ALNY

It has been about a month since the last earnings report for TG Therapeutics (TGTX). Shares have added about 15.1% in that time frame, outperforming the S&P 500. Will the recent positive trend continue leading up to its next earnings release, or is TG Therapeutics due for a pullback? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at its most recent earnings report in order to get a better handle on the important drivers. TG Therapeutics reported earnings of 5 cents per share for the second quarter of 2026, missing the Zacks Consensus Estimate of 41 cents. The company had reported earnings of 17 cents per share in the year-ago quarter. Total revenues in the second quarter were $240.3 million, up almost 70.3% year over year, driven by strong demand for the company’s sole marketed drug, Briumvi. The figure beat the Zacks Consensus Estimate of $231 million. The top line comprised product sales from Briumvi and license, royalty and other revenues. Total product revenues were $235.8 million in the reported quarter, reflecting a 69.9% year-over-year increase. Total product revenues included sales of Briumvi to TG Therapeutics’ licensing partner, Neuraxpharm, in ex-U.S. markets, of $8.1 million. Briumvi's net product sales in the United States were $227.7 million in the second quarter, up 64% year over year. Sales of the drug came in ahead of management’s guided range of $220 million. License, milestone, royalty and other revenues were $4.5 million in the second quarter, compared with $2.3 million reported in the year-ago quarter. Research and development (R&D) expenses (excluding stock-based compensation) surged 217.5% year over year to $87.3 million due to higher expenses related to ongoing clinical studies. Selling, general and administrative (SG&A) expenses (excluding stock-based compensation) totaled $62.3 million, up 43.2% from the year-ago quarter’s level, due to higher commercialization costs for Briumvi as well as other personnel costs. As of June 30, 2026, TG Therapeutics had cash, cash equivalents and investments worth $612.3 million compared with $572.8 million as of March 31, 2026. TG Therapeutics raised its total revenue guidance. The company now expects worldwide total revenues of around $950 million in 2026, compared with the previous expectation of around $925 million. The company now expects net product revenues of $890-$905 million from Briumvi sales in the United States in 2026, up from the previous expectation of $885-$900 million. Excluding non-cash compensation, total operating expenses, defined as R&D and SG&A, are now expected to be around $350-$400 million in 2026, compared with the previous expectation of around $350 million. It turns out, estimates revision have trended downward during the past month. At this time, TG Therapeutics has a poor Growth Score of F, a grade with the same score on the momentum front. Charting a somewhat similar path, the stock was allocated a score of D on the value side, putting it in the bottom 40% for this investment strategy. Overall, the stock has an aggregate VGM Score of F. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been broadly trending downward for the stock, and the magnitude of these revisions indicates a downward shift. Notably, TG Therapeutics has a Zacks Rank #3 (Hold). We expect an in-line return from the stock in the next few months. TG Therapeutics is part of the Zacks Medical - Biomedical and Genetics industry. Over the past month, Alnylam Pharmaceuticals (ALNY), a stock from the same industry, has gained 12.4%. The company reported its results for the quarter ended June 2026 more than a month ago. Alnylam reported revenues of $1.29 billion in the last reported quarter, representing a year-over-year change of +66.9%. EPS of $1.84 for the same period compares with $0.32 a year ago. For the current quarter, Alnylam is expected to post earnings of $2.19 per share, indicating a change of -24.5% from the year-ago quarter. The Zacks Consensus Estimate has changed -0.7% over the last 30 days. Alnylam has a Zacks Rank #3 (Hold) based on the overall direction and magnitude of estimate revisions. Additionally, the stock has a VGM Score of C. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report TG Therapeutics, Inc. (TGTX) : Free Stock Analysis Report Alnylam Pharmaceuticals, Inc. (ALNY) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Make better investment decisions with Simply Wall St's easy, visual tools that give you a competitive edge. Alnylam Pharmaceuticals stock has fallen 46.8% over the past year, yet the valuation checks still flag it as leaning expensive rather than a clear bargain. With fresh clinical data on its RNAi programs coming at the ESC Congress 2026, investors are weighing that share price slump against what the current market valuation implies. The share price decline of 46.8% over the last 12 months signals that expectations have come down sharply and raises the question of whether sentiment has weakened more than the underlying business outlook. Upcoming data on AMVUTTRA and zilebesiran at the ESC Congress 2026 can support confidence in Alnylam Pharmaceuticals' long term revenue potential, while clinical or regulatory setbacks remain a key risk that could limit how much valuation support those programs provide. With a value score of 2 out of 6, the broader checks suggest Alnylam Pharmaceuticals does not screen as a clear bargain on current multiples. The issue now is whether Alnylam Pharmaceuticals' current price fairly reflects that mix of weaker recent returns and a valuation profile that still leans expensive. Find out why Alnylam Pharmaceuticals' -46.8% return over the last year is lagging behind its peers. The P/E ratio is a useful measure for Alnylam Pharmaceuticals because earnings are now a key reference point for how the market prices its RNAi platform. The stock trades on a P/E of 40.8x, which is more than double the Biotechs industry average of 17.8x and above the peer group average of 34.0x. This already suggests that investors are paying a premium for Alnylam Pharmaceuticals compared with many other listed biotechs. The fair P/E ratio implied by the valuation model is 32.4x, which is lower than where Alnylam Pharmaceuticals trades today. This gap indicates that the current share price reflects richer expectations than the model suggests, based on the company’s profile and risk mix. Although the planned ESC Congress 2026 data on AMVUTTRA and zilebesiran may support continued interest in the company, the market is already assigning a premium multiple to the stock. On the P/E multiple alone, Alnylam Pharmaceuticals stock currently appears overvalued relative to its tailored fair ratio and to sector peers. See what the numbers say about this price — find out in our valuation breakdown. Simply Wall St Narratives for Alnylam Pharmaceuticals pick up where this valuation puzzle leaves off and spell out which combinations of growth, margins and earnings would need to hold for the stock to be worth materially more or less than today’s price, using Alnylam Pharmaceuticals' Community page as the hub. Rather than relying on a single multiple or model line, each narrative lays out the assumptions behind its view of fair value so you can compare them with future results as they come through. One of the top community narratives on Alnylam Pharmaceuticals: 46% undervalued Read one of the top narratives on Alnylam Pharmaceuticals Do you think there's more to the story for Alnylam Pharmaceuticals? Head over to our Community to see what others are saying! For Alnylam Pharmaceuticals, the current market multiples still point to an overvalued stock, even after weaker recent returns. The key issue is whether upcoming clinical readouts and execution on the existing portfolio can eventually justify that premium P/E, or whether the market has leaned too far ahead of what earnings can support. The crux for investors is how confident you are that Alnylam Pharmaceuticals can grow into its valuation without material stumbles on the clinical or regulatory side. This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. Companies discussed in this article include ALNY. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email [email protected]

This story was originally published on PharmaVoice. To receive daily news and insights, subscribe to our free daily PharmaVoice newsletter. You’d think a drug that brought in more than $1 billion in quarterly sales would signal success. But when Alnylam Pharmaceuticals reported $1.01 billion in second-quarter Amvuttra sales — below published consensus estimates — and trimmed its full-year outlook for the broader transthyretin franchise in late July, its shares tumbled nearly 30%. Amvuttra lowers production of a protein called transthyretin, which can misfold and form amyloid deposits in organs and tissues. Alnylam cut 2026 revenue guidance for Amvuttra and Onpattro, another player in its transthyretin franchise, by $200 million to the $4.2 billion to $4.5 billion range. The company attributed the revision mainly to normalizing second-line demand after an initial wave of patients came onto the treatment after Amvuttra’s 2025 expansion into ATTR cardiomyopathy, or ATTR-CM. That adjusted revenue revision fell 4% short of Wall Street expectations. The FDA first approved Amvuttra in 2022 for polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, then expanded its use in March 2025 to cardiomyopathy caused by wild-type or hereditary ATTR amyloidosis. The indications were steadily expanding; the modality seemed like a safe bet. But investors may have also been responding to additional background factors. Amvuttra competes in ATTR-CM with stabilizers including Pfizer’s Vyndamax and BridgeBio’s Attruby. Wainua, an AstraZeneca-Ionis gene silencer approved for the polyneuropathy form of hereditary ATTR amyloidosis, had been a potential rival in cardiomyopathy before failing a phase 3 trial in July. That failure initially appeared to remove a competitor, but the limited top-line results exposed another wrinkle: Wainua showed no treatment effect among patients already taking a stabilizer. Some investors read that subgroup result as potentially relevant to Amvuttra, although cross-trial comparisons are limited and full Wainua data had not yet been presented. Alnylam remains confident. CEO Yvonne Greenstreet said the company would continue to “invest robustly in this franchise” as it works to establish Amvuttra as “a foundational therapy.” Even so, the episode illustrates how a blockbuster can disappoint when investors have priced in faster growth. But Amvuttra wasn’t the only high-profile candidate to fall short of analyst expectations this year. Three other franchises face pressure — for different reasons. AbbVie’s Imbruvica narrowly missed Q2 analyst expectations, generating $532 million in second-quarter global net revenue against a consensus estimate of roughly $533 million. Sales fell 29.4% year over year. The decline came as Imbruvica faced pressure from Medicare’s newly effective negotiated price, set 38% below its 2023 list price, and growing competition from newer BTK inhibitors. The lower negotiated price bargained under the Inflation Reduction Act, which reduced the list price from $14,934 in 2023 to $9,319 in 2026, isn’t the only setback the drug has faced in recent years. After its 2013 approval, it quickly became a mainstay oncology therapy, primarily in blood cancers, such as chronic lymphocytic leukemia. But second-and-third generation BTK inhibitors, such as AstraZeneca’s Calquence, BeOne Medicines’ Brukinsa, and Eli Lilly’s Jaypirca, which produce fewer side effects, have eroded its market share. Longer term, Imbruvica could face generic competition, although AbbVie does not expect U.S. generic entry before March 2032. Merck’s chickenpox vaccine Varivax, its MMR-II vaccine for measles, mumps and rubella, and the MMRV combination vaccine ProQuad generated $592 million in Q2. That was about 2.6% below the $608 million analysts expected, according to Reuters, and 2.8% below the year-earlier period. Merck attributed the year-over-year decline primarily to lower U.S. demand, partly offset by higher U.S. net pricing, increased European demand and favorable private-sector purchasing patterns for MMR-II in the U.S. Federal vaccine policy has become more volatile under HHS Secretary Robert F. Kennedy Jr., who dismissed all 17 members of the CDC’s Advisory Committee on Immunization Practices last year. A January schedule that moved six vaccines out of the universally recommended category was later stayed in a preliminary injunction, which the administration appealed. Merck did not attribute this quarter’s decline specifically to those policy changes. Roche’s Vabysmo generated about $1.27 billion in Q2, 7.1% below analyst consensus and down 1% year over year. CEO Teresa Graham attributed the shortfall partly to slower retinal-market growth, which she said was settling into a “new normal” of 2% to 3%. Vabysmo grew rapidly after its 2022 approval, but momentum slowed in the second half of 2025 as closures of some copay-assistance foundations contributed to a contraction in the U.S. branded retinal-drug market. That slowdown was not an across-the-board sales decline: Roche reported first-half 2026 Vabysmo sales up 8% at constant exchange rates. Vabysmo also competes with Regeneron’s branded Eylea and Eylea HD. Graham nevertheless called consensus peak-sales expectations of about $7.4 billion (6 billion Swiss francs) “very reasonable” and said Roche was “confident that we’re on track to achieve this number.” More than 60% of U.S. Vabysmo patient starts were treatment-naïve as of January, and the drug is being studied in phase 3 for a potential fourth indication, myopic choroidal neovascularization Recommended Reading RNAi looked doomed to fail — until Alnylam’s science chief found a way

Positive Interim Data Shared in 2Q 2026 from the MyPEAK™-1 and RIDGE™-1 Clinical Trials Each Demonstrated Meaningful Improvements in Key Disease Characteristics Additional Data Releases Plus Updates on Regulatory Discussions on Pivotal Trial Plans for TN-201 and TN-401 Anticipated in 4Q 2026 TN-301 Advancing toward Phase 2 Trial Start in 2H 2027 $10 million Upfront Payment Received from Alnylam Collaboration Extends Cash Runway Through Q3 2027 SOUTH SAN FRANCISCO, Calif., Aug. 05, 2026 (GLOBE NEWSWIRE) -- Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today announced financial results for the second quarter ended June 30, 2026, and provided a corporate update. “The second quarter marked an important period of execution for Tenaya as we shared new safety and clinical benefit data for TN-201 and TN-401,” said Faraz Ali, Chief Executive Officer of Tenaya. “We remain excited by the encouraging results emerging from our TN-201 MyPEAK-1 clinical trial in patients with MYBPC3-associated disease and the most recent RIDGE-1 data add to our confidence in TN-401’s potential as a highly promising candidate to address the underlying cause of PKP2-associated ARVC. We are engaging with regulators to discuss the efficient late-stage development and approval pathways for each candidate.” Mr. Ali continued, “We also believe that advancing TN-301 toward Phase 2 represents an opportunity to create significant value while further diversifying our pipeline. We remain focused on disciplined execution, efficient use of capital, and advancing programs with the greatest potential to deliver meaningful impact for patients and stockholders.” Business and Program Updates TN-201 – Gene Therapy for MYBPC3-Associated Hypertrophic Cardiomyopathy (HCM) In June 2026, Tenaya shared promising new safety and efficacy data from the ongoing MyPEAK-1 Phase 1b/2 clinical trial of TN-201 in adults with MYBPC3-associated HCM. The data shared reflected 78-104 weeks of follow-up for three patients who received TN-201 at the 3E13 vg/kg dose (Cohort 1), and 26-52 weeks of follow-up for four patients at the 6E13 vg/kg dose (Cohort 2). Key findings include: Tenaya has completed enrollment needed in the MyPEAK-1 clinical trial to characterize dose response and inform dose selection for late-stage clinical trials. In June 2026, Tenaya announced that TN-201 received PRIority MEdicine (PRIME) designation by the European Medicines Agency (EMA) and was accepted into the Food and Drug Administration’s Rare Disease Evidence Principles (RDEP) process for severe pediatric patients. Tenaya is pursuing alignment with regulatory authorities on late-stage pivotal trial plans for TN-201. The company plans to provide an update on the status of these discussions in the fourth quarter of 2026. TN-401 – Gene Therapy for PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) At the ASGCT Annual Meeting, Tenaya presented positive interim data from the ongoing RIDGE-1 Phase 1b/2 clinical trial of TN-401 gene therapy. The data set included three patients dosed at 3E13 vg/kg (Cohort 1) with follow-up ranging from Week 32-52 and three patients dosed at 6E13 vg/kg (Cohort 2) with 20-32 weeks of follow-up. Key findings include: Tenaya has completed enrollment needed in the RIDGE-1 clinical trial to characterize dose response and inform dose selection for late-stage clinical trials, In May 2026, Tenaya announced receipt of PRIME designation by the EMA. Tenaya is currently engaging with regulators on late-stage pivotal trial planning for TN-401 and plans to provide an update on the status of its discussions in the fourth quarter of 2026. TN-301 – Small Molecule HDAC6 Inhibitor for the Potential Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF) and Related Cardiac, Metabolic, or Muscular Diseases Tenaya is currently conducting enabling toxicology work to support the advancement of TN-301 toward clinical trials in patients. The company intends to share additional details regarding its TN-301 development plans in the fourth quarter of 2026, and to initiate at least one company-sponsored proof-of-activity Phase 2 clinical trial in the second half of 2027. HFpEF and Duchenne muscular dystrophy are among the most promising potential indications identified to date. Corporate Updates In June 2026, Tenaya announced the appointment of Eric Hyllengren as Chief Financial Officer of Tenaya, effective July 13, 2026. In June 2026, Tenaya entered into a Lease Termination Agreement for its Genetic Medicines Manufacturing Center (GMMC) which was decommissioned in 2025. Exiting this lease is part of the company’s ongoing efforts to reduce costs. Tenaya has sufficient inventory of TN-201 and TN-401 to support its ongoing clinical trials and plans to work with a global contract development manufacturing organization for cGMP material to support future needs. In April 2026, under the terms of the Alnylam collaboration agreement, Tenaya received an upfront payment of $10.0M and is eligible for future development, regulatory and sales-based milestones totaling up to $1.1 billion, in addition to reimbursement of associated research costs. Second Quarter 2026 Financial Highlights Cash: As of June 30, 2026, cash and cash equivalents were $78.1 million, including the $10.0 million upfront payment received from the collaborative agreement with Alnylam. Tenaya expects existing cash and cash equivalents will be sufficient to fund planned operations through Q3 of 2027. Research & Development (R&D) Expenses: R&D expenses were $16.6 million for the second quarter of 2026, compared to $17.4 million for the same period in 2025. Non-cash stock-based compensation included in R&D expense was $0.9 million for the second quarter of 2026 compared to $1.9 million for the same period in 2025. General & Administrative (G&A) Expenses: G&A expenses were $5.4 million for the second quarter of 2026 compared to $6.7 million for the same period in 2025. Non-cash stock-based compensation included in G&A expense was $0.8 million for the second quarter of 2026 and $1.8 million for the same period in 2025. Net Loss: Net loss was $43.4 million, or $0.20 loss per share, for the second quarter ended June 30, 2026, compared to a net loss of $23.3 million, or $0.14 per share, for the same period in 2025. The increase in net loss was primarily due to a $21.8 million non-cash impairment charge related to the early termination of the Company's Union City GMMC facility lease. About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Tenaya’s pipeline includes clinical-stage candidates TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM); TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC); and TN-301, a highly specific small molecule HDAC6 inhibitor with broad potential clinical utility in cardiac, metabolic and muscular conditions, including heart failure with preserved ejection fraction (HFpEF) and Duchenne muscular dystrophy (DMD). Tenaya has employed a suite of integrated internal capabilities including modality agnostic target discovery and validation, to generate a portfolio of novel medicines based on genetic insights, aimed at the treatment of both rare genetic disorders and more prevalent heart conditions.   For more information, visit www.tenayatherapeutics.com. Forward Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “anticipated,” “potential,” “believe,” “focused,” “promising,” “plans,” “expects,” “intends,” “will,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, planned timing for sharing data from RIDGE-1 and MyPEAK-1 and the expected content of such data releases; the therapeutic potential for TN-201 as a treatment for MYBPC3-associated HCM and TN-401 as a treatment for PKP2-associated ARVC; the potential for TN-301 to create significant value for Tenaya; Tenaya’s focus on disciplined execution, efficient use of capital and advancing programs with the greatest potential; planned timing for sharing updates on regulatory interactions for the TN-201 and TN-401 programs; planned timing for sharing additional details regarding TN-301 development plans; the sufficiency of Tenaya’s cash resources to fund the company through Q3 of 2027; and statements made by Tenaya’s chief executive officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: availability of data at the referenced times; the timing and progress of Tenaya’s clinical trials; unexpected concerns that may arise as a result of the occurrence of adverse safety events by patients who received Tenaya products; the potential failure of Tenaya’s product candidates to demonstrate safety and/or efficacy in clinical testing; the potential for any clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; the potential for the FDA to conclude at any time that Tenaya’s clinical programs may not have an appropriate risk/benefit profile; Tenaya’s ability to enroll and maintain patients in clinical trials; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s ability to develop, initiate or complete preclinical studies and clinical trials, and obtain approvals, for any of its product candidates; Tenaya’s continuing compliance with applicable legal and regulatory requirements; regulatory developments in the United States and foreign countries; Tenaya’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to comply with specified operating covenants and restrictions in its loan agreement; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates and platform technology; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Tenaya ContactsMichelle CorralVP, Corporate Communications and Investor [email protected] InvestorsAnne-Marie FieldsPrecision AQ [email protected] MediaWendy RyanTen Bridge [email protected]

