Company Performance - ADC Therapeutics SA (ADCT) has gained approximately 35.2% year-to-date, significantly outperforming the average return of -7.2% for Medical companies [4] - The Zacks Consensus Estimate for ADCT's full-year earnings has increased by 4.2% over the past three months, indicating improved analyst sentiment [4] - ADC Therapeutics SA currently holds a Zacks Rank of 2 (Buy), suggesting a positive outlook for the stock [3] Industry Context - ADC Therapeutics SA is part of the Medical - Biomedical and Genetics industry, which consists of 490 companies and currently ranks 143 in the Zacks Industry Rank [6] - The average performance of stocks in the Medical - Biomedical and Genetics industry has been a gain of 0.5% this year, indicating that ADCT is performing better than its industry peers [6] - Another notable performer in the Medical sector is Alnylam Pharmaceuticals (ALNY), which has seen a year-to-date increase of 70.8% and also holds a Zacks Rank of 2 (Buy) [5]

Core Viewpoint - Alnylam Pharmaceuticals reported strong second-quarter earnings and raised its 2025 sales guidance, indicating positive momentum in its product launches and overall financial performance [1][3]. Financial Performance - The company reported adjusted earnings of 32 cents for Q2 2025, a decrease from 56 cents year-over-year, but significantly better than analysts' expectations of a loss of 79 cents [1]. - Quarterly sales reached $773.69 million, reflecting a 17% year-over-year increase and surpassing the consensus estimate of $638.55 million [1]. Product Revenue - Global net product revenues for Amvuttra and Onpattro were $492 million and $53 million, respectively, while Givlaari and Oxlumo generated $81 million and $47 million in revenue for the same quarter [2]. - The launch of Amvuttra for ATTR-CM has been particularly successful, with approximately 1,400 patients treated by June 30, 2025, contributing to an estimated $150 million increase in revenue [4]. Guidance and Analyst Outlook - Alnylam raised its fiscal 2025 sales guidance from $2.7 billion-$3 billion to $3.3 billion-$3.55 billion, exceeding the consensus of $2.89 billion [3]. - Analysts from Chardan Research and William Blair expressed positive outlooks, with Chardan highlighting the strong start of Amvuttra's launch [3][6]. Analyst Ratings and Price Forecasts - Various analysts have upgraded their price forecasts for Alnylam, with Chardan raising its target from $325 to $400, and UBS increasing its forecast from $403 to $550 [5][8]. - Morgan Stanley maintained an Equal-Weight rating while increasing its price forecast from $312 to $405, and Piper Sandler raised its target from $304 to $449 [7].

Core Insights - Alnylam Pharmaceuticals reported second-quarter 2025 earnings of $0.32 per share, significantly surpassing the Zacks Consensus Estimate of a loss of $0.03, primarily due to increased revenues from its lead drug, Amvuttra [1][11] - Total revenues for the quarter reached $773.7 million, exceeding the Zacks Consensus Estimate of $673 million, and reflecting a 17% year-over-year increase [2] - The company's net product revenues were $672.2 million, a 64% increase year-over-year, driven by strong demand for Amvuttra, Givlaari, and Oxlumo [3] Revenue Breakdown - Alnylam's net product revenues from Amvuttra amounted to $492 million, representing a 114% increase year-over-year, aided by expanded label use and patient switches from Onpattro [8][11] - Givlaari generated sales of $80.8 million, a 30% year-over-year increase, while Oxlumo recorded revenues of $46.9 million, up 15% year-over-year [9] - Net revenues from collaborators were $61.5 million, down 73% from the previous year, primarily due to a significant milestone payment received in the prior quarter [4] Financial Guidance - Alnylam raised its 2025 product revenue guidance to a range of $2.65 billion to $2.8 billion, up from the previous range of $2.05 billion to $2.25 billion [11][16] - The guidance for net revenues from collaborations and royalties remains unchanged at $650 million to $750 million [16] Research and Development - Adjusted R&D expenses increased by 11% year-over-year to $274.1 million, reflecting costs associated with new studies in partnership with Roche [13] - Adjusted SG&A expenses rose by 26% year-over-year to $261.2 million, driven by higher employee compensation and marketing investments related to Amvuttra [14] Cash Position - As of June 30, 2025, Alnylam's cash, cash equivalents, and marketable securities totaled $2.86 billion, an increase from $2.63 billion as of March 31, 2025, primarily due to net cash inflows from operating activities [15]

