Part I. Financial Information [Financial Statements (Unaudited)](index=6&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS%20%28Unaudited%29) For the first quarter of 2025, Alnylam reported a **20% year-over-year increase** in total revenues to **$594.2 million**, driven by strong product sales, while recording a net loss of **$57.5 million**, an improvement from the **$65.9 million** loss in the same period last year, with total assets at **$4.21 billion** and sufficient capital to fund operations for at least the next 12 months [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Balance Sheet Summary (as of March 31, 2025) | Metric | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Current Assets** | $3,268,258 | $3,295,285 | | **Total Assets** | $4,213,811 | $4,239,983 | | **Total Current Liabilities** | $1,075,623 | $1,186,272 | | **Total Liabilities** | $4,098,376 | $4,172,895 | | **Total Stockholders' Equity** | $115,435 | $67,088 | [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Statement of Operations Summary (Three Months Ended March 31) | Metric | 2025 (in thousands) | 2024 (in thousands) | Change | | :--- | :--- | :--- | :--- | | **Total Revenues** | $594,189 | $494,333 | +20.2% | | Net Product Revenues | $468,538 | $365,163 | +28.3% | | Net Revenues from Collaborations | $99,185 | $118,548 | -16.3% | | **Income (Loss) from Operations** | $18,077 | $(43,435) | N/A | | **Net Loss** | $(57,479) | $(65,935) | +12.8% | | **Net Loss per Share** | $(0.44) | $(0.52) | +15.4% | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Cash Flow Summary (Three Months Ended March 31) | Activity | 2025 (in thousands) | 2024 (in thousands) | | :--- | :--- | :--- | | Net cash used in operating activities | $(118,314) | $(81,515) | | Net cash provided by (used in) investing activities | $113,769 | $(67,620) | | Net cash provided by financing activities | $44,084 | $28,911 | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) - The company has six marketed products and generates revenue from four: AMVUTTRA, ONPATTRO, GIVLAARI, and OXLUMO[24](index=24&type=chunk) - Based on the current operating plan, the company believes its cash, cash equivalents, and marketable securities as of March 31, 2025, are sufficient to fund operations for at least the next 12 months[29](index=29&type=chunk) Net Product Revenues by Product (Three Months Ended March 31) | Product | 2025 (in thousands) | 2024 (in thousands) | Change | | :--- | :--- | :--- | :--- | | **AMVUTTRA** | $309,992 | $195,241 | +59% | | **ONPATTRO** | $49,489 | $69,217 | -29% | | **GIVLAARI** | $66,968 | $58,056 | +15% | | **OXLUMO** | $42,089 | $42,649 | -1% | | **Total** | **$468,538** | **$365,163** | **+28%** | - Net revenues from collaborations decreased to **$99.2 million** in Q1 2025 from **$118.5 million** in Q1 2024, primarily because the 2024 period included a **$65.0 million** milestone payment from Roche, partially offset by a **$30.0 million** payment from Vir Biotechnology in Q1 2025[39](index=39&type=chunk)[53](index=53&type=chunk)[71](index=71&type=chunk) - The company is involved in patent infringement lawsuits against Pfizer/BioNTech and Moderna concerning their mRNA COVID-19 vaccines, and is also being sued by the University of Texas over its ONPATTRO product[96](index=96&type=chunk)[106](index=106&type=chunk)[108](index=108&type=chunk) [Management's Discussion and Analysis (MD&A)](index=25&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses the company's performance, highlighting a **28% increase** in net product revenues, driven by AMVUTTRA's **59% growth**, while advancing its late-stage pipeline and executing its Alnylam P⁵x25 strategy to achieve sustainable operating profitability by the end of 2025, despite a **7% rise** in operating expenses and a **14% increase** in SG&A due to marketing investments, maintaining a strong liquidity position with **$2.63 billion** in cash and marketable securities [Overview and Pipeline](index=25&type=section&id=Overview%20and%20Pipeline) - The company is executing its **"Alnylam P⁵x25" strategy**, aiming to become a top-tier biotech company by the end of 2025 with sustainable innovation and strong financial performance[118](index=118&type=chunk) - AMVUTTRA received FDA approval in March 2025 for the treatment of the cardiomyopathy of ATTR amyloidosis, a significant label expansion[119](index=119&type=chunk) - Key late-stage pipeline programs include zilebesiran (hypertension), nucresiran (ATTR amyloidosis), and mivelsiran (Alzheimer's disease and CAA)[126](index=126&type=chunk)[127](index=127&type=chunk) [Results of Operations](index=31&type=section&id=Results%20of%20Operations) Revenue Breakdown (Three Months Ended March 31) | Revenue Type | 2025 (in thousands) | 2024 (in thousands) | % Change | | :--- | :--- | :--- | :--- | | Net product revenues | $468,538 | $365,163 | +28% | | Net revenues from collaborations | $99,185 | $118,548 | -16% | | Royalty revenue | $26,466 | $10,622 | +149% | | **Total Revenues** | **$594,189** | **$494,333** | **+20%** | - The **28% increase** in net product revenues was primarily driven by increased patient demand for AMVUTTRA, partially offset by a decrease in ONPATTRO sales due to patient switches to AMVUTTRA[158](index=158&type=chunk) - Collaboration revenue decreased mainly due to the recognition of a **$65.0 million** milestone from Roche in Q1 2024, partially offset by a **$30.0 million** payment from Vir and increased revenue from the Regeneron collaboration in Q1 2025[160](index=160&type=chunk)[164](index=164&type=chunk) - Royalty revenue increased **149%** due to higher global net sales of Leqvio by collaborator Novartis[160](index=160&type=chunk) - Selling, general and administrative (SG&A) expenses increased **14%** to **$239.9 million**, primarily due to increased marketing investment for TTR therapies and higher employee compensation[168](index=168&type=chunk) [Liquidity and Capital Resources](index=35&type=section&id=Liquidity%20and%20Capital%20Resources) - Net cash used in operating activities was **$118.3 million** for the quarter, an increase from **$81.5 million** in the prior year period, mainly due to higher bonus payouts and interest payments[174](index=174&type=chunk)[175](index=175&type=chunk) - The company believes its cash, cash equivalents, and marketable securities as of March 31, 2025, are sufficient to meet its capital and operating needs for at least the next 12 months[180](index=180&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=36&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) The company reports no significant changes in its financial market risk exposures, primarily related to interest rates, since December 31, 2024 - There have been no significant changes to the financial market risks described as of December 31, 2024[181](index=181&type=chunk) [Controls and Procedures](index=36&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal controls over financial reporting during the quarter - The CEO and CFO concluded that disclosure controls and procedures were effective at a reasonable assurance level as of March 31, 2025[182](index=182&type=chunk) - No changes in internal control over financial reporting occurred during the quarter that have materially affected, or are reasonably likely to materially affect, internal controls[183](index=183&type=chunk) Part II. Other Information [Legal Proceedings](index=37&type=section&id=ITEM%201.%20LEGAL%20PROCEEDINGS) This section refers to Note 12 of the financial statements, which details the company's material pending legal proceedings, including patent infringement lawsuits filed by Alnylam against Pfizer and Moderna, and a lawsuit filed against Alnylam by the University of Texas - For a discussion of material pending legal proceedings, the report refers to Note 12, Commitments and Contingencies, in the financial statements[184](index=184&type=chunk) [Risk Factors](index=37&type=section&id=ITEM%201A.%20RISK%20FACTORS) The company outlines significant risks to its business, including a history of **$7.35 billion** in accumulated losses and the need for substantial funding, heavy dependence on third parties for collaborations and manufacturing, prominent industry risks such as potential clinical trial failures, regulatory hurdles, intense competition for products like AMVUTTRA, pricing pressures from regulations like the Inflation Reduction Act, and significant legal risks from ongoing patent litigation with Pfizer, Moderna, and the University of Texas - The company has a history of significant operating losses, with an accumulated deficit of **$7.35 billion** as of March 31, 2025[196](index=196&type=chunk) - The company relies on third parties for manufacturing and collaborations, and failure by collaborators like Roche, Novartis, or Sanofi to perform could delay or terminate product development and commercialization[189](index=189&type=chunk)[216](index=216&type=chunk)[221](index=221&type=chunk) - AMVUTTRA faces competition from Pfizer's VYNDAQEL/VYNDAMAX and BridgeBio's ATTRUBY for ATTR-CM, both of which are oral medications with lower list prices[366](index=366&type=chunk) - The Inflation Reduction Act (IRA) could negatively impact business, for example by requiring rebates if drug prices increase faster than inflation or by subjecting products to Medicare price negotiation[301](index=301&type=chunk) - The company is engaged in significant patent litigation, including lawsuits against Pfizer and Moderna for infringement related to their mRNA COVID-19 vaccines, and is being sued by the University of Texas over its ONPATTRO product[351](index=351&type=chunk)[354](index=354&type=chunk) - The company has **$1.04 billion** in convertible notes outstanding and may not have sufficient cash flow to service this indebtedness or repurchase the notes if required[384](index=384&type=chunk)

