Financial Data and Key Metrics Changes - In Q3 2024, Alnylam Pharmaceuticals achieved a 34% year-over-year growth in global net product revenue, generating $420 million across its four marketed products [6][38] - Net revenue from collaborations decreased by $370 million compared to the previous year, primarily due to the recognition of a $310 million upfront payment from Roche in Q3 2023 [39] - Royalty revenue for the quarter was $23 million, more than double the amount recognized in Q3 2023, driven by higher sales of Leqvio [40] - Gross margin on product sales improved to 80% from 75% in Q3 2023, attributed to lower costs associated with canceled manufacturing commitments in 2023 [41] Business Line Data and Key Metrics Changes - The TTR franchise generated $309 million in global net product revenues, reflecting a 34% increase year-over-year [11] - The rare franchise, including GIVLAARI and OXLUMO, delivered $111 million in combined net product sales, representing an 8% increase compared to Q2 2024 and 34% growth compared to Q3 2023 [18] Market Data and Key Metrics Changes - In the U.S., combined sales of ONPATTRO and AMVUTTRA increased by 37% year-over-year, driven by a 31% increase in demand for AMVUTTRA [13] - Internationally, the TTR franchise grew by 31% year-over-year, despite a 9% quarter-on-quarter decrease due to gross to net adjustments [14] Company Strategy and Development Direction - Alnylam aims to establish its TTR portfolio as a flagship franchise, similar to EYLEA for Regeneron, to drive long-term growth and investment in R&D [7] - The company is focused on advancing its pipeline, with plans to file proprietary INDs for 9 programs by the end of 2025, targeting various disease areas [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving the Alnylam P5x25 goals by year-end 2025, emphasizing a strong pipeline of first and/or best-in-class product candidates [9] - The management highlighted the significant unmet need in ATTR cardiomyopathy and the potential for vutrisiran to address this market upon regulatory approval [15][16] Other Important Information - Alnylam announced the decision to stop clinical development of ALN-KHK, focusing resources on more promising programs [35] - The company ended Q3 2024 with cash, cash equivalents, and marketable securities of $2.8 billion, an increase from $2.4 billion at the end of 2023 [45] Q&A Session Summary Question: Can you elaborate on the work done to improve RNAi delivery to adipose tissue and muscle? - Management highlighted the well-tolerated nature of RNAi therapeutics and the sustained knockdown of disease-causing proteins, guided by human genetics for disease validation [49][50] Question: Regarding ALN-HTT02, what are the expectations for Phase 1 data? - Management expressed excitement about the Huntington's program, emphasizing the potential for sustained knockdown and unique efficacy due to targeting the exon 1 fragment of the gene [54][56] Question: How has the second silencer impacted the market for polyneuropathy? - Management noted a 37% year-over-year growth in the U.S. for polyneuropathy treatments, indicating strong demand despite new competition [60][61] Question: What are the payer discussions regarding potential label expansion? - Management discussed the importance of clinical outcomes in payer discussions and the company's patient access philosophy, which aims to minimize co-pay burdens for patients [71][73] Question: How does the company view the potential for a bolus of patients seeking new treatments? - Management indicated that the fast progression of ATTR cardiomyopathy will lead to early diagnosis and treatment, positioning AMVUTTRA as a first-line therapy [82][84] Question: What are the expectations for the acoramidis label and its relevance to Alnylam's launch? - Management expressed confidence in their data from HELIOS-B and indicated that they are closely monitoring the acoramidis label [87][88] Question: How should spending levels in SG&A be viewed relative to the upcoming launches? - Management indicated an expectation of double-digit growth in SG&A as they prepare for the launches in both the U.S. and Europe [93] Question: What are the company's thoughts on potential business development activities? - Management emphasized the focus on internal pipeline growth while remaining open to opportunities that enhance their platform [102]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 ____________________________________________ FORM 10-Q ____________________________________________ ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Title of Each Class Trading Symbol(s) Name of Each Exchange on Which Registered Common Stock, $0.01 par value per share ALNY The Nasdaq Stock Market LLC For the quarterly period ended September 30, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 O ...

