ALNYLAM PHARMACEUTICALS, INC. Q3 FY2024 earnings call

• Commercially, Alnylam achieved 34% year-over-year growth in global net product revenue in Q3 2024, generating $420 million across four marketed products. - Made progress with the TTR franchise, sharing additional results from the HELIOS-B study of vutrisiran and filing regulatory submissions. Hosted a TTR Investor Day to highlight plans for potential ATTR cardiomyopathy launch. - Early pipeline saw momentum, including initiation of a Phase 1 study of ALN-HTT02 in Huntington's disease and initial results from the multi-dose portion of the Phase 1 study of mivelsiran in early onset Alzheimer's disease. - Stopped clinical development of ALN-KHK, an investigational RNAi therapeutic for type 2 diabetes mellitus. - Working towards filing proprietary INDs for 9 programs by the end of 2025 against targets in multiple tissues.

The TTR franchise achieved $309 million in global net product revenues in the third quarter of 2024, representing a 34% increase compared with the third quarter of 2023. The rare franchise, including GIVLAARI and OXLUMO, delivered $111 million in combined net product sales during the third quarter, which is an 8% increase compared with the second quarter of 2024 and a 34% growth compared with the third quarter of 2023.

• Reiterated 2024 guidance: combined net product revenues are expected to be within the range of $1.575 billion to $1.65 billion. - Collaboration and royalty revenue guidance range is $575 million to $650 million. - Non-GAAP R&D and SG&A expenses guidance remains between $1.775 billion and $1.875 billion.

Q: Just in terms of your earlier-stage pipeline, can you elaborate a bit on some of the work that you've done to improve the ability to deliver RNAi to adipose tissue and muscle? And how are you thinking about what makes the most sense as initial targets or diseases in these tissues? And any specific advantages to your approach versus other modalities?

A: Yes. Thanks, Ellie. As Jeff highlighted, we're excited about the emerging profile of RNAi therapeutics. These therapies appear well tolerated and allow sustained knockdown of disease-causing proteins with infrequent administration. We're guided by human genetics in pursuing diseases. Adipose and muscle are areas in our 225 strategy. We'll talk more about this at an R&D Day early next year.

Q: I wanted to ask one question regarding the ALN-HTT02. It seems like very impressive data in nonhuman primates. I believe this is one of very few showing actual knocking down in nonhuman primate brains instead of most of others showing rodent brain. So I know everyone is using 50% as a benchmark. Is that something you are looking for? What else you will be looking for regarding the Phase 1 data?

A: Yeah. Thanks, Gena. The Huntington's program is exciting as it's our third CNS program in clinic. We've seen sustained knockdown of disease-causing genes in preclinical studies. We're moving forward with the single ascending dose study, looking at safety, tolerability, PK, PD, changes in mutant Huntington levels, and clinical/imaging/biomarker measures. The study is in start-up mode in U.K., Canada, and has green light in U.S. with a dose cap, but we'll work with FDA to lift it over time.