Lyell Immunopharma, Inc.

Previous wording

We are a late-stage clinical cell therapy company advancing a pipeline of proprietary next-generation autologous CAR T-cell product candidates for patients with cancer. Our goal is to fully realize the curative potential of cell therapy for patients with hematologic malignancies and solid tumors. To achieve this, we are pioneering novel approaches designed to generate T‑cell therapies that drive long-lasting clinical responses. Our investigational CAR T-cell therapies start with the identification of promising cancer targets. We then engineer the patient’s own living immune cells and arm them with our innovative enhancements, including CAR constructs, technologies or manufacturing protocols that are designed to endow T cells with more potent cancer cell killing capabilities.

Current wording

We are a late-stage clinical cell therapy company advancing a pipeline of proprietary next-generation autologous chimeric antigen receptor (CAR) T-cell product candidates for patients with cancer. Our goal is to fully realize the curative potential of cell therapy for patients with hematologic malignancies and solid tumors. To achieve this, we are pioneering novel approaches designed to generate T‑cell therapies that drive long-lasting clinical responses. Our investigational CAR T-cell therapies start with the identification of promising cancer targets. We then engineer the patient’s own living immune cells and arm them with our innovative enhancements, including CAR constructs, technologies or manufacturing protocols that are designed to endow T cells with more potent cancer cell killing capabilities.

Previous wording

We are currently conducting two pivotal trials with ronde-cel. The first, PiNACLE, is a single-arm clinical trial that is a seamless expansion of the third- or later line (3L+) cohort in the Phase 1/2 trial. This trial is expected to report additional data in the second half of 2026 and pivotal data in mid-2027, with submission of a Biologics License Application (BLA) expected to follow in 2027. The PiNACLE trial is evaluating ronde‑cel in patients with relapsed/refractory (R/R) LBCL receiving treatment in the 3L+ setting. We commenced dosing in the first-of-its-kind Phase 3 head-to-head CAR T-cell therapy randomized controlled trial, PiNACLE-H2H, for patients with LBCL receiving treatment in the second-line (2L) setting. Patients are randomized to either ronde-cel or investigator’s choice of axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel).

Current wording

We are currently conducting two pivotal trials with ronde-cel in patients with relapsed/refractory (R/R) large B‑cell lymphoma (LBCL). The first, PiNACLE, is a single-arm clinical trial that is a seamless expansion of the third- or later-line (3L+) cohort in the Phase 1/2 trial. In November 2026, we announced updated clinical data from this trial in abstracts accepted for presentation at the 68th American Society of Hematology (ASH) Annual Meeting and Exposition (ASH 2026), taking place December 12–15, 2026. The data are detailed below under “Our Pipeline Programs—Ronde-Cel: Clinical Data.” Updated data from the PiNACLE clinical trial are expected to be reported during the ASH 2026 presentation, including data in additional patients and longer follow-up. The dataset from the fully enrolled pivotal trial is expected in mid-2027, with submission of a Biologics License Application (BLA) expected to follow in the second half of 2027. The PiNACLE trial is evaluating ronde‑cel in patients with R/R LBCL receiving treatment in the 3L+ setting. Dosing is also ongoing in the first-of-its-kind Phase 3 head-to-head CAR T-cell therapy randomized controlled trial, PiNACLE-H2H, for patients with LBCL receiving treatment in the second-line (2L) setting. Patients are randomized to either ronde-cel or investigator’s choice of axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel).

Previous wording

To realize the potential of cell therapy for solid tumors, we acquired an exclusive global license for LYL273 (excluding mainland China, Hong Kong, Macau and Taiwan), a guanylyl cyclase C (GCC)-targeted CAR T-cell product candidate, from Innovative Cellular Therapeutics Holdings Limited and Innovative Cellular Therapeutics (collectively, ICT) in November 2025. A 67% overall response rate and an 83% disease control rate with a manageable safety profile have been reported at the highest dose level tested in patients with 3L+ R/R mCRC in a U.S. Phase 1 clinical trial as of the data cutoff date of October 28, 2025. In June 2026, updated safety data from the ongoing trial were shared. The protocol was recently amended to a Phase 1/2 design to enable seamless expansion into a potential pivotal single-arm Phase 2 trial, pending regulatory alignment, and adds new cohorts, including a 2L cohort and a cohort evaluating a combination strategy with radiotherapy. LYL273 is enhanced with CD19 CAR expression and controlled cytokine release designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile tumor microenvironment. Clinical proof-of-concept for this program was initially demonstrated in 15 patients with mCRC in an investigator-sponsored clinical trial conducted in China and published in JAMA Oncology (September 2024).

Current wording

To realize the potential of cell therapy for solid tumors, we acquired an exclusive global license for LYL273 (excluding mainland China, Hong Kong, Macau and Taiwan), a guanylyl cyclase C (GCC)-targeted CAR T-cell product candidate, from Innovative Cellular Therapeutics Holdings Limited and Innovative Cellular Therapeutics (collectively, ICT) in November 2025. A 67% overall response rate and an 83% disease control rate with a manageable safety profile have been reported at the highest dose level tested in patients with 3L+ R/R metastatic colorectal cancer (mCRC) in a U.S. Phase 1/2 clinical trial as of the data cutoff date of October 28, 2025. In June 2026, updated safety data from the ongoing trial were shared. The protocol was recently amended to a Phase 1/2 design to enable seamless expansion into a potential pivotal single-arm Phase 2 trial, pending regulatory alignment, and adds new cohorts, including a 2L cohort and a cohort evaluating a combination strategy with radiotherapy. LYL273 is enhanced with CD19 CAR expression and controlled cytokine release designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile tumor microenvironment. Clinical proof-of-concept for this program was initially demonstrated in 15 patients with mCRC in an investigator-sponsored clinical trial conducted in China and published in JAMA Oncology (September 2024).

