Hello, and welcome to the Alnylam Pharmaceuticals Annual Meeting of Stockholders. All participants are currently in a listen-only mode. I would now like to turn the meeting over to Amy Schulman, Chair of the Board. Please go ahead.
Good morning, and thank you for your participation today. I would like to call to order the 2026 Annual Meeting of Stockholders of Alnylam Pharmaceuticals, which is being held virtually via the internet. I am Amy Schulman, Chair of the Board of Directors of the company. I would like to introduce the other directors who are with us today for the annual meeting. Stuart A. Arbuckle, Dennis A. Ausiello, Olivier Brandicourt, Yvonne Greenstreet, who is the company's Chief Executive Officer, Margaret A. Hamburg, Peter N. Kellogg, David E.I. Pyott, Colleen F. Reitan, and Elliott Sigal, constituting all of the members of our board.
Along with us today are several members of the company's Senior Management and Investor Relations team, including Pushkal Garg, Chief Research and Development Officer, Jeff Poulton, Chief Financial Officer, Tolga Tanguler, Chief Commercial Officer, Bryan Supran, Chief Legal Officer and Corporate Secretary, Melissa McLaughlin, Chief Human Resources Officer, Kevin Fitzgerald, Chief Scientific Officer, Piyush Sharma, Chief Ethics and Compliance Officer, Timothy Maines, Chief Technical Operations and Quality Officer, Christine Akinc, Chief Corporate Communications Officer, and Josh Brodsky, Vice President, Investor Relations. Representatives of PricewaterhouseCoopers LLP, the company's independent auditors, including PricewaterhouseCoopers Partner John Charters, also are participating and will be available following the formal portion of the meeting to respond to appropriate questions from stockholders submitted online. On behalf of the Board of Directors and management, I welcome all stockholders in attendance today at our 2026 annual meeting.
I also want to thank all stockholders who voted today, whether by proxy in advance of the meeting or online. Thank you for your interest in the company's mission and business and future prospects. I will now turn the meeting over to Bryan Supran, the company's Corporate Secretary, who will conduct the formal part of the annual meeting and serve as Secretary of the meeting. Bryan?
Good morning. Thank you, Ms. Schulman, and welcome to all of our stockholders participating online today. We will now begin the formal portion of the annual meeting. During the meeting, stockholders participating online may submit questions to the virtual meeting platform by typing your question into the Ask a Question field and clicking Submit. Questions pertinent to meeting matters will be answered following the formal portion of the meeting, subject to time constraints. Any questions pertinent to meeting matters that cannot be answered due to time constraints will be posted online and answered on Alnylam's website under the investor section. Following the formal meeting, Mr. Brodsky will present a brief company update and be available to answer any additional questions submitted online during his presentation.
As indicated in the notice of meeting and in the company's proxy statement that was made available on the internet, the following matters have been proposed by the board for approval or ratification by the stockholders who are stockholders of record as of the record date. First, to elect three members to the board of directors to serve as Class I directors, each for a term of three years. Second, to approve in a non-binding advisory say-on-pay vote the compensation of the company's named executive officers. Third, to ratify the appointment by the company's board of directors of PricewaterhouseCoopers LLP as the company's independent auditors for the current fiscal year ending December 31st, 2026. We will consider each item in turn in the same order that it appears in the notice of meeting.
The polls will open when the first matter is called to a vote and will remain open until I announce that the polls are closed. You may vote your shares during the meeting online through the virtual meeting platform. You will need the 16-digit control number included on your proxy card or voting instruction form. If you previously voted, that will not limit your right to vote online during the meeting through the virtual meeting platform, and your online vote will supersede the vote you submitted previously. No online votes, ballots, or proxies, or revocations of, or changes to online votes, ballots, or proxies will be accepted after the polls are closed. I will announce the preliminary voting results on each matter following the tabulation of the voting.
I have received an affidavit from Broadridge Financial Solutions, the company's agent for distribution, certifying that the notice of the annual meeting was sent to all stockholders of record as of March 25th, 2026, and the proxy statement was made available on the internet as of April 6th, 2026. This affidavit is available for inspection by any stockholder. I'd like to now introduce Mr. Louis Larson. Mr. Larson, a representative of Broadridge Financial Solutions, has been appointed to act as Inspector of Election and has taken the Inspector of Election oath. I'd like to ask Mr. Larson to state the number of shares present at this meeting.
There are present at this meeting in person or through representation by proxy 125,816,704 shares of common stock, representing approximately 94% of the outstanding shares of common stock of the company as of 10:30 A.M. Eastern Time this morning.