Financial Data and Key Metrics Changes - In Q2 2024, Alnylam Pharmaceuticals achieved a 34% year-over-year growth in global net product revenues, totaling $410 million, primarily driven by a 37% increase in the TTR business [7][11][25] - The company raised its revenue guidance for the year by 11% at the midpoint, reflecting strong commercial performance [7][30] - Total product revenue for Q2 was $410 million, a 34% increase compared to Q2 2023, with TTR and rare franchises growing by 37% and 25%, respectively [25][26] Business Line Data and Key Metrics Changes - The TTR franchise generated $307 million in global net product revenues, marking a 16% increase from Q1 2024 and a 37% increase from Q2 2023 [11][12] - The rare disease franchise, including GIVLAARI and OXLUMO, reported $13 million in global revenues, with a 25% year-over-year growth [16] - GIVLAARI sales increased by 7% year-over-year, while OXLUMO saw a robust 68% growth [16] Market Data and Key Metrics Changes - In the U.S., combined sales of ONPATTRO and AMVUTTRA increased by 16% from Q1 and 40% year-over-year, driven by strong demand for AMVUTTRA [12] - Internationally, TTR franchise growth also increased by 16% from Q1 and 35% year-over-year, primarily due to AMVUTTRA demand [13] Company Strategy and Development Direction - Alnylam aims to become a top-tier biotech company by developing transformative medicines for rare and prevalent diseases, supported by a high-yielding pipeline [9] - The company is preparing for a potential launch of vutrisiran in ATTR cardiomyopathy, which is expected to significantly enhance its commercial portfolio [8][15] - Alnylam is focused on establishing vutrisiran as the standard of care in ATTR-CM, leveraging its strong relationships with TTR centers and integrated customer-facing teams [15] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving financial goals, including a compounded annual growth rate of over 40% and sustainable non-GAAP operating income [30] - The positive results from the HELIOS-B study are expected to position vutrisiran as a first-line treatment option, addressing significant unmet medical needs [19][38] Other Important Information - Alnylam plans to host a TTR Investor Day on October 9, 2024, to discuss its leadership in ATTR amyloidosis [9][31] - The company is advancing its pipeline with multiple clinical studies, including a supplemental NDA filing for vutrisiran in late 2024 [20][32] Q&A Session Summary Question: Can you discuss the reimbursement landscape in ATTR cardiomyopathy? - Management highlighted the importance of seamless patient access and minimizing co-pay burdens, leveraging the physician-administered nature of AMVUTTRA [33][35] Question: What feedback have you received from physicians regarding vutrisiran? - Physicians are enthusiastic about the potential of vutrisiran to become the standard of care, especially given the impressive HELIOS-B results [37][39] Question: Will you report KM curves and time to events kinetics at the ESC? - Management confirmed plans to provide detailed results, including baseline characteristics and primary endpoint data, at the upcoming ESC Congress [43][46] Question: Can you provide updates on the ALN-APP program? - The ALN-APP program is progressing well, with ongoing studies in both Alzheimer's disease and cerebral amyloid angiopathy [50][60] Question: How has the nature of discussions with physicians changed since Eplontersen's launch? - Discussions have evolved positively, with increased clarity on product differentiation and the potential for market growth [62][64] Question: What is the strategy for growing the market beyond taking share from tafamidis? - Management emphasized the importance of demonstrating the efficacy of vutrisiran and its unique mechanism of action to access a broader patient population [78][80]

