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Item 1. Business

2026-03-12 compared with 2025-03-11 · 518 added, 377 removed, 315 unchanged (74% of the section changed)

We are a clinical-stage cell therapy company expecting to enter pivotal trials in 2025 and advancing a pipeline of proprietary next-generation autologous chimeric antigen receptor (CAR) T-cell product candidates for patients with hematologic malignancies and solid tumors.

We are pioneering novel approaches designed to generate T cells 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.

In hematologic malignancies, we are focused on advancing to pivotal trials a product candidate designed to deliver improved outcomes over first-generation CD19 CAR T-cell therapies for patients with B-cell lymphomas.

Our lead program, IMPT-314, currently under evaluation for the treatment of aggressive large B-cell lymphoma, 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.

IMPT-314 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+ cells to generate more naïve and central memory CAR T cells with enhanced stemlike features and antitumor activity.

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 consistent and long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment.

In October 2024, we acquired ImmPACT, a privately-owned clinical stage biotechnology company developing next-generation CAR T-cell product candidates, including IMPT-314.

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

Lyell’s Pipeline

Our goal is to realize the potential of next-generation CAR T-cell therapies for patients with cancer.

We are advancing an innovative CAR T-cell therapy for hematologic malignancies designed to improve outcomes over first‑generation products and are progressing the next wave of innovation of CAR T-cell therapy for solid tumors.

Lyell was founded by leaders in the fields of oncology and cell therapy who have interrogated and elucidated the mechanisms of T‑cell biology and its interactions with cancer for decades.

To realize the potential of cell therapy for cancer, Lyell utilizes a suite of technologies to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and achieve

consistent and long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment.

Our product candidates target carefully selected tumor antigens and are enhanced with our proprietary technologies and manufacturing protocols designed to generate potent, tumor-reactive, long-lasting and functional T cells to drive durable tumor cytotoxicity.

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 CAR T-cell product candidates 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 and manufacturing protocols that are designed to endow T cells with more potent cancer cell killing capabilities.

In hematologic malignancies, we are focused on delivering therapies that provide 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 therapy 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.

We are currently conducting a pivotal single-arm clinical trial (PiNACLE) evaluating ronde-cel in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the third- or later-line (3L+) setting and a Phase 3 randomized controlled head-to-head CAR T-cell therapy trial (PiNACLE-H2H) for patients with LBCL receiving treatment in the second-line setting (2L).

Patient dosing has commenced in the PiNACLE-H2H Phase 3 trial, which randomizes patients to either ronde-cel or investigator’s choice of axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel).

To realize the potential of cell therapy for solid tumors, in November 2025 we acquired an exclusive global license for LYL273 (excluding mainland China, Hong Kong, Macau and Taiwan), an autologous guanylyl cyclase C (GCC)-targeted CAR T-cell product candidate previously known as GCC19CART, from Innovative Cellular Therapeutics Holdings Limited and Innovative Cellular Therapeutics, Inc.

(together, ICT).

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 to date in patients with advanced metastatic colorectal cancer (mCRC) in a U.S.

Phase 1 clinical trial as of the data cutoff date of October 28, 2025.

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 LYL273 was initially demonstrated in 15 patients with mCRC in an investigator-sponsored clinical trial conducted in China and published in JAMA Oncology (September 2024).

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 enhancements are designed to endow CAR T cells with attributes needed to drive durable tumor cytolytic activity 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.

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

Lyell’s Clinical Pipeline

Lyell’s mission is to fully realize the curative potential of next-generation CAR T-cell therapies and meaningfully improve outcomes for patients with cancer.

Today we are advancing next-generation innovative CAR T-cell therapies for patients with hematologic malignancies, including R/R LBCL, designed to improve outcomes over first‑generation products, and are aggressively progressing the next wave of cell therapy innovation for patients with solid tumors, including patients with advanced mCRC.

To realize the potential of cell therapy for cancer, our product candidates target carefully selected tumor antigens or targets with high expression on cancer cells and low to no expression in normal tissues or that are inaccessible in normal tissues, to avoid on-target, off-tumor toxicity.

We then arm our cells with enhancements to improve the CAR T cell’s ability to fight cancer.

Specifically, we utilize enhancements, including the ability to resist exhaustion and maintain qualities of durable stemness, designed to improve the functional activity of T cells in the hostile tumor microenvironment to drive durable tumor cytolytic activity and achieve consistent and long-lasting clinical responses.

Our product candidates are designed to be one-time CAR T-cell treatments that can achieve lasting remission for patients with cancer so they can return to their normal lives with extended disease-free, treatment-free periods.

Key components of our business strategy to achieve this goal include:

• Efficiently advance our clinical-stage pipeline of next-generation CAR T-cell product candidates — We believe our autologous T‑cell therapies have the potential to deliver improved, durable clinical outcomes for patients with hematologic malignancies and solid tumors.

Our most advanced wholly‑owned CAR T-cell product candidate, IMPT-314, has the potential to provide meaningfully differentiated benefit in overall and complete response rates and in the duration of the responses over first‑generation CD19 CAR T-cell therapies in patients with relapsed/refractory aggressive large B-cell lymphoma.

IMPT-314 is currently in Phase 1/2 development, and we recently reported positive initial clinical data in patients with aggressive large B-cell lymphoma in the 3 rd line or later (3 rd line+) setting.

We expect to initiate two pivotal clinical programs:

one for patients being treated in the 3 rd line+ setting in mid-2025, and another for patients in the 2 nd line setting by early 2026.

• Advance novel targets and technologies to generate a robust pipeline of next-generation cell therapies designed to deliver durable anti-tumor activity for cancer indications with high unmet medical need and of substantial market size — We are committed to continuing the advancement of disruptive technologies designed to revolutionize cell therapy and its promise to improve the lives of patients with hematologic malignancies and solid tumors.

In addition to developing novel CAR constructs that target undisclosed tumor antigen targets, we are advancing a suite of stackable proprietary technologies to arm T cells to overcome the barriers presented by solid tumors.

Our preclinical programs under development target antigens in solid tumors with high unmet medical need in indications with substantial market size.

We have previously validated our proprietary anti-exhaustion technology and intend to stack newer technologies expressing novel chimeric proteins designed to fully arm our CAR T-cell product candidates to optimize CAR T‑cell killing in the hostile tumor microenvironment and enable durable anti-tumor function in the solid tumor setting.

We anticipate submitting an Investigational New Drug (IND) application for a second CAR T-cell product candidate armed with multiple proprietary technologies and targeting a solid tumor indication in 2026.

• Efficiently advance our lead late-stage clinical program evaluating ronde-cel for patients with LBCL — We believe our autologous dual-targeting CD19/CD20 CAR T‑cell product candidate, ronde-cel, has the potential to deliver improved, durable clinical outcomes for patients with R/R LBCL over first‑generation approved CD19 CAR T-cell therapies.

Ronde-cel is currently under evaluation in a pivotal single-arm trial, PiNACLE, in the 3L+ setting.

This trial is a seamless expansion of the 3L+ cohort in our ongoing Phase 1/2 clinical trial and is expected to enroll approximately 120 patients at approximately 25 sites.

The primary endpoint is the best overall response rate.

We have also recently initiated the first-of-its-kind Phase 3 randomized controlled head-to-head CAR T-cell therapy clinical trial, PiNACLE-H2H.

Patient dosing commenced in February 2026 in this trial, and site activation is underway in the United States, Canada and Australia.

We expect to randomize approximately 400 patients 1:1 to either ronde-cel or investigator’s choice of axi-cel or liso-cel.

The primary endpoint is event-free survival.

We recently reported updated clinical data in patients with aggressive LBCL in the 3L+- and 2L- settings from a multi-cohort multi-center Phase 1/2 clinical trial (NCT05826535) at the December 2025 American Society of Hematology Annual Meeting and Exposition (ASH 2025).

The oral presentation included updated data from the 3L+ cohort (now the ongoing PiNACLE pivotal trial) including a best overall response rate of 93% and a complete response rate of 76% in 29 efficacy-evaluable patients with R/R LBCL.

The median progression-free survival was 18 months as of the data cutoff date of September 5, 2025.

Updated data were also presented from the 2L cohort, including 18 efficacy evaluable patients (94% with high-risk primary refractory disease) and demonstrated an 83% best overall response rate and a 61% complete response rate.

The safety profile was

appropriate for outpatient administration of ronde-cel.

Data from 25 patients treated with ronde-cel and receiving dexamethasone prophylaxis revealed no reports of Grade 3 or higher cytokine release syndrome (CRS) and one case (4%) of Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS).

• Efficiently advance our Phase 1 clinical program evaluating LYL273 for patients with advanced mCRC — We believe our autologous guanylyl cyclase C-targeting CAR T‑cell product candidate, LYL273 (previously known as GCC19CART), 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, has the potential to deliver improved, durable clinical outcomes for patients with advanced mCRC over currently approved therapies in the 3L+ mCRC setting.

A 67% best overall response rate, an 83% disease control rate and an 8-month median progression-free survival with a manageable safety profile have been reported as of the data cutoff date of October 28, 2025.

LYL273 is currently undergoing evaluation in an ongoing Phase 1 trial to establish the recommended Phase 2 dose.

• Advance novel targets and technologies to generate a robust pipeline of next-generation cell therapies designed to deliver durable antitumor activity for cancer indications with high unmet medical need and of substantial market size — We are committed to continuing the advancement of disruptive technologies designed to achieve the promise of cell therapy to significantly improve the outcome for patients with hematologic malignancies and solid tumors.

Our objective is to select promising CAR T-cell therapy targets that are highly expressed on cancers that impact a large number of patients with high unmet medical need, but not on normal tissues to avoid on-target, off tumor toxicity.

We then arm the CAR T cells with enhancements designed to optimize cancer cell killing.

Specifically, our strategy centers around the utilization of enhancements, including the ability to resist exhaustion, maintain qualities of durable stemness and function in the hostile tumor microenvironment, designed to improve T cell functional activity, drive durable tumor cytolytic activity and achieve consistent and long-lasting clinical responses.

• Maintain state‑of‑the‑art infrastructure and expert capabilities to control and innovate cell product manufacturing — We have built and operate a dedicated manufacturing facility, the LyFE Manufacturing Center™ (LyFE), that produces cell product for our clinical trials.

At full capacity, LyFE has the capacity to manufacture more than 1,000 CAR T-cell doses/year and therefore has the capability to support early commercial launch.

At full staffing and capacity, we expect LyFE to have the capacity to manufacture more than 1,200 CAR T-cell doses/year and support commercial launch.

We have invested in infrastructure that enables real‑time monitoring of our manufacturing processes and the ability to incorporate insights into our research, manufacturing and clinical development efforts.

Through our recent acquisition of ImmPACT, we acquired the cell manufacturing facility based in Los Angeles that has produced all of the IMPT-314 doses used in clinical trials to date.

As we accelerate development of IMPT-314, we are supplementing our Los Angeles manufacturing capacity through a manufacturing technology transfer to LyFE.

Our manufacturing strategy includes seeking new ways to efficiently, rapidly and cost-effectively scale manufacturing capacity for our cell product candidates for future clinical trials and potential commercialization.

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• Opportunistically pursue strategic opportunities to maximize the potential of our pipeline and capabilities — We consider a variety of ways to collaborate with external partners.

Our technologies can be applied in a target and modality agnostic manner to CAR, tumor infiltrating lymphocyte (TIL) and T-cell receptor (TCR) therapies to improve the functionality of T cells.

We will evaluate options for partnering programs, indications or geographies with pharmaceutical or biotechnology companies for the development and/or commercialization of our product candidates designed to address large patient populations.

We evaluate options for partnering programs, indications or geographies with pharmaceutical or biotechnology companies for the development and/or commercialization of our product candidates designed to address large patient populations.

We also consider opportunities to acquire or license rights or invest in differentiated product candidates or technologies to complement our pipeline.

Our Pipeline Programs

We are advancing a pipeline of next-generation CAR T-cell product candidates, including our lead program, IMPT-314, that is in clinical development for aggressive large B-cell malignancies.

Our preclinical programs target solid

tumor indications.

Each of our programs target cancers with large unmet need with substantial patient populations (see Table 1).

CAR T-cell therapies have demonstrated the curative potential of genetically-engineered autologous cell therapy for cancer.

CARs are synthetic receptors that link an extracellular antigen-binding moiety, usually a single chain variable fragment (scFv) derived from a monoclonal antibody, to intracellular signaling domains.

CARs redirect T-cell functional activity, including cytotoxicity and cytokine secretion, toward cancer cells that share a common target without the limitation of human leukocyte antigen restriction.

