Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [6][37] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [38] - Gross margin on product sales remained at 85%, consistent with Q1 2024, but is expected to decrease for the remainder of the year due to escalating royalty rates [39][41] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase year-over-year, with U.S. sales growing by 45% [14][15] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, reflecting an 8% growth year-over-year [13] - The TTR franchise's growth was primarily driven by increased demand for ONPATTRO and Ambutra, with a 32% increase in demand noted [15][16] Market Data and Key Metrics Changes - In the U.S., Ambutra captured approximately 70% of new patient starts in the first quarter of 2025, indicating strong market leadership despite new competition [18] - Internationally, the TTR franchise grew by 24% compared to the first quarter of 2024, driven by robust patient uptake [16] - The company noted that about 80% of the global addressable population remains untreated, presenting significant growth opportunities [19] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [5][9] - The company is committed to achieving sustainable non-GAAP profitability in 2025 while continuing to advance its high-value pipeline [7][10] - Alnylam's strategy includes leveraging its innovative pipeline with multiple multibillion-dollar opportunities and maintaining strong financial performance through disciplined capital allocation [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning despite uncertainties related to potential policy changes, tariffs, and FDA reorganizations [7][8] - The management highlighted the strong early progress in the launch of Ambutra for ATTR cardiomyopathy and reiterated guidance for continued growth [6][37] - The company remains optimistic about achieving its 2025 goals, which include expanding access to its therapies and enhancing patient outcomes [10][26] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR cardiomyopathy, with positive opinions from regulatory bodies in Brazil and the EU [20][29] - The company is advancing its pipeline with new clinical programs targeting various diseases, including a Phase I study for ALN434 targeting Type 2 diabetes [34][35] Q&A Session Summary Question: What is the profile of prescribers for Ambutra? - Management noted a broad uptake among both experienced prescribers and new doctors, indicating strong initial engagement with the product [48][51] Question: How does the revenue from ATTR cardiomyopathy compare to previous products? - Management clarified that the revenue from ATTR cardiomyopathy did not contribute to Q1 results, as the approval came late in the quarter [55][60] Question: What strategies are being employed to compete with tafamidis? - Management emphasized the unique mechanism of action of Ambutra and its compelling clinical data, which positions it as a first-line treatment option [62][64] Question: What are the dynamics of reimbursement for Ambutra? - Management explained that Ambutra has a single price across indications and highlighted the effectiveness of their patient support programs in facilitating access [68][70] Question: What are the expectations for formulary inclusion? - Management aims to complete formulary inclusion for all priority health systems by year-end, with encouraging early results already seen [81][82] Question: How is the early uptake of Ambutra characterized? - Management indicated that early uptake includes both switch patients and new patients, reflecting a strong initial market response [100][102]

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 Insights - Vaxcyte, Inc. has appointed Dr. Olivier Brandicourt, former CEO of Sanofi S.A., to its Board of Directors, enhancing its leadership with significant biopharmaceutical expertise [1][2] - Dr. Brandicourt's experience in the global vaccine market is expected to be instrumental as Vaxcyte advances its pneumococcal conjugate vaccine (PCV) candidates towards potential commercialization [2] - Vaxcyte is focused on developing high-fidelity vaccines to combat bacterial diseases, with its lead candidates VAX-31 and VAX-24 targeting invasive pneumococcal disease [6][8] Company Overview - Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines aimed at preventing bacterial diseases [6] - The company is developing broad-spectrum conjugate and novel protein vaccines, including VAX-31, a 31-valent PCV candidate, and VAX-24, a 24-valent PCV candidate [6][8] - Vaxcyte utilizes modern synthetic techniques and the XpressCF™ cell-free protein synthesis platform to produce complex vaccines efficiently [7] Leadership Background - Dr. Brandicourt has a distinguished career in the biopharmaceutical industry, previously serving as CEO of Sanofi S.A. and Bayer HealthCare AG, and has extensive experience at Pfizer [3][4] - His leadership roles have included advancing vaccine portfolios and strategic insights in commercial execution within the vaccine market [2][4] Strategic Goals - Vaxcyte aims to set a new standard of care in the prevention of invasive pneumococcal disease and contribute to combating antimicrobial resistance [2][6] - The company is committed to addressing unmet needs in bacterial disease prevention through its innovative vaccine candidates [2][8]

