Earnings Call Transcript - NKTR Q1 FY2026

Operator

Hello, and thank you for standing by. Welcome to the Nectar Therapeutics first quarter 2026 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that today's conference call is being recorded. I would now like to hand the conference over to Vivian Wu from Nectar Investor Relations to kick things off. Please go ahead.

Vivian Wu, Head of Investor Relations

Thank you, Crystal, and good afternoon, everyone. Thank you for joining us today. On today's call, you will hear from Howard Robin, our President and Chief Executive Officer, Dr. Jonathan Zalewski, our Chief Research and Development Officer, and Sandra Gardner, our Chief Financial Officer. Dr. Mary Tagliaferri, our Chief Medical Officer, will also be available during the Q&A. Before I begin, I would like to remind you that we will be making forward-looking statements regarding our business, including statements related to the therapy potential and development plans for RESPEG-ALS-LUGIN, the timing and expectations for clinical data presentations, regulatory interactions, and other statements regarding the future of our business. Because forward-linking statements relate to the future, they are subject to uncertainties and risks that are difficult to predict, and many of which are outside of our control. For a discussion of these risks and uncertainties, please refer to our filings with the SEC, including our FERC, most recent Form 10-K, and subsequent filings. We undertake no obligation to update these four legitimate statements, except as required by law. A live webcast and replay of this call will be available on the Investor Relations section of our website at Nectar.com. With that, I will turn the call over to Howard.

Howard Robin, CEO

Thank you, Vivian, and good afternoon, everyone. We are exceptionally proud of the progress we've made at the company. The data we've reported over the last year from our Phase 2B studies in ectopic dermatitis and alopecia areata demonstrate that ResBeg could produce clinically meaningful outcomes in two distinct autoimmune and inflammatory disease settings. And importantly, the datasets reported in February and April of this year highlight the potential for ResPeg to offer further improvement for patients over time. In February of this year, we reported the long-term monthly and quarterly dosing results from the 36-week maintenance portion of Resolve-AD in patients with ectopic dermatitis. These data showed a significant durability and further deepening of efficacy and established a highly differentiated profile for ResPeg as a novel regulatory T-cell mechanism. Supported by these results, we're moving quickly to initiate the Zenith AD Phase III program in patients with moderate to severe ectopic dermatitis by July of this year. We have completed our meetings with regulatory authorities on the Phase III program, and Jay-Z will discuss the elements of the program later in the call. We expect to have the first data from the Phase III program in mid-2028, and this would support our goal of submitting a BLA in 2029. There remains a need for novel mechanisms in ectopic dermatitis beyond those currently available in the treatment landscape. In the U.S., there are over 15 million people with moderate to severe ectopic dermatitis, and fewer than 10% are receiving biologic treatments for this chronic skin disorder, with many patients not responding well to the existing agents. Roughly half of patients on existing approved agents, which includes Depixent and other IL-13-based mechanisms, fail to respond or lose treatment effect over time. This leaves a significant opportunity for ResPeg to enter the treatment paradigm in a lead position as a novel immune-modulating mechanism that could offer in both naive and experienced patients a differentiated efficacy and safety profile and monthly or quarterly long-term maintenance dose. Turning to alopecia areata, in April, we announced positive 52-week top-line results from the blinded treatment extension period in the Phase II Resolve AA study. These data also demonstrated a deepening of efficacy and clinically meaningful improvement across numerous SALT measurements with twice-monthly dosing of ResPeg. We believe ResPeg can now be advanced as a compelling first-in-class biologic candidate that can change the treatment paradigm for patients with this condition. Nearly 6.7 million people in the U.S. have alopecia areata, and the vast majority are untreated. More than half of dermatologists have been reluctant to prescribe the only approved systemic therapies, JAK inhibitors, because of box warnings and ongoing clinical monitoring challenges. We know there remains an unmet need for an efficacious and safe biologic with a better safety, efficacy, and dosing profile. Based on our KOL enthusiasm and market research, we believe there's a strong opportunity for Respeg to capture frontline share in this indication. We plan to initiate the phase three program in alopecia areata in the first part of 2027 to add a second potential indication to Nectar's BLA submission for Respeg. The global markets for ectopic dermatitis and alopecia areata combined are expected to reach close to $40 billion over the next five years. And we believe that this market has the potential to grow even further with the adoption of novel mechanisms like Respec. We've seen this with the introduction of new mechanisms in the psoriasis market over time, where the number of patients served grew tenfold over the span of 15 years and now support seven blockbuster products. That growth was not only driven by drugs competing for the same patients. Each new mechanism brought in new adopting treatment physicians who are not yet prescribing systemic therapies. And we believe ectopic dermatitis and alopecia areata could be at a similar inflection point today. And as a truly novel MLA, we believe ResPec can transform the treatment paradigm in both these indications. And importantly, we believe that TREG biology and ResPeg has potential application beyond ectopic dermatitis and alopecia areata. Nectar is now in a very strong financial position to support the advancement of ResPeg. Since year-end, we've raised approximately $783 million in net proceeds through two financings. We ended the first quarter of 2026 with $731 million in cash, and this does not include our April financing, which adds another $350 million to our balance sheet, bringing total cash and investments today to over $1 billion. With this financial strength, we could advance into phase three in both indications with a cash runway that brings us into the third quarter of 2028, well past anticipated data readouts. I'll now turn the call over to Jay-Z to go over our clinical programs in more detail.

