Lyell Immunopharma (LYEL) Morgan Stanley 22nd Annual Global Healthcare Conference summary

Platform overview and technology focus

• Developing innovative cell therapies for cancer using CAR T-cell and TIL approaches, with proprietary anti-exhaustion technologies to enhance T-cell persistence and effectiveness.

• Technologies aim to overcome T-cell exhaustion and promote durable stemness, enabling precise targeting and killing of cancer cells.

• Two clinical programs: ROR1 CAR T-cell (LYL797) with recent data, and TIL therapy (LYL845) with data expected by year-end.

LYL797 clinical progress and expansion

• LYL797 showed dose-dependent activity in late-line solid tumor patients, with a 40% objective response rate and 60% clinical benefit rate at the highest dose.

• Anti-exhaustion technology validated by strong T-cell expansion and tumor infiltration, outperforming comparator studies.

• Pneumonitis observed, especially in patients with lung metastases, but is predictable and managed with steroids and prophylactic dexamethasone.

• Expansion into ovarian, endometrial, multiple myeloma, and CLL indications, with ongoing patient enrollment.

• No evidence of on-target, off-tumor toxicity observed in clinical experience.

Next-generation ROR1 CAR T and pipeline strategy

• LYL119, a next-gen ROR1 CAR T, incorporates c-Jun overexpression and NR4A3 knockout for enhanced potency, showing tenfold improved efficacy in preclinical models.

• Both LYL797 and LYL119 will advance in parallel, with data-driven decisions on indication prioritization.

• Anti-exhaustion technologies are platform-agnostic and can be applied to any CAR, TIL, or TCR therapy.