Noxopharm White Paper

NOXOPHARM L IMITED White Paper 16 Veyonda® – IONIC program continued Cancer exploits the complexity of the immune system in a number of ways that not only mean that it avoids being attacked by immune cells, but to the point of help it avoid mechanisms exploited, three stand out: 1. Immune checkpoints. This is a mechanism designed to prevent over-zealous behaviour by immune cells. It involves proteins expressed on the surface of cells known as immune checkpoints designed to hold the immune cell at arm’s length. The more of these checkpoint proteins a cell displays, the harder it is for the immune cell to attack the cell. Many cancer cells express high levels of these checkpoints, effectively acting as a suit of armour protecting them from immune attack. 2. Helper/suppressor cells. Some immune cells promote an immune response (‘helper’ T cells), while the role of others is to prevent an over-response by subduing the response (‘suppressor’ T cells. Cancers can switch off the ‘helper’ T cells, while promoting the activity of the ‘suppressor’ T cells. 3. Eradication of immune cells. As an ultimate exploitation, cancers can eradicate immune cells from the tumour, creating an ‘immune sterile’ environment in which the cancer cells are free to grow. Most human tumours are believed to carry out this ultimate step, referred to as turning a tumour to ‘COLD’ (devoid of immune function) from ‘HOT’ (normal immune function). Drugs known as immune checkpoint inhibitors have been developed to block the ability of the checkpoint proteins from masking the cancer cell from the attacking immune cell. Without the protective immune checkpoint coat, the cancer cell becomes immediately susceptible to immune attack. However... to be effective, checkpoint inhibiting drugs need the presence of an active immune system. Removing a cancer cell’s protective coat only works when there are immune cells present to take advantage of that situation. The overwhelming majority of cancers fail to respond to immune checkpoint inhibitor therapy, pointing to most cancers employing a range of exploitation steps, including in particular the elimination of active immune cells from the tumour. Idronoxil has two known primary immunological actions, suggesting optimal complementary function to immune checkpoint inhibitor therapy: • Activation of ‘helper’ T-cells (CD4+ and CD8+ cells). • Increased trafficking of T-cells and their re-entry to tumours.