Our Pipeline Clinical Programs

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

Our lead program, IMPT-314, is targeting patients with aggressive relapsed/refractory large B-cell non-Hodgkin lymphoma (NHL).

Target Market and Approved Therapies

Our lead program, ronde-cel, is targeting patients with aggressive R/R 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.

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NHL is the more common form of lymphoma, representing approximately 90% of all lymphomas.

The American Cancer Society estimates that more than 80,000 people will be diagnosed with NHL in the United States in 2025 and 545,000 will be diagnosed worldwide.

NHL encompasses a diverse group of blood cancers, with over 90 distinct subtypes, generally classified based on (i) the type of lymphocytes involved (B-cell or T-cell), (ii) the lymphocytes’ phenotype, defined as large cell or small cell and (iii) the disease's rate of progression, which can be characterized as either aggressive or indolent (Figure 1).

We are initially focused on developing IMPT-314 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), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL) and Grade 3B follicular lymphoma (FL3B).

DLBCL and PMBCL represent approximately 31% and 3% of patients diagnosed with NHL each year, respectively, while tFL and FL3B each represent approximately 1 to 2% of NHL patients diagnosed with follicular lymphoma each year.

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 are currently pursuing include diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), transformed marginal zone B-cell lymphoma (tMZBCL), transformed mantle cell lymphoma (tMCL) 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 the transformed lymphomas 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.

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 IMPT-314 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, transformed PMBCL, transformed FL (tFL) and Grade 3B follicular lymphoma (FL3B).

The majority of patients with NHL are successfully treated with frontline combination chemotherapy or targeted agents, but some do not stay in remission for 12 months (relapsed) and others fail to achieve a remission to therapy (refractory).

Aggressive lymphomas such as DLBCL and other large B-cell lymphoma subtypes are more likely to relapse or be refractory to therapy.

Approximately 40% of patients with DLBCL have refractory disease or relapse after their first line of treatment.

Prior to the approval of CD19 CAR T-cell therapies, the prognosis of patients with relapsed/refractory aggressive large B-cell lymphoma was poor, with the then current standard of care resulting in overall response rates of 26% and complete response rates of 7%.

The median overall survival was 6.3 months and only 20% of patients were alive at 2 years.

The three currently approved CD19 CAR T-cell therapies, axicabtagene ciloleucel (axi-cel, YESCARTA ® ), tisagenlecleucel (tisa-cel, KYMRIAH ® ), or lisocabtagene maraleucel (liso-cel, BREYANZI ® ) transformed the treatment landscape by improving overall response rates (72%, 50% and 73%, respectively) with complete response rates (51%, 32% and 54%, respectively) in the 3 rd line+ setting.

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, including up to 50% of patients who progress on first-line therapy and receive a second chemotherapy regimen prior to CAR while awaiting referral and/or apheresis scheduling (Figure 1).

Ronde-cel is targeting the multi-billion dollar CD19 CAR T-cell market.

While the first generation of CD19 CAR T-cell therapies delivered a major advance in treatment for patients with B-cell lymphoma, there remains a need for therapies that deliver more complete and durable responses.

More than 40% of patients with aggressive large B-cell lymphoma treated in the 3 rd line+ setting with a CD19 CAR T-cell therapy are not disease-free after treatment and 30% of patients do not respond at all.

Of these patients treated with an approved CD19 CAR T-cell therapy, approximately 50% of patients progress or relapse within six months, and the overall survival at one year for patients treated with a CD19 CAR is only 50% to 60%.

IMPT-314 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 in October 2024.

A dual-targeting, or bispecific, CAR recognizes two targets.

IMPT-314 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 naive and central memory T cells.

More than 40% of patients with aggressive LBCL treated in the 3L+ setting with a CD19 CAR T-cell therapy are not disease-free after treatment and 30% of patients do not respond at all.

Of these patients treated with an approved CD19 CAR T-cell therapy, approximately 50% of patients progress or die within six months, and the overall survival at one year for patients treated with a CD19 CAR T-cell therapy is only 50% to 60%.

The median progression-free survival for the approved CD19 CAR T-cell therapies for patients in the 3L+-setting is 6 to 7 months.

Importantly, the pivotal trials in the 3L+ setting for axi-cel and liso-cel did not enroll patients over the age of 75, and the axi-cel ZUMA-1 trial did not allow patients to receive bridging therapy between apheresis and CAR T-cell therapy infusion, potentially excluding patients who were progressing too rapidly to wait for CAR T-cell therapy manufacturing.

In the 2L setting, the ZUMA-7 randomized controlled trial of axi-cel versus standard of care chemoimmunotherapy did not enroll patients above the age of 75 and the only bridging therapy allowed was steroids.

In ZUMA-7, the complete response rate was 65% and the median progression-free survival in all enrolled patients was 14.7 months.

For those with primary refractory disease, the median progression-free survival was only 7 months.

The complete response rate for patients with primary refractory disease was not reported.

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 in the

liso-cel arm.

Data for patients with primary refractory disease in the 2L were not reported from this trial.

The second pivotal single-arm trial conducted for liso-cel (PILOT), did allow patients over the age of 75 and included patients ineligible for transplant with primary refractory disease, relapse before 12 months or relapse after 12 months to enroll into the trial.

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 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%.

The approved CD19 CAR T-cell therapies for NHL are expected to achieve worldwide sales in 2026 of approximately four billion dollars.

YESCARTA ® has been the market leader since approval, but recently BREYANZI ® has been gaining market share, presumably due to lower rates of neurotoxicity.

This “switching” behavior of CAR T-cell therapy prescribers has also been reported in the multiple myeloma market with CARVYKTI ® taking market share from ABECMA ® , presumably due to enhanced efficacy (Figure 2).

CAR T-cell therapy treating physicians have a historical willingness to “switch” CAR T-cell therapies based on the strength of efficacy and safety clinical data.

Mechanism of Action

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.

A dual-targeting, or bispecific, tandem CAR recognizes two targets with a single construct.

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:

• Ability to target lower or heterogenous CD19 antigen density and result in a higher percentage of complete responses than with a single targeting CAR agent;

• Increase in duration of responses by preventing relapse due to CD19 antigen escape

• Better cell engraftment, persistence and reduced exhaustion to provide longer duration of responses

IMPT-314 consists of autologous T cells that are genetically modified through transduction with a lentiviral vector expressing a CAR construct composing anti-CD19 and anti-CD20 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 IMPT-314 from cell therapies and other therapeutic modalities that singularly target CD19, CD20 or CD22, or bispecific CARs that target two antigens but without full potency as compared to single-targeting CARs.

IMPT-314 contains separate, tandem single-chain variable fragment (scFV) antibody domains designed to target both CD19 and CD20 and is manufactured using a CAR that contains the 4-1BB costimulatory domain and is manufactured with a process to enrich for CD62-positive naïve and central memory T cells.

• Ability to target lower or heterogeneous CD19 antigen density and result in a higher percentage of complete responses than with a single-targeting CAR construct;

• Increase in the duration of responses by preventing relapse due to CD19 antigen escape;

• Better cell expansion, persistence and reduced exhaustion to provide longer duration of responses.

Ronde-cel consists of autologous T cells that are genetically modified through transduction with a lentiviral vector expressing a tandem 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 3).

This differentiates ronde-cel from cell therapies and other therapeutic modalities that singularly target CD19, CD20 or CD22.

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.

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 IMPT-314’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 lymphoma who may have a lower or heterogeneous CD19 antigen density.

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.

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.

CD20 expression has been shown to be more stable following single-targeted CAR T-cell treatment, as compared to CD19 and CD22.

IMPT-314’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 those malignant B-cells that have limited or no expression of CD19 to achieve a higher overall response rate.

Additionally, IMPT-314 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.

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.

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 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 or refractory large B-cell lymphoma 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.

ImmPACT licensed its dual-targeting CD19/CD20 CAR T-cell product candidate from the University of California Los Angeles (UCLA).

Interim Phase 1 data in 13 patients with relapsed/refractory aggressive NHL treated in a UCLA‑sponsored single-center clinical trial were initially published and updated data were presented (Figure 3).

CAR T‑cell naïve patients with relapsed/refractory DLBCL or PMBCL after at least two lines of therapy or MCL, or FL were evaluated.

Autologous T cells were obtained and enriched for CD62L-positive naïve or memory T cells.

Two doses were to be evaluated including 50 and 200 million cells.

Three patients received cell doses below 50 million cells due to manufacturing issues.

The overall response rate was 92% with a complete response rate of 77% (10/13 patients).

The median progression-free survival was 50.1 months, and median overall survival was not reached with a median follow‑up of 32 months (range:

5.7 – not estimable).

The overall survival at three years was 65%.

A favorable safety profile was observed with no cases of cytokine release syndrome (CRS) above Grade 1 and no reported cases of immune effector cell‑associated neurotoxicity syndrome (ICANS).

Two patients in this study who achieved a complete response but experienced disease progression after approximately 18 months and four years respectively were both successfully retreated with the UCLA CD19/CD20 CAR T-cell product and both patients again achieved a complete response.

Interim Phase 1 data in 13 patients with relapsed/refractory aggressive NHL treated with UCLA-314 in a UCLA‑sponsored clinical trial were presented at the 2024 American Association for Cancer Research Special Conference in Cancer Research:

Tumor Immunology and Immunotherapy.

UCLA licensed the CD19/CD20 dual-targeting CAR construct to ImmPACT, who developed a GMP manufacturing process and initiated a Phase 1/2 clinical trial with their product candidate IMPT-314.

We acquired ImmPACT in October 2024 and are continuing the development of IMPT-314.

Phase 1/2 Clinical Trial of IMPT-314

Our ongoing Phase 1/2 trial of IMPT-314 is a multi-center, open-label dose-escalation and dose-expansion clinical trial designed to evaluate the safety and clinical benefit of IMPT-314 and to determine a recommended Phase 2 dose in patients with relapsed/refractory aggressive large B-cell lymphoma.

IMPT-314 has received Fast Track designation from the U.S.

Food and Drug Administration (FDA) for the treatment of relapsed/refractory aggressive large B-cell lymphoma

in the 3 r d line+ setting.

The trial is enrolling patients with relapsed/refractory DLBCL, PMBCL, high-grade B-cell lymphoma (HGBCL), FL3B and tFL.

The trial is enrolling CAR T-cell therapy naïve patients in the 3 rd line+ and 2 nd line settings.

If successful, we may expand into other types of B-cell NHL.

Phase 1/2 Clinical Data

We reported initial data from the ongoing Phase 1/2 trial at the American Society of Hematology 2024 Annual Meeting (ASH).

As of October 22, 2024 (the data cutoff date for the presentation at ASH), 23 patients with relapsed or refractory CAR T-naive large B-cell lymphoma received IMPT-314 and comprised the safety population.

The efficacy evaluable population consisted of 17 patients and was defined as patients with a response assessment at Day 84 or later or an earlier scan with a complete response or progressive disease.

Of the six patients not included in the efficacy evaluable population presented at ASH, 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 four patients who had not yet reached their Day 84 scan.

The demographic and baseline characteristic data from the patients enrolled into the trial demonstrated a median age of 65 (range, 21 – 87) years, the majority (61%) of patients with DLBCL, and a median of three prior lines of therapy (range, 2 – 6).

Approximately 50% of patients had elevated lactate dehydrogenase levels suggesting high disease burden and 53% of patients received bridging therapy.

The overall response rate for the efficacy evaluable patients was 94% (16/17 patients), with 71% (12/17 patients) achieving a complete response by three months (Table 2 and Figure 4).

At the time the data were presented, three of those four patients were continuing on in the study.

The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were experiencing a response when these data were reported.

Best overall response in CAR T-cell therapy naïve patients in the 3 rd line+ cohort in the initial data presented at the 2024 American Society of Hematology annual meeting.

Data cutoff October 22, 2024.

Initial data from the Phase 1/2 trial in patients with relapsed/refractory aggressive large B-cell lymphoma treated with IMPT-314 were presented at American Society of Hematology 2024 Annual Meeting 2024.

The efficacy evaluable population consisted of 17 patients.

The overall response rate was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months.

The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were experiencing a response when these data were reported.

In the safety evaluable population of 23 patients, no Grade 3 or greater CRS was reported.

Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of five days, and rapid improvement to Grade 2 or lower with standard therapy.

Four patients had Grade 3 infections including bacteremia not otherwise specified, tooth infection, urinary tract infection and a herpes zoster infection, all of which responded to treatment and resolved.

