Summary of Arrowhead Pharmaceuticals (ARWR) Conference Call Company Overview - **Company**: Arrowhead Pharmaceuticals (ARWR) - **Event**: BofA Annual Healthcare Conference - **Date**: May 14, 2025 Key Points Strategic Developments - The recent deal with Sarepta has significantly changed Arrowhead's strategic outlook, allowing the company to focus on core assets and reducing dependence on capital markets for a period of time [2][4][5] - The core assets from the Sarepta deal include two muscle assets, ARO DM1 and ARO DUX4, which Arrowhead is excited about due to Sarepta's expertise in drug approval [3][4] Pipeline and Research Focus - Arrowhead has a strong presence in cardiometabolic diseases, with ongoing projects targeting APOC3 and obesity [6][7] - The company is expanding its capabilities to address various tissue types, including adipocytes, and plans to introduce new metabolic targets in the clinic next year [8][9][10] FCS and SHTG Opportunities - The company views the FCS (Familial Chylomicronemia Syndrome) market as a gateway to the larger SHTG (Severe Hypertriglyceridemia) opportunity, with an estimated 3-4 million patients in the U.S. having triglyceride levels above 500 [12][14] - Arrowhead's Phase 3 data showed an 80% reduction in triglycerides from baseline, which is significantly higher than competitors [13][19] Competitive Landscape - Arrowhead believes it has a competitive edge over Ionis in the FCS market due to its superior triglyceride reduction capabilities and less frequent dosing [20][19] - The company is preparing for potential payer restrictions based on patient profiles but expects to address a broad patient population [23][24] Clinical Trials and Timelines - Arrowhead is currently enrolling patients for multiple Phase 3 studies, with expectations to launch in the SHTG market by 2027 [33][35] - The company has sufficient cash to sustain operations until 2028, allowing for multiple product launches around that time [35] Obesity Research - Arrowhead is exploring the ALK7 and Inhibin E pathways for obesity treatment, with promising animal data indicating high-quality weight loss without caloric restriction [42][43] - The company is considering combination therapies with existing GLP-1 drugs to enhance weight loss outcomes [51][52] Neuromuscular Programs - Arrowhead is advancing its neuromuscular programs, particularly ARO DM1 and ARO DUX4, with data disclosures expected this year [59][61] - The company anticipates triggering $300 million in milestone payments based on dosing in the DM1 study [62] Safety and Efficacy Considerations - Arrowhead emphasizes the importance of safety in drug development, aiming to use lower doses compared to competitors while maintaining efficacy [63][64] - The potential for subcutaneous administration of their drugs could be a significant advancement in the field [65][66] Additional Insights - Arrowhead is optimistic about the educational aspect of the market, believing that both it and Ionis can benefit from increased awareness of triglyceride management [18] - The company is open to exploring various avenues for funding future trials, including business development and partnerships [38] This summary encapsulates the key discussions and insights from the Arrowhead Pharmaceuticals conference call, highlighting the company's strategic direction, pipeline developments, and competitive positioning in the biotech landscape.

Financial Data and Key Metrics Changes - The net loss for Q1 2025 was $173.1 million, or $1.39 per share, compared to a net loss of $132.9 million, or $1.24 per share, in Q1 2024 [45] - Revenue for Q1 2025 was $2.5 million, down from $3.6 million in Q1 2024, primarily due to changes in collaboration agreements [46] - Total operating expenses increased to $163.9 million in Q1 2025 from $140.1 million in Q1 2024, driven by higher candidate costs and salaries [46][47] - Cash and investments totaled $552.9 million at the end of Q1 2025, with a pro forma cash balance of $1.4 billion including upcoming payments from Sarepta [47][48] Business Line Data and Key Metrics Changes - The company closed a significant collaboration agreement with Sarepta Therapeutics, expecting a total of $1.375 billion in cash payments, including an upfront payment of $500 million [5][7] - The first commercial launch of Plazasiran is anticipated to drive substantial growth, with potential annual sales of $2 billion to $3 billion in the severe hypertriglyceridemia market [10][21] - The obesity pipeline includes two early-stage programs, ARO INHBE and ARO ALK7, which are expected to provide clarity on their roles in obesity treatment [11][12] Market Data and Key Metrics Changes - The FDA accepted the NDA for Plazasiran for the treatment of familial chylomicronemia syndrome (FCS), with a PDUFA action date set for November 18, 2025 [21][26] - The company is actively working on global regulatory submissions for Plazasiran and anticipates launching in the U.S. and potentially the EU [49][80] Company Strategy and Development Direction - The company aims to build a growing cardiometabolic pipeline, focusing on obesity and CNS programs, while also exploring non-core assets for potential partnerships [15][17] - The collaboration with Sarepta is seen as a critical step to balance the business model and reduce R&D expenses as Sarepta assumes clinical development responsibilities [8][9] - The company plans to expand its cardiometabolic presence with new candidates targeting APOC3 and PCSK9 [18][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential driven by internal development activities, particularly in Plazasiran, obesity treatments, and CNS pipeline [8][14] - The company is well-funded into 2028, allowing for multiple commercial launches and continued development of its pipeline [48] - Management highlighted the importance of educating physicians and patients about new treatment options in previously untreatable diseases [88] Other Important Information - The company is on track to complete enrollment for several Phase III studies by the end of 2025, which would enable study completion in 2026 [29][49] - The company anticipates initial data readouts from various programs, including obesity and CNS candidates, later in 2025 [49] Q&A Session Summary Question: Can you discuss the obesity programs ARO INHBE and ARO ALK7? - Management indicated that both programs are being studied as monotherapy and in combination with existing therapies, with no specific bogey set for data [54][55] Question: What is the competitive positioning of Plazasiran relative to other treatments? - Management highlighted Plazasiran's significant triglyceride reduction and its potential to achieve guideline-directed risk thresholds for patients with FCS as key differentiators [84][86] Question: What are the plans for commercialization in Europe? - The company is planning for commercialization in European markets alongside a commercial partner, with more details to be provided in the future [78]