Alnylam Pharmaceuticals(ALNY) - 2025 Q2 - Quarterly Results

Executive Summary Alnylam reported strong Q2 2025 results, with 64% total net product revenue growth, driven by TTR, and revised full-year guidance upwards Q2 2025 Performance Overview Alnylam Pharmaceuticals reported strong Q2 2025 financial results, with total net product revenues growing 64% year-over-year, driven by the TTR franchise, leading to an upward revision of full-year 2025 revenue guidance - Total Net Product Revenues for Q2 2025 reached $672 Million, marking a 64% growth compared to Q2 2024[1] - Total TTR Revenues were $544 Million, showing a 77% growth compared to Q2 2024, largely due to AMVUTTRA sales in ATTR-CM[1][2] - Approximately 1,400 ATTR-CM patients were on AMVUTTRA as of June 30, 2025[1] - AMVUTTRA received approvals for ATTR-CM treatment in the European Union, Brazil, the United Kingdom, and Japan[1] - The company initiated the TRITON-CM Phase 3 Trial of Nucresiran in patients with wild-type or hereditary ATTR-CM[1] FY 2025 Guidance Update | Metric | Prior FY 2025 Guidance | Updated FY 2025 Guidance | Change at Midpoint | | :--------------------------------------- | :--------------------- | :----------------------- | :----------------- | | Total TTR net product revenues | $1,600M - $1,725M | $2,175M - $2,275M | +$575M / 27% | | Total net product revenues | $2,050M - $2,250M | $2,650M - $2,800M | +$575M / 27% | Second Quarter 2025 and Recent Significant Business Highlights This section details Alnylam's product performance, pipeline advancements, and key upcoming events for Q2 2025 Product Performance Highlights Alnylam's product portfolio demonstrated strong growth in Q2 2025, particularly the TTR franchise driven by AMVUTTRA, while the Rare franchise also contributed positively. ONPATTRO experienced a decline due to patient migration to AMVUTTRA Total TTR: AMVUTTRA (vutrisiran) & ONPATTRO (patisiran) The TTR franchise saw substantial growth, primarily fueled by AMVUTTRA's strong uptake in ATTR-CM patients and global regulatory approvals. ONPATTRO's revenue decreased as patients transitioned to AMVUTTRA TTR Net Product Revenues | Product | Q2 2025 Net Product Revenues | Q2 2024 Net Product Revenues | % Change | | :-------- | :--------------------------- | :--------------------------- | :------- | | AMVUTTRA | $492 million | $230 million | 114% | | ONPATTRO | $53 million | $77 million | (32)% | | Total TTR | $544 million | $307 million | 77% | - Approximately 1,400 ATTR-CM patients were on AMVUTTRA as of June 30, 2025[7] - AMVUTTRA received regulatory approvals for ATTR-CM in Brazil, the European Commission, UK MHRA, and Japanese PMDA[7] - Additional 42-month data from the HELIOS-B Phase 3 trial reinforced vutrisiran's effect on all-cause mortality (36% reduction) and CV mortality (33% reduction) in the overall population[7] Total Rare: GIVLAARI (givosiran) & OXLUMO (lumasiran) The Total Rare franchise, comprising GIVLAARI and OXLUMO, achieved solid revenue growth in Q2 2025 Rare Net Product Revenues | Product | Q2 2025 Net Product Revenues | Q2 2024 Net Product Revenues | % Change | | :---------- | :--------------------------- | :--------------------------- | :------- | | GIVLAARI | $81 million | $62 million | 30% | | OXLUMO | $47 million | $41 million | 15% | | Total Rare | $128 million | $103 million | 24% | Pipeline & Clinical Development Updates Alnylam made significant strides in its pipeline, initiating a new Phase 3 trial for nucresiran in ATTR-CM, presenting positive Phase 1 data for mivelsiran in Alzheimer's, and advancing other programs - Initiated the TRITON-CM Phase 3 trial of nucresiran in patients with ATTR-CM, an event-driven cardiovascular outcomes trial targeting 1,200 patients[7] - Nucresiran received Fast Track Designation from the FDA for the treatment of ATTR-CM to reduce mortality, cardiovascular hospitalizations, and urgent heart failure visits[7] - Presented Phase 1 data for mivelsiran in Alzheimer's disease, showing robust, durable, dose-dependent reductions of soluble amyloid precursor protein beta (sAPPβ) in CSF[8] - Initiated a Phase 1 clinical trial for ALN-4324, an insulin sensitizer targeting GRB14 for type 2 diabetes[8] - Partner Agios Pharmaceuticals received IND clearance for AG-236 (ALN-TMP) for polycythemia vera (PV) and initiated a Phase 1 study[8] Key Upcoming Events Alnylam has several important clinical data presentations and trial initiations planned for the second half of 2025, including results for zilebesiran and