Novel advanced encapsulation system for delivery and protection of next-generation cell-based therapies

Project Information

NOAHs-ARK

Grant agreement ID: 957127

DOI

10.3030/957127

Project closed

EC signature date 2 September 2020

Start date 1 October 2020

End date 30 November 2022

Funded under

• INDUSTRIAL LEADERSHIP - Innovation In SMEs

Total cost

No data

EU contribution

€ 102 662,50

Coordinated by

STEMMATTERS, BIOTECNOLOGIA E MEDICIINA REGENERATIVA SA
Portugal

Periodic Reporting for period 1 - NOAHs-ARK (Novel advanced encapsulation system for delivery and protection of next-generation cell-based therapies)

Reporting period: 2020-10-01 to 2022-11-30

Summary of the context and overall objectives of the project

Cell and gene therapies holds tremendous therapeutic promise for patients worldwide and represent a valuable global market opportunity. Still, cell-based therapies present challenges that are fundamentally distinct from traditional small-molecule medicines and are related chiefly to cell retention, engraftment and survival. Minimally invasive cell delivery and improved retention by means of an encapsulation technology is a driver for generating more predictable clinical outcomes with lesser immune rejection in a variety of disease areas such as musculoskeletal, neurological, immunological or metabolic.

Despite of its disruptive breakthrough potential and high market potential, technological challenges across several fronts in translational research and modern medicine has strongly limited the relative success of current approaches. The lack of enabling technologies for cell delivery and retention in areas of considerable need and significant market dimension beckons as a large unmet business opportunity.
Considering its transformational and impactful nature, cell therapy is of strategic importance to Europe. Long-term benefits for European industry and society will result from offering of enabling technologies supporting improved cost effectiveness and performance of cell-based therapies, which are likely to improve patient treatment in areas of high unmet medical need.

The establishment of cell encapsulation platform for cell-based therapies requires an experienced cell therapy expert in-house, with advanced industrial expertise in product development. Stemmatters aims to recruit a specialist supporting expansion of Stemmatters library and supervise development of new candidates for neurological, immunological and metabolic indications. The focus of NOAHs-ARK is to recruit such highly experienced and technically skilled IA for the design, implementation and management of the innovation process envisioned by Stemmatters, namely the development of new generation hydrogels for cell encapsulation.

The project aimed to address the following specific objectives:
Improve its innovation strategy through refinement of market segmentation, implementation of competitive benchmarking and refinement of competitive positioning.
Define therapeutic targets for cell encapsulation technology, by establishing key functional requirements and developing target product profiles for new biomaterial candidates;
Design and implement in vitro studies demonstrating key features and performance of encapsulation technology in target applications;
Design viable and cost-effective manufacturing processes for biomaterials and related cell-based therapies;
Devise by design a product development strategy addressing regulatory and normative requirements.

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

On boarding of each IA at Stemmatters was carried out, and a set of tasks were implemented aimed at providing a comprehensive programme for each IA to ensure integration program, internal training and external training. A thorough external and internal analysis has been conducted. The external analysis focussed on global market trends and competitive landscape. The project allowed for the development of a novel innovation strategy that is currently under implementation at Stemmatters, based on the development of a product platform that is therapeutic agnostic using key chemical entities intended to support formulation development across multiple therapeutic domains. This innovation strategy is based on predefined set of chemical entities that can be used alone or in combination as building blocks to enable advanced therapies. This approach enables Stemmatters to provide targeted solutions for cell delivery and biomaterial-based formulations. This design approach enables a basis for customizing and personalising formulations to distinct final application requirements, and provides synergies between the biomaterial platform and Stemmatters’ R&D and manufacturing services to serve a broad range of potential clients in different therapeutic domains. This strategy is currently under development at Stemmatters with the support of the R&D team and in coordination with all the Stemmatters departments (Business, Financial, Logistics). Despite the sort duration of the project, substantial developments have been attained on what concerns new composition of matter and development of novel protocols for synthesis and characterization of proposed building blocks. In addition, proof of concept studies have demonstrated the applicability and merits of the proposed building blocks for distinct application.

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)

In the proposed innovation strategy, a versatile set of building blocks was developed. In these, functional groups in the parent molecule were targeted by suitable chemical strategies, generating new chemical entities with interesting potential to support formulation development of advanced therapies, which constitute a progress beyond state of the art. During the project, research activity plans were implemented to develop and characterize each building block. Adequate analytical panels were implemented for characterisation of the polymers. Experimental efforts were made to characterise and assess the performance of the new building blocks: STM-228B/STM-234B: a purified version of the parent molecule to be used alone or as a precursor for subsequent modification; STM-236B and STM-237B: a molecule rendering peptide coupling enabling two distinct building blocks with cell-instructive properties and enzyme sensitive domains; STM-229B: a biocompatible, arthroscopically deliverable cell encapsulation matrix endowed with appropriate gelation kinetics and improved tissue adhesiveness; and STM-231B, STM-232B and STM-233B: covalently crosslinkable molecules in the presence of a photoinitiator and light. Based on these building blocks, IA developed an innovation strategy that can be used to address specific needs when formulating advanced therapies. The proposed strategy and established building block are expected to be explored in formulation development projects serving the advanced therapies community, by which Stemmatters will seek to license its intellectual property to other companies in target markets.

Representative 3D hydrogels