Alnylam Pharmaceuticals, Inc. Q3 FY2025 earnings call

• TTR leadership: AMVUTTRA cardiomyopathy launch had strong quarter, with focus on establishing long-term TTR leadership. • Growth through innovation: Pipeline includes two new Phase III trials (zilebesiran in hypertension, nucresiran in hATTR-PN), ALN-6400 in HHT Phase II, ALN-5288 in Alzheimer's Phase I. • Strong financial performance: Q3 total net product revenues $851 million, up 103% year-over-year. Increased net product revenue guidance for 2025. • Commercial performance: TTR franchise revenues $724 million, up 135% YoY; U.S. TTR franchise net sales $543 million, 194% YoY growth. • Pipeline updates: ZENITH Phase III cardiovascular outcomes trial of zilebesiran initiated, TRITON-PN study of nucresiran in hATTR-PN to initiate, ALN-6400 in HHT Phase II, ALN-5288 in Alzheimer's Phase I.

The TTR franchise was the primary growth engine. Global TTR net revenues reached $724 million in Q3, up 33% quarter-over-quarter and 135% year-over-year. U.S. TTR franchise net sales grew 42% quarter-over-quarter and 194% year-over-year, driven by the AMVUTTRA ATTR-CM launch. The rare disease portfolio achieved $127 million in sales in Q3, up 14% versus Q3 2024. TTR franchise revenues were $724 million or 135% year-over-year growth, with U.S. TTR revenues at $543 million, 194% year-over-year growth. The rare portfolio contributed 14% growth year-over-year in Q3.

• Increased net product revenue guidance for 2025 from $2.65 billion to $2.8 billion to $2.95 billion to $3.05 billion. • TTR franchise guidance revised to $2.475 billion to $2.525 billion from $2.175 billion to $2.275 billion. • Non-GAAP operating expense guidance narrowed to $2.15 billion to $2.2 billion. • Gross margin on product sales expected to decrease in Q4 due to higher AMVUTTRA royalty rates.

• Potential impact of CMS reimbursement changes on PYP scintigraphy and category growth. • Legal risk related to subpoena from the U.S. Attorney General regarding government price reporting. • Competition in the hATTR polyneuropathy legacy business.

Q: Could you speak with regard to AMVUTTRA, how the momentum is going in the first-line versus switchers population and maybe talk about any combo use? And any clarity here on ex U.S. pricing would be helpful as well.

A: Yvonne Greenstreet and Tolga Tanguler responded, stating strong momentum in TTR business, adoption across settings, first-line share growing, and ongoing ex U.S. pricing negotiations.

Q: Just a quick question again on AMVUTTRA. I guess like what gives you confidence that you're going to continue to see an acceleration in patient adds next year and going into the end of this year? And also, it seems like there was somewhat of a contribution from switches from ONPATTRO in the U.S. this quarter versus last quarter. Again, any color on patient switches from stabilizers would really be helpful. And then just really quick on MAPT, can you just talk about what led to the decision to pursue that program and your confidence in the target? Does this say anything about your ALN-APP program in Alzheimer's as well?

A: Yvonne Greenstreet and Tolga Tanguler and Pushkal Garg responded, discussing confidence in AMVUTTRA's growth, ONPATTRO contribution, and MAPT program details.

Q: I wanted to get some color on payer dynamics as you get into the launch now more like your third or fourth quarter in almost. How are you getting feedback from payers? Our survey work seems to indicate that we're not seeing any pushback yet even as the drug gets adopted to formulary. But as you're thinking about or currently negotiating 2026 status, can you share with us some of the feedback that you're getting from payers? Is there going to be any risk of payers preferring a stabilizer to a silencer or at least ordering which of the products that are currently available, they might prefer?

A: Yvonne Greenstreet and Tolga Tanguler responded, stating no payer headwinds, payers understanding value, and ongoing 2026 policy negotiations.

Q: Congrats on a great quarter. Wondering if you can comment more on just the inventory demand number for third quarter and how to think about that for fourth quarter, along with gross to net? And can you walk us through your expectations for fourth quarter revenues in the EU and how to think about the ramp up there?

A: Yvonne Greenstreet and Jeff Poulton and Tolga Tanguler responded, discussing inventory and gross to net dynamics, and EU revenue expectations.

Q: Congrats on a great quarter. Maybe just want to confirm I heard it correct that the price for AMVUTTRA will be declined at the mid-single digit year-over-year in the U.S.? And a related question is that once you launch ATTR cardiomyopathy in Europe, how should we think about price change in Europe? Should we expect a huge dip or largely aligned with the U.S.? And then second question is regarding the AMVUTTRA in ATTR cardiomyopathy in the U.S. Just wondering if you can share a little bit more color regarding the ratio between the first-line versus second-line. Are we talking about roughly 50-50 or second-line is slightly higher?

A: Yvonne Greenstreet and Tolga Tanguler responded, discussing price trends, Europe price expectations, and first-line vs second-line ratio in U.S.

Q: Just back to Europe, Tolga. Can you talk about what degree of commercial investment is needed in Europe to expand beyond the PN indication. We're trying to figure out how to balance that against any potential lower cost. And then just a very quick follow-up. As we think about that first-line dynamics, how much does center type impact first-line use, basically, if they're in commercial hospital systems versus patient characteristics?

A: Tolga Tanguler responded, discussing commercial investment in Europe and impact of center type on first-line use.

Q: The tafamidis trends show a clear NRx jump from fourth quarter to first quarter in both 2024 and 2025. Should we model a similar jump up for AMVUTTRA, thinking that is it because of IRA Part D modifications in the past year or normal seasonality?

A: Tolga Tanguler responded, discussing category growth expectations and positioning of AMVUTTRA in ATTR-CM market