Pharmacokinetic data were available from 16 of the efficacy-evaluable patients.

IMPT-314 demonstrated robust expansion and peak cell expansion occurred between Days 7 and 28 after IMPT-314 infusion (median T max = 10 days).

Median peak of expansion (C max ) was 93,723 copies/µg gDNA (range 2,338 – 555,284).

IMPT-314 cells persisted multiple weeks post infusion across multiple patients with median expansion at Day 28 of 11,766 copies/µg gDNA (range 56 – 555,284).

The median peak expansion of IMPT-314 is approximately four‑fold higher than the median peak expansion reported for lisocabtagene maraleucel, a CD19 CAR T-cell therapy approved for patients with relapsed or refractory (R/R) large B-cell lymphoma.

Greater CAR T-cell expansion has been associated with improved treatment response in patients with B-cell lymphoma.

Additionally, the final drug product contained the desired naïve and central memory cell phenotype (median, 91%;

range, 82 – 99%) that has been associated with improved overall survival in other CAR T‑cell clinical studies.

Based on these promising initial and emerging data from the Phase 1/2 IMPT-314 clinical trial and following appropriate regulatory interactions, we intend to initiate a pivotal trial in the 3 rd line+ setting in mid-2025 and a pivotal trial in the 2 nd line setting by early 2026.

Target Markets

We are initially developing IMPT-314 for the treatment of aggressive large B-cell NHL.

NHL is a common blood cancer in the United States and worldwide.

There are more than 60 NHL subtypes that have been identified by the World Health Organization.

Aggressive lymphomas grow and spread quickly and cause more severe symptoms, and these account for approximately 60% of all NHL cases.

B‑cell lymphoma is the most common type of NHL, comprising approximately 85% of all lymphomas in the United States.

We are initially focusing on the subtypes classified as large B-cell lymphomas;

of these diffuse large B-cell lymphoma (DLBCL) is the most common.

Annually, it is estimated that approximately 80,000 people in the United States and 545,000 worldwide will be diagnosed with NHL.

Approximately 200,000 cases of DLBCL are expected to be treated in the U.S., European Union (EU), United Kingdom (UK), China and Japan in 2025, with approximately 24,000 and 13,000 patients receiving treatment in the 2 nd and 3 rd line and later settings, respectively, in the U.S.

and approximately 62,000 and 24,000 patients receiving treatment in the 2 nd and 3 rd line and later settings,

respectively, in the U.S., EU, UK, China and Japan.

Today, the approved CD19 CAR T-cell therapy products have worldwide projected sales of approximately $3 billion and this is expected to nearly double by 2030.

Beyond DLBCL, other subtypes of B-cell NHL that could be evaluated in future trials of IMPT-314 include FL, MZL and MCL, where approximately 200,000, 79,000 and 38,000 patients are expected to be treated in the U.S., EU, UK, China and Japan in 2025.

Our Preclinical Programs

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.

During ASH 2025, we orally presented translational data from our ongoing Phase 1/2 clinical trial that showed that ronde-cel manufactured with CD62L-positive enriched cells achieved robust expansion and high expression of memory-related genes after infusion in patients with LBCL.

An evaluation of ronde-cel and published data for approved CD19 CAR T-cell products demonstrated that ronde-cel had a higher proportion of CD62L-positive T cells with a higher proportion of memory-cell phenotype prior to infusion (ronde-cel, N = 34;

axi-cel, N = 110;

and tisagenlecleucel (tisa-cel), N = 31).

In addition, ronde-cel had up to a three-fold higher expansion in patients after infusion compared to the expansion of approved CD19 CAR T-cell products.

Ronde-cel product memory-cell phenotype was positively correlated with expansion.

Peripheral blood samples collected from patients one month after infusion (N = 9) also had a higher proportion of CAR T cells with a memory phenotype compared to cells from axi-cel-treated patients (N = 4).

Ronde-cel CAR-positive

T cells collected from patients one (N = 7) and two months (N = 3) after infusion demonstrated sustained capacity to proliferate, kill tumor cells over 72 hours and secrete cytokines.

Clinical Development Strategy

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 ASH 2025.

Based on these data, as well as our recent 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.

The PiNACLE trial (Figure 4), 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 pivotal trial evaluating ronde-cel at a dose of 100 x 10 6 CAR T cells in patients with LBCL treated in the 3L+ setting.

The trial is expected to enroll approximately 120 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).

The PiNACLE single-arm pivotal trial schematic.

The PiNACLE trial is expected to enroll approximately 120 patients with R / R LBCL.

CAR, chimeric antigen receptor;

Cy, cyclophosphamide;

DLBCL, diffuse large B-cell lymphoma;

3BFL, Grade 3B follicular lymphoma;

Flu, fludarabine;

PMBCL, primary mediastinal B-cell lymphoma.

The PiNACLE-H2H trial is a Phase 3 head-to-head CAR T-cell therapy randomized controlled trial that will evaluate 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 10 6 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).

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.

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

The PiNACLE-H2H Phase 3 randomized controlled head-to-head CAR T-cell therapy trial of ronde-cel versus investigator’s choice of axi-cel or liso-cel.

Clinical Data

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 10 6 CAR T cells.

Two patients were treated at Dose Level 2 (300 x 10 6 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.

Sixty-nine patients with R/R LBCL received ronde-cel as of September 5, 2025 (the data cutoff date for the presentation at ASH 2025).

Patient demographics and baseline disease characteristics were consistent with a high-risk, heavily pre-treated patient population, particularly as compared to historical trials of CD19 CAR T-cell products:

median ages of 64 and 65 years with 16% (6/37) and 21% (5/24) of patients being 75 years or older in the 3L+ and 2L settings, respectively;

and primary refractory disease in 43% (16/37) and 92% (22/24) of patients in the 3L+ and 2L settings, respectively.

The efficacy evaluable population, defined as those patients with Day 84 assessments or prior disease progression or death, consisted of 47 patients (29 in the 3L+ setting and 18 in the 2L setting).

Patients Treated with Ronde-Cel in the 3L+ Setting

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 6 and summarized here:

• The best overall response rate was 93% (27/29 patients), with 76% (22/29) of patients achieving a complete response

• 72% (13/18) of patients with complete response remained in complete response at 6 months or longer

• Median progression-free survival was 18 months

The PiNACLE single-arm pivotal trial is a seamless expansion of this 3L+ cohort and is ongoing.

The trial design is presented in Figure 4.

Patients with HGBCL are no longer included in the PiNACLE single-arm trial to focus the trial on those patients most likely to achieve high durable response rates.

The response rate and duration of response in patients enrolled with HGBCL (N = 8) was shorter than that observed for patients with other histologies.

High rates of durable complete responses were observed in patients treated with ronde-cel in the 3L+ setting.

3L+, third- or later-line setting, LBCL, large B-cell lymphoma.

Patients Treated with Ronde-Cel in the 2L Setting

There were 18 efficacy-evaluable patients enrolled in the 2L setting with a median follow-up time of 9 months as of the data cutoff date.

Of these efficacy-evaluable patients, 94% had primary refractory disease.

Data from these patients are presented in Figure 7 and summarized here:

• The overall response rate was 83% (15/18 patients), with 61% (11/18) achieving a complete response

• 70% (7/10) of patients with complete response remained in complete response at ≥ 6 months

• The median duration of complete response was not reached

High rates of durable complete responses were observed in patients treated with ronde-cel in the 2L setting.

2L, second-line setting, LBCL, large B-cell lymphoma.

In 69 patients, including all patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed.

No Grade 3 or higher CRS was observed.

Twenty-five of the 69 patients received protocol-directed dexamethasone prophylaxis (10 mg/day for 3 days).

One case (4%) of Grade 3 or higher ICANS was reported in a patient with high disease burden;

no case of Grade 2 ICANS was reported.

In all 69 patients, as of the data cutoff date, low rates of Grade 1 (32%) or Grade 2 (29%) CRS were reported;

ICANS rates were reported as follows:

Grade 1 (9%), Grade 2 (3%) and Grade 3 or higher (12%) of patients.

The median time to complete resolution of all reports of ICANS was 4 days.

Cell pharmacodynamic data demonstrated robust CAR T‑cell expansion and persistence that were similar in patients with or without dexamethasone prophylaxis.

No deaths were determined to be related to ronde-cel administration.

Data are presented in Figure 8.

Adverse events of interest with and without dexamethasone prophylaxis for patients in both the 3L+ and 2L settings.

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;

IV, intravenous;

LDH, lactate dehydrogenase;

PO, per os (oral).

Pharmacokinetic Data

Pharmacokinetic data evaluating ronde-cel cell expansion using the droplet digital polymerase chain reaction (ddPCR) method are presented in Figure 9.

The data showed robust cell expansion with or without dexamethasone prophylaxis (dexamethasone 10 mg by oral or intravenous administration once daily for 3 days) with no significant differences observed in peak CAR T-cell expansion (C max ) or overall exposure (AUC) between patients who received dexamethasone (N = 25) and those who did not (N = 42).

Ronde-cel cell expansion was robust in patients who did or did not receive dexamethasone prophylaxis, 10 mg by oral or intravenous administration daily for three days.

CAR, chimeric antigen receptor;

ddPCR, digital droplet polymerase chain reaction;

DNA, deoxyribonucleic acid;

IQR, interquartile range;

LLOQ, lower limit of quantitation;

LLOD, lower limit of detection.

Assay used for measuring B cells/µl (Epiontis ID®) can detect as low as 2 cells/µl with high accuracy.

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

The FDA has also granted ronde-cel Orphan Drug Designation for the treatment of DLBCL/HGBCL with MYC and BCL2 rearrangements.

Based on the clinical data observed to date and an End-of-Phase 1 meeting with the FDA, we have initiated the Phase 3 randomized controlled head-to-head CAR T-cell trial evaluating ronde-cel versus investigator’s choice of an approved CD19 CAR T-cell therapy (axi-cel or liso-cel).

LYL273 (formerly known as GCC19CART):

Guanylyl cyclase C-targeted CAR T-cell product candidate for the treatment of mCRC and other GCC-expressing cancers

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, formerly GCC19CART) with promising dose-dependent clinical activity, including a 67% best overall response rate, disease control rate of 83% and a median progression-free survival of 8 months in patients with advanced mCRC in a Phase 1 trial conducted in the U.S.

Investigational New Drug (IND) and Phase 1 trial initiation were supported by single-center data from an investigator‑sponsored study of 15 patients conducted in China and published in JAMA Oncology in 2024.

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.

Target Market and Approved Therapies

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 expected to die from CRC in the U.S.

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.

Despite the remaining tremendous unmet medical need for new effective therapies for mCRC, the worldwide net sales for currently approved CRC products is expected to reach 12 billion dollars by 2032 (Figure 10).

However, the benefit of approved therapies for mCRC in the 3L+ setting is limited.

With the approved products, only six percent or less of patients achieve a partial or complete response to their next line of therapy, the median progression-free survival is 6 months or less and the median overall survival is 11 months or less (Figure 10).

The worldwide market for therapies approved for colorectal cancer is six billion dollars and growing.

However, currently approved standard-of-care therapies in the 3L+ setting do not achieve meaningful response rates and provide limited survival benefit.

Mechanism of Action

LYL273 is a GCC-targeted CAR T-cell therapy armed with enhancements including CD19 CAR expression and release of multiple cytokines in a controlled manner upon T-cell activation.

Together, these enhancements were designed to increase CAR T-cell expansion, immune cell infiltration and cancer cell killing (Figure 11).

GCC is a receptor that plays a key role in the regulation of intestinal electrolyte homeostasis.

It is expressed on more than 95% of colorectal cancers and a majority of pancreatic adenocarcinomas.

Its expression in healthy tissue is limited to the gastrointestinal tract, where it is sequestered by tight junctions from the circulation.

There are currently no CAR T-cell therapies approved to treat patients with solid tumors.

LYL273 was specifically designed to overcome two key barriers that have previously prevented successful treatment of solid tumors with CAR T‑cell therapies.

The first is lack of sufficient in vivo CAR T-cell expansion to allow for adequate tumor infiltration.

The second is inhibition of antitumor activity such as tumor cell killing and cytokine production due to the hostile tumor immunosuppressive or “cold” tumor microenvironment.

GCC is an excellent target because it is highly expressed in the vast majority of colorectal cancers and metastases and expressed at lower levels in normal gut tissue and generally inaccessible to the circulation.

However, our approach is to arm CAR T-cell therapies with additional enhancements to increase the CAR T cell’s ability to kill cancer cells.

