Great, let's go ahead and get started. Welcome, everyone. My name is Vikram Purohit. I'm one of the biotech analysts with the Morgan Stanley research team. Happy to have with me on stage, Lynn Seely, CEO, and Charlie Newton, CFO of Lyell. Thanks for joining us. Appreciate it.
Great to be here.
Just quick mention of a disclosure statement before we get started. For all important disclosures, please see morganstanleyresearchdisclosures.com. With that, Lynn, Charlie, why don't we get into it? So I feel like everyone is likely familiar with the Lyell platform at this point, but just to level set, it might be helpful to start with just a quick overview of the thesis behind the targets you choose, specifically ROR1, how you feel that Lyell can develop differentiated therapies for solid and liquid tumors, and then we can go into specifics from there.
Sure. So Lyell is an oncology company focused on developing innovative cell therapies for patients suffering from cancer, and we do that in a unique way. We are a little bit differentiated in that we have both chimeric antigen receptor CAR T-cell therapies, as well as tumor-infiltrating lymphocyte therapies, and what we do is we harvest the patient's own T- cells, we take them to our manufacturing center in Bothell, Washington, and we reprogram them. In the setting of CAR T-cell, we give them a target, so we make a very precise medicine out of their living cells, and we also reprogram them with genetic and epigenetic enhancements to make them more effective at killing cancer cells, and our platform technologies, which are proprietary and backed by strong intellectual property, are really focused on helping our T-cell therapies overcome exhaustion.
It turns out that in the solid tumor setting, and even now we understand much better in the hematologic malignancy setting, CAR T-cells and TIL can become exhausted, so they don't persist, they can't kill cells over time. And so our technologies help the cells resist exhaustion in the hostile tumor microenvironment, and they also help them have what we call durable stemness to be able to persist over time. And so we expand these cells from millions to hundreds of millions, in the case of TIL, even billions of cells, and then give them back to the patient to really very precisely target their cancer. And we're very proud. We currently have two programs in the clinic. One is our lead ROR1 CAR T-cell program, where we recently brought out clinical data in June.
And then we have another program, our TIL therapy, which we expect to bring out clinical data in the back half of this year, coming up very soon.
Great. Great, that's a helpful overview, and I think a good segue maybe into 797. Maybe just educate us a little bit on the construct of this program, and then also just recap what you thought were some of the highlights from a safety perspective, from an efficacy perspective, excuse me, from the recent data update that you had from your phase I trial.
Sure. LYL797 is a ROR1 targeted CAR T-cell. We're developing it in patients with solid tumors. Specifically, we just had some additional initial clinical data that we brought out at the end of June in patients with triple-negative breast cancer, also a few patients with non-small cell lung cancer, so about 20 patients. These are late-line relapsed refractory patients, and what we were able to show was dose-dependent clinical activity. And at the highest dose that we cleared at the time of the data release, 150 million CAR T-cells, we saw a 40% objective response rate in those patients. We also saw a 60% clinical benefit rate, which includes stable disease as well.
Also in that data set, we were able to show that really validating our anti-exhaustion technologies, that we got very nice cell expansion. And it was great because we had a comparator, ROR1, a ROR1 CAR T-cell with similar binder, was used at the Fred Hutch Cancer Center, and really, they didn't see any responses in that study. They weren't able to see very good CAR T-cell expansion. But when we added our anti-exhaustion technologies, c-Jun overexpression, which helps the T-cells resist exhaustion, we were able to see this clinical activity, T-cell expansion, and very importantly, for the first time, we were able to show that the CAR T-cells were infiltrated into the tumor itself.
So we took on-study tumor biopsies and were able to show, using very specific immunohistochemistry, the CAR T-cells infiltrated in the tumor tissue, which is exactly what we hoped would happen. If we could help the T- cells overcome exhaustion, they could better infiltrate and kill the tumor. So we're very pleased with this initial data. We have some work to do. We did see some pneumonitis or lung inflammation in the study. Fortunately, we saw no ICANS related to the treatment, very mild cytokine release syndrome, but some patients did have pneumonitis. Particularly, it was those patients who had lung involvement, so lung metastatic disease, in particular, and so that's something that we're working. It turns out, fortunately for us, it's very predictable and manageable.
Got it. Got it. So quite a bit to unpack there. Maybe first, from the efficacy standpoint.
That 40% ORR, just help frame for us how clinically impactful that is, given what other treatments patients for this kind of line of therapy currently use, what response rates they see there, and where, based on a 40% response rate, if you were to see this again in future studies, where do you LYL797 could kind of fall in the treatment paradigm for these patients?
