Mary: 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, you know, are patients able to maintain those easy 100 responses, the 30% of patients that achieved that, and the IgA zero and one 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 zero and one. So we'll be very eager to see the durability of maintaining the EZ75, the EZ100, and the VIGA01. 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.
Operator: Thank you. Our next question comes from Mark Fromm from TD Cowan. Your line is open.
Mark Fromm: Thanks for taking my questions and congrats on all the progress getting the trials designed. Maybe just on that bio experience. 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?
Mary: Great. Thanks, Mark, for the question. 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 had to have had an inadequate response to topical medications. 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 three or four.
Mark Fromm: 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?
Mary: 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.
Operator: Okay, thank you.
Mary: Yeah, thank you for the question.
Operator: Thank you. Our next question comes from from B. Riley. Your line is open.
Mayank: Yes, good afternoon, team. Thanks for taking our questions and congrats on the progress. Just on the prior comment on the AD off-therapy durability data, you know, I'm 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, JV, just was curious how you're thinking of developing that maybe relative to V165, and maybe just remind us what are the key milestones to watch out for those two programs?
Seth: I can start with the last question first, Mayank. So for 166, so as we've mentioned, it's a bispecific. right, 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, right, 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.
Mary: Yeah, thanks. So as you know, 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 Respec, 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 EZ-75 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 Dupixent, patients have to take 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 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: Thank you, Maddie.
Operator: Thank you. Our next question comes from Arthur Hay from H.C. Wainwright. Your line is open.
Arthur Hay: Hey, Howard team. Congrats on the progress. So, I had two quick questions on the alopecia areata program. So, first, could you remind us how you picked the 24-week treatment period at the first place? Why not longer? And also, for the Phase III study, Are you guys contemplating to include a JAK inhibitor experience or refractory patient in the phase three study for LPCI-Rata? Thank you.
Mary: 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 a 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 experienced. 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 a 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 Hay: Thanks, Mary. Thanks, Seth.
Operator: Thank you. Our next question comes from Andy Shea from William Blair. Your line is open.
Andy Shea: 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. Are they not comfortable with the safety database? Especially now you have hundreds of patients in safety databases. So just I'm curious about why there's such a regulatory pushback in a moderate population. Thank you.
Mary: 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%. 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 a SALT 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.
Andy Shea: Got it. That's helpful. Thanks, Mary.
Mary: Yep. Thank you.
Operator: Thank you. And our next question comes from Jessica Thigh from J.P. Morgan. Your line is open.
Jessica Thigh: Thanks for taking our question. This is also for Jess. It seems like you have much of a plan in place for the phase three in alopecia. So, I wonder if you can, you know, what are the points that you can hammer, you want to hammer out with FDA at the end of phase two meeting? Thanks.
Mary: Yep. Thanks. 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 uh phase three clinical trial for this indication as we mentioned um pfizer was able to um have their jack 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 fba after our end of phase two meeting in addition um you know we have submitted uh you know our 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' dose 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.
Jessica Thigh: Very helpful. Thank you.
Operator: 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: 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, 5 Prime, True North, and most recently, Adverum. 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 three studies in ectopic dermatitis in the coming months. and advancing alopecia areata into phase three 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.
