Objectives of HemAcure
The overall objective of the HemAcure project is to develop and refine the tools and technologies for a novel ex vivo prepared cell based therapy to treat the bleeding disease, haemophilia A (caused by genetic deficiency in clotting factor VIII (FVIII)) that should ultimately lead to improved quality of life of the patients.
The approach will be implemented as follows:
- Isolation and culture of Blood Outgrowth Endothelial Cells (BOECs) from patients’ blood.
- Manipulation of patient’s cells to correct the genetic defect by ex vivo introduction of the correct genetic form of coagulation factor VIII (mutations in this gene lead to haemophilia A). After optimization, this step will be implemented into GMP conditions by Partner 1 UKW and Partner 2 IMS.
- Automation of cell expansion in a novel and passage-less scalable bioreactor (Constellation Cell Culture System) that was developed by Partner 4 UNILO. During and after expansion, the cells are analysed with respect to their safety profile (e.g. lack of tumourigenicity), functionality (e.g. FVIII secretion) and senescence state to evaluate and define release criteria for the therapeutic cell product for future human clinical studies.
- Cell transplantation into a novel, proprietary implantable medical device (Cell Pouch™) for targeted delivery of therapeutic Factor VIII. The Cell Pouch System™ was developed, manufactured and tested by Partner 5 SERC over a 6 year period and is currently being used in clinical studies for the treatment of diabetes using pancreatic ß-islets. Dosing, proof of concept and safety studies will be conducted in appropriate animal models, including the haemophilia A animal model generated by Partner 3 UPO specifically for this autograph (self-cell) indication.
- All steps will be designed and conducted according to European GMP-regulations to ensure that the product will fully comply with the requirements for quality of the European authorities.
The final objectives will be to provide sets of design and manufacturing protocols, based on current European GMP regulations and to prepare an Investigational Medicinal Product Dossier (IMPD) for an Investigational Medicinal Product (IMP), composed of therapeutic cells and an implantable medical device (Cell Pouch™), a so-called combined Advanced Therapeutic Medicinal Product (combined ATMP). The IMPD will summarize all information related to cell isolation and manipulation, to the quality-controlled production, and to the release criteria including functional behavior and safety aspects, which will form the basis of further clinical trial applications subsequent to the completion of this program.