Core Insights - Alnylam Pharmaceuticals reported a revenue of $773.69 million for the quarter ended June 2025, reflecting a year-over-year increase of 17.3% and a surprise of +14.96% over the Zacks Consensus Estimate of $673 million [1] - The company's EPS was $0.32, down from $0.56 in the same quarter last year, with an EPS surprise of +1166.67% compared to the consensus estimate of -$0.03 [1] Revenue Breakdown - Product revenues were $672.21 million, exceeding the average estimate of $540.14 million by analysts, representing a year-over-year increase of +63.9% [4] - Royalty revenue reached $39.98 million, surpassing the average estimate of $32.74 million, with a year-over-year change of +78.5% [4] - Net Product Revenue from Oxlumo was $46.87 million, slightly above the estimated $46.64 million, marking a +15.4% change year over year [4] - Net Product Revenue from Givlaari was $80.85 million, exceeding the average estimate of $72.59 million, reflecting a +30.1% year-over-year increase [4] - Net Product Revenue from Amvuttra was $491.95 million, significantly higher than the estimated $365.41 million, showing a +113.8% change compared to the previous year [4] - Net Product Revenue from Onpattro was $52.24 million, below the average estimate of $45.89 million, indicating a -32.4% year-over-year decline [4] Research Collaborator Revenues - Net revenues from research collaborators totaled $61.5 million, falling short of the average estimate of $90.07 million, representing a -73% change year over year [4] - Other net revenues from research collaborators were $10.69 million, exceeding the estimated $3 million, with a remarkable +872.4% change compared to the previous year [4] - Net revenues from Regeneron Pharmaceuticals were $32.54 million, significantly lower than the estimated $17.5 million, reflecting an -84.3% change year over year [4] - Net revenues from Roche were $18.27 million, surpassing the average estimate of $12 million, with a +10.7% year-over-year change [4] Stock Performance - Alnylam's shares returned +3% over the past month, outperforming the Zacks S&P 500 composite's +2.7% change [3] - The stock currently holds a Zacks Rank 3 (Hold), indicating potential performance in line with the broader market in the near term [3]

Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][37] - The TTR franchise generated $544 million in revenues, reflecting a 77% increase year-over-year [8][11] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, a 27% increase at the midpoint [9][42] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined sales of ONPATTRO and Ambutra rise by 80% compared to Q1 2025, driven primarily by the launch of Ambutra [14][16] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][11] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the demand from the ATTR Centimeters launch [15][11] Market Data and Key Metrics Changes - International markets are expected to contribute to Ambutra's revenues in the second half of 2025, with launches in Germany and Japan [15][27] - The U.S. TTR franchise achieved $383 million in Q2 2025, indicating robust growth dynamics [16][11] - The company has yet to recognize any ATTR Centimeters revenue internationally, but anticipates strong growth as international launches commence [15][11] Company Strategy and Development Direction - Alnylam focuses on three core elements: TTR leadership, growth through innovation, and strong financial performance [6][7] - The company aims to establish long-term leadership in TTR and expand its pipeline of RNAi therapeutics [6][9] - Alnylam is committed to disciplined capital allocation and sustainable growth, with a focus on patient and customer centricity [28][9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early performance of Ambutra and its potential for sustainable growth [9][28] - The company highlighted the importance of real-world evidence generation and the development of next-generation RNAi therapeutics [27][9] - Management remains optimistic about achieving its Alnylam Pizza Fit by 25 goals, reinforcing its position as a top-tier biotech company [10][9] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, enhancing its development prospects [9][31] - Alnylam's gross margin on product sales was 79% for the quarter, down from 84% in 2024, primarily due to increased royalties [39][37] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.9 billion, an increase from $2.7 billion at the end of 2024 [41][37] Q&A Session Summary Question: Can you provide details on the patient profiles for Ambutra? - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy mix emerging [48][49] Question: How are you thinking about net price for Ambutra moving forward? - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [56][57] Question: Was there any bolus effect in cardiomyopathy scripts in Q2? - Management confirmed solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [60][61] Question: Can you comment on the criteria physicians are using for stabilizer progressors? - Clinical evidence suggests that 30% to 50% of patients on stabilizers may progress, and physicians are using a variety of factors to determine treatment [81][82] Question: How should we think about the rate of new patient starts per quarter? - Management expects both categories of patients to continue growing, with a balanced uptake between new patients and stabilizer progressors [97][98]

Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][35] - The TTR franchise generated revenues of $544 million, reflecting a 77% increase year-over-year [7][35] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, marking a $575 million or 27% increase at the midpoint [9][39] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined Q2 sales of ONPATTRO and Ambutra rise by 80% compared to Q1, driven primarily by the Ambutra launch [13][35] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][35] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the ATTR Centimeters launch [14] Market Data and Key Metrics Changes - Approximately 1,400 cardiomyopathy patients were receiving Ambutra by the end of Q2, contributing an estimated $150 million in revenue [13][23] - International markets are expected to begin contributing to Ambutra sales in the second half of the year, with launches in Germany and Japan [8][26] - The U.S. TTR franchise achieved $383 million in Q2, representing an 80% quarter-over-quarter growth [15] Company Strategy and Development Direction - Alnylam is focusing on TTR leadership, growth through innovation, and strong financial performance as key strategic pillars [4][6] - The company aims to establish itself as a top-tier biotech firm by delivering sustainable innovation and value creation [5][10] - The launch of Ambutra is seen as a flagship commercial franchise with robust long-term growth potential [6][27] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early launch performance of Ambutra and the potential for continued growth [9][39] - The company remains committed to advancing care through real-world evidence generation and the development of next-generation RNAi therapeutics [26][34] - Management highlighted the importance of disciplined execution and patient-centricity in driving long-term growth [27][39] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, which is expected to streamline the review process [9][31] - The gross margin on product sales was reported at 79%, down from 84% in the previous year, primarily due to increased royalties on Ambutra [37] Q&A Session Summary Question: Details on patient profiles for Ambutra - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy share of first-line patients emerging [45][46] Question: Thoughts on net price for Ambutra - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [50][52] Question: Bolus effect in cardiomyopathy scripts - Management indicated solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [56][57] Question: Assumptions underpinning updated TTR franchise guidance - Management expects steady growth in both first-line and second-line patient flows, with a healthy trend in first-line use observed [65][70] Question: Criteria for stabilizer progressors - Clinical evidence suggests that one-third to half of patients on stabilizers progress, and physicians are using a variety of factors to determine eligibility for Ambutra [76][82] Question: Rate of new patient starts per quarter - Management is pleased with the initial uptake and expects both categories of patients to continue growing, though specific numbers will not be reported [91][94] Question: Payer requirements for Ambutra treatment - Broad coverage is reported across Medicare and commercial payers, with minimal step edits required for access [98][102]

Financial Performance - Total Q2 Net Product Revenues reached $672 million, a 64% increase year-over-year[17, 24] - Total TTR Net Revenues in Q2 were $544 million, representing a 77% year-over-year growth[17] - Rare Franchise Net Product Revenues in Q2 totaled $128 million, a 24% increase year-over-year[28] - Alnylam increased its 2025 Total Net Product Revenue Guidance to a range of $2650 million to $2800 million[17, 74] - The company's Q2 Non-GAAP Operating Income was $95 million[70] Commercial Highlights - U S ATTR-CM launch contributed approximately $150 million in revenue during Q2[33, 34] - There are approximately 1,400 ATTR-CM patients receiving AMVUTTRA as of June 30, 2025[17, 37, 45] - U S TTR franchise experienced 125% year-over-year growth in Q2[32] - GIVLAARI saw a 30% year-over-year growth, driven by an approximately 18% increase in global patients on therapy[29] - OXLUMO experienced a 15% year-over-year growth, driven by an approximately 16% increase in global patients on therapy[29] Pipeline Development - The TRITON-CM Phase 3 study for nucresiran in ATTR-CM has been initiated, with a targeted launch around 2030[17, 60] - Phase 1 multidose results for mivelsiran in Alzheimer's Disease were announced[17] - A Phase 1 study for ALN-4324 in Type 2 Diabetes was initiated[17]

