Please be advised that today's conference is being recorded. I'd like to hand the conference over to our first speaker today, Bohan Wei, Vice President of Corporate Development and New Product Planning. Please go ahead. Thank you, operator. Good morning, and thank you for joining the Palvella Therapeutics phase III SELVA top-line results in microcystic lymphatic malformations call. This morning, we issued a press release announcing positive top-line results from our phase III SELVA study of QTORIN 3.9% rapamycin in hydrogel for the treatment of microcystic lymphatic malformations, a serious, rare, and chronically debilitating disease for which there are currently no FDA-approved therapies. Our press release detailing today's announcement can be found in the investors section of our website at www.palvellatx.com. Before we begin, please note that today's remarks may include forward-looking statements regarding our development program, regulatory strategy, commercial planning, and financial outlook. These statements are based on current assumptions and are subject to risks and uncertainties that could cause actual results to differ materially. Please refer to our SEC filings for a full discussion of these risk factors. On today's call, we are joined by Wes Kaupinen, Palvella's Founder and Chief Executive Officer, Dr. Jeff Martini, our Chief Scientific Officer, and Matthew Korenberg, our Chief Financial Officer. We are also very pleased to have with us today Dr. Michael Kelly, a pediatric hematologist-oncologist and physician-scientist at the Cleveland Clinic and a nationally recognized expert in vascular anomalies. Over more than two decades, he has cared for thousands of children and adults with vascular anomalies, including microcystic lymphatic malformations, and he also serves as Executive Director of the Lymphangiomatosis & Gorham's Disease Alliance. Dr. Kelly is an investigator in our phase III SELVA trial, where his clinical insight has been instrumental. We are truly honored to be joined by someone who is on the front lines caring for children as well as adults with microcystic lymphatic malformations. With that, I would like to turn the call over to Wes. Thank you, Bohan. Good morning, everyone. Welcome to our phase III SELVA top-line results call. I'd like to begin by expressing my sincere gratitude and the collective gratitude of everyone here at Palvella to the SELVA study participants and their families, as well as the caregivers, investigators, clinical research staff, patient advocates, and research partners who made the landmark phase III SELVA study possible. The trust that the patient and clinical communities have in Palvella is profoundly meaningful to us. We recognize the responsibility that comes with that trust, and we're committed to earning that trust every day by conducting our clinical programs with integrity, scientific rigor, and an unwavering focus on putting patients first in every decision we make. Palvella in Finnish means to serve. The mission of our company is to serve patients living with serious rare diseases, and specifically those rare diseases with no FDA-approved therapies, and to develop transformative, high clinical impact treatments for the patients who need them most. We exist for individuals who have long been overlooked by the biotech industry and who have been told to wait, endure, and suffer with a lifelong genetic disease. Today's positive phase III SELVA results in microcystic lymphatic malformations are more than just a milestone. They are evidence that Palvella's mission, vision, and strategy are translating into tangible progress for rare disease communities who deserve a biopharmaceutical company to stand with them and behind them. These positive results further energize our team at Palvella to build the leading rare disease biopharmaceutical company dedicated to serious rare skin diseases and vascular malformations. Today represents a defining step forward in realizing that ambition. SELVA in Finnish means clear, and with the positive phase III study results announced this morning, we see a clear path forward for QTORIN rapamycin to potentially become the first FDA-approved therapy for children and adults who are afflicted with microcystic lymphatic malformations, a chronically debilitating and lifelong genetic disease. In this SELVA study, QTORIN rapamycin demonstrated a highly statistically significant outcome on the primary endpoint, the key secondary to endpoint, and all four additional secondary endpoints. On the primary endpoint, QTORIN rapamycin demonstrated a +2.13 improvement on the microcystic lymphatic malformation Investigator Global Assessment Scale, resulting in a p-value of less than 0.001. We believe this large magnitude effect size is clinically transformative and even more compelling when viewed in the context of a disease where patients currently have no FDA-approved therapies. At week 24, 95% of participants completing the 24-week efficacy evaluation period improved on the mLM-IGA primary endpoint. 86% of participants completing the efficacy evaluation period were rated as much improved, plus two, or very much improved, plus three. QTORIN rapamycin was well-tolerated, similar to the results we've previously seen in our clinical studies. At the conclusion of the efficacy evaluation period, participants were given the option to continue on QTORIN rapamycin as part of an open-label treatment extension. In SELVA, 98% of completers at week 24 elected to roll into the extension period, which we view as very encouraging. Based on the SELVA results and the results from our phase II study, as well as the extensive market research our team has conducted, we believe QTORIN rapamycin has the potential to be a first-line and standard of care therapy for microcystic lymphatic malformations. I will now pass the call over to our Chief Scientific Officer, Dr. Jeff Martini. Jeff? Thank you, Wes. Microcystic lymphatic malformations is a disease that fits Palvella's strategy. It is serious, debilitating, and lifelong, with no FDA-approved therapies. We want to be first for these patients. The genetics are well characterized. Monogenic somatic mutations lead to hyperactivation of mTOR signaling, which drives the disease pathology. The disease course is proliferative and progressive with no regression. Clinically, the lesions present at birth and persist throughout a patient's life. These lesions are characterized by lymphorrhea and deep infections, which may result in hospitalization. As pioneers in this disease, we've conducted multiple epidemiology studies, all of which indicated diagnosed U.S. prevalence exceeding 30,000 patients. I want to point out the photos on the right-hand side of this slide. These are actual pre-treatment photos from four patients who enrolled in the SELVA study. You can see the significant disease burden, and Dr. Kelly will describe the clinical impact to these patients later in the presentation. QTORIN is our platform for reproducibly generating novel topical products and is specifically designed to deliver complex molecules like rapamycin to the skin. Rapamycin is a biologically potent yet inherently challenging molecule, highly lipophilic, poorly soluble, it's unstable, large, and prone to crystallization. QTORIN was designed to address these challenges. Importantly, starting concentration is only one piece of the complex puzzle of topical delivery. QTORIN enables hydro uploading while maintaining rapamycin in a stable, molecularly dispersed state, protecting against breakdown and crystallization so that it can be made bioavailable. QTORIN also drives rapamycin across the skin, achieving concentration in the dermis that exceed the IC90 required for mTOR inhibition. QTORIN was optimized for chronic dosing. It promotes skin retention while limiting systemic exposure, minimizing the side effects common with oral rapamycin. Our objective has always been to develop a product with transformational efficacy for patients with mTOR-driven skin diseases. We are thrilled that the SELVA results today support this. We established base and upside goals grounded in what we believe would meaningfully improve patients' lives while supporting a compelling commercial opportunity. As shown here, SELVA exceeded our predefined objectives across every major dimension. We observed a highly statistically significant mLM-IGA improvement of +2.13, well above our upside threshold of 1.5 points. Importantly, 95% of patients were plus one or greater on the scale. 