Previous wording

We were incorporated in June 2018. We wholly own and operate the LyFE Manufacturing Center TM (LyFE) capable of providing clinical trial material for our ongoing clinical trials, as well as for commercial launch. We expect LyFE to have the capacity to manufacture more than 1,200 CAR T-cell doses/year. Our primary activities to date have included clinical development of investigational T‑cell therapies, conducting research and development, building and operating LyFE, acquiring technology, entering into strategic collaboration and license agreements, enabling and executing manufacturing activities in support of our product candidate development efforts, executing clinical trials, organizing and staffing the company, business planning, establishing and maintaining our intellectual property portfolio, regulatory submissions and other preparations to initiate and execute clinical trials, raising capital and providing general and administrative support for these activities.

Current wording

LyFE to have the capacity to manufacture more than 3,000 CAR T-cell doses/year. Our primary activities to date have included clinical development of investigational T‑cell therapies, conducting research and development, building and operating LyFE, acquiring technology, entering into strategic collaboration and license agreements, enabling and executing manufacturing activities in support of our product candidate development efforts, executing clinical trials, organizing and staffing the company, business planning, establishing and maintaining our intellectual property portfolio, regulatory submissions and other preparations to initiate and execute clinical trials, raising capital and providing general and administrative support for these activities.

Previous wording

Our pipeline of next-generation CAR T-cell product candidates target cancers with large unmet need and is summarized in Table 1 below:

Current wording

Our pipeline of next-generation CAR T-cell product candidates targets cancers with large unmet need and is summarized in Table 1 below:

Previous wording

2L, second line; 3L+, third- or later-line; BLA, Biologics License Application; CAR, chimeric antigen receptor; CD62L+, CD62L or L‑selectin positive T cells; CRC, colorectal cancer; EOP1, End-of-Phase 1; GCC, guanylyl cyclase C; LBCL, large B-cell lymphoma.

Current wording

2L, second line; 3L+, third- or later-line; BLA, Biologics License Application; CAR, chimeric antigen receptor; CD62L+, CD62L or L‑selectin positive T cells; CRC, colorectal cancer; GCC, guanylyl cyclase C; LBCL, large B-cell lymphoma.

Previous wording

The worldwide sales for currently approved CD19 CAR T-cell products are expected to exceed $5 billion by 2030 (Figure 1). Of the approximately 30,000 patients in the U.S. with LBCL, 40% to 50% are refractory to, or relapse following, first-line treatment and we estimate approximately 12,000 to 15,000 patients in the United States with LBCL progress to 2L treatment. We estimate the 3L+ patient population to be approximately 6,000 to 7,000 patients. This estimate reflects findings from a retrospective analysis presented by investigators from Memorial Sloan Kettering Cancer Center that up to 50% of patients with LBCL who progress on first-line therapy received a second regimen of chemotherapy prior to undergoing leukapheresis for CAR T-cell therapy. In a separate Medicare fee-for-service claims analysis, a similar percentage (57%) of patients with LBCL classified as receiving CAR T-cell therapy in the 2L been administered a second chemotherapy regimen prior to CAR while awaiting referral and/or scheduling for leukapheresis (Figure 2).

Current wording

The worldwide sales for currently approved CD19 CAR T-cell products are expected to exceed $5 billion by 2030 (Figure 1). Of the approximately 30,000 patients in the U.S. with LBCL, 40% to 50% are refractory to, or relapse following, first-line treatment and we estimate approximately 12,000 to 15,000 patients in the United States with LBCL progress to 2L treatment. We estimate the 3L+ patient population to be approximately 6,000 to 7,000 patients. This estimate reflects findings from a retrospective analysis presented by investigators from Memorial Sloan Kettering Cancer Center that up to 50% of patients with LBCL who progress on first-line therapy received a second regimen of chemotherapy prior to undergoing leukapheresis for CAR T-cell therapy. In a separate Medicare fee-for-service claims analysis, a similar percentage (57%) of patients with LBCL classified as receiving CAR T-cell therapy in the 2L had been administered a second chemotherapy regimen prior to CAR while awaiting referral and/or scheduling for leukapheresis (Figure 2).

Previous wording

Liso-cel was evaluated in two pivotal trials conducted in the 2L setting. The first pivotal trial was a randomized controlled trial of liso-cel versus standard-of-care chemoimmunotherapy (TRANSFORM), which did not enroll patients over the age of 75 but did allow bridging therapy with chemotherapy. The complete response rate was 66% and the median progression-free survival was 14.8 months, and the median event-free survival was 10.1 months in the liso-cel arm. Data for patients with primary refractory disease in the 2L were not published from this trial; however, a poster presentation suggested these younger patients (median age of 61 years) with low disease volume (9% of patients with a Sum of Product Diameter > 50 cm 2) had similar clinical outcomes between primary refractory and relapsed subgroups. The second pivotal single-arm trial conducted for liso-cel (PILOT), did allow patients over the age of 75 to enroll and included patients ineligible for transplant with primary refractory disease, relapse before 12 months or relapse after 12 months. The complete response rate in the overall patient population was 54% and was 42% in the primary refractory patient population. The package insert for YESCARTA® lists the rate of Grade 3 or higher cytokine release syndrome (CRS) as 9% and the rate of Grade 3 or higher neurotoxicity as 31%. The package insert for BREYANZI® lists the rate of Grade 3 or higher CRS as 3% and the rate of Grade 3 or higher neurotoxicity as 10%.