PART I. FINANCIAL INFORMATION [Financial Statements (Unaudited)](index=6&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS%20%28UNAUDITED%29) This section presents unaudited condensed consolidated financial statements for Q2 2025, including balance sheets, statements of operations, and cash flows, reporting a net loss of $66.3 million Balance Sheet Summary (in thousands) | Financial Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Assets** | $4,566,019 | $4,239,983 | | **Total Liabilities** | $4,315,428 | $4,172,895 | | **Total Stockholders' Equity** | $250,591 | $67,088 | Condensed Consolidated Statements of Operations (in thousands) | Income Statement Item | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Revenues** | $773,689 | $659,825 | | **Total Operating Costs and Expenses** | $789,888 | $611,211 | | **Net Loss** | $(66,277) | $(16,889) | | **Net Loss Per Share (basic and diluted)** | $(0.51) | $(0.13) | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Detailed disclosures support financial statements, covering accounting policies, revenue breakdowns, collaboration agreements, and legal contingencies, highlighting strong AMVUTTRA product revenue growth Net Product Revenues (in thousands) | Product Revenue (in thousands) | Q2 2025 | Q2 2024 | YTD 2025 | YTD 2024 | | :--- | :--- | :--- | :--- | :--- | | **AMVUTTRA** | $491,953 | $230,109 | $801,945 | $425,350 | | **ONPATTRO** | $52,538 | $77,244 | $102,027 | $146,461 | | **GIVLAARI** | $80,849 | $62,127 | $147,817 | $120,183 | | **OXLUMO** | $46,872 | $40,608 | $88,961 | $83,257 | | **Total Net Product Revenues** | **$672,212** | **$410,088** | **$1,140,750** | **$775,251** | Collaboration Revenues (in thousands) | Collaboration Revenue (in thousands) | Q2 2025 | Q2 2024 | YTD 2025 | YTD 2024 | | :--- | :--- | :--- | :--- | :--- | | **Roche** | $18,267 | $16,506 | $35,323 | $91,186 | | **Regeneron Pharmaceuticals** | $32,542 | $207,429 | $83,581 | $234,193 | | **Novartis AG** | $0 | $2,304 | $0 | $16,820 | | **Other** | $10,687 | $1,099 | $41,777 | $3,687 | | **Total** | **$61,496** | **$227,338** | **$160,681** | **$345,886** | - The company is involved in patent infringement lawsuits filed in March 2022 against Moderna and Pfizer concerning their mRNA COVID-19 vaccines, with court rulings generally **unfavorable to Alnylam** and judgments of **non-infringement** entered, though appeals are being considered[107](index=107&type=chunk)[111](index=111&type=chunk)[112](index=112&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations (MD&A)](index=27&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses strong AMVUTTRA product revenue growth, offset by decreased collaboration revenue, detailing the Alnylam P5x25 strategy, pipeline updates, and operating expense analysis [Overview and Pipeline](index=27&type=section&id=Overview%20and%20Pipeline) Alnylam, a commercial-stage biopharmaceutical company, executes its 'Alnylam P5x25' strategy, driven by AMVUTTRA's expanded approval and a robust late-stage pipeline - The company is pursuing its **"Alnylam P5x25" strategy** with the goal of becoming a **top-tier biotech company by the end of 2025**, focusing on **sustainable innovation and strong financial performance**[126](index=126&type=chunk) - A **major growth driver** is the recent approval of AMVUTTRA for the treatment of cardiomyopathy of ATTR amyloidosis in the **U.S. (March 2025)**, **EU (June 2025)**, and other key global markets[127](index=127&type=chunk) - Key late-stage pipeline programs include: - **Zilebesiran (Hypertension):** Partnered with Roche, with a Phase 3 trial expected to start in H2 2025 - **Nucresiran (ATTR Amyloidosis):** Phase 3 trial (TRITON-CM) initiated - **Mivelsiran (Alzheimer's & CAA):** Phase 2 trial in AD expected in H2 2025; Phase 2 in CAA initiated[134](index=134&type=chunk)[135](index=135&type=chunk) [Results of Operations](index=33&type=section&id=Results%20of%20Operations) Q2 2025 total revenues increased 17% to $773.7 million, driven by 64% growth in net product revenues from AMVUTTRA, despite a 73% decrease in collaboration revenue Total Revenues (in thousands) | Revenue Line Item (in thousands) | Q2 2025 | Q2 2024 | % Change | | :--- | :--- | :--- | :--- | | Net product revenues | $672,212 | $410,088 | 64% | | Net revenues from collaborations | $61,496 | $227,338 | (73)% | | Royalty revenue | $39,981 | $22,399 | 78% | | **Total revenues** | **$773,689** | **$659,825** | **17%** | - The sharp decrease in collaboration revenue in Q2 2025 compared to Q2 2024 was primarily driven by the recognition of **$185.0 million** in revenue from Regeneron in June 2024 related to a license for cemdisiran[164](index=164&type=chunk)[168](index=168&type=chunk) Operating Costs and Expenses (in thousands) | Operating Costs (in thousands) | Q2 2025 | Q2 2024 | % Change | | :--- | :--- | :--- | :--- | | Cost of goods sold | $142,029 | $67,271 | 111% | | Research and development | $323,621 | $294,142 | 10% | | Selling, general and administrative | $323,314 | $248,397 | 30% | | **Total operating costs** | **$789,888** | **$611,211** | **29%** | [Liquidity and Capital Resources](index=38&type=section&id=Liquidity%20and%20Capital%20Resources) As of June 30, 2025, the company held $1.11 billion in cash and $1.74 billion in marketable securities, sufficient to fund operations for at least 12 months Condensed Consolidated Statements of Cash Flows (in thousands) | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash provided by operating activities | $35,416 | $42,643 | | Net cash used in investing activities | $(27,612) | $(33,680) | | Net cash provided by financing activities | $97,841 | $160,407 | - The company believes its cash, cash equivalents, and marketable securities of **$2.86 billion** as of June 30, 2025, are sufficient to fund operations for **at least the next 12 months** from the filing date[186](index=186&type=chunk)[216](index=216&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) No significant changes to financial market risks, primarily interest rate-related, were reported since fiscal year 2024 - There have been **no significant changes** to the company's financial market risk exposures, which are mainly related to **interest rates**, as of June 30, 2025, compared to December 31, 2024[187](index=187&type=chunk) [Controls and Procedures](index=38&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management concluded disclosure controls and procedures were effective as of June 30, 2025, with no material changes in internal control over financial reporting - The CEO and CFO concluded that as of June 30, 2025, the company's disclosure controls and procedures were **effective at the reasonable assurance level**[189](index=189&type=chunk) - **No changes** in internal control over financial reporting occurred during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, these controls[190](index=190&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=40&type=section&id=ITEM%201.%20LEGAL%20PROCEEDINGS) This section refers readers to Note 12 of the condensed consolidated financial statements for material pending legal proceedings - For a discussion of material pending legal proceedings, the report refers to **Note 12, "Commitments and Contingencies,"** in the financial statements section[192](index=192&type=chunk) [Risk Factors](index=40&type=section&id=ITEM%201A.%20RISK%20FACTORS) This section outlines significant risks including commercial success, financial losses, future funding needs, third-party reliance, and drug development uncertainties [Financial and Commercial Risks](index=41&type=section&id=Financial%20and%20Commercial%20Risks) The company faces significant financial and commercial risks, including AMVUTTRA's success, an accumulated deficit of $7.41 billion, and securing substantial future funding - The **commercial success** of approved products, especially AMVUTTRA for ATTR amyloidosis with cardiomyopathy, is uncertain and **critical to achieving profitability**[201](index=201&type=chunk) - The company has a history of **significant operating losses**, with an **accumulated deficit of $7.41 billion** as of June 30, 2025, and may not achieve or sustain profitability[204](index=204&type=chunk) - **Substantial funds are required** to continue research, development, and commercialization activities, and **additional funding may be necessary** but might not be available on acceptable terms[206](index=206&type=chunk)[208](index=208&type=chunk) [Risks Related to Dependence on Third Parties](index=45&type=section&id=Risks%20Related%20to%20Dependence%20on%20Third%20Parties) Alnylam's business heavily relies on third-party collaborators and CMOs for development, commercialization, and supply, posing risks of partnership termination or manufacturing disruptions - The company's business could be **adversely affected** if collaborators like Roche, Regeneron, or Novartis **terminate their agreements** or **fail to perform their obligations**, potentially delaying or halting the development and commercialization of key products[227](index=227&type=chunk) - There is a risk that **Roche could