86% were a plus two or greater. The blinded key secondary endpoint, the mLM-MCSS, was also highly statistically significant. This assessment was performed by independent clinicians who reviewed randomized, time-blinded photographs from baseline and week 24, evaluating the core signs of disease, lesion height, leaking and bleeding, and vesicle appearance. From a safety perspective, QTORIN rapamycin was well tolerated in both children and adults, supporting chronic dosing across all ages. Retention was exceptionally strong, with 98% of week 24 completers electing to roll in the extension period, supporting durability and continued treatment benefit. When we look at the whole picture, SELVA exceeded what we hoped to see, not just on efficacy, but on durability and safety as well. Ultimately, that's what translates into meaningful impact for patients of all ages diagnosed with microcystic lymphatic malformations. SELVA is a single-arm, baseline-controlled study evaluating once-daily QTORIN rapamycin in patients three and older, with efficacy assessed over 24 weeks, followed by an extension period. FDA guidance supports single-arm trials for rare diseases with well-understood pathophysiology and a well-defined disease course. The study and endpoints were informed by our successful phase II study and meaningful input from both patients and clinicians. We designed the study to capture both global changes in disease severity and changes in the individual signs that matter most to patients. In the 24-week study, 50 patients received QTORIN rapamycin, 49 in the ITT population, including one- three- to five-year-old. We are very pleased with the nearly 90% retention rate at week 24. Of those who completed the study, 98% elected to enter the extension study. Of note, the program was supported by an FDA Orphan Products Grant, with two tranches of non-dilutive funding awarded, reflecting recognition of both the unmet need and the robustness of the study design. The study included a broad age range, capturing the early onset and chronic lifelong nature of microcystic LMs. Importantly, the enrolled patient population represented patients with meaningful disease burden. Nearly three-quarters of patients failed prior procedures or medical therapies before study enrollment, underscoring the clinical need for effective and safe therapies for this population. The data from SELVA demonstrate a transformative outcome for patients. On the primary endpoint, the mLM-IGA, we observed a mean improvement of +2.13 at week 24, which was highly statistically significant, with a p-value of less than 0.001. In a pre-specified analysis, the mean improvement was statistically significant at every post-baseline time point and continued to improve through each visit. We also observed a high magnitude of effect across all age cohorts. 95% of patients demonstrated improvement on the mLM-IGA, which was consistent across both adult and pediatric patients. On the key secondary endpoint, the blinded mLM-MCSS, we again observed highly statistically significant improvement. This endpoint incorporated independent, blinded review of randomized photographs from pre and end of treatment, adding an important layer of objectivity to the trial. The MCSS is the sum of the three static severity scales, capturing the core signs of disease, lesion height, leaking and bleeding, and vesicle appearance. In a pre-specified analysis, each of these individual components were also statistically significant. All four secondary endpoints, PGIC, Live MCSS, CGIS, and PJS, demonstrated highly statistically significant improvements. These endpoints capture both clinician and patient-reported outcomes, providing a comprehensive assessment of treatment effect. We believe the results presented here today are unequivocally positive and clinically meaningful. When I step back and look at the totality data, what stands out is the consistency. We see concordance across adult and pediatric patients, across every time point, across global assessment, individual signs of disease, and across both static and dynamic scales. We plan to present these, as well as additional sensitivity analyses in more detail at upcoming medical conferences. QTORIN rapamycin was well tolerated in the SELVA study. 17 participants experienced treatment-emergent adverse events that were deemed by investigators to be treatment-related. The most common included application site acne, discoloration, and pruritus. Consistent with previous studies, systemic rapamycin remained below two nanograms per mL for all patients across all time points in the study, showing minimal systemic exposure. Before I hand the call over to Dr. Kelly to review the case studies as well as the striking photos, I'd like to take a moment to thank everyone who made this study possible, from trial design through execution and data QC. Thank you to my clinical operations colleagues, led by Kathy Goin and Emily Cook, and to the site coordinators who worked tirelessly to ensure flawless study conduct. Thank you to our investigators for your partnership in trial design, endpoint refinement, and for your engagement throughout the training process. Most importantly, thank you to the patients and families. This was a long and demanding study requiring real commitment. We are deeply grateful to you for taking that first step in being first. I'll now hand the call over to Dr. Kelly, who will discuss some of the patient cases. Thank you, Jeff. Before we show the photographs, I want to take a moment to give context about previous treatments. Nearly three-quarters of the participants enrolled in SELVA had failed prior procedures or medical therapies before joining the study. These therapies can change lesional biology and impact patients' psychological expectations, often negatively affecting how they respond to new treatments. As a result, patients who have been pretreated often respond worse than those who are treatment naive. With this in mind, the high clinical impact of QTORIN rapamycin in the SELVA study is especially significant. The first case that I want to discuss is a 10-year-old girl with an extensive microcystic lymphatic malformation involving her shoulder. Bleeding and leaking were her major symptoms. She had previous laser therapy without a meaningful or durable response. At baseline, she had fluid-filled vesicles of various sizes that are clearly elevated above the skin. After 24 weeks of QTORIN rapamycin, we observed a visible reduction in the number of vesicles, the vesicle height, and lightening of the lesion color with more normalized skin appearance. These findings are consistent with the clinician plus two change on the mLM-IGA scale. This patient elected to continue therapy during the treatment extension period. The second case involves a 10-year-old boy with a microcystic lymphatic malformation affecting his inner thigh. He experienced episodes of leakage complicated by serious infections such as cellulitis, which required antibiotics. Clothing, like pants and underwear, constantly irritated the area, leading to new episodes of leakage, bleeding, and pain. He did not respond to conservative measures like wrapping or interventional measures like sclerotherapy procedures. At baseline, he had an extensive lesion with elevated fluid and blood-filled vesicles coalescing into large plaques on the skin. Following 24 weeks of QTORIN rapamycin, he experienced a significant reduction in the number and height of vesicles, with more normal skin in the affected area. What is noticeable in these pictures is the visible flattening of the lesion, suggesting