Core Viewpoint - Xenon Pharmaceuticals Inc. is set to report its first quarter 2025 financial results and provide a business update on May 12, 2025, after the U.S. financial markets close [1]. Group 1: Financial Reporting - The financial results and business update will be announced after the close of U.S. financial markets on May 12, 2025 [1]. - A conference call and webcast will take place on the same day at 4:30 pm Eastern Time [2]. Group 2: Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to developing therapeutics for conditions such as epilepsy and depression [3]. - The company is advancing an ion channel product portfolio, with Azetukalner being the most advanced potassium channel modulator in late-stage clinical development [3].

Core Insights - AbbVie reported strong first-quarter results for 2025, exceeding expectations and indicating a solid start to the year, with a focus on pipeline advancements and strategic investments [2][3] Financial Performance - First-quarter diluted EPS was $0.72 on a GAAP basis, a decrease of 6.5%, while adjusted diluted EPS was $2.46, an increase of 6.5% [3][19] - Net revenues for the first quarter reached $13.343 billion, an increase of 8.4% on a reported basis and 9.8% on an operational basis [3][4] - The immunology portfolio generated global net revenues of $6.264 billion, up 16.6% on a reported basis and 18.1% operationally [3][4] - Skyrizi net revenues were $3.425 billion, reflecting a 70.5% increase on a reported basis, while Rinvoq net revenues were $1.718 billion, up 57.2% [4][19] - Humira net revenues decreased by 50.6% to $1.121 billion [4][19] - Neuroscience portfolio revenues were $2.282 billion, an increase of 16.1% [4][19] - Oncology portfolio revenues reached $1.633 billion, up 5.8% [4][19] - Aesthetics portfolio revenues were $1.102 billion, a decrease of 11.7% [4][19] Guidance and Outlook - AbbVie raised its 2025 adjusted diluted EPS guidance from $11.99 - $12.19 to $12.09 - $12.29, accounting for an unfavorable impact of $0.13 per share related to acquired IPR&D and milestones expense [3][9] Recent Developments - The European Commission granted marketing authorization to Rinvoq for treating giant cell arteritis in adults, marking the eighth approved indication for the drug in the EU [7] - AbbVie announced a collaboration with Xilio Therapeutics to develop novel immunotherapies for cancer [7] - A Biologics License Application was submitted to the FDA for trenibotulinumtoxinE for treating moderate to severe glabellar lines, which could be the first neurotoxin of its kind available [7][8]

Core Viewpoint - Jazz Pharmaceuticals and Harmony Biosciences are significant players in the neuroscience sector, particularly in sleep disorders, with Jazz having a more diversified portfolio and stronger financial performance compared to Harmony [1][2][22]. Group 1: Company Overview - Jazz Pharmaceuticals markets several neuroscience drugs, including the oral sleep disorder drug Xywav and the CBD drug Epidiolex, while Harmony Biosciences has one marketed drug, Wakix, for narcolepsy [1][10]. - Jazz derives over two-thirds of its total revenues from its neuroscience franchise, while Harmony generates all its revenue from Wakix sales [3][11]. Group 2: Financial Performance - Jazz's total revenues for 2024 rose 6% year over year to $4.1 billion, with $2.9 billion from neuroscience and $1.1 billion from oncology drugs [9]. - Harmony's 2024 sales increased 23% year over year to $715 million, with expectations for 2025 sales between $820 million and $860 million, indicating an 18% year-over-year growth [11]. Group 3: Product Pipeline and Development - Jazz's Xywav sales rose 16% year over year to $1.5 billion in 2024, and Epidiolex sales increased 15% year over year to $972 million [4][5]. - Harmony is developing next-generation formulations of Wakix and has acquired Zynerba Pharmaceuticals to explore the cannabis space [12][13]. Group 4: Market Position and Valuation - Jazz has a diversified product lineup, including five oncology drugs, which accounted for 29% of its 2024 product revenues [6]. - Harmony's shares trade at a higher price/earnings (P/E) ratio of 8.63 compared to Jazz's 5.07, indicating that Harmony is more expensive [19]. Group 5: Investment Outlook - Jazz is viewed as a better investment option due to its diversified portfolio, rising EPS estimates, and robust cash reserves, while Harmony's reliance on a single product presents a concentration risk [22][23]. - Jazz holds a Zacks Rank 2 (Buy), while Harmony has a Zacks Rank 3 (Hold), reinforcing Jazz's favorable investment standing [24].

