Lyell Immunopharma, Inc.

Previous 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 hematologic malignancies and solid tumors. The Company is currently conducting a pivotal clinical trial for its lead product candidate, LYL314, a dual-targeting CD19/CD20 CAR T‑cell therapy in development for large B-cell lymphoma in the third- or later-line (3L+) setting and in a Phase 1/2 study in the second-line (2L) setting. We are pioneering novel approaches designed to generate T‑cell therapies that drive long-lasting clinical responses. The patient’s own living cells are the starting point for our investigational CAR T-cell therapies, and we enhance them with our innovative CAR constructs, technology and manufacturing protocols.

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 one or more of 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

In hematologic malignancies, we are focused on advancing our lead product candidate, LYL314, which is designed to deliver improved outcomes over first-generation CD19 CAR T-cell therapies for patients with B-cell lymphomas. LYL314 is a 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. The PiNACLE trial, which is the first of two planned pivotal trials of LYL314 for the treatment of patients with relapsed and/or refractory large B-cell lymphoma (LBCL), is now underway. LYL314 is designed with a true ‘OR’ logic gate to target B cells that express either CD19 or CD20 with full potency and is manufactured with a process that enriches for CD62L‑positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity.

Current wording

In hematologic malignancies, we are focused on delivering patients meaningfully improved outcomes over currently approved, first-generation CD19 CAR T cell products. Our lead product candidate, rondecabtagene autoleucel (ronde-cel, also known as LYL314), is a 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. Ronde-cel is designed with a true ‘OR’ logic gate to target B cells that express either CD19 or CD20 with full potency and is manufactured with a process that enriches for CD62L‑positive cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity.

Previous wording

To realize the potential of cell therapy for solid tumors, we are also developing next-generation CAR T-cell product candidates enhanced with our anti-exhaustion and additional arming technologies and manufactured with our proprietary protocols. These approaches are designed to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and achieve high rates of long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile solid tumor microenvironment.

Current wording

Our research scientists are also developing next-generation CAR T-cell product candidates for additional solid tumor indications enhanced with our anti-exhaustion and additional arming technologies and manufactured with our proprietary protocols. These approaches are designed to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and achieve high rates of long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile solid tumor microenvironment.

Previous wording

LYL314 (formerly IMPT-314): A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of responses as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of large B-cell lymphoma

Current wording

Rondecabtagene autoleucel (ronde-cel, also known as LYL314): A next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of responses as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of large B-cell lymphoma

Previous wording

Our lead program, LYL314, is targeting patients with aggressive relapsed and/or refractory large B-cell non‑Hodgkin lymphoma (NHL), more commonly referred to as LBCL. Lymphoma is a blood cancer that begins in lymphocytes and spreads primarily in lymph nodes, but can also metastasize to the liver, kidney, brain and other organs. Lymphomas are broadly classified as either Hodgkin or non‑Hodgkin lymphoma, with NHL present in multiple groups of lymph nodes whereas Hodgkin lymphoma is typically located in a single group of lymph nodes, generally in the upper body. NHL is the more common form of lymphoma, representing approximately 90% of all lymphomas.

Current wording

Our lead program, ronde-cel, is targeting patients with aggressive relapsed and/or refractory large B-cell non‑Hodgkin lymphoma (NHL), more commonly referred to as LBCL. Lymphoma is a blood cancer that begins in lymphocytes and spreads primarily in lymph nodes, but can also metastasize to the liver, kidney, brain and other organs. Lymphomas are broadly classified as either Hodgkin or non‑Hodgkin lymphoma, with NHL present in multiple groups of lymph nodes whereas Hodgkin lymphoma is typically located in a single group of lymph nodes, generally in the upper body. NHL is the more common form of lymphoma, representing approximately 90% of all lymphomas.

Previous wording

We are initially focused on developing LYL314 for the treatment of patients with NHL subtypes representing approximately 35% of the over 80,000 patients estimated to be diagnosed with NHL in the United States in 2025 and 545,000 patients worldwide. The NHL subtypes we intend to initially pursue include diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL) and Grade 3B follicular lymphoma (FL3B). DLBCL represents approximately 31% of patients diagnosed with NHL each year (of which approximately 5% are HGBCL). PMBCL represents approximately 3% and FL3B and tFL each represent approximately 1 to 2% of patients diagnosed with NHL each year. We may choose to further expand development to include additional NHL subtypes in the future.

Current wording

We are initially focused on developing ronde-cel for the treatment of patients with NHL subtypes representing approximately 35% of the over 80,000 patients estimated to be diagnosed with NHL in the United States in 2025 and 545,000 patients worldwide. The NHL subtypes we intend to initially pursue include diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL) and Grade 3B follicular lymphoma (FL3B). DLBCL represents approximately 31% of patients diagnosed with NHL each year (of which approximately 5% are HGBCL). PMBCL represents approximately 3% and FL3B and tFL each represent approximately 1 to 2% of patients diagnosed with NHL each year. We may choose to further expand development to include additional NHL subtypes in the future.

