LTI-03 / Rein Therapeutics - LARVOL DELTA

Inhaled LTI-03 for Idiopathic Pulmonary Fibrosis: A Randomized Dose Escalation Study. (PubMed, medRxiv) - "Any queries regarding clinical study data must be submitted in writing to https://info@reintx.com . A data supplement for this article is available via the Supplements tab at the top of the online article."

Journal • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CAV1 • TSLP

Rein Therapeutics Announces New Scientific Publication Demonstrating LTI-03 May Reduce Lung Scarring and Protect Cells Needed for Lung Repair in IPF (GlobeNewswire) - "According to the authors, LTI-03 was generally well tolerated, and samples collected from treated patients showed reductions in multiple fibrosis-associated biomarkers. These biomarkers include proteins and inflammatory signals linked to disease progression, offering evidence that the drug is reaching the lung and engaging its intended targets. The investigators also reported that LTI-03 helped preserve alveolar epithelial type II (AT2) progenitor cells, which are essential for lung repair and regeneration."

Clinical data • Idiopathic Pulmonary Fibrosis

Rein Therapeutics…announced that the U.S. Food and Drug Administration (FDA) has lifted the full clinical hold on the Company’s Phase 2 'RENEW' trial evaluating LTI-03 in patients with idiopathic pulmonary fibrosis (IPF) (GlobeNewswire) - "FDA lifts clinical hold following review of Company’s Complete Response submission. Company expects to restart U.S. enrollment in late 2025 or early 2026 across 20 clinical sites....Initial topline data is expected in Q3 2026."

Enrollment status • FDA event • P2 data • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Receives European Regulatory Approval to Initiate Phase 2 Trial of LTI-03 in Idiopathic Pulmonary Fibrosis (GlobeNewswire) - "The approvals cover clinical trial sites in Germany and Poland, which will serve as key European centers for the global study.....The study will enroll up to 120 patients globally, with a treatment duration of 24 weeks across two dosing groups."

Trial status • Idiopathic Pulmonary Fibrosis

LTI-03 peptide demonstrates anti-fibrotic activity in ex vivo lung slices from patients with IPF. (PubMed, iScience) - "Modulation was comparable to nintedanib but without the induction of apoptosis or necrosis pathways. These results demonstrate LTI-03's potential therapeutic efficacy in a highly relevant translational disease model and support LTI-03 as a promising next-generation therapeutic to halt IPF progression and improve patient outcomes."

Journal • Preclinical • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CAV1 • PTEN

Peer-reviewed publication highlights potential breakthrough anti-fibrotic properties of LTI-03 in lung tissue from IPF patients (GlobeNewswire) - "LTI-03 reduced multiple scarring pathways (including TGFβ, VEGF, PDGF, and FGF), while also lowering collagen production and inflammatory signals in diseased lung tissue. Unlike nintedanib, the FDA-approved standard-of-care drug, LTI-03 achieved these effects without causing cell damage or death in patient samples, reinforcing the drug’s strong safety profile."

Preclinical • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Wins U.K. Approval to Launch Phase 2 Clinical Trial of LTI-03 in Idiopathic Pulmonary Fibrosis (GlobeNewswire) - "The RENEW trial is expected to enroll up to 120 patients worldwide, evaluating two dose groups of LTI-03 against a placebo. The primary objective of the trial is to assess safety and tolerability over 24 weeks of treatment. Secondary endpoints will include measures of lung function and imaging-based assessments of fibrosis progression....Rein is actively working with clinical sites in the UK to begin patient recruitment soon, with initial data expected in 2026."

P2 data • Trial status • Idiopathic Pulmonary Fibrosis

Rein Therapeutics to Present Novel IPF Science and Clinical Development Insights at IPF Summit 2025 (GlobeNewswire) - "Dr. Hogaboam will...The role of key immune cells in idiopathic pulmonary fibrosis (IPF) called lung-resident macrophages; How macrophage modulation may be critical to stopping the disease from getting worse; How Caveolin-scaffolding domain (CSD) peptides, the class of molecules Rein is advancing, target multiple drivers of fibrosis and could potentially help repair lung tissue...Dr. Windsor’s....will provide: An overview of Rein’s Phase 2 trial of LTI-03, which will enroll up to 120 patients, assess safety and tolerability, and focus on lung function as a key outcome; A discussion of trial design, strategies around patient recruitment, and how Rein is working to make the study feasible and relevant in a fast-changing treatment landscape."

Clinical • Trial status • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Enters into Agreements for up to $21 Million in Flexible Financing (GlobeNewswire) - "Rein Therapeutics...announced that it has entered into two strategic financing agreements with an affiliate of Yorkville Advisors Global, LP, providing the potential for access to up to $21 million in capital. The financing includes: A $6 million pre-paid advance agreement, with an initial $1 million advance funded at signing. A $15 million standby equity purchase agreement (SEPA), which Rein may use at its discretion over 36 months, subject to an effective registration statement. Rein intends to use the proceeds from these facilities to support its RENEW Phase 2 trial of its lead asset – LTI-03 – for the treatment of idiopathic pulmonary fibrosis (IPF), for the research and development of other product candidates, and for working capital and other general corporate purposes."