Core Insights - Xenon Pharmaceuticals Inc. announced multiple presentations at the American Academy of Neurology Annual Meeting (AAN 2025) focusing on azetukalner for focal onset seizures (FOS) [1][5] - The company highlighted long-term data from the ongoing X-TOLE open-label extension study, showing sustained monthly reduction in seizure frequency and a consistent safety profile for azetukalner [2][5] Company Overview - Xenon Pharmaceuticals is a neuroscience-focused biopharmaceutical company dedicated to developing therapeutics for unmet medical needs, particularly in epilepsy and depression [4] - Azetukalner is a novel, highly potent Kv7 potassium channel opener, currently in late-stage clinical development for multiple indications [4] Upcoming Presentations - Three posters will be presented at AAN 2025, including: - Long-term safety and efficacy data from the X-TOLE study [2][5] - Exploratory analysis of efficacy across FOS seizure subtypes [5][6] - Patient survey findings on mental health and comorbidity burdens associated with FOS [5][6] Presentation Details - Poster 9-001 will present long-term safety and efficacy data, with Dr. Jacqueline A. French as the presenter [2][6] - Poster 9-012 will focus on the efficacy of azetukalner in FOS subtypes, presented by Dr. Constanza Luzon Rosenblut [6] - Poster 9-003 will address the mental health burden of epilepsy, presented by Dr. Joanne M. Wagner [6]

Core Viewpoint - AbbVie is expanding its presence in the obesity treatment market by in-licensing GUB014295, a long-acting amylin analog, from Gubra, with a total potential deal value of $2.225 billion [1][2][3] Industry Overview - The obesity market is projected to reach $100 billion by 2030, with current dominance by GLP-1 drugs from Eli Lilly and Novo Nordisk [3] - Major pharmaceutical companies, including Merck, Pfizer, Amgen, and AstraZeneca, are actively pursuing opportunities in the obesity space through in-house development or licensing deals [3] AbbVie's Product Performance - AbbVie has successfully launched Skyrizi and Rinvoq, generating combined sales of $17.7 billion in 2024, particularly excelling in the inflammatory bowel disease market [5][6] - The company anticipates combined sales of Skyrizi and Rinvoq to exceed $31 billion by 2027, driven by market growth and new indications [7] Pipeline and Acquisitions - AbbVie has a robust pipeline with several early/mid-stage candidates and expects multiple regulatory submissions and approvals in the next 12 months [8][9] - The company has been active in acquisitions, signing over 20 early-stage deals in 2024 to enhance its pipeline in immunology, oncology, and neuroscience [11][12] Sales Trends and Challenges - AbbVie is experiencing declining sales from Humira due to biosimilar competition, with a sharper decline expected in 2025 [13] - The aesthetics portfolio, including Juvederm fillers, has also seen a decline, with a 14.6% drop in sales in 2024 [14][15] Stock Performance and Valuation - AbbVie stock has outperformed the industry with a 14.8% increase over the past year [16][18] - The stock trades at a price/earnings ratio of 16.52, slightly below the industry average of 17.80, but higher than many large drugmakers [19][20] Earnings Estimates - The Zacks Consensus Estimate for AbbVie's 2025 earnings has increased from $12.24 to $12.29 per share, indicating positive sentiment [22]

Financial Data and Key Metrics Changes - In Q4 2024, total revenue was $259.6 million, up 12% year-over-year, while full year revenue reached $957.8 million, up 32% from the prior year [59] - DAYBUE sales in Q4 were $96.7 million, an 11% increase year-over-year, and full year sales were $348.4 million, a 97% increase compared to $177.2 million in 2023 [60] - NUPLAZID sales in Q4 were $162.9 million, a 13% increase year-over-year, with full year sales of $609.4 million, up 11% from $549.2 million in the prior year [61] Business Line Data and Key Metrics Changes - DAYBUE's gross-to-net was 18.8% for the year, with a sequential growth of 5% in volume and 1% in net price in Q4 [60] - NUPLAZID's gross-to-net for Q4 was 23.2%, with full year gross-to-net at 26.1%, indicating a balanced growth from both volume and net price [61] Market Data and Key Metrics Changes - The company anticipates U.S. net sales for DAYBUE in 2025 to be between $380 million and $405 million, with expected volume growth of 9% to 16% year-over-year [63] - NUPLAZID's 2025 net sales are projected to be in the range of $650 million to $690 million, with growth expected to be split evenly between volume and net price [68] Company Strategy and Development Direction - The corporate strategy focuses on expanding neuroscience and neuro rare disease franchises, with plans to explore additional investments in rare diseases [11] - The company aims to achieve over $1 billion in annual net sales by 2025, joining a select group of biotech companies [73] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential of both DAYBUE and NUPLAZID, highlighting the importance of expanding the prescriber base and patient engagement [20][25] - The company plans to initiate a Phase 2 study for ACP-204 in Lewy body dementia psychosis and expects to see top-line results for ACP-101 in Prader-Willi syndrome in the first half of 2026 [74] Other Important Information - The company has submitted a marketing application for trofinetide in the EU, anticipating approval in Q1 2026 [42] - The cash balance at the end of 2024 was $756 million, significantly up from $438.9 million at the end of 2023, driven by operational cash flows and the sale of a priority review voucher [63] Q&A Session Summary Question: How should we think about the evolution of growth-to-net for DAYBUE and NUPLAZID? - Management indicated that DAYBUE's growth-to-net is expected to remain in the low 20% range, influenced by Medicare Part D redesign [80] - For NUPLAZID, a 300 basis points price benefit is expected in growth-to-net, with gradual increases anticipated over the next several years [81] Question: Is there a target number of patients for DAYBUE by year-end? - Management stated that the patient base is stable, with around 70% of the Rett population yet to try DAYBUE, indicating significant growth potential [91] Question: Can you discuss the increase in diagnosed U.S. Rett patients? - The increase in diagnosed patients from 5,000 to 5,800 is attributed to improved diagnostics and awareness driven by the launch of DAYBUE [95] Question: What are the secondary endpoints for ACP-101 in Prader-Willi syndrome? - Management expressed confidence that multiple mechanisms of action will be needed to treat patients in areas of unmet medical need like Prader-Willi syndrome [118]

