The Company previously announced positive data from Cohort 1 of the ongoing Phase 1b clinical trial evaluating low-dose LTI-03 (2.5 mg BID) in patients with IPF. Following inhaled administration of low-dose LTI-03 in 12 patients over the course of 14 days, a positive trend was observed in seven out of eight biomarkers with evidence of reduced expression among multiple profibrotic proteins produced by basal-like cells and fibroblasts that contribute to the progression of IPF, including data from three biomarkers (collagen synthesis, inflammation, and fibrogenesis) that was statistically significant, reinforcing the potential of LTI-03 to improve lung function and reverse the course of IPF. The [poster][abstracts] being presented at ICLAF will summarize the previously disclosed data from Cohort 1.
Pre-clinical data presented at ICLAF further supports the potential therapeutic effectiveness of LTI-03 for IPF through precision cut lung slices (PCLS) performed ex-vivo. Pre-clinical studies demonstrated molecular activity in IPF PCLS explants indicative of fibrosis during five days in culture and LTI-03 broadly attenuated pro-fibrotic proteins and pathways.
Additionally, the Company recently announced completion of enrollment in Cohort 2 of the ongoing Phase 1b clinical trial evaluating high-dose LTI-03 (5 mg BID) in 12 patients with IPF. In the trial, eligible patients (n=24) are randomly assigned (3:1) to receive either inhaled LTI-03 or placebo. The primary objective of the trial is to evaluate the safety and tolerability of LTI-03 in patients with IPF after treatment for 14 consecutive days, with measurement of multiple protein biomarkers as exploratory endpoints. The Company expects to report topline data for this cohort in the near-term.
About the Phase 1 Clinical Trial of LTI-03:
The Phase 1b clinical trial of LTI-03 is a randomized, double-blind, placebo controlled, multi-center, dose escalation trial in patients recently diagnosed with IPF that have not received prior treatment with anti-fibrotic agents for at least two months (NCT05954988). Eligible patients are randomly assigned (3:1) to receive one of two doses of inhaled LTI-03 or placebo. The primary objective of the trial is to investigate the safety and tolerability of LTI-03 in patients with IPF after treatment for 14 consecutive days, with measurement of multiple protein biomarkers as exploratory endpoints.
About IPF:
IPF is a chronic lung disease characterized by progressive tissue scarring that prevents proper lung function. It is a progressive, fatal, age-associated lung disease affecting approximately 100,000 people in the United States1. IPF typically presents in adults 65 or older and is usually fatal within two to five years after diagnosis2.
About LTI-03 and Caveolin-1 (Cav1):
LTI-03 is a seven amino acid peptide, the sequence of which is derived from the caveolin scaffolding domain (CSD), an important binding region of the Cav1 protein. Cav1 normally serves a critical function in the prevention of fibrosis by maintaining a balance between pathways that both initiate and arrest lung repair and cell movement. Through the CSD, caveolin interacts with a large number of signaling molecules, all of which possess a caveolin binding domain region. Cav1 expression is decreased in IPF lung tissues and has been demonstrated to decrease during the fibrotic phase of bleomycin lung injury in mice. Restoring the balance of important biological signals in the lung may not only slow lung function decline but could also restore healthy lung function through the protection of healthy epithelial cells.
About Aileron Therapeutics:
Aileron Therapeutics is a biopharmaceutical company advancing a novel pipeline of first-in-class medicines to address significant unmet medical needs in orphan pulmonary and fibrosis indications. Aileron's lead product candidate, LTI-03, is a novel, synthetic peptide with a dual mechanism targeting alveolar epithelial cell survival as well as inhibition of profibrotic signaling. Currently, LTI-03 is being evaluated in a Phase 1b clinical trial for the treatment of idiopathic pulmonary fibrosis. Aileron's second product candidate, LTI-01, is a proenzyme that has completed Phase 1b and Phase 2a clinical trials for the treatment of loculated pleural effusions. LTI-01 has received Orphan Drug Designation in the US and EU and Fast Track Designation in the US.
