Werewolf Therapeutics has dosed the first subject in the Phase I/Ib clinical trial of WTX-124 to treat solid tumours. 

The multicentre, first-in-human, open-label trial will analyse WTX-124 as a single agent, and along with Merck’s Keytruda (pembrolizumab), in immunosensitive advanced or metastatic solid tumour patients. 

These patients should have failed standard of care, including checkpoint inhibitor treatment.

Part 1 of the trial will be a dose escalation study analysing WTX-124 as monotherapy, along with pembrolizumab. 

Part 2 will have four arms where the therapy will be evaluated as a single agent, and with pembrolizumab in advanced or metastatic cutaneous malignant melanoma, or advanced or metastatic renal cell carcinoma patients.

A lead INDUKINE molecule of the company, WTX-124 is a conditionally-activated Interleukin-2 (IL-2) prodrug.

The design of WTX-124 comprises a wild-type IL-2 cytokine attached to an inactivation domain for hindering activation in off-target tissue, a tumour protease-sensitive linker that permits the activation in the tumour microenvironment (TME). 

It also contains a half-life extension domain to boost tumour exposure. 

In preclinical models, IL-2’s selective release in the TME elicits anti-tumour immune responses causing tumour regressions and reducing toxicities linked to recombinant IL-2’s systemic delivery.

Werewolf Therapeutics founder and CEO Daniel Hicklin said: “WTX-124 is the first programme from our portfolio of novel INDUKINE molecules to enter the clinic, and its progress into clinical investigation further highlights our team’s ability to execute efficiently and move our pipeline forward. 

“We believe WTX-124 presents a tremendous opportunity, not only to improve outcomes for patients with hard-to-treat solid tumours but also to validate our novel approach of developing conditionally activated cytokines as innovative cancer therapy.”