Previous wording

Figure 1: NHL is comprised of over 90 distinct subtypes, of which DLBCL is the most common form accounting for ~31% of all patients diagnosed with NHL. We are initially focused on developing LYL314 for the treatment of patients with NHL subtypes representing approximately 35% of the patients estimated to be diagnosed with NHL. The NHL subtypes we intend to initially pursue include DLBCL, PMBCL, tFL and Grade 3B follicular lymphoma (FL3B).

Current wording

Figure 1: NHL is comprised of over 90 distinct subtypes, of which DLBCL is the most common form accounting for ~30% of all patients diagnosed with NHL. We are initially focused on developing ronde-cel for the treatment of patients with NHL subtypes representing approximately 35% of the patients estimated to be diagnosed with NHL. The NHL subtypes we intend to initially pursue include DLBCL, PMBCL, tFL and Grade 3B follicular lymphoma (FL3B).

Previous wording

LYL314 is an autologous dual-targeting CD19/CD20 CAR T-cell therapy designed to kill B cells expressing CD19 and/or CD20 antigens for the treatment of patients with aggressive B-cell malignancies. We acquired this product candidate through our acquisition of ImmPACT Bio USA Inc. (ImmPACT) in October 2024.

Current wording

Ronde-cel is an autologous dual-targeting CD19/CD20 CAR T-cell therapy designed to kill B cells expressing CD19 and/or CD20 antigens for the treatment of patients with aggressive B-cell malignancies. We acquired this product candidate through our acquisition of ImmPACT Bio USA Inc. (ImmPACT) in October 2024.

Previous wording

A dual-targeting, or bispecific, CAR recognizes two targets. LYL314 is rationally designed with a true CD19/CD20 “OR” logic-gated CAR targeting either CD19 or CD20 with full potency, and the cell therapy product is enriched for naïve and central memory T cells. Together, this novel construct and the cell enrichment for naïve and central memory T cells are designed to provide multiple clinical benefits over CD19 CAR T-cell therapies, including:

Current wording

A dual-targeting, or bispecific, CAR recognizes two targets. Ronde-cel is rationally designed with a true CD19/CD20 “OR” logic-gated CAR targeting either CD19 or CD20 with full potency, and the cell therapy product is enriched for naïve and central memory T cells. Together, this novel construct and the cell enrichment for naïve and central memory T cells are designed to provide multiple clinical benefits over CD19 CAR T-cell therapies, including:

Previous wording

LYL314 consists of autologous T cells that are genetically modified through transduction with a lentiviral vector expressing a CAR construct composed of anti-CD19 and anti-CD20 single-chain variable fragments (scFvs) in tandem and an intracellular portion that contains the T-cell signaling zeta chain (CD3-ζ) and the 4-1BB co-stimulatory domain (Figure 2). This differentiates LYL314 from cell therapies and other therapeutic modalities that singularly target CD19, CD20 or CD22.

Current wording

Ronde-cel consists of autologous T cells that are genetically modified through transduction with a lentiviral vector expressing a CAR construct composed of anti-CD19 and anti-CD20 single-chain variable fragments (scFvs) in tandem and an intracellular portion that contains the T-cell signaling zeta chain (CD3-ζ) and the 4-1BB co-stimulatory domain

Previous wording

Figure 2: LYL314 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 2: 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.

Previous wording

Antigen heterogeneity, which refers to variation in the expression levels of tumor antigens across cancer cells, can limit the effectiveness of targeted therapies, including CD19 CAR T-cell therapy. Nonclinical data demonstrated that LYL314’s optimized tandem CAR design is capable of killing target cells that express CD19 only, CD20 only or both antigens with full potency, thus it has the potential to achieve a higher percentage of complete responses than a single‑targeting agent, particularly in those patients with malignant B cells with a lower or heterogeneous CD19 antigen density.

Current wording

Antigen heterogeneity, which refers to variation in the expression levels of tumor antigens across cancer cells, can limit the effectiveness of targeted therapies, including CD19 CAR T-cell therapy. Nonclinical data demonstrated that ronde-cel’s optimized tandem CAR design is capable of killing target cells that express CD19 only, CD20 only or both antigens with full potency, thus it has the potential to achieve a higher percentage of complete responses than a single‑targeting agent, particularly in those patients with malignant B cells with a lower or heterogeneous CD19 antigen density.

