Spero Therapeutics (SPRO) investor relations material

Strategy and development timeline

• Development-stage focus shifted to SP001, a third-generation anti-CD40 ligand antibody; planned phase II trial in IgG4-RD to start in Q2 2027.

• Innovent is guided to initiate a phase II Sjögren's trial by early 2027; evidence in Sjögren's is expected to evolve alongside progress in IgG4-RD.

• IgG4-RD was selected for its early treatment-market lifecycle, unmet need, and potential to address disease biology beyond B-cell-targeted approaches.

Evidence and clinical considerations

• SP001 has a fully silent Fc region; across two phase I healthy-volunteer trials and one phase Ib Sjögren's trial, more than 100 subjects had no observed thrombotic events; safety monitoring remains a priority.

• Phase Ib Sjögren's study was small: three dose cohorts, eight active and two placebo participants, and four months of treatment; activity was observed across all doses.

• Dose selection will assess PK/PD, safety, and tolerability across the full human dataset; planned IgG4-RD phase II will test two doses and inform potential registrational dosing.

• Phase II will collect evidence on CD40 ligand's role in IgG4-RD, including potential impact on fibrosis; trial design is contemplated to reflect prior phase II studies in the indication.

Differentiation and treatment approach

• CD40 ligand acts upstream of T cells, B cells, and antigen-presenting cells; the intended differentiation is broader disease control than flare management alone, including tissue damage, fibrosis, and organ preservation.

• Current formulation is once-monthly IV; phase II will use IV dosing to establish proof of concept, with other delivery modalities potentially explored to improve convenience.

• IgG4-RD phase II will include metrics to monitor infection risk, tolerability, and safety; existing Innovent data are expected to support FDA discussions.