Jonathan Zalevsky, Other

Thank you, Howard. Good afternoon, everyone. As Howard said over the past year, our clinical data generated from the Resolve-AD and Resolve-AA studies have confirmed that our approach with RESPEG to stimulate regulatory T-cells translates into a differentiated clinical profile, compelling efficacy, a favorable safety profile, extended dosing frequency and responses that deepen over time. Unlike therapies that block a single inflammatory pathway downstream, RESPEG acts upstream, restoring the fundamental immune balance that is disrupted in autoimmune and inflammatory diseases. Last June, we reported the 16-week induction period in the Resolve AD study in which RESPEG demonstrated a rapid onset of efficacy on key metrics of EZ75 and DITCH. RESPEG also achieved statistical significance on the primary endpoint of mean percent change in EZ score, and for the high-dose, met statistical significance on all key secondary endpoints at week 16. In the 24-week crossover data of patients originally assigned to placebo and crossed over to treatment with high-dose RESPEC Q2 week, we saw further deepening of response with no sign of plateau. These data bolstered our decision to advance a 24-week induction period into phase three. In the 36-week maintenance phase, where patients continued on to less frequent monthly and quarterly dosing of RESPEC, we continued to see durability of the induction responses and observed increased responses for EZ75, 90, VIGA, and itch over time. This also included up to a five-fold increase in EZ100 rates, which represents complete skin clearance, a level of response rarely achieved for patients. A key differentiating finding from our Resolve AD study was the improvement in patient reported comorbid asthma. Approximately 25% of patients with moderate to severe atopic dermatitis also have asthma, and most approved therapies do not address this comorbidity. RESPEG produced statistically significant improvements in the Asthma Control Questionnaire, or ACQ5, scores at week 16 versus placebo, including in patients with uncontrolled asthma at baseline. Outside of Dupixin, no other approved agent or late-stage candidate has demonstrated to this. We are including ACQ5 as the secondary endpoint in the Phase III program with the goal of potentially including this in the label. In Q1 of 2027, we expect to report 52-week off-treatment data from Resolve AD. These data will allow us to assess the remittive potential of RESPEC beyond 52 weeks, and we are looking forward to those data. We have completed the end of phase two meeting with the FDA and the scientific advice process with the EMA and will initiate the first trial in the global phase three program by July of this year. Our planned registrational program called Zenith AD is expected to include three trials in total, two global monotherapy studies with 510 biologic naive patients 12 years and older in each study, along with a separate study in 510 treatment experienced patients 12 years and older. For the two pivotal biologic-naive studies, patients will be randomized two to one to receive 24 micrograms per kilogram every two weeks or placebo during a 24-week induction phase to be followed by a 28-week maintenance period, evaluating monthly and quarterly dosing regimens through week 52. The overall design is intended to be consistent with prior registrational studies supporting approval of biologics in atopic dermatitis. The first two studies in biologic naive patients will begin first starting in July of this year, and the third study in biologic experience will initiate a few months after that. Our market research supports usage of RESPEG as the first-line and second-line biologic therapy, and we have designed the program to capture this and the potential label. In addition to these three pivotal phase 3 studies, the program will also contain other studies to support registration. These will also include a 200-patient open-label adolescent study and a long-term extension study. Additionally, we plan to launch RESPEG with an auto-injector, and the BLA submission will also include a PK bridging study to support this. The agency is not requiring a vaccine study, as has been done in some prior Phase III programs in this indication. The Phase III studies are designed to support both U.S. and EU registration, with an IGA-related primary endpoint for U.S. registration and an EZ75 co-primary endpoint to support European approval. A series of multiplicity protected endpoints for itch and other important patient-reported outcome measures such as sleep, quality of life, and asthma control are designed to the studies as well. We expect a similar country distribution as phase two, with the addition of other selected countries in Asia to reflect the global footprint. As Howard stated, we expect the first data readouts from the phase three program in the middle of 2028. Moving now to alopecia areata, we recently reported the 52-week top-line results from the blinded 16-week treatment extension of our Phase IIb Resolve AA study. As a reminder, our Phase IIb Resolve AA trial enrolled 92 adult patients with severe to very severe alopecia areata. Patients received subcutaneous RESPAC at 24 micrograms per kilogram every two weeks, 18 micrograms per kilogram every two weeks, or placebo. The primary and key secondary endpoints were assessed at the end of