Inhaled LTI-03 for Idiopathic Pulmonary Fibrosis: A Randomized Dose Escalation Study

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, placebo-controlled, dose-escalation study, 24 participants with IPF were randomized 3:1 into 2 sequential dose cohorts to LTI-03 (5 or 10 mg/day) or placebo for 14 days ( <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> : <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT05954988">NCT05954988</ext-link> ). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and changes from baseline in expression of biomarkers related to fibrotic processes and epithelial integrity. Inhaled LTI-03 was well-tolerated, with no treatment-related discontinuations and only mild or moderate TEAEs; cough was the most common treatment-related TEAE. There was no evidence of airway obstruction by symptoms or spirometry. In bronchoscopy-derived deep bronchial brushing samples, both doses of LTI-03 significantly reduced interleukin-11 and thymic stromal lymphopoietin compared to placebo. Additionally, LTI-03 10 mg/day significantly reduced the expression of collagen type 1 alpha chain 1, CXC chemokine ligand 7 and galectin-7 compared to placebo. A trend in the reduction of plasma surfactant protein D was also observed in the LTI-03 10 mg/day group compared to placebo. The favorable safety and tolerability profile in addition to a reduction of disease-related biomarkers supports further evaluation of inhaled LTI-03 for IPF in a Phase 2 study (RENEW; <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> : <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT06968845">NCT06968845</ext-link> ).