Nektar Therapeutics (NKTR) Earnings Call Transcript & Summary

Welcome, everyone, to the afternoon start for the 44th Annual Goldman Sachs Healthcare Conference. My name is Chris Shibutani, member of the Biopharma Equity Research team. We are very pleased to have Nektar Therapeutics join us once again. On the dice with me are some veterans of the industry, of the company. Jonathan Zalevsky, also known as JZ, Chief Research and Development Officer; and Jen Ruddock, Chief Business Officer. Thank you both for joining us.

Thank you.

You guys have been really a part of so many aspects of the journey for the company. We're at an interesting intersection right now. A lot of changes going over the past 6 months, and probably changes that are not necessarily understood or recognized or appreciated as much. And I always think that just in general, people and things that have success, success, success kind of boring, and like oftentimes the most informed dimensions come from when there are challenges or issues that have to be addressed. When people have to pivot, et cetera, it really grounds you in that opportunity to think about what are some sort of core competencies? How do we really optimally utilize resources? How do we make decisions? How do we communicate those and whatnot. So, I think that this is a session that I'm expecting that we'll learn a lot of specifics in terms of how you're thinking about detailed assets, but also just to really understand about how you navigate this because across the board, every single company faces some of these challenges, and I think investors should always recognize that I think, when there are setbacks, this can be opportunity and this is where there is an opportunity for investors to further understand that and see what could come next. So, a great vantage point here that you guys have in the experiences, and we go back a number of years. So, maybe we'll just start off a little bit with how you'd like to summarize events. Should I turn that over to you, Jen?

Yes, so I'll start. Thanks, Chris. Certainly, this first part of the year has been a time of great change for us. One of the things that we made a decision to do in April was not only implement a cost restructuring plan, which we thought was critically important in the landscape. So, from the standpoint of cash preservation, we made sure that we extended -- we're enacting an operating plan now that extends our cash runway through at least the middle of 2026, and that was an important component of it. But I think, an even more important component was the focus of the company in the area of immunology and inflammation. So this has definitely been an analysis process for us. We went through with [[ great diligence all of the assets in our pipeline, and we think made a very well-informed decision ]] on a pipeline focus that would get us to milestones and catalysts within our cash runway guidance that would be pivotal for the company. And I can talk a little bit about those assets or JZ can in a moment, but one of the core assets that has been a focus for us in the last couple of months here is REZPEG. So, this is an IL-23 regulatory stimulator that we've determined we're going to focus our late-stage clinical efforts on. As part of that transition to a pure-play immunology company, we are going to seeking a strategic partnership for our IL-15 asset in immuno-oncology, and we can talk more about that in a bit. But we think the REZPEG asset really represents for Nektar a very great pivot point in a reasonable time frame, and what I mean by that is that we're initiating a Phase IIb study in atopic dermatitis. We have very good data, and we expect to report additional final data soon and shortly. The program itself has great opportunity as a first of its class mechanism in atopic dermatitis. And we have designed a study, and JZ can spend some time talking about that in a bit, that we think is a very big value pivot for this company. It's a Phase IIb study, well-powered, that we expect to have data on in the first half of 2025. Within our cash runway guidance, we can accomplish that, still be at least a year out on cash runway and get to a very important milestone for the pipeline and for value inflection. And I think, I'll stop there, but part of the restructuring was us bringing the company size down quite a bit. We're now a very lean company, with 55 employees out of our San Francisco R&D facility. We're focused on some early stage research assets in immunology that we think are going to emerge as very important assets and mechanisms as well. One of which is an antibody program. It's the first of its kind for Nektar. But I do think to your comment earlier, Chris, that the idea of focus and the idea of facing challenges has been, in some ways, very productive for us. We've now created a company that we think is much stronger that will enable us to get through to the next value-enhancing catalysts as quickly as we possibly can.

