Nektar Therapeutics (NKTR) Earnings Call Transcript & Summary

Great. Good afternoon, everyone. My name is Jess Fye. I'm one of the senior biotech analysts at JPMorgan. And we're continuing the health care conference today with Nektar Therapeutics. I'm joined by the company's CEO, Howard Robin. And unlike typically at the conference where we would go across the hall for question and answers, this session is going to move seamlessly into a Q&A session once Howard is done with the presentation. And if you use the blue ask-the-question button online, you can send questions to me via the portal, and I can ask them to management in our virtual breakout session. So with that, let me pass it over to Howard.

Okay. Thank you, Jessica, for inviting us to speak again at the JPMorgan Healthcare Conference and kick off the New Year. Before I get started, I will show you a slide on forward-looking statements. So please go to the next slide. And I'm going to be making some forward-looking statements today, and I refer you to our last 10-Q filing for more information. So please move to Slide 3. Next slide, please. So if you're looking at the therapeutic areas where we're working, the breadth of our pipeline, I'm very proud of how our company has built such a focused pipeline from a platform of immune science. And this is a pipeline with a large number of clinical trials ongoing in the areas of immuno-oncology, immunology, and virology. And today, I'm going to focus on the important work we've accomplished in the area of cytokine therapeutics and starting here on the next slide, #4. Next slide, please. So Nektar is the leader in the development of medicines in the cytokine field. With IL-2, we have worked to harness multiple components of the IL-2 pathway. First with BEMPEG, which captures the immune-activating potential of the IL-2 pathway; and then with NKTR-358, which captures the immune regulating potential of the IL-2 pathway. So taking this important and versatile modulating cytokine and engineering design approaches to harness its significant potential to help cancer patients and also those with autoimmune conditions. We are now also highly focused on IL-15, which is a pathway that has enabled us to stimulate the immune system with NK cell proliferation and T-cell stimulation which, through the NK cell mechanism, has broad potential in hematological malignancies as well as solid tumors. And I'm going to start with BEMPEG on Slide 5. So next slide, please. So to start, let's focus on our most advanced program, which is BEMPEG, which causes a proliferation of effector T-cells and where we've shown its capacity to both increase lymphocyte production in patients, in particular, tumor-infiltrating lymphocytes, and where we've also been able to see that BEMPEG increases PD-1 expression, very important. And now we'll show you how we've designed BEMPEG to be unique in this field. So please go to next Slide 6. What is so unique about BEMPEG? I just said that. First, we could think -- I think we all agree, that the IL-2 pathway is exceptionally important. The IL-2 biological pathway has 3 receptor subunits; alpha, beta, and gamma. And what we've done with BEMPEG is really quite novel by preferentially signaling to the dimeric beta-gamma portion of IL-2, which stimulates the growth of T-cells and natural killer cells needed to attack cancer. However, without overactivating the alpha portion of the pathway that can lead to down-regulation of the immune system and, of course, significant side effects. Now we're really the pioneers in this field, and based on our scientific work, we concluded that it was very important to retain some small amount of transient binding to the alpha receptor, and that's so you can enhance the priming in the lymph nodes. The other advantage of BEMPEG is that it's a prodrug. And the prodrug design means that we have designed it to avoid the risk of overactivation of the IL-2 pathway, which we know can result in cytokine storm issues. And lastly, I think a very unique advantage is that BEMPEG could be given on an antibody-like dosing schedule, in fact, once every 3 weeks in an outpatient setting, and we're very pleased with that, particularly when our goal is to combine with checkpoint inhibitors, where the dosing schedules can work easily together. So let me show you how the development program for BEMPEG looks on the next slide, Slide 7, please. So here is the very broad program that we have running right now with all of our clinical work on BEMPEG. As you know, this is a broad-based mechanism. And since we are designed to combine with PD-L1 agents like OPDIVO and KEYTRUDA, we've taken an approach that looks at the solid tumor setting, where we see approvals for these agents and a clear development path in combination with BEMPEG. So I want to focus for a moment the significant list of registrational trials that we have underway with BEMPEG plus OPDIVO, and that would be on the next slide, Slide #8. Shown here, we have a total of 5 registrational trials that are in progress, 2 new ones which recently started, and 3 studies that have been ongoing for the past year or so that position us to have potential data readouts in the next 12 to 18 months. And these are melanoma, renal cell carcinoma, and cis-ineligible bladder cancer. And I'd like to show you what this means in terms of data timelines as well as the opportunities ahead. So let's go to Slide 9, which is the next slide. You can see that over the next 12 months, we are expecting some key data readouts from metastatic melanoma Phase III study, the RCC study, and the study in cis-ineligible bladder cancer patients. And when you look at the opportunity here, as we combine BEMPEG with PD-1 inhibitors in these tumor settings, it's clearly significant. 