Lyell Immunopharma (LYEL) H.C. Wainwright 26th Annual Global Investment Conference 2024 summary

Key program updates

• Lead ROR1 CAR T cell program (LYL797) showed 40% objective response and 60% clinical benefit at 150M cell dose in phase I, with dose-dependent activity and expansion to six tumor types.

• Next-generation CAR T (LYL119) incorporates four proprietary anti-exhaustion technologies, recently cleared IND, and will enter clinic soon, initially targeting ovarian and endometrial cancers.

• Tumor-infiltrating lymphocyte (TIL) program (LYL845) for advanced melanoma is enrolling, with first data on ~20 patients expected before year-end, using proprietary Epi-R manufacturing for stem-like and effector T cells.

• IND submission for hematologic malignancies (multiple myeloma, CLL) planned for this year, expanding ROR1 CAR T reach.

• Multiple clinical milestones expected through 2027, supported by $490M cash balance and in-house manufacturing capacity of 500 doses/year.

Technology and clinical insights

• Proprietary technologies include c-Jun overexpression, NR4A3 knockout (genetic), and Epi-R, Stim-R (epigenetic/manufacturing), designed to enhance T cell persistence and anti-tumor activity.

• LYL797 demonstrated CAR T cell infiltration, expansion, and persistence in solid tumors, with translational data supporting anti-exhaustion approach.

• Safety profile manageable; pneumonitis observed in patients with lung involvement is treated with steroids and mitigated by dexamethasone prophylaxis.

• 100% manufacturing success rate achieved, validating investment in proprietary manufacturing center.

• Preclinical models show LYL119 controls tumors at lower doses than LYL797, indicating a step change in potency.

Forward-looking statements and milestones

• Ongoing dose escalation in LYL797 aims to improve durability and response rates, with further data updates expected late 2024/early 2025.

• LYL119 clinical progress and data updates anticipated in 2025.

• LYL845 TIL data for advanced melanoma to be presented before end of 2024.

• IND filings for hematologic malignancies and continued expansion into new tumor types planned for 2024.

• Financial runway extends into 2027, supporting advancement of all key programs.