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=6&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS%20%28Unaudited%29) Alnylam Pharmaceuticals' unaudited financial statements for Q2 2024 show increased assets and revenues, a narrowed net loss, and positive operating cash flow [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet as of June 30, 2024, reflects an increase in total assets and a significant improvement in stockholders' deficit Balance Sheet Items (In thousands) | Balance Sheet Items (In thousands) | June 30, 2024 | December 31, 2023 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $968,492 | $812,688 | | Total current assets | $3,172,856 | $2,982,697 | | **Total assets** | **$4,009,634** | **$3,829,880** | | **Liabilities & Stockholders' Deficit** | | | | Total current liabilities | $1,055,251 | $967,786 | | **Total liabilities** | **$4,012,701** | **$4,050,524** | | **Total stockholders' deficit** | **$(3,067)** | **$(220,644)** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The statements of operations show a substantial increase in revenues and a significant reduction in net loss for both the quarter and six-month periods ended June 30, 2024 Statement of Operations (In thousands) | Statement of Operations (In thousands) | Three Months Ended June 30, 2024 | Three Months Ended June 30, 2023 | Six Months Ended June 30, 2024 | Six Months Ended June 30, 2023 | | :--- | :--- | :--- | :--- | :--- | | **Total revenues** | **$659,825** | **$318,754** | **$1,154,158** | **$638,044** | | Net product revenues | $410,088 | $305,705 | $775,251 | $582,033 | | Net revenues from collaborations | $227,338 | $5,844 | $345,886 | $42,306 | | Income (loss) from operations | $48,614 | $(229,831) | $5,179 | $(379,638) | | **Net loss** | **$(16,889)** | **$(276,024)** | **$(82,824)** | **$(450,125)** | | Net loss per common share | $(0.13) | $(2.21) | $(0.66) | $(3.62) | [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Cash flow statements for the first half of 2024 indicate a positive shift in operating cash flow and an overall net increase in cash and equivalents Cash Flow Activities (In thousands) | Cash Flow Activities (In thousands) | Six Months Ended June 30, 2024 | Six Months Ended June 30, 2023 | | :--- | :--- | :--- | | Net cash provided by (used in) operating activities | $42,643 | $(225,461) | | Net cash used in investing activities | $(33,680) | $(84,930) | | Net cash provided by financing activities | $160,407 | $99,765 | | **Net increase (decrease) in cash** | **$156,309** | **$(208,580)** | | Cash, cash equivalents and restricted cash, end of period | $971,193 | $659,976 | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes provide detailed insights into revenue drivers, significant liabilities, and ongoing patent infringement litigation - The company's strategy, **Alnylam Px25**, aims to transition it to a **top-tier biotech company** by the end of 2025 by delivering transformative medicines and achieving **strong financial performance**[29](index=29&type=chunk) Net Product Revenues (Six Months Ended June 30, In thousands) | Net Product Revenues (Six Months Ended June 30, In thousands) | 2024 | 2023 | | :--- | :--- | :--- | | ONPATTRO | $146,461 | $193,951 | | AMVUTTRA | $425,350 | $233,904 | | GIVLAARI | $120,183 | $105,805 | | OXLUMO | $83,257 | $48,373 | | **Total** | **$775,251** | **$582,033** | Net Revenues from Collaborations (Six Months Ended June 30, In thousands) | Net Revenues from Collaborations (Six Months Ended June 30, In thousands) | 2024 | 2023 | | :--- | :--- | :--- | | Roche | $91,186 | $— | | Regeneron Pharmaceuticals | $234,193 | $17,153 | | Novartis AG | $16,820 | $23,560 | | **Total** | **$345,886** | **$42,306** | - In June 2024, the company amended its agreement with Regeneron, granting a worldwide license for cemdisiran as a monotherapy, which resulted in the immediate recognition of **$191.5 million** in revenue[56](index=56&type=chunk)[61](index=61&type=chunk) - The company has filed **patent infringement lawsuits** against Pfizer/BioNTech and Moderna related to their mRNA COVID-19 vaccines, seeking damages, and these cases are ongoing[105](index=105&type=chunk)[106](index=106&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=28&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses the significant revenue growth, controlled expense increases, narrowed net loss, and strong liquidity position for the first half of 2024 [Overview](index=28&type=section&id=Overview) This section provides an overview of Alnylam's focus on RNAi therapeutics, its strategic goals, commercialized products, and recent positive clinical trial results - The company's **Alnylam Px25 strategy**, launched in 2021, focuses on transitioning to a **top-tier biotech company** by the end of 2025 through sustainable innovation and strong financial performance[110](index=110&type=chunk) - **Positive topline results** from the **HELIOS-B trial** of **vutrisiran** in patients with **ATTR amyloidosis with cardiomyopathy** were reported in June 2024, with plans for global regulatory