Nektar Therapeutics (NKTR) Earnings Call Transcript & Summary

And I believe we're live, if I counted down in my head correctly. Hello, everyone, good afternoon. My name is Chris Shibutani. I'm a member of the Goldman Sachs biotech equity research team now apparently. I'm joined by my colleague, CJ Zopf. CJ, wave to your fans.

Hello there.

We're here together with Nektar Therapeutics. We're very excited to have joining us today, Jennifer Ruddock, Senior Vice President of Strategy and Corporate Affairs, different shop, but I'll continue my tradition, CFO, Gil Labrucherie, which we'll just call you Gil for short; and of course, everybody knows JZ as well, Jonathan Zalevsky, who's beaming down from his location to join us so that he can tackle all the tough questions that CJ always asks so politely. So we're excited to get to catch up with you. Thank you for joining us.

We will make sure to cover as much as we can. We have 40 minutes, which is better than the usual allotted 25-minute nonsense and then pushing each other in the hallways. A lot of things are -- we've been waiting for. I think we've been paying attention to you guys for a long time. BEMPEG has had quite a journey. And I think one of the things that we think is going to be important to awaken people to is to refocus again because I think that we'll have some cards turning over. We'll have some data coming up over the next 6 to 12 months. So perhaps if we could just start out the level set as a reminder of what are the pivotal readouts that we're going to see and timelines across some of the different indications in melanoma, renal cell and bladder. And where are we in terms of being on track with all of that progress there. So I'll jump ball at who's the best person, maybe Jennifer, so that we get the most accurate, correct version.

I think JZ has this one.

Oh, okay. Wow, you've been given permission. Go for it, man.

Thank you, JZ.

And thank you also to Goldman for having us. And so firstly, like through our partnership with BMS is we have 5 ongoing registrational studies, BEMPEG plus nivo, and all of them are proceeding very nicely, so the first 3 registrational studies to read out in the first half of 2022. Our first-line metastatic melanoma, first-line renal cell carcinoma. And then in the cis-ineligible bladder cancer urothelial carcinoma, CPS less than 10. So firstly, for the first-line metastatic melanoma study, this one is being run by our partner, BMS. BMS has indicated that the data from the trial would be available over the time frame of late this year or in the very first part of 2022. And this study evaluates the combination of BEMPEG plus nivolumab versus nivolumab. Sorry, Siri. And the design is modeled on median progression-free survival, or PFS, of course. And then in that study, what we modeled it on is nivolumab having a 6.9 month PFS, which was observed in CheckMate 067. And since PFS is an event-driven analysis, a number of factors, including the rate of PFS event accumulation, they might impact the ultimate timing. And then the next study, and this is a study at Nektar is running, is a Phase III first-line renal cell carcinoma study. And we expect that we can reach our first interim analysis for the primary end point of overall survival sometime in the first half of 2022. Here at BMS and Nektar, we're taking a very comprehensive approach to the development of BEMPEG plus nivo in this tumor time. In fact, earlier, we just kicked off a Phase I/II study in RCC that combines BEMPEG plus nivo with a TKI. And this allows us to compare this treatment to a nivo-TKI regimen to pave the way for a TKI-inclusive regimen in RCC for the BEMPEG plus nivo doublet as well. And then with respect to the Phase II study in first-line cis-ineligible urothelial carcinoma, this study is designed to serve as a basis for a potential filing for accelerated approval with the primary endpoint of overall response rate and then duration to response as determined by central radiology. And the patient population here, we're enrolling about 110 system cis-ineligible urothelial carcinoma patients who have that baseline CPS score of 10 or lower. This is how we measure PD-L1 expression in this tumor type. The DoR is very important for this combination. And it's important to support the responses that we see to overall provide for the basis for the filing. So for this study, we're looking to achieve a median power-up for measuring duration of response of at least 18 months. And we expect the first data from this study in the middle of 2022. And then in addition, we have more Phase III studies that further build on this work in both urothelial carcinoma and melanoma. So first, our muscle-invasive bladder cancer study, which is being run by BMS, is enrolling approximately 540 patients who will receive BEMPEG plus nivo versus nivo monotherapy, and this is in the periadjuvant setting, of the 12-month treatment period following surgery. This is a very large study. And we expect the first data readouts to be in 2024. And this study is also designed to serve as a confirmatory trial for the potential accelerated approval in the cis-ineligible urothelial carcinoma setting. Second, we have the adjuvant melanoma trial, and this is enrolling approximately 950 patients within a 12-month treatment period post surgery, and the end point is event-free survival. And this study is designed to position BEMPEG as a standard of care for the treatment of melanoma, and really build on the recent nivo approval in this setting. And this study, if successful, could really substantially increase the number of melanoma patients that can benefit from the BEMPEG plus nivo combination. And we expect initial data from this study also in 2024. And then, Chris, in addition to these 5 registrational trials of BEMPEG in combination with nivo, we also have our new registrational Phase II/III trial in head and neck cancer, which combines BEMPEG with pembro. And we're very excited where we -- SFJ is the sponsor of the study, and in clinical collaboration with Merck for the execution of this study. But we're on track to start the study in the second half this year. This trial is a 500-patient study. It's designed to support a potential global registration for the BEMPEG plus pembrolizumab doublet. It includes an interim analysis of ORR after the first 200 patients are enrolled. And then if the ORR passes a prespecified futility boundary, the study continues and the remaining 300 patients would be enrolled to the Phase III portion of the study. And then all 500 patients will be evaluated for the primary end point of overall survival and objective response rate. We're excited about the potential of this doublet to increase and deepen the responses versus pembro alone in this immune-sensitive cancer, especially given the data that we've seen combining BEMPEG plus nivo in melanoma which is another immune-sensitive cancer. Now historically, IL-2 has shown activity in head and neck cancer with several published studies in both the metastatic and adjuvant setting, and we're very excited to be developing BEMPEG now in this frontline indication. Additionally, this is kind of a unique and open landscape because there have been some recent late-stage failures in the head and neck cancer in the frontline setting. So there's kind of a lot of room -- potential to grow in this setting. So this is, we think, a very unique opportunity for us to establish BEMPEG as the first IL-2 mechanism in head and neck cancer.

