High-throughput combinatory drugs testing on in vitro 3D cells model platform

Project Information

SYNEBIO

Grant agreement ID: 101100823

DOI

10.3030/101100823

Project closed

EC signature date 7 October 2022

Start date 1 January 2023

End date 30 June 2024

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

ECOLE SUPERIEURE DE PHYSIQUE ET DECHIMIE INDUSTRIELLES DE LA VILLE DEPARIS
France

Periodic Reporting for period 1 - SYNEBIO (High-throughput combinatory drugs testing on in vitro 3D cells model platform)

Reporting period: 2023-01-01 to 2024-06-30

Summary of the context and overall objectives of the project

The SYNEBIO project, titled "High-throughput combinatory drugs testing on in vitro 3D cells model platform," aims to advance drug testing methodologies by leveraging innovative microfluidic systems. These systems are designed to test drug combinations on cells embedded in 3D hydrogel environments, which better mimic the in vivo conditions of human tissues compared to traditional 2D cell cultures. This approach addresses the critical need for more accurate preclinical drug testing models, which are essential for predicting the efficacy and safety of new treatments in humans.
Traditional 2D cell cultures have been the cornerstone of preclinical drug testing; however, they fall short in replicating the complex 3D architecture of human tissues, leading to discrepancies in drug responses observed in laboratory settings versus clinical trials. The SYNEBIO project seeks to bridge this gap by providing a high-throughput, scalable platform that offers a more realistic tissue environment. This advancement is expected to streamline the drug development process, reduce costs, and ultimately lead to more effective therapies.
The impact of the SYNEBIO project spans scientific, medical, and economic domains:
1. Enhanced Drug Development Efficiency: The platform's ability to perform high-throughput testing of drug combinations in a 3D environment is poised to accelerate the drug development process. By providing more reliable preclinical data, the project aims to reduce the time and resources needed to bring new drugs to market.
2. Improved Drug Efficacy and Safety: Testing drugs in a 3D environment that closely simulates human tissues can lead to better predictions of how drugs will perform in clinical settings. This can minimize the risk of adverse effects and improve the overall efficacy of treatments, particularly for complex diseases such as cancer.
3. Advancements in Cancer Treatment: Initially focused on lung cancer, the platform has the potential to be adapted for other types of cancer and diseases. This adaptability supports the development of personalized medicine approaches, where treatments are tailored to the specific needs of individual patients based on the detailed understanding of drug interactions within a 3D cellular context.
4. Economic and Industrial Benefits: The project supports the creation of a spin-out company, fostering innovation and economic growth. Collaborations with pharmaceutical companies like Sanofi and engagement with potential investors highlight the strong industrial interest and potential for significant commercial impact. The project has already secured additional funding from various sources, further underscoring its potential.

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

Main technical achievements

- Technical and Scientific Breakthroughs: Established a robust protocol for culturing lung cancer cells in 3D hydrogels, accurately simulating in vivo conditions and validating the microfluidic platform for high-throughput drug testing.
- Validation of Microfluidic System: Successfully demonstrated the platform's ability to test drug combinations, identifying effective treatments and drug synergies, significantly contributing to personalized medicine approaches.
- Advanced Image Analysis: Implemented sophisticated image analysis techniques and AI models, enhancing the accuracy of drug efficacy assessments and offering insights into cellular responses at a high resolution.
- Industrialization Readiness: Adapted manufacturing processes for scalability, ensuring the platform's compatibility with industrial standards, which is crucial for commercial application.
- Business and Market Strategy: Engaged extensively with industry experts, potential investors, and academic leaders to align the project's outputs with market needs, paving the way for successful commercialization.

Outcomes of the action

The SYNEBIO project culminated in a validated proof of concept for a high-throughput drug testing platform that leverages 3D cell cultures and microfluidic technology. The project's outcomes include:

- Protocols for using the microfluidic chip and preliminary data validating its effectiveness.
- Scalable methods for creating cell-embedded hydrogels and live cell staining protocols adjusted for microfluidics.
- AI and machine learning models for automatic image analysis and predicting drug responses.
- A microfluidic device compatible with pharmaceutical industry standards, ready for large-scale production.
- A comprehensive business plan, investor deck, and strategic roadmap, positioning the project for future growth and investment.

Overall, the project significantly advanced the field of combinatory drug testing, offering a powerful tool for personalized medicine and enhancing the understanding of drug interactions in complex biological systems .

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 main deliverable of this project was the development of a microfluidic device that enables high-throughput combinatorial drug testing. This device, validated with a proof of concept, demonstrated its suitability for assessing drug combinations on 3D cell cultures. It reaches the maximizes the amount of data obtained per amount of cellular material, in the case of drug synergies characterized by phenotypic screening.
The project also tackled the industrialization feasibility of the microfluidic chip. Transitioning from PDMS to PMMA, a thermoplastic compatible with industrial manufacturing methods, the team successfully adapted the manufacturing process. This shift not only improved compatibility with pharmaceutical industry standards but also increased the throughput of microfluidic chip fabrication by over ten times. This step was crucial for scaling up production and ensuring the technology's readiness for market adoption.

To ensure further uptake and success, several key needs were identified:
1. Further Research: Continued development of AI models and image analysis algorithms to enhance the device's accuracy and efficiency.
2. Demonstration and Validation: Extensive validation studies with diverse cell lines and drug combinations to strengthen the device's credibility and reliability.
3. Access to Markets and Finance: Engaging with potential investors and securing additional funding to support commercialization efforts.
4. Commercialization and IPR Support: Developing a robust business plan and securing intellectual property rights to protect innovations.
5. Internationalization: Expanding collaborations with international partners to broaden the technology's reach and impact.
6. Supportive Regulatory Framework: Navigating regulatory landscapes to ensure compliance and facilitate market entry .

In summary, the SYNEBIO project delivered a groundbreaking microfluidic platform for high-throughput drug testing, achieving results that extend beyond current capabilities. The integration of AI, optimized manufacturing processes, and strategic market insights positioned the project for significant impact in the pharmaceutical industry, paving the way for more effective and personalized cancer treatments.

microfluidic network