Xilio Therapeutics (XLO) Leerink Global Healthcare Conference 2026 summary

Key disclosures and pipeline updates

• Announced a new dual-targeted PSMA/STEAP1 cell engager for prostate cancer, integrating masking on CD3 and co-stimulatory CD2 signaling, with no delay to IND timelines.

• The modular platform enables parallel development and optimization of components, allowing for rapid selection of the most promising molecule.

• Only the CD3 domain is masked in the new molecule, based on non-human primate data showing optimal safety and efficacy.

• Dual targeting aims to address tumor heterogeneity and antigen escape, potentially benefiting up to 95% of advanced prostate cancer patients.

• IND filings for both the dual-targeted prostate and claudin 18.2 cell engager programs are planned for 2027, with clinical data expected in 2028.

Technology and scientific rationale

• The CD2 co-stimulatory domain was chosen for its tumor selectivity and dependence on TCR signaling, minimizing off-target effects.

• The masking technology is designed for high efficiency, enabling potent activity in the tumor microenvironment while reducing peripheral toxicity.

• The dual-targeted molecule operates as an OR gate, binding either PSMA or STEAP1, increasing patient coverage and potentially improving durability.

• Extensive design cycles and preclinical de-risking have increased confidence in manufacturability and clinical translation.

• Preclinical models show a positive therapeutic index, supporting the masking approach for both prostate and claudin programs.

Additional pipeline and partnership updates

• The CTLA-4 antagonist program demonstrated 26% response in late-line MSS CRC and up to 40% in high plasma TMB subgroups, with strong tumor selectivity and reduced side effects.

• Active partnership discussions are ongoing for the CTLA-4 asset, with interest driven by recent biomarker findings.

• The Gilead IL-12 program is approaching a $75M opt-in milestone, with Phase I/II data expected in the first half of next year.

• The PD-1 IL-2 program, featuring a masked, potent IL-2, is set for IND midyear and aims for best-in-class efficacy and tolerability.

• Masking technology in the PD-1 IL-2 program enables tumor-focused activity and avoids peripheral IL-2 toxicity, as shown in preclinical studies.