Financing • Idiopathic Pulmonary Fibrosis

A Phase 2 Study of LTI-03 in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Rein Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

US FDA puts on hold Rein Therapeutics' lung disease drug trial (Reuters) - "Rein Therapeutics...has paused patient enrollment and dosing in a mid-stage trial of its lung disease drug in the U.S. after the Food and Drug Administration placed a clinical hold, the drug developer said on Thursday. Shares of the company fell nearly 10% after the bell. The company was testing a drug named LTI-03 to treat patients with idiopathic pulmonary fibrosis (IPF)....Rein said in a filing that it is actively working with the FDA to remove the clinical hold."

Trial suspension • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Announces First Patient Dosed in RENEW Phase 2 Trial of LTI-03 in Patients with IPF (Streetinsider.com) - "Rein Therapeutics...announced today that the first patient has been dosed in the RENEW Phase 2 trial of its lead asset, LTI-03, a novel, multi-pathway, Caveolin-1-related peptide for the treatment of IPF....Topline interim data from RENEW is expected in the first half of 2026."

P2 data • Trial status • Idiopathic Pulmonary Fibrosis

Evaluating Alveolar Regenerative Properties of Caveolin Scaffolding Peptides (CSD) in Three Dimensional (3D) Alveolospheres from IPF and Normal Donor Lung Samples (PRNewswire) - "Rein Therapeutics...announced that the Company and its collaborators presented...posters supporting the potential therapeutic effectiveness of LTI-03 in idiopathic pulmonary fibrosis (IPF) at the American Thoracic Society (ATS) 2025 International Conference....Cav1 scaffolding domain peptides LTI-03 or LTI-2355 sustained AEC2s in IPF lung organoids or alveolospheres, further supporting LTI-03's ability to promote alveolar epithelial cell survival. At the 10.0 μM dose, both LTI-03 and LTI-2355 increased the size of IPF alveolospheres compared to placebo at Day 28. Both LTI-03 and LTI-2355 appeared to protect normal lung alveolopheres, while nintedanib demonstrated significant growth-inhibiting or toxic effects on normal donor lung organoids at Day 28."

Preclinical • Idiopathic Pulmonary Fibrosis

Pre-clinical Proof-of-concept of Anti-fibrotic Activity of Caveolin-1 Scaffolding Domain Peptide LTI-03 in Ex Vivo Precision Cut Lung Slices (PCLS) from Patients with Idiopathic Pulmonary Fibrosis (PRNewswire) - "Rein Therapeutics...announced that the Company and its collaborators presented...posters supporting the potential therapeutic effectiveness of LTI-03 in idiopathic pulmonary fibrosis (IPF) at the American Thoracic Society (ATS) 2025 International Conference....LTI-03 dose-dependently stimulated production of solRAGE, a factor indicative of AEC1 health that is a critically important aspect of IPF and has gone largely unaddressed by current treatment options. LTI-03 reduced the expression of profibrotic proteins in IPF PCLS, including Col-1α1 and platelet-derived growth factor receptor beta (PDGFRB)."

Preclinical • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (PRNewswire) - "The Company and its collaborators will present two posters at the upcoming American Thoracic Society (ATS) 2025 International Conference in May 2025. Poster details include: Presentation Title: Pre-clinical Proof-of-concept of Anti-fibrotic Activity of Caveolin-1 Scaffolding Domain Peptide LTI-03 in Ex Vivo Precision Cut Lung Slices from Patients with Idiopathic Pulmonary Fibrosis; Poster #: P1422...; Date & Time: Monday, May 19, 2025, at 11:30 AM PT/2:30 PM ET."

Preclinical • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Announces Initiation of RENEW Phase 2 Trial of LTI-03 in Patients with IPF (PRNewswire) - "Rein Therapeutics...announced that the RENEW Phase 2 trial of its lead asset, LTI-03, a novel, multi-pathway, Caveolin-1-related peptide for the treatment of idiopathic pulmonary fibrosis (IPF), has been initiated with screening and recruitment of patients underway....The RENEW trial is a Phase 2 multi-center, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and efficacy of LTI-03 in patients with IPF....The RENEW Phase 2 trial will enroll up to 120 IPF patients with topline data expected in the first half of 2026."

New P2 trial • Idiopathic Pulmonary Fibrosis

A Phase 2 Study of LTI-03 in Patients With Idiopathic Pulmonary Fibrosis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Rein Therapeutics

New P2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Rein Therapeutics and Qureight Ltd Announce Planned Integration of Deep-Learning Platform for Phase 2 Trial of LTI-03 in Patients with IPF (PRNewswire) - "Rein Therapeutics...today announced a collaboration for the integration of Qureight's deep-learning platform into Rein's planned Phase 2 trial of its lead asset LTI-03, a novel, multi-pathway, Caveolin-1-related peptide, for the treatment of idiopathic pulmonary fibrosis (IPF)....'We are taking the evaluation of biomarkers a step further with the application of cutting-edge deep-learning imaging technology and detailed AI-based data analysis by collaborating with Qureight on this Phase 2 trial. These tools will be critical in gaining a deeper understanding of the potential therapeutic effect of LTI-03'....Rein plans to announce further details on the design of the Phase 2 trial of LTI-03 in IPF in the near term."

