Why IgE?

Potent immune effector function

• IgE has evolved to provide immunity to parasites which requires very potent immune effector function
• Mediated by high-affinity IgE receptor FcεRI on cells of myeloid lineage, including macrophages and monocytes
• Very tight binding of IgE by FcεRI receptor redirects tropism of myeloid cells and facilitates immunosurveillance
• IgE repolarises macrophages towards the anti-cancer, pro-inflammatory M1 phenotype
• IgE facilitates tumour permeation by macrophages
• IgE is able to kill tumour cells expressing very low levels of antigen, a strong point of differentiation

Unique Mechanism of Action facilitates combinations with other modalities

• IgE has demonstrated strong single agent activity and its unique MoA allows combination with other modalities such as checkpoint inhibitors and ADCs

Longer tissue half-life

• IgE has a long tissue half-life of 2 weeks versus 2–3 days for IgG
• The converse is true in serum where IgE has a half-life of 2–3 days versus 2–3 weeks for IgG
• IgE’s long tissue half-life is ideal for treating solid tumours representing 92% of all cancers

IgE has no inhibitory receptor and is present at very low levels in serum

• Therapeutic IgE would be expected to have greater potency and lower dose levels in man
• Phase I data backs this up with dose levels >100X lower than typical IgG doses