Palvella Therapeutics, Inc. (PVLA) September 2026 Conference Transcript

All right.

Well, good afternoon, everyone, and welcome to our next session. I'm Sarah Nick from H.C. Wainwright's healthcare research team. It's my pleasure to introduce Palvella Therapeutics, a clinical stage company developing therapies for patients with rare diseases. And presenting today on behalf of the company is founder and CEO, Wes Kopanen. Please join me in welcoming them. And Wes, the floor is yours.

Great. Thank you, Sarah. Appreciate you and Andrew on the H.C. Wainwright hosting Palvella today and the great research coverage you've provided us since we went public. I'm going to start with the name Paul Vella. Paul Vella in Finnish means to serve. The mission of our company is to serve patients that have serious rare diseases, and we exclusively focus on those diseases where there are no approved therapies. We want to build the enduring leader addressing rare skin diseases and serious vascular anomalies. And our strategy can be summed up in a word, which is first, we're built to go from zero to one. We want to develop first and disease therapies for these patients who previously have had nothing and in doing so create outsized value for both patients and also for investors. The way we want to do this is through repeatably unlocking what we think could be multi-billion dollar opportunities in these markets. We do that through what's listed on the slide here, focusing on diseases where we can be first, where the biology is clear, where we're leveraging some existing human proof-of-concept data, oftentimes from off-label use, of a molecule that provides that clinical validation, and then applying our QTORN platform. Our QTORN platform is our platform for reproducibly generating novel topical product candidates that can be first in disease. The two areas we're focused on can be described as high unmet need and low competitive intensity. We think these dynamics lend themselves to building an enduring leader in the space. Rare skin diseases and rare vascular malformations together make up close to 700 diseases, and over 98% of those don't have a single approved therapy. Our team is working day in and day out to change that treatment paradigm. What we've assembled since going public just under two years ago is now four diseases, which we think are each in large multibillion-dollar total addressable markets where there's no approved therapies and where our market research suggests that we could potentially have a first-line cutorin therapy. Microcystic lymphatic malformations, we estimate more than 30,000 patients. Cutaneous venous malformations, more than 75,000. Angiokeratomas, more than 50,000 patients. And disseminated superficial actinic porokeratosis, we also believe to have more than 50,000 patients. So these are large orphan markets, an order of magnitude greater than ultra orphan markets, and we're excited about the opportunity to bring forward what could be first in disease therapies. What's new at Paul Vela? There is always something new at Paul Vela. I'm excited to report that our NDA submission on our lead product candidate, cutorin rapamycin for microcystic lymphatic malformations, has now been submitted. It is being reviewed by the FDN or a rolling review, which was granted to us after our pre-NDA meeting. And so at the top of the slide, you can see that we are investing significant capital resources and human resources behind what we anticipate will be the launch of cutorin rapamycin in microcystic lymphatic malformations. We've added some great talents since the beginning of the year to our board, Matt Pauls, my former colleague from InnsMed, Jen McDonough, who was crucial to the successful launch of Vyjavec at Crystal Biotech, and also Ken Taylor, who previously led the sales organization, Wally Arcudis. In terms of our lead product candidate and our lead indication, we believe that cutorin rapamycin is poised to be the first FDA-approved therapy for microcystic lymphatic malformation, and our research indicates that it could be first line and establish a new standard of care in this disease. Across our Phase II and Phase III studies, we believe the efficacy data supports the broad applicability of this drug in both pediatric and adult patient populations across severities, and in treatment-naive and treatment-experienced patients. We also anticipate long-term chronic administration of the drug. One of the benefits of Cutorin as a platform is that it enables a constant, steady flow of catalysts. We have two additional clinical stage programs, one in cutaneous venous malformations, where we expect to start a phase three study later this year. There we have FDA's fast-track designation. In clinically significant angiokeratomas, we have an ongoing phase two study. Expect that to read out in the second half of next year. Also have been granted FDA's fast track designation and under four, five, and six are earlier stage programs. We expect to start a phase two study in DSAP in Q4 of this year. And by the end of the year, we will also be making two announcements. One will be an announcement of a third Q-Torin program. The other will be our fourth indication for Q-Torin rapamycin. So very exciting time at Paul Vella. Our platform, which we refer to as Qtorin, is a platform for reproducibly developing novel topical product candidates that can be first in disease therapies for rare skin diseases or rare vascular malformations. Several elements to Qtorin. We start with an attunable anhydrous gel. We attempt to get high drug loading of each molecule that we bring into the platform. We think that that high solubility can lend itself