CAMBRIDGE, Mass.--(BUSINESS WIRE)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced its preliminary* fourth quarter and full year 2023 global net product revenues for ONPATTRO, AMVUTTRA, GIVLAARI, and OXLUMO and provided additional updates on the products’ commercial launches. Preliminary Fourth Quarter and Full Year 2023 Commercial and Financial Performance* Total TTR: ONPATTRO® (patisiran) & AMVUTTRA® (vutrisiran) Preliminary global net product rev ...

Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) Q3 2023 Earnings Conference Call November 2, 2023 8:30 AM ET Company Participants Christine Lindenboom - Senior Vice President-Investor Relations and Corporate Communication Yvonne Greenstreet - Chief Executive Officer Tolga Tanguler - Chief Commercial Officer Pushkal Garg - Chief Medical Officer and EVP, Development & Medical Affairs Jeff Poulton - Chief Financial Officer Conference Call Participants Ritu Baral - TD Cowen Paul Matteis - Stifel Lisa Munro - RBC El ...

Nathan (USA) Diagnosed with AHP Third Quarter 2023 Financial Results November 2, 2023 1 © 2023 Alnylam Pharmaceuticals, Inc. Agenda Welcome ...

PART I. FINANCIAL INFORMATION [Financial Statements (Unaudited)](index=6&type=section&id=ITEM%201%2E%20FINANCIAL%20STATEMENTS%20%28Unaudited%29) Alnylam reported a **$147.8 million net income** in Q3 2023, a significant turnaround from a prior year loss, with total assets increasing to **$3.84 billion** and a narrowed nine-month net loss [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) The balance sheet highlights an increase in total assets to **$3.84 billion** by September 30, 2023, while the total stockholders' deficit slightly widened Condensed Consolidated Balance Sheet Highlights (In thousands) | Account | Sep 30, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $1,033,024 | $866,394 | | Total current assets | $2,985,452 | $2,692,247 | | **Total assets** | **$3,839,073** | **$3,546,359** | | **Liabilities & Stockholders' Deficit** | | | | Total current liabilities | $949,785 | $767,915 | | Convertible debt | $1,019,809 | $1,016,942 | | Liability related to the sale of future royalties | $1,355,009 | $1,292,204 | | **Total liabilities** | **$4,004,939** | **$3,704,582** | | **Total stockholders' deficit** | **($165,866)** | **($158,223)** | [Condensed Consolidated Statements of Operations and Comprehensive Income (Loss)](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Income%20%28Loss%29) The statement of operations shows a **$147.8 million net income** for Q3 2023, a significant improvement from a **$405.9 million net loss** in Q3 2022 Statement of Operations Summary (In thousands, except per share amounts) | Metric | Q3 2023 | Q3 2022 | 9 Months 2023 | 9 Months 2022 | | :--- | :--- | :--- | :--- | :--- | | Total revenues | $750,530 | $264,306 | $1,388,574 | $702,383 | | Net product revenues | $313,153 | $232,267 | $895,186 | $632,654 | | Net revenues from collaborations | $427,472 | $29,297 | $469,778 | $64,267 | | Total operating costs and expenses | $536,663 | $522,346 | $1,554,345 | $1,298,841 | | Income (loss) from operations | $213,867 | ($258,040) | ($165,771) | ($596,458) | | **Net income (loss)** | **$147,753** | **($405,920)** | **($302,372)** | **($923,663)** | | Net income (loss) per share - diluted | $1.15 | ($3.32) | ($2.43) | ($7.62) | [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Operating activities generated **$134.0 million** in cash for the nine months ended September 30, 2023, a significant improvement from cash usage in the prior year Cash Flow Summary for the Nine Months Ended September 30 (In thousands) | Activity | 2023 | 2022 | | :--- | :--- | :--- | | Net cash provided by (used in) operating activities | $133,951 | ($409,296) | | Net cash (used in) provided by investing activities | ($95,694) | $309,265 | | Net cash provided by financing activities | $132,903 | $362,316 | | **Net increase in cash, cash equivalents and restricted cash** | **$166,654** | **$253,236** | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's strategic goals, product revenue breakdown, key collaboration agreements, and ongoing patent litigation - The company's strategy, **Alnylam P5x25**, aims to transition it to a top-tier biotech company by the end of **2025** by delivering transformative medicines for rare and prevalent diseases[27](index=27&type=chunk) Net Product Revenues by Product (In thousands) | Product | Q3 2023 | Q3 2022 | 9 Months 2023 | 9 Months 2022 | | :--- | :--- | :--- | :--- | :--- | | ONPATTRO | $81,589 | $144,950 | $275,540 | $435,387 | | AMVUTTRA | $148,680 | $25,229 | $382,584 | $25,229 | | GIVLAARI | $54,148 | $45,659 | $159,953 | $126,086 | | OXLUMO | $28,736 | $16,429 | $77,109 | $45,952 | | **Total** | **$313,153** | **$232,267** | **$895,186** | **$632,654** | - In