On February 28, 2023 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, 2022 (Press release, Lyell Immunopharma, FEB 28, 2023, View Source [SID1234627856]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"Lyell continued to gain momentum in 2022 with the initiation of two Phase 1 clinical trials for our wholly-owned CAR T cell and TIL product candidates, and we head into 2023 with a goal of accelerating this momentum to generate clinical data from these trials as rapidly as possible," said Lynn Seely, M.D., Lyell’s President and CEO. "We continued to invest in our innovative reprogramming technologies and recently announced two product candidates in preclinical development that incorporate new stackable technologies designed to further enhance T-cell potency and cytotoxicity to defeat solid tumors. Our strong financial position with cash runway into 2026 positions us to demonstrate the value of our two lead clinical programs that target solid tumors with large unmet needs while continuing to invest in and develop our innovative pipeline."
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 and two additional product candidates, LYL119 and a TIL product candidate incorporating novel genetic and epigenetic reprogramming technologies, are in preclinical development.
LYL797 – A ROR1 CAR T-cell product candidate genetically reprogrammed using 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. Initial clinical data from the Phase 1 trial of LYL797 are expected in the first half of 2024.
•Presented nonclinical data at the American Association of Cancer Research 2022 Annual Meeting characterizing LYL797 and demonstrating that Lyell’s c-Jun overexpression and Epi-R reprogramming technologies can overcome barriers of T-cell exhaustion and lack of durable stemness in engineered T cells using a set of in vitro and in vivo models, including an aggressive syngeneic mouse tumor model and a xenograft lung cancer model.
•Presented nonclinical data demonstrating LYL797 showed improved expansion and anti-tumor activity and prolonged survival compared to conventional ROR1 CAR T cells in an established human ROR1-positive H1975 mouse xenograft model at the American Society of Gene and Cell Therapy Annual Meeting.
LYL119 – An innovative ROR1 CAR T-cell product designed for enhanced cytotoxicity
•LYL119 incorporates four of Lyell’s stackable reprogramming technologies, including two novel technologies – a genetic knockout of NR4A3 (NR4A3-KO) and Stim-R. These technologies, which are complementary to c-Jun and Epi-R, are designed to further improve the anti-tumor potency and durability of T-cells.
•An IND for LYL119 is expected to be submitted in the first half of 2024.
•Presented nonclinical data demonstrating that the combination of two genetic reprogramming technologies, NR4A3 gene knockout and c-Jun overexpression, enhances the functional activity of ROR1 CAR T cells as shown by higher levels of cytokine production, increased CAR T-cell persistence and reduced surface expression of inhibitory receptors after repetitive antigen stimulation, as well as significant improvement in tumor control in vivo at The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2022 Annual Meeting (SITC 2022).
•Presented nonclinical data at SITC (Free SITC Whitepaper) 2022 demonstrating that Lyell’s proprietary Stim-R epigenetic reprogramming technology, which enables precise control and optimized delivery of activation molecules during T-cell production, generates potent CAR T-cell product candidates with increased cell proliferation and persistence, as well as improved tumor control in vivo.
LYL845 – A novel epigenetically reprogrammed TIL product candidate designed for differentiated potency and durability
•Announced clearance of the IND for LYL845 in October 2022; enrollment in the Phase 1 clinical trial for LYL845 is ongoing. Initial clinical data from the Phase 1 trial of LYL845 are expected in 2024.
•Presented nonclinical data at SITC (Free SITC Whitepaper) 2022 demonstrating the ability of Lyell’s Epi-R technology to successfully expand TIL in both hot and cold tumors and to retain qualities linked with anti-tumor functionality and improved outcomes in previous TIL clinical trials. These qualities present in Lyell’s Epi-R TIL include a greater proportion of CD8+ T cells, enrichment for T cells with stem-like profiles, better metabolic fitness and preserved polyclonality compared to control TIL preparations.
•Presented bioinformatic analyses, including comprehensive analyses of transcriptomic profiles, polyclonality and prediction of tumor-reactive T cell clones in Lyell’s LYL845 product candidate, at SITC (Free SITC Whitepaper) 2022. These analyses demonstrated that LYL845 expanded at clinical scale using Epi-R technology remained highly polyclonal and preserved approximately 94% of the predicted tumor reactive clones. Further, the preserved predicted tumor reactive clones in LYL845 have increased stemness and reduced exhaustion‑associated genes compared to TIL products derived from the standard process.
Corporate and Operational Updates
•In December, Lynn Seely, M.D., a member of the company’s board since May 2021 and former President and CEO of Myovant Sciences, was named President and CEO. Dr. Seely has extensive biopharmaceutical leadership experience with a track record of success building companies and developing new medicines in oncology and women’s health.
•In September, Rahsaan W. Thompson was named Chief Legal Officer. Mr. Thompson is a biopharmaceutical industry veteran with more than 20 years of experience with development stage and commercial companies.
•In January, Gary Lee, Ph.D. was named Chief Scientific Officer. Dr. Lee is a veteran biotech leader with more than a decade of experience heading translational cell and gene therapy programs.
Fourth Quarter and Full Year 2022 Financial Results
Lyell reported a net loss of $8.4 million and $183.1 million for the fourth quarter and year ended December 31, 2022, respectively, compared to a net loss of $83.7 million and $250.2 million for the same periods in 2021. 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 $0.3 million and $104.2 million for the fourth quarter and year ended December 31, 2022, respectively, compared to $41.7 million and $147.9 million for the same periods in 2021.
Revenue
•Revenue was $48.4 million and $84.7 million for the fourth quarter and year ended December 31, 2022, respectively, compared to $2.8 million and $10.7 million for the same periods in 2021. The increase in revenue was driven primarily by recognizing the remaining deferred revenue from the GSK collaboration agreement.
GAAP and Non-GAAP Operating Expenses
•Research and development (R&D) expenses were $38.0 million and $159.2 million for the fourth quarter and year ended December 31, 2022, respectively, compared to $19.3 million and $138.7 million for the same periods in 2021. The increase in fourth quarter 2022 R&D expenses was primarily driven by non-cash expenses related to the change in the estimated fair value of success payment liabilities. The increase in annual 2022 R&D expenses was due primarily to increases in personnel and infrastructure costs to support the expansion of our R&D and manufacturing capabilities. 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, 2022, were $41.0 million and $147.6 million, respectively, compared to $32.2 million and $119.7 million for the same periods in 2021.
•General and administrative (G&A) expenses were $26.3 million and $117.3 million for the fourth quarter and year ended December 31, 2022, respectively, compared to $31.9 million and $89.1 million for the same periods in 2021. The decrease in fourth quarter 2022 and increase in annual 2022 G&A expenses were both primarily driven by changes 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, 2022 were $12.3 million and $52.1 million, respectively, compared to $13.4 million and $42.2 million for the same periods in 2021. The increase in annual 2022 non-GAAP G&A expenses was driven by increased legal and corporate expenses and public company operating costs.
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 December 31, 2022 were $710.3 million, compared to $898.3 million as of December 31, 2021. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2026.