And JZ, in particular, I think one of the things I've learned about you was -- and I think more in the investor community has always thought about you as an oncology guy, right? And yet the background, perhaps the sharpest tools in your kit come from an original academic, and intellectual basis in immunology. So, tell us a little bit about how we should think about you in this role because even as the company pivots again, there was this historical sense that the oncology guy conversation that we had around JPMorgan conference was just that, actually, you're sort of nesting in an area that you feel like is an endogenous home for you. Tell us a little bit about your background here, and then I will go into the REZPEG next journey that Jen had mentioned.

Yes. I mean, I think the most kind of germane to this discussion is my kind of career through the industry, which span more than 2 decades, has been always in immunology-based pursuits and immunology-based drug discovery and drug development. And that goes through all the companies that I've spent time at. Before coming to Nektar, I actually was a traditional kind of Immunology Discovery Head when I worked at the large pharmaceutical company, in Takeda. And in fact, one of the things that we did there was we pioneered the approach that developing new drugs, targeting immune pathways is actually a therapeutic area agnostic approach. Because basically, every disease has some component of the immune system, either a direct or an indirect driver, whether it's either the underlying pathology or the key symptomatology is driving that disease. And so we were, at that time, doing something that is much more common now, but back then was sort of cutting edge to be not aligned with the therapeutic area. And my team that I led at Takeda actually delivered INDs to every therapeutic area of the company. So my actual focus is actually kind of bread and butter immunology, and that's my background. At Nektar, I spent a lot of time doing immuno-oncology because that was our one focus. And we definitely made a lot of intensive area moves across the cytokine portfolio that we developed, focused on that. Maybe kind of near term, that is what you kind of came to note with is my reputation, but I'm actually an immunology subject matter expert by my training and by my pedigree.

Sure. I think on the fore of the key discussion is talking about REZPEG in AD. But for the purposes of the discussion here and to again, I think it's very helpful, to get your views in terms of the recent history, REZPEG as well, there was the Lilly relationship. There was the aim to do clinical development in lupus. The Phase IIb results from that study did miss the primary endpoint. You guys have continue to speak positively, as did Lilly, but they really provided commentary in terms of how it didn't fit within sort of the parameters of their go-forward decision. And I remember going just back to years that there was KOL commentary and positive feedback that has always been a part of it. It never seemed as binary as such a decision that you've just gone through is, but there's a spectrum of ways of looking at the data and thinking about it, especially in something like lupus, where the degree of difficulty is just kind of in vain and the unmet need is also very significant. Can you talk about signals of efficacy that you and some of the KOLs continue to possibly see in lupus? And what level of expectation we might be able to say as a basis for considering still development in lupus? Just help us understand that before we move on to the primary force, which is the AD going forward. But let's go back on the [indiscernible].

