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 Insights - Axsome Therapeutics (AXSM) has initiated a phase III study named FORWARD to evaluate AXS-14 (esreboxetine) for managing fibromyalgia, marking a significant step in its drug development process [1][8] - AXS-14 is an investigational oral drug aimed at increasing norepinephrine levels in the brain to alleviate chronic pain and related symptoms associated with fibromyalgia [1] Study Details - The FORWARD study is a phase III double-blind, placebo-controlled withdrawal trial involving patients with fibromyalgia, where participants who respond to treatment during a 12-week open-label period will be randomized to either continue AXS-14 at 8 mg once daily or switch to placebo for up to 12 weeks [2] - The primary endpoint of the study is to measure the time from randomization to the loss of therapeutic response [2][8] Market Performance - Over the past year, AXSM's shares have increased by 89.4%, significantly outperforming the industry average rise of 18.7% [3] Regulatory Background - Axsome submitted a new drug application (NDA) for AXS-14 for fibromyalgia in May 2025, which was delayed from an earlier timeline of the first quarter of 2024 [5] - In June 2025, the FDA issued a Refusal to File (RTF) letter regarding the NDA, citing inadequacies in one of the placebo-controlled studies, prompting Axsome to initiate the FORWARD study to address these concerns [6][8] Disease Context - Fibromyalgia is a chronic neurological pain disorder affecting approximately 17 million people in the United States, characterized by widespread pain, fatigue, sleep disturbances, and other symptoms [7]

Core Insights - Avadel Pharmaceuticals presented new data on LUMRYZ, a once-nightly sodium oxybate treatment for narcolepsy, at World Sleep 2025, highlighting its efficacy in improving symptoms for both new and returning patients [1][2][3] Group 1: Efficacy of LUMRYZ - The REFRESH study demonstrated that patients switching from twice-nightly oxybate to LUMRYZ experienced clinically meaningful improvements in excessive daytime sleepiness (EDS) and other narcolepsy symptoms [4] - 70% of switch participants and 90% of non-switch participants reported improvement on the Patient Global Impression of Change after 4 months of therapy [4] - The study also indicated a reduction in severity of narcolepsy symptoms from moderate to mild, with significant improvements in quality of life metrics such as fatigue, brain fog, and mood [4] Group 2: Presentation Highlights - A total of 17 abstracts were accepted for presentation at World Sleep 2025, including one oral presentation and 16 posters, focusing on the benefits of LUMRYZ [1][2] - Presentations reinforced the advantages of LUMRYZ in addressing hallmark symptoms of narcolepsy, including EDS and sleep-related hallucinations [3] Group 3: Regulatory and Market Position - LUMRYZ is the first and only once-at-bedtime treatment for cataplexy or EDS in patients aged seven years and older with narcolepsy, receiving FDA approval in May 2023 and October 2024 [8][10] - The FDA granted LUMRYZ seven years of Orphan Drug Exclusivity due to its clinical superiority over existing treatments, emphasizing its once-nightly dosing regimen [10]

LUMRYZ Opportunity and Strategy - LUMRYZ aims to transform the narcolepsy treatment market and Avadel into a high-growth biopharmaceutical company[5] - The company has a clear strategy for significant growth and value creation, building on a strong foundation[8] - Avadel has a focused strategy with clear priorities, including driving demand, securing reimbursement, and investing in lifecycle management[20, 21, 22] - LUMRYZ has significant potential for future peak revenue, potentially exceeding $1 billion, with a target market share of 50-60% and a potential patient base exceeding 10,000[27, 28] LUMRYZ Differentiation and Clinical Data - LUMRYZ is a new and highly differentiated treatment for narcolepsy, addressing an unmet need for a once-at-bedtime oxybate[6, 13] - 94% of patients who switched from first-generation oxybates prefer LUMRYZ dosing[13] - The FDA has determined LUMRYZ to be clinically superior to twice-nightly oxybates, granting it Orphan Drug Exclusivity (ODE)[13, 63] - Clinical data supports LUMRYZ's efficacy, with the REST-ON Phase III study achieving statistical significance (P<0.001) for all three co-primary endpoints[57] Launch and Market Dynamics - The oxybate narcolepsy market has plateaued at approximately $18 billion with approximately 16,000 patients[178] - Approximately 45% of oxybate-naive patients refuse first-generation oxybates when offered[186] - Market research indicates that LUMRYZ has the potential to expand the new-to-oxybate patient market by +35% to 113%[84] - The company's field team has reached approximately 1,100 sleep specialist offices, representing 66% of top-tier targets[250]

Core Insights - Avadel Pharmaceuticals is presenting new data on LUMRYZ, a treatment for narcolepsy, at the SLEEP 2025 conference, highlighting its efficacy and real-world impact on patients [1][2][3] Group 1: Efficacy and Clinical Data - Interim analysis of the REFRESH study shows significant improvement in excessive daytime sleepiness (EDS) for patients switching from twice-nightly oxybate to once-at-bedtime LUMRYZ [1][2] - Post-hoc analysis from the Phase 3 REST-ON trial indicates that LUMRYZ participants with severe sleepiness achieved median Epworth Sleepiness Scale (ESS) scores within the normal range by Week 13 [2][3] - Data from the REFRESH study indicates that 67 patients, including those new to oxybate and those switching from twice-nightly oxybate, experienced clinically significant reductions in sleepiness [3][4] Group 2: Safety and Tolerability - A post-hoc analysis from the RESTORE study involving 115 participants showed that only 4% discontinued LUMRYZ due to treatment-related adverse events, indicating long-term tolerability [3][4] - The safety profile of LUMRYZ aligns with known adverse events of oxybates, with no worsening of apnea-hypopnea index (AHI) observed in patients with mild sleep apnea [2][3] Group 3: Regulatory and Market Position - LUMRYZ received FDA approval as the first and only once-at-bedtime treatment for cataplexy or EDS in adults and pediatric patients with narcolepsy, supported by significant clinical trial results [6][7][8] - The FDA granted LUMRYZ 7 years of Orphan Drug Exclusivity due to its clinical superiority over existing treatments, emphasizing its once-nightly dosing regimen [8][9] Group 4: Conference Presentations - Avadel will present 14 abstracts, including four oral presentations, at SLEEP 2025, focusing on the benefits of LUMRYZ for narcolepsy patients [1][3] - Key presentations will cover topics such as the long-term safety of LUMRYZ, improvements in daytime sleepiness, and the impact on sleep-related eating disorder [4][5]