Conference Transcript - NKTR 2026-06-03

Roger Song, Analyst — Jefferies

All right. Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior in Kavasimika Biotech. It's my pleasure to have our next company doing the Fireside Nectar Therapeutics, and then we have JD with me.

Jonathan Zalevsky, Analyst — Other

Hello. Thank you, Roger.

Roger Song, Analyst — Jefferies

Awesome. All right. JD, why not you do a state of art for Nectar? You have RESPEC as the lead and across multiple indications, and then also, you know, anything else you want to highlight before we dive in?

Jonathan Zalevsky, Analyst — Other

Yeah, well, we're definitely heavily focused on regulatory T-cell biology. I think it's one of the components and approaches medically that we've really taken and, you know, and really defines, you know, our pipeline, and it defines our work, and I think we've established a level of expertise and certainly the most clinically mature data. in this field, demonstrating that ResPeg, with its Treg mechanism of action, is efficacious in multiple disease settings such as atopic dermatitis, alopecia areata, and even other conditions such as lupus and others and psoriasis where we've shown clinical activity with ResPeg. We've sort of used that as a springboard, and we've used that to propel our R&D pipeline. We've been focusing in a TNFR2 agonist as a target because that also interacts with a Treg compartment, and it interacts with a different subset and classification of Tregs. The two major types are native, the ones that form in the thymus and the induced, the ones that can form when T cells that are undifferentiated undergo a fate change and decide if they could become induced regulatory T cells and that's the target of the TNFR2 program and we're advancing multiple assets based on that target one is a traditional bivalent antibody and another is utilizing the fact that it works as a single arm which allows us to also make bispecifics out of that same molecule we call that nectar 0166 and we plan to have an IND from at least one of those programs next year but but I know that the majority of questions today will be focused on ResPag and that really takes up the majority of our resources in the

Roger Song, Analyst — Jefferies

company. Yeah, no, it's good. Good to be focused. But on the other side is you do have a platform and then I do know, notice you have a couple other earlier pipeline. You know, a plug here, we just put out the atopidermatitis landscape update with the Doc Surveyor, US-based dermatologist. I think ResPag come up pretty positively from that result and then the piece and then And basically, you are one of the three major pipeline product in development can take up a meaningful market share in the future ADA, which is translated to multi-billion opportunity. So, you know, with that, you know, you already reported the phase 2B data, you know, recent, and then with the induction and the maintenance, I know you're well waiting for off treatment without next year, but you also full speed ahead into the phase 3. Just tell us, okay, before you start a phase three, what are the gating factors or any steps you need to go through before you can start a phase three?

Jonathan Zalevsky, Analyst — Other

Yeah, so we've already had our end of phase two meeting for atopic dermatitis with FDA. We had that last year. You know, and we've also carried that out and received general health authority advice, you know, across other regions, such as Europe and other different regions as well. So we're in a very strong position where we now have all of the health authority feedback that we need for global trial to execute. And to that regard, we're extremely excited to say that the first clinical study sites open this month in our Phase 3 atopic dermatitis program. And we expect the first patient to randomize in July, you know, probably the early part of July with sites opening this month. That whole program, which now fully kicks off in earnest, has a number of pivotal trials that make up the clinical development plan. So two of the studies, which are each 510 patient trials, and they're duplicate trials in adolescents ages 12 and up, and they'll be evaluating ResPeg versus placebo. It's a moderate to severe patient population. and we'll be treating people for 24 weeks of induction with the 24 microgram per kilogram twice a month dose of ResPeg which was the most efficacious dose in the phase 2b study it's pretty clear and then a 24 week duration of induction as we've shown that extended duration further improve the response rate over the 16 week induction that we used in the phase 2b study we'll also be advancing patients that are responders into a maintenance portion where they'll be re-randomized to receive either placebo or monthly or quarterly dosing of ResPeg out to one year and I think as many of you are familiar with our 52 week maintenance data that we presented for ResPeg from that Phase 2B study we saw excellent performance in both the monthly and the quarterly dose regimens which was you know I think a real differentiating feature for ResPeg certainly has a very convenient dose presentation and frequency. Then the third study, oh, and those two bio-naive patient studies will begin enrolling patients first in July, second in August. And then in the third quarter of this year, the bio-experienced patient population study will kick off. And that will be a study, again, in 510 patients. all of the patients had failed a prior IL-13 or other biologic or they could have failed the JAK inhibitor as well and then again same study design same ages 12 and up patient population same six month duration and so forth so we're very excited about this clinical development plan path that kicks off and we expect the first top-line induction data from the first of those bio naive

Roger Song, Analyst — Jefferies

studies around the middle of 2028. Okay, great. Yeah, exciting to see a new mechanism into the phase 3 for atopidomatitis. As I mentioned earlier, we looked through all the pipeline. Yes, we have a long list of the pipeline drugs, but very, very few is actually exploring new biology. You know, a lot of them are validated biology as a mono or multi-specific, you know, so I think ResPak I think it turns out to be a very good new mechanism. We know OX40, but it seems to have some issue there. I think ResPeg flowed to the top in terms of the stage development.