Previous wording

CD19 antigen escape, a mechanism by which tumor cells evade the host immune system or targeted therapy through loss, downregulation or modification of target antigens, is a known mechanism contributing to disease relapse. LYL314’s dual-targeting of both CD19 and CD20 was designed to overcome CD19 antigen escape and potentially prolong the duration of responses, as well as to target malignant B cells with limited or no expression of CD19 to achieve a higher overall response rate. In a nonclinical xenograft model of mixed tumor cells (75% CD19-positive/CD20-positive, 25% CD19-negative/CD20-positive), mice treated with CAR T cells that targeted CD19 and CD20 in this manner eliminated tumors and overcame a subsequent tumor re-challenge, whereas CD19 CAR T-cell treatment failed to control the tumors.

Current wording

CD19 antigen escape, a mechanism by which tumor cells evade the host immune system or targeted therapy through loss, downregulation or modification of target antigens, is a known mechanism contributing to disease relapse. Ronde-cel’s dual-targeting of both CD19 and CD20 was designed to overcome CD19 antigen escape and potentially prolong the duration of responses, as well as to target malignant B cells with limited or no expression of CD19 to achieve a higher overall response rate. In a nonclinical xenograft model of mixed tumor cells (75% CD19-positive/CD20-positive, 25% CD19-negative/CD20-positive), mice treated with CAR T cells that targeted CD19 and CD20 in this manner eliminated tumors and overcame a subsequent tumor re-challenge, whereas CD19 CAR T-cell treatment failed to control the tumors.

Previous wording

Additionally, LYL314 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. 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 engraftment, improved persistence, reduced exhaustion and lower 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. Data from the ZUMA-7 pivotal trial of axicabtagene ciloleucel in patients with relapsed and/or refractory 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. 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 engraftment, improved persistence, reduced exhaustion and lower 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. Data from the ZUMA-7 pivotal trial of axicabtagene ciloleucel in patients with relapsed and/or refractory 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.

Previous wording

Our Phase 1/2 trial of LYL314 is a multi-center, open-label dose-escalation and dose-expansion clinical trial designed to evaluate the safety and clinical benefit of LYL314 and to determine a recommended Phase 2 dose in patients with relapsed and/or refractory aggressive LBCL. Following our End-of-Phase 1 meeting with the U.S. Food and Drug Administration (FDA), we initiated the pivotal PiNACLE trial, which is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial. The PiNACLE trial is a single-arm pivotal trial evaluating LYL314 at a dose of 100 x 106 CAR T cells in patients with LBCL treated in the 3L+ setting. The trial is expected to enroll approximately 120 patients with relapsed and/or refractory DLBCL, PMBCL, HGBCL, FL3B or tFL who have not previously received CAR T-cell therapy. Patients may be treated with LYL314 in the 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 overall response rate, including an evaluation of duration of response. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535).

Current wording

The PiNACLE trial, which is underway and enrolling patients, is a seamless expansion of the 3L+ cohort of the Phase 1/2 trial. PiNACLE is a single-arm pivotal 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 enroll approximately 120 patients with relapsed and/or refractory DLBCL, PMBCL, HGBCL, FL3B or tFL who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in the 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 overall response rate, including an evaluation of duration of response. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535).

Previous wording

The Phase 1/2 trial continues to enroll CAR T-cell therapy naïve patients with relapsed and/or refractory LBCL receiving treatment in the 2L setting and we remain on track to initiate a pivotal trial for these patients by early 2026. If successful, we may expand into other types of B-cell NHL.

Current wording

In the future, we may expand into other types of B-cell NHL.

Previous wording

We presented new data from the ongoing Phase 1/2 trial in an oral session at the 18 th International Conference on Malignant Lymphoma (ICML) in June 2025. As of April 15, 2025 (the data cutoff date for the presentation at ICML), 51 patients with relapsed and/or refractory CAR T-naïve LBCL received LYL314 and comprised the safety population. The efficacy evaluable population consisted of 36 patients with Day 84 assessments or prior disease progression or death, including 25 patients treated in the 3L+ setting and 11 patients treated in the 2L setting. Patient demographics and baseline disease characteristics were consistent with high-risk patient populations: median ages of 65 and 69 years in the 3L+ and 2L settings, respectively, 41% of 3L+ and 65% of 2L patients had Stage IV disease at trial entry, and 47% of 3L+ and 82% of 2L patients had primary refractory disease. There were 49 patients who received the recommended Phase 2 dose of 100 x 106 CAR T cells; two patients received a dose of 300 x 106 CAR T cells. CD19/CD20 screening was not required prior to enrollment. Of the patients not included in the efficacy evaluable population presented at ICML, two were excluded because they had T-cell histiocyte-rich lymphoma, a histologic subtype with a poor prognosis that is not included in the clinical trial moving forward, and 13 patients who had not yet reached their Day 84 scan.

