Lyell Immunopharma (LYEL) Goldman Sachs 45th Annual Global Healthcare Conference summary

Technology and program overview

• Focus on novel cell therapies for solid tumors using proprietary T cell reprogramming technologies to resist exhaustion and maintain stemness.

• Four core technologies are integrated across CAR T and TIL programs, including c-Jun overexpression, Epi-R, NR4A3 knockout, and Stim-R for physiological T cell activation.

• Lead programs include a ROR1-targeted CAR T cell (LYL797) and a TIL program, both in phase 1, with a third program (LYL119) entering the clinic in the second half of the year.

• Technologies aim to improve T cell persistence, tumor infiltration, and anti-tumor activity in hostile microenvironments.

Clinical development and data expectations

• LYL797 phase 1 data, including at least 20 patients, is expected by the end of June, targeting a 25%-30% response rate and 4-5 months durability.

• The clinical bar is set based on FDA expectations for late-line triple-negative breast cancer, with plans for a single-arm pivotal trial for accelerated approval.

• Data will include clinical outcomes, safety, and deep translational analysis to assess T cell exhaustion resistance and persistence.

• Translational endpoints include CAR T cell expansion, tumor infiltration, and exhaustion marker reduction, benchmarked against prior Fred Hutch studies.

Preclinical validation and benchmarking

• Preclinical models show c-Jun overexpression and Epi-R reduce exhaustion markers (TIGIT, LAG-3, PD-1) and prolong T cell function.

• LYL119, the next-generation CAR T, combines c-Jun overexpression and NR4A3 knockout, showing step-change potency in preclinical models, controlling tumors at lower cell doses.

• Technologies are validated against non-enhanced ROR1 CARs, with clinical data expected to confirm preclinical predictiveness.