Jonathan Zalevsky, Analyst — Other

No, we definitely agree with you. I mean, so one of the big differences is ResPeg is an agonist. All of those other drugs in the pipeline you mentioned, they're all antagonists of various Most of them of the IL-4 and 13 pathway or combinations of that in IL-31 or TISLIP or some other kinds of targets that have sort of been somewhat recycled through the atopic dermatitis pipelines over the years. We think ResPeg represents a whole new class that can be positioned in a new way because it actually affects the patient's, you know, immune status internally. By agonizing regulatory T-cells, it switches the cellular complement, you know, that people have each time they take an administration of ResPeg, and that can have really really lasting effects and I think we've seen that represent itself in terms of how broadly RESPEG can act it can help with people that have a comorbidity such as asthma which is a different presentation you know of TH2 inflammation in a different tissue but RESPEG can impact both atopic dermatitis and asthma we've seen RESPEG impact TH1 mediated inflammation in the setting for example in alopecia or in lupus and also TH17 mediated inflammation such as in the setting of psoriasis so it has a mechanism that has much more breadth because of the cellular you know mechanism of action that RASPG induces with Treg biology and because sort of Tregs help regulate the underlying inflammation at its source at the actual initiator and the trigger of inflammation it also has demonstrated very high durability we saw that with very infrequent dosing in the phase 2b and even in our first phase 1 study we saw six months of durability after a 12-week treatment cycle that we published a few years ago so we think all of those things really could position ResPag as a whole new approach to treating these diseases and with this phase 3 campaign that we're kicking off in atopic derm and in alopecia in the first and second quarters of next year we think that's gonna really give us a a chance to establish ResPag as this whole new approach treating diseases.

Roger Song, Analyst — Jefferies

Good, I think we'll touch on the alopecia areata in a moment. Maybe just a couple of detailed question related to the phase three. I think you give us the design, how you will do the phase three, which is very rational. So we notice maybe this time, because it's a global trial, you expand the patient population into some of the demographic, maybe, such as APAC or Asian, so how do you think the baseline will be different compared to the trial you have been reviewing in terms of, you know, TH2, TH17-driven ethyped dermatitis?

Jonathan Zalevsky, Analyst — Other

Well, so, firstly, we've evaluated the PK-PD profile in patients of Asian descent and in that multiple forms of that kind of genetic lineage, and we've seen the same PK and the same Treg induction profile, so that was important. We've also, in other clinical trials, such as in our lupus study, we had a number of patients from multiple Japanese sites. So we've also had experience in studying in that region of the world. You are correct, there are some slight biological differences, you know, in atopic dermatitis. There's a little bit more, say, a TH17 complement in the disease patient's evasion descent than there is in Caucasian, for example. But we feel very confident because we've seen with ResPeg the activity to work broadly, you know, across different forms of inflammation. So in contrast to a targeted therapy, say like an IL-13 blocker, it only blocks the IL-13 pathway, and that's it. If the patient escapes, you know, and maybe develops a Th1 or a Th22 component to their disease, right, it's very difficult for an IL-13 inhibitor to block that. But with ResPeg, we've seen activity in very different kinds of T-cell inflammatory conditions, including Th1, including Th17, and others. So we feel very confident that the genetic differences in that patient population in the APAC region will not be an issue for ResPeg. And we're very excited to be including, you know, numerous sites from the APAC region in this global study.

Roger Song, Analyst — Jefferies

Okay, great. And then it's interesting you will be, you know, separate the biologic naive versus experience into different phase three. I think it's a very, very rational design because all the signals so far is biological naive. I understand that we ask the question many different ways. You're very confident about the activity post-biologics. But it will be a lot cleaner if you can design the trial, just separate them whatsoever. and then just show the result. I think we should have a lot higher confidence for the naive and then the experience, we should have a pretty good kind of a chance you're going to hit that. So that design, maybe an interesting question is how you think this design is going to differentiate your label compared to the current A.W. dermatitis drugs? I believe you are the first one to do that in a controlled setting.