Current wording

We presented data from the ongoing Phase 1/2 trial in an oral session at ICML in June 2025. As of April 15, 2025 (the data cutoff date for the presentation at ICML), 51 patients with relapsed and/or refractory CAR T-naïve LBCL received ronde-cel and comprised the safety population. The efficacy evaluable population consisted of 36 patients with Day 84 assessments or prior disease progression or death, including 25 patients treated in the 3L+ setting and 11 patients treated in the 2L setting. Patient demographics and baseline disease characteristics were consistent with high-risk patient populations: median ages of 65 and 69 years in the 3L+ and 2L settings, respectively, 41% of 3L+ and 65% of 2L patients had Stage IV disease at trial entry, and 47% of 3L+ and 82% of 2L patients had primary refractory disease. There were 49 patients who received the recommended Phase 2 dose of 100 x 106 CAR T cells; two patients received a dose of 300 x 106 CAR T cells. CD19/CD20 screening was not required prior to enrollment. Of the patients not included in the efficacy evaluable population presented at ICML, two were excluded because they had T-cell histiocyte-rich lymphoma, a histologic subtype with a poor prognosis that is not included in the clinical trial moving forward, and 13 patients who had not yet reached their Day 84 scan.

Previous wording

Figure 3: Data from the Phase 1/2 trial in patients with relapsed and/or refractory aggressive LBCL treated with LYL314 were presented at ICML. The efficacy evaluable population of patients treated in the 3L+ setting consisted of 25 patients. The overall response rate was 88% (22/25 patients), with 72% (18/25 patients) achieving a complete response. The median follow up was 9 months (17 maximum). When the data were reported, 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months.

Current wording

Figure 3: Data from the Phase 1/2 trial in patients with relapsed and/or refractory aggressive LBCL treated with ronde-cel were presented at ICML. The efficacy evaluable population of patients treated in the 3L+ setting consisted of 25 patients. The overall response rate was 88% (22/25 patients), with 72% (18/25 patients) achieving a complete response. The median follow up was 9 months (17 maximum). When the data were reported, 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months.

Previous wording

Table 3 and Figure 4: Initial data from the Phase 1/2 trial in patients with relapsed and/or refractory aggressive LBCL treated with LYL314 were presented at the ICML in June 2025. The efficacy evaluable population of patients treated in the 2L setting consisted of 11 patients. The overall response rate was 91% (10/11 patients), with 64% (7/11 patients) achieving a complete response. The median follow up was 5 months (maximum 10 months). At data presentation, 100% (7/7) of patients with complete response were in complete response at last assessment, including 3/3 at ≥ 6 months. In patients with primary refractory disease, a difficult to treat population, 70% (7/10) achieved a complete response.

Current wording

Table 3 and Figure 4: Initial data from the Phase 1/2 trial in patients with relapsed and/or refractory aggressive LBCL treated with ronde-cel were presented at the ICML in June 2025. The efficacy evaluable population of patients treated in the 2L setting consisted of 11 patients. The overall response rate was 91% (10/11 patients), with 64% (7/11 patients) achieving a complete response. The median follow up was 5 months (maximum 10 months). At data presentation, 100% (7/7) of patients with complete response were in complete response at last assessment, including 3/3 at ≥ 6 months. In patients with primary refractory disease, a difficult to treat population, 70% (7/10) achieved a complete response.

Previous wording

In the safety evaluable population of 51 patients, including patients from both the 3L+ and 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade ≥ 3 and low rates of Grade 1 (22%) or Grade 2 (35%) events of cytokine release syndrome (CRS) were reported. Adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 6% (Grade 1), 2% (Grade 2) and 14% (Grade ≥ 3) of patients. The median time to complete resolution of all reports of ICANS was 5 days, with rapid improvement (median of 2 days) to Grade 2 or lower with standard therapy. No deaths were related to LYL314 administration.

Current wording

In the safety evaluable population of 51 patients, including patients from both the 3L+ and 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade ≥ 3 and low rates of Grade 1 (22%) or Grade 2 (35%) events of cytokine release syndrome (CRS) were reported. Adverse events of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 6% (Grade 1), 2% (Grade 2) and 14% (Grade ≥ 3) of patients. The median time to complete resolution of all reports of ICANS was 5 days, with rapid improvement (median of 2 days) to Grade 2 or lower with standard therapy. No deaths were related to ronde-cel administration.

Previous wording

LYL314 demonstrated robust expansion with a time to peak of 10 days (N = 51). The final drug product contained the desired CD62L-positive naïve T-cell phenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment using a highly sensitive and robust method.

