Macrophages and Disease

Macrophages are major constituents of the microenvironment in many solid cancers, promoting carcinogenesis, malignant progression and resistance to therapy making them attractive targets for therapeutic intervention.

Macrophage Pharma’s initial clinical focus is to develop a new generation of powerful small-molecule oncology drugs which inhibit the ability of tumour polarised macrophages to release immunosuppressive cytokines such as IL-10. This in turn is expected to lead to an increase in anti-tumour T-cell numbers and function. This reprogramming of the tumour immune system is necessary to enhance the activity of both cytotoxic and immuno-oncology therapies such as the checkpoint antibodies.

The company therefore intends to pursue development programmes, like MPL-5821, aimed at blocking the activity of macrophage derived immunosuppressive cytokines such as IL-10 and restoring levels of stimulatory molecules such as IL-12 & IFN-γ.

Through focussing on additional elements of the immune system by targeting the macrophage we expect to be able to address a wider range of tumour types (e.g. where T cells are not anti-PD-1 responsive due to macrophage repression mechanisms) and broader patient populations. Macrophages play central roles in driving or modifying several other diseases including autoimmunity, inflammation, fibrosis, and allergic asthma. In our PI3 kinase, inflammasome and immune kinase programs we aim to design first-in-class macrophage-targeted molecules to interfere with key molecular drives of these disease.

Our approach in cancer is to manipulate immunosuppressive tumour associated macrophages towards a pro-inflammatory phenotype that support anti-tumour immune responses.