TO AEs 9 (12%) (1) Hallucination (1) Restless Legs (1) Anxiety (2) Dizziness (1) Feeling Abnormal (1) Confusion (1) Constipation (1) Mental Impairment 1 (3%) (1) Adenocarcin
Slide 10: Primary Population: Efficacy Measures
10 PRIMARY POPULATION: EFFICACY MEASURES
Slide 11: Essential1 Efficacy Measures
11 Essential1 Efficacy Measures ADL = activities of daily living; AE = adverse event; CUL = combined upper limb; PS = performance subscale; TETRAS = TRG Essential Tremor Rating Assessment Scale; UL = upper limb. • Change from baseline to Day 56 on the TETRAS modified Activities of Daily Living (mADL
Slide 12: Modified ADLs: A Modified Measure of TETRAS Activities of Daily Living
12 Modified ADLs: A Modified Measure of TETRAS Activities of Daily Living (ADLs) 1. Speaking 2. Feeding with a spoon 3. Drinking from a glass 4. Hygiene 5. Dressing 6. Pouring 7. Carrying food trays, plates or similar items 8. Using keys 9. Writing 10. Working 11. Overall disability with most affect
Slide 13: mADL and ADL Improvement Over Placebo at Day 56
13 mADL and ADL Improvement Over Placebo at Day 56 -3.01 -1.44 -3.6 -1.07 IM PR OV EM EN T No dose related difference in efficacy between 60 mg and 100 mg groups p=0.126 ULIXACALTAMIDE (n=78) ULIXACALTAMIDE (n=78) PLACEBO (n=38) PLACEBO (n=38) MMRM, Adjusted by baseline value, propranolol use and fa
Slide 14: More Patients Taking Ulixacaltamide Showed Improvements in ADL Scores
14 -30 -25 -20 -15 -10 -5 0 5 10 15 More Patients Taking Ulixacaltamide Showed Improvements in ADL Scores Compared to Patients on Placebo Observed ADL Change - mITTObserved mADL Change - mITT -30 -25 -20 -15 -10 -5 0 5 10 15 CH AN GE IN M AD L SC OR E AT D AY 5 6 More daily functions restored ULIXAC
Slide 15: Consistent Effect Relative to Placebo Across ADL Scored Items
15 Ulixacaltamide Demonstrated Consistent Effect Relative to Placebo Across ADL Scored Items Difference from Placebo in ADL Items - mITTDifference from Placebo in mADL Items - mITT IM PR OV EM EN T TETRAS-PS items
Slide 16: Patients and Investigators Reported Higher Overall Improvement with Ulixacaltamide
16 Patients and Investigators Reported Higher Overall Improvement in Status with Ulixacaltamide vs Placebo CGI-S= clinical global impression improvement scale; PGI-C = patient global impression of change , all p-values are nominal *RANK ANALYSIS **RANK ANCOVA NO CHANGE IMPROVED NO CHANGE IMPROVED WO
Slide 17: Post-hoc Analysis
17 POST-HOC ANALYSIS
Slide 18: TETRAS-ADL Items Feedback
18 TETRAS-ADL ITEMS FEEDBACK* “In contrast, the Activities of Daily Living (TETRAS-ADL) subscale allows for assessment of meaningful change in patients’ ability to function on activities of daily living (ADL) and has the potential to be an acceptable clinical endpoint. Therefore, we recommend that y
Slide 19: Improvement Over Placebo in the mADL Excluding PS at Day 56
19 Ulixacaltamide Demonstrated Improvement Over Placebo in the mADL Excluding PS at Day 56 MMRM, Adjusted by baseline value, propranolol use and familial history of ET, all p values are nominal -3.01 -1.44 -2.69 -0.88 -3.6 -1.07 IM PR OV EM EN T p=0.126 ULIXACALTAMIDE (n=78) ULIXACALTAMIDE (n=78) PL
Slide 20: Consistent Effect Observed Across Both Dosing Regimens
20 Consistent Effect Observed Across Both Dosing Regimens MMRM, Adjusted by baseline value, propranolol use and familial history of ET mADL Excluding PS Placebo-adjusted Change - mITT -0.07 -1.44 -1.74 -1.82 -2.5 -2 -1.5 -1 -0.5 0 0.5 Day 14 Day 28 Day 42 Day 56 IM PR OV EM EN T Regimen 2 Regimen 1