Current wording

Ronde-cel demonstrated robust expansion with a time to peak of 10 days (N = 51). The final drug product contained the desired CD62L-positive naïve T-cell phenotype (median, 95%). Rapid and durable depletion of B cells was demonstrated through month 6 and up to the month 12 assessment using a highly sensitive and robust method.

Previous wording

LYL314 is currently under evaluation in the pivotal PiNACLE trial for patients with relapsed and/or refractory LBCL that has progressed on two or more prior lines of therapy (Phase 2 portion of ongoing Phase 1/2 multi-center clinical trial of LYL314). The Phase 1/2 clinical trial is ongoing and currently enrolling patients with relapsed and/or refractory LBCL who are receiving treatment in the 3L+ and 2L settings and have not previously received CAR T-cell therapy. LYL314 has received Regenerative Medicine Advanced Therapy (RMAT) as well as Fast Track designations from the FDA for the treatment of adults with relapsed and/or refractory diffuse LBCL in the 3L+ setting.

Current wording

Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) as well as Fast Track designation from the FDA for the treatment of adults with relapsed and/or refractory diffuse LBCL in the 3L+ setting and has also received RMAT designation for the treatment of LBCL in the 2L setting.

Previous wording

•Following an End-of-Phase 1 meeting with the FDA, we initiated the pivotal PiNACLE single-arm trial in patients with relapsed and/or refractory LBCL in the 3L+ setting who have not yet received CAR T-cell therapy. There are 17 sites in the United States currently enrolling patients in this trial. We are expanding the number of trial sites up to approximately 35 to accelerate enrollment and expect to provide an update on the trial progress in late 2025.

Current wording

•The pivotal PiNACLE single-arm trial in patients with R/R LBCL in the 3L+ setting who have not yet received CAR T-cell therapy is ongoing.

Previous wording

For our solid tumor pipeline, we are targeting large markets with substantial unmet medical need. We carefully evaluate and select CAR targets to ensure that binding to normal tissues is limited and manageable for safety. Selecting an appropriate antigen target and designing a potent CAR construct, however, are necessary but insufficient for achieving durable clinical responses in most solid tumors. Based on nonclinical evidence and clinical data, we believe there are multiple mechanisms limiting the efficacy and durability of cell therapy for solid tumors. To address this need, we are advancing solid tumor CAR T‑cell product candidates with new CAR targets and that are armed with a suite of our proprietary anti-exhaustion and durable stemness technologies, as well as new enhancements designed to overcome the hostile tumor microenvironment. Our next-generation CAR T-cell product candidates are fully-armed, meaning they incorporate multiple technologies, each designed to address different efficacy barriers to cell therapies for solid tumors, including T‑cell exhaustion, lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment. Our technologies and manufacturing approaches designed to generate CAR T cells that can achieve potent and durable anti‑tumor cytotoxicity are summarized in Table 4 described below.

Current wording

For our solid tumor pipeline, we are targeting large markets with substantial unmet medical need. We carefully evaluate and select CAR targets to ensure that binding to normal tissues is limited and manageable for safety. Selecting an appropriate antigen target and designing a potent CAR construct, however, are necessary but insufficient for achieving durable clinical responses in most solid tumors. Based on nonclinical evidence and clinical data, we believe there are multiple mechanisms limiting the efficacy and durability of cell therapy for solid tumors. T cells require three different types of signals for optimal immune activation:

Previous wording

Our LyFE Manufacturing Center™ located in Bothell, Washington is approximately 73,000 square feet and is comprised of manufacturing suites, laboratories and offices. LyFE is manufacturing LYL314 for the pivotal PiNACLE trial and the ongoing Phase 1/2 clinical trial for patients with relapsed and/or refractory LBCL. At full staffing and capacity, we expect to be able to manufacture >1,200 patient CAR T‑cell products/year and support our clinical development needs for LYL314 and other pipeline programs, as well as early commercial launch of LYL314, if approved.

Current wording

Our LyFE Manufacturing Center™ located in Bothell, Washington is approximately 73,000 square feet and is comprised of manufacturing suites, laboratories and offices. LyFE is manufacturing ronde-cel for the pivotal PiNACLE trial and the ongoing Phase 1/2 clinical trial for patients with relapsed and/or refractory LBCL and, upon successful transition of manufacturing from ICT, is expected to manufacture LYL273 for the ongoing U.S. Phase 1 clinical trial for patients with refractory mCRC. At full staffing and capacity, we expect to be able to manufacture greater than 1,200 patient CAR T‑cell products/year and support our clinical development needs for ronde-cel, LYL273 and other pipeline programs, as well as early commercial launch of ronde-cel and LYL273, if approved.

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, the ongoing geopolitical conflicts in Ukraine, armed conflicts and turmoil in the Middle East and related U.S. involvement, tensions in U.S.-China relations, inflationary pressures, fluctuations in the interest rate environment, instability in the banking industry, supply constraints and overall market volatility. Economic uncertainty may persist through the remainder of 2025 and beyond, and the market dynamics discussed above and similar adverse conditions may negatively impact our business.

