Nektar at H.C. Wainwright Conference: Strategic Updates on Respegg Trials

On Thursday, 27 March 2025, Nektar Therapeutics (NASDAQ: NKTR) participated in the H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference. The company provided a strategic overview of its novel therapy, Respegg, highlighting its progress in clinical trials for autoimmune disorders. The discussion included both promising prospects and challenges as Nektar aims to differentiate Respegg from existing treatments.

Key Takeaways

• Nektar completed enrollment for its Phase 2b trials of Respegg in atopic dermatitis and alopecia areata, with results expected in June and the fourth quarter of 2024, respectively.
• The company has a strong cash position of $269 million, projected to support operations until the fourth quarter of 2026.
• A new collaboration with TriNet aims to explore Respegg’s potential in treating type 1 diabetes.
• Nektar is advancing its TNFR2 agonist antibody program, with an IND submission planned by the end of 2024.
• The company is focused on minimizing placebo effects in trials and aims to achieve sustained treatment outcomes.

Financial Results

• Nektar ended Q2 2024 with $269 million in cash.
• The cash runway is projected to extend into the fourth quarter of 2026.
• Funds will support ongoing Phase 2b trials and the TNFR2 agonist antibody program.

Operational Updates

• Respegg - Atopic Dermatitis:

- Enrollment completed for a 400-patient Phase 2b study.

- Top-line results from the 16-week induction period expected in June.

- The study includes three dose levels and a placebo arm.

- Patients achieving an EASI 50 response can enter a maintenance period.

• Respegg - Alopecia Areata:

- Enrollment completed for a 90-patient Phase 2b study.

- Results anticipated in the fourth quarter of 2024.

- The study aims for sustained hair growth by restoring immune privilege in hair follicles.

• Respegg - Type 1 Diabetes:

- New collaboration with TriNet for a study on new onset type 1 diabetes.

- The study will assess Respegg’s impact on preserving insulin production.

• TNFR2 Agonist Antibody Program:

- The program is advancing towards an IND submission by the end of 2024.

Future Outlook

• Near-Term Data Readouts:

- Atopic Dermatitis Phase 2b results expected in June.

- Alopecia Areata Phase 2b results expected in the fourth quarter of 2024.

• Strategic Priorities:

- Replicate Phase 1b results in the Atopic Dermatitis Phase 2b study.

- Establish Respegg as a novel treatment mechanism.

- Demonstrate potential for less frequent dosing regimens.

- Achieve competitive hair growth results in the Alopecia Areata study.

- Advance the TNFR2 agonist antibody program.

Q&A Highlights

• Respegg Mechanism of Action:

- Respegg acts as an agonist targeting regulatory T cells to manage inflammation.

• Managing Placebo Effect:

- Steps include minimizing U.S. enrollment and ensuring stable disease baselines.

• Alopecia Areata Rationale:

- Chosen due to strong translational hypothesis for Tregs in this indication.

For more detailed information, readers are encouraged to refer to the full transcript below.

Full transcript - H.C. Wainwright 3rd Annual Autoimmune & Inflammatory Disease Virtual Conference:

Arthur He, Senior Biotech Chemist, HC Wainwright: My name is Arthur He, senior biotech chemist at HC Wainwright. Thanks for joining us for to have a conversation with the management of Nektar Therapeutics. A little bit about Nektar. The Nektar is a global biopharmaceutical company focused on developing novel therapies that selectively modulate the immune system to treat autoimmune disorders by leveraging the company’s, expertise in polymer chemistry. Joining me here are Doctor.

Jonathan Zalewski, Chief R and D Officer and Ms. Jennifer Rodock, Chief Business Officer. Jay Z and Jennifer, welcome. Hello.

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Thank you for having us.

Arthur He, Senior Biotech Chemist, HC Wainwright: So I guess, right now, Fastback is obviously the talk of the town. But before we dive into the rail business, I’m just curious if you guys can give us a quick overview of, Respac’s history. How did it transition from a collaborative program with Lilly to your own hands?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Sure. Yeah. So so Nectar invented Respecific based on a lot of the learnings and understanding we had around both our polymer chemistry platform and also around the protein interleukin two. From inception to our first in human dosing was about a fifteen month period of time that we took the molecule forward. We entered into a partnership with Eli Lilly at that time, roughly in in in 2017.

And then with Lilly, we advanced the program through nine completed clinical studies, two studies that Nectar ran themselves, and then seven studies that were run by Eli Lilly. We then terminated the collaboration in April of twenty twenty three. We’ve been operating the program, wholly owned asset since then. And we’ve just recently, just this year, completed the enrollment of two very large Phase 2b studies, a Phase 2b study in patients with moderate to severe atopic dermatitis, which is a 400 patient study, which we completed enrollment of in January. And we will have the top line results from that study in June of this year, and those are the results from the sixteen week induction period.

