Spyre is developing next-generation antibodies that are engineered for prolonged activity in the body and formulated for delivery as monotherapies or combination therapies. Our innovative approach enables the exploration of treatment options with the potential to deliver uncompromising efficacy and convenience
Our
approach
At Spyre, our aim is to develop novel therapies for gastrointestinal and rheumatic diseases built upon three validated approaches:
Engineering novel antibodies against validated targets
Incorporating the YTE modification to prolong drug activity and reduce administration frequency, with potential for improved clinical outcomes through dose optimization and higher drug exposures
Developing rational drug combinations in simple high-concentration coformulations that may address distinct disease drivers and lead to superior efficacy and convenience
Together, if successful, we believe our approach will deliver new therapies to patients that have best-in-indication efficacy and convenience and represent a significant improvement over today’s standard of care
Novel antibodies engineered against validated targets
Spyre is progressing a pipeline of novel antibodies engineered against validated targets in gastrointestinal and rheumatic conditions
α4β7
A commercially-validated target in ulcerative colitis and Crohn’s disease
The integrin α4β7 plays a key role in directing immune cells in the blood stream to the gut,
fueling inflammation in IBD
TL1A
A clinically-validated target in ulcerative colitis and Crohn’s disease, with non-clinical validation in several rheumatic conditions such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA)
Tumor necrosis factor-like ligand 1A (TL1A) amplifies inflammation by enhancing immune cell responses, potentially exacerbating inflammation and fibrosis in immune-mediated diseases
IL-23
A commercially-validated target in ulcerative colitis and Crohn’s disease and other inflammatory conditions
IL-23 is a cytokine that upregulates the expansion of pro-inflammatory T helper cells and sustains inflammatory pathways that drive IBD progression
Harnessing the power of the body’s natural recycling mechanism for antibodies
Each of Spyre’s novel antibodies incorporates modifications for extended half-life, potentially enabling less frequent dosing. Spyre's investigational antibodies have the potential for quarterly or biannual dosing, which would be a substantial improvement in convenience compared to today's antibodies which are dosed as frequently as every two weeks
YTE modification
A commercially‑validated antibody modification that harnesses the body’s natural antibody recycling mechanism, prolonging activity in the body. YTE‑modified antibodies have shown a half‑life of more than 3‑times longer than typical antibodies and each of Spyre’s antibodies incorporate the YTE modification, which may allow for quarterly or biannual dosing
Higher drug exposures via extended half-life and dose optimization may also result in improved clinical outcomes
Rational combinations addressing the diverse pathophysiology of immune-mediated diseases
The gastrointestinal and rheumatic diseases that Spyre aims to treat are driven by multiple biologic pathways. Spyre aims to address the diverse pathophysiology of these diseases using drug combinations that simultaneously target α4β7 and TL1A, α4β7 and IL-23, and TL1A and IL-23
Fixed-dose combinations
Third-party clinical trials have validated the potential for combined advanced therapies in IBD to deliver additive improvements in efficacy. Spyre aims to develop fixed-dose combinations of each of its antibodies that may be delivered in a single injector based on high-concentration coformulations for simple chronic administration on an infrequent quarterly or biannual basis
Scientific Publications
ARTHRITIS RESEARCH & THERAPY, 2020
Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF
Lancet Gastroenterol Hepatol, 2023
Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA): a randomised, double-blind, controlled, phase 2, proof-of-concept trial
BioDrugs, 2023
Translational Approach for Predicting Human Pharmacokinetics of Engineered Therapeutic Monoclonal Antibodies with Increased FcRn‑Binding Mutations
Expert Review of Clinical Pharmacology, 2024
Exposure–efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn’s disease and ulcerative colitis
BONE, 2017
CCL3 and MMP-9 are induced by TL1A during death receptor 3 (TNFRSF25)-dependent osteoclast function and systemic bone loss
