Xencor (XNCR) investor relations material

Strategic evolution and late-stage development

• Transitioning from a platform and partnership focus to advancing proprietary XmAb molecules into late-stage development, with pivotal studies planned for next year.

• The upcoming ESMO data set for the ENPP3-targeted T-cell engager in RCC will define the go-forward dose and clinical profile, supporting a registrational study.

• Expansion cohorts in refractory, late-stage RCC are being analyzed for safety, efficacy, and durability, with lower bounds on durability to inform pivotal study design.

• Multiple late-stage solid tumor T-cell engager programs are advancing, both internally and with partners, with several pivotal data readouts expected by year-end.

• The company aims to establish itself as a leader in T-cell engagers for solid tumors, with a focus on clinical execution and late-stage advancement.

Clinical data and market opportunity in RCC

• ENPP3 T-cell engager showed a 25% response rate in early cohorts, with a clean toxicity profile, setting a benchmark for further development.

• The late-stage RCC market is large, with over $11 billion in annual global sales across PD-1 inhibitors, VEGFR TKIs, and HIF-2 alpha inhibitors.

• Sub-studies are underway in post-IO, pre-TKI settings, and combination studies with PD-1 inhibitors are planned to expand into earlier lines of therapy.

• The program is also being explored in papillary RCC, MSS colorectal cancer, and non-small cell lung cancer, with patient selection based on ENPP3 expression.

• The company is positioning its novel agent to disrupt the TKI class and capitalize on the growing RCC market.

Pipeline updates and combination strategies

• Claudin-6 T-cell engager in gynecologic tumors showed modest activity, prompting a shift to combination with B7H3 CD28 to enhance efficacy and selectivity.

• The AND gate approach, combining different antigen targets for CD3 and CD28, aims to broaden the therapeutic index and improve selectivity in solid tumors.

• Multiple late-stage programs, including ASP2138, zalarutamig, and partner-led combinations, are advancing in pivotal testing.

• The 2+1 platform enables selectivity for high-expressing tumor cells, reducing toxicity to healthy tissue and opening new solid tumor targets.

• The AND gate study is starting this quarter, with partner data from J&J expected before year-end.