ARWR/IONS: sHTG and pancreatitis-Does SHASTA signal or CORE command?

Ahead of ARWR’s phase III SHASTA-3/4 in 3Q26, we have published a new in-depth report on the ARWR/IONS sHTG debate, challenging the view that Ionis is comfortably ahead. The key question is straightforward: can SHASTA-3/4 deliver a statistically significant reduction in acute pancreatitis? And if so, will that reduction look better than what has already been shown with olezarsen?

We answer this and other debate questions that matter most going into the catalyst:

• Can SHASTA-3/4 deliver a statistically meaningful Acute pancreatitis result?

• How much room is there for SHASTA-3/4 to produce a result that looks competitive rather than only positive?

• Does plozasiran show any clear efficacy advantage over olezarsen on the measures that matter most commercially?

• Does plozasiran have a credible path to meaningful commercial differentiation, even without a decisive efficacy win?

• What is the balance between first-mover advantage, tolerability, and long-term share in APOC3?

• How much of ARWR’s optionality depends on true superiority, versus simply delivering a clean positive phase III outcome?