Yes. I think it's a really important kind of study to look at and to dive into. . So lupus patients have a very mixed immune system, right? They have systemic inflammation, that's why it's called systemic lupus, right? So their disease is throughout their body, and it's a mixed to T cell disease. It has a lot of Th1 characteristics, but it also has apparent Th1 issues, and then lupus patients also have a dearth of T regs. They either have lower numbers or they're lower in function. They're less suppressive. They also have lower levels of IL-2 intrinsically, so they -- and as they progress, that tends to define a lot of their underlying immune imbalances. So in this study, we had a chance to study patients with moderate to severe lupus. And we tested 3 dose levels, a 300, a 900 and 1800 flat dose dosed every 2 weeks for 6 months of treatment. So we definitely observed that one of the dose levels, which is the dose level we've studied across other indications, was less well tolerated in lupus patients, so that was the high dose. And so in that case, we had more discontinuations. And that was a dose level that in classic dose range finding study fashion tells you that dose level is not worth studying any further. But, we had a lot of very clinically meaningful takeaways from the other dose levels. And when we first saw the data, to us, it was striking that the BILAG-dependent parameters which are the BICLA endpoint as well as the LLDAS endpoint. With the second of those, the LLDAS being the closest thing we have to remission, when we treat patients with lupus. So an LLDAS response is that, by far, the strongest response you could hope to achieve therapeutically. And we saw that both those parameters at the middle dose showed very, very rapid separation. And then, very significant depth of response. And so, we first saw that and we thought it was notable, and we had the chance to present that data to KOLs, and we had about 6 or 7 KOLs, major luminaries in the field that we presented the data to and all of them were extremely impressed by that result for a couple of reasons. One is the BICLA is the most contemporary endpoint for lupus studies, and the most recently approved drug, [indiscernible], actually relied on BICLA as their primary driver of approval. They actually had 2 Phase III studies. One of those failed on SRI-4 but passed on BICLA. They had a chance to change the primary endpoint between the first and second one read out to BICLA, in order to actually achieve their approval. And it is the most contemporary and modern endpoint of lupus, and we saw that response there. Then the second thing was the speed of the response because normally, lupus doctors expect 6 months and they can barely see an effect relative to placebo. In our study, that effect was seen as early as 4 weeks, so that was very notable. And then, the third piece is the LLDAS. So reaching 15%, 20% responses across that endpoint is just not something you expect to see. That's a depth of response and clinical benefit. It's very high. So when we showed that data to the lupus community, their belief is that as a Phase IIb dose range finding study, you actually got where you wanted, which is you learn the dose range, you learn the sample size, and you learned about the endpoint, that you had which you needed to advance to a Phase III study. And the group that we showed it to supported that, so that was very encouraging for us to hear, and that even with the knowledge that the higher dose is not something that you need to take forward for the risk-benefit argument. Now as a company, we have to stay focused right? So, we are -- we acknowledge this and we like it. And we know that in the future, there may be opportunities for us to kind of go into that kind of registrational potential pathway in lupus. But for now, we really need to focus on atopic dermatitis. And so to be very clear, that is what we are undertaking, that will be the next study that will begin. We're sure we'll talk about it in a couple of minutes. But we really have that lupus data kind of there in the background and the opportunity to return to it, say, with positive atopic derm data and other kinds of things, catalytic events that can lead us to advance even more, into larger Phase III type programs in lupus.

Okay. No, that's very helpful just to have that opportunity that you have a data set that would enable you to consider that. And yet the strategic focus, the difficult decision making, the prioritization is what's there. So let's talk about AD. Phase IIb trial here. Plans are to start that this year. Are we still on track with that?

Yes, third quarter.

Okay, cool. What can you help us to understand about the strategy behind the design?

Yes. So one of the things we'll be focused on in that study is we'll focus on biologic naive patients, and this is the same patient population that we studied in Phase Ib. And so, it's really important that we don't change patient population.

And remind us about that Phase I data as well, just we can contextualize it over the course of this discussion, and people who are relatively newer to the story, seeing a different type of opportunity can understand. So tell us about the Phase Ib, so that we have foundational basis for this.

