On March 12, 2026 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a late-stage clinical company advancing a pipeline of next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with cancer, reported financial results and business highlights for the fourth quarter and year ended December 31, 2025. Lyell has since commenced patient dosing in the first-of-its-kind Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of rondecabtagene autoleucel (ronde-cel) versus investigator’s choice of axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) with disease progression on at least one prior line of therapy (PiNACLE-H2H). Lyell has dosed seven new patients with metastatic colorectal cancer (mCRC) with LYL273, an enhanced guanylyl cyclase C (GCC)-targeted CAR T-cell product candidate, since its November 2025 acquisition, without dose-limiting toxicity and including dose escalation to Dose Level 3.

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Lyell also recently announced it has closed the sale of an additional $50 million of shares of its common stock to investors from its July 2025 equity private placement of up to $100 million, following achievement of a clinical milestone within its PiNACLE pivotal trial evaluating ronde-cel in patients with R/R LBCL in the third- or later-line setting (3L+), and the appointment of Smital Shah as its Chief Financial and Business Officer.

"Lyell is on track to achieve multiple clinical milestones in the next 12 to 18 months. We have now advanced ronde-cel into two pivotal clinical trials, with the pivotal data supporting BLA submission from the PiNACLE trial expected to be reported mid-next year," said Lynn Seely, M.D., President and Chief Executive Officer of Lyell. "With the encouraging emerging safety profile and clinical activity observed with LYL273 in patients with metastatic colorectal cancer, we believe Lyell is well-positioned with two next-generation CAR T‑cell product candidates."

Fourth Quarter Updates and Recent Business Highlights

Ronde-cel: A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to approved CD19‑targeted CAR T-cell therapies for the treatment of LBCL

Ronde-cel is an autologous CAR T-cell product candidate with a true ‘OR’ logic gate to target B cells that express either CD19 or CD20 with full potency and is manufactured with a process that enriches for CD62L-positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity. Ronde-cel has received from the U.S. Food and Drug Administration (FDA) Regenerative Medicine Advanced Therapy (RMAT) designation as well as Fast Track designation for the treatment of adults with R/R LBCL.

•The pivotal PiNACLE single-arm trial is a seamless expansion of the 3L+ cohort in the Phase 1/2 multi-cohort trial and is evaluating ronde-cel at a dose of 100 x 106 CAR T cells in patients with R/R LBCL. The trial is expected to enroll approximately 120 patients in the inpatient or outpatient setting, and there is no upper age limit for eligibility. The primary endpoint of the trial is the overall response rate, including an evaluation of duration of response.

•Patient dosing commenced in February 2026 in PiNACLE-H2H, the Phase 3 randomized controlled trial evaluating ronde-cel versus investigator’s choice of axi-cel or liso-cel in patients with R/R LBCL in the 2L setting. The trial is expected to enroll approximately 400 patients (200 per arm) at sites in the US, Canada and Australia. Patients may be treated in either the inpatient or outpatient setting. The trial’s primary endpoint is event-free survival.
•Updated data from the ongoing Phase 1/2 clinical trial were presented at the December 2025 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2025):
◦A best overall response rate of 93% and a complete response rate of 76% in 29 efficacy-evaluable patients with R/R LBCL in the 3L+ setting. The median progression-free survival was 18 months as of the data cutoff date of September 5, 2025.
◦Data were also presented from the 2L cohort in the Phase 1/2 multi-cohort clinical trial, including an efficacy-evaluable population of 18 patients (94% with high-risk primary refractory disease) and demonstrated an 83% best overall response rate and a 61% complete response rate.
◦The safety profile was appropriate for outpatient administration. Data from 25 patients treated with ronde-cel who received dexamethasone prophylaxis in the 3L+ and 2L settings revealed no events of ≥ Grade 3 cytokine release syndrome and a 4% rate of ≥ Grade 3 immune cell-associated neurotoxicity syndrome.
LYL273 (formerly known as GCC19CART): A next-generation GCC-targeted CAR T-cell product candidate for the treatment of mCRC and other GCC-expressing cancers
LYL273 is a GCC-targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release, designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile tumor microenvironment. In November 2025, we acquired global rights (excluding mainland China, Hong Kong, Macau and Taiwan) to LYL273, which has shown promising dose-dependent clinical activity in patients with advanced mCRC in a Phase 1 trial conducted in the U.S. LYL273 received from the FDA Fast Track designation for the treatment of mCRC.
•The U.S. Phase 1 clinical trial is continuing to enroll patients to determine the recommended Phase 2 dose. Seven additional patients with mCRC have been treated with LYL273 since the November 2025 acquisition without dose-limiting toxicity and including dose escalation to Dose Level 3.

