ulixacaltamide (PRAX-944) / Praxis Precision Medicines - LARVOL DELTA

Praxis Precision Medicines to Present on Late-Stage Programs across Epilepsy and Movement Disorders at the American Academy of Neurology 2025 Annual Meeting (GlobeNewswire) - "Praxis Precision Medicines, Inc...today announced that that it will present data from its four late-stage programs in epilepsy and movement disorders at the American Academy of Neurology (AAN) 2025 Annual Meeting taking place from April 5 to 9, 2025 in San Diego, California."

Clinical data • Essential Tremor

Praxis Precision Medicines Provides Update on Essential3 and Corporate Update (GlobeNewswire) - "Praxis Precision Medicines, Inc...today provided an update on the interim analysis for Study 1 of the Essential3 program of ulixacaltamide in essential tremor (ET), an update on other therapies in development and a financial update...The Independent Data Monitoring Committee (IDMC) overseeing the interim analysis of Study 1 of the Essential3 program has provided Praxis with the outcome of such analysis. Based on the predefined decision framework for Study 1, the IDMC has recommended that the study be stopped for futility, due to the results being unlikely to meet the primary efficacy endpoint under the parameters set by the statistical model...Given the advanced state of enrollment for both Study 1 and Study 2 in the Essential3 program, and in the context of the advice received by the IDMC, Praxis has decided to continue both studies to completion, with topline results expected in the third quarter of 2025."

DSMB • P2 data • P3 data • CNS Disorders • Essential Tremor

Characteristics of Adult Essential Tremor Patients Seeking Participation in a Decentralized US Clinical Trial: Pre-screener Findings from the Essential3 Program Evaluating Efficacy and Safety of Ulixacaltamide (AAN 2025) - "Findings from the largest ET survey to date show that patients seeking participation in a clinical trial report ET as a high-burden, inadequately managed disorder impacting several activities of daily living. Findings also suggest a degree of normalization of ET impact (likely necessitating ongoing patient and physician education) and emphasize the urgent need for innovation in developing effective, well-tolerated treatments."

Clinical • Essential Tremor • Movement Disorders

Essential3: An Innovative Multi-Study Phase 3 Program to Evaluate the Efficacy and Safety of Ulixacaltamide (MDS Congress 2024) - P2, P3 | "In addition to providing evidence of ulixacaltamide safety and efficacy, the Essential3 program is expected to set the foundation for future clinical trial design in ET and other neurologic disorders."

Clinical • P3 data • CNS Disorders • Essential Tremor

Assessing Clinically Meaningful Improvement Associated with Ulixacaltamide Treatment in Adults with Essential Tremor on Concomitant Propranolol: Findings from Essential1 (AAN 2024) - P2 | "Building on findings from Essential1 and focusing on measures determined to be most meaningful to patients, these results highlight the potential for ulixacaltamide to revolutionize the treatment of ET, with evidence of meaningful improvement both alone and in combination with chronic propranolol use."

Clinical • Essential Tremor • Movement Disorders

An Innovative Multi-study Phase 3 Program to Evaluate the Efficacy and Safety of Ulixacaltamide: The Future of Clinical Trial Design in Essential Tremor (AAN 2024) - P2, P3 | "In addition to providing evidence of ulixacaltamide safety and efficacy, the Essential3 program is expected to set the foundation for future clinical trial design in ET and other neurologic disorders."

Clinical • P3 data • CNS Disorders • Essential Tremor • Movement Disorders

A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=133 | Completed | Sponsor: Praxis Precision Medicines | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Feb 2024

Trial completion • Trial completion date • Essential Tremor • Movement Disorders

Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET) (clinicaltrials.gov) - P3 | N=620 | Recruiting | Sponsor: Praxis Precision Medicines | Not yet recruiting ➔ Recruiting

Enrollment open • Essential Tremor • Movement Disorders

A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Trial completion date: Sep 2023 ➔ Dec 2023

Trial completion date • Essential Tremor • Movement Disorders

Essential 3 - Decentralized, Phase 3 Study Evaluating the Safety and Efficacy of Ulixacaltamide in Essential Tremor (ET) (clinicaltrials.gov) - P3 | N=620 | Not yet recruiting | Sponsor: Praxis Precision Medicines

