LTI-03

What is LTI-03?

LTI-03 is a synthetic peptide of seven natural L-amino acids, phenylalanine–threonine–threonine–phenylalanine–threonine–valine–threonine (FTTFTVT). The sequence comes from the scaffolding domain of caveolin-1, a membrane protein that helps regulate how lung cells respond to injury. The full scaffolding-domain peptide spans amino acids 82 to 101 of caveolin-1 (DGIWKASFTTFTVTKYWFYR), and LTI-03 is residues 89 to 95, the seven-residue stretch inside it that kept the anti-scarring activity in mouse studies. In academic papers it is called CSP7. It is being developed for idiopathic pulmonary fibrosis (IPF), a progressive scarring disease of the lungs. The drug is a micronised, excipient-free dry powder in 2.5 mg capsules that patients inhale twice a day through a commercially available dry-powder inhaler. Inhalation puts the peptide where the disease is: in the Phase 1b trial, LTI-03 was measurable in fluid washed from the lungs but undetectable in blood. The developer is Rein Therapeutics of Austin, Texas. The peptide came out of Sreerama Shetty's laboratory at the University of Texas Health Science Center at Tyler and was developed by Lung Therapeutics. Aileron Therapeutics acquired Lung Therapeutics on 31 October 2023 and renamed itself Rein Therapeutics on 10 January 2025. LTI-03 is not approved anywhere. The FDA granted it Fast Track designation on 20 August 2026, it holds US Orphan Drug Designation, and the EU granted orphan designation for the FTTFTVT peptide in IPF on 9 January 2026. The only legitimate way to receive it is through Rein's Phase 2 RENEW trial.

What LTI-03 Is Investigated For

LTI-03 is studied for one disease: idiopathic pulmonary fibrosis. Everything else is laboratory work. The human evidence so far is one small trial. In a randomized, double-blind Phase 1b study published in Nature Communications in July 2026 (Molyneaux et al.), 24 people with recently diagnosed, untreated IPF inhaled LTI-03 at 5 mg a day, 10 mg a day or placebo for 14 days. The primary goal was safety. LTI-03 was well tolerated, with no severe adverse events, no treatment-related dropouts and no sign of airway narrowing on spirometry. In airway brushings, both doses lowered interleukin-11 and thymic stromal lymphopoietin, two signals linked to scarring, and the higher dose also lowered collagen type 1 (COL1A1), the chemokine CXCL7 and galectin-7. Other biomarkers did not change. Those are encouraging biology signals, but they are not evidence that patients breathe better or live longer. Fourteen days is far too short to measure lung function, and with 9 patients per dose the study could not test that. The answer will come from RENEW (NCT06968845), a 24-week Phase 2 trial of about 120 patients that measures safety first and then forced vital capacity (FVC) and scarring on CT. Rein has guided to interim data in the second half of 2026. Until then, LTI-03 is an interesting investigational drug and not a treatment option outside the trial. People with IPF should be under pulmonology care, where the approved antifibrotics nintedanib, pirfenidone and, since October 2025 in the US, nerandomilast slow lung-function decline.