a reduction in proliferative tissue burden, along with improvement in vesicle morphology and decreased evidence of active disease. From my perspective, this represents improvement across structural and functional domains, not just a change in the surface appearance. The next patient is a 14-year-old young lady with a microcystic lymphatic lesion involving her neck. This is an anatomically sensitive and cosmetically visible area. Complications included episodes of leaking with inflammation, leading to red and painful lesional skin. She was previously treated with compounded rapamycin and reported skin irritation as a result. At baseline, the lesion showed elevated fluid-filled vesicles, a few blood-filled vesicles, and a mild discoloration of the surrounding skin, all consistent with active microcystic disease. Following treatment, we see resolution of vesicles on the surface, replaced with what appears to be normal skin. The clinician and patient reported three plus on the clinical change scales. Palvella included qualitative interviews as part of their protocol to capture the patient voice, which are highly impactful. I especially want to read a direct quote from this patient, that I believe reflects the clinical significance of this treatment. She said, "I've seen great changes. I've seen a lot of the red color before turn to, like, just my skin color, and the texture of the lesion has gone down. It's basically almost flat." The final patient is a seven-year-old girl diagnosed with a microcystic lymphatic malformation involving her inner elbow, an area subject to constant movement, resulting in friction and recurrent irritation. Her major symptoms were episodes of bleeding, leaking, and irritation, causing pain. She failed previous laser therapy. At baseline, you can see elevated fluid and blood-filled vesicles coalescing into plaques. The underlying skin is erythematous, suggesting an inflammatory inflammation and irritation. After 24 weeks of treatment with QTORIN rapamycin, you can see a dramatic reduction in the vesicle height and color, with more normal-appearing skin in the lesional area. Both the clinician and the patient reported plus three on clinical change scales. She elected to continue treatment in the extension period. From my perspective, this case demonstrates the effectiveness of once-daily administration of QTORIN rapamycin in managing a very challenging disease in a difficult anatomic location. In summary, QTORIN rapamycin is designed to directly target the underlying pathophysiology of microcystic lymphatic malformations, addressing disease at its source. In two prospective trials, QTORIN rapamycin has demonstrated a large and consistent treatment effect, reinforcing its ability to positively impact patient outcomes. Coupled with a favorable safety profile that supports chronic long-term therapy, QTORIN rapamycin has the potential to become a first-line treatment and establish a new standard of care for patients living with microcystic lymphatic malformations. I will now pass it back to Wes for some concluding remarks. Thank you, Dr. Kelly. Our NDA team is assembled, regulatory interactions are underway. We are planning on an NDA submission in the second half of 2026, doing so under multiple expedited FDA programs, including Breakthrough Therapy and Fast Track designation, which have previously been granted to QTORIN rapamycin by the FDA. In parallel, U.S. launch preparations are accelerating. We've recruited exceptional commercial and medical affairs leadership, including Ashley Kline, our Chief Commercial Officer, and Vimal Patel, our Head of Medical Affairs. Both microcystic lymphatic malformations and cutaneous venous malformations are multi-billion dollar total addressable market opportunities. We estimate peak U.S. sales potential between $1 billion-$3 billion dollars for QTORIN rapamycin across our first two indications in microcystic lymphatic malformations and cutaneous venous malformations, both of which have attractive commercial dynamics, given the absence of FDA-approved therapies. Our pipeline and a product strategy for QTORIN rapamycin marches on. We're working closely with scientific and clinical leaders to prioritize additional clinical indications across a broad field of mTOR-driven skin diseases, plan to announce a fourth indication for QTORIN rapamycin in the second half of this year. Our QTORIN platform remains our foundational asset. Under the leadership of David Osborne, our Chief Innovation Officer, we are increasing the pace of new product candidate generation from the platform while maintaining our core pillars of scientific rigor, discipline, development, selectivity, and capital efficiency. With that, we'd be happy to open the line, operator, for questions. Thank you. At this time, we'll conduct a question-and-answer session. As a reminder, to ask a question, you'll need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Josh Schimmer of Cantor. Your line is now open. Great. Thanks so much for taking the questions, and congrats on the remarkable data. Two quick ones, or actually one quick one, maybe one less quick one. Can you talk to the gating steps to the NDA filing? Separately, maybe you can talk to the strength of the QTORIN platform IP, and what gives you confidence that generics won't be able to find viable workaround solutions? Thank you. Josh, thanks for the questions. On your first question, the NDA remains fully on track to be submitted in the second half of this year. Modules have already been drafted. We'll now take the clinical data from the SELVA study, have that clinical data populate the clinical module. That will include completing the clinical study report from the phase III study. That's really the key step for the completion of the NDA. On your second question, as it relates to intellectual property. At Palvella, we have a multilayered exclusivity strategy. Number one, patents. Two, our trade secrets, both manufacturing and regulatory, as well as or regulatory exclusivities. On our patents, Josh, we have six granted patents in the United States, with broad claims across both the anhydrous formulations of rapamycin and other mTOR inhibitors, as well as method of use. Our trade secrets are both manufacturing and formulation related. Those are some of our most significant innovations, which are not included in our patents, and we're grateful to the FDA for the orphan designation we have in microcystic lymphatic malformations, which would provide us with seven years of exclusivity. I think importantly, it'll be very challenging to reproduce QTORIN without both the manufacturing and formulation trade secrets. We know our technology well, and small changes in the formulation result in very significant differences in product performance. That's gonna provide what we think very significant barriers to any generic formulations. Great. Thanks very much, and congrats again. Thank you. Thank you. We'll move in for our next question. Our next question comes from the line of Graig Suvannavejh of Mizuho. Your line is now open. Thanks for taking my question. Good morning, and congrats on the superb data. Two questions, if I could. One, just was notable to see the remarkable continuation into the extension study and was wondering what you think that could mean for compliance. A second question I had just really had to do, maybe the KOL can answer this, where it seems like the clinician scores were slightly better than the patient-related scores, and I was wondering, you know, any thoughts around that? Yeah, Graig, thanks for both questions and your kind words about the quality of the SELVA data. We're encouraged, very encouraged, in fact, by the compliance. As you referenced, the conversion rate from completers in the SELVA study was 98%. We had 43 out of 44 patients roll over from week 24 into the open label extension period. We designed this formulation many years ago with a team of leading formulation scientists, and we made many decisions as it relates to the product configuration to optimize this vehicle