Current wording

Liso-cel was evaluated in two pivotal trials conducted in the 2L setting. The first pivotal trial was a randomized controlled trial of liso-cel versus standard-of-care chemoimmunotherapy (TRANSFORM), which did not enroll patients over the age of 75 but did allow bridging therapy with chemotherapy. The complete response rate was 66% and the median progression-free survival was 14.8 months, and the median event-free survival was 10.1 months in the liso-cel arm. Data for patients with primary refractory disease in the 2L were not published from this trial; however, a poster presentation suggested these younger patients (median age of 61 years) with low disease volume (9% of patients with a Sum of Product Diameter > 50 cm 2) had similar clinical outcomes between primary refractory and relapsed subgroups. The second pivotal single-arm trial conducted for liso-cel (PILOT), did allow patients over the age of 75 to enroll and included patients ineligible for transplant with primary refractory disease, relapse before 12 months or relapse after 12 months. The complete response rate in the overall patient population was 54% and was 42% in the primary refractory patient population. An analysis by Crombie, et al. of real-world outcomes in patients with R/R LBCL receiving liso-cel using data collected in the Center for International Blood and Marrow Transplant Research Registry from February 2021 to February 2025 was recently published in the journal Blood. In the supplementary appendix, data in 2L patients with primary refractory LBCL treated with liso-cel were reported and demonstrated a 12-month progression-free survival rate of 38%, substantially lower than that for patients with early relapse disease which had a 12-month progression-free survival rate of 62%.

Previous wording

Figure 3: Ronde-cel contains separate, tandem scFv antibody domains designed to target both CD19 and CD20 and is manufactured using a CAR construct that contains a 4-1BB costimulatory domain and is manufactured with a process to enrich for CD62-positive naïve and central memory T cells.

Current wording

Figure 3: Ronde-cel contains separate, tandem scFv antibody domains designed to target both CD19 and CD20 and is manufactured using a CAR construct that contains a 4-1BB costimulatory domain and is manufactured with a process to enrich for CD62L-positive naïve and central memory T cells.

Previous wording

Additionally, ronde-cel is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a process that enriches for CD62L-expressing cells. CD62L is a surface protein that acts as a homing beacon, guiding white blood cells to sites of inflammation. CD62L enrichment in ronde-cel’s manufacturing process substitutes for the CD4/CD8 enrichment step in traditional CAR T-cell manufacturing, and generates cell products that are comprised of more than 95% naïve or central memory T cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity, which we believe could result in both increased complete response rates and more durable responses. Naïve T cells are mature T lymphocytes that have differentiated in the bone marrow and undergone central tolerance selection in the thymus, but have not interacted with their antigen. CAR T cells generated from these CD62L-positive less differentiated T cells have been associated with better cell expansion, improved persistence, reduced exhaustion and lower adverse cytokine production compared to CAR T cells generated from traditional processes. The enrichment of CD62L-expressing T cells does not increase the manufacturing time, which is similar to that of the approved CD19 CAR T-cell therapies with a median vein to site time of 16 days. Data from the ZUMA-7 pivotal trial of axi-cel in patients with R/R LBCL demonstrated an improved overall survival in those patients with a higher median percentage of T cells with a naïve/stem memory phenotype in the administered cell product.

Current wording

Additionally, ronde-cel is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a process that enriches for CD62L-expressing cells. CD62L is a surface protein that acts as a homing beacon, guiding white blood cells to sites of inflammation. CD62L enrichment in ronde-cel’s manufacturing process substitutes for the CD4/CD8 enrichment step in traditional CAR T-cell manufacturing, and generates cell products that are comprised of more than 95% naïve or central memory T cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity, which we believe could result in both increased complete response rates and more durable responses. Naïve T cells are mature T lymphocytes that have differentiated in the bone marrow and undergone central tolerance selection in the thymus, but have not interacted with their antigen. CAR T cells generated from these CD62L-positive less differentiated T cells have been associated with better cell expansion, improved persistence, reduced exhaustion and lower adverse cytokine production compared to CAR T cells generated from traditional processes. The enrichment of CD62L-expressing T cells does not increase the manufacturing time, which is similar to that of the approved CD19 CAR T-cell therapies with a current median vein to ship time of 16 days, expected to be 14 days at the time of potential regulatory approval and commercial launch of ronde-cel. Data from the ZUMA-7 pivotal trial of axi-cel in patients with R/R LBCL demonstrated an improved overall survival in those patients with a higher median percentage of T cells with a naïve/stem memory phenotype in the administered cell product. A recent publication in Nature Medicine reported an analysis of the phenotypic product attributes of axi-cel from 580 patients with NHL across multiple clinical trials with a median follow-up of 42 months. The most significant feature associated with prolonged progression-free survival for axi-cel was a high proportion of naïve-like T cells in the product.

Previous wording

Translational analyses were presented at the European Hematology Association Annual Congress in June 2026 (EHA 2026), providing a biological basis for ronde-cel’s durable responses, including enhanced memory potential of cytotoxic effector cells from CD62L+ enrichment and CD19/CD20 dual-targeting to overcome low antigen expression.

Current wording

Translational analyses for ronde-cel were presented at the European Hematology Association Annual Congress in June 2026 (EHA 2026), providing a biological basis for ronde-cel’s durable responses, including enhanced memory potential of cytotoxic effector cells from CD62L+ enrichment and CD19/CD20 dual-targeting to overcome low antigen expression.

Previous wording

Our ongoing Phase 1/2 trial of ronde-cel is a multi-cohort, multi-center, open-label dose-escalation and dose‑expansion clinical trial designed to evaluate the safety and clinical benefit of ronde-cel (NCT05826535). We presented positive data, detailed below, from the 3L+ and 2L cohorts from the ongoing Phase 1/2 trial during an oral presentation at the American Society of Hematology Annual Meeting and Exhibition in December 2025 (ASH 2025). Based on these data, as well as our End-of-Phase 1 meetings with the U.S. Food and Drug Administration (FDA), we announced the initiation of two pivotal trials of ronde-cel: PiNACLE and PiNACLE-H2H.

Current wording

We first presented positive data, detailed below under “Our Pipeline Programs—Ronde-Cel: Clinical Data,” from the 3L+ and 2L cohorts from the ongoing Phase 1/2 trial during an oral presentation in December at ASH 2025. Based on these data, as well as our End-of-Phase 1 meetings with the U.S. Food and Drug Administration (FDA), we announced the initiation of two pivotal trials of ronde-cel: PiNACLE and PiNACLE-H2H.

