Spyre Therapeutics Announces Positive Phase 1 Results for Anti-TL1A Antibody Programs and Phase 2 Clinical Development Plans

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-17

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Spyre Therapeutics announced positive interim Phase 1 results for SPY002 and SPY072, two investigational, extended half-life monoclonal antibodies targeting TL1A. Both were well-tolerated and showed prolonged half-lives, supporting less frequent dosing. The company is advancing SPY002 into the SKYLINE-UC Phase 2 platform trial for ulcerative colitis and SPY072 into the SKYWAY-RD Phase 2 basket trial for rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis. Nine Phase 2 readouts are expected over the next two years.

Key Highlights

  • Positive interim Phase 1 results for SPY002 and SPY072 met all objectives, showing extended half-life and good tolerability.
  • SPY002 will advance to the SKYLINE-UC Phase 2 platform trial for ulcerative colitis.
  • SPY072 will advance to the SKYWAY-RD Phase 2 basket trial for rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.
  • Nine Phase 2 readouts are expected over the next two years.

Incidence and Prevalence

Global Burden of Ulcerative Colitis

The global burden of ulcerative colitis (UC) is substantial and continues to evolve. Several studies provide estimates, but variations exist due to methodologies and data sources. Here's a summary of some of the latest findings:

  • 2019: The Global Burden of Disease (GBD) 2019 study estimated approximately 4.9 million cases of UC globally. While age-standardized prevalence and incidence rates showed a slight decrease from 1990 to 2019, the total number of cases increased. The highest age-standardized prevalence and incidence rates were in North America, while the lowest were in Oceania. The study also highlighted an increasing disease burden in middle and low socio-demographic index locations.

  • 2020: Another study using multiple claims datasets estimated that 2.39 million Americans were diagnosed with IBD, extrapolated from a prevalence of 721 per 100,000 population. This study also highlighted racial disparities, with lower diagnosis rates in Black, Asian, and Hispanic Americans.

  • 2023: A recent estimate places the global prevalence of UC at 5 million cases, with the incidence increasing worldwide.

It's important to note that while some studies show a decrease in age-standardized rates, the absolute number of UC cases is increasing globally, largely due to population growth and increased diagnosis rates in developing nations. Furthermore, the burden of UC is not evenly distributed, with higher rates observed in developed nations and among certain racial and ethnic groups.

Challenges in Estimating Global Burden

Accurately estimating the global burden of UC is challenging due to several factors:

  • Variations in Case Definitions: Different studies use different criteria for diagnosing UC, leading to inconsistencies in estimates.

  • Data Availability: Reliable epidemiological data are not available for all regions of the world, particularly in developing countries.

  • Methodological Differences: Variations in study design and data collection methods can affect the accuracy and comparability of estimates.

  • Diagnostic Delay: The delay between symptom onset and diagnosis can lead to underestimation of the true prevalence of UC.

Despite these challenges, ongoing research and improved data collection methods are providing a clearer picture of the global burden of UC, which is crucial for informing public health interventions and resource allocation.

SPY002 (AS002), a novel PPARĪ³ agonist, is primarily mentioned in the context of ulcerative colitis (UC). One source discusses its evaluation in UC patient biopsies ex vivo and in mouse models of colitis in vivo. Specifically, the in vivo studies used low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis models in mice. The study investigated both preventive (administration starting 2 days before colitis induction) and curative (administration from days 3 to 8) treatment approaches with AS002. The results showed AS002 protected against macroscopic and histological damage and lowered inflammatory markers in these models. While this source highlights the potential of AS002 for topical maintenance treatment of UC, it doesn't mention other indications for which it is being trialed.