to be tolerable for patients that have a genetic skin disease. Seeing these types of efficacy results, but also patients electing to stay on the drug, really is encouraging to us, and we think it's a testament to the formulation and its tolerability profile and the benefit that these patients are experiencing. We'll pass it over to Dr. Kelly, Graig, to comment on the numerical differences between the clinician-reported outcomes and patient-reported outcomes. I just want to note that both the patient-reported outcomes and clinician-reported outcomes that were pre-specified were all statistically significant. Dr. Kelly? Thanks, Wes, and thanks, Graig, for the question. I think it's pretty common to see differences in patient-reported and clinician-reported outcomes in clinical trials. I will say that, you know, you have to remember the patient perspective in this process, and that they have a lifelong disease. They've lived with this disease. They have basically accommodated this disease. I think that, you know, their interpretation of severity of disease often differs from that of the more, probably more objective clinician in this case. I will say that, what is really, I think, empowering about these results is that there is a concordance, meaning that there may be slight differences in the numeric values, but both see positive changes and significant positive changes, you know, with the QTORIN rapamycin. I think the consistency of that across two clinical trials is actually, quite meaningful and really is very encouraging with regard to, ultimate success of this, of this drug. Thanks again. I'll jump back in the queue. Thank you. We'll move for our next question. Our next question comes from the line of Sam Slutsky of LifeSci Capital. Your line is now open. Hey, everyone, congrats on the data update today, and thanks for taking the questions. I guess for Dr. Kelly, be curious how you would incorporate QTORIN rapamycin into your clinic, once approved, hopefully, in terms of, like, what percentage of patients could get this. Could you talk about kind of durability of treatment? For the Palvella team, if you could just kind of review again some of the market, opportunity work as it relates to epidemiology, pricing, as well as kind of the range of daily dose that patients may need as you think about, the range of patient backgrounds? Great. Thanks for the question, Sam. Dr. Kelly, do you want to respond to the first part of Sam's question? Absolutely. Thanks for the question, Sam. I think that, you know, the simple answer to where I would place, you know, QTORIN in my therapeutic algorithm, it would be first. You know, I think that it, the demonstration of efficacy in the clinical trials has really been remarkable and is actually has far exceeded any sort of standard cares that we use, either, you know, compounded topical sirolimus, or procedural interventions like laser and/or sclerotherapies. I think that the ability to apply this medication at home in a once-daily fashion will actually promote adherence and compliance rather than having to come in, you know, to a procedural center or a clinic in order to get infusions and/or applications. Again, I think that this quickly becomes the first-line therapy for myself and many of my colleagues. I think that the safety and durability of the response speaks, you know, to the longevity that will likely be required for use of this drug to mediate or moderate the symptoms of microcystic lymphatic malformations. Thank you, Dr. Kelly. Sam will respond to your second question in terms of the market opportunity. As you know, this is a rare disease where nothing is approved. We feel that it's incumbent upon Palvella as the pioneer in this disease, to do multiple epidemiological studies to try to understand both the diagnosed prevalence of the disease as well as the annual incidence of the disease. The data that we generated across three different studies, two of those being claims analysis, which we view as the gold standard way to pursue understanding diagnosed prevalence and annual incidence, suggests that there's over 30,000 diagnosed U.S. patients currently within clinical medicine. In addition to that, we estimate there's an incident pool of about 1,500 new patients per year that will be added to that prevalent pool. From a pricing perspective, we've put out some guidance around that. Our plans would be to price the drug between $100,000-$200,000 per patient per year. We will retest on pricing now that we have phase III data on hand, and then eventually announce a launch price at FDA approval. In terms of the range of daily dosing, most of these patients are able to actuate our airless pump once, get two fingertip unit of drug, which is enough drug product to cover the average lesion. There is a smaller cohort of patients that have larger lesions, that may require more than one pump or more medication compared to the average lesion. That's something that our Medical Affairs team and Commercial team, Scientific team with Jeff Martini, are working to understand, just what percentage of patients have those larger lesions. Thank you. One moment for our next question. Our next question comes from the line of Ritu Baral of TD Cowen. Your line is now open. Good morning, guys. Congratulations on the data. A few questions from me. One, the key secondary, the MCSS, Could, Dr. Kelly, could you speak to the meaningfulness of that change, the, delta of three on the centrally read and the delta of four on the live? Is there, like, an aspect or subscale of that scale that makes it key either? Whether that's from, like, an FDA perspective, and was there a requirement there, or, from a clinician meaningfulness perspective? Then I've got a question on the dropout. Great. Thanks, Ritu, for those questions. I'll actually pass it over to Jeff just to give everyone an overview of the key secondary endpoints. You're right, you refer to it as a blinded key secondary endpoint, and Jeff will give an overview of the scale, the range on the score, and then we can pass it over to Dr. Kelly to talk about the three components of the scale, which are height, vesicle appearance, and leaking and bleeding. Jeff? The MCSS is an endpoint that we proposed to the FDA, and it involves an independent group of clinicians, so they were not study site investigators. They got randomized photos, either from pretreatment or at the end of treatment, in scrambled order, and they evaluated the three key signs of the disease on a five-point static scale ranging from one to five, and those, as Wes mentioned, were height, vesicle appearance, and leaking and bleeding. We did see a statistically significant reduction in the composite or addition of all three, as well as we saw a statistically significant reduction or improvement on each of the individual subscores. The reason we call it the key secondary endpoint, to address that question, is just due to the statistical hierarchy in our statistical analysis plan. The primary endpoint was first, and then we listed this as the key secondary endpoint, which was analyzed from the hierarchy, second. I'll just add that these were our static severity scores. The primary endpoint was a dynamic change scale. We want to have evidence that supports an effect both on the dynamic change scales as well as the static severity scales. Dr. Kelly, did you wanna address Ritu's question around the changes that we're seeing in the SELVA study? Sure, I'd be happy to do that. Thank you for the question. I think that the clinical relevance is really described best by looking at the pictures and the clinical scenarios that were presented, you know, toward the end of the talk. What we have here are basically, you know, changes in the aspects of the disease that are very meaningful to the patient. So leaking, which can cause irritation, inflammation, infection, bleeding, which can be cosmetically problematic and lead to infection as well, and basically, you know, change in lesional appearance. Again, that has both a cosmetic and a functional, you