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, the ongoing geopolitical conflicts in Ukraine, conflicts in the Middle East and related U.S. involvement, tensions in U.S.-China relations, inflationary pressures, fluctuations in the interest rate environment, instability in the banking industry, supply constraints and overall market volatility. Economic uncertainty may persist through the remainder of 2025 and beyond, and the market dynamics discussed above and similar adverse conditions may negatively impact our business.

Previous wording

Research and development expenses also include non-cash expenses related to the change in the estimated fair value of the success payment obligations over their respective requisite service terms granted to Fred Hutchinson Cancer Center (Fred Hutch) and The Board of Trustees of the Leland Stanford Junior University (Stanford). Fred Hutch and Stanford have provided the requisite service obligation to earn the potential success payment consideration under their collaboration agreements as of December 31, 2022 and September 30, 2024, respectively. For reporting periods beginning on January 1, 2023, for Fred Hutch, and October 1, 2024, for Stanford, the change in the success payment liability fair value is recognized in other income (expense), net, as the requisite service obligations had been met. See Note 4, License, Collaboration and Success Payment Agreements, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q. Research and development expenses related to our success payment liabilities are unpredictable and may vary significantly from quarter‑to‑quarter and year‑to‑year due to changes in our assumptions used in the calculation.

Current wording

Research and development expenses also include non-cash expenses related to the change in the estimated fair value of the success payment obligations over their respective requisite service terms granted to Fred Hutchinson Cancer Center (Fred Hutch) and The Board of Trustees of the Leland Stanford Junior University (Stanford). Fred Hutch and Stanford have provided the requisite service obligation to earn the potential success payment consideration under their collaboration agreements as of December 31, 2022 and September 30, 2024, respectively. For reporting periods beginning on January 1, 2023, for Fred Hutch, and October 1, 2024, for Stanford, the change in the success payment liability fair value is recognized in other (expense) income, net, as the requisite service obligations had been met. See Note 4, License, Collaboration and Success Payment Agreements, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q. Research and development expenses related to our success payment liabilities are unpredictable and may vary significantly from quarter‑to‑quarter and year‑to‑year due to changes in our assumptions used in the calculation.

Previous wording

Other operating loss (income), 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 (expense), net consists primarily of the change in fair value associated with our contingent consideration payable and success payment liabilities to Fred Hutch and Stanford for the three and six months ended June 30, 2025. Other income (expense), net consists primarily of the change in fair value associated with our success payment liabilities to Fred Hutch and changes to the fair value of our marketable equity security that is publicly traded for the three and six months ended June 30, 2024.

Current wording

Other (expense) income, net consists primarily of the change in fair value associated with our contingent consideration payable, success payment liabilities to Fred Hutch and Stanford and the SPA put/call for the three and nine months ended September 30, 2025. Other (expense) income, net consists primarily of the change in fair value associated with our success payment liabilities to Fred Hutch and changes to the fair value of our marketable equity security that is publicly traded for the three and nine months ended September 30, 2024.

Previous wording

Research and development expenses were $34.9 million and $40.3 million for the three months ended June 30, 2025 and 2024, respectively. The $5.4 million decrease was primarily due to a $2.9 million reduction in research activities, collaborations and outside services due primarily to a reduction in costs associated with research and laboratory supplies and collaboration agreements, a $2.4 million decrease in personnel‑related expenses primarily due to reduced stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards and a $0.9 million reduction in facilities, technology and depreciation expenses primarily due to decreased depreciation on leasehold improvements in 2025 following the impairment of these assets in December 2024. The decrease in research and development expenses was partially offset by a change of $0.8 million in success payments due to recognizing the Stanford success payment liability fair value changes in other income (expense), net for the three months ended June 30, 2025.

Current wording

Research and development expenses were $28.2 million and $39.5 million for the three months ended September 30, 2025 and 2024, respectively. The $11.3 million decrease was due primarily to a $4.4 million reduction in research activities, collaborations and outside services due primarily to a reduction in costs associated with research and laboratory supplies, collaboration agreement expenses and consulting expenses, a $4.2 million decrease in personnel‑related expenses primarily due to lower headcount and a $2.8 million reduction in facilities, technology and depreciation expenses due primarily to decreased depreciation in 2025 following our prior year impairment of long-lived assets.

