Q4 & FY 2025 Financial Results & Business Update February 24, 2026 Copyright © 2026 Harmony Biosciences. All rights reserved. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding our full year 2025 net product revenue, expectations ...

Core Message - NeuroPace aims to transform the lives of individuals suffering from epilepsy by reducing or eliminating debilitating seizures, which is central to the company's mission and decision-making process [3]. Company Overview - NeuroPace is represented by CEO Joel Becker, who emphasizes the company's commitment to patients and clinicians involved in epilepsy care [2][3]. - The company is led by a strong team dedicated to its mission and operational goals [4].

Group 1 - The article does not provide any relevant content regarding company or industry insights [1]

Azetukalner Efficacy and Safety - Azetukalner demonstrated a 90.9% median percent change (MPC) reduction in monthly focal onset seizure (FOS) frequency after 48 months in the open-label extension (OLE) [92] - A subset of patients receiving 1-2 anti-seizure medications (ASMs) at double-blind period (DBP) baseline experienced a 100% monthly reduction in FOS frequency [92] - 38% of patients treated with azetukalner for at least 48 months achieved seizure freedom for one year or longer [92] - Azetukalner's safety and tolerability profile in the OLE remained consistent with the DBP [92, 73] - In the Phase 2b X-TOLE study, azetukalner showed statistically significant and dose-dependent seizure reduction, with up to a 52.8% median percent change from baseline [34] Commercial Opportunity and Market Insights - Xenon Pharmaceuticals has $555.3 million in cash, cash equivalents, and marketable securities as of September 30, 2025, with anticipated cash runway into 2027 [18] - An estimated 2.6 million adults in EU4 + UK, 3.0 million in Japan, and 0.8 million in the U.S have diagnosed epilepsy [95] - Focal onset seizures (FOS) represent the largest segment of the epilepsy population [95] - Up to 50% of epilepsy patients may require additional treatment options, presenting a significant commercial opportunity [102, 97] Clinical and Patient Burden - Depression is a significant burden for patients with FOS, highlighting the need for therapeutics that do not exacerbate mood disorders [92, 79] - Titration of anti-seizure medications (ASMs) poses a significant burden for both patients and healthcare professionals (HCPs), underscoring the need for simplified or no-titration ASMs [92, 87]

Company Overview - Harmony Biosciences Holdings, Inc. is focused on developing and commercializing innovative therapies for patients with rare neurological diseases, particularly those with unmet medical needs [10] - The company was established in 2017 and is headquartered in Plymouth Meeting, Pennsylvania [10] Product Development - The company is conducting a Phase 3 ARGUS trial for EPX-100 (clemizole hydrochloride) aimed at treating Dravet syndrome, showing clinically meaningful reductions in seizure activity [1][3] - EPX-100 is also being evaluated in the Phase 3 LIGHTHOUSE trial for Lennox-Gastaut syndrome, both trials being global, multicenter, randomized, double-blind, placebo-controlled studies [3] Clinical Trial Results - Initial open-label extension data from the ARGUS trial indicated a median reduction of approximately 50% in countable motor seizure frequency per 28 days, with 50% of participants achieving at least a 50% reduction [8] - The treatment was generally well-tolerated, with the most common adverse events being seizures, pyrexia, and upper respiratory tract infections, while gastrointestinal adverse events were minimal [8] Future Outlook - The company anticipates advancing its epilepsy franchise and is progressing towards topline data readout from the ARGUS trial expected in 2026 [3]

Core Insights - Praxis Precision Medicines presented significant clinical updates at the American Epilepsy Society Annual Meeting, highlighting the potential of relutrigine and vormatrigine in treating epilepsy [2][3] Group 1: Relutrigine for Developmental and Epileptic Encephalopathies (DEEs) - The EMBOLD study demonstrated a 53% placebo-adjusted reduction in seizures (p < 0.0002) and a 66% increase in motor seizure-free days (p = 0.034) [8] - Relutrigine was well-tolerated, showing rapid and significant seizure reduction over time, with broad functional improvements in behavior, alertness, communication, and overall status [4][8] - The company plans to meet with the FDA to discuss the next steps for the New Drug Application (NDA) [4] Group 2: Vormatrigine for Focal Onset Seizures (FOS) and Generalized Epilepsy - The RADIANT study indicated a 54% median reduction in seizures for patients taking vormatrigine over 8 weeks, with 58% achieving at least a 50% reduction in week 1, increasing to 61% by week 8 [9] - FOS patients reached a 100% median weekly seizure reduction after 8 weeks, maintained through 16 weeks, with over 11% experiencing seizure freedom for the entire 8-week period [9] - Vormatrigine is positioned as a best-in-class therapy with fast-acting efficacy, sustained reduction, and favorable safety profiles [5] Group 3: Company Commitment and Future Studies - The company is committed to accelerating treatment options for patients and advancing the broader DEE study, EMERALD, along with ASO programs and FOS studies toward registration [3] - Praxis has completed recruitment for the POWER1 pivotal study in FOS and is on track to complete the POWER2 study in the second half of 2026, with the POWER3 study set to begin in the first half of 2026 [10]

