Werewolf Therapeutics (HOWL) 7th Annual Evercore ISI HealthCONx Healthcare Conference summary

Technology and clinical program overview

• Developing conditionally activated cytokine prodrugs (INDUKINE) to target immune-stimulating effects to tumors while minimizing systemic toxicity.

• Lead programs: WTX-124 (IL-2) in phase I expansion and WTX-330 (IL-12) transitioning to phase I/II.

• INDUKINE molecules retain full cytokine potency, using a novel masking approach to activate only in tumor tissue.

• Clinical data show high tumor exposure and monotherapy activity with favorable tolerability.

Clinical data and efficacy insights

• WTX-124 shows responses in post-checkpoint patients with melanoma, renal cell, and cutaneous squamous cell cancers.

• Complete response observed in a refractory cutaneous squamous cell patient, durable over a year off drug.

• Dose response evident: anti-tumor activity emerges at 12 mg, with 18 mg chosen for expansion based on efficacy and biomarkers.

• Expansion arms for monotherapy and combination are open for enrollment.

• WTX-330 (IL-12) demonstrates immune cell infiltration and activity in cold tumors, including MSS-CRC, with 22-fold higher safe IL-12 delivery than prior systemic approaches.

Safety and tolerability profile

• WTX-124 does not induce vascular leak, cytokine release syndrome, or infusion reactions; main adverse event is arthralgia, similar to low-dose IL-2.

• No recurrence of immune-related adverse events in patients with prior checkpoint inhibitor toxicity.

• Low-grade adverse events observed are manageable and not clearly inflammatory.

• WTX-330 (IL-12) allows much higher dosing without historical toxicity, with only low-grade cytokine release syndrome observed.