terminate** the zilebesiran collaboration before the Phase 3 trial begins, which would result in the **loss of a significant milestone payment** and could impact the company's ability to achieve operating profitability in 2025[229](index=229&type=chunk) - The company relies on a **limited number of third-party Contract Manufacturing Organizations (CMOs)** for drug substance and all drug product requirements, where the loss of a supplier or their inability to provide sufficient supply could **delay clinical trials** and **harm commercial supply**[233](index=233&type=chunk)[234](index=234&type=chunk) [Risks Related to Development, Clinical Testing and Regulatory Approval](index=51&type=section&id=Risks%20Related%20to%20Development%2C%20Clinical%20Testing%20and%20Regulatory%20Approval) Product candidates face high failure risks in development due to expensive, lengthy, and uncertain clinical trials, with potential for undesirable side effects and extensive ongoing regulatory oversight - Product candidates may **fail in development or experience significant delays**, as nonclinical and clinical testing is expensive, lengthy, and has a **high historical failure rate**[257](index=257&type=chunk) - **Undesirable side effects or unexpected adverse properties** in products or product candidates could **delay or prevent regulatory approval**, limit commercial potential, or result in significant negative consequences post-approval[268](index=268&type=chunk) - Marketed products and approved candidates are subject to **extensive and ongoing regulatory oversight**, and **failure to comply** with continuing U.S. and foreign requirements could result in **limited or withdrawn approvals** and other penalties[286](index=286&type=chunk) [Risks Related to Competition](index=71&type=section&id=Risks%20Related%20to%20Competition) The company faces intense competition from large pharmaceutical companies and existing treatments, with AMVUTTRA competing against lower-priced oral drugs and alternative technologies - The company faces **intense competition** from large pharmaceutical companies with **greater resources** and from existing approved drugs for the same conditions[371](index=371&type=chunk) - **AMVUTTRA for ATTR-CM competes with orally administered drugs** VYNDAQEL/VYNDAMAX (Pfizer) and ATTRUBY (BridgeBio), which have **lower list prices** in the U.S., potentially impacting AMVUTTRA's commercial success[372](index=372&type=chunk) - The company faces **direct competition from other companies developing RNAi therapeutics** (e.g., Arrowhead, Roche, Silence Therapeutics) and from **alternative platforms like antisense technology** (e.g., Ionis)[378](index=378&type=chunk)[379](index=379&type=chunk) [Other Information](index=76&type=section&id=ITEM%205.%20OTHER%20INFORMATION) This section discloses that during Q2 2025, certain officers and directors entered into Rule 10b5-1 trading plans for the future sale of company securities - During the quarter ended June 30, 2025, certain officers and directors adopted **Rule 10b5-1 trading plans** for the sale of company securities, including: - **Dennis A. Ausiello, M.D.** (Director) - **Colleen F. Reitan** (Director) - **Tolga Tanguler** (Chief Commercial Officer)[405](index=405&type=chunk)[406](index=406&type=chunk)[407](index=407&type=chunk)[408](index=408&type=chunk) [Exhibits](index=77&type=section&id=ITEM%206.%20EXHIBITS) This section lists exhibits filed with the Form 10-Q, primarily consisting of certifications from the principal executive and financial officers and Inline XBRL documents - The exhibits filed with this report include **certifications by the CEO and CFO** pursuant to SEC rules, as well as **Inline XBRL data files**[409](index=409&type=chunk)

[Executive Summary](index=1&type=section&id=Executive%20Summary) 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](index=1&type=section&id=Q2%202025%20Performance%20Overview) 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](index=1&type=chunk) - Total TTR Revenues were **$544 Million**, showing a **77% growth** compared to Q2 2024, largely due to AMVUTTRA sales in ATTR-CM[1](index=1&type=chunk)[2](index=2&type=chunk) - Approximately **1,400 ATTR-CM patients** were on AMVUTTRA as of June 30, 2025[1](index=1&type=chunk) - AMVUTTRA received approvals for ATTR-CM treatment in the European Union, Brazil, the United Kingdom, and Japan[1](index=1&type=chunk) - The company initiated the TRITON-CM Phase 3 Trial of Nucresiran in patients with wild-type or hereditary ATTR-CM[1](index=1&type=chunk) 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](index=2&type=section&id=Second%20Quarter%202025%20and%20Recent%20Significant%20Business%20Highlights) This section details Alnylam's product performance, pipeline