2020 sales of PD-1s in these tumor types were in excess of $5 billion. So we're very excited to have a program that positions BEMPEG with a market-leading mechanism. And if our studies are successful, we have the opportunity to capture significant value at BEMPEG. And I'd like to show you some of the data that has driven the excitement for BEMPEG. So let's move on to Slide 10. So this is the data that we showed at the 2020 SITC just last November, and this is a cohort of patients with first-line Stage IV metastatic melanoma. Now this data is all centrally read radiology review, not investigator-assessed. So I think it's very important to point that out. And I think this is a very good indicator of the potential of BEMPEG in melanoma and the importance of this type of mechanism in general. So if you look at this data, which we presented at SITC, you can see that 34% of the patients had a complete response. And you can recall that this data led to a breakthrough designation for the doublet in 2019. In addition to the 34% complete response, we had 47%, almost half of the patients, who experienced a 100% reduction in target lesions. And that translates into an overall 78.5% median reduction in target lesions for all patients in the group. Very notable when you look at historical single-agent nivo in the published literature, where the median depth of response was about 35% and even ipi/nivo doublet, where the median depth of response was about 52%. This was 78.5%. In patients that had good prognosis such as those -- or excuse me, patients who had a poor prognosis, such as those with liver mets, we saw 50% of those patients experience complete responses. So 50% of the patients who had a poor prognosis, liver mets had complete responses, a dramatic depth in these more heavily metastatic and difficult-to-treat patients. In fact, 90% of the patients who responded went on to experiencing a 100% reduction in their RECIST target lesions. Very notable and really great news for these melanoma patients. And now I want to show you why we think depth of response is so important in melanoma. So let's move to the next slide, which is Slide 11. If you remember at ASCO in 2019, the FDA presented meta data where they looked at melanoma, and they looked at how depth of response correlates with PFS and survival for both TKI therapies and IO therapies in this metastatic setting. And they found that if you can get to a 76% or greater depth of response, and this is highlighted here on the right side of the graph, you have a very high likelihood that's translating into better PFS and ultimately better overall survival. And I'd like to show you how we did on PFS. So next slide, which is 12. So if we -- if you look at the depth of response we observed and how do they convert to PFS, well here -- shown here is the median PFS for this cohort, and you can see that at a follow-up time point of 29 months, we had a median PFS of 30.9 months. This is an extraordinarily high PFS in this first-line setting, and we're very happy again for the patients and their families that were in this study. Now a year ago, when I was presenting at this very same conference, we certainly expected that we could exceed 20 months PFS and I think I even said that. So 30.9 months PFS is really notable and I think extremely important. And I'd like to show you how we sort of stacked up against other IO therapies in this same setting. So please go to Slide 13. Shown here our current standards of care regimens of first-line and the PFS for single-agent nivolumab which is actually the comparator in our Phase III study, which has a 6.9-month PFS. And even another standard of care, ipi plus nivo, which demonstrated a median PFS of 11.5 months in the checkpoint 067 study, compare that to BEMPEG's 30.9 months. Based on this, we remain very optimistic that BEMPEG will deliver a strong Phase III data that is very differentiated. And that BEMPEG will have the potential to become an important part of the future standard of care of first-line melanoma. Now this is in addition to a very large program with BMS for BEMPEG plus nivo, we're running the PROPEL study. So in addition to everything we're doing here with nivolumab, we are running the PROPEL study, and I want to show you that on the next slide, Slide 14. So here's the PROPEL study, which is looking at BEMPEG plus PEMBRO in patients with first-line non-small cell lung cancer. This study has really progressed well. And our enrollment is well ahead of schedule with a high number of patients enrolled recently in November and December. So we're close to enrolling the study completely now. And our objective here is to demonstrate that we can enhance efficacy of single-agent PEMBRO and see a positive ORR signal here as compared to the historical rates of PEMBRO, and we'll look at this by PD-L1 subgroup. And of course, the data will inform a future potential Phase III registrational study. In particular, the less than 1% data generated in PROPEL will be extremely informative. And as you know, we have seen conversion of PD-L1 negative patients to PD-L1 positive in other tumors, and this is what we really hope to see -- we really do hope to see a similar phenomenon in the PROPEL study. And importantly, we now expect to report on the full cohort of 60 or so patients in the second half of this year. So the study is moving along very well, almost fully enrolled, and we will have data on that study this year. So very, very exciting. Now I'd like to shift gears and talk about our IL-15 program on the next slide, that's Slide 15. Our IL-15 program, known as NKTR-255, is our second major IO cytokine program with a broad-based mechanism of immune stimulation. And IL-15 is an immune-stimulating mechanism that we believe could become extremely important in IO, and I think a lot of people feel that way. And why is IL-15 so important? Well, it causes the proliferation of natural killer cells and the expansion of CD8 