Lyell

Lyell Immunopharma, Inc. (Nasdaq: LYEL) is a late-stage clinical-stage biotechnology company headquartered in South San Francisco, California, that develops next-generation chimeric antigen receptor (CAR) T-cell therapies for hematologic malignancies and solid tumors. Founded in 2018, the company's scientific premise is to engineer T cells that resist exhaustion and retain durable "stemness," addressing limitations that have constrained the durability and solid-tumor reach of approved cell therapies.

The lead program is rondecabtagene autoleucel (ronde-cel, formerly LYL314 / IMPT-314), an autologous dual-targeting CD19/CD20 CAR T-cell candidate with an "OR" logic gate that targets B cells expressing either antigen, manufactured with a process enriching for CD62L-positive cells to produce more naive and central memory CAR T cells. Ronde-cel holds FDA Regenerative Medicine Advanced Therapy and Fast Track designations for relapsed/refractory large B-cell lymphoma and is in two pivotal trials: the single-arm PiNACLE trial (approximately 120 patients, third-line or later, primary endpoint overall response rate) and PiNACLE-H2H (NCT07188558), a Phase 3 randomized head-to-head trial versus investigator's choice of axicabtagene ciloleucel or lisocabtagene maraleucel in second-line patients, targeting approximately 400 patients across the US, Canada and Australia with event-free survival as the primary endpoint. The second program is LYL273 (formerly GCC19CART), a guanylyl cyclase C-targeted CAR T-cell candidate enhanced with CD19 CAR expression and controlled cytokine release, in Phase 1 for metastatic colorectal cancer and holding FDA Fast Track designation.

Earlier programs have been discontinued as the company narrowed its pipeline, including LYL797 (ROR1-targeted CAR T for solid tumors), LYL845 (tumor-infiltrating lymphocyte therapy), LYL119 and IMPT-514. Manufacturing is centralized at the company-operated LyFE Manufacturing Center in Bothell, Washington, described as cGMP-qualified and paperless with capacity for more than 1,000-1,200 CAR T-cell doses annually and commercial launch capability.

Founding story

The company was founded in 2018 by a group of cell therapy and oncology researchers: Rick Klausner, M.D., former director of the National Cancer Institute and co-founder of Juno Therapeutics and GRAIL, who serves as Board Chair; Crystal Mackall, M.D., an expert in pediatric oncology and T-cell immunology; and Stan Riddell, M.D., known for foundational work in adoptive T-cell therapy whose research contributed to the Juno therapy Breyanzi. The founders sought to overcome T-cell exhaustion and improve the durability of cell therapies, particularly in solid tumors, by genetically and epigenetically reprogramming T cells.

Business model

Lyell is a clinical-stage therapeutics developer without significant commercial revenue. It funds R&D through equity capital markets and in-licensing/acquiring clinical assets, and manufactures its own cell therapy products at an internal facility rather than relying solely on contract manufacturers.

The company is described as not yet generating significant commercial revenue; historically it received funding from a partnership with GSK valued at $250 million over three years, which GSK exited. Future revenue would depend on approval and commercialization of its CAR T-cell candidates.

Traction

Ronde-cel produced a 93% best overall response rate and 76% complete response rate in 29 efficacy-evaluable third-line-or-later R/R LBCL patients with 18-month median progression-free survival (September 5, 2025 cutoff), and an 83% best overall response rate with 61% complete responses in an 18-patient second-line cohort; among 25 patients receiving dexamethasone prophylaxis there were no Grade 3 or higher cytokine release syndrome events and a 4% rate of Grade 3 or higher neurotoxicity. Earlier reported Phase 1/2 figures were an 88% overall response rate and 72% complete response rate in CAR T-naive 3L+ patients, with 71% of complete responses maintained at least six months. LYL273 showed a 50% overall response rate in a Phase 1 trial in refractory metastatic colorectal cancer.

Latest developments

In its Q4 and full-year 2025 results reported March 12, 2026, Lyell disclosed cash of approximately $247.2 million at year-end 2025 excluding a $50 million tranche closed in March 2026, with runway into the second quarter of 2027. Patient dosing began in February 2026 in PiNACLE-H2H; pivotal data from PiNACLE supporting a BLA submission is expected mid-2027 per management guidance of "mid-next year." Seven additional metastatic colorectal cancer patients were dosed with LYL273 since the November 2025 acquisition without dose-limiting toxicity, with escalation to Dose Level 3. Smital Shah joined as Chief Financial and Business Officer in March 2026.