New P3 trial • Essential Tremor • Movement Disorders

Patient-Focused, Clinically Meaningful Endpoints as Evidence of Improved Outcomes and Durability of Effect Following Ulixacaltamide Treatment in Adults with Essential Tremor: Findings from Essential1 (MDS Congress 2023) - P2 | "This is the first time an MSD is defined in ET using a large patient dataset and a focus on measures determined to be most meaningful to patients. We highlight mADL11 as a reliable, patientfocused COA related to ulixacaltamide efficacy and durability, with important decision-making implications for ET therapies."

Clinical • Late-breaking abstract • CNS Disorders • Essential Tremor

Praxis Precision Medicines Announces Upcoming Ulixacaltamide Presentations & Events (GlobeNewswire) - "Ulixacaltamide essential tremor end-of-phase 2 meeting with FDA scheduled for June 2023....Praxis Precision Medicines...today announced the following upcoming ulixacaltamide presentations and events focused on Essential Tremor (ET)."

FDA event • P2 data • CNS Disorders • Essential Tremor

A Phase 2, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating Efficacy, Safety and Tolerability of PRAX-944 in Adults with Parkinson’s Disease and Motor Fluctuations (AAN 2023) - "Secondary endpoints will include change from baseline to Day 77 in the MDS-UPDRS Part III tremor sub-score (OFF state) and Part II score; and Patient Global Impression of Severity and Clinician Global Impression of Severity. Conclusions The PRAX-944-231 trial is expected to provide proof-of-concept for use of PRAX-944 in the treatment of PD."

Clinical • P2 data • CNS Disorders • Movement Disorders • Parkinson's Disease

Praxis Precision Medicines Announces Topline Results from the Essential1 Study of Ulixacaltamide for the Treatment of Essential Tremor and Continued Advancement of Program to Phase 3 (GlobeNewswire) - "'The impact of essential tremor transcends the action tremor that is the hallmark of the disease. Essential tremor can be debilitating, causing significant disruption of everyday activities. There is significant unmet need for an effective and tolerable precision medicine that can improve patient functioning, and to date there exists no medicine specifically developed for tremor,' said William G. Ondo, M.D..."

Media quote

Praxis Precision Medicines Provides Corporate Update and Reports Fourth Quarter and Full Year 2022 Financial Results (Yahoo News) - "The Company is also conducting a randomized, double-blind, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of once-daily treatment of up to 100 mg of ulixacaltamide as a non-dopaminergic treatment for the motor symptoms of Parkinson’s disease. The primary endpoint for the study is change from baseline in the International Parkinson and Movement Disorder Society Unified Parkinson’s Disease Rating Scale (UPDRS), Part III (motor examination) score in the OFF state. Topline results are expected in the fourth quarter of 2023."

P2 data • CNS Disorders • Parkinson's Disease

A Clinical Trial of 2 Doses of PRAX-944 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=131 | Active, not recruiting | Sponsor: Praxis Precision Medicines | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2022 ➔ Jul 2023 | Trial primary completion date: Sep 2022 ➔ Feb 2023

Enrollment closed • Trial completion date • Trial primary completion date • Essential Tremor • Movement Disorders

Praxis Precision Medicines Provides Corporate Update and Reports Third Quarter 2022 Financial Results (GlobeNewswire) - “Recent Business Highlights and Upcoming Milestones: The Company expects to initiate a randomized, double-blind, placebo-controlled Phase 2 trial to evaluate the efficacy, safety and tolerability of once-daily treatment of up to 100 mg of PRAX-944 as a non-dopaminergic treatment for the motor symptoms of Parkinson’s disease in the first quarter of 2023. Topline results are expected in the second half of 2023….Research and development expenses were $30.4 million for the three months ended September 30, 2022…The decrease in research and development expenses of $2.7 million was primarily attributable to $6.5 million in decreased clinical-related spend for the Company's Psychiatry franchise, partially offset by $5.2 million in increased expenses for the Company's Movement Disorders and Epilepsy franchises.”