Sure. So right now we're studying very late-line relapsed refractory patients. In fact, the mean number of lines of prior therapy for our patients was six. These patients were heavily pretreated. We did see this 40% objective response rate at the high dose, and so I think, you know, the bar for these patients is very low. At this point in time, usually they're going to hospice, quite frankly. There are very few. They've exhausted all treatment paradigms. So I like to think, what is the minimum bar for approval here? It's probably a response rate in the 25%-30% range. We do need to see better durability.
So our durability of these responses was not as long as we might like, and so I think typically you're gonna have to see four to five months of duration of response to get accelerated approval, which is what we hope to do. Now, in cell therapy, you know, as we believe as we get to higher dose levels, that we're gonna be able to get better duration. And the reason we think this is because we are seeing this nice cell expansion that seems to be trending in a dose-dependent fashion, and we're seeing beautiful CAR T-cell infiltration. We think we just need more, and to get more cells persisting longer.
Of interest, we had a non-study tumor resection that was sort of by serendipity, and at four months out, one of our patients with triple-negative breast cancer had a lung tumor removed, as well as a lymph node. The lymph node was completely free of disease, and the lung tumor, four months after treatment, still had CAR T-cells present, showing really nice persistence. So I think we're absolutely on the right track, and we're really looking forward to presenting higher doses.
Got it. And then for those higher dose levels, do you think that 25%-30% response rate, four to five months durability, that should be the hurdle people have in mind for future data sets?
You know, we're all about bringing products for patients, and so.
That's the minimum. Obviously, we want as much better than that as we can get.
Sure. Sure. Understood. And then on the topic of dose escalation, you mentioned at the time of data release that, the respiratory Grade 4 and Grade 5 AEs, they resulted in kind of a bifurcation of dose escalation. Could you kind of walk us through exactly how the study is now unrolling?
Yeah. So let's be very careful. We did have one patient who died with pneumonitis, which would be one Grade 5 event. That was the index case. Pneumonitis was not something that we would have expected, and so it was recognized maybe a little bit later than we might recognize it today. What we have learned, and we have had some patients who've had Grade 3 pneumonitis. Again, those are patients who have underlying lung metastasis, and Grade 3 means you required oxygen. So it's a little bit, It's not as severe necessarily as it sounds. It's very easy to diagnose because as soon as the patient becomes hypoxic, and remember, you can measure that just with a pulse oximeter on the finger. These patients are now being treated aggressively with steroids, with very nice response.
And I think when you think about toxicities, what physicians want is something that's predictable and manageable. And here, the pneumonitis comes at a very predictable time, typically within the first four to 10 days after treatment, and it's treated very well with steroids. And maybe 10 years ago, physicians would have been a little bit more afraid of pneumonitis, but these days, in a typical oncology practice, they're coming across pneumonitis from checkpoint inhibitors. It's a very common side effect. They're coming across pneumonitis with antibody-drug conjugates, and so it's much more. They're able to manage it and with steroids. And now, so what we've done to help ourselves get to higher doses is we're now using prophylactic dexamethasone to help mitigate the pneumonitis right from the beginning to decrease the incidence and the severity.
And we feel very confident about that because that's something that's used in CD19 CARs to decrease the incidence and severity of CRS, and it's actually in their label. And so that's something that we're exploring now as we move to higher doses.
Got it. Got it. Okay. Helpful clarification. You've also announced LYL797 is now moving beyond triple-negative breast cancer. You're looking at more indications now. Could you just kind of talk us through what areas you hope to now LYL797 in, and when people can start to expect to see some data updates across all these different indications?
Sure. So this was a very exciting data set for us. It did a couple of things, this clinical data set. It allowed us to validate our preclinical models, which I'm gonna talk about another program that will be important in, and it also really validated our anti-exhaustion technology, and so we know we're on the right track. And so what we've done is we've now expanded into two other solid tumor indications where we know ROR1 is important, that is, Ovarian cancer and Endometrial cancer. These are, again, relapsed refractory patients that have about 50% of patients in each tumor type express ROR1, and so we're really interested in getting data in these patients. We've already begun enrolling patients with these tumor types, and I will say the GYN oncology community is really excited about T-cell therapy in this patient population.