What a simple question I thought I asked in a huge list. But I mean embedded within that is so much that you guys have been working very hard on, that the vastness of the opportunity, we can go back to, what was it, February 2019. When Bristol signed the partnership, there was really significant ambition in terms of just so many directions that you could go. And here we are now approaching mid-2021 and some readouts coming over the next 6 or 12 months. I'd say what we've all lived through is the recognition that perhaps especially in immuno-oncology, the challenge is trying to figure out what we can sort of expect and translate from earlier stages of clinical work to later stages, right, what can we extrapolate? And particularly, let's start with melanoma as an indication. Can you talk about what you'd expect to see as far as the PIVOT study? The data there, particularly on the PFS has been very impressive progressively. How do you develop confidence or how do you guide people to think about what we could see in the Phase III work?

Yes. Well, I think it's very important to compare the design of the Phase II to the Phase III that you're doing and to compare the patient population, then enrolling right and compare the nature of the therapy that you're giving. So one of the important things about PIVOT-02 is that the inclusion criteria and the overall demographics and baseline history and prognostic factors in the patients that we enrolled into the melanoma cohort, are virtually identical to the CheckMate 067 patient population. So if you look at the proportion of patients that had high risk factors such as elevated lactate dehydrogenase, elevated for the presence of liver metastases, for the proportion of patients that are M1c or M1d, the most advanced in the AJCC scoring criteria. The patients that we enrolled into PIVOT-02, virtually identical to the CheckMate 067 patients and virtually identical to the ongoing Phase III study that we're running now, at best is operationalizing. And it's interesting, the only difference is so subtle, Chris, it's just that the AJCC scoring criteria went from version 7 to an update to version 8. That's the only difference. But that difference just incorporates LDH into the M1 staging status as opposed to reporting it separately. It's the only difference between the 7 and -- version 7 and version 8 criteria. So that's something that gives us a lot of confidence in kind of the translatability of Phase II data. And then the other things that give us a lot of confidence really drives down into the target. We're talking about IL-2. It's already approved, right, in the treatment of metastatic melanoma. It's a highly validated target. And then the biological and mechanistic elements of BEMPEG's pharmacodynamics that we've measured, both systemically in the patient as well as in the tumor microenvironment, they also give us an enormous amount of confidence, right? We've seen those kind of systemic events across many, many patients. And we've seen that as a consistent element of how BEMPEG works and how it really adds to a checkpoint inhibitor.

