Xilio Therapeutics (XLO) Status Update summary

Key clinical data and efficacy

• Vilastobart plus atezolizumab achieved a 40% overall response rate (ORR) in MSS colorectal cancer (CRC) patients with high plasma tumor mutational burden (TMB), with deep and durable responses and a favorable safety profile.

• All evaluable responders were plasma TMB-high, with 62.5–63% of trial patients classified as high plasma TMB and no responses in TMB-low patients; the correlation between high plasma TMB and response was statistically significant (p=0.05).

• High plasma TMB prevalence was 55–63% in trial and real-world MSS CRC cases, much higher than tissue-based estimates, expanding the eligible population.

• ctDNA reductions were significantly associated with best overall response, supporting ctDNA as a potential early biomarker.

• Responses included reductions in target lesions up to 71% from baseline.

Safety and tolerability

• The combination therapy was generally well-tolerated, with most adverse events being Grade 1 or 2, a 5% discontinuation rate, and 7% experiencing colitis of any grade.

• Safety profile was similar to atezolizumab monotherapy, with low rates of serious toxicity.

Biomarker and clinical practice insights

• Plasma TMB is a dynamic, non-invasive biomarker that can increase over time, is more reflective of current tumor status than tissue TMB, and is integrated into routine blood-based diagnostics.

• Plasma-based TMB assays identify a much larger high-TMB population (up to 55%) compared to tissue-based assays (<10%), enabling broader patient selection.

• ctDNA may serve as an early response marker, and plasma TMB is supported by real-world data as a predictive biomarker.