LYL273 is a single product consisting of a mixture of three key cell types:

GCC CAR T cells, CD19 CAR T cells that release specific cytokines upon activation and doublet cells that have both GCC and CD19 CAR expression.

Upon activation, these doublet cells are also engineered to release either interferon gamma (IFNγ), interleukin 12 (IL-12) or interleukin-6 (IL-6).

The CD19 CAR expressing T cells engage B cells and jumpstart CAR T-cell activation and cell expansion upon infusion.

As the CAR T cells infiltrate into the cancer, the cytokines enhance further cell expansion, remodel or “warm up” the suppressive tumor microenvironment and enhance immune cell infiltration and cancer cell killing.

The level of cytokines is carefully regulated by specific vector design and usage during manufacturing.

The Miltenyi CliniMACS PRODIGY ® closed, automated manufacturing system is used to manufacture LYL273 and it is a standardized 7-day manufacturing process that is easily transferable and scalable.

LYL273 is a GCC-targeted CAR T-cell product candidate armed with enhancements including CD19 and the controlled release of cytokines including IFNγ, IL-12 and IL-6.

It is a single product enhanced with three key CAR T-cell types including GCC CAR T cells, CD19 CAR T cells that release cytokines upon activation and engagement of B cells.

LYL273 is designed to enhance in vivo cell expansion and to remodel the tumor microenvironment to improve tumor infiltration and cancer cell killing.

Clinical Development Strategy

LYL273 is under evaluation in an ongoing Phase 1 clinical trial to determine the recommended Phase 2 dose and regimen, and to determine the tolerability and pharmacokinetics of LYL273.

The IND was filed and the trial initiated based upon 15 patients with refractory mCRC from an investigator-sponsored study in China published in JAMA Oncology , 2024.

Patients were evaluated at either Dose Level 1 (1 x 10 6 CAR-positive cells/kg;

N = 8) or Dose Level 2 (2 x 10 6 CAR‑positive cells/kg;

Across both dose levels, the overall response rate was 40% (6/15).

The disease control rate was 73%.

At Dose Level 2, the median overall survival was 25 months (95% confidence interval [CI] of 13.4 to 26.1) and the median progression-free survival was 6 months (95% CI, 3.0 to not applicable).

No deaths occurred during the study period.

Adverse events of interest included CRS (86%, Grade 1 or 2), ICANS (14%, Grade 4), diarrhea (57%, Grade 3, all resolved), leukopenia (57%, Grade 3).

Prior to these data, ICT reported unpublished data in 20 patients at various doses with various manufacturing processes across multiple different centers in China.

During the study treatment period, five deaths were reported at these trial sites.

The trial was subsequently focused at one expert center with CAR T-cell therapy experience.

Clinical Data

Response Rates

Phase 1 clinical trial is ongoing at four centers in the United States, including the Dana Farber Cancer Institute, the University of California, San Francisco Comprehensive Cancer Center, the University of Colorado Cancer Center and the City of Hope Comprehensive Cancer Center.

Patients with refractory mCRC treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor therapy and anti-epidermal growth factor receptor therapy for RAS wild-type tumors and checkpoint inhibitor treatment for microsatellite-instability high or mismatch repair deficient tumors are eligible if they have one measurable lesion per Response Evaluation Criteria for Solid Tumors, version 1.1.

Liver metastases are allowed, but limited to no more than seven lesions with the largest lesion less than 3 cm.

The patient must be determined to have no surgical options with curative intent.

A single dose of lymphodepleting chemotherapy consisting of cyclophosphamide, 300 mg/m 2 , and fludarabine, 30 mg/m 2 is administered prior to CAR T-cell infusion.

Two dose levels have been evaluated as of the data cutoff date of October 28, 2025 and include Dose Level 1 at 1 x 10 6 CAR T cells/kg (N = 6 patients) and Dose Level 2 at 2 x 10 6 CAR T cells/kg (N = 6 patients).

The patients enrolled had a median age of 49 (range, 39 to 57), had a median of 3 prior lines of therapy (range, 2 to 6), with 25% receiving prior treatment with LONSURF ® and 100% receiving prior treatment with AVASTIN ® .

All patients were microsatellite stable and 33% had disease with RAS mutations.

The best 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 best 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 12).

For patients treated at Dose Level 2, the disease control rate was 83%, and the median progression-free survival was 7.8 months.

Phase 1 clinical trial, 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.

For patients treated at Dose Level 2, the disease control rate was 83%, and the median progression-free survival was 7.8 months.

In this trial, the incidence and severity of treatment-related adverse events were highest at Dose Level 2, where the most common adverse events were cytokine release syndrome in 83% (5/6) of patients (Grade 1, 67%;

Grade 2, 17%) and diarrhea in 83% (5/6) of patients (Grade 1, 33%;

Grade 2, 33%;

Grade 3, 17%) as of the data cutoff date of October 28, 2025.

The median duration of diarrhea was 11 days.

Immune effector cell-associated neurotoxicity syndrome occurred in 33% (2/6) of patients (Grade 2, 17%;

Grade 3, 17%) and resolved rapidly with treatment.

One patient experienced a dose‑limiting toxicity at Dose Level 2, including Grade 3 diarrhea, Grade 4 enterocolitis and death from fungal sepsis 48 days post-infusion.

No Grade 3 or higher diarrhea occurred in the last three patients treated since establishing an optimized management protocol for diarrhea, including prophylaxis with vedolizumab, infliximab and budesonide.

Pharmacokinetic Data

LYL273 is a single product candidate consisting of a mix of three key cell types including GCC CAR T cells, CD19 CAR T cells and GCC/CD19 doublet CAR T cells.

A consistent cell expansion profile was observed across patients, as exemplified by the cell expansion data from Patient 11 who achieved a 100% partial response (Figure 13).

All three cell types expanded, with the high level of expansion observed in the doublet cell population which accounted for more than 80% of all GCC CAR-expressing T cells at peak.

After 21 days, the steadily expanded GCC CAR T cells made up the majority CAR T cells in peripheral blood.

LYL273 cell expansion data from Patient 11 in the U.S.

Phase 1 clinical trial.

The plot shows the proportion of T cells in the peripheral blood of each of the three key cell types comprising LYL273.

Our Nonclinical Programs

Cell therapy has demonstrated profound results in some patients suffering from hematologic malignancies, but there remains a need for therapies that deliver more complete and durable responses.

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And while there has been recent progress with new cell therapies approved for solid tumors, overall response rates and the duration of response remain low.

To complement our clinical programs, we continue to invest in earlier stage cell therapy research and development utilizing our proprietary technologies.

We expect to submit an IND application in 2026 for a new, armed solid tumor CAR T-cell product candidate with a new target, anti-exhaustion and durable stemness technologies, as well as a new technology designed to overcome the hostile tumor microenvironment.

We continue to invest in earlier stage cell therapy research and development utilizing our proprietary technologies.

We are advancing a fully-armed solid tumor CAR T-cell product candidate with an undisclosed target, with the CAR T cells enhanced by multiple technologies, each designed to address different barriers to effective cell therapies, including T‑cell exhaustion, lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment.

Our T-cell Enhancement and Manufacturing Technologies

At Lyell, we believe that careful selection and evaluation of our CAR targets is important to ensure we are aiming for larger markets with substantial unmet medical need and 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 most solid tumors.

Based on nonclinical evidence and clinical data, we believe there are multiple mechanisms limiting 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 proprietary anti-exhaustion and durable stemness technologies, as well as new enhancements designed to overcome the hostile tumor microenvironment.

T-cell exhaustion remains a major barrier for the development of effective CAR T-cell therapy.

We have previously demonstrated Lyell’s proprietary anti-exhaustion technology improves anti-tumor functions in in vitro and in vivo preclinical models.

In patients with triple-negative breast cancer we have shown that our anti-exhaustion technology reduces T-cell exhaustion and improves CAR T-cell pharmacokinetics and tumor infiltration.

Recently, alternative approaches that arm CAR T cells with transforming growth factor beta (TGF-β) blockade or constitutive cytokine signaling to enhance their anti-tumor functionality in the suppressive tumor microenvironment have shown promise in the solid tumor settings.

In addition to developing novel CAR constructs targeting undisclosed tumor antigen targets, our research activities explore stacking these additional approaches to our proprietary anti-exhaustion technology via the expression of novel chimeric protein or polypeptide to optimize CAR T-cell killing in the hostile tumor microenvironment for application in future solid tumor product candidates.

Our technologies and manufacturing approaches designed to generate CAR T cells that can achieve potent and durable anti-tumor cytotoxicity are summarized in Table 3 described below.

Lyell has a suite of technologies designed to enhance the potency and durability of our CAR T-cell product candidates.

Two of our technologies, c-Jun overexpression and our Epi-R manufacturing protocol, have been clinically validated in a Phase 1 study in patients with triple-negative breast cancer, and we are advancing an additional anti‑exhaustion technology, knockout of NR4A3 by gene editing, that has demonstrated even more potent anti-tumor functionality in nonclinical models.

More recently, we have explored new strategies to express novel chimeric proteins to optimize CAR T-cell killing in the hostile tumor microenvironment.

For our solid tumor nonclinical 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:

Antigen-specific recognition + CD3ζ (zeta) chain

Co-stimulation such as with CD28 or 4-1BB to augment Signal 1

Cytokine signaling

Our aim in designing a fully-armed CAR T-cell candidate is to optimize each signaling pathway with one or more enhancements from our suite of novel technologies to optimize CAR T-cell activation and function.

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 and insufficient cell expansion, as well as immune suppression within the hostile tumor microenvironment.

Our technologies and manufacturing approaches, designed to enhance CAR T-cell function so they can achieve potent and durable cancer cell killing, are summarized in Table 2.

Lyell CAR T-Cell Enhancements Designed to Augment the Potency and Durability of our CAR T-Cell Product Candidates.

et al., Nature , 2019;

et al., Nature Biotechnology 2018;

et al., Scientific Reports 2024;

Arcangeli et al., JCI 2022, Sommermeyer et al., Leukemia 2016, Chen et al., Cancer Discovery 2021, Aldoss et al., Clin Cancer Res 2023.

AP-1, activator protein-1;

CAR, chimeric antigen-receptor;

NR4A3, nuclear receptor 4A3;

TGF-β, transforming growth factor beta, TME, tumor microenvironment.

Two of our technologies, c-Jun overexpression and our Epi-R manufacturing protocol, have been clinically validated in a Phase 1 trial in patients with triple-negative breast cancer, and we are advancing an additional anti‑exhaustion technology, knockout of NR4A3 by gene editing, that has demonstrated even more potent antitumor functionality in nonclinical models.

More recently, we have explored new strategies to express novel chimeric proteins to improve CAR T-cell killing in the hostile tumor microenvironment.

c-Jun Overexpression

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This work was fully described in a Nature publication in 2019.

Overexpression of c-Jun was recently validated in a Phase 1 clinical study where a ROR1-targeted CAR T-cell products overexpressing c-Jun demonstrated clinical responses, improved pharmacokinetics, less CAR T-cell exhaustion and CAR T-cell tumor infiltration on histologic examination of on-study tumor biopsies.

These data demonstrated improvement over the clinical data from a prior study conducted at the Fred Hutchinson Cancer Center (Fred Hutch) of a similar ROR-1 CAR T-cell product, but without c-Jun overexpression, in a similar patient population where no responses were observed after a single CAR T-cell treatment and high levels of CAR T-cell exhaustion occurred rapidly.

Overexpression of c-Jun was recently validated in a Phase 1 clinical trial where a ROR1-targeted CAR T-cell product overexpressing c-Jun demonstrated clinical responses, improved pharmacokinetics, less CAR T-cell exhaustion and CAR T-cell tumor infiltration on histologic examination of on-study tumor biopsies.

These data demonstrated improvement over the clinical data from a prior trial conducted at the Fred Hutchinson Cancer Center (Fred Hutch) of a similar ROR-1 CAR T-cell product, but without c-Jun overexpression, in a similar patient population where no responses were observed after a single CAR T-cell treatment and high levels of CAR T-cell exhaustion occurred rapidly.

NR4A3 Gene Knockout

NR4A3 gene knockout builds on the approach of reprogramming of the AP-1 transcription factor pathway to delay exhaustion and improve antitumor function.

NR4A3 gene knockout builds on the approach of reprogramming the AP-1 transcription factor pathway to delay exhaustion and improve antitumor function.

We and others have previously observed that the NR4A family of transcription factors is upregulated in exhausted T cells and may contribute to T‑cell exhaustion, in part by restricting the activity of AP-1.