Yes. So one of the things that makes us very excited to move into that Phase II study in atopic dermatitis is the early proof-of-concept data that we've already obtained. When we were in our collaboration with Eli Lilly. So Lilly ran a study in patients with moderate to severe atopic dermatitis. It evaluated 2 dose levels of REZPEG, a 12-microgram per kilogram Q2 week dose and the 24-microgram per kilogram Q2 week dose. Those are about the same as the 900 and 1,800 flat doses that I mentioned earlier from lupus. And what we saw is very profound efficacy and a very nice well-tolerated safety profile to go along with that. So from the efficacy perspective in that study, we saw, relative to placebo, we saw a depth of reduction of the EASI score, which is the primary measure of eczema in these patients, that was right in line with the standard of care drugs like DUPIXENT. So those drugs in their Phase III studies had about a minus 60%, minus 65% reduction, and we saw minus 66% reduction in the interim data set that it was presented at EADV last year. We also saw EASI-75 responder rate, an IgA responder rate and an Itch NRS responder rate that was also very consistent with that standard of care benchmark at a 12-week induction period, which we used, whereas those other drugs require a 16-week induction. So it took a month less time to reach that same level of efficacy. So that was very positive. And really, the AE profile had no systemic toxicities, and only minor injection site reactions is really the only notable treatment emergent for [indiscernible]. So it was a very favorable profile. But there was the second element to the results that were really, really noteworthy and quite important for the dermatology community, and that is that after we stop dosing at week 12, we followed patients for an additional 36 weeks and we saw that patients maintained durable disease control over that period. There was no relapse. And so the kind of remittive quality of this drug's potential was something that was very notable because you just don't see that in any of the other drugs that are used to treat atopic dermatitis, whether they're IL-13 inhibitors or JAK inhibitors or even dual IL-4/13 inhibitors. All of those drugs are known that when you stop treatment, the disease comes roaring back. And it's quite quick in some cases, after a couple of months or in the case of a JAK inhibitor, after a couple of weeks. So the medical community, particularly at the AAD conference very recently, they actually presented our data. And it was at the end of the keynote lecture given by Dr. Simpson, an important KOL in dermatology. And he just flashed up our results and said, is this the future a potential remittive therapy? So the medical community is really acknowledging that there's a unique data and a unique potential with the T reg mechanism that could provide a lasting, long-ranging kind of efficacy. And so, that's what gives us a lot of excitement and enthusiasm to advance into our Phase II study in atopic dermatitis and prioritize atopic dermatitis work. So, the study that we're planning to do that will kick off in the third quarter will focus on biologic-naive patients, which is the same patient population that we studied in the Phase Ib with the data that I just mentioned. They'll have the same kind of inclusion criteria for their moderate to severe atopic dermatitis, and this is going to be a large, very well-powered study. It will be just under 400 patients in size. It will have 3 different regimens of REZPEG versus placebo evaluated over an 18-week induction period. And then, after that induction, patients that meet a threshold to advance from induction to maintenance. They will be re-randomized into 1 of 2 maintenance regimens that will continue for another 30-plus weeks. The whole study will take approximately 54 weeks to conduct of time. But in the maintenance period, we're going to be evaluating patients on both a monthly or a once every 3 months dosing regimen. And a once every 3-month regimen in maintenance is very unique and very differentiated. We saw -- the data that we saw with that long duration of effect in our Phase Ib gives us a lot of confidence that you really don't need to dose frequently, right, after you reach the end of induction. And a Q12-week induction regimen in this field would be completely different than any of the other drugs that are offered where right now, a monthly regimen is probably the best that's offered and that comes from lebrikizumab. So those are some of the high-level features. The FDA is evaluating our study design, and we look forward to kind of updating everyone with the final design once we get the FDA's feedback soon.

We, on the street, are often left equipped only to do cross-trial comparisons, which we always say caveat, caveat, and there's a usual sentence. Almost it's like sneezing. To what extent is the biologic naive, what are the right benchmark studies that we should make sure that we're penciling in as reasonably-ish legit to do the inevitable comparisons that we'll do?

Yes. Well, so first of all, people have already started to do that with this data. But interestingly, they've taken the interim data set, and they've used that to do their comparisons. And so, we're very excited that we have final data now. We'll be looking to update that and we'll have opportunity to really extend those observations, and that will be quite, quite interesting for people that like to do those comparisons. But in terms of what to look at, what is the right benchmark, I mean, we really look at the standard of care kind of drug. So DUPIXENT is the standard of care. So it's easy score, and it's EASI-75 responder rate and its IgA responder rate, are three of the kind of key efficacy comparisons. And as I mentioned, you have about a minus 60% to minus 65% reduction in EASI score from the group mean, the average. You have about a 40%, mid-40% range for EASI-75, and you have kind of like higher 30% range for the IgA. So those are very important benchmarks. Lebrikizumab used those benchmarks as well to kind of guide through their Phase III studies. Adbry although, which is approved, has a little bit worse across those 3 parameters but sort of in that range. So those are the very important benchmarks for kind of what is setting the class right now. And then, of course, none of those agents have a remittive kind of component to their mechanism. So to us, those are important benchmarks because we feel that even if we hit just the benchmark, right, the fact that it's a novel mechanism really provides a whole new opportunity, right? This is a field where doctors expect to cycle patients through different therapies because none of these drugs are really curative. So you're on chronic cycling for a long time, just like in rheumatic RA diseases and others where you cycle through TNF inhibitors or [ ORENCIA ] and others, so it's very similar. But if all of those drugs are virtually the same mechanism, then you have a new mechanism that you can provide that gives a unique opportunity. And then, JAK inhibitors are also in the space. The JAK inhibitors, while they have very nice efficacy profile and rapid result because they're small molecules. They, of course, have black box warnings, right? And so, there's a lot of contraindication with using them especially in at-risk patient populations, and you really can't use them chronically because of the long-term cardiovascular risk. So, we think all of that gives us a unique opportunity for positioning REZPEG. It already comes on the basis of having proof-of-concept data in hand, which is unique, and it's monotherapy, proof-of-concept data that came from a well-controlled placebo-controlled study. So we're very excited to move to Phase II.

