Summary of Alnylam Pharmaceuticals (ALNY) FY Conference Call - August 12, 2025 Company Overview - Alnylam Pharmaceuticals was founded in February 2002 and is recognized as a global leader in RNA interference technology, which has led to the development of a new class of medications [4][5] - The company has established a robust pipeline with six approved medications and aims to drive long-term growth through three pillars: leadership in transthyretin amyloidosis (ATTR), growth through innovation, and outstanding commercial performance [5][6] Core Points and Arguments Leadership in ATTR - The recent approval of Ambutra for ATTR cardiomyopathy is expected to set a new standard of care, addressing a significant unmet need in a rapidly growing patient segment [5][6] - Ambutra's clinical profile and the growing patient population present a strong franchise opportunity for Alnylam [5] Commercial Performance - Alnylam reported $492 million in revenues for the quarter, exceeding consensus estimates by 34% [8] - The launch of Ambutra has been successful, with half of the priority healthcare systems adding it to their formularies within five to six weeks of launch [12] - The company anticipates continued growth through increased diagnosis rates and treatment penetration among existing patients [15] Patient Demographics and Treatment Dynamics - Globally, there are approximately 300,000 patients affected by ATTR cardiomyopathy, with about 80% remaining undiagnosed [14] - In the U.S., around 150,000 patients are affected, with an estimated 10,000 new patients presenting annually [16] - There is a significant opportunity to treat patients who are stabilizer progressors, with about 45,000 patients globally on stabilizers, and 30-50% of them may continue to progress [19] Competitive Landscape - Alnylam positions Ambutra as the first RNAi silencer approved for both manifestations of ATTR, emphasizing its unique mechanism of action [21][22] - The company is focused on establishing Ambutra as a first-line treatment option, leveraging its robust clinical data package [24] - Future competition from gene editing technologies is acknowledged, but Alnylam is advancing its next-generation RNA silencer, Neuquesiran, which could provide significant benefits [28][29] International Expansion and Regulatory Considerations - Alnylam has received regulatory approvals in Europe, Brazil, and Japan, with international launches expected to ramp up in 2026 [30][31] - The company is monitoring the Most Favored Nation (MFN) policy but continues to move forward with its launch processes [31][33] Pipeline Developments - The Zalbeceran program targets hypertension, addressing a significant unmet need as up to 80% of patients on therapy do not meet blood pressure targets [35][36] - Alnylam is planning to start a cardiovascular outcomes trial for Zalbeceran later this year [41] - The company is also advancing its Melvisiran program targeting cerebral amyloid angiopathy (CAA), a condition with no approved therapies [44][45] Future Outlook - Alnylam is focused on internal growth and innovation, while remaining open to external opportunities that align with its strategic goals [54] Other Important Content - The company emphasizes the importance of adherence to treatment regimens, particularly in rapidly progressing conditions like ATTR and hypertension [27][36] - Alnylam's approach to treatment includes a focus on patient quality of life and functional capacity, which resonates with both physicians and patients [23]

Financial Data and Key Metrics Changes - The net income for the quarter ended March 31, 2025, was $370.4 million or $2.75 per share, compared to a net loss of $125.3 million or $1.02 per share for the same quarter in 2024 [48] - Revenue for the quarter was $542.7 million, with no revenue recorded in the same quarter of the previous year, primarily due to the license and collaboration agreement with Sarepta [48][49] - Total operating expenses increased to $161.5 million from $126.2 million in the prior year, driven by increased costs associated with the clinical pipeline [51] Business Line Data and Key Metrics Changes - The company is preparing to launch Flodasiran, targeting severe hypertriglyceridemia (SHTG) with a PDUFA date set for November 18, 2025 [10][28] - Phase three studies for Flodasiran showed triglyceride reductions of about 80% from baseline in genetically defined patients, with significant results in reducing triglyceride levels below critical thresholds [11][41] - The company is also advancing obesity candidates ARO INHBE and ARO ALK7, with initial data expected by the end of 2025 [15][44] Market Data and Key Metrics Changes - The company has engaged with payers representing a significant number of US covered lives, delivering content on the clinical value of Flodasiran [39] - Market research indicates strong interest in Flodasiran's ability to reduce triglycerides and the risk of acute pancreatitis, with 75% of patients achieving triglyceride levels below 880 mg/dL [41] Company Strategy and Development Direction - Arrowhead Pharmaceuticals is transitioning from a development stage to a commercial stage, with plans for multiple product launches over the next few years [7][8] - The company aims to leverage its RNAi technology platform to address various diseases, including CNS disorders and obesity, while maintaining a strong pipeline of clinical assets [18][21] - The recent collaboration with Sarepta Therapeutics significantly strengthened the company's balance sheet, providing $500 million upfront and additional milestone payments [22][23] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's financial strength and the potential for significant value creation despite current market challenges in the biotech sector [9][24] - The company anticipates that the upcoming launches and ongoing clinical trials will drive substantial value for shareholders [53] Other Important Information - The company has a strong cash position of $1.1 billion as of March 31, 2025, providing funding through 2028 [52] - Arrowhead is actively pursuing regulatory approvals in multiple jurisdictions, including the US, Europe, Canada, and Japan [28] Q&A Session Summary Question: What are the expectations for initial monotherapy and potential combo data for ARO INHBE and ARO ALK7? - The company is not providing specific guidance on expectations but is optimistic based on compelling animal data showing weight loss and retention of lean muscle mass [56][57] Question: How robust is the pancreatitis data for Flodasiran? - Management indicated that they have not had labeling negotiations with the FDA yet, and the focus remains on how low triglycerides can be reduced in patients [64][66] Question: What are the expectations for acute pancreatitis rates in the SHTG population? - The baseline for acute pancreatitis is expected to be around 2000 mg/dL, similar to the FCS population [72][74]