Image source: The Motley Fool. Thursday, July 30, 2026, at 8:30 a.m. ET Vice President of Investor Relations - Josh Brodsky Chief Executive Officer - Yvonne Greenstreet Chief Financial Officer - Jeff Poulton Chief Commercial Officer - Tolga Tanguler Chief Research and Development Officer - Pushkal Garg Operator: Thank you for standing by. My name is Sprilla, and I will be your conference operator today. At this time, I would like to welcome everyone to the Alnylam Pharmaceuticals Q2 Earnings Conference Call. [Operator Instructions] I would now like to turn the conference over to the company. You may begin. Josh Brodsky: Good morning. I'm Josh Brodsky, Vice President of Investor Relations at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Jeff Poulton, Chief Financial Officer; Tolga Tanguler, Chief Commercial Officer; and Pushkal Garg, Chief Research and Development Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined on Slide 2, Yvonne will offer introductory remarks and provide some general context. Jeff will review our financials and guidance. Tolga will provide an update on our global commercial progress, and Pushkal will discuss our TTR franchise, our confidence in TRITON-CM and upcoming pipeline milestones before we open the call for your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provisions. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important risks and uncertainties, including those discussed under the heading Risk Factors in our most recent periodic report available on our website and on file with the SEC. We disclaim any obligation to update such statements. And with that, I'll now turn the call over to Yvonne. Yvonne? Yvonne Greenstreet: Thanks, Josh, and thank you, everyone, for joining the call today. During the second quarter, we demonstrated strong performance across all aspects of the business. Notably, it marks the first time AMVUTTRA revenues exceeded $1 billion in a single quarter, representing an annual run rate of more than $4 billion, just 15 months into the ATTR cardiomyopathy launch, a testament to both the commercial opportunity and Alnylam's execution. As we reflect on the launch, several insights reinforce our confidence in the durability of AMVUTTRA growth over the years ahead. First, this has been an impressive launch by industry benchmarks when looking across market share, access and revenue generation. Second, the fundamentals of our TTR business are strong, and they include AMVUTTRA's compelling clinical profile and label, the strong access that we established at launch, which continues to improve, and our robust and expanding provider network. Third, patient demand for AMVUTTRA continues to grow robustly, particularly in the first-line setting, which has been our focus as we aspire to market leadership, given AMVUTTRA's clinical differentiation and desirability as a foundational therapy for newly diagnosed patients. Tolga will discuss how we are now further investing in broadening our AMVUTTRA prescriber base and supporting overall category growth, the latter of which has been accelerating. Finally, our geographic expansion strategy continues to gain momentum. And today, we are pleased to announce our collaboration with BeOne through which they will have exclusive commercialization and distribution rights for AMVUTTRA in Mainland China and Macau, subject to AMVUTTRA receiving marketing authorization. Together with BeOne, we aim to help advance awareness and support diagnosis of ATTR amyloidosis and if approved, bring the strength of TTR silencing with AMVUTTRA to patients in these underserved regions. As Jeff will describe shortly, we are lowering our 2026 revenue guidance today to reflect a better understanding with hindsight of the first few quarters of our U.S. launch, specifically that early second-line demand growth in 2025 benefited significantly from pent-up demand for a new therapy that has since normalized. With that learning and our strong 2026 second quarter performance, our confidence in AMVUTTRA's growth trajectory has never been stronger. First-line new patient starts are now responsible for about 80% of category growth in this accelerating market, and we believe we're making great progress in establishing AMVUTTRA as a foundational therapy. I will now turn to recent developments in the competitive landscape, specifically the negative outcome of the CARDIO-TTRansform study of eplontersen. We recognize investor interest in understanding any potential implications of that study's failure for our probability of success in TRITON-CM, our Phase III cardiovascular outcomes trial of nucresiran. Let me be clear. This outcome does not alter our conviction in the TRITON-CM study. And as Pushkal will share in greater detail, our strong confidence is grounded in the established clinical evidence for RNAi therapeutics in TTR and the track record of our clinical organization. At the same time, we have a variety of options at our disposal to potentially adapt the study and position it for optimal success. We will carefully review the full eplontersen data set when it becomes available and adapt our study plan, if appropriate. We have successfully navigated complex TTR development before and believe we are exceptionally well positioned to do so again with nucresiran. Additionally, in the quarter, we were pleased to announce a series of strategic AI collaborations across the enterprise, including with Inceptive to expand the next frontier in the discovery of RNAi therapeutics and the collaboration we are pleased to announce today with a large health care system in California aimed at supporting early identification of ATTR cardiomyopathy in routine care. This builds on our previously announced partnerships with Viz AI and Komodo Health. Altogether, this cohesive AI strategy from discovery and evidence generation to disease identification, clinical practice and commercial execution reflects our long-term conviction that AI will fundamentally reshape how medicines are discovered, developed and ultimately delivered to patients. Finally, we also continue to progress our deep pipeline of investigational medicines, initiating a Phase II trial of ALN-6400 in von Willebrand disease and a Phase II trial of mivelsiran in Down syndrome associated Alzheimer's disease, and we look forward to a series of clinical data readouts in the back half of this year, including presentation of initial Phase I results of ALN-HTT02 in patients with Huntington's disease at EHDN in October. All of this progress builds on our momentum towards accelerating innovation, scaling our impact as we look to deliver on our 5-year vision Alnylam 2030. And our strategy is anchored around 3 pillars. The first pillar is to establish global leadership in TTR while continuing to build a durable franchise. The momentum we have built in ATTR cardiomyopathy to date, along with the recent developments in the competitive landscape, including the CARDIO-TTRansform Phase III top line results and the delay in expected U.S. generic entry for tafamidis until mid-2031, further reinforce the strength of our position and the significant opportunity ahead to establish AMVUTTRA as a foundational therapy and realize our TTR leadership ambitions. The second pillar is growing through sustainable innovation, where we aim to deliver therapies that not only slow the progression of disease, but prevent, halt or reverse it. And the third pillar is scaling with discipline and agility to enable durable, profitable growth. Alnylam 2030 represents our commitment to becoming the leading science-driven, fully integrated global biopharmaceutical company and to maximize the full potential of RNAi therapeutics for patients. With that, let me now turn the call over to Jeff for a review of our second quarter financial results and 2026 guidance. Jeff? Jeffrey Poulton: Thanks, Yvonne, and good morning, everyone. This morning, I'll be presenting a summary of Alnylam's second quarter 2026 financial results and discussing updates to our full year guidance. Let's begin with a summary of our P&L results for the second quarter. Total global net product revenues were approximately $1.2 billion, representing 74% growth versus Q2 last year, driven by the continued uptake of AMVUTTRA and ATTR cardiomyopathy. The second quarter of 2026 marks the first time we achieved more than $1 billion of TTR revenue. These results reflect a substantial improvement in quarter-on-quarter growth compared with growth in Q1 this year, consistent with the phasing expectations we discussed on our year-end and Q1 earnings calls earlier this year. Tolga will share more details on our TTR performance in the quarter. In Q2, collaboration revenue was $47 million, or a 23% decrease, compared with the same period last year due to lower revenue recognized from our Regeneron collaboration, partially offset by increased revenue from our Roche collaboration, driven by higher reimbursable development activities related to the ZENITH Phase III clinical trial of zilebesiran. Royalty revenue for the second quarter increased 79% to $72 million, driven by higher LEQVIO sales by Novartis. Gross margin on product sales was 75%, or 4% lower than Q2 last year. The decrease in margin was primarily driven by increased royalties on AMVUTTRA as higher revenues in 2026 resulted in an increase in the average royalty rate payable to Sanofi. Our non-GAAP R&D expenses of $377 million increased 38% compared to last year, primarily driven by costs associated with our 3 ongoing Phase III clinical studies, including the ZENITH Phase III cardiovascular outcomes trial for zilebesiran and the TRITON-CM and PN studies for nucresiran. Beyond the pivotal studies, we also continue to increase investment to support important programs for bleeding disorders, Huntington's disease and CAA. Non-GAAP SG&A expenses of $297 million increased 14% compared to last year, driven primarily by investments in support of the AMVUTTRA-ATTR cardiomyopathy launch in the U.S. and key international markets. We achieved non-GAAP operating income of $318 million, more than triple the amount we achieved last year, driven primarily by the strong top line results that I've previously highlighted. Finally, we ended the second quarter with cash, cash equivalents and marketable securities of $3.3 billion compared with $2.9 billion as of year-end 2025. The primary driver of the increase in cash year-to-date is our strong operating performance. Now turning to our full year 2026 guidance. As Yvonne noted, we are revising our total net product revenue guidance to $4.7 billion to $5.1 billion, driven fully by an update of our TTR revenue guidance to $4.2 billion to $4.5 billion, representing a $200 million reduction from our original TTR guidance at the midpoint and still reflects a robust 75% growth year-over-year. Guiding the market's expectations appropriately is important, and we didn't get it right with our original guidance. We own that. The revised guidance we are sharing today reflects a better understanding of the evolution of second-line demand as our launch has progressed. Let me provide some additional color on the basis for this revision. Overall, the AMVUTTRA cardiomyopathy launch continues to perform ahead of analogs. And importantly, we are pleased with uptake in the first-line portion of the market, which has been and remains the primary focus of our commercial efforts given the importance of this segment to driving long-term growth. When AMVUTTRA was launched in April 2025, the compelling HELIOS-B data and our team's success in establishing access enabled physicians to rapidly transition existing patients who are progressing on stabilizers onto AMVUTTRA. As a result, second-line demand volumes remain consistently robust throughout 2025, which informed our original 2026 guidance. However, as the launch progressed into 2026 and with the benefit of hindsight, it is now clear that a greater-than understood proportion of early second-line volume growth was driven by pent-up demand from patients who are waiting for a new treatment option. Consistent with the trend we highlighted on our Q1 2026 earnings call, growth in second-line volumes began to moderate in early 2026 to what we now recognize as a normalized level. This normalization of second-line demand is the driver of the $200 million reduction in TTR guidance that we are announcing today. Tolga will share more perspective in just a few moments on our confidence in future TTR growth, which is grounded in 3 key elements: the strength of our current market fundamentals, positive impact we expect from new investments we're making based on early launch learnings and, lastly, the favorable competitive developments that Yvonne mentioned in her opening remarks. Now back to updating our guidance. We are also updating our guidance for collaboration and royalty revenues to a revised range of $575 million to $625 million, representing a $150 million increase at the midpoint of the range, driven primarily by strong performance of LEQVIO and the resulting royalties from Novartis as well as higher cost reimbursement from Roche favorably impacting collaboration revenue, driven by the pace of enrollment in our ZENITH Phase III study with zilebesiran. The remainder of our non-GAAP financial guidance remains unchanged. Let me now turn it over to Tolga to provide more color on our commercial performance in the second quarter. Tolga? Tolga Tanguler: Thanks, Jeff, and good morning. I'm pleased to share our continued progress in bringing Alnylam's therapies to patients globally. AMVUTTRA is delivering a category-defining ATTR-CM launch and is on track towards delivering on our Alnylam 2030 ambitions. As Yvonne and Jeff mentioned, we have gained valuable insights as the launch has progressed. These learnings have sharpened our understanding of demand dynamics while also reinforcing our confidence in the fundamental drivers of sustainable growth. Overall, we remain highly confident in our path to achieving TTR leadership. The momentum of the business, coupled with an increasingly favorable competitive landscape, reinforce our conviction in achieving our long-term ambitions. Q2 marked another quarter of strong commercial execution and growth. Specifically, we delivered $1.17 billion in combined net product revenues, up 74% year-over-year and 13% over Q1 2026. In just 5 quarters since our CM launch, we have generated over $4 billion in total revenue, reflecting both a strong base and a clear growth trajectory. Our rare disease portfolio also continues to deliver meaningful impact for patients and consistent performance for our business. In Q2, we generated $142 million in rare disease net revenue, up 11% year-over-year. Turning to our TTR franchise. Global TTR net revenues reached $1.03 billion in the second quarter, increasing 13% versus Q1 and 89% year-over-year, reflecting the continued strength of the launch and the robust execution of our global teams. In the U.S., TTR revenues increased 15% versus Q1 and 114% year-over-year, reflecting robust underlying demand with reported revenue partially held back by changes in inventory days on hand during Q2. Access remained broad, pull-through was strong and adherence continued to exceed 90%. Outside the U.S., TTR revenues increased 7% versus Q1 and 31% year-over-year. Continued ATTR-CM uptake in Japan, the U.K. and Germany, along with strong polyneuropathy performance across our international markets drove Q2 growth despite pricing headwinds related to ongoing CM launches in several countries. Double-clicking on our Q2 TTR performance in the U.S., underlying demand was exceptionally strong, increasing by $129 million in the quarter, more than doubling the demand growth achieved in Q1. A portion of that demand was offset by inventory dynamics, which reduced reported growth by $21 million and to a lesser extent, by the continued and anticipated modest reduction in net price. As a reminder, our Q1 U.S. TTR growth was more modest and was impacted by several seasonal phasing dynamics, and we are, therefore, pleased by the robust reacceleration in demand in Q2 and the continuing strength of the business. AMVUTTRA's differentiated clinical profile underpins our confidence in the long-term growth opportunity. We believe that AMVUTTRA stands apart as a first-line choice on attributes that matter to physicians and patients. It is the first and only product approved in the U.S. for both ATTR-CM and hereditary ATTR-PN. It works upstream at the source, delivering rapid, deep and sustained knockdown of the disease-causing protein. In the pivotal HELIOS-B study, AMVUTTRA met 10 out of 10 endpoints and demonstrated robust treatment effects in the primary endpoint of all-cause mortality and recurring CV events and secondary endpoints of functional capacity and health-related quality of life. Across all of these endpoints, consistent treatment effects with or without background stabilizers were observed, combined with the convenience of once quarterly health care-provided administration and real-world data that suggests greater than 90% adherence, we believe AMVUTTRA is uniquely positioned to address the needs of the growing ATTR-CM patient population. The first 5 quarters of launch have provided valuable insights that are informing where we increase investment and how we position the business for its next phase of growth. During the initial quarters following approval, many of our high-volume early adopters transitioned a substantial number of stabilizer-treated progressing patients to AMVUTTRA. While those transitions continue, we are now seeing that portion of demand volume growth normalize toward a more sustainable underlying rate, and we continue to capture leadership share of second-line starts. Today, approximately 80% of new treatment initiations are first-line starts. Establishing AMVUTTRA as first-line treatment choice has been our priority since launch, and we continue to strengthen our competitive position. What's more, while our strategy has never dependent on competitors' outcomes, 2 favorable developments in the external landscape have cleared the path for us to be even more competitive in the first-line setting. First, we now anticipate tafamidis U.S. loss of exclusivity in 2031. AMVUTTRA is already challenging the 7-year incumbent for leadership share of new patient starts, and we see a significant opportunity to continue strengthening that position years ahead of genericization of the stabilizer class. Second, based on the CARDIO-TTRansform study top line results, we now anticipate fewer branded ATTR-CM competitor in both the first-line and stabilizer progressive segments. Finally, category growth continues to accelerate and our competitive first-line share, coupled with this clear competitive path to greater first-line penetration, aligns well with where we see the largest opportunity. With an estimated 80% of patients still untreated and additional physicians and health systems initiating treatment of ATTR-CM, we expect the robust growth in first-line starts to continue. And we're helping to drive that category growth. More specifically, we're accelerating our investments in diagnosis-enabling initiatives, investments to identify patients earlier to expand the treatable population and ultimately to improve patient outcomes. Taken together, these insights provide great confidence in our ability to expand leadership across both ATTR-CM and hereditary ATTR-PN and deliver on our 2030 ambitions of TTR leadership at a 25% revenue CAGR during the period. As we shared today, our differentiated profile has translated into exceptional launch momentum and that experience has sharpened