know, component. I think that the fact that we're seeing, you know, significant reductions in severity across all of those components are really something that patients comment on, and basically, want to see in any kind of effective treatment. Again, we're affecting the biology of the underlying lesion, which then affects the sort of functional outcome of that particular lesion. Got it. Thank you. If we could get a little more color on the one TRAE, the Treatment-Related Adverse Event, that drug discontinuation, and if you guys have any other color on the other four patients, who dropped out between first treatment and evaluation complete. Great. Thanks for those questions. Jeff? Yeah, in the trial, I want to point out that, first of all, it's a 24-week trial, it's a long trial for the patients, it was, you know, did require a number of visits. We are really appreciative of all the time they put in. We had six patients who enrolled in the trial, were dosed with QTORIN rapamycin and withdrew early. Five of those six patients were unrelated to study drug. Those are things like lifestyle changes or logistical issues that they experienced, unrelated. We had one participant who had an AE that was possibly related to QTORIN rapamycin. This was an individual who had a history of lymphorrhea. She withdrew before day 60 in the trial, and the AE with which she withdrew from was, lymphorrhea. Thank you. One moment for our next question. Our next question comes from the line of Annabel Samimy of Stifel. Line is now open. Hi, thanks for taking my questions, and congratulations on these excellent results. I just had a follow-up for Dr. Kelly. Thank you for sharing where you would put this in the treatment regimen. Just to get a little bit more granular, for the patients that you would see as appropriate for this, is it across the spectrum of severities? Would you start patients more at the moderate stage of disease, given that this is a progressive disease, to try to sort of stave off any increase in severity? For Palvella, if you could just help us understand what kind of label you might expect with the patient population that you enrolled in the study. I know that there was only one three to five-year-old patient. Do you think you might be able to get an expansion into that younger population with only one patient that was in the study? Thanks. Annabel, thanks for being on. We appreciate the questions. Passing it over to Dr. Kelly to address your first question, the Palvella team will respond to your second question. Dr. Kelly? Thanks, Annabel, it's for the question. I think that from a use perspective, as I stated before, I think that, you know, Palvella or the QTORIN rapamycin becomes a first-line therapy for most patients. Your comment is, and question is actually quite relevant in that, you know, until now, we really did not have an intervention that had high efficacy and was had a great safety profile. With that in mind, you know, using this particular drug formulation in less severe patients, I think will be advantageous in order to kind of change the natural history of this particular disease. So, i.e., to help prevent more serious complications from occurring. again, I think that many of the patients or all of the patients with moderate and severe disease, this becomes a first-line therapy, and then I think it opens up additional therapeutic options to those that have less severe disease that are likely to progress. Great. Thanks, Dr. Kelly. Annabel, to address your question on the FDA label and what's anticipated there, I'll just begin by saying we had a very collaborative relationship with the FDA on this program. They granted us Breakthrough Therapy designation. They're supporting the SELVA trial with funding through the FDA Orphan Products Grants Program. We were pleased midway through the trial that they allowed us to dose this younger cohort of three to five-year-olds. Our objective would be to strive for a label of three and above. When we think about the three to five-year-old cohort today and what's available to them, Dr. Kelly articulated it well. It's procedures which are invasive, low efficacy, high recurrence. There's oral rapamycin, which is an immunosuppressive and inflicts a number of unwanted acute toxicities, and then there's unapproved and unproven compounded formulations. We think that, given the data that we've developed and continue to develop, that there is a persuasive rationale for the FDA to consider our proposal of a label of three and above. If we need to develop more data, and we hear that definitively from the FDA, we're gonna try to hear that early in the NDA process so that our clinical team can move quickly to develop the evidence needed to be able to obtain that label of three and above. Great. Thank you so much. Thank you. We'll move for our next question. Our next question comes from the line of Catherine Novack Jones. Your line is now open. Hi. Good morning, Wes and team. Thanks for taking my questions. Congrats on the data. Dr. Kelly, I was wondering if you can comment on reimbursement for both compounded topicals or sclerotherapy. You know, how would an FDA-approved product change the landscape from your perspective? Great. Thanks for the questions, Catherine. Dr. Kelly, do you want to speak to the reimbursement around a compounded topical rapamycin as well as sclerotherapy? I think that from, you know, current available therapies, none are FDA approved, and that can be a barrier to insurance approval. Particularly the compounded solution, which has not been studied in any detail with regard to efficacy and/or safety. Sclerotherapy has been used in a number of patients with different types of lymphatic malformations. In those patients, it's easier because of the sort of literature component, the medical literature that's available, supporting the use of, you know, procedures like sclerotherapy and laser therapy to get insurance approval. However, I think having an FDA-approved, you know, treatment will make insurance approval easier, and particularly, you know, a treatment with very significant clinical impact and safety, that we see with the QTORIN and rapamycin. Great. I was wondering if you can speak to, if you have experience with patient compliance with topical compounded rapamycin. You know, do patients find it hard to stick with chronic dosing, and would you expect this to be different for a product with QTORIN and rapamycin's profile? Thanks for the follow-up question, Catherine. Dr. Kelly? Sure. A very good question, and I think that, the compliance with a compounded sirolimus, in my experience, has been variable. A lot of that variability really is reflected in the fact that, there's a lot-to-lot, differences, both in effectiveness. Mm. Potential AEs that we see in patients. Tolerability from lot to lot can change, and this actually influences patient compliance over, you know, over a long duration. I think with a much more reliable, and effective and safe therapies, compliance will not be a problem for the duration of the treatment period. I think that's underscored by the fact that not only have patients completed six months of therapy in the SELVA trial, but many and most of them have elected to continue with the extension, the extension therapy as well. Got it. Thanks for taking my questions. Thanks, Catherine. Thank you. One moment for our next question. Our next question comes from the line of Whitney Ijem with Canaccord Genuity. Your line is now open. Hey, guys. Adding my congrats on the data. I guess quickly, just wanted to follow up on Dr. Kelly's comment. I think you just said, this would be, kind of your first reach for most patients. I guess what are the patients who this isn't the first reach or these, you know, you think would not be good candidates for QTORIN and rapamycin, and what reasons? Sure. Thanks, Whitney. Dr. Kelly, do you want to respond? Whitney, thanks for the question. I think that, I never like to say all or never. You know, all patients that have significant, you know, mLMs involving the skin, would