Periodic Reporting for period 1 - ASTEROID (Multi-organ toxicity and efficacy test platform for Personalized medicine & Drug development)
Berichtszeitraum: 2024-09-02 bis 2025-09-01
BOTH HOSPITAL AND PHARMA NEED MORE PREDICTIVE MODELS FOR ASSESSING DRUG’S EFFECTS: There is a strong demand in the pharmaceutical and medical fields for more predictive models of the effect of drugs on patients. On the one hand, the pharmaceutical industry needs to replace animal tests and improve the human predictability of preclinical models (huge drug development attrition rate) to avoid unnecessary animal suffering and reduce overall drug development times and costs.
Numerous publications as well as feedback from the pharmaceutical industry and hospitals, show that organ-on-a-chip technology has become the preferred avenue of exploration for solving human drug effect prediction challenges. Indeed, thanks to their physio mimetic capabilities, these models are today the most capable of providing data as close as possible to human physiology.
However, despite several promising results, none of the existing and under-development technologies, has yet achieved the physio mimetic level required by hospital and pharmaceutical players to be sufficiently confident in the adoption and use of these new technologies.
Our joint work with pharmaceutical and hospital KOLs, has enabled us to identify 3 Scientific and 2 critical industrial problems in existing 3D culture systems, explaining the low adoption rate that can be summarized in the need for more complex biological feature, and industrial workflow integration.
This project is aiming at induystrializing our 3 propretary technology in the field of Microphysiological Systems (MPS) as well as to provide a validated protocol database to help industrial to standardized their protocols as well as improving the reproducibility of the results.
Our MPS, named CubiX, is able to precisely control the microenvironment of complex 3D cell culture (organoids) in a precise and dynamic manner. We have proved that the level of organoids complexity enable by our technologies is allowing to have an improved predictability of a drug effect on human.
IMPACT: Offering a truly predictive model of the effect of drugs will also have a high impact on the sustainable Development Goals defined by United Nation: Good human health, animal welfare, UE technological innovation, decent work and economic growth and contribute to gender equality.
REGULATION CONTEXT: Recent changes in European and American regulations, such as the FDA modernization act 2.0 of 2022, FDA modernisation act 3.0 in Dec 2024, the NIH phase out roadmap in February 2025 and the expecting European Commission phase out roadmap in March 2026 are strongly pushing toward a drastic reduction in the animal use for scientific purpose, and strongly encouraging the use of alternative technology such as the one developed by Cherry Biotech.
Numerous publications as well as feedback from the pharmaceutical industry and hospitals, show that organ-on-a-chip technology has become the preferred avenue of exploration for solving human drug effect prediction challenges. Indeed, thanks to their physio mimetic capabilities, these models are today the most capable of providing data as close as possible to human physiology.
However, despite several promising results, none of the existing and under-development technologies, has yet achieved the physio mimetic level required by hospital and pharmaceutical players to be sufficiently confident in the adoption and use of these new technologies.
Our joint work with pharmaceutical and hospital KOLs, has enabled us to identify 3 Scientific and 2 critical industrial problems in existing 3D culture systems, explaining the low adoption rate that can be summarized in the need for more complex biological feature, and industrial workflow integration.
This project is aiming at induystrializing our 3 propretary technology in the field of Microphysiological Systems (MPS) as well as to provide a validated protocol database to help industrial to standardized their protocols as well as improving the reproducibility of the results.
Our MPS, named CubiX, is able to precisely control the microenvironment of complex 3D cell culture (organoids) in a precise and dynamic manner. We have proved that the level of organoids complexity enable by our technologies is allowing to have an improved predictability of a drug effect on human.
IMPACT: Offering a truly predictive model of the effect of drugs will also have a high impact on the sustainable Development Goals defined by United Nation: Good human health, animal welfare, UE technological innovation, decent work and economic growth and contribute to gender equality.
REGULATION CONTEXT: Recent changes in European and American regulations, such as the FDA modernization act 2.0 of 2022, FDA modernisation act 3.0 in Dec 2024, the NIH phase out roadmap in February 2025 and the expecting European Commission phase out roadmap in March 2026 are strongly pushing toward a drastic reduction in the animal use for scientific purpose, and strongly encouraging the use of alternative technology such as the one developed by Cherry Biotech.