our understanding of what will drive the next phase of growth. First, after 5 quarters in the market, AMVUTTRA's compelling profile and our focused efforts have driven broad coverage and efficient patient access with no meaningful reimbursement headwinds. We believe the strong access foundation will continue to support physician confidence and patient adoption as we expand the franchise. Second, we continue to deepen adoption among physicians who have already incorporated AMVUTTRA into their practice. Among prescribers using AMVUTTRA, it now represents more than 50% of new patient starts, underscoring the strong physician preference that develops with experience. And from our TTR-CM launch through the end of Q2, we have added over 1,700 new prescribers. Third, and perhaps most importantly, we have significant opportunity to expand the breadth of prescribers who have experienced with AMVUTTRA, which we estimate at about 1/3 of the growing pool of TTR prescribers. While we now -- we know that experience drives preference, there are many more physicians, including many who are new to the category, who have not yet prescribed AMVUTTRA. To capture that opportunity, we are intensifying our focus and increasing our investment in customer-facing activities to expand the breadth of prescribing. We are already seeing early progress from these efforts with accelerated growth in new AMVUTTRA prescribers during the second quarter, we believe we are in the early stages of that expansion opportunity. While we're still early in the commercialization journey, we believe AMVUTTRA is well positioned to capture the significant opportunity ahead as we bring this differentiated therapy to more patients living with ATTR-CM. With that, I will now turn it over to Pushkal. Pushkal Garg: Thank you, Tolga, and good morning, everyone. As Tolga just highlighted, we believe AMVUTTRA has a remarkable clinical profile that supports it being the first-line treatment of choice for patients with ATTR cardiomyopathy. These key attributes are highlighted here with data from the landmark HELIOS-B study. First and foremost, we've seen substantial benefits with regard to improving clinical outcomes, both all-cause mortality and cardiovascular events with reductions of nearly 40% over 48 months across these 2 endpoints. Second, the treatment effects are largest when we intervene early. You can see that in the forest plot on the bottom left, where patients with lower BNP, greater walking ability and younger age have had even greater reductions in the composite endpoint of 47%, 42% and 45%, respectively. And importantly, in data recently presented at ESC heart failure and shown on the lower right quadrant, we see that the treatment effect is preserved irrespective of background medications, including TTR stabilizers. These attributes, along with the quarterly dosing that supports adherence in our view, represents an ideal profile for a first-line agent for patients with ATTR cardiomyopathy. Now the strength of these HELIOS-B results, along with our many learnings from our deep experience in TTR amyloidosis, provide us with staunch conviction in the value of nucresiran, our next-generation investigational RNAi TTR silencer, which we believe has the potential for even greater improved efficacy by a greater knockdown, over 95% with just 2 doses per year. As you're aware, we continue to advance nucresiran in the TRITON Phase III program. TRITON-CM is a randomized double-blind, event-driven outcome study of nucresiran versus placebo. We announced last quarter that we utilized a prespecified option in our protocol to expand enrollment by about -- by approximately 500 patients to 1,750 in total, further mitigating the potential risk of low event rates while maintaining or potentially even accelerating time lines for this important study. Now given recent competitor data and given that many patients in TRITON-CM will be on a background stabilizer, we understand that there have been many questions raised about the feasibility of delivering positive results from this clinical trial. While we still have more to learn about the eplontersen results, we believe they're likely attributable to a combination of molecule and study-specific issues. And as we compare what we know about nucresiran with what's been reported about eplontersen, I want to assure you that we remain highly confident in nucresiran and TRITON-CM. I'll explain more in a moment, but first, let me share what we'll be looking for in the upcoming data presentations of the CARDIO-TTRansform results at ESC to better understand the reasons why the study did not meet its primary endpoint. First, we'll be interested to learn more about the population and baseline characteristics of the CARDIO-TTRansform study, particularly in the 2 key subgroups of monotherapy and in the patients on background stabilizers. As I noted, in HELIOS-B, we saw that treatment effects with AMVUTTRA were greatest in early patients. And so a drug signal may be obscured if many advanced patients were enrolled. We already know from published data that the CARDIO-TTRansform study enrolled 17% NYHA Class III patients, nearly double that in HELIOS-B, patients with higher NAC stage and patients with higher BNPs. Importantly, as I'll explain further in a moment, we believe deep rapid knockdown of TTR is critical to improving outcomes in ATTR cardiomyopathy. Graphs in the primary manuscript for the eplontersen PN study indicated it took longer to get to peak knockdown than AMVUTTRA, but the depth and variability of knockdown are also important. So we'll be looking for those details. Safety will be important given what we know about ASOs in the past and the frailty of the ATTR cardiomyopathy population. Did patients stay on drug? And were there any competing risks that impacted study outcomes. We also want to look at study execution and completeness of follow-up. And finally, we'll want to take a much deeper look at the outcomes data. For example, how did the individual components of their primary endpoint, CV mortality and CV events look? And what about all-cause mortality, which is part of our primary endpoint? How did these accrue over time and did the results vary in particular subgroups, particularly by disease severity. Bottom line is there are a lot of details not yet known about the failure of CARDIO-TTRansform. However, we are in an ideal position to learn from it. With enrollment ongoing and a projected launch for nucresiran in 2030 for ATTR cardiomyopathy, we have plenty of time to digest this information, thoroughly consider our options and implement appropriate changes to TRITON-CM, assuming any are even warranted. Let me return now to why we remain confident in TRITON-CM following the CARDIO-TTRansform top line release. The reasons come down to 3 key factors: the specific attributes of our molecule, nucresiran, key design elements of the TRITON-CM study and the track record of our team here at Alnylam. Starting with the molecule. First, RNAi therapeutics are fundamentally different than antisense oligonucleotides. In our hands, RNAi has been able to deliver rapid, deep and durable TTR knockdown, which we believe has implications on treating the course of disease. There are now several recent examples of ASOs and RNAis silencing the same genetic target with very different profiles. We've also seen that the safety profiles of these 2 approaches differ as well. Second, nucresiran's depth of TTR knockdown is expected to be best-in-class based on preliminary Phase I results showing over 95% TTR knockdown with much tighter intra-patient variability. I'll explain why we believe that will result in strong efficacy in a moment. And finally, we have data from 2 prior studies evaluating RNAi in ATTR cardiomyopathy patients, APOLLO-B and HELIOS-B, both of which generated data supporting a combination benefit. You've seen the HELIOS-B data in label, which shows a clear benefit of RNAi-mediated TTR silencing in a population that included heavy stabilizer use and consistent effects in combination and monotherapy. But as I'll show you in a moment, we saw the same effect with patisiran as well. Moving to the study. TRITON-CM now with 1,750 patients will be the largest study conducted in ATTR-CM, which will allow us to accrue more outcome events. And further to that point, we designed TRITON-CM as an event-driven study. Given the evolving treatment landscape, patients with somewhat milder disease on baseline on average and other dynamics, we determined that a time-based primary endpoint was not ideal. Instead, we'll continue the study until we have enough endpoint events to ensure sufficient study power. Third, we've used our insights to define entry criteria that enrich for patients who are most likely to benefit based on our prior learnings. And finally, we have an outstanding experienced team here at Alnylam. We've been focused on TTR drug development for well over 15 years, delivering 2 approved products. We've amassed tremendous experience across study design, execution and analysis to maximize the probability of success of a trial in this area. Part of this experience and history of conducting TTR trials is our vast database of deep patient-level insights that we can leverage to optimize study design and conduct. And to that last point, we have a track record of meticulous execution to ensure study success. This was most recently exemplified by how we optimize the endpoint structure and analytic plan for HELIOS-B to deliver remarkable results, resulting in a strong label that Tolga highlighted earlier. Before I move on, I'd like to underscore a few of the points I just made by sharing some clinical data that support the additive benefits of RNAi-mediated silencing on top of a stabilizer. As you'll recall, the HELIOS-B study demonstrated an approximately 41% reduction in the risk of all-cause mortality up to 42 months when AMVUTTRA was given to patients on a stabilizer at baseline, highlighting both the residual unmet need in these stabilizer-treated patients as well as the additive benefit of vutrisiran. But what you may not know is that we saw a nearly identical effect in APOLLO-B. As shown here, with just 24 months of follow-up in a comparable population in that study, we saw an estimated 44% reduction in all-cause mortality. Hence, we have data from 2 different molecules in 2 different studies showing comparable improvements in outcomes, which provides the strongest evidence of a combo effect. We believe these clinical data results from the knockdown profile of these 2 medicines. There are many ways to look at TTR knockdown, but what we believe matters is the speed and depth of knockdown and particularly getting as many patients as possible to deep knockdown. Here, we show TTR knockdown from our polyneuropathy studies, which have the richest sampling of TTR levels. Both show median knockdown of approximately 90% at steady state. Now we don't know exactly what level of knockdown is critical for efficacy in cardiomyopathy, but we have robust data in hereditary ATTR, where we have more sensitive endpoints that suggest, on a population basis, achieving 80% knockdown or greater is associated with halting of polyneuropathy. And based on our depth, speed and variability of knockdown, the large majority of patients, that 82% to 84% of vutrisiran-treated patients reached that threshold at steady state. So how does this compare to other molecules? Here, we plotted the same data as on the prior slide for vutrisiran, now shown as bar graphs. You see 91% median knockdown with about 82% of patients achieving that 80% threshold of deep knockdown. So how does that compare to the data reported for eplontersen? Our team used published data from the eplontersen PN study, which showed median knockdown of 84% at steady state as well as available data on variability to model the expected proportion of patients who will reach that same 80% knockdown threshold. Our model estimates that only about 67% of eplon-treated patients would reach that same deep level of knockdown. Or said another way, 1/3 of patients may not reach the threshold of knockdown we've seen to be associated with strong efficacy, nearly double that calculated for vutrisiran. These are estimates and should be interpreted with appropriate caution, but they highlight that the TTR knockdown data in CARDIO-TTRansform will be critical to review and insufficient knockdown is one plausible contributor to the failure of that study. We ran the same modeling exercise for nucresiran using the same dosing regimen that we are using in the TRITON-CM and PN studies. And the good news is that by these same metrics, nucresiran has the potential to be even better than vutrisiran's high mark. With median knockdown of 95% and low variability, over 99% of patients choosing nucresiran are expected to surpass this deep knockdown threshold. So in sum, we don't believe that the top line results shared a few weeks ago negate the hypothesis and rationale of using a silencer for ATTR-CM patients who are already on a stabilizer. More likely, as we see it, they may demonstrate that the type and depth of silencing, along with aspects of the study design are what really matter. With that, I'd like to remind you that we're progressing a broad pipeline of medicines beyond TTR with over 25 clinical programs spanning multiple therapeutic areas across rare specialty and prevalent indications. This robust pipeline represents a tremendous opportunity to improve patient health and create value in the years ahead. To that end, we look forward to a lot of pipeline momentum in the next two years. This year, in 2026, we continue to execute on our 3 ongoing pivotal studies, including 2 cardiovascular outcomes trials. We also anticipate 4 key data readouts in the second half, which I'll outline on the next slide. And looking ahead, we anticipate many more data readouts and pivotal trial starts in '27 and '28. Additionally, in 2028, we anticipate the launch of nucresiran in hATTR polyneuropathy, assuming positive Phase III data and regulatory approval. And of course, we'll continue to build the pipeline through the filing of 3 to 4 new INDs each year as we scale to meet our Alnylam 2030 ambitions. Coming back to '26 and our pipeline goals for the remainder of the year, we're looking forward to 4 important data readouts from 3 key programs. For ALN-6400, we plan to share healthy volunteer data from the ongoing Phase I study as well as initial results from the Phase II study in patients with hereditary hemorrhagic telangiectasia. We also expect to initiate Phase I data from both ALN-HTT02, our Huntington's disease program and ALN-2232 in development for obesity and weight management. With that, let me turn it back to Josh to coordinate our Q&A session. Josh? Josh Brodsky: Thank you, Pushkal. Operator, we'll now open the call for questions. [Operator Instructions] Operator: [Operator Instructions] Your first question comes from the line of Paul Matteis with Stifel. Paul Matteis: I wanted to just talk about, like, the change in guidance. By our math, under the new guide, you're growing around 50-ish percent at the midpoint in the second half of this year. And for 2030, I think you still guided to this 25% CAGR. Given this drop-off versus your original expectations and when you gave this long-term guidance. I was wondering if you could talk a little bit more about the next sort of 12- to 24-month outlook and your confidence that you can keep the growth rate on track likely above that 25% number for a while and still meet your long-term goals. Yvonne Greenstreet: Thanks for the question. Clearly, we're not pleased to be lowering guidance. As Jeff said, we own it. But I think it's really important to emphasize that we believe that the fundamentals driving our opportunity are really strong, particularly market growth and our first-line momentum. And it's difficult to know every single factor when you kick off a launch from the get-go. But we are very pleased with the outlook that we have in front of us, both in the near future, but also in the longer term in reaching our 2030 goals. Jeff, do you want to add some color? Jeffrey Poulton: I mean, I'll just comment on the second half of '26 and what the revised guidance implies. And then maybe Tolga would like to make some comments on longer-term confidence in the Alnylam 2030 guide. Paul, the revised guidance that we've given of $4.2 billion to $4.5 billion in terms of the midpoint of that, just relative to the growth that we just put up in the second quarter. The midpoint to achieve the midpoint, we would need to deliver growth in Q3 and Q4 that's consistent with what we just put up in Q2. And I think we do have confidence in that, given some of the things that Tolga talked about, particularly strength in the first-line part of the market in terms of demand we saw in the quarter in the U.S. But Tolga, any more comments on the confidence in the longer term? Tolga Tanguler: Yes. Maybe I'll combine both Yvonne and Jeff's point, which is, first and foremost, we are competing in a highly untapped market. 80% of patients remain untreated. And within that category, in a short 15 months, we've already been able to actually build a very strong base for our business. And what's exciting about that, frankly, to me is while we're obviously normalizing our second-line new business, our first-line business is really rapidly replacing that. And if you think about the fact that 80% in this category comes in as new patients as first line, we really like how we're positioned with the existing prescriber bases. And as I highlighted in my remarks, one of the areas where we still need to do some work, which I believe we'll be able to do is continue to expand our prescriber bases. And that's where we're really investing our efforts. And we've already done that. So given -- matching that with actually the access that we've been able to secure and good adherence rates, our ability to demonstrate 25% CAGR growth year-over-year is definitely within our reach. Yvonne Greenstreet: And if I can add, we're actually even more confident now with the results of the CARDIO-TRRansform study. I mean there's likely to be one less branded competitor on the market. And Pushkal touched on all the reasons why our confidence in nucri and TRITON-CM is undiminished. So I think if anything, actually, we're sort of more confident about our future outlook given these developments. Next question please. It's from Salveen. Tommie Reerink: This is Tommie on for Salveen. Curious on if you're seeing a slower rate of second-line patients taf progressors per year, given trends in earlier diagnosis and potentially patients staying on taf for longer? And also, if you could maybe comment on how you expect the timing for your diagnosis and awareness efforts to start playing a key role in first-line capture. Yvonne Greenstreet: That's a great question, first to Tolga. Tolga Tanguler: So it's a good question around the early diagnosis. Frankly, when we started, just like any launch, when you have an orthogonal mechanism of action product like we do, we knew that there was going to be a level of pent-up demand. And certainly, over time, we've seen that be normalizing. So we're still seeing actually a healthy number of patients that are coming into the category. That's about 20%, both switch and combo. That will continue to be the same. What's even more important to me is these early diagnosis is actually going to hopefully help increase the category growth and accelerating that category growth. We've already seen that. It's gone up from the prior years into -- since we launched an acceleration of these new patients. So in fact, those patients that are getting treated early is going to be a nice tailwind for us. Operator: Your next question comes from the line of Tazeen Ahmad with Bank of America. Tazeen Ahmad: I wanted to get a little bit more color about your comments about frontline is now about 80% of new starts. Can you just tell me what the split is for use in community physician practices versus centers of excellence? And I guess the question that a lot of people are asking is for better or for worse, right now, physicians are looking at stabilizers as being similar in efficacy to silencers. How do you, kind of, maintain that growth that you're seeing in frontline with needing to balance educating physicians, presumably community-based physicians on the real differences between silencers and stabilizers. Tolga Tanguler: Yes. So I'll say a few words, maybe I'll-- Scott will-- look, I mean, first and foremost, we continue to compete for category leadership against the product that's been in the market for approximately 7 years. And obviously, we remain ahead of the other recent entrants. But more importantly, how the business is evolving beneath the overall share, I think, is really, really important. Early in the launch, growth was more balanced between first and second-line patients. Today, second-line demand, as we described, has moved toward a more sustainable rate, an increasing proportion of our growth is now coming from first-line patients, which represents the larger and the more durable opportunity. At the same time, I think this is really important. We are deepening adoption within existing accounts and rapidly expanding that prescriber base. So we're essentially maintaining a strong overall share while improving the underlying composition of the business through a broader physician adoption. Now you brought up the point around the COEs and community experts. What's been really