• Non-GAAP Operating Loss: $345 million, a significant improvement compared to 2024 guidance.
• Total Revenue: $705 million, exceeding 2024 guidance by more than $130 million.
• SPINRAZA Royalties: $216 million for the year.
• WAINUA Product Sales: $85 million for the year, with $20 million in royalties.
• Fourth Quarter WAINUA Growth: 84% increase in product revenue compared to the third quarter.
• Sales and Marketing Expenses: Increased by 12% year-over-year, reflecting investments in TRYNGOLZA and Donidalorsen launches.
• Projected 2025 Revenue: More than $600 million, with a shift towards commercial revenue.
• Projected 2025 Operating Expenses: Expected to increase in the high single-digit percentage range compared to last year.
• Projected 2025 Non-GAAP Operating Loss: Less than $495 million.
• Projected Year-End Cash and Investments: Approximately $1.7 billion.

• Warning! GuruFocus has detected 3 Warning Signs with IONS.

Release Date: February 19, 2025

For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Positive Points

• Ionis Pharmaceuticals Inc (NASDAQ:IONS) successfully launched TRYNGOLZA, their first independently launched medicine, for familial chylomicronemia syndrome (FCS), with rapid uptake and positive feedback from patients and healthcare providers.
• The company is on track to deliver three additional independent launches over the next three years, including treatments for hereditary angioedema, severe hypertriglyceridemia (SHTG), and Alexander's disease, representing significant revenue potential.
• Ionis Pharmaceuticals Inc (NASDAQ:IONS) exceeded their 2024 revenue guidance by more than $130 million, achieving $705 million in revenue, driven by strong performance from SPINRAZA and WAINUA.
• The company has a robust pipeline with multiple late-stage data readouts and regulatory actions expected, positioning them to bring transformational medicines to market.
• Ionis Pharmaceuticals Inc (NASDAQ:IONS) has a scalable and experienced commercial organization in place, ready to support multiple upcoming product launches and drive long-term growth.

Negative Points

• Ionis Pharmaceuticals Inc (NASDAQ:IONS) reported a non-GAAP operating loss of $345 million, highlighting ongoing financial challenges despite revenue growth.
• The launch of TRYNGOLZA for FCS is expected to have a gradual buildup of momentum due to the rare and under-recognized nature of the disease, potentially impacting short-term revenue growth.
• The company anticipates lower R&D revenue in 2025 compared to the previous year, which may affect overall revenue performance.
• Ionis Pharmaceuticals Inc (NASDAQ:IONS) faces challenges in patient identification and diagnosis for FCS, with the majority of the patient population remaining unidentified and undiagnosed.
• The company is reliant on partnerships for certain programs, such as the collaboration with Novartis for the next-generation Lp(a) targeting asset, which may impact control over development timelines and outcomes.

Q & A Highlights

Q: What insights can be drawn from the ESSENCE study for Olezaresen and its impact on the core studies for SHTG? A: Brett Monia, CEO, explained that the ESSENCE study focuses on a different patient population with mildly elevated triglycerides, primarily serving as a safety study. The key insights will be related to safety and APOC3 reductions, which will help validate the safety profile seen in FCS patients. While triglyceride reductions will be observed, they may not directly predict outcomes in SHTG due to the different patient population.

Q: How is Ionis performing in the TTR polyneuropathy market with WAINUA? A: Brett Monia, CEO, reported strong demand for WAINUA, with a 40% new-to-brand share and significant quarter-over-quarter growth. The drug is being prescribed by both centers of excellence and community physicians, with a mix of naive patients, switches, and combination treatments contributing to its success.

Q: Can you elaborate on the design and expectations for the SHTG Phase 3 study? A: Brett Monia, CEO, stated that the SHTG Phase 3 study is powered for triglyceride reductions, the primary endpoint. Although the study is not specifically powered for acute pancreatitis outcomes, the large patient population may allow for meaningful insights. The study aims to demonstrate significant triglyceride lowering, which is crucial for reducing acute pancreatitis risk.

Q: What are the early launch experiences and challenges with TRYNGOLZA for FCS? A: Kyle Jenne, EVP of Commercial, highlighted the positive reception of TRYNGOLZA, with several hundred patients identified and diagnosed. The launch is progressing well, with a broad label allowing for both clinically and genetically diagnosed patients. The focus is on efficient prescription processes and patient support through the Ionis Every Step program.

Q: What are the plans for the Angelman Syndrome program, and how is it being powered? A: Eugene Schneider, EVP of Clinical Development, explained that the Angelman Syndrome Phase 3 study is powered based on natural history data and encouraging Phase 2 results. The primary endpoint is expressive communication, with the study designed to assess two dose levels against placebo. The study aims to enroll patients efficiently, given the significant unmet need in this population.

For the complete transcript of the earnings call, please refer to the full earnings call transcript.