Ladies and gentlemen, thank you for standing by, and welcome to the Nektar Therapeutics Third Quarter 2020 Financial Results. [Operator Instructions]. I would now like to hand the conference over to your speaker today, Ms. Jennifer Ruddock, Head of Corporate Affairs. Ma'am, you may begin.

Thank you, Crystal. Good afternoon, everyone, and thank you for joining us today. With us on the call are Howard Robin, our President and CEO; Gil Labrucherie, our COO; Dr. Jonathan Zalevsky, our Head of Research and Development; and Dr. Wei Lin, our Head of Development. On today's call, we expect to make forward-looking statements regarding our business, including clinical trial enrollment and clinical trial results, timing and plans for future clinical trials, timing and plans for future clinical data presentations, the therapeutic potential of our drug candidates, outcomes and plans for health authority regulatory actions and decisions, estimates and predictions of the COVID-19 pandemic's impact on our business and clinical trials, financial guidance and certain other statements regarding the future of our business. Because these forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in the Form 10-Q that we filed on August 7, 2020, which is available at www.sec.gov. We undertake no obligation to update any of these forward-looking statements, whether as a result of new information, future developments or otherwise. A webcast replay of this call will be available on the IR page at Nektar's website at nektar.com. Before turning over the call to Howard, as we are all dialing in from separate locations, I will moderate the Q&A session for our team, so we can avoid technical issues during the session. We appreciate your patience as we work to ensure that there are no technology disruptions for all of those listening. With that said, I will hand the call over to our President and CEO, Howard Robin. Howard?

Thank you, Jennifer, and thank you to everyone for joining us on the call today. Over the past quarter, we've continued to advance our joint development program for bempeg with our partner, Bristol-Myers Squibb, including the start of 2 new studies in Q3, a phase III registrational study in adjuvant melanoma patients that Nektar is sponsoring and a new Phase I/II study that BMS is sponsoring, which expands the development of bempeg in renal cell carcinoma with a triplet regimen of bempeg plus nivo in combination with a TKI agent. The bempeg joint development program with BMS now has 6 separate studies ongoing for our lead cytokine candidate, including 5 registrational studies. The registrational program for bempeg collectively aims to benefit quite a large patient population across melanoma, renal cell carcinoma and bladder cancer. And this joint development program for bempeg plus nivo reflects a large investment into bempeg, and it underscores the excitement for how this unique and differentiated IL-2 agent may serve as an important backbone therapy with the checkpoint inhibitor, nivolumab, for the treatment of solid tumors. We're also advancing our development of bempeg with the checkpoint inhibitor pembrolizumab in the PROPEL study in non-small cell lung cancer, which is one of the largest solid tumor opportunities for bempeg. We are well ahead of our enrollment projections for the PROPEL study, and I'll let Wei share more about this program -- more about the progress that we've made in the program in that study in a moment. Next week at SITC, we will present several new data sets from our immune-oncology pipeline, including updated PIVOT-02 data for bempeg in melanoma with more than 30 months of follow-up for those patients as well as the first data for our NKTR-255 program, our IL-15 candidate. As you know, for…

Thank you, Howard. I'd like to review the progress and time lines for our bempeg registrational program, which includes 5 separate registrational studies designed to position bempeg as the standard of care in front-line metastatic and adjuvant settings in melanoma as well as the kidney cancer and bladder cancer. Let me begin with the first-line metastatic melanoma study, which has been run by our partner, BMS. This summer, BMS successfully restarted enrollment activities for the study in many countries. Since then, they have been able to bring more investigational sites online in effort to remedy time lost as a result of the COVID-19 pause. As Howard mentioned earlier, we have received a breakthrough therapy destination for bempeg plus nivo based on the high complete response rate we observed in the first-line melanoma population. In the Phase III study, we have 3 endpoints: overall response rate or ORR; progression-free survival or PFS; and overall survival, OS. The first readout will be an interim look comparing the ORR in the doublet arm of bempeg plus nivo to the ORR in the nivo monotherapy arm and will include about 2/3 of the patients in the study who have at least 6 months of follow-up. This endpoint was designed for a potential early accelerated approval submission for the doublet, which would enable us to bring this innovative therapy to patients more quickly if approved. The application for full approval of bempeg in the U.S. and in Europe will be based on PFS and OS. Because of our high complete response rate, many of you have asked whether we could use this as an endpoint for registration instead of ORR. After discussion with multiple global health authorities, BMS and Nektar have made the decision to leave the current protocol intact with existing endpoints. So this…

