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

Rhea-AI Summary

Lyell Immunopharma (NASDAQ: LYEL) presented new clinical and translational data for rondecabtagene autoleucel (ronde-cel) at ASH on Dec 7, 2025 showing high responses in large B-cell lymphoma (LBCL). In 3L+ patients (n=29 efficacy-evaluable) ronde-cel achieved a 93% ORR, 76% CR rate and median progression-free survival of 18 months. In 2L patients (n=18 efficacy-evaluable; 94% primary refractory) it showed an 83% ORR and 61% CR rate with durable CRs.

Safety was manageable for outpatient use: no Grade ≥3 CRS and ≤5% Grade ≥3 ICANS after dexamethasone prophylaxis. Two pivotal trials (PiNACLE – H2H and PiNACLE) are underway.

Positive

• 3L+ ORR 93% (27/29 efficacy-evaluable patients)
• 3L+ CR 76% (22/29) with median PFS 18 months
• No Grade ≥3 CRS reported across 69 treated patients
• 2L ORR 83% and CR 61% in predominantly primary refractory patients
• RMAT designation from FDA for 2L and 3L+ R/R LBCL

Negative

• Small efficacy cohorts: 29 patients (3L+) and 18 patients (2L) efficacy-evaluable
• ICANS Grade ≥3 up to 12% overall (all grades breakdown reported)
• Imaging assessments were performed locally, not centrally read

Key Figures

Overall response rate 3L+ 93% R/R LBCL patients in third-or-later-line setting

Complete response rate 3L+ 76% R/R LBCL patients in third-or-later-line setting

Median PFS 3L+ 18 months R/R LBCL third-or-later-line efficacy-evaluable cohort

Overall response rate 2L 83% Predominantly primary refractory LBCL in second-line setting

Complete response rate 2L 61% Predominantly primary refractory LBCL in second-line setting

Durable CRs 2L 70% 2L patients with CR remaining in CR ≥6 months

Patients treated 69 patients CAR T-naïve R/R LBCL patients receiving ronde-cel

Grade ≥3 CRS rate 0% No Grade 3 or greater cytokine release syndrome in 69 patients

Market Reality Check

$25.25 Last Close

Volume Volume 33,583 is below the 20-day average of 43,978, suggesting no pre-news rush. normal

Technical Shares at $25.25 are trading above the 200-day MA of $12.50 and sit 1.9% below the 52-week high.

Peers on Argus

Peers show mixed moves (e.g., CADL +2.3%, AVIR +2.59%, NMRA -2.2%), while LYEL is down 0.51%, pointing to stock-specific dynamics around its trial update.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 12	Earnings and update	Positive	-1.3%	Q3 2025 financials, cash runway into 2027, and RMAT expansion for ronde-cel.
Nov 10	Asset acquisition	Positive	+1.0%	Acquisition of LYL273 rights with promising Phase 1 mCRC efficacy metrics.
Nov 03	Clinical data update	Positive	-0.7%	Announcement of upcoming ASH oral presentations with high response rates for ronde-cel.
Sep 03	Phase 3 trial start	Positive	+0.2%	Initiation of PiNACLE-H2H Phase 3 head-to-head CAR T trial and pivotal PiNACLE trial.
Sep 02	Investor conferences	Neutral	+0.2%	Participation in two September 2025 healthcare investor conferences to engage shareholders.

Pattern Detected

Clinical and strategic updates often generate modest, sometimes negative, next-day moves despite generally positive content.

Recent Company History

Over the past six months, Lyell has steadily advanced its CAR T pipeline. Multiple positive clinical trial updates for ronde-cel/LYL314 and IMPT-314 emphasized high response rates and manageable safety, while pivotal trials PiNACLE and PiNACLE–H2H were launched or expanded. An acquisition of LYL273 added a metastatic colorectal cancer program alongside a Q3 2025 update highlighting a $320M-level liquidity position and RMAT status. Historically, these constructive milestones have produced only small share moves, sometimes negative, providing context for the current ASH data release.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-08-12

An effective S-3 shelf filed on Aug 12, 2025 registers the resale of 3,753,752 shares issued in a July 2025 private placement. It enables selling stockholders to resell shares through July 25, 2028; Lyell receives no proceeds from these resales.

Market Pulse Summary

This announcement highlights mature ronde-cel data with high response rates in both 2L and 3L+ LBCL, a favorable safety profile without Grade ≥3 CRS, and active pivotal programs (PiNACLE and PiNACLE–H2H). Prior clinical updates and the recent acquisition of LYL273 show a consistent strategy in CD19/CD20 CAR T. Investors may watch future readouts, regulatory interactions, and capital structure developments, including registered resales under the S-3, as key milestones.

Key Terms

progression-free survival medical

"76% complete response rates with median progression-free survival of 18 months"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

cytokine release syndrome (crs) medical

"no high-grade CRS and ≤ 5% of patients with Grade ≥ 3 ICANS"

An excessive immune reaction in which the body’s defense system releases large amounts of inflammatory signals (cytokines) all at once, like an overactive alarm system that triggers too many responders and causes collateral damage. It matters to investors because this side effect can halt clinical trials, prompt safety warnings or recalls, and increase development costs and regulatory scrutiny for drugs or therapies, affecting a company’s valuation and future revenue prospects.

icans medical

"no high-grade CRS and ≤ 5% of patients with Grade ≥ 3 ICANS"

ICANS (Immune effector Cell-Associated Neurotoxicity Syndrome) is a range of brain-related side effects that can occur after certain immune-cell cancer therapies, such as CAR-T. Symptoms can include confusion, speech problems, seizures or reduced consciousness, and they are caused by an overactive immune response affecting the brain. Investors care because ICANS can influence patient safety, trial outcomes, regulatory approvals, treatment labeling and adoption, all of which affect a therapy’s commercial prospects and development costs.

event-free survival medical

"The primary endpoint of the trial is event-free survival"

Event-free survival measures the length of time after a treatment or diagnosis during which a patient does not experience a predefined negative outcome, such as disease progression, relapse, or death. For investors, longer event-free survival in clinical trials signals that a therapy may be effective and durable, improving its chances of regulatory approval and commercial success — think of it like a warranty period before problems reappear.

phase 3 medical

"PiNACLE – H2H is a Phase 3 head-to-head CAR T-cell therapy randomized"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

AI-generated analysis. Not financial advice.

• 93% overall response and 76% complete response rates with median progression-free survival of 18 months in patients with large B-cell lymphoma in the 3L+ setting
• 83% overall response and 61% complete response rates in cohort comprised predominantly of patients with primary refractory large B-cell lymphoma in the 2L setting
• Manageable safety profile appropriate for outpatient administration; no high-grade CRS and ≤ 5% of patients with Grade ≥ 3 ICANS following dexamethasone prophylaxis
• Lyell management will host an investor webcast with presenting author and ronde-cel investigator Sarah M. Larson, MD, Associate Professor at the David Geffen School of Medicine, University of California, Los Angeles, at 8:30 AM ET on Monday, December 8^th

SOUTH SAN FRANCISCO, Calif., Dec. 07, 2025 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with cancer, today announced new clinical and translational data from the ongoing clinical trial of rondecabtagene autoleucel (ronde-cel, also known as LYL314) in patients with large B-cell lymphoma (LBCL), which were presented today in two oral presentations at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition. 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.

Ronde-cel is an autologous dual-targeting CD19/CD20 CAR T-cell product candidate in pivotal development for patients with R/R LBCL. Ronde-cel CAR T cells are designed to have enhanced antitumor activity through a proprietary manufacturing process that enriches for CD62L-positive cells to produce a CAR T-cell product with a higher proportion of naïve and central memory T cells. The United States Food and Drug Administration (FDA) has granted ronde-cel Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of patients with R/R LBCL in the 3L+ and 2L settings.

“These data from the ongoing clinical trial showing high rates of durable complete responses along with a manageable safety profile in patients with high-risk large B-cell lymphoma represent the potential of ronde-cel to improve patient outcomes,” commented Sarah M. Larson, MD, Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. “The two pivotal trials underway, including the first-of-its kind head-to-head CAR T-cell trial, are expected to provide a comprehensive and robust evaluation of the potential for ronde-cel to demonstrate differentiated benefit over approved CD19 CAR T-cell therapies.”

Sixty-nine CAR T-cell naïve patients with R/R LBCL received ronde-cel as of the data cutoff date for the presentation. The efficacy evaluable population, defined as those patients with Day 84 assessments or prior disease progression or death, consisted of 47 patients (29 in the 3L+ and 18 in the 2L settings). Imaging assessments were performed locally by the sites. Patient demographics and baseline disease characteristics were consistent with a high-risk, heavily pre-treated patient population, particularly as compared to historical trials of CD19 CAR T-cell products: median ages of 64 and 65 years with 20% (9/45) and 21% (5/24) of patients being 75 years or older in the 3L+ and 2L settings, respectively; and primary refractory disease in 49% (22/45) and 92% (22/24) of patients in the 3L+ and 2L settings, respectively.

Patients Evaluated in the 3L+ Setting

There were 29 efficacy-evaluable 3L+ patients with R/R LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular lymphoma) with a median follow up time of 12 months as of the data cutoff date. In these patients:

• The overall response rate was 93% (27/29 patients), with 76% (22/29) of patients achieving a complete response
• 72% (13/18) of patients with complete response remained in complete response at 6 months or longer
• Median progression-free survival was 18 months
  

Patients Evaluated in the 2L Setting

There were 18 efficacy-evaluable patients enrolled in the 2L setting with a median follow-up time of 9 months as of the data cutoff date. Of these efficacy-evaluable patients, 94% had primary refractory disease. In these patients:

• The overall response rate was 83% (15/18 patients), with 61% (11/18) achieving a complete response
• 70% (7/10) of patients with complete response remained in complete response at 6 months or longer
• The median duration of complete response was not reached
  

Safety Data

In 69 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade 3 or greater cytokine release syndrome (CRS) was observed in any patient. Twenty-five of the 69 patients received protocol-directed dexamethasone prophylaxis (10 mg/day for 3 days). One case (4%) of Grade 3 or greater ICANS was reported in a patient with high disease burden; no case of Grade 2 ICANS was reported.

In all 69 patients, as of the data cutoff date, low rates of Grade 1 (32%) or Grade 2 (29%) CRS were reported; ICANS rates were reported as follows: Grade 1 (9%), Grade 2 (3%), and Grade 3 or greater (12%) of patients. The median time to complete resolution of all reports of ICANS was 4 days. Cell pharmacodynamic data demonstrated robust CAR T-cell expansion and persistence that were similar in patients with or without dexamethasone prophylaxis. No deaths were determined to be related to ronde-cel administration.

Pivotal Clinical Trials

Lyell has initiated two pivotal clinical trials of ronde-cel: PiNACLE – H2H and PiNACLE.

PiNACLE – H2H is a Phase 3 head-to-head CAR T-cell therapy randomized controlled clinical trial of ronde-cel versus investigator’s choice of either lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients with R/R LBCL receiving treatment in the 2L setting. Patients randomized to ronde-cel will be treated with a dose of 100 x 10⁶ CAR T cells; patients in the control arm will be treated as per the product label. The primary endpoint of the trial is event-free survival and the trial is expected to enroll approximately 200 patients per arm (N = 400) with R/R LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular or transformed mantle cell lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE – H2H trial can be found on clinicaltrials.gov (NCT07188558) here.

PiNACLE is a single-arm trial of ronde-cel that is enrolling up to 120 patients receiving treatment in the 3L+ setting. This registration trial is a seamless expansion of the 3L+ cohort from the Phase 1/2 trial. The dose is 100 x 10⁶ CAR+ cells and the primary endpoint is overall response rate. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535) here.

Ronde-cel Translational Data

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). In addition, ronde-cel had up to a three-fold higher expansion in patients after infusion compared to the expansion of approved CD19 CAR T-cell products. The product memory-cell phenotype was positively correlated with expansion. Peripheral blood samples collected from patients one month after infusion (N = 9) also had a higher proportion of CAR T cells with a memory phenotype compared to cells from axi-cel-treated patients (N = 4). Ronde-cel CAR-positive T cells collected from patients one (N = 7) and two months (N = 3) after infusion demonstrated sustained capacity to proliferate, kill tumor cells over 72 hours, and secrete cytokines (N = 3).

The clinical data were highlighted in an oral presentation by Sarah M. Larson, MD, Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Translational data were presented in a separate oral presentation by Akil Merchant, MD, Associate Professor and Co-Director of the Lymphoma Program at the Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Conference Call Details

Lyell’s management will host an investor conference call and webcast to review these data at 8:30 AM ET on Monday, December 8th. The webcast registration link can be accessed here. A replay of the event and presentation materials will be available on the Investor page of the Lyell Website following the end of the event.

About Rondecabtagene Autoleucel (Ronde-cel)

Rondecabtagene autoleucel (ronde-cel, also known as 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 the responses as compared to the approved CD19 targeted CAR T-cell therapies for the treatment of R/R LBCL.

Ronde-cel is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both, each with full potency. Ronde-cel is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

Ronde-cel has received RMAT designation from the FDA for the treatment of patients with R/R LBCL in the 3L+ and 2L settings, as well as Fast Track Designation for the treatment of patients with R/R LBCL in the 3L+ setting.

About Lyell

Lyell is a clinical stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with hematologic malignancies and solid tumors. To realize the potential of cell therapy for cancer, Lyell utilizes a suite of technologies to arm CAR T cells with enhancements needed to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness, and function in the hostile tumor microenvironment. Lyell’s LyFE Manufacturing Center™ has commercial launch capability and can manufacture more than 1,200 CAR T-cell doses at full capacity. To learn more, please visit www.lyell.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: the potential clinical benefits and therapeutic potential of ronde-cel; Lyell’s expectations around the progress of the PiNACLE and PiNACLE H2H trials, including expectations around enrollment; the sufficiency of the capacity of LyFE to manufacture drug supply through potential commercial launch; and other statements that are not historical fact. These statements are based on Lyell’s current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: interim results of a clinical trial as of the data cutoff are not necessarily indicative of final results and one or more of the clinical and safety outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, as follow-up on the outcome of any particular patient continues and as more patient or final data becomes available; Lyell’s limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; the nonclinical profiles of Lyell’s product candidates or technology not translating in clinical trials; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; significant adverse events, toxicities or other undesirable side effects associated with Lyell’s product candidates, including the risk that the ultimate safety profile of ronde-cel may not support outpatient administration; the translational data presented above is not based on a head-to-head trial and differences exist between trial designs and subject characteristics, and caution should be exercised when comparing data across trials; Lyell’s ability to submit planned Investigational New Drug Applications or initiate or progress clinical trials on the anticipated timelines, if at all; RMAT and Fast Track designations may not actually lead to faster development, regulatory review or approval process, and do not assure ultimate FDA approval; the significant uncertainty associated with Lyell’s product candidates ever receiving any regulatory approvals; Lyell’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; the complexity of manufacturing cellular therapies and Lyell’s ability to manufacture and supply its product candidates for its clinical trials; implementation of Lyell’s strategic plans for its business and product candidates; Lyell’s realization of the expected benefits of its strategic plans for its business and product candidates, including the license of its product candidate LYL273; the potential reduction of Lyell’s cash resources and fluctuations in Lyell’s operating results and financial condition as a result of Lyell’s milestone, royalty and success payment obligations; the sufficiency of Lyell’s capital resources and need for additional capital to achieve its goals; the effects of macroeconomic conditions, including the effects of disruption between the U.S. and its trading partners due to tariffs or other policies, and any geopolitical instability; potential changes to U.S. drug pricing, including the potential for “most-favored nations” pricing limitations; other risks, including general economic conditions and regulatory developments, not within our control; and other risks, including those described under the heading “Risk Factors” in Lyell’s Annual Report on Form 10‑K for the fiscal year ended December 31, 2024, filed with the Securities Exchange Commission (SEC) on March 11, 2025, and Lyell’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the SEC on November 12, 2025. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law.

Contact:

Ellen Rose
Senior Vice President, Communications and Investor Relations
erose@lyell.com

FAQ

What were the key ronde-cel results Lyell reported at ASH Dec 7, 2025 for LYEL?

Ronde-cel showed a 93% ORR and 76% CR in 3L+ LBCL (n=29) and an 83% ORR with 61% CR in 2L LBCL (n=18) as of Sept 5, 2025 cutoff.

How durable were rondé-cel complete responses in the LYEL data?

72% of 3L+ CRs and 70% of 2L CRs remained in CR at 6 months or longer; median duration of CR in 2L was not reached.

What safety profile did Lyell report for ronde-cel in the ASH 2025 presentation?

Across 69 treated patients there were no Grade ≥3 CRS; ICANS rates included Grade 3+ cases and ≤5% Grade ≥3 following dexamethasone prophylaxis.

What pivotal trials is Lyell running for ronde-cel and what is the LYEL ticker implication?

Lyell is conducting two pivotal trials: PiNACLE – H2H (Phase 3 head-to-head vs liso-cel or axi-cel in 2L, ~400 patients) and PiNACLE (single-arm 3L+ registration, up to 120 patients).

Will ronde-cel be developed for outpatient administration according to LYEL data?

Yes; Lyell reported a manageable safety profile appropriate for outpatient administration and allows outpatient treatment in the pivotal trials.