Previous wording

The PiNACLE trial, which is underway and enrolling patients, is a seamless expansion of the 3L+ cohort of our Phase 1/2 trial. PiNACLE is a single-arm trial evaluating ronde-cel at a dose of 100 x 106 CAR T cells in patients with LBCL treated in the 3L+ setting. The trial is expected to treat approximately 100 patients with R/R DLBCL, PMBCL, FL3B or tFL who have received two or more prior lines of therapy and have not received CAR T-cell therapy. Patients may be treated with ronde-cel in the inpatient or outpatient setting, with observation near the site limited to 14 days. There is no upper age limit for eligibility, which broadens the addressable patient population. The primary endpoint of the trial is the best overall response rate, including an evaluation of duration of response. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535). Additional data from the PiNACLE trial are expected to be reported in the second half of 2026. Pivotal data from the PiNACLE trial are expected in mid-2027, with a BLA submission expected to follow in the second half of 2027.

Current wording

The PiNACLE trial, which is underway and enrolling patients, is a seamless expansion of the 3L+ cohort of our Phase 1/2 trial. PiNACLE is a single-arm trial evaluating ronde-cel at a dose of 100 x 106 CAR T cells in patients with LBCL treated in the 3L+ setting. The trial is expected to treat approximately 100 patients with R/R DLBCL, PMBCL, FL3B or tFL who have received two or more prior lines of therapy and have not received CAR T-cell therapy. Patients may be treated with ronde-cel in the inpatient or outpatient setting, with observation near the site limited to 14 days. There is no upper age limit for eligibility, which broadens the addressable patient population. The primary endpoint of the trial is the best overall response rate, including an evaluation of duration of response. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535). Updated data from the 3L+ cohort, including additional patients and longer follow-up, are expected to be presented at ASH 2026. The data described in the accepted and published ASH 3L+ abstract are provided below. Pivotal data from the PiNACLE trial are expected in mid-2027, with a BLA submission expected to follow in the second half of 2027.

Previous wording

The PiNACLE-H2H trial is a first-of-its-kind Phase 3 head-to-head CAR T-cell therapy randomized controlled trial evaluating ronde-cel versus investigator’s choice of approved CD19 CAR T-cell therapies (axi-cel or liso-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. The primary endpoint of the trial is event-free survival. The trial is expected to enroll approximately 400 patients with R/R LBCL (200 per arm), including DLBCL, PMBCL, HGBCL, FL3B, tFL, tMCL or tMZBCL who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. Patient dosing commenced in February 2026, and clinical site activation is ongoing in the

Current wording

The PiNACLE-H2H trial is a first-of-its-kind Phase 3 head-to-head CAR T-cell therapy randomized controlled trial evaluating ronde-cel versus investigator’s choice of approved CD19 CAR T-cell therapies (axi-cel or liso-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. The primary endpoint of the trial is event-free survival. The trial is expected to enroll approximately 400 patients with R/R LBCL (200 per arm), including DLBCL, PMBCL, HGBCL, FL3B, tFL, tMCL or tMZBCL who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. Patient dosing commenced in February 2026, and clinical site activation is ongoing in the United States, Canada and Australia. More information about the PiNACLE-H2H trial can be found on clinicaltrials.gov (NCT07188558). A progress update from the PiNACLE-H2H trial is expected in the second half of 2026. Now that the PiNACLE-H2H trial is enrolling patients, the 2L cohort in our Phase 1/2 multi-cohort trial is no longer recruiting patients. The data described in the accepted and published ASH 2L abstract are provided below.

Previous wording

We presented new clinical and translational data from our ongoing Phase 1/2 clinical trial of ronde-cel in patients with LBCL at ASH 2025. The trial is a multi-cohort, multi-center, dose-escalation, dose-expansion trial. Patients had not previously received CAR T-cell therapy and there was no upper age limit nor requirement for CD19/CD20 screening prior to enrollment. Data were presented from the 3L+ and 2L cohorts. Bridging therapy was optional and lymphodepletion included fludarabine, 30 mg/m 2, and cyclophosphamide, 500 mg/m 2, each for three days. The cell manufacturing median vein to site time was 16 days and the recommended Phase 2 dose was established at 100 x 106 CAR T cells. Two patients were treated at Dose Level 2 (300 x 106 CAR T cells). Imaging response assessments were conducted locally at Day 28, Month 3 and every three months for 24 months. The trial objectives were safety and tolerability, best overall response rate and complete response rate, duration of response, selection of the recommended Phase 2 dose and cell expansion pharmacokinetics.

Current wording

In November 2026, we announced updated data from the 3L+ and 2L cohorts of the Phase 1/2 trial in abstracts accepted for presentation at ASH 2026. The ongoing trial is a multi-cohort, multi-center, dose-escalation, dose-expansion trial. Enrolled patients had not previously received CAR T-cell therapy and there was no upper age limit nor requirement for CD19/CD20 screening prior to enrollment. Bridging therapy was optional and lymphodepletion included fludarabine, 30 mg/m 2, and cyclophosphamide, 500 mg/m 2, each for three days. The cell manufacturing median vein to ship time was 16 days and the recommended Phase 2 dose was established at 100 x 106 CAR T cells. Imaging response assessments were conducted locally at Day 28, Month 3 and every three months for 24 months. The ongoing trial objectives are safety and tolerability, best overall response rate and complete response rate, duration of response, selection of the recommended Phase 2 dose and cell expansion pharmacokinetics. Day 84 efficacy-evaluable patients are those patients who have a Day 84 imaging response assessment or who have progressed or died.