Based on the number of shares reported as present at this meeting, I am happy to report that a quorum exists. Voting today is by proxy and virtual ballot. It is not necessary for stockholders to vote by virtual ballot if they have already submitted their proxy cards or voted virtually, unless they wish to change their vote. Virtual ballots are available for any stockholder who wishes to vote by virtual ballot or to change their vote. Stockholders may do so online through the virtual meeting platform. Your submission of a virtual ballot will revoke all prior proxies. Voting is now open for all matters to be presented. Voting will be closed after we go through the proposals to be voted upon. I will now review the proposals. The first matter to be voted on is the election of 3 Class I directors, each for a term of three years.
The nominees for election are Mr. Stuart A. Arbuckle, Dr. Yvonne Greenstreet, and Dr. Elliott Sigal. The second matter to be voted on is the non-binding advisory vote on executive compensation. The third and final matter to be voted on is the ratification of the appointment of PricewaterhouseCoopers LLP as the company's independent auditors for the 2026 fiscal year. This concludes the business items on the agenda for this annual meeting. The polls are now closed. No additional virtual ballots, proxies, or votes, and no changes or revocations will be accepted.
I have been informed by the Inspector of Elections that the preliminary vote report shows that a majority of the votes cast at this meeting have been voted in favor of the election of each of the directors nominated to serve as a Class I director of the company, the advisory resolution to approve executive compensation, and the ratification of the appointment of PricewaterhouseCoopers LLP as the company's independent auditors for fiscal 2026. All matters have been approved as recommended by the board. We will be reporting the final voting results in a Form 8-K to be filed with the SEC within four business days. This concludes the formal business of today's meeting, and the formal part of the meeting is now adjourned.
In closing, I'd like to again thank the stockholders in attendance for your participation this morning in our virtual annual meeting and for your continued support of Alnylam. We will now take questions from stockholders related to the annual meeting matters. Mr. Brodsky, are there any questions from stockholders relating to matters properly brought before the meeting?
There are no questions from stockholders related to such matters at this time.
Thank you, Mr. Brodsky. The directors will now depart from the meeting. We welcome stockholders to remain online to listen to a brief presentation about the company by Mr. Brodsky. Following his presentation, Mr. Brodsky will also be happy to answer any additional pertinent questions submitted online.
Thank you very much, Mr. Supran. Good morning, everyone. My name is Josh Brodsky. I'm Vice President of Investor Relations at Alnylam. Before I begin, please note that the presentation that follows contains forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those in our most recent periodic report on file with the SEC. Any forward-looking statements represent our views only as of the date of this presentation and should not be relied upon as representing our views of any subsequent date. We specifically disclaim any obligation to update such statements. Alnylam possesses a unique profile in the biotech industry. What makes us so unique is that we have an established and sustainable innovation engine coupled with commercial excellence that has fueled our success and that we'll continue to harness to drive durable long-term growth.
This begins with the leadership that we've established in RNAi, with a proven organic product engine and a reproducible and modular process to developing our medicines that has resulted in outsized historical success rates. We also have a high-yielding pipeline with over 25 programs currently in active clinical development. In addition to the success and leadership we've demonstrated on the R&D side, there are now six Alnylam-invented medicines on the market that are collectively generating multibillion-dollar annual revenue streams and treating hundreds of thousands of patients around the world through our global footprint. These value-creating features give Alnylam a truly one-of-a-kind profile and one which is rarely seen across the biopharma landscape. Let me quickly highlight the progress we've made in the commercial side of the business. The first quarter was another strong quarter of commercial execution and marked our first quarter exceeding $1 billion in product revenue.
Specifically, we delivered $1,036,000,000 in combined net product revenues, up 121% year-over-year and four percent over Q4 2025. Turning specifically to our TTR franchise, one year into the ATTR cardiomyopathy launch, AMVUTTRA continues to show strong momentum. Global TTR net revenues reached $910 million in the first quarter, up six percent from Q4 and 153% year-over-year. There were a few phasing dynamics that we highlighted on our earnings call that affected both U.S. and international growth, which played out pretty much as we had expected.
For the rest of the year, we remain confident in our 2026 TTR revenue guidance as we continue to expect more substantial quarter-over-quarter growth in TTR revenues, both in the U.S. and across the world over the balance of the year. As we move into the next phase of the U.S. ATTR-CM launch, our focus is grounded in the strong foundation that we established in the first year of launch in 2025. First, physician preference and utilization. AMVUTTRA's clinical profile has driven a strong and compelling first-line positioning, with strong preference demonstrated by physicians who have experience using it. Second, patient access and affordability. Over 90% of patients are covered with first-line access, and most pay 0 in out-of-pocket costs.
