Rein Therapeutics publishes LTI-03 IPF data in Nature Communications

Rein Therapeutics has published clinical data from its first-in-human study of LTI-03 in Nature Communications, reporting that the inhaled peptide reduced multiple markers of lung scarring and inflammation in patients with idiopathic pulmonary fibrosis (IPF). The paper, which cleared independent peer review after appearing as a preprint in November 2025, underpins the rationale for the company's ongoing Phase 2 RENEW trial.

The randomised, placebo-controlled study enrolled 24 IPF patients who received inhaled LTI-03 at 5 mg or 10 mg daily, or placebo, for 14 days. The candidate was well-tolerated at both doses, with no treatment-related discontinuations and only mild or moderate adverse events. Importantly, no systemic absorption was detected, which the company says is consistent with LTI-03's design as a locally acting lung therapy.

Biomarker findings

Analysing samples collected from deep lung tissue, researchers measured a range of proteins and inflammatory signals associated with IPF progression. At both doses, LTI-03 significantly reduced IL-11, a driver of scar-producing cell activation, and TSLP, an inflammatory signal that promotes fibrosis. At the higher dose, reductions were additionally observed in COL1A1, a direct marker of collagen deposition; the inflammatory chemokine CXCL7; and galectin-7, which is associated with epithelial fibrosis in the distal lung.

A trend toward reduced surfactant protein D (SP-D), a blood marker of lung epithelial health, was also seen at the higher dose. Rein noted that the magnitude of SP-D reduction was comparable to that observed with approved IPF therapies after 12 weeks of treatment, despite this study running for only a fortnight. The company also reported evidence suggesting LTI-03 may help preserve alveolar progenitor cells, an activity it describes as unaddressed by existing treatments.

Chief scientific officer Cory Hogaboam said: "LTI-03 simultaneously reduced five separate markers of fibrosis, inflammation, and epithelial damage after only fourteen days of treatment. This breadth of activity reflects LTI-03's design as a caveolin-1 mimetic, a molecule that effectively targets a master regulator of multiple scarring pathways."

RENEW trial and competitive context

The RENEW Phase 2 trial is a randomised, placebo-controlled study targeting enrolment of approximately 120 patients across multiple countries. The primary efficacy endpoint is change from baseline in forced vital capacity (FVC), the most commonly used functional measure in IPF trials. Rein has not disclosed a data readout timeline.

IPF remains a high-unmet-need indication with limited treatment options. Two antifibrotic agents, nintedanib (Boehringer Ingelheim) and pirfenidone (Roche), are approved and slow disease progression but do not halt or reverse scarring. Both are oral agents; Rein's inhaled, locally delivered approach is intended to sidestep the systemic tolerability issues that limit oral antifibrotics in some patients. Several other companies, including those developing lysophosphatidic acid receptor antagonists and CTGF inhibitors, have encountered late-stage setbacks in IPF, underlining the difficulty of the indication and the need for robust biomarker-driven Phase 2 evidence before advancing to pivotal trials.

LTI-03 carries Orphan Drug Designation in the US. The peer review publication in Nature Communications adds credibility to the dataset and may support partnership conversations, though Rein has not announced any licensing or collaboration activity. Investors will be watching for RENEW enrolment updates and interim safety data as the next near-term catalysts.