encouraging for us is as we establish that early base business, that business didn't just come from the COEs. We actually had a very healthy balance of COEs, academic centers as well as community experts. What we need to continue to do is to actually expand out those community expert centers, and we know how to do that. Some of the challenges we faced with that early on was, well, okay, I don't know what the differences are between the silencers and stabilizers. Now those physicians have actually adopted AMVUTTRA and all other stabilizers, we actually have a significantly higher market share. When it comes to, oh, well, I don't know how to buy and build this product, particularly around the community expert centers, we know how to bring them along with that, whether through building their -- helping their own practice or creating alternative sites of care for their injections. So it is something we've done already, and now we're essentially intensifying our efforts to make sure that actually that adoption curve continues to get deeper. Pushkal Garg: Yes. And Tazeen, I'll just add to what Tolga said in response to your question. Look, there's no head-to-head data, of course, we know between these different classes of medicines. But as I tried to highlight in the main presentation, we think we have actually an incredibly unique profile for AMVUTTRA. It starts with the outcomes data, which we think are really quite remarkable. I've shown you substantial impact on outcomes. And importantly, the fact that we've seen now in 2 studies, additive benefits on top of stabilizers, which suggests there is efficacy left that's not fully addressed by the stabilizers alone. It's indirect evidence, but we think it's very strong and reproducible evidence. We've also seen that starting these class of agents early silencers has the greatest treatment effect and even approaching almost 45% reductions in mortality, which I think is quite remarkable. And we're seeing evidence of disease remodeling when we look at echocardiographic parameters, we look at cardiac MRI, et cetera. So look, our job, as Tolga has highlighted, is to continue to educate on those attributes, continue to generate evidence. You've seen at recent meetings more and more that we're putting out and to continue to educate. And so as Tolga has talked about expanding the prescriber base, an important aspect of educating these prescribers on the attributes of this class of medicines. And we've seen that once they gain experience with it that they find that it actually becomes a dominant part of their practice in terms of the prescribing. So that's going to be our effort. Operator: Your next question comes from the line of Konstantinos Biliouris with Oppenheimer. Konstantinos Biliouris: One on Europe. Given that VYNDAQEL will soon be generic in Europe, to what extent do you think the commercial dynamics between AMVUTTRA and a generic drug in Europe will reflect what may happen in the U.S. post 2031 when tafamidis goes generic? Yvonne Greenstreet: Thank you very much. Tolga? Tolga Tanguler: So thank you, Kostas, for that question. First and foremost, I think we've always highlighted that the contribution of growth for Europe is going to be relatively modest, similar to the growth that we had last year. And that's a lot to do with the fact that we were going to actually make appropriate price adjustments in order to capture a larger cardiomyopathy volume. Now in terms of tafamidis, the 80 milligram, the 4 pills a day option is going to be going generic. I believe 61 milligram will continue to be available for a while. Now in respect to our ability to actually capture those reimbursements, since these are single-payer systems, these systems have already anticipated that genericization transition. And what I'm pleased to say that we've actually, in most cases, been able to secure premium pricing versus tafamidis and quite pleased with the ongoing negotiations we have whether it's Germany, Spain, Italy. And Japan, we've highlighted the fact that we are competing very effectively, essentially exceeding all analogs and a good uptake. So while, again, because of the pricing changes, we're going to have a modest growth contribution, particularly in '26, we see '27 and beyond the launches is going to have a meaningful impact on our overall business. Operator: Your next question comes from Ellie Merle with Barclays. Eliana Merle: Just curious if you could give us more color on what a steady-state level of second-line starts look like. I think you said 80% of starts in 2Q were from the front line. So is 20% a steady state for second-line starts? Or do you expect that to decline over time? And then I guess, what drives your confidence that the frontline starts will continue at this cadence going forward? And specifically, if you could give us more color on if we strip out the second-line starts, have you seen growth in first-line starts or a stable number of first-line starts each quarter? Tolga Tanguler: Yes. Thank you, Ellie, for that question. I mean just to be clear, when we talk about 80-20 perspective, that's mainly driven by the overall category. And what we've seen essentially is not a market share loss on second line, but the overall volume shift into a lesser contribution of the new brands from switches for the entire category. What I'm really pleased about is while we're continuing to maintain and having a nice gradual progression of our market share, that market share growth is actually being contributed by the first-line share. So that's actually a very healthy sign of our business. And in respect to the first-line contributions, as I alluded to earlier, those physicians that actually use all 3 products predominantly use AMVUTTRA as their first-line choice. That's the analysis that we have. So now the question is, how can we actually continue to expand the prescriber base. So more physicians actually test and understand and experience AMVUTTRA because they experience begets preference. And this is where we're really honing our efforts in. And we've been able to expand that prescriber base at 1,500 new prescribers since the launch, and we believe we're going to be able to continue to do that. And again, the goal has always been actually on first line. And this is -- this normalization is just a question actually, frankly, not just the dynamic, but also the strategy. Operator: Your next question comes from Luca Issi with RBC. Luca Issi: Maybe a quick one for Tolga. Pretty clear that AstraZeneca did not show any additive effect between stabilizer and silencers in their trial based on the press release. Again, I appreciate that's a different molecule as Pushkal nicely articulated. But are you seeing any impact commercially based on that data? Are you seeing payers forcing docs to pick one versus the other and no longer allowing patients to be on the combo? Any color there, much appreciated. And then super quickly, can you comment on the evolution of net price in the U.S. for the rest of the year? Tolga Tanguler: So that's a 3-parter, right, I guess. So maybe I'll start. I mean, obviously, Pushkal laid it out very clearly why we believe, what we believe. Look, in terms of the payer pushback, obviously, it's too early to say. But what I can tell you is this, overall access to AMVUTTRA remains very strong. Some Medicare Advantage policies that are already placed that already puts limitation on combination use. And in fee-for-service coverage always follows label. And frankly, physicians continue to have pathways to pursue access when they believe a particular treatment approach is medically appropriate given the severity of this disease. What's also very important is CARDIO-TTRansform does not change AMVUTTRA's evidence or its label. It was a study of a different molecule. We would not expect payers to alter AMVUTTRA coverage based on those results. Our priority remains ensuring appropriate patients can access AMVUTTRA, whether they're initiating first-line therapy or switching from another treatment. So we're not seeing any pushback, again, given the fact that actually the policies are already in place. And yet when the physician wants to have access, they obtain it if they provide the right appropriate materials. Yvonne Greenstreet: Thanks for that. Look, I think there are many examples of drugs in similar classes where one drug fails and the other succeeds. And we really believe what we have here are 2 distinct molecules with different mechanisms as well as different profiles in a different study. And really, our job is to get out there, as Tolga was saying, and educate physicians on the compelling benefits that we see for AMVUTTRA with a focus on first line because we believe this should be a foundational therapy as well as explaining the benefits that we've seen in 2 separate studies as Pushkal explained with respect to combination use. Jeffrey Poulton: There was one question on net price in terms of what we expect. And I think the slide that Tolga showed that showed the first half dynamics showed the modest quarter-to-quarter decreases in net price, we expect that will continue for the second half. And if we were to show you that on a year-over-year basis, the way we had guided was mid-single-digit net price decrease year-over-year. We're still on track for that, Luca. Operator: The next question comes from Jessica Fye with JPMorgan. Jessica Fye: Question for Pushkal. Recognizing that this is hypothetical, can you elaborate on some of those potential changes available to you with TRITON-CM to maximize its probability of success? And then maybe as a follow-up to that, are there potentially other paths to approval for nucresiran in ATTR-CM beyond TRITON-CM? For example, would it be feasible to run a non-inferiority trial against AMVUTTRA? Pushkal Garg: Yes. Thanks, Jess, for your question. Look, again, we feel really good about what we have in our hands, both in terms of the molecule nucresiran for all the reasons I talked about and the study that we have. So again, I want to reinforce, we may not need to do anything different from what we already have ongoing. That said, we do have options at our disposal. We'll look at the data and we'll consider. I think they broadly fall into a couple of buckets. One is whether we modify enrollment in certain subpopulations, for instance, and enrich in certain ways for those. Again, we've done that already in the context of the study, but we could potentially further do that based on information that we see. The other thing would be to make modifications around the analytic plan in terms of how we think about various endpoints, the hierarchy, et cetera. And so they're largely in those 2 big buckets. I mean, to the second part of your question, is there a possibility that if we wanted to, we could do additional studies? Yes, certainly, those things are potential. I'm not going to speculate though further on what those might look like. But I think broadly speaking, I think there's a variety of options in our hand. Again, we're playing the long game here. I think our commitment is to deliver a successful study. We've done that in the past. We think nucresiran has the opportunity to be an amazing medicine for patients, and we're committed to delivering a positive study for that. And so we will consider all the potential options at hand. As I said, they fall into several key buckets, and we'll kind of consider all those opportunities and see if anything at all is warranted. Operator: The next question comes from Whitney Ijem with Canaccord Genuity. Whitney Ijem: Just-- sorry if I missed it, but can you remind us on how -- any updated thinking, I guess, around the total U.S. patient population or TAM for ATTR-CM and where you are with diagnosis rate currently? And then just as a point of comparison ahead of the 6,400 Phase II data later this year, what are the comparable numbers for HHT U.S. TAM in terms of patient numbers and diagnosis rate? Tolga Tanguler: So for TTR, what I can tell you is in our latest estimates, if you go back to our TTR webinar, we've highlighted we estimate around 200,000 patients and about 80% of those remain untreated. What to me is sort of a good confirmatory data set is the fact that you're seeing around 40% year-over-year growth of the category with a single option on the table. That has actually accelerated since we launched. So -- and that remains very robust. So we believe more competitors, more awareness, more education and frankly, some of those initiatives that we've just actually laid will continue to help accelerate those patients getting diagnosed. And as you all know, we have excellent data that demonstrates those patients that are treated earlier end up actually getting more benefits from AMVUTTRA. So we're very actually excited about that. And again, our position on first line gives us the confidence that we can actually continue to be the leading option on the table in this growing category. Pushkal Garg: Yes. And with regard to hereditary hemorrhagic telangiectasia, there are -- there really are no approved treatments for this disease. It's actually the second most common rare bleeding disorder that's out there. I think globally, there's about 1.5 million patients with this disease. I think when we think about the addressable population in the United States, I think, again, those estimates vary. I think there's a number of these patients who don't actually get to medical attention. But we think there's probably about 70,000 or so patients in the United States who may be addressable with this condition. But again, that epidemiology will firm up again, as we've seen with rare diseases where there are treatments once there are effective treatments, more and more come to attention. So that's probably a ballpark though, for you. Operator: And that concludes our question-and-answer session. I will hand it back to the company for closing remarks. Yvonne Greenstreet: Thank you. So to close, we continue to build momentum across our business as we execute against our strategy and advance towards our 2030 goals. And I'd like to thank everyone who's joined us today. Thank you. Operator: Thank you, presenters. And ladies and gentlemen, this concludes today's conference call. 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Image source: The Motley Fool. Thursday, July 30, 2026, at 8:30 a.m. ET Vice President of Investor Relations - Josh Brodsky Chief Executive Officer - Yvonne Greenstreet Chief Financial Officer - Jeff Poulton Chief Commercial Officer - Tolga Tanguler Chief Research and Development Officer - Pushkal Garg Operator: Thank you for standing by. My name is Sprilla, and I will be your conference operator today. At this time, I would like to welcome everyone to the Alnylam Pharmaceuticals Q2 Earnings Conference Call. [Operator Instructions] I would now like to turn the conference over to the company. You may begin. Josh Brodsky: Good morning. I'm Josh Brodsky, Vice President of Investor Relations at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Jeff Poulton, Chief Financial Officer; Tolga Tanguler, Chief Commercial Officer; and Pushkal Garg, Chief Research and Development Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined on Slide 2, Yvonne will offer introductory remarks and provide some general context. Jeff will review our financials and guidance. Tolga will provide an update on our global commercial progress, and Pushkal will discuss our TTR franchise, our confidence in TRITON-CM and upcoming pipeline milestones before we open the call for your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provisions. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important risks and uncertainties, including those discussed under the heading Risk Factors in our most recent periodic report available on our website and on file with the SEC. We disclaim any obligation to update such statements. And with that, I'll now turn the call over to Yvonne. Yvonne? Yvonne Greenstreet: Thanks, Josh, and thank you, everyone, for joining the call today. During the second quarter, we demonstrated strong performance across all aspects of the business. Notably, it marks the first time AMVUTTRA revenues exceeded $1 billion in a single quarter, representing an annual run rate of more than $4 billion, just 15 months into the ATTR cardiomyopathy launch, a testament to both the commercial opportunity and Alnylam's execution. As we reflect on the launch, several insights reinforce our confidence in the durability of AMVUTTRA growth over the years ahead. First, this has been an impressive launch by industry benchmarks when looking across market share, access and revenue generation. Second, the fundamentals of our TTR business are strong, and they include AMVUTTRA's compelling clinical profile and label, the strong access that we established at launch, which continues to improve, and our robust and expanding provider network. Third, patient demand for AMVUTTRA continues to grow robustly, particularly in the first-line setting, which has been our focus as we aspire to market leadership, given AMVUTTRA's clinical differentiation and desirability as a foundational therapy for newly diagnosed patients. Tolga will discuss how we are now further investing in broadening our AMVUTTRA prescriber base and supporting overall category growth, the latter of which has been accelerating. Finally, our geographic expansion strategy continues to gain momentum. And today, we are pleased to announce our collaboration with BeOne through which they will have exclusive commercialization and distribution rights for AMVUTTRA in Mainland China and Macau, subject to AMVUTTRA receiving marketing authorization. Together with BeOne, we aim to help advance awareness and support diagnosis of ATTR amyloidosis and if approved, bring the strength of TTR silencing with AMVUTTRA to patients in these underserved regions. As Jeff will describe shortly, we are lowering our 2026 revenue guidance today to reflect a better understanding with hindsight of the first few quarters of our U.S. launch, specifically that early second-line demand growth in 2025 benefited significantly from pent-up demand for a new therapy that has since normalized. With that learning and our strong 2026 second quarter performance, our confidence in AMVUTTRA's growth trajectory has never been stronger. First-line new patient starts are now responsible for about 80% of category growth in this accelerating market, and we believe we're making great progress in establishing AMVUTTRA as a foundational therapy. I will now turn to recent developments in the competitive landscape, specifically the negative outcome of the CARDIO-TTRansform study of eplontersen. We recognize investor interest in understanding any potential implications of that study's failure for our probability of success in TRITON-CM, our Phase III cardiovascular outcomes trial of nucresiran. Let me be clear. This outcome does not alter our conviction in the TRITON-CM study. And as Pushkal will share in greater detail, our strong confidence is grounded in the established clinical evidence for RNAi therapeutics in TTR and the track record of our clinical organization. At the same time, we have a variety of options at our disposal to potentially adapt the study and position it for optimal success. We will carefully review the full eplontersen data set when it becomes available and adapt our study plan, if appropriate. We have successfully navigated complex TTR development before and believe we are exceptionally well positioned to do so again with nucresiran. Additionally, in the quarter, we were pleased to announce a series of strategic AI collaborations across the enterprise, including with Inceptive to expand the next frontier in the discovery of RNAi therapeutics and the collaboration we are pleased to announce today with a large health care system in California aimed at supporting early identification of ATTR cardiomyopathy in routine care. This builds on our previously announced partnerships with Viz AI and Komodo Health. Altogether, this cohesive AI strategy from discovery and evidence generation to disease identification, clinical practice and commercial execution reflects our long-term conviction that AI will fundamentally reshape how medicines are discovered, developed and ultimately delivered to patients. Finally, we also continue to progress our deep pipeline of investigational medicines, initiating a Phase II trial of ALN-6400 in von Willebrand disease and a Phase II trial of mivelsiran in Down syndrome associated Alzheimer's disease, and we look forward to a series of clinical data readouts in the back half of this year, including presentation of initial Phase I results of ALN-HTT02 in patients with Huntington's disease at EHDN in October. All of this progress builds on our momentum towards accelerating innovation, scaling our impact as we look to deliver on our 5-year vision Alnylam 2030. And our strategy is anchored around 3 pillars. The first pillar is to establish global leadership in TTR while continuing to build a durable franchise. The momentum we have built in ATTR cardiomyopathy to date, along with the recent developments in the competitive landscape, including the CARDIO-TTRansform Phase III top line results and the delay in expected U.S. generic entry for tafamidis until mid-2031, further reinforce the strength of our position and the significant opportunity ahead to establish AMVUTTRA as a foundational therapy and realize our TTR leadership ambitions. The second pillar is growing through sustainable innovation, where we aim to deliver