Lyell Immunopharma (LYEL) investor relations material

Clinical program updates

• Two next-generation cell therapy products in oncology are in pivotal trials: ronde-cel for large B-cell lymphoma and LYL273 for metastatic colorectal cancer.

• Ronde-cel pivotal trials include a single-arm study with BLA submission planned next year and a head-to-head clinical trial in the second line.

• LYL273, licensed in 2025, showed 40–50% overall response rates in late-line metastatic colorectal cancer, with median overall survival up to 25 months in early studies.

• Safety management for LYL273 includes GI prophylaxis, reducing Grade 2+ diarrhea from 55% to 10%, with no Grade 3 or higher CRS, ICANS, or diarrhea seen with prophylaxis.

• Efficacy and safety data updates for LYL273 are expected in the second half of the year at a medical meeting.

Regulatory and trial design strategy

• The LYL273 phase I protocol was amended to phase I-II, enabling a potential single-arm pivotal trial if FDA agrees.

• End of phase I meeting with FDA is expected by year-end, focusing on recommended phase II dose, patient criteria, and trial design.

• FDA's Project FrontRunner may allow accelerated approval using response rates as endpoints.

• For late-line metastatic colorectal cancer, a 20–30% response rate is considered a strong approval bar; LYL273 has shown higher rates.

• Median overall survival for standard care is less than 12 months; LYL273 data suggest potential to double this.

Mechanism of action and patient experience

• LYL273 targets guanylyl cyclase C (GCC), highly expressed in colorectal cancers, and uses CD19 CARs that secrete cytokines to enhance T-cell expansion and tumor infiltration.

• The GI prophylaxis regimen includes infliximab, vedolizumab, and budesonide, all familiar to physicians and well-tolerated.

• LYL273 is administered with a single day of lymphodepletion and as a one-time treatment, making side effects more manageable compared to ongoing chemotherapy.

• The trial allows moderate liver metastases (up to seven, none >3 cm) to assess efficacy in a challenging subgroup.

• Rising incidence of colorectal cancer in younger adults increases demand for one-time, low-toxicity treatments.