be treated with QTORIN and rapamycin as a first-line therapy. I think that, you know, there could possibly be situations, where you have, you know, deeper lesions, in addition to the skin lesions that require, a more systemic effect. In my experience, even in those situations, we often use both the topical and a systemic agent in order to get the type of skin penetration and clinical results that we're looking for. Got it. That's really helpful. Then on the kinetics of response, I think you touched on this, but what were you seeing in terms of kind of the shape of that curve, I suppose? Do you like, is there room for additional improvement over time? Sorry, another part of this question, will you be taking any other looks at the data in the open label extension? Could we expect any updates on that later this year? Great. Thanks, Whitney, for the questions. Jeff? Thanks, Whitney. What we observed was a statistically significant improvement on the mLM-IGA at all time points where efficacy was measured. That started at day 60, 90, and then week 24, or day 168, same thing. We saw what we saw was increased clinical response with increased exposure to the drug over time. As the patients were exposed to QTORIN rapamycin, they had increased clinical benefit. This was similar to what we observed in the phase II trial, so really indicating a strong pharmacological effect. What we do know from oral dosing of rapamycin and both in microcystic lymphatic malformations and cutaneous or venous malformations, is that with oral drug, it usually takes often 12 to 18 months to reach maximal effect. You know, there likely could be additional treatment benefit for some of these patients, which, you know, from just from the data perspective, with 98% rolling over into that treatment extension, these patients felt like there was a good risk-benefit profile for the drug. As far as collecting data, the extension study, the treatment extension study, only collects safety data. We'll be presenting that additional safety data at a future medical conference. Thank you. One moment for our next question. Our next question comes on the line of Danielle Brill of Truist Securities. Your line is now open. Hi, guys. Good morning. Allow me to also extend my huge congratulations on the outstanding result here. I guess I was wondering if you had any insights on the two nonresponders that completed the 24 weeks of treatment. Did they have more severe disease or any unique characteristics relative to the rest of the patients involved? Then on the flip side, were there any parameters or characteristics associated with those that achieved 3-point improvements? I know Dr. Kelly mentioned prior treatment often had weaker responses. Did you see this translate in the data? Thank you. Great, Catherine. Thanks for the question. You referenced the two patients who did not show a treatment benefit on the mLM-IGA. What we did with both of those patients is to actually analyze their full results from the clinical study, and so evaluating in addition to the mLM-IGA, the patient-reported outcomes and other clinician-reported outcomes, so we really understand their experience in the SELVA study. I'll start with, both of those patients elected to roll over into the treatment extension study, which we felt like was encouraging, and then as we worked our way through the hierarchy of endpoints, both of the patients reported improvements on patient-reported outcomes. Therein lies the value of having multiple endpoints in a study, so you better understand that patient's experience. While the mLM-IGA didn't detect that treatment effect, our conclusion from looking at both of those patients' full clinical workup, as well as the fact that they elected to stay in the open label study, is that they're very likely receiving some benefit from the therapy. It just wasn't showing up on the mLM-IGA at week 24. In terms of others, and whether there's any sort of parameter that's predictive of a large effect size, we saw large effect sizes across the study population in all of the sub-analyses, pre-specified sub-analyses, that Jeff mentioned. There was no parameter that we're aware of to date that predicts whether a patient's going to have one of these plus two or plus three responses. Thanks for the questions, Danielle. Thank you. We'll move for our next question. Our next question comes to the line of Andrew Fein of H.C. Wainwright & Co. Your line is now open. Hey, good morning. Congratulations. Just a, I guess, a question for you, Wes. Given that these results seemingly surpassed, you know, all of the expectations you guys had sort of set forth ahead of the data, how do you think about revisiting, you know, all of the market forecasts you've spoken about in terms of either penetration, you know, you've referenced pricing a little bit earlier in the call, or you know, the regulatory process, the speed of the regulatory process? What kind of metrics are you revisiting now that you have the data in hand that have seemingly, you know, performed better than even you guys had expected? Thank you. Thanks a lot for the questions, Andrew. We agree that we surpassed the upside case here, as Jeff articulated earlier. We are revisiting each of the elements you mentioned, Andrew. We'll do additional pricing testing with this new clinical data to understand what our pricing corridor looks like and whether that pricing corridor shifts up as a result of the phase three study. From a penetration perspective, what this data allows our medical affairs and commercial teams to do, pending FDA approval, is it allows us to have a very robust data set across clinician-reported outcomes, patient-re-reported outcomes, the key secondary endpoint, the primary endpoint, to really push the speed of adoption with this first line and standard of care positioning that Michael Kelly articulated. From a speed of regulatory perspective, we've been building for this moment for years. Our NDA team is hard at work. We've recently hired Shama Munim to lead regulatory affairs. She's excellent, has a lot of experience navigating the FDA and the most recent drug that she was able to lead approval for was also for a rare disease where Breakthrough Therapy was granted as well as Priority Review. We're gonna push as hard as we possibly can. We're gonna do that for the patients. We want to get this drug to patients as soon as possible, and we're gonna use all resources available to us to make that a reality. Thank you. One moment for our next question. Our next question comes from the line of Ryan Deschner of Raymond James. Your line is now open. Thanks. Congratulations on the excellent data here. The primary endpoint result is very impressive. To me, the clinician and patient-reported severity metrics on a five-point scale are also remarkably strong and very interesting. What's your rationale for the improved result here versus what we saw in phase II? Would you expect further improvements in these metrics going forward based on the longitudinal results that you see? I have a follow-up question. Thanks. Ryan, thanks for the questions. We also were encouraged by the effect sizes on the severity scales. Jeff referenced it earlier, I'll reiterate it. The use of oral rapamycin in vascular malformations, including lymphatic and venous malformations as well, there's a lot to be learned from all the real-world evidence that's out there. With this patient population, with microcystic LMs, oftentimes when they have an internal lymphatic malformation, they're treated for 12 or 18 months before they see a peak therapeutic effect. There may be, you know, additional benefit to accrue for patients with longer duration of dosing. We think some of the movements that you referenced on the static severity scales could be that incremental change in extending the study from 12 weeks- 24 weeks. That was a key change that Jeff recommended after the phase two results. We had Markov modeling that suggested that some patients may benefit from longer duration of dosing. That's what we believe to be the