therapies that not only slow the progression of disease, but prevent, halt or reverse it. And the third pillar is scaling with discipline and agility to enable durable, profitable growth. Alnylam 2030 represents our commitment to becoming the leading science-driven, fully integrated global biopharmaceutical company and to maximize the full potential of RNAi therapeutics for patients. With that, let me now turn the call over to Jeff for a review of our second quarter financial results and 2026 guidance. Jeff? Jeffrey Poulton: Thanks, Yvonne, and good morning, everyone. This morning, I'll be presenting a summary of Alnylam's second quarter 2026 financial results and discussing updates to our full year guidance. Let's begin with a summary of our P&L results for the second quarter. Total global net product revenues were approximately $1.2 billion, representing 74% growth versus Q2 last year, driven by the continued uptake of AMVUTTRA and ATTR cardiomyopathy. The second quarter of 2026 marks the first time we achieved more than $1 billion of TTR revenue. These results reflect a substantial improvement in quarter-on-quarter growth compared with growth in Q1 this year, consistent with the phasing expectations we discussed on our year-end and Q1 earnings calls earlier this year. Tolga will share more details on our TTR performance in the quarter. In Q2, collaboration revenue was $47 million, or a 23% decrease, compared with the same period last year due to lower revenue recognized from our Regeneron collaboration, partially offset by increased revenue from our Roche collaboration, driven by higher reimbursable development activities related to the ZENITH Phase III clinical trial of zilebesiran. Royalty revenue for the second quarter increased 79% to $72 million, driven by higher LEQVIO sales by Novartis. Gross margin on product sales was 75%, or 4% lower than Q2 last year. The decrease in margin was primarily driven by increased royalties on AMVUTTRA as higher revenues in 2026 resulted in an increase in the average royalty rate payable to Sanofi. Our non-GAAP R&D expenses of $377 million increased 38% compared to last year, primarily driven by costs associated with our 3 ongoing Phase III clinical studies, including the ZENITH Phase III cardiovascular outcomes trial for zilebesiran and the TRITON-CM and PN studies for nucresiran. Beyond the pivotal studies, we also continue to increase investment to support important programs for bleeding disorders, Huntington's disease and CAA. Non-GAAP SG&A expenses of $297 million increased 14% compared to last year, driven primarily by investments in support of the AMVUTTRA-ATTR cardiomyopathy launch in the U.S. and key international markets. We achieved non-GAAP operating income of $318 million, more than triple the amount we achieved last year, driven primarily by the strong top line results that I've previously highlighted. Finally, we ended the second quarter with cash, cash equivalents and marketable securities of $3.3 billion compared with $2.9 billion as of year-end 2025. The primary driver of the increase in cash year-to-date is our strong operating performance. Now turning to our full year 2026 guidance. As Yvonne noted, we are revising our total net product revenue guidance to $4.7 billion to $5.1 billion, driven fully by an update of our TTR revenue guidance to $4.2 billion to $4.5 billion, representing a $200 million reduction from our original TTR guidance at the midpoint and still reflects a robust 75% growth year-over-year. Guiding the market's expectations appropriately is important, and we didn't get it right with our original guidance. We own that. The revised guidance we are sharing today reflects a better understanding of the evolution of second-line demand as our launch has progressed. Let me provide some additional color on the basis for this revision. Overall, the AMVUTTRA cardiomyopathy launch continues to perform ahead of analogs. And importantly, we are pleased with uptake in the first-line portion of the market, which has been and remains the primary focus of our commercial efforts given the importance of this segment to driving long-term growth. When AMVUTTRA was launched in April 2025, the compelling HELIOS-B data and our team's success in establishing access enabled physicians to rapidly transition existing patients who are progressing on stabilizers onto AMVUTTRA. As a result, second-line demand volumes remain consistently robust throughout 2025, which informed our original 2026 guidance. However, as the launch progressed into 2026 and with the benefit of hindsight, it is now clear that a greater-than understood proportion of early second-line volume growth was driven by pent-up demand from patients who are waiting for a new treatment option. Consistent with the trend we highlighted on our Q1 2026 earnings call, growth in second-line volumes began to moderate in early 2026 to what we now recognize as a normalized level. This normalization of second-line demand is the driver of the $200 million reduction in TTR guidance that we are announcing today. Tolga will share more perspective in just a few moments on our confidence in future TTR growth, which is grounded in 3 key elements: the strength of our current market fundamentals, positive impact we expect from new investments we're making based on early launch learnings and, lastly, the favorable competitive developments that Yvonne mentioned in her opening remarks. Now back to updating our guidance. We are also updating our guidance for collaboration and royalty revenues to a revised range of $575 million to $625 million, representing a $150 million increase at the midpoint of the range, driven primarily by strong performance of LEQVIO and the resulting royalties from Novartis as well as higher cost reimbursement from Roche favorably impacting collaboration revenue, driven by the pace of enrollment in our ZENITH Phase III study with zilebesiran. The remainder of our non-GAAP financial guidance remains unchanged. Let me now turn it over to Tolga to provide more color on our commercial performance in the second quarter. Tolga? Tolga Tanguler: Thanks, Jeff, and good morning. I'm pleased to share our continued progress in bringing Alnylam's therapies to patients globally. AMVUTTRA is delivering a category-defining ATTR-CM launch and is on track towards delivering on our Alnylam 2030 ambitions. As Yvonne and Jeff mentioned, we have gained valuable insights as the launch has progressed. These learnings have sharpened our understanding of demand dynamics while also reinforcing our confidence in the fundamental drivers of sustainable growth. Overall, we remain highly confident in our path to achieving TTR leadership. The momentum of the business, coupled with an increasingly favorable competitive landscape, reinforce our conviction in achieving our long-term ambitions. Q2 marked another quarter of strong commercial execution and growth. Specifically, we delivered $1.17 billion in combined net product revenues, up 74% year-over-year and 13% over Q1 2026. In just 5 quarters since our CM launch, we have generated over $4 billion in total revenue, reflecting both a strong base and a clear growth trajectory. Our rare disease portfolio also continues to deliver meaningful impact for patients and consistent performance for our business. In Q2, we generated $142 million in rare disease net revenue, up 11% year-over-year. Turning to our TTR franchise. Global TTR net revenues reached $1.03 billion in the second quarter, increasing 13% versus Q1 and 89% year-over-year, reflecting the continued strength of the launch and the robust execution of our global teams. In the U.S., TTR revenues increased 15% versus Q1 and 114% year-over-year, reflecting robust underlying demand with reported revenue partially held back by changes in inventory days on hand during Q2. Access remained broad, pull-through was strong and adherence continued to exceed 90%. Outside the U.S., TTR revenues increased 7% versus Q1 and 31% year-over-year. Continued ATTR-CM uptake in Japan, the U.K. and Germany, along with strong polyneuropathy performance across our international markets drove Q2 growth despite pricing headwinds related to ongoing CM launches in several countries. Double-clicking on our Q2 TTR performance in the U.S., underlying demand was exceptionally strong, increasing by $129 million in the quarter, more than doubling the demand growth achieved in Q1. A portion of that demand was offset by inventory dynamics, which reduced reported growth by $21 million and to a lesser extent, by the continued and anticipated modest reduction in net price. As a reminder, our Q1 U.S. TTR growth was more modest and was impacted by several seasonal phasing dynamics, and we are, therefore, pleased by the robust reacceleration in demand in Q2 and the continuing strength of the business. AMVUTTRA's differentiated clinical profile underpins our confidence in the long-term growth opportunity. We believe that AMVUTTRA stands apart as a first-line choice on attributes that matter to physicians and patients. It is the first and only product approved in the U.S. for both ATTR-CM and hereditary ATTR-PN. It works upstream at the source, delivering rapid, deep and sustained knockdown of the disease-causing protein. In the pivotal HELIOS-B study, AMVUTTRA met 10 out of 10 endpoints and demonstrated robust treatment effects in the primary endpoint of all-cause mortality and recurring CV events and secondary endpoints of functional capacity and health-related quality of life. Across all of these endpoints, consistent treatment effects with or without background stabilizers were observed, combined with the convenience of once quarterly health care-provided administration and real-world data that suggests greater than 90% adherence, we believe AMVUTTRA is uniquely positioned to address the needs of the growing ATTR-CM patient population. The first 5 quarters of launch have provided valuable insights that are informing where we increase investment and how we position the business for its next phase of growth. During the initial quarters following approval, many of our high-volume early adopters transitioned a substantial number of stabilizer-treated progressing patients to AMVUTTRA. While those transitions continue, we are now seeing that portion of demand volume growth normalize toward a more sustainable underlying rate, and we continue to capture leadership share of second-line starts. Today, approximately 80% of new treatment initiations are first-line starts. Establishing AMVUTTRA as first-line treatment choice has been our priority since launch, and we continue to strengthen our competitive position. What's more, while our strategy has never dependent on competitors' outcomes, 2 favorable developments in the external landscape have cleared the path for us to be even more competitive in the first-line setting. First, we now anticipate tafamidis U.S. loss of exclusivity in 2031. AMVUTTRA is already challenging the 7-year incumbent for leadership share of new patient starts, and we see a significant opportunity to continue strengthening that position years ahead of genericization of the stabilizer class. Second, based on the CARDIO-TTRansform study top line results, we now anticipate fewer branded ATTR-CM competitor in both the first-line and stabilizer progressive segments. Finally, category growth continues to accelerate and our competitive first-line share, coupled with this clear competitive path to greater first-line penetration, aligns well with where we see the largest opportunity. With an estimated 80% of patients still untreated and additional physicians and health systems initiating treatment of ATTR-CM, we expect the robust growth in first-line starts to continue. And we're helping to drive that category growth. More specifically, we're accelerating our investments in diagnosis-enabling initiatives, investments to identify patients earlier to expand the treatable population and ultimately to improve patient outcomes. Taken together, these insights provide great confidence in our ability to expand leadership across both ATTR-CM and hereditary ATTR-PN and deliver on our 2030 ambitions of TTR leadership at a 25% revenue CAGR during the period. As we shared today, our differentiated profile has translated into exceptional launch momentum and that experience has sharpened our understanding of what will drive the next phase of growth. First, after 5 quarters in the market, AMVUTTRA's compelling profile and our focused efforts have driven broad coverage and efficient patient access with no meaningful reimbursement headwinds. We believe the strong access foundation will continue to support physician confidence and patient adoption as we expand the franchise. Second, we continue to deepen adoption among physicians who have already incorporated AMVUTTRA into their practice. Among prescribers using AMVUTTRA, it now represents more than 50% of new patient starts, underscoring the strong physician preference that develops with experience. And from our TTR-CM launch through the end of Q2, we have added over 1,700 new prescribers. Third, and perhaps most importantly, we have significant opportunity to expand the breadth of prescribers who have experienced with AMVUTTRA, which we estimate at about 1/3 of the growing pool of TTR prescribers. While we now -- we know that experience drives preference, there are many more physicians, including many who are new to the category, who have not yet prescribed AMVUTTRA. To capture that opportunity, we are intensifying our focus and increasing our investment in customer-facing activities to expand the breadth of prescribing. We are already seeing early progress from these efforts with accelerated growth in new AMVUTTRA prescribers during the second quarter, we believe we are in the early stages of that expansion opportunity. While we're still early in the commercialization journey, we believe AMVUTTRA is well positioned to capture the significant opportunity ahead as we bring this differentiated therapy to more patients living with ATTR-CM. With that, I will now turn it over to Pushkal. Pushkal Garg: Thank you, Tolga, and good morning, everyone. As Tolga just highlighted, we believe AMVUTTRA has a remarkable clinical profile that supports it being the first-line treatment of choice for patients with ATTR cardiomyopathy. These key attributes are highlighted here with data from the landmark HELIOS-B study. First and foremost, we've seen substantial benefits with regard to improving clinical outcomes, both all-cause mortality and cardiovascular events with reductions of nearly 40% over 48 months across these 2 endpoints. Second, the treatment effects are largest when we intervene early. You can see that in the forest plot on the bottom left, where patients with lower BNP, greater walking ability and younger age have had even greater reductions in the composite endpoint of 47%, 42% and 45%, respectively. And importantly, in data recently presented at ESC heart failure and shown on the lower right quadrant, we see that the treatment effect is preserved irrespective of background medications, including TTR stabilizers. These attributes, along with the quarterly dosing that supports adherence in our view, represents an ideal profile for a first-line agent for patients with ATTR cardiomyopathy. Now the strength of these HELIOS-B results, along with our many learnings from our deep experience in TTR amyloidosis, provide us with staunch conviction in the value of nucresiran, our next-generation investigational RNAi TTR silencer, which we believe has the potential for even greater improved efficacy by a greater knockdown, over 95% with just 2 doses per year. As you're aware, we continue to advance nucresiran in the TRITON Phase III program. TRITON-CM is a randomized double-blind, event-driven outcome study of nucresiran versus placebo. We announced last quarter that we utilized a prespecified option in our protocol to expand enrollment by about -- by approximately 500 patients to 1,750 in total, further mitigating the potential risk of low event rates while maintaining or potentially even accelerating time lines for this important study. Now given recent competitor data and given that many patients in TRITON-CM will be on a background stabilizer, we understand that there have been many questions raised about the feasibility of delivering positive results from this clinical trial. While we still have more to learn about the eplontersen results, we believe they're likely attributable to a combination of molecule and study-specific issues. And as we compare what we know about nucresiran with what's been reported about eplontersen, I want to assure you that we remain highly confident in nucresiran and TRITON-CM. I'll explain more in a moment, but first, let me share what we'll be looking for in the upcoming data presentations of the CARDIO-TTRansform results at ESC to better understand the reasons why the study did not meet its primary endpoint. First, we'll be interested to learn more about the population and baseline characteristics of the CARDIO-TTRansform study, particularly in the 2 key subgroups of monotherapy and in the patients on background stabilizers. As I noted, in HELIOS-B, we saw that treatment effects with AMVUTTRA were greatest in early patients. And so a drug signal may be obscured if many advanced patients were enrolled. We already know from published data that the CARDIO-TTRansform study enrolled 17% NYHA Class III patients, nearly double that in HELIOS-B, patients with higher NAC stage and patients with higher BNPs. Importantly, as I'll explain further in a moment, we believe deep rapid knockdown of TTR is critical to improving outcomes in ATTR cardiomyopathy. Graphs in the primary manuscript for the eplontersen PN study indicated it took longer to get to peak knockdown than AMVUTTRA, but the depth and variability of knockdown are also important. So we'll be looking for those details. Safety will be important given what we know about ASOs in the past and the frailty of the ATTR cardiomyopathy population. Did patients stay on drug? And were there any competing risks that impacted study outcomes. We also want to look at study execution and completeness of follow-up. And finally, we'll want to take a much deeper look at the outcomes data. For example, how did the individual components of their primary endpoint, CV mortality and CV events look? And what about all-cause mortality, which is part of our primary endpoint? How did these accrue over time and did the results vary in particular subgroups, particularly by disease severity. Bottom line is there are a lot of details not yet known about the failure of CARDIO-TTRansform. However, we are in an ideal position to learn from it. With enrollment ongoing and a projected launch for nucresiran in 2030 for ATTR cardiomyopathy, we have plenty of time to digest this information, thoroughly consider our options and implement appropriate changes to TRITON-CM, assuming any are even warranted. Let me return now to why we remain confident in TRITON-CM following the CARDIO-TTRansform top line release. The reasons come down to 3 key factors: the specific attributes of our molecule, nucresiran, key design elements of the TRITON-CM study and the track record of our team here at Alnylam. Starting with the molecule. First, RNAi therapeutics are fundamentally different than antisense oligonucleotides. In our hands, RNAi has been able to deliver rapid, deep and durable TTR knockdown, which we believe has implications on treating the course of disease. There are now several recent examples of ASOs and RNAis silencing the same genetic target with very different profiles. We've also seen that the safety profiles of these 2 approaches differ as well. Second, nucresiran's depth of TTR knockdown is expected to be best-in-class based on preliminary Phase I results showing over 95% TTR knockdown with much tighter intra-patient variability. I'll explain why we believe that will result in strong efficacy in a moment. And finally, we have data from 2 prior studies evaluating RNAi in ATTR cardiomyopathy patients, APOLLO-B and HELIOS-B, both of which generated data supporting a combination benefit. You've seen the HELIOS-B data in label, which shows a clear benefit of RNAi-mediated TTR silencing in a population that included heavy stabilizer use and consistent effects in combination and monotherapy. But as I'll show you in a moment, we saw the same effect with patisiran as well. Moving to the study. TRITON-CM now with 1,750 patients will be the largest study conducted in ATTR-CM, which will allow us to accrue more outcome events. And further to that point, we designed TRITON-CM as an event-driven study. Given the evolving treatment landscape, patients with somewhat milder disease on baseline on average and other dynamics, we determined that a time-based primary endpoint was not ideal. Instead, we'll continue the study until we have enough endpoint events to ensure sufficient study power. Third, we've used our insights to define entry criteria that enrich for patients who are most likely to benefit based on our prior learnings. And finally, we have an outstanding experienced team here at Alnylam. We've been focused on TTR drug development for well over 15 years, delivering 2 approved products. We've amassed tremendous experience across study design, execution and analysis to maximize the probability of success of a trial in this area. Part of this experience and history of conducting TTR trials is our vast database of deep patient-level insights that