During the first 12 month of the project advancement is as follow:
WP1: Final design CubiX RUO (TRL7)
- Software update, and deployment on docker made, ready for production scale-up and overtime maintenance of the CubiX fleet Deployment in the CubiX Platform ongoing
- Code is properly documented, hosted on GitLab. Code coverage is increasing TRL7
- MPL and Cherry BioApp Store API made, ensuring together with Docker a Continuous Integration Continuous development
- Hardware modularity is implemented for 2 out of the 3 main components
- Fluidic circuit standardization and simplification for a better user experience and robustness of the results
- Production standardization and quality fit to anticipate scale up, QMS implementation, design freeze and support the TRL increase up to 7
- Compliance with RUO applicable regulation is initiated and considered in all development steps
- MPL different design validated by users (TRL7) for specific fit for purpose (Air liquid interface, high shear stress, organoid)
WP2: Development of RUO organ model kits
- Validated protocol for DIVI, Adipose organoids from SVF & Luminal B Breast Cancer Patient Derived Organoids
- Validation made by customers based on their selected readouts
- 2 Protocols already included in the Cherry Bio App store
- More declinations of each model are upcoming
WP3: Project management and administration
- Monthly follow up set up and running
- Identification of risks and mitigation during monthly advancement meeting with the team
- Anticipation of post EIC accelerator financing needs
- Maintenance and growing team for Cherry Biotech
WP1: Final design CubiX RUO (TRL7)
- Software update, and deployment on docker made, ready for production scale-up and overtime maintenance of the CubiX fleet Deployment in the CubiX Platform ongoing
- Code is properly documented, hosted on GitLab. Code coverage is increasing TRL7
- MPL and Cherry BioApp Store API made, ensuring together with Docker a Continuous Integration Continuous development
- Hardware modularity is implemented for 2 out of the 3 main components
- Fluidic circuit standardization and simplification for a better user experience and robustness of the results
- Production standardization and quality fit to anticipate scale up, QMS implementation, design freeze and support the TRL increase up to 7
- Compliance with RUO applicable regulation is initiated and considered in all development steps
- MPL different design validated by users (TRL7) for specific fit for purpose (Air liquid interface, high shear stress, organoid)
WP2: Development of RUO organ model kits
- Validated protocol for DIVI, Adipose organoids from SVF & Luminal B Breast Cancer Patient Derived Organoids
- Validation made by customers based on their selected readouts
- 2 Protocols already included in the Cherry Bio App store
- More declinations of each model are upcoming
WP3: Project management and administration
- Monthly follow up set up and running
- Identification of risks and mitigation during monthly advancement meeting with the team
- Anticipation of post EIC accelerator financing needs
- Maintenance and growing team for Cherry Biotech
The first beyond state-of-the-art result is on the maintenance of human mature adipose tissue organoids, with physiological stem cell differentiation over 28 days.
Aim of the study:
1) Maintained human fresh mature adipocytes in culture (single lipid droplet
2) Add a functional vascular interface
Results:
1) Mature human adipocytes obtained from tissue culture and after tissue dissociation with unilocular mature adipocytes
2) Vascular network (neo-angiogenesis) obtained from SVF + pre-adipocytes
3) 28 days of culture
Beyond-state-of-the-art:
1) Neo-angiogenesis obtained in 9days with a growing vascular network
2) Live imaging follow-up of the culture
3) Small volume (5mL) of dilution, preventing the need of a high compound quantity per test
4) Primary cell from dissociated fresh tissue (high physiological relevance)
The second beyond state-of-the-art result is on the prediction of clinical outcomes of a breast cancer patient using Patient Derived Organoids:
Aim of the study:
1) Cultivating patient-derived organoids of Luminal B breast cancer
2) Re-creating the tumor microenvironment
3) Assess the efficacy of treatments that have been administered to the patient
Results:
1) Luminal B tumor cells from aptient in their microenvironment (Cancer Associated Fibroblast, endothelial cells, macrophages, extra cellular matrix) has been maintained for >7 days
2) Patient treatments have been tested
Beyond stats-of-the-art:
1) We have replicate the clinical outcomes of the patient response to the administered treatment in a retrospective study (efficacy and a resistance in a second step)
2) We have been able to explain a possible mechanism underlying the resistance
Aim of the study:
1) Maintained human fresh mature adipocytes in culture (single lipid droplet
2) Add a functional vascular interface
Results:
1) Mature human adipocytes obtained from tissue culture and after tissue dissociation with unilocular mature adipocytes
2) Vascular network (neo-angiogenesis) obtained from SVF + pre-adipocytes
3) 28 days of culture
Beyond-state-of-the-art:
1) Neo-angiogenesis obtained in 9days with a growing vascular network
2) Live imaging follow-up of the culture
3) Small volume (5mL) of dilution, preventing the need of a high compound quantity per test
4) Primary cell from dissociated fresh tissue (high physiological relevance)
The second beyond state-of-the-art result is on the prediction of clinical outcomes of a breast cancer patient using Patient Derived Organoids:
Aim of the study:
1) Cultivating patient-derived organoids of Luminal B breast cancer
2) Re-creating the tumor microenvironment
3) Assess the efficacy of treatments that have been administered to the patient
Results:
1) Luminal B tumor cells from aptient in their microenvironment (Cancer Associated Fibroblast, endothelial cells, macrophages, extra cellular matrix) has been maintained for >7 days
2) Patient treatments have been tested
Beyond stats-of-the-art:
1) We have replicate the clinical outcomes of the patient response to the administered treatment in a retrospective study (efficacy and a resistance in a second step)
2) We have been able to explain a possible mechanism underlying the resistance