Ionis Pharmaceuticals (IONS) TD Cowen Genetic Medicines & RNA Summit summary

Wainua launch and market dynamics

• Wainua launched in late January after approval for ATTR polyneuropathy, reporting $5 million in partial quarter revenue and strong initial uptake.

• High receptivity from clinicians and patients, with self-administration via autoinjector seen as a key differentiator.

• Focus is on newly diagnosed patients, as over 80% of those with ATTR polyneuropathy are not currently on treatment.

• Some patients are switching from other approved treatments, but the main strategy targets new diagnoses.

TTR cardiomyopathy clinical strategy and study design

• The biology of TTR cardiomyopathy is not fully understood due to lack of predictive preclinical models; clinical data drives understanding.

• Silencing therapies are expected to be effective by reducing toxic amyloid fibrils and amyloid buildup in the heart.

• The ongoing phase III study is the largest to date, powered for cardiac hospitalizations and mortality, with a balanced mix of monotherapy and combination with tafamidis.

• Drop-in rates for tafamidis during the study are low and unlikely to impact results.

• Mortality benefit is a key secondary endpoint; strong trends, even without statistical significance, are considered valuable.

Angelman syndrome program and clinical development

• Phase II data for ION582 in Angelman syndrome will be presented in July, showing 60-70% of patients benefited across multiple parameters.

• The study included a broad patient population and leveraged robust natural history data to inform phase III design.

• Consistent benefit observed across various assessment instruments, supporting confidence in results.

• Plans are to meet with the FDA first to finalize phase III design and primary endpoints, with EMA discussions to follow.