filings later in the year[110](index=110&type=chunk) [Our Product Pipeline](index=30&type=section&id=Our%20Product%20Pipeline) The company maintains a robust product pipeline spanning commercial products and numerous clinical programs, with recent positive data readouts and regulatory advancements - The pipeline features **five commercial products** and a **broad range of clinical programs** across rare, specialty, and prevalent diseases[115](index=115&type=chunk) - Recent **positive data readouts** include the **HELIOS-B Phase 3 study** for vutrisiran and the **KARDIA-2 Phase 2 study** for zilebesiran[122](index=122&type=chunk) - Collaboration partner **Sanofi** has submitted **regulatory filings** for **fitusiran** in China, Brazil, and the U.S., with a U.S. FDA target action date of March 28, 2025[122](index=122&type=chunk) [Results of Operations](index=34&type=section&id=Results%20of%20Operations) Operating results for the first half of 2024 show substantial revenue growth, particularly from collaborations, alongside increased operating expenses and a significantly reduced net loss Financial Performance (Six Months Ended June 30, in thousands) | Financial Performance (Six Months Ended June 30) | 2024 (in thousands) | 2023 (in thousands) | % Change | | :--- | :--- | :--- | :--- | | **Total revenues** | **$1,154,158** | **$638,044** | **81%** | | Net product revenues | $775,251 | $582,033 | 33% | | Net revenues from collaborations | $345,886 | $42,306 | >500% | | **Total operating costs and expenses** | **$1,148,979** | **$1,017,682** | **13%** | | Research and development | $555,137 | $479,095 | 16% | | Selling, general and administrative | $459,194 | $398,348 | 15% | | **Net loss** | **$(82,824)** | **$(450,125)** | **(82)%** | - The increase in collaboration revenue was primarily driven by the modification of the Regeneron agreement, which resulted in the immediate recognition of **$191.5 million** for the cemdisiran monotherapy license[134](index=134&type=chunk) - **R&D expenses increased** due to costs for preclinical activities, clinical trials for zilebesiran (KARDIA-3) and mivelsiran (cAPPRicorn-1), and expenses related to the HELIOS-B trial data readout[141](index=141&type=chunk) [Liquidity and Capital Resources](index=38&type=section&id=Liquidity%20and%20Capital%20Resources) The company's liquidity position is strong, with sufficient cash to fund operations and achieve self-sustainability without future equity financing, supported by positive operating cash flow - The company believes its current cash position will be sufficient to achieve a **self-sustainable profile** without the need for **future equity financing**[151](index=151&type=chunk) Cash Flow Summary (Six Months Ended June 30, In thousands) | Cash Flow Summary (Six Months Ended June 30, In thousands) | 2024 | 2023 | | :--- | :--- | :--- | | Net cash provided by (used in) operating activities | $42,643 | $(225,461) | | Net cash used in investing activities | $(33,680) | $(84,930) | | Net cash provided by financing activities | $160,407 | $99,765 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=39&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) There have been no significant changes to the company's financial market risk exposures, primarily related to interest rates, since the prior fiscal year-end - There have been **no significant changes** to the company's financial market risk exposures, which are mainly related to **interest rates**, since December 31, 2023[152](index=152&type=chunk) [Item 4. Controls and Procedures](index=39&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management concluded that disclosure controls and procedures were effective as of June 30, 2024, with no material changes to internal control over financial reporting - As of June 30, 2024, the CEO and CFO concluded that the company's disclosure controls and procedures were **effective**[153](index=153&type=chunk) - **No material changes** were made to the internal control over financial reporting during the quarter ended June 30, 2024[154](index=154&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=41&type=section&id=ITEM%201.%20LEGAL%20PROCEEDINGS) This section refers to Note 13 for details on material pending legal proceedings, primarily patent infringement lawsuits against Pfizer and Moderna - For details on legal proceedings, the report refers to Note 13, which discusses ongoing **patent infringement lawsuits** against Pfizer and Moderna[156](index=156&type=chunk) [Item 1A. Risk Factors](index=41&type=section&id=ITEM%201A.