Jonathan Zalevsky, Analyst — Other

Yeah, that's exactly spot on. We think it's a very strategic and kind of like the most recent, you know, 2026 onward approach to doing this. The other drugs that are approved have a very kind of what I'd call a general indication statement. They're indicated as a drug for the treatment of atopic dermatitis, you know, with maybe some body weight and age range kind of additional parameters around that statement. And that's fine. That's a general statement. But as we're prospectively running a large study in a, basically, a biologic failure, like a second-line indication, then if we win in that study, we can be a lot more aggressive with our label aspirations because we would be the first to have demonstrated prospectively efficacy in that patient population, which can now start allowing us to add that into our indication statement. And when you start thinking about the landscape and the fact that there is, you know, quite likely a biosimilar Dupixent coming, and you start thinking about the landscape of patients needing to probably step through, you know, agents having a label that includes a second line and being a different MOA rather than another version of the same MOA, all of those things we see as being you know very compelling differentiating elements and that was a lot of our thought process in separating the patient populations and in doing that kind of a study design there aren't a lot of benchmarks because not many standalone placebo controlled randomized parallel design studies have been done so we'll be among the first if not the first yeah in the way power the

Roger Song, Analyst — Jefferies

trial do you have a little bit lower expectation or assumption on the effect size compared to the naive patient population I know the power the size probably not driven by the efficacy because it's a placebo control so it's

Jonathan Zalevsky, Analyst — Other

it's highly likely you're gonna hit us that's it yeah and you know with 510 patients and you know look at more patients on drug than placebo yeah I mean they're very very highly powered studies for sure and and a lot of the size of the studies really is is really intended to ensure that the size of our safety databases is really robust right so we want to enroll and randomize more patients and take more patients to one year plus of safety follow-up especially for this first registration because that really sets respac up very well right in future indications to come so yeah so when we kind of going back to that bio experienced you know it is 510 patients so you're absolutely right it's it's It's a very, very well-powered study, not a highly-powered and overpowered study. When we designed the statistics around it, we were being more conservative, for sure, Because it's not been studied in that patient population. From first principles, we don't expect any difference in efficacy based on the mechanism of action of RESPECT, and also based on the fact that the patients that will be in that study will be a mixture of people that were intolerant to the prior therapies that would have failed not necessarily for efficacy but for safety reasons and others will have failed for efficacy so you also have a range of different kinds of patients that would be eligible for that trial but yeah we were more conservative

Roger Song, Analyst — Jefferies

in the statistical design yeah in terms of the mix of the patient that you say intolerant failed what what I know what's the you know distribution we're gonna look like it we have in like a min max for each subpopulation and they And also, if it's a fail, would you include those patients fail, like a refractory patient versus a relapse patient?

Jonathan Zalevsky, Analyst — Other

I think a good kind of proxy is there was a trial run by Lebrechizumab called the ADAPT It was published recently, and that gives a good example of what the patient population is in a kind of a dupy failure. And as I said, the four common types are people that are immediately intolerant or that acquire an intolerance. Those are kind of the two most common on the safety side of patient. And then another are the efficacy side, people that were never responders or people that lost a response or maybe had an insufficient amount of response. Like maybe they just barely reached an easy 75 but couldn't hold it. In our study, we also will include people that will have failed a jack as well. I suspect there will probably be less, you know, patients that are in that category because likely people that failed a drug like DUPI are more likely to join our study probably than to take a JAK, so those will all be the kinds of patients that we would expect to have enrolled.

Roger Song, Analyst — Jefferies

And if they only failed JAK, that's not a population?

Jonathan Zalevsky, Analyst — Other

Well, so if they followed the FDA-approved treatment guidance, JAK has to be used second Right, so we would expect that people are treated correctly, so then they would have had to have failed an IL-13 first, and then they would have taken a JAK. Maybe they were, again, intolerant to the JAK. It's very common to have adverse events that have caused you to discontinue a JAK inhibitor and so on.

Roger Song, Analyst — Jefferies

And then I understand, yeah, statistically you can be conservative on the effect size and the way you design, but on the clinical perspective, based on your feedback from your advisor, will physician or patient expect how much lower, or if at all, in terms of the effect size after they fail DUPI? For example, they DUPI, you know, 40%, 50% response, and then when they fail, using other drugs, they are expecting a lower response, or, you know?

Jonathan Zalevsky, Analyst — Other

Yeah, again, there aren't a lot of benchmarks here, but in the ADAPT clinical trial, so the efficacy to Lebre was very close in that patient population, as it was in the phase Again, with some caveats that that was a single-arm open-label study, but that's really kind of the only benchmark data that exists. Obviously, when you run a study, it's very important to set expectations for patients, and the informed consent does that partly, and then the kind of the investigator and their sort of discussions with the patient do as well. And we'll make sure that we work very hard to set expectations for patients so that, you know, there's high adherence, and that trial is done as best as it can be done.