the 36-week induction period, which we reported last December. These data demonstrated a proof of concept in alopecia areata and showed that ResPag met the target product profile of standard of care, low-dose JAK inhibitor. The extension phase was specifically designed to evaluate whether continued treatment with ResPag beyond week 36 could drive additional patients to achieve a SALT score 20 response. SALT score 20 represents a patient achieving 80% or more scalp hair coverage, which is the established registrational endpoint in alopecia areata. This was an important question in order to determine if our phase three program in alopecia areata should have a 36-week or 52-week primary endpoint treatment period. The data in April showed that continued treatment with ResPag drove meaningful new responses in patients who had not yet reached SALT score 20 at 36 weeks. 29% and 31% of the 31 patients in the 18 and 24 microgram per kilogram dose arms who entered the blinded treatment extension, respectively, achieved new SALT score 20 responses between weeks 36 and 52, with no new responses in placebo. Across other SALT measurements we looked at, increasing proportions of patients achieved clinically meaningful hair growth thresholds. Importantly, ResPag achieved the target product profile with 52 weeks of twice-monthly dosing. Of note, nearly all of the patients, or 94%, who entered the blinded 16-week extension period completed treatment to week 52. And this demonstrates that when patients understand the promise of ResPag to grow hair, they will continue on twice-monthly treatment. As Howard stated, our plan is to hold an end of Phase II meeting with the FDA this quarter, with the EMA scientific advice coming later this year, to align on the global registrational path forward in alopecia areata. Our ongoing Phase IIb Resolve AA study also has a 24-week off-treatment observation period for all patients. This data is expected in Q4, 2026. These data will give us an opportunity to understand what dosing regimens of RESPEG to use beyond 52 weeks in alopecia areata patients, and whether we include a less frequent dosing regimen in the registrational program. We believe the 52-week data for RESPEG is well-positioned to address several key unmet First, the long-term safety profile is differentiated, including the suitability for chronic use without the safety and monitoring limitations associated with the JAK inhibitor class. Second, the twice-monthly dosing profile enables better potential compliance. And third, the opportunity for more durable and deepening efficacy over time. Beyond our two lead indications, we are pursuing the broader potential of the TREG mechanism. In type 1 diabetes, the ongoing phase 2 study of RESPEG is being sponsored and funded by TrialNet, evaluating ResPag in patients with new-onset stage 3 type 1 diabetes. TrialNet, as a reminder, is the same consortium that ran the foundational studies for teplizumab, the only approved therapy in this setting, and they bring expertise and a deep commitment to finding better options for patients with this diagnosis. In the study, patients are randomized two-to-one to ResPag or placebo and receive treatment every two weeks for six months across three sequential age cohorts, starting with adults 18 to 45 and stepping down to patients as young as 12 and then 8 years of age. The primary endpoint is the change in C-peptide levels after a mixed meal tolerance test at 12 months of treatment. We expect initial data from the study in 2027. Given the challenges with administration and safety of teplizumab, RESPEG could be well positioned for new onset type 1 diabetes. We are also planning to initiate a proof of concept study in at least one new indication in the second half of 2026, with initial data expected in 2027. We are analyzing the disease settings where a T regulatory mechanism has demonstrated clinical activity, and this will help inform our decision on which indication to prioritize with the goal of achieving an additional data catalyst for RESPEG in 2027. And turning to our earlier pipeline programs, Nectar 0165 and Nectar 0166. Nectar 0165 is our TNFR2 agonist antibody, a molecule with very high specificity for signaling through TNFR2 on Tregs to enhance their ability to regulate the immune system. We believe this mechanism has potential across a range of indications, including MS, ulcerative colitis, and vitiligo. In Q1, we announced an academic research collaboration with Dr. Stephen Hauser at UCSF to explore the role of TNFR2 agonism in neurodegeneration, neuroprotection, and cell repair with a focus on patient-derived B-cell models of MS. We look forward to working with Dr. Hauser to inform the future development of this program. We expect to present preclinical data from Nectar 0165 at a scientific conference in the second half of this year. Building on the learnings from Nectar 0165, we have designed Nectar 0166, a bispecific molecule that combines a TNFR2 agonist epitope with an antagonist epitope previously validated in rheumatology. This dual mechanism gives Nectar 0166 the potential to modify disease pathogenesis across multiple autoimmune settings, and we are planning IND submissions for at least one of these programs in 2027. With that, I'll turn it over to Sandy to review our financial results for Q1 2026. Thank you, Jay-Z, and good afternoon, everyone.