Financial Data and Key Metrics Changes - Total net product revenue for 2024 was $386 million, reflecting high double-digit year-over-year growth for Avelity and Sunosi [7][12] - Total product revenues for Q4 2024 were $118.8 million, representing a year-over-year growth of 6688% [12][13] - Net loss for Q4 2024 was $74.9 million, or $1.54 per share, compared to a net loss of $98.7 million, or $2.08 per share for Q4 2023 [17][18] - The company ended 2024 with $315.4 million in cash and cash equivalents, down from $386.2 million at the end of 2023 [18] Business Line Data and Key Metrics Changes - Avelity net product sales were $291.4 million for the full year 2024, representing a year-over-year growth of 89124% [13][14] - Sunosi net product revenues were $94.3 million for the full year 2024, reflecting a year-over-year growth of 1626% [14][15] - Avelity prescriptions reached approximately 158,000 in Q4 2024, showing a 10% quarter-over-quarter growth and 87% growth compared to Q4 2023 [20][21] - Sunosi total prescriptions were approximately 49,000 in Q4 2024, representing 4% sequential growth and 16% growth versus Q4 2023 [22] Market Data and Key Metrics Changes - Avelity access is 78% of all lives across channels and 63% of lives in commercial [21] - Payer coverage for Sunosi in Q4 was stable at 83% of lives covered across channels [22] Company Strategy and Development Direction - The company aims to commercialize seven products or indications through 2027, focusing on CNS conditions [6][9] - The company plans to submit NDAs for AXS-five and AXS-twelve in the second half of 2025 [9][10] - The launch of Simbravo is anticipated to enhance the company's portfolio in the migraine treatment market [8][24] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about continued growth in 2025, supported by sales force expansion and improved market access dynamics [7][19] - The company expects to achieve cash flow positivity based on the current operating plan [18] - Management highlighted the importance of their digital-centric commercialization platform in driving growth [19] Other Important Information - The company completed five pivotal trials and initiated three Phase III trials in 2024, positioning for several important milestones in 2025 [9][11] - The company is actively engaged with payers to expand access for its products in 2025 [21] Q&A Session Summary Question: DTC promotional activities for Avelity and Simbravo - Management plans to launch a broad-based media outreach plan for Avelity in the coming months, considering seasonality in media spending [27][28] Question: Sales force expansion for Avelity - Approximately 40 additional representatives were added to the Avelity sales team, creating potential synergies with the prescriber base for Simbravo [32][34] Question: NDA submission for AXS-five - The submission is a top priority, with updates expected in the second half of the year [35][36] Question: Alzheimer's disease agitation filing - The filing approach has not been confirmed yet, but updates will be provided soon [41][43] Question: Seasonal cadence of scripts and revenues for Avelity - Q1 is expected to be a growth quarter, albeit slower than the previous year, with sales force expansion anticipated to drive growth [52][54] Question: M&A and business development strategy - The company is open to opportunities that complement its pipeline, focusing on both commercial and development-stage assets [58][59] Question: Impact of Medicare Part D restructure on Avelity revenues - No significant impact is expected from the Medicare Part D restructure on Avelity revenues [103][104] Question: Launch trajectory for Simbravo - The company is optimistic about Simbravo's impact on the acute migraine market, with a targeted approach to headache specialists [72][73] Question: Market opportunity for AXS-twelve in narcolepsy - The company sees a compelling market opportunity for AXS-twelve, particularly among patients dissatisfied with existing treatments [100][101]