We also completed enrollment of approximately ninety patient alopecia areata Phase 2b study as well. We announced that roughly a month ago. And in the fourth quarter of this year, we expect results from the thirty six week treatment period from that study as well. So that’s a very abridged timeline of many years worth

Arthur He, Senior Biotech Chemist, HC Wainwright: of time. Well, that’s very helpful. So, I guess let’s, moving back a little bit. So, so could you walk us through the Respects, the Phase 1b data in the atopic dermatitis? So what are the key difference between your analysis from the initial findings there?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. So, what I’ll say is, so in the clinical study that was operated by our former partner Eli Lilly, we conducted a very straightforward Phase 1b study. It was a randomized, double blind, placebo controlled study. There were two doses of Respegg explored, twelve microgram per kilogram given twice a month subcutaneously was the low dose treated for twelve weeks. And twenty four micrograms per kilogram given twice a month subcutaneously for a twelve week treatment was the high dose of Respek.

And then after twelve weeks of treatment, patients were followed through week nineteen. And then patients that had an EASI fifty or better could continue in the study all the way to week 48. And so we definitely saw a lot of key elements of data from the study. We saw dose dependent efficacy. We also saw a drop in EASI score change from baseline that was quite notable.

We saw a very rapid onset of efficacy as well. And then we saw a very important finding, which was a remitted potential of ResPag, whereas even though we stopped treatment at week twelve, the majority of people, in fact, the vast majority of people maintained their responses and they maintained disease control all the way through week forty eight for six months off drug, which is a feature that’s quite different than what you’d expect to see from the standard of care drug is whether they’re Dupixent or even the JAK inhibitors and so on. In terms of the specific data differences, after we terminated the collaboration, we did identify that there was a data issue in the way that the EASI scores were calculated by the contractor that Lilly hired to run the study, both in the atopic dermatitis study with the EASI endpoint and in the psoriasis study with the PASI endpoint. There was a systematic error made, and both of the scores were miscalculated. And the basic, feature of the error was that in both of the scores, you calculate the disease specific severity.

And it’s specific for eczema, specific for psoriasis, right, depending on the different skin features. But then in both instruments, you also need to calculate the area of the skin that’s affected and the proportion of that skin across all four geographical regions of the body, your head, your trunk, your upper limbs, and your lower limbs. And that’s the systematic error that was made. So both the EASI score and the PASI score by our former partner were miscalculated, and they omitted, you know, those two area scores. And after we received the data, we’ve corrected that.

And the corrected data was first presented, you know, in 2023, but it was really formally presented in our publication in Nature Communications in October of last year.

Arthur He, Senior Biotech Chemist, HC Wainwright: Thank you. Thank you, Jay Z, for such a detailed, comprehensive description. So we know that ResMed, the way the ResMed treats the AD is completely different from the other pros currently in most drug in the market, right? So, could you tell us a little bit more about what’s the potential benefit for targeting Tregs by ResMed compared to the other approach for the AD?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. So, you know, our our drug is an agonist. All of the other drugs we’ve talked about are inhibitors or antagonists. Right? So the for example, the IL 13 or IL four thirteen class is really trying to block cytokines in that pathway.

It’s targeted therapy. JAK inhibitors are trying to block the JAK enzymes, right, of course, that are kinases. Our molecule is an agonist. We agonize the immune system, but we agonize normal pathways of immune resolution. And so those are at the level of the regulatory T cell whose job it is in our bodies is to control peripheral tolerance and turn off unwanted inflammation, wherein an antigen is triggering an autoreactive cell to have an inflammatory reaction.

That same antigen can trigger a Treg to block, that cell in a very specific way. And so that’s one really big fundamental difference. We’re agonizing the body’s natural defense mechanisms and the natural sort of feedback loops that the body normally has in place to block unwanted inflammation. The other thing that’s quite important is as a Treg is our main sort of focus mechanistically, that Treg is able to control many different kinds of inflammation. So we know in atopic dermatitis, while there can be a TH2 dominance, there are also TH1, TH17 additional signatures that people have, especially adults that have, you know, really advanced disease where they’ve had multiple relapses and multiple flares throughout their life.

They become much more mixed in their presentation. And again, those are all things where our Treg mechanism is not quite broad, right? And it can work against many different kinds of inflammation as opposed to a targeted cytokine blocker, which can really just block one cytokine.

