OUR TECHNOLOGY

Patients with Dry AMD present with patches of atrophy known as Geographic Atrophy (GA) – areas of retinal pigment epithelium (RPE) and neural retinal loss that continue to expand, resulting in blinding complications.

AMD is a complex multigenic disease of the innate immune system, with significant epigenetic overlay.

1. Smoking/diet/lifestyle are associated with disease

2. Genetic associations include innate immunity, lipid metabolism, oxidative stress and tissue remodeling

The patches of damage can be measured and serve as a clinical trial endpoint, however etiology of patch formation, expansion or phenotypic characteristics, is not well described.

The innate immune system is highly associated with AMD, and is comprised of a non-cellular (complement cascade) & cellular arm (ocular phagocytes).

We focus on the cellular arm of the innate immune system, primarily macrophages.

Macrophages are important phagocytic cells responsible for maintaining tissue homeostasis in the retina. They can express a variety of polarized phenotypes based on environmental conditions and signals. Their activation and behaviour is tightly regulated at the transcriptional level. Macrophages are associated with Dry AMD and GA, and markers of their activation and phenotypic expression are found in patient specimens.

Our lead candidate TMi-018 is a first-in-class transcriptional modulator of macrophage activity. TMi-018 reduces transcription of DNA to RNA and therefore multiple downstream proteins. Most other drugs target an individual cytoplasmic, receptor or secreted protein.