We hypothesize that disruption of NR4A3 expression, along with c-Jun overexpression, may further unleash the potential for maximal c-Jun activity and endow greater functional resistance to exhaustion.

Our nonclinical data suggest the combination of these two technologies, NR4A3 gene knockout and c-Jun overexpression, can act in a complementary fashion and may have the potential to further improve the potency and durability of our CAR therapy (Figure 5).

Epi-R Manufacturing Protocol

Epi‑R is our proprietary ex vivo manufacturing protocol that is designed to generate populations of stem-like T cells with reduced exhaustion and improved proliferation and antitumor activity.

T cells with properties of durable

stemness have an increased ability to self-renew and persist to drive durable tumor cytotoxicity.

Lyell developed technology based upon the science conducted at the National Cancer Institute, where it was demonstrated that products with more stem-like and functional T cells can be achieved by altering the metabolic state of the cells during expansion.

Epi‑R is our proprietary ex vivo manufacturing protocol that is designed to generate populations of stemlike T cells with reduced exhaustion and improved proliferation and antitumor activity.

T cells with properties of durable stemness have an increased ability to self-renew and persist to drive durable tumor cytotoxicity.

We developed this technology based upon the science conducted at the National Cancer Institute, where it was demonstrated that products with more and functional T cells can be achieved by altering the metabolic state of the cells during expansion.

CD62L - Positive Enrichment

Our lead product candidate, IMPT-314 is manufactured with a process that enriches for CD62L positive cells.

This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity that we believe could result in both increased complete response rates and more durable responses.

Our lead product candidate, ronde-cel, is manufactured with a process that enriches for CD62L-positive cells.

This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity that we believe could result in both higher complete response rates and more durable responses.

Naïve T cells are CD62L-positive 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.

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 cytokine production compared to CAR T cells generated from traditional processes.

The enrichment of CD62L-positive T cells does not increase the manufacturing time, which is similar to that of the approved CD19 CAR T-cell therapies.

Stim-R Technology

Stim‑R is our proprietary synthetic-cell mimetic composed of lipid-coated silica micro-rods that mimic the physiological cell-like presentation of signals to control T-cell activation in the manufacturing process.

Current manufacturing platforms typically utilize antibody-conjugated beads that were developed decades ago for expanding T cells.

This standard approach does not provide precise control over the strength or duration of the signaling that drives T‑cell expansion ex vivo.

Our Stim‑R platform optimizes signaling parameters during T‑cell activation using degradable lipid-coated silica rods that can be functionalized to regulate cell activation, more closely mimicking natural T‑cell stimulation.

This technology allows for greater control over the duration, intensity and type of signals delivered during cell expansion and manufacturing, resulting in the generation of more potent T‑cell products with desirable phenotypic and functional properties.

Nonclinical data demonstrate that CAR T cells enhanced with four technologies (c-Jun overexpression, NR4A3 knockout and manufactured with Epi-R and Stim-R) mediated anti-tumor response and enhanced survival in a murine xenograft tumor model, even at a very low CAR T‑cell dose of 100,000 CAR T cells.

Additionally, both in vitro and in vivo nonclinical data demonstrated that the combination of all four of these technologies resulted in superior cytotoxicity, improved proliferation and sustained cytokine production upon repeated antigen stimulation compared to various controls lacking one or more of the reprogramming technologies.

Dual CAR Expression

Our clinical candidates are designed to target more than a single antigen.

Ronde-cel expresses a tandem “OR” gated CAR to target both CD19 and CD20 that are expressed on B-cell lymphoma.

This approach was designed to improve the complete response rate, as well as durability of response for patients with aggressive lymphoma.

LYL273 is composed of several key CAR T-cell populations, including a novel doublet CAR T-cell population that expresses both GCC-targeted and CD19-targeted CARs.

Upon infusion, expression of the CD19 CAR enables B-cell engagement that jumpstarts doublet CAR T-cell activation, cytokine release and cell expansion.

Improved expansion may facilitate tumor infiltration and cancer cell killing.

Undisclosed New Technologies

Recently, alternative approaches that arm CAR-T cells with TGF-β blockade or constitutive cytokine signaling to enhance their anti-tumor functionality in the suppressive tumor microenvironment have shown promise in the solid tumor settings.

In addition to developing novel CAR constructs that target undisclosed tumor antigen targets, our research activities explore stacking our proprietary anti-exhaustion technology and these additional approaches targeting the tumor microenvironment via the expression of novel chimeric proteins or polypeptides (Table 3) to optimize more durable CAR T-cell killing for application in future solid tumor product candidates.

In the solid tumor setting, CAR T cells need to overcome the suppressive tumor microenvironment to optimally kill cancer cells.

We believe two key approaches to achieve this are to provide resistance to inhibitory signals such as TGF–β, and to enable locally-released supportive cytokine signaling to enhance the antitumor functionality of the CAR T cells.

Our nonclinical research activities explore stacking our proprietary anti-exhaustion technologies with these additional approaches via the expression of novel chimeric proteins and vector design to generate fully-armed CAR T-cell product candidates.

Our Manufacturing Capabilities

We believe it is critically important to control and continuously monitor all aspects of the cell therapy manufacturing process to mitigate risks, including challenges in managing production, supply chain, patient specimen chain of custody and quality control.

As we developed our technologies, we made a strategic decision to invest in building our own manufacturing facility to control our supply chain, maximize efficiencies in cell product production time, optimize cost and quality, protect proprietary aspects of our reprogramming technologies, and have the ability to rapidly incorporate advancements and new innovations.

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Our LyFE Manufacturing Center™ located in Bothell, Washington is approximately 73,000 square feet and is comprised of manufacturing suites, laboratories and offices.

At full staffing and capacity, we expect to be able to manufacture >1,000 patient CAR T‑cell products/year, able to support our clinical development needs for IMPT-314 and other pipeline programs, as well as early commercial launch if IMPT-314 is approved.

LyFE is manufacturing ronde-cel for the pivotal PiNACLE and PiNACLE-H2H trials and the ongoing Phase 1/2 clinical trial for patients with R/R 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 advanced mCRC.

At full staffing and capacity, we expect to be able to manufacture more 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.

LyFE was commissioned and designed to be in compliance with U.S.

and EU current Good Manufacturing Practices (cGMP) standards and has a flexible and modular design enabling CAR T‑cell, TIL, TCR T-cell therapies and cGMP viral vector production to control and de-risk the manufacturing sequence and timing of the major components of our supply chain.

and European Union (EU) current Good Manufacturing Practices (cGMP) standards and has a flexible and modular design enabling T-cell therapies and cGMP viral vector production to control and de-risk the manufacturing sequence and timing of the major components of our supply chain.

Owning our own facility has enabled seamless collaboration across research, process development and manufacturing for high-quality reproducibility at manufacturing scale.

Clinical supply for our Phase 1/2 trial of IMPT-314 is currently manufactured in our manufacturing facility in Los Angeles, California, that we acquired in connection with the acquisition of ImmPACT.

As we accelerate development of IMPT-314, we are supplementing our Los Angeles manufacturing capacity through a manufacturing technology transfer to LyFE.

We are focused on maintaining a manufacturing strategy that is operationally efficient to maximize our capacity and avoid any disruption to clinical trial supply.

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Any product candidates that we successfully develop and commercialize will compete with existing treatments and new treatments that may become available in the future.

In addition, during development and clinical trials, our product candidates may compete against other experimental treatments, whether cell therapy or other modalities, for patients with certain histologies or patients with tumors expressing certain antigen targets of interest.

If approved, our product IMPT-314 will need to compete against other products approved in the 2 nd and 3 rd line+ settings in our approved indications, including any approved CD19 CAR T‑cell therapies, monoclonal antibodies targeting CD19, antibody-drug conjugates, selective inhibitors of exportin 1 and bispecific antibodies.

In addition, during development and clinical trials, our product

candidates may compete against other experimental treatments, whether cell therapy or other modalities, for patients with certain histologies or patients with tumors expressing certain antigen targets of interest.

If approved, ronde-cel will need to compete against other products approved in the 2L and 3L+ settings in our approved indications, including approved CD19 CAR T‑cell therapies, monoclonal antibodies targeting CD19, antibody‑drug conjugates, bispecific antibodies and selective inhibitors of exportin 1.

If approved, LYL273 will need to compete against other products approved in the 3L+ setting in our approved indications such as mCRC, including any approved kinase inhibitors, antibody-drug conjugates, cytotoxic chemotherapies and immunotherapies.

We are also aware of a number of companies using autologous or allogeneic CAR T-cell therapy approaches to treat hematologic malignancies and solid tumors.

Some of these companies have substantially greater financial and other resources than we have, such as larger research and development staff and well-established marketing and sales forces, or operate in jurisdictions where we do not have staffing or resources.

CAR T‑cell therapies for the treatment of hematologic malignancies and solid tumors are being developed by a number of companies, including but not limited to Arcellx, Inc., Allogene Therapeutics, Inc., Arsenal Biosciences, Inc., AstraZeneca plc, Autolus Therapeutics plc, Bristol Myers Squibb Co., Caribou Biosciences, Inc., Cargo Therapeutics, Inc., Gilead Sciences Inc., Immunocore Holdings plc, Johnson & Johnson, Nanjing Legend Biotech, Novartis AG and Poseida/F.

Hoffmann-La Roche AG .

Some of the companies developing competitive products have substantially greater financial and other resources than we have, such as larger research and development staff and well-established marketing and sales forces, or operate in jurisdictions where we do not have staffing or resources.

CAR T‑cell therapies for the treatment of hematologic malignancies and solid tumors are being developed by a number of companies, including but not limited to Agenus Inc., Akeso, Inc., Arcellx, Inc., Allogene Therapeutics, Inc., Arsenal Biosciences, Inc., AstraZeneca plc, Autolus Therapeutics plc, Bristol Myers Squibb Co., Caribou Biosciences, Inc., Gilead Sciences Inc., Immunocore Holdings plc, Johnson & Johnson, Nanjing Legend Biotech, Novartis AG, Pfizer Inc., Poseida/F.

Hoffmann-La Roche AG and Summit Therapeutics Inc.

We are also aware that other companies are developing therapies in modalities such as bispecific antibodies for B-cell lymphomas, including AstraZeneca, F.

Hoffmann-La Roche AG and Amgen Inc.

Among companies developing CAR T-cell therapies for hematologic malignancies and solid tumors, we believe we are substantially differentiated by our technologies, manufacturing protocols and capabilities, knowledge, experience, scientific personnel and robust intellectual property portfolio.

New treatments for colorectal cancer that may change the therapeutic landscape, including bispecific antibodies like PD-1/VEGF or PD-1/CTLA-4 bispecifics, are being developed by companies such as Summit Therapeutics, AbbVie, Akeso, Agenus, and Pfizer.

CytomX has moved beyond dose escalation in a Phase 1 trial for a novel masked, conditionally activated antibody-drug conjugate directed against epithelial cell adhesion molecule under evaluation in patients with colorectal cancer.

Among companies developing CAR T-cell therapies for hematologic malignancies and solid tumors, we believe we are substantially differentiated by our technologies, manufacturing protocols, capabilities, knowledge, experience, scientific personnel and robust intellectual property portfolio.

We believe there are many factors affecting the success of any of our product candidates, including efficacy, safety, accessibility, price and scale and cost of manufacturing.

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UCLA License Agreement

As a result of our acquisition of ImmPACT, we assumed its rights and obligations under a license agreement with the Regents of the University of California, acting through The Technology Development Group of UCLA, dated February 18, 2021, as amended (the UCLA License Agreement).

Pursuant to the UCLA License Agreement, UCLA granted us an

exclusive, royalty‑bearing license, with the right to sublicense through a specified number of tiers, under certain patent rights owned by UCLA and certain patent rights co‑owned by UCLA and the Seattle Children’s Hospital doing business as the Seattle Children’s Research Institute (SCRI) and a non‑exclusive, royalty‑bearing license, with the right to sublicense through a specified number of tiers, under related technical information, in each case related to our CD19/CD20 program, for the development, use and sale of products or services associated with certain inventions made in the course of research by UCLA and SCRI in all fields of use.

As a result of our October 2024 acquisition of ImmPACT, we acquired rights and assumed obligations under a license agreement with the Regents of the University of California, acting through The Technology Development Group of UCLA, dated February 18, 2021, as amended (the UCLA License Agreement).

