rondecabtagene autoleucel (LYL314) / Lyell Immunopharma - LARVOL DELTA

Rondecabtagene autoleucel, an autologous, dual-targeting CD19/CD20 CAR T-cell candidate manufactured from CD62L+ enriched T cells, achieves durable responses in patients with large B-cell lymphoma (ASH 2025) - P1/2 | "Following a standard 3-day LD regimen of fludarabine and cyclophosphamide, patients received a single dose of ronde-cel, in the outpatient or inpatient setting, at the recommended Phase 2 dose (RP2D) of 100 x 106 CAR cells...Grade 1 or 2 cytokine release syndrome (CRS) was reported in 62% (37/60) patients, with no ≥ Grade 3 CRS, and 42% (25/60) of all patients receiving tocilizumab...Grade ≥ 3 ICANS was reported in 13% (8/60) of patients, including 7% (1/15) of patients after the Introduction of routine dexamethasone prophylaxis, and resolved promptly with standard therapy (median time to < Grade 3 was 2.5 days)... Ronde-cel achieved high overall response and complete response rates with an encouraging safety profile in high-risk patients with LBCL in a Phase 1/2 multi-center trial. Complete responses were durable, including 100% CR at ≥ 6 months among patients treated in the 2L setting. A single-arm pivotal trial of ronde-cel is ongoing in patients treated in..."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

CD62L enrichment achieves robust expansion and memory phenotype post-infusion in patients with LBCL treated with rondecabtagene autoleucel, an autologous, dual-targeting CD19/CD20 CAR T-cell candidate (ASH 2025) - P1/2 | "Rondecabtagene autoleucel (ronde-cel, LYL314) is an autologous, dual-targeting CD19/CD20 CAR T-cell therapy product candidate manufactured from CD62L+ enriched cells... Ronde-cel manufactured after CD62L enrichment resulted in increased stem-like and effector-memory properties in the infusion product compared to FDA approved CD19 CAR T-cell therapies in LBCL. These properties are positively correlated with robust expansion observed in patients and a high memory phenotype post infusion. These findings support the potential of ronde-cel to achieve improved clinical outcomes through enhanced product characteristics."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CCR7 • CD8 • IL7R • LAG3 • TIGIT

PiNACLE-H2H: A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Ronde-cel Translational Data (GlobeNewswire) - "Translational data from the ongoing Phase 1/2 clinical trial showed that ronde-cel manufactured with CD62L enrichment achieved robust expansion and high expression of memory-related genes after infusion in patients with LBCL. An evaluation of ronde-cel and published data for CD19 CAR T-cell products demonstrated that ronde-cel had a higher proportion of CD62L-positive T cells with a higher proportion of memory-cell phenotype prior to infusion (ronde-cel, N = 34; axi-cel, N = 110 and tisagenlecleucel (tisa-cel), N = 31)."

Biomarker • P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma Presents New Clinical Data from Ongoing Trial of Ronde-Cel Showing High Rates of Durable Complete Responses in Patients with Large B-cell Lymphoma at the 67th ASH Annual Meeting and Exposition (GlobeNewswire) - "As of the data cutoff date of September 5, 2025, ronde-cel continued to demonstrate robust clinical responses with a manageable safety profile appropriate for outpatient administration. A 93% overall response rate, a 76% complete response rate, and median progression-free survival of 18 months were reported for patients with relapsed and/or refractory (R/R) LBCL in the third- or later-line (3L+) setting. Patients evaluated in the second-line (2L) setting (94% with difficult-to-treat primary refractory disease) achieved an 83% overall response rate and a 61% complete response rate, and 70% of patients with a complete response remained in complete response at 6 months or longer."

P1/2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Primary Mediastinal Large B-Cell Lymphoma

A CD19/CD20-Directed Bispecific CAR-T Cell Therapy in Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (NHL) (ASH 2023) - P1, P1/2 | "The primary objective of Phase 2 is to estimate the efficacy of IMPT-314 as measured by CR rate. Secondary endpoints include evaluation of pharmacokinetics and time to event outcomes."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD20 • CD8

PiNACLE - H2H is a Phase 3 head-to-head CAR T-cell therapy trial, which will evaluate ronde-cel versus an investigator’s choice of approved CD19 CAR T-cell therapies (lisocabtagene maraleucel or axicabtagene ciloleucel) in patients with aggressive LBCL receiving treatment in the 2L setting (GlobeNewswire) - "The trial is expected to enroll approximately 400 patients with R/R LBCL (200 per arm)....Clinical site initiation is underway for PiNACLE - H2H in the United States, Canada and Australia, and the first patient is expected to be enrolled by early 2026."