we can leverage to optimize study design and conduct. And to that last point, we have a track record of meticulous execution to ensure study success. This was most recently exemplified by how we optimize the endpoint structure and analytic plan for HELIOS-B to deliver remarkable results, resulting in a strong label that Tolga highlighted earlier. Before I move on, I'd like to underscore a few of the points I just made by sharing some clinical data that support the additive benefits of RNAi-mediated silencing on top of a stabilizer. As you'll recall, the HELIOS-B study demonstrated an approximately 41% reduction in the risk of all-cause mortality up to 42 months when AMVUTTRA was given to patients on a stabilizer at baseline, highlighting both the residual unmet need in these stabilizer-treated patients as well as the additive benefit of vutrisiran. But what you may not know is that we saw a nearly identical effect in APOLLO-B. As shown here, with just 24 months of follow-up in a comparable population in that study, we saw an estimated 44% reduction in all-cause mortality. Hence, we have data from 2 different molecules in 2 different studies showing comparable improvements in outcomes, which provides the strongest evidence of a combo effect. We believe these clinical data results from the knockdown profile of these 2 medicines. There are many ways to look at TTR knockdown, but what we believe matters is the speed and depth of knockdown and particularly getting as many patients as possible to deep knockdown. Here, we show TTR knockdown from our polyneuropathy studies, which have the richest sampling of TTR levels. Both show median knockdown of approximately 90% at steady state. Now we don't know exactly what level of knockdown is critical for efficacy in cardiomyopathy, but we have robust data in hereditary ATTR, where we have more sensitive endpoints that suggest, on a population basis, achieving 80% knockdown or greater is associated with halting of polyneuropathy. And based on our depth, speed and variability of knockdown, the large majority of patients, that 82% to 84% of vutrisiran-treated patients reached that threshold at steady state. So how does this compare to other molecules? Here, we plotted the same data as on the prior slide for vutrisiran, now shown as bar graphs. You see 91% median knockdown with about 82% of patients achieving that 80% threshold of deep knockdown. So how does that compare to the data reported for eplontersen? Our team used published data from the eplontersen PN study, which showed median knockdown of 84% at steady state as well as available data on variability to model the expected proportion of patients who will reach that same 80% knockdown threshold. Our model estimates that only about 67% of eplon-treated patients would reach that same deep level of knockdown. Or said another way, 1/3 of patients may not reach the threshold of knockdown we've seen to be associated with strong efficacy, nearly double that calculated for vutrisiran. These are estimates and should be interpreted with appropriate caution, but they highlight that the TTR knockdown data in CARDIO-TTRansform will be critical to review and insufficient knockdown is one plausible contributor to the failure of that study. We ran the same modeling exercise for nucresiran using the same dosing regimen that we are using in the TRITON-CM and PN studies. And the good news is that by these same metrics, nucresiran has the potential to be even better than vutrisiran's high mark. With median knockdown of 95% and low variability, over 99% of patients choosing nucresiran are expected to surpass this deep knockdown threshold. So in sum, we don't believe that the top line results shared a few weeks ago negate the hypothesis and rationale of using a silencer for ATTR-CM patients who are already on a stabilizer. More likely, as we see it, they may demonstrate that the type and depth of silencing, along with aspects of the study design are what really matter. With that, I'd like to remind you that we're progressing a broad pipeline of medicines beyond TTR with over 25 clinical programs spanning multiple therapeutic areas across rare specialty and prevalent indications. This robust pipeline represents a tremendous opportunity to improve patient health and create value in the years ahead. To that end, we look forward to a lot of pipeline momentum in the next two years. This year, in 2026, we continue to execute on our 3 ongoing pivotal studies, including 2 cardiovascular outcomes trials. We also anticipate 4 key data readouts in the second half, which I'll outline on the next slide. And looking ahead, we anticipate many more data readouts and pivotal trial starts in '27 and '28. Additionally, in 2028, we anticipate the launch of nucresiran in hATTR polyneuropathy, assuming positive Phase III data and regulatory approval. And of course, we'll continue to build the pipeline through the filing of 3 to 4 new INDs each year as we scale to meet our Alnylam 2030 ambitions. Coming back to '26 and our pipeline goals for the remainder of the year, we're looking forward to 4 important data readouts from 3 key programs. For ALN-6400, we plan to share healthy volunteer data from the ongoing Phase I study as well as initial results from the Phase II study in patients with hereditary hemorrhagic telangiectasia. We also expect to initiate Phase I data from both ALN-HTT02, our Huntington's disease program and ALN-2232 in development for obesity and weight management. With that, let me turn it back to Josh to coordinate our Q&A session. Josh? Josh Brodsky: Thank you, Pushkal. Operator, we'll now open the call for questions. [Operator Instructions] Operator: [Operator Instructions] Your first question comes from the line of Paul Matteis with Stifel. Paul Matteis: I wanted to just talk about, like, the change in guidance. By our math, under the new guide, you're growing around 50-ish percent at the midpoint in the second half of this year. And for 2030, I think you still guided to this 25% CAGR. Given this drop-off versus your original expectations and when you gave this long-term guidance. I was wondering if you could talk a little bit more about the next sort of 12- to 24-month outlook and your confidence that you can keep the growth rate on track likely above that 25% number for a while and still meet your long-term goals. Yvonne Greenstreet: Thanks for the question. Clearly, we're not pleased to be lowering guidance. As Jeff said, we own it. But I think it's really important to emphasize that we believe that the fundamentals driving our opportunity are really strong, particularly market growth and our first-line momentum. And it's difficult to know every single factor when you kick off a launch from the get-go. But we are very pleased with the outlook that we have in front of us, both in the near future, but also in the longer term in reaching our 2030 goals. Jeff, do you want to add some color? Jeffrey Poulton: I mean, I'll just comment on the second half of '26 and what the revised guidance implies. And then maybe Tolga would like to make some comments on longer-term confidence in the Alnylam 2030 guide. Paul, the revised guidance that we've given of $4.2 billion to $4.5 billion in terms of the midpoint of that, just relative to the growth that we just put up in the second quarter. The midpoint to achieve the midpoint, we would need to deliver growth in Q3 and Q4 that's consistent with what we just put up in Q2. And I think we do have confidence in that, given some of the things that Tolga talked about, particularly strength in the first-line part of the market in terms of demand we saw in the quarter in the U.S. But Tolga, any more comments on the confidence in the longer term? Tolga Tanguler: Yes. Maybe I'll combine both Yvonne and Jeff's point, which is, first and foremost, we are competing in a highly untapped market. 80% of patients remain untreated. And within that category, in a short 15 months, we've already been able to actually build a very strong base for our business. And what's exciting about that, frankly, to me is while we're obviously normalizing our second-line new business, our first-line business is really rapidly replacing that. And if you think about the fact that 80% in this category comes in as new patients as first line, we really like how we're positioned with the existing prescriber bases. And as I highlighted in my remarks, one of the areas where we still need to do some work, which I believe we'll be able to do is continue to expand our prescriber bases. And that's where we're really investing our efforts. And we've already done that. So given -- matching that with actually the access that we've been able to secure and good adherence rates, our ability to demonstrate 25% CAGR growth year-over-year is definitely within our reach. Yvonne Greenstreet: And if I can add, we're actually even more confident now with the results of the CARDIO-TRRansform study. I mean there's likely to be one less branded competitor on the market. And Pushkal touched on all the reasons why our confidence in nucri and TRITON-CM is undiminished. So I think if anything, actually, we're sort of more confident about our future outlook given these developments. Next question please. It's from Salveen. Tommie Reerink: This is Tommie on for Salveen. Curious on if you're seeing a slower rate of second-line patients taf progressors per year, given trends in earlier diagnosis and potentially patients staying on taf for longer? And also, if you could maybe comment on how you expect the timing for your diagnosis and awareness efforts to start playing a key role in first-line capture. Yvonne Greenstreet: That's a great question, first to Tolga. Tolga Tanguler: So it's a good question around the early diagnosis. Frankly, when we started, just like any launch, when you have an orthogonal mechanism of action product like we do, we knew that there was going to be a level of pent-up demand. And certainly, over time, we've seen that be normalizing. So we're still seeing actually a healthy number of patients that are coming into the category. That's about 20%, both switch and combo. That will continue to be the same. What's even more important to me is these early diagnosis is actually going to hopefully help increase the category growth and accelerating that category growth. We've already seen that. It's gone up from the prior years into -- since we launched an acceleration of these new patients. So in fact, those patients that are getting treated early is going to be a nice tailwind for us. Operator: Your next question comes from the line of Tazeen Ahmad with Bank of America. Tazeen Ahmad: I wanted to get a little bit more color about your comments about frontline is now about 80% of new starts. Can you just tell me what the split is for use in community physician practices versus centers of excellence? And I guess the question that a lot of people are asking is for better or for worse, right now, physicians are looking at stabilizers as being similar in efficacy to silencers. How do you, kind of, maintain that growth that you're seeing in frontline with needing to balance educating physicians, presumably community-based physicians on the real differences between silencers and stabilizers. Tolga Tanguler: Yes. So I'll say a few words, maybe I'll-- Scott will-- look, I mean, first and foremost, we continue to compete for category leadership against the product that's been in the market for approximately 7 years. And obviously, we remain ahead of the other recent entrants. But more importantly, how the business is evolving beneath the overall share, I think, is really, really important. Early in the launch, growth was more balanced between first and second-line patients. Today, second-line demand, as we described, has moved toward a more sustainable rate, an increasing proportion of our growth is now coming from first-line patients, which represents the larger and the more durable opportunity. At the same time, I think this is really important. We are deepening adoption within existing accounts and rapidly expanding that prescriber base. So we're essentially maintaining a strong overall share while improving the underlying composition of the business through a broader physician adoption. Now you brought up the point around the COEs and community experts. What's been really encouraging for us is as we establish that early base business, that business didn't just come from the COEs. We actually had a very healthy balance of COEs, academic centers as well as community experts. What we need to continue to do is to actually expand out those community expert centers, and we know how to do that. Some of the challenges we faced with that early on was, well, okay, I don't know what the differences are between the silencers and stabilizers. Now those physicians have actually adopted AMVUTTRA and all other stabilizers, we actually have a significantly higher market share. When it comes to, oh, well, I don't know how to buy and build this product, particularly around the community expert centers, we know how to bring them along with that, whether through building their -- helping their own practice or creating alternative sites of care for their injections. So it is something we've done already, and now we're essentially intensifying our efforts to make sure that actually that adoption curve continues to get deeper. Pushkal Garg: Yes. And Tazeen, I'll just add to what Tolga said in response to your question. Look, there's no head-to-head data, of course, we know between these different classes of medicines. But as I tried to highlight in the main presentation, we think we have actually an incredibly unique profile for AMVUTTRA. It starts with the outcomes data, which we think are really quite remarkable. I've shown you substantial impact on outcomes. And importantly, the fact that we've seen now in 2 studies, additive benefits on top of stabilizers, which suggests there is efficacy left that's not fully addressed by the stabilizers alone. It's indirect evidence, but we think it's very strong and reproducible evidence. We've also seen that starting these class of agents early silencers has the greatest treatment effect and even approaching almost 45% reductions in mortality, which I think is quite remarkable. And we're seeing evidence of disease remodeling when we look at echocardiographic parameters, we look at cardiac MRI, et cetera. So look, our job, as Tolga has highlighted, is to continue to educate on those attributes, continue to generate evidence. You've seen at recent meetings more and more that we're putting out and to continue to educate. And so as Tolga has talked about expanding the prescriber base, an important aspect of educating these prescribers on the attributes of this class of medicines. And we've seen that once they gain experience with it that they find that it actually becomes a dominant part of their practice in terms of the prescribing. So that's going to be our effort. Operator: Your next question comes from the line of Konstantinos Biliouris with Oppenheimer. Konstantinos Biliouris: One on Europe. Given that VYNDAQEL will soon be generic in Europe, to what extent do you think the commercial dynamics between AMVUTTRA and a generic drug in Europe will reflect what may happen in the U.S. post 2031 when tafamidis goes generic? Yvonne Greenstreet: Thank you very much. Tolga? Tolga Tanguler: So thank you, Kostas, for that question. First and foremost, I think we've always highlighted that the contribution of growth for Europe is going to be relatively modest, similar to the growth that we had last year. And that's a lot to do with the fact that we were going to actually make appropriate price adjustments in order to capture a larger cardiomyopathy volume. Now in terms of tafamidis, the 80 milligram, the 4 pills a day option is going to be going generic. I believe 61 milligram will continue to be available for a while. Now in respect to our ability to actually capture those reimbursements, since these are single-payer systems, these systems have already anticipated that genericization transition. And what I'm pleased to say that we've actually, in most cases, been able to secure premium pricing versus tafamidis and quite pleased with the ongoing negotiations we have whether it's Germany, Spain, Italy. And Japan, we've highlighted the fact that we are competing very effectively, essentially exceeding all analogs and a good uptake. So while, again, because of the pricing changes, we're going to have a modest growth contribution, particularly in '26, we see '27 and beyond the launches is going to have a meaningful impact on our overall business. Operator: Your next question comes from Ellie Merle with Barclays. Eliana Merle: Just curious if you could give us more color on what a steady-state level of second-line starts look like. I think you said 80% of starts in 2Q were from the front line. So is 20% a steady state for second-line starts? Or do you expect that to decline over time? And then I guess, what drives your confidence that the frontline starts will continue at this cadence going forward? And specifically, if you could give us more color on if we strip out the second-line starts, have you seen growth in first-line starts or a stable number of first-line starts each quarter? Tolga Tanguler: Yes. Thank you, Ellie, for that question. I mean just to be clear, when we talk about 80-20 perspective, that's mainly driven by the overall category. And what we've seen essentially is not a market share loss on second line, but the overall volume shift into a lesser contribution of the new brands from switches for the entire category. What I'm really pleased about is while we're continuing to maintain and having a nice gradual progression of our market share, that market share growth is actually being contributed by the first-line share. So that's actually a very healthy sign of our business. And in respect to the first-line contributions, as I alluded to earlier, those physicians that actually use all 3 products predominantly use AMVUTTRA as their first-line choice. That's the analysis that we have. So now the question is, how can we actually continue to expand the prescriber base. So more physicians actually test and understand and experience AMVUTTRA because they experience begets preference. And this is where we're really honing our efforts in. And we've been able to expand that prescriber base at 1,500 new prescribers since the launch, and we believe we're going to be able to continue to do that. And again, the goal has always been actually on first line. And this is -- this normalization is just a question actually, frankly, not just the dynamic, but also the strategy. Operator: Your next question comes from Luca Issi with RBC. Luca Issi: Maybe a quick one for Tolga. Pretty clear that AstraZeneca did not show any additive effect between stabilizer and silencers in their trial based on the press release. Again, I appreciate that's a different molecule as Pushkal nicely articulated. But are you seeing any impact commercially based on that data? Are you seeing payers forcing docs to pick one versus the other and no longer allowing patients to be on the combo? Any color there, much appreciated. And then super quickly, can you comment on the evolution of net price in the U.S. for the rest of the year? Tolga Tanguler: So that's a 3-parter, right, I guess. So maybe I'll start. I mean, obviously, Pushkal laid it out very clearly why we believe, what we believe. Look, in terms of the payer pushback, obviously, it's too early to say. But what I can tell you is this, overall access to AMVUTTRA remains very strong. Some Medicare Advantage policies that are already placed that already puts limitation on combination use. And in fee-for-service coverage always follows label. And frankly, physicians continue to have pathways to pursue access when they believe a particular treatment approach is medically appropriate given the severity of this disease. What's also very important is CARDIO-TTRansform does not change AMVUTTRA's evidence or its label. It was a study of a different molecule. We would not expect payers to alter AMVUTTRA coverage based on those results. Our priority remains ensuring appropriate patients can access AMVUTTRA, whether they're initiating first-line therapy or switching from another treatment. So we're not seeing any pushback, again, given the fact that actually the policies are already in place. And yet when the physician wants to have access, they obtain it if they provide the right appropriate materials. Yvonne Greenstreet: Thanks for that. Look, I think there are many examples of drugs in similar classes where one drug fails and the other succeeds. And we really believe what we have here are 2 distinct molecules with different mechanisms as well as different profiles in a different study. And really, our job is to get out there, as Tolga was saying, and educate physicians on the compelling benefits that we see for AMVUTTRA with a focus on first line because we believe this should be a foundational therapy as well as explaining the benefits that we've seen in 2 separate studies as Pushkal explained with respect to combination use. Jeffrey Poulton: There was one question on net price in terms of what we expect. And I think the slide that Tolga showed that showed the first half dynamics showed the modest quarter-to-quarter decreases in net price, we expect that will continue for the second half. And if we were to show you that on a year-over-year basis, the way we had guided was