T-cells and memory cells. So there's certainly increasing interest in the area of NK cells because of the potential to combine with ADCC antibodies. And I'd like to show you how this works on Slide 16. So please go to the next slide. So if you think about it, one of the problems with these wonderful drugs, these great drugs, ADCC antibodies, RITUXAN, Erbitux, dara. They're all fantastic drugs, but they deplete NK cells. And as they deplete NK cells, they stop working. So if you can combine a drug like IL-15, NKTR-255, that enhances the proliferation of NK cells. Combine that mechanism with an ADCC antibody, you should have a very, very profound effect. And I'm going to talk about what we're doing here in a moment. Also if you look at the bottom of this slide, in the area of cell therapy, we know that CAR-T is also very effective for some patients. But this could also be a relatively short period of time. As we look at the characteristics of patients who do best, there's been an observation that levels of IL-15 are higher in those patients with durable responses to these cell therapies. So by adding IL-15, you should be able to get a much better durable duration of response with these cell therapy approaches. And -- so how are we doing this and how are we different in the field of IL-15, and I want to show you that on the next slide, which is Slide 17. So we've taken an approach of pegylating IL-15 to preserve the full biology of IL-15. And we know that others approaches in this area, such as muteins and fusions approaches, shown here on the right, they don't preserve the full biology. In particular, we know that our approach can fully engage by IL-15 receptor for a longer period of time. I'm going to show you our effect on proliferation of NK cells that we've already seen in the first patients enrolled in our clinical study. Our goal with preserving the full IL-15 biology was to ensure that we're getting high levels of intracellular granzyme B secretion to support the tumor cell killing abilities of the NK cells. So we can achieve the same levels of -- as native IL-15, but with longer PK and longer engagement of the IL-15 receptor. In fact, we still achieve -- we're achieving engagement of 95% of these receptors after 3 days -- still after 3 days. So now let's look at NK cell proliferation with NKTR-255 on the next slide, Slide 18. So here are the mean increases in a cell numbers in the first patients enrolled in the initial 2 dose cohorts of our clinical study being conducted in heme malignancies. Now this is NKTR-255 as a single agent in patients with either relapsed or refractory multiple myeloma and Non-Hodgkin's Lymphoma. And as you can see from this graph, we show a clear dose-dependent response in the first 2 dose cohorts, in dose escalation, and this is the increase after the patient's first dose of therapy. And you could see that we are increasing the average number of NK cells in these patients. We also saw that NKTR-255 also did NK cell proliferation and CD8 T-cell proliferation, which continued over multiple subsequent doses. So very, very exciting. And I want to talk to you next about the early clinical strategy with NKTR-255. So please go to Slide 19. So what we're doing in the clinic with NKTR-255? Well, as I just stated, we're pursuing a clinical study in hematological malignancies and relapsed/refractory patients with multiple myeloma and Non-Hodgkin's Lymphoma. We plan to combine NKTR-255 with 2 very important ADCCs, rituximab and dara, in the second part of this study. We have a collaboration with Janssen for them to supply us with dara for a portion of this study. And we also recently started a study in solid tumors, notably head and neck cancer and colorectal cancer, combining with cetuximab in these relapsed settings. And as you know, cetuximab has a very low response rate, about 10% or 15%, in these patients. So we hope to improve upon that with the addition of NKTR-255. So we really have an agent here that can be used in both liquid and solid tumors, and we know that we're increasing NK cell levels in a meaningful way. We also have an approach that can allow us to build a dose regimen with these antibodies. And I'm going to share with you now some of the very early clinical data with NKTR-255 if you move on to Slide 20. So next slide, please. So here are a few case studies for patients that were ones enrolled in the studies on the very first cohort of NKTR-255 in the liquid tumor study. Here, you can see the early encouraging signs of activity with this agent. Both of these patients shown here were on for many cycles of single-agent NKTR-255 given every 3 weeks where their disease progression held at bay. The patient on the left is the first multiple myeloma patient enrolled in the study at the 1.5 mg per kg dose, and this patient has been treated with all the novel agents that we currently have available and entered the study as a fourth line patient. And you could see on the right hand side of the graph for that patient. If you pay particular attention to the kappa like chain markers, which is a measure of disease, you can see from baseline up until cycle 4, the patient was responding in stable disease through 9 cycles is something un -- fairly unprecedented for a patient with heavily pretreated multiple myeloma. The scan on the right are for the second patient enrolled in the study who had DLBCL also at the 1.5 mg per kg dose, and the patient experienced a metabolic response in the index lesion in the spleen, and notably, this was a response to NKTR-255 monotherapy treatment. So again, just the first patients enrolled in the initial dose cohort and those -- in the dose-escalation, and we see early signs of activity. So we're very excited of the potential of NKTR-255 and we look forward to advancing this program in the clinic this year. Now I'm going to switch gears and