Spyre Therapeutics Accelerates SPY003 Clinical Timelines and UEGW Presentations Highlighting Leading Antibodies

Spyre Therapeutics, Inc., a clinical-stage biotechnology company focused on innovative treatments for inflammatory bowel disease (IBD), recently shared updates on its pipeline progress and scientific presentations at the United European Gastroenterology Week (UEGW) Congress. The company's latest advancements include the upcoming first-in-human dosing of SPY003, an anti-IL-23 monoclonal antibody, as well as promising preclinical data on SPY003 and its combination with other investigational antibodies.

Spyre Therapeutics has announced that the first-in-human dosing of SPY003 in healthy volunteers is expected to commence in the first quarter of 2025. SPY003, a novel monoclonal antibody with an extended half-life, targets IL-23p19 and has shown potential for quarterly or biannual maintenance dosing. Current approved IL-23 inhibitors for moderate-to-severe IBD are typically administered six times a year. Spyre aims to deliver interim data from the accelerated trial in the second half of 2025.

At the UEGW Congress, Spyre presented preclinical data on SPY003, highlighting its comparable potency to risankizumab and a three-fold increase in half-life in non-human primates (NHPs). The data demonstrated SPY003's high selectivity and affinity for IL-23, effectively inhibiting downstream cellular signaling. The extended half-life in NHPs suggests that SPY003 could offer effective and well-tolerated treatment for Crohn's disease (CD) and Ulcerative Colitis (UC) with less frequent dosing compared to existing therapies.

The company's portfolio now includes three extended half-life antibodies targeting α4β7, TL1A, and IL-23, which may be administered on a unified Q8W-Q12W dosing schedule in maintenance. Additionally, Spyre presented preclinical data combining SPY003 with either SPY001 (anti-α4β7) or SPY002 (anti-TL1A). The combination studies in vitro and in vivo models demonstrated enhanced efficacy and pharmacodynamics.

In these studies, IL-23 and TL1A showed synergistic promotion of IL-17 secretion from immune cells, and the combination of anti-IL-23 with anti-TL1A was more effective in suppressing IL-17 than either agent alone. In a T-cell transfer model of IBD, combining anti-IL-23 with anti-β7 improved body weight and reduced colonic CD4+ infiltration and IL-17 levels compared to monotherapy.

Additional preclinical data on SPY001 and SPY002, presented at UEGW, included in vitro potency, nonclinical safety, and pharmacokinetics demonstrating extended half-life in NHPs. The presentations also described the characterization of two SPY002 development candidates planned for first-in-human studies in Q4 2024. Human pharmacokinetic simulations for SPY001 and SPY002 support potential Q8-12W dosing regimens in IBD.

Cameron Turtle, DPhil, CEO of Spyre, highlighted the significant progress made in advancing their investigational molecules into first-in-human studies within a nine-month window. With these promising antibodies targeting the top three validated targets in IBD, Spyre aims to develop monotherapy and combination products that could significantly improve both efficacy and convenience over current standard care.

The UEGW Congress featured several Spyre presentations:
- SPY001 targeting Integrin ɑ4β7 for IBD: In Vitro Properties and Non-Human Primate Pharmacokinetics and Safety
- Two novel extended half-life monoclonal antibodies targeting TL1A for IBD
- Development and characterization of SPY003 targeting IL-23 for IBD
- Combining IL-23 blockade with anti-ɑ4β7 or anti-TL1A for IBD treatment supported by in vitro and mouse IBD model experiments

These findings underscore Spyre Therapeutics' commitment to pioneering new treatments for IBD through advanced antibody engineering and combination therapies.