LYL797 / Lyell Immunopharma - LARVOL DELTA

LYL797-101: A Study to Investigate LYL797 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=57 | Terminated | Sponsor: Lyell Immunopharma, Inc. | N=100 ➔ 57 | Trial completion date: Dec 2026 ➔ Nov 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Nov 2024; Pipeline Reprioritization

Enrollment change • Platinum resistant • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer • ROR1

LYL797 ROR-1 CAR T-cell translational data demonstrated T-cell reprogramming limited exhaustion, maintained stemness, and resulted in tumor infiltration and cell killing in patients with solid tumors (SITC 2024) - P1 | "In multiple samples, including biopsies from patients with confirmed responses, evidence of T-cell mediated tumor lysis was observed, consistent with preclinical xenograft models.Phenotypically, LYL797 demonstrated a significantly lower frequency of TIGIT expression in CD8+CAR+ T-cells at peak expansion compared to a previously reported ROR1-targeted CAR T-cell clinical trial.1 Additionally, the LYL797 transcriptional profile of known exhaustion markers more closely resembled that of CD19 CAR T-cells as opposed to fully exhausted TILs.6–8 LYL797 cells in the PB also retained a substantial proportion of stem-like and effector-memory-like subsets (range 57–84%, median 74%) and a low proportion of terminal effector subsets (range 15–43%, median 24%) at Days 11 and 22 post infusion.Conclusions c-Jun overexpression and Epi-R manufacturing delayed exhaustion and increased stem-like properties in the ROR1-targeted CAR T-cell product candidate LYL797, resulting in T-cell..."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • JUN • ROR1 • TIGIT

LYL797-101: A Study to Investigate LYL797 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Lyell Immunopharma, Inc. | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer • ROR1

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

LYL797-101: A Study to Investigate LYL797 in Adults with Solid Tumors (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | N=54 ➔ 100 | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Mar 2025 ➔ Dec 2025

CAR T-Cell Therapy • Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Endometrial Cancer • Fallopian Tube Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer • ROR1

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2024 (GlobeNewswire) - "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)....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."

IND • P1 data • Trial status • Chronic Lymphocytic Leukemia • Endometrial Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast 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) - "Investor Webcast with David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute and a lead investigator in the Phase 1 clinical trial, scheduled for 8:30 am ET today."

Announcement

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) - "LYL797: 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 data from at least 20 patients from the Phase 1 clinical trial of LYL797 are expected this quarter."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2023 (GlobeNewswire) - "LYL797: Enrollment in the Phase 1 clinical trial of LYL797 is ongoing....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."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

A Study to Investigate LYL797 in Adults With Solid Tumors (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Lyell Immunopharma, Inc.

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ROR1

Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) (SITC 2023) - P1 | "After successful LYL797 manufacturing, pts receive fludarabine and cyclophosphamide followed by a single infusion of LYL797 at the protocol-assigned dose level. Study objectives include assessment of safety and tolerability (primary), as well as anti-tumor activity and pharmacokinetics (secondary) of LYL797. Additional exploratory objectives include evaluation of the effects of Lyell’s genetic and epigenetic reprogramming technologies on T-cell phenotype and activity, as well as evaluation of the relationship between ROR1 expression and LYL797 activity."

CAR T-Cell Therapy • Metastases • P1 data • Breast Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • JUN • ROR1

Lyell Immunopharma Reports Business Highlights and Financial Results for the Third Quarter 2023 (GlobeNewswire) - "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."

P1 data • Trial status • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Lyell Immunopharma Presentations at SITC Highlight New Nonclinical Data on Product Candidates and Innovative Technology to Shorten TIL Manufacturing (GlobeNewswire) - "Two additional presentations highlight the design of Lyell’s two ongoing Phase 1 clinical trials in progress....A presentation titled 'Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC)' describes the design of this dose-escalation, dose-expansion Phase 1 trial in patients with ROR1-positive relapsed refractory TNBC and NSCLC; A presentation titled 'Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors' describes the design of this dose-escalation, dose-expansion Phase 1 trial in advanced solid tumors, including advanced melanoma, NSCLC and colorectal cancer."

