Xencor (XNCR) 12th Annual Cantor Fitzgerald Global Healthcare Conference summary

Strategic evolution and late-stage development

• Transitioning from a partner-driven to a self-driven late-stage development model, focusing on advancing proprietary XmAb molecules into pivotal studies and registration, with a key data set for ENPP3-targeted T-cell engager in RCC to be presented at ESMO soon.

• The upcoming data will define the go-forward dose, clinical profile, and support the design of a registrational study targeted to start next year.

• Multiple expansion cohorts with double-digit patients are being evaluated, with safety, efficacy, and lower bounds on durability to be disclosed.

• The RCC landscape is characterized by heavily pretreated patients, with current benchmarks for response rates in the teens and median PFS around 5 months.

• ENPP3 T-cell engager is positioned as a novel, orthogonal approach with a promising 25% response rate and clean toxicity profile in early data.

Market opportunity and pipeline expansion

• RCC market is estimated at $11 billion globally, with opportunities to disrupt TKI use in later lines and expand into earlier lines through ongoing and planned sub-studies.

• Sub-studies are underway in post-IO, pre-TKI settings, and combination studies with PD-1 inhibitors are planned for early next year.

• Additional tumor types under exploration include papillary renal cell, MSS colorectal cancer, and non-small cell lung, with patient selection based on ENPP3 expression.

• Three late-stage solid tumor T-cell engager programs are advancing with partners, and a fourth may emerge by year-end.

• Commercial benchmarks include belzutifan, now exceeding $1 billion in annual sales, highlighting the potential for novel agents.

Clinical development strategy and competitive positioning

• The 25% ORR from earlier cohorts is seen as a strong benchmark for monotherapy development and planning for registration-enabling studies.

• Durability data, though early, will inform pivotal study design and regulatory discussions.

• Strategic decisions are driven by the ability to be best-in-class; Claudin-6 T-cell engager development in gynecologic tumors was paused to pursue a combination approach with B7H3 due to competitive response rates and toxicity concerns.

• The AND gate concept, combining different T-cell engager targets, is being explored to enhance selectivity and therapeutic index, with clinical proof-of-concept data expected from partner programs before year-end.

• The 2+1 platform enables selectivity for high-expressing tumor cells, and the AND gate approach aims to further reduce off-tumor toxicity.