nucresiran, and a new Phase 2 trial for mivelsiran - Results from the KARDIA-3 Phase 2 trial of zilebesiran in hypertension will be presented at the European Society of Cardiology (ESC) Congress on August 30, 2025[10] - Expected to initiate a Phase 3 cardiovascular outcomes trial of zilebesiran in collaboration with Roche in H2 2025[13] - Expected to initiate the TRITON-PN Phase 3 trial of nucresiran in hATTR-PN in H2 2025[13] - Expected to initiate a Phase 2 trial of mivelsiran in Alzheimer's disease in H2 2025[13] - Partner Regeneron Pharmaceuticals plans to share results from the Phase 3 trial of cemdisiran in myasthenia gravis in H2 2025[11] Financial Results for the Quarter Ended June 30, 2025 This section provides a detailed analysis of Alnylam's Q2 2025 financial performance, including revenues, operating expenses, and other financial items Consolidated Financial Results Overview Alnylam reported a 17% increase in total revenues for Q2 2025 compared to Q2 2024, but experienced a GAAP operating loss and a significant increase in GAAP net loss per common share, primarily due to increased operating expenses and a decrease in non-GAAP operating income Consolidated Financial Performance | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | % Change | | :-------------------------------------- | :--------------------- | :--------------------- | :------- | | Total revenues | $773,689 | $659,825 | 17% | | GAAP (Loss) income from operations | $(16,199) | $48,614 | (133)% | | Non-GAAP Income from operations | $95,481 | $137,902 | (31)% | | GAAP Net loss per common share – basic | $(0.51) | $(0.13) | 292% | | Non-GAAP Net income per common share – basic | $0.34 | $0.58 | (41)% | Revenue Analysis Total net product revenues surged by 64% year-over-year, driven by AMVUTTRA's strong performance, partially offset by ONPATTRO's decline. Net revenues from collaborations significantly decreased due to a prior-year licensing deal with Regeneron, while royalty revenue saw substantial growth Revenue Breakdown by Product and Type | Revenue Type | Q2 2025 (in thousands) | Q2 2024 (in thousands) | % Change | % Change at CER | | :---------------------------- | :--------------------- | :--------------------- | :------- | :-------------- | | AMVUTTRA | $491,953 | $230,109 | 114% | 112% | | ONPATTRO | $52,538 | $77,244 | (32)% | (33)% | | Total TTR net product revenues| $544,491 | $307,353 | 77% | 75% | | GIVLAARI | $80,849 | $62,127 | 30% | 29% | | OXLUMO | $46,872 | $40,608 | 15% | 13% | | Total Rare net product revenues| $127,721 | $102,735 | 24% | 23% | | Total net product revenues | $672,212 | $410,088 | 64% | 62% | | Net revenues from collaborations| $61,496 | $227,338 | (73)% | (73)% | | Royalty revenue | $39,981 | $22,399 | 78% | 78% | | Total revenues | $773,689 | $659,825 | 17% | 16% | - Total net product revenues increased 64% (62% at CER) due to AMVUTTRA growth from increased patient demand, mainly in ATTR-CM in the U.S., partially offset by ONPATTRO patient switches, and growth from GIVLAARI and OXLUMO[15] - Net revenues from collaborations decreased 73% primarily due to a $185.0 million revenue recognition in Q2 2024 from a collaboration modification with Regeneron Pharmaceuticals[16] Operating Expenses Analysis Operating expenses increased across the board in Q2 2025. Cost of goods sold rose significantly due to higher AMVUTTRA sales and associated royalties. R&D expenses increased due to clinical trial startup activities for zilebesiran and nucresiran, while SG&A expenses grew due to higher employee compensation and marketing investments for AMVUTTRA's launch Operating Expenses | Expense Type | Q2 2025 (in thousands) | Q2 2024 (in thousands) | % Change | | :----------------------------------------- | :--------------------- | :--------------------- | :------- | | Cost of goods sold | $142,029 | $67,271 | 111% | | % of net product revenues | 21.1% | 16.4% | | | Cost of collaborations and royalties | $924 | $1,401 | (34)% | | GAAP Research and development expenses | $323,621 | $294,142 | 10% | | Non-GAAP Research and development expenses | $274,069 | $246,027 | 11% | | GAAP Selling, general and administrative expenses | $323,314 | $248,397 | 30% | | Non-GAAP Selling, general and administrative expenses | $261,186 | $207,224 | 26% | - Cost of goods sold increased 111% primarily due to increased AMVUTTRA sales and associated royalties[18] - GAAP and non-GAAP R&D expenses increased 10% and 11% respectively, driven by clinical trial startup activities for