IO4COLON

Industrial research to discover new immunotherapy drugs for the treatment of colon cancer

The main objective of ‘IO4COLON: Industrial research to discover new immunotherapy drugs for the treatment of colon cancer’ is the discovery and preclinical development of new medicinal product candidates for the treatment of colon cancer by activating the immune system (IS), to be used in monotherapy, or in combination with each other or with other therapeutic agents.

The project is being led by the companies Oncostellae, GalChimia and AMSLab, with the support of the University of Santiago de Compostela, LEITAT Technological Centre and the companies Palo Biofarma, IDIFARMA and Eurofins.

IO4COLON will study the efficacy of two new medicinal products, an ALK5 inhibitor and a GR antagonist, through various mechanisms, while also studying their synergistic effect in the treatment of colon cancer. This initiative also represents a considerable qualitative leap in comparison to previous projects, as the aim is to complete Preclinical Development, Pharmaceutical Development, the production of capsules for clinical trials, the preparation of the regulatory documentation and the potential use of the results by applying for new invention patents.

This project was subsidised by the Galician Innovation Agency (GAIN), through the CONECTA-PEME Programme, and the European Regional Development Fund within thematic objective 1, “Strengthening research, technological development and innovation“, included within the framework of the FEDER Galicia 2014-2020 operational programme, and will also be supported by the Galician Ministry for the Economy, Employment and Industry.

In the second year of the project, significant progress has been made.

Total project budget: 1,095,700.00 euros

Results of IO4COLON

At the end of the project, the following results have been achieved:

• Based on the results of the NEOGALFARM project (2016–2018), a structural optimization has been carried out that has resulted in the selection of two new candidates, an ALK5 inhibitor and a GR receptor antagonist.
• Analytical methodologies have been developed using high performance liquid chromatography (HPLC) coupled with tandem mass spectrometry (MS / MS) for the determination of both compounds in biological samples.
• Scaling-up of synthetic routes for the production of both compounds on a kilogram scale has been successfully completed. Likewise, analytical methods have been validated for their quality control.
• The toxicity and safety of both candidates have been evaluated in vivo. Neither the ALK5 inhibitor nor the GR antagonist have adverse effects related to respiratory, cardiovascular, and neurological functions. Furthermore, their pharmacokinetic profiles have indicated low systemic plasma levels and preferential absorption in the gastrointestinal tract, which makes these compounds especially indicated for the treatment of colon cancer.
• The regulatory documentation for both candidates has been prepared, in the form of an Investigator’s Manual and Investigative Drug Dossier, for presentation to the Spanish Agency for Medicines and Health Products (AEMPS).
• GMP batches of both candidates have been prepared and their high stability under normal and stress conditions has been confirmed.
• The formulation of the ALK5 inhibitor has been completed and the clinical batch of capsules has been produced for use in the phase I trial that will begin in April 2021 at the Sant Pau Hospital in Barcelona.
• The formulation of the GR antagonist candidate is well advanced, and capsule production is expected to be completed in the next quarter. The phase I clinical trial will begin in September 2021 at the Hospital del Vall d’Hebron in Barcelona.
• An analytical methodology based on bottom-up proteomics and HPLC MS / MS has been developed for the quantification of TGFβ1 in mouse plasma and tumor samples.
• The protection of the intellectual property of the 2 new candidates has been ensured through patent applications, which have been submitted both nationally and internationally.

AMSlab thanks all the members and collaborators of the IO4COLON project for their involvement and teamwork that have been key to obtaining these results. We also thank GAIN for its support in fostering cooperation between SMEs and the other agents of the Regional Innovation System. The CONECTA-PEME calls have allowed 3 Galician SMEs to lead large-scale projects such as IO4COLON, also demonstrating that in Galicia there is potential to carry out drug discovery projects by having the agents and knowledge necessary for this.