In addition, you know, one of the things that's happened is we've learned over the last few years that exhaustion is. T-cell exhaustion is actually really important also in hematologic malignancies. And so we've seen this with the CD19 CARs, and that there, those CARs, the T-cells that become more exhausted, don't get the response and the persistence that those with less exhaustion do. And so we are now taking our ROR1 CAR T-cell therapy into multiple myeloma and into chronic lymphocytic leukemia. 95% or so of patients with CLL have ROR1 expression, and then about 60% of patients with multiple myeloma. And so while some people feel like, "Oh, there's so many treatments in hematologic malignancy," these patients, these diseases continue to progress through these lines of therapies.
And so, investigators in these areas are always looking for novel targets, and so ROR1 is a very attractive target for them.
Got it. And I think, you know, as you expand, your evaluation LYL797, i think one natural question that might come up is, what is the level of ROR1 expression in healthy cells that may be out there, and what is the risk of kind of off-target effects? So any thoughts on.
Yeah.
On the topic?
No, it's a great question. At this point, we've treated a number of patients. We haven't seen any evidence of on-target, off-tumor toxicity. I would say there was a clinical study done at the Fred Hutch Cancer Center, about 14 patients. Similarly, they didn't see any on-target, off-tumor toxicity. Then a number of other antibody-drug conjugates that are targeting ROR1 have been out there. I think, while there is some expression on parathyroid cells and pancreatic cells, we haven't seen any evidence of problems with that. We think ROR1 remains a good target, and we think that with our anti-exhaustion technology, we're really in a good position to be successful. In fact, we've doubled down on it.
We have a next-generation ROR1 CAR T-cell program that now has the same two technologies LYL797, which is c-Jun overexpression and our Epi-R technology. But also now, we're doing additional genetic engineering, where we're knocking out NR4A3 to make it even more potent. And these both c-Jun overexpression and NR4A3 act on the AP-1 transcription factor pathway, and so one steps on the gas, if you will, the c-Jun overexpression, whereas the other one is a negative regulator. When you remove NR4A3, it's like taking your foot off the brake, and so it's really allowing the T-cells to resist exhaustion. And when we study this in preclinical models, we're finding a really remarkable difference.
And so just to help give you a picture of this, when we have a preclinical model, which has now been validated with our clinical data, and LYL797 in that preclinical model, if you give the animals that express a non-small cell lung cancer tumor, a million CAR T-cells, it can control the tumor very nicely and enhance their survival. LYL119, at 100,000 CAR T-cells, so tenfold lower dose, you can get similar benefit. So it's a really step change in benefit. And so, we're very proud to say that the FDA has cleared that IND, and so we're busy activating centers and getting that up and going.
Great. And thank you for correcting me in your response. I meant off-tumor, not off-target effect. So, necessary clarification. But then one question that comes up with one one nine is, why have a next gen version of your ROR1 product so relatively closely behind the first generation?
Yeah. So science evolves. We're a very science-driven company, and I think, this is, in our hands, a significant step change. And I would say probably two things happened. The science came, very LYL797 was a little slower than we might have liked, so maybe they're closer than we might have originally anticipated. But quite frankly, the data are coming beautifully now, and it's gonna give us an opportunity to make very good choices. And so, we're data-driven. We're gonna make decisions about what we move forward based upon the data. And so we talked about we LYL797 moving forward. We're continuing to enroll patients with triple-negative breast cancer and non-small cell lung cancer, which, we're very excited about.
We've added the GYN malignancies and the hematologic malignancies, so we're gonna have just a lot of data coming in that program, and now LYL119, we're actually starting with the GYN malignancies, so everything we're learning and building LYL797 will carry through LYL119, and I think we're gonna have a real opportunity to, with data, optimally place these two programs.
That was gonna be my next question, is the LYL119 data. Should we think about that as a natural decision point for Lyell choosing one ROR1 CAR T versus another to kind of progress forward across indications? Or do you think there's a world where both can live in different indications and keep progressing to later stage development concurrently?
Yeah, I think absolutely there's a world when both, both can continue. You know, we'll see what the data show. If seven nine seven is doing beautifully, why would we slow it down? We're gonna keep it moving forward. We may choose to take them in different indications, or we may switch altogether. But I think right now we're full speed ahead with both, and then we'll see how the data play out. We're about developing products for patients and as many indications as we can, and it's one of the reasons we like ROR1, because there are so many tumor types which do in fact express ROR1. So when we find an effective therapy, it's gonna be very important.
Got it.
I might add one other comment to that too.