Pursuant to the UCLA License Agreement, UCLA granted us (i) an exclusive, royalty‑bearing license, with the right to sublicense through a specified number of tiers, under certain patent rights owned by UCLA and certain patent rights co‑owned by UCLA and the Seattle Children’s Hospital doing business as the Seattle Children’s Research Institute (SCRI) and (ii) a non‑exclusive, royalty‑bearing license, with the right to sublicense through a specified number of tiers, under related technical information, in each case related to our CD19/CD20 program, for the development, use and sale of products or services associated with certain inventions made in the course of research by UCLA and SCRI in all fields of use.

In accordance with the Patent and Trademark Law Amendments Act (the Bayh‑Dole Act), UCLA granted the U.S.

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We are also required, subject to certain exceptions, to provide UCLA with an affordable access plan within a specified time following the first commercial sale of a licensed product that is intended to support affordable access to licensed products in certain low‑ and middle‑income countries and other countries in which we do not intend to commercialize licensed products.

UCLA and SCRI reserved, for themselves and for other nonprofit and academic research institutions, their rights to use the patent rights and technical information licensed to us for education and research purposes and to publish results arising therefrom, and for UCLA to offer and perform clinical diagnostic and prognostic services for patients in the University of California healthcare system, in each case subject to certain exclusions.

University of California healthcare system, in each case subject to certain exclusions.

Our rights under the UCLA License Agreement are also subject to certain government rights.

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ImmPACT reimbursed UCLA for all patent costs incurred prior to the effective date of the UCLA License Agreement, and we are obligated to reimburse UCLA for all patent costs incurred by them during the term of the license agreement.

The license agreement will expire, on a product-by-product and country-by-country basis, on the later of (a) the expiration of the last to expire valid claim of the patent rights covering such product in such country and (b) ten (10) years after the date of the first commercial sale of such product in such country.

The UCLA License Agreement will expire, on a product-by-product and country-by-country basis, on the later of (a) the expiration of the last to expire valid claim of the patent rights covering such product in such country and (b) ten (10) years after the date of the first commercial sale of such product in such country.

UCLA has the right to terminate the agreement in the event of our uncured material breach, subject to a specified notice and cure period, or upon certain insolvency events.

We may terminate the agreement for convenience, subject to a specified notice period.

ICT License Agreement

On November 6, 2025, we entered into an Exclusive License Agreement with ICT for the development and commercialization of LYL273, a novel GCC-targeted CAR T-cell product candidate for the treatment of mCRC and other GCC-expressing cancers (the ICT License Agreement).

Pursuant to the terms of the ICT License Agreement, we received exclusive global rights, outside of mainland China, Hong Kong, Macau and Taiwan, to research, develop, manufacture, commercialize and otherwise exploit certain product candidates and products, including LYL273, worldwide in exchange for an upfront payment of $40 million in cash and the issuance of 1.9 million shares of our common stock.

In addition, ICT is eligible to receive additional cash and equity payments of (i) a potential $30 million clinical milestone payment, up to $115 million upon the achievement of certain late-stage regulatory milestones and up to $675 million in commercial sales milestones;

(ii) up to an additional 1.85 million shares of our common stock based on the achievement of certain clinical and regulatory milestones;

and (iii) tiered royalties ranging from mid-single-digits up to 10% on annual net sales in the United States and low- to mid-single-digit royalties on annual net sales in other countries within the licensed territory.

The ICT License Agreement includes customary representations, warranties and covenants, including, but not limited to, covenants by us and ICT to conduct the research, development, manufacture, commercialization and other exploitation of the product candidates and products, and their other obligations under the ICT License Agreement, in compliance with the terms of the ICT License Agreement and all other applicable laws and marketing approvals.

The ICT License Agreement may be terminated, among other circumstances, (i) by either party for uncured material breach, (ii) by either party due to the insolvency of the other party, (iii) by us for safety or regulatory reasons or (iv) by us on a product-by-product and country-by-country basis in our sole discretion after providing certain notice.

The ICT License Agreement (and any right or obligation thereunder) may not be assigned without the prior written consent of the other party, except to an affiliate or third party that acquires the business of the assigning party by way of a merger or sale of assets.

Intellectual Property

We strive to protect and enhance the proprietary technology, inventions and improvements that are commercially important to our business, including seeking, maintaining and defending patent rights, whether developed internally or licensed from our collaborators or other third parties.

Our policy is to seek to protect our proprietary position by, among other methods, filing patent applications in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements and product candidates that are important to the development and implementation of our business.

We seek to protect our proprietary position by, among other methods, filing patent applications in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements and product candidates that are important to the development and implementation of our business.

We also rely on trade secrets and know-how relating to our proprietary technology and product candidates, continuing innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position in the field of cell and gene therapy.

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and to operate without infringing on the valid and enforceable patents and other proprietary rights of third parties.

We have in-licensed and procured, and filed for numerous patent applications, which include claims directed to compositions, methods of use, processes, dosing and formulations, and possess substantial know-how and trade secrets relating to the development and commercialization of our cell engineering technology platforms and related product

candidates, including related manufacturing processes and protocols.

Our intellectual property strategy is designed to provide multi-layered protection covering our technologies and manufacturing protocols, including but not limited to c-Jun, NR4A3, CD62L + enrichment, Epi‑R and Stim‑R, as well as various aspects of our product candidates, including but not limited to CAR constructs.

Our intellectual property strategy is designed to provide multi-layered protection covering our product candidates, including ronde-cel, LYL273 and our next-generation solid tumor programs, as well as our various platform technologies and manufacturing protocols, including but not limited to c‑Jun, NR4A3, CD62L-positive cell enrichment, tumor restricted IL-12 variants and Epi‑R.

For all patent applications, we determine claiming strategy on a case-by-case basis.

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Notwithstanding these efforts, we cannot be sure that any patents will be granted with respect to any patent application we have licensed or filed or may license or file in the future, and we cannot be sure that any patents we have licensed or patents that may be licensed or granted to us in the future will not be challenged, invalidated or circumvented or that such patents will be commercially useful in protecting our technologies.

As of December 31, 2024, our patent portfolio consists of over 50 issued patents and over 250 pending patent applications that we either own or have licensed.

Our portfolio covers various aspects of our technologies and manufacturing protocols, including but not limited to c-Jun, NR4A3, CD62L + enrichment, Epi‑R and Stim‑R, as well as our product candidates.

As of December 31, 2025, our patent portfolio consists of at least 45 issued patents and 150 pending patent applications that we either own or have licensed.

Our portfolio covers our product candidates, including ronde-cel, LYL273 and our next-generation solid tumor programs, as well as various aspects of our technologies and manufacturing protocols, including but not limited to c-Jun, NR4A3, CD62L-positive cell enrichment, tumor restricted IL-12 variants and Epi‑R.

The patents and patent applications in our portfolio are held primarily in the United States, Europe, Canada, Japan and Australia.

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In addition, in certain instances, the patent term of a U.S.

patent that covers an FDA‑approved drug may also be eligible for extension to recapture a portion of the term effectively lost as a result of clinical trials and the FDA regulatory review period, such extension is referred to as patent term extension.

patent that covers an FDA‑approved drug may also be eligible for extension to recapture a portion of the term effectively lost as a result of clinical trials and the FDA regulatory review period.

Such an extension is referred to as patent term extension.

The restoration period cannot be longer than five years and the total patent term, including the restoration period, must not exceed 14 years following FDA approval.

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The actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent.

As of December 31, 2024, our registered trademark portfolio contains over 135 registered trademarks and pending trademark applications, consisting of approximately one trademark registration and four pending trademark applications in the United States, and approximately 121 foreign trademark registrations and approximately 10 foreign pending trademark applications.

We may also rely, in some circumstances, on trade secrets to protect our technology.

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Given our stage of development, we have not yet established a commercial organization or distribution capabilities.

We intend to either build a commercial infrastructure to support sales of any approved products or outsource

some or all of this function to third parties.

We intend to evaluate opportunities to work with partners that enhance our capabilities with respect to the development and commercialization of IMPT-314 and any other product candidates we may develop.

In addition, we intend to commercialize our product candidates, if approved, in key markets either alone or with partners to maximize the worldwide commercial potential of our programs.

We intend to either build a commercial infrastructure to support sales of any approved products or outsource some or all of this function to third parties.

We intend to evaluate opportunities to work with partners that enhance our

capabilities with respect to the development and commercialization of ronde-cel, LYL273, and any other product candidates we may develop.

In addition, we intend to commercialize our product candidates, if approved, in key markets either alone or with partners to maximize the worldwide commercial potential of our programs for ronde‑cel and LYL273.

Government Regulation

The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of biologics such as those we are developing.

We, along with third-party contractors, will be required to navigate the various nonclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct trials or seek approval or licensure of our product candidates.

We, along with our third-party contractors, will be required to navigate the various nonclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct trials or seek approval or licensure of our product candidates.

The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

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• completion of nonclinical laboratory tests and animal studies performed in accordance with the FDA’s Good Laboratory Practice requirements (GLP);

• submission to the FDA of an IND application, which must become effective before clinical trials may begin;

• submission to the FDA of an IND application, which must become effective before human clinical trials may begin;

• approval by an Institutional Review Board (IRB) or ethics committee at each clinical site before the trial is commenced;

• performance of adequate and well-controlled human clinical trials according to the FDA’s regulations (commonly referred to as GCP), regulations and any additional requirements for the protection of human research subjects and their health information to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose;

• performance of adequate and well-controlled human clinical trials according to the FDA’s regulations (commonly referred to as GCPs) and any additional requirements for the protection of human research subjects and their health information to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose;

• preparation of and submission to the FDA of a Biologics License Application (BLA), after completion of all pivotal clinical trials;

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• FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States.

Before testing any biological product candidate in humans, the product candidate enters the nonclinical testing stage.

Nonclinical tests, also referred to as preclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate.

The conduct of the nonclinical tests must comply with federal regulations and requirements including GLPs.

Prior to beginning the first clinical trial with a product candidate in the United States, we must submit an IND to the FDA.

An IND is a request for authorization from the FDA to administer an investigational new drug to humans.

The central focus of an IND submission is on the general investigational plan and the protocol(s) for clinical trials.

The IND also includes results of animal and in vitro studies assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product;

chemistry, manufacturing and controls information;

and any available human data or literature to support the use of the investigational product.

An IND must become effective before human

clinical trials may begin.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

An IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin.

Submission of an IND, therefore, may or may not result in FDA authorization to begin a clinical trial.

A clinical hold can additionally be imposed by the FDA at any time during the conduct of a clinical trial under an IND.

In addition to the submission of an IND to the FDA before initiation of a clinical trial in the United States, certain human clinical trials involving recombinant or synthetic nucleic acid molecules are subject to oversight of an Institutional Biosafety Committee (IBC) as set forth in the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules (the NIH Guidelines).

Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.

The IBC assesses the safety of the research and identifies any potential risk to public health or the environment, and such review may result in some delay before initiation of a clinical trial.

The IBC assesses the safety of the

research and identifies any potential risk to public health or the environment, and such review may result in some delay before initiation of a clinical trial.

While the NIH Guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.

Furthermore, an IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed.

Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives.

Some studies also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a Data Safety Monitoring Committee, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Some trials also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a Data Safety Monitoring Committee, which provides authorization for whether or not a trial may move forward at designated checkpoints based on access to certain data from the trial and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.

For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

• Phase 1—The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.

These trials are designed to test the safety, dosage tolerance, absorption, metabolism and excretion of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.

• Phase 2—The investigational product is administered to a limited patient population with a specified disease or condition to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

• Phase 3—The investigational product is administered to an expanded patient population to further evaluate dosage, to provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval.

In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product in the intended therapeutic indication, particularly for long‑term safety follow-up.

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The FDA may also convene an advisory committee to provide clinical insight on application review questions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

The FDA is not bound by the recommendations of an advisory committee, but it may consider such recommendations carefully when making decisions.

Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

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For a product candidate that is also a human cellular or tissue product, the FDA also will not approve the application if the manufacturer is not in compliance with cGTPs.

These are FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues and cellular and tissue-based products (HCT/Ps), which are human cells or tissue intended for implantation, transplant, infusion or transfer into a human recipient.

These are FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues and cellular and tissue-based products (HCT/Ps),

which are human cells or tissue intended for implantation, transplant, infusion or transfer into a human recipient.

The primary intent of the GTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission and spread of communicable disease.

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An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

A CRL will describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections, testing submitted product lots and/or reviewing proposed labeling.

A CRL describes all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections, testing submitted product lots and/or reviewing proposed labeling.

In issuing the CRL, the FDA may recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional information or clarification.

The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed.

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Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace.

