Ionis Pharmaceuticals (IONS) Morgan Stanley 24th Annual Global Healthcare Conference summary

Year outlook and pipeline

• Two 2026 FDA approvals secured: TRYNGOLZA for severe hypertriglyceridemia in June and ZANVASTRO, the first disease-modifying Alexander disease treatment, last week.

• Third approval expected in October with GSK for chronic HBV; reported functional cures described as unprecedented.

• Angelman phase III enrollment complete, with data expected in H2 2026; salanersen and sapablursen also entered phase III with partners.

• Diranersen showed first proof of concept in tau, with reported cognitive and functional benefits; ION775 is in phase II for severe hypertriglyceridemia.

• CARDIO-TTRansform missed its primary endpoint, and the pelacarsen phase III outcome in Lp(a) cardiomyopathy was negative; full pelacarsen data presentation by Novartis is anticipated.

TRYNGOLZA launch

• Severe hypertriglyceridemia label expansion extends the addressable U.S. population from ~3,000 FCS patients to more than 3 million; U.S. peak sales goal remains $3B+.

• July and August launch months were described as very good, with strong HCP enthusiasm and prescriptions; more detailed launch update planned for Q3 earnings.

• Payer coverage is developing through medical exceptions and prior authorizations; policies and discussions are securing coverage across the label for triglycerides above 500 mg/dL.

• Initial prescribing is focused on high-risk patients, including triglycerides above 880 mg/dL or prior acute pancreatitis; prescriptions are also coming from patients in the 500–800 mg/dL range without prior pancreatitis.

• Monthly 50 mg or 80 mg dosing, no monitoring, and a simple auto-injector are resonating; management expects continued growth and highlighted 2027 as a major year.

TRYNGOLZA development and competition

• Phase I ION775 data showed durable, dose-dependent APOC3 and triglyceride reductions with good safety and tolerability; phase II is enrolling, with phase III potentially starting in 2027.

• ION775 may complement TRYNGOLZA or potentially become a next-generation option; phase III design work is underway, with plans to move faster than the prior phase III program.

• Management considers liver-fat increases on TRYNGOLZA small and on-target; the 50 mg change was not statistically significant, while the 80 mg increase was statistically significant at phase III end and waned toward baseline with continued dosing.

• Management views a second competitor as an opportunity to expand disease awareness and the market; the competing program may be about a year behind, while first-mover efforts target payer contracts and high-risk patients.