Sure
That I don't want it to be lost on people, is that our technologies, we're exploring them and evaluating them in the ROR1 setting, but these can be used for any CAR, any TIL, any TCR. They are actually technologies to enhance the cell's performance once it is deployed, and so we think that's really important as well.
Understood. No, that's helpful, helpful to know. I guess finding ROR1 cancers may be a bit of a naive question, but is there a basic test that patients need to have administered? And if so, how are you thinking about planning for that across different tumor types, where that may not be the standard procedure that patients go through?
It's a great question. It is a true statement that right now there are no approved ROR1 therapies, so it's not something patients typically get tested for. We have developed our own ROR1 immunohistochemistry assay, and we've made a decision that we are actually testing patients before these phase I clinical trials. Some people will just say, "Let's get safety data as quickly as possible." We've been enriching our patient populations by selecting ROR1 positive tumors, if you will, to include in the study. We send a biopsy of the tumor to our lab. We test it for ROR1. We've set a 10% cutoff for ROR1 positivity. It's more pragmatic than anything.
We want to enrich to include patients more likely to respond, but not exclude too many patients in the population. And so far, that seems to be working well for us.
Got it.
Ultimately, we'll correlate expression with response, but that'll take a larger data set.
Sure. Sure. One more question on ROR1, and then I'd like to move to the TIL program.
Oh, yeah.
Some of the tumor types you're going after with ROR1 affect pretty large patient populations. Do you have plans to, at some point, look into a partnership maybe to explore later-stage development?
Charlie, you want to take that?
LYL797 LYL119? or do you think you can prosecute them independently, just kind of given your cash balance for the foreseeable future?
I think in the near- term, we feel very comfortable with our existing cash balance that we can continue to advance the programs. That said, as we get closer to commercialization, I think we're going to be very thoughtful about how we can really maximize the commercial opportunity, and potentially leverage a larger partner to help outside of the U.S. perhaps, or even perhaps in the U.S., if that would make sense. But I think we'll be very thoughtful and pragmatic about that at the appropriate time. But while we have sufficient cash to really push forward on our own, continue to build value in the programs, we'd like to do that on our own and preserve that value.
Got it. Got it. Makes sense. Okay, any questions from anyone in the room on ROR1 before we pivot to TIL? Okay, so LYL845, your TIL program, you mentioned data coming up by the end of the year. Basic question, how has this program been engineered to be differentiated versus more traditional TIL therapies?
Oh, well, the whole program was designed to build upon what was already out there, what had come out of the National Cancer Institute, and Lyell has a team that came from the National Cancer Institute. And what we really wanted to do is develop TIL, which mirrored the cells that had been shown from their own data set to be most likely to bring about clinical response. And so there was a publication in Science that talked about the phenotype of the cells from patients who had responded to the NCI TIL and what that phenotype of the cells was. And it turned out that it was skewed towards CD8 effector cells. It had the cells that had stem-like characteristics were more likely to generate responses. And so our scientists developed a proprietary technology that is in our manufacturing process.
It's basically a manufacturing protocol, where we use a very specific mix of media, cytokines, and ways of activating the cells so that we develop in that manufacturing process a higher percentage of these stem-like cells that we're looking for. This is what we call our Epi-R manufacturing protocol. It, in essence, is developing cells which we believe are more stem-like and more able to persist and kill. It does that by switching the cell's metabolic pathway from a glycolytic pathway to an oxidative phosphorylation pathway, which is what stem-like cells use. People say, "Well, does it take extra? Are you having to time? Do you have to select the cells?" No, it happens very naturally in the expansion protocol. People sometimes don't realize that we take...
The way we make TIL is we take a patient's tumor biopsy, we send it to our manufacturing plant, where they extract the TIL, the tumor-infiltrating lymphocytes, and then expand them from millions to billions of cells. And if you don't do that just right, you don't end up with the right T-cell type. And so, the standard TIL prep tends to be more differentiated, more late-stage effector cells, and that maybe don't persist as long. And so that was what our TIL were designed to do. We really optimized them and defined them very clearly in the preclinical setting at this point, where we can show that they have quite a differentiated transcriptomic profile, where they're more stem-like than an exhausted phenotype that you see in the standard prep. We've been able to show that we can preserve polyclonal, because that's really important.
If you expand out the wrong cells, right, if you lose those tumor reactive clones, you're not gonna have the benefit that you want. And so we've been able to show at clinical scale that we can preserve the predicted tumor reactive clones at a very, very high percentage, which we think is a critical success factor. And so if I boil it all down, I think when you're making TIL, you have to have cell number. Cell number matters, we know that. You have to have the right phenotype, and so in our hands, as we've designed our process specifically to have the right stem-like features. And then you need the right polyclonal. You need to make sure that the TCRs, the predicted tumor reactive clones, are present in your end product to kill the cancer cell.