Arthur He, Senior Biotech Chemist, HC Wainwright: I see. So let’s dive into the phase two b study. Okay. So you we we know this data update data readout in the in the June. So, so before we talk about that, could you walk through us the trial design of the phase two b study?

And I know recently you share the dose level for the study at the three dose different dose levels. What’s the rationale behind dose selection, especially? Sure.

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. So the study is about a 400 patient trial design that’s randomized three to three to three to two on drug to placebo. So we’re expecting roughly seventy to seventy five people in the placebo group and roughly 105 to 110 or so in the three drug treatment groups. So that gives you a sense of the size. Now the doses that we’re using for the study are twenty four micrograms per kilogram, given twice oh, we could do slides.

Okay. Twenty four micrograms per kilogram given twice a month. That’s the RMA shown in orange at the top. We also have that same twenty four microgram per kilogram dose level given once a month. That’s arm B and arm C is eighteen micrograms per kilogram given twice a month.

Now what is the thinking behind those dose levels? So the first is ARM A and ARM B are the top dose that we used in the Phase 1b study of Respegg in patients to moderate, severe atopic dermatitis. So that, of course, was a very efficacious dose level. We saw an eighty three percent change from baseline EASI score at that dose level at the end of twelve weeks. We saw very rapid onset of efficacy.

And we also saw the durability after we stopped dosing along with very nice results across the easy responder endpoints, IGA, NRSH as well as DLQI and So we wanted to definitely build off of what we learned from that dose level. We also wanted to test a once a month regimen at that same dose level so that we could test the hypothesis of the same Cmax, but half of the AUC, right, because we’re giving it once a month instead of twice a month. And then we also saw from the Phase 1b that the twelve microgram per kilogram dose level, which was the lower dose in that study, It did show activity, but we thought it was a little bit too low and we really wanted to get more kind of dose information from the study. So we bumped up that dose level to eighteen micrograms per kilogram, right, to create a different dose paradigm. So that’s a lot of the thinking in how the doses were selected.

One important element of this study though, the patient population is exactly the same as the Phase 1b. It’s the same biologic naive patient population with the same inclusion criteria. However, in this study, we’re extending the induction period from twelve weeks in Phase 1b to sixteen weeks in Phase 2b. So there’s additional treatment. We believe that this additional treatment is really a benefit because even though a number of people showed great control after twelve weeks of treatment, there were people that could have done better with more dosing.

And the other thing is in that study, we withdrew the dose altogether at week twelve, whereas here you can see we’re maintaining the dosing into the maintenance period. And this is something we’re very excited about because we’re interested to see if there’s going to be the potential of even greater efficacy with continued dosing. And that’s what this study is really well designed to test. So in June, we’ll reach the it will be the final analysis for that sixteen week induction period. So basically, the last patient reaching their week sixteen assessment is the cutoff date, right, for that database lock.

And then eventually, when we present that in June of this year, it’ll be the final analysis for the week sixteen induction endpoint. In terms of the way the study is designed, at week sixteen, each patient basically has two choices. If they have an easy 50 or better response, then they can move into the maintenance period where they’ll stay on the same dose level, but switch to either a once a month or once every three months dose administration and maintenance. Patients that have not reached an EZ50 response, they have the option to enter into what we call the escape arm. And in the escape arm, it’s they would switch to the twenty four microgram per kilogram twice a month, which is the high dose in the study, and they would remain on that dose through that thirty six week maintenance period.

And then at the end of the maintenance period, which would be at one year of total treatment, there is another one year of follow-up off drug where our intention is to assess that remitiv potential and durability of response. So we expected June data event from the study for the induction. The first quarter of next year would be a data event for the maintenance portion of this study.

Arthur He, Senior Biotech Chemist, HC Wainwright: I see. So speak of the June readout, besides the EZ score reduction, mean reduction, so what other data point we could expect from the June readout?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. Well, we definitely have to save some data for a medical presentation, but you can expect that we would give enough information to really set a good color, right, for the results of the study. So so that would include the easy, which is the primary endpoint. Probably some of the key secondary endpoints, you know, we would we would we would note, and of course, we would we would mention about what was seen from the safety standpoint as well, right, because that’s a key endpoint. But our goal would be to make it informative.

Arthur He, Senior Biotech Chemist, HC Wainwright: I see. So maybe I just push a little bit. So for those kind of readout you guys planned, what would a positive outcome look like for you guys?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Well, I mean, we’re really excited with the Phase 1b data. And so we really want to replicate our Phase 1b results, right? So that’s always sort of first and foremost in what we’re doing. But then we also realize that we’re a novel mechanism. Right?