Thanks, Wei. Let me begin with a brief update on NKTR-358. Many autoimmune disorders, including systemic lupus, are associated with decreased Treg numbers, reduced Treg function and/or reduced production of interleukin-2. Treg deficiencies are important in the pathogenesis of these autoimmune diseases. With NKTR-358, our goal is to address these Treg abnormalities and to develop an IL-2-like molecule that could selectively stimulate Tregs in a more effective manner than native IL-2. At ACR yesterday, we shared new data from our Phase Ib study evaluating NKTR-358 in patients with mild-to-moderate lupus. And I'd like to call out a few key takeaways. As we reported at EULAR earlier in the year, NKTR-358 led to a selective, dose-dependent expansion of CD25 bright Tregs. This was maintained through multiple administrations. In the data yesterday, we showed that NKTR-358 resulted in dose-dependent and increased Treg activation markers and genes associated with Treg functionality. For the first time, we also reported on disease activity that was observed in patients treated with NKTR-358. The study enrolled patients with mild-to-moderate disease, and the patients only received 3 doses of NKTR-358. So it was very short in treatment duration. And in our analysis, we looked at a subset of patients who had moderate disease activity with CLASI-A activity scores that were greater than or equal to 4. In these patients, NKTR-358 led to a dose-dependent reduction in CLASI-A score from baseline. Notably, patients at all dose levels with NKTR-358 experienced a reduction in CLASI-A, while the placebo patients did not. And 7 of 18 patients had a 4 or more point score reduction by day 43 as compared to their baseline scores. And 1 patient, at the highest dose level of 24 micrograms per kilogram, experienced a reduction in CLASI-A score from 22 at baseline to 5 by day…

Great. Thank you, JZ, and good afternoon, everyone. On this call, I will review our 2020 financial guidance. Starting with our strong financial position, we ended the quarter with $1.2 billion in cash and investments and no debt on our balance sheet. We still plan to end 2020 with over $1 billion in cash and investments. Now turning to our annual financial guidance. Our full year 2020 GAAP revenue projection remains between $140 million and $145 million. This includes $50 million of milestone payments from BMS and $90 million to $95 million of royalties, product sales and other revenue. Under the BMS collaboration, we recognized a $25 million milestone for the start of the muscle-invasive bladder cancer study in Q1 and recognized a second $25 million milestone related to the start of the adjuvant melanoma study in Q2. For our GAAP R&D expense guidance, we now anticipate 2020 GAAP R&D expense will range between $415 million and $425 million, which includes approximately $60 million of noncash depreciation and stock compensation expense. This decrease in our R&D expense forecast is a result of a number of factors, including the timing of R&D expenditures for certain of our earlier-stage and non-oncology programs due to COVID, lower-than-projected noncash stock compensation and depreciation expense, and reduced travel and other costs due to the impact of the COVID-19 pandemic. Our G&A expense for 2020 is still projected to be between $105 million and $115 million, which includes approximately $45 million of noncash stock compensation and depreciation expense. Finally, due to the impact of the COVID-19 pandemic on the financial markets and lower-than-expected yields on our investment portfolio, we now project that interest income will be approximately $20 million for 2020. Importantly, we have not experienced any significant realized or unrealized losses on our portfolio of investments. We continue to closely manage our operating expenses and remain highly focused on the execution of our broad portfolio of research and development programs. And as I stated earlier, we still plan to end 2020 with over $1 billion in cash and investments. And with that, I'll open the call to questions. Operator?

[Operator Instructions]. Our first question comes from Peter Lawson from Barclays.

