MTX110 is a solubilised formulation of the histone deacetylase (HDAC) inhibitor, Panobinostat. The product is delivered via convection-enhanced delivery (CED) at potentially chemotherapeutic doses directly to the site of the tumour. Panobinostat has so far not been suitable for treatment of brain cancers owing to poor blood-brain barrier penetration and inadequate brain drug concentrations.
Glioblastoma (GBM) is the most common and devastating primary malignant brain tumour in adults encompassing close to 15% of all primary brain and central nervous system neoplasms and over 50% of all malignant brain tumours. With an incidence of approximately 2-4 per 100,000 population in both the EU and USA, over 250,000 new cases of GBM are diagnosed per annum worldwide. Standard of care for treatment of primary GBM 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.
Diffuse Midline Glioma
Paediatric Diffuse Midline Glioma (DMG), K27M-mutated (previously known as Diffuse Intrinsic Pontine Glioma – DIPG) is a rare malignant tumour primarily located in the pontine and thalamic areas of the brain. DMG affects children of all age with an incidence of 1-2 cases per 100,000 population though it mainly is diagnosed between the ages of 5 and 7. It makes up to 15% of all brain tumours in children and up to 80% of all paediatric gliomas. The prognosis of DMG is dismal due to the absence of effective therapies. After diagnosis, median survival is usually nine months. Only 10% live for more than two years.
Current treatment options include radiotherapy (either conventional fractionated or hypofractionated), re-irradiation upon progression and palliative symptomatic treatment. Despite numerous treatments in development, none have so far demonstrated significant extension of survival in these patients.
Medulloblastoma is the most common malignant tumour in children and accounts for approximately 25% of all primary brain tumours. The tumour originates from embryonic cells and is a grade III-IV one, according to the latest WHO classification. Medulloblastoma is classified based on the presence of mutations into 4 groups: WNT-activated, SHH-activated, group 3 and group 4. Classifying individual tumours is important as this has significant impact on the prognosis level with WNT-activated having the mildest course and group 3 being the most aggressive, often manifesting with tumour spread into the leptomeningeal space. Medulloblastoma treatment consists of maximal safe resection, followed by radiotherapy in different modalities, chemo- and targeted therapy and stem cells treatment. Survival prognosis depends on group classification, age, level of spreading and ranges from 30 to 85% at 5 years. Upon recurrence, there is no standard treatment and survival rate is poor, usually less than a year.