And the landscape of treatment of options, biologic naive, but to a certain extent, there's the encroaching opportunity to use topical therapies, et cetera, especially among the more moderate end of the spectrum versus the severely affected. Just remind us what the patient inclusion/exclusion criteria are about? Beyond the steroids, there's more choices that come in tubes and stuff. How could that mess things up or hopefully be well defined?

Yes, yes. So to start with the patients that are included, they already have a disease that's not controlled by topical medicines, right? So topical corticosteroids, Calcineurin inhibitors, others like [ Arrow ], Hydrocarbon. I mean those drugs are no longer effective, and these are patients that have progressed to needing a biologic systemic therapy. They'll have an entry EASI score that's at least 16 and they'll have an IgA score of 3 or 4. So that basically identifies a minimum moderate, but it's really the majority of patients cross from moderate into severe. And then, being biologic-naive really, yes, that means that all of those topicals that you mentioned, they're no longer effective for these patients.

Got it. . And then beyond that, the usual questions about obviously, the balance sheet is quite healthy. You're now going to be financing this on your own. I guess, the prior structure had been nearly 75%, et cetera. I imagine that your anticipated plans with the study that you outlined is what's baked into the foundational runway expecting cash to go in through '26. Is that fair?

Yes, that's exactly right. Yes.

Yes, that's correct. The only thing that's not in the cash runway forecast would be any partnering cash that would come in for [ 255 ]. So we've deliberately kept out any potential upside from partnering activities [indiscernible].

Okay, and we'll talk about that in a second. So we're data junkies, when, when, when. What's reasonable, prudent and fair to think about when we could learn about results from this Phase II study?

Yes. So as I mentioned, we -- the FDA is evaluating our protocol. It's a very straightforward protocol. Like you said, you'd like to compare and benchmark. I mean, we're not reinventing the wheel here, right? We're doing an atopic dermatitis study that's very, very reasonable kind of industry standard that is evaluating our protocol. We expect to begin in the third quarter of this year, and we think in the first half of 2025 is when we'd have data. So that would include all the time for enrolling all the patients. And then, it's an 18-week induction period, so you have to build in the time for waiting to get through the end of that period plus the data.

And naturally, the U.S. is still, for better or worse, the best market to be. Just remind us, the enrollment will be U.S. based solely? Some global component to it? And do you have an eye towards engagement at all with any regulators to make sure? Because they tend to be a little bit persnickety about all sorts of things on the clinical front outside of the U.S., although the U.S. is getting weird, too. But, just let us know about the U.S. international opportunity with the trial and with the regulatory prospects.

So the answer is yes to all. So yes, so we're -- the trial will be..

Wasn't that an old question? Okay, never mind. Yes. Yes to all.

It's an and, and, and.

Okay.

Yes. So North America is going to be a large component of the trial footprint, but we will have sites in Europe as well as in Asia, including in Australia. And then, that does also involve health authority interactions, obviously, outside of the FDA. And there are some differences. Like for example, in Europe, like EASI-75 is a much greater component of the European approval. IgA is there, too, but it's not as dominant whereas in the U.S., IgA is a much more dominant, right, than EASI. Those endpoints go together. You usually can't get down to EASI to a score of 1 without reaching a 75% or better clearance anyway. But yes, we're prepared for all of those things, and obviously engaging all of the individual regional health authority interactions for the study.

