On May 13, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with cancer, reported financial results and business highlights for the first quarter ended March 31, 2025 (Press release, Lyell Immunopharma, MAY 13, 2025, View Source [SID1234652978]). Lyell’s lead clinical program, LYL314 (formerly known as IMPT-314), is an autologous CD19/CD20 dual-targeting CAR T-cell product candidate under evaluation in a Phase 1/2 trial enrolling patients with relapsed and/or refractory large B-cell lymphoma (LBCL). LYL314 was recently granted RMAT designation by the United States FDA in recognition of its potential to address significant unmet needs in patients with aggressive LBCL in the third- or later-line setting.
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"We are pleased with the progress we are making with our LYL314 clinical development strategy and look forward to presenting new clinical data from patients with aggressive large B-cell lymphoma who have not previously received CAR T-cell therapy at the International Conference on Malignant Lymphoma in Lugano, Switzerland in June," said Lynn Seely, M.D., President and CEO of Lyell. "Based on promising clinical data, Lyell remains on track to initiate two pivotal programs for LYL314: one for patients in the third- or later-line setting by mid-2025 and a second for patients in the second-line setting by early 2026. In addition, our LyFE Manufacturing Center in Bothell, Washington is now manufacturing the LYL314 clinical supply following completion of a successful technology transfer and FDA clearance of an IND amendment."
First Quarter Updates and Recent Business Highlights
Lyell is advancing a pipeline of next-generation CAR T-cell product candidates. Its lead program, LYL314, is in Phase 1/2 clinical development for relapsed and/or refractory LBCL and its preclinical programs target solid tumor indications. Lyell’s programs target cancers with large unmet need with substantial patient populations.
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 the 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. LYL314 is currently being evaluated in a multi-center, open-label trial that is enrolling patients in the third- or later-line and second-line settings who have not previously received CAR T-cell therapy. The trial is designed to evaluate the tolerability and clinical benefit of LYL314 in patients with relapsed and/or refractory LBCL and determine a recommended Phase 2 dose. The FDA has granted LYL314 RMAT and Fast Track designations for the treatment of relapsed and/or refractory diffuse LBCL in the third- or later-line 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.
New clinical data from the Phase 1/2 multi-center clinical trial of LYL314 in patients with relapsed and/or refractory LBCL will be presented at the 18th International Conference on Malignant Lymphoma in June, including more mature data from patients treated in the third- or later-line setting and initial data from patients treated in the second-line setting. The data will be highlighted 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 R/R large B-cell lymphoma" to be presented on June 18th at 5:40 pm CEST.
Initial clinical data in 23 patients treated with LYL314 from the ongoing Phase 1/2 clinical trial were presented at the American Society for Hematology 2024 Annual Meeting on December 9, 2024. The efficacy evaluable population consisted of 17 patients with relapsed and/or refractory LBCL in the third- or later-line setting who had not previously received a CAR T-cell therapy prior to LYL314 administration. The overall response rate was 94% (16/17) of patients, and 71% (12/17) of patients achieved a complete response by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients experienced a response at last follow-up. In the safety evaluable population of 23 patients, no event of Grade 3 or greater cytokine release syndrome was reported. Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 13% (3/23) of patients with a median time to ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy.
LYL314 clinical supply is now manufactured at the LyFE Manufacturing Center in Bothell, Washington following successful technology transfer and clearance by the FDA of an IND amendment. LyFE is a state-of-the-art cell therapy manufacturing facility with the capacity to provide drug supply for Lyell’s ongoing and planned pivotal trials and through potential commercial launch, with a capacity over 1,000 CAR T-cell therapy doses per year.
A pivotal trial in the third- or later-line setting is expected to be initiated in mid-2025 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy.
More mature data from the ongoing Phase 1/2 trial in the second-line setting are expected to be presented in late-2025.
A pivotal trial in the second-line setting is expected to be initiated by early 2026 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy.
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.
An abstract titled "Engineered T Cells Combining Stackable Reprogramming Technologies Enable Durable Anti‑tumor Activity in Xenograft Solid Tumors" has been accepted for an oral presentation at the 28th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper), on May 16, 2025, in New Orleans, LA. The presentation will highlight preclinical data demonstrating that engineered T cells enhanced with c-Jun overexpression, a chimeric co-stimulatory receptor and localized cytokine signaling technologies exhibit potent tumor cell killing in vitro, T-cell viability in vitro and in vivo without cytokine support and effective durable antitumor activity in preclinical solid tumor models.
An abstract titled "Optimizing Stim-R, a synthetic stimulatory agent, for feeder-free tumor-infiltrating lymphocyte manufacturing" was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025. The presented work demonstrated that Stim-R, Lyell’s customizable synthetic T-cell activation reagent designed to emulate natural antigen presentation, has the potential to overcome scalability limitations in tumor-infiltrating lymphocyte manufacturing processes by providing a synthetic replacement for feeder cells.
First Quarter 2025 Financial Results
Lyell reported a net loss of $52.2 million for the first quarter ended March 31, 2025, compared to a net loss of $60.7 million for the same period in 2024. The $8.5 million decrease in net loss was primarily driven by $13.0 million in impairment expenses recognized in the prior year period that did not occur in 2025, partially offset by lower interest income of $3.0 million primarily driven by lower interest rates in 2025, coupled with lower cash equivalent and marketable securities balances. 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, increased to $46.3 million for the first quarter ended March 31, 2025, compared to $37.5 million for the same period in 2024 due primarily to increased personnel costs and lower interest income in 2025.
GAAP and Non-GAAP Operating Expenses
Research and development (R&D) expenses were $43.4 million for the first quarter ended March 31, 2025, compared to $43.2 million for the same period in 2024. The increase in first quarter 2025 R&D expenses of $0.3 million was primarily due to a $3.1 million increase in personnel expenses, due primarily to severance expenses resulting from Lyell’s 2025 workforce reduction related to the closure of the West Hills manufacturing facility acquired as part of Lyell’s acquisition of ImmPACT in 2024, partially offset by reductions in collaboration agreement and leasehold improvement depreciation costs. 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 first quarter ended March 31, 2025 were $41.1 million compared to $38.9 million for the same period in 2024.
General and administrative (G&A) expenses were $14.0 million for the first quarter ended March 31, 2025, respectively, compared to $13.5 million for the same period in 2024. The increase in first quarter 2025 G&A expenses of $0.6 million was primarily driven by an increase of $2.4 million in personnel‑related expenses due to higher headcount associated with Lyell’s acquisition of ImmPACT and severance expenses related to the West Hills facility closure, partially offset by $1.7 million in decreased stock-based compensation expense due to a decrease in the value of awards granted. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the first quarter ended March 31, 2025 were $10.4 million, compared to $8.1 million for the same period in 2024. The $2.3 million increase in first quarter 2025 non-GAAP G&A expenses was primarily driven by increased headcount and severance expenses.
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 March 31, 2025 were $330.1 million compared to $383.5 million as of December 31, 2024. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.