Xilio Therapeutics (XLO) investor relations material

Pipeline and strategy

• Masked immuno-oncology protein engineering platform; fourth IND cleared mid-2026 for a PD-1-masked IL-2 program.

• 2027 plans include advancing PD-1/IL-2 and masked T-cell engagers with multi-targeting and built-in co-stimulation.

• Clinical experience showed tumor activation with initial antibody and cytokine programs; active partnerships include Gilead and AbbVie.

• Masking aims to improve immunotherapy’s therapeutic index by limiting peripheral activity and enabling tumor-focused dosing.

XTX501

• Design combines bivalent PD-1 binding, alpha-optimized IL-2 and full masking; preclinical work showed minimal activity masked and potent tumor regressions unmasked.

• First patients enrolled in a lung cancer dose-escalation study using a BOIN design; starting dose is 1 mg/kg, described as close to a potentially efficacious human dose.

• Q4 2027 is the target for initial data, with efficacy data planned; exploratory study endpoints will assess pharmacodynamics.

• Study focus is post-PD-1/PD-L1 lung cancer across U.S.-representative histologies; combination and expansion plans will depend on initial safety and efficacy data.

• Long-term goal is potential frontline use with chemotherapy, subject to a safety profile that permits combination treatment.

T-cell engagers

• Modular platform supports masking different molecule components, multi-antigen targeting and built-in co-stimulation; two TCE INDs are targeted for Q4 2027.

• PSMA-STEAP1 design addresses heterogeneous prostate tumor antigen expression by targeting either antigen; candidate selection included screening more than 1,800 molecules.

• For prostate cancer, clinical assessment will consider radiographic response and PCWG criteria alongside PSA reductions, and examine key disease subtypes.

• XTX602 targets CLDN18.2, including lower-expression settings, with affinity-matured binding, masking and co-stimulation; primate studies showed no target-mediated drug disposition and a favorable GI toxicity profile.

• Gastric, esophageal and pancreatic cancers are potential initial indications; pancreatic adenocarcinoma was highlighted for unmet need and a strong stromal component.