Sandra Gardiner, CFO

On today's call, I'll review our quarterly financials for the first quarter of 2026 and provide updated cash guidance. We ended the first quarter of 2026 with $731.6 million in cash and investments with no debt on our balance sheet. In the first quarter, we completed an underwritten public offering and sales under our existing ATM facility, resulting in approximately $525 million in net cash proceeds. This does not include an additional $351 million in net proceeds from our April financing. As Howard mentioned earlier, our current cash balance exceeds $1 billion, and we expect to end 2026 with approximately $800 to $825 million in cash investments. Now turning to the income statement, our first quarter 2026 non-cash royalty revenue totaled $10.9 million. Full year revenue for 2026 is still expected to total $40 to $45 million. Our R&D expenses were $35.7 million for the first quarter of 2026, and we still anticipate full year R&D expense to range between $200 and $250 million, including approximately $5 to $10 million of non-cash depreciation and stock-based compensation expense. As we discussed on our March call, we are still completing the planning and budgeting activities for the RESPEG Phase 3 program. We do, however, expect R&D expense to increase on a quarterly basis in 2026 as these Phase III clinical studies are initiated. Our G&A expenses were $13.4 million for the first quarter. We continue to expect G&A expenses for the full year of 2026 to be between $60 and $65 million, including approximately $5 million of non-cash depreciation and stock-based compensation expense. Non-cash interest expense for the first quarter was $7.9 million and is expected to remain at a similar level for the remaining three quarters, totaling approximately $30 to $35 million in 2026. Our net loss for the first quarter was $44.9 million, or $1.82 basic and diluted net loss per share. And, as I stated earlier, we now expect to end 2026 with between $800 and $825 million in cash and investments. I'll now turn it over to the operator for Q&A.

Operator

Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. In the interest of time, we do ask that you please limit yourself to one question at this time. Please stand by. We compile the Q&A roster. And our first question will come from Yasmeen Rahimi from Piper Sandler. Your line is open.

Dominic, Analyst — Piper Sandler

Hi, this is Dominic on for Yasmeen Rahimi. Thank you for taking our question and congrats on a great quarter and appreciate all the updates. So we're excited for you to be kicking off the Phase 3 AD program soon. Could you just remind us of what are some of the rate-limiting steps left for those? I guess you have the two trials that are starting here shortly. And then could you walk us through some nuggets of detail? I know you said there will be some sites similar to the Phase 2B. So what would the site overlap, I guess, look like for that? Do you have any nuggets of detail on the CRO selection? Anything like that would be very helpful.

Dr. Mary Tagliaferri, Other

Hi, Dominique. This is Mary. Thank you for your question. we too are very excited to move forward with the phase three study. We right now are activating sites and we have the final protocol written. In terms of sites, remember in the Resolve AD phase two, we enrolled 17% of the patients from the United States and 28% from North America. And we had 67% of the patients came from Europe and 5% from Australia. In the Phase III program, we're going to have a larger footprint, particularly in the APAC region or the Asian Pacific region. We, in general, expect to enroll roughly 15 to 25% of patients from North America with a similar proportion of patients specifically from the United States as in our Phase IIb trial, And then approximately 40% to 55% of patients will come from Europe and roughly 20% to 30% from APAC. We will have a number of clinical sites that participated in our Phase 2B program, participating in the Phase 3 as well. We had roughly 130 sites that were activated for the Phase 2B trial, and we'll have roughly 150 sites activated for each one of the Phase 3 studies. Thanks for your question.