This is Waleed on for Peter. Just a question here on your PIVOT study in frontline melanoma, just how we should be thinking about the bar here for efficacy? What would be considered positive results in your pivotal data that could help support approval?

Thanks, Waleed [ph]. Wei, I'm going to ask you to answer that.

Yes, sure. I think the way we kind of look at this data is really looking at the control arm, which is the standard care right now is the nivolumab. And so our comparator is set up very well and it's well recognized worldwide and would serve as a basis for worldwide registration. So our registrational strategy really is -- it's a two step process. One is we're going to aim for accelerated approval based on ORR, and then followed by a full approval based on progression-free survival with subsequent supplement by overall survival. So it's really looking at these two benchmark numbers. So nivolumab in this setting, the baseline response rate is around 40%. So we would like to clear that with ORR. That's roughly 10% to 15% higher than response rate of nivolumab single agent. I think then we can demonstrate unequivocally in a statistically significant fashion that we have a superior response rate compared to nivolumab. So that, together with durable response and the safety profile, that will be the final package that will enable a third approval for -- based on ORR. Now subsequently, the progression-free survivor, PFS, which would allow us to gain full approval will be, not only a second shot at goal, but also a potential conversion if we were to gain third approval based on ORR. And that will be benchmarked against the 6 to 7 months PFS that's been observed historically for nivolumab in this setting. And so as many of you will recognize that we've been generally early-phase data in PIVOT-02 and specifically with regard to our melanoma cohort, the patients who were enrolled in that cohort have actually experienced fairly phenomenal benefit from the combination of bempeg plus nivolumab with. I think at the last prior earnings call, with even 21 months of follow-up, we have not reached the median progression-free survival. So at the upcoming SITC, we'll be providing even further update with longer follow-up. And so all of us are certainly very encouraged by the data from PIVOT-02. And if the Phase III registrational study were to be able to replicate the data from PIVOT-02, then we should have a fairly significant margin improvement in PFS compared with nivolumab single agent. And that would bring huge value in extension of survival for patients with first-line metastatic melanoma.

Our next question comes from Alexander Duncan from Piper Sandler.

One on bempeg and one on 255. So for bempeg, the recent uptake in PROPEL enrollment is great to see. Just curious to understand the dynamics here a little bit more if you can elaborate on that. Is this largely due to discontinuation of the nivo-bempeg trial? And secondly for the 255 monotherapy, dose escalation update at SITC, what safety signals are you paying particularly close attention to? And then whether or not you identify the MTD, how are you going to use the 255 monotherapy biomarker data to inform safe-dose selection to use with the combination cohorts? I guess my question here is what's your confidence that the combination of 255 and RITUXAN, for example, won't potentiate an adverse event such as infections and liver mets.

Thanks, Alex. Wei, I'm going to ask you to answer the first part of the question about the PROPEL study. And then, JZ, I'll ask you to take the second one.

Yes. Thanks. Yes. So PROPEL study, as you know, is a study that we hope that would actually engage registration study in first-line non-small cell lung cancer. And to that end, we're trying to generate data, currently with the doublet of bempeg plus pembrolizumab, building upon the foundation of pembrolizumab as the current standard care in PD-L1-positive patients. So the -- now the -- right now, with the COVID pandemic happening, everyone has experienced challenges in enrollment. And our study team has really navigated this extraordinarily well. As we have shared earlier in an earlier earnings call that with the PROPEL study, while we were planning to open the sites in both Europe as well as in the U.S., we had some challenges because the first wave of pandemic in Europe coincided with our plan to initiate the sites. But the -- we were very vigilant in both working with the sites, finding out the best time to open the sites. And while initially we had a delay in opening the sites in Europe, but as soon as the first wave of pandemic passed, we're able to get our sites up going, and the enrollment has been really, really brisk. I think that just reflects -- while pembro has really brought a huge improvement in overall survival for patients suffering from non-small cell lung cancer. Its benefit is still limited with monotherapy to about 2 years or so. So there's still a tremendous need for these patients for better improved therapy and especially for things that are chemo-sparring. And hence -- and that's reflected by how well this study has enrolled after we have gotten the sites in the U.S. and in Europe up and going. So we've seen a gradual improvement for the combination and also is reflecting the need that the doctor continues to see in spite of the pembro monotherapy being a wonderful established standard of care to really build upon that and really improve that and extending patient's life in its indications. So we're certainly enthused about the study, enthused about the data we're able to deliver next year and also the potential -- the data and evaluating the possibility of a Phase III to follow up on that data analysis.

