Lyell Immunopharma (LYEL) investor relations material

Strategic positioning and pipeline overview

• Advancing next-generation CAR T-cell therapies for hematologic malignancies and solid tumors, focusing on first-in-class innovation for improved patient outcomes.

• Two lead programs: Ronde-cel for large B-cell lymphoma (LBCL) and LYL273 for metastatic colorectal cancer (mCRC), both targeting large, high unmet-need markets.

• Ronde-cel is a dual-targeting CD19/CD20 CAR T-cell therapy with enhancements for stem-like T-cell enrichment, aiming for high response rates and durable remissions.

• LYL273 is a GCC-targeted CAR T-cell therapy for mCRC, engineered for enhanced expansion, immune infiltration, and controlled cytokine release.

• State-of-the-art LyFE Manufacturing Center supports scalable, commercial-ready production for both programs.

Clinical development and efficacy data

• Ronde-cel demonstrated a 93% overall response rate and 76% complete response rate in 3L+ LBCL, with median progression-free survival of 18 months.

• High efficacy also observed in high-risk 2L LBCL patients, with 83% overall and 61% complete response rates; 94% of patients had primary refractory disease.

• LYL273 showed a 50% overall response rate in Phase 1 mCRC trial, with manageable safety and promising durability, including responses in patients with liver metastases.

• Proof-of-concept data from China support U.S. results, with 40% response rate and median overall survival of 25 months at higher dose levels.

• Both programs are advancing toward pivotal trials, with key data readouts and regulatory submissions expected in 2026–2027.

Safety profile and risk management

• Ronde-cel exhibited low rates of high-grade cytokine release syndrome (CRS) and neurotoxicity (ICANS), with 0% grade ≥3 CRS and 8% grade ≥3 ICANS using dexamethasone prophylaxis.

• No deaths attributed to Ronde-cel; robust CAR T-cell expansion observed regardless of prophylaxis.

• LYL273 safety improved with GI prophylaxis, reducing grade ≥2 diarrhea/colitis from 55% to 10%; no grade ≥3 CRS, ICANS, or GI toxicity at recommended dose.

• Safety management protocols and dose optimization are ongoing, with expansion into new cohorts and combination strategies.

• Manufacturing success rates exceed 97% for Ronde-cel, supporting reliable clinical and future commercial supply.