Operator

Great. Thank you so much. Thank you. Our next question comes from Julian Harrison from BTIG. Your line is open.

Dominic, Analyst — Piper Sandler

Hi. Congratulations on all the progress, and thanks for taking the question. On your Phase III plan and atopic dermatitis, I'm wondering if you could talk more about the decision to have a separate biologic experience study versus maybe mixing both naive and inexperienced patients across two larger studies?

Dr. Mary Tagliaferri, Other

Yeah, thank you, Julian, for that question. Obviously, the cytokine blocking agents that came before us enrolled patients that were biologic naive, and we do feel it is important to be able to compare the results of the RESPEG study on the EZ75, the IGA, and other secondary endpoints directly to those cytokine blocking agents. And for that reason, we do want to have just a naive patient population. In terms of the experienced patients, we do believe that we'll have similar efficacy in that population. and that's certainly what has been seen in the lebrachizumab trial that evaluated patients who had previously been treated with dupixin. The EZ75 and the IGA score was similar to what was seen with lebrachizumab in the naive patient population. However, we have not yet studied the biologic experience in the JAK inhibitor experience patients yet. Likewise, there may be different clinical sites that has a larger patient population with the biologic experience patients, and it'll be easier for us to find the footprint and enroll those and activate those sites for the experience study. So, we think operationally there are advantages to do it, and likewise, again, having the ability to compare directly to Dupixit and Librakizumab and Trelakizumab that just enrolled the naive patients, we believe will be an advantage. So thanks for the question.

Operator

Thank you. Our next question will come from Jay Olson from Oppenheimer. Your line is open.

Jay Olson, Analyst — Oppenheimer

Oh, hey. I'll add my congrats on all the progress, including getting genus AD up and running in the near term. We had a question on Alopecia Arriata. Can you please provide some updates on your thinking around the Phase 3 study design for RESPEG and AA, and especially in terms of the enrollment criteria, in terms of age of patients and baseline SALT score, and then whether or not you think a single Phase 3 study is sufficient?

Dr. Mary Tagliaferri, Other

Hi, Jay. Thank you for your question. We are having our end of phase two meeting with the FDA this quarter. So we will have more information following the regulatory meeting that we're having. That being said, the phase three study design will be 52 weeks. We will evaluate ResPeg 24 micrograms per kilogram versus placebo. We think a study roughly the size of 600 patients and one single study should be accepted by the FDA. The reason we believe this is that Pfizer did run one phase three study for full load, their JAK inhibitor, and the FDA did accept one single phase three study. So we have asked the FDA to confirm this precedence would also be applied to our program. In terms of age, patients would be 12 years and older. And in terms of baseline SALT score, we will enroll patients with severe and very severe alopecia areata, which is a SALT score of 50 or above. Many people have asked us, you know, could we develop ResPeg for patients with moderate alopecia areata? And we do think the answer to that question is yes. However, that would come after we, you know, would have an approval for the severe, the very severe population. And, of course, JAK inhibitors are not appropriate for that patient population, given, you know, the black box warnings that Howard referred to and the difficulty in managing patients on JAK inhibitors. However, we think there's a huge opportunity for ResTag in that patient population as well.

Jay Olson, Analyst — Oppenheimer

Super helpful. Thank you. Congrats again on all the progress.

Dr. Mary Tagliaferri, Other

Thank you, Jay.

Operator

Thank you. Our next question comes from Chacha Yang from Jefferies. Your line is open.

Cha Cha Yang, Analyst — Jefferies

Hi. Thanks so much for taking my questions. This is Chacha on for Roger Song. So I have a question about your earlier pipeline program, especially in T1D. Can you just tell us more about the collaboration with TrialNet and what that looks like, and particularly what rights that Nectar has to that data and to future development rights? And then my second question related to that is, can you tell us more about the baseline characteristics for the T1D study

Jonathan Zalevsky, Other

and how they might compare to the PROTECT study? Sure. Hey, Sasha. So, in that collaboration with TrialNet, which is part of the NIH and the NIDDK, the TrialNet and the TrialNet Consortium is, you know, besides funding, is also executing the study. So, we work together on the design of the study protocol. It leverages all of their expertise, including the really large data set that they have on the change in C-peptide levels in patients that are newly diagnosed, really this patient population. We also work closely with the lead investigators, and even on our call when we announced the start of the collaboration, the two lead PIs joined that call with us to present the study and the concept behind RESPEG in this indication. So we'll be, you know, working with them, but they're responsible for really, you know, driving the execution of the study. The patient population is very, very, you know, typical in these studies. So they're patients that are within 100 days of their first diagnosis of type 1 diabetes. So these are patients that have really just had their first clinical episode of disease, and they're enrolled into the study within 100 days. So a very typical patient population, you know, for these kind of new onset stage three type one study. And in terms of the rights, you know, Nectar maintains the rights to ResPag, you know, and the future development in type one diabetes that would come subsequent to this if this study is possible. Thank you. Great. Thank you. Thank you. Our next question

