On February 28, 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 reported financial results and business highlights for the fourth quarter and year ended December 31, 2023 (Filing, 3 mnth, DEC 31, Lyell Immunopharma, 2024, FEB 28, 2024, View Source [SID1234640591]).

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"We are focused on generating clinical data in our two Phase 1 clinical trials and advancing new reprogramming technologies designed to generate T cells with the ability to resist exhaustion and maintain the stem-like qualities needed to drive durable cytotoxic functionality in solid tumors. This year, we plan to share clinical and translational data from our lead CAR T-cell and TIL product candidates that we expect will provide the first of several opportunities to understand the potential of our T-cell preprogramming technologies to deliver meaningful advances in cell therapy for patients with solid tumors," said Lynn Seely, M.D., Lyell’s President and CEO. "With our strong cash position that is expected to fund operations into 2027, we can advance our lead programs through multiple clinical milestones while continuing to invest in innovative technology platforms and earlier stage product candidates."
Fourth 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. Two additional product candidates, LYL119 and a second-generation tumor infiltrating lymphocyte (TIL) product candidate, are in preclinical development and our T-cell rejuvenation technology is in research.
LYL797 – A ROR1-targeted Chimeric Antigen Receptor (CAR) T-cell product candidate genetically reprogrammed to overexpress c-Jun and epigenetically reprogrammed using Lyell’s proprietary Epi-RTM manufacturing protocol, designed for differentiated potency and durability
•Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study includes patients with relapsed or refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC).
•Initial clinical and translational data from at least 20 patients in the Phase 1 trial of LYL797 are expected in the first half of 2024.
•Initiated a CAR T-cell manufacturing proof-of-concept collaboration with Cellares as part of an overall manufacturing strategy to build scale and reduce cost. Under the collaboration, the companies have agreed on a proof-of-concept technology transfer process for the manufacture of Lyell’s LYL797 CAR T-cell therapy, using Cellares’ Cell ShuttleTM.
•Announced initial results from Lyell’s ROR1 screening program indicating that expression of ROR1 in TNBC and NSCLC, 53% (N=77) and 33% (N=18), respectively, is consistent with what has been reported in the literature. The screening program is designed to support Lyell’s current and future clinical trials.

•Presented a LYL797 Trial in Progress poster at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
LYL845 – A novel epigenetically reprogrammed TIL product candidate using Lyell’s proprietary Epi-RTM manufacturing protocol, designed for differentiated potency and durability
•Enrollment in the Phase 1 clinical trial for LYL845 is ongoing. The study includes patients with relapsed and/or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.
•Initial clinical and translational data from the Phase 1 trial of LYL845 are expected in the second half of 2024.
•Received FDA Orphan Drug Designation for LYL845 for the treatment of stage IIB-IV melanoma.
•Presented nonclinical data at SITC (Free SITC Whitepaper) highlighting the Epi-R P2 manufacturing process, which is designed to shorten TIL manufacturing time to less than three weeks without impacting cell number and phenotype. Epi-R P2 is expected to be incorporated into the Phase 1 trial of LYL845 in 2024.
•Presented a LYL845 Trial in Progress poster at SITC (Free SITC Whitepaper).
LYL119 – A ROR1-targeted CAR T-cell product candidate incorporating Lyell’s four stackable and complementary reprogramming technologies for enhanced cytotoxicity
•LYL119 is a ROR1-targeted CAR T-cell product enhanced with Lyell’s four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology.
•An investigational new drug (IND) application for LYL119 is expected to be submitted in the first half of 2024.
•Presented posters highlighting preclinical development of LYL119 at the American Society for Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) and at SITC (Free SITC Whitepaper). In preclinical studies, LYL119 demonstrated superior cytotoxicity and sustained cytokine production upon repeated antigen stimulation compared to various controls lacking one or more of the reprogramming technologies and showed robust in vivo antitumor efficacy and prolonged survival in a mouse xenograft tumor model at very low cell doses.
Rejuvenation – Novel partial reprogramming technology designed to maintain T-cell identity while reducing cells’ epigenetic age
•Presented nonclinical data at the International Society for Stem Cell Research (ISSCR) 2023 Annual Meeting demonstrating that Lyell’s T-cell Rejuvenation technology generates cells with improved expansion capacity and increased expression of biomarkers associated with T-cell stemness, that also exhibit improved antitumor properties compared with non-rejuvenated T-cell controls in sequential cell-killing assays.
•Presented nonclinical data at SITC (Free SITC Whitepaper) demonstrating that TIL generated with Lyell’s Rejuvenation technology retain a broad TCR repertoire and demonstrate improved T-cell function and antitumor properties.
Corporate Updates
•Appointed Matt Lang, J.D., Chief Business Officer. Mr. Lang, who also serves as Lyell’s Chief Legal Officer and Corporate Secretary, is an experienced company builder who has successfully led growth in complex organizations.
Fourth Quarter and Full Year 2023 Financial Results
Lyell reported a net loss of $52.9 million and $234.6 million for the fourth quarter and year ended December 31, 2023, respectively, compared to a net loss of $8.4 million and $183.1 million for the same periods in 2022. 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 $43.9 million and $177.4 million for the fourth quarter and year ended December 31, 2023, respectively, compared to $0.3 million and $104.2 million for the same periods in 2022.
Revenue
•Revenue was approximately zero and $0.1 million for the fourth quarter and year ended December 31, 2023, respectively, compared to $48.4 million and $84.7 million for the same periods in 2022. No research and development pursuant to our collaboration and license agreement with GlaxoSmithKline (GSK Agreement) was performed in 2023 due to the termination of the GSK Agreement in December 2022, which drove the decrease in revenue.

GAAP and Non-GAAP Operating Expenses
•Research and development (R&D) expenses were $47.0 million and $182.9 million for the fourth quarter and year ended December 31, 2023, respectively, compared to $38.0 million and $159.2 million for the same periods in 2022. The increase in fourth quarter 2023 R&D expenses of $9.0 million was primarily driven by non-cash expenses related to the change in the estimated fair value of success payment liabilities. The increase in annual 2023 R&D expenses of $23.8 million was primarily driven by a $11.2 million increase in personnel-related expenses, including $4.6 million for one-time severance payments and other employee-related costs in connection with the reduction in workforce, and an increase of $8.8 million in research activities, collaborations and outside services costs primarily due to research and laboratory costs associated with clinical trials. 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 and year ended December 31, 2023, were $42.9 million and $165.7 million, respectively, compared to $41.0 million and $147.6 million for the same periods in 2022. The increase in fourth quarter 2023 non-GAAP R&D expenses was driven by an increase in research and laboratory costs primarily associated with clinical trials.
•General and administrative (G&A) expenses were $13.2 million and $67.0 million for the fourth quarter and year ended December 31, 2023, respectively, compared to $26.3 million and $117.3 million for the same periods in 2022. The decrease in both fourth quarter 2023 and annual 2023 G&A expenses were both primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the fourth quarter and year ended December 31, 2023 were $8.5 million and $38.1 million, respectively, compared to $12.3 million and $52.1 million for the same periods in 2022. The decrease in 2023 non-GAAP G&A expenses was driven by a decrease in legal and corporate 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."