Previous wording

There were 29 efficacy-evaluable 3L+ patients with R/R LBCL (DLBCL, PMBCL, 3BFL or tFL) with a median follow‑up time of 12 months as of the data cutoff date. The data are presented in Figure 4 and summarized here:

Current wording

There were 29 efficacy-evaluable 3L+ patients with R/R LBCL (DLBCL, PMBCL, FL3B or tFL) with a median follow‑up time of 12 months as of the data cutoff date. The data are presented in Figure 4 and summarized here:

Previous wording

Updated safety data from the Phase 1/2 trial were presented at EHA 2026. One hundred and eight patients with R/R LBCL received ronde-cel as of the EHA 2026 data cutoff date of May 5, 2026. In 108 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile potentially appropriate for outpatient administration was observed. Sixty-four of the 108 patients (59%) received dexamethasone prophylaxis (10 mg/day for 3 days). No Grade 3 or higher CRS was reported in any patient. Five cases (8%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in patients receiving dexamethasone prophylaxis. The median time to onset of CRS was 6 days and of ICANS was 7 days in those patients receiving prophylaxis. The median time to resolution of CRS or of ICANS was 3 days. Data are presented in Figure 6.

Current wording

Updated safety data for ronde-cel from the Phase 1/2 trial were presented at EHA 2026. One hundred and eight patients with R/R LBCL received ronde-cel as of the EHA 2026 data cutoff date of May 5, 2026. In 108 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile potentially appropriate for outpatient administration was observed. Sixty-four of the 108 patients (59%) received dexamethasone prophylaxis (10 mg/day for 3 days). No Grade 3 or higher CRS was reported in any patient. Five cases (8%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in patients receiving dexamethasone prophylaxis. The median time to onset of CRS was 6 days and of ICANS was 7 days in those patients receiving prophylaxis. The median time to resolution of CRS or of ICANS was 3 days. Data are presented in Figure 6.

Previous wording

CRS, cytokine release syndrome; HGBCL, high grade B-cell lymphoma; ICANS, immune effector cell-associated neurotoxicity; IEC-HS, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome; HLH, hemophagocytic lymphohistiocytosis; IV, intravenous; LDH, lactate dehydrogenase; PO, per os (oral).

Current wording

CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; IEC-HS, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome; HLH, hemophagocytic lymphohistiocytosis; IV, intravenous; PO, per os (oral).

Previous wording

In November 2025, we acquired an exclusive global license, outside of mainland China, Hong Kong, Macau and Taiwan, from ICT for a next-generation GCC-targeted CAR T-cell product candidate (LYL273) with promising dose‑dependent clinical activity in patients with R/R mCRC in a Phase 1 trial conducted in the U.S. LYL273 is a GCC‑targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile solid tumor microenvironment. LYL273 was granted Fast Track designation for the treatment of mCRC by the FDA. Clinical proof-of-concept was initially demonstrated in an investigator-sponsored clinical trial conducted in China prior to the submission to the FDA of an Investigational New Drug Application. Data from this single-center clinical trial in 15 patients with mCRC conducted in China were published in JAMA Oncology (September 2024).

Current wording

In November 2025, we acquired an exclusive global license, outside of mainland China, Hong Kong, Macau and Taiwan, from ICT for a next-generation GCC-targeted CAR T-cell product candidate (LYL273) with promising dose‑dependent clinical activity in patients with R/R mCRC in a Phase 1 trial conducted in the U.S. LYL273 is a GCC‑targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile solid tumor microenvironment. LYL273 was granted Fast Track designation for the treatment of mCRC by the FDA. Clinical proof-of-concept was initially demonstrated in an investigator-sponsored clinical trial conducted in China prior to the submission to the FDA of an Investigational New Drug Application (IND). Data from this single-center clinical trial in 15 patients with mCRC conducted in China were published in JAMA Oncology (September 2024).

Previous wording

In the ongoing U.S. Phase 1 clinical trial, as of the data cutoff date of October 28, 2025, the overall response rate was 50% (6 of 12 patients) and the disease control rate was 83% across both dose levels. At Dose Level 2, the highest dose tested, the overall response rate was 67%, including one patient with a pathological complete response, one patient with complete reduction in tumor volume of the target lesions (100% partial response) and two additional patients with confirmed partial responses (Figure 7). For patients treated at Dose Level 2, the disease control rate was 83%, and the median progression‑free survival was 7.8 months.

Current wording

In the ongoing U.S. Phase 1/2 clinical trial, as of the data cutoff date of October 28, 2025, the overall response rate was 50% (6 of 12 patients) and the disease control rate was 83% across both dose levels. At Dose Level 2, the highest dose tested, the overall response rate was 67%, including one patient with a pathological complete response, one patient with complete reduction in tumor volume of the target lesions (100% partial response) and two additional patients with confirmed partial responses (Figure 7). For patients treated at Dose Level 2, the disease control rate was 83%, and the median progression‑free survival was 7.8 months.

Previous wording

Additional data from patients treated in the 3L+ setting of the U.S. Phase 1 trial, and an End-of-Phase 1 FDA meeting, are expected in the second half of 2026.

Current wording

Additional data from patients treated in the 3L+ setting of the U.S. Phase 1/2 trial, and an End-of-Phase 1 FDA meeting, are expected in 2027.

Previous wording

Figure 7: Data shown are from 12 patients enrolled in the U.S. Phase 1 clinical trial, six at Dose Level 1 and six at Dose Level 2. The left panel depicts target tumor volume change from baseline (%) and the right panel depicts the best overall response and survival after CAR T-cell administration.

Current wording

Figure 7: Data shown are from 12 patients enrolled in the U.S. Phase 1/2 clinical trial, six at Dose Level 1 and six at Dose Level 2. The left panel depicts target tumor volume change from baseline (%) and the right panel depicts the best overall response and survival after CAR T-cell administration.

