Alnylam Pharmaceuticals, Inc.

With me today are Yvonne Greenstreet, Chief Executive Officer, Bova Tanguilar, Chief Commercial Officer, Krish Pagard, Chief Research and Development Officer, and Jeff Fulton, Chief Financial 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.onilam.com slash events. During today's call, as outlined in slide two, Yvonne will offer introductory remarks and provide some general context. Tova will provide an update on our global commercial progress. Bush will review pipeline updates and clinical progress, and Jeff will review our financials and guidance, followed by a summary of upcoming milestones before we open the call to your questions. I'd 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 provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent periodic report on file of the SEC. In addition, any forward-looking statements represent our views as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Yvonne. Yvonne?

Thanks, Christine, and thank you, everyone, for joining the call today. As shown in our Q2 results announced today, our 9M is firing on all cylinders. And we're swiftly establishing ourselves as a top-tier biotech company. We're doing so by focusing on three core elements of the business that we believe will drive sustainable growth and value creation for years to come. The first is TTR leadership. As highlighted in today's press release, the launch is off to a very strong start. And whilst it's still early days, we're encouraged by the pace. And we're deeply focused on laying the groundwork for long-term leadership in TTR. The next is growth through innovation, focused on the potential multi-billion dollar opportunities within our pipeline and an R&D engine set up to deliver sustainable innovation and value creation. To that end, I'd like to acknowledge the recent promotion of Pushkol Garg to Chief Research and Development Officer. Pushkol has been instrumental in progressing our pipeline. And in this role, Pushkol will oversee an integrated R&D organization to drive this exciting pipeline and platform into the future. Congratulations, Pushkol. The third element is strong financial performance with robust commercial execution and disciplined capital allocation approach, providing us with the opportunity to sustain profitability going forward. As Tolga and Jeff will highlight later, The strong therapeutic profile of Ambutra and ATTR-CM, combined with a large and underserved market, positioned this as a flagship commercial franchise with robust and durable long-term growth potential. And of course, all of this is underpinned by a best-in-class team and our award-winning culture. Our results this quarter fit within each of these strategic pillars and represent one of the most impactful quarters to date for our nylon. Our commercial performance was driven by TTR franchise revenues of $544 million, 77% year-over-year growth, with growth largely attributable to the Amfutra CM launch. This was just the first full quarter of the ATTR CM launch, and as of June 30th, approximately 1,400 cardiomyopathy patients were receiving Amfutra, and this is a remarkable achievement. This performance reflects results from our cardiomyopathy launch in the U.S. only. International markets are coming online for Ambutra for CM and are expected to begin to contribute to the CM launch in the second half of the year. Kudos to our team for delivering these impressive early results. In addition to these commercial results, we continue to advance our leading pipeline of RNAi therapeutics. We initiated the Triton CM Phase 3 study of Nucreceram further establishing our commitment to leadership in TTR and are pleased to be announcing today that the FDA has granted fast-track designation to Nucleusiran for ATTR-CM. We also just shared encouraging phase one multi-dose data for Mifelsiran in Alzheimer's disease and kicked off a phase one study for ALN4324 in type 2 diabetes earlier in the quarter. And with regard to financial performance, we're reporting our strongest quarter to date as a company with $672 million in total net product revenues or 64% growth year over year. As a result, we've increased our total net product revenues guidance for 2025 from a range of $2.05 to $2.25 billion to a revised range of $2.65 billion to $2.8 billion representing an increase of $575 million, or 27% at the midpoint, underscoring our confidence in the ATTR-CM launch and our other commercial products in the balance of the year. So zooming out from the success of Q2, this progress represents stellar execution towards our nylon pizza fits by 25 goals, which we seek to achieve by the end of this year. Doing so will further establish our nylon, as a unique top-tier biotech company delivering sustainable innovation to patients for many years to come. With that, let me now turn the call over to Tolga for a view of our commercial performance. Tolga?