Previous wording

Research and development expenses were $78.3 million and $83.4 million for the six months ended June 30, 2025 and 2024, respectively. The $5.1 million decrease was due primarily to a decrease of $4.4 million in research activities, collaborations and outside services due primarily to a reduction in costs associated with collaboration agreements and a decrease of $1.7 million in facilities and technology costs primarily due to decreased depreciation on leasehold improvements in 2025 following the impairment of those assets in December 2024. These decreases were partially offset by a $0.7 million increase in personnel-related expenses mainly due to severance expenses resulting from the Company’s workforce reduction related to the closure of the West Hills manufacturing facility, partially offset by decreased stock-based compensation expense and a change of $0.3 million in success payments due to recognizing the Stanford success payment liability fair value changes in other income (expense), net for the six months ended June 30, 2025.

Current wording

Research and development expenses were $106.5 million and $122.9 million for the nine months ended September 30, 2025 and 2024, respectively. The $16.5 million decrease was due primarily to a decrease of $8.8 million in research activities, collaborations and outside services due primarily to a reduction in costs associated with collaboration agreements and a decrease of $4.5 million in facilities and technology costs primarily due to decreased depreciation following our prior year impairment of long-lived assets and a $3.5 million decrease in personnel-related expenses due to decreased stock-based compensation expense due to lower headcount. These decreases were partially offset by a change of $0.3 million in success payments due to recognizing the Stanford success payment liability fair value changes in other (expense) income, net for the nine months ended September 30, 2025.

Previous wording

General and administrative expenses were $9.8 million and $12.3 million for the three months ended June 30, 2025 and 2024, respectively. The $2.5 million decrease was primarily due to a $1.7 million decrease in stock-based compensation expense primarily related to a decrease in the value of new awards granted and a $0.8 million decrease in outside services primarily due to a $0.5 million reduction in legal expenses.

Current wording

General and administrative expenses were $10.7 million and $11.8 million for the three months ended September 30, 2025 and 2024, respectively. The $1.1 million decrease was primarily due to a $0.8 million decrease in stock-based compensation expense primarily related to a decrease in the value of new awards granted and a $0.2 million reduction in legal expenses.

Previous wording

General and administrative expenses were $23.8 million and $25.8 million for the six months ended June 30, 2025 and 2024, respectively. The $1.9 million decrease was primarily due to a $0.9 million decrease in legal expenses and a $0.8 million reduction in personnel costs, including a $3.4 million decrease in stock-based compensation expense, primarily related to a decrease in the value of new awards granted and an increase of $2.6 million in personnel-related expenses primarily due to severance expenses resulting from the Company’s workforce reduction related to the West Hills facility closure.

Current wording

General and administrative expenses were $34.5 million and $37.5 million for the nine months ended September 30, 2025 and 2024, respectively. The $3.0 million decrease was primarily due to a $1.7 million decrease in legal expenses and a $1.6 million reduction in personnel costs, including a $4.2 million decrease in stock-based compensation expense, primarily related to a decrease in the value of new awards granted and an increase of $2.6 million in severance expenses resulting from the Company’s workforce reduction related to the West Hills facility closure.

Previous wording

Other operating loss (income), net was $1.1 million and $(1.0) million for the three months ended June 30, 2025 and 2024, respectively, and $0.9 million and $(2.1) million for the six months ended June 30, 2025 and 2024, respectively. The decreases in other operating loss (income), net of $2.0 million and $3.0 million for the three and six months ended June 30, 2025, respectively, are primarily due to losses on property and equipment disposals of $2.4 million and $3.7 million, respectively, associated with the Company’s closure of the West Hills facility, partially offset by increased sublease income for the three and six months ended June 30, 2025.

Current wording

Other operating income, net was $0.6 million and $2.8 million for the nine months ended September 30, 2025 and 2024, respectively. The decrease in other operating income, net of $2.1 million for the nine months ended September 30, 2025, is due primarily to increased losses on property and equipment disposals of $3.1 million principally associated with the Company’s closure of the West Hills facility, partially offset by increased sublease income of $1.0 million.

Previous wording

Impairment of long-lived assets was $1.4 million for both the three and six months ended June 30, 2025 and zero for both the three and six months ended June 30, 2024, consisting of the impairment of our West Hills, Los Angeles right‑of‑use lease asset resulting from the planned closure of the facility subsequent to the successful technology transfer to the Company’s LyFE manufacturing center.

Current wording

Impairment of long-lived assets was zero and $1.4 million for the three and nine months ended September 30, 2025, respectively, and zero for both the three and nine months ended September 30, 2024, 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 the Company’s LyFE Manufacturing Center TM.

Previous wording

Interest income, net was $3.3 million and $6.4 million for the three months ended June 30, 2025 and 2024, respectively, and $7.1 million and $13.2 million for the six months ended June 30, 2025 and 2024, respectively. The decrease in interest income, net for the three and six months ended June 30, 2025 was primarily driven by decreased interest rates in 2025 coupled with lower cash equivalent and marketable securities balances.