discuss the immune regulation approach we took with the cytokine IL-2. If you go to the next slide, Slide 21. So this program is NKTR-358. It is really the polar opposite of BEMPEG's mechanism. Instead of stimulating cytotoxic T-cells, NKTR-358 is designed to induce regulatory T-cells by biasing to the trimeric IL-2 receptor. And I'll show you the mechanism on the next slide. So please go to Slide 22. This is a schematic of the novel biology that we're unlocking with NKTR-358. We have selective binding in the high affinity trimeric IL-2 receptor to stimulate production and function of T regulatory cells. And this really could be a novel treatment approach for autoimmune disorders, and it could be a resolution therapeutic that resolves and restores the normal functioning of a patient's immune system without broad-based immunosuppression, which is a problem in patients with autoimmune and inflammatory conditions. This important program is being developed with our partner, Eli Lilly, and in fact, this is actually their slide that they provided to us. This year, we completed several early studies, and the program has expanded considerably. And in our early studies, we have been able to achieve a peak 15-fold increase in CD25bright Tregs that was highly dose-dependent. Now I'd like to show you a piece of the data from that study in lupus patients on the next slide, Slide 23, please. So shown here are the data from our multiple ascending dose study in lupus patients. Now this study was not designed to show clinical benefit. It was designed to help us choose doses for Phase II. But what we're really excited about is the CLASI-A score results, and it's a score that measures the skin manifestations of lupus. And when we look at 22 patients across all the dose cohorts that came in with moderate scores of 4 or higher, and the scores were in a large range, but we see a dose-dependent drop in the average scores in these patients. And this helps us understand the dose-dependent stimulation of T regulatory cells, and how it could potentially correlate to improvement of disease. Now 7 of the 18 patients who are on the drug treatment arms had score drops of 4 or more. So it's exciting to see this that we can achieve this with NKTR-358. And these data has led Lilly to launching a Phase II study in lupus patients and expanding the program considerably, which I'll show you on the next slide. So please go to Slide 24. Now you could see on the table that our partner, Lilly, has taken over the development of NKTR-358. They're running the program now all the way through registrational trials. Just to remind you of the economics, it was $150 million upfront. There is a $250 million in development milestones and the maximum share -- cost share to us is 25% Nektar, 75% Lilly. Our agreement has significant double-digit royalties in the mid-teens and low 20s, and we have the option to co-promote as well. And with the broad mechanism of NKTR-358 edge potential in a number of autoimmune and inflammatory conditions, we're really truly excited about how large an opportunity this could be. And again, shown here, these are the studies that are currently underway. We have a 280 patient Phase II study in patients with lupus, 200-patient Phase II studies that is opening now in ulcerative colitis, and 2 Phase Ib studies in psoriasis and atopic dermatitis. So we're really poised to have a steady stream of data coming from these studies in the future. We're pleased with the thoughtful and comprehensive approach that Lilly is taking with this molecule. We expect there will be several more Phase II studies in the works as well. So I'd like to now summarize quickly what to expect over the next 18 months on our last slide. So please go to Slide 25. So here are the milestones for the next 18-month period for Nektar. We ended 2020 with $1.2 billion in cash and equivalents. For BEMPEG, we have 60 patients or more data set across all PD-L1 expression cohorts from PROPEL for the BEMPEG plus PEMBRO doublet and we expect this to be relatively mature data in the second half of 2021, second half of this year, which hopefully could lead us to a decision to move into Phase III in non-small cell lung cancer. For the BEMPEG plus nivo studies, as I showed you earlier, the first potential data from the Phase III study in metastatic melanoma, also from the Phase III study in renal cell carcinoma and the Phase II study in cis- ineligible bladder cancer in low PD-L1 expressing patients should come over the next 18-month period. These studies have positive, hopefully, lead to a path to launch BEMPEG and allow Nektar to begin driving real value from this program. For NKTR-255, we should have early clinical data from the 2 Phase I/II studies in liquid tumors and in solid tumors. And lastly, with NKTR-358, we expect our partner, Lilly, to present the data from the psoriasis and atopic dermatitis studies at a major medical meeting. We also expect that in the first half of next year, they'll start a third Phase II study in an additional autoimmune setting, which has not yet been disclosed. So I think this is an outstanding portfolio of important clinical studies with data readouts and very large indications over this year and next. We've made major progress in our invention of novel medicines, which have the potential to greatly help patients fighting cancer and autoimmune disease. And so we're very excited about where we are today. And I also want to thank all of our employees for doing such a fantastic job this year, especially in light of all the COVID lockdowns and COVID crisis we're facing. Everybody has just done a spectacular job, and I want to thank them for it. So I'd like to thank all of you for listening. And with that, I'll stop my presentation. I think Jessica will now lead us and our key members of our executive team in a Q&A discussion. Thank you.

