Financial Data and Key Metrics Changes - In Q1 2025, the company achieved total net product revenue of $612 million, representing a 70% growth year-over-year [7][40] - Elevitus sales reached $375 million, marking a 180% increase compared to the same quarter last year [7][40] - The PMO franchise generated $237 million in revenue, up 5% year-over-year [7][40] - Total revenues for Q1 were $745 million, an increase of $331 million or 80% year-over-year [41] Business Line Data and Key Metrics Changes - The PMO franchise revenue grew by 5%, while Elevitus saw a significant increase of 180% [7][40] - The company reported a GAAP operating loss of $448 million and a non-GAAP operating loss of $332 million for Q1 2025 [43][44] - R&D expenses on a GAAP basis were $773 million, a year-over-year increase of $573 million, primarily due to the Arrowhead collaboration [42] Market Data and Key Metrics Changes - The company is revising its net product revenue guidance for 2025 to a range of $2.3 billion to $2.6 billion, reflecting a 37% increase from 2024 at the midpoint [8][44] - The company anticipates Q2 revenue could be as much as 20% lower than Q1 due to various factors including a safety event and administrative delays [19][20] Company Strategy and Development Direction - The company is focused on addressing administrative complexities and enhancing site capacity to improve patient access to Elevitus [22][23] - A comprehensive promotional campaign for Elevitus has been launched to increase awareness and understanding among healthcare providers and patients [23] - The company plans to expand its LGMD portfolio and continue advancing its siRNA platform, with significant data expected to be shared later in the year [30][34] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenging environment in biotech but emphasized the company's strong position due to approved therapies and revenue generation [6][7] - The tragic safety event involving a patient infused with Elevitus has led to a more cautious outlook, but management remains confident in the therapy's overall safety profile [8][9] - Management expects a recovery in demand starting in the summer, with a significant uptick anticipated in the second half of the year [64] Other Important Information - The company has a strong cash position with $647 million in cash and equivalents, and an additional $600 million available through a revolving credit facility [39][44] - The FDA has confirmed receipt of a labeling supplement that includes the recent patient death, with a target review date set for no later than Q4 2025 [78] Q&A Session Summary Question: What has been the biggest driver of potential downside pressure leading to revised guidance? - Management indicated that it is a mix of all three factors: cycle times, administrative processes, and the safety event, with cycle times being the most mechanically impactful [48][49] Question: How does the company plan to direct patients to sites with more capacity? - Management stated that the issue is more about focus rather than the number of sites, emphasizing the need for increased education and outreach to secondary sites [58][59] Question: What percentage of sales does Elevitus represent in the new guidance? - Management confirmed that the revision in total net product revenue was exclusively related to Elevitus, which is the primary driver of the guidance change [66] Question: What are the expectations regarding the potential label update for Elevitus? - Management indicated that a labeling supplement was submitted in April, and the FDA has set a target completion date for the review by Q4 2025 [78] Question: How is the company interacting with the FDA regarding the limb girdle programs? - Management reported that interactions with the FDA have remained positive, with confirmation of the accelerated approval pathway for the limb girdle programs [84]

Financial Data and Key Metrics Changes - For Q4 2024, the company reported total revenues of $658.4 million, an increase of $261.6 million compared to $396.8 million in Q4 2023 [64] - Net product revenue for Q4 2024 was $638 million, growing 75% year-over-year, and full-year net product revenue was $1.8 billion, representing a 56% increase [14][64] - The company achieved a GAAP net income of $159 million for Q4 2024, compared to $45.7 million in Q4 2023, and a non-GAAP net income of $206 million, up from $86.6 million [67] Business Line Data and Key Metrics Changes - ELEVIDYS sales for Q4 2024 were $384.2 million, a 112% increase from the previous quarter, and total sales since approval exceeded $1 billion [15][28] - The PMO franchise generated $254 million in Q4 2024, growing approximately 9% compared to Q4 2023, with individual revenues of $137.6 million for EXONDYS 51, $40.2 million for VYONDYS 53, and $76.2 million for AMONDYS 45 [31][32] Market Data and Key Metrics Changes - The company noted that ELEVIDYS has only treated about 5% of the on-label addressable patient population, indicating significant growth potential ahead [33][114] - The PMO franchise continues to perform well, growing organically without price increases, reflecting an increase in patients served in the Duchenne community [30] Company Strategy and Development Direction - The company aims to build on the success of Project Moonshot, focusing on expanding its gene therapy pipeline and achieving multiple potential blockbuster siRNA launches by the end of the decade [9][13] - The strategic collaboration with Arrowhead is expected to diversify the company's future, adding a broad platform of siRNA programs across various therapeutic areas [12][13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving 2025 net product revenue guidance of $2.9 billion to $3.1 billion, representing approximately 70% growth over 2024 [42] - The company anticipates continued growth quarter-over-quarter throughout 2025, driven by the strong performance of ELEVIDYS and the PMO franchise [81] Other Important Information - The company plans to transition to suspension manufacturing to improve cost of goods sold (COGS) and has several significant milestones expected in 2025 [20][21] - The company has approximately $1.5 billion in cash and investments as of December 31, 2024, and secured a $600 million revolving credit facility [72][73] Q&A Session Summary Question: What is the cadence of patient onboarding in Q1? - Management reiterated confidence in guidance for 2025, expecting growth quarter-over-quarter as the launch ramps up [80] Question: What is the prevalence of limb-girdle muscular dystrophy type 2E? - Management indicated that type 2E is an ultra-rare disease, with a 50-50 split between ambulatory and non-ambulatory patients [85][87] Question: Will the upcoming data for FSHD and DM1 be conclusive? - Management emphasized the importance of early data as proof of biology, with expectations for safety and efficacy signals [108][110] Question: What is the status of ELEVIDYS and PMO reinvestment? - Management noted early days for drawing conclusions on reinvestment but indicated some instances of reimbursement for both therapies [116] Question: What is the timeframe for the $500 million share repurchase program? - The program has an 18-month timeframe, with plans to be opportunistic in deploying capital as cash reserves are built back up [124]