For the quarter ended December 2023, Alnylam Pharmaceuticals (ALNY) reported revenue of $439.72 million, up 31.2% over the same period last year. EPS came in at -$1.10, compared to -$1.68 in the year-ago quarter.The reported revenue represents a surprise of -1.31% over the Zacks Consensus Estimate of $445.57 million. With the consensus EPS estimate being -$1.20, the EPS surprise was +8.33%.While investors closely watch year-over-year changes in headline numbers -- revenue and earnings -- and how they compar ...

Core Insights - Alnylam Pharmaceuticals reported strong financial performance in 2023, achieving $1.24 billion in global net product revenues and treating over 5,000 patients with its commercial medicines [2][10][12] - The company demonstrated leadership in RNAi therapeutics with significant clinical advancements, including the first gene silencing in the human brain [2][5] - Looking ahead, Alnylam anticipates important milestones in 2024, including results from key clinical studies and the initiation of several new studies [2][9] Financial Performance - For Q4 2023, Alnylam's total net product revenues reached $346.3 million, a 32% increase compared to Q4 2022, while full-year revenues were $1.24 billion, up 39% year-over-year [10][12] - The company reported a GAAP net loss of $137.9 million for Q4 2023, compared to a loss of $207.5 million in Q4 2022, and a full-year net loss of $440.2 million [10][40] - Cash, cash equivalents, and marketable securities increased to $2.44 billion as of December 31, 2023, primarily due to significant upfront payments from partnerships [17] Product Revenue Highlights - Alnylam's TTR therapies, ONPATTRO and AMVUTTRA, generated Q4 revenues of $79 million and $175 million, respectively, with annual growth of 40% compared to 2022 [3][11] - The Ultra-Rare disease therapies, GIVLAARI and OXLUMO, achieved Q4 revenues of $59 million and $33 million, respectively, reflecting a 35% annual growth [4][11] Research and Development Updates - Alnylam announced updates to the HELIOS-B Phase 3 study of vutrisiran, with topline results expected in late June or early July 2024 [5][9] - Positive initial results from the KARDIA-1 Phase 2 study of zilebesiran were presented, and the FDA has cleared the initiation of the multiple-dose part of the ALN-APP Phase 1 study [6][7] Future Guidance - For 2024, Alnylam projects combined net product revenues for its key therapies to be between $1.4 billion and $1.5 billion, representing a growth of 13% to 21% compared to 2023 [19][20] - The company expects net revenues from collaborations and royalties to range from $325 million to $425 million [19]

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].

Cavan Images One niche area of biotech that I've followed closely over the past several years has been the treatment and pipeline for transthyretin amyloidosis (ATTR). ATTR is a rare genetic disease where a mutation in the TTR gene causes the liver to produce a misfolded protein called transthyretin, which can build up in the body resulting in polyneuropathy and cardiomyopathy. This progressive disease is often diagnosed later in life only after patients start to experience a high disease burden, which incl ...

Company Overview - Alnylam Pharmaceuticals is a leading company in RNA interference (RNAi) therapeutics, aiming to transform the lives of patients with rare and prevalent diseases through innovative medicines [5][6] - The company has developed several commercial RNAi therapeutic products, including ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran) [5] - Alnylam is executing its "Alnylam P5x25" strategy to deliver transformative medicines while maintaining exceptional financial performance, establishing a strong position in the biotech industry [6] Leadership Recognition - Yvonne Greenstreet, CEO of Alnylam, has been named the 2024 Woman of the Year by the Healthcare Businesswomen's Association (HBA) for her extraordinary contributions to healthcare and women's advancement in the workplace [1][2] - Under Yvonne's leadership, Alnylam has been recognized as a socially responsible company and an exceptional workplace, earning accolades such as being listed among Fortune's Best Workplaces for Women and the Bloomberg Gender Equality Index [2][3] Leadership Background - Yvonne Greenstreet has over three decades of experience in the biopharmaceutical industry, having held significant positions at Pfizer and GlaxoSmithKline prior to joining Alnylam [3][4] - She has a medical degree from The University of Leeds and an MBA from INSEAD Business School, showcasing her strong educational background [4]

Alnylam Pharmaceuticals (ALNY) reported preliminary full-year 2023 net product revenues of $1.24 billion, representing 39% growth at a constant exchange rate. The Zacks Consensus Estimate for the same is pegged at $1.83 billion.The company’s net product revenues comprise sales of its four marketed products, such as Onpattro, Amvuttra, Givlaari and Oxlumo.In 2023, preliminary global net product revenues for Onpattro and Amvuttra were approximately $355 million and $558 million, respectively, representing a 4 ...

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)