53 Analysis of translational challenges across 19 brain tumour therapeutic development programmes: Insights from the BTR-NTA accelerator

Abstract Introduction Development of novel therapies for brain tumours faces high attrition rates, with few programmes reaching approval. This thematic analysis synthesises translational challenges identified through the Brain Tumour Research Novel Therapeutics Accelerator (BTR-NTA), an international multidisciplinary programme providing structured expert guidance to accelerate novel brain tumour treatments toward clinical application. Methods Between 2023 and 2025, BTR-NTA received 33 applications from academic and industry groups developing novel brain tumour therapies. Nineteen programmes were selected based on scientific merit and clinical potential and received up to 240 hours of multidisciplinary input across preclinical, clinical, regulatory, commercialisation, and patient advocacy domains. A structured analysis of feedback reports from 19 programmes was conducted to identify recurring translational challenges. Themes were stratified by applicant type, development stage and modality. Results Analysis identified five recurring translational challenges: (1) all programmes required guidance on defining data packages to support milestone decisions (e.g., IND-enabling studies, go/no-go criteria); (2) 95% had insufficient CNS penetration or tumour-site distribution data from clinically relevant disease models; (3) all programmes needed guidance on timing and scope of regulatory engagement; (4) 79% lacked manufacturing readiness despite scientific maturity; and (5) 53% required support developing patient and public involvement strategies. Six of 11 eligible programmes (55%) completed a one-year follow-up survey. All respondents had adapted their development strategy based on BTR-NTA guidance and secured follow-on funding from governmental, charitable, or venture capital sources. Conclusions There appear to be systemic translational challenges that risk delaying progression into the clinic of potential therapies built on robust scientific data. Earlier expert guidance may accelerate therapy development and improve success rates. Wider dissemination of these insights may support improvement in translational pathways across the brain tumour therapeutic development landscape.