Lyell Immunopharma (LYEL) investor relations material

Clinical trial results for ronde-cel in large B-cell lymphoma

• Ronde-cel achieved a 93% overall response rate and 76% complete response rate in third or later line patients, with a median progression-free survival of 18 months and a safety profile suitable for outpatient use.

• In the second line, primarily primary refractory patients had an 83% overall response rate and 61% complete response rate, with 70% of complete responders maintaining response for six months or more; median duration of complete response was not reached at data cutoff.

• No Grade 3 or higher CRS events were reported; Grade 3 or higher ICANS was reduced to less than 5% with dexamethasone prophylaxis, and no deaths were attributed to treatment.

• The patient population was high-risk, heavily pre-treated, including many over age 75 and those with primary refractory disease.

• Ronde-cel is being evaluated in two pivotal trials: PiNACLE (single-arm, third or later line) and PiNACLE Head-to-Head (Phase 3, randomized vs. approved CAR T therapies in 2L), with ongoing regulatory engagement and FDA RMAT/Fast Track designations.

Comparative efficacy and market positioning

• Ronde-cel's response and progression-free survival rates compare favorably to approved CD19 CAR T-cell therapies, which show lower response rates and shorter median progression-free survival.

• The differentiated safety and efficacy profile is expected to drive switching from current market leaders, with the CAR T-cell market projected to grow beyond $5 billion.

• Physicians have historically switched CAR T-cell products based on new clinical data, supporting potential rapid adoption.

Translational and mechanistic/manufacturing insights

• Ronde-cel is a dual-targeting CD19/CD20 CAR T-cell product enriched for CD62L+ stem-like T cells, designed to overcome antigen loss and improve durability, with >96% CD62L+ of CD3+ cells and a median vein-to-site time of 16 days.

• CD62L enrichment yields a high proportion of naïve and central memory T cells, correlating with better expansion, persistence, and improved clinical outcomes.

• Ronde-cel CAR T-cells demonstrated up to 3-fold higher expansion post-infusion, sustained proliferation, cytotoxicity, and cytokine secretion two months post-infusion compared to approved CD19 CAR T-cell products.

• Translational data support the clinical benefit of CD62L+ enrichment, with ongoing correlative analysis in the pivotal trial.

• Proprietary manufacturing process enables commercial-scale production of CAR T cells with enhanced antitumor activity.