Ionis Pharmaceuticals (IONS) Barclays 28th Annual Global Healthcare Conference summary

Platform and portfolio overview

• Focus on genetic medicines targeting RNA for diseases with high unmet need, with 2026 expected to be transformational following strong momentum in 2025.

• Launched first two independent medicines in 2025: TRYNGOLZA for FCS and DAWNZERA for hereditary angioedema, both showing strong commercial performance.

• Achieved positive phase III readouts for TRYNGOLZA in severe hypertriglyceridemia and a new drug for Alexander disease, both with significant clinical impact.

• Anticipates approval and launch of TRYNGOLZA for sHTG in July and Alexander disease drug in the fall, with five additional phase III readouts expected in 2024.

Commercial trajectory and pricing strategy

• TRYNGOLZA for FCS continues to see strong demand and revenue growth, despite new competition and pricing pressure.

• sHTG launch will target a much larger population, prompting a significant step-down in price to maximize access and value.

• Initial net price estimates for sHTG were $10,000–$20,000, but final WAC price will be announced at launch after extensive market research.

• Launch will focus on highest-risk sHTG patients, with revenue expected to dip initially due to price change, then accelerate in the second half of 2024 and beyond.

• Peak U.S. sales for TRYNGOLZA in sHTG projected at over $2 billion.

Major clinical and pipeline catalysts

• Five phase III readouts expected in 2024, including eplontersen for ATTR cardiomyopathy, pelacarsen for Lp(a) cardiovascular disease, an IgA nephropathy drug, and a second ALS drug.

• Eplontersen phase III study in ATTR cardiomyopathy aims to provide first robust data on combination therapy with stabilizers, with potential for $5+ billion peak sales.

• Pelacarsen phase III HORIZON study for Lp(a) CVD is powered for 20% relative risk reduction; any statistically significant benefit would be clinically meaningful.

• Phase II CELIA study for tau in Alzheimer's disease expected midyear, aiming to validate tau production blockade as a therapeutic approach.

• Angelman syndrome program shows strong early data; first pivotal readout from a competitor expected in 2024, with high confidence in internal program's potential.