Core Insights - MiMedx reported quarterly earnings of $0.06 per share, matching the Zacks Consensus Estimate, but down from $0.07 per share a year ago [1] - The company generated revenues of $88.21 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 2.56% and up from $84.71 million year-over-year [2] - MiMedx shares have declined approximately 28.1% year-to-date, contrasting with the S&P 500's decline of 5.5% [3] Earnings Outlook - The current consensus EPS estimate for the upcoming quarter is $0.07 on revenues of $93.5 million, and for the current fiscal year, it is $0.29 on revenues of $375 million [7] - The estimate revisions trend for MiMedx is mixed, resulting in a Zacks Rank 3 (Hold), indicating expected performance in line with the market [6] Industry Context - The Medical - Biomedical and Genetics industry, to which MiMedx belongs, is currently ranked in the top 32% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Alnylam Pharmaceuticals, another company in the same industry, is expected to report a quarterly loss of $0.56 per share, reflecting a significant year-over-year decline of 250% [9]

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].

Financial Data and Key Metrics Changes - Total revenue for Q4 2024 was $21.5 million, with product revenue of $9.8 million and R&D revenue of $11.6 million. For the year ended December 31, 2024, revenue was $59.3 million compared to $62 million in the prior year [29][31] - The net loss for Q4 2024 was $10.4 million, down from $15.3 million in Q4 2023. The net loss for the year was $65.3 million compared to $84.4 million in the prior year [37][40] - Product gross margin was 63% in Q4 2024, down from 71% in Q4 2023. For the year, gross margin was 56%, compared to 63% the prior year [34][35] Business Line Data and Key Metrics Changes - The company is focused on expanding its Pharma Biocatalysis business, which has shown growth and stable gross margins, providing a solid foundation for investment in new technologies [32][33] - The ECO Synthesis platform is expected to achieve commercial liftoff in 2025, transitioning from development to commercial execution [10][11] Market Data and Key Metrics Changes - The company is seeing increased customer engagement for its RNA ligase and ECO Synthesis platforms, with multiple feasibility studies completed with leading siRNA innovator companies [9][12] - The company aims to secure a CDMO scale-up partner in 2025 to facilitate larger scale manufacturing for clinical trials and commercial production [21][23] Company Strategy and Development Direction - The company is transitioning from a declining business model to one focused on growth, particularly through its ligase and ECO Synthesis platforms [32][33] - The strategy includes building a full-service development and manufacturing offering to capture the emerging drug innovator market [22][26] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving improved revenue growth in 2025 and beyond, driven by the maturation of the ligase and ECO services platform [32][38] - The company is guiding for total 2025 revenue in the range of $64 million to $68 million, expecting double-digit growth across its entire revenue base [38][40] Other Important Information - The company ended 2024 with $73.5 million in cash, cash equivalents, and short-term investments, which is expected to fund operations until achieving cash flow positivity by the end of 2026 [40] Q&A Session Summary Question: What will drive the value proposition in rare disease markets? - Management believes both validated platforms and successful case studies from larger indications will drive interest in rare disease markets [58] Question: How will the company communicate progress to the market? - The company will carefully balance communication of progress while maintaining confidentiality with partners [62] Question: Can you elaborate on the customer pipeline and revenue conversion? - The company indicated that relationships with customers are multifaceted and evolve over time, making it difficult to categorize them neatly [71][74] Question: What are the expectations for gross margins in 2025? - Management expects gross margins to improve year-over-year as they retire lower-margin products [85] Question: How will the GMP facility impact cash flow guidance? - The GMP facility is still in planning phases, and more visibility will be available in the summer [91] Question: Will the company consider alternative payment structures with cash-strapped innovators? - The company is open to sensible upfront payments in exchange for back-end economics, recognizing the financial constraints of smaller innovators [125]

