Xilio Therapeutics (XLO) TD Cowen 45th Annual Healthcare Conference summary

Technology and platform overview

• Tumor-activated technology enables preferential activation of molecules within the solid tumor microenvironment, enhancing efficacy and minimizing systemic toxicity.

• Over 200 patients have been treated across diverse clinical programs, with iterative design cycles improving efficiency and clinical translation.

• Molecules use a masking domain and protease-cleavable linkers, with 3D conformation critical for tumor-specific activation.

• In-house bank of 1,000+ human tumor samples enables testing of molecule activation in real tumor biopsies.

• Pipeline has evolved to include more complex molecules, such as bispecifics and trispecifics, with multiple pharma collaborations.

Clinical program highlights

• Lead molecule is a tumor-activated, Fc-enhanced anti-CTLA-4 in Phase II, studied with atezolizumab in MSS colorectal cancer; next data readout expected mid-year.

• Tumor-activated IL-12 program in Phase I dose escalation, partnered with Gilead.

• Early clinical data show high tumor selectivity (70–96% activation in tumor, <15% in circulation) and improved safety profile.

• Preliminary 27% response rate in late-stage MSS CRC, with deepening responses and symptom improvement.

• Low rates of severe colitis (5%) and few discontinuations due to toxicity in combination therapy.

Strategic direction and partnerships

• Seeking a partner to advance the anti-CTLA-4 program beyond proof-of-concept, with openness to various partnership models.

• Multi-program collaboration with AbbVie includes masked T-cell engagers and antibodies, with $52M upfront and up to $2.1B in milestones.

• Collaboration with Roche on the anti-CTLA-4 program and with Gilead on masked IL-12.

• Additional undisclosed programs with AbbVie focus on masked cell engagers.