{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T03:03:36Z","timestamp":1772766216076,"version":"3.50.1"},"posted":{"date-parts":[[2025,10,29]]},"group-title":"Respiratory Medicine","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  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 (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                  :\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05954988\">NCT05954988<\/jats:ext-link>\n                  ). 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;\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                  :\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06968845\">NCT06968845<\/jats:ext-link>\n                  ).\n                <\/jats:p>","DOI":"10.1101\/2025.10.28.25338981","type":"posted-content","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T21:50:11Z","timestamp":1761774611000},"source":"Crossref","is-referenced-by-count":1,"title":["Inhaled LTI-03 for Idiopathic Pulmonary Fibrosis: A Randomized Dose Escalation 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