Thanks, Ivan, and good morning, everyone. I'm excited to share with you the results of our Q2 commercial performance. As Ivan indicated, we are firing on all cylinders, and our Q2 performance was exceptional. for the full portfolio. On a global basis, our commercial portfolio delivered $672 million in net product revenues, representing 64% year-over-year and 43% quarter-over-quarter growth. As you will see in a moment, the US TTR performance was the major driver of growth given the ATTR-CM launch for Ambutrem. It is also encouraging that we saw very robust double-digit growth compared with Q1 across both our TTR and Rare franchises across the globe. All parts of our business are operating with focus and excellence. Let's quickly start with our Rare franchise. Our Givlari and Oxlumo teams stayed focused and delivered $128 million in combined Q2 sales, up 24% versus last year. Growth was largely demand driven with a tailwind from favorable give large growth to net adjustments in the US. Now, turning our attention to TTR franchise where we delivered $544 million in global net product revenues during the quarter, representing a 77% increase compared with the second quarter of 24 and a robust 51% increase compared with the first quarter of 2025. In the US, combined Q2 sales of Onpatro and Ambutra rose 80%, up roughly $170 million from Q1, driven primarily by Ambutra's ATTR-CM launch. We closed the quarter with approximately 1,400 cardiomyopathy patients on therapy, contributing an estimated $150 million in revenue. This performance was fueled by strong execution and faster than anticipated access across payers and providers. Regarding the year-over-year dynamics, the US TTR franchise grew 125% compared with the second quarter of 2024, primarily driven by the significant increase in demand from the ATTR CRM launch that I just highlighted. Turning to our international markets, we delivered 18% year-over-year growth, driven by continued strength in our HATTR PM business, which remains a solid growth engine. Importantly, we have yet to recognize any ATTR CM revenue internationally, as launches in Germany and Japan are slated to begin contributing in third quarter. Now, let me provide some additional perspectives on the US TTR revenue dynamics, where the franchise achieved $383 million in the second quarter, representing a very robust 80% quarter-over-quarter growth. While we don't have the ability to report revenue by indication, the underlying trend is clear. From Q1 24 through Q1 25, the US TTR franchise delivered steady growth of around $15 to $20 million on average every quarter. In Q2 2025, we saw a pronounced step change, indicating an estimated $150 million contribution from ATTR cardiomyopathy. I will now provide some additional launch metrics to further contextualize Onwutra's launch performance in ATTR cardiomyopathy. Our launch began on March 20, 2025, and Q2 marked our first full quarter post-approval. It is still early, and there is more work to do, but we're very encouraged by the strong momentum we're seeing. As we've described on prior calls, we've been focused on three key enablers around the U.S. launch of Amutra in ATTR cardiomyopathy. Health system set up, access and affordability, and treatment choice. The headlines are here, and I will go into more detail on each in the following slides. As we've shared on prior calls, there are approximately 170 priority health systems through which approximately 80% of ATTR cardiomyopathy patient volume flows. The majority of these provider accounts now have Amutra on formulary, enabling therapy initiation throughout these health systems where ATTR-CM patients present. What's more, nearly all of the priority health systems have already begun treating patients with Amutra for ATTR cardiomyopathy. This, together with the broad network of more than 2,000 alternate sites of care, has allowed us to achieve our aspirations. roughly 90% of patients in the U.S. are able to receive armature treatment within about 10 miles of where they live. Bottom line, our priority was to enable broad provider account setup in our first year of launch. This has happened faster than we had initially anticipated. Since now, at the end of our first quarter of launch, we are largely there. In addition, patients are getting first-line access to Ambutra across all payer segments. Coverage is now confirmed by payers covering the majority of U.S. patient lives, inclusive of Medicare Fee-for-Service, Medicare Advantage, and commercial. We can therefore confirm that the large majority of patients have access to Ambutra as a first-line treatment, meaning without requiring patients to step through another product first. Most patients are indeed paying zero in out-of-pocket costs. And consistent with what we've seen in Poneuropathy, there has been very limited use of our Quick Start program, quite simply because patients are not experiencing delays in coverage. We're also seeing patient initiations flowing through all payer segments, Medicare Free-for-Service, Medicare Advantage, and commercial. These access dynamics are consistent with what we've long seen in HA-ATTR-PN, and we're encouraged to see them replicated in ATTR-CM. This reflects our deep experience engaging with payers and the advantage of our fully integrated in-house patient support services. Now, most importantly, physicians and patients are choosing Amutra, a testament to its highly differentiated, and compelling profile, including its rapid knockdown of the disease-causing protein. By the end of second quarter, approximately 1,400 ATTR-CM patients had initiated treatment. While we don't plan to regularly report patient numbers going forward, we felt it was important to share this clear signal of early momentum in our first full quarter post-launch. This strong uptake also gives us early insight into utilization patterns, which so far have been broad and balanced. More specifically, very early initial uptake was more pronounced among stabilizer progressors. However, within just three short months, utilization has become relatively balanced between first line, new starts, and stabilizer progressors. We're seeing steady growth across both sources of business. And we have a clear focus on making Amutra the first line treatment of choice. We also see balanced utilization across academic and community settings. And lastly, physician adoption has been broad. Since launch, the total Amutra prescriber base has tripled quarter over quarter. This reflects growing awareness and confidence in amateurs across both cardiology and multidisciplinary practices. Bottom line, we're highly encouraged by the early progress post-launch. The trajectory supports sustainable growth and positions us for long-term leadership in TTR amyloidosis. In summary, access ramped faster than expected, and the value proposition is resonating. We've seen rapid payer adoption and broad physician engagement. The clinical differentiator of Ambutra is clearly being recognized. We're seeing robust growth in an underserved and expanding ATTR-CM population. Look, this is a devastating disease, and we remain deeply committed to advancing care through real-world evidence generation and development of our next-generation RNAi therapeutics. Finally, global expansion is underway. With regulatory approvals secured in Europe, Japan, and Brazil, we've now launched in Germany and Japan, unlocking access to more patients worldwide. We're also maintaining stable growth in the HHTTR vulnerability business, both in the U.S. and globally. These drivers underpin our increased revenue guidance, and reinforce our conviction in significant revenue growth going forward. We're just getting started and we remain focused on discipline execution anchored in patient and customer centricity and delivering long-term innovation-driven growth. I'll now turn it over to Pushkal to share more about our work to advance the science in ATTR and beyond. Pushkal.