Spyre Therapeutics Reports Positive Interim Phase 1 Results for SPY001 in Treating Inflammatory Bowel Disease

Spyre Therapeutics, Inc., a biotechnology company focused on innovative treatments for inflammatory bowel disease (IBD), recently revealed promising interim Phase 1 data for SPY001, a new extended half-life monoclonal antibody targeting α4β7. The company reported that SPY001 demonstrated a favorable safety profile and exceeded pharmacokinetic (PK) expectations with a half-life of over 90 days.

The interim results, as of October 30, 2024, suggest that SPY001 has the potential to advance as a next-generation anti-α4β7 therapy and form the basis for combination treatments in IBD. The data indicate that SPY001 could improve or accelerate efficacy compared to current anti-α4β7 therapies. The findings support potential maintenance dosing every three to six months via a single subcutaneous injection.

In the Phase 1 trial, SPY001 was administered in single doses up to 1000 mg and multiple doses up to 600 mg. The trial involved 56 healthy adults divided into five single-ascending dose (SAD) and two multiple-ascending dose (MAD) cohorts. SPY001 was well-tolerated with no serious adverse events reported, and all adverse events were mild. The most common treatment-emergent adverse events were headache and nasopharyngitis. There were no adverse events leading to trial discontinuation.

PK data showed that SPY001 has a significantly extended half-life compared to vedolizumab, which has a human half-life of 25 days. This extended half-life supports the potential for maintenance dosing every three to six months using a high-concentration, citrate-free formulation. There was no apparent impact of anti-drug antibodies on pharmacokinetic exposures, and the pharmacodynamic (PD) data demonstrated complete saturation of α4β7 receptors at the latest time point available.

Spyre plans to initiate a Phase 2 platform trial for SPY001 in ulcerative colitis in mid-2025, pending regulatory feedback. This trial will be a double-blind, randomized, placebo-controlled study targeting patients with moderately-to-severely active ulcerative colitis. The platform trial will efficiently evaluate each of Spyre's monotherapy and combination therapies against a common placebo control, aiming to explore the safety and efficacy of SPY001 and the contributions of each therapy component.

The Phase 2 trial will include approximately 500 subjects, with a 12-week placebo-controlled induction period followed by a 38-week maintenance period. This trial will initially feature SPY001 and placebo arms, with additional arms for SPY002 (TL1A), SPY003 (IL-23), and combination therapies added based on clinical and nonclinical data and regulatory feedback.

Given the favorable PK results for SPY001, Spyre is updating its guidance for maintenance dosing across its portfolio to every three to six months for both monotherapies and combination therapies. This reflects Spyre's unique capability to target a product profile that could offer best-in-class efficacy and convenience for patients with IBD.

Spyre Therapeutics is committed to developing next-generation IBD treatments through best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. SPY001 represents a significant step forward, potentially offering a more convenient and effective treatment option for individuals with IBD.