Welcome to today's call that highlights Lyell's new ronde-cel clinical and translational data presented at ASH 2025. For those of you who are joining us via Zoom, if you would like to ask a question, please raise your hand by clicking the raise hand at the bottom of your Zoom window. You can raise your hand at any point during the call to enter the queue, and you will be called upon during the Q&A session. Once called upon, please unmute your audio to ask your question. I will now pass the call over to your host, Ellen Rose, to begin today's presentation. Thank you, Operator. Good morning, everyone, and welcome. Today we are pleased to highlight new clinical and translational data for ronde- cel in patients with large B-cell lymphoma that were highlighted in two oral presentations at the 67th American Society of Hematology, or ASH, annual meeting and exposition yesterday. Please review the press release issued yesterday and Form 8-K filed earlier today, along with the slides being presented on this call that can be found on the investor pages of our website at lyell.com. Speakers on today's call include Dr. Lynn Seely, our President and Chief Executive Officer; Dr. Sarah Larson, an investigator in the ronde- cel clinical trials and presenting author of the clinical abstract at ASH; and Dr. Gary Lee, our Chief Scientific Officer. Dr. David Shook, our Chief Medical Officer, will also join the call for Q&A. Before we begin, I'd like to remind you that during today's presentation, we will be making forward-looking statements that are subject to certain risks, uncertainties, and other factors that could cause actual results to differ materially from those referred to in any forward-looking statements. For a discussion of the risks and uncertainties associated with our forward-looking statements, please see our press release issued yesterday, as well as our most recent filings with the SEC. We disclaim any obligations to update our forward-looking statements. And with that, I'd like to turn the call over to Lynn. Thank you, Ellen, and welcome everyone to today's conference call. Lyell's purpose is to give patients with cancer the gift of time by delivering on the promise of cell therapy. Lyell is focused on advancing next-generation autologous CAR T-cell therapies for patients with cancer, including both hematologic malignancies and solid tumors. We believe harnessing the patient's own immune system to deliver a one-time treatment with long-lasting benefit is the best way to bring patients with cancer what they are looking for: a return to their prior lives without ongoing treatment. Our vision is a world where more people with cancer can receive a one-time treatment with a cell therapy that delivers durable remissions and even cures. Today, we are delighted to highlight new clinical and translational data for ronde- cel, our next-generation CD19/CD20 CAR T-cell candidate with the potential to be the new standard of care for the treatment of relapsed or refractory large B-cell lymphoma. We also briefly will tell you about our newest next-generation CAR T-cell therapy candidate and clinical development for patients with metastatic colorectal cancer. We believe we are well on our way to creating an industry-leading pipeline of next-generation CAR T-cell therapies in oncology. Our strategy is to identify promising targets, those expressed at high levels in the majority of patients with a particular cancer type to enhance benefit, and those that are expressed at low levels or are inaccessible in normal tissues to minimize side effects. We then arm our CAR T-cells with specific product enhancements designed to improve the T-cell's ability to fight cancer. Our enhancements are designed to endow the cells with a greater ability to expand, maintain qualities of stemness, prevent exhaustion, and infiltrate tumors, all with the ultimate goal of increasing cancer cell killing. We are on a mission to develop next-generation CAR T-cell therapies armed with innovative enhancements to deliver lasting remission or even cures for patients with cancer. Today, we are going to focus on new clinical and translational data from our ongoing clinical trial presented in two oral presentations yesterday at the American Society of Hematology Conference in Orlando. Ronacabtagene autoleucel, or ronde-cel, is a dual-targeting CD19/CD20 CAR T-cell candidate with potential to be the new standard of care for relapsed or refractory large B-cell lymphoma based on the high rates of durable complete responses achieved with a safety profile appropriate for outpatient administration. Ronde-cel CAR T-cells are manufactured with CD62L enrichment, and we presented data for the first time demonstrating sustained cytotoxicity from CAR T-cells collected from patients two months after infusion and following robust CAR T-cell expansion. We will also be discussing our two registration trials for ronde-cel. The first pivotal trial, PiNACLE, is underway, and the second, PiNACLE Head-to-Head, will begin enrollment by early 2026. In addition to ronde -cell, I want to remind you that we recently broadened our pipeline with a very novel clinical stage CAR T-cell program in development for patients with metastatic colorectal cancer. LYL 273 is a CAR T-cell candidate that targets guanylyl cyclase C, or GCC, and that is also enhanced with CAR T-cells expressing CD19 CARs, elegantly engineered to deliver controlled cytokine release upon activation. In a Phase 1 clinical trial, LYL273 had high response rates in refractory patients with a manageable safety profile. Specifically, data from a Phase 1 clinical trial conducted in the United States at leading cell therapy centers evaluating our new product candidate, LYL273, showed a 67% overall response rate and an 83% disease control rate at the highest dose of LYL273 evaluated to date in patients with refractory metastatic colorectal cancer in the third or later line setting. This clinical benefit was observed with a manageable safety profile. We are continuing to enroll patients in this Phase 1 trial and look forward to providing updates in 2026. To Lyell's advantage, we own and operate our Lyell Manufacturing Center in Bothell, Washington, a scalable manufacturing facility. We are manufacturing