Coming on the heels of ASCO in particular, kind of a loaded question, but a real question in terms of CheckMate 067. How relevant a bar do you still see that? I mean I think out of consistency, you've always framed it there and you just described how the patient populations are quite similar. But coming out of the tail end of ASCO here, what are your thoughts, particularly first-line melanoma, which has always been just sort of base camp for all the I-O therapies, right?

Yes. I mean I think that's a really good question. And I mean, I think that the first thing is that like, I have to remember the Phase III study that we're running is designed and modeled on the CheckMate 067, and the LAG-3 study is very similar, right, in the design of CheckMate 067. There are a few differences that we can talk about later or with this question. But one of the things that I think is really critical is that CheckMate 067 has led to an approval, right, and a real establishment of ipi/nivo as a far-running standard of care. And it's set a bar for the level of efficacy that is really critical. And I don't think we've seen data yet that's transformational and displaces the ipi/nivo doublet. So I think there are some -- a lot of positives in the LAG-3 plus nivo data set. It will impact, I think, the algorithm of how we treat melanoma. But I don't think it's a transformation of data set that displaces ipi/nivo. I mean -- and I think that, that's the presentations that we observed from Dr. Lipson. And some of the other commentaries that we've heard, I think, are consistent with that. So to me, and I represent how we think about it at Nektar, CheckMate 067 is really still the standard or the bar. And we also think that there is a great opportunity because if the data that we are able to achieve in Phase III is reproducing of what we saw in PIVOT-02 with Phase II. Even if it is a little bit worse, but it's within, say, 50% or 2/3, that has a real opportunity to set a new transformational bar in the treatment of metastatic melanoma, potentially become the new de facto and frontline regimen. And so we are very, very excited about the study. And what we've seen in PIVOT-02, it gives us confidence in our ongoing Phase III study.

Got it. Let's move on to renal cell. Boy, talk about an indication for which the paradigm has shifted so much over the last 5 years, right, in terms of various monotherapies, combinations. Now we've seen the checkpoint inhibitor with TKI combinations show some responses greater than 50% and some very impressive clear survival benefits. So can you talk a little bit about how you view the TKI-sparing opportunity, kind of what do you think you need to see in your Phase III to have an opportunity to see some relevant uptake? And I think you also have a triple combination study that's in the works with Bristol. Maybe just if you could throw in where the update on where that is.

Yes. Well, so we definitely recognize as you mentioned that the RCC landscape is highly evolving. Right now, you have nivolumab plus ipi combination and also multiple checkpoints plus TKI. You have pembrolizumab and nivolumab, and you have multiple TKI regimens coming in from the older sunitinib to the more LENVIMA, right, the more modern kinds of approaches. And I think there are 2 key points here. And so one is that the combination of BEMPEG plus nivo offers another treatment option. And that gives a lot of flexibility. You have a TKI that can be used in multiple settings, so it can be used in combination with the checkpoint in the first-line setting or it can be used later as a monotherapy or even in additional immunotherapy regimens. And we've talked to different physicians around the world, and we see that a lot of thought leaders are taking advantage of these options and using them differently in different regions. And so there are still some physicians who prefer to use an IO-IO combo first-line setting. Others would like to use a TKI combo in the first line or save that drug, right, for a later setting. And I think that one of our main objectives, right, in our ongoing RCC study is to provide another meaningful treatment choice for physicians to have, particularly in a TKI-sparing selection kind of avenue. So one of the things that we believe we can deliver with BEMPEG plus nivolumab, right, is we've seen a depth of response. We have the potential to elevate the real quality of the responses that are seen such as driving substantial tumor shrinkage and a very, very durable response driving the CR rates that are durable, for example. And then all of that comes with a safety profile that's really, really different than a TKI-inclusive regimen. I mean you know these TKI regimens, 50% to 60% of the patients have grade 3 adverse events. A lot of them have a lot of difficulties in tolerating. This is why you're even seeing a whole variety of different TKI kind of dosing regimens, very exotic regimens, just to figure out how to allow patients to tolerate these kind of agents better. Now we also -- it's very nice to work with BMS here because they have a lot of experience in the setting. So obviously, with CheckMate 214, we had tremendous data with ipi/nivo in a TKI-sparing setting and then in the setting of cabozantinib, they have great data with nivo plus the TKI. So they were successful, right, in generating very important activity in this tumor type, both in the absence and in the presence of TKI. And we're excited to be working with them because of the study that's ongoing now. We're really focusing on TKI-sparing regimen. And we've kicked off a study that's currently enrolling where we're evaluating the combination of BEMPEG plus nivolumab with a TKI, right? And in that study, yes, we have the option of evaluating multiple TKIs. But of course, we're very interested to focus on the cabo-nivo-BEMPEG combination since that already has a label with nivo.