Great. Thanks, Howard, and we'll give just a second for everyone's video to come back online. Okay. Great. [Operator Instructions] We do have 1 so far which is with the PROPEL update not coming to the back half of the year, what's in the abstract -- what's the abstract for World Lung going to be now?

So I will -- I would -- let's have JZ answer that question.

Hello, everyone, and thank you for the question, Jessica. So one of the important things that we've noted is constellation of 2 things happening at the very end of last year. So the first is that our investigators working on the study had a very, very great amount of enthusiasm. And that, coupled with the fact that COVID started to wane, particularly in Europe, led to a very rapid enrollment, particularly in the last quarter of last year. And so even though earlier, we had talked about targeting roughly 30 patients worth of data that we were targeting to present, we've now almost completely enrolled that entire study, as Howard described earlier. And so that puts us in a great position to be able to report data on a much, much larger, and a much more mature data set. And of course, if you remember the way that trial is designed, there are 3 subgroups; PD-L1 low, PD-L1 to 49, and a PDL greater than 50. And now we're looking forward to reporting data on approximately 60 patients across the cohorts with a relatively mature data set of 2 scans or more for each of those patients. Now you asked a very provocative question. We haven't given guidance on which conference we would be targeting at the end of the year -- the second half, I mean, of the year. But what we will do is we'll provide additional information on that as we get closer to that event.

