Spyre Therapeutics Inc. (SYRE): First Take: SPY002 shows attractive monotherapy profile

Research evidence excerpt

Spyre Therapeutics Inc. (SYRE): First Take: SPY002 shows attractive monotherapy profile

Equity Research

15 June 2026 | 1:34PM EDT

Spyre Therapeutics Inc. (SYRE): First Take: SPY002 shows attractive

monotherapy profile

This morning, SYRE announced positive topline induction results for SPY002 (long Paul Choi

+1(212)902-5217 | paul.k.choi@gs.com

acting, anti-TL1A) from Part A of the Phase 2 SKYLINE study evaluating the Goldman Sachs & Co. LLC

candidate as a monotherapy in moderately-to-severely active ulcerative colitis (UC). Daniel Ni, Ph.D.

Briefly, the data were positive with a statistically significant result on the primary +1(212)902-2365Goldman Sachs & Co.| daniel.ni@gs.comLLC

endpoint of change from baseline at Week 12 in Robart’s Histopathology Index (RHI)

of -10.7 points (p<0.0001) with a 33% clinical remission rate. Among other

secondary endpoints, SPY002 resulted in a 33% endoscopic improvement rate and

-3.7 point change in the modified Mayo score. Recall that SYRE recently announced

(link) that SPY001 (α4β7) showed a change in RHI from baseline of -9.2 points

(p<0.0001) and a 40% clinical remission rate. In our view, the headline efficacy

results for SPY002 reinforce the principle that targeting TL1A can be a valid

therapeutic approach in UC, and SPY002 has the potential to be a differentiated

monotherapy not only in that no commercially approved agent targets TL1A but also

in that it could achieve better disease control with a convenient dosing profile.

With regard to safety, 4.2% of patients (n=2/48) experienced a severe (Grade ≥3)

adverse event with one case of exacerbation of UC and one case of hospitalization

for worsening heart failure though both cases were deemed not to be drug-related

but did lead to discontinuation of treatment.