Ionis Pharmaceuticals (IONS) Wells Fargo 21st Annual Healthcare Conference summary

Strategic and clinical milestones

• Achieved two FDA approvals for TRYNGOLZA (severe hypertriglyceridemia) and ZANVASTRO (Alexander disease), both first-in-class for high unmet needs.

• Anticipates a third FDA approval for chronic HBV by partner GSK later this year, with unprecedented functional cure rates.

• Three phase III readouts completed this year, with two more expected; pipeline continues to advance with new phase II studies in sHTG and Dravet syndrome.

• Launch momentum for TRYNGOLZA is strong, with rapid uptake among high-risk patients and positive payer engagement.

• DAWNZERA for HAE is gaining market share, especially from switches, and shows high patient retention.

Key program updates and challenges

• Angelman syndrome program remains on track, with no negative read-through from competitor setbacks; full data expected in the second half of next year.

• Lp(a) program with Novartis (pelacarsen) showed strong biomarker reduction but failed to meet clinical endpoints; no path forward for this asset.

• CARDIO-TTRansform study for eplontersen in ATTR cardiomyopathy showed strong efficacy as monotherapy but no added benefit in combination with stabilizers; AstraZeneca is evaluating next steps.

• Eplontersen offers self-administration and could serve as a frontline or second-line therapy, but regulatory path is uncertain due to missed primary endpoint.

Competitive landscape and pipeline strategy

• TRYNGOLZA faces competition from Arrowhead’s product, but maintains a first-mover advantage, clean safety profile, and flexible dosing.

• siRNA follow-on (ION775) aims for once or twice yearly dosing, with phase II data supporting high efficacy and safety; phase III decision expected in 2027.

• Focus remains on sHTG for ION775, with no plans to pursue moderate HTG or cardiovascular outcomes at this stage.

• Bepirovirsen approved in Japan for HBV, with U.S. approval expected in October; phase III data for sefaxersen in IgA nephropathy due later this year.

• CNS pipeline continues to advance, including a new phase II study in Dravet syndrome.