IONIS PHARMACEUTICALS INC Q4 FY2024 earnings call

Launch Activities - Tringolza launched in late December 2024 for FCS, with the team executing the launch flawlessly. Plans for three additional independent launches over the next three years: Donidalorsen for hereditary angioedema, olezarsen for severe hypertriglyceridemia, and Zilganersen for Alexander disease. - Partnered medicines like SPINRAZA and WAYLIVRA generate revenue and growth potential. The commercial team focuses on patient-finding, HCP education, and support programs like Ionis Pharmaceuticals, Inc. Every Step to aid patients and prescribers. - Pipeline achievements include positive late-stage data, regulatory submissions, and preparations for multiple launches, leveraging first-mover advantage in FCS and SHTG.

Ionis Pharmaceuticals, Inc. saw SPINRAZA contribute $216 million in royalties in 2024. WAYLIVRA had $85 million in product revenue and $20 million in royalties. The company launched Tringolza for familial chylomicronemia syndrome (FCS) in late 2024, marking the start of independent commercialization. SPINRAZA remained a key revenue source, while WAYLIVRA showed accelerating sequential growth. Tringolza's revenue contribution is expected to grow as patient identification and diagnosis progress.

Revenue Projection - Projected 2025 revenue over $600 million, with commercial revenue from Tringolza, Donidalorsen (assuming approval), SPINRAZA, and WAYLIVRA. ### Expenses and Cash - Anticipate non-GAAP operating loss less than $195 million in 2025, with cash and investments around $1.7 billion. ### Long-Term Potential - Long-term potential includes multibillion-dollar peak revenue from own medicines (e.g., olezarsen, ION-582) and significant royalty income from partnered medicines.

Regulatory Uncertainty - Uncertainty around regulatory approvals for upcoming launches (e.g., Donidalorsen, olezarsen). ### Patient Identification - Challenges in patient identification and diagnosis for rare diseases like FCS. ### Competitive Landscape - Competitive landscape and market adoption of new therapies pose risks.

Q: Mike Ulz asked about ESSENCE study readout and its relation to CORE studies for olezarsen in SHTG.

A: Brett Monia responded that ESSENCE is a safety study for a different patient population, but safety and APOC3 reductions are key read-throughs to CORE studies.

Q: Jessica Fye inquired about WAYLIVRA market capture in ATTR polyneuropathy.

A: Brett Monia said WAYLIVRA has a 40% new-to-brand share, with growth from new patients and switches, driven by quality of life, safety, and access.

Q: Akash Tewari asked about SHTG phase three design and event rate assumptions.

A: Brett Monia and Eugene Schneider discussed powering for triglyceride reduction and lack of clinical consensus on acute pancreatitis meaningfulness.

Q: Yanan Zhu followed up on WAYLIVRA growth and Biogen collaborations.

A: Kyle Jenne talked about WAYLIVRA growth from new patients and market expansion, while Brett Monia discussed retained global rights for alpha-synuclein and LRRK2 programs.

Q: Jay Olson asked about Tringolza launch metrics and patient diagnosis.

A: Kyle Jenne discussed early launch progress, physician prescribing, and Ionis Pharmaceuticals, Inc. Every Step program's role.

Q: Chi asked about Tringolza insurance documentation and diagnosis mix.

A: Kyle Jenne and Brett Monia talked about genetic vs. clinical diagnosis, insurance processes, and progress in patient identification.

Q: Ike Lee asked about SHTG trial timeline and TG lowering benefit.

A: Brett Monia and Richard Geary discussed primary endpoint at six months, TG reduction rationale, and clinical risk reduction.

Q: Gary Nachman asked about commercial scaling and Angelman program enrollment.

A: Kyle Jenne talked about commercial team scaling for new launches, and Brett Monia discussed Angelman program enrollment timeline.

Q: Yaron Werber asked about Angelman phase three study design and revenue guidance.

A: Eugene Schneider discussed phase three design and Beth Hougen talked about revenue guidance with back-half loaded R&D revenues.

Q: Jake asked about SHTG ex-US launch and Novartis Lp(a) asset.

A: Brett Monia discussed securing OUS partners for SHTG and the status of Novartis' Lp(a) asset development.