all products for our clinical trials for ronde-cel, and Lyell is capable of commercial launch with the capacity to produce more than 1,200 CAR T-cell doses per year at full capacity. Finally, our cash runway into 2027 is expected to get us through multiple clinical milestones, which we will describe in detail on the next slide. As you have just heard, we are advancing a robust pipeline of next-generation CAR T-cell product candidates. We are developing ronde-cel manufactured to be enriched for more naive and stem-like CD62L- positive cells. Currently, the PiNACLE pivotal trial is ongoing in the third or later line setting, and we intend to provide an additional data update in the second half of 2026. In mid-2027, we expect to have in hand the final data needed for our BLA submission planned for the end of 2027. Several sites are activated for our second pivotal trial designed for approval in the second-line setting. PiNACLE Head-to-Head is a Phase 3 CAR T-cell therapy randomized control trial of ronde-cel versus investigators' choice of axicabtagene ciloleucel, referred to as, or lisocabtagene maraleucel, referred to as liso-cel, for patients with large B-cell lymphoma. We expect to begin enrolling patients by early 2026. The Phase 1 trial of LYL273 continues to enroll patients with metastatic colorectal cancer, and we expect to share updated clinical data twice in 2026 with initiation of the pivotal program for this CAR T-cell candidate in early 2027. On this slide is a summary of the new clinical data from our ongoing ronde-cel clinical trial presented at ASH that Dr. Larson will review for you in detail. Patients who received ronde-cel in the third or later line setting achieved a 93% overall response rate and a 76% complete response rate. The median progression-free survival was 18 months. Patients who received ronde-cel in the second line setting, nearly all of whom were difficult to treat primary refractory patients, achieved an 83% overall response rate and a 61% complete response rate. 70% of patients who achieved a complete response remained in complete response for six months or longer. These data were achieved with a safety profile appropriate for outpatient administration. There were no events of Grade 3 or higher CRS, and following implementation of dexamethasone prophylaxis, the rate of Grade 3 or higher ICANS was less than 5%. So how do we think about these data in the context of the treatment landscape? And why, you may ask, do patients need another CAR T-cell therapy for large B-cell lymphoma? Data from the third-line pivotal trials evaluating the three approved CD19 CAR T-cell products in patients with relapsed or refractory large B-cell lymphoma are shown in the upper panel. Let's focus on the market leaders, Yescarta, or axi-cel, and Breyanzi, or liso-cel. If you look at the overall response rates for these CD19 CAR T-cell products in the third or later line setting, they are 72% and 73%, respectively, with complete response rates of 51% and 54%. More importantly, the median progression-free survival in those trials was only six to seven months. Also note the safety profiles. Yescarta had a 31% rate of Grade 3 or greater neurotoxicity. The data to date for ronde-cel are reported in the purple panel at the bottom. While these data were not generated in head-to-head studies against the other products, ronde-cel demonstrated overall and complete response rates of 93% and 76%, plus a remarkable median progression-free survival of 18 months in the third or later line setting. The safety data presented for ronde-cel represent all data for patients in the second or later line settings. Only 4% of patients who received dexamethasone prophylaxis had Grade 3 or higher ICANS. In all patients with or without prophylaxis, the rate of Grade 3 or higher ICANS was 12%. All patients will receive dexamethasone prophylaxis moving forward. This slide tells the story of why we believe it is very possible for a next-generation CD19/CD20 CAR T-cell product to disrupt the CD19 CAR market. As you can see from the bar chart on the left, it is an established and growing multi-billion-dollar opportunity. The worldwide sales are just below $3 billion and are projected to grow to over $5 billion in the coming years. But importantly, physicians who treat patients with CAR T-cell therapies have historically demonstrated a willingness to switch CAR T-cell products based upon the strength of clinical data in both the lymphoma and multiple myeloma markets. In the middle graph, you see the initial market leader, Yescarta, in green, losing market share over time to Breyanzi in purple, potentially due to its better safety profile over that of Yescarta. Similarly, Abecma rapidly lost market share to Carvykti in multiple myeloma, likely due to its better efficacy profile. These market data are why we believe that with the differentiated clinical data in hand to date, ronde-cel will be well positioned to replace the currently approved CD19 CAR T-cell therapies. If approved with substantially enhanced clinical outcomes and a safety profile amenable to outpatient administration, the ronde-cel data are predicted to drive switching as well as market growth. I am now pleased to turn the call over to Dr. Sarah Larson, Associate Clinical Professor of Medicine, Division of Hematology Oncology at the David Geffen School of Medicine at the University of California, Los Angeles. As one of the initial investigators at the institution where ronde-cel was invented and first studied, Dr. Larson has extensive clinical experience with ronde-cel. Thank you, Lynn. On behalf of my co-authors, I'm pleased to be here today to highlight the data we presented yesterday at ASH from the ongoing Phase 1/2 clinical trial evaluating Ronacabtagene autoleucel, or ronde-cel, in patients with aggressive B-cell lymphoma. CD19 CAR T-cell therapy has substantially improved outcomes for patients with relapsed or refractory large B-cell lymphoma, yet important limitations remain. Only 40% of patients treated in the third line or later remain in complete response at six months, resulting in a median progression-free survival of less than seven months. Additionally, the pivotal trials that led to the approval of axi-cel and liso-cel