Spero Therapeutics (SPRO) H.C. Wainwright 28th Annual Global Investment Conference summary

Investment position and development focus

• Cash runway extends into H2 2029, supporting planned proof-of-concept work in the lead indication.

• SP001 is a third-generation, Fc-silent anti-CD40 ligand antibody being developed for IgG4-related disease, with potential across other immune-mediated conditions, including Sjögren’s disease.

• CD40 ligand is positioned as a differentiated upstream target relative to B-cell-focused therapies, with potential to affect both innate and adaptive immune pathways.

SP001 profile and prior data

• Fc engineering eliminates detectable Fc receptor and complement binding while preserving FcRn interactions and an IgG-like half-life; design aims to address platelet-related safety concerns of earlier anti-CD40 ligand agents.

• In a mouse immune-response study, SP001 at 1 mg/kg suppressed response more than a competing antibody at 3 mg/kg.

• In a phase I-B Sjögren’s trial in ~30 patients, SP001 was well tolerated with no SAEs; AEs were largely balanced between active and placebo arms.

• Sjögren’s results showed dose-dependent improvement in ESSDAI and ESSPRI and rheumatoid factor; cross-trial comparison showed a stronger ESSDAI response in moderate-to-severe patients after four doses at week 16 than agents dosed over six months.

• Data showed linear PK, ~28-day half-life supporting once-monthly dosing, and ~4% immunogenicity in the phase I-B Sjögren’s study.

IgG4-related disease opportunity

• IgG4-related disease can affect multiple organs, causing inflammation, scarring and fibrosis; an estimated 20,000–40,000 U.S. patients are diagnosed, and 60% present with organ damage.

• Current care commonly uses steroids with or without DMARDs during flares, followed by biologics if needed; rituximab is often used off-label as a B-cell depleter.

• The approved and investigational therapies described target B cells; SP001 is intended to act upstream and address T-cell as well as B-cell biology.

• CD40 ligand targeting could potentially reduce flares, offer greater tolerability than B-cell depletion, and address fibrotic signals as well as antibody production and antigen presentation.