Spero Therapeutics (NASDAQ:SPRO) plans to initiate a Phase II trial of its lead immunology candidate, SP001, in immunoglobulin G4-related disease, or IgG4-RD, in the second quarter of 2027, Chief Executive Officer Esther Rajavelu said during a company presentation.
SP001 is a third-generation anti-CD40 ligand antibody. Rajavelu said the company has repositioned around the program after previously gaining approval for its first drug and out-licensing commercialization to GSK. Spero also completed a $105 million non-dilutive, non-recourse financing transaction through a partial monetization of commercial milestones tied to that product.
The financing is expected to support the company through a planned Phase II data readout in IgG4-RD, with cash runway extending into the second half of 2029, according to Rajavelu.
Why Spero Chose IgG4-RD
Rajavelu described IgG4-RD as an early-stage therapeutic market with significant unmet need. She said the first approved drug for the condition was cleared only last year, while other agents in development have primarily focused on B-cell targeting.
Spero believes SP001 may offer a differentiated approach because CD40 ligand acts upstream of both innate and adaptive immune responses, including pathways involving T cells, B cells and antigen-presenting cells. The company aims to assess whether the mechanism can address disease features beyond flare control, including tissue damage, fibrosis and preservation of organ function.
“Our objective is to gather data points in the Phase II trial that would really help us characterize the benefits of targeting CD40 ligand for this population,” Rajavelu said, adding that those measures could include the treatment’s impact on fibrosis.
The company also sees Sjögren’s disease as an attractive opportunity. Rajavelu said Spero’s partner, Innovent, has guided to beginning a Phase II Sjögren’s trial by early 2027. However, Spero selected IgG4-RD as its initial development focus for SP001.
Safety History and Existing Data
Rajavelu addressed the historical safety concerns associated with earlier CD40 ligand antibodies. First-generation antibodies had active Fc regions that were associated with thrombotic events in early clinical trials, she said.
SP001 has a fully silent Fc region designed to address that issue. The candidate has been evaluated in two Phase I healthy-volunteer trials and a Phase Ib Sjögren’s study. Across more than 100 human subjects, Rajavelu said the company has not observed evidence of thrombotic events.
She cautioned that safety monitoring will remain a key component of future trials, particularly because immunomodulatory therapies can carry infection-related risks. Spero plans to include metrics in its Phase II study to continue evaluating tolerability and safety, including upper respiratory infections and other potential infections.
Rajavelu said the Phase Ib Sjögren’s data should be viewed as contextual rather than as a direct comparison with results from other programs. The study included three dose cohorts, with eight actively treated patients and two placebo patients, and treatment lasted four months. Despite the small data set, she said Spero saw evidence of activity at all tested doses.
Phase II Design and Competitive Positioning
The planned IgG4-RD Phase II study will test two doses of SP001. Rajavelu said dose selection will incorporate pharmacokinetic, pharmacodynamic, safety and tolerability findings from Innovent’s healthy-volunteer and Phase Ib Sjögren’s studies. Results from the Phase II trial are also expected to inform dose selection for any future registrational study.
Spero has not yet determined where SP001 could fit within the IgG4-RD treatment landscape. Rajavelu said therapies focused on B cells have produced compelling results in flare management, but the company’s objective is to investigate whether CD40 ligand inhibition can address broader disease features.
SP001 is currently formulated for once-monthly intravenous administration. Rajavelu said Spero will use the IV formulation to establish proof of concept in Phase II, while potentially exploring other delivery formats in the future to improve patient convenience.
The company’s next stated catalyst is the planned launch of the IgG4-RD Phase II trial in the second quarter of 2027.
About Spero Therapeutics (NASDAQ:SPRO)
Spero Therapeutics, Inc is a clinical-stage biopharmaceutical company focused on developing treatments for serious bacterial infections and other infectious diseases. The company’s research programs are aimed at addressing drug-resistant pathogens and conditions for which existing therapies may be limited.
Spero’s pipeline has included tebipenem pivoxil hydrobromide, an orally administered carbapenem antibiotic being developed for complicated urinary tract infections, including pyelonephritis.