zilebesiran (Phase 3 cardiovascular outcomes) and nucresiran (TRITON-CM Phase 3)[19] - GAAP and non-GAAP SG&A expenses increased 30% and 26% respectively, due to higher employee compensation costs and increased marketing investment for AMVUTTRA's ATTR-CM launch[20] Other Financial Items Interest expense included a significant portion related to the sale of future Leqvio royalties. Total other expense, net, was impacted by a charge from the change in fair value of the development derivative liability. The company recorded an income tax provision primarily due to income generated in Switzerland - Interest expense for Q2 2025 was $40.2 million, with $36.5 million attributed to the liability related to the sale of future Leqvio royalties[21] - Total other expense, net, was $19.2 million, including a $15.3 million charge from the change in fair value of the development derivative liability, driven by updates to estimated royalties due to Blackstone on AMVUTTRA sales[22] - Provision for income taxes was $30.9 million, mainly due to income in Switzerland and state income taxes in the U.S[23] Financial Position & Cash Flow Alnylam's cash, cash equivalents, and marketable securities increased to $2.86 billion as of June 30, 2025, primarily driven by net cash inflows from operating activities and proceeds from employee stock option exercises - Cash, cash equivalents and marketable securities were $2.86 billion as of June 30, 2025, up from $2.63 billion as of March 31, 2025[26] - The increase in cash was primarily driven by net cash inflows from operating activities and proceeds from the exercise of employee stock options[26] - Net cash provided by operating activities included $14.4 million of payments associated with the Leqvio royalties liability[26] - Net cash provided by financing activities included $27.5 million of payments to Blackstone for development and regulatory approval milestones and AMVUTTRA sales royalties[26] 2025 Financial Guidance Alnylam has raised its full-year 2025 financial guidance for total TTR net product revenues and total net product revenues, reflecting strong performance, particularly from the TTR franchise. Guidance for Total Rare net product revenues, net revenues from collaborations and royalties, and non-GAAP operating income was reiterated Updated FY 2025 Financial Guidance | Item | Prior FY 2025 Guidance | Updated FY 2025 Guidance | | :---------------------------------------- | :--------------------- | :----------------------- | | Total TTR net product revenues (PN & CM) | $1,600M - $1,725M | $2,175M - $2,275M | | Total Rare net product revenues | $450M - $525M | $475M - $525M | | Total net product revenues | $2,050M - $2,250M | $2,650M - $2,800M | | Net product revenues growth vs. 2024 (actual) | 25% to 37% | 61% to 70% | | Net product revenues growth vs. 2024 (CER) | 26% to 39% | 59% to 68% | | Net revenues from collaborations and royalties | $650M - $750M | Reiterate FY guidance | | GAAP R&D and SG&A expenses | $2,370M - $2,530M | $2,445M - $2,575M | | Non-GAAP R&D and SG&A expenses | $2,100M - $2,200M | Reiterate FY guidance | | Non-GAAP Operating income | Achieve profitability | Reiterate FY guidance | Use of Non-GAAP Financial Measures Non-GAAP measures provide insights into Alnylam's operations by excluding non-cash and non-recurring items for clearer performance evaluation - Non-GAAP measures exclude stock-based compensation expenses and realized/unrealized gains or losses on marketable equity securities[29] - The company believes non-GAAP measures provide useful information to management and investors for evaluating performance, allocating resources, and planning[31] - Percentage changes in revenue growth at Constant Exchange Rates (CER) are presented to show underlying business performance without foreign currency fluctuations[30] Company and Product Information This section provides detailed information about Alnylam Pharmaceuticals and its key commercial products About AMVUTTRA (vutrisiran) AMVUTTRA is an RNAi therapeutic for transthyretin (ATTR) amyloidosis, administered quarterly via subcutaneous injection. It is approved in over 15 countries for hATTR-PN and in the U.S., EU, Brazil, UK, and Japan for ATTR-CM to reduce cardiovascular mortality and hospitalizations - AMVUTTRA is an RNAi therapeutic that rapidly knocks down transthyretin (TTR), addressing the underlying cause of ATTR amyloidosis[34] - Administered quarterly via subcutaneous injection by a healthcare professional[34] - Approved in over 15 countries