Lantibio

Development of Lancovutide (Moli1901) for Cystic Fibrosis

While current therapies for cystic fibrosis only treat symptoms, lancovudite (formerly known as Moli1901) is aimed at treating CF’s abnormalities at a root cause. Lancovutide is a 19 amino acid polycyclic peptide produced from the fermentation of Streptomyces cinnamoneus. It promotes the hydration of epithelial tissue by opening an alternate salt channel. Lancovutide and other agents or hormones that stimulate secretion are commonly referred to as “secretagogues”. In cystic fibrosis, inhaled lancovutide solution has the potential to correct the abnormal salt balance in the lungs, normalize mucus hydration and improve mucociliary clearance.

The molecular target of lancovutide is the phospholipid phosphatidylethanolamine (PE) present in the cellular membrane. Moli1901 binds to the polar head of PE and induces changes in intracellular calcium levels, which in turn activate calcium dependent chloride channels. These alternative calcium activated chloride channels produce an output of chloride and water. Delivery of the drug via an inhaled aerosol could result in increased hydration and normalization of the mucus composition in CF patients. By opening an alternate salt channel in normal and diseased lungs, lancovutide is meant to improve the hydration of mucus in the lungs, normalizing mucus consistency, thus preventing mucus retention. The interruption of this progression of the disease will prevent inflammation and bacterial infection inherent in CF disease.

Lancovutide presents an opportunity to prevent the respiratory symptoms of CF without engaging in the challenges inherent in the leading developmental treatment approach of gene therapy. Phase I and II clinical studies conducted in healthy volunteers and CF patients demonstrated safety of up to 28 daily doses delivered by inhalation.

Lancovutide is currently in late Phase II clinical development in Europe through a collaborative agreement with AOP Orphan Pharmaceuticals, AG (AOP), Vienna, Austria. A study to assess the safety of 28 daily doses in adults and pediatric patients with CF, designated Moli1901-010A, has been completed. Results of the study demonstrated that subjects tolerated daily administration of lancovutide by the inhalation route, with no unexpected safety concerns and with improved quality of life. AOP has immediate plans to initiate a follow-on multi-center, dose regimen ranging efficacy and safety trial across Europe.

A Phase 2B study, Moli1901-010B, evaluating the safety and efficacy of longer term exposure to lancovutide is in progress in countries throughout the EU and Eastern Europe. The study, with a dose ranging design, will support the selection of a dose regimen for the upcoming Phase 3 development slated to begin late in 2009.

A Scientific Advisory Board (SAB) has been chartered to provide expert input to the international development of lancovutide for Cystic Fibrosis. The SAB is Chaired by Michael Freissmuth, MD, Medical Consultant to AOP Orphan Pharmaceuticals in Vienna, Austria and Professor of Pharmacology and Chairman of the Institute of Pharmacology at the Medical University of Vienna, Austria. Members include Gerd Döring, Ph.D., Professor at the University of Tubingen in Germany and past President of the European Cystic Fibrosis Society (ECFS); Ernst Eber, M.D., Associate Professor of Pediatrics and Assistant Director of the Respiratory and Allergic Disease Division of the Pediatric Department at the Medical University of Graz in Austria; Irmgard Eichler, M.D., Associate Professor of Pediatrics in the Division of Pulmonology and Director of the CF Center at the University Children’s Hospital in Vienna, Austria; and Richard B. Moss, M.D., Chief, Pediatric Pulmonology and Allergy Department at Stanford University in California. Under the guidance of these experts and the collaborative relationship between Lantibio and AOP Orphan, the program is slated to progress through ICH-compliant development.

There are currently no FDA-approved treatments specifically designed and indicated to address the underlying ion-transport defect in cystic fibrosis. The focus of available treatments is the relief of the symptoms of the disease. Current treatments target the symptoms of CF focus on the respiratory problems that affect CF patients involve clearing the mucus, thinning the mucus, facilitating breathing, controlling inflammation and fighting infection. These drugs are being used in combination for the treatment of CF. Due to the proposed treatment mechanism, it is likely that therapy with lancovutide will postpone or preclude the use of these products.