Spyre Therapeutics (SYRE) investor relations material

Clinical trial design and endpoints

• Combination therapies are being developed as single-shot co-formulations, with dosing optimized based on efficacy results from low and high doses.

• Efficacy is prioritized due to the high cost and severity of the disease, with product profiles refined after efficacy is established.

• The UC trial uses the RHI histologic score as a primary, centrally read, objective endpoint, with additional secondary endpoints including endoscopic improvement and clinical remission.

• RHI benchmarks from previous studies range from a 5 to 7 point change from baseline, with double-digit changes not observed in prior trials.

• Patient enrollment targets a 50/50 split between naïve and experienced patients, with stricter ratios enforced in later trial phases.

Readout timelines and regulatory strategy

• All three Part A readouts for the UC trial (alpha-4, TL1A, IL-23) are expected next year, with more specific timing to be provided as 2026 approaches.

• The trial design includes an initial Part A to generate preliminary safety and efficacy data, followed by a randomized Part B for more controlled comparisons.

• The approach allows for productive use of early enrollment periods and avoids delays associated with regulatory sequencing.

Combination therapy rationale and competitive landscape

• Strong evidence supports additive efficacy from combination therapies, with real-world, animal, and genetic data backing the approach.

• Ongoing studies like DUET and VEGA are closely watched for insights into combination efficacy, especially in refractory populations.

• Co-formulation is favored over bispecifics due to lower risk of immunogenicity and better target engagement, as bispecifics have shown high ADA rates and PK issues.

• The company is advancing combinations such as TL1A with alpha-4 beta-7, and plans to test these in Crohn's disease as well.