Okay. Cool. . Jen, you mentioned [ 255 ]. This is an asset and there's an opportunity here to figure out how to be strategic, potentially monetize partner. How should we think about this asset? Remind us, what it is as well, again, so that we have in the ecosystem of this transcript for this discussion, people to familiarize themselves. And what your thinking and plan is?

So this is an IL-15-based agonist asset. It's a cytokine. We've done quite a bit of development work on it to understand the proof of mechanism in the clinic both as a monotherapy and as a combination therapy. But, it truly is designed to be a combination therapy, which is one of the reasons that led to our partnering decision-making here. We have two different partnering-type paths that we could take with this asset. The first is we do have a solid tumor study ongoing right now with avelumab, which is an anti PD-L1 asset that Merck KGaA owns. They are currently running that study, and we do expect to have those data sometime, at least the first interim readout, sometime in the second part of 2024. That is in bladder cancer in the maintenance setting, and there's an opportunity there, obviously, for a partner to pursue potentially bladder cancer or a GU solid tumor strategy there. The other pathway for us is in cell therapy, and this has been something that's been evolving for us over the last 1.5 years or so. We have a clinical trial ongoing at Fred Hutchinson Cancer Center in combination with BREYANZI. And that study is looking in patients with DLBCL on the label -- BREYANZI label, looking at CAR-T expansion by adding IL-15, or drug, 255, as a maintenance therapy following CAR-T therapy. And what's interesting about what we're observing, and we've talked about this publicly, is that we are observing the expansion of the CAR-T cells. And so as we think about whether or not that translates into efficacy, we'll be watching that, but we do think the opportunity with cell therapy companies could be significant here. So, out of the cell therapy landscape, there are a lot of companies working in the autologous space as well as the allogeneic space. This asset clearly could have complementarity to all of those platforms. And so, as we move forward here, I think our eye is on 2 different types of partners, and we have good interest. I think, our goal right now is to see if we can accomplish a strategic partnership that makes sense for the asset by the end of this year, and that's what we're working towards for the program. As I mentioned earlier, none of the economics in a potential partnership for 255 are included in the cash runway, so that would be upside, if we're able to execute a partnership by the end of this year, which is the goal.

And it's interesting because when you think about the potential role that this could play, almost -- it's just like it's an asset, it's a consideration. All of the immuno-oncology dimension's process, especially solid tumors, have proven to be super difficult, right? And so, I think in a best case scenario, you're looking for like an exclusive partnership, et cetera, and proprietary ownership, and you talk about two different paths which relate to two different combinations. Are you being -- considering being open-minded about almost enabling a structure with potential partnerships that perhaps could do more in the way of developing data as proof of concept? Perhaps potentially, you would sacrifice some economics on this. At the moment, you have a healthy enough balance sheet. But talk to me about the varieties of strategies with 255? Because to get to something by the end of this year, I would think that you'll have to consider different options. And the cell therapy folks are also -- have seen better days. It's -- we know that cell therapy is very difficult and allogeneic and like, [ c***], bispecifics, they're coming in here for real. So, if you're going to be a potential tool that could partner with some of these other assets, maybe talk beyond -- it's very logical to do the two structures, but what's your mindset?

Yes. So, I think that's an important point. I mean, we are having a very creative mindset on this, and I think we're open to looking at a lot of different partnering structures. There are a range of cell therapy companies that are doing quite well. So we can't put them all in one bucket, right? And so I think, the way that we're looking at this, and we do think this asset could be very valuable to a company who's got a cross cell therapy platform pipeline, right? And I think that's one of the goals for us in terms of the partnering conversations. But certainly, depending upon whatever levers we have to pull, as we look at whether or not we move forward with a partnership from what it looks like, we'll be thinking about cash runway and other elements and trying to maintain flexibility, in what we're looking for into the partnership. So whether that's creative on the economic side or on the structure of it, a geographic side, we don't know yet, but we're certainly maintaining that outlook as we go into this project.