Previous wording

We provided a safety update in June 2026 (data cutoff date of May 5, 2026) from the U.S. Phase 1 trial following the implementation of gastrointestinal (GI) prophylaxis and a new safety management plan because of previously reported dose-limiting toxicities in one patient at Dose Level 2, including Grade 3 diarrhea, Grade 4 enterocolitis and death from fungal sepsis 48 days post-infusion. Gastrointestinal prophylaxis consisted of infliximab, vedolizumab and budesonide after infusion and prior to symptom onset. Safety data from patients enrolled at Dose Levels 1 and 2 included data from 9 patients who did not receive GI prophylaxis and 10 patients who did receive prophylaxis. The median age of the patients enrolled was 52 years (range, 39 to 74), the patients had received a median of 4 prior lines of therapy for mCRC (range, 2 to 7) and all patients had microsatellite stable disease. No difference in patient demographics and disease characteristics were observed between the two groups.

Current wording

We provided a safety update in June 2026 (data cutoff date of May 5, 2026) from the U.S. Phase 1/2 trial following the implementation of gastrointestinal (GI) prophylaxis and a new safety management plan because of previously reported dose-limiting toxicities in one patient at Dose Level 2, including Grade 3 diarrhea, Grade 4 enterocolitis and death from fungal sepsis 48 days post-infusion. Gastrointestinal prophylaxis consisted of infliximab, vedolizumab and budesonide after infusion and prior to symptom onset. Safety data from patients enrolled at Dose Levels 1 and 2 included data from 9 patients who did not receive GI prophylaxis and 10 patients who did receive prophylaxis. The median age of the patients enrolled was 52 years (range, 39 to 74), the patients had received a median of 4 prior lines of therapy for mCRC (range, 2 to 7) and all patients had microsatellite stable disease. No difference in patient demographics and disease characteristics were observed between the two groups.

Previous wording

No Grade ≥ 3 or higher CRS, ICANS or diarrhea/colitis was reported in any patient receiving GI prophylaxis, across Dose Levels 1 and 2. Reports of Grade ≥ 2 or higher diarrhea/colitis decreased from 55% to 10% with GI prophylaxis. Grade 3 or higher diarrhea/colitis occurred in 22% (2/9) of patients who did not receive GI prophylaxis. Evaluation of GCC-CAR cell expansion kinetic data revealed that both peak GCC CAR T-cell expansion and overall exposure are similar with and without GI prophylaxis at Dose Levels 1 and 2.

Current wording

No Grade ≥ 3 CRS, ICANS or diarrhea/colitis was reported in any patient receiving GI prophylaxis, across Dose Levels 1 and 2. Reports of Grade ≥ 2 diarrhea/colitis decreased from 55% to 10% with GI prophylaxis. Grade 3 or higher diarrhea/colitis occurred in 22% (2/9) of patients who did not receive GI prophylaxis. Evaluation of GCC-CAR cell expansion kinetic data revealed that both peak GCC CAR T-cell expansion and overall exposure are similar with and without GI prophylaxis at Dose Levels 1 and 2.

Previous wording

Based on the new safety data and cell expansion kinetics, we amended the Phase 1 U.S. trial to enable seamless expansion into a pivotal single-arm Phase 1/2 trial, pending FDA agreement. New centers are being activated to support trial expansion and new cohorts to explore LYL273 in patients with 2L mCRC and in combination with radiotherapy were also added.

Current wording

Based on the new safety data and cell expansion kinetics, the protocol was amended to a Phase 1/2 design to enable seamless expansion into a potential pivotal single-arm Phase 2 trial, pending FDA agreement. New centers are being activated to support trial expansion and new cohorts to explore LYL273 in patients with 2L mCRC and in combination with radiotherapy were also added.

Previous wording

Colorectal cancer is the second leading cause of cancer deaths worldwide, and the incidence of colorectal cancer is rising in people younger than 55 years old. In the United States, there were estimated to be 154,000 total new colorectal cancer diagnoses and about 1 in 5 of these diagnoses will occur in people younger than 55 years old. Approximately 53,000 people were estimated to have died from CRC in the U.S. in 2025. Approximately 25% of patients have metastatic disease at the time of diagnosis and up to 60% of patients diagnosed with colorectal cancer will develop distant metastases at some point during their disease journey.

Current wording

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, and the incidence of colorectal cancer is rising in people younger than 55 years old. In the United States, there were estimated to be 154,000 total new colorectal cancer diagnoses and about 1 in 5 of these diagnoses will occur in people younger than 55 years old. Approximately 53,000 people were estimated to have died from CRC in the U.S. in 2025. Approximately 25% of patients have metastatic disease at the time of diagnosis and up to 60% of patients diagnosed with colorectal cancer will develop distant metastases at some point during their disease journey.

Previous wording

Our business and operations may be affected by worldwide economic conditions, which may continue to be impacted by global macroeconomic challenges such as the effects of disruption between the U.S. and its trading partners due to tariffs or other policies, ongoing geopolitical conflicts (including military conflicts, threatened hostilities and conflicts or heightened tension in geopolitical relations) and related U.S. involvement, inflationary pressures, fluctuations in the interest rate environment, instability in the banking industry, supply constraints and overall market volatility.

Current wording

Our business and operations may be affected by worldwide economic conditions, which may continue to be impacted by global macroeconomic challenges such as the effects of disruption between the U.S. and its trading partners due to tariffs or other policies, ongoing geopolitical conflicts (including military conflicts, threatened hostilities and conflicts or heightened tension in geopolitical relations) and related U.S. involvement, supply and commodity price increases, inflationary pressures, fluctuations in the interest rate environment, instability in the banking industry, supply constraints and overall market volatility. Economic uncertainty may persist throughout the remainder of 2026, and the market dynamics and potential business disruptions discussed above and similar adverse conditions may negatively impact our business.

Previous wording

Other operating (income) loss, net consists primarily of service and occupancy fees received associated with subleases as well as losses on the retirement of property and equipment.

Current wording

Other operating income, net consists primarily of service and occupancy fees received associated with subleases as well as losses on the retirement of property and equipment.

