Servicio de Información Comunitario sobre Investigación y Desarrollo - CORDIS

FP7

SADEL Informe resumido

Project ID: 278042
Financiado con arreglo a: FP7-HEALTH
País: Italy

Periodic Report Summary 1 - SADEL (Scaffolds for alternative delivery)


Project Context and Objectives:

The SADEL consortium, which stands for “Scaffolds for Alternative DELivery”, initiated a collaboration to develop oral-formulation of a Nanofitin®-based drug in Inflammatory Bowel Diseases (IBD). The two main phenotypes of IBD, Crohn’s Disease (CD) and Ulcerative Colitis (UC), are chronically relapsing intestinal inflammatory conditions with a typical onset in young adulthood and with an unpredictable disease course that may lead to debilitating complications. The clinically validated target chosen by the Consortium is TNFα, a cytokine considered a key regulator of immune cells and involved in systemic inflammation. The objective of the SADEL project is to advance existing Nanofitins® hits against TNFα towards the preparation of Phase I Clinical trials in UC.

Nanofitins® constitute a new class of non-antibody affinity ligands able to selectively bind a wide range of targets. As an addition to their antibody-like properties, Nanofitins® have a small size (optimal tissue penetration), pH resistance (favorable stomach passage), resistance to human intestinal fluids (long half-life in digestive track) and high affinity (low effective concentration needed). They also demonstrate strong potential for optimizing pharmacological properties, including reducing immunogenicity.

Consequently, the SADEL project is designed to address unmet technical challenges by making optimal use of the Nanofitins® protein scaffold. The Nanofitins®-based drugs will progress through routes not travelled by antibodies while interacting with targets not modulated by chemical compounds. They will be administered orally, reducing the systemic exposure and avoiding the safety issues reported with systemic administration of antibodies. This requires large quantities of proteins for frequent administration, which is compatible with Nanofitins® manufacturing in bacterial systems, broadly adopted in the industry with a low cost of goods.

Project Results:

The main goal to be reached during the first 18 months of the project was to select 3 Nanofitin leads based on in vivo efficacy, biochemical characterization, and compliance with subsequent industrial development. Such leads were selected from the nearly 30 hits previously identified by Affilogic.

Then, in vivo evaluation based on rectal administration was performed as a preliminary screening before oral administration. The results are beyond the consortium’s expectancies, as several non-optimized Nanofitins reach a level of efficacy similar to the positive, commercial control, in the gold standard evaluation animal model. Fine analytical methods were developed and allowed to correlate this efficacy level to biochemical parameters, enabling a better understanding of the potential progress to be made. Furthermore, humanized TNF-specific in vivo models have been optimized for upcoming oral administration. The manufacturing process was translated to pilot-scale, and the manufacturing yield has been increased by nearly 50-fold, which is extremely promising for industrialization. General immunogenic potential of Nanofitin was assessed, with very promising results.

Finally, a specific Target Product Profile was established with the contribution of an industrial third party whose involvement in SADEL should be made official in the early days of the second period. Such profile clearly draws the roadmap for the lead optimization and development step.

Potential Impact:

Globally, SADEL has made very significant progress in developing an orally available anti-TNF compound to treat Inflammatory Bowel Diseases. A significant amount of work is still to be carried out, the first hurdles have been successfully crossed in due time, outperforming the set milestones. The starting second period will consist in validating and fine-tuning the lead compound for an actual oral administration, starting with experiments in humanized TNF models and formulation evaluation.

The final expected outcome of the project is to prepare the data package for a first-in-man administration after the project is terminated. After the 60 months allotted to SADEL, the clinical development of the lead compound has already been considered through an agreement with a European Industrial partner. This agreement is expected to be signed in the early weeks of the second period. It will ensure that a successful product will seamlessly progress along the drug development pathway, and will ultimately be available to patients, in particular in Europe. The consortium has indeed made a commitment to deliver, beyond excellent research, a first-in-class, patient-friendly treatment for Inflammatory Bowel Diseases.

List of Websites:

http://www.sadelproject.eu/


Contacto

Ilaria Bonetti, (European Project Manager)
Tel.: +39 02 85155230
Síganos en: RSS Facebook Twitter YouTube Gestionado por la Oficina de Publicaciones de la UE Arriba