%20RISK%20FACTORS) The company faces diverse risks including financial performance, operational dependencies, clinical and regulatory challenges, intellectual property disputes, and market competition - Key business risks include the unsuccessful marketing of approved products, a history of financial losses (**$7.09 billion accumulated deficit** as of June 30, 2024), and the need for substantial future funding[158](index=158&type=chunk)[169](index=169&type=chunk) - The company is **highly dependent on third parties** for collaborations (e.g., Roche, Regeneron, Novartis), manufacturing, and conducting clinical trials, and failure by these parties could delay or terminate programs[158](index=158&type=chunk)[178](index=178&type=chunk) - Significant industry risks include potential **clinical trial failures**, inability to obtain **regulatory approval** (as exemplified by the FDA's CRL for patisiran for cardiomyopathy), ongoing regulatory oversight, and **unfavorable pricing regulations** or healthcare reforms like the Inflation Reduction Act[159](index=159&type=chunk)[190](index=190&type=chunk)[199](index=199&type=chunk) - **Intellectual property** is a major risk area, with potential for **patent challenges**, **litigation costs** (including ongoing lawsuits against Pfizer and Moderna), and the need to license third-party patents[163](index=163&type=chunk)[221](index=221&type=chunk) - The company faces **intense competition** from existing drugs and new technologies, including other RNAi and antisense therapies, which could render its products obsolete or noncompetitive[164](index=164&type=chunk)[226](index=226&type=chunk) [Item 5. Other Information](index=76&type=section&id=ITEM%205.%20OTHER%20INFORMATION) This section discloses executive Rule 10b5-1 trading plans and corrects the deadlines for stockholder proposals for the 2025 annual meeting - Executive Vice President Kevin Fitzgerald and Director Dennis A. Ausiello entered into **Rule 10b5-1 trading plans** in May 2024 for the potential sale of company stock[239](index=239&type=chunk)[240](index=240&type=chunk)[241](index=241&type=chunk) - The company **corrected the deadlines** for **stockholder proposals** for the 2025 annual meeting: proposals for inclusion in proxy materials are due by December 2, 2024, and other business must be noticed between January 16, 2025, and February 15, 2025[242](index=242&type=chunk)[243](index=243&type=chunk) [Item 6. Exhibits](index=77&type=section&id=ITEM%206.%20EXHIBITS) This section lists the exhibits filed with the Form 10-Q, including stock award agreements and required officer certifications - Exhibits filed include forms of **Performance Stock Unit**, **Restricted Stock Unit**, and **Nonstatutory Stock Option agreements**, as well as required **CEO and CFO certifications**[245](index=245&type=chunk)

Financial Data and Key Metrics Changes - In Q1 2024, Alnylam Pharmaceuticals reported total product revenues of $365 million, reflecting a 32% year-over-year growth compared to Q1 2023 [7][26] - The gross margin on product sales was 85%, consistent with Q1 2023, but expected to decrease for the remainder of 2024 due to higher royalties on AMVUTTRA [27][28] - Non-GAAP R&D expenses increased by 13% year-over-year, driven by investments in zilebesiran and the HELIOS-B trial [27] - Non-GAAP SG&A expenses rose by 15% year-over-year, indicating operating leverage as product sales grew by 32% [27] Business Line Data and Key Metrics Changes - The TTR franchise achieved $264 million in global net product revenues, representing a 29% growth year-over-year [11][12] - The rare franchise delivered $101 million in combined global net product revenue, marking a 40% increase compared to Q1 2023 [16][17] - AMVUTTRA's U.S. sales increased by 35% year-over-year, driven by strong patient uptake [11][12] Market Data and Key Metrics Changes - The U.S. TTR sales saw a 39% increase in total demand compared to Q1 2023, despite a decrease in patients switching from ONPATTRO to AMVUTTRA [12][14] - International TTR franchise growth increased by 23% year-over-year, primarily due to AMVUTTRA demand in newly launched markets [13][14] Company Strategy and Development Direction - Alnylam aims to position itself as a leader in treating cardiovascular disease through its zilebesiran hypertension program, which has shown positive results in