Werewolf Therapeutics (HOWL) Study Update summary

Program overview and objectives

• WTX-124 is a conditionally activated IL-2 prodrug (INDUKINE) designed to deliver potent cytokine activity selectively to tumors, aiming to overcome toxicity and expand IL-2 therapy utility.

• The program addresses unmet needs for patients relapsed/refractory to standard of care, including checkpoint inhibitors, and those ineligible for high-dose IL-2.

• Enables potential safe combination with standard agents and exploration in other immunotherapy-sensitive solid tumors.

Study design and patient population

• Phase 1/1b open-label trial with 47 patients (35 monotherapy, 12 combination) across dose levels up to 28mg.

• Monotherapy and combination dose escalations ran in parallel; expansion arms now open for melanoma, renal cell carcinoma, cutaneous squamous cell carcinoma, and other immune-sensitive tumors.

• Patients were heavily pretreated, all having progressed on standard-of-care immune checkpoint inhibitors, with over half having at least three prior lines of therapy.

Safety and tolerability

• WTX-124 was well tolerated as monotherapy and in combination, with most adverse events being Grade 1/2 and manageable Grade 3 events at higher doses.

• No Grade 4/5 events, vascular leak syndrome, or severe cytokine release syndrome observed.

• Combination with pembrolizumab did not increase toxicity; side effect profiles were similar to monotherapy.