History & Discovery

LTI-03 sits at the end of two decades of work on caveolin-1 in lung scarring. In 2006, Augustine Choi's group at the University of Pittsburgh (Wang et al., J Exp Med) reported that caveolin-1 is sharply reduced in IPF lungs and fibroblasts and that restoring it limits fibrosis in mice. In 2008, Tourkina, Hoffman and colleagues showed that a peptide copying caveolin-1's scaffolding domain could do much of the same job, suppressing collagen production by scleroderma lung fibroblasts and protecting bleomycin-injured mouse lungs. Sreerama Shetty, working with Idell and colleagues at the University of Texas Health Science Center at Tyler, took the idea toward a drug. Their group linked caveolin-1 to p53 and the urokinase–PAI-1 system in dying epithelial cells and in proliferating fibroblasts, then narrowed the 20-mer down to a seven-amino-acid fragment, CSP7 (FTTFTVT), that kept the anti-fibrotic effect. The 2019 Science Translational Medicine paper, co-authored with Austin-based Lung Therapeutics and University of Texas at Austin pharmaceutics researchers, showed CSP7 working against established fibrosis in three mouse models and in human IPF tissue. The UT Austin team developed the excipient-free, jet-milled dry powder that made inhaled dosing practical. Shetty and Idell disclosed equity in Lung Therapeutics. As LTI-03, the peptide entered a Phase 1a study in 71 healthy adults (NCT04233814, January 2020 to December 2021) and then a Phase 1b in 24 IPF patients (NCT05954988, July 2023 to September 2024). Aileron Therapeutics acquired Lung Therapeutics on 31 October 2023 and renamed itself Rein Therapeutics on 10 January 2025. A preprint of the Phase 1b appeared in October 2025, and the peer-reviewed paper was published in Nature Communications on 31 July 2026. The Phase 2 RENEW trial dosed its first patient in May 2025, but on 10 June 2025 the FDA put the US part of the trial on clinical hold over the lack of a no-observed-adverse-effect level in a 26-week rat inhalation study. Ex-US sites continued, the hold was lifted in late 2025, and Rein announced the first patient dosed after the US restart on 3 March 2026. The EU granted orphan designation on 9 January 2026, the FDA granted Fast Track on 20 August 2026, and the Phase 1b data were shown as a late-breaking poster at the European Respiratory Society Congress in Barcelona on 8 September 2026. Interim RENEW data are guided for the second half of 2026.

How It Works

Caveolin-1 is a protein that acts like a brake on scarring signals in the lung. In idiopathic pulmonary fibrosis, the scar-making cells (fibroblasts) have too little of it. LTI-03 is a seven-amino-acid piece of the part of caveolin-1 that does the braking. When inhaled, it is meant to do two things at once: help the delicate cells lining the air sacs survive, and stop fibroblasts from piling up collagen. In mice and in donated human lung tissue, it did both. In people, it has so far only been shown to change some scarring signals in the airways over two weeks.

Caveolin-1 (Cav-1) is the principal structural protein of caveolae, and its scaffolding domain (residues 82–101) binds and restrains a range of signalling proteins. Wang and colleagues showed in 2006 that Cav-1 expression is markedly reduced in IPF lung tissue and in fibroblasts from IPF patients, that TGF-β1 suppresses Cav-1 in human lung fibroblasts, and that restoring Cav-1 reduced bleomycin-induced fibrosis and TGF-β1-driven matrix production through effects on JNK signalling. Tourkina and colleagues showed in 2008 that a peptide equivalent to the full scaffolding domain inhibited collagen, tenascin-C and α-smooth muscle actin expression in lung fibroblasts from scleroderma patients and, given systemically to bleomycin-treated mice, blocked epithelial apoptosis and fibrotic changes. The Shetty laboratory at UT Health Science Center at Tyler framed the disease around a cell-type paradox. Injured alveolar type II epithelial cells in fibrotic lungs show high Cav-1 and high p53, which pushes them toward apoptosis, while fibrotic lung fibroblasts show very low Cav-1 and p53 with increased mdm2-mediated p53 degradation, which lets them proliferate and resist death. Their 2019 Science Translational Medicine paper found that CSP7, the seven-residue FTTFTVT fragment, reproduced the full peptide's effects. Given during the established fibrotic phase in three mouse models (single-dose bleomycin, repeated bleomycin and adenoviral active TGF-β1), it reduced extracellular-matrix markers, increased epithelial survival and improved lung function. It also reduced matrix production in explanted end-stage human IPF tissue and was negative in Ames and micronucleus genotoxicity tests. Later work filled in pathways. In fibroblasts, CSP7 regulates a p53–microRNA-34a feedback loop (Hogan 2022). In mouse alveolar type II cells, it reversed p53-linked senescence markers and telomere dysfunction, and mice lacking urokinase (uPA) did not respond to it, pointing to the fibrinolytic system (Puthusseri 2025). Other reports describe effects on autophagy, ER stress and fibroblast glycolysis. Translational evidence comes from human tissue. In precision-cut lung slices from IPF patients, LTI-03 dose-dependently reduced collagen protein, suppressed pro-fibrotic cytokines and pathways, and activated protective PTEN and PPAR signalling. Its effect was comparable to nintedanib but without inducing apoptosis or necrosis pathways (MacKenzie 2025, Rein-authored). Because the peptide has limited aqueous solubility, it was formulated as a jet-milled, excipient-free dry powder with a mass median aerodynamic diameter of about 1.6 µm and a fine-particle fraction above 90%, suited to deep-lung deposition (Zhang 2020). In Phase 1b, plasma levels were below the limit of quantification after inhalation while bronchoalveolar lavage levels were measurable in some participants, consistent with lung-confined exposure. The airway biomarker changes at day 14 (lower IL-11, TSLP and, at 10 mg/day, COL1A1, CXCL7 and galectin-7) fit the proposed mechanism but do not yet establish clinical benefit.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about LTI-03:

