Xilio Therapeutics (XLO) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Platform overview and technology

• GPS platform enables tumor-selective activation of potent immunotherapies, minimizing systemic exposure and adverse events.

• Each molecule is custom-engineered with masking domains and protease cleavage sites, activated by MMPs prevalent in solid tumors.

• Consistent protease targets are used, based on analysis of over 1,000 tumor samples, with redundancy built into each molecule.

• Tumor selectivity is achieved with minimal peripheral activation, confirmed in over 100 patients across three programs.

• 3D structure and conformation are critical for effective protease interaction and activation.

XTX101 (masked CTLA-4) program

• XTX101 is a next-generation CTLA-4 with 10x potency over ipilimumab, enhanced Fc for ADCC, and tumor-selective activation.

• Phase I showed 70-90% tumor activation, 15% or less in periphery, and a durable response in a PD-L1 negative NSCLC patient with liver metastases.

• Phase II proof-of-concept in MSS colorectal cancer (CRC) includes patients with and without liver metastases, targeting 40 patients.

• Initial data from the first 20 patients expected in Q4, with full 40-patient data and longer follow-up in Q1 next year.

• Safety profile shows low colitis, minimal skin/endocrine AEs, and improved tolerability compared to other CTLA-4s.

XTX301 (masked IL-12) program

• IL-12 aims to convert immunologically cold tumors to hot, enabling IO combinations, but has historically been limited by toxicity.

• Masking technology allows high dosing (up to 60 mcg/kg), with minimal peripheral activation and promising preclinical regressions.

• Priming dose strategy blunts interferon gamma spike, improving safety at high doses.

• Phase I includes all-comer solid tumors, with safety, PK/PD, and tumor PD data expected in Q4.

• Next steps include phase II and combination studies, with Gilead as a strategic partner and option deal structure.