Financial Data and Key Metrics Changes - In 2024, the company achieved combined net product revenues of over $1.646 billion, representing a 33% growth compared to 2023, and reached the upper end of the revised guidance range [8][44] - The company reported a non-GAAP operating income of $95 million for the full year, marking a significant milestone and a $156 million improvement compared to 2023 [8][47] - The gross margin on product sales was 81% for the full year, a 3% increase from 2023, primarily due to non-recurring prior year expenses [44][46] Business Line Data and Key Metrics Changes - The TTR franchise generated $343 million in global net product revenues in Q4 2024, a 35% increase compared to Q4 2023, driven by increased patient uptake [12][13] - The Rare franchise, including GIVLAARI and OXLUMO, delivered $108 million in combined product sales in Q4 2024, representing an 18% year-over-year growth [30][31] Market Data and Key Metrics Changes - In the U.S., the TTR franchise saw a 42% year-over-year increase in sales, driven by strong demand for AMVUTTRA and ONPATTRO [12][14] - Internationally, the TTR franchise grew 12% in Q4 compared to Q3 2024 and increased by 25% year-over-year [16] Company Strategy and Development Direction - The company aims to establish TTR leadership with vutrisiran potentially becoming a new standard of care in ATTR cardiomyopathy, supported by the advancement of next-generation TTR assets [9][10] - The strategy includes growth through innovation with a robust pipeline of clinical programs and a disciplined approach to capital allocation to sustain profitability [10][11] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism for 2025, highlighting it as a potential landmark year with expectations of continued growth driven by the TTR franchise and the upcoming launch of AMVUTTRA for ATTR cardiomyopathy [8][11] - The company is preparing for the regulatory decision on vutrisiran, with a PDUFA date set for March 23, 2025, and anticipates a ramp-up in demand post-approval [17][54] Other Important Information - The company ended 2024 with cash, cash equivalents, and marketable securities of $2.7 billion, an increase from $2.4 billion at the end of 2023 [48] - The company plans to host an R&D Day on February 25, 2025, to provide more comprehensive updates on its pipeline and development programs [41][54] Q&A Session Summary Question: How long will it take to establish payer policies after the approval of vutrisiran? - Management indicated that the formulary uptake will likely be meaningful in the second half of the year, with existing value-based agreements expected to facilitate this process [58][60] Question: Thoughts on AMVUTTRA's pricing and step edits for commercial insured patients? - Management expressed confidence in AMVUTTRA's product profile and anticipated smooth coverage from payers, similar to previous experiences with polyneuropathy [64][67] Question: Key factors impacting pricing adjustments for AMVUTTRA? - Management emphasized the importance of the product's value to patients and the ecosystem, with a J-code already in place to facilitate access [71][74] Question: Expectations for vutrisiran's potential revenue mix among naive patients versus switches from tafamidis? - Management expects a good mix of new patients and switches, positioning AMVUTTRA as a potential standard of care [96][98] Question: Competitive dynamics with Wainua in polyneuropathy? - Management noted strong growth in the TTR franchise despite competition, highlighting a differentiated product profile and continued market growth [102][105] Question: How will payer dynamics evolve in this category? - Management anticipates favorable coverage for AMVUTTRA, similar to previous experiences with polyneuropathy, and expects patient affordability to drive therapy adherence [115][118]

Fourth Quarter and Full Year 2024 Financial Results February 13, 2025 © 2025 Alnylam Pharmaceuticals, Inc. 1 Agenda Welcome • Christine Lindenboom Chief Corporate Communications Officer Overview • Yvonne Greenstreet, MBChB, MBA Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Pipeline • Pushkal Garg, M.D. Chief Medical Officer Financial Summary and Upcoming Milestones • Jeff Poulton Chief Financial Officer Q&A Session 2 Alnylam Forward Looking Statements This presentat ...

