Praxis Precision Medicines Provides Corporate Update and Reports Second Quarter 2025 Financial Results RADIANT study with vormatrigine in focal onset seizure (FOS) patients over eight weeks demonstrated 56.3% median reduction in seizure frequency from baseline, with 22% at 100% seizure reduction in last 28 days Initiated two registrational studies for Developmental and Epileptic Encephalopathies (DEEs) programs: EMERALD for broad DEEs with relutrigine and EMBRAVE3 for SCN2A Gain-of-Function (GoF) with elsun ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission File Number: 001-39620 PRAXIS PRECISION MEDICINES, INC. (Exact Name of Registrant as Specified in its Charter) Delaware 47-5195942 (State or other ...

Core Insights - Praxis Precision Medicines reported positive results from the RADIANT study, showing a 56.3% median reduction in seizure frequency over eight weeks in focal onset seizure patients, with 22% achieving 100% seizure reduction in the last 28 days [1][2][3] - The company has initiated two registrational studies for Developmental and Epileptic Encephalopathies (DEEs): EMERALD for broad DEEs with relutrigine and EMBRAVE3 for SCN2A Gain-of-Function with elsunersen [1][2] - Relutrigine received U.S. FDA Breakthrough Therapy Designation for treating seizures associated with SCN2A and SCN8A DEEs, facilitating expedited development [1][2] - As of June 30, 2025, Praxis had approximately $447 million in cash and investments, providing a financial runway into 2028 [1][5] Clinical Development - The RADIANT study demonstrated a rapid and sustained response, with around 60% of patients achieving a 50% response rate [3] - Enrollment for the POWER1 pivotal study for vormatrigine is progressing well, with plans to initiate POWER2 and POWER3 studies soon [2][3] - The EMERALD study for relutrigine is expected to enroll up to 160 patients, with completion anticipated in 2026 [6] - The EMBRAVE3 study for elsunersen has been initiated, targeting SCN2A patients aged 2 to 18 years [6] Financial Performance - For Q2 2025, Praxis reported a net loss of $71.1 million, compared to a net loss of $32.7 million in Q2 2024 [10][21] - Research and development expenses increased to $63.0 million in Q2 2025 from $27.3 million in Q2 2024, primarily due to investments in the Cerebrum™ platform [8][21] - General and administrative expenses rose to $13.1 million in Q2 2025 from $10.6 million in Q2 2024 [9][21] Future Outlook - Praxis plans to present additional data at the 36th International Epilepsy Congress on August 31, 2025, and at the American Epilepsy Society Annual Meeting in December 2025 [3] - The company is on track to nominate development candidates for its early-stage ASO therapeutic initiatives by the end of 2025 [6]

Vormatrigine Efficacy and Development - RADIANT study showed a 56.3% overall median seizure reduction with vormatrigine[21] - A significant proportion of patients achieved ≥50% seizure reduction, independent of baseline seizure burden[26] - Vormatrigine is being developed as a potential stand-alone agent, with POWER3 study expected to initiate in 1H 2026[40, 42] - POWER2 study is staged to initiate this quarter and complete enrollment in 2H 2026, with a sample size of approximately 400 patients[37] Safety and Tolerability - In the RADIANT study, 59% of patients experienced ≥1 treatment-emergent adverse event (TEAE) with vormatrigine 30 mg[33] - 4.9% of patients experienced severe adverse events (AEs) and serious AEs (SAEs) with vormatrigine 30 mg[33] - 1.6% of patients experienced a related SAE with vormatrigine 30 mg[33] Pipeline and Catalysts - The company has assets in late stage development, with clinical readouts expected in the next 4 quarters[7] - Topline results for the RADIANT Phase 2 study are expected by mid-2025[8] - Finalization of the POWER1 Phase 2/3 study is expected in Q4 2025[8] - Candidate declaration for PRAX-100 (SCN2A LoF) is expected by mid-2025, and for PRAX-080 (PCDH19) and PRAX-090 (SYNGAP1) by year-end 2025[8] Financial Position - The company has a cash runway into 2028[7]