Commercial • New P2 trial • P2 data • CNS Disorders • Parkinson's Disease

A Phase 2 Randomized, Double-blind, Placebo-controlled Trial of PRAX-944 for the Treatment of Essential Tremor (MDS Congress 2022) - P2 | "Expanding on preliminary findings, the Essential1 trial will further examine the safety, tolerability and efficacy of PRAX-944 in adults with ET, and will determine optimal doses and endpoints for evaluation in later phase studies. Importantly, the unique design seeks to address the sub-optimal benefit-risk profile of current therapies and associated unmet needs in ET."

Clinical • P2 data • CNS Disorders • Essential Tremor

A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor (MDS Congress 2022) - P2 | "Eligible participants were receiving no medications or a stable dose of 1 tremor medication excluding primidone. Our findings provide preliminary evidence that PRAX-944 can reduce tremor symptoms of ET at well-tolerated doses. Part B topline results are expected in 1H2022 following completion of the randomized withdrawal phase and will inform dose selection in later phase studies."

Clinical • P2 data • PK/PD data • CNS Disorders • Essential Tremor

Praxis Precision Medicines Provides Corporate Update and Reports First Quarter 2022 Financial Results (GlobeNewswire) - "Praxis Precision Medicines, Inc...today provided a corporate update, including a video highlighting recent business and pipeline progress, and reported financial results for the first quarter 2022....The FDA cleared the Investigational New Drug (IND) submission for a Phase 2 study of PRAX-944 for the treatment of Parkinson’s disease. Praxis intends to initiate a Phase 2, placebo-controlled trial to evaluate the safety, pharmacokinetics (PK) and efficacy of PRAX-944 as a non-dopaminergic treatment for the motor symptoms of Parkinson's disease in the second half of 2022."

IND • New P2 trial • CNS Disorders • Parkinson's Disease

A Clinical Trial of PRAX-944 in Participants With Essential Tremor (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Praxis Precision Medicines | Recruiting ➔ Completed

Trial completion • Essential Tremor • Movement Disorders

Translational Pharmacology?of PRAX-944, a Novel T-type Calcium Channel Blocker for the Treatment of Essential Tremor (AAN 2022) - "Administration of PRAX-944 in rats and humans produced strong and consistent effects on sigma-power, which may represent a robust and translatable biomarker of TTCC blockade. In rats, PRAX-944 reduced sigma-power at concentrations that reduced tremor without locomotor side-effects. In healthy participants, comparable sigma-power reductions indicate that TTCC blockade was achieved at well-tolerated doses that may hold therapeutic promise for tremor reduction in patients with ET."

CNS Disorders • Essential Tremor • Movement Disorders

PRAX-944-222: A Phase 2 Randomized, Double-blind, Placebo-controlled Trial of PRAX-944 for the Treatment of Essential Tremor (AAN 2022) - P2 | "Expanding on preliminary findings, the PRAX-944-222 trial will further examine the safety, tolerability and efficacy of PRAX-944 in adults with ET, and will determine optimal doses and endpoints for evaluation in later phase studies. Importantly, the unique trial design seeks to address the sub-optimal benefit-risk profile of current therapies and associated unmet needs in ET."

Clinical • P2 data • Essential Tremor • Movement Disorders

PRAX-944-221: A Phase 2 Clinical Trial Evaluating the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Adults with Essential Tremor (AAN 2022) - P2 | "Five (83%) participants included in efficacy analysis were taking concomitant propranolol during the intervention period. Findings from the PRAX-944-221 trial provide preliminary evidence that PRAX-944 can reduce tremor symptoms of ET at well-tolerated doses. Continuing investigations, including an expanded dose range up to 120 mg daily with a placebo arm (PRAX-944-221 Part B), as well as an 8-week, dose-range finding, placebo-controlled trial (PRAX-944-222, NCT05021991) will determine optimal doses of PRAX-944 for evaluation in later phase studies."

Clinical • P2 data • PK/PD data • Essential Tremor • Movement Disorders

A Clinical Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of PRAX-944 in Essential Tremor - Part B (ANZCTR) - P2 | N=12 | Recruiting | Sponsor: Praxis Precision Medicines

New P2 trial • Essential Tremor • Movement Disorders