excluded key populations, making comparison to contemporary trials difficult. For example, ZUMA-1 and ZUMA-7, which supported axi-cel's approval in the third and second line, respectively, allowed limited or no bridging, leading to exclusion of many patients with rapidly progressive disease. These trials also enrolled few patients over the age of 75. Similarly, the TRANSFORM trial, which supported liso-cel's approval in the second line, excluded these older patients. Outcomes in high-risk subgroups are poor. For example, in the PILOT trial, which did evaluate older patients, the complete response rate with liso-cel was only 42% among patients with primary refractory disease in the second line. Furthermore, duration of response among patients with primary refractory disease treated in this population is limited, with a median progression-free survival of approximately seven months. Finally, toxicity continues to limit outpatient treatment, particularly Grade 3 or higher CRS and ICANS. It is clear next-generation CAR T-cell products with improved safety and efficacy are needed. ronde-cel is an autologous dual-targeting CD19/CD20 CAR T-cell product candidate based on a construct initially developed and tested at UCLA. It is an OR logic-gated CAR with full potency at either B-cell antigen CD19 or CD20, making ronde-cel less susceptible to tumor evasion via antigen loss. Additionally, ronde-cel is manufactured with a process that enriches for stem-like CAR T-cells. Naive T-cells are associated with improved outcomes following CAR T-cell therapy. Ronacabtagene autoleucel is manufactured using CD62L selection to enrich for these naive and central memory T-cells. CD62L- positive cells are associated with improved persistence, reduced exhaustion, and lower adverse cytokine production. The data presented here come from an ongoing Phase 1/2 multicohort multicenter trial, which evaluated ronde- cel in patients with large B-cell lymphoma. This presentation focuses on the cohorts evaluating patients with large B-cell lymphoma who had two or more prior lines of therapy or had one prior line of therapy and were primary refractory or had relapsed less than 12 months from first line therapy. No patient had prior CAR T-cell therapy, and there was no upper age limit. Patients were enrolled without CD19 expression testing and received a standard fludarabine and cyclophosphamide lymphodepletion regimen following optional bridging therapy. ronde-cel was given as a flat dose administration of 100 million CAR positive cells, which may be given as an outpatient. Manufacturing was efficient and reliable with a 16-day turnaround time. Imaging response assessments were done locally at the sites. As of September 5th, 2025, the trial had enrolled and treated 69 patients, with 45 patients in the third or later line cohort and 24 patients in the second line cohort. The median age was 64 in the third line and 65 in the second line cohort. Both cohorts treated patients older than 85, and at least 20% of patients in both cohorts were 75 or older. This was a high-risk, heavily pretreated cohort, as investigators selected this trial for patients who may not have been ideal candidates for commercially available CD19 CAR T-cell therapy. For example, almost half of the patients in the third line cohort and over 90% of the patients in the second line cohort had primary refractory disease. Additionally, greater than 40% of patients had an elevated LDH in both cohorts, and more than half received bridging therapy after leukapheresis. Patients who received bridging therapy were confirmed to have measurable disease prior to start of lymphodepletion with a new baseline scan, and 20% of patients still had bulky disease. As previously discussed, the enrolled patient population significantly influences interpretation of trial results. In this trial, investigators selected patients over approved CD19 CAR T-cell therapy, resulting in a very high-risk population. In the third line setting, eight patients with morphologic high-grade B-cell lymphoma were evaluated separately from morphologic large B-cell lymphoma, which included those patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, follicular lymphoma 3B, and primary mediastinal B-cell lymphoma. Those with high-grade B-cell lymphoma were older and had worse clinical status, with most having ECOG performance scores of one. In addition, those with high-grade B-cell lymphoma, 88% had elevated LDH, and half had bulky disease. Patients with large B-cell lymphoma in the ongoing clinical trial who were treated with ronde- cel in the third or later line cohort had an overall response rate of 93% and a complete response rate of 76%. Median progression-free survival among those with large B-cell lymphoma was 18 months after a median duration of follow-up of 12 months. 72% of patients who achieved a complete response remained in complete response at six months or later. Those with high-grade B-cell lymphoma had similar overall response rates, yet only one of three responders remained in complete response at six months or later. PiNACLE is a single-arm pivotal trial evaluating ronde-cel for the treatment of large B-cell lymphoma in the third or later line and is a seamless expansion of this third line cohort. The PiNACLE trial will only include those patients with large B-cell lymphoma histology in order to ensure enrollment of those patients most likely to benefit from the single-arm trial. Individual patient trajectories in the 29 patients with large B-cell lymphoma are shown in this swimmer plot, demonstrating the high response rate and favorable duration of response. As you can see, several patients remained in complete response well past 12, 15, and even 18 months. Those who improved from partial response in blue to complete response in green did so without any additional therapy or cell infusions, and this improvement was often associated with a long-term response. Patients with the purple triangle on the y- axis had primary refractory disease, a group known to have poor response to therapy. The median progression-free survival was 18 months. The second line efficacy evaluable population was 18 patients, consisting of those with a day 84 or later response assessment or who had prior disease progression or death from any cause. This population was also heavily enriched with high-risk patients, with nearly all patients having primary refractory disease, again denoted by the purple triangles on the y-axis. In this context, the overall response rate in this cohort was 83%, and the complete response rate was especially encouraging at 61%. 