All right, welcome everyone to a Jeffrey's 2026 global healthcare conference. My name is Roger Song senior and it covers me about tech It's my pleasure to have our next company doing the fireside chat nectar therapeutics, and then now we have the JD with me Hello, thank you Roger. Awesome. All right JD why not you do our you know state-of-art for Nectar? You have ResPak as the lead and across multiple indications. And then also, you know, anything else you want to highlight before we dive in?

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 I know that the majority of questions today will be focused on ResPeg, and that really takes up the majority of our resources in the 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 uh you know a plug here we just put out a top of dermatitis landscape update with a doc surveyor u.s based dermatologist i think redspec come up pretty positively from that result and then the piece and then basically you are one of the three major pipeline product in development can take up a meaningful market share in the future which is translated to multibillion opportunity. So with that, you already reported the phase 2B data recent and then with the induction and the maintenance, I know you are well waiting for off treatment result next year, but you also So full speed ahead into the phase three. Just tell us, okay, before you start the phase three, what are the gating factors or any steps you need to go through before you can start the phase three?

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 three 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 their duplicate trials in adolescents ages 12 and up and they'll be evaluating res peg versus placebo it's in 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 ResPag 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 ResPag out to one year and I think as many of you are familiar with our 52 week maintenance data that we presented for ResPag 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 ResPag 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 age as 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 studies around the middle of 2028 okay great yeah exciting to see a new mechanism into the phase 3 for a top of dermatitis as I mentioned earlier we looked through the 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 at the mono or multi-specific you know so I think a red packet turns out to be a very good new mechanism we know ox 40 but seems to we have some issue there I think a respect flow to the top in terms of the stage development yeah no we

definitely agree with you I mean so one of the the big differences is respeg is an agonist all of those other drugs in the pipeline you mentioned they're all antagonists of various kind most of them of the IL-4 and 13 pathway or combinations of that at 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 respect 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 the respite can impact both atopic dermatitis and asthma we've seen respite 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 uh you know mechanism of action that raspeg 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 IIb, and even in our first Phase I 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 Respeg as a whole new approach to treating these diseases, and with this Phase III 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 going to really give us a chance to establish ResPag as this whole new approach to treating diseases.

Good. I think we'll touch on the alopecia areata in a moment. Maybe just a couple of detailed questions 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 global trial, you expand the patient population into some of the demographic, maybe, such as APAC or Asian. So how do you think of the baseline will be different compared to the trial you have been re-enrolling in terms of, you know, TH2, TH17-driven etapa dermatitis?

Well, so, firstly, we've evaluated the PKPD 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 also have 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.

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 biologically naive. I understand that we ask the question many different ways. is that 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 8W dermatitis drugs? I believe you are the first one to do that in a controlled setting.

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, you know, 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 depiction 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 And the way you power the 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 highly likely you're going to hit the static.

And, you know, with 510 patients and, you know, like more patients on drug than placebo, yeah, I mean, they're very, very highly powered studies for sure. And a lot of the size of the studies really is really intended to ensure that the size of our safety database 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 RESPEC up very well, right, in future indications to come. So, yeah, so when we kind of going back to that bio experience, you know, it is 510 patients. So you're absolutely right. It's a very, very well-powered study, not a highly powered, an overpowered study. When we designed the statistics around it, we were being more conservative, for sure, right? 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 RESPEG 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. They 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 in the statistical design.

Yeah, in terms of the mix of the patient that you say intolerant, failed, what's the distribution going to look like? Do you have a mean max for each subpopulation? And then also, if it's a fail, would you include those patients fail, like a refractory patient versus a relapse patient?

Yeah, I think a good kind of proxy is there was a trial run by Lebrechizumab called the ADAPT study. 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.

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

Well, so if they followed the FDA-approved treatment guidance, JAK has to be used second 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 cause you to discontinue a JAK inhibitor and Dr. Got it.

And then I understand, yeah, strategically, you can be conservative on the effect size and then when 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?

Yeah, again, there aren't a lot of benchmarks here, but in the ADAPT clinical trial, so 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.

And then on the statistical method, how would you handle the missing data and the discontinuation data is also the multiple imputation like you did before?

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 the lack of efficacy or a prohibited med is taken, then they would be non-responders.

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

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

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

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 DERM 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 respite 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 that's not, 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.

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?

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

They will still be blinded for those? Oh, okay, so you have an entire, like, a two-year trial. You know, one year's LTE.

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.

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?

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 base 3, we'll continue to do the same thing.

So the one year is for the safety for the initial BOA submission for AWM time. For AA, you know, I think the phase two, including the long-term 52 weeks data, looks pretty good. I think the investors 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 or missing data going to end the phase three?

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, then they're 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. So again, very similar.

Yeah, and then your expectation for the discontinuation patient would be lower than the phase two?

Oh, indeed, yeah. So firstly, if you just look across and almost any indication between phase two and phase three, the discontinuation rate always drops in the phase threes and that's driven by a few things the first is that when you do the phase two you don't approve 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 And like we did in atopic derm, and that was really, you know, for resource kind of issues for us. But in the phase three 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 two, 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. So we fully expect that the discontinuation rate will be much lower in Phase 3 than it was in Phase 2.

Got it. And then the Phase 2, there's 24-week off-treatment data later this year. Do you need that data package for your end of phase two 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 already had the end of phase two 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 three 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 the dose that we'll be using is 24 micrograms per kilogram, dose 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 ResPeg 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.

Excellent.

So, last minute, ResPak, you have T1D with the investigator, and then I think you also thinking about other indication including maybe lupus or any others so how much we you cannot say say right now for the indications yeah so so so yeah so firstly the the type 1 diabetes study is being run by trial net and they're 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 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 III studies are moving and before the first Phase III 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 excellent all right thank you JD for joining us and I thank you everyone watching NSC.