mid-single-digit net price decrease year-over-year. We're still on track for that, Luca. Operator: The next question comes from Jessica Fye with JPMorgan. Jessica Fye: Question for Pushkal. Recognizing that this is hypothetical, can you elaborate on some of those potential changes available to you with TRITON-CM to maximize its probability of success? And then maybe as a follow-up to that, are there potentially other paths to approval for nucresiran in ATTR-CM beyond TRITON-CM? For example, would it be feasible to run a non-inferiority trial against AMVUTTRA? Pushkal Garg: Yes. Thanks, Jess, for your question. Look, again, we feel really good about what we have in our hands, both in terms of the molecule nucresiran for all the reasons I talked about and the study that we have. So again, I want to reinforce, we may not need to do anything different from what we already have ongoing. That said, we do have options at our disposal. We'll look at the data and we'll consider. I think they broadly fall into a couple of buckets. One is whether we modify enrollment in certain subpopulations, for instance, and enrich in certain ways for those. Again, we've done that already in the context of the study, but we could potentially further do that based on information that we see. The other thing would be to make modifications around the analytic plan in terms of how we think about various endpoints, the hierarchy, et cetera. And so they're largely in those 2 big buckets. I mean, to the second part of your question, is there a possibility that if we wanted to, we could do additional studies? Yes, certainly, those things are potential. I'm not going to speculate though further on what those might look like. But I think broadly speaking, I think there's a variety of options in our hand. Again, we're playing the long game here. I think our commitment is to deliver a successful study. We've done that in the past. We think nucresiran has the opportunity to be an amazing medicine for patients, and we're committed to delivering a positive study for that. And so we will consider all the potential options at hand. As I said, they fall into several key buckets, and we'll kind of consider all those opportunities and see if anything at all is warranted. Operator: The next question comes from Whitney Ijem with Canaccord Genuity. Whitney Ijem: Just-- sorry if I missed it, but can you remind us on how -- any updated thinking, I guess, around the total U.S. patient population or TAM for ATTR-CM and where you are with diagnosis rate currently? And then just as a point of comparison ahead of the 6,400 Phase II data later this year, what are the comparable numbers for HHT U.S. TAM in terms of patient numbers and diagnosis rate? Tolga Tanguler: So for TTR, what I can tell you is in our latest estimates, if you go back to our TTR webinar, we've highlighted we estimate around 200,000 patients and about 80% of those remain untreated. What to me is sort of a good confirmatory data set is the fact that you're seeing around 40% year-over-year growth of the category with a single option on the table. That has actually accelerated since we launched. So -- and that remains very robust. So we believe more competitors, more awareness, more education and frankly, some of those initiatives that we've just actually laid will continue to help accelerate those patients getting diagnosed. And as you all know, we have excellent data that demonstrates those patients that are treated earlier end up actually getting more benefits from AMVUTTRA. So we're very actually excited about that. And again, our position on first line gives us the confidence that we can actually continue to be the leading option on the table in this growing category. Pushkal Garg: Yes. And with regard to hereditary hemorrhagic telangiectasia, there are -- there really are no approved treatments for this disease. It's actually the second most common rare bleeding disorder that's out there. I think globally, there's about 1.5 million patients with this disease. I think when we think about the addressable population in the United States, I think, again, those estimates vary. I think there's a number of these patients who don't actually get to medical attention. But we think there's probably about 70,000 or so patients in the United States who may be addressable with this condition. But again, that epidemiology will firm up again, as we've seen with rare diseases where there are treatments once there are effective treatments, more and more come to attention. So that's probably a ballpark though, for you. Operator: And that concludes our question-and-answer session. I will hand it back to the company for closing remarks. Yvonne Greenstreet: Thank you. So to close, we continue to build momentum across our business as we execute against our strategy and advance towards our 2030 goals. And I'd like to thank everyone who's joined us today. Thank you. Operator: Thank you, presenters. And ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect. Before you buy stock in Alnylam Pharmaceuticals, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Alnylam Pharmaceuticals wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. Consider when Netflix made this list on December 17, 2004... if you invested $1,000 at the time of our recommendation, you’d have $397,081!* Or when Nvidia made this list on April 15, 2005... if you invested $1,000 at the time of our recommendation, you’d have $1,166,221!* Now, it’s worth noting Stock Advisor’s total average return is 889% — a market-crushing outperformance compared to 203% for the S&P 500. Don't miss the latest top 10 list, available with Stock Advisor, and join an investing community built by individual investors for individual investors. See the 10 stocks » *Stock Advisor returns as of July 30, 2026. 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Alnylam Pharmaceuticals ALNY reported second-quarter 2026 adjusted earnings of $1.84 per share, missing the Zacks Consensus Estimate of $2.05. The company had reported adjusted earnings of 28 cents in the year-ago quarter. Alnylam recorded total revenues of $1.29 billion in the quarter, missing the Zacks Consensus Estimate of $1.32 billion. In the year-ago quarter, total revenues were $773.7 million. The top line rose 67% year over year on a reported basis and at a constant exchange rate (CER), mainly driven by increased sales of its lead drug, Amvuttra (vutrisiran), following label expansion. ALNY stock declined 28.3% on Thursday as investors were likely disappointed by the dismal second-quarter performance and the downward revision of total product sales guidance. Net product revenues increased 74% on a reported basis and at CER to $1.17 billion, driven by strong growth in patient demand for Amvuttra and its other marketed drugs, Givlaari (givosiran) and Oxlumo (lumasiran). Amvuttra is approved in the United States and EU to treat adult patients with polyneuropathy of hATTR amyloidosis (hATTR-PN). A label expansion for the drug has also been approved in the United States and the EU for treating cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits. Amvuttra generated sales of $1.01 billion, up 106% year over year, driven by increased patient demand, mainly among ATTR-CM patients in the United States. This marked the first time Amvuttra revenues exceeded $1 billion in a quarter. Amvuttra sales, however, missed the Zacks Consensus Estimate of $1.05 billion. Onpattro sales declined 65% year over year to $18.5 million as patients continued transitioning to Amvuttra. Onpattro sales missed the Zacks Consensus Estimate of $24.2 million. Givlaari, approved for the treatment of acute hepatic porphyria, sales increased 11% year over year on a reported basis to $89.8 million, supported by growth in the number of patients receiving treatment. Givlaari sales beat the Zacks Consensus Estimate of $82.6 million. Oxlumo revenues also rose 11% on a reported basis to $52.1 million. Oxlumo sales missed the Zacks Consensus Estimate of $53.7 million. Collaboration revenues declined 23% year over year to $47.2 million. Lower revenues recognized under the Regeneron REGN collaboration more than offset increased revenues from Roche RHHBY. The increase in Roche revenues reflected higher reimbursable development activities related to the phase III ZENITH study of zilebesiran, which will evaluate zilebesiran to treat patients with hypertension at high cardiovascular risk. ALNY entered a strategic collaboration with RHHBY to co-develop and co-commercialize zilebesiran for the treatment of hypertension in 2023. Year to date, Alnylam shares have plunged 48.3% against the industry’s 2.8% growth. Image Source: Zacks Investment Research Alnylam, in collaboration with Regeneron, is advancing cemdisiran as a monotherapy and in combination studies for the treatment of complement-mediated diseases. Per Regeneron, regulatory filings in the United States and the EU for cemdisiran in AChR antibody-positive generalized myasthenia gravis are currently under review. An FDA decision is expected in November 2026, while an EU decision is anticipated in the second half of 2027. Per the 2019 agreement, ALNY and REGN are also currently advancing multiple other programs. Royalty revenues jumped 79% to $71.7 million, driven by increased volumes and royalty rates on global Leqvio sales by Novartis NVS. Alnylam has granted Novartis exclusive global rights to manufacture and commercialize RNAi therapeutics targeting PCSK9, including Leqvio, for the treatment of hypercholesterolemia and other diseases. The FDA has approved Leqvio for several heart disease indications, alongside diet and statins. As of June 2026, Leqvio is approved in more than 109 countries. Adjusted research and development (R&D) expenses increased 38% year over year to $377.2 million. The rise primarily reflected increased clinical study costs associated with the ZENITH phase III cardiovascular outcomes study in partnership with Roche. Increased expenses associated with the phase III TRITON-CM and TRITON-PN studies, evaluating nucresiran in patients with ATTR-CM and hATTR-PN, respectively, also contributed to higher R&D costs. The company also increased spending on programs targeting bleeding disorders, Huntington's disease and cerebral amyloid angiopathy. Adjusted selling, general and administrative (SG&A) expenses rose 14% to $297.2 million, mainly due to investments supporting the global Amvuttra launch in ATTR-CM. Despite higher expenses, adjusted operating income increased to $318.1 million from $95.5 million in the year-ago quarter. Product gross margin was 75%, down four percentage points year over year due primarily to higher royalties payable on Amvuttra sales. Cash, cash equivalents and marketable securities totaled $3.3 billion as of June 30, 2026, compared with $3 billion as of March 31, 2026. The increase was primarily driven by net cash inflows from operating activities. Management said Amvuttra access remained broad, while patient adherence continued to exceed 90%. First-line patients now represent about 80% of new treatment initiations in the ATTR-CM market. Alnylam is increasing customer-facing investments to broaden the drug's prescriber base. Management estimated that only about one-third of the growing pool of transthyretin prescribers has used Amvuttra, indicating room to expand physician adoption. Alnylam Pharmaceuticals, Inc. price-consensus-eps-surprise-chart | Alnylam Pharmaceuticals, Inc. Quote Alnylam lowered its 2026 net product revenue guidance to $4.7-$5.1 billion from $4.9-$5.3 billion. The revised range implies year-over-year growth of 57-71% at CER. The company reduced its combined Amvuttra and Onpattro revenue forecast to $4.2-$4.5 billion from $4.4-$4.7 billion. Management attributed the cut to normalized second-line Amvuttra demand after early launch volumes benefited from pent-up demand among patients progressing on stabilizer therapy. Alnylam reiterated its Givlaari and Oxlumo revenue forecast of $500-$600 million and adjusted R&D and SG&A expense guidance of $2.7-$2.8 billion. The company raised its collaboration and royalty revenue outlook to $575-$625 million from $400-$500 million. The upward revision reflects stronger Leqvio royalties and higher Roche reimbursements tied to enrollment progress in the ZENITH study. Alnylam's second-quarter results disappointed, with both earnings and revenues missing expectations, triggering a sharp selloff in the stock. Although total revenues surged year over year, fueled by blockbuster Amvuttra sales that exceeded $1 billion for the first time, the drug still fell short of consensus estimates. Higher R&D spending on late-stage pipeline programs and increased commercialization investments further weighed on the quarter, overshadowing continued strength in Givlaari, Oxlumo and Leqvio royalty revenues. Investor sentiment was further dented by management's decision to lower its 2026 product sales guidance, reflecting a normalization in Amvuttra demand following the initial surge from previously untreated ATTR-CM patients. While Alnylam continues to highlight broad market access, strong patient adherence and significant room for physician adoption, the guidance cut suggests that near-term growth could be slower than previously anticipated. We believe the company's long-term growth story remains intact, but the reduced outlook is likely to weigh on the stock until Amvuttra's commercial momentum reaccelerates. Alnylam currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Alnylam Pharmaceuticals, Inc. (ALNY) : Free Stock Analysis Report Regeneron Pharmaceuticals, Inc. (REGN) : Free Stock Analysis Report Novartis AG (NVS) : Free Stock Analysis Report Roche Holding AG (RHHBY) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Interested in Alnylam Pharmaceuticals, Inc.? Here are five stocks we like better. Second-quarter revenue surged 74% to approximately $1.2 billion, driven by AMVUTTRA, which generated more than $1 billion in quarterly revenue for the first time. Non-GAAP operating income rose to $318 million, and Alnylam ended the quarter with $3.3 billion in cash and securities. Alnylam lowered its 2026 TTR revenue outlook to $4.2 billion–$4.5 billion as second-line demand normalized, but said roughly 80% of new ATTR-CM treatment starts are now first-line. The company still sees substantial growth potential, estimating that about 80% of U.S. ATTR-CM patients remain untreated. The company highlighted a favorable competitive and pipeline outlook, including delayed generic tafamidis entry, a competitor’s negative Phase 3 result, the ongoing TRITON-CM study of nucresiran, and a new AMVUTTRA commercialization partnership with BeOne in mainland China and Macau. The Phase 3 Failure That Sent Biotech Winners and Losers in Opposite Directions Alnylam Pharmaceuticals (NASDAQ:ALNY) reported second-quarter 2026 global net product revenue of approximately $1.2 billion, up 74% from a year earlier, driven by continued uptake of AMVUTTRA for transthyretin amyloidosis with cardiomyopathy, or ATTR-CM. Chief Executive Officer Yvonne Greenstreet said the quarter marked the first time AMVUTTRA revenue exceeded $1 billion in a single quarter. The company said the result represents an annualized revenue run rate of more than $4 billion about 15 months after the ATTR-CM launch. → Why SK hynix Could Be the Best AI Chip Stock to Buy Now Alnylam Stock Soars 65%: Find Out What’s Behind the Gains However, Alnylam reduced its full-year TTR franchise revenue outlook, citing a revised view of second-line demand following the early phase of the U.S. launch. The company said early demand from patients transitioning from stabilizer therapies had benefited from pent-up demand that has since normalized. Chief Financial Officer Jeff Poulton said total TTR net revenue reached $1.03 billion during the second quarter, increasing 13% sequentially and 89% year over year. Combined net product revenue was $1.17 billion, while rare disease portfolio revenue totaled $142 million, up 11% from the prior-year period. → 3 Value ETFs to Consider as Growth Stocks Lag Behind 3 biotech powerhouses poised to thrive amid sector rebound Alnylam revised its 2026 total net product revenue guidance to a range of $4.7 billion to $5.1 billion. TTR revenue guidance was reduced to $4.2 billion to $4.5 billion, a $200 million reduction at the midpoint from the company’s prior outlook. The revised range still implies 75% annual TTR revenue growth at the midpoint, Poulton said. The company raised its outlook for collaboration and royalty revenue to $575 million to $625 million, representing a $150 million increase at the midpoint. Poulton attributed the increase largely to higher royalties from Novartis’ LEQVIO sales and greater cost reimbursement from Roche related to enrollment in the ZENITH Phase III trial of zilebesiran. → 5 AI Stocks Are Pulling Back—Which Growth Catalysts Still Look Strongest? For the quarter, collaboration revenue declined 23% year over year to $47 million, while royalty revenue rose 79% to $72 million. Alnylam reported non-GAAP operating income of $318 million, more than triple the prior-year amount, and ended the quarter with $3.3 billion in cash, cash equivalents and marketable securities. Chief Commercial Officer Tolga Tanguler said approximately 80% of new treatment initiations in the ATTR-CM category are now first-line starts. The company views this segment as the larger and more durable growth opportunity, while second-line demand from patients previously treated with stabilizers has moved toward what management described as a sustainable underlying rate. In the U.S., TTR revenue increased 15% sequentially and 114% year over year. Underlying demand increased by $129 million during the quarter, though reported growth was reduced by $21 million due to inventory changes, Tanguler said. Outside the U.S., TTR revenue grew 7% sequentially and 31% year over year, supported by ATTR-CM uptake in Japan, the U.K. and Germany and polyneuropathy performance in international markets. Management said AMVUTTRA access remains broad and adherence exceeds 90%. Since the ATTR-CM launch, Alnylam has added more than 1,700 prescribers, though Tanguler said the company estimates it has reached only about one-third of the growing pool of TTR prescribers. The company plans to increase customer-facing investment to broaden adoption, particularly among community-based physicians. Alnylam estimated that approximately 200,000 U.S. ATTR-CM patients exist and that about 80% remain untreated. Management said investments in diagnosis and patient identification are intended to expand the treatable population and support earlier treatment. Greenstreet said recent competitive developments reinforce Alnylam’s view of the TTR opportunity. The company noted a delay in expected U.S. generic entry for tafamidis until mid-2031 and cited the negative top-line result from the CARDIO-TTRansform study of eplontersen, which Alnylam expects could leave one fewer branded competitor in ATTR-CM. Chief Research and Development Officer Pushkal Garg said the eplontersen study outcome has not changed Alnylam’s confidence in TRITON-CM, its Phase III cardiovascular outcomes study of investigational RNA interference therapy nucresiran. He said the company will review the full competitor data set when available and could consider changes involving patient enrollment or the trial’s analytic plan if warranted. TRITON-CM is now expected to enroll roughly 1,750 patients and is designed as an event-driven trial. Garg said Alnylam believes nucresiran’s expected TTR knockdown profile differentiates it from eplontersen. Based on preliminary Phase I results, nucresiran produced more than 95% knockdown with twice-yearly dosing, according to the company. Garg also cited results from the HELIOS-B and APOLLO-B studies as evidence supporting RNAi-mediated TTR silencing alongside stabilizer treatment. He said the company has observed treatment effects in patients using background stabilizers, while noting that Alnylam will continue assessing the detailed CARDIO-TTRansform data. Alnylam announced a collaboration with BeOne under which BeOne will receive exclusive commercialization and distribution rights for AMVUTTRA in mainland China and Macau, subject to marketing authorization. The companies plan to support awareness and diagnosis of ATTR amyloidosis in the regions. The company also said it initiated a Phase II trial of ALN-6400 in von Willebrand disease and a Phase II trial of migalastat in Down syndrome-associated Alzheimer’s disease. In the second half of 2026, Alnylam expects four data readouts from three programs, including initial Phase I results for ALN-HTT02 in Huntington’s disease and Phase I data for ALN-2232 in obesity and weight management. Alnylam Pharmaceuticals, Inc (NASDAQ: ALNY) is a biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics. Founded to translate the scientific discovery of RNAi into new medicines, Alnylam applies small interfering RNA (siRNA) technology to silence disease-causing genes. The company develops therapies designed to provide durable disease modification by targeting underlying genetic drivers across a range of rare and more prevalent conditions. Alnylam has advanced multiple siRNA-based products into commercialization, initially using lipid nanoparticle delivery and more recently employing GalNAc-conjugate chemistry to enable targeted delivery to the liver with subcutaneous dosing. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Alnylam Pharmaceuticals Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for July 2026.