clinical trials [8][21] - The company is focused on advancing its pipeline with plans to file proprietary INDs for nine programs by the end of 2025, aiming to double its clinical pipeline [24][29] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in a strong start to 2024, with expectations for continued revenue growth and successful outcomes from ongoing clinical trials [7][9] - The company remains optimistic about the HELIOS-B Phase 3 study results, which are expected to support a supplemental NDA filing by the end of 2024 if positive [9][20] Other Important Information - Alnylam ended Q1 2024 with cash, cash equivalents, and marketable securities of $2.4 billion, indicating a stable financial position [28] - The company reiterated its 2024 guidance for combined net product revenues between $1.4 billion and $1.5 billion, reflecting a growth rate of 13% to 21% [29] Q&A Session Summary Question: What is the relevant improvement over the control arm for HELIOS-B? - Management emphasized that delivering outcomes in the HELIOS-B study is crucial and that they are focused on demonstrating clinical significance in terms of mortality and hospitalization [34][36] Question: What would be the organizational changes if HELIOS-B succeeds or fails? - If HELIOS-B succeeds, no changes to spending guidance are anticipated. However, if it fails, prioritization across the business would be necessary [40][41] Question: How important is the ratio between hospitalization events and deaths in HELIOS-B? - Management indicated that both hospitalization and mortality events are clinically meaningful and should trend in the same direction [70][72] Question: What proportion of patients are mixed phenotype in ATTR? - It was noted that a significant proportion of patients with wild type ATTR may have concomitant polyneuropathy, highlighting the complexity of the disease [75][76] Question: Will subgroup information be shared in the top line release for HELIOS-B? - Management confirmed that they plan to provide information on primary and secondary endpoints, including subgroup analyses, during the top line results presentation [61][80]

Financial Performance - Alnylam's combined net product revenue reached $365 million, a 32% year-over-year growth compared to Q1 2023[10] - The company's total revenue increased by 55% year-over-year, reaching $494 million in Q1 2024[37] - Alnylam is reiterating its full-year 2024 net product revenue guidance of $1400 million to $1500 million, representing a 13% to 21% growth compared to 2023[38] - Non-GAAP operating profit was $2 million, a significant improvement compared to a $110 million loss in Q1 2023[37] - Cash and investments totaled $2371 million as of March 31, 2024[37] Commercial Highlights - AMVUTTRA is a clear market leader in the treatment of hATTR-PN, with over 95% of patients complying with the dosing regimen[14] - U S TTR franchise YoY growth was +35%, driven by demand for AMVUTTRA[13] - OXLUMO YoY growth of +77% driven by strong demand[18] Pipeline Development - Topline results from the HELIOS-B Phase 3 clinical study of Vutrisiran in ATTR amyloidosis patients with cardiomyopathy are expected in late June/early July 2024[21] - Zilebesiran continues to demonstrate the potential to transform the treatment of hypertension[24] - Alnylam plans to file 3 new INDs (Investigational New Drug applications)[40]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 ____________________________________________ FORM 10-Q ____________________________________________ ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Title of Each Class Trading Symbol(s) Name of Each Exchange on Which Registered Common Stock, $0.01 par value per share ALNY The Nasdaq Stock Market LLC For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15 ...

Fourth Quarter and Full Year 2023 Financial Results February 15, 2024 1 © 2024 Alnylam Pharmaceuticals, Inc. Agenda Welcome • Christine Lindenboom ...

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) Q4 2023 Earnings Conference Call February 15, 2024 8:30 AM ET Company Participants Christine Lindenboom - Senior Vice President, Investor Relations and Corporate Communications Yvonne Greenstreet - Chief Executive Officer Tolga Tanguler - Chief Commercial Officer Pushkal Garg - Chief Medical Officer Jeff Poulton - Chief Financial Officer Akshay Vaishnaw - Chief Innovation Officer Conference Call Participants Ritu Baral - TD Paul Matteis - Stifel Ellie Merle - UBS ...

