The CLINGLIO project aims to advance a novel drug, 2OHOA, for the treatment of glioblastoma towards an initial market entry in Europe. For this purpose, the CLINGLIO project will encompass a demonstrative phase IIB clinical study to evaluate the efficacy of an innovative therapy, based on 2OHOA and SoC in subjects with primary newly diagnosed glioblastoma. In addition, planned studies with patient samples and glioma cells have the objective to further characterize biomarkers for predictive (diagnosis and prognosis with threshold biomarkers and omics signatures), pharmacodynamic/pharmacogenomic and stratification (patient treatment assignation) purposes.
The main objective of the clinical trial is to assess the therapeutic potential (Progression Free Survival, PFS, as primary endpoint and Overall Survival, OS) and safety of 2OHOA plus SoC, compared with SoC plus placebo, through a controlled, randomised, double blind adaptive Phase IIB clinical trial with interim dose selection and sample size re-estimation.
To be able to carry out the clinical study, we will develop a new drug presentation form based on the formulation previously developed in order to reduce 2OHOA production, distribution and storage costs and to facilitate drug use by the patients.
CLINGLIO project comprises an in-depth study of the molecular mechanism of action of 2OHOA underlying its efficacy in glioma treatment. To do so, we will investigate the role of SMS1, SMS2 and other proteins in tumorigenesis and in 2OHOA's mechanism of action. We will analyse 2OHOA-SMS interactions by molecular modelling and we will study the connection between membrane lipid composition and protein translocation from or to glioma cell membrane, which might be involved in regulation of the "proliferation switch" in response to 2OHOA treatment. The effect of 2OHOA on glioma cell line energetics and metabolites will also shed light on its mechanism of action and could be useful to discover new biomarkers.
Predictive biomarker threshold and omics signature will be studied at interim evaluation, and final design will permit to seek conditional marketing authorization on either the full (cohort 1 + 2) or a sub population (cohort 2).To study and validate potential innovative biochemical and genetic biomarkers in patients to allow accurate diagnosis, prognosis, patient stratification, assessment of response and glioma grade/subtype classification.
We also aim to develop and implement a strong Intellectual Property strategy to ensure adequate protection of the results of the project. To elaborate a realistic exploitation and a marketing plan in all major markets worldwide, in order to ensure the translation of the project results to patients suffering from glioma/glioblastoma.
With the achievement of these specific objectives, CLINGLIO aims at strategically contribute to advance the development of a new therapeutic option, through the performance of an innovative clinical trial, in order to increase the life expectancy and quality of life of patients with glioblastoma.