ALNYLAM PHARMACEUTICALS, INC. Q4 FY2024 earnings call

• 2024 was a strong year with strong research, program development, and commercial execution, including positive results from HELIOS-B Phase 3 study leading to regulatory filings for vutrisiran in ATTR cardiomyopathy.
• TTR franchise had 35% growth in Q4 2024 and full year 2024 revenue growth in the U.S. despite new competition.
• Upcoming PDUFA target action date for vutrisiran in late March, with preparations for expanded label and launch of TTR-CM.
• R&D progress includes advancing Zilebesiran, Mivelsiran, and new Phase 1 programs, with plans to host R&D Day on February 25, 2025.

The TTR franchise achieved $343 million in global net product revenues during Q4 2024, representing a 35% increase compared with Q4 2023. Full year 2024 TTR revenue in the U.S. was $705 million, a 39% growth compared with 2023. For 2025, TTR product sales are guided to be between $1.6 billion and $1.725 billion, representing a 36% increase at the midpoint of the guidance. The Rare franchise had combined product sales of $108 million in Q4 2024, a 3% decline compared with Q3 2024 but an 18% growth compared with Q4 2023. Full year 2025 Rare franchise revenue is guided to be between $450 million and $525 million, representing a 15% increase at the midpoint.

• 2025 combined net product revenue for four commercial products is anticipated to be within $2.05 billion to $2.25 billion, a 31% increase at midpoint from 2024.
• TTR product sales guided $1.6 billion to $1.725 billion, assuming approval and launch of AMVUTTRA for ATTR cardiomyopathy.
• Rare franchise sales guided $450 million to $525 million.
• Collaboration and royalty revenue guidance $650 million to $750 million, with anticipation of a $300 million milestone payment from Roche.

Q: How long will it take to establish payer policies after approval of vutri and how will it impact the initial launch trajectory?

A: Tollerant Tanguler stated uptake will be meaningful in the second half of the year as formulary uptake takes time.

Q: Thoughts on AMVUTTRA's premium pricing and step edits for commercial insured patients?

A: Tolga Tanguler mentioned expectations of smooth coverage similar to PN, with 70% of patients currently paying zero co-pay.

Q: Key factors impacting AMVUTTRA pricing and J-code status?

A: Yvonne Greenstreet and Tolga Tanguler noted consideration of product value and patient access, with AMVUTTRA already having a J-code.

Q: Label discussion progress and inclusion of preservation and quality of life?

A: Pushkal Garg stated excitement about FDA review and expectation of label reflecting study results including mortality and quality of life benefits.

Q: Expectations for vutrisiran's revenue mix between naive patients and switches from tafamidis?

A: Tolga Tanguler expected a good mix of naive patients and switches, with the product well-positioned as a standard of care.

Q: Competitive dynamics in polyneuropathy and Part B/Part D play in cardiomyopathy approval?

A: Tolga Tanguler mentioned consistent growth despite competition and similar payer mix dynamics to PN.

Q: Early acoramadis scripts implication and AMVUTTRA's net price evolution?

A: Tolga Tanguler expressed encouragement about market growth and AMVUTTRA's strong clinical profile.

Q: Payer dynamics and formularies in the category?

A: Tolga Tanguler expected similar payer mix dynamics to PN, with focus on patient affordability.

Q: Phase 3 study for Inclisiran in ATTR-CM timing and interim analysis?

A: Pushkal Garg stated more detail would be provided at R&D Day, with focus on derisked asset and best-in-class potential.

Q: Gross margin outlook going forward?

A: Jeff Poulton explained gross margin expected to be lower in 2025 due to AMVUTTRA's royalty burden and growth, but offset by high margin collaboration and royalty revenue and potential benefits from Nucresiran.