• 01Efficacy on lung function: no data yet show that LTI-03 slows FVC decline, reduces exacerbations or improves survival. RENEW's 24-week FVC and HRCT results are the first real test.
• 02Durability and long-term inhaled safety: human exposure is limited to 14 days in 18 IPF patients plus an unpublished healthy-volunteer study, and the rat finding of bronchiolar mucus cell hyperplasia without a clear NOAEL needs to be put in human context.
• 03Dose selection: Phase 1b tested 5 and 10 mg/day and saw more biomarker changes at the higher dose, along with more cough. Whether either dose is optimal is unknown.
• 04Combination with approved antifibrotics: whether LTI-03 adds benefit on top of nintedanib, pirfenidone or nerandomilast, or changes their tolerability, has not been studied.
• 05Biomarker validity: IL-11, TSLP, COL1A1, CXCL7 and galectin-7 are plausible fibrosis signals, but none is an accepted surrogate for clinical benefit in IPF, and an exploratory panel in 24 people carries a real risk of chance findings.
• 06Human proof of the dual mechanism: epithelial protection plus fibroblast restraint is shown in mice and in ex vivo human tissue, mostly by the originating lab or the company, but not yet in patients.
• 07Other fibrotic lung diseases: animal work in silica injury and cigarette-smoke models raises the question of progressive pulmonary fibrosis beyond IPF, which no trial has addressed.

Forms & Administration

LTI-03 exists clinically only as an investigational dry powder for inhalation: 2.5 mg of micronised, excipient-free peptide per capsule, inhaled through a capsule-based dry-powder inhaler (the RENEW registration lists the Plastiape Monodose RS01 Model 7). Trial participants self-administer twice a day after training. Placebo capsules contain lactose powder. There is no injectable, oral or nebulised product in clinical development, and no approved or compounded form. Material sold online as 'LTI-03' or 'CSP7' is not the investigational product and is not made to the standards needed for anything entering the lungs.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

LTI-03 is not approved for any use. The doses above come only from Rein Therapeutics' trial protocols; anyone with IPF should be under the care of a pulmonologist.

Timeline of Effects

Monitoring & Measurement

Common Questions

Who LTI-03 Is NOT For

Drug & Supplement Interactions

No drug-interaction studies have been published. Two practical points come from the trials. First, RENEW allows stable background nintedanib, pirfenidone or nerandomilast, so it will produce the first data on LTI-03 alongside approved antifibrotics; until then, the combination is untested. The Phase 1b trial excluded antifibrotic users entirely. Second, the trials bar N-acetylcysteine and supplements such as quercetin, omega-3 fatty acids, DHEA, polyphenols and other phytochemicals, and limit systemic corticosteroids to 10 mg/day of prednisone or less. These rules keep the results clean rather than reflecting known interactions, but they mean the effects of combining LTI-03 with these products are unknown. Because plasma levels after inhalation were undetectable in Phase 1b, interactions with drugs acting elsewhere in the body seem unlikely in principle. Interactions with other inhaled medicines, such as bronchodilators or inhaled steroids, have not been studied.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions