Local activation of the innate immune system is a promising area for cancer drug discovery. However, all current approaches require direct injection of innate activating molecules into tumours to avoid excessive systemic activation of the immune system and associated toxicity. We are developing Bicycles for the systemic delivery of tumour targeted innate immune activators, such as STING and Toll Like Receptor (TLR) agonists, to locally activate the immune system and “turn cold tumours hot.” The targeting Bicycle shields the payload and directs it to where it needs to act in the body. This approach avoids the need for direct tumour injection, allowing inaccessible tumours to be reached, while enabling rapid systemic elimination of excess payload in an inactive form. In the tumour microenvironment, the payload is released, engaging both innate and adaptive immune responses. Bicycle is developing an array of STING and TLR agonists, targeted to novel and validated tumour targets.