Alnylam Pharmaceuticals, Inc. 2026 Q3 Earnings Call

I am Josh Brodsky, Vice President of Investor Relations at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer, Tolga Tanguler, Chief Commercialization Officer, Pushkal Garg, Chief Research and Development Officer, and Jeff Poulton, 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.alnylam.com/events. 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 provision. 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.

With that, I will now turn the call over to Yvonne.

Yvonne? Thanks, Josh, and thank you everyone for joining the call today.

I am going to begin by putting the quarter into context and discussing why our commercial portfolio and pipeline give us confidence in Alnylam's growth. Tolga will then review our commercial performance and the work underway to expand AMVUTTRA adoption and support patient access. Pushkal will walk through our decision to further expand TRITON-CM enrollment and important progress across our pipeline. Finally, Jeff will review our Q3 financial results and our outlook for the fourth quarter and full year before we go to Q&A. I want to start by why we remain confident in the opportunity ahead of Alnylam. AMVUTTRA has demonstrated significant benefits for patients with ATTR cardiomyopathy, including reductions in mortality and cardiovascular events with quarterly dosing.

We believe that this profile and AMVUTTRA's unique mechanism of action position it to become a foundational treatment in a market where many patients remain untreated and many physicians are still gaining experience with the medicine. Now moving on to the quarter. Our third quarter product revenues grew 52% year-over-year to approximately $1.3 billion, led by continued AMVUTTRA uptake, establishing a strong foundation for our TTR franchise. We generated total TTR revenues of $1.15 billion during the third quarter, representing nearly 60% growth year-over-year. We have deep conviction in the commercial initiatives and investments we authorized earlier this year and have now fully implemented. Given the magnitude of the opportunity in front of us, we believe these are the right actions to broaden AMVUTTRA's prescriber base, deepen physician engagement, and over time, drive adoption at scale.

That said, we're not yet satisfied with the underlying demand growth we have observed, and this is reflected in the full year outlook that Jeff Poulton will discuss shortly. As Tolga Tanguler will describe in more detail, our sales force expansion is increasing physician engagement, but that engagement takes time to translate into additional patient starts. We have more work to do, and accelerating that translation is a clear priority for us. With what we believe is a best-in-class clinical profile demonstrated by continued evidence generation from PDSB, AMVUTTRA continues to offer a significant opportunity to expand physician adoption and reach more patients in a growing ATTR market. At the same time, the performance of our TTR franchise is funding the future drivers of Alnylam's growth. We're investing in and advancing the next wave of medicines as we build a more diversified multi-franchise business.

Within the TTR category, nucresiran gives us the opportunity to build on AMVUTTRA's success with deeper TTR lowering and twice-yearly dosing. We have a high level of conviction in a positive TRITON-CM outcome, and today we announce further expansion of enrollment in the study to approximately 2,250 patients. This expansion optimizes nucresiran's chances for success and strengthens our long-term TTR position. Pushkal Garg will go into more detail, but importantly, this expansion does not change our expected ATTR cardiomyopathy launch timing of 2030, subject to positive study results and regulatory approval. Beyond TTR, the early brezosiran results we recently reported in Huntington's disease are particularly encouraging. The target engagements and safety findings to date support our preparations to initiate a pivotal study in 2027, pending regulatory alignment. Longer term, our Alnylam 2030 vision continues to guide our priorities and investments for the next half of the decade.

Alnylam 2030 represents our aspiration to become the leading science-driven, fully integrated global biopharmaceutical company, and to maximize the full potential of RNAi therapeutics for patients. It also means driving commercial execution with laser-like focus and urgency while continuing to invest in the science that can sustain Alnylam's growth over time. We have a substantial opportunity in front of us, and our responsibility is to turn it into results for patients and shareholders. With that, let me now turn the call over to Tolga Tanguler, who will take you through our commercial progress, including our efforts to expand the prescriber base and reach more patients.

Tolga? Thanks, Yvonne, and good morning.

We delivered significant year-over-year growth in the third quarter and continued to bring our therapies to more patients around the world. Today, I will discuss what drove our revenue, where underlying demand has room to grow, and the plans we have in place to capture the opportunity ahead. In the third quarter, we generated $1.29 billion in combined net product revenues, an increase of 52% year-over-year and 10% compared with the second quarter, including the impact of foreign exchange. This performance reflects continued execution across our portfolio, led by the TTR franchise and complemented by our rare disease therapies. Turning to our TTR franchise, global net product revenues reached $1.15 billion in the third quarter, increasing 12% compared with Q2 and 59% year-over-year. in the U.S., TTR revenues increased 12% sequentially and 69% year-over-year.

This approximate $100 million in U.S. quarter-over-quarter revenue growth was driven primarily by an $81 million increase in demand, along with an inventory benefit of $17 million. Net price during Q3 modestly increased from Q2 and benefited from approximately $10 million in one-time gross-to-net adjustments. Jeff will cover these items in more detail. Outside the U.S., TTR revenues increased 10% sequentially and 28% year-over-year. Year-over-year growth was primarily driven by ATTR-CM uptake in Japan and Germany, partially offset by the impact of CM launch price reductions. We are excited by the speed with which we are obtaining access in new markets across Europe. With favorable pricing, recognizing the value of AMVUTTRA over stabilizers, ex-U.S. markets have contributed significantly to tafamidis growth over time, and there is significant opportunity here to support our TTR global leadership ambitions. Taken together, these results reflect sustained global growth across the TTR franchise.

Looking beyond quarterly revenue, we continue to see encouraging indicators of expansion across the U.S. TTR market and the AMVUTTRA prescriber base. Total ATTR-CM prescriptions grew nearly 40% year-over-year in the third quarter. While the rate of growth can vary quarter to quarter, category growth continues to be robust and sustained. What is more, approximately 80% of prevalent ATTR-CM patients remain untreated, underscoring the substantial long-term potential to bring therapy to many more patients. Since the AMVUTTRA CM launch in the United States, more than 2,000 new unique prescribers have prescribed AMVUTTRA. This metric is particularly encouraging given what we know about prescribing behavior among physicians with AMVUTTRA experience. As we highlighted on our Q2 earnings call, we have seen that utilization deepens with experience.

Put it simply, trial begets preference, and only with approximately a third of all active prescribers having prescribed AMVUTTRA to date, we see a significant opportunity to drive broader adoption and deepen utilization. This was a key factor behind our decision to expand our customer-facing teams to broaden our reach and engage more prescribers. Now, with that expansion in place, we have indeed increased the reach and volume of HCP customer engagements. While these increased engagements have not yet translated into increased demand growth, we are encouraged by the breadth and depth of HCP engagement, positive message resonance, and continued growth in the AMVUTTRA prescribing base, with utilization balanced across both centers of excellence and community settings. That said, we recognize there is more work to do to drive demand growth.