Core Insights - Praxis Precision Medicines announced topline results from the Phase 2 RADIANT study, showing that dosing with vormatrigine over 8 weeks led to a 56.3% median reduction in seizure frequency [1] - Approximately 22% of patients achieved a 100% reduction in seizure frequency during the last 28 days of treatment [1] - Over 54% of patients experienced a 50% response in the first week, indicating a rapid and sustained response [1] - Vormatrigine demonstrated a favorable safety profile and was generally well tolerated [1] Company Overview - Praxis Precision Medicines is a clinical-stage biopharmaceutical company focused on developing therapies for central nervous system disorders characterized by neuronal excitation-inhibition imbalance [7] - The company is applying genetic insights to discover and develop therapies for both rare and prevalent neurological disorders through its proprietary platforms [7] - Praxis has established a diversified CNS portfolio, including multiple programs across epilepsy and movement disorders, with four clinical-stage product candidates [7] Product Details - Vormatrigine is a next-generation, functionally selective small molecule targeting hyperexcitable sodium channels in the brain, developed as a once-daily oral treatment for adult focal onset seizures and generalized epilepsy [6] - Preclinical data suggests that vormatrigine has the potential to be best-in-class for focal epilepsy, demonstrating superior selectivity for disease-state NaV channel hyperexcitability [6] - Initial results from the RADIANT study indicate robust seizure reduction and a generally safe and well-tolerated profile for vormatrigine [6] Future Developments - Praxis plans to complete the pivotal 12-week POWER1 study in Q4 2025 and expects to initiate the POWER2 study shortly based on the results from RADIANT [2] - Additional data from the RADIANT study will be presented at the 36th International Epilepsy Congress on August 31, 2025, in Lisbon, Portugal [4] - A late-breaker abstract for the full study results will be submitted for presentation at the American Epilepsy Society Annual Meeting in December 2025 in Atlanta, Georgia [4]

Core Insights - Praxis Precision Medicines, Inc. is set to report topline results from the RADIANT trial of vormatrigine and its financial results for Q2 2025 on August 4, 2025, before market opening [1] - A live webcast will be hosted on the same day at 8:30am ET, accessible via a registration link and available for replay for 90 days [2] Company Overview - Praxis Precision Medicines is a clinical-stage biopharmaceutical company focused on developing therapies for CNS disorders linked to neuronal excitation-inhibition imbalance, utilizing genetic insights [3] - The company employs proprietary platforms, Cerebrum™ for small molecules and Solidus™ for antisense oligonucleotides, to target shared biological mechanisms in the brain [3] - Praxis has a diversified CNS portfolio with multiple programs addressing epilepsy and movement disorders, featuring four clinical-stage product candidates [3]

Core Insights - The U.S. FDA has granted Breakthrough Therapy Designation (BTD) for relutrigine, a sodium channel functional state modulator, aimed at treating pediatric patients with SCN2A and SCN8A developmental and epileptic encephalopathies (DEEs) [1][2] - The EMBOLD cohort 2 pivotal trial is expected to deliver topline results in the first half of 2026, with a New Drug Application (NDA) filing to follow [1][3] - Praxis has initiated the EMERALD study to evaluate relutrigine in a broader DEE patient population [1][3] Clinical Trial Results - The EMBOLD cohort 1 study included a severely affected DEE population, with patients averaging three failed treatments prior to enrollment [2] - Results from the open-label extension of the study showed approximately 90% reduction in seizures and an average of 67 days without seizures compared to 3 days in the baseline period [2][4] - During the double-blind period, a placebo-adjusted monthly motor seizure reduction of 46% was observed, with over 30% of patients achieving seizure freedom while on relutrigine [2][4] Drug Mechanism and Designation - Relutrigine is a first-in-class small molecule that preferentially inhibits persistent sodium current, a key driver of seizure symptoms in severe DEEs [4] - The drug has received Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation from the FDA for SCN2A-DEE and SCN8A-DEE, in addition to the BTD [4][5] Company Overview - Praxis Precision Medicines is focused on developing therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance, utilizing genetic insights [6] - The company has a diversified CNS portfolio, including multiple programs across epilepsy and movement disorders, with four clinical-stage product candidates [6]