July 2023, Alnylam entered into a strategic collaboration with Roche for the joint development of zilebesiran, an investigational treatment for hypertension. The agreement included a **$310.0 million upfront payment** to Alnylam, which was recognized as revenue in Q3 2023[43](index=43&type=chunk)[45](index=45&type=chunk)[48](index=48&type=chunk) - Under the collaboration with Regeneron, Alnylam earned a **$100.0 million milestone** in Q3 2023 for achieving certain criteria in the early clinical development of its CNS program, ALN-APP. A **cumulative catch-up adjustment of $65.0 million** was recognized in net revenues from collaborations[49](index=49&type=chunk) - The company is involved in ongoing patent infringement lawsuits filed in March 2022 against **Pfizer/BioNTech** and **Moderna**, seeking damages related to the use of Alnylam's biodegradable cationic lipid technology in their respective **mRNA COVID-19 vaccines**[102](index=102&type=chunk)[103](index=103&type=chunk)[232](index=232&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=29&type=section&id=ITEM%202%2E%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management highlights **significant Q3 2023 revenue growth** from AMVUTTRA and the Roche collaboration, leading to net income and a strong cash position to fund the 'Alnylam P5x25' strategy [Overview](index=29&type=section&id=Overview) Alnylam, a commercial-stage biopharmaceutical company, focuses on RNAi therapeutics with five marketed products and aims for top-tier biotech status by **2025** - Alnylam is a commercial-stage biopharmaceutical company focused on **RNAi therapeutics**, with **five marketed products**: ONPATTRO, AMVUTTRA, GIVLAARI, OXLUMO, and the partnered product Leqvio (inclisiran)[107](index=107&type=chunk) - The company's '**Alnylam P5x25**' strategy aims to transition it into a top-tier biotech company by the end of **2025** through sustainable innovation and strong financial performance[107](index=107&type=chunk) - In October 2023, the FDA issued a **Complete Response Letter (CRL)** for the supplemental New Drug Application (sNDA) for **patisiran (ONPATTRO)** for the treatment of **ATTR amyloidosis with cardiomyopathy**, stating that clinical meaningfulness was not established[107](index=107&type=chunk) [Results of Operations](index=34&type=section&id=Results%20of%20Operations) Total revenues surged by **184%** in Q3 2023, primarily driven by collaboration revenue and strong AMVUTTRA sales, while operating costs increased moderately Revenue Breakdown (In thousands) | Revenue Source | Q3 2023 | Q3 2022 | % Change | | :--- | :--- | :--- | :--- | | Net product revenues | $313,153 | $232,267 | 35% | | Net revenues from collaborations | $427,472 | $29,297 | >500% | | Royalty revenue | $9,905 | $2,742 | 261% | | **Total revenues** | **$750,530** | **$264,306** | **184%** | - The substantial increase in collaboration revenue for Q3 2023 was primarily due to recognizing **$310.0 million** from the new Roche agreement and a **$65.0 million cumulative catch-up adjustment** from a milestone achieved under the Regeneron collaboration[132](index=132&type=chunk) - Net product revenue growth was driven by the strong launch of **AMVUTTRA**, which saw sales increase by **489% YoY** in Q3 2023. This was partially offset by a **44% YoY decline** in **ONPATTRO** revenue, largely due to patients switching to AMVUTTRA[129](index=129&type=chunk)[130](index=130&type=chunk) Operating Costs and Expenses (In thousands) | Expense Category | Q3 2023 | Q3 2022 | % Change | | :--- | :--- | :--- | :--- | | Cost of goods sold | $79,473 | $36,507 | 118% | | Research and development | $253,179 | $245,371 | 3% | | Selling, general and administrative | $199,175 | $235,859 | (16)% | | **Total operating costs and expenses** | **$536,663** | **$522,346** | **3%** | - Cost of goods sold as a percentage of net product revenues increased from **15.7%** in Q3 2022 to **25.4%** in Q3 2023, primarily due to an inventory impairment for **ONPATTRO** following the negative regulatory decision for its **cardiomyopathy indication**[134](index=134&type=chunk)[135](index=135&type=chunk) [Liquidity and Capital Resources](index=39&type=section&id=Liquidity%20and%20Capital%20Resources) Net cash from operating activities significantly improved to **$134.0 million** for the first nine months of 2023, supported by strong cash reserves - Net cash provided by operating activities for the first nine months of 2023 was **$134.0 million**, a significant improvement from the **$409.3 million used** in the same period of 2022. This was primarily due to the **$310.0 million upfront payment** from Roche and stronger cash receipts from product sales[145](index=145&type=chunk)[146](index=146&type=chunk) - Management believes that its cash, cash