70% of patients with complete response remained in complete response for six months or later. Median duration of complete response was not yet reached after a median follow-up of nine months. Of note, one patient with high-grade B-cell lymphoma who progressed after nine months of complete response was successfully retreated with previously manufactured product and re-entered response. The safety data of 69 patients reflects the positive impact of dexamethasone prophylaxis, with a reduction in Grade 3 or higher ICANS to less than 5%. Beginning in early 2025, patients in this trial received 10 milligrams of dexamethasone once daily on days zero, one, and two in order to limit high-grade toxicities. Notably, no cases of Grade 3 or higher CRS were reported regardless of dexamethasone prophylaxis. 52% of patients with prophylaxis developed low-grade CRS, with most cases being Grade 1. Grade 1 or 2 ICANS was reported in eight patients, including only two cases after prophylaxis. Grade 3 or higher ICANS was reported in eight patients, with only a single case among the 25 patients who received dexamethasone prophylaxis. This case was a patient with high-grade B-cell lymphoma with high tumor burden and high LDH. Median time to resolution for ICANS was four days. 12% of patients had grade three or higher infections and all recovered. Importantly, steroids did not negatively impact the infection rate, and only one grade three or higher infection occurred among all patients who received prophylaxis. Percentages of prolonged cytopenias were similarly low across both groups. No deaths related to ronde-cel were reported. Overall, ronde-cel had a manageable safety profile and notably had no inpatient requirement. Outpatient utilization is left to site and investigator discretion. Given the critical role of CAR T-cell expansion in anti-tumor activity, the impact of dexamethasone prophylaxis on the pharmacokinetics of ronde-cel was evaluated by comparing the cell expansion data from patients who received dexamethasone to those who did not. As you can see, the cell expansion curves reveal no significant impact to Cmax or to area under the curve, or AUC, in those patients who received dexamethasone. In conclusion, in this multicenter trial of ronde-cel, high response rates were observed in high-risk, heavily pretreated patients with large B-cell lymphoma. The overall response rate was 93%, and the complete response rate was 76% in the third or later line setting. These responses were durable, with a median progression-free survival of 18 months, comparing favorably to CD19 CAR T-cell therapy. In the second line setting, almost all patients had primary refractory disease. The overall response rate was 83%, and the complete response rate was 61%. Importantly, 70% of patients with a complete response remained in complete response at the six-month or later assessment. Overall, the safety profile appeared manageable in a patient population that includes a significant number of patients older than age 75 and is appropriate for outpatient use. There have been no cases of Grade 3 or higher CRS, and dexamethasone prophylaxis reduced Grade 3 or higher ICANS to less than 5% without any impact on CAR T-cell expansion. Finally, we observed robust CAR T-cell expansion and persistence in this uniquely manufactured CD62L-enriched drug product candidate. In a separate oral presentation, it was demonstrated for the first time sustained cytotoxicity of CAR T-cells obtained from patients two months after infusion. Based on the strength of these data, ronde-cel is currently being evaluated in two pivotal trials. The PiNACLE Head-to-Head CAR T-cell trial is a Phase 3 randomized controlled trial of ronde-cel versus investigators' choice of axi-cel or liso-cel. This trial will enroll patients with early or late relapsing disease, as well as those with disease that is refractory, including those with high-grade B-cell lymphoma. The primary endpoint is event-free survival. PiNACLE, a seamless expansion of the third or later line cohort of this Phase 1 trial, continues to enroll. Like PiNACLE- H2H, there is no upper age limit and will enroll patients with relapsed or refractory disease. Patients with high-grade B-cell lymphoma will not be included in PiNACLE. The primary endpoint of this single-arm trial is overall response rate. These two pivotal trials, including the first of its kind head-to-head CAR T-cell trial, are expected to provide a comprehensive and robust evaluation of the potential role for ronde-cel to demonstrate differentiated benefit over approved CD19 CAR T-cell therapies. Now, I'd like to turn the presentation back to the Lyell team and Dr. Gary Lee, who will highlight some of the translational data presented in a separate oral abstract at ASH. Thank you, Sarah. We would like to now briefly summarize the translational data from our second oral presentation at ASH. This slide lists the four key translational findings. First, we observed that CD62L selection leads to drug products with high expression of memory-related genes when benchmarked against data published for axi-cel and tisa-cel. Second, we found ronde-cel had up to three-fold higher grade expansion after infusion in patients compared to that of approved CD19 CAR T-cell products. Interestingly, we also observed that the level of ronde-cel expansion was positively correlated with high expression of memory-related genes. Third, we looked at ronde-cel CAR T-cells collected from patients after infusion. We found that CAR-positive cells also had greater expression of memory-related genes at the one-month time point following infusion compared to similar data for axi-cel. Finally, we successfully developed an assay to functionally evaluate ronde-cel CAR T-cells and were able to show sustained proliferation, cytotoxicity, and cytokine secretion two months after infusion. I'm going to highlight