Okay, great. But we should expect that PROPEL update to come at a medical conference as opposed to a press release?

Yes, we would target a medical conference. It's much more appropriate venue for this data.

Okay.

Jess, this is Gil. I just wanted to clarify that the trial -- the World Lung presentation will be a trials in progress poster. So that will be the data presentation. It was moved from the fall to earlier this year. So that will just be a trials in progress for PROPEL.

Okay. Got it. And can you elaborate on what response rates you would want to see in each of those PD-L1 expression groups and PROPEL to get you confident, you have a signal worth pursuing in Phase III?

JZ, you want to follow-up with that?

Sure. Yes, yes, no problem. So one of the really important features of PROPEL is that it's designed to help inform us of a potential to moving beyond the Phase II PROPEL study into a registrational Phase III study in first-line non-small cell lung cancer. Now what's important is that we've designed the study to sample of the 3 main subgroups of PD-L1 positivity that's studied in this tumor type. So we have a subgroup of PD-L less than 1% as the low subgroup and intermediate of 1 to 49 and then the high of greater than 50%. And then we're able to use information from the performance historically at single-agent PEMBRO in those different tumor types. So for example, for the less than 1% PEMBRO, it's a single agent, the early response rate data gives it about a 7% to 8% performance in that subgroup. For the intermediate data from KEYNOTE-042 demonstrated that the efficacy was about 17% for single-agent PEMBRO in the intermediate. And now we expect a 40% to 45% efficacy rate in the greater than 50%. Now what's really important about the design of the study is that it lets us focus on those different subgroups. And in particular, when we look at the 2 lower subgroups such as the less than 1 and the 1 to 49, there, we know the performance of PEMBRO is a little bit worse than it is in the greater than 50. So we can always look in a very close detail into that subgroup for the effect size and magnitude and numeric kind of differences. So for example, Jess, if we see, like, say, doubling of a response rate in the PD-L less than 1 or 1 to 49, that would give us very high confidence that the mechanism of action of BEMPEG, adding the immunological components of the immunotherapy combined with PEMBRO is really giving a very robust signal of activity. So those are the kinds of ranges of efficacy targets and thresholds that we would be looking for.

Okay. Great. We've got another investor question here. It says Nektar is clearly the most advanced company within the next-gen IL-2 landscape. But can you provide commentary on the emerging IL-2 programs, for example, THOR-707, Zilio, Werewolf, et cetera, and how you expect them to be positioned relative in that competitive landscape down the road?

Well, look, I'll let JZ answer the technical side of that. I can tell you that and as I described in my presentation, why we think our approach to IL-2, a biased approach, is very important. And I think, look, we're certainly much more advanced, and I believe we have the best molecule. And in addition to being a biased molecule, it's also a prodrug. So I can think of a lot of reasons why BEMPEG is the best choice in -- as an IL-2 therapy. I'll let JZ comment on some of the more technical aspects of comparing BEMPEG to those other molecules.

Yes. Thank you, Howard. I mean we certainly have the pole position in this case. So we were the first company that really brought back the scientific interest in the cytokine space. And we showed the impact that our polymer chemistry platform can have on the biology of these molecules. And it really unlocked their pharmacological potential and that's really well evidenced in what Howard presented today with almost the armada of registrational studies that are reading out within the next 12 to 18 months, as we described. Now in terms of some of the unique sort of biological features, we're very, very confident in what you need to get out of IL-2 signaling in order to engage the lymphocyte immune system cause the consistent and continuous proliferation of the immune cells that you need to add that -- really that extra powerful kick to the immunotherapy when combining with a checkpoint inhibitor such as nivolumab or pembrolizumab. It also is important to note that really, again, so we presented so much more data than any of these other companies. I mean there's really opacity of data from the other companies. So we really enjoy our forward position well in advance and are looking in the rearview mirror.

Okay. Great. Maybe turning to the Phase III trial in melanoma for BEMPEG, can you help us understand the communication around the ORR-based interim in that study? If the interim takes place, but it doesn't hit, would you communicate that to The Street? And if it does hit on the interim, would you stop the study or run it out for PFS? And just how would those scenarios work? I guess, could interim ORR data alone be a basis for approval?

