LYL119 / Lyell Immunopharma - LARVOL DELTA

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 (SITC 2024) - "These vendors use their own IRB-approved protocol and consent process. In vivo experiments presented in this abstract were approved by Lyell Immunopharma's Institutional Animal Care and Use Committee (EB17-010-117)."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • CD8 • FOXP3 • JUN • NR4A3 • ROR1

Lyell Immunopharma Reports Business Highlights and Financial Results for the Third Quarter 2024 (GlobeNewswire) - "Presenting a poster at the SITC 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."

Preclinical • Non Small Cell Lung Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the Third Quarter 2024 (GlobeNewswire) - "LYL119...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...Initial clinical data are expected in the second half of 2025."

New P1 trial • P1 data • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor

Lyell Pipeline Prioritization (GlobeNewswire) - "Lyell is discontinuing development of LYL797, its ROR1-targeted CAR T-cell product candidate to focus on the Phase 1 clinical trial of its next-generation ROR1-targeted CAR T-cell product candidate LYL119, which is expected to initiate enrollment of patients with platinum-resistant ovarian cancer or relapsed/refractory endometrial cancer this year or early next year. The LYL845 tumor-infiltrating lymphocyte (TIL) program is also being discontinued as the clinical data in patients with advanced melanoma did not meet our rigorous pre-determined criteria for continued development. Its next-generation TIL and rejuvenation programs that are in preclinical development will also be discontinued."

Discontinued • New trial • Endometrial Cancer • Melanoma • Ovarian Cancer • Solid Tumor

Lyell Immunopharma Announces the Acceptance Abstracts for Presentation at 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "The three presentations highlight anti-exhaustion technology and product candidates being advanced in Lyell’s pipeline of cell therapies for solid tumors and hematologic malignancies, including...translational data from the LYL797 Phase 1 clinical trial demonstrating solid tumor infiltration and cell killing by reprogrammed ROR1 CAR T cells; Multiomic profiling of LYL119..."

P1 data • Preclinical • Hematological Malignancies • Oncology • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2024 (GlobeNewswire) - "Second Quarter Updates and Recent Business Highlights:...(i) LYL845:...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; (ii) LYL119:...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....Initial clinical data are expected in the second half of 2025."

IND • New P1 trial • P1 data • Endometrial Cancer • Melanoma • Ovarian Cancer

Lyell Immunopharma Reports Dose-dependent Clinical Activity from Phase 1 Trial of LYL797, a ROR1-targeted CAR-T Cell Product Candidate Enhanced with its Proprietary Anti-exhaustion Technology (GlobeNewswire) - P1 | N=54 | NCT05274451 | Sponsor: Lyell Immunopharma, Inc. | "Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and 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 to date. Common treatment-related adverse events 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....'We have submitted an IND for LYL119 and expect to enter the clinic this year'."

IND • New trial • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the First Quarter 2024 (GlobeNewswire) - "LYL119: An investigational new drug (IND) application for LYL119 is expected to be submitted this quarter."

IND • Oncology • Solid Tumor

LYL119, an investigational ROR1-targeted CAR T-cell product incorporating four novel reprogramming technologies designed for effective cell therapy for solid tumors (AACR 2024) - "Lastly, LYL119 derived from NSCLC patient donor T cells also demonstrated enhanced cytotoxicity in vitro compared to control CAR T cells. These nonclinical data suggest LYL119, which combines c-Jun overexpression, NR4A3 KO, Epi-R protocols, and Stim-R technology, can limit exhaustion, maintain stem-like features, and has the potential to provide effective and durable CAR T-cell antitumor activity in patients with ROR1+ solid tumors."

CAR T-Cell Therapy • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HAVCR2 • IL7R • JUN • NR4A3 • ROR1

Lyell Immunopharma Announces the Acceptance of Three Abstracts for Presentation at 2024 AACR Annual Meeting (GlobeNewswire) - "New nonclinical data on LYL119, Lyell’s second-generation ROR1-targeted CAR T-cell therapy, will be presented in a poster....In this study, LYL119 demonstrated superior in vivo antitumor efficacy in a mouse xenograft tumor model across a 10-fold dose range, including at very low cell doses. In addition, following repeated rounds of tumor cell killing, LYL119, displayed reduced expression of exhaustion-related gene signatures and retained unique cell subsets characterized by upregulation of memory and effector-associated gene signatures."

Preclinical • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2023 (GlobeNewswire) - "LYL119: An investigational new drug (IND) application for LYL119 is expected to be submitted in the first half of 2024."

IND • Oncology • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Third Quarter 2023 (PRNewswire) - "An investigational new drug (IND) application for LYL119 is expected to be submitted in the first half of 2024."