equivalents, and marketable securities of **$2.41 billion** as of September 30, 2023, along with expected revenues, will be sufficient to fund operations for at least the next **12 months**[150](index=150&type=chunk)[179](index=179&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=40&type=section&id=ITEM%203%2E%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) The company states that there have been no significant changes to its financial market risks, primarily related to interest rates, since the end of 2022 - There have been **no significant changes** to the company's financial market risk exposures, mainly **interest rate risk**, as of September 30, 2023, compared to December 31, 2022[151](index=151&type=chunk) [Controls and Procedures](index=40&type=section&id=ITEM%204%2E%20CONTROLS%20AND%20PROCEDURES) Management, including the CEO and CFO, evaluated the company's disclosure controls and procedures as of September 30, 2023, and concluded they were effective at a reasonable assurance level - The CEO and CFO concluded that the company's disclosure controls and procedures were **effective** as of September 30, 2023[152](index=152&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[153](index=153&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=41&type=section&id=ITEM%201%2E%20LEGAL%20PROCEEDINGS) The company refers to Note 13 of its financial statements for a discussion of material pending legal proceedings, primarily patent infringement lawsuits against Pfizer/BioNTech and Moderna - For details on material legal proceedings, the report refers to Note 13 of the financial statements, which discusses patent infringement lawsuits against **Pfizer** and **Moderna**[155](index=155&type=chunk) [Risk Factors](index=41&type=section&id=ITEM%201A%2E%20RISK%20FACTORS) The company faces significant risks including commercialization challenges, a history of losses, dependence on collaborators, regulatory hurdles, intense competition, and ongoing patent litigation - The commercial success of approved products is not guaranteed, and the company may be unable to expand indications, as exemplified by the FDA's **Complete Response Letter (CRL)** for patisiran's sNDA for **cardiomyopathy** in October 2023[169](index=169&type=chunk) - The company has a history of significant operating losses, with an accumulated deficit of **$6.87 billion** as of September 30, 2023, and may not achieve or maintain profitability[170](index=170&type=chunk) - Alnylam is dependent on strategic alliances with companies like **Roche**, **Novartis**, and **Regeneron** for development, commercialization, and funding, and the failure of these partners to perform could harm the business[182](index=182&type=chunk)[184](index=184&type=chunk) - The company faces **intense competition** from large pharmaceutical companies and other firms developing **RNAi**, **antisense** (e.g., Ionis), and other novel drug technologies, which could render its products obsolete or noncompetitive[237](index=237&type=chunk)[239](index=239&type=chunk) - Alnylam is involved in significant intellectual property litigation, including lawsuits against **Pfizer** and **Moderna** for patent infringement related to **mRNA COVID-19 vaccines**, which could incur substantial costs and divert management attention[232](index=232&type=chunk) - The **Inflation Reduction Act of 2022 (IRA)** introduces Medicare price negotiation, which could impact future revenues. The company decided not to pursue a Phase 3 trial for vutrisiran in Stargardt Disease to avoid losing the single-orphan exemption for **AMVUTTRA** from these negotiations[217](index=217&type=chunk) [Other Information](index=78&type=section&id=ITEM%205%2E%20OTHER%20INFORMATION) During Q3 2023, two directors adopted Rule 10b5-1 trading plans for the potential sale of company common stock, setting pre-determined conditions for share sales - Director **Michael W. Bonney** established a Rule 10b5-1 trading plan on August 10, 2023, to sell up to **30,000 shares** of common stock between November 2023 and December 2024, subject to price conditions[252](index=252&type=chunk) - Director **David E.I. Pyott** established a Rule 10b5-1 trading plan on August 11, 2023, to sell up to **32,450 shares** of common stock between November 2023 and November 2024, subject to price conditions[253](index=253&type=chunk) [Exhibits](index=79&type=section&id=ITEM%206%2E%20EXHIBITS) This section lists the exhibits filed with the Form 10-Q, including the Collaboration and License Agreement with Roche and Genentech, and officer certifications - Key exhibits filed include the Collaboration and License Agreement with **F. Hoffmann-La Roche Ltd.** and **Genentech, Inc.**, and officer certifications pursuant to the Securities Exchange Act of 1934[255](index=255&type=chunk)