The FDA may require one or more Phase 4

post-marketing trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing studies.

The FDA may require one or more Phase 4 post-marketing trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing trials.

Expedited Development and Review Programs

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RMAT designation provides all the benefits of Breakthrough Therapy Designation, including more frequent meetings with the FDA to discuss the development plan for the product candidate and eligibility for rolling review and Priority Review.

meaningful number of clinical trial sites, including through expansion of trials to additional sites.

Product candidates granted RMAT designation may also be eligible for Accelerated Approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of clinical trial sites, including through expansion of trials to additional sites.

RMAT-designated products that receive Accelerated Approval may, as appropriate, fulfill their post-approval requirements through submission of clinical evidence, clinical trials, patient registries or other sources of real-world evidence (such as electronic health records);

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Fast Track, Breakthrough Therapy Designation, Priority Review, Accelerated Approval and RMAT designation do not change the standards for approval but may expedite the development or approval process.

Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product candidate no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Orphan Drug Designation and Exclusivity

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In addition, if a product that has ODD subsequently receives the first FDA approval for a particular drug or biologic for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.

Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

Orphan drug exclusivity does not prevent the

FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

Orphan product exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval of the same biological product as defined by the FDA or if our product candidate is determined to be contained within the competitor’s product for the same indication or disease.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received the ODD.

In addition, Orphan Drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Post-Approval Requirements

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The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market.

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with

regulatory requirements, may result in revisions to the approved labeling to add new safety information;

imposition of post‑market studies or clinical trials to assess new safety risks;

Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information;

imposition of post‑marketing studies or clinical trials to assess new safety risks;

or imposition of distribution restrictions or other restrictions under a REMS program.

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the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product;

• injunctions or the imposition of civil or criminal penalties.

or injunctions or the imposition of civil or criminal penalties.

The FDA closely regulates the marketing, labeling, advertising and promotion of biologics.

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The FDA does not regulate the behavior of physicians in their choice of treatments.

The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

The FDA does, however, restrict sponsors’ communications on the subject of off-label use of their products.

Biosimilars and Reference Product Exclusivity

The Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the ACA), includes a subtitle called the Biologics Price Competition and Innovation Act (BPCIA), which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.

The Biologics Price Competition and Innovation Act (BPCIA) created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.

The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency, can be shown through analytical studies, animal studies and a clinical trial or trials.

Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

relative to exclusive use of the reference biologic.

However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the FDA.

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In addition, the approval of a biosimilar product may not be made effective by the FDA until twelve (12) years from the date on which the reference product was first licensed.

data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product.

During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing that applicant’s own nonclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of its product.

The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products.

At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be readily substituted by pharmacies, which are governed by state pharmacy law.

A biological product can also obtain pediatric market exclusivity in the United States.

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Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation.

As a result, the ultimate impact, implementation and impact of the BPCIA is subject to significant uncertainty.

As a result, the ultimate impact and implementation of the BPCIA is subject to significant uncertainty.

Government Regulation Outside of the United States

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In all cases, clinical trials must be conducted in accordance with GCP, applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

Applications for marketing approval in the EU and other third countries must also follow detailed laws and procedures that vary from those in the US.

Moreover, in countries outside of the US, including the EU and countries in Eastern Europe, Latin America or Asia, the requirements governing product licensing, pricing and reimbursement vary from country to country.

Applications for marketing approval in the EU and other countries must also follow detailed laws and procedures that vary from those in the US.

Moreover, in countries outside of the U.S., including the EU and countries in Eastern Europe, Latin America or Asia, the requirements governing product licensing, pricing and reimbursement vary from country to country.

If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Other Healthcare Laws

Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business and may constrain the financial arrangements and relationships through which we research, sell, market and distribute any products for which we obtain marketing approval.

Such laws include, without limitation, federal and state anti-kickback, fraud and abuse, false claims, data privacy and security, price reporting and physician and other health care provider transparency laws and regulations.

If our operations are found to be in violation of any of such laws or any other governmental regulations that apply, we may be subject to penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of operations, integrity oversight and reporting obligations, exclusion from participation in federal and state healthcare programs and imprisonment.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs.

The term remuneration has been interpreted broadly to include anything of value.

The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other.

There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution.

The exceptions and safe harbors are drawn narrowly and practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor but the exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection.

Failure to meet all of the requirements of a particular applicable statutory exception or regulatory

safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute.

Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances.

Additionally, the intent standard under the Anti-Kickback Statute and the criminal healthcare fraud statutes under the federal Health Insurance Portability and Accountability Act of 1996 (as amended by the Health Information Technology for Economic and Clinical Health Act, HIPAA) was amended by the ACA to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

In addition, the ACA codified case law that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act (FCA) (discussed below).

The FCA prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to, or approval by, the federal government or knowingly making, using or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government.

As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the U.S.

Pharmaceutical and other healthcare companies have been prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-covered, uses.

HIPAA also created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

Additionally, the federal Physician Payments Sunshine Act within the ACA, and its implementing regulations, require that certain manufacturers of commercial drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) annually report information related to certain payments or other transfers of value made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physician assistants and nurse practitioners) and teaching hospitals and certain ownership and investment interests held by these physicians and their immediate family members.

Such laws include, without limitation, the U.S.

Foreign Corrupt Practices Act of 1977 (FCPA), federal and state anti-kickback, fraud and abuse, false claims, data privacy and security, price reporting and physician and other health care provider transparency laws and regulations

The FCPA prohibits any U.S.

individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.

The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring us to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs.

The federal False Claims Act (FCA) prohibits, among other things, any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to, or approval by, the federal government or knowingly making, using or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government.

The federal Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) (as amended, HIPAA), also created federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Additionally, the federal Physician Payments Sunshine Act, and its implementing regulations, require that certain manufacturers of commercial drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) annually report information related to certain payments or other transfers of value made or distributed to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other health care professionals (such as physician assistants and nurse practitioners) and teaching hospitals and certain ownership and investment interests held by these physicians and their immediate family members.

We may also be subject to data privacy and security regulations by both the federal government and the states in which we conduct our business.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and its implementing regulations, impose requirements on covered entities, including certain healthcare providers, health plans, healthcare clearinghouses and their respective business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity as well as their covered subcontractors relating to the privacy, security and transmission of individually identifiable health information.

Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to business associates, independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of pharmaceutical products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

HIPAA imposes requirements on covered entities, including certain healthcare providers, health plans, healthcare clearinghouses and their respective business associates that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity as well as their covered subcontractors relating to the privacy, security and transmission of individually identifiable health information.

We may also be subject to foreign and state law equivalents of each of the federal laws described above, such as anti-kickback and false claims laws which may apply to items or services reimbursed by state health insurance programs or any third-party payor, including commercial insurers.

Further, in order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of pharmaceutical products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

Several states have enacted legislation requiring pharmaceutical companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, track and report gifts, compensation and other remuneration made to physicians and other healthcare providers, clinical trials and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to

pharmaceutical companies for use in sales and marketing, and to prohibit certain other sales and marketing practices.

All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

If our operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, or refusal to allow us to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations

If our operations are found to be in violation of any of the healthcare laws described above or any other federal, state or foreign laws or governmental regulations that apply to us, we may be subject to significant penalties, including without limitation, civil, criminal and/or administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, injunctions, private “qui tam” actions brought by individual whistleblowers in the name of the government, integrity oversight and reporting obligations or refusal to allow us to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Coverage and Reimbursement

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Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.

Reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that a product is safe, effective and medically necessary;

Reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that a product is safe,

effective and medically necessary;

appropriate for the specific patient;

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Healthcare Reform

In the United States, in March 2010, the ACA was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers, and significantly affected the pharmaceutical industry.

In the United States, in March 2010, the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively, the ACA), was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers, and continues to impact the pharmaceutical industry.

There have been executive, judicial and Congressional challenges and amendments to certain aspects of the ACA.

Further, on August 16, 2022, the Inflation Reduction Act of 2022 (the IRA) was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost through a newly established manufacturer discount program.

On July 4, 2025, the One Big Beautiful Bill Act (the OBBBA) was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

It is possible that the ACA will be subject to additional challenges in the future.

It is unclear how any such additional challenges and healthcare reform measures of the second Trump administration will impact the ACA and our business.

Other legislative changes have also been proposed and adopted in the United States since the ACA was enacted.

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There has been heightened governmental scrutiny recently over the manner in which pharmaceutical companies set prices for their marketed products, which has resulted in several Congressional inquiries and proposed federal legislation, as well as state efforts, designed to, among other things, bring more transparency to product pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain high-expenditure, single-source biologics that have been on the market for at

least eleven years covered under Medicare (the Medicare Drug Price Negotiation Program) and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions began to take effect progressively in fiscal year 2023, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.

On August 15, 2024, HHS announced the agreed-upon prices of the first ten drugs that were subject to price negotiations which take effect in January 2026.

On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act of 1980 (Bayh-Dole Act) was announced.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights that for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies.

Recent actions include (1) directing agencies to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again (MAHA) Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability or commercialize our products (if approved).

In addition, it is possible that there will be further legislation or regulation that could harm our business, financial condition and results of operations, particularly in light of the recent U.S.

Presidential and Congressional elections.

In addition, it is possible that there will be further legislation or regulation that could harm our business, financial condition and results of operations.

Other Data Privacy and Security Laws

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We are, or may become, subject to numerous data privacy and security obligations, including federal, state, local and foreign laws, regulations, guidance and industry standards related to data privacy and security in the jurisdictions in which we are established or in which we sell or market any approved products or run clinical trials.

Such obligations may include those from, without limitation, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (CPRA) (collectively, CCPA), the EU’s General Data Protection Regulation 2016/679 (EU GDPR), the EU GDPR as it forms part of UK law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (UK GDPR) and the ePrivacy Directive.

Several states within the United States have also enacted or proposed data privacy and security laws.

For example, Virginia passed the Consumer Data Protection Act, and Colorado passed the Colorado Privacy Act.

Such laws may include those from, without limitation, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (CPRA) (collectively, CCPA), the EU’s General Data Protection Regulation 2016/679 (EU GDPR), the EU GDPR as it forms part of UK law by virtue of section 3 of the European Union (Withdrawal) Act 2018 (UK GDPR) and the ePrivacy Directive.

Several states within the United States have also enacted or proposed comprehensive data privacy and security laws.

Additionally, we are, or may become, subject to various U.S.

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The CCPA, CPRA and EU GDPR are examples of the increasingly stringent and evolving regulatory frameworks related to personal data processing that may increase our compliance obligations and exposure for any noncompliance.

For example, the CCPA imposes obligations on covered businesses to provide specific disclosures related to a business’ collecting, using and disclosing personal data and to respond to certain requests from California residents related to their personal data (for example, requests to know of the business’ personal data processing activities, to delete the individual’s personal data and to opt out of certain personal data disclosures).

For example, the CCPA imposes obligations on covered businesses to provide specific disclosures related to a business’ collecting, using and disclosing personal data and to honor certain requests from California residents related to their personal data.

Also, the CCPA provides for civil penalties and a private right of action for data breaches that may include an award of statutory damages.

In addition, the CPRA expanded the CCPA by giving California residents the ability to limit use of certain sensitive personal data, establishing restrictions on personal data retention, expanding the types of data breaches that are subject to the CCPA’s private right of action and establishing a new California Privacy Protection Agency to implement and enforce the new law.

Foreign data privacy and security laws (including but not limited to the EU GDPR and UK GDPR) impose significant and complex compliance obligations on entities that are subject to those laws.

As one example, the EU GDPR applies to any company established in the European Economic Area, which is comprised of the 27 Member States of the EU plus Norway, Iceland and Liechtenstein (collectively, the EEA) and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA.

These obligations include limiting personal data processing to only what is necessary for specified, explicit and legitimate purposes;

requiring a legal basis for personal data processing;

requiring the appointment of a data protection officer in certain circumstances;

increasing transparency obligations to data subjects;

requiring data protection impact assessments in certain circumstances;

limiting the collection and retention of personal data;

increasing rights for data subjects;

formalizing a heightened and codified standard of data subject consents;

the implementation and maintenance of technical and organizational safeguards for personal data;

mandating notice of certain personal data breaches to the relevant supervisory authorities and affected individuals;

and mandating the appointment of representatives in the UK and/or the EU in certain circumstances.

See the section titled “Risks Related to Regulation and Legal Compliance” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.

Foreign Corrupt Practices Act

Foreign Corrupt Practices Act of 1977 (FCPA), prohibits any U.S.

