Periodic Reporting for period 1 - TraffikGene-Tx (TraffikGene-Tx: Targeted Peptide Carriers for RNA Delivery)
Reporting period: 2023-06-01 to 2024-05-31
Rare and complex genetic diseases lead to significant disability, death and associated cost burdens for society. Complex genetic diseases include cardiovascular diseases and cancer, the two leading causes of death in the EU, and rare genetic diseases, which affect up to 36 million Europeans. Nucleic acid therapeutics represent a potential treatment, but they are hampered by the “delivery problem.” Systemically administered naked RNA is quickly degraded by endonucleases, can provoke adverse immune reactions and has off-target toxicity. Viral and lipid nanoparticle delivery vectors have toxic side-effects and are difficult to produce and target to specific tissues.
TraffikGene-Tx’s delivery platform is an alternative based on small peptide carriers that can be easily conjugated with hydrophobic tails. The peptides used are safe, as they are biodegradable, non-immunogenic and are rapidly cleaved in cells, avoiding the detergent effect of lipid nanoparticle components. In contrast to classical lipid nanoparticles, which typically accumulate in the liver, these compounds have shown targeting to other organs such as spleen, with excellent delivery to the cytosol. Their production is simple, cheap, and can be automated. The modular design and the possibility for high-throughput screening allows the collection of big amounts of data that can be used to develop a predictive model and facilitate the design of future carriers with the optimal delivery properties for a given function, accelerating the development of new carriers.
TraffikGene-Tx capitalises on the current breakthroughs in healthcare represented by nucleic acid therapeutics. RNA-based therapeutics are now emerging driven by the success of mRNA vaccines and TraffikGene-Tx aims to deliver them to the tissues where they are needed, breaking new ground in the field of RNA. Our objective is to validate our delivery vehicles in industrially and regulatory relevant contexts and start developing our pipeline to advance to the preclinical trial stage with therapeutic RNAs, with the goal of launching a company that will develop both and internal and external therapeutic pipelines. Our products will contribute to bring many promising nucleic acid therapeutics to the market, and help millions of patients, while reducing health care costs.
TraffikGene-Tx’s delivery platform is an alternative based on small peptide carriers that can be easily conjugated with hydrophobic tails. The peptides used are safe, as they are biodegradable, non-immunogenic and are rapidly cleaved in cells, avoiding the detergent effect of lipid nanoparticle components. In contrast to classical lipid nanoparticles, which typically accumulate in the liver, these compounds have shown targeting to other organs such as spleen, with excellent delivery to the cytosol. Their production is simple, cheap, and can be automated. The modular design and the possibility for high-throughput screening allows the collection of big amounts of data that can be used to develop a predictive model and facilitate the design of future carriers with the optimal delivery properties for a given function, accelerating the development of new carriers.
TraffikGene-Tx capitalises on the current breakthroughs in healthcare represented by nucleic acid therapeutics. RNA-based therapeutics are now emerging driven by the success of mRNA vaccines and TraffikGene-Tx aims to deliver them to the tissues where they are needed, breaking new ground in the field of RNA. Our objective is to validate our delivery vehicles in industrially and regulatory relevant contexts and start developing our pipeline to advance to the preclinical trial stage with therapeutic RNAs, with the goal of launching a company that will develop both and internal and external therapeutic pipelines. Our products will contribute to bring many promising nucleic acid therapeutics to the market, and help millions of patients, while reducing health care costs.
In the context of TraffikGene-Tx, it is highly relevant to establish a strong Chemistry, Manufacturing and Control (CMC) package early on to provide a solid foundation in our efforts to develop new advanced therapeutics. In this sense, we have focused on pushing forward one of our most promising candidates, TG1, for which we have already achieved therapeutic proof of concept data in vivo. We are currently scaling-up its production under GMP-like conditions, including the development of a throrough analytical package, which is being done in collaboration with a qualified industrial CDMO partner. In a further effort towards the standardization of our technical development activities, we are also exploring different methods for the formulation and production of mRNA-loaded particles of defined size. We have developed SOPs for critical processes in the project and we are currently working on formulation QC procedures.
We have expanded the peptide library with new compounds, and we will explore their targeting properties in the near future, to identify new carriers with affinity to other organs. Regarding the rational design of novel carriers, we have recently contacted an expert for machine-learning analysis of the previously acquired data to develop a predictive structure-activity relationship model.
We have also investigated the safety and efficacy of TG1-based formulations in mice. Using reporter genes, the efficiency of delivery and the expression kinetics after administration via different routes was explored, showing activity in all of them. In addition, we studied the effect of multiple administrations, observing no activity loss nor the development of antibodies against the formulation. We are currently studying the effect of the formulation in cytokine induction and the type of immune response developed. The efficacy of the formulation as a cancer vaccine was assayed on a preclinical cancer model, with some of the formulations tested showing the ability to reduce tumour growth and increase survival in mice.
We have expanded the peptide library with new compounds, and we will explore their targeting properties in the near future, to identify new carriers with affinity to other organs. Regarding the rational design of novel carriers, we have recently contacted an expert for machine-learning analysis of the previously acquired data to develop a predictive structure-activity relationship model.
We have also investigated the safety and efficacy of TG1-based formulations in mice. Using reporter genes, the efficiency of delivery and the expression kinetics after administration via different routes was explored, showing activity in all of them. In addition, we studied the effect of multiple administrations, observing no activity loss nor the development of antibodies against the formulation. We are currently studying the effect of the formulation in cytokine induction and the type of immune response developed. The efficacy of the formulation as a cancer vaccine was assayed on a preclinical cancer model, with some of the formulations tested showing the ability to reduce tumour growth and increase survival in mice.
TraffikGene-Tx aims to facilitate the development of new nucleic acid therapeutics by solving the delivery problem. This enabling technology will contribute to a new generation of nucleic acid therapeutics reaching the market, both through the development of an internal pipeline and by making the delivery system available through licensing. The new therapeutics will have an impact on patient health and health economics.
At the beginning of the project, the technology was at TRL3-4, with the objective of reaching TRL5-6 at the end of the project. Regarding IP, the patent of the technology was extended to PCT and to Taiwan and the trademarks for the name and logo were registered. From the scientific point of view, we have progressed during the first year of the project, with the advances in the formulation and the encouraging results of the preclinical mouse model, but succeeding in having a therapeutic candidate validated for clinical trials will require further work. Some key milestones include the definition of the Drug Development Plan, by establishing a regulatory roadmap (currently in the works), and meeting with regulatory agencies for advice; the completion of the GLP-Tox study and the preparation of a pitch presentation and a business plan to attract investors, as well as the establishment of a spin-off company.
At the beginning of the project, the technology was at TRL3-4, with the objective of reaching TRL5-6 at the end of the project. Regarding IP, the patent of the technology was extended to PCT and to Taiwan and the trademarks for the name and logo were registered. From the scientific point of view, we have progressed during the first year of the project, with the advances in the formulation and the encouraging results of the preclinical mouse model, but succeeding in having a therapeutic candidate validated for clinical trials will require further work. Some key milestones include the definition of the Drug Development Plan, by establishing a regulatory roadmap (currently in the works), and meeting with regulatory agencies for advice; the completion of the GLP-Tox study and the preparation of a pitch presentation and a business plan to attract investors, as well as the establishment of a spin-off company.