Summary of Praxis Precision Medicines Conference Call Company Overview - **Company**: Praxis Precision Medicines (PRAX) - **Event**: Jefferies Global Healthcare Conference 2025 - **Date**: June 04, 2025 Key Points on Clinical Development Sodium Channel Modulators - Praxis is developing sodium channel modulators, specifically vermatrogene and rilutrogen, targeting epilepsy treatment [2][4] - Vermatrogene is focused on adult patients with focal onset seizures and generalized epilepsies, with two ongoing studies [4][5] - Rilutrogen is aimed at pediatric patients with SCN2A and SCN8A mutations, which are difficult to treat [37] Clinical Trials and Expectations - The first study, Radiance, is expected to report results mid-year, focusing on pharmacology and seizure reduction [5][8] - A significant cohort of patients is involved, with a target seizure reduction of 40-60% [6][7] - The Power One study will follow, with results anticipated by the end of the year [7][8] - A registrational package for vermatrogene is expected to be completed within the next 12-18 months [8] Patient Population and Inclusion Criteria - High screen failure rates in trials are viewed positively, indicating rigorous patient selection [6][31] - Inclusion of patients on background sodium channel blockers is justified by preclinical data showing no negative impact on efficacy [20][22] Market Potential - There are approximately 3 million adults in the U.S. with epilepsy, many of whom are undertreated [11] - Both vermatrogene and rilutrogen have significant market opportunities, with potential revenues reaching hundreds of millions to billions [45] Rilutrogen Development - Rilutrogen has shown over 40% seizure reduction in a 16-week study, with additional benefits in communication and behavior [37][38] - The company is adding registrational cohorts to expedite the process for patients with severe conditions [40] - A new study, EMERALD, is being initiated to treat seizures in a broader patient population [42] Future Catalysts - Upcoming milestones include results from the Radiance and Power One studies, as well as the nomination of ASO PRX100 for autism spectrum disorder [54] - The company is also working on other programs, including Syngap and essential tremor treatments, with potential NDA submissions in the future [56] Additional Insights - The company emphasizes the importance of understanding patient needs and drug interactions in developing effective treatments [10][12] - There is a focus on multimodal therapies, similar to approaches seen in spinal muscular atrophy (SMA) treatments [50] - The enrollment process for trials is robust, with a significant percentage of patients coming from a dedicated initiative to understand epilepsy better [32][35] This summary encapsulates the critical aspects of Praxis Precision Medicines' conference call, highlighting their ongoing clinical developments, market potential, and future catalysts.

Financial Data and Key Metrics Changes - The company is focused on executing across its entire portfolio with four programs in late-stage development expected to reach pre-commercial stages within the next twelve to eighteen months [4][5] - The upcoming catalyst for vormatrogene, a sodium channel modulator for common epilepsies, includes a phase two open-label study with data expected by midyear [5][6] Business Line Data and Key Metrics Changes - The company has multiple studies planned for its key assets, including vormatrogene and lexicaltimide, with significant data readouts anticipated in the coming months [5][7][8] - Lexicaltimide's studies are continuing despite an interim review board's recommendation to stop due to futility, with results expected in Q3 [8][9] Market Data and Key Metrics Changes - The focal epilepsy space is described as competitive, prompting the company to stagger the enrollment of its registrational studies to avoid internal competition for patients [6][7] - The company is also expanding its focus on ralutrogene, which targets developmental epilepsies, with a broader study planned to enroll patients based on seizure burden rather than genetic mutation [10][12] Company Strategy and Development Direction - The company aims to derisk its assets through comprehensive data collection and analysis before proceeding with regulatory filings [33][34] - There is a strategic emphasis on balancing the need for rapid drug delivery to patients with the necessity of thorough clinical characterization to ensure market acceptance [27][28] Management's Comments on Operating Environment and Future Outlook - Management acknowledges the challenges in the epilepsy treatment landscape but emphasizes the importance of their unique approaches and methodologies in clinical trials [20][21] - The company is committed to addressing the significant unmet needs in the epilepsy market, particularly for patients with severe conditions [34][35] Other Important Information - The company is initiating several broader studies and expects to provide updates on these initiatives throughout the year [15][16] - There is a focus on leveraging existing data to inform future studies and improve patient outcomes [10][12] Q&A Session Summary Question: How does the company manage to enroll quickly while maintaining data quality compared to competitors? - The company utilizes a prescreening initiative that accounts for about 30% of patient throughput, significantly speeding up recruitment [21][22] - Management emphasizes a micromanagement approach to identify and address enrollment impediments daily [23][24] Question: How does the company balance optimizing programs versus getting drugs to market quickly? - The company focuses on achieving proof of concept and derisking assets before applying more capital, ensuring a balance between patient benefit and shareholder return [33][34] Question: How does the company view the potential overlap between its various drug candidates? - Management believes that while there may be overlaps, each drug serves distinct patient needs, and the company will continue to develop both small molecules and ASOs as appropriate [40][41]

Company Overview - Praxis Precision Medicines, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance [3] - The company utilizes genetic insights to create therapies for both rare and prevalent neurological disorders through its proprietary platforms, Cerebrum™ and Solidus™ [3] - Praxis has a diversified CNS portfolio that includes multiple programs across epilepsy and movement disorders, with four clinical-stage product candidates [3] Upcoming Events - The company will participate in three investor conferences, including a fireside chat at the H.C. Wainwright 3rd Annual BioConnect Investor Conference on May 20 at 9:30 am ET [4] - Praxis management will also attend the Mizuho Neuro & Ophthalmology Summit in New York City on May 21 [4] - A corporate overview will be presented at the Jefferies Global Healthcare Conference on June 4 at 8:10 am ET [4] Investor Engagement - The company will be available for one-on-one meetings during all events, encouraging interested investors to contact their representatives [1] - Webcasts of the events will be accessible for 90 days through the "Events & Presentations" page on the company's website [2]