Roger Song, Analyst — Jefferies

Yeah, got it. And then on the statistical method, how would you handle the missing data and the discontinuation data as also the multiple imputation like you did before?

Jonathan Zalevsky, Analyst — Other

Yeah, that's really commonplace. You know, nowadays, that's what the agencies recommend. So missing data is treated with imputation. And then people that had any kind of prohibited uses, they become intercurrent events, right? So, for example, if they discontinued to lack of efficacy or a prohibited med is taken, then they would be non-responders.

Roger Song, Analyst — Jefferies

And then this will be similar to library, I think, as more modern study. They're not treating those missing or discontinuation patients as a non-responder. They're just treating at the multiple imputation.

Jonathan Zalevsky, Analyst — Other

They treated them as missing, and missing data was imputed.

Roger Song, Analyst — Jefferies

Okay, got it. And then the last point, Adi, is you will have the one year of treatment data next year, but you will start phase three this quarter in the next month. So how those data are going to inform your pivotal or potential label and maybe the real world use, and how are they going to use that data?

Jonathan Zalevsky, Analyst — Other

Well, I think one of the things that's important is that the IEC has just sort of issued a kind of a consensus guidance on the definition of remission, right? It was a JAMA-DURM article. And so that's very interesting because now the field is starting to come up with a consensus criteria of what could constitute remission. Now, there hasn't really been any study that's used it yet. We might be one of the first that, you know, assesses our data using that kind of new metric. For us, like, what we think about, you know, whether RESPEG is able to be withdrawn for extended periods of time or if you take it you know four times a year or something that's all a win right I mean that's great that's a great medicine right as far as I'm concerned if the medicine can be stopped or taken with very low frequency it's a successful you know we see that successfully so that's one thing but on the other thing is we also see that respect has shown tremendous durability right and we've seen that in the phase one study that we published in our Nature communications paper in 2024 and this coming one year off drug right is going to be the next data point I do think that it for us it's related to how Respec can be a whole new class you know of agent because ultimately we believe that if we fix the underlying immunological problem it should create lasting benefit for the patient and we know that can reflect itself in preference whether it's doctors that would prefer patients would prefer and and other things like that now in terms of how we're dealing with that in our clinical development plan in the design of the phase three program we have multiple periods where the patients are re-randomized onto placebo throughout the sort of the duration of the program so for example in the phase three after the induction period ends at six months responders are re-randomized to either placebo or monthly or quarterly. So that's the first sort of withdrawal assessment. Then at the end of one year, responders, again, can be re-randomized to stay on drug or to placebo. So we'll be assessing off-drug from six months and off-drug from 12 months. So we'll be assessing multiple sort of patient populations and multiple time of exposure relative to drug withdrawal. And that'll all be, you know, ultimately a big part of our entire package.

Roger Song, Analyst — Jefferies

So that's your phase three. You have 24 weeks and then 52 weeks. And after 52 weeks, you have another year kind of off and then treatment?

Jonathan Zalevsky, Analyst — Other

So into the LTE. LTE, okay. Then, yeah, patients, again, are re-randomized to either stay on drug or to move on to placebo.

Roger Song, Analyst — Jefferies

They will still be blinded for those? So you have an entire, like, two years trial. One year is LTE.

Jonathan Zalevsky, Analyst — Other

Yeah, so the phase three is one year, and this LTE is the study afterwards. So, again, for us, this is very important because ResPeg has shown this extended off-drug potential, so we want to continue to explore that as part of the phase three program and into registration.

Roger Song, Analyst — Jefferies

Yeah, and then you don't need the second year data to support the initial approval and the label, but that data will be updating the label once you get the data. And then the data will be, the initial label will be based on the first 24 weeks data or you need the first year, the whole year data?

Jonathan Zalevsky, Analyst — Other

So you like to have in the safety database for the VLA package, right? You want to have as long of a duration as possible. But we start to set the clock on the number of patients that have one year of exposure, right? So that starts to become the anchor point of your safety database. And then it's typical to do an integrated safety summary where you pool all of the safety data in the program to date all together and continue to bolster that safety database. And when we move through the alopecia phase three, we'll continue to do the same thing.