Thanks, Wei. And Alex, thank you for the question. So regarding 255, so as you know, this is the first-in-human study. And in the dose escalation part, we're taking patients with pretty advanced disease, either non-Hodgkin's lymphoma or multiple myeloma and treating them with escalating doses of NKTR-255 delivered intravenously. Now what we're looking for in terms of the safety signals are things that both were informed from our preclinical toxicology and other studies but also what we know experience-wise from the groups of involvement in others that have also used IL-15 as an agent clinically. So we're looking for those same kinds of effects. We're studying key cytokine-related toxicities and adverse events. We're looking at secondary cytokines, which are essential because, of course, we expect IL-15 agonism of cells that express IL-15 receptor complexes to induce cytokine responses. And we're also studying the downstream cellular dynamics associated with IL-15. And as you know, it can have a lot of homeostatic effects. So you were asking if the MTD in the study has been reached, and it did not. We're still dose escalating. And we have a very rich biomarker program that we can use to inform dose selection. And this is, again, a page of the playbook that we played, for example, with bempeg where we have a lot of markers that assess the target engagement of IL-15 with its receptors. And you can assess that, both in the national killer cell compartment in terms of cellular response changes, activation, functional changes of the cells as well as their subsets as well as in the CD8 compartment, and then you can assess that both in the blood as well as in secondary tissues as well. So we use all of those things to inform our dose selection and give us a very, very clear confidence that we have engaged target or getting the kind of pharmacodynamic response that we want. So then when we identify a go-forward recommended Phase II dose for the expansion cohort, you're absolutely right. We're going to pay a lot of attention to what happens when we combine either of daratumumab or rituximab. And in that case, as you know, these are both antibodies that have an IgG1. There are also antibodies that are known to have something like a tumor lysis syndrome. It can be seen when you have a very rapid lysis of B cells, for example, with rituximab, when it clears them so quickly, with clearance either through the liver or through the spleen in the fixed tissue cells. So we'll be looking very closely at those things. We'll be looking very closely at the cellular changes and also monitoring the patients very, very closely to ensure that we're not seeing any kind of adverse events of the combination because, in fact, we try to do the exact opposite, which is substantially improve cell clearance not just in the blood compartments, but particularly in the secondary lymphoid compartments where these tumors reside.

And our next question comes from Jessica Fye from JPMorgan.

This is Daniel for Jessica Fye. Staying with 255, you stated that you're going in colorectal cancer in head and neck initially in solid tumors. Can you help us think about the opportunity of 255 in solid tumors? Why you're able to choose those 2 different tumor types? And then do you see combination as an ideal approach for this program as you advance it forward? Or is there an opportunity to evaluate it as a monotherapy as well?

Yes. Wei, I'm going to ask you to take that.

Sure. Yes. So we really see tremendous opportunity in solid tumors for -- in IL-2 agents like 255 because now monoclonal antibody has become the standard of care in cancer, in general, but both in heme and solid tumors. And in fact, one of the first-approved monoclonal antibody in any cancer type was Herceptin in HER2-positive breast cancer. So there's a long history, a tradition of monoclonal antibody analysis become well-established standard of care in many, many tumor types. And as we think about how to develop 255 within the solid tumor space, we really look at which are the indications where the usage of a monoclonal antibody still remain not in first line but in later line and whether standard of care is still -- leaves a lot of room for improvement. And that's what really threw us to really cetuximab in the indication of head and neck cancer as well as colorectal cancer. Specifically in head and neck cancer, for quite a while, cetuximab initially was approved as monotherapy in a late-line setting but eventually moved to the first-line setting based on the EXTREME trial. And then the regimen of cetuximab plus platinum chemotherapy plus 5-FU have become in standard of care in head and neck cancer in the first-line setting for quite a while until more recent times when pembrolizumab plus chemotherapy has improved upon that standard of care. And then -- so then the use of cetuximab had returned back to a later-line use monotherapy. And with that change, it creates an opportunity to really improve upon the late-line benefit that the cetuximab really brings. If you take a look in the late-line setting, cetuximab as monotherapy only has about a 15% response rate. And so that obviously leaves a lot of room for improvement. And…

And our next question comes from George Farmer from BMO Capital Markets.