for you some of these data that were presented in detail yesterday at ASH. Shown on the left side of this slide is an illustration of how CD62L enrichment was incorporated during ronde-cel manufacturing. We used a standard commercially available instrument for CD62L enrichment. It is a simple process that does not increase overall manufacturing time compared to other similar products that enrich for all T-cells. Flow cytometric analysis on 84 ronde-cel products showed a median 96% of cells in the final drug products were CD62L- positive. These data confirmed that CD62L enrichment during manufacturing had the intended outcome, and ronde-cel products are comprised primarily of CD62L- positive cells. At the conference, we presented data showing CD62L enrichment enables ronde-cel products to have T-cells with greater relative expression of memory-related genes and a lesser relative expression of the short-lived effector phenotype-related genes than did axi-cel or tisa-cel products. Higher CAR T-cell expansion has been associated with improved treatment outcome. Shown here on the left is the expansion of ronde-cel in peripheral blood after infusion in patients enrolled in the Phase 1/2 clinical trial. Expansion was measured using droplet digital PCR assay and represented as copies per microgram of DNA. The solid line represents the median across 67 patients at various time points after infusion, and the arrow bars indicate the interquartile ranges. Peak expansion was seen at about two weeks after infusion and was sustained at high levels through one month after infusion. Shown here on the right are the key expansion metrics of ronde-cel in comparison with tisa-cel and liso-cel. Note that axi-cel was not included since axi-cel expansion was assessed using a different method and cannot be compared directly to these other CAR T-cells. Both Cmax, which indicates peak expansion, and AUC, which indicates overall exposure following infusion to day 28, were up to threefold or higher for ronde-cel compared to tisa-cel and liso-cel. We also showed data at the conference that suggests higher ronde-cel expansion after infusion is positively correlated with stronger memory gene phenotype in the products. Post-infusion functional analyses have not been reported in CD19 CAR T-cell clinical trials to our knowledge, but they provide key insights into sustained functional capacity of CAR T-cells. We evaluated proliferative capacity, cytotoxicity, and cytokine secretion of CAR-positive cells two months after ronde-cel infusion following co-culture of peripheral blood cells with a tumor B-cell line. This evaluation was feasible to our knowledge for the first time because of greater CAR T-cell expansion and persistence of ronde-cel compared to approved CD19 CAR T-cells. The higher memory phenotype and enhanced expansion of ronde-cel enables sustained functional capacity. The plot on the left indicates the percentage of cells proliferating in CAR-positive versus CAR-negative cells of three patients as assessed by flow cytometry. Greater than 80% of CAR-positive cells from all three patients had the capacity to proliferate five days after when activated by co-culture with a tumor B-cell line. In contrast, less than 7% of CAR-negative cells proliferated. This demonstrated the CAR-positive fraction in the sample could respond to antigens and expand even at two months after infusion. The plot in the middle showed killing capacity of ronde-cel as assessed by measuring the live tumor cell using the Incucyte instrument. The solid gray ascending line indicates the tumor cell alone condition. In the absence of functional CAR T-cells, tumor cells continue to grow. The color lines each indicate a patient sample culture with the tumor B-cells. As you can see, tumor B-cells were killed by 72 hours after co-culture for all three patient samples. The plot on the right indicates the interferon gamma secretion assessed for the three patients from the same co-culture after 72 hours. Note that the tumor cell alone sample had interferon gamma levels below the limit of detection and therefore not plotted. Similar functional data were also obtained on seven patient samples collected at the one-month time point after infusion. Collectively, these data showed that ronde-cel had sustained functional activity even two months after infusion. To further illustrate this, shown here is the video highlighting the killing capacity of ronde-cel from two months post-infusion. The pink cells are the tumor cells, and the gray cells are the peripheral blood cells. As you can see, by three days after in vitro co-culture, the tumor cells were eliminated by the peripheral blood cells. The tumor cells were eliminated by ronde-cel. In summary, our translational science data suggests that CD62L enrichment of T-cells achieved robust expansion, memory phenotype, and sustained T-cell function after infusion in patients with large B-cell lymphoma. Correlative analysis of translational data to clinical response from PiNACLE, which is a single-arm pivotal trial in third- or later-line patients, is ongoing, and we look forward to sharing more data with you in the future. And now, I'd like to turn the call back to Lynn. Lynn? Thank you, Gary. Before we open the call for Q&A, I'd like to briefly highlight LYL273, our newest pipeline program for the treatment of metastatic colorectal cancer that is currently in Phase 1 clinical development. We believe LYL273 further strengthens our pipeline with a clinical stage CAR T-cell therapy program for solid tumors that represents a tremendous opportunity to bring a potentially transformative therapy to patients. LYL273 exhibited significant anti-tumor activity in patients with refractory metastatic colorectal cancer with a manageable safety profile consistent with CAR T-cell therapy and the GCC target. Specifically, in a U.S. Phase 1 clinical trial, a 67% overall response rate and an 83% disease control rate were observed at the highest dose studied. Phase 1 data from China published in JAMA Oncology in 2024 support the U.S. Clinical data with a 40% overall response rate in 15 patients across two dose levels, a median overall survival at the high dose of 25 months with a median progression-free survival of six