Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible interstitial lung disease. Despite antifibrotic therapies such as pirfenidone and nintedanib, many patients continue to experience lung-function decline and poor quality of life. SB17170 is a first-in-class oral small molecule that binds to post-translationally modified high-mobility group box 1 (HMGB1) protein, inhibiting macrophage-driven inflammation and fibrogenic signaling. SMARTT-004, a Phase IIa study, was designed to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SB17170 in patients with IPF. Methods SMARTT-004 is a multicenter, randomized, double-blind, placebo-controlled, exploratory Phase IIa trial at five sites in Korea. Thirty patients meeting 2022 ATS/ERS/JRS/ALAT IPF criteria will be randomized (2:2:1) to receive the monotherapy of SB17170 250 mg, 500 mg, or placebo, respectively, once daily for 12 weeks. Eligible patients are required to have percent-predicted forced vital capacity (FVC) ≥ 45% and diffusing capacity for carbon monoxide (DLCO) ≥ 25%(adjusted for hemoglobin). Patients are not allowed to be on background of anti-fibrotic therapy and must have discontinued previous therapy at least 4 weeks before prior to baseline. The primary endpoint is absolute change in FVC (mL) from baseline to Week 12. Secondary endpoints include percent-predicted changes in FVC and DLCO, patient-reported outcomes (PROs), and safety/tolerability. PK of SB17170 and PD biomarkers will be evaluated. Exploratory analyses include multi-omics profiling of plasma and peripheral blood mononuclear cells. Results As of 24 October 2025, 15 patients had been randomized in the SMARTT-004 study. The mean age was 72.8 years, and 87% of the participants were male. At baseline, the mean percent-predicted FVC was 92.1%, and the mean DLCO was 61.7% predicted, indicating moderate functional impairment. Additional baseline characteristics, including patient-reported outcomes (PROs) and smoking status, will be presented at the conference. SUMMARY: SMARTT-004 will provide translational evidence supporting HMGB1 pathway modulation as a potential therapeutic strategy for IPF in patients who are non-responsive or intolerant to standard antifibrotics. Interim baseline data show that the enrolled population reflects typical clinical features of IPF, reinforcing the study’s relevance for evaluating the clinical and biomarker effects of SB17170. This abstract is funded by: Spark Biopharma
Song et al. (Fri,) studied this question.