Financial Performance - Total revenues for the year ended December 31, 2023, were $1,828,292, a 76% increase from $1,037,418 in 2022[221]. - Net product revenues increased to $1,241,474 in 2023, up 39% from $894,329 in 2022, primarily due to the launch of AMVUTTRA[225]. - Net revenues from collaborations surged to $546,185 in 2023, a 305% increase from $134,912 in 2022, driven by revenue from Roche and Novartis[226]. - The net loss for 2023 was $440,242, a 61% reduction compared to a net loss of $1,131,156 in 2022[221]. - Total revenues for the year 2023 reached $1.83 billion, a 76.2% increase from $1.04 billion in 2022[270]. - The company recorded a net loss of $440.2 million for 2023, compared to a net loss of $1.13 billion in 2022, indicating a 61.0% improvement[270]. Operating Costs and Expenses - Operating costs and expenses rose to $2,110,467 in 2023, reflecting a 16% increase from $1,822,490 in 2022[221]. - Research and development expenses increased to $1.0 billion in 2023, a 14% increase from $883.0 million in 2022, driven by higher headcount and clinical trial costs[229][233]. - Selling, general and administrative expenses rose to $795.6 million in 2023, a 3% increase from $770.7 million in 2022, attributed to investments supporting strategic growth[236]. - Total operating costs and expenses increased by 16% in 2023, reaching $2.1 billion compared to $1.8 billion in 2022[229]. Cash Flow and Liquidity - Net cash provided by operating activities for the year ended December 31, 2023, was $104.2 million, a significant increase from a cash used of $(541.3) million in 2022, primarily due to a $310.0 million up-front payment from Roche and a $100.0 million payment from Regeneron[241]. - As of December 31, 2023, the company had cash, cash equivalents, and marketable securities totaling $2.44 billion, up from $2.19 billion in 2022[245]. - Cash and cash equivalents decreased to $812.7 million in 2023 from $866.4 million in 2022, a decline of 6.2%[265]. - The total cash, cash equivalents, and restricted cash shown in the consolidated statements of cash flows was $814,884 as of December 31, 2023, down from $868,556 in 2022, a decrease of about 6.2%[367]. Revenue Sources - ONPATTRO's total net revenues decreased by 36% to $354,546 in 2023, compared to $557,608 in 2022, due to patient switches to AMVUTTRA[225]. - AMVUTTRA generated total net revenues of $557,838 in 2023, marking a significant increase of 495% from $93,795 in 2022[225]. - Royalty revenue increased to $40,633 in 2023, a 397% rise from $8,177 in 2022[226]. - GIVLAARI's total net revenues increased to $219.3 million in 2023 from $173.1 million in 2022, reflecting a growth of approximately 26.7%[319]. - OXLUMO's total net revenues rose to $109.8 million in 2023, compared to $69.8 million in 2022, marking a growth of about 57.3%[319]. Collaborations and Agreements - Revenue from collaborations recognized an additional $30.0 million in 2023 compared to 2022, primarily from commercialization and regulatory milestones achieved under the Novartis Collaboration Agreement[227]. - Roche made an upfront, nonrefundable payment of $310 million as part of a collaboration agreement for the development of zilebesiran, with potential contingent payments of up to $1.24 billion based on milestones[329]. - Regeneron Pharmaceuticals made an upfront payment of $400.0 million as part of the collaboration agreement[336]. - The company will lead the global clinical development for zilebesiran, sharing development costs with Roche at a ratio of 40% to 60%[329]. Assets and Liabilities - The company had an accumulated deficit of $7.01 billion as of December 31, 2023[218]. - Total assets increased to $3.83 billion in 2023, compared to $3.55 billion in 2022, marking a 7.9% growth[265]. - Total liabilities rose to $4.05 billion in 2023, up from $3.70 billion in 2022, reflecting a 9.5% increase[266]. - The liability related to the sale of future royalties was recorded at $1.38 billion as of December 31, 2023, with an interest expense of $106.6 million recognized for the year[261]. Stock and Compensation - The company reported stock-based compensation expense of $221,680 thousand for 2023, slightly down from $230,649 thousand in 2022[277]. - The total stock-based compensation expense for research and development in 2023 was $97,273 thousand, compared to $92,161 thousand in 2022[378]. - As of December 31, 2023, there were 1,025 thousand time-based restricted stock units outstanding, with a weighted-average fair value of $185.24 per share[385]. Future Outlook - The company aims to achieve financial self-sustainability by the end of 2025 while continuing to incur operating losses[218]. - The company anticipates a decrease in net revenues from collaborations in 2024, primarily due to reduced revenues from the Roche Collaboration and License Agreement[227]. - The company expects research and development and selling, general and administrative expenses to increase in 2024 as it advances its product candidates and expands its global commercial infrastructure[236]. Legal and Regulatory Matters - The company has ongoing patent infringement lawsuits against Pfizer and Moderna related to its biodegradable cationic lipids used in mRNA COVID-19 vaccines[410].