Biodexa Pharmaceuticals PLC announced that it will be presenting an update on the recruitment and treatment of patients in the ongoing Phase 1 study of MTX-110 (also known as MAGIC-G1 study) in patients with recurrent glioblastoma (rGB) during a poster session on 22 September 2023, at the 2023 annual EANO meeting in Rotterdam, the Netherlands (NCT 05324501). MAGIC-G1 is an open-label, dose escalation study designed to assess the feasibility and safety of intermittent infusions of MTX-110 administered by convection enhanced delivery (CED) via implanted refillable pump and catheter. The study aims to recruit two cohorts, each with a minimum of four patients; while patients in both cohorts will receive MTX-110 via intermittent repeated CED infusions, patients in the second cohort will be allowed CED catheter repositioning upon first in-study clinical and/or radiographic confirmed progression.

As of the time of this announcement, three patients have been dosed in the first cohort of the study. No dose-limiting toxicities have been observed at any dose level; and all study-related, non-surgical adverse events were grade 1 or 2 and correlated with the location of the lesion being treated. Patient 1 has received 13 treatment cycles over 19 weeks of study treatment period, whereas patient 2 received 10 cycles over 13 weeks of study treatment period; patient 3 has been recently enrolled and continues to receive treatment.

GB is the most common and devastating primary malignant brain tumour in adults encompassing 14.3% of all primary brain and central nervous system neoplasms(1). With an incidence of approximately 3.2 per 100,000 population in the USA, approximately 12,300 people in the USA will be diagnosed with GB per annum. Standard of care for treatment of GB is typically maximal surgical resection followed by radiotherapy plus concomitant and maintenance temozolomide chemotherapy with or without the Optune® device.

Notwithstanding, the multidisciplinary approach, almost all patients experience tumour progression with nearly universal mortality. The median survival from initial diagnosis is less than 21 months(2). Currently, no standard of care is established for rGB.

MTX110 is a water-soluble form of panobinostat free base, achieved through complexation with hydroxypropyl-ß-cyclodextrin (HPBCD), that enables convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor). The currently available oral formulation of panobinostat lactate (Farydak®) is not suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations.

Based on favourable translational science data, MTX110 is being evaluated clinically as a treatment for recurrent glioblastoma (NCT05324501), paediatric DMG (NCT04264143) and recurrent medulloblastoma (NCT04315064). MTX110 is delivered directly into and around the patient?s tumour via a catheter system (e.g. CED or fourth ventricle infusions) to bypass the blood-brain barrier. This technique exposes the tumour to very high drug concentrations while simultaneously minimising systemic drug levels and the potential for toxicity and other side effects.

Panobinostat has demonstrated high potency against DIPG and GBM tumour cells in vitro and in vivo models, and in a key study it was the most promising of 83 anticancer agents tested in 14 patient-derived DIPG cell lines (Grasso et al, 2015. Nature Medicine 21(6), 555-559).