Clinical protocol • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lyell Immunopharma Announces the Acceptance of Six Abstracts for Presentation at 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting (GlobeNewswire) - "Two additional presentations highlight the design of Lyell’s ongoing Phase 1 clinical trials in progress: LYL797, a ROR1-targeted CAR T-cell therapy being evaluated in a Phase 1 trial in patients with relapsed refractory triple-negative breast cancer and non-small cell lung cancer, and LYL845, a tumor infiltrating lymphocyte (TIL) therapy being evaluated in a Phase 1 trial in advanced solid tumors."

Clinical protocol • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Cellares and Lyell to Evaluate Automated Manufacturing of Lyell’s CAR T-Cell Therapy on Cellares’ Cell Shuttle Platform (GlobeNewswire) - "Cellares...and Lyell Immunopharma...announced Lyell will evaluate Cellares’ automated manufacturing platform, the Cell Shuttle™, through Cellares’ Technology Adoption Partnership (TAP) program. As part of 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 the Cell Shuttle....Lyell is enrolling patients with triple-negative breast cancer and non-small cell lung cancer in a Phase 1 clinical trial evaluating LYL797."

Licensing / partnership • Trial status • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2023 (GlobeNewswire) - "Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study includes patients with relapsed or refractory triple-negative breast cancer or non-small cell lung cancer and is now open at 14 sites. Initial clinical data from the Phase 1 trial of LYL797 are expected in the first half of 2024."

P1 data • Trial status • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

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

Phase I study of LYL797, a ROR1-targeted CAR T-cell therapy with genetic and epigenetic reprogramming for the treatment of advanced solid tumors (ESMO 2022) - P1 | "After leukapheresis and manufacturing, pts receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by LYL797 infusion at the protocol-assigned dose level. Primary objectives include LYL797 RP2D determination and safety and tolerability; secondary objectives include anti-tumor activity and PK. The trial began screening in March 2022."

CAR T-Cell Therapy • P1 data • Breast Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ROR1

Lyell Immunopharma Presents First in Human Trial Design of LYL797 at ESMO 2022 (GlobeNewswire) - "Lyell Immunopharma, Inc....announced today that a poster describing the first-in-human Phase 1 trial design for LYL797...the treatment of solid tumors, is being presented today at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris, France."

Clinical protocol • Oncology • Solid Tumor

Preclinical Development of LYL797, a ROR1-Targeted CAR T-Cell Therapy Enhanced with Genetic and Epigenetic Reprogramming for Solid Tumors (ASGCT 2022) - "These studies collectively demonstrate that Gen-R and Epi-R technologies can give rise to enhanced and prolonged anti-tumor functional capacity of CAR T-cell therapy in solid tumors. Based on these promising preclinical data, LYL797 is being studied in a phase I clinical trial to assess the safety, pharmacokinetics, immunogenicity, efficacy, and duration of effect for patients with ROR1+ TNBC and NSCLC."

CAR T-Cell Therapy • Preclinical • Hematological Disorders • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • JUN • ROR1

Lyell Immunopharma to Present Preclinical Data for Two Product Candidates in Clinical Development at ASGCT Annual Meeting (GlobeNewswire) - "The presentations will highlight preclinical data characterizing two investigational products in Phase 1 clinical development...The first abstract presents preclinical data for LYL797 demonstrating that Gen-R and Epi-R can enhance and prolong anti-tumor functions of ROR1-targeting CAR T-cell therapy in solid tumor model systems. The second abstract presents preclinical data for LYL132 demonstrating that Epi-R creates populations of stemlike NY-ESO-1-targeting TCR T cells that lead to products with increased proliferative capacity and prolonged functional activity in the presence of persistent antigen exposure."

Preclinical • Oncology • Solid Tumor

LYL797, a ROR1 CAR T-cell therapy with genetic and epigenetic reprogramming for solid tumors (AACR 2022) - "In preclinical studies LYL797 cells reprogrammed with Gen-R and Epi-R led to improved functional activity in the presence of ROR1+ tumor cells compared to conventional ROR1 CAR T cells.Additional studies are underway to determine the mechanisms by which antitumor activity of LYL797 in ROR1-positive solid tumor xenograft models is enhanced. LYL797 is anticipated to enter into Phase 1 clinical trials for TNBC and NSCLC in 2022."

CAR T-Cell Therapy • Breast Cancer • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • JUN • ROR1