On August 7, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors or hematologic malignancies, reported financial results and business highlights for the second quarter ended June 30, 2024 (Press release, Lyell Immunopharma, AUG 7, 2024, View Source [SID1234645498]).
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"We are pleased that initial data from our Phase 1 trial of LYL797 demonstrated dose-dependent clinical activity and that LYL797 CAR T cells expanded, infiltrated solid tumors and killed cancer cells in patients. Based on these promising initial data, we have expanded the cancer indications under evaluation in this trial to include patients with ovarian and endometrial cancers, and we plan to file an IND to initiate a new trial evaluating LYL797 in multiple myeloma and chronic lymphocytic leukemia," said Lynn Seely, M.D., Lyell’s President and CEO. "In addition, our IND for LYL119, a next generation ROR1-targeted CAR T‑cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion, has been cleared by the FDA, and we expect to report initial clinical data from the Phase 1 trial in the second half of 2025. We remain on track to report initial clinical data from our lead TIL program in the second half of this year. Our strong cash position enables us to advance multiple product candidates through critical clinical milestones and fund operations into 2027."
Second Quarter Updates and Recent Business Highlights
Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845, are in Phase 1 clinical development, and LYL119 is entering Phase 1 clinical development. A second-generation tumor infiltrating lymphocyte (TIL) product candidate is in preclinical development.
LYL797 – A ROR1-targeted CAR T-cell product candidate enhanced with anti-exhaustion technology designed for improved tumor infiltration and tumor cell killing
•Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study was initiated in patients with relapsed/refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). Based on the initial clinical data that demonstrated dose-dependent anti-tumor activity, the trial has been expanded to include patients with platinum-resistant ovarian or endometrial cancers and an investigational new drug (IND) application is expected to be submitted in the second half of this year to initiate a second Phase 1 clinical trial of LYL797 in multiple myeloma and chronic lymphocytic leukemia (CLL).
•Initial clinical and translational data from the Phase 1 clinical trial of LYL797 were reported in June 2024. The initial dataset of 20 patients (16 patients with TNBC and four patients with NSCLC) demonstrated dose-dependent antitumor clinical activity and the ability of LYL797 CAR T cells to proliferate, infiltrate tumors and kill cancer cells in patients with relapsed/refractory disease. Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and a clinical benefit rate (CBR) of 60% at the 150 x 106 CAR T cell dose level, with a CBR of 38% across all dose levels evaluable at the time data were reported. Common treatment-related adverse events (TRAE) in patients without lung metastases included Grade 1 and 2 cytokine release syndrome (CRS) and headache, and the expected cytopenia from lymphodepletion. There were no reports of immune effector cell‑associated neurotoxicity syndrome (ICANS) attributed to LYL797. Pneumonitis occurred in some patients with lung metastases, including the index patient who experienced Grade 5 respiratory failure on Day 41. All patients are now given dexamethasone prophylaxis and dose escalation is continuing separately and more gradually in patients with lung involvement. No dose‑limiting toxicities have been reported in patients without lung involvement.
•Updated data from the ongoing Phase 1 trial in solid tumor indications, including the initiation of dose expansion, are expected in late 2024 – early 2025.
LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability
•Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The trial is designed to include patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.
•Initial clinical and translational data from the Phase 1 trial of LYL845 in patients with advanced melanoma are expected in the second half of 2024.
LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate incorporating four stackable and complementary anti-exhaustion technologies designed for enhanced potency
•LYL119 is a ROR1-targeted CAR T-cell product enhanced with four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology.
•An IND application for LYL119 has received clearance from the U.S. Food and Drug Administration (FDA).
•The Phase 1 trial is designed as an open‑label dose‑escalation and ‑expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum‑resistant ovarian cancer or endometrial cancer. It is estimated that approximately 50% of patients with ovarian cancer and approximately 50% of patients with endometrial cancer have ROR1‑positive tumors.
•Initial clinical data are expected in the second half of 2025.
Second Quarter Financial Results
Lyell reported a net loss of $45.8 million for the second quarter ended June 30, 2024, compared to a net loss of $63.9 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash 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, was $39.1 million for the second quarter ended June 30, 2024, compared to $45.6 million for the same period in 2023.
GAAP and Non-GAAP Operating Expenses
•Research and development (R&D) expenses were $40.3 million for the second quarter ended June 30, 2024, compared to $47.5 million for the same period in 2023. The decrease in second quarter 2024 R&D expenses of $7.2 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. 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, 2024, were $37.2 million, compared to $41.6 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.
•General and administrative (G&A) expenses were $12.3 million for the second quarter ended June 30, 2024, compared to $19.0 million for the same period in 2023. The decrease in second quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2024, were $7.8 million, compared to $10.1 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce.
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, 2024, were $491.1 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.