Previous wording

Other income, net consists primarily of the changes in fair value of our success payment liabilities for the three months ended June 30, 2026, and the changes in fair value of our success payment liabilities and SPA put/call (defined below) for the six months ended June 30, 2026. Other income, net consists primarily of the changes in fair value associated with our contingent consideration payable related to the ImmPACT acquisition and success payment liabilities for the three and six months ended June 30, 2025.

Current wording

Other income (expense), net consists primarily of the changes in fair value of our success payment liabilities and the SPA put/call (defined below) for the three and nine months ended September 30, 2026. Other income (expense), net consists primarily of the changes in fair value associated with our contingent consideration payable related to the ImmPACT acquisition, success payment liabilities and the SPA put/call for the three and nine months ended September 30, 2025.

Previous wording

Research and development expenses were $39.5 million and $34.9 million for the three months ended June 30, 2026 and 2025, respectively. The $4.7 million increase was due primarily to a $8.8 million increase in research activities, collaborations and outside services due to increased clinical trial activity, partially offset by a $1.6 million decrease in personnel‑related expenses and a $2.6 million reduction in facilities, technology and depreciation expenses primarily due to lower headcount associated with the successful technology transfer of ronde-cel to LyFE in 2025 and reduced depreciation expenses.

Current wording

Research and development expenses were $40.9 million and $28.2 million for the three months ended September 30, 2026 and 2025, respectively. The $12.7 million increase was due primarily to a $12.2 million increase in research activities, collaborations and outside services due to increased clinical trial activity and a $1.2 million increase in personnel‑related expenses, partially offset by a $0.7 million reduction in facilities, technology and depreciation expenses primarily due to lower headcount associated with the successful technology transfer of ronde-cel to LyFE in 2025 and reduced depreciation expenses.

Previous wording

Research and development expenses were $76.1 million and $78.3 million for the six months ended June 30, 2026 and 2025, respectively. The $2.2 million decrease was due primarily to a decrease of $9.1 million in personnel expenses and $5.3 million in facilities, technology and depreciation costs primarily due to lower headcount associated with the successful technology transfer of ronde-cel to LyFE in 2025 and reduced depreciation expenses, partially offset by a $12.2 million increase in research activities, collaborations and outside services due primarily to increased clinical trials activity.

Current wording

Research and development expenses were $117.0 million and $106.5 million for the nine months ended September 30, 2026 and 2025, respectively. The $10.6 million increase was due primarily to a $24.4 million increase in research activities, collaborations and outside services due primarily to increased clinical trials activity, partially offset by a decrease of $7.9 million in personnel expenses and $6.0 million in facilities, technology and depreciation costs primarily due to lower headcount associated with the successful technology transfer of ronde-cel to LyFE in 2025 and reduced depreciation expenses.

Previous wording

General and administrative expenses were $9.6 million and $9.8 million for the three months ended June 30, 2026 and 2025, respectively. The $0.2 million decrease was primarily due to a decrease in professional and outside services expenses.

Current wording

General and administrative expenses were $9.3 million and $10.7 million for the three months ended September 30, 2026 and 2025, respectively. The $1.4 million decrease was primarily due to a decrease in professional and outside services expenses.

Previous wording

General and administrative expenses were $19.1 million and $23.8 million for the six months ended June 30, 2026 and 2025, respectively. The $4.7 million decrease was primarily due to a $3.8 million reduction in personnel costs, including a $1.9 million decrease in stock-based compensation expense, primarily due to decreased headcount from the successful technology transfer of ronde-cel in 2025, in addition to a decrease in professional and outside services expenses.

Current wording

General and administrative expenses were $28.4 million and $34.5 million for the nine months ended September 30, 2026 and 2025, respectively. The $6.1 million decrease was primarily due to a $4.3 million reduction in personnel costs, including a $2.7 million decrease in stock-based compensation expense, primarily due to decreased headcount from the successful technology transfer of ronde-cel in 2025, in addition to a decrease in professional and outside services expenses.

Previous wording

Other operating (income) loss, net was $(1.8) million and $1.1 million for the three months ended June 30, 2026 and 2025, respectively, and $(3.7) million and $0.9 million for the six months ended June 30, 2026 and 2025, respectively. The changes of $2.8 million and $4.6 million for the three and six months ended June 30, 2026, respectively, were primarily due to increased sublease income and reduced losses on disposals of property and equipment; we recognized $2.5 million and $3.8 million of such losses for the three and six months ended June 30, 2025, respectively, primarily in connection with the closure of the West Hills facility in 2025 following the technology transfer of ronde-cel.

Current wording

Other operating income, net was $1.9 million and $1.6 million for the three months ended September 30, 2026 and 2025, respectively, and $5.6 million and $0.6 million for the nine months ended September 30, 2026 and 2025, respectively. The increase of $4.9 million for the nine months ended September 30, 2026, was primarily due to increased sublease income and reduced losses on disposals of property and equipment; we recognized $3.5 million of such losses for the nine months ended September 30, 2025, primarily in connection with the closure of the West Hills facility in 2025 following the technology transfer of ronde-cel.

Previous wording

Impairment of long-lived assets was $1.4 million for the three and six months ended June 30, 2025, consisting of the impairment of our West Hills, Los Angeles right‑of‑use lease asset resulting from the closure of the facility subsequent to the successful transition of the manufacturing of ronde‑cel to our LyFE Manufacturing Center TM. No impairment was recognized for the three and six months ended June 30, 2026.

Current wording

Impairment of long-lived assets was $1.4 million for the nine months ended September 30, 2025, consisting of the impairment of our West Hills, Los Angeles right‑of‑use lease asset resulting from the closure of the facility subsequent to the successful transition of the manufacturing of ronde‑cel to our LyFE Manufacturing Center TM. No impairment was recognized for the three and nine months ended September 30, 2026 and three months ended September 30, 2025.

Previous wording

Interest income, net was $2.2 million and $3.3 million for the three months ended June 30, 2026 and 2025, respectively, and $4.4 million and $7.1 million for the six months ended June 30, 2026 and 2025, respectively. The decrease in interest income, net for the three and six months ended June 30, 2026 was primarily driven by decreased interest rates in 2026 coupled with lower cash equivalent and marketable securities balances.