Licensing / partnership • Idiopathic Pulmonary Fibrosis

Rein Therapeutics Granted Two Patents Covering the Novel Formulation and Administration Methods of Dry Powder LTI-03 for the Treatment of Respiratory Diseases (PRNewswire) - "Rein Therapeutics...announced that the U.S. Patent and Trademark Office (USPTO) granted two new patents related to Rein's lead product candidate, LTI-03, a novel, synthetic peptide with a dual mechanism targeting alveolar epithelial cell survival as well as inhibition of profibrotic signaling, which is administered through dry powder inhalation. U.S. Patent No. 12,280,088 and U.S. Patent No. 12,280,089, both titled, 'Dry Powder Formulation of Caveolin-1 Peptides and Methods of Use Thereof', were issued on April 22, 2025. The patents cover LTI-03 dry powder inhalation formulation and its therapeutic use for treating various lung diseases including interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and other inflammatory or fibrotic lung conditions."

Patent • Asthma • Chronic Obstructive Pulmonary Disease • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

A Study to Evaluate LTI-03 in Newly Diagnosed Idiopathic Pulmonary Fibrosis (IPF) Patients (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Rein Therapeutics | Active, not recruiting ➔ Completed | Trial completion date: Feb 2025 ➔ Sep 2024

Biomarker • Trial completion • Trial completion date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Rein Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (PRNewswire) - "Rein advanced the clinical development of its lead asset, LTI-03, and aims to initiate a Phase 2 trial for the treatment of idiopathic pulmonary fibrosis (IPF) in the first half of 2025."

New P2 trial • Idiopathic Pulmonary Fibrosis

A Study to Evaluate LTI-03 in Newly Diagnosed Idiopathic Pulmonary Fibrosis (IPF) Patients (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Lung Therapeutics, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2024 ➔ Feb 2025 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Biomarker • Enrollment closed • Trial completion date • Trial primary completion date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Aileron Therapeutics Announces Positive Topline Data from Cohort 2 of the Phase 1b Clinical Trial of LTI-03 in Idiopathic Pulmonary Fibrosis (IPF) (PRNewswire) - P1 | N=24 | NCT05954988 | Sponsor: Lung Therapeutics, Inc | "Aileron Therapeutics, Inc...announced positive topline data from Cohort 2 of its Phase 1b clinical trial...Reduced expression of multiple profibrotic proteins active in both pathologic basal-like cells and fibroblasts, with four biomarkers (IL-11, CXCL7, TSLP and GAL-7) showing statistically significant decreases in the combined data set supporting the potential of LTI-03 to reduce fibrosis, inflammation and associated functional changes in the lung. Dose dependent trends were observed in five biomarkers, including COL1A1, CXCL7, TSLP, GAL-7, and Surfactant protein D (SPD) which provide evidence of active LTI-03 pharmacodynamics. SPD, an indicator of epithelial cell health that is significantly linked to decline in lung function, decreased by 5% in Cohort 2 at 14 days of treatment, while current standard of care for IPF reduced SPD by 4% at 12-weeks in precedent trials1, 2."

P1 data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Aileron Therapeutics to Present Previously Announced Data from the Phase 1b Clinical Trial Evaluating Low-Dose LTI-03 in Idiopathic Pulmonary Fibrosis (IPF) at the 22nd International Colloquium on Lung and Airway Fibrosis (PRNewswire) - "Aileron Therapeutics, Inc...announced the presentation of two abstracts detailing LTI-03's pre-clinical and Phase 1b (NCT05954988) results in Idiopathic Pulmonary Fibrosis (IPF) at the 22nd International Colloquium on Lung and Airway Fibrosis (ICLAF)....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....The Company expects to report topline data for this cohort in the near-term."

P1 data • Preclinical • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

Aileron Therapeutics Completes Enrollment in Cohort 2 of the Ongoing Phase 1b Clinical Trial Evaluating LTI-03 in Idiopathic Pulmonary Fibrosis (IPF) (PRNewswire) - "Aileron Therapeutics, Inc...announced the completion of enrollment in Cohort 2 of the ongoing Phase 1b clinical trial of LTI-03 in IPF patients. The last patient was enrolled in mid-September, with a total of 24 patients enrolled in the trial. Eligible patients are randomly assigned (3:1) to receive either inhaled LTI-03 or placebo....'we are excited to assess the safety, tolerability and biomarkers of 5 mg twice daily of inhaled LTI-03 and expect to report topline data in the near term.'"

Enrollment closed • P1 data • Idiopathic Pulmonary Fibrosis • Pulmonary Disease • Respiratory Diseases