Core Viewpoint - Analysts forecast a quarterly loss of $0.56 per share for Alnylam Pharmaceuticals, indicating a significant year-over-year decline of 250%, while revenues are expected to increase by 19% to $588.18 million [1]. Earnings Estimates - The consensus EPS estimate has been revised downward by 4.6% in the past 30 days, reflecting a reassessment by covering analysts [2]. - Revisions to earnings projections are crucial for predicting investor behavior and are linked to short-term stock price performance [3]. Revenue Projections - Analysts estimate 'Revenues- Product revenues, net' at $464.60 million, representing a year-over-year increase of 27.2% [5]. - 'Revenues- Royalty revenue' is projected to reach $30.71 million, indicating a substantial year-over-year increase of 189.1% [5]. - 'Revenues- Net revenues from research collaborators' are expected to be $93.37 million, showing a decline of 21.2% year-over-year [5]. Product Revenue Estimates - 'Net Product Revenues- Oxlumo' is estimated at $44.67 million, reflecting a 4.7% increase from the prior year [6]. - 'Net Product Revenues- Givlaari' is projected to be $67.46 million, indicating a 16.2% increase from the previous year [6]. - 'Net Product Revenues- Amvuttra' is expected to reach $300.02 million, showing a significant year-over-year increase of 53.7% [6]. - 'Net Product Revenues- Onpattro' is estimated at $51.23 million, indicating a year-over-year decline of 26% [7]. Stock Performance - Alnylam shares have decreased by 5.6% over the past month, contrasting with the Zacks S&P 500 composite's decline of 0.8% [7].

