Preclinical development of a nanomedicine candidate for Fabry rare disease treatment to enter clinical phase

Project Information

Nano4Rare

Grant agreement ID: 101136772

DOI

10.3030/101136772

EC signature date 27 September 2023

Start date 1 November 2023

End date 31 October 2026

Funded under

• The European Innovation Council (EIC)

Total cost

€ 2 498 563,75

EU contribution

€ 2 498 563,75

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 1 - Nano4Rare (Preclinical development of a nanomedicine candidate for Fabry rare disease treatment to enter clinical phase)

Reporting period: 2023-11-01 to 2024-10-31

Summary of the context and overall objectives of the project

Despite the development of new orphan medicines in recent years, there are still limited treatment options available for rare diseases. Nano4Rare team has developed a patent protected nanoencapsulation KET for the development of cost-effective therapies for rare diseases, based on biomolecules. Nano4Rare team has successfully used this technology for the development of a new patent protected medicinal product candidate, named nanoGLA, for the treatment of Fabry disease, which is one of the most devasting LSD rare diseases. NanoGLA has been designated, on January 2021, as Orphan Drug by the European Medicine Agency (EMA) and the European Comission. With the Smart4Fabry EU project (#720942), nanoGLA was brought to an advanced stage of preclinical development (first GLP toxicology in rats included). Under Phoenix EU Project (#953110)(2021-2025), nanoGLA production will be scaled-up and brought to GMP conditions. As a first objective, Nano4Rare project will use nanoGLA engineered batches produced in the frame of Phoenix project to complete the preclinical phase and generate sufficient quality data on safety, efficacy, and quality in order to get approval by regulators to proceed with clinical phase. As a second objective, a new spin-off company will be created for the advancement of the nanoGLA towards the market and the commercialisation of the patent-protected nanoencapsulation platform to generate new product candidates for rare disease treatments.
Overall, the objective of Nano4Rare is to advance the nanoGLA up to TRL5/6, getting closer to clinical phases and benefitting Fabry patients with an improved treatment. During this first reporting period we have worked to advance in that direction. The development of a new effective treatment is necessary to improve patients' quality of life and reduce premature deaths, impacting not only on patients but also to society.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Substantial progress has been achieved in the preclinical studies aimed at advancing the nanoGLA formulation towards market readiness. Ongoing efforts are focused on conducting comprehensive stability studies to assess the robustness, reproducibility, and long-term performance of the nanoformulation (nanoGLA). These studies are essential to ensure the formulation’s stability under different storage and handling conditions, supporting its scalability and regulatory compliance.
Simultaneously, preclinical assays are being conducted in the first animal species, rodents. These studies are designed to evaluate the safety profile, pharmacokinetics, and efficacy of the nanoGLA formulation. Importantly, this phase is critical to gather the data required before progressing to studies in a second, non-rodent species. The results will provide essential insights into the formulation's behavior in vivo and will inform subsequent development phases, including dose optimization and regulatory submissions.
Together, these activities represent key milestones in the translational development of nanoGLA and bring the project closer to achieving its ultimate goal of delivering a novel therapeutic solution for the treatment of Fabry disease.

The spin-off company Delbios Pharmaceuticals SL has been created. It will be key for the transfer of the nanoGLA medicinal product to the clinical phase and the commercialization of the nanoencapsulation platform.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The development of the nanoGLA formulation represents a significant advancement beyond the current state of the art in the treatment of Fabry disease. One of the most important milestones achieved so far is the demonstration that nanoGLA is capable of crossing the blood-brain barrier and reaching the brain. This is a critical breakthrough, as existing therapies for Fabry disease fail to effectively target and treat neurological manifestations of the disease.
Fabry disease can lead to severe neurological complications, including strokes and cognitive impairment, which are not adequately addressed by current enzyme replacement therapies. The ability of nanoGLA to reach the brain opens up new possibilities for improving patient outcomes by addressing both systemic and neurological symptoms.
If further studies confirm that nanoGLA meets all the necessary safety, efficacy, and regulatory requirements to reach the market, it could become a superior therapeutic option compared to existing treatments. This advancement not only has the potential to improve the quality of life of patients but also represents a major step forward in the treatment of other lysosomal storage disorders.
These promising results have been recently published in the high-impact journal Science Advances (DOI: 10.1126/sciadv.adq4738) highlighting the innovative nature and transformative potential of the nanoGLA formulation.

Representative Image of Nano4Rare