The work plan for Smart-4-Fabry has been thoroughly designed taking into account the specificities of this project. To respond to the challenge of efficiently organizing the work, Smart-4-Fabry is divided into 9 core work packages (WP), distributed across 4 specific stages
Nanoformulation of the GLA in multifunctional nanoliposomes.
Physico-Chemical characterization tools for quality control.
In vitro and in vivo evaluation of GLA-nanoformulation
Regulatory pre-clinical studies
Scale-up and GMP production
Critical Regulatory activities.
Business model and Exploitation activities.
Dissemination and Communication
Project Management.
This WP is devoted on the one hand to the preparation and optimization of the current GLA-nanoformulation, to obtain a final formulation, with enhanced intracellular and BBB penetration, and higher in vitro efficacy, ready to enter the pre clinical phase.
On the other hand, and at the same time that the preclinical assays are being performed, the impact of the change
of peptide nature on the self-assembling of liposomal membrane components and on the GLA-nanoformulation will be
explored. Indeed, a deep physico-chemical characterization will be performed over the different systems functionalized
with the selected targeting peptides.
A deep physico-chemical characterization of the different nano-GLA formulations provided by WP1, following different protocols developed for this purpose, will be carried out. The rationale behind this is to monitor the development of the GLA-nanoformulation towards the final and definitive one, and to establish correlations between structural nanoformulation characteristics and the in vivo efficacy, intracellular penetration, and BBB crossing.
Therefore, different parameters will be carefully analyzed in order to control the quality of the self-assembled nanoformulation. Well-established methodologies will be used for the detailed and statistical characterization of GLA-nanoformulations, at molecular, supramolecular and nanoscopic level.
After an initial assessment of results achieved in previous WP1 and WP2, the Smart4Fabry consortium will proceed to the assignment and experimental evaluation of the specific critical quality attributes (CQAs) and critical process parameters (CPPs) to define the quality target profiles (QTPs) of nanoformulated GLA, that will lead towards the final process and product design.
The objective of this WP is to test the efficacy of the nanoformulations obtained in previous work packages.
For that purpose, cellular and animal models will be used.
Smart-4-Fabry will perform preclinical safety/efficacy studies to advance GLA nanoformulation along drug development. A regulatory assessment with regard to the value of the preclinical biological activity data generated at this stage of the development and the entire preclinical safety,
pharmacokinetic and toxicological plan, in compliance with applicable GLP and GMP as appropriate, will be performed. European regulatory authorities (central) will be consulted in the context of scientific advice procedures to get valuable inputs to incorporate to the development plan.
Medicinal products regulation is a critical issue for the development of innovative pharmaceutical production processes and products. In this sense, Smart-4-Fabry will follow the regulatory requirements in the development of GLA-nanoformulation,
including formulation, manufacturing and nonclinical tests. The regulatory requirements will be implemented according to the expert partner (DDR) by providing appropriate inputs to any of the WP, and by ensuring frequent interaction with the relevant European regulators in the form of scientific advice procedures.
A detailed business plan will be implemented, together with an update of the already developed market study, including:
identification of key exploitable results, IPR management, market assessment (size, volume, distribution), constitution of an exploitation team, detailed financial projections, taking into account remaining costs for clinical development, detailed cost evaluation for the production process and the obtained products, marketing costs and foreseen revenue, commercialization roadmap and risk assessment. This business plan will be supported by a detailed Exploitation Plan in order to catch all the exploitable items to be transferred to markets or to be serve as a basis for future R&D efforts. Exploitation will be understood in a wide manner at different levels, as exploitation interest will differ between industrial and academic partners, but in a full complementary way.
This WP aims to formulate a Plan for Use and Dissemination of the Project’s Results drawing the dissemination strategy in accordance with the knowledge management strategy and relevant IP issues at stake. Furthermore, to raise the awareness in diverse stakeholder communities about the aims of the Smart-4Fabry project and various activities that will be undertaken is a part of the project from the outset.
This WP is focused on the optimization of the application of the resources, creating an appropriate management framework, linking together all project components, as well as all the technical work among the partners in order to follow-up all the aspects required by the EC.
