Biotheus' 4-1BB agonist is a humanized VHH that targets a unique membrane-proximal epitope on 4-1BB situated on the CRD4 domain to maintain agonist activity but in turn reduce toxicity risk. Activation of 4-1BB can improve immune effector function and memory. By pairing with an anti-PD-L1 binder, PM1003 can both inhibit PD-L1 function and activate 4-1BB in PD-L1-enriched tumours. Fc function has been depleted to reduce effector function towards PD-L1+ and 4-1BB+ cells and minimize FcR-mediated crosslinking. In preclinical studies, single-agent activity has been observed, and PM1003 may be used for treating multiple solid tumour types.