advancements, and key upcoming events for Q2 2025 [Product Performance Highlights](index=2&type=section&id=Product%20Performance%20Highlights) 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)](index=2&type=section&id=Total%20TTR%3A%20AMVUTTRA%20(vutrisiran)%20%26%20ONPATTRO%20(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](index=7&type=chunk) - AMVUTTRA received regulatory approvals for ATTR-CM in Brazil, the European Commission, UK MHRA, and Japanese PMDA[7](index=7&type=chunk) - 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](index=7&type=chunk) [Total Rare: GIVLAARI (givosiran) & OXLUMO (lumasiran)](index=2&type=section&id=Total%20Rare%3A%20GIVLAARI%20(givosiran)%20%26%20OXLUMO%20(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](index=2&type=section&id=Pipeline%20%26%20Clinical%20Development%20Updates) 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](index=7&type=chunk) - 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](index=7&type=chunk) - 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](index=8&type=chunk) - Initiated a Phase 1 clinical trial for ALN-4324, an insulin sensitizer targeting GRB14 for type 2 diabetes[8](index=8&type=chunk) - Partner Agios Pharmaceuticals received IND clearance for AG-236 (ALN-TMP) for polycythemia vera (PV) and initiated a Phase 1 study[8](index=8&type=chunk) [Key Upcoming Events](index=3&type=section&id=Key%20Upcoming%20Events) 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](index=10&type=chunk) - Expected to initiate a Phase 3 cardiovascular outcomes trial of zilebesiran in collaboration with Roche in H2 2025[13](index=13&type=chunk) - Expected to initiate the TRITON-PN Phase 3 trial of nucresiran in hATTR-PN in H2 2025[13](index=13&type=chunk) - Expected to initiate a Phase 2 trial of mivelsiran in Alzheimer's disease in H2 2025[13](index=13&type=chunk) - Partner Regeneron Pharmaceuticals plans to share results from the Phase 3 trial of cemdisiran in myasthenia gravis in H2 2025[11](index=11&type=chunk) [Financial Results for the Quarter Ended June 30, 2025](index=3&type=section&id=Financial%20Results%20for%20the%20Quarter%20Ended%20June%2030%2C%202025) 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](index=3&type=section&id=Consolidated%20Financial%20Results%20Overview) 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](index=4&type=section&id=Revenue%20Analysis) 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](index=15&type=chunk) - 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](index=16&type=chunk) [Operating Expenses Analysis](index=4&type=section&id=Operating%20Expenses%20Analysis) 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](index=18&type=chunk) - 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](index=19&type=chunk) - 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](index=20&type=chunk) [Other Financial Items](index=5&type=section&id=Other%20Financial%20Items) 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](index=21&type=chunk) - 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](index=22&type=chunk) - Provision for income taxes was **$30.9 million**, mainly due to income in Switzerland and state income taxes in the U.S[23](index=23&type=chunk) [Financial Position & Cash Flow](index=5&type=section&id=Financial%20Position%20%26%20Cash%20Flow) 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](index=26&type=chunk) - The increase in cash was primarily driven by net cash inflows from operating activities and proceeds from the exercise of employee stock options[26](index=26&type=chunk) - Net cash provided by operating activities included **$14.4 million** of payments associated with the Leqvio royalties liability[26](index=26&type=chunk) - 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](index=26&type=chunk) [2025 Financial Guidance](index=6&type=section&id=2025%20Financial%20Guidance) 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](index=6&type=section&id=Use%20of%20Non-GAAP%20Financial%20Measures) 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](index=29&type=chunk) - The company believes non-GAAP measures provide useful information to management and investors for evaluating performance, allocating resources, and planning[31](index=31&type=chunk) - Percentage changes in revenue growth at Constant Exchange Rates (CER) are presented to show underlying business performance without foreign currency fluctuations[30](index=30&type=chunk) [Company and Product Information](index=7&type=section&id=Company%20and%20Product%20Information) This section provides detailed information about Alnylam Pharmaceuticals and its key commercial products [About AMVUTTRA (vutrisiran)](index=7&type=section&id=About%20AMVUTTRA%20(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](index=34&type=chunk) - Administered