Material Event (Form 8-K)

On June 17, 2025, Lyell Immunopharma, Inc. (the "Company") announced new clinical data from its ongoing multi-center Phase 1/2 clinical trial of LYL314, including data from patients with large B-celllymphoma ("LBCL") treated in the third- or later-line ("3L+") setting. LYL314 is an autologous dual-targeting CD19/CD20 chimeric antigen receptor ("CAR") T-cellproduct candidate designed to increase complete response rates and prolong the duration of the responses as compared to approved CD19-targeted CAR T-celltherapies for the treatment of LBCL.

PiNACLE, the single-armpivotal trial of LYL314, 100 x 10⁶ CAR T cells, is underway in patients with large B-celllymphoma treated in the 3L+ setting. The trial is expected to enroll approximately 120 patients with relapsed and/or refractory ("R/R") diffuse large B-celllymphoma, primary mediastinal B-celllymphoma, high grade B-celllymphoma, grade 3B follicular lymphoma, or transformed follicular lymphoma who have not previously received CAR T-celltherapy. Patients may be treated with LYL314 in either the inpatient or outpatient setting. The primary endpoint of the trial is the overall response rate.

Fifty-oneCAR T-naivepatients with R/R LBCL received LYL314 as of April 15, 2025 (the data cutoff date for the presentation at the International Conference on Malignant Lymphoma). The efficacy evaluable population consisted of 36 patients with Day 84 assessments or prior disease progression or death. Patient demographics and baseline disease characteristics were consistent with high-risk patient populations: median ages of 65 and 69 years in the 3L+ setting and second-line ("2L") setting, respectively, 41% of 3L+ and 65% of 2L patients had Stage IV disease at trial entry, and 47% of 3L+ and 82% of 2L patients had primary refractory disease. There were 49 patients who received the recommended Phase 2 dose of 100 x 10⁶ CAR T cells; two patients received a dose of 300 x 10⁶ CAR T cells. CD19/CD20 screening was not required prior to enrollment.

In efficacy-evaluable 3L+ patients, with a median follow up of 9 months (N = 25):

In initial data from efficacy-evaluable 2L patients, with a median follow up of 5 months (N = 11):

In 51 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade ≥ 3 and low rates of Grade 1 (22%) and Grade 2 (35%) cytokine release syndrome (CRS) were reported. Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 6% (Grade 1), 2% (Grade 2), and 14% (Grade ≥ 3) of patients. The median time to complete resolution of all reports of ICANS was 5 days, with rapid improvement (median of 2 days) to Grade 2 or lower with standard therapy. No deaths were related to LYL314 administration. LYL314 demonstrated robust expansion with a time to peak of 10 days (N = 51). The final drug product contained the desired CD62L-positive naïve T-cellphenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment.

The Company expects to initiate a randomized pivotal trial of LYL314 in patients with R/R LBCL in the 2L setting by early 2026.

The Company's clinical supply is manufactured in the Company's LyFE Manufacturing Center^TM ("LyFE") in Bothell, Washington. At full staffing and capacity, the Company expects to be able to manufacture over 1,200 CAR T-celltherapy doses at LyFE and support the Company's clinical development needs for LYL314 and other pipeline programs, as well as early commercial launch of LYL314, if approved.