Periodic Reporting for period 3 - Cells in Matrix (Cells in Matrix – an innovative 3D model for R&D of Diabetes)
Periodo di rendicontazione: 2022-09-01 al 2023-02-28
The International Diabetes Federation estimates that 537m people worldwide are living with diabetes, or ~10% of adults. Of these, 5-10% have type 1 diabetes mellitus (T1D). The global cost of diabetes and related illnesses is set to double by 2030 to reach €2.3Trillion. Annually, 5-10% of Diabetic patients stop responding to the currently available diabetes drugs. Therefore, there is a constant need for more effective diabetes solutions and medications. One of the main obstacles in developing new diabetes drugs is the poor predictability of the current model systems for the identification of lead compounds during drug discovery. The failure rate of new drugs development is about 90%.
The Cells in Matrix (CIM) Project aims to develop an innovative 3D model for R&D of Diabetes -an Engineered Micro Pancreas (EMP) based on organ-derived 3D scaffold combined with human insulin-producing cells as a novel tool for accelerating and reducing the cost of diabetes drug research and testing.
The project is based on collaboration between Betalin Therapeutics Ltd (BT) and Kugelmeiers (KG) both SME developing 3D cellular model systems. The consortium also includes academic research partners: Technische Universität Dresden (TUD) and University Hospital Zurich (USZ). These research institutes study and develop new diabetes drugs and hence serve as design partners and beta site for the new disruptive approach.
The 3D EMP model developed by this collaborative FTI project mimics the natural human pancreatic insulin secretion and is comprised of two components: (1) a proprietary organ-derived 3D micro-scaffold called Micro-Organ-Matrix (MOM) is developed and manufactured by BT and (2) human insulin-producing islets extracted from cadaveric donors or stem-cell derived beta cells that can be grown in a standardized manner using KUG plate technology. The EMPs in combination with the proprietary plates will serve as a system for efficient screening of existing and newly developed diabetes drugs.
This technology is intended to be used by diabetes research centers, CRO companies and the pharmaceutical industry, it is expected to be cost-effective and enable a long-term culture of human-insulin-secreting cells and better predictability capacity.
The Partners are willing to invest resources and efforts in developing this disruptive new EMP technology that will promote preclinical testing and shorten the bench-to-market time and cost.
The main objectives of this project are to optimize, validate and industrialize the EMP component production, implement EMPs in trials at customer sites in cooperation between the partners and stakeholders, and penetrate commercial markets.
Exploitation and dissemination
The CIM consortium made efforts to disseminate the project's results and findings and raise awareness about the EMP technology and its potential benefits. BT has issued several press releases published in The Guardian, The Jerusalem post, and also in social media such as LinkedIn and YouTube. The newly aired website of Betalin Therapeutics also describes the technology and future endeavors. An internal conference was organized in Betalin to expose potential investors, potential pharma collaborators and opinion makers to our technology. Scientific papers were published in peer-reviewed journals: Nature Reviews Endocrinology, Cell Death & Disease and Xenotransplantation.
CiM project resulted in two potential products
1- Betalin MOMs based product combined with insulin-producing cells as a research tool (as well as a bio implant for the treatment of diabetic patients).
2- Kugelmeier’s SP5D based product
The high-throughput Sphericalplate 5D, allowing to generate uniform, size-controlled cell clusters at high numbers and clinical quality. The microwell structure enables mass production of the cells.
Feedback and input received during Cells in Matrix from possible users (academia, industry, pharma) confirmed demand for such a product. The outcomes of the CIM project will enable consistent planning of preclinical diabetic R&D and provide higher prediction reliability. The product is expected to accelerate and reduce the costs of research and drug development.
The Cells in Matrix (CIM) Project aims to develop an innovative 3D model for R&D of Diabetes -an Engineered Micro Pancreas (EMP) based on organ-derived 3D scaffold combined with human insulin-producing cells as a novel tool for accelerating and reducing the cost of diabetes drug research and testing.
The project is based on collaboration between Betalin Therapeutics Ltd (BT) and Kugelmeiers (KG) both SME developing 3D cellular model systems. The consortium also includes academic research partners: Technische Universität Dresden (TUD) and University Hospital Zurich (USZ). These research institutes study and develop new diabetes drugs and hence serve as design partners and beta site for the new disruptive approach.
The 3D EMP model developed by this collaborative FTI project mimics the natural human pancreatic insulin secretion and is comprised of two components: (1) a proprietary organ-derived 3D micro-scaffold called Micro-Organ-Matrix (MOM) is developed and manufactured by BT and (2) human insulin-producing islets extracted from cadaveric donors or stem-cell derived beta cells that can be grown in a standardized manner using KUG plate technology. The EMPs in combination with the proprietary plates will serve as a system for efficient screening of existing and newly developed diabetes drugs.