Operator

comes from Samantha Semenko from Citi. Your line is open. Hi, good afternoon, and thanks very much

Vivian Wu, Head of Investor Relations

for taking the question. I just have one on the upcoming off-treatment data sets that we're expecting for both atopic derm and alopecia areata. How should we be thinking about what good data would look like in these readouts? Is there a bar for easy maintenance, for example, or salt score maintenance that you would like to see from each of these or some other metric

Dr. Mary Tagliaferri, Other

that you're tracking closely? Thank you. Hi, Sam. So, I think I'll start with alopecia areata first. You know, we continue to dose those 27 patients for an additional 16 weeks, and we just shared those data. And as you saw, there were eight new SALT score, eight new patients that reached the SALT score, less than or equal to 20. The big question that we have is what type of maintenance dosing will be best suited for these patients that have achieved the SALT score less than 20 or have 80% of their hair regrowth. We figured that out in our atopic dermatitis program, the ideal maintenance dosing after a 16 or 24 week induction period should be one month and three months. In terms of alopecia areata, after 52 weeks of treatment, we don't yet know what the maintenance dosing should be. And so for that off-treatment data that we're going to have at the end of this year, it's going to be highly informative to us to understand how we should continue to dose patients in the alopecia areata program after 52 weeks of treatment given 24 micrograms per kilogram every two weeks. In terms of the data from the Resolve AD study, you're absolutely right. We'll continue to follow the durability of those patients' responses and those patients who achieved an EZ75, an EZ90, an IGA0, and 1, and we'll continue to look at the durability of those responses. As we saw with Q monthly dosing and Q three-month dosing, we had exceptional durability, and we also saw deepening of responses. Now, with the off-treatment, we'll be able to determine, And, you know, are patients able to maintain those easy 100 responses, the 30% of patients that achieved that, and the IGA 0 and 1 responses? And remember, we had roughly 60% of patients who had an easy 75 or VIGA at the time of re-randomization achieving an IGA of 0 and 1. So we'll be very eager to see the durability of maintaining the EZ-75, the EZ-100, and the VIGA-01. I think this will be highly informative, again, to understand the dosing frequency for these patients after they're treated with 52 weeks of treatment. So you're absolutely right. the standard endpoints that we use for clinical trials will also be the endpoints that we'll look at in the off-treatment timeframe. Thanks for the question. Thank you. Our next question comes

Operator

from Mark Fromm from TD Cowan. Your line is open. Thanks for taking my questions. Congrats on all

Dominic, Analyst — Piper Sandler

the progress getting the trials designed. Maybe just on that bioexperienced patient study in atopic dermatitis. Can you just walk through kind of how you're defining bioexperience there? You know, will patients be required to have, you know, overtly failed therapy, or could they have discontinued for any other reason? Just, you know, how long do they have to have been off therapy, things like that? And will that include JAK experience patients, or just focused on the IL-413 pathway? Great. Thanks, Mark, for the question.

Dr. Mary Tagliaferri, Other

So, all the candidates have to require systemic therapy. So, they have to have a history of atopic dermatitis for at least 12 months, and they have to have had an inadequate response to topical medication. And then, in addition to that, these patients have to have then had either a biologic or a JAK inhibitor. So, we will be enrolling patients that have also been on JAK inhibitors. In terms of washouts for biologic, patients will have to have been off treatment for 12 weeks or five half-lives, whichever is longer. And then for JAK inhibitors, it'll be a washout of four weeks. The eligibility criteria for moderate to severe atopic dermatitis is very similar for both studies. Of course, patients have to have an easy score of 16 or higher, a body surface area of 10% or more, and have an entry of a VIGA, or excuse me, an IGA of

Dominic, Analyst — Piper Sandler

three or four. Okay, I think that's very helpful. And do you think you need to be successful in all three trials to get approved, or is two out of three enough for approval, do you think?