Right. Time line, can you hint with the time line?

Yes. So that study, it's enrolling. You can see that it's active. BMS is running that study. So we'll work very closely with BMS on when we can provide any updates on that drug.

Got it. And then I'll just talk about bladder. The first-line cis-ineligible bladder has also been an evolving landscape here. Originally, I remember talking a lot with you guys about the PD-L1 negative population. I guess, the recent FDA ODAC discussions around accelerated approvals for the checkpoint inhibitors in the maintenance setting. Has any of that changed your calculus at all in terms of thinking about what the opportunity could be in bladder?

Yes. It's a really good question. I mean I think that those series of ODAC meetings, they really -- they covered multiple areas from solid to liquid tumors. They looked at all accelerated approvals in general, right, not just like we're focusing on a specific one here. But I just thought it was telling to see the overall success rate run confirmatory studies. And I think that FDA was noting that it's just not quite as high, in any setting as they would like to see. And in some settings like heme, it's probably particularly low, right, that it is even in the solid tumor setting. So those are very important discussions. We paid a lot of attention to those, as you can imagine, with our study in the cis-ineligible urothelial carcinoma. Right now, the FDA has not changed any of their practice, right, on how they're reviewing this. There were a couple of decisions, but not in the realm that we're talking about here in this case. So we're monitoring this very, very closely. One of the things that's important to remember is that for an accelerated approval, I mean, you're really only judged against the standard of care, right? And so any AA opportunity is an assessment of the totality of the data, all of the benefits of the potential therapy, any of risks, right? And benefits are everything from response rates and durability and risk related to AEs or like escape or other kinds of progressions or things like that to happen. You weigh the totality of all of that against an available standard of care. But we're still on track to do that. And if we have any kind of changes with that, when the FDA changes any of its components, we'll have to react accordingly.

Got it. So we'll stay tuned there. I'm going to turn it over to my colleague, CJ, to talk about lung since everybody knows that lung is what makes everybody hyperventilate. And so to spare us all a live online physiologic collapse, I'll turn it over to my youthful colleague. CJ, take it away.

Yes. So we're all obviously very excited for that readout later this year. And I think you've been pretty clear about sort of go, no-go thresholds for different stratifications of patients in that study. Would you say it's fair to take the view that the clearest opportunity for you might be in the lowest checkpoint -- or excuse me, in the lowest PD-L1 expression group?

Yes. It's a very interesting point. So pembro monotherapy is approved in a broad spectrum of patients. But we do think that in the PROPEL study, the subgroups that are very, very informative for the BEMPEG plus pembro combination of the less than 1% PD-L1 expression and the 1% to 49% PD-L1 expression subgroups because there, you have really the weakest performance, right, in a single agent of pembrolizumab. So like the dynamic ratings, right, is substantially different because you have much worse performance in pembro. Additionally, if we demonstrate a cyclical improvement, let's say, a doubling of response rate, for example, in the 1% to 49% cohort or say, maybe tripling of response rate in the less than 1%, then what we know of BEMPEG and its mechanism of action, and the way that it could impact the tumor microenvironment, the way it can convert tumors from PD-L1 negative to PD-L1 positive, right, that can really unlock the power of the complete totality of that immunological immunotherapy regimen when you have a PD-1 checkpoint inhibitor on board. We've seen this kind of effect in other tumor types, this kind of information that we've been able to drive. We've seen it in PD-L low expressing tumors such as in urothelial carcinoma. And even in tumors that were completely low, not just completely undetectable to the lowest PD-L1 expression. Again, this is a kind of action that sensitizes the tumor, right, to the immunotherapy regimen. And then pitting the registrational study for a doublet of pembro plus BEMPEG versus pembro monotherapy. I mean, even in that kind of a design, it would have to be limited to the 1% of PD-L1 positive population because pembro mono is only approved in the greater than 1%. It's the monotherapy standard in greater than 50%. And in the 1% to 49%, there is both a monotherapy approval in the U.S. as well as a chemo containing regimen that's given to patients in that subgroup. Overall, the data in the less than 1% subgroup is going to be extremely informative because of what we know about IL-2 and its mechanism of action. What we've seen in the PIVOT-02 studies across multiple tumor types. And overall, will we report the data from PROPEL in the second half of the year? I mean we're going to look at all of the available data that we've collected, all the patients that have been enrolled, all of the treatment duration for all of those patients. We'll look at the totality of the response data. Everything from the ORR, just the basic RECIST reporting, to the depth of response, to proportion of patients with complete responses, partial responses, long durability responses, long durability of stable disease. Any kind of time to event data that we've collected. And of course, all that will come in addition with all of the safety information as well as all of the biomarker and translational data that we've been collecting in the study as well. So we look forward to a very rich and robust data set. You have to remember that the study is still ongoing, right? Patients will still be in follow-up. But our aim is to present the most robust and most mature update of the ongoing trial.