This technology is intended to be used by diabetes research centers, CRO companies and the pharmaceutical industry, it is expected to be cost-effective and enable a long-term culture of human-insulin-secreting cells and better predictability capacity.
The Partners are willing to invest resources and efforts in developing this disruptive new EMP technology that will promote preclinical testing and shorten the bench-to-market time and cost.
The main objectives of this project are to optimize, validate and industrialize the EMP component production, implement EMPs in trials at customer sites in cooperation between the partners and stakeholders, and penetrate commercial markets.
Exploitation and dissemination
The CIM consortium made efforts to disseminate the project's results and findings and raise awareness about the EMP technology and its potential benefits. BT has issued several press releases published in The Guardian, The Jerusalem post, and also in social media such as LinkedIn and YouTube. The newly aired website of Betalin Therapeutics also describes the technology and future endeavors. An internal conference was organized in Betalin to expose potential investors, potential pharma collaborators and opinion makers to our technology. Scientific papers were published in peer-reviewed journals: Nature Reviews Endocrinology, Cell Death & Disease and Xenotransplantation.
CiM project resulted in two potential products
1- Betalin MOMs based product combined with insulin-producing cells as a research tool (as well as a bio implant for the treatment of diabetic patients).
2- Kugelmeier’s SP5D based product
The high-throughput Sphericalplate 5D, allowing to generate uniform, size-controlled cell clusters at high numbers and clinical quality. The microwell structure enables mass production of the cells.
Feedback and input received during Cells in Matrix from possible users (academia, industry, pharma) confirmed demand for such a product. The outcomes of the CIM project will enable consistent planning of preclinical diabetic R&D and provide higher prediction reliability. The product is expected to accelerate and reduce the costs of research and drug development.
The primary objectives of the project were to address various challenges in the project, including the industrial adaptation of the MOM (scaffold production), establishing a clear path for accessing human insulin secreting cells for research purposes, optimizing the production of the Engineered Micro Pancreas (EMP), and enhancing the company's understanding of the market landscape and the positioning of the Cell in Matrix (CiM) within that landscape.
During P1, the development team accomplished the following:
• Developed an industrial manufacturing process for the MOM scaffold.
• Established a standard process for preparing islets and defined specific release criteria for islets to be used with the scaffold.
• Assessed automation capabilities by examining current market solutions and evaluating potential options that could be suitable for the product.
• Identified suitable suppliers for human islets and devised a plan to determine optimal shipment conditions.
• Explored alternative sources of beta cells and conducted feasibility studies with these cells.
In addition, during the first phase of this project, the consortium has established a detailed plan and study with the aim to deliver an improved method for human islets transportation around the world will benefit the entire islets community and resolve problems that many in the field are faced with.
In P2&P3, the development team achieved the following:
• Completed product optimization, including optimizing product components and commencing product manufacturing.
• Defined testing protocols and prepared samples for validation testing.
• Obtained authorization for importing a specific tissue derived from porcine for testing the MOMs with Islets at the partner's labs (since Islets cannot be shipped).
During P1, the development team accomplished the following:
• Developed an industrial manufacturing process for the MOM scaffold.
• Established a standard process for preparing islets and defined specific release criteria for islets to be used with the scaffold.
• Assessed automation capabilities by examining current market solutions and evaluating potential options that could be suitable for the product.
• Identified suitable suppliers for human islets and devised a plan to determine optimal shipment conditions.
• Explored alternative sources of beta cells and conducted feasibility studies with these cells.
In addition, during the first phase of this project, the consortium has established a detailed plan and study with the aim to deliver an improved method for human islets transportation around the world will benefit the entire islets community and resolve problems that many in the field are faced with.
In P2&P3, the development team achieved the following:
• Completed product optimization, including optimizing product components and commencing product manufacturing.
• Defined testing protocols and prepared samples for validation testing.
• Obtained authorization for importing a specific tissue derived from porcine for testing the MOMs with Islets at the partner's labs (since Islets cannot be shipped).
Encountering and handling the technological challenges along the development process produced extra value in several aspects: the problem of islets unavailability drove the team to look for alternatives that we now realize as superior to the initial use of cadaveric human islets. We started incorporating into the MOMs stem-cell derived beta cells which offer an unlimited source for insulin-secreting cells, with very good results. This may contribute to reducing the price of the product for either research or clinical use. Also, working with other non-pancreatic endocrine cells opened up new potential applications for studying diseases other than diabetes, so wider populations and research areas can benefit from this technology. In parallel, the standardization of cells grown as spheroids, which was enabled by the SP5D plates, holds extra value for research areas such as cancer research and regenerative cell therapy. Indeed, BT served as a beta site for the plate technology and experimented spheroid formation and culture of stem cell-derived beta cells using the SP5D plates, with promising results. Altogether, the collaborative efforts by all partners extended the usefulness of the developed technologies to broad areas of translational research which will benefit the European and the global society.