Wei, can you comment a bit on what the bar for success would be in PROPEL? 30 patients that are basically going to be distributed among different PD-L1 subgroups, are you expecting to see any differences there? And I know 30 patients is a good number to hit, but it's spread across all these different subgroups. It might get a little thin per subgroup. And then, JZ, I know there was some discussion about this yesterday. But could you talk about the significance of the CLASI-A score and how that relates to SLEDAI score in lupus and how we can think about the 2 different scoring systems?

Thanks, George. Wei, do you want to?

Sure. Yes, I'll take the first part of the question. Yes. Thanks for that great question. So it's something we've thought a lot about because that the registrational goal decision is an important decision for development of any drug. For bempeg, in particular and for the PROPEL study, as you well know that the current standard of care really segments that population in the first-line metastatic non-small cell lung cancer population into 3 subgroups. And that's less than 1% of PD-L1 expression, 1% to 49% and 50% above. And then we have either early phase data or registrational data that we can use to benchmark against the historical numbers that pembrolizumab has in each of the subpopulations. So first of all, looking at the population of less than 1%, pembrolizumab as a single agent-based on the early phase data really had a response rate of 7% to 8%. So really in the single-digit range in the 5% to 10% range, and that's what we expect. Right? So that's a benchmark for that population of patients. For the 1% to 49%, the response rate is typically hovering around 17% or so from past trials, specifically KEYNOTE-042. And so we're really looking at a benchmark of pembrolizumab in that population patients of 1% to 49%, ranging about 15% to 20% response rate. And then finally, the benchmark for the 50% above PD-L1 expression subgroup, looking at data from KEYNOTE-024 as well as 42, we're looking at the numbers that are really in the 40% to 50% range. So that's the baseline response rate for monotherapy pembrolizumab. So I think to your point, because of these subgroups, we have -- when we do generate the 30-plus patient worth of data, we'd be looking at data by segmenting into each of these subgroups. And…

And JZ, do you want to take the CLASI-A versus SLEDAI question that...

Yes. George, thanks for the question. So you asked about the CLASI versus SLEDAI kind of how they're related. And so to start off with the CLASI is a score that specifically zeros in on the cutaneous manifestations of lupus disease, so really looking at the skin. It's not directly linked to the psoriasis SLEDAI, but we always use CLASI along with those other instruments because we use them to characterize lupus patients. But there is one important connection, and remember, lupus patients are characterized by their secondary organ involvement, and the SLEDAI as well as BILAG, they both take into account the additional accessory tissues. And since these are multicomponent scales, you get scoring ranging of everything from the presence or absence of autoantibodies to the presence or absence of secondary organ involvement and then the subcutaneous lupus that will contribute to the SLEDAI score. So there is a level of relationship. Now we really focused in on it because we know that there is a really good long-standing biology about Tregs and Treg action, particularly in the skin. You know that with Lilly, we are currently in the process of 2 Phase Ib studies that focus on dermal application, right? So there, we're treating patients in 1 study with atopic dermatitis; and in another study, we're treating patients with psoriasis. And even if you remember from David's presentation yesterday, he showed that low-dose IL-2 showed quite a bit of efficacy in patients with psoriasis and other skin diseases because he showed that large table of phenotypes of patients treated in TRANSREG study. So really, we're both extremely excited and encouraged that we saw dose-dependent reduction in CLASI. The effect was really quite pronounced. As you saw one patient that was enrolled in the study had a pretty severe skin evolving with the 22-score baseline. And that patient had a 17-point reduction in their CLASI over the course of treatment. That patient was enrolled at the highest dose level of NKTR-358. So it's a very encouraging piece of information, and it's very, very consistent with the dose-dependent relationship we see in Tregs, and it's one of the main reasons why we're so excited that we're now in the Phase IIb dose-range finding study with Lilly. That study began just a couple of months ago in the summertime, and it's currently enrolling patients. And a second Phase II study is around the corner as well in ulcerative colitis and additional ones will follow next year.