for hATTR-PN and in the U.S., Brazil, EU, UK, and Japan for ATTR-CM to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits[34] About ONPATTRO (patisiran) ONPATTRO is an intravenously administered RNAi therapeutic approved in the U.S., Canada, EU, Switzerland, Brazil, and Japan for the treatment of hATTR amyloidosis with polyneuropathy. It works by silencing TTR messenger RNA to reduce pathogenic protein production - ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR)[35] - Approved in the U.S., Canada, EU, Switzerland, Brazil, and Japan for hATTR amyloidosis with polyneuropathy[35] - Designed to silence TTR messenger RNA, reducing TTR protein production and amyloid deposits[35] About GIVLAARI (givosiran) GIVLAARI is an RNAi therapeutic targeting ALAS1, approved in the U.S., Brazil, and EU for acute hepatic porphyria (AHP) in adults and adolescents. It significantly reduces porphyria attacks and is administered monthly via subcutaneous injection - GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1)[36] - Approved in the U.S., Brazil, and EU for the treatment of adults and adolescents (12+) with acute hepatic porphyria (AHP)[36] - Significantly reduces the rate of porphyria attacks requiring hospitalization, urgent healthcare visits, or IV hemin[36] - Administered once monthly via subcutaneous injection, utilizing Alnylam's Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology[36] About OXLUMO (lumasiran) OXLUMO is an RNAi therapeutic targeting HAO1, approved by the FDA and EMA for primary hyperoxaluria type 1 (PH1) in all age groups. It lowers urinary and plasma oxalate levels by inhibiting glycolate oxidase production, with injection site reactions being the most common adverse reaction - OXLUMO is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1), which encodes glycolate oxidase (GO)[37] - Approved by the FDA and EMA for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients[37] - Utilizes Alnylam's ESC-GalNAc-conjugate technology for subcutaneous dosing[37] - Demonstrated significant reductions in urinary oxalate in pivotal trials, with injection site reactions as the most common drug-related adverse reaction[37] About Alnylam Pharmaceuticals Alnylam is a leading RNAi therapeutics company, translating Nobel Prize-winning science into innovative medicines for rare and prevalent diseases. The company is executing its 'Alnylam P x25' strategy to deliver transformative medicines, achieve sustainable profitability, and solidify its position as a top-tier biotech company - Alnylam is a leading RNAi therapeutics company, founded in 2002, focused on translating RNA interference into innovative medicines[40] - Commercial RNAi therapeutic products include AMVUTTRA, ONPATTRO, GIVLAARI, and OXLUMO, with Leqvio and Qfitlia commercialized by partners[40] - Executing on its 'Alnylam P x25' strategy to deliver transformative medicines, achieve sustainable profitability, and become a leading biotech company[40] Alnylam Forward Looking Statements This section outlines Alnylam's forward-looking statements, including commercial and pipeline expectations, and associated risks - Statements regarding Alnylam's ability to deliver and enable commercial access to medicines, advance its pipeline, and achieve P5x25 goals are forward-looking[41] - Actual results may differ materially due to risks and uncertainties including successful execution of strategy, efficacy and safety of product candidates, regulatory actions, manufacturing, intellectual property, and dependence on third parties[41][42] - The company explicitly disclaims any obligation to update forward-looking statements, except as required by law[42] Condensed Consolidated Financial Statements This section presents Alnylam's condensed consolidated financial statements, including balance sheets, statements of operations, and reconciliations of GAAP to non-GAAP measures Condensed Consolidated Balance Sheets Alnylam's balance sheet as of June 30, 2025, shows an increase in total assets, driven by higher cash and accounts receivable. Total liabilities also increased, with a notable rise in accrued expenses and development derivative liability, while total stockholders' equity significantly improved Condensed Consolidated Balance Sheets | Item | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :---------------------------------------- | :--------------------------- | :------------------------------- | | Cash and cash equivalents | $1,113,685 | $966,428 | | Marketable debt securities | $1,743,900 | $1,719,920 | | Accounts receivable, net | $567,112 | $405,308 | | Total current assets | $3,643,699 | $3,295,285 | | Total assets | $4,566,019 | $4,239,983 | | Accrued expenses | $918,966 | $793,692 | | Development derivative liability (current) | $120,788 | $93,780 | | Total current liabilities | $1,300,847 | $1,186,272 | | Convertible debt | $1,026,522 | $1,024,621 | | Total liabilities | $4,315,428 | $4,172,895 | | Total stockholders' equity | $250,591 | $67,088 | Condensed Consolidated Statements of Operations For Q2 2025, Alnylam reported a 17% increase in total revenues but a significant GAAP net loss of $66.3 million, compared to a net loss of $16.9 million in Q2 2024. This was driven by higher operating costs, particularly R&D and SG&A, and increased provision for income taxes, despite strong product revenue growth Condensed Consolidated Statements of Operations | Item | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :------------------------------------ | :---------------------------------------------- | :---------------------------------------------- | | Net product revenues | $672,212 | $410,088 | | Net revenues from collaborations | $61,496 | $227,338 | | Royalty revenue | $39,981 | $22,399 | | Total revenues | $773,689 | $659,825 | | Cost of goods sold | $142,029 | $67,271 | | Research and development | $323,621 | $294,142 | | Selling, general and administrative | $323,314 | $248,397 | | Total operating costs and expenses | $789,888 | $611,211 | | (Loss) income from operations | $(16,199) | $48,614 | | Total other expense, net | $(19,159) | $(59,781) | | Provision for income taxes | $(30,919) | $(5,722) | | Net loss | $(66,277) | $(16,889) | | Net loss per common share — basic and diluted | $(0.51) | $(0.13) | Reconciliation of GAAP to Non-GAAP Measures This section provides a reconciliation of GAAP to non-GAAP financial measures, primarily adjusting for stock-based compensation expenses and realized/unrealized gains/losses on marketable equity securities. These adjustments convert GAAP net loss to non-GAAP net income, offering an alternative view of the company's operational profitability GAAP to Non-GAAP Reconciliation | Item | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :---------------------------------------- | :---------------------------------------------- | :---------------------------------------------- | | GAAP Research and development expenses | $323,621 | $294,142 | | Less: Stock-based compensation expenses | $(49,552) | $(48,115) | | Non-GAAP Research and development expenses| $274,069 | $246,027 | | GAAP Selling, general and administrative expenses | $323,314 | $248,397 | | Less: Stock-based compensation expenses | $(62,128) | $(41,173) | | Non-GAAP Selling, general and administrative expenses | $261,186 | $207,224 | | GAAP (Loss) income from operations | $(16,199) | $48,614 | | Add: Stock-based compensation expenses | $111,680 | $89,288 | | Non-GAAP Operating income | $95,481 | $137,902 | | GAAP Net loss | $(66,277) | $(16,889) | | Add: Stock-based compensation expenses | $111,680 | $89,288 | | Add: Realized and unrealized loss on marketable equity securities | $1,350 | $1,367 | | Less: Income tax effect of GAAP to non-GAAP reconciling items | $(2,631) | — | | Non-GAAP Net income | $44,122 | $73,766 | | Non-GAAP Net income per common share – basic | $0.34 | $0.58 | | Non-GAAP Net income per common share – diluted | $0.32 | $0.56 | Reconciliation of GAAP to Non-GAAP Product Revenue Growth at Constant Currency This reconciliation adjusts reported product revenue growth rates for the impact of foreign currency translation, providing a 'constant currency' view to better reflect underlying business performance. For Q2 2025, total net product revenue growth at constant currency was 62%, slightly lower than the reported 64% Product Revenue Growth at Constant Currency | Product/Category | Reported Growth | Impact of Foreign Currency Translation | Growth at Constant Currency | | :-------------------------------- | :-------------- | :------------------------------------- | :-------------------------- | | AMVUTTRA net product revenue | 114% | (2)% | 112% | | ONPATTRO net product revenue | (32)% | (1)% | (33)% | | Total TTR net product revenue | 77% | (2)% | 75% | | GIVLAARI net product revenue | 30% | (1)% | 29% | | OXLUMO net product revenue | 15% | (2)% | 13% | | Total Rare net product revenue | 24% | (1)% | 23% | | Total net product revenue | 64% | (2)% | 62% | | Total revenue | 17% | (1)% | 16% |