GRB14

Achieved global net product revenues for AMVUTTRA and ONPATTRO for the first quarter of $310 million and $49 million , respectively, representing 36% growth compared to Q1 2024. Achieved global net product revenues for GIVLAARI and OXLUMO for the first quarter of $67 million and $42 million , respectively, representing 8% growth compared to Q1 2024. Strong progress making AMVUTTRA available for ATTR-CM in various global markets. Received U.S. FDA approval of the supplemental New Drug Application (sNDA) for AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Received approval from ANVISA ( Brazilian Health Regulatory Agency ) for ATTR-CM. Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of vutrisiran for the treatment of ATTR-CM. Marketing authorization applications based on data from the landmark HELIOS-B Phase 3 clinical trial are currently under review by several global health agencies including the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Presented new data from HELIOS-B at the American College of Cardiology Scientific Session 2025, further supporting vutrisiran’s compelling therapeutic profile, including: Echocardiographic data demonstrating that treatment with vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. HELIOS-B included the largest systematic echocardiographic study conducted to date in an ATTR pivotal trial. An exploratory subgroup analysis demonstrating that vutrisiran reduced all-cause mortality and recurrent cardiovascular events compared to placebo across a range of baseline heart failure severities in patients with ATTR-CM. These data were also published in the Journal of the American College of Cardiology . A separate analysis confirming that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. These data were also published in the Journal of the American College of Cardiology . Presented updates from the Company’s robust pipeline and organic platform at R&D Day. Disclosed two new clinical programs: ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Shared encouraging data from our expanding neuroscience franchise, including an update on the new ALN-HTT02 program, which has a highly differentiated exon-1-targeting approach to lower huntingtin (HTT) for Huntington’s disease. Presented new preclinical data on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue and for crossing the blood-brain barrier, supporting Alnylam’s aspiration to unlock every major tissue for RNAi therapeutics by 2030. Received U.S. FDA approval of the supplemental New Drug Application (sNDA) for AMVUTTRA for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Received approval from ANVISA ( Brazilian Health Regulatory Agency ) for ATTR-CM. Received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of vutrisiran for the treatment of ATTR-CM. Marketing authorization applications based on data from the landmark HELIOS-B Phase 3 clinical trial are currently under review by several global health agencies including the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Echocardiographic data demonstrating that treatment with vutrisiran led to significant improvements in diastolic function and attenuation of declines in left ventricular (LV) and right ventricular (RV) systolic function at Month 18, compared to placebo. HELIOS-B included the largest systematic echocardiographic study conducted to date in an ATTR pivotal trial. An exploratory subgroup analysis demonstrating that vutrisiran reduced all-cause mortality and recurrent cardiovascular events compared to placebo across a range of baseline heart failure severities in patients with ATTR-CM. These data were also published in the Journal of the American College of Cardiology . A separate analysis confirming that vutrisiran significantly maintained or improved functional capacity, and patient-reported health status and quality of life, compared to placebo over 30 months. These data were also published in the Journal of the American College of Cardiology . Disclosed two new clinical programs: ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Shared encouraging data from our expanding neuroscience franchise, including an update on the new ALN-HTT02 program, which has a highly differentiated exon-1-targeting approach to lower huntingtin (HTT) for Huntington’s disease. Presented new preclinical data on delivery solutions with best-in-class potential for adipose, muscle, heart, and kidney tissue and for crossing the blood-brain barrier, supporting Alnylam’s aspiration to unlock every major tissue for RNAi therapeutics by 2030. ALN-6400, targeting liver-derived plasminogen, which could represent a universal hemostatic agent for the treatment of bleeding disorders without the risk of thrombosis. ALN-4324, targeting GRB14, a potential insulin sensitizer for the treatment of type 2 diabetes. Alnylam announces today that a Phase 1 clinical trial for ALN-4324 has been initiated. Net product revenues increased 28% and 30% at actual currency and CER, respectively, during the three months ended March 31, 2025 , as compared to the same period in 2024, due to growth from AMVUTTRA driven by increased patient demand, partially offset by a decrease in ONPATTRO due to patient switches to AMVUTTRA, as well as an increased number patients on GIVLAARI. Net revenues from collaborations decreased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to recognition of $65.0 million of revenue associated with a milestone under our Roche Collaboration from dosing the first patient in the zilebesiran KARDIA-3 clinical trial during the three months ended March 31, 2024 , which did not reoccur during the three months ended March 31, 2025 . This was partially offset by increased revenue recognized in connection with our Regeneron Collaboration during the three months ended March 31, 2025 as a result of an increase in activities under our licensed programs and recognition of a $30.0 million payment in connection with the amendment to our agreement with Vir Biotechnology, Inc. in March 2025 . Cost of goods sold as a percentage of net product revenues was consistent during the three months ended March 31, 2025 , as compared to the same period in 2024. GAAP R&D expenses increased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to: increased stock-based compensation expense; and increased clinical trial expenses primarily associated with zilebesiran in the KARDIA-3 clinical trial and mivelsiran in the cAPPRicorn-1 clinical trial due to increased Phase 2 activities, as well as startup activities and other clinical trial expenses associated with zilebesiran in the KARDIA-6 cardiovascular outcomes trial and nucresiran in the TRITON-CM Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy. increased stock-based compensation expense; and increased clinical trial expenses primarily associated with zilebesiran in the KARDIA-3 clinical trial and mivelsiran in the cAPPRicorn-1 clinical trial due to increased Phase 2 activities, as well as startup activities and other clinical trial expenses associated with zilebesiran in the KARDIA-6 cardiovascular outcomes trial and nucresiran in the TRITON-CM Phase 3 clinical trial in patients with ATTR amyloidosis with cardiomyopathy. decreased expenses within other clinical programs, specifically the HELIOS-B Phase 3 clinical trial of vutrisiran due to the wind-down of clinical activities. GAAP and non-GAAP SG&A expenses increased during the three months ended March 31, 2025 , as compared to the same period in 2024, primarily due to increased marketing investment associated with the promotion of our TTR therapies and increased employee compensation expenses. Interest expense for the three months ended March 31, 2025 of $38.6 million included interest of $35.0 million attributed to the liability related to the sale of future Leqvio royalties. Other expense, net for the three months ended March 31, 2025 of $59.7 million included a charge associated with the change in fair value of the development derivative liability of $58.9 million , attributed to valuation updates primarily driven by the regulatory approval of AMVUTTRA for the treatment ATTR-CM. During the three months ended March 31, 2025 , we recorded a provision for income taxes of $15.9 million , primarily due to income generated in Switzerland . We will utilize deferred tax assets in Switzerland to offset current cash tax liabilities and will continue to maintain a full valuation allowance against our net deferred tax assets in the U.S. and certain deferred tax assets in Switzerland . Cash, cash equivalents and marketable securities were $2.63 billion as of March 31, 2025 , as compared to $2.69 billion as of December 31, 2024 , with the decrease primarily driven by operating activities. Net cash used in operating activities for the three months ended March 31, 2025 of $118.3 million , included $61.7 million of payments associated with the liability related to the sale of future Leqvio royalties allocated to interest. Net cash provided by financing activities for the three months ended March 31, 2025 of $44.1 million , included $5.3 million of payments associated with an achieved development milestone for the development derivative liability.