Objectives & Work Plan

Advance BEA-17 through chemistry, manufacturing and controls, plus GLP preclinical safety studies, aiming to produce a pharmaceutical and non-clinical package that can support a future Clinical Trial Application.¹

Develop candidate predictive and pharmacodynamic biomarker readouts intended to support future patient selection, translational decisions, and assessment of BEA-17 activity.

Aim to build the regulatory documentation and biomarker strategy needed to support a future European CTA, subject to successful completion of the planned studies and regulatory review.²

GLIOBREAK will optimise the BEA-17 manufacturing route for scalability and reproducibility, establish analytical characterisation of the drug substance, and qualify stability-indicating methods aligned with regulatory expectations.

The project will conduct GLP-compliant toxicology studies with ADME profiling, CNS penetration assessment, bioanalytical method qualification, and safety pharmacology covering cardiovascular, CNS, and respiratory systems.

The intended output is a documented drug candidate supported by chemistry and non-clinical safety data designed to support a future CTA or IND. Submission will depend on successful study completion and regulatory feedback.²

WP5: BEA-17 is tested alone and in combination with standard-of-care treatments (surgical resection, image-guided radiotherapy, and oral chemotherapy) across multiple immunocompetent GBM mouse models. Tumour tissue from these treated animals is collected and prepared for the molecular profiling described in the cards below.²

WP6: Single-cell and spatial multi-omics profiling of that BEA-17-treated tumour tissue defines candidate transcriptional and epigenetic markers linked to BEA-17 sensitivity, especially tumours with high LSD1/CoREST activity and immune suppression. These markers form the basis of a candidate patient-selection signature for later validation.

WP6: Candidate signatures identified in the mouse tissue are cross-checked against independent human glioblastoma datasets, including the GLIOMATCH patient cohort. This cross-species step tests whether the signatures hold up in human disease before any clinical use is considered.

Practical feasibility, including sample handling, reproducibility, and turnaround time, is assessed using existing clinical tissue samples from the GLIOMATCH network. Establishing this ahead of prospective use reduces the risk of an assay that works in principle but not in routine practice

Matched biopsy profiling, using the same single-cell and spatial platforms applied to patient selection, will track changes in LSD1/CoREST levels, chromatin state, immune gene expression, and ERV de-repression before and after BEA-17 treatment, with liquid biopsy approaches added where feasible. This pharmacodynamic monitoring is intended to provide direct evidence that BEA-17 engages its target and remodels the tumour immune environment as expected.

The biomarker programme aims to generate a candidate assay concept and patient-selection signature from the evidence generated above. Any decision thresholds or companion-diagnostic use arising from this work would require further analytical and prospective clinical validation under the applicable regulatory framework.³

The regulatory workstream will consolidate evidence from manufacturing, formulation, pharmacokinetics, toxicology, in vivo efficacy, and bioanalysis, identifying and closing the gaps that must be addressed before a Clinical Trial Application.

GLIOBREAK aims to assemble quality, non-clinical, and supporting clinical documentation intended to support a future European CTA and first-in-human study planning, subject to study outcomes and regulatory feedback.²

Candidate patient-selection and pharmacodynamic biomarkers could inform a future clinical-development strategy. Assay development and any use in a first-in-human study would require further validation and consideration of the applicable EU regulatory framework.⁵