Thank you, and thanks to Kevin for inviting us here to present today. I'm delighted to have a chance to tell you about Lyell Immunopharma, a cell therapy company focused on delivering next-generation CAR T-cell therapies armed with innovative technologies to deliver on the promise of cell therapy to defeat cancer. I will be making forward-looking statements during this presentation, so please consult our security filings or website for additional information. Lyell's vision is to advance next-generation CAR T-cell therapies to bring meaningful clinical improvements and outcomes to patients suffering both with solid tumor as well as hematological malignancies. We're doing this by arming our CARs with innovative technologies to bring about these better outcomes. I want to start with a very simple slide that very specifically tells you why now is a great time to invest in Lyell.
First and foremost, we have near-term key clinical milestones coming, first in mid-2025 and then in late 2025. Based on the emerging data from these clinical milestones, we have committed to entering pivotal trials in 2025, and these open up for us multi-billion dollar commercial opportunity. We have already built and operate our manufacturing facility that has commercial capabilities for launch, and we have cash runway into 2027. This is a great time to invest in Lyell. Let me unpack this in a little bit more depth. Lyell is a late-stage clinical company entering pivotal trials with a strong balance sheet. Our lead program, IMPT-314, is a dual-targeting autologous CD19/CD20 CAR T-cell product candidate with potential, we believe, to be disruptive, a disruptive innovation for the treatment of second and third-line aggressive large B-cell lymphoma.
In addition, we are also developing solid tumor programs, next-generation fully armed CAR T-cell programs with a suite of proprietary technologies, not only our anti-exhaustion and durable stemless technologies, but also technologies to address the hostile tumor microenvironment. We have scalable manufacturing. We own our own LyFE manufacturing facility in Bothell, Washington, that has the capacity to make 1,000 doses per year and to launch commercially. We have a strong balance sheet. As of our last filing, we had $460 million. Soon you'll be seeing in our K that we ended the year with $384 million, based upon the acquisition of IMPT-314 and ImmPACT Bio. We also have a very disciplined expense cash position, where we have guided that we'll be spending about $175 million-$185 million in 2025, and that this gives us a cash runway into 2027.
Finally, of course, we have the team that's experienced product developers to deliver this for patients and to create value for investors. Let's talk more about this lead program, IMPT-314, this dual-targeting CD19/CD20 CAR T-cell product candidate. This is expected to enter third-line pivotal trials in aggressive large B-cell lymphoma by mid this year, based upon data that we presented at the American Society of Hematology in 2024, showing a 94% overall response rate and a 71% complete response rate, all with a manageable safety profile, no high-grade CRS, and a low rate of Grade 3 ICANS. What are the key differentiators of this dual-targeting CAR T-cell therapy? It was designed very specifically to bring more complete responses and longer duration of responses in the approved CD19 CARs.
It is a true 19/20 or gated CAR designed to target either CD19 or CD20 with full potency, and it is the only product that we're aware of that's enriched for CD62L positive expressing cells, or naive T-cells. This is a one-time treatment that has the potential to provide patients a longer disease-free, treatment-free interval, and even the promise of cure. We are so excited about this emerging clinical trial data that we have committed to not only doing the third-line pivotal trial, but also initiating a second-line pivotal trial. This is the pipeline that we're supporting with our strong balance sheet through cash through 2027. You see at the top the third-line program in aggressive large B-cell lymphoma, where we have Fast Track designation. We'll be presenting more mature data mid this year in 2025, as well as initiating the pivotal trial.
In addition, the initial second-line data will be presented mid this year, followed by more mature data at the end of the year. Again, we're committing to initiating a second-line pivotal trial by early 2026. As I said, we're continuing to develop in solid tumors a new undisclosed target at this point, but incorporating multiple different technologies in our suite of technologies, including for anti-exhaustion, durable stemness, and for the tumor microenvironment. The first IND for this program will be in 2026. Many of you know that CD19 CAR T-cells have been transformative for aggressive large B-cell lymphoma, so you may be wondering, why do we need a new treatment? Let me tell you why. There is a tremendous need for higher complete response rates and longer duration of response.
Yes, the CD19 CAR T-approved therapies have been transformative, but still a great need remains. As it turns out, approximately 50% of patients in the third-line setting with an approved CD19 CAR T-cell therapy do not achieve complete response. 30% do not respond at all. Equally, approximately 50% of patients in the third line treated with an approved CD19 CAR progress or die by six months. You can see this in the graph on the right-hand side of the slide, which is progression-free survival from the Yescarta third-line registration trial. The overall survival of the approved CD19 CAR T-cell therapies in the third line is only 50%-60%. There is a lot of room to improve upon these initial first CD19 CAR T-cell therapies. We are developing IMPT-314 to be a disruptive addition to this marketplace. This is a multi-million dollar marketplace.