Dr. Mary Tagliaferri, Other

Yeah, you know, I think that this is a great regulatory question, and as we, you know, unblind the data and have conversations with our regulatory advisors, I do believe that, you know, showing efficacy in two well-controlled randomized trials would be sufficient for regulatory approval, but we, again, will have to have those conversations with the FDA at the time of our BLA submission. Okay. Thank you. Yeah. Thank you for the question. Thank you. Our next question

Operator

comes from Mayank Bantani from B. Riley. Your line is open. Yes. Good afternoon, team. Thanks

Mayank Bantani, Analyst — B. Riley

for taking your questions, and congrats on the progress. Just on the prior comment on the AD off-therapy, durability data, you know, just curious how do you expect an endpoint like EZ100 to sort of evolve over time there? And then on the earlier stage pipeline, the 1665-specific program, Jay-Z, this was curious how you're thinking of developing that maybe relative to 0165 and maybe just remind us what are the key milestones to watch out for those two programs?

Jonathan Zalevsky, Other

I can start with the last question first, Mayank. So for 166, so as we mentioned, it's a bispecific that contains a TNFR2 agonist on one arm and then a validated target for rheumatology indications on the other arm. So our indications are definitely in the rheumatology setting. And then we have the opportunity to have basically multiple mechanisms that we bring forward, one that's known as well as adding a TNFR2 second component for a potential differentiating novel approach to treating rheumatology diseases. In terms of the main milestones that we have across that program is we have IND enabling studies around 165, and then the 166 program is a little bit further behind, but it's also undergoing those same IND-enabling studies as well. And I'll turn it over to you, Mary, for the other question. Yeah, thanks. So, as you know,

Dr. Mary Tagliaferri, Other

we did publish data from our Phase 1b in Nature Communications, and this was published in 2024. And what we did show is that patients were dosed with the highest dose of ResPeg 24 micrograms per kilogram, and then those patients, after 12 weeks of treatment, were off therapy for a total of nine months. And we did see that, you know, these patients were able to maintain their EZ75, and there was remarkable durability, and you can see that in the publication. So, you know, if we replicate the data from the early phase one, we would see, you know, durability for potentially, you know, nine to 12 months off therapy. Again, I think the goal here is to find a treatment regimen that's highly differentiating from the current available therapies. And as you know, with dupixin, patients have to take, you know, an injection every two weeks indefinitely. And so we really believe if we can get to a dosing regimen of ResPeg that's monthly or every three, you know, quarterly, just like SkyRizzy, four times a year, this will be a huge advantage for patients and quite a transformation in this field. Hopefully, the data will also show durability off treatment, and therefore, if patients go for longer than three months without dosing, especially if they, you know, get to an easy 100, complete clearance of disease and have this level of durability, this will be a huge advantage for patients. I think we're all eager to see the data and to see the length of time that patients can maintain their, you know, IGA0 or, you know, the EZ75, EZ90, and EZ100. So we really look forward to having those data in the first quarter of next year. Thank you for the question.

Mayank Bantani, Analyst — B. Riley

Thank you, Ma'am.

Operator

Thank you. Our next question comes from Arthur Hay from H.C. Wainwright. Your line is open.

Arthur Hayes, Analyst — H.C. Wainwright

Hey, how are you, Tim? Congrats on the progress. So, I had two quick questions at the alopecia areata program. So, first, could you remind us how you picked the 24-week of treatment period at the first place? Why not longer? And also, for the phase 3 study, are you guys contemplating to include JAK inhibitor experience or refractory patients in the phase 3 study for alopecia? Thank you, Sherriana. Thank you.

Dr. Mary Tagliaferri, Other

Thanks, Arthur. So, we chose the 24-week off treatment period because you may know with JAK inhibitors, patients start to lose hair relatively quickly. And so, we felt like that was the sufficient amount of time to potentially see a differentiation between JAK inhibitors and ResPeg. And in terms of the phase three, we are going to go with patients who are JAK inhibitor naive. However, you know, there are multiple other ways to evaluate ResPeg in a patient population that is JAK inhibitor experience. We do believe that in this particular indication, ResPeg could be a first-line therapy. And, you know, for those of you who were able to listen to our presentation for the 52-week data in alopecia areata, all of our KOLs said that the vast majority of patients, and in fact, Jonathan Zilberg said 90% of his patients would use ResPeg in the first-line setting. So we do and we are positioning ResPeg in the first-line setting for alopecia areata, and we do believe the drug will be effective as well in patients who have already experienced the JAK inhibitor and will find another pathway to explore ResPeg and evaluate ResPeg in that patient population as well. So thanks for the question, Arthur.

