ALNYLAM PHARMACEUTICALS, INC. Q1 FY2025 earnings call

Management Statement and Operational Highlights

• TTR Leadership: Progressing with the AMVUTTRA launch in ATTR-CM, focusing on securing broad access, driving awareness, and supporting treatment initiation. Early signs show robust patient initiations across payer segments, with widespread payer coverage and health system formulary inclusion within short timeframes.
• Growth through Innovation: Pipeline advancements include nucresiran, a next-generation RNAi therapeutic for TTR with potential for deeper knockdown and biannual dosing. Initiated Phase 1 study for ALN-4324 targeting type 2 diabetes. Updates on delivery solutions with potential for targeting major tissues by 2030.
• Strong Financial Performance: Q1 2025 total product revenues were $469 million, a 28% year-over-year growth. Collaboration revenue was $99 million, a 16% decrease YOY. Royalty revenue was $26 million, a $16 million increase YOY. Non-GAAP operating profit was $75 million, a $73 million improvement YOY.

Segment Performance

• Rare Franchise: GIVLAARI and OXLUMO together generated $109 million in combined product sales in Q1 2025, representing 8% year-over-year growth. GIVLAARI patient-on-therapy growth was ~15%, and OXLUMO was ~20%. Revenue growth for OXLUMO was lower due to gross adjustments in European markets and order timing. Full-year rare franchise product sales growth is expected to be approximately 15%.
• TTR Franchise: The TTR franchise delivered $359 million in global net revenues in Q1 2025, a 36% increase compared to Q1 2024. U.S. sales of ONPATTRO and AMVUTTRA saw a robust 45% year-over-year growth. Internationally, the TTR franchise grew 24% YOY. AMVUTTRA launched in ATTR-CM late in Q1, with early progress in access setup, payer coverage, and health system formulary inclusion.

Guidance

• Reiterating 2025 guidance, including TTR product sales growth. Assumes foreign exchange rates as of December 31, 2024; current weak U.S. dollar may provide ~$50 million currency upside relative to current product sales guidance. Tariffs currently in place have no material impact; potential pharma tariffs are expected to have limited exposure due to global supply chain and U.S.-based intellectual property.
• Upcoming milestones: Initiate TRITON-CM Phase 3 study in the first half of 2025, TRITON-PN by the end of 2025, AMVUTTRA approvals in Japan in Q2 and the EU in Q3, and report data from the KARDIA-3 Phase 2 trial in the second half of 2025.

Risks

• Uncertainty related to potential policy evolutions such as tariffs, FDA personnel reorganization, and other biotech industry initiatives. However, Alnylam believes it is well-positioned and insulated from potential impacts associated with key announced initiatives.

Question and Answer

Q: About prescriber base for AMVUTTRA in CM launch A: Tolga Tanguler stated there's broad uptake, including both familiar and new cardiologists to AMVUTTRA, with half of 170 priority health systems having AMVUTTRA on formulary within 4 weeks.

Q: Benchmarking ATTR franchise revenue growth and CM contribution A: Tolga mentioned category growth with tafamidis and Attruby, and no CM revenue in Q1 as AMVUTTRA approval was late in Q1.

Q: Leveraging commercial expertise for capturing tafamidis progressors A: Tolga stated AMVUTTRA's new mechanism of action and HELIOS-B results make it a clear first-line option, with broad uptake across prescribers.

Q: AMVUTTRA use, formulary access, and pricing A: Tolga said there's a single price for both indications, limited use of Quick Start program, and broad formulary inclusion in health systems with no prior authorization for Medicare FFS.

Q: Launch indicators, formulary goals, and patient profile in first line A: Jeff Poulton said Q2 data will show revenue uptake and pull through; Tolga explained formulary goals to be met by year end, and Pushkal Garg discussed doctors recognizing stabilizer progressors using clinical factors.

Q: AMVUTTRA uptake from switch vs new patients, access metrics A: Tolga said uptake is broad, including first line and switch patients, with strong support from commercial teams; Luca's question on access metrics was addressed with no step edits seen on payer mix.

Q: Uptake granularity, Medicare FFS access speed A: Tolga said AMVUTTRA is a professionally administered product with quick coordination, neutral to payer mix, and patients starting therapy regardless of insurance; Paul's question on prescriber metrics and Medicare FFS speed was answered.

Q: Cardiomyopathy diagnosis rate shift and outlook A: Yvonne Greenstreet said category growth is accelerating, similar to polyneuropathy, but difficult to predict exact diagnosis rate end of year.