•A 67% best overall response rate, an 83% disease control rate and an 8-month median progression-free survival with a manageable safety profile have been reported at the highest dose level tested as of the data cutoff date of October 28, 2025 (Dose Level 2) in patients with refractory mCRC in the U.S. Phase 1 clinical trial.

Fourth Quarter and Full Year 2025 Financial Results

Lyell reported a net loss of $140.7 million and $274.4 million for the fourth quarter and year ended December 31, 2025, respectively, compared to a net loss of $191.9 million and $343.0 million for the same periods in 2024. Net loss for the fourth quarter and year ended December 31, 2025 included $66.3 million in acquired in-process research and development (IPR&D) expense as part of the acquisition of our rights to LYL273, and $19.7 million in stock-based compensation expense for an equity milestone deemed probable related to the LYL273 license acquisition. Net loss for the fourth quarter and year ended December 31, 2024 included $87.2 million in acquired IPR&D expense as part of our acquisition of ImmPACT Bio and $51.3 million of long‑lived asset impairment expense. Non‑GAAP net loss, which excludes stock-based compensation, non-cash expenses related to the change in the estimated fair value of success payment liabilities and securities purchase agreement put/call liability, long‑lived asset impairment expense and certain non-cash investment gains and charges, was $33.1 million and $144.8 million for the fourth quarter and year ended December 31, 2025, respectively, compared to $45.9 million and $159.5 million for the same periods in 2024.

GAAP and Non-GAAP Operating Expenses

•Research and development (R&D) expenses were $52.2 million for the fourth quarter ended December 31, 2025, compared to $48.7 million for the same period in 2024. The increase in fourth quarter 2025 R&D expenses of $3.5 million was primarily due to $19.7 million in stock-based compensation expense for an equity milestone deemed probable related to the LYL273 license acquisition. The increase in fourth quarter 2025 R&D expenses was partially offset by an $8.9 million reduction in personnel costs and a $4.7 million reduction in additional facilities and technology costs primarily due to reduced headcount following the successful technology transfer of ronde-cel to our LyFE Manufacturing CenterTM (LyFE) and associated workforce reduction in the first half of 2025. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the fourth quarter ended December 31, 2025, were $30.1 million compared to $45.4 million for the same period in 2024 due to the workforce reduction related to the successful technology transfer of ronde-cel.
•General and administrative (G&A) expenses were $10.6 million for the fourth quarter ended December 31, 2025, compared to $14.5 million for the same period in 2024. The decrease in fourth quarter 2025 G&A expenses of $3.9 million was primarily due to a $4.1 million decrease in personnel costs associated with the workforce reduction related to the successful ronde-cel technology transfer, partially offset by a $0.8 million increase in collaborations and licenses expenses.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable U.S. generally accepted accounting principles (GAAP) measures to non‑GAAP financial measures, is presented below under "Non-GAAP Financial Measures."
Cash, cash equivalents and marketable securities
Cash, cash equivalents and marketable securities as of December 31, 2025 were approximately $247.2 million (excluding the $50 million tranche received in March 2026), compared to approximately $383.5 million as of December 31, 2024. Lyell believes that its current cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into the second quarter of 2027.

(Press release, Lyell Immunopharma, MAR 12, 2026, View Source [SID1234663501])