EC917 Eva Gallardo, MD Medical Manager, Biocompatibles UK Drug Eluting Bead: Future Product Applications

EC917 Malignant Gliomas are most frequent primary brain tumours Total surgical resection is challenging due to infiltrative nature Median Survival: Low-grade Glioma: 5 years (most die of progression to high-grade) High-Grade Glioma: <5% survival at 2 years Polymer drug release post-resection has improved treatment outcomes (this therapy is under further development) DEB in Glioma: Background

EC917 DEB in Glioma: Methods Study in glioblastoma rat model to evaluate efficacy of Irinotecan and Doxorubicin Bead Control Group: 1-3 µL of µm beads injected Dose ranging study: 1-3 µL of loaded µ m beads injected. Histogical evaluation 12 days post-tumour implant Survival study: 1 µ L of µ m loaded beads injected. Animal activity and well-being assessed twice daily. Euthanised if low scores or sudden neurological signs. Histological evaluation: tumour size, histomorphology, bead location and amount, drug distribution

EC917 No histological tissue damage found with bland beads Tumoural citotoxic effect of both drugs with tumour necrosis Neuronal, glial and capillary cells were also destroyed by doxorubicin (not by irinotecan) DEB in Glioma: Results

EC917 DEB in Glioma: Results P Bead vs Dox Bead P Bead vs Iri Bead

EC917 DEB in Glioma: Results DEB could be a promising new local therapy for glioma Doxorubin showed the longer survival but with a dose limiting toxicity Further evaluation is required

EC917 DEB in Peritoneal Carcinomatosis: Background Peritoneal carcinomatosis leading to malignant ascites is a complication of several solid tumors (ovarian, gastric, liver and pancreatic cancers) Appears in late disease stage – difficult to manage Is the life-limiting factor and leads to severe complications – bowel obstruction Symptoms include severe pain and dyspnea

EC917 DEB in Peritoneal Carcinomatosis: Methods Doxorubicin or Mitoxantrone loaded Beads were used in a peritoneal colorectal carcinomatosis mice model Control Group: direct intraperitoneal injection of unloaded beads at 7, 10 and 12d Direct intraperitoneal injection of free drug or loaded Bead (single low dose/single high dose/multiple doses)

EC917 Dox and Mitox induced dose-dependent reduction in cell proliferation whether free or delivered by DEB Free drug was more effective at reducing cell viability over time, although DEB was seen to be most effective at 72h (slow release of the drug) Multiple free Dox was lethal (Dox and Mitox Bead were well tolerated) DEB in Peritoneal Carcinomatosis: Results

EC917 DEB in Peritoneal Carcinomatosis: Results Multiple free Mitox administration induced significant weight decrease (Mitox Bead did not)

EC917 Multiple administration of Dox or Mitox DEB was very efficacious in reducing tumor volume A single administration of Dox or Mitox DEB with 100mg/kg dose was both well tolerated and efficacious DEB in Peritoneal Carcinomatosis: Results

EC917 IP free drugs had efficacy against tumor cells in vivo, but multiple applications of free drug were lethal or had significant effect on body weight indicating poor tolerability Single application of high dose, or multiple application of lower dose DEB were well tolerated and had a significant effect on reducing tumor volume DEB could offer a new treatment for peritoneal carcinomatosis DEB in Peritoneal Carcinomatosis: Conclusion