Currently, the approved CD19 CARs are selling $3 billion. This is expected to increase by 2030 to $6 billion, based upon growth in the second line, which is a still unpenetrated marketplace. We think with a more efficacious potential for a good safety profile, there's lots of room for growth here. We are incredibly excited to bring IMPT-314 into this space. Let's talk about exactly what that unmet medical need is. This is a busy slide with a lot of data, but it's really important to spend some time on. What you see in the top right panel are the approved therapies. At the top line, you see Yescarta. This is data from the third-line registration trial. If you look overall, you can see overall response rate of 72%. The line below shows Breyanzi, the second approved CAR T-cell therapy. Overall response rate 73%.
If you move over, complete response rate of 51%, 54%. There's that median progression-free survival, only 6 months-7 months. A lot of room left to go. If you look down below, you're going to see in the shaded table, phase I data, first from UCLA. This is where 314 was designed and invented, and they ran a single center study, mixed lymphoma histologies. What they showed was an overall response rate of 92%, with a complete response rate of 77%. Really nice data. Single center. This was outlicensed to ImmPACT Bio, which was recently acquired by Lyell. They ran a multi-center trial in the U.S., 15 centers, 94% overall response rate, 71% complete response rate. This is all large cell aggressive lymphoma. What you also see, this data has the potential to be quite practice-changing if it continues to look like this as it matures.
In addition, note the safety profile. If you look up above Grade 3 neurotoxicity for Yescarta, 31%. If the neurotoxicity looks more Breyanzi-like, around 10%, we have an opportunity to bring something to market with excellent efficacy and the potential for a very nice safety profile. Some people say, well, why are you developing in both the second and the third line? Isn't the second line standard of care for CAR T-cell therapy in lymphoma? First and foremost, large B-cell lymphoma is a very large market worldwide with more than 200,000 cases treated. Most patients are treated in the first line in the community setting. They progress in the community setting, and then they get started on second-line therapy, often bridging therapy while they're being referred into a CAR T-cell center. Now, once they get there, maybe they've progressed and they're all ready for the third line.
Maybe it takes them some time to get referred, but there is a nice mix of patients going to CAR T-cell centers, both in the second and the third line. The second line is the larger market, and you can see here with 62,000 patients worldwide. We are developing in both spaces. What is the biology? What is the secret behind IMPT-314? Why are we so pleased with this dual-targeting CD19/CD20 CAR? First and foremost, it is that dual-targeting. This is a true or logic gated CAR with full potency both at CD19 and at CD20. It is a 4-1BB CAR. What this allows us to treat is patients who are malignant B-cells with antigen heterogeneity. Maybe some malignant B-cells have low CD19, for example, and then can be treated with a CD20 component. This dual-targeting CAR is designed to give more complete responses.
You see also that it's being selected for CD62L enrichment. This is part of the manufacturing process. It doesn't take very long at all. The overall manufacturing time is about eight days. What you can see is CD62L selected cells are T-naive or central memory cells that we believe give us a better chance for engraftment, persistence, and duration of response. Really nice biology. Probably some of the best data in support of the CD62L selection comes from the Yescarta ZUMA- 7 clinical trial. What you see here are overall survival data from this trial. What they did is they looked at patients whose cell product had high naive T-cell phenotype versus low naive T-cell phenotype. What you can see here is those who had more naive T-cells had better overall survival.
That's one of the key clinical reasons why we're pursuing these naive T-cells. On the right-hand panel, you can see that when patients who receive CD19 CAR, they have a tendency to drop their CD19 antigen. Similarly, if you receive a single CD22 CAR, for example, you tend to drop your CD22 antigen. This gives us an opportunity to treat both CD19 and CD20 to maintain duration of responses for a longer period of time to avoid antigen escape. The first data that came out of this with this novel design came out of UCLA. This is a single center data I was referring to previously. Right off the top, what you see in purple, 92% overall response rate, 77% complete response rate in this swimmer's plot. Each line represents a patient. Green is complete response.
You can see that these patients, the majority of them, were treated with quite low cell numbers, only 50 million cell doses. You can see along the bottom, the y-axis. This is in years with some patients in complete response for four years. It's a really impressive initial data, mixed histology, single center coming out of UCLA with very long duration of responses. In fact, their median progression-free survival is reported here at 50.1 months. Small numbers of patients, but even if it's half that, it's still substantially longer than what is observed with the CD19 approved CARs and also with a very strong safety profile. This is an excellent example of a patient.
