Spyre Therapeutics (SYRE) investor relations material

Strategic approach and pipeline overview

• Focus on elevating care in major autoimmune markets by engineering best-in-class, long-acting antibodies and co-formulating them for optimal product profiles.

• Combination therapies are prioritized to achieve additive efficacy without significant safety trade-offs, with the most advanced work in inflammatory bowel disease (IBD).

• SKYLINE Part B study is testing combinations in IBD, with data expected next year; TL1A is being evaluated as both monotherapy and in combinations across multiple indications.

• Early data suggest their antibodies match or exceed first-generation products in efficacy, with improved dosing profiles.

• Efficient development plans and co-formulation strategies differentiate their pipeline from competitors using less optimized combinations.

Industry context and competitive landscape

• The field has seen major advances with combination therapies, notably after J&J's VEGA study doubled remission rates in ulcerative colitis without added safety risks.

• Real-world use of combinations is increasing due to unmet needs, despite payer resistance and lack of formal studies.

• Competitors often combine agents with mismatched dosing and delivery, while this pipeline is designed for high-concentration, co-formulated, long-acting combinations.

• Product profiles are positioned as more convenient and potentially more efficacious than those of J&J and AbbVie, with a focus on subcutaneous and IV options.

Indication-specific updates and forward plans

• In hidradenitis suppurativa (HS), TL1A is being advanced based on promising internal and external data, with a decision on monotherapy versus combination expected soon.

• Combination of TL1A and IL-17A/F in HS is ongoing, aiming to address unmet needs and leverage additive efficacy.

• In rheumatology, TL1A showed benefit and strong tolerability in RA, with ongoing studies in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA); combinations with IL-17 and IL-23 are under consideration.

• Additional data in atopic dermatitis and MASH are expected, though expectations are more modest.