Company Overview - Alnylam Pharmaceuticals (ALNY) is expected to report a year-over-year decline in earnings with a quarterly loss of $0.56 per share, reflecting a -250% change, while revenues are anticipated to be $587.72 million, an increase of 18.9% from the previous year [3][12]. Earnings Expectations - The consensus EPS estimate has been revised 5.17% lower in the last 30 days, indicating a bearish sentiment among analysts regarding the company's earnings prospects [4][10]. - The Earnings ESP for Alnylam is -12.28%, suggesting a lower Most Accurate Estimate compared to the Zacks Consensus Estimate, which complicates the prediction of an earnings beat [11][10]. Historical Performance - Alnylam has beaten consensus EPS estimates three times in the last four quarters, with a notable surprise of +128.57% in the last reported quarter [12][13]. Industry Context - In the broader Zacks Medical - Biomedical and Genetics industry, GSK is expected to report earnings of $1.08 per share, reflecting a -0.9% year-over-year change, with revenues projected at $9.54 billion, up 2.2% from the previous year [17]. - GSK's consensus EPS estimate has also been revised 1.9% lower, resulting in an Earnings ESP of -0.93%, making it difficult to predict an earnings beat [18].

Company Overview - Alnylam Pharmaceuticals (ALNY) shares increased by 8.5% to close at $243.27, following a notable trading volume, contrasting with a 6% loss over the past four weeks [1] - The company is expected to report a quarterly loss of $0.55 per share, reflecting a year-over-year decline of 243.8%, while revenues are projected to be $587.45 million, an increase of 18.8% from the previous year [2] Earnings Estimates - The consensus EPS estimate for Alnylam has been revised 1.5% lower in the last 30 days, indicating a negative trend in earnings estimate revisions, which typically does not lead to price appreciation [3] - Alnylam holds a Zacks Rank of 3 (Hold), suggesting a neutral outlook [3] Industry Comparison - Alnylam is part of the Zacks Medical - Biomedical and Genetics industry, where Immunome, Inc. (IMNM) also operates, having seen an 11.7% increase in its stock price to $6.21, despite a -36.3% return over the past month [3] - Immunome's consensus EPS estimate has increased by 18.3% over the past month to -$0.67, representing a year-over-year change of -97.1%, and it also holds a Zacks Rank of 3 (Hold) [4]

Dublin, March 28, 2025 (GLOBE NEWSWIRE) -- The "Innovation Insights: siRNA gene silencing" report has been added to ResearchAndMarkets.com's offering. In terms of deals, there have been 334 deals totaling US$107 billion in the siRNA gene silencing sector. The United States and Ireland stand out with two major M&A deals worth $54.9 billion. The highest deal volume was observed in 2023, while the highest deal value was seen in 2020. The slight decline in 2021, followed by a slight increase in 2022, may indic ...