This article first appeared on GuruFocus. Total Global Net Product Revenues: Approximately $1.2 billion, representing 74% growth versus Q2 last year. Global TTR Net Revenues (Amvutra): $1.03 billion in Q2, increasing 13% versus Q1 and 89% year-over-year. Rare Disease Net Revenue: $142 million in Q2, up 11% year-over-year. Collaboration Revenue: $47 million in Q2, a 23% decrease compared to the same period last year. Royalty Revenue: $72 million in Q2, an increase of 79% driven by higher Leqvio sales by Novartis. Gross Margin on Product Sales: 75% in Q2, 4% lower than Q2 last year. Non-GAAP R&D Expenses: $377 million in Q2, increased 38% compared to last year. Non-GAAP SG&A Expenses: $297 million in Q2, increased 14% compared to last year. Non-GAAP Operating Income: $318 million in Q2, more than triple the amount achieved last year. Cash Equivalents and Marketable Securities: $3.3 billion as of Q2 2026, compared with $2.9 billion as of year-end 2025. Full Year 2026 Total Net Product Revenue Guidance: Revised to $4.7 billion to $5.1 billion. Full Year 2026 TTR Revenue Guidance: Revised to $4.2 billion to $4.5 billion. Full Year 2026 Collaboration and Royalty Revenue Guidance: Updated to $575 million to $625 million. Warning! GuruFocus has detected 3 Warning Sign with ALNY. Is ALNY fairly valued? Test your thesis with our free DCF calculator. Release Date: July 30, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Alnylam Pharmaceuticals Inc (NASDAQ:ALNY) reported strong Q2 2026 performance with total global net product revenues of approximately $1.2 billion, representing 74% year-over-year growth. Amvutra revenues exceeded $1 billion in a single quarter for the first time, achieving an annual run rate of more than $4 billion just 15 months into the ATTR Cardiomyopathy launch. First-line new patient starts now account for about 80% of category growth, indicating strong progress in establishing Ambutra as a foundational therapy. The company maintains strong confidence in its Phase III Triton-CM study for nucrisiran, citing the established clinical evidence for RNAi therapeutics in TTR and a track record of successful clinical development. Alnylam announced a strategic collaboration with B1 for exclusive commercialization and distribution rights for Ambutra in mainland China and Macau, expanding its geographic reach. Alnylam Pharmaceuticals Inc (NASDAQ:ALNY) lowered its 2026 total net product revenue guidance to $4.7 billion to $5.1 billion, driven by a $200 million reduction in TTR revenue guidance at the midpoint. The guidance revision was attributed to a normalization of second-line demand growth, which had previously benefited from pent-up demand that has since moderated. The company acknowledged it did not get its original guidance right, stating, 'We own that,' regarding the need to adjust market expectations. Gross margin on product sales decreased to 75%, down 4% from Q2 last year, primarily due to increased royalties payable to Sanofi on higher Ambutra revenues. The negative outcome of the Cardio-Transform study for Eplontersen introduces uncertainty in the competitive landscape, though Alnylam asserts it does not alter its confidence in its own programs. Here are the key highlights from the Alnylam Pharmaceuticals Inc (NASDAQ:ALNY) Q2 2026 earnings call. Q: Can you elaborate on the change in 2026 revenue guidance and your confidence in the long-term 25% CAGR goal? A: (Yvonne Greenstreet, CEO; Jeff Poulton, CFO; Tolga Tanguler, CCO) The guidance revision reflects a better understanding of second-line demand dynamics. Early launch growth benefited from pent-up demand from patients waiting for a new therapy, which has now normalized. However, the fundamentals are strong, with first-line new patient starts now driving ~80% of category growth. The company remains confident in its 2030 goals due to a highly untapped market (80% of patients untreated), strong first-line momentum, and a favorable competitive landscape following the CardioTransform failure. Q: What is your confidence in the Triton-CM study for nucrisiran following the failure of the CardioTransform study for eplontersen? A: (Pushkal Garg, Chief R&D Officer) The outcome does not alter our conviction. Confidence is grounded in three factors: 1) Molecule attributes: RNAi therapeutics deliver rapid, deep, and durable TTR knockdown. Nucrisiran is expected to achieve >95% knockdown with low variability, with modeling suggesting >99% of patients will reach a deep knockdown threshold, compared to an estimated 67% for eplontersen. 2) Study design: Triton-CM is an event-driven study with 1,750 patients, the largest in ATTR-CM, and uses entry criteria to enrich for patients most likely to benefit. 3) Track record: Alnylam has over 15 years of TTR experience and has shown additive benefits of RNAi silencing on top of stabilizers in two separate studies (Helios-B and Apollo-B). Q: What is the split of Amvuttra use between first-line and second-line patients, and how do you plan to maintain growth in the first-line setting? A: (Tolga Tanguler, CCO) In Q2, approximately 80% of new treatment initiations in the category were first-line starts. While second-line demand has normalized, the company is maintaining a strong share of second-line starts. Growth is driven by deepening adoption among existing prescribers (Amvuttra now represents >50% of their new starts) and expanding the prescriber base. The company is increasing investment in customer-facing activities to educate community physicians on the differentiated profile of silencers versus stabilizers, as experience drives preference. Q: Are you seeing any commercial impact or payer pushback on combination use (silencer + stabilizer) following the CardioTransform results? A: (Tolga Tanguler, CCO) It is too early to see significant impact, but payer access for Amvuttra remains very strong. CardioTransform was a study of a different molecule and does not change Amvuttra's evidence or label. Payers are not expected to alter coverage based on those results. While some Medicare Advantage policies already limit combination use, physicians continue to have pathways to access for medically appropriate patients. Q: What are the potential options available to you to adapt the Triton-CM study to maximize its probability of success? A: (Pushkal Garg, Chief R&D Officer) While we may not need to change anything, we have options at our disposal. These fall into two buckets: 1) Modifying enrollment to further enrich for certain subpopulations, and 2) Making modifications to the analytic plan, such as the endpoint hierarchy. The company will review the full CardioTransform dataset and consider if any changes are warranted, emphasizing a long-term commitment to delivering a successful study. For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Alnylam Pharmaceuticals (ALNY) reported $1.29 billion in revenue for the quarter ended June 2026, representing a year-over-year increase of 66.9%. EPS of $1.84 for the same period compares to $0.32 a year ago. The reported revenue represents a surprise of -2.09% over the Zacks Consensus Estimate of $1.32 billion. With the consensus EPS estimate being $2.05, the EPS surprise was -10.24%. While investors scrutinize revenue and earnings changes year-over-year and how they compare with Wall Street expectations to determine their next move, some key metrics always offer a more accurate picture of a company's financial health. Since these metrics play a crucial role in driving the top- and bottom-line numbers, comparing them with the year-ago numbers and what analysts estimated about them helps investors better project a stock's price performance. Here is how Alnylam performed in the just reported quarter in terms of the metrics most widely monitored and projected by Wall Street analysts: Revenues- Product revenues, net: $1.17 billion versus the seven-analyst average estimate of $1.21 billion. The reported number represents a year-over-year change of +74.4%. Revenues- Net revenues from collaborations: $47.17 million versus the five-analyst average estimate of $51.11 million. The reported number represents a year-over-year change of -23.3%. Revenues- Royalty revenue: $71.67 million versus $56.25 million estimated by five analysts on average. Compared to the year-ago quarter, this number represents a +79.3% change. Net Product Revenue - Total TTR: $1.03 billion versus the four-analyst average estimate of $1.08 billion. Net Product Revenue- Oxlumo: $52.12 million compared to the $53.69 million average estimate based on four analysts. The reported number represents a change of +11.2% year over year. Net Product Revenue- Givlaari: $89.76 million versus the four-analyst average estimate of $82.64 million. The reported number represents a year-over-year change of +11%. Net Product Revenue - Total Rare: $141.89 million versus $138.3 million estimated by four analysts on average. Net Product Revenue- Onpattro: $18.46 million versus the three-analyst average estimate of $24.19 million. The reported number represents a year-over-year change of -64.7%. Net Product Revenue- Amvuttra: $1.01 billion versus the three-analyst average estimate of $1.05 billion. The reported number represents a year-over-year change of +105.7%. View all Key Company Metrics for Alnylam here>>> Shares of Alnylam have returned -5% over the past month versus the Zacks S&P 500 composite's -1.5% change. The stock currently has a Zacks Rank #3 (Hold), indicating that it could perform in line with the broader market in the near term. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Alnylam Pharmaceuticals, Inc. (ALNY) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Alnylam Pharmaceuticals (ALNY) came out with quarterly earnings of $1.84 per share, missing the Zacks Consensus Estimate of $2.05 per share. This compares to earnings of $0.32 per share a year ago. These figures are adjusted for non-recurring items. This quarterly report represents an earnings surprise of -10.24%. A quarter ago, it was expected that this RNA interference drug developer would post earnings of $1.43 per share when it actually produced earnings of $1.99, delivering a surprise of +39.16%. Over the last four quarters, the company has surpassed consensus EPS estimates three times. Alnylam, which belongs to the Zacks Medical - Biomedical and Genetics industry, posted revenues of $1.29 billion for the quarter ended June 2026, missing the Zacks Consensus Estimate by 2.09%. This compares to year-ago revenues of $773.69 million. The company has topped consensus revenue estimates two times over the last four quarters. The sustainability of the stock's immediate price movement based on the recently-released numbers and future earnings expectations will mostly depend on management's commentary on the earnings call. Alnylam shares have lost about 27.9% since the beginning of the year versus the S&P 500's gain of 6.9%. While Alnylam has underperformed the market so far this year, the question that comes to investors' minds is: what's next for the stock? There are no easy answers to this key question, but one reliable measure that can help investors address this is the company's earnings outlook. Not only does this include current consensus earnings expectations for the coming quarter(s), but also how these expectations have changed lately. Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions. Investors can track such revisions by themselves or rely on a tried-and-tested rating tool like the Zacks Rank, which has an impressive track record of harnessing the power of earnings estimate revisions. Ahead of this earnings release, the estimate revisions trend for Alnylam was mixed. While the magnitude and direction of estimate revisions could change following the company's just-released earnings report, the current status translates into a Zacks Rank #3 (Hold) for the stock. So, the shares are expected to perform in line with the market in the near future. You can see the complete list of today's Zacks #1 Rank (Strong Buy) stocks here. It will be interesting to see how estimates for the coming quarters and the current fiscal year change in the days ahead. The current consensus EPS estimate is $2.22 on $1.47 billion in revenues for the coming quarter and $8.98 on $5.62 billion in revenues for the current fiscal year. Investors should be mindful of the fact that the outlook for the industry can have a material impact on the performance of the stock as well. In terms of the Zacks Industry Rank, Medical - Biomedical and Genetics is currently in the top 37% of the 250 plus Zacks industries. Our research shows that the top 50% of the Zacks-ranked industries outperform the bottom 50% by a factor of more than 2 to 1. One other stock from the same industry, Protagonist Therapeutics (PTGX), is yet to report results for the quarter ended June 2026. This biopharmaceutical company is expected to post quarterly earnings of $2.11 per share in its upcoming report, which represents a year-over-year change of +483.6%. The consensus EPS estimate for the quarter has been revised 12.6% higher over the last 30 days to the current level. Protagonist Therapeutics' revenues are expected to be $220.34 million, up 3870.1% from the year-ago quarter. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Alnylam Pharmaceuticals, Inc. (ALNY) : Free Stock Analysis Report Protagonist Therapeutics, Inc. (PTGX) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

This story was originally published on BioPharma Dive. To receive daily news and insights, subscribe to our free daily BioPharma Dive newsletter. Alnylam Pharmaceuticals lost nearly 30% — or close to $12 billion — of its market value after the company surprised investors by lowering financial forecasts for its most important drug franchise by $200 million. The RNA-focused biotechnology company had previously predicted those drugs, the transthyretin amyloidosis medications Amvuttra and Onpattro, would bring in $4.4 billion to $4.7 billion. But in an earnings report Thursday, it dropped that estimate to between $4.2 billion and $4.5 billion, revealing that Amvuttra’s early launch spike benefitted from “pent-up demand” that’s since “normalized.” Alnylam has been in a high-stakes battle over the last year to carve out a share of the multibillion-dollar “TTR cardiomyopathy” market, which has become increasingly competitive thanks to drugs like Pfizer’s Vyndamax, BridgeBio’s Attruby and, potentially, AstraZeneca and Ionis Pharmaceuticals’ eplontersen. Alnylam had already seen its share price slide by a double-digit percentage after a study setback for eplontersen in July raised thorny questions about how useful drugs like Amvuttra are in patients on other treatment. The latest news, then, represented a “one-two punch” for Alnylam that may hang over the company until the presentation of that failed study at a medical meeting in late August, wrote Cantor Fitzgerald analyst Olivia Brayer Saunders. “We knew expectations for 2026 were ambitious, but we weren’t expecting a guidance cut,” she wrote. Oppenheimer analyst Kostas Biliouris echoed that sentiment in his own note. While some investors may have been expecting a guidance reduction, “it comes as a surprise to us” for one to come this early in the year, especially since prescription rates tracked by healthcare data specialist Iqvia suggest the company could meet its original predictions. Amvuttra sales totaled $1.01 billion for the quarter, or 3% below the average analyst estimate of $1.05 billion, according to Biliouris. Alnylam shares traded around $200 apiece by late Thursday afternoon, down from a $286 close the previous day. The earnings miss and guidance cut invites “major” questions on the outlook of Alnylam’s TTR business, wrote Jefferies analyst Faisal Khurshid. The “bull/bear debate ... is real, and today’s update underscores the complexity.” Khurshid added that his team doesn’t envision “the overhang passing easily,” and is “not convinced there’s enough investor interest” in Alnylam’s pipeline to “make up for TTR uncertainty.” Recommended Reading Alnylam reaches new highs on strong sales of closely watched rare disease drug