RNA - Genetherapys
Spoke 10 - Pre-clinical Development, GMP Manufacturing and Clinical Trials of GTMP

Led by IRCCS Ospedale Pediatrico Bambino Gesù, Spoke 10 coordinates activities related to pre-clinical development, Good Manufacturing Practices (GMP) and clinical trials of Gene Therapy Medicinal Products (GTMPs).

Spoke 10 is built upon the partnership amongst top-level academic and industrial partners with strong expertise in the development of Gene Therapy Medicinal Products (GTMPs). Spoke 10 aims to harness globally recognized scientific and technical expertise to boost the advancement of GTMPs through in-depth in vitro and in vivo investigations into the mechanism of action (MOA), potency, as well as the biodistribution and toxicology properties of these innovative products. In addition, thanks to the availabilities of Good Manufacturing Practices (GMP) approved facilities, the partners will progress the most promising GTMPs towards the production of clinical-grade products and the finalization of Investigational Medicinal Product Dossiers (IMPDs). Spoke 10 leaders will design and submit clinical trials for the early clinical evaluation of at least 3 developed GTMPs to the competent regulatory agency, which will ultimately promote the advancement of the clinical portfolio of gene therapies available for the treatment of patients with oncological, hematological, and genetic disorders.

You might be interested in:

Program Who we are Spoke flagships Cross-spoke activities

PROGRAM

Academia faces a significant hurdle in progressing Gene Therapy Medicinal Products (GTMP) projects toward a clinical application due to the relevant financial, technical, and logistical challenges associated with the process development, scale-up, and manufacturing under the current Good Manufacturing Practice (cGMP). This often leads to the discontinuation of products despite initial proof-of-principle, which results in high costs and prolonged delays for the few projects that do persevere.

Spoke 10 aims to overcome this challenge by capitalizing on the widely recognized scientific and technical expertise within its membership. The goal is to enhance and fully optimize the translation of cutting-edge pre-clinical research into clinical trials for novel GTMPs. To accomplish this objective, Spoke 10 will implement several pilot training projects, chosen strategically for their exemplary significance. Spoke 10 will develop and lead the early clinical testing of innovative chimeric antigen receptor (CAR)-based approaches. Such testing will tackle some of the most clinically relevant unmet medical needs in pediatric hematology/oncology, including T-cell acute lymphoblastic leukemia (T-ALL), B-ALL relapsing after allogeneic stem cell transplantation, acute myeloid leukemia (AML), brain tumors, and severe B-cell mediated autoimmune diseases. Spoke 10 will develop cutting-edge gene therapies to provide a definitive cure to genetic disorders, such as thalassemia, lysosomal storage disorders with bone involvement, metachromatic leukodystrophy, and Stargardt disease. Each of these pilot projects will specifically target key obstacles faced in the field, which aim to demonstrate potential solutions and to facilitate the advancement of GTMPs from pre-clinical research to clinical trials.

Researcher will make use of existing facilities, which will undergo further enhancements and scaling-up to align with the National Center mission. Following an initial phase focused on training and enabling, Research results will be poised to accommodate projects from other Italian Academic Institutions. Additionally, Spoke 10 is deeply committed to establishing and strengthening mutually beneficial collaborations with pharmaceutical and life science biocompanies, including Takis Biotech, IRBM Research Group, InnovaVector, and Performing Beyond Limits (PBL Srl). The companies affiliated to the Spoke will substantially contribute to the activities that will be pursued by the Spoke 10, facilitating the transferability of research results to industry, increasing the value of the intellectual properties (IPs) owned by Italian research centers through the out-licensing of more mature technologies.

These perspectives, coupled with the training of a new generation of scientists, biotechnologists, clinicians, and experts in emerging techniques, will advance Italy’s biotechnology level to attract investors and developers from abroad.

dna structure spoke 10

WHO WE ARE

Consiglio Nazionale delle Ricerche
InnovaVector s.r.l.
IRBM passionate about science
P.B.L. srl
Takis srl
Fondazione Telethon ETS
Fondazione Matilde Tettamanti Menotti De Marchi Onlus
Università degli Studi “G. d’Annunzio” di Chieti-Pescara
Università degli Studi della Campania “Luigi Vanvitelli”
Università degli Studi di Padova
Università Vita-Salute San Raffaele
OSPEDALE PEDIATRICO BAMBINO GESÙ
Chiesi Farmaceutici
Stevanato Group S.p.A
Eurofins BioPharma Product Testing

SPOKE FLAGSHIPS

Each participant possesses the necessary equipment to execute the proposed tasks, and Spoke 10 will harness their synergy across each Work Package (WP). Additionally, Spoke 10 ambitiously intends to adapt existing infrastructures to international standards (Spoke flagships).
The refurbishing of the GMP facility of Ospedale Pediatrico Bambino Gesù (OPBG)/San Raffaele Telethon Institute for Gene Therapy (SR-TIGET)Fondazione Tettamanti will increase its capability. This scale-up of GMP-compatible processes will ensure that innovative drug products can be tested for early-stage clinical trials.

CROSS-SPOKE ACTIVITIES

The strong collaborative efforts of Spoke 7 will provide the development of a comprehensive bioinformatics environment for omics data analysis when cloning vector-transduced cell populations. This work aims to monitor the fate of individual gene-corrected cells in vivo, assess vector integration and, thus, biosafety. The generated drug predictions based on Computational Systems Biology and integrative data analysis offered by Spoke 7 will provide Spoke 10 activities with the computational tools needed to discover novel targets and develop immunotherapeutic approaches.

Spoke 10 expertise and infrastructures will be available across the National Center for Gene Therapy and Drugs based on RNA Technology for the development of clinical grade GTMPs for all Vertical Spokes (1-5).