On November 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 third quarter ended September 30, 2024 (Press release, Lyell Immunopharma, NOV 7, 2024, View Source [SID1234647935]).

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"With our acquisition of ImmPACT now complete, we plan to accelerate the development of IMPT-314, a dual-targeting CD19‌/‌CD20 CAR T-cell product candidate we believe has the potential to deliver increased complete response rates with longer duration of response over approved CD19 CAR T-cell therapies for patients with aggressive B‑cell non‑Hodgkin’s lymphoma," said Lynn Seely, M.D., Lyell’s President and CEO. "We look forward to presenting the initial data from the Phase 1 trial of IMPT-314 at ASH (Free ASH Whitepaper) next month and expect to initiate a pivotal clinical trial in 2025. In addition, site selection and initiation is progressing well for our Phase 1 trial of LYL119, our next-generation ROR1‑targeted CAR T‑cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion. Our strong cash position enables us to advance our pipeline through important clinical milestones and fund operations into 2027."

Third Quarter Updates and Recent Business Highlights

Lyell is advancing two wholly-owned product candidates: IMPT-314 is in Phase 1-2 clinical development and LYL119 is entering Phase 1 clinical development. Lyell is also advancing next-generation CAR T-cell product candidates for solid tumors, which are in preclinical development.

IMPT-314 – A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed for improved response rates with enhanced durability for the treatment of large B-cell lymphoma (LBCL)

IMPT-314 is an autologous CAR T-cell product candidate enriched with naïve and central memory T cells during the manufacturing process. The Phase 1-2 clinical trial is a multi-center, open-label clinical trial designed to evaluate the tolerability and clinical benefit of IMPT-314 in patients with relapsed/refractory LBCL and determine a recommended Phase 2 dose. The trial is enrolling three cohorts of patients including CAR T-naïve patients in the third-line setting, CAR T-naïve patients in the second-line setting and CAR T-experienced patients. IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of relapsed/refractory aggressive B-cell lymphoma.
Initial data from Phase 1-2 trial will be presented at the ASH (Free ASH Whitepaper) 2024 Annual Meeting on December 9, 2024.
Expect to initiate a pivotal trial in 2025 in patients with relapsed/refractory large B-cell lymphoma in the third-line setting who have not yet been exposed to CAR T-cell therapy.
LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate enhanced with four stackable and complementary anti-exhaustion technologies

LYL119 is an autologous ROR1-targeted CAR T-cell product candidate enhanced with four novel technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology designed to enable T-cells to resist exhaustion and to enhance their stem-like qualities.
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.
Presenting a poster at the SITC (Free SITC Whitepaper) 2024 Annual Meeting titled "Multiomic profiling of LYL119: A Reprogrammed ROR1 CAR T Product Generates T cells with Reduced Exhaustion and Enhanced Memory Characteristics Associated with Increased AP-1 and Reduced NR4A Bindings." In a validated preclinical xenograft model of non-small cell lung cancer, LYL119 achieves complete tumor control and prolonged survival even at very low doses compared to LYL797, Lyell’s first generation ROR1-targeted CAR T‑cell product candidate. The study presents potential molecular mechanisms underlying the functional reduction of T-cell exhaustion and enhancement of memory‑related characteristics of LYL119 CAR T cells after antigen encounter in vitro and in vivo.
Initial clinical data are expected in the second half of 2025.
Third Quarter Financial Results

Lyell reported a net loss of $44.6 million for the third quarter ended September 30, 2024, compared to a net loss of $50.9 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 $37.1 million for the third quarter ended September 30, 2024, compared to $43.0 million for the same period in 2023.

GAAP and Non-GAAP Operating Expenses

Research and development (R&D) expenses were $39.5 million for the third quarter ended September 30, 2024, compared to $43.8 million for the same period in 2023. The decrease in third quarter 2024 R&D expenses of $4.3 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 third quarter ended September 30, 2024, were $35.9 million, compared to $40.5 million for the same period in 2023. The decrease in third quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.
General and administrative (G&A) expenses were $11.8 million for the third quarter ended September 30, 2024, compared to $15.5 million for the same period in 2023. The decrease in third 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 third quarter ended September 30, 2024, were $7.8 million, compared to $9.5 million for the same period in 2023. The decrease in third 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 September 30, 2024, were $460.7 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.