Trial status • Large B Cell Lymphoma

Data from…PiNACLE…trial are expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting (GlobeNewswire)

FDA filing • Large B Cell Lymphoma

First Results of IMPT-314, an Autologous Bispecific CD19/CD20 Chimeric Antigen Receptor (CAR) in Enriched Naive and Central Memory T Cells, for the Treatment of Large B Cell Lymphoma (LBCL) (ASH 2024) - P1, P1/2 | "Conclusions : Initial results of IMPT-314 suggest a manageable tolerability profile, robust expansion, cellular persistence, and high rates of complete response in R/R, CAR T-naive LBCL. Additional results will be presented at the meeting."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Rondecabtagene Autoleucel, an Autologous, Dual-Targeting CD19/CD20 CAR T-Cell Candidate Manufactured from CD62L+ Enriched T Cells, Achieves Durable Responses in Patients with Large B-Cell Lymphoma (GlobeNewswire) - "Lyell Immunopharma...announced...new clinical and translational data...will be presented at the 67th American Society of Hematology (ASH) Annual Meeting....The presentation will highlight new clinical data from the ongoing Phase 1/2 trial of ronde-cel in patients with LBCL. As of the abstract’s June 27, 2025 data cut-off date, high-risk patients with LBCL treated with ronde-cel achieved high overall response rates and complete response rates with an encouraging safety profile. New safety and efficacy data from patients receiving treatment in both the second-line and the third- or later-line settings will be presented."

P1/2 data • Large B Cell Lymphoma

CD62L Enrichment Achieves Robust Expansion and Memory Phenotype Post-Infusion in Patients with LBCL Treated with Rondecabtagene Autoleucel, an Autologous, Dual-Targeting CD19/CD20 CAR T-Cell Candidate (GlobeNewswire) - "Lyell Immunopharma...announced...new clinical and translational data...will be presented at the 67th American Society of Hematology (ASH) Annual Meeting....This presentation will review translational data from the ongoing Phase 1/2 clinical trial in patients receiving treatment in the second or third- or later-line settings, highlighting that CD62L-positive cell enrichment achieves greater memory phenotype expression and in vivo cell expansion compared to published data from U.S. Food and Drug Administration-approved CAR T-cell therapies for LBCL."

P1/2 data • Large B Cell Lymphoma

MPCT-012L: Study of LYL314 in Aggressive Large B-Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | Trial completion date: Jan 2028 ➔ Jun 2031 | Trial primary completion date: Aug 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

PiNACLE-H2H: A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Lyell Immunopharma, Inc.

New P3 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Lyell Immunopharma Announces the Initiation of a Phase 3 Head-to-Head CAR T-Cell Therapy Clinical Trial in Aggressive Large B-Cell Lymphoma… (GlobeNewswire) - "The trial is evaluating rondecabtagene autoleucel (ronde-cel, also known as LYL314) compared to lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the 2L setting....Clinical site initiation is underway in the United States and Australia, and the first patient is expected to be enrolled by early 2026."

New P3 trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Primary Mediastinal Large B-Cell Lymphoma

Second Quarter Updates and Recent Business Highlights (GlobeNewswire) - "Data from...the PiNACLE...trial is expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting."

FDA filing • Large B Cell Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2025 (GlobeNewswire) - "An update on the progress of the PiNACLE trial is planned for late 2025....More mature data from the ongoing Phase 1/2 trial in the 2L setting are expected to be presented in late 2025....A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL."

New P3 trial • P1/2 data • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

LYL314, A CD19/CD20 CAR T-CELL CANDIDATE ENRICHED FOR CD62L+ STEM-LIKE CELLS, ACHIEVES HIGH RATES OF DURABLE COMPLETE RESPONSES IN R/R LARGE B-CELL LYMPHOMA (ICML 2025) - P1/2 | "Following a standard lymphodepletion regimen of fludarabine and cyclophosphamide, patients received a single dose of LYL314... A high overall response rate (94%) and complete response rate (74%) with a manageable safety profile were achieved with LYL314 in patients with R/R LBCL in an ongoing Phase 1/2 multi-center trial. Complete responses were durable at 6 months (76%). A pivotal trial of LYL314 is ongoing in patients treated in the 3L+ setting without prior CAR T-cell exposure (PiNACLE Trial)."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Lyell Immunopharma Announces Positive New Clinical Data Demonstrating High Rates of Durable Complete Responses from the Phase 1/2 Trial of LYL314 for the Treatment of Aggressive Large B-cell Lymphoma (GlobeNewswire) - P1/2 | N=270 | NCT05826535 | Sponsor: Lyell Immunopharma, Inc. | "Lyell Immunopharma, Inc...announced positive new clinical data from the multi-center Phase 1/2 trial of LYL314, including data from patients with large B-cell lymphoma (LBCL) treated in the third- or later-line (3L+) setting....In efficacy-evaluable 3L+ patients, with a median follow up of 9 months (N = 25): The overall response rate was 88% (22/25 patients), with 72% (18/25) of patients achieving a complete response; 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months; In initial data from efficacy-evaluable 2L patients, with a median follow up of 5 months (N = 11): The overall response rate was 91% (10/11 patients), with 64% (7/11) achieving a complete response; 100% (7/7) of patients with complete response were in complete response at last assessment, including 3/3 at ≥ 6 months."

