Project: Alginate derived oligosaccharide G-block as a new drug candidate in the treatment of cystic fibrosis.

AIM_x000D_ OligoG is a new, inhaled dual-acting drug candidate developed from alginate. It is being developed for the treatment of cystic fibrosis. This project aims to progress the project until end of phase 2 and to evaluate lung deposition of OligoG using gamma scintigraphy and pharmacokinetic profiling._x000D_ _x000D_ BACKGROUND_x000D_ Cystic fibrosis (CF) is a disease in which pulmonary function is compromised by elevated mucus viscosity, secondary to a defect in the Cystic Fibrosis Transmembrane Regulator (CFTR) protein. The elevated viscosity is associated with mucin polymer cross-linking. Chronic pulmonary colonization of Pseudomonas spp. represents a significant clinical problem in CF patients, especially as the mucoid phenotype expresses biofilm which again acts as a protective layer for the bacteria. One innovative approach towards developing new drugs for this condition would thus be to design a drug which promotes sputum clearance whilst also increasing the effectiveness of current antibiotics in situ. _x000D_ Model systems and ex vivo studies on CF sputum indicate that OligoG indeed: (1) reduces CF sputum viscosity and weakens microbial biofilms via inhibition of polymeric cross-linking (this may increase pulmonary clearance of sputum, and may promote diffusion of antimicrobial agents into microbial biofilms and augment their effectiveness); and (2) shows antimicrobial properties through intrinsic antimicrobial effects of OligoG, and through reduction in MICs for selected antibiotics._x000D_ In this project, we further wish to evaluate the lung deposition of OligoG. To achieve this, an inhalation formulation (6% solution nebulised using the Sidestream Plus and Portaneb (Phillips Respironics) aerosol delivery system) will be evaluated using ex vivo testing. The aim of the study will be to generate in vivo data using gamma scintigraphy and pk profiling. _x000D_ _x000D_ TECHNICAL APPLICATIONS_x000D_ The project is comprised of 3 separate work packages:_x000D_ • WP1 Consortium Administration and Management (Month 1-36)_x000D_ • WP2 A pharmaco-scintigraphic study to measure lung deposition and pharmacokinetics (Month 1-36)_x000D_ • WP3 A phase IIb clinical dose-response trial, SMR-2176 (Month 1-36)_x000D_ _x000D_ MARKET APPLICATIONS_x000D_ The market size for mucolytics is estimated to EUR 0,6 billion based on the reported sales figures from the market leaders. AlgiPharma is aiming to be the market leader in mucolytics for CF patients capturing over 50% of this market. The designation as Orphan Medicinal Product gives AlgiPharma a 10 year exclusivity to the European CF market for mucolytics once the product can be marketed to patients. AlgiPharma has recently filed an application for orphan drug status also in the US._x000D_ _x000D_ CONSORTIUM_x000D_ The Ps are selected based on complementary qualifications. The CO participant in the consortium is AlgiPharma, the holder of the drug and application patent licence and the owner of several supporting patents. AlgiPharma is managed by professionals with decades of experience and top level expertise in development and use of alginates in various medicinal products, R&D, industrial manufacturing, international sales and marketing. _x000D_ _x000D_ Conduct of clinical trials is a profession in its own, requiring international competency and capacity. Smerud Medical Research CRO Group is a Contract Research Organisation (CRO) with more than 17 years' experience in directing and managing clinical research projects, in particular early phase studies or clinical proof-of-concept trials. Smerud has top level competence in advanced medical statistics, including adaptive design expertise and are responsible for commercialisation (clinical development until marketing authorisation is obtained) of several early phase compounds for the biotech industry._x000D_ _x000D_ Bio-Images Research are experts in scintigraphic clinical trials on drug delivery systems. _x000D_ Information obtained from these studies provide reliable early stage in vivo data to the global pharmaceutical industry, enabling strategic formulation development. Bio-Images undertakes all aspects of the clinical trial process, and their ward facilities accommodate overnight patient stays, as required. They are regularly inspected by the MHRA and client auditors; all clinical work is fully ICH GCP-compliant._x000D_ _x000D_ Pharmaterials Ltd is a science driven contract research organization specializing in the optimization of drug substance physical forms (salt, polymorphs and co-crystals), the development of preclinical and early phase formulations and the manufacture of clinical trials materials. Pharmaterials work with a wide range of organisations, including start-up companies, mid-size and multinational companies, and provide a complete formulation service for inhaled drug delivery using dry powder inhaler (DPI) and pressurized metered dose inhaler (pMDI) systems.

Acronym OligoG (Reference Number: 6628)
Duration 01/09/2011 - 30/11/2014
Project Topic OligoG is a new, inhaled dual-acting drug candidate developed from alginate. It is being developed for the treatment of cystic fibrosis. This project aims to progress the project until end of phase 2 and to evaluate lung deposition of OligoG using gamma scintigraphy and pharmacokinetic profiling.
Project Results
(after finalisation)
AlgiPharma has an alginate oligosaccharide drug candidate OligoG under clincial development as a new treatment for cystic fibrosis (CF). The Eurostars Project E!6628 enabled the following achievements:_x000D_- A new dry powder for inhalation (DPI) for OligoG was developed, to replace a 6% solution for nebulisation used in previous preclinical and clinical studies. The manufacturing process was established according to GMP._x000D_- Excellent safety of the DPI was demonstrated in a 4 weeks rat toxicity study._x000D_- More than twice increased lung deposition as compared to the nebulised solution was demonstrated in cystic fibrosis patients. _x000D_- Phase 2B studies to investigate the efficacy of the OligoG DPI in cystic fibrosis patients was started in 18 clinical sites in five European countries. _x000D_- Funding from the US based Cystic Fibrosis Foundation to complete the clinical studies was secured, based on results achieved in the Eurostars project E!6628.
Network Eurostars
Call Eurostars Cut-Off 6

Project partner

Number Name Role Country
5 AlgiPharma AS Coordinator Norway
5 Pharmaterials Ltd Partner United Kingdom
5 Bio-Images Research Ltd Partner United Kingdom
5 Simbec Research Ltd Observer United Kingdom
5 Smerud Medical Research International AS Partner Norway