Roger Song, Analyst — Jefferies

Yeah, okay. So the one year is for the safety for the initial BLA submission for AWD. Okay, for AA, you know, I think the phase two, including the long-term 52 weeks data looks pretty good. I think the rest are probably just a little bit confused about the statistical method you're using the multiple imputation. I understand it's early data, right, so you don't want to, you know, kind of too conservative on the discontinuation patient. You have the rationale to choose that. So how should we think about the phase three design if you, you know, do the same thing? Or how are you going to expect the discontinuation of missing data in the phase three?

Jonathan Zalevsky, Analyst — Other

So in the exact same way, same as in the atopic derm. Again, it's very common practice to use imputation for missing data. And that's our approach again. So if patients, you know, have an intercurrent event, which means that they took either a prohibited med or they discontinued due to progression, than their non-responders. Any patient that has missing data, however, their missing data can be imputed. And, of course, patients that don't have missing data are not imputed, right? They're actual data.

Roger Song, Analyst — Jefferies

So, again, very similar. Yeah, and then your expectation for the discontinuation patient would be lower than the phase 2?

Jonathan Zalevsky, Analyst — Other

Oh, indeed, yeah. So, firstly, if you just look across in almost any indication, between phase 2 and phase 3, the discontinuation rate always drops in the phase 3s. And that's driven by a few things. The first is that when you do the phase two, you don't approve of concept, right? So nobody really knows what will happen. And you might also have dose responses, which includes lower efficacious doses and stuff. So all of those change in phase three because you've established efficacy and you've established your dose. So that's one big difference. Another big difference is that in our phase two study, we didn't offer a crossover or an escape arm. And like we did in atopic derm. And that was really, you know, for resource kind of issues for us. But in the Phase 3 program in alopecia, that won't be the case, right? We'll offer patients, you know, a chance to cross over at the end of the induction. So that also has a big impact. But I think the biggest impact is when we ran Phase 2, we just didn't know how long it would take and how efficacious RESTPEG might be. That was really a proof-of-concept study. But now we do. And so we can set expectations adequately with patients, with doctors. we can put it into the informed consent you know this is how long this trial will take and this is what you might experience and all of those things completely you know change the mindset and they have a very positive effect we so we fully expect that the discontinuation rate will be much lower in

Roger Song, Analyst — Jefferies

phase three than it was in phase two got it and then the phase two does 24 week off treatment data later this year do you need that data package for your interface to meeting with the FDA to design the phase three or you know internally how much you want to see from that data no because firstly we've

Jonathan Zalevsky, Analyst — Other

already had the end of phase 2 meeting with the FDA and so and I can you know share a little bit that you know our intention as we've guided is we'll be doing one registrational phase 3 study it will be also an adolescence age 12 and up and we will be doing it for a 52 week duration for the primary endpoint and And the dose that we'll be using is 24 micrograms per kilogram, dosed twice a month, all the way for 12 months, so through 52 weeks. So that's a key element, you know, and that's what we've guided to, and that's our objective. And in the first to second quarter of next year is when we'll kick off that registrational program for ResPag and alopecia areata. The off-drug data that comes in December of this year, that helps us inform how we'll conduct the long-term extension in the alopecia study. So in alopecia, one year and the endpoint, and then patients will roll into an extension study. And in the extension study, what we're looking at is do we continue dosing Q2 week, or do we use a lower frequency regimen, such as maybe monthly or so on? And in atopic derm, remember, we use that phase one off-drug data to give us confidence to use monthly and quarterly dosing in the maintenance portion of the phase two. And in alopecia, we'll use this 24-week off-drug data to inform that same kind of, you know, decision and design of the LTE.

Roger Song, Analyst — Jefferies

Excellent. So last minute, ResPak, you have T1D with the investigator. And then I think you're also thinking about other indications, including maybe lupus or any others. So how much you can say right now for the indications?

Jonathan Zalevsky, Analyst — Other

So, yeah. So, firstly, the type 1 diabetes study is being run by TrialNet, and they're underway. You know, with the start of the study, multiple sites are open and patients are being screened, and there's a chance that we could have data in 2027 from that. So that's one item. And then for us, in parallel with that, we also are exploring other opportunities with RESPEG, particularly in this period of time while the phase three studies are moving and before the first phase three study reads out in the middle of 2028 for atopic dermatitis. So we've seen activity in multiple indications, like I mentioned earlier, other cutaneous indications, for example, cutaneous lupus and so on. So we're exploring what's feasible in terms of a study that can be clear enough and interpretable enough, but also executed in the correct time frame. So for example, choosing a 12-month endpoint is, you know, perhaps not the right indication, right? So also just sort of mapping those things, and we'll give more guidance on that later this year.

Roger Song, Analyst — Jefferies

Excellent. All right. Thank you, JD, for joining us, and I think everyone watching NSC.