Xencor (XNCR) investor relations material

Study design and patient population

• Phase 1, multicenter, open-label, dose-escalation and expansion study of XmAb819 in advanced clear cell RCC, with both IV and SC cohorts; data cut-off September 19, 2025.

• 69 heavily pretreated patients enrolled, all with prior anti-PD1 and VEGF-TKI therapy; median of 4 prior regimens, 36% had HIF2α inhibitor exposure.

• No preselection for ENPP3 expression, but retrospective testing confirmed most were high expressors.

• Study objectives include safety, tolerability, pharmacokinetics, and anti-tumor activity using a 3+3+3 dose-escalation design.

Safety and tolerability

• XmAb819 was generally well tolerated, with 4% discontinuation due to adverse events and over 90% reaching target dose.

• Most common adverse events were CRS, rash, and GI toxicities, mainly Grade 1 or 2; Grade 3 CRS was 4% with correct dosing.

• No treatment-related ICANS or Grade 5 events; most adverse events were manageable and transient.

• Dose prep errors led to higher Grade 3 CRS rates (28% in error group vs 4% with correct prep); mitigated by site retraining and new formulation planned for 2026.

• Grade 3 treatment-related events included rash (16%) and liver enzyme elevations (7%); one dose-limiting Grade 4 liver enzyme elevation.

Efficacy and clinical activity

• In the target dose range, XmAb819 showed a 25% objective response rate (all partial responses) and 70% disease control rate in heavily pretreated patients.

• Majority of patients experienced tumor reduction, with sustained disease control and some deepening responses over time.

• Responses included patients with prior progression on belzutifan and those with low ENPP3 expression.

• 50% of efficacy-evaluable patients in the target dose range remain on treatment; all five responders remain on therapy.

• One patient with initial progression had a 47% reduction in lesions and remains on treatment.