Great. And you bring up the chemotherapy combination, which obviously is important in the lower PD-L1 expressing tumors. You've also talked about running a triplet arm of BEMPEG plus pembro plus chemo, but I believe that's lagging a little bit. So how should we be thinking about the opportunity for the triplet as well as would it be a separate regulatory path? Or would that be all rolled into one multi-arm Phase III study comparing all the subgroups and all the regimens?

Yes. That's a great question, CJ. So one of the things that I think is interesting to kind of just take a step back is that there was a really important presentation that the FDA made over the weekend on Sunday, where they looked at the data in non-small cell lung cancer, specifically in patients in the 1% to 49% subgroup. And they did a meta-analysis of all available data from trials that have monotherapy pembro versus trials that had pembro plus chemo, right? And then they did a substantial meta-analysis, over 1,000 patients included in that analysis group. And the results, I thought were pretty striking. If you looked at the overall activity on OS, PFS, even by age, right, in all cases, the pembro plus chemo doublet really outperformed the pembro monotherapy in that 1% to 49% subgroup. Now so I think that's just a very interesting nuance. We know, of course, that only in the U.S. is the greater than 1% monotherapy label approved for pembro, and in the rest of the world, pembro plus chemo is the preferred regimen in that 1% to 49% subgroup. So it's going to be interesting to see like overall in the future, what the FDA does with this kind of information. And the same way, Chris, you asked about ODAC's for accelerated approval. It's possible that FDA might take a look at this label setting. We'll have to see what the FDA does with this information. But to us, that leads to the next sort of very natural question you're going to ask, CJ, about really bringing in a chemo-containing regimen where there is BEMPEG plus pembro plus chemo. Because the reality is a chemo-containing I-O regimen is given to 2/3 of lung cancer patients, right? Each of those sub-groups is approximately 1/3 of the total epidemiology in lung cancer. So roughly 2/3 of the patients, less than 1% in the 1% to 49% get a pembro plus chemo regimen. So it really makes a lot of strategic sense for us, right, to bring in BEMPEG into that setting, the same way we brought it in, into the chemo-sparing component. And so we have kind of opened that element of the study, and we're kicking those cohorts off. But we did start -- you're absolutely right, we started off in front in PROPEL, in the chemo-sparing kind of cohorts, so they're much further ahead than the chemo-containing ones. Those are just getting underway now. And then in terms of your last question, so the different kinds of clinical trials, right, they'd have to depend on how they're designed relative to the patient population you're studying and comparing to this. So you basically have 2 different standard of cares. So in the chemo sparing, it's a different population than it is than in a chemo containing. So while you could design an exotic mega study with the most simple kinds of -- it's probably much simpler to have actually different registrational programs. And an example of that is you could look at Merck. So Merck has done a really nice job with that in their combination studies with LENVIMA, right? So they have chemo-sparing pembro plus LENVIMA trial in first-line non-small cell lung cancer that's due to read out soon. And then roughly 2 years behind that, they have a chemo-pembro-LENVIMA trial, right? So it makes a little bit more sense.