This patient was screened and was found to have a follicular lymphoma that was CD20 positive, but CD19 dim or negative, low CD19 antigen, maybe a patient that wouldn't respond so well to CD19 CAR T-cell therapy. This patient got the CD19/CD20, went into complete response, did well for 18 months, and then relapsed. This patient then received cells that were initially manufactured right at the beginning, was retreated, and went back into complete response because the tumor continued to exhibit CD20 positivity. Based on these very promising data, UCLA outlicensed this program to ImmPACT Bio, now acquired by Lyell, and they designed a phase I/II program. This trial enrolled only patients with aggressive large B-cell lymphoma that you can see here and studied two doses. The primary dose or the recommended phase II dose moving forward is likely to be 100 million cells.
They had multiple cohorts. Today, we're focused on two cohorts, that in the third line CAR naive population and also the second line CAR naive population. Let's look at the initial data that was presented at ASH at the end of last year. First and foremost, you see the demographics. Again, this is a multi-center trial being conducted in the U.S. What you can see is that these patients have a very typical multi-center type of demographic and patient characteristics. With a median age of 65, you can see most of the patients had DLBCL. You can see that about 40% had, or I'm sorry, 70% had an ECOG performance status of one, which is, again, not the least sick patients. You can see that the majority, about 50% of patients had an elevated lactate dehydrogenase, which represents a higher tumor burden.
A nice, sick, non-cherry-picked patient population typical of a multi-center trial. If you look at the safety data, it had a very manageable safety profile with no Grade 3 cases of cytokine release syndrome. For ICANS, 13% of patients had Grade 3 ICANS. It was a short-term induration, readily treatable with standard therapies. You can see very low incidence of prolonged cytopenias and no significant infections, about 17%, but common infections like UTI. Overall, a very manageable safety profile. Here's the overall response data with 94% of patients achieving an overall response and 71% in complete response. The median over 71% of patients were in response at the follow-up with a median follow-up of 6.3 months. We're looking forward to showing more data mid this year. This is the swimmer's plot from this study.
You can see again that each patient represents, each line represents an individual patient. The green is complete response. The blue is partial response. Again, really nice overall response rate of 94%. Here are the expansion data. What you can note here on the left-hand side is very robust cell expansion persisting over several weeks. You can see some of the product characteristics on the right-hand side with a significant enrichment in these naive T-cells, which again, we believe are going to be important for duration of response. I'll just spend a minute talking about the next generation CAR T-cell therapy programs in solid tumors, which we're continuing to develop to take advantage of the work that we've done. As you know, we have a suite of technologies which are designed to enhance CAR T-cell function in solid tumors. These are multiple types.
We have clinically validated anti-exhaustion technology as well as enhanced stemness. We have technologies that can enhance proliferative capacity and persistence and to improve cytotoxicity. We're basically now creating what we call fully armed CARs, which take advantage not only of the anti-exhaustion technologies we've developed, but also have enhanced cytokine secretion to help with the hostile tumor microenvironment. We have some new undisclosed targets that we're working on, and we expect that these will be entering the clinic in 2026. Just to summarize, I'll tell you that we have multiple upcoming milestones. We have data that are going to be coming mid 2025, more mature data in the third line, as well as the first presentation of data in the second line. We'll be initiating the pivotal trial in the third line by mid this year.
We'll look forward to bringing out more mature data in the second line by the end of the year, followed by initiation of the pivotal trial in the second line. In summary, I hope I have convinced you that now is a really great time to invest in Lyell with multiple upcoming clinical milestones, pivotal trials starting this year, giving us access to a multi-billion dollar opportunity. Just to remind you, we have our own manufacturing facility, which gives us great control over our destiny. It's incredibly important in cell therapy with cash runway into 2027. Thank you. I think I'll stop here and take questions.
By the doctors, how many patients are we expecting in that? What's the median follow-up?
We haven't guided exactly how many patients will be in that data set, but you can expect that those patients we presented previously will have continued to mature data. There will be some additional new patients. Both the third line patients and the second line cohorts are actively enrolling. Yes. This is one cohort with, I mean, one trial with multiple cohorts. We'll be presenting more mature third line data and the initial look at the second line data, much like the third line data I just showed you that was presented at ASH. We'll be seeing more mature data at the end of the year. A nice rolling cadence of data presentations. I think also what will be coming this year is the clarification of the registration pathway as we conduct our regulatory interactions.