Sure, sure. That's helpful. That said, what do you think is the best way for people to interpret the data that we're going to see in melanoma by year-end, especially in comparison to the data we have from Iovance?
So yes, we've started and have been focusing on advanced melanoma because that's where the benchmark is. You know, and with Iovance, and I think good for Iovance. They've successfully developed a cell therapy for solid tumors that's approved, but the bar is still 30% response rate, and so I think that's what the bar is, and we need to beat that. And I think it's not a high bar. I think it's something that's achievable, and so that's what we're looking to do. We're going to present data by the end of the year in about 20 patients, and we think that that will be enough to give investors an opportunity to see if our response rate is differentiated and also enough durability that. We're never going to have the type of mature durability that Iovance has.
I mean, they've been doing that for over many years. But I think enough durability is not as big of an issue until when you get the responses. Typically, they tend to be durable. So I think enough durability that investors will see we're on the right track.
Got it. Got it. I guess a broader question then on the commercial opportunity for LYL845. Has the Amtagvi relaunch process progress that we've seen so far, has that impacted your view on the commercial opportunity for TIL in melanoma? And do you think that this could be a space where there's room for two, three, plus more branded players?
Oh, I think there's room for more and particularly better.
Players, differentiated players, absolutely. And I think, you know, look, I think the Iovance launch is progressing. They're building momentum. I think they went to great lengths to show that at their last earnings, and we're out at these sites. I mean, we're talking to these physicians all the time, and I think we know that they're very enthusiastic about TIL therapy, particularly in advanced melanoma, where they have the most experience. And it just takes some time. These are very complex processes, right? And these centers have to get their process, their personnel trained, the payer situation set out. It's a very complicated thing, but once they do, it will happen. And so the way we look at it is, Iovance is out there paving the road, and then it's going to be a lot easier for others traveling behind them.
Usually you don't want to be second, but sometimes there's some advantages to being second, and I think this is one of them. I think we're cheering for them, and I think, you know, their success will help others be successful as well, and we intend to follow in their footsteps and then hopefully exceed.
Got it. Got it.
I would add one other comment, is that we're starting in advanced melanoma, but we've never for a moment thought that was the end game. I mean, the beautiful thing about TIL, if you can really successfully develop it and make TIL in other tumor types, is that's where the real market is. And so I think we're starting with advanced melanoma, but, the goal is to expand to non-small cell lung cancer and colorectal cancer.
Got it, and I know that the initial studies enrolling patients across all three tumor types, right? Melanoma, NSCLC, and colorectal?
So, yep, right now we're focused on advanced melanoma.
Got it
Primarily, yeah.
Got it. And you haven't guided yet to data for the other two indications yet?
No, not yet. I mean, I think when we bring out our data, that'll be a good time for us to sort of lay the stage for future indications.
Got it. Got it. Okay. In terms of a filing pathway for.
Yeah
LYL845 and melanoma, do you think it's going to be a very similar data package you'll have to provide to the FDA, kind of in line with what Iovance had to do?
Yeah, I mean, I think there's still room for accelerated approval here and a differentiated product. Absolutely.
Okay. Got it. Maybe we can switch over then to manufacturing. Just remind us, now that you have initial clinical data set out, what has your success rate been with manufacturing product, and what is your current capacity, both from a CAR T perspective and also from a TIL perspective?
Yeah.
Yeah, so on the data set that we presented a couple months ago or so now, we had 100% manufacturing success rate. So we've really been clicking on all cylinders there. And as I think you know, we own all of our own manufacturing, so we manufacture for CAR as well as TIL and lentiviral. The facility that we have, the way it's currently constructed, we can do about 500 doses per year, and that's across all three of those things. If we were to specialize just in CAR, we could probably do closer to 1,200 doses per year, if it were just TIL, closer to 800 doses per year. So it gives us a lot of flexibility to be able to push forward in clinical development on our own without having to rely upon a CDMO.
Importantly, from a cost standpoint, given we've already invested in the facility, that's behind us, the incremental cost of manufacturing product is quite small, particularly in CAR. Just the bill of materials are tens of thousands of dollars, not hundreds of thousands of dollars. It really provides a lot of operating leverage for us.
Got it. Just to clarify, so you mentioned 500 doses per year currently across the CAR T and the TIL programs?
