Xilio Therapeutics (XLO) Study Update summary

Platform and study overview

• Tumor-activated immunotherapies leverage dysregulated proteases for selective activation in solid tumors.

• Vilastobart (XTX-101) is a high-affinity, Fc-enhanced anti-CTLA-4 antibody, tenfold more potent than ipilimumab, with enhanced effector function and Treg depletion.

• The phase 2 trial evaluates vilastobart plus atezolizumab in metastatic microsatellite stable colorectal cancer (MSS-CRC), a population resistant to immunotherapy.

• The study enrolled 40 heavily pretreated patients, with over 70% having received three or more prior lines of chemotherapy.

• The trial is co-funded in collaboration with Roche and is a multi-center, open-label Phase 1/2 trial.

Clinical results and efficacy

• Among 18 response-evaluable patients, 11 had no liver metastases and 7 had liver metastases.

• In patients without liver metastases, three partial responses were observed (two confirmed, one pending), yielding a preliminary ORR of 27%.

• Disease control rate was 55% in patients without liver metastases and 14% in those with liver metastases.

• A fourth patient without liver metastases showed a 24% tumor reduction and normalization of CEA.

• Tumor reductions were rapid, often seen at the first assessment at nine weeks, and responses deepened over time.

Activity in challenging subgroups and biomarker insights

• No confirmed responses yet in patients with liver metastases, but some show stable disease and biomarker declines, suggesting possible delayed responses.

• ctDNA and CEA reductions were observed in both responders and some liver metastasis patients, indicating potential for future responses.

• Pseudoprogression was noted in at least one patient, with initial symptom worsening followed by significant clinical and radiographic improvement.

• All responding patients remain on treatment, and biomarker reductions (ctDNA, CEA) correlated with tumor shrinkage.

• The trial includes ongoing monitoring for deeper and more durable responses, especially in liver metastasis cases.