IONS: Thoughts on Phase 2 CELIA Data — We View the Results as Positive

Research evidence excerpt

IONS: Thoughts on Phase 2 CELIA Data — We View the Results as Positive

Equity Research

Flash Comment — May 14, 2026

Biotechnology

Ionis Pharmaceuticals, Inc.

Thoughts on Phase 2 CELIA Data — We View the Results as Overweight

Positive Price Target: $100.00

Ticker IONS

Our Call Upside/(Downside) to Target 31.5%

Today's topline results of tau ASO in early Alzheimer's disease suggested to us that the Price (05/14/2026) $76.02

primary endpoint failed the study rather than the other way around. 52 Week Range $32.00 - 86.74

Market Cap (MM) $12,534

Source: Company Data, Wells Fargo Securities estimates, and Factset.Initial Thoughts NA = Not Available, NC = No Change, NE = No Estimate

With all 3 treatment arms showing less cognitive decline than PBO, we view the Ph2

data as +ve. The primary endpoint was set as "dose response" — probably because the Yanan Zhu, PhD

study was too small to show individual arms' efficacy and a dose-response endpoint could Equity Analyst | Wells Fargo Securities, LLC

Yanan.Zhu@wellsfargo.com | 415-396-3194

increase power. With the finding that the lowest dose actually showed the best result, the

endpoint was naturally not met. We think this is an endpoint design issue rather than the Jeff Stith

study failing to show potential treatment effect. Associate Equity Analyst | Wells Fargo Securities, LLC Jeff.Stith@wellsfargo.com | 631-790-7157

Kuan-Hung Lin, PhD

Event. IONS & BIIB reported topline data from Ph2 CELIA evaluating diranersen (IONIS- Associate Equity Analyst | Wells Fargo Securities, LLC

MAPTRx/BIIB080) in individuals w/ early Alzheimer’s disease (BIIB is covered by Mohit Kuan-Hung.Lin@wellsfargo.com | 628-629-7566

Bansal; see note). Although the study missed its primary endpoint of dose response for