Well, look, you know that, of course, we're running that study together with BMS and BMS is actually operationalizing that study. So of course, in terms of disclosures, we have to work closely with BMS to align on what the proper disclosure vehicle is. I would say though that the registration process is really a 2-step process. If we reach an interim ORR, we're going to evaluate a filing for accelerated approval based on that ORR and then follow-up by conversion to a full approval based on PFS. So I think we'll see how that looks. Now remember, for nivolumab in that study, the baseline response rate is 40%, so we want to see what we look like compared to that 40%. And that, together with the durable responses and an excellent safety profile, will be the final package that could get us to an accelerated approval based on ORR. Subsequent to that, if you look at PFS data, that would allow us to gain full approval and the benchmark for PFS data is 6 to 7 months PFS, which has been what has been observed with nivolumab as a single agent which we're comparing against, and as you noted and as you saw in the PIVOT-02 studies, we achieved 30.9 months. So I think anything that is a significant improvement over what I would expect to see with nivo alone should hopefully allow us to achieve a full approval. But the disclosure of that will come as a joint working effort between BMS and Nektar. And I really can't tell you exactly how we'll lay that out at this point.

Okay. Can you talk about your expectations for ORR and DoR in the pivotal trial for bladder cancer? What do you see as the bar in that setting?

JZ, you want to cover that?

Yes, sure. So we reached our enrollment goal last year for that study. And of course, the patients enrolled in that study have the ability to serve as a potential for accelerated approval in that indication. And the primary endpoints in that study are both ORR as well as duration of response. And here, we're looking at efficacy evaluated by independent central radiology, targeting about 110 patients with metastatic urothelial carcinoma with CPS score less than 10. So the hard to treat population. And the duration of response is a very critically important endpoint in this cis-ineligible patient population because this endpoint was the differentiating key factor that led to the accelerated approvals originally for the checkpoint inhibitors in the set, and that's when they compare themselves with the gemcitabine, carbo standard of care. And so for this study, we are looking to achieve a median follow-up for measuring duration of response of 18 months. And so this brings a timeline for the first data from that study to be next year, approximately in the middle of the year. And then what are the some of the bars that we're looking at for activity. So just like any accelerated approval, there's a totality of risk-benefit that's made against the appropriate standard of care in the setting at the time. And we will use the totality of the data to discuss with the FDA a possibility of AA filing. And that includes both the response rate -- the complete response rate, the duration of response, and all of those against the overall safety and tolerability profile because you know these patients being cis-ineligible, they are frail, right? And so the overall combination of risk and benefit is a very, very important feature. So we'll be using all of those when we discuss that with the FDA.

Okay. Great. Time for 1 more question, and there's no more coming in through the portal. So maybe switching to NKTR-262. Following the dose escalation data and selection of a recommended Phase II dose, what's the timeline to see data from the expansion cohorts for the REVEAL study that would include antitumor activity? And based on the escalation data, do you have any expectations for what range ORR could fall in?

So again, I'm going to ask JZ to cover that.

Yes. So we gave an update on dose escalation at SITC last year. We recently expanded the study to evaluate now the recommended Phase II dose of NKTR-262 combined with BEMPEG is a doublet or with BEMPEG plus nivolumab is a triplet. And we're setting that in approximately 24 relapsed/refractory melanoma patients in these regimen. So those cohorts are ongoing. Now in the dose-escalation phase, we observed very high levels of TLR activation in the tumor microenvironment. And we were able to characterize both the safety and target engagement for NKTR-262, both on its own before we dosed with BEMPEG and then after when we tested them as a combination. And we'll be benchmarking these results against other TLR agonists that have been studied in the same patient population. So we haven't provided a timeline yet for that data since we're still enrolling both cohorts, but we expect it to be roughly 12 to 18 months before we present data on those expansion cohorts for those doublet and triplet regimens.

Okay. Great. Thanks for that. It looks like we're out of time. So thanks, everyone, for tuning in, and thanks to the management team as well.

Thank you, Jessica. Thank you.

Thank you. Thanks, Jess.

Take care, everyone.