Correct.
Yeah.
So you think about the trajectory that we have in the clinic moving forward with all of these programs. We feel very comfortable that we'll have adequate capacity to be able to deliver all of the clinical stage product that we'll need. As we get closer to commercialization, we think this could be a facility that we could use for early commercial launch, but undoubtedly, we're going to need more capacity as we get to commercialization. That could be in the form of another facility. It could be in the form of working with a CDMO that could help expand our capacity in a more cost-efficient way.
Got it. Okay. Just taking a big step back from ROR1 and LYL845, what are some of the key areas of investment, and kind of earlier stage pipeline exploration that the Lyell platform is being oriented towards? I mean, what are some interesting areas of biology that you're looking into to identify new targets and new therapies?
I think a couple of things that we've talked about publicly. I mean, first of all, we've just said we've validated our anti-exhaustion technologies, and so additional CAR targets is obviously of great interest to us. I think we have a program in rejuvenation, and we also have a TIL 2.0 program, which has epigenetic and genetic modifications. And so all of those things are in the works. We've not talked a lot about it, but I think this field and, you know, cell therapy, like, you know, all fields, waxes and wanes. There was a lot of froth that's kind of cooled an awful lot. But from where we sit, it's really the tide is now turning, and it's really starting to take off.
As we're learning more and more about how these cell therapies work and what it takes to be successful, there's just enormous opportunity, and so we are super excited what we're doing now, but this field's gonna continue to evolve, and we intend to evolve with it.
Yes, from your experience interacting with centers and running some of the studies that you've been running now, what do you think is, I guess, the most misunderstood feature on the commercial opportunity from investors and analysts? Thinking about kind of, cell therapies, especially for solid tumors, broadly.
Yeah. Well, maybe I'll, I'll start with hematologic malignancies.
Right? Because they're leading the way, right? I mean, that's where they came first. And it just, you think about the whole evolution and when CRS and ICANS first came, everybody thought, "Oh, nobody's ever gonna use these products," right? Well, guess what? They're manageable, predictable, people have learned how to work through them. And now in the hematologic malignancies, I mean, they're running frontline trials with CAR, and now you're getting CAR after CAR. And so you can envision this world where you start with, I mean, what do patients want? Patients want a treatment, and then they want a disease-free time, a time when they're not having to go to the doctors all the time. And so you get a CAR therapy, you get a prolonged period of off treatment, right, where you're not sick.
Maybe your disease does recur again, then you go and you get another CAR therapy. I mean, this is what's happening in hematologic malignancies now. You get a disease-free time, and so what they're looking for is novel mechanisms and ways in which you can really treat patients with that. Let's get away from chemotherapy, where you're constantly being given toxic agents, and let's come up with treatments. Yes, they're intense that one time, but then they give you this disease-free time. And so I think that's what we're looking for. We need to do more in solid tumors. I think great in hematologic malignancies, and I think we're gonna see it come in solid tumors as well. I think we're off to a great start. Others are coming along as well.
We're learning a lot more that maybe naked CAR alone is not sufficient, but as you start to armor the CAR, you start to get this right, these anti-exhaustion technologies, durable stemness. We're really starting to see some benefits, so we're super excited about this, and it's complex, but as we learn more and more about the complex things, they start to become commonplace and understood, and I think there's so many features about these treatments which will be attractive to patients when we get the benefit to warrant the investment.
Great. We have about a minute left. This might be a good time to just kind of touch on cash balance. I know we spoke about it broadly, but just to put a fine point on it, Charlie, could you just remind us of your current cash balance, the associated runway, and the kind of pipeline development contemplated in the runway for LYL797 and LYL845? Like, how far could you prosecute these programs with that.
Sure.
That cash balance?
Yeah. So the cash balance that we have is $491 million as of the end of the last quarter, and we've guided that provides cash into 2027. If you look at our burn on a trailing 12 month basis, it's about $140 million on a trailing 12 month basis. That'll, you know, begin to build a little bit more as we continue to enroll more patients. But importantly, to your point, that runway gets us through all of the major catalysts on each of the programs, so advancing everything that you see on the pipeline today through that time period into 2027.
So we get the clinical readouts LYL797, additional data there, the initial data on LYL119 in the back half of next year, and then obviously LYL845 later this year.
Got it. Great. With that, we're actually at time, so let's go ahead and close out. Lynn, Charlie, thanks so much for joining us. Really appreciate it. Thanks, everyone.
Thanks.
Thank you.