[Operator Instructions]. And our next question comes from Difei Yang from Mizuho.

This is Alex on for Difei. And apologies if this was addressed already, but quick question on non-small cell lung cancer and bempeg combo with pembro. Assuming you show positive data here in the upcoming readouts, what would be the strategy going forward? And would there be an opportunity to pursue kind of an accelerated pathway to approval?

Thanks, Alex. Wei, I'll ask you to comment again briefly on that.

Sure. Yes. So I think -- I mean it's a great idea. It's certainly something that we would be willing to interest in for -- with the health authorities. Now the -- historically, in the first-line setting, there has not been an example of accelerated approval based on just a response rate, certainly not -- with exception of like a TKI such as [indiscernible] so now -- so the -- so it's something that we will have to explore with the health authorities, and it really depends on the robustness of the data we generate from PROPEL.

And our next question comes from Arlinda Lee from Canaccord.

On 358, given the potentially broad applicability of the Treg mechanism that you're [indiscernible] presented yesterday, I'm kind of curious about how you guys chose the first two indications. And is there a sense to explore others as well?

Thanks, Elanda. JZ, I'm going to ask you to answer that.

Yes. Arlinda, great question. So about the indications for Treg. So there's definitely very large realm of autoimmune indications in chronic inflammatory diseases where you can consider the Treg mechanism. And it kind of sort of breaks apart into some of the different pathobiologies. So one of the key reasons why we focused on SLE as the first indication is that's a disease that has a very clear and characteristic dysfunction in the Treg compartment. So those patients have, especially as they get more severe in the disease progression, they have both a drop in Treg levels, and then the Tregs that have recovered from those patients are far less suppressive so they're much less functionally active. Now if you also remember, David talked about T follicular helper cells yesterday. Tregs antagonize those cells and T follicular helper cells are the main T cells that drive the germinal cellular reaction, which leads to antibody production, which in autoimmune diseases is really detrimental because it leads to autoantibody production. And in those same patients that have a drop in Treg, they have an expansion of T follicular helper cells. So that was one of the very strong reasons why some of those early studies in the earliest cases of treating lupus patients with low-dose IL-2 specifically to reduce a Treg increase in those patients led to some of the very encouraging results that have been reported. And that's now been replicated in multiple studies. But low-dose IL-2, you can really only achieve so much of a Treg normalization. So really with NKTR-358, we can reach far, far higher levels of Treg elevation and sustain those levels for much longer periods of time than is possible with low dose IL-2. So that's why this is a key lead indication for us. Second…

Our next question comes from Jay Olson from Oppenheimer.

And congrats on the 358 update yesterday. I had a question about, it seems like a dose-dependent increase in NK cells. And I was wondering how you would interpret those findings.

JZ, I'll ask you to take that.

