On August 12, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a late-stage clinical company advancing next-generation CAR T-cell therapies for patients with cancer, reported financial results and business highlights for the second quarter ended June 30, 2025 (Press release, Lyell Immunopharma, AUG 12, 2025, View Source [SID1234655158]). Lyell’s lead clinical program, LYL314, is a next-generation autologous dual-targeting CD19/CD20 CAR T-cell product candidate under evaluation in PiNACLE, a single-arm pivotal trial enrolling patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) in the 3L+ setting and in a Phase 1/2 study in the 2L setting.

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"Based on the high rate of durable complete responses achieved by LYL314 in patients with aggressive LBCL presented at the International Conference on Malignant Lymphoma in Lugano, Switzerland, in June, we believe that our CD19/CD20 CAR T-cell therapy will disrupt the therapeutic landscape by delivering meaningfully increased complete response rates and improved durability over the currently approved CD19 CAR T-cell therapies," said Lynn Seely, M.D., President and CEO of Lyell. "Our recent private placement with well-respected investors significantly derisks our business, extends our cash runway into mid-2027 and enables us to focus on rapidly advancing the clinical development of LYL314. We have initiated the PiNACLE single-arm pivotal trial for patients with LBCL receiving treatment in the third- or later-line setting and are on track to begin a second pivotal trial of LYL314 for patients with LBCL in the second-line setting by early 2026."

Second Quarter Updates and Recent Business Highlights

Lyell is advancing a pipeline of next-generation CAR T-cell product candidates targeting cancers with large unmet need and substantial patient populations. Its lead program, LYL314, is in pivotal development for patients with R/R LBCL and its preclinical programs target solid tumor indications.

LYL314: 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

LYL314 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 that 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. Following a successful End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA), LYL314 is currently being evaluated in the pivotal PiNACLE trial, which is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial of patients with R/R LBCL. The Phase 1/2 trial continues to enroll CAR T-cell therapy naïve patients receiving treatment in the 2L setting and a pivotal trial for these 2L patients is expected be initiated by early 2026. The FDA has granted LYL314 Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for the treatment of R/R diffuse LBCL in the 3L+ setting. RMAT provides all the benefits of the Fast Track and Breakthrough Therapy designation programs and enables increased frequency of communications with the FDA on the development of LYL314.

PiNACLE is a single-arm pivotal trial evaluating LYL314 at a dose of 100 x 106 CAR T cells in patients with LBCL receiving treatment in the 3L+ setting. The trial is expected to enroll approximately 120 patients with R/R diffuse large B-cell lymphoma, high grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma or Grade 3B follicular lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with LYL314 in either 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.
New clinical data from the Phase 1/2 multi-center clinical trial of LYL314 in patients with R/R LBCL were presented at the 18th International Conference on Malignant Lymphoma in June and included more mature data from patients treated in the 3L+ setting and initial data from patients treated in the 2L setting. The data were presented in an oral presentation titled "LYL314, a CD19/CD20 CAR T‑cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in relapsed and/or refractory large B-cell lymphoma". Highlights include:
Fifty-one CAR T-naive patients with R/R LBCL received LYL314 as of April 15, 2025 (the data cutoff date for the presentation). 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+ and 2L, 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.
In efficacy-evaluable 3L+ patients, with a median follow-up of 9 months (N = 25): The overall response rate was 88% (22/25 patients), with 72% (18/25) of patients achieving a complete response. 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months.
In initial data from efficacy-evaluable 2L patients, with a median follow-up of 5 months (N = 11): The overall response rate was 91% (10/11 patients), with 64% (7/11) achieving a complete response. 100% (7/7) of patients with complete response were in complete response at their last assessment, including 3/3 patients at ≥ 6 months. In patients with primary refractory disease, a difficult to treat population, 70% (7/10) achieved a complete response.
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%) or 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.​ The final drug product contained the desired CD62L-positive naïve T-cell phenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment.
An update on the progress of the PiNACLE trial is planned for late 2025. Data from this trial is expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting.
More mature data from the ongoing Phase 1/2 trial in the 2L setting are expected to be presented in late 2025.
A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL.

Preclinical Pipeline, Technologies and Manufacturing Protocols

Lyell is advancing next-generation fully-armed CAR T-cell product candidates, each including multiple technologies, designed to overcome T-cell exhaustion and lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment.

The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in 2026.

Corporate Updates

In July, Lyell entered into a securities purchase agreement for a private placement with certain institutional and other accredited investors, for gross proceeds of up to approximately $100 million. The initial closing of approximately $50 million of common stock at a price of $13.32 per share occurred on July 25, 2025.
After deducting offering expenses, Lyell expects to use net proceeds from the private placement, together with its existing cash, cash equivalents, and marketable securities, to advance two pivotal-stage clinical trials of LYL314 as well as working capital for other general corporate purposes.

Second Quarter 2025 Financial Results

Lyell reported a net loss of $42.7 million for the second quarter ended June 30, 2025, compared to a net loss of $45.8 million for the same period in 2024. The $3.1 million decrease in net loss was primarily due to a decrease of $3.3 million in stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. 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 certain non-cash investment gains and charges, decreased to $37.8 million for the second quarter ended June 30, 2025, compared to $39.1 million for the same period in 2024, primarily due to lower interest income primarily driven by decreased interest rates in 2025 coupled with lower cash equivalent and marketable securities balances.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $34.9 million for the second quarter ended June 30, 2025, compared to $40.3 million for the same period in 2024. The decrease in second quarter 2025 R&D expenses of $5.4 million was primarily due to a $2.9 million reduction in research activities, collaborations and outside services due primarily to a reduction in costs associated with research and laboratory supplies and collaboration agreements and a $2.4 million decrease in personnel‑related expenses primarily due to reduced stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards. 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 second quarter ended June 30, 2025 were $32.6 million, compared to $37.2 million for the same period in 2024.
General and administrative (G&A) expenses were $9.8 million for the second quarter ended June 30, 2025, compared to $12.3 million for the same period in 2024. The decrease in second quarter 2025 G&A expenses of $2.5 million was primarily due to a $1.7 million decrease in stock-based compensation expense primarily related to a decrease in the value of new awards granted and a $0.8 million decrease in outside services primarily due to a reduction in legal expenses. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2025 were $7.1 million, compared to $7.8 million for the same period in 2024.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable 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 June 30, 2025 were approximately $297 million, compared to approximately $384 million as of December 31, 2024. Lyell believes that its cash, cash equivalents and marketable securities balances totaling approximately $347 million inclusive of the initial $50 million of proceeds from its recent private placement, will be sufficient to meet working capital and capital expenditure needs into mid-2027.