Periodic Reporting for period 3 - PRECIOUS (Scaling-up biodegradable nanomedicines for multimodal for multimodal precision cancer immunotherapy)
Reporting period: 2018-11-01 to 2020-04-30
Despite the access to different classical treatment strategies such as chemotherapy, radiotherapy and surgery, cancer is still a leading cause of death worldwide accounting for over 9.6 million deaths per year. Often, tumour cells that have become resistant to chemo- and radiotherapy ultimately lead to the death of a patient. Therefore, radically innovative approaches are highly needed to increase survival rates. In the past 5 years, immunotherapy has completely overhauled the cancer field with several new types of therapies entering the market at a rapid pace. The great benefit of immunotherapy is that it attacks tumour cells via a completely different mechanism than chemo- and radiotherapy, harnessing the power of the body’s own immune system to fight cancer. However, current immunotherapies are challenged by low efficacy, partially due to the immunosuppressive tumour micro-environment.
The PRECIOUS project will establish a platform for the development of new medicines that contain immunomodulating components acting at multiple levels. Nanoparticles offer the optimal platform for a combinational immunotherapy, as they are able to encapsulate immunomodulators in biodegradable particles. Currently, immunomodulating nanomedicines are not used to their full potential due to is challenging manufacturing requirements. PRECIOUS will develop a manufacturing process at industrial scale for immunomodulating nanomedicines and test the potential of these nanoparticle-based immunotherapies in the clinic. To ensure that these novel treatment strategies will reach patients, a first in human clinical study will be carried out, as well as the development of a marketing and commercialisation strategy for these novel medicines is an important part of the project. Together, PRECIOUS will realize a major improvement in cancer therapy to provide cancer patients with enhanced quality of life.
To achieve this, a platform is formed with 6 leading industrial partners to produce large scale GMP nanomedicines and an excellent immunomodulator track record, together with 5 renowned academic partners to perform clinical studies.
In WP2, toxicity/efficacy of (A) lead and (B) next-generation PLGA is pre-clinically validated. The mice models have been studied extensively by various partners for Pharmacokinetic and Pharmacodynamics (PK/PD) of PLGA- and conjugate particles in vivo. Also, a tox study has been carried out with the PLGA particles produced for the clinical study to determine any adverse effects.
WP3 is to optimise manufacturing process for production of PLGA particles. During this project this manufacturing process will be further optimised from small laboratory scale towards industrial scale GMP production of complex nanoparticles. So far, a manufacturing protocol for the production of a large scale GMP batch of PLGA nanoparticles was established. Additionally, a series of quality control tests were also performed to assess the functioning of the PLGA molecules. A GMP production pipeline was set up at RUMC and three clinical batches have been produced.
WP4 entails the development and management of clinical trial files. We have progressed significantly, and all the documents have been submitted to the respective regulatory authorities for approval (see deliverable 4.1). A delay in approval has been caused here due to the coronavirus pandemic, which stopped/delayed all processes at RUMC.
In WP5, we will perform Phase I clinical trials to demonstrate the potential of this large scale GMP production platform. We have not started this WP yet. No progress in so far, as a clinical trial is expected to start in Q3 2020. The start of trial has been delayed by the COVID-19 pandemic.
The development of a business model and marketing strategy is the aim of WP6. Before the start of PRECIOUS we have already initiated a market analysis and the development of a feasible business case. The PRECIOUS consortium has specifically conceived a sub-objective to develop such plans for the results from the entire PRECIOUS project. So far, we have updated our market research plan and our business plan (see deliverable 6.7 & 6.9).
The aim of WP7 is to ensure dissemination of results and the day-to-day operational project management. We are managing this project continuously and will make sure that all partners disseminate the results when appropriate. Several meetings have been organized so far and recently, we organized a review meeting (virtual) with all partners including the EC and external contact on the 18th of May. Additionally, for this period, the project progress report (3rd) is being prepared.
PRECIOUS will deliver:
(1) a novel PLGA-based immunomodulating nanomedicine platform that allows for combinatorial cancer immunotherapy, using different immunomodulating compounds;
(2) protocols to generate GMP-grade clinical trial material of PLGA particles;
(3) clinical safety and tolerability data of the platform;
(4) preclinical data on safety and efficacy of all individual compounds administered locally using the PLGA particles and the combinations thereof.