Spero Therapeutics (SPRO) investor relations material

Strategic focus and asset overview

• Lead asset SP001 is a third-generation Fc-silent anti-CD40 ligand monoclonal antibody targeting immune-mediated diseases, with initial focus on IgG4-related disease.

• SP001 is designed to address both innate and adaptive immune pathways, offering broader therapeutic potential than B-cell targeted agents.

• The antibody's Fc region is engineered for safety, avoiding platelet-driven risks seen in earlier generations.

• Preclinical and phase I-B data indicate best-in-class potency and favorable safety profile.

• Cash runway extends into the second half of 2029, supporting proof-of-concept milestones.

Clinical data and competitive positioning

• In a phase I-B trial for Sjögren's disease, SP001 showed dose-dependent improvements in disease activity and autoantibody markers, with a favorable safety profile.

• Cross-trial comparisons suggest SP001 outperforms other agents in moderate to severe Sjögren's patients on key efficacy measures.

• Linear pharmacokinetics and a 28-day half-life support once-monthly dosing; immunogenicity rate was low at 4%.

• The mechanism targets upstream immune signaling, potentially reducing flares and addressing fibrosis in IgG4-related disease.

• SP001 is differentiated from current and pipeline therapies, which primarily target B cells.

Market need and development plan

• IgG4-related disease affects 20,000–40,000 in the U.S., with high unmet need and frequent organ damage at diagnosis.

• Current treatments rely on steroids and B-cell depleters, with frequent relapses and limited chronic management options.

• Planned phase II trial for IgG4-related disease will be open-label, enrolling patients with multi-organ involvement and active disease.

• The trial will test two doses over six months, with primary endpoint being change in IgG4 responder index at week 24.

• Trial initiation is targeted for Q2 2027, with ongoing exploration of additional indications.