Aileron Reports Positive Phase 1b Trial Data for LTI-03 in IPF

Aileron Therapeutics, Inc., a company focused on developing innovative therapies for orphan pulmonary and fibrosis conditions, has announced promising data from the first cohort of its Phase 1b clinical trial assessing inhaled LTI-03 for idiopathic pulmonary fibrosis (IPF). The trial primarily aimed to evaluate the safety and tolerability of LTI-03, a novel peptide linked to Caveolin-1, which plays a critical role in inhibiting pro-fibrotic signaling and supporting epithelial cell survival in the lungs.

The initial findings indicate that low-dose LTI-03 (2.5 mg BID) shows a positive trend in seven out of eight biomarkers. Notably, there was a reduction in several profibrotic proteins produced by basal-like cells and fibroblasts, which are known to contribute to IPF progression. Among these biomarkers, GAL-7, TSLP, and Col-1α1 showed statistically significant decreases, reinforcing LTI-03's potential to mitigate lung fibrosis, reduce inflammation, and improve lung function. Additionally, LTI-03 increased the expression of solRAGE, a factor indicating the health of type I epithelial cells, which is crucial for addressing IPF effectively.

Brian Windsor, Ph.D., President and CEO of Aileron, expressed optimism about these results, noting the achievement of statistical significance in multiple biomarkers. This data supports the potential of LTI-03 to stabilize or even reverse IPF. The ongoing study will continue to evaluate LTI-03, with results from a higher dose cohort expected later this year.

Twelve patients participated in the Phase 1b trial's first cohort, with nine receiving the active treatment and three on placebo. Participants underwent bronchoscopy at the start and after 14 days of LTI-03 administration. Follow-up studies showed no serious adverse events, indicating that LTI-03 is generally well-tolerated.

Dr. Andreas Gunther, Head of the Center for Interstitial and Rare Lung Diseases at Justus Liebig University in Germany, highlighted the importance of these findings. The significant reductions in collagen deposition and inflammation underscore LTI-03's potential to address both fibroblasts and epithelial cells, which are key factors in the development and progression of IPF. The results offer hope for patients suffering from this debilitating disease and suggest that LTI-03 could significantly improve lung function and quality of life.

The Phase 1b clinical trial is randomized, double-blind, placebo-controlled, and involves dose escalation. It includes patients recently diagnosed with IPF who have not received anti-fibrotic treatments for at least two months. The primary goal is to assess LTI-03's safety and tolerability over 14 consecutive days, with exploratory endpoints focusing on multiple biomarkers.

IPF is a chronic, progressive lung disease characterized by tissue scarring that hinders lung function. It predominantly affects older adults, with approximately 100,000 cases in the United States. Most patients face a prognosis of two to five years post-diagnosis.

LTI-03, derived from the caveolin scaffolding domain (CSD) of the Caveolin-1 (Cav1) protein, is designed to restore the balance of biological signals in the lungs. Cav1 plays a crucial role in preventing fibrosis by modulating lung repair and cell movement. Reduced Cav1 expression is associated with IPF, and restoring its function may slow disease progression and support lung health.

Aileron Therapeutics is committed to advancing its pipeline of first-in-class medicines for pulmonary and fibrosis conditions. The company also has another product candidate, LTI-01, aimed at treating loculated pleural effusions, which has completed Phase 1b and Phase 2a trials and received Orphan Drug and Fast Track designations.

Further results from the high-dose cohort of the LTI-03 trial are anticipated in the third quarter of 2024, which will provide more insights into the drug's efficacy and safety profile. The ongoing research and positive preliminary data position Aileron Therapeutics as a key player in developing novel treatments for IPF and other related conditions.