Arthur Hayes, Analyst — H.C. Wainwright

Thanks, Mary.

Operator

Thank you. Our next question comes from Andy Shea from William Blair. Your line is open.

Andy Shea, Analyst — William Blair

Thanks for taking our question. Just follow up on Jay's question previously. Mary, you mentioned about having to basically conduct a phase three trial in alopecia and getting a label before conducting a trial in a moderate population. So I'm curious, one, do you have to go back to a phase two or you can start a phase three after that? And then the other one is really about understanding FDA's pushback. Is it, are they not comfortable with the safety database? You know, especially now you have, you know, hundreds of patients in safety databases. So just, I'm curious about why there's such a regulatory pushback in a moderate population.

Dr. Mary Tagliaferri, Other

Thanks, Andy. So we, you know, do have to speak to the agency about the moderate population. But after speaking with our steering committee members, you know, the placebo effect for alopecia areata for patients who have severe and very severe disease is very low. You know, for SALT20, it's single digits between, you know, 2 and 5 percent. So running a clinical trial where the placebo effect for your primary efficacy endpoint is low, and, you know, testing the same population as in our Phase IIb AA study, you know, gives us a high probability of technical success for our registrational program. Now, that being said, in the moderate patient population, the, you know, per our KOLs and our steering committee, the placebo effect could be higher in the population of patients that have, say, you know, a SALT score that's actually less than 50, so in the 30 to 50 range. So, you know, we believe that the best path forward is to go with the clear regulatory precedence where there is a clear endpoint for the patient population that's with assault 50 or above, and we will have a conversation with the FDA about the moderate patient population. We have not gotten feedback yet through our end of phase two or regarding the moderate population, so we have not received any pushback. We just haven't had the conversation yet, Andy. Got it. That's helpful. Thanks, Mary. Thank you.

Operator

Thank you. And our next question comes from Jessica Fai from JPMorgan. Your line is open.

Jessica Fai, Analyst — JPMorgan

Thanks for taking our question. This is also for Jess. It seems like you have much of a plan in place for the Phase 3 in alopecia. So I wonder if you can, you know, what are the points that you can hammer, you want to hammer out with FTA at the end of Phase 2 meeting?

Dr. Mary Tagliaferri, Other

Of course, you know, a lot has come up about, you know, can you run one phase three clinical trial versus two? And, you know, again, there's precedence for one phase three clinical trial for this indication. As we mentioned, Pfizer was able to have their JAK inhibitor with FULO approved with one phase three. So I would say that's probably the most important question and answer that we want to have from the FDA after our end of phase two meeting. In addition, you know, we have submitted, you know, our study design, and we want to make sure that the FDA agrees with the powering of our trial and the eligibility criteria. And I think the third and also important point is the totality of our safety data. As Andy Shea just brought up, you know, we do have a very large safety database with over 1,000 patients dosed in an inflammatory skin disease, and so we also want alignment with the agency over the safety database for alopecia areata when we file our BLA. So, those are three of the most important topics that we want to have clarity and alignment with the agency. Thanks for the question.

Operator

Very helpful. Thank you. Thank you, and I'm showing no further questions from our phone lines, and I'd like to pass the conference back to Howard Robin for any closing remarks.

Howard Robin, CEO

Well, before I end the call today, I want to comment that Sandy, our current interim CFO, will be retiring on May 15th. And as our interim chief financial officer, Sandy has played an instrumental role in supporting Nectar over the last three years, and we're very grateful for her contributions, and we'll miss her. For continuity, we're bringing in another partner from FLG Partners, Linda Rubenstein, who will take over Sandy's role as interim CFO. Linda has 35 years of experience and has served as interim or permanent CFO, leading finance and financial reporting at a number of biotechnology companies, including Celexa, Five Prime, True North, and most recently, Edverum. Her early career was in M&A banking, and all of us do wish Sandy the very best in her retirement. I want to thank everyone today for joining us and for your continued support. We really appreciate it. I also want to thank our employees who have worked tirelessly to advance our research in pursuit of novel treatment options for patients, and together, we've transformed our scientific hypothesis into real and potentially meaningful therapeutic options. We look forward to initiating our Phase III studies in ectopic dermatitis in the coming months and advancing alopecia areata into Phase III as well, and we will also be exploring other RESPEC potential in T-cell-mediated diseases. So we thank you very much for joining us today, and stay tuned.

Operator

Thank you. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.