IND • Oncology

Preclinical development of LYL119, a ROR1-targeted CAR T-cell product incorporating four novel T-cell reprogramming technologies to overcome barriers to effective cell therapy for solid tumors (SITC 2023) - "1x106 CAR T cells (figure 2). Conclusions These data suggest that LYL119, which combines c-Jun overexpression, NR4A3 KO, Epi-R protocol, and Stim-R technology, can limit exhaustion, maintain stem-like features, and has potential to provide effective and durable CAR T-cell antitumor activity in patients with ROR1+ solid tumors."

CAR T-Cell Therapy • Preclinical • Lung Cancer • Oncology • Solid Tumor • EGFR • IL2RA • IL7R • JUN • NR4A3 • ROR1

Lyell Immunopharma Presentations at SITC Highlight New Nonclinical Data on Product Candidates and Innovative Technology to Shorten TIL Manufacturing (GlobeNewswire) - "New nonclinical data on LYL119...is highlighted in a presentation titled 'Preclinical development of LYL119, a ROR1-targeted CAR T-cell product incorporating four novel T-cell reprogramming technologies to overcome barriers to effective cell therapy for solid tumors.' ...In this study, 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 in a mouse xenograft tumor model at very low cell doses."

Preclinical • Oncology • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2023 (GlobeNewswire) - "An investigational new drug (IND) application for LYL119 is expected to be submitted in the first half of 2024."

IND • Oncology • Solid Tumor

Lyell Immunopharma Reports Business Highlights and Financial Results for the First Quarter 2023 (GlobeNewswire) - "An abstract highlighting preclinical development of LYL119 has been selected for presentation at the American Society for Gene and Cell Therapy (ASGCT) 26th Annual Meeting taking place in Los Angeles, CA May 16-20, 2023."

Preclinical • Oncology

Preclinical Development of LYL119, a ROR1-Targeted CAR T-Cell Product Candidate Incorporating Four Novel T-Cell Reprogramming Technologies to Overcome Barriers to Effective Cell Therapy for Solid Tumors (ASGCT 2023) - "Finally, we incorporated NR4A3 KO + c-Jun and Stim-R into the Epi-R protocol and showed that combining our four reprogramming technologies in ROR1 CAR T cells showed additive benefits to prolong in vitro cytotoxicity using A549 tumor cells compared to controls (Figure 1B). Together these data suggest that stacking these four technologies can limit exhaustion and has the potential to provide effective and durable ROR1 CAR T-cell functional activity in patients with ROR1+ solid tumor malignancies."

CAR T-Cell Therapy • IO biomarker • Preclinical • Oncology • Solid Tumor • EGFR • JUN • NR4A3 • ROR1

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2022 (GlobeNewswire) - "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....An IND for LYL119 is expected to be submitted in the first half of 2024....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. "

IND • P1 data • Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

Lyell Immunopharma to Participate in 41st Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Lyell Immunopharma, Inc...announced today that members of its senior management team will present and participate in the 41st Annual J.P. Morgan Healthcare Conference on Tuesday, January 10 at 4:30 pm Pacific Time. At the conference, Lyell executives will highlight the company’s growing pipeline of product candidates targeting solid tumors and T-cell reprogramming technologies, including its: Lead CAR T cell and TIL product candidates, LYL797 and LYL845, which are in Phase 1 clinical development; Second-generation ROR1 targeting CAR T-cell product candidate, LYL119, that incorporates two new reprogramming technologies; Newest stackable genetic and epigenetic reprogramming technologies: NR4A3 gene knockout, that is being incorporated along with c-Jun overexpression to enhance the functional activity of CAR T cells; and; Stim-RTM, a programmable cell-signaling platform that optimizes signaling parameters during T-cell activation in order to generate more potent CAR T cells."

Clinical data • Pipeline update • Oncology • Solid Tumor

Lyell Immunopharma to Present Preclinical Data Highlighting New T-Cell Reprogramming Technologies and its Growing Pipeline at 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Lyell Immunopharma....announced today that five abstracts highlighting preclinical data on its product candidates and new genetic and epigenetic reprogramming technologies were accepted for presentation at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)....The combination of these two genetic reprogramming technologies is being incorporated in Lyell’s new product candidate, LYL119, a second generation investigational ROR1 targeting CAR T-cell therapy....Two presentations will feature preclinical data from LYL845...designed to create products with higher proportions of stem-like T cells. Lyell will also present preclinical data from its new genetic reprogramming technology designed to further limit T cell exhaustion, as well as data on its new epigenetic reprogramming technology, Stim-R™, designed to generate a more potent T cell product by controlling delivery of activation molecules during T cell production."

Preclinical • Oncology