Great to hear that we won't have to wait for that for a registrational study of the doublet. So the head and neck study that you started with SFJ in collaboration with Merck is another interesting opportunity. Can you remind us a little bit of -- when you have that interim analysis, is this possible that at that point, would there be potential for an accelerated approval?

Yes. So the first thing is that the study that we're doing, just to remind you, it's a Phase II/III where BEMPEG plus pembro is combined in a doublet versus pembro in first-line patients with metastatic or unresectable recurrent squamous cell carcinoma. And all the patients here are going to PD-L1 positive, so all patients with PD-L1 greater than or equal to 1. Now the study is really going well, as I described earlier, in terms of getting underway. We have added a number of discussions, working with all of the different clinical collaborators as well as SFJ, our partner. We've had multiple meetings working on and completing all the preparatory activities from the protocol to all of the different sites, the site selection. And we're very excited that this study is going to get underway before the end of the year. Now just to really simply answer your question, so at that Phase II/III period, it's really an ORR assessment focused on futility analysis.

So from a structural standpoint, and here, I'll tap into Gil a little bit, just trying to think about resources. You've had a golden goose with the Bristol Payment for a long time. There's a whole bunch of potential opportunities here. There's potential registrational filing with some milestone payments that could come to the floor over the next 12 to 24 months, the structure around the relationship, how you structured SFJ. Gil, can you just talk to us about balance sheet mapping out where we see some potential for some inflows? And then maybe how you're thinking about potentially allocating that across either internal pipeline versus exploring external opportunities as well?

Yes. Great, Chris. Happy to do that. I think first to come, maybe some thinking behind the SFJ partnership that we had. And you're right, it really had a number of components for us that gave us both financial and operational leverage. We were particularly pleased to see SFJ's financial sponsors, Abingworth and Blackstone Life Sciences, put the $150 million fully at risk behind the success of the BEMPEG program. So that was an important element and a real vote of confidence for the program. And I think equally important to our calculus in this partnership was that SFJ really brings quite a remarkable track record of oncology to the partnership. Over the last 10 years, 7 of 9 partnerships have been successful and have led to FDA approval. So when we looked across the various partners and ways to get leverage here, we have both had a blue chip financial backer and also a party that's been very, very successful in executing these studies, which was extraordinarily important to us. And when you look also at the financial structure, it's a very attractive cost of capital when you really dig into it. We wouldn't even begin to make success payments until about the 2025 time frame when the head and neck study is completed. And even then, the payments are spread over a 5- to 7-year period. And there's also another important feature of the deal for us in that we have the flexibility to buy out these multiyear payment streams based on what we think is a very attractive discount rate. We've agreed with SFJ not to disclose the buyout terms. But when you look at other publicly disclosed deals, they're in the 5% to 6% range. So you can imagine that our buyout arrangement is much more attractive. So it gives us a lot of flexibility in the future financially. And you're right, Chris. We do have a very large stream of milestones coming in from BMS, so about $1.4 billion associated with the first 4 approvals and launches of BEMPEG. And of course, we've retained significant economics in the BEMPEG deal. But when we look out on the horizon for where we're going to invest going forward, I think one of our first priorities is going to go -- just to what JZ was talking about earlier and all the opportunities we have for BEMPEG and lung cancer. And I also think we're going to look for franchise consolidation around BEMPEG and other indications and with other synergistic combinations. I think there's a lot of possibilities out there for us. And probably equally important, we plan to invest heavily in our IL-15 program, NKTR-255, which is showing a lot of early promise in both hematological and solid tumor settings. So I think it's very possible, the way the time line is going to roll out with that program is it may well coincide with our plans to kick off registrational studies based on Phase II data. So that will help us fund a very broad program there as well. And of course, we'll continue to build the pipeline. And JZ and his very smart scientists, will continue with many, many great ideas, both internally. And I think you'll also see us look to externalization opportunities in the future to add to the pipeline.

Great. With 5 minutes left, you did mention -- let's talk 255. Wholly owned, we love that, right? And you've started to talk about some of the Phase I trial data. But we do have some upcoming data readouts. Perhaps you can remind us. I think we have monotherapy escalation readout. Is that later this year 2021? And there's obviously other opportunities as well. Thinking about combinations. I think the combination with cetuximab has already gotten underway. Give us a sense for how that's progressing, when we're going to learn about that.