rationale as to why some of those endpoints are moving as they are. Got it. Okay. Also curious on any thoughts you might have on the read-through from the plausible mechanism guidance yesterday from FDA? Yeah, thanks for the question, Ryan. We've been pretty busy here at Palvella, we're still digesting the plausible mechanism guidance. Glad you asked the question. We take a lot of pride here in really understanding these innovative pathways and how they might apply to the diseases that we have under evaluation. With rapamycin, specifically in some of these diseases, we think there's more than a plausible mechanism. In many ways, there's data to support that rapamycin's mechanism is validated, and I think layering the cell data on top of that further validates the mechanism in microcystic lymphatic malformation. I can assure you, Jeff and I will read that guidance very carefully. We'll discuss it with our outside regulatory advisors. We have great partners on the regulatory front. If the plausible mechanism pathway is potentially available for some of our programs, we'll pursue that path. For microcystic LMs specifically, we're post-phase III now, so that's not a pathway that we're gonna pursue for microcystic LMs. We have four programs under development: cutaneous VMs, also angiokeratomas and porokeratosis with our QTORIN pitavastatin. We'll, we'll evaluate whether plausible mechanism may be a good fit for those three programs. Thank you. We'll move for our next question. Our next question comes on line of Kaveri Pohlman of Clear Street. Your line is now open. Yes, good morning. Thanks for taking my questions, congratulations on the excellent data. I was wondering if you can provide further granularity on what percentage of patients were much improved versus very much improved. If you can also comment on, you know, I know you commented on a bit on commercialization efforts, but any further details on commercialization and manufacturing efforts? For commercialization specifically, are there any particular centers where most patients are treated? You know, one question for Dr. Kelly. Maybe this is like a follow-up, but based on your experience, how have compounded or conventional topical formulations performed in patients? You know, in what way does QTORIN and rapamycin differ from these, you know, older approaches? Thank you. Thank you, Kaveri. All great questions. I'll begin with the first one: 86% of week 24 completers were either plus two or plus three. We intend to present some more specific data on the primary outcome at one of the many upcoming medical meetings where we have a lot more cell data to share. We look forward to sharing that with you and everyone else. On the commercialization front, I'll speak to your question around patient concentration. We conducted a very extensive claims analysis, which we published at a medical congress last year. Over the last 20 years, there's been vascular anomaly centers that have organically developed at pediatric hospitals. These vascular anomaly centers, like the one where Dr. Kelly practices have a very large patient volume for microcystic lymphatic malformations as well as venous malformations. Our claims data suggests that about 50%, or call it 15,000, of the microcystic LM patients are in about 400 centers. The great thing about group claims data is that we now know the identity of those 400 centers, and our medical affairs team is actively speaking with clinicians at those specific centers. From a manufacturing perspective, our CMC module is on track. Our CMC team is led by Jason Burdette. Jason has a very impressive track record in the area of CMC. We have two drug product manufacturers, each of which have clean FDA inspection histories and recent FDA inspection histories, and we also have multiple sources of rapamycin from a drug substance perspective. Dr. Kelly, did you want to hit on Kaveri's second part of Kaveri's question? Absolutely. Thank you for the question. I think that my experience with compounded sirolimus has really been variable. It's the word I would use, in that many patients actually respond, but of that cohort, almost all have incomplete responses. In addition, there's a great deal of variability in response and side effect profiles from lot to lot. We see variability not only in the outcome, but also in the tolerance of the compounded sirolimus drug. I think that, you know, the QTORIN rapamycin, you know, formulation actually offers a much more stable and reliable alternative. The expectation is, you know, from what we've seen in phase II and phase III, clinical trials, is that the clinical impact is great, and the tolerability is actually, predictable and low. Those are, those are my thoughts. Thank you. We'll move it for our next question. Our next question comes from the line of Dev Prasad of Lucid Capital Markets. The line is now open. Hi, congratulations on the data. I have just one quick question. Maybe if you can talk about what percentage of estimated 30,000 patients are managed by top 100 centers or top centers? Also, outside of those vascular anomaly center, how much education do you anticipate is needed for, say, community dermatologists to prescribe the drug post-approval? Thank you. Yeah, great, Dev. Thanks for those questions. You know, the data that we've shared is that it's really from a commercial focus. It's really 400 centers that we wanna be focused on, because those 400 centers get us to 15,000 patients. You know, and I think that, you know, from a community dermatologist perspective, I think let's just talk about the call point. You know, depending on the report you look at, there's about 10,000 dermatologists in the United States. It's a call point that we believe we'll be able to interact with, collaborate with from a medical perspective, and then pending FDA approval, promote to and do so with a sales force of about 20-40 orphan sales reps. We're gonna augment that with Vimal Patel and his team of medical science liaisons. I think importantly here, Dev, just in terms of what level of, you know, promotion you need to community dermatologists on QTORIN rapamycin, if approved, this is a disease where there are no approved therapies. Current modalities are invasive, they're nonspecific, they're not durable, high recurrence. When we think about the Palvella strategy at its core, it's to be in these diseases where there's nothing, where we can have more attractive commercial dynamics and hopefully, again, another core pillar of the company, have a more capital-efficient approach to driving that revenue line. When you juxtapose that compared to much more competitive and common indications, where you're battling large incumbents, large pharmaceutical companies, we don't expect to have those dynamics. I also think it's important that if you look at the investigators in both our phase two and phase three study, including Dr. Kelly, these are the true thought leaders in the areas of microcystic lymphatic malformations. Oftentimes, what we see is that these thought leaders, should the data support it, are very willing to go to their colleagues and talk about their experience in these investigational clinical trials and how that positively impacted patients. We have two veterans on the commercial and medical affairs front, Ashley Kline and Vimal Patel, and we expect them to execute very well in terms of this positioning of being that first approved therapy and a therapy that could be first line in standard of care in this disease. Thank you. One moment for our next question. Our next question comes from the line of Geulah Livshits of Chardan. Your line is now open. Good morning, wanted to add my congrats as well on the excellent data. Maybe a couple of quick ones for me. Did want to follow up briefly on the different endpoints here. How concordant were the different efficacy endpoints at the individual patient level? For example, the mLM-IGA versus the mLM-MCSS versus the patient-reported outcomes? I know you touched on this a little bit, I have a follow-up. Thanks, Geulah, for being