First-in-Class Treatment for LPE

Loculated Pleural Effusion

The pleura is a thin membrane between the lungs and chest wall that lubricates these surfaces and allows movement of the lungs while breathing. A Pleural Effusion occurs when fluid fills this gap and separates the lungs from the chest wall. Pleural effusions are currently addressed with aggressive antibiotic treatment, and if necessary, fluid drainage through a chest tube.

The condition is more serious when the fluid becomes infected (termed a complicated parapneumonic effusion (CPE) or empyema). Fibrotic scar tissue may develop, creating pockets of fluid in the pleural cavity, preventing effective drainage of the fluid. This condition is designated as a Loculated Pleural Effusion (LPE) and leads to pain and shortness of breath, as the lungs are not able to properly expand. More critically, this can also rapidly lead to sepsis.

CPE and empyema are common clinical problems which are associated with mortality of about 20 percent and considerable morbidity (Corcoran et al., 2013; Grijalva et al., 2011; Rahman et al., 2011; Sonnappa et al., 2006), often due to the formation of LPE.

Current Treatment

There are currently no approved drug treatments for LPE.  If an LPE cannot be adequately drained by a chest tube, the only approved procedures are invasive surgical procedures, such as video-assisted thoracoscopic surgery (VATS) or open chest surgery (thoracotomy).  Surgery represents a number of risks to the patient, including bleeding, infection, and persistent chest pain. Surgery typically results in significant days of hospitalization post procedure, with some reports indicating average hospital stays of elderly patients of 20-25 days or longer. Moreover, many patients are not operative candidates, having significant co-morbidities that often accompany patients hospitalized with pneumonia.

Given the risks of surgery and extensive days of hospitalization post-surgery, intrapleural fibrinolytic therapy (IPFT) has been used off label in patients with LPE to promote pleural drainage and to avoid surgery. These drugs are not approved for LPE, have not been optimized for dosing, and their effectiveness has been highly inconsistent.  Despite this, the off-label drugs are now used in many places as a first line treatment for LPE, as doctors are desperate to avoid surgery in this very sick patient population. 


LTI-01 is the first pharmaceutical agent specifically developed for treating non-draining LPE. LTI-01 has completed a Phase 1b clinical trial demonstrating preliminary signs of efficacy with no safety concerns.

LTI-01 is a proenzyme, or zymogen, that breaks down the fibrinous adhesions that cause LPELTI-01 has demonstrated a longer, more sustained activity than fibrinolytics used off label. The mechanism and preclinical and clinical data of LTI-01 suggest that it will have a better safety and efficacy profile compared to off label fibrinolytic drugs.

Phase Ib Clinical Trial

LTI-01 has been assessed in a first-in-human, open-label, dose escalation safety study (Beckert et al., 2019) in patients presenting with pneumonia and CPE/empyema. LTI-01 was administered once per day for up to three consecutive days.

At the doses tested, LTI-01 was well tolerated with no safety signals of concern. No local or systemic bleeding was observed. All adverse events observed were considered unrelated to study drug.  Additionally, LTI-01 showed preliminary signs of efficacy, with reductions in pleural opacity and declines in pleural infection indicators.  These results suggest that the compound effectively clears scar tissue with once-a-day dosing for 3 days and promotes fluid drainage around the lungs without any significant bleeding and other side effects.

Current status 

LTI-01 is currently in a Phase 2, randomized, placebo-controlled, double-blind, dose-ranging study evaluating LTI-01 in patients with infected, non-draining loculated pleural effusions.

LTI-01 has received Orphan Drug Designation in the US and EU and Fast Track Designation in the US.