Spyre Therapeutics (SYRE) Study Result summary

Study design and objectives

• Phase I trial was randomized, double-blind, placebo-controlled, with single and multiple ascending dose cohorts in healthy adults, up to four months follow-up at data cutoff.

• Doses ranged from 100 to 1,000 mg, administered subcutaneously or intravenously, with primary endpoint of safety and secondary endpoints of PK, ADA, and exploratory PD.

• Each cohort included eight subjects (6 active, 2 placebo), with well-balanced baseline characteristics; total enrollment was 56 healthy adults.

• Interim data were analyzed in a blinded fashion, with safety and PK data pooled within cohorts.

• SPY001 and vedolizumab bind the same epitope, but SPY001 is an optimized analog with extended half-life and higher induction exposures.

Key interim results

• SPY001 demonstrated a mean and median half-life of over 90 days, with population PK modeling suggesting ~100 days, about 4x longer than vedolizumab.

• No dose-dependent increase in adverse events; all AEs were mild, with only one drug-related event (injection site discomfort); no serious adverse events or discontinuations.

• No significant anti-drug antibody (ADA) impact on PK/PD or exposure observed.

• PK was dose-proportional across 300–1,000 mg; population PK model developed to inform phase II dosing.

• Exploratory PD data showed complete saturation of alpha-4 beta-7 receptors at all time points with the lowest dose, sustained for at least 12 weeks.

Implications for dosing and efficacy

• Extended half-life supports potential for quarterly or twice-annual subcutaneous maintenance dosing, with as few as 2–4 injections per year.

• Modeling predicts all phase II patients can achieve exposures in the fourth quartile of vedolizumab, potentially improving efficacy.

• Simulations indicate maintenance with one subcutaneous injection every three or six months is feasible.

• Market research suggests strong preference for less frequent dosing among physicians and patients.

• Single doses resulted in full receptor saturation for the longest follow-up, supporting expected mechanism.