And we’re a novel mechanism that’s not the third or fourth IL 13 variation. Right? So we also know that even if we’re in line with the standard of care, that we would have a chance to have a drug that has a lot of potential being a novel mechanism and providing physicians an alternative, right, to the third or fourth agent in the same class. Also with the different kind of dosing regimens, as you know, we’re exploring like a once every three months treatment regimen. We also have the opportunity to provide the patients additional convenience, in that kind of a regimen approach.

So we really have a range of activities, but we’re all very excited to reproduce our Phase 1b data, of course.

Arthur He, Senior Biotech Chemist, HC Wainwright: Yeah. Same here. So, So, speak of the other competitor drugs for the AD space, we all have been aware of that the placebo effect in the recent AD study. And, so what’s your general, what’s your view on the placebo effect in the AD study and what kind of steps have you guys taken to minimize the potential impact for your Phase 2b?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Mhmm. Yeah. We’ve we’ve definitely been given a lot of guidance from our steering committee that in The US in particular, if you just look at different trials over recent readouts, the placebo rate in The US is going up. And so and that’s probably a combination of a multiple factors. Access to medicine is definitely one.

Sort of the more moderate and maybe even barely moderate patients are being reserved for clinical studies because doctors don’t want them to have the chance to end up on placebo for a severe patient. They’d rather put the severe patient straight onto Dupixent. And also, use of sites that are not board certified dermatologists in The US coupled with access to medicine also is one of the things that can contribute, you know, because definitely, you wanna make sure that you have a highly skilled dermatologist or at least an immunologist at minimum, right, that has experience scoring the disease and can really adequately select patients for the study, you know, participate. So we were given the guidance to really minimize our footprint in The U. S.

And when we set off, we were anticipating about thirty percent of our patients to be enrolled from The U. S, but actually it was seventeen percent after we completed enrollment. So that was one thing. The other is that by far the vast majority of patient of study sites in our studies are led by board certified dermatologists. So that’s another key thing.

We also were given great guidance that in many of the studies, they just collect baseline disease once it’s screening. And you can’t really tell or be able to understand if you have a patient that might be in an active flare, maybe a flare that’s resolving. Right? And so we also measured our baseline disease twice, roughly a month apart between screening and baseline to ensure we were focused on patients that had stable disease. And so that’s an example of kind of a flavor of some of the things that we did that are we believe modern practice, at least should be modern practice to help ensure your study is the most protected as it can be.

Arthur He, Senior Biotech Chemist, HC Wainwright: Well, that’s very, super helpful, JC. So let’s shift the gear to alopecia side. I think obviously first question is, so why did you choose alopecia as the next indication for ResVac? I know this scientific rationale behind that as well as the commercial landscape wise. So maybe you can tell us a little bit about that part.

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. Well, so it’s interesting. I mean, one of the things comes also from our own just observations clinically. So the very first study we did in Phase 1b was in mild to moderate lupus patients and it was a very short six week study. So it was really too short to kind of read out a lupus kind of efficacy endpoint.

But what we noticed is that all the patients that had secondary cutaneous manifestations of disease, they showed a very rapid and dose dependent clearance of their skin skin symptoms, their class e score. The class e score is resolved. And so that is really, you know, that first observation that led us to both the psoriasis and atopic dermatitis Phase 1Bs, which were run-in parallel. And of course, Respegg showed activity in both indications as well. So we really seen three indications of skin inflammatory diseases with different kinds of underlying biology with Respeck showing efficacy.

So we’ve definitely are seeing an effect here, right, in three different kinds of skin diseases. So we wanted to continue to explore that. Alopecia is a very interesting disease. It’s actually also a skin disease, but it’s focused on the scalp and it’s really focused on the interaction between the follicles or the hair cells in the skin in this regard. And it’s a disease where you have a normal hair follicle compartment that should be in a complete immune privileged state, meaning it should be totally devoid and barren of any immune system infiltrate.

But you have that whole system broken down in patients with alopecia areata and they have a very highly inflammatory environment. Then the role of the TBEG in normal individuals is actually to help maintain that barrier and help entrust that an immunopoietic state exists. So our whole, you know, concept with the study besides it being another skin disease, there’s a very strong translational hypothesis for Tregs in this indication. And the real holy grail here, Arthur, is to be able to restore immune privilege and actually fix the problem because the JAK inhibitors can regrow air, but they just block the inflammation symptoms. So the second the patient goes off the JAK inhibitor, whatever hair they grew falls out again.

