Spyre Therapeutics (SYRE) investor relations material

Strategic priorities and pipeline focus

• Aims to improve care in autoimmune diseases, initially focusing on inflammatory bowel disease (IBD) with three validated targets: alpha-4 beta-7, TL1A, and IL-23, developed as both monotherapies and advanced co-formulated combinations.

• Exploring TL1A as a pipeline-in-a-product candidate for multiple rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis.

• Next 12 months will see five additional phase II readouts, including monotherapy and combination data in IBD and rheumatic diseases, with combination therapy readouts expected in 2027.

• Anticipates multiple products could become indication-leading across large markets.

Differentiation and technology approach

• Focuses on high-concentration, long-acting, co-formulatable antibodies, overcoming challenges in co-formulation and ensuring additive efficacy in a convenient format.

• Unique ability to deliver both agents at high concentration in a single injection, unlike existing antibodies.

• Chose co-formulation over bispecifics to independently block targets, avoid unwanted immune activation, and allow flexible dosing ratios.

• Co-formulation may reduce immunogenicity compared to bispecifics, supported by external data.

Clinical data and expectations

• Lead asset SPY001 targets alpha-4 beta-7, showing higher clinical remission rates at increased drug exposure, potentially matching or exceeding ENTYVIO efficacy.

• Expects 002 and 003 to replicate first-generation efficacy with less drug due to long-acting modifications, enabling single-shot co-formulations.

• Maintenance efficacy for TL1A may improve with better saturation, with data expected next year; IL-23 and alpha-4 beta-7 appear saturated in maintenance.