Public Funding for Glg Pharma (UK) Ltd

"**Vision:** GLG Pharma UK (GLG), part of GLG Pharma USA, has recently been incorporated (September 2017) to exclusively focus on treatments for brain tumours. Its mission is to apply genomics to rapidly and reliably identify responders to STAT3 inhibition (with its repurposed drugs), and to synergistically treat difficult-to-treat paediatric brain tumours in combination with other anti-cancer agents. GLG will use a novel human genome technology-driven tumour cell capture platform (""Genomic-PDx"") with potential to significantly accelerate identification of the most promising drug combinations from its small molecule library to produce the most effective brain tumour treatment. This project is to undertake a feasibility study to test the _ex vivo_ system and assess its potential impact compared to existing approaches in paediatric oncology. **Key objectives of the study** 1\. GLG will deploy ""Genomic-PDx"" in the UK for technical feasibility to use with its proprietary anticancer small molecule library. 2\. Banked paediatric brain biopsies will be screened _ex-vivo_ against this library as a companion diagnostic to identify drug combinations (STAT3 inhibitor plus one or more anticancer therapies) appropriate for the tumour's characteristics and as a genomics tool for standardisation of optimal results for future drug approvals. 3\. Explore feasibility with respect to clinical, regulatory and other adoption factors. **Focus:** GLG is targeting brain tumours that have constitutively activated STAT3 (p-STAT3), including : DIPG (diffuse intrinsic pontine glioma), High grade gliomas (HGG), Glioblastoma(GBM), Primary CNS Lymphoma, Paediatric Ependymoma, Metastatic Brain Tumors. DIPGs, the most common and fatal brainstem tumours in childhood, affect around 300 children in the US and 40 in the UK each year, sadly with no current cure. **Innovation in our proposal** 1\. The Genomics PDx cell capture system (from biopsied patient tumours) that informs combinatorial drug screening is proprietary, developed by CelBridge in Boston, USA, and licensed exclusively to GLG. 2\. Combinations of several targeted agents are novel and necessary to observe an effect given the multiple chromosomal alterations found for example in DIPG. This ""combination"" approach will not only potentially increase therapeutic efficacy but also reduce the likelihood of drug resistance with higher chances for tumour control 3\. We believe p-STAT3 to also be an important target in brain tumours. These will be tested in the subgroup of patients that show higher STAT3 expression. Research in glioblastoma multiforma (GBM), an aggressive adult primary brain malignancy, shows that STAT3 inhibition can induce apoptosis in GBM cell lines (Sherry et al 2009)."