Werewolf Therapeutics (HOWL) 24th Annual Needham Virtual Healthcare Conference summary

Platform overview and technology

• Predator Platform enables tunable, tissue-targeted immunomodulators called INDUKINE, designed for improved therapeutic index over recombinant cytokines.

• INDUKINE molecules use native cytokines, half-life extension domains, and protease-cleavable linkers for tumor-specific activation.

• Technology addresses off-tumor toxicity and short half-life issues of native cytokines by conditional activation in the tumor microenvironment.

• Platform validated in two clinical-stage compounds: WTX-124 (IL-2 prodrug) and WTX-330 (IL-12 prodrug).

• Masking technology is adaptable to other modalities, including T cell engagers, bispecifics, and ADCs.

WTX-124 (IL-2 INDUKINE) clinical program

• Selectively releases potent IL-2 in tumors, aiming to replace high-dose IL-2 with improved safety and broader eligibility.

• Completed dose escalation in first-in-human trial; 18 mg IV every two weeks chosen for expansion based on anti-tumor activity, safety, and biomarker data.

• Dose expansion ongoing in renal cell carcinoma, cutaneous melanoma, cutaneous squamous cell carcinoma, and PD-L1+ NSCLC.

• Early data show objective responses and durable complete responses, including in patients refractory to checkpoint inhibitors.

• No vascular leak syndrome or severe cytokine release syndrome observed; safety profile allows for combination with checkpoint inhibitors.

WTX-124 biomarker and efficacy insights

• Biomarker analysis shows preferential expansion of effector T cells over Tregs, with upregulation of granzyme B and IL-2 receptor A.

• Responses occur rapidly, often within first two cycles; durable responses seen over 12 months off therapy.

• 18 mg dose selected for both monotherapy and combination based on clinical and biomarker activity.