Studies of Lancovutide in Cystic Fibrosis

Phase I/II Clinical Trials

Four Phase I and three Phase II clinical studies have been conducted thus far in healthy adults and adults with CF to test the safety of topically applied and inhaled doses of lancovutide (Moli1901) administration.  Proof of principle for the mechanism of action was explored in the nasal mucosa of CF patients and normal volunteers. The nasal mucosal cells are identical anatomically and physiologically to those found in the conductive airways in the lungs at the sites of progressive pulmonary disease in CF.  Lancovutide activated water transport mechanisms in nasal epithelium of both healthy volunteers and CF patients, demonstrating the proof of principle.  These nasal studies proved that lancovutide does indeed stimulate chloride secretion in the nasal mucosal cells of both healthy participants and those with CF, suggesting that one can expect the same potentially therapeutic effect in the pertinent lung epithelial cells.

The Phase I and II studies have demonstrated that daily doses of inhaled lancovutide dosed up to 28 days, are safe and tolerated.

Moli1901-010A

Notably, a recent Phase II, once daily dosing, multi-center study has been completed in Europe, assessing the safety and tolerability of 28 daily doses of lancovutide for Inhalation.  This first chronic dosing study demonstrated that lancovutide for inhalation is safe at a total daily dose of 2.5 mg.

The study featured two cohorts; 9 subjects aged 16 years and older, followed by 9 subjects aged 12-16 years.  Safety and tolerability were assessed by spirometric evaluation of pulmonary function, vital signs, pulse oximetry, physical examinations, clinical laboratory tests, electrocardiogram (ECG), and by monitoring adverse events. Efficacy was assessed by pre-treatment and post-treatment pulmonary function evaluation measuring forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced expiratory flow 25-75% of FVC. Exercise tolerance and quality of life were also assessed.

Results of the study demonstrated that subjects ages 12 and older tolerated daily administration of lancovutide over 28 days of daily dosing by the inhalation route and analysis of the data did not reveal unexpected safety concerns.  Furthermore, no traces of lancovutide were detected in the plasma of subjects indicating that the drug has limited or no systemic absorption. Notably, although the study was not powered to demonstrate efficacy, patients who received 2.5 mg lancovutide per day demonstrated a statistically significant improvement of lung function as demonstrated by FEV1, a standard measure of lung capacity in CF patients. The median FEV1 change from day 1 to the final evaluation on day 56 amounted to -3% in the placebo group and 2% in the lancovutide group (Wilcoxon test, p=0.0217).

Further statistically significant improvements of the patients receiving lancovutide were observed in the patients' subjective health perception as measured by the CF-validated Quality of Life Questionnaire.

Other Studies

A multi-center, dose regimen-finding efficacy and safety trial, Moli1901-010B, is in propress in study centers throughout the EU and Eastern Europe. The study is being conducted under the oversight of the EMEA and local regulatory authorities in the countries in which the study is being conducted.

Scientific Oversight

A Scientific Advisory Board (SAB) has been chartered to provide expert input to the international development of lancovutide for Cystic Fibrosis.  Under their guidance and the collaborative relationship between Lantibio and AOP, the program is slated to progress through ICH-compliant development.

Complementary Animal and Human Data

Data acquired from animal and human studies to date show that inhalation of lancovutide is an effective way to deliver the drug to the affected organ, and that it binds tightly to the cells of the lung lining, offering the possibility of a prolonged duration of action with little or no systemic absorption. This profile suggests that the drug will be safe to other organs and body systems, while offering direct benefit to the target organ, the lungs.