quarterly via subcutaneous injection by a healthcare professional[34](index=34&type=chunk) - 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](index=34&type=chunk) [About ONPATTRO (patisiran)](index=7&type=section&id=About%20ONPATTRO%20(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](index=35&type=chunk) - Approved in the U.S., Canada, EU, Switzerland, Brazil, and Japan for hATTR amyloidosis with polyneuropathy[35](index=35&type=chunk) - Designed to silence TTR messenger RNA, reducing TTR protein production and amyloid deposits[35](index=35&type=chunk) [About GIVLAARI (givosiran)](index=7&type=section&id=About%20GIVLAARI%20(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](index=36&type=chunk) - Approved in the U.S., Brazil, and EU for the treatment of adults and adolescents (12+) with acute hepatic porphyria (AHP)[36](index=36&type=chunk) - Significantly reduces the rate of porphyria attacks requiring hospitalization, urgent healthcare visits, or IV hemin[36](index=36&type=chunk) - Administered once monthly via subcutaneous injection, utilizing Alnylam's Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology[36](index=36&type=chunk) [About OXLUMO (lumasiran)](index=7&type=section&id=About%20OXLUMO%20(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](index=37&type=chunk) - 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](index=37&type=chunk) - Utilizes Alnylam's ESC-GalNAc-conjugate technology for subcutaneous dosing[37](index=37&type=chunk) - Demonstrated significant reductions in urinary oxalate in pivotal trials, with injection site reactions as the most common drug-related adverse reaction[37](index=37&type=chunk) [About Alnylam Pharmaceuticals](index=8&type=section&id=About%20Alnylam%20Pharmaceuticals) 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](index=40&type=chunk) - Commercial RNAi therapeutic products include AMVUTTRA, ONPATTRO, GIVLAARI, and OXLUMO, with Leqvio and Qfitlia commercialized by partners[40](index=40&type=chunk) - Executing on its 'Alnylam P x25' strategy to deliver transformative medicines, achieve sustainable profitability, and become a leading biotech company[40](index=40&type=chunk) [Alnylam Forward Looking Statements](index=8&type=section&id=Alnylam%20Forward%20Looking%20Statements) 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](index=41&type=chunk) - 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](index=41&type=chunk)[42](index=42&type=chunk) - The company explicitly disclaims any obligation to update forward-looking statements, except as required by law[42](index=42&type=chunk) [Condensed Consolidated Financial Statements](index=10&type=section&id=Condensed%20Consolidated%20Financial%20Statements) 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](index=10&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) 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](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) 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](index=12&type=section&id=Reconciliation%20of%20GAAP%20to%20Non-GAAP%20Measures) 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](index=13&type=section&id=Reconciliation%20of%20GAAP%20to%20Non-GAAP%20Product%20Revenue%20Growth%20at%20Constant%20Currency) 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% |

Core Viewpoint - The market anticipates Alnylam Pharmaceuticals (ALNY) to report a year-over-year decline in earnings despite an increase in revenues for the quarter ended June 2025, with actual results being crucial for stock price movement [1][2]. Financial Expectations - Alnylam is expected to report a quarterly loss of $0.03 per share, reflecting a year-over-year change of -105.4% [3]. - Revenues are projected to be $671.11 million, which is a 1.7% increase from the same quarter last year [3]. Estimate Revisions - The consensus EPS estimate has been revised 62.96% higher in the last 30 days, indicating a reassessment by analysts [4]. - A positive Earnings ESP of +831.25% suggests that analysts have recently become more optimistic about Alnylam's earnings prospects [12]. Earnings Surprise History - In the last reported quarter, Alnylam was expected to post a loss of $0.56 per share but actually reported a loss of -$0.01, resulting in a surprise of +98.21% [13]. - Over the past four quarters, Alnylam has beaten consensus EPS estimates three times [14]. Industry Comparison - Incyte (INCY), another player in the Zacks Medical - Biomedical and Genetics industry, is expected to post earnings of $1.4 per share for the same quarter, indicating a year-over-year change of +176.9% [18]. - Incyte's revenues are expected to reach $1.15 billion, up 10.3% from the previous year [18].