PRodrug technology for Immunotherapy-priming via patient-friendly at-home MEtronomic dosing

Project Information

PRIME

Grant agreement ID: 101138100

DOI

10.3030/101138100

Project closed

EC signature date 28 September 2023

Start date 1 October 2023

End date 31 March 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

UNIVERSITAETSKLINIKUM AACHEN
Germany

Periodic Reporting for period 1 - PRIME (PRodrug technology for Immunotherapy-priming via patient-friendly at-home MEtronomic dosing)

Reporting period: 2023-10-01 to 2025-03-31

Summary of the context and overall objectives of the project

The PRIME project aimed to overcome the challenges associated with traditional chemo- and immunotherapy approaches and make those more accessible and effective. The main objectives of the project were to assess the technical and commercial feasibility of a modular prodrug technology to enable at-home metronomic dosing of immunogenic drugs for cancer immunotherapy. To this end, we set out to establish a synthetic and formulation strategy to produce a more tolerable immunogenic prodrug platform. Furthermore, we aimed to develop injectable formulations of the prodrugs, and we evaluated the prodrug performance in combination with immunotherapy at different doses in preclinical models. Finally, we also explored the feasibility of different routes of administration (intravenous vs. subcutaneous) of injectable (nano-)formulations, as well as screened competitors’ landscape and explored market opportunities for future commercialization.

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

In order to explore the innovation potential of our prodrug platform technology, and pave the way towards industrial development and commercialization, we aimed to test, optimize, assess and validate the prodrug technology at two levels in parallel: technical and commercial. In brief, at the technical level our activities were focused on the following key aspects: technical and preclinical validation, including synthesis, formulation, tolerability and efficacy assessment in terms of immuno-priming. This also included proof-of-concept of administration feasibility and targeting via different routes of administration, including subcutaneous. Additionally, we also explored further intellectual property foreground and the best route(s) to market, including a clinical and market landscape assessment, as well as potential partner identification.

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)

We have assessed the technical and commercial feasibility of a modular immuno-priming prodrug platform technology for cancer immunotherapy.

At the technical level, we have successfully (i) optimized the synthetic strategy of the prodrug platform, increasing production rate via implementing semi-automatic purification chromatographic methods. We have also (ii) developed injectable formulations to enable safe administration of the prodrug platform in vivo, coupled to both doxorubicin and gemcitabine, as proof-of-concept immunogenic chemotherapeutic drugs, thus showing the versatility and applicability of the platform technology. The different immunogenic prodrugs were effectively formulated in both clinically relevant Cremophor-based solubilizing agents, and into biocompatible, proprietary PEGylated HPMA-based polymeric micelles, resulting in stable injectable formulations. Furthermore, we (iii) have extensively evaluated the preclinical performance of the doxorubicin-based immunogenic prodrug, formulated in Cremophor and into the polymeric micelles, and applied as monotherapy and in combination with immune checkpoint inhibitors in orthotopic and syngeneic breast cancer mouse models. This also included a first evaluation of the feasibility for subcutaneous (pro)drug administration in vivo using the proprietary polymeric micelle formulation, which confirmed efficient targeting of and drug delivery into tumors and lymph nodes, thereby opening opportunities for further research into developing an at-home subcutaneously administrable product for cancer immunotherapy.

At the commercial level, we have (iv) refined the IP landscape, and started preparing foreground IP for the newly developed prodrugs (gemcitabine- and oxalipatin-prodrugs). Finally, together with the help of a consulting company specialized in grants and innovation, we have (v) focused on analyzing the immuno-oncology and immuno-priming clinical and market landscape, including carrying out several interviews to key opinion leaders in the fields of immuno-oncology, as well as to experts in regulatory and drug pricing aspects. Together, this has allowed us to set a plan for further technology transfer evaluation (with the RWTH innovation office) and eventual incorporation of our prodrug platform in clinical trials regimens (with the Center for Translational & Clinical Research, CTCA, in Aachen), as well as towards future commercialization of a potential product based on our platform technology.