Periodic Reporting for period 1 - IMMUTOL (ADVANCED ANTIGEN-SPECIFIC DENDRITIC CELL-BASED THERAPY TO RE-ESTABLISH TOLERANCE IN IMMUNE-MEDIATED DISEASES)
Reporting period: 2023-05-01 to 2024-10-31
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, often diagnosed in people (mostly women) aged 20 to 40, leading to increasing disability and greatly reducing the quality of life for patients. The introduction of a broad range of anti-inflammatory and immunosuppressive drugs improves disease control, but these treatments must be given life-long and are not devoid of adverse effects.
Therefore, there is a significant and unmet medical need for safe and effective new therapies for MS that target the cause of the disease to reduce the duration and frequency of treatments as well as limit side effects. Innovative therapies based on the infusion of a specialized subset of immune cells, named tolerogenic DC, have been recently tested in patients with active forms of MS, showing that the treatment is feasible, safe, and well tolerated with no side effects.
With the goal of improving the curative efficacy of tolerogenic DC in MS, IMMUTOL aims to develop a second generation of tolerogenic DC product by applying artificial intelligence to predict and optimize the quality of the product; by optimizing the generation of the advanced product and characterize its activity in vitro and in vivo; by optimizing the protocol for the manufacturing of the product. All these activities are guided by a regulatory roadmap continuously assessed by regulatory bodies and patients and by building a business plan to guarantee the advanced product's commercial application.
IMMUTOL will develop a more potent and durable treatment for autoimmune diseases with an unmet medical need, in particular MS, and will pave the way for new tolerogenic cell-based therapies to cure/reverse several autoimmune conditions.
Therefore, there is a significant and unmet medical need for safe and effective new therapies for MS that target the cause of the disease to reduce the duration and frequency of treatments as well as limit side effects. Innovative therapies based on the infusion of a specialized subset of immune cells, named tolerogenic DC, have been recently tested in patients with active forms of MS, showing that the treatment is feasible, safe, and well tolerated with no side effects.
With the goal of improving the curative efficacy of tolerogenic DC in MS, IMMUTOL aims to develop a second generation of tolerogenic DC product by applying artificial intelligence to predict and optimize the quality of the product; by optimizing the generation of the advanced product and characterize its activity in vitro and in vivo; by optimizing the protocol for the manufacturing of the product. All these activities are guided by a regulatory roadmap continuously assessed by regulatory bodies and patients and by building a business plan to guarantee the advanced product's commercial application.
IMMUTOL will develop a more potent and durable treatment for autoimmune diseases with an unmet medical need, in particular MS, and will pave the way for new tolerogenic cell-based therapies to cure/reverse several autoimmune conditions.
In the first 18 months, progress has been made in the establishment of assays to detect the conversion of T cells to regulatory T cells (Tr1/Treg), in the identification of deficiency in MS monocytes, in standardizing flow cytometry measurements using a novel computational approach, in defining the protocol for the differentiation of the advanced product. Characterization of the advanced product's functional properties and the screening of peptides able to elicit a T cell response in MS patients have also been performed. The in vitro assays to assess the impact on B cell responses, the migratory ability, and the optimal in vivo pre-clinical model of EAE suitable for dissecting the efficacy and mode-of-action of the advanced product have been implemented.
A Regulatory Road Map for the advanced product provides preliminary regulatory, chemistry, manufacturing, and controls, preclinical, and clinical requirements to design a clinical protocol according to the regulatory requirements for the first-in-human (FIH) application of the advanced product in MS patients has been prepared
The economic assessment indicated that relapsing-remitting multiple sclerosis (RRMS) is the primary target indication for the advanced product therapy based on its high unmet medical need and suitable regulatory pathways.
A Regulatory Road Map for the advanced product provides preliminary regulatory, chemistry, manufacturing, and controls, preclinical, and clinical requirements to design a clinical protocol according to the regulatory requirements for the first-in-human (FIH) application of the advanced product in MS patients has been prepared
The economic assessment indicated that relapsing-remitting multiple sclerosis (RRMS) is the primary target indication for the advanced product therapy based on its high unmet medical need and suitable regulatory pathways.
Results obtained thus far indicate that the advanced product is superior, at least in vitro, to the original product in terms of tolerogenic potential and ability to promote regulatory T cells, the long-lasting arm to restore and maintain tolerance in vivo. Further research is required to identify the most suitable peptide to be used to generate vectors to engineered DC. In case no specific peptide is identified, additional experiments have already been conducted to validate the Ag-pulsing of the advanced product.
In the remaining period, IMMUTOL will demonstrate the efficacy and mode of action of the advanced product and prepare all the required information to design an interventional clinical study.
To ensure sustainable therapeutic agent production and uptake by health systems and rapid access to patients, a robust regulatory and Health Technology Assessment (HTA) strategy has been in place from the start of the proposal, which supports the selection of target indications/populations, develop target product profiles for the selected indications, and create health economic models and Net Present Value of the development project.
In the remaining period, IMMUTOL will demonstrate the efficacy and mode of action of the advanced product and prepare all the required information to design an interventional clinical study.
To ensure sustainable therapeutic agent production and uptake by health systems and rapid access to patients, a robust regulatory and Health Technology Assessment (HTA) strategy has been in place from the start of the proposal, which supports the selection of target indications/populations, develop target product profiles for the selected indications, and create health economic models and Net Present Value of the development project.