Current wording

Interest income, net was $3.3 million and $6.0 million for the three months ended September 30, 2025 and 2024, respectively, and $10.4 million and $19.1 million for the nine months ended September 30, 2025 and 2024, respectively. The decrease in interest income, net for the three and nine months ended September 30, 2025 was primarily driven by decreased interest rates in 2025 coupled with lower cash equivalent and marketable securities balances.

Previous wording

Impairment of other investments was zero for both the three months ended June 30, 2025 and June 30, 2024, and zero and $13.0 million for the six months ended June 30, 2025 and 2024, respectively, which consisted of the full impairment of one of our other investments. See Note 6, Other Investments, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q, for additional details regarding the impairments of other investments.

Current wording

Impairment of other investments was zero for both the three months ended September 30, 2025 and September 30, 2024, and zero and $13.0 million for the nine months ended September 30, 2025 and 2024, respectively, which consisted of the full impairment of one of our other investments. See Note 6, Other Investments, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10‑Q, for additional details regarding the impairments of other investments.

Previous wording

Since our inception, we have funded our operations primarily through the sale and issuance of convertible preferred stock, the sale of common stock in connection with our IPO and in a private placement financing and business development activities. As of June 30, 2025, we had $296.8 million in cash, cash equivalents and marketable securities excluding restricted cash, which does not include the gross proceeds of approximately $50 million, before deducting transaction expenses, from the sale of our common stock in a private placement pursuant to a Securities Purchase Agreement (the Purchase Agreement) in July 2025. See Note 15, Subsequent Events, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q, for additional details regarding the July 2025 private placement. 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 number of years, if ever. We had an accumulated deficit of $1.4 billion as of June 30, 2025. From June 29, 2018 (inception) through June 30, 2025, we raised an aggregate of $1.4 billion in gross proceeds from sales of our convertible preferred stock and the IPO.

Current wording

Since our inception, we have funded our operations primarily through the sale and issuance of convertible preferred stock, the sale of common stock in connection with our IPO and in a private placement financing and business development activities. As of September 30, 2025, we had $319.6 million in cash, cash equivalents and marketable securities excluding restricted cash. We have not yet commercialized any product candidates, and we do not expect to generate revenue from sales of any product candidates for a number of years, if ever. We had an accumulated deficit of $1.5 billion as of September 30, 2025. From June 29, 2018 (inception) through September 30, 2025, we raised an aggregate of $1.5 billion in gross proceeds from sales of our convertible preferred stock, the IPO and our July 2025 private placement of our common stock.

Previous wording

On February 28, 2024, we entered into a sales agreement (the Sales Agreement) with Cowen and Company, LLC as our sales agent (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 the Agent shares of our common stock having an aggregate offering amount of up to $150.0 million (the Placement Shares). Sales of the Placement Shares, if any, will be 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 will pay commissions to the Agent of up to 3% of the gross proceeds of the sale of the Placement Shares sold under the Sales Agreement and reimburse the Agent for certain expenses. Neither us nor the Agent is obligated to sell any shares and, to date, we have not made any sales under the Sales Agreement.

Current wording

In February 2024, we entered into a sales agreement (the Sales Agreement) with Cowen and Company, LLC as our sales agent (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 the Agent shares of our common stock having an aggregate offering amount of up to $150.0 million (the Placement Shares). Sales of the Placement Shares, if any, will be 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 will pay commissions to the Agent of up to 3% of the gross proceeds of the sale of the Placement Shares sold under the Sales Agreement and reimburse the Agent for certain expenses. Neither we nor the Agent is obligated to sell any shares and, to date, we have not made any sales under the Sales Agreement.

Previous wording

Pursuant to the Purchase Agreement, the investors under the Purchase Agreement have the right to purchase, and upon the achievement of a milestone we will have the right to sell to such investors, $50.0 million of additional common stock (or pre-funded warrants in lieu thereof) under the Purchase Agreement on the terms specified therein, and subject to specified conditions. See Note 15, Subsequent Events, in the accompanying notes to the unaudited condensed consolidated financial statements included in Part I, Item 1 of this Quarterly Report on Form 10-Q, for additional details regarding the terms of the Purchase Agreement.

Current wording

On July 25, 2025, we issued 3,753,752 shares of common stock at a purchase price of $13.32 per share at an initial closing pursuant to the Securities Purchase Agreement (the SPA) with certain institutional and other accredited investors (the Purchasers) for gross proceeds of approximately $50.0 million. Pursuant to the SPA, the Purchasers have the right to purchase, and upon the achievement of a milestone we will have the right to sell to such investors, $50.0 million of additional common stock (or pre-funded warrants in lieu thereof) under the SPA on the terms specified therein, and subject to specified conditions.