Slide 21: Prognostic Factors Exploration
21 PROGNOSTIC FACTORS EXPLORATION
Slide 22: Intention Tremor
22 Intention tremor is a type of tremor characterized by rhythmic and high amplitude oscillations during directed and purposeful motor movements, which worsen as the target is approached. It is often associated with dysfunction of the cerebellum, a brain structure responsible for motor coordination,
Slide 23: mADL and mADL Excluding PS Improvement Excluding Intention Tremor Patients
23 mADL and mADL Excluding PS Improvement Over Placebo at Day 56 mITT Excluding ET Patients with Intention Tremor MMRM, Adjusted by baseline value, propranolol use and familial history of ET, all p values are nominal -3.12 -0.41 -2.86 -0.01 IM PR OV EM EN T p=0.032 ULIXACALTAMIDE (n=60) ULIXACALTAMI
Slide 24: Consistent Effect Across Both Dosing Regimens Excluding Intention Tremor
24 Consistent Effect Observed Across Both Dosing Regimens mITT Excluding ET Patients with Intention Tremor MMRM, Adjusted by baseline value, propranolol use and familial history of ET mADL Excluding PS Placebo-adjusted Change -1.03 -2.71 -2.85 -4 -3.5 -3 -2.5 -2 -1.5 -1 -0.5 0 Day 14 Day 28 Day 42 D
Slide 25: Post-hoc Analysis of Observed mADL Scored Items
25 Post-hoc Analysis of Observed mADL Scored Items mITT Excluding ET Patients with Intention Tremor Difference from Placebo in mADL Excluding PS Items Pouring Disability Carry trays, plates or similar Dressing Writing Using Keys Hygiene Drinking from a glass Feeding with a spoon Working Speaking IM
Slide 26: Breaking Ground with Essential1 - Path Forward Towards Registration
26 • Prepare and conduct an End of Phase 2 meeting with the FDA within ~100 days • Preliminary elements of Phase 3 program planned to start in 2H23: • Parallel design with 60 mg and placebo treatment arms • Primary endpoint of mADL excluding PS • 6-week treatment duration NEXT STEPS • Clinically mea
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Slide 28: Post-hoc Responder Analysis Using MCID Distribution Method
28 0.5 SD threshold 1.0 SD threshold Post-hoc Responder Analysis Using MCID Distribution Method mITT Population *Chi-sq comparisons in response rates between Ulixacaltamide and Placebo One standard deviation equals 4.92 for mADL and 4.07 for mADL excluding PS Mouelhi et al. Health and Quality of Lif
Slide 29: Endpoints Analysis for mITT Population
29 LS MEANS DIFF LOWER 95% CI UPPER 95% CI ADL scale mADL -1.576 -3.604 0.451 ADL -2.529 -4.753 -0.305 Status PGI-C -0.462 -0.871 -0.053 CGI-S -0.313 -0.562 -0.063 Performance Scale PS -0.144 -2.053 1.765 CUL -0.046 -1.535 1.444 UL -0.412 -1.321 0.497 Endpoints Analysis for mITT Population mADL = mo
Slide 30: Post-hoc Analysis Excluding ET Patients with Intention Tremor at Baseline
30 Post-hoc Analysis Excluding ET Patients with Intention Tremor at Baseline MMRM, all p values are nominal Presence of intention tremor was assessed by Investigator during screening Observed ADL ChangeObserved mADL Change CH AN GE IN M AD L SC OR E AT D AY 5 6 ULIXACALTAMIDE PLACEBO CH AN GE IN A D
Slide 31: Post-hoc Analysis Excluding ET Patients with Intention Tremor at Baseline
31 Post-hoc Analysis Excluding ET Patients with Intention Tremor at Baseline Difference from Placebo in ADL Items - mITTDifference from Placebo in mADL Items - mITT IM PR OV EM EN T TETRAS-PS items