LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF

Idiopathic pulmonary fibrosis (IPF) features excessive extracellular matrix deposition driven by activated fibroblasts and dysregulated signaling pathways. To assess the anti-fibrotic effects of LTI-03, a caveolin-1 scaffolding domain peptide, ex vivo precision-cut lung slices (PCLS) from patients with IPF were evaluated using bulk RNA sequencing, Ingenuity Pathway Analysis, and immunofluorescence. LTI-03 dose-dependently reduced collagen protein levels, suppressed pro-fibrotic cytokines, inhibited pro-fibrotic pathways, and activated protective mechanisms such as PTEN and PPAR signaling. Modulation was comparable to nintedanib but without the induction of apoptosis or necrosis pathways. These results demonstrate LTI-03's potential therapeutic efficacy in a highly relevant translational disease model and support LTI-03 as a promising next-generation therapeutic to halt IPF progression and improve patient outcomes.

• MacKenzie, B.
• Mahavadi, P.
• Pinho Jannini-Sa, Y. A.
• Creyns, B.
• Coelho, A. L.
• Espindola, M.
• Ruppert, C.
• Windsor, B.
• Aigner, C.
• Hogaboam, C. M.
• Guenther, A.