Third, the provider network that we've built is very robust and has resulted in about 90% of patients in the U.S. able to access AMVUTTRA within about 10 miles of their home. These fundamentals enabled a highly differentiated launch with rapid uptake and strong utilization across lines of therapy. Importantly, our initial success has shown that physician experience with AMVUTTRA leads to deeper and sustained use over time. Moving forward, we're focused on the three indicators of continued launch success that are shown on this slide here. First, prescriber base expansion. We've already built a large and expanding base with more than 1,200 new U.S. prescribers since the cardiomyopathy launch. What we've observed is that experience with AMVUTTRA has translated into durable preference, and we also see significant opportunity coming from expanding the number of prescribers.
We'll do this by increasing engagement with physicians who don't yet have experience with AMVUTTRA. Second, sustained category growth. ATTR-CM remains significantly underdiagnosed and undertreated, with an estimated 200,000 patients in the U.S. and more than 80% still untreated. We're addressing this gap directly as part of our TTR leadership agenda, advancing AI-enabled partnerships with the aim of facilitating earlier diagnosis and treatment. Third, adherence and persistence, supported by quarterly dosing and actual patient adherence. This profile translates into sustained benefit for patients and, by extension, into sustained revenue, which is, of course, central to any long-term growth outlook. Let me switch gears now and talk about another key pillar of growth for our company going forward, our sustainable innovation engine. At Alnylam, we have built out this robust and high-yielding pipeline that you see here across rare, specialty, and prevalent indications and spanning multiple therapeutic areas.
A critical enabler of our building out this pipeline is our unique engine for sustainable innovation. Of course, at the core of this engine is the Nobel Prize-winning science of RNAi. We're going to leverage our leadership and expertise to continue to invest in the power of human genetics, where we now have access to more than 2 million lives through various biobanks to uncover new genetically validated targets to sustain our pipeline and our leadership for the future. We'll also expand the delivery of RNAi therapeutics into 10 or more major tissues by 2030. We'll enhance the fundamental attributes of siRNAs and advance our capabilities with continued platform refinements. Since our founding in 2002, we have pioneered the RNAi revolution, solving hepatic delivery, improving the platform, resulting in six approved RNAi therapeutics. We'll build on this foundation as we drive towards our vision for 2030 and beyond.
We plan to accelerate innovation and build on our competitive advantage by delivering to 10 or more new tissue types and utilizing potential combinations in polygenic approaches. We'll also look to continue our leadership in platform enhancements while selectively pursuing complementary modalities through business development. On our recent first quarter earnings call, we reiterated our 2026 net product revenue guidance. Specifically, we're expecting total combined product sales between $4.9 and $5.3 billion, driven by our TTR franchise guidance of $4.4 to $4.7 billion, or 83% growth at the midpoint. This indicates our strong conviction in the opportunity, reflecting robust growth and strong commercial execution. Let me turn now to our 2026 pipeline goals to drive our next phase of growth. We have an exciting year lined up in which we expect four clinical data readouts.
We're advancing three phase III studies, planning to initiate three phase II studies, and file three to four new INDs. Earlier this year, we were excited to launch our next ambitious set of five-year goals for the company, Alnylam 2030: Accelerating Innovation, Scaling Impact. These goals rest upon three strategic pillars. It starts with achieving global TTR leadership and building a durable TTR franchise. Specifically, we intend to lead the market in TTR revenue by 2030, and also cumulatively across the five-year period. We also plan to launch the best-in-class next generation TTR silencer, nucresiran, first in polyneuropathy by the end of 2028, and then in cardiomyopathy by the end of 2030. The next pillar is growing through sustainable innovation. Most medicines today simply slow the progression of disease. We aim to do better than that and deliver therapies that prevent, halt, or reverse disease.
This includes delivering two or more new transformative medicines beyond TTR that have blockbuster potential. If we include nucresiran, that makes three new transformative medicines. We also aim to expand to 10 tissue types and build out a pipeline of over 40 clinical programs. In addition, we aim to invest about 30% of our revenues in non-GAAP R&D to accelerate organic internal innovation and selectively access external innovation. The final pillar upon which our Alnylam 2030 goals rest is scaling with discipline and agility, where we plan to drive sustained, profitable growth. Specifically, we aim to achieve 25% or greater total revenue CAGR through the end of 2030 and deliver an approximately 30% non-GAAP operating margin across the period. Alnylam 2030 represents our strategy to become the leading science-driven, fully integrated global biopharmaceutical company and maximize the potential of RNAi therapeutics for patients.
In closing, I'd like to thank all our stockholders participating in this annual meeting for their engagement and interest in Alnylam and the patients we serve. Seeing no further questions, this will conclude the annual meeting. Thank you all. Have a good day.
This concludes today's meeting. Thank you for joining. You may now disconnect.