IONS: Thoughts on Olezarsen's CORE-OLE data in sHTG

Research evidence excerpt

IONS: Thoughts on Olezarsen's CORE-OLE data in sHTG

NORTH AMERICA | Biotechnology

Ionis Pharmaceuticals EquityJuneResearch12, 2026

FLASH NOTEIONS: Thoughts on Olezarsen's CORE-OLE data

RATING BUYin sHTG

PRICE $73.82^

IONS presented Olezarsen's prelim. OLE data in sHTG. We'll note: #1) mean

hepatic fat fraction (HFF) trended back to baseline by month 24 w/ 80mg dose PRICE TARGET | % TO PT $113.00 | +53%

#2) less pronounced HFF change in pts switching from 50mg dose to 80mg 52W HIGH-LOW $86.74 - $34.78

dose in the OLE #3) no new safety signals emerged during the OLE period. FLOAT (%) | ADV MM (USD) 100.0% | 125.41

Overall, we remain unconcerned about pot'l longer-term liver fat monitoring MARKET CAP $12.0B

requirements & remain bullish into Tryngolza launch; model PS of $4Bn in sHTG TICKER IONS ^Prior trading day's closing price unless otherwise

noted.

Bottom line: We got Olezarsen's preliminary OLE data from CORE studies. In a CORE trial subset

(N=53) with elevated baseline liver fat enrolled in the MRI-PDFF substudy, hepatic fat fraction (HFF)

trended toward baseline by 24 months on Olezarsen 80 mg. Notably, no new safety signals emerged

during the OLE period.

Stepping back, when Olezarsen's full Ph3 CORE data came out, there were some investor concerns

around the dose-dependent liver fat increases (+2.3-4.2ppt at 50-80mg vs +0.1ppt pbo by month

12). However, we noted the changes appeared like a byproduct of triglyceride (TG) lowering rather

than a meaningful safety concern that would outweigh the benefit of oleza's efficacy benefits +

noted plateau /decrease in the HFF (HERE). We think the current data continues to validate our

original conviction.

Here's what we'll highlight:

#1) Current OLE data from the MRI-PDFF substudy clearly shows hepatic fat fraction (HFF)