Nathan (USA) Diagnosed with AHP Second Quarter 2023 Financial Results August 3, 2023 1 © 2023 Alnylam Pharmaceuticals, Inc. Agenda Welcome ...

Financial Data and Key Metrics Changes - Total product revenues for Q2 2023 were $306 million, representing a 43% year-over-year growth compared to Q2 2022 [27] - Gross margin on product sales was 75%, a 9% decrease compared to Q2 2022, primarily due to fees associated with canceling manufacturing commitments for ONPATTRO [28] - Non-GAAP operating loss for the quarter was $154 million, showing a $7 million improvement compared to Q2 2022 [30] Business Line Data and Key Metrics Changes - The TTR franchise achieved $224 million in global net product revenues for ONPATTRO and AMVUTTRA, representing a 46% growth year-over-year [10] - GIVLAARI and OXLUMO together delivered $82 million in combined product sales during Q2, representing a 37% growth compared to Q2 2022 [13] Market Data and Key Metrics Changes - In the US, combined sales of ONPATTRO and AMVUTTRA increased by 72% year-over-year, marking the fourth consecutive quarter of TTR growth exceeding 70% [11] - AMVUTTRA demand in Japan is particularly encouraging, with new patient growth driven by switches from tafamidis and patients naive to therapy [10] Company Strategy and Development Direction - The company entered into a strategic partnership with Roche for the development and commercialization of zilebesiran, aiming to disrupt the global treatment paradigm for hypertension [6] - The company is focused on achieving its Alnylam P5x25 goals, positioning itself as a top-tier biotech company developing transformative medicines for rare diseases [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the upcoming catalysts, including the initial data from the KARDIA Phase 2 program and the potential launch of ONPATTRO for ATTR amyloidosis with cardiomyopathy [7] - The management highlighted the importance of maintaining high ethical standards in business conduct, especially in interactions with healthcare providers and patients [6] Other Important Information - The US Attorney's Office for the District of Massachusetts concluded its case regarding the marketing and promotion of ONPATTRO with no action taken [6] - Akshay Vaishnaw transitioned to the role of Chief Innovation Officer, focusing on the future of the R&D engine [8] Q&A Session Summary Question: Any updated thoughts on the upcoming AdCom ONPATTRO and ATTR CM? - Management is actively preparing for the advisory committee and believes the focus will be on the clinical meaningfulness of changes in the six-minute walk test and KCCQ [35] Question: Clarification on the Roche deal for zilebesiran? - The deal includes $310 million upfront and $365 million in potential development milestones, with Roche covering 60% of development costs [40] Question: Consideration by the FDA regarding the PDUFA date for ONPATTRO? - Management anticipates the PDUFA date of October 8th and is working towards that, with no changes communicated by the FDA at this time [44] Question: Timing and reasoning behind Akshay's role change? - The transition to Chief Innovation Officer allows for a more focused role in driving R&D success, with no specific reason for the timing [51] Question: Details on the expanded access program for patisiran? - The program enrolled 200 patients rapidly, highlighting the significant demand for alternative therapies for patients experiencing progression [69]

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 June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15( ...