months. And importantly, including patients with and without liver metastases, the safety profile was manageable. LYL273 is enhanced with CD19 CAR expression and controlled cytokine release. GCC is expressed on more than 95% of colorectal cancers and a majority of pancreatic cancers. This novel GCC-targeted CAR T-cell product candidate is designed to enhance CAR T-cell expansion, immune cell infiltration, and cancer cell killing. LYL273 is manufactured with an automated closed system that is highly scalable. This case study describes one of the patients reported in the JAMA Oncology publication. The patient was a 48-year-old woman diagnosed with refractory metastatic colorectal cancer. She underwent surgical resection followed by four lines of chemotherapy and three courses of radiation to liver and lung metastases. She was eventually treated with 2 million CAR T-cells per kilogram. Adverse events included Grade 1 CRS, no ICANS, and Grade 3 diarrhea, which resolved. You can see on the CT and PET scans on the right hand that the patient had a dramatic reduction in liver metastases with a partial response and 50% tumor reduction on CT scan, as well as a 96% reduction on PET scan. The duration of this partial response after the single-agent CAR T-cell product candidate was eight months, and most importantly, this patient lived 46 months, almost four years following CAR T-cell therapy. Based on compelling cases such as these and allowance by the FDA to proceed under a U.S. IND, a clinical trial was undertaken in the United States. LYL273 is targeting a very large market. Not only is colorectal cancer the second leading cause of cancer deaths worldwide, it represents a large and growing $6 billion market that is projected to reach $12 billion worldwide net sales by 2032. There are more than 150,000 new cases and more than 50,000 deaths from colorectal cancer expected this year in the United States alone. Unfortunately, the outcomes for patients with metastatic colorectal cancer are very poor. The median overall survival of patients in the third or later line setting is less than 12 months, and the overall response rates of approved therapy are less than 6%. On this slide, you see the impressive results seen thus far with LYL273 in an ongoing U.S. dose escalation dose expansion trial in patients with metastatic colorectal cancer who received at least two prior lines of therapy before receiving single-agent LYL273. A dose response with more and deeper responses following treatment at dose level two as compared with dose level one is evident. A 67% overall response rate has been observed in the first six patients treated at dose level two with a 50% overall response rate across both dose groups. These high overall response rates, including one pathological complete response represented in green and one partial response with 100% target lesion tumor reduction, were achieved with a manageable safety profile. These data represent, to our knowledge, the most compelling response rates observed to date in the third or later line setting in colorectal cancer. This clinical benefit has been achieved with a manageable safety profile. Here are the adverse events of interest and other common events. To date, Grade 1 and Grade 2 CRS events have been short and resolved with standard therapy. As you can see, no cases of Grade 3 or higher CRS were reported. There were two cases of ICANS at dose level two, one Grade 2 event, and one Grade 3 event that resolved in three days. Diarrhea was the most common event with a median duration of 11 days. Grade 1 or 2 diarrhea occurred in 58% of patients. One patient treated at dose level two experienced a dose-limiting toxicity of Grade 3 diarrhea that evolved to an episode of Grade 4 colitis requiring treatment with aggressive immunosuppression. Unfortunately, the patient died of fungal sepsis 48 days after the infusion. The management of diarrhea was then optimized, including protocol-directed medical prophylaxis resulting in markedly improved symptom control, such that the last three patients treated did not experience Grade 3 or higher diarrhea. Other common adverse events included Grade 1 or 2 fatigue and nausea. Cell therapy has seen lots of failures in solid tumors, most often for lack of efficacy. That lack of efficacy is generally associated with low CAR T-cell expansion, rapid cell exhaustion, and limited infiltration into the hostile tumor microenvironment. So what is the breakthrough that we believe is enabling the promising clinical data observed to date with LYL273? First, an excellent target has been identified. The target, guanylyl cyclase C or GCC, is highly expressed in more than 95% of colorectal cancers, including metastases. Its primary known role is to regulate intestinal fluid and electrolyte balance. A great target is necessary, but not sufficient for success. LYL273's GCC CAR T-cells are also armed with two enhancements, CD19 CARs elegantly engineered with controlled cytokine release. The CD19 CAR expressing T-cells release cytokines after engaging B-cells, resulting in expansion of CAR T-cells that express GCC CAR, CD19 CAR, or both. When the GCC and cytokine-releasing CD19 CAR T-cells expand, they can infiltrate into tumors and kill cancer cells. It is this partnering of GCC CARs with CD19 CARs, plus the controlled cytokine release, that are central to the scientific breakthrough of this novel CAR T-cell product candidate. In essence, the CD19 plus cytokine enhancement ensures adequate cell expansion to achieve tumor infiltration and then assists in turning the immunologically cold solid tumor microenvironment into a more favorable immunologically warm environment and attracting other important cancer-fighting immune cells. Finally, here is a summary of our potential clinical milestones over the next two years. As I described earlier, we have a robust list of anticipated milestones across our two next-generation clinical stage CAR T-cell product candidates. We look forward to continuing to execute on the development of these two novel and potentially transformational product candidates. Now, I'd like to ask David Shook, our Chief Medical Officer, to join us and open the call for questions. Operator? We will now move into our Q&A