Yes. Sure. So we have 2 ongoing Phase I/II clinical studies going on for NKTR-255. One of them is in solid tumors, the other is in heme tumors. So let me just kind of quickly remind you of what they are. In the heme space we're evaluating right now 255 in the monotherapy dose escalation. And in this portion of the study, we're including patients that have either multiple myeloma or non-Hodgkin's lymphoma. We're also bringing in patients that are post CAR-T. Very unique trial design, Chris, that we're allowing patients that are CAR-T failures to enter into the study as well. So it's a very unique patient population. And so we've been dose escalating. We're through multiple dose levels, and we've presented already some data at SITC last year, where we showed a couple of examples of unique insights. So First, we showed very clear target engagement, huge pharmacodynamic increase in natural killer cells. And we've also shown that it's not just the number of natural killer cells that increases, they're proliferative and they express markers associated with NK function, which is markers of degranulation and in additional markers that we look forward to disclosing more later this year that are really, really indicative of their activated state. We also saw evidence in the post-CAR-T setting, where we looked at a patient that we presented at SITC that they were 4 months prior to their previous CAR-T treatment, and this patient had progressed on CAR-T. And after the patient went into [ D5 in just a ] few cycles, the total amount of CAR-T cells elevated. So we've basically recovered, in a very good proportion, roughly 50% to 60% of the CAR-T cells in this patient 4 months after their prior therapy. But even more interesting is that we changed the proportion of CD8 to CD4 cells in the CAR-T population. So this patient, when they entered the study, they had about 70% CD4 CAR-Ts and about 30% CD8s. And of course, CD8s are the most cytotoxic, right? But after going on to 255, it flipped. It was 70-30, but now 70% CD8 T cells. So both the total number of CARs and the proportionality of CD8s increased in the fraction. So we'll be looking to present some additional data from the heme study later this year. One of our additional goals in that study is, as we identify a recommended Phase II dose, then this study moves into a range or parallel cohorts. So some cohorts continue to evaluate monotherapy 255. Other cohorts in multiple myeloma evaluate a combination with daratumumab. And other cohorts in NHL evaluate the combination with rituximab. So as soon as we hit the RP2D and the dose escalation, we'll open those cohorts. Now in parallel, we're running a study in solid tumors. We're right out of the gate, we're in the doublet combining NKTR-255 with cetuximab. And we're treating patients that are really quite advanced, patients that have colorectal CRC or patients that have head and neck but in very late-line kind of a setting. As you know, cetuximab, especially as a monotherapy, I think it isn't even used in this kind of setting. But we have so much preclinical data demonstrating how NKTR-255 potentiates the ADCC mechanism of antibodies like cetuximab, that we are really moving very, very aggressively into this study and into these patient populations. So we also look forward to presenting some data from the early cohorts from that study as well later this year.

There's -- we're right up against our time. There's actually so much more that we can cover. I'll try to behave. I'm not BEMPEG obsessed, I'm just disorganized. But that's okay, because we always actually love listening to you, JZ. And I think there's a lot to discuss as well for 358 ultimately from another conversation. Whisper in my ear, so that now that Lilly has all this Alzheimer's like money coming their way, are they going to accelerate stuff with you guys on 358?

Well, we know they're very, very excited about 358. They talk about that in multiple engagements. And I think you've seen the way they have invested in this program with so many Phase II studies going on in parallel. If you think about it, even a lot of times in a large pharma, they don't go so broad in Phase II, right? They do a little bit of a different signal-seeking approach. But here, we're going right out of the gate across 4 different Phase II indications, 2 of which are open and enrolling and the other 2 are around the corner. So I think it's definitely -- it's a big signal, right, of their interest, and how important a resolution therapeutic is to their overall technology strategy.

Yes. No, a whole stick and a whole another 40-minute conversation. Clearly, the opportunity is in all those autoimmune diseases. Lupus was interesting with some data last year. So I'll just get you online live, Jennifer to promise me that we'll get another opportunity with investors to spend some time focusing there, and we'll try not to make it all about BEMPEG. But thank you very much. Really appreciate you joining us for this. Hopefully, it will be live and in person the next time that we speak and connect. But we really appreciate your insights and comments, all of you. Thank you so much.

Great. Thanks, Chris. Thanks, CJ. Bye.

Bye.