Financial Data and Key Metrics Changes - Total product revenues for Q1 2023 were $276 million, representing a 48% increase compared to Q1 2022, primarily driven by growth in TTR product revenues from the AMVUTTRA launch [36][37] - Net revenue from collaborations was approximately $36 million, a 41% increase year-over-year, attributed to increased activities with Regeneron [36] - Gross margin on product sales was 85%, a 2% decrease from Q1 2022, mainly due to increased royalties on AMVUTTRA sales [37] - Non-GAAP operating loss for Q1 2023 was $110 million, showing a $7 million improvement compared to Q1 2022 [38] Business Line Data and Key Metrics Changes - The TTR franchise achieved $204 million in global net product revenues, a 49% growth compared to Q1 2022, with U.S. market growth at 75% [10][12] - Ultra-rare products GIVLAARI and OXLUMO generated $72 million in combined product sales, reflecting a 45% increase year-over-year [13] - AMVUTTRA's launch contributed significantly to the TTR franchise, with over 3,160 patients on treatment worldwide, marking a 6% quarterly growth [10][11] Market Data and Key Metrics Changes - In international markets, total TTR product sales increased 9% compared to the previous quarter, driven by strong demand in Japan [12] - The U.S. market saw a 5% increase in combined sales of ONPATTRO and AMVUTTRA, with a 7% increase in demand [11] Company Strategy and Development Direction - The company aims to expand its TTR franchise and address more common disease areas beyond rare diseases [8] - Alnylam is focused on sustainable innovation through new platform enhancements and genetically validated targets to drive pipeline expansion [9] - The company is committed to advancing its clinical-stage product candidates for ATTR amyloidosis and exploring new therapeutic areas such as hypertension with zilebesiran [30][34] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing growth trajectory of AMVUTTRA and the overall TTR franchise, highlighting strong patient uptake and prescriber expansion [11][65] - The company anticipates continued strong performance from its pipeline, particularly with upcoming data presentations and clinical milestones [40] Other Important Information - The FDA has accepted the supplemental New Drug Application for patisiran for cardiomyopathy, with a PDUFA date set for October 8 [31] - The company has received regulatory approval to begin Part B of the ALN-APP Phase 1 study in Canada, while a partial clinical hold is in place in the U.S. [27][28] Q&A Session Summary Question: Can you talk about the upcoming 18-month data from APOLLO-B? - Management confirmed that the data will include ongoing follow-up and key secondary endpoints, with high retention rates in the study [44][46] Question: What is the market share impact of AMVUTTRA on ONPATTRO? - Management indicated a healthy switch rate from ONPATTRO to AMVUTTRA while also adding new patients, suggesting a positive growth trajectory for the TTR franchise [49][51] Question: Can you discuss the timelines for the CAA program? - Management highlighted the potential for ALN-APP in both Alzheimer's and CAA, with ongoing studies to establish safety and efficacy [53][55] Question: What are the expectations for zilebesiran in hypertension? - Management expressed excitement about zilebesiran's potential, with ongoing Phase 2 studies expected to provide pivotal data for future registrational programs [57][62]

Financial Performance - Alnylam reported a 48% increase in net product revenues in Q1 2023 compared to Q1 2022, reaching $276 million [63] - Total revenues increased by 50% to $319 million in Q1 2023 compared to $213 million in Q1 2022 [63] - The company's cash and investments stood at $2071 million as of March 31, 2023 [63] - Alnylam reiterates its full-year 2023 net product revenue guidance of $1200 million to $1285 million, representing a 34% to 44% growth compared to 2022 [64] Commercial Highlights - Global TTR net product revenue grew by 49% year-over-year [13] - U S TTR QoQ growth of +5% primarily driven by demand growth +7% due to strong AMVUTTRA demand more than offsetting decrease in ONPATTRO demand [14] - ROW QoQ growth +9% primarily due to AMVUTTRA launch demand in Japan & Germany, ONPATTRO demand in markets where AMVUTTRA not yet available, and timing of orders in partner markets [14] - Total Ultra Rare global Q1 2023 net product revenues were $72 million [15] - Ultra Rare YoY % Growth: GIVLAARI 36%, OXLUMO 66%, Total Ultra Rare 45% [16] Pipeline Development - ALN-APP Phase 1 study in Early-Onset Alzheimer's Disease (EOAD) showed that single doses of ALN-APP were well tolerated to date [28] - ALN-APP Phase 1 Study in EOAD – Interim Results showed Robust and Sustained Reduction in sAPP and sAPP in CSF at the Highest Dose Tested [29] - Topline Phase 1 data for ALN-TTRsc04, an investigational RNAi therapeutic for potential treatment of ATTR Amyloidosis, is expected in late 2023 [53] - Zilebesiran demonstrated >90% mean serum AGT reduction for 6 months after single dose of zilebesiran 800mg [56]

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 Large accelerated filer x Accelerated filer ☐ Non-accelerated filer ☐ Smaller reporting company ☐ ...