session. For those of you who are joining us via Zoom, if you would like to ask a question at this time, please raise your hand by clicking the raise hand at the bottom of your Zoom window. Once called upon, please unmute your audio to ask your question. Our first question comes from Salveen Richter with Goldman Sachs. Please unmute your line and ask your question. Good morning. Thank you for taking my question. I was wondering, just given the differences in baseline characteristics and bridging therapy between the Phase 3 trials for the approved assets and the Phase 3 head-to-head trial that you're conducting, how you expect Yescarta and Breyanzi to fare in this trial and what superiority would look like? Thanks, Salveen. Great questions. Maybe I'll let Dr. Larson begin with just talking about the importance of patient characteristics and disease characteristics in looking at comparisons between the two products. Yeah, I think that's part of what's so important about head-to-head is because none of these trials have had the same patient populations, have had the same bridging requirements. And so really, this is going to be the first time where the playing field is level across the different CAR T-cell products. We do a lot of cross-trial comparisons and obviously point out all the differences with the level playing field. If we use the data from the cross-trial comparisons, that's where I would see favoring ronde-cel because all of the characteristics in these patients seem to be higher risk. Bridging is allowed. Older patients are given, and yet the outcomes to date are improved. And I think one of the reasons we were so leaned into this head-to-head trial, getting back to what Dr. Larson said, is that we want to leave no doubt about the benefit. And so this will give physicians the information that they need to switch their prescribing. And maybe Dr. Larson, you can comment on how CAR T-cell prescribers really use data and making a decision about which products they're going to use. Yeah, I think that's one of the benefits of the cell therapy field is obviously there has been a want to be giving patients the best possible product. And we've been very quick to shift products. And thankfully, I'm the medical director for the IEC program at UCLA, and it's very easy to onboard products, especially now that there's no REMS program. So I think each time that there are data that support the use of one product versus another, at least to date, clinicians are very easy in making that move to the additional product. Did we answer your question, Salveen? I think we're super excited about this head-to-head trial. And I think when you look at this, it's going to be the opportunity to really show the differences in event-free survival and safety in the differences between the CD19 and the CD19/20 product. Perfect. Thank you so much. Our next question will come from Mitchell Kapoor with H.C. Wainwright & Co. Please unmute yourself and ask your question. Hey, team. Congrats on the update here. A couple of questions. First one is for Dr. Larson. Do you see any key differences that you can explain between the primary refractory second-line population and the third-line population that may explain numerical differences between the performance in second-line and third-line for ronde-cel? Yes. What we saw on the trial is what we would actually expect. The primary refractory patients have worse disease. So it's really the functional prognostication there. And so we would expect patients with primary refractory disease to have a lower response rate, lower CR rate, and shorter PFS or duration of response. So for them to have a slightly shorter or slightly lower response rate, even though it was only slightly in this case, would be expected. This is a much higher risk patient population. Okay, great. And you can even. Yeah, sorry. Go ahead. I was just going to add, Mitchell, to that, that you can even see that if you look at the ZUMA-7 data, their overall data versus their data in the primary refractory patients, for example, for median progression-free survival is definitely shorter. So this is sort of known in the field. Perfect. Thank you. And then second question here is just on the landscape of CD19/20 CAR Ts. There's quite a few now, and a couple of them are shaping up with similar efficacy profiles. Dr. Larson, what will you and your colleagues be focused on for choosing which one is right for which patient? And kind of how do you see the landscape as it is now? And maybe Mitchell, I'll start with that question. I think it's really important when you're sort of looking at the various products that are out there. I think what you're seeing is that Gilead believes the next generation of CD19/20. That's why they're developing. And they certainly understand the CD19 marketplace and the switching behavior. I think J&J is developing a CD19/20. They too understand the switching marketplace. And I think where we find ourselves is with a product which is really differentiated in a couple of ways. Not only is it a 19/20, but we're selecting with a CD62L enrichment. And we're the only product that is doing that. No product candidate is doing that so that we have these more naive and central memory T-cells. And I think what was so important about the translational data that was presented here was that it really underscores what we believe to be the importance of this and the scientific basis for this CD62L selection. And then the second differentiation thing I think we have is that our pivotal trials are open. They're ongoing. And I think we've put up data with 69 patients. And that I think each time you look at a data set for a CAR T-cell product, you really have to look at the patient disease characteristics to make sure that you're really looking at apples to apples. So once all this is set out, maybe Dr. Larson, you can sort of talk about how you would make a decision about which product to use. Yeah, I completely agree. From the clinician side, of course, we're looking at what has the best efficacy, best safety profile. And really what we worry about in this space is really persistence. And I think that's where the most important differentiating factor here really is that CD62L selection. We previously