P1/2 data • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the First Quarter 2025 (GlobeNewswire) - "First Quarter Updates and Recent Business Highlights:...(i) LYL314 clinical supply is now manufactured at the LyFE Manufacturing Center in Bothell, Washington following successful technology transfer and clearance by the FDA of an IND amendment....; (ii) A pivotal trial in the third- or later-line setting is expected to be initiated in mid-2025 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy; (iii) More mature data from the ongoing Phase 1/2 trial in the second-line setting are expected to be presented in late-2025; (iv) A pivotal trial in the second-line setting is expected to be initiated by early 2026 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy."

Commercial • New trial • P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma Announces Oral Presentation of New Clinical Data from the Phase 1/2 Trial of LYL314 for the Treatment of Large B-cell Lymphoma at the International Conference on Malignant Lymphoma (ICML) 2025 (GlobeNewswire) - "Lyell Immunopharma...announced that an abstract highlighting new clinical data from the Phase 1/2 trial of LYL314 (formerly IMPT-314) in large B-cell lymphoma will be presented as an oral presentation at the International Conference on Malignant Lymphoma (ICML) 2025....Details of the presentation are below: LYL314, a CD19/CD20 CAR T-cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in R/R large B-cell lymphoma...; Presentation Date & Time: June 18, 2025, 5:40 pm CEST (11:40 am ET)....Presentation Number: 106."

P1/2 data • Large B Cell Lymphoma

MPCT-012L: Study of LYL314 in Aggressive Large B-Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | N=150 ➔ 270 | Trial completion date: Dec 2029 ➔ Jan 2028 | Trial primary completion date: Jun 2025 ➔ Aug 2026

Enrollment change • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Lyell Immunopharma Receives Regenerative Medicine Advanced Therapy (RMAT) Designation for LYL314 for the Treatment of Relapsed and/or Refractory Large B-Cell Lymphoma (GlobeNewswire) - "Lyell Immunopharma...announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to LYL314 (formerly IMPT-314) for the treatment of adult patients with relapsed and/or refractory large B-cell lymphoma after two or more prior lines of therapy. LYL314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of aggressive large B-cell lymphoma (LBCL)....'The RMAT designation for LYL314, is based on promising clinical data from our ongoing Phase 1/2 trial...'"

FDA event • Large B Cell Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2024 (GlobeNewswire) - "Fourth Quarter Updates and Recent Business Highlights:...IMPT-314:...More mature data from the ongoing Phase 1/2 trial in the 3rd line+ setting and initial data from patients in the 2nd line setting are expected to be presented in mid-2025. Pivotal trial in the 3rd line+ setting is expected to be initiated in mid-2025 in patients with relapsed/refractory aggressive LBCL who have not previously received CAR T-cell therapy. Pivotal trial in the 2nd line setting expected to be initiated by early 2026 in patients with relapsed/refractory aggressive LBCL who have not previously received CAR T-cell therapy."

New trial • P1/2 data • Large B Cell Lymphoma

Lyell to Highlight Vision for its Next-Generation CAR T-Cell Therapy Pipeline at 43rd Annual JP Morgan Healthcare Conference (GlobeNewswire) - "Upcoming Milestones and Financial Outlook...For IMPT-314, a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate for the treatment of large B-cell lymphoma: Present data from the ongoing Phase 1-2 trial in mid-2025, including more mature data from the 3rd line+ cohort and initial data from the 2nd line cohort; Present more mature clinical data from the 2nd line cohort in late 2025 Initiate a pivotal trial in the 3rd line+ setting in mid-2025; Initiate a pivotal trial in the 2nd line setting by early 2026...For early-stage solid tumor programs: Submit first IND application for a new solid tumor CAR T-cell product candidate in 2026....Lyell expects net cash use in 2025 to be $175 million - $185 million, which extends its cash runway further into 2027 through multiple clinical milestones."

Commercial • IND • New trial • P1/2 data • Large B Cell Lymphoma

Lyell Presents Positive Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the Treatment of B-cell Lymphoma at the 2024 ASH Annual Meeting (GlobeNewswire) - P1/2 | N=150 | NCT05826535 | Sponsor: ImmPACT Bio | "As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy."

P1/2 data • Non-Hodgkin’s Lymphoma