As one example, the EU GDPR applies to any company established in the European Economic Area (EEA) and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA.

Under the GDPR, companies may face temporary or definitive bans on data processing and other corrective actions;

fines of up to 20 million Euros under the EU GDPR;

17.5 million pounds sterling under the UK GDPR or, in each case, 4% of the annual global revenue, whichever is greater;

or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.

See the section titled “Risks Related to Our Business and Industry” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.

Employees and Human Capital Management

We are a clinical cell therapy company entering pivotal trials and advancing a pipeline of proprietary next‑generation CAR T-cell product candidates for patients with cancer.

We are pioneering novel approaches designed to generate T cells that drive long-lasting clinical response.

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.

We strive to create an environment where everyone can do their best work, be themselves, and thrive personally and professionally.

Our culture is grounded by innovative science and a focus on patients with cancer who need better therapies.

Their need drives our sense of urgency to achieve our important mission.

We believe success comes when we align our core values with our mission to translate our ground-breaking science into therapies with the potential to transform patients’ lives.

Our culture is grounded by innovative science and a passion to identify and deliver better therapies for patients.

The needs of patients drive our sense of urgency to achieve our important mission.

We believe success comes when we align our core values with our mission;

this gives us focus and direction in how we do our work.

Our core values are:

We value evidence over opinion and focus and execute on the critical efforts that matter most.

We value evidence over opinion and we focus and execute on the critical efforts that matter most.

We challenge the status quo – we are bold and willing to think and act differently.

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We work together to create value, working across teams to solve our most challenging problems to continually improve and learn.

In 2024, with active participation from our employees, we created behavior expectations to describe how Lyellites demonstrate our values at work.

Leaders and employees attended workshops where we defined behavior statements that have been embedded in our performance management and development programs.

These behaviors exemplify our values as well as principles of patient-centricity, innovation and inclusion.

Our values are further defined as specific ways of working that are embedded in our performance management processes.

Our ways of working, or the Lyell Behaviors, exemplify our values as well as principles of patient-centricity, innovation and inclusion.

High performers at Lyell not only achieve their goals, but consistently and effectively demonstrate the Lyell Behaviors.

Our Employees

Our people drive our mission.

We compete in the highly competitive biotechnology industry, and attracting, retaining and developing a diverse group of talented employees is crucial to our strategy and we believe is a competitive advantage.

Our organization is designed to support research, product development and manufacturing efforts and is ready to scale to meet future plans for commercializing our product candidates, if approved.

A strategic priority is attracting and retaining talent with the skills we need now and in the future.

The labor market continues to reflect a limited pool of skilled individuals with substantial experience discovering, developing and manufacturing cell therapy medicines, and we expect this is likely to continue.

We also operate in areas such as data capture and analytics.

As a result, competition for talent is intense and the turnover rate can be high.

We face substantial competition among numerous biopharmaceutical companies and academic institutions as well as technology companies for individuals with these skills.

For these reasons, we continue to develop our culture through people systems that establish clear expectations, ensure employees have ongoing feedback and provide opportunities for skill and career development as well as competitive pay and benefits.

We compete in the highly competitive biotechnology industry;

attracting, retaining and developing a diverse group of talented employees is crucial to our strategy and we believe is a competitive advantage.

What sets Lyell apart from our peers is the breadth of work we do;

from discovery research to drug development and manufacturing, we are a high-performing team across our many functions.

Lyell provides the opportunity to see first-hand how cell therapy is brought to life and gives employees opportunities to engage and make meaningful contributions.

The labor market continues to reflect a limited pool of skilled individuals with substantial experience discovering, developing and manufacturing cell therapy medicines.

As we plan for commercialization, this level of competition will continue to be a challenge, and we will continue to compete for talent against businesses that are much larger and more heavily resourced.

Considering these challenges, our culture is central to our strategy to retain and engage our employees made real by the work of employees and leaders.

Grounded in our values and behaviors, we foster a collaborative community across our three locations.

Employee-led initiatives, anchored by employees from various levels at each of our sites and sponsored by our Executive Leaders, celebrate individuals and diverse perspectives through monthly activities and recognition events.

We rally as one team to support local organizations in the San Francisco Bay Area and Seattle Region as part of April Volunteer Month, as well as with our support to Blood Cancer United’s Light the Night event in San Francisco and Seattle.

Leaders at Lyell recognize the important role they play in attracting, retaining and engaging our people.

To that end, leaders are guided by our Talent Philosophy.

Five components make up our Talent Philosophy:

• Performance is a constant focus of our organization;

we set stretch goals and strive for exceptional outcomes that bring our innovative treatments to patients and differentiate to recognize high performance

• Behaviors translate our values into action.

We demonstrate these behaviors as they lead to high performance and foster a workplace where each of us can do our best work

• Development is a mindset that means all employees can build their skills and increase their capabilities;

leaders guide development of their team members

• Transparency is ensured by our leaders so that individuals understand what is expected of them and know where they stand throughout the year

• Accountability is key to ensuring Lyellites are proud of their work and take ownership;

leaders are accountable to their people and have a priority to develop and grow their team members

Our Talent Philosophy is a blueprint for leadership.

Leaders take seriously the role they play in creating a place where employees feel valued and engaged.

Our people management processes place emphasis on establishing clear expectations, providing routine, ongoing feedback and creating opportunities to learn and develop in the current role, as well as in preparation for progression within the company.

As of December 31, 2025, we had 161 employees, over 80% of whom were engaged in research and development activities, technical operations and process sciences.

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Many of our employees have experience with the development of cell therapies.

The majority of our employees are located in California and Washington, with all employees based in the United States.

Most of our employees are located in California and Washington, with all employees based in the United States.

None of our employees are subject to a collective bargaining agreement nor represented by labor unions.

We consider our relationship with our employees to be good.

Developing our employees is important, and we focus on providing learning opportunities for development and advancement.

We value our relationship with our employees and evaluate this as good given our Great Place to Work certification in 2024 where 81% of employees participated.

To track our progress, we conducted a 2025 pulse survey using Great Place to Work questions.

Seventy-one percent of our staff participated, and 86% responded that Lyell is a great place to work.

Developing our employees is a central component of our Talent Philosophy.

All employees have the opportunity for development and advancement.

Starting with annual expectations, each employee has a development goal;

this is one area of growth that will help the individual perform more effectively in their current role.

Training, coaching, routine feedback, and a systematic approach to employee advancement are key components of our talent strategy.

We hold talent discussions regularly, which include leaders identifying talent for promotion across all functions.

Foundations of our talent management practice include career frameworks for progression and development, individual goal setting for all staff including one development goal to continue to improving skills and abilities in the current role and a compensation approach that recognizes differentiated performance and shares performance feedback regularly.

In 2024, we participated in the Great Place to Work survey for the first time and, based on employee responses to the survey, we received certification as a Great Place to Work.

With 81% of employees participating in the survey, we received high ratings in multiple areas, with engagement, culture, inclusion and innovation being specific areas of strength.

Employee feedback, through independent and anonymous surveys, provide us with the data on an ongoing basis that we need to ensure that our leadership, culture and people practices are supporting the talented workforce that we need to advance our mission.

Since inception, our employee turnover has remained consistently below average for the U.S.

We hold talent discussions regularly, which include leaders discussing development aspirations of staff and aligning with talent plans in the Spring, identifying talent for promotion through our twice-yearly promotional review process and culminating in year-

end performance calibration to ensure we pay for performance.

Our talent is managed on a foundation of clear expectations, ongoing feedback and development.

Since inception, voluntary employee turnover at Lyell has remained consistently below average compared to the U.S.

life sciences industry generally, as well as for life sciences companies located in Northern California and the Pacific Northwest.

Given our need to retain and attract talent, we continually assess employee turnover, effectiveness of recruitment initiatives, compensation and benefits programs, health and safety practices, diversity and inclusion and other matters relevant to human capital management.

These outcomes and updates are routinely reviewed with our board of directors.

To retain and attract talent, we continually assess employee turnover, effectiveness of recruitment initiatives, compensation and benefits programs, health and safety practices, inclusion and other matters relevant to human capital management.

These outcomes and updates are routinely reviewed with our executive leaders and board of directors.

Our Compensation and Benefits

Given the highly competitive nature of our industry and the importance of recruitment and retention to our success, we strive to provide our employees with what we believe is a competitive and comprehensive total rewards package of compensation, benefits and services.

This package includes competitive market pay, healthcare benefits for employees and family members, a flexible spending account or health savings account, paid time off benefits, family leave, flexible work schedules, flexible work locations, 401(k) matching, an employee assistance program and a wellness program.

This package includes competitive market pay, healthcare benefits for employees and family members, flexible spending accounts, health savings accounts, paid time off benefits, family leave, flexible work schedules, flexible work locations, 401(k) matching, an employee assistance program and a wellness program.

In addition, we offer employees the benefit of equity ownership in the company through stock option grants and/or restricted stock units.

Our employees are also eligible to participate in an employee stock purchase plan, which offers the opportunity to purchase our common stock at a discount of 15%.

Our Commitment to Diversity, Belonging, Inclusion and Equity

We strongly believe in a diverse workplace where all employees can thrive in an inclusive environment free from discrimination, harassment, bias and prejudice.

We aim to treat all individuals with respect and dignity and to provide all employees with equal opportunity and fair treatment.

By embracing diversity and inclusion, we seek to create an organization committed to collaboration and innovation consistent with our values and in support of accomplishing our mission.

Our Commitment to Inclusion

We strongly believe in a workplace where all employees can thrive.

This means an environment free from discrimination, harassment, bias and prejudice.

We intend to treat all individuals with respect and dignity and to provide each employee with equal opportunity and fair treatment.

By embracing inclusion, we offer an organization committed to collaboration and innovation consistent with our values and in support of accomplishing our mission.

Not only is a diverse, equitable and inclusive mindset and culture critical to an engaged and committed workplace, but it is also imperative to understanding and meeting the needs of the patients we seek to help with our medicines.

In 2020, with the support and sponsorship of our executive leadership team, we established a Diversity, Belonging, Inclusion and Equity (DBIE) working group comprised of a diverse group of employees tasked with designing and implementing specific initiatives to promote greater diversity, belonging, inclusion and equity at Lyell.

We continue to externally benchmark our efforts with respect to best practices across industries.

The DBIE working group is guided by a collaboratively developed DBIE mission statement.

The working group is comprised of volunteers across each of our work locations representing various levels in the organization.

This team, sponsored by our Chief Executive Officer and Senior Vice President of Human Resources, creates an annual strategic and tactical plan to advance our focus on the importance of DBIE to our culture.

Our DBIE team has continued to develop and implement an annual plan that includes many opportunities for learning and engagement open to all employees.

In addition to the DBIE employee working group, our Human Resources practices emphasize diversity and inclusion as key indicators of success.

Recruitment, progression and development processes emphasize the importance of fostering a workforce that is representative of our diverse patient population.

Employee feedback from our Great Place to Work survey rated the organization very high on four key questions on inclusion:

(1) People here are treated fairly regardless of their sexual orientation;

(2) People here are treated fairly regardless of their race;

(3) People here are treated fairly regardless of their gender;

and (4) People here are treated fairly

regardless of their age.

We continue to evolve our workplace practices to ensure that our culture embeds fair treatment for all and is seen as a place where individuals can be their authentic selves at work.

We have plans to continue to build on our early years and continue to mature our DEI strategy and practices in the years ahead working from this strong foundation.

We believe in equitable pay and our compensation practices are reviewed regularly.

We establish components and ranges of compensation based on market and benchmark data.

Within this context, we strive to pay all employees equitably within a market-competitive range, taking into consideration factors such as role, market data for similar roles in related industry, internal equity, job location, relevant experience and individual performance.

Our compensation practices are reviewed regularly for fairness and consistency.

Ranges of compensation and other components of total compensation are based on benchmark data refreshed annually using externally validated information from peer companies.

Within this context, our practices drive pay decisions that position employees equitably within a market-competitive range, taking into consideration factors such as role, market data for similar roles in related industry, internal equity, job location, relevant experience and individual performance.

Ongoing pay progression is guided by our compensation philosophy;

we recognize differentiation in rewards, where our highest performing employees receive the highest rewards.

At the same time, we are committed to pay equity;

we have a review process that is conducted on at least an annual basis.

At the same time, we monitor for pay equity;

we have a review process that is formally conducted annually, as well as ad-hoc as requested for review.

If we identify employees with unjustified pay gaps that do not align with our pay philosophy, we review and take appropriate action to ensure fidelity between our stated philosophy and actions.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business