had a construct similar to this at UCLA. So we also have—I also have a much longer time frame of working with this. And so I think the persistence here is really going to be the additional differentiating factor compared to the other 19-20 products. Excellent. Thank you, everyone. Our next question comes from Jason Zemansky at Bank of America. Please unmute your line and ask your question. Hi, this is Jackie on for Jason. First off, congrats on the progress. I have two questions for you. So for ronde-cel, what's the one-year relapse rate in the different patient populations? And then for LYL273, so it secretes IL-6, and there's quite a few studies that indicate that increased IL-6 production has been related to colorectal cancer progression. Is this a concern for you all? And what went into the rationale for including IL-6 as one of the cytokines to be secreted? Thank you. Thanks, Jackie. So I don't know that we have the one-year relapse rates for each off the top of our head, but we have been very transparent about the way we've presented the data. So you can see the swimlane plots with the histology associated with it. So all of the data are out there. I think the really great news is what we're showing is in the median progression-free survival of 18 months. And that compares very favorably to the median progression-free survival of six-seven months from the CD19 CARs. So I think that really is the most clear data that you'll see in the presentation. With respect to LYL273, Gary, I think I'll give you that question to talk about the cytokine secretion and the benefit of that and the role of IL-6. Yeah, absolutely. Thank you for the question. So I think one thing we know about cytokines overall in general is there's a really important arm to get the immune system to function properly. And most of these cytokines have this functional range and ratios. So I think it's really subtle and important how much you control each of the cytokine expressions. So I think, as Lynn outlined, these cytokines, as engineered into LYL273, is engineered to produce a specific level that's also regulated by the activation of the T-cell itself. And I can refer you back to the JAMA Oncology paper that the amount of cytokine is finely tuned in the system. So the majority of the cytokine that's being produced is the interferon gamma. And we do see an important effect of the IL-12 as well. So they do work in a combination of all three to the point that you made. So far, obviously, we've seen clinical benefit in the patient with these treatments. But of course, this is new science, and we'll keep a very close eye to assess the different cytokine level in patients and learn from there. All right, great. Thank you so much. Our last question will come from Christopher Liu with Lucid Capital. Please unmute your line and ask your question. Hey, guys. Congrats on the data. And thanks for the questions. So for the first question, I just wanted to ask about the second-line data set. With the understanding that it's in primary refractory patients, are there data sets with Breyanzi and Yescarta? And you mentioned some of it before, but best comparables with the current standard of care in that particular primary refractory patient population? And then I have a follow-up question as well. Sure. Dave, do you want to take that? Yeah. Yeah, I think thanks for the question, Chris. I think it highlights what we have been reemphasizing here, that patient population matters and how you do these cross-trial comparisons matter, why we're very excited about head-to-head to be able to compare these. And I think we'll answer these questions more definitively. But to your point, I think subgroup analyses have been done. For instance, the data in ZUMA-7, which looked at that primary refractory population that was presented earlier this year at the Tandem meeting, showed that among that primary refractory population, the progression-free survival, the median progression-free survival was just over seven months. And then in the PILOT study as well, in that primary subgroup population, showed less than half of patients responded in primary refractory. So you really have to look at these subgroup analyses to understand how we're comparing these patients, more apples to apples rather than kind of on balance. Maybe just overall, Dr. Larson, you should comment on your interpretation of the second-line data. Yeah, I was so impressed with the second-line data because, again, this is an older primary refractory patient population with a patient over 85 years old treated in it. So this really is a patient population where we have a much lower CR rate and a much lower duration of response. Because we don't have larger trials that would have a similar patient population, it's the problem with cross-trial comparisons, the other benefit of having something head-to-head, which I think is why the field is so excited about having that, because otherwise we're forced to make these small subgroup analysis comparisons. But certainly, when I saw this data, I was incredibly impressed because I was, even though, again, I've used this construct before, I've been very impressed with it. I wasn't expecting the data to be this good. Thank you. And maybe for the follow-up, I was just curious on your thoughts regarding the median progression-free survival, which looks quite impressive, and any read-through to long-tail durability? Yeah. Dr. Larson? Yeah. I think that's what, with continued follow-up, I think we're going to continue to see that flattening of the curve like we do with the CD19s where there are long-term responders. And certainly, that's what we've seen with the UCLA data that does have longer follow-up. And we need to present that soon just so that can continue to show. But again, I think it's that CD62L that really contributes to that additional persistence. Got it. Thank you guys very much. Thank you. There are no further questions. I'll now hand back to Lynn Seely for closing remarks. Thank you all for joining us this morning. We are really excited about our two programs which are moving forward rapidly in the clinic. And we're going to continue to execute for patients and update you on our progress. Thanks for joining us this morning.