on. Thanks for the questions. Pass it over to Jeff to respond. Thanks, Geulah, for the question. You know, when I was reviewing the data, what I was really impressed with was the high concordance amongst all the endpoints and all the subgroup analysis. We were really pleased with that. What I'm really also looking forward to and digging in from a data perspective as well is going out to medical conferences and presenting is the patient qualitative interviews. That's something that's just so important for rare disease drug development. We have an independent group that interviews the patients at baseline and end of treatment, and we're putting that data together now, and I think that'll be really meaningful as we get the word out here about the study results. Great. Separately, how does this SELVA data set, now that you have it, impact your thinking with respect to read through for cVM, and particularly for, the significant angiokeratomas in terms of trial design, particularly things like endpoint selection, timing, and 12 versus 24 weeks, and things of that nature? Yeah, thanks for those questions. You know, I'm glad you asked the question about endpoints. When you're in these rare diseases where nothing's approved, there's a lot of layers of innovation that companies have to undertake, and one of those is around endpoints. We're constantly working with Dr. Kelly, folks like Dr. Jim Treat at CHOP, understanding these diseases and then applying efficacy assessments that measure the key clinical signs. In our cVM phase II study, we're very pleased with the phase II results, where we saw 73% of patients respond, including two-thirds that were either much or very much improved. That study design was a single-arm, baseline controlled study. We're in the process of interacting with the FDA. Following a Breakthrough Therapy advice meeting, we're gonna submit for Breakthrough Therapy designation, and then also land on a phase III study design in that particular study. For angiokeratomas, our phase II study will also be single arm and baseline controlled. That's a disease where there's no evidence of spontaneous regression. Interestingly, angiokeratomas have recently been classified as a lymphatic malformation, so they have some shared aberrant lymphatic biology with microcystic lymphatic malformations. Huge unmet need there, more than 50,000 patients in the U.S., nothing approved. So our clinical team is working very diligently to dose the first patients in that study in the second half of this year. Both cVM and angiokeratomas benefit from FDA's Fast Track designation. Thank you. One moment for our next question. Our next question comes from the line of Jeet Mukherjee of BTIG. Your line is now open. Great. Thanks for taking the question. I wanted to extend my congratulations as well on this really impressive data. Two quick questions from me. For the team, you had mentioned some additional sensitivity analysis and data from this study later on. If you could just elaborate on what that analysis might show. For Dr. Kelly, looking ahead to perhaps real-world duration of treatment with QTORIN rapamycin, some of the case studies show patients with essentially complete disease resolution. For patients like that, would you anticipate advocating or prescribing continued treatment, or would you wait for the disease to worsen before asking patients to go back on treatment? Thanks. Thanks a lot, Jeet, for those questions. Jeff will respond to your first question, and then we'll pass it over to Dr. Kelly to address your second question. Jeff? Yeah, thanks, Jeet, for the question. You know, definitely looking forward to presenting all this data at future medical conferences. You know, what we observed was high concordance of response across endpoints with 86% of being a plus two or a plus three on the mLM. We will dig into each of the scales. I think that'll be important to show the, you know, the individual signs of the disease, how they're driving the global change. That'll be one particular endpoint that or one particular sensitivity analysis that we'll be doing. We'll also look at things like age, prior medical history, all the various sensitivity analysis based on the baseline population. Thanks, Jeff. Dr. Kelly? Yeah, thanks for the question. I think that really what you're getting at is how are we going to use this formulation and drug moving forward? Again, as you state, there are patients that had early and near-complete responses. ... and others that had, you know, had responses but yet still incomplete. I think that, you know, from my perspective, this is a learning process. Once drugs are approved, we still need to understand, you know, better understand the target population and then also outcome parameters that will drive continued therapy versus coming off therapy. We do know that patients who have been treated with systemic sirolimus for deeper microcystic lesions often stay on therapy for years. A subset of those patients, you can actually stop therapy and get a relative durable response off therapy, but almost always they recur within months to years after sirolimus. I'm not trying to hedge the answer. I think that I think it's gonna be a combination of, you know, long-duration therapy, that in some patients might be intermittent, based upon severity of the patient's symptoms. Thank you. One moment for our next question. Our next question comes from the line of Albert Lowe of Craig-Hallum. Your line is now open. Hi, congratulations on the spectacular data. I have a question for Dr. Kelly. How old are these patients at the typical time of diagnosis? Do you think QTORIN rapamycin is a drug that physician would start using when the patient is diagnosed, or is there any more involved workup needed at that time of presentation? Great, Albert. Thanks for the questions. Dr. Kelly, do you want to address Albert's questions, please? Yes. Thanks, Albert. I think that most patients that present early in life, so within the first one to two decades of life. This, as Jeff and others have alluded to, is a progressive process that increases in severity over, you know, over the lifetime of the patient. Individuals that have symptomatic microcystic lesions involving the skin should be treated. Again, I think that, in my opinion, earlier treatment offers an opportunity to change, you know, the severity profile of the disease moving forward, but also may change the natural history of the disease. Again, I would advocate to my patients for early treatment compared to waiting for, you know, severe side effects or severe symptoms of their underlying disease before advocating for topical therapy. Thank you. This concludes the question- and- answer session. I'll now turn it back to Wes Kaupinen for closing remarks. Great. I wanna just thank everyone for joining today's call for the excellent, robust discussion around our phase III SELVA results. Thanks especially to Dr. Kelly for taking care of these patients and for the great insights that he gave today in contextualizing the phase III data. We'll close with saying that 2026 is off to an exceptional start for Palvella. These positive phase III results provide significant momentum as we head into a steady cadence of catalysts throughout the remainder of 2026. We're concurrently advancing QTORIN-derived programs across four rare diseases, each which have no FDA-approved approvals and each representing an opportunity for Palvella to be first for patients. We also expect to announce two new programs in the second half of this year, our fourth indication for QTORIN rapamycin, and our third product candidate from the QTORIN platform. The entire Palvella team remains firmly committed to both delivering on our mission for patients and executing on our vision to lead in the development of innovative targeted therapies for rare skin diseases and vascular malformations. Thank you all for joining us today. Operator, you may now conclude the call. Thank you for your participation in today's conference. This concludes the program. You may now disconnect.