Our goal is to, a, see, you have Respegg, you know, grow, you know, induce the induction of hair growth And then b, just like in atopic dermatitis, withdraw the drug and show that the patients don’t relapse that they keep their hair in this case. And that would be truly transformational. And and all of this also just dovetails nicely as you also set up in the kind of commercial and other considerations. There are no biologics approved in alopecia areata. And we’ve seen time and time again from RA to psoriasis, the topic of dermatitis, that as biologics come in, they start to really establish a really substantial growth commercially in these indications.

And so we’d be very excited to see if we can get the kind of result that we hope we can see from the study.

Arthur He, Senior Biotech Chemist, HC Wainwright: Yeah, I completely agree. I think especially for the commercial side, the alopecia, the landscape is definitely even more favorable than the AD side. So I guess, for the sake of the time, so, so the alopecia readout is in fourth quarter, I believe. Right? So what kind of data set we can expect it and what’s your expectation for the for the positive readout?

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Yeah. So this shows the study design of that study. It’s a thirty six week treatment and our fourth quarter top line would be the thirty six week treatment or this thirty six week induction results. The primary endpoint is the mean percent improvement in SALT at week thirty six relative to placebo. So that would obviously be one.

And then the other really important endpoints here are the proportion of people that reach SALT twenty and SALT 10 because those are the two registrational endpoints. And our benchmark here is we want to be at least in line with the JAK inhibitor. And we think even the low dose of the JAK inhibitor is quite meaningful, because there are so many ways that we can differentiate from a JAK inhibitor with the mechanism of action of this drug. So that kind of gives a sense of what we’re thinking about.

Arthur He, Senior Biotech Chemist, HC Wainwright: Okay. So that’s great. So I guess for the red spec, I gotta ask Brian for one question for the I know you guys already you just recently get the collaboration ongoing for the type one diabetes with TriNet. So maybe you can share a little bit of a story behind the scene how you guys land this partnership with them.

Brian Kotzin: Well, thank you, Arthur. You know, we’ve had, it’s been a long history of of thinking about different indications for Respek where, in fact, the induction of regulatory t cells might, have a have an important role. And and we’ve always had on the list type one diabetes, you know, because, there’s considerable evidence that, you know, I there’s a dysregulation of IL two as well as a dysregulation of the of of the regulatory T cells that need to control the T cells so that are destroying the beta cells in the pancreas, so the insulin producing cells. And a considerable evidencing could be genetic evidence, animal, model data. And so we’ve always kind of had it on the list as something that we would like to do.

And I’ve been working with the TrialNet individuals all along to try to kind of move this study forward. And we now have a collaboration with the premier trialist in type one diabetes. It’s a study where, we’ll enroll 66 individuals, enroll two to one, to either Respegg or placebo. It actually is in different stages, so that in the first stage, it’ll be adults, and then we’ll move and these are in patients who have new onset type one diabetes. So they have to be within a period of time of presenting with type one diabetes, diabetes, and they have to have at least partially preserved, insulin or c peptide, production so that we can see the impact of a drug that might preserve what’s remaining in these individuals, and that could be highly clinically meaningful.

So the sixty six patients, will be enrolled. And as I said, it’ll be in stages. The first stage is adults. And if we have good safety record there, then we’ll move to adolescence to be included in the study. And then if that’s good, then we’ll move into younger children where where the frequency of new onset type one diabetes is the is the most frequent.

And so very excited about this, and it will be, it’ll be executed by the TrialNet individuals. And, as many people know, they are the premier trialist in in type one diabetes.

Arthur He, Senior Biotech Chemist, HC Wainwright: Gotcha. Thank you. Thank you, Brian, for for all these information. And, so I guess I save the best for the last for the ladies. Jennifer, so can you remind us for the about the current cash position and it’s your projected runway now?

Jennifer Rodock, Chief Business Officer, Nektar Therapeutics: Yeah. Sure. Thanks, Arthur. Nice to see everybody. We ended 02/2004 with $269,000,000 in cash, and we’re projecting currently projecting our runway to take us into the fourth quarter of twenty twenty six.

And so that covers, you know, the cost of the Phase 2b trials that we’re running right now in atopic dermatitis and alopecia, as well as the work that JZ is doing on our tnfr2 agonist antibody program that’s advancing nicely. We intend to submit an IND for that at the end of this year.

Arthur He, Senior Biotech Chemist, HC Wainwright: Awesome. So great. So JZ, Brian, and, Jennifer, thanks so much for your great insight today. Yeah. And, I would like to thank to thank our audience who are tuning in, today online.

Thanks again from the HCYONY team. Thank you.

Jennifer Rodock, Chief Business Officer, Nektar Therapeutics: Thank you, Arthur.

Jonathan Zalewski, Chief R and D Officer, Nektar Therapeutics: Thank you, everyone.

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