Yes. Thanks, Jay, for the question. So we do observe low-level increases in NK cells. And we only really observed that at the highest dose level tested, 24-microgram per kilogram dose level. Now it's also important to note that what we presented yesterday was we dove into the NK subsets. And so there are several, but the two primary types that occur in humans are the CD56 bright, CD16 dim subset. These are the ones that cannot participate in ADCC. They cannot bind to Fc because they lack the CD16 receptor. And then there's the CD56 dim, CD16 bright. And the 16 dim -- sorry, the 56 dim, 16 bright are the majority of the NK cells in the body. They're also the ones that are the most hyperactive, and they possess the CD16, so they bind Fc and antibody receptors. And what you saw in our presentation is we saw very little change in that compartment, where we saw the majority of change in the 56 bright, 16 dim. And actually, a lot of scientists consider those to be like regulatory NK cells. And why they're coined that way is because we don't secrete killer cytokines or inflammatory cytokines in response to stimulus. So they're almost a kind of cell that is the opposite function that you have with the traditional NK cells. So that's one important component. That's why we presented that data, Jay, to show the delineation and that this is really a subset-specific effect. The other important point is that what we learned is very consistent with what's been known and studied with the use of IL-2 throughout many historical uses. So we've always seen that, that 56 bright, CD16 dim subset is much more sensitive to IL-2 than the other NK subset. And we've also seen the same NK cells elevated in multiple studies of low dose IL-2 and not just the studies from David Klatzmann lab, even in Kohn Koreth's studies in chronic graft-versus-host disease patients. We also saw an expansion of NK cells, only the 56 bright subset. And they really haven't led to any sequela. So it's something that we'll be following in all of our studies because obviously, in Phase II, we will be going to a much longer treatment duration. And so we'll be studying that very, very closely. But so far, it doesn't look like that seems to have any clinically negative significance at all.

And our next question comes from Paul Choi from Goldman Sachs.

This is Corinne Jenkins on for Paul. I was hoping you could talk a little bit about your strategy in melanoma. I think you're going to have potentially a combination in adjuvant but also two separate combinations in metastatic melanoma. I was just hoping you could talk a little bit more about how you think about all of those kind of in the same indication.

Yes. Thanks, Corinne. Wei, I'm going to ask you to comment on this. Thanks.

Sure. Yes. Can you -- maybe can you elaborate what you mean by 2 different combinations in metastatic?

Bempeg, next week. So I was just hoping, pending obviously positive data, but how would you think about development and kind of how those combinations worked together in that market?

I sorry, I didn't catch the first part of what you were saying.

With the SITC data of NKTR-262 and bempeg, plus your ongoing bempeg plus nivo studies in metastatic melanoma, how are you thinking about that?

Right. Right. So yes. So the 262, it's -- right now, the patient population being addressed is in the post IO setting, so relapsed/refractory to IO versus the bempeg plus nivo combination that is really being developed in the first-line metastatic melanoma. So the -- I think -- so the thinking there is really in the first-line setting, we're trying to improve upon the standard of care, which is the nivolumab single agent build on top of that by introducing a combination doublet of bempeg plus nivolumab and really displacing nivo as standard care in that setting. Now after the patient who has failed IO therapy in the first-line setting, whether it be check inhibitor or PD-L1 plus a CTLA-4 combination, I think those are the patients being -- really being addressed with the 2 combinations that are currently in our REVEAL study. That's the 262 program. These 2 combinations are the 262 molecule, which is a toll-like receptor 7/8 in combination with bempeg, or the second combination is a triplet of 262 plus bempeg plus nivolumab. So that's a triple combination. And either combination is really designed to address a patient who have progressed on a checkpoint inhibitor in the first-line setting, whether the addition of a toll-like receptor agonist, which would ignite the innate immunity. Because, so far, I think if you think about whether you're talk about CTLA-4 or you're talking about a PD-L1 agent or you're talking about a bempeg agent, which is IL-2 targeting T cells, all of these are really trying to harness the body's adaptive immunity in the fight against cancer. And the 262 agent and any toll-like receptor agent is really going the other side, really try to trigger immune response -- trying to trigger adapting immunity through the activation of innate…

And that does conclude our question-and-answer session for today's conference. I'd now like to turn the call back over to Howard Robin for any closing remarks.

Well, thank you, everyone, for joining us today. And I'd like to first thank our incredible employees for their continued hard work and tireless efforts during these challenging times. Their dedication to advancing our clinical studies while keeping our business on track to make me especially proud. As I stated earlier, we're well positioned with a strong balance sheet, a maturing portfolio of immuno-oncology and immunology programs, and we thank our shareholders for their ongoing support and look forward to continuing to provide you with updates on our progress. And please join us at our analyst event on November 11. And lastly, we sincerely hope that you and your families stay safe and healthy throughout the coming months. So thank you very much for joining us today.

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and you may now disconnect. Everyone, have a wonderful day.