Financial Performance - Total revenues for 2024 reached $2,248,243, an increase of 23% compared to $1,828,292 in 2023, and a significant increase of 76% from $1,037,418 in 2022[491]. - Net product revenues increased to $1,646,228 in 2024, up 33% from $1,241,474 in 2023, driven primarily by sales of AMVUTTRA[492]. - The company reported a net loss of $278,157 for 2024, a decrease of 37% from a net loss of $440,242 in 2023[491]. - Total operating costs and expenses for 2024 were $2,425,128, reflecting a 15% increase from $2,110,467 in 2023[491]. - Net revenues from collaborations decreased to $510,221 in 2024, down 7% from $546,185 in 2023, primarily due to reduced revenue from the Roche collaboration[496]. - Royalty revenue increased significantly to $91,794 in 2024, a 126% increase from $40,633 in 2023, attributed to higher royalties from Leqvio sales by Novartis[496]. - The accumulated deficit as of December 31, 2024, was $7.29 billion, reflecting ongoing investments in research and development[488]. - The company anticipates achieving financial self-sustainability by the end of 2025, despite expected fluctuations in operating results[488]. Sales Performance - Sales of ONPATTRO decreased by 29% in 2024 compared to 2023, while AMVUTTRA sales surged by 74% during the same period[493]. - The company expects net revenues from collaborations to increase in 2025, driven by anticipated higher revenues under the Roche collaboration[498]. - AMVUTTRA sales in the United States surged to $630.6 million in 2024, compared to $411.2 million in 2023, reflecting a 53.3% growth[627]. Cost and Expenses - Cost of goods sold increased to $306.5 million in 2024, up 14% from $268.2 million in 2023, with a significant increase of 91% from $140.2 million in 2022[500]. - Cost of goods sold as a percentage of net product revenues decreased to 18.6% in 2024 from 21.6% in 2023, attributed to one-time charges in 2023 that did not recur[501]. - Research and development expenses rose to $1.1 billion in 2024, a 12% increase from $1.0 billion in 2023, and a 14% increase from $883.0 million in 2022[505]. - Selling, general and administrative expenses increased to $975.5 million in 2024, a 23% rise from $795.6 million in 2023, driven by marketing investments and higher employee compensation[507]. Cash Flow and Investments - Net cash used in operating activities was $(8.3) million in 2024, a decrease of $112.5 million compared to $104.2 million in 2023, primarily due to decreased cash received from collaborators[512]. - Net cash used in investing activities decreased to $(116.8) million in 2024 from $(336.4) million in 2023, mainly due to the timing of investments in marketable debt securities[514]. - Net cash provided by financing activities increased to $294.2 million in 2024, up $122.0 million from $172.1 million in 2023, primarily due to increased proceeds from stock options[515]. - Cash outflows for capital expenditures were $34.3 million in 2024, compared to $62.2 million in 2023, with expectations for an increase in 2025 to support manufacturing and production capacity needs[517]. Liabilities and Future Obligations - The liability related to the sale of future royalties totals approximately $1.02 billion, with no principal payments expected within the next 12 months[517]. - Payments to Blackstone associated with the liability related to the sale of future royalties were $57.0 million in 2024, with an estimated $131.8 million to be paid within the next 12 months[517]. - The company has established a development derivative liability of $486.9 million as of December 31, 2024[683]. Market Position and Strategy - The company aims to transition to a top-tier biotech company by the end of 2025 under its Alnylam P x25 strategy, focusing on sustainable innovation and exceptional financial performance[563]. - The company has five marketed products as of December 31, 2024, including one product commercialized by a collaborator[516]. - Alnylam has five marketed products as of December 31, 2024, generating worldwide product revenues primarily from ONPATTRO, AMVUTTRA, GIVLAARI, and OXLUMO[563]. Accounting and Revenue Recognition - The company recognizes revenue when control of promised goods or services is transferred to a customer, following a five-step model[8]. - Net product revenues are recognized net of variable consideration, with the expected value method used for estimating variable consideration related to product sales[11]. - The liability related to the sale of future royalties is accounted for as debt financing, with interest recognized using the effective interest rate method[14]. - The company does not capitalize any costs to obtain contracts as of December 31, 2024, and 2023[10]. Collaborations and Agreements - Roche made an upfront, non-refundable payment of $310.0 million as part of the collaboration agreement for the development of zilebesiran[637]. - The total transaction price under the Roche Agreement was determined to be $1.31 billion as of December 31, 2024, an increase of $457.5 million from the previous year[651]. - The Roche Agreement includes a $310.0 million upfront payment and $547.0 million in additional variable consideration related to development and manufacturing services[647]. - The company has earned $180.0 million in milestones from the collaboration with Novartis AG and is entitled to royalties ranging from 10% to 20% based on annual worldwide net sales[680].

·2 Alnylam Third Quarter 2024 Financial Results October 31, 2024 1© 2024 Alnylam Pharmaceuticals, Inc. Agenda Welcome • Christine Lindenboom Chief Corporate Communications Officer Overview • Yvonne Greenstreet, MBChB, MBA Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Alnylam Pipeline • Pushkal Garg, M.D. Chief Medical Officer Financial Summary and Upcoming Milestones • Jeff Poulton Chief Financial Officer Q&A Session 2 Alnylam Forward Looking Statements This present ...