And to the extent that you're keeping the ball dribbling on 255 on your own, Nektar's current commitment is to CD19 CAR-T and BAVENCIO. But would you anticipate the potential for a partner to reinitiate efforts in multiple myeloma solid tumors as well? Is that what I'm hearing you saying?

I mean, I think we're open to anything the partner is willing to do. I don't know, JZ, if you want to talk a little bit more about our plans there? But we really focus in on two areas where we see comparative results being relatively in the near term for the asset. And I think, as we look at the ADCC combinations or even potentially bispecific antibody-type combinations, those are all possibilities for the asset in terms of the development plan moving forward with the partner.

Okay. You do also as well, just from the legacy of the company, have some pre-clinical programs. If we can touch on those briefly? Anti-TNFR2, PEG-CSF1 assets. What are just -- frame what these assets could potentially go in towards, I think, autoimmune indications? Just help us understand there.

Yes, yes. Both of them are targeting autoimmune and chronic inflammatory diseases in different ways and different types. . So I'm starting briefly with PEG-CSF1, that's Colony Stimulating Factor 1. Traditionally kind of a myeloid targeting cytokine that's involved in monocyte development and monocyte mobilization. But, what we've done is we've been able to kind of really address the different ways that it interacts with the receptor to specifically try to target immune-resolving pathways. Because one of the things that CSF1 does is in the right kind of cytokine milieu, which is like more like Th2 cytokines, is it creates the kind of resolution macrophages that you love to have whenever you need to turn off any inflammatory response. So these are the kind of antagonistic macrophages, they're not the M1s or the M2s, and they're the kind of -- we call them efferocytosis, where they eat debris and they eat residue, they even eat scars in the case of fibrosis. So the therapeutic hypothesis with that program is we've been able to tune the receptor interactions to really drive that kind of resolution macrophage phenotype. That's what we're approaching. So that has an opportunity in multiple inflammatory indications, including fibrosis. TNFR2, as Jennifer said, is for us the first antibody program we've made. So we work with an outside partner that has antibody discovery capability to generate the lead and development candidate that we've identified in the program. Many of us before Nektar had a lot of experience in antibodies, have decades working with antibodies, and so kind of brought that kind of capability here. But TNFR2 is a very unique target, right? So there are 2 TNF receptors. And of course, the field is known by the drug with Humira infliximab, right? Enbrel, right? They're very, very classic, almost like staple drugs that worked for a lot of different indications where TNF is an initiator cytokine. But that soluble TNF alpha really can only signal through the R1 receptor, and that one has a depth domain that drives inflammation. TNFR2 is quite different. It only signals through transmembrane TNF, and it's the resolution receptor. So it actually antagonizes TNF receptor 1, and it drives wound healing, and again, suppression of inflammation. And it has some unique even properties in the CNS where it's been known, for example, in the case of a demyelinated sheath in MS, TNFR2 signaling can cause remyelination, right? You can actually promote healing. And so it's very -- it's been a target that has been a bit of a holy grail for many years. We're very excited that we've identified antibodies that have single-arm agonists of the TNFR2 receptor. They wouldn't even require to be bivalent. And so, we're excited about this program. It's a very unique profile, and we're advancing that forward. Our goal is with one of those two programs to have an IND by the end of 2024 next year.

'24. Okay. No, that makes sense. And again, the breadth and history of the science of the company is there, and the logic is also as well immune. Just for the -- in particular, for the purposes of this being an investment conference, I have to bring up a question. You recently informed investors of a delisting warning notice from Nasdaq. Help us understand what options you're considering to potentially meet the minimum price requirements? For instance, is a share repurchase on the table? I think, very valid and important for the audience here to understand about, considering how to plan?

I think we have a 6-month period on that, obviously. But certainly, we've considered a lot of different options. I probably don't want to go into all of them. But in addition, new news coming from the company could also drive the share price higher. So, I think we'll be monitoring that here in the next couple of months and probably make some decisions on sort of what the next steps could be for that type of scenario.

I think a very relative and important gating factor. But Jen, JZ, always good to see you guys. Carry on.

Thank you.

When the going gets tough, et cetera. Wish you well.

Thank you, Chris.

Thank you, everybody.