Core Insights - Xenon Pharmaceuticals Inc. is set to present multiple research findings at the American Epilepsy Society Annual Meeting (AES 2025) from December 5-9, 2025, focusing on their lead molecule azetukalner for epilepsy treatment [1][5][9] - The presentations will include long-term data from the X-TOLE open-label extension study, which supports the potential for extended seizure freedom with azetukalner [1][5][6] - Additional findings will address the impact of depression on epilepsy patients and new pre-clinical data from the NaV1.1 program targeting Dravet syndrome [1][5][9] Presentation Details - Seven posters will be presented, including: - Long-term safety and efficacy data of azetukalner in adults with focal epilepsy, with a ≥48-month interim analysis from the ongoing 7-year X-TOLE study [6] - Characterization of long-term seizure freedom in the ongoing open-label extension of X-TOLE [6] - Studies on depression symptoms among epilepsy patients and their impact on treatment outcomes [6][5] - A symposium titled "Exploring Depression and Anxiety in Epilepsy" will be held in partnership with the Epilepsy Foundation of America [5] Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to drug discovery and development of therapeutics for epilepsy and other neurological disorders [9] - The company's lead molecule, azetukalner, is a selective KV7 potassium channel opener currently in Phase 3 clinical trials for epilepsy, major depressive disorder, and bipolar depression [9] - Xenon is also advancing early-stage programs targeting potassium and sodium channels for potential pain treatment [9]

Core Viewpoint - Avenue Therapeutics has announced the acquisition of its subsidiary Baergic Bio by Axsome Therapeutics, which includes the global rights to BAER-101, a novel therapy for epilepsy, potentially enhancing treatment options in a field with high unmet needs [1][2][7]. Company Overview - Avenue Therapeutics, Inc. is a specialty pharmaceutical company focused on developing therapies for neurologic diseases, headquartered in Miami, FL, and founded by Fortress Biotech, Inc. [5]. Transaction Details - The acquisition involves Axsome obtaining worldwide commercial, development, and manufacturing rights to BAER-101, with Baergic shareholders eligible for up to approximately $82 million in potential payments, including a $0.3 million upfront payment and milestone payments based on development and sales achievements [1][7]. - Avenue expects to receive approximately 74% of all future payments and royalties under the agreement [7]. Product Information - BAER-101, now referred to as AXS-17 by Axsome, has shown a promising safety and tolerability profile in clinical studies involving over 700 patients and is being evaluated for its anti-convulsant effects in epilepsy [3][2].

Core Insights - JAZZ Pharmaceuticals has signed an agreement with Saniona to acquire worldwide rights to the investigational epilepsy drug SAN2355 [1][8] - SAN2355 is designed to selectively activate Kv7.2/Kv7.3 potassium channels, aiming to avoid safety issues associated with previous therapies like GSK's Potiga [2][3] - The deal allows JAZZ to enhance its neuroscience pipeline, complementing its existing epilepsy treatment, Epidiolex, which is expected to achieve blockbuster status [7][9] Financial Terms of the Deal - JAZZ will pay Saniona an upfront cash payment of $42.5 million, with potential milestone payments up to $192.5 million for development and regulatory achievements, and up to $800 million for commercial milestones [4] - Saniona will also receive royalties on future sales of SAN2355 [4] Market Context - JAZZ's stock has seen a decline of 3% year-to-date, contrasting with a 3% growth in the industry [5] - The acquisition of SAN2355 positions JAZZ for future innovation in the epilepsy market, potentially serving as a successor to Epidiolex once it loses exclusivity [9]

Summary of Praxis Precision Medicine Conference Call Company and Industry Overview - **Company**: Praxis Precision Medicine - **Industry**: Epilepsy treatment and pharmaceutical development Key Points and Arguments 1. **Market Size and Opportunity**: The epilepsy market in the U.S. is estimated to be around 3 to 3.5 million patients, with many existing drugs failing to adequately address the needs of these patients, indicating significant opportunities for new treatments [11][12][19] 2. **Efficacy of Vormetrigine**: The drug has shown promising results in treating focal onset seizures, with a median seizure reduction of 56.3% and 50% of patients experiencing a reduction in seizures [62][64] 3. **Patient Demographics**: 81% of patients in the study were on sodium channel blockers, which is typical for this patient population. Many patients were on multiple medications, indicating a complex treatment landscape [43][46][55] 4. **Recruitment Success**: The company successfully dosed 61 patients in the trial, demonstrating that patient recruitment for focal epilepsy studies is feasible, contrary to common beliefs [31][32] 5. **Background Therapy Impact**: The drug's efficacy was observed even in patients already on sodium channel blockers, suggesting that it can provide additional benefits in a heavily medicated population [20][62] 6. **Discontinuation Rates**: 23% of patients discontinued the study, which is consistent with industry norms. The reasons for discontinuation were primarily patient choice rather than adverse events [78][90] 7. **Adverse Events (AEs)**: The treatment emerged with a 59% rate of treatment-emerging AEs, which is considered manageable and comparable to other drugs in the market [100][101] 8. **Future Studies**: The company plans to conduct further studies (POWER 1, 2, and 3) to explore the drug's efficacy as a monotherapy and its potential to replace existing treatments [104][116] Additional Important Insights 1. **Sodium Channel Modulation**: Modulating sodium channels is identified as a key mechanism for treating focal seizures, with the drug positioned to potentially replace existing therapies [16][50] 2. **Market Dynamics**: The market is not winner-takes-all; multiple drugs can coexist, and the company aims to capture a significant share by demonstrating the efficacy of its drug [108][110] 3. **Patient-Centric Approach**: The company emphasizes the importance of understanding patient needs and the limitations of current treatments, aiming to provide a better therapeutic option [59][92] 4. **Data Analysis Methodology**: The company uses a robust methodology for analyzing patient data, including handling discontinuations in a way that reflects true treatment efficacy [81][88] This summary encapsulates the key discussions and insights from the conference call, highlighting the company's strategic positioning within the epilepsy treatment landscape and the promising data surrounding its lead drug, vormetrigine.