Current wording

Interest income, net was $1.9 million and $3.3 million for the three months ended September 30, 2026 and 2025, respectively, and $6.3 million and $10.4 million for the nine months ended September 30, 2026 and 2025, respectively. The decrease in interest income, net for the three and nine months ended September 30, 2026 was primarily driven by decreased interest rates in 2026 coupled with lower cash equivalent and marketable securities balances.

Previous wording

Other income, net was $0.4 million and $1.2 million for the three months ended June 30, 2026 and 2025, respectively. The decrease of $0.8 million was primarily due to a $0.9 million gain recognized in the prior year period from the change in fair value of our contingent consideration payable related to the ImmPACT acquisition that did not recur.

Current wording

Other income (expense), net was $0.9 million and $(4.9) million for the three months ended September 30, 2026 and 2025, respectively. The change of $5.7 million was primarily due to a loss of $4.0 million on the SPA put/call recognized in the prior year period that did not recur.

Previous wording

Other income, net was approximately $18.3 million and $2.5 million for the six months ended June 30, 2026 and 2025, respectively. The increase of $15.8 million was primarily driven by a $17.6 million gain from the change in fair value of our SPA put/call, which was settled in the first quarter of 2026 upon the Milestone Closing, partially offset by a $2.1 million gain recognized in the prior year period from the change in fair value of our contingent consideration payable that did not recur.

Current wording

Other income (expense), net was approximately $19.2 million and $(2.4) million for the nine months ended September 30, 2026 and 2025, respectively. The change of $21.5 million was primarily driven by a $17.6 million gain from the change in fair value of our SPA put/call, which was settled in the first quarter of 2026 upon the Milestone Closing, and the $4.0 million prior year loss on the SPA put/call discussed above that did not recur, partially offset by a $1.7 million gain recognized in the prior year period from the change in fair value of our contingent consideration payable that did not recur.

Previous wording

Since our inception, we have funded our operations primarily through the sale and issuance of convertible preferred stock, business development activities and the sale of common stock in connection with our IPO, in a private placement financing and pursuant to an at-the-market offering program discussed below. As of June 30, 2026, we had $228.0 million in cash, cash equivalents and marketable securities excluding restricted cash. Since our inception, we have incurred significant operating losses. We have not yet commercialized any product candidates, and we do not expect to generate revenue from sales of any product candidates for a few years, if ever. We had an accumulated deficit of $1.7 billion as of June 30, 2026. From June 29, 2018 (inception) through June 30, 2026, we raised an aggregate of $1.5 billion in gross proceeds primarily from the sales of our convertible preferred stock, our IPO and private placements in July 2025 and March 2026 of our common stock pursuant to the SPA.

Current wording

Since our inception, we have funded our operations primarily through the sale and issuance of convertible preferred stock, business development activities and the sale of common stock in connection with our initial public offering (IPO), in a private placement financing and pursuant to an at-the-market offering program discussed below. As of September 30, 2026, we had $194.0 million in cash, cash equivalents and marketable securities excluding restricted cash. Since our inception, we have incurred significant operating losses. We have not yet commercialized any product candidates, and we do not expect to generate revenue from sales of any product candidates for a few years, if ever. We had an accumulated deficit of $1.7 billion as of September 30, 2026. From June 29, 2018 (inception) through September 30, 2026, we raised an aggregate of $1.5 billion in gross proceeds primarily from the sales of our convertible preferred stock, our IPO and private placements in July 2025 and March 2026 of our common stock pursuant to the SPA.

Previous wording

In February 2024, we entered into a sales agreement (Sales Agreement) with TD Securities (USA) LLC (formerly known as Cowen and Company, LLC) (TD Cowen) as our sales agent with respect to an at-the-market offering program. In accordance with the terms of the Sales Agreement, we may offer and sell from time to time through TD Cowen shares of our common stock having an aggregate offering amount of up to $150.0 million (the Placement Shares). Sales of the Placement Shares are made at prevailing market prices on Nasdaq at the time of sale, or as otherwise agreed with the Agent, by any method permitted by law deemed to be an “at-the-market offering” as defined in Rule 415 of the Securities Act of 1933, as amended (the Securities Act). We pay commissions to TD Cowen of up to 3% of the gross proceeds of the sale of the Placement Shares sold under the Sales Agreement and reimburse TD Cowen for certain expenses. Neither us nor TD Cowen is obligated to sell any shares. During the six months ended June 30, 2026, we sold 65,092 shares of our common stock under the Sales Agreement for net proceeds of approximately $1.7 million. No shares were sold during the three months ended June 30, 2026 or the three and six months ended June 30, 2025.

Current wording

In February 2024, we entered into a sales agreement (Sales Agreement) with TD Securities (USA) LLC (formerly known as Cowen and Company, LLC) (TD Cowen) as our sales agent with respect to an at-the-market offering program. In accordance with the terms of the Sales Agreement, we may offer and sell from time to time through TD Cowen shares of our common stock having an aggregate offering amount of up to $150.0 million (the Placement Shares). Sales of the Placement Shares are made at prevailing market prices on Nasdaq at the time of sale, or as otherwise agreed with TD Cowen, by any method permitted by law deemed to be an “at-the-market offering” as defined in Rule 415 of the Securities Act of 1933, as amended (the Securities Act). We pay commissions to TD Cowen of up to 3% of the gross proceeds of the sale of the Placement Shares sold under the Sales Agreement and reimburse TD Cowen for certain expenses. Neither us nor TD Cowen is obligated to sell any shares. During the nine months ended September 30, 2026, we sold 65,092 shares of our common stock under the Sales Agreement for net proceeds of approximately $1.7 million. No shares were sold during the three months ended September 30, 2026 or the three and nine months ended September 30, 2025.