LTI-03 reduces inflammation, scarring in IPF lung samples: Study
Unlike approved treatment Ofev, experimental therapy didn't induce cell death
LTI-03, an experimental treatment for idiopathic pulmonary fibrosis (IPF) that’s currently in clinical testing, was shown to reduce inflammation and scarring in experiments done on lung tissue collected from IPF patients, according to a study.
The study showed that LTI-03’s effects on inflammation and scarring were similar to those of the approved IPF treatment Ofev (nintedanib). However, contrary to Ofev, LIT-03 did not induce cell death, which researchers said suggests that this investigational therapy may offer a safer alternative.
The study, “LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF,” was published in iScience. Rein Therapeutics, the company developing LTI-03, sponsored the work.
LTI-03 aims to increase levels of key protein
IPF is caused by progressive scarring, or fibrosis, and inflammation in the lungs, which makes it harder for the lungs to take in oxygen and deliver it to the body.
LTI-03 is a dry powder inhalation therapy containing part of a protein called caveolin-1 (Cav1) that helps prevent fibrosis. People with IPF typically have low levels of this protein; LTI-03 aims to increase Cav1 levels to reduce disease-driving fibrosis and inflammation.
In this study, scientists carried out ex vivo tests — experiments performed on lung tissue samples taken from people with IPF and treated with LTI-03 outside the body in a laboratory setting.
Results showed that LTI-03 treatment reduced the activity of several molecular signaling pathways known to drive inflammation and fibrosis in IPF. The treatment also decreased production of collagen, a protein that forms the main component of scar tissue, in a dose-dependent manner.
LTI-03 exhibited a similar pattern of inhibition and activation compared with [Ofev] treatment, but without the noted toxicity observed with [Ofev].
Ofev, sold by Boehringer Ingelheim, is an approved IPF treatment that blocks signaling pathways that drive fibrosis. In the ex vivo tests, the researchers found that LTI-03 and Ofev had similar effects on several disease-associated molecular pathways. However, the researchers noted that Ofev treatment increased the activity of pathways associated with cell death, whereas LTI-03 decreased the activity of these pathways, suggesting the investigational treatment may be less toxic.
“LTI-03 exhibited a similar pattern of inhibition and activation compared with [Ofev] treatment, but without the noted toxicity observed with [Ofev],” the researchers wrote.
LTI-03 is already in clinical testing. Results from a Phase 1b trial (NCT05954988) indicated the therapy decreased markers of fibrosis. A Phase 2 study called RENEW trial (NCT06968845) is now ongoing at sites in the U.S., and Rein recently started work to open sites in the U.K. Initial trial data is expected in 2026.
“Using a highly relevant translational model, this peer-reviewed publication provides further validation of LTI-03’s broad anti-fibrotic effects in IPF lung tissue. These data support our ongoing Phase 2 RENEW trial, where we are evaluating LTI-03 in patients living with IPF, a disease with very limited treatment options and high unmet need,” Brian Windsor, PhD, CEO of Rein Therapeutics, said in a press release.
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