Core Insights - The U.S. FDA has approved Alnylam Pharmaceuticals' supplemental application for Amvuttra, making it the first and only therapeutic approved for treating ATTR-CM and hATTR-PN in adults [1][2] Group 1: Drug Approval and Indication - Amvuttra is indicated for adults with cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM), aimed at reducing cardiovascular mortality, hospitalizations, and urgent heart failure visits [1][2] - ATTR-CM is characterized by the misfolding of transthyretin (TTR) protein, leading to heart stiffness and potential heart failure [2] Group 2: Market Opportunity and Analyst Insights - JPMorgan has upgraded Alnylam to an Overweight rating, raising the price target from $280 to $328, citing a significant multi-billion dollar opportunity for Amvuttra in TTR amyloidosis [3][4] - Analyst Jessica Fye projects Amvuttra sales in cardiomyopathy to reach approximately $81 million in 2025, an increase from the previous estimate of $79 million [3] Group 3: Stock Performance - Following the news, ALNY stock rose by 3.50%, reaching $293.25 [5]

Alnylam Pharmaceuticals (ALNY) shares soared 11.8% in the last trading session to close at $283.34. The move was backed by solid volume with far more shares changing hands than in a normal session. This compares to the stock's 1% gain over the past four weeks.The sudden rise in the stock price can be attributed to the FDA approval of Alnylam's regulatory filing seeking the label expansion of its lead drug, Amvuttra (vutrisiran), for treating the cardiomyopathy of wild-type or hereditary transthyretin-mediat ...

Waiting is often the most frustrating part of biotech investing, as the stocks can drift without clear positive drivers, and such has been the case with Alnylam Pharmaceuticals, Inc. (NASDAQ: ALNY ) for much of the past year, withAnalyst’s Disclosure: I/we have a beneficial long position in the shares of ALNY, RHHBY either through stock ownership, options, or other derivatives. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alph ...

Core Viewpoint - Alnylam Pharmaceuticals received FDA approval for the label expansion of its lead drug, Amvuttra, to treat cardiomyopathy associated with transthyretin-mediated amyloidosis, marking a significant milestone as it becomes the first and only approved therapy for both ATTR-CM and hATTR-PN in adults [1][3][4] Company Overview - Amvuttra is an RNAi therapeutic previously approved for treating polyneuropathy associated with transthyretin-mediated amyloidosis in adults [2] - The drug generated sales of $970.5 million in 2024, reflecting a 74% year-over-year increase, driven by new patient treatments and switches from Onpattro [11] Clinical Data and Efficacy - The approval is based on positive results from the pivotal phase III HELIOS-B study, which met all primary and secondary endpoints with statistical significance [4] - Amvuttra demonstrated a reduction in mortality and cardiovascular events, while improving functional capacity, quality of life, and heart failure symptoms in ATTR-CM patients [6] Safety Profile - The safety profile of Amvuttra in the HELIOS-B study was consistent with its known profile for treating hATTR amyloidosis, with similar rates of adverse events between Amvuttra and placebo groups [7] Market Potential - Amvuttra enjoys near-universal insurance coverage for hATTR-PN, and similar coverage is anticipated for ATTR-CM, supported by strong clinical data [8] - Regulatory applications for Amvuttra's ATTR-CM indication are under review in the EU, Brazil, and Japan, with further applications expected in 2025 [9][10] Growth Prospects - Alnylam believes that Amvuttra has the potential to become the new standard of care for ATTR-CM, which could significantly expand the eligible patient population and drive substantial growth for the company [10]

Core Insights - The U.S. FDA approved Alnylam Pharmaceuticals' supplemental application for Amvuttra to treat adults with ATTR-CM, aiming to reduce cardiovascular mortality, hospitalizations, and urgent heart failure visits [1][2]. Group 1: Approval and Indications - Amvuttra is now the first and only FDA-approved therapy for both ATTR-CM and hATTR-PN in adults [2]. - ATTR-CM affects approximately 150,000 individuals in the U.S. and over 300,000 globally [2]. Group 2: Clinical Trial Results - The approval is based on the HELIOS-B Phase 3 clinical trial, which showed statistical significance on all 10 primary and secondary endpoints compared to placebo [3]. - Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 28% during a treatment period of up to 36 months [3]. - Mortality was significantly reduced by 36% through 42 months in a secondary endpoint analysis [4]. - In the monotherapy population, Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 33% and the risk of mortality by 35% through 42 months [4]. Group 3: Market Dynamics and Financials - Amvuttra in hATTR-PN is covered by insurers for around 99% of patients, with most paying nothing out-of-pocket, and similar coverage is expected for ATTR-CM [5]. - In 2024, Amvuttra sales reached $970.45 million, an increase from $557.84 million the previous year [6]. Group 4: Future Prospects - Marketing authorization applications based on HELIOS-B data are under review by several global health agencies, including the European Medicines Agency and the Brazilian Health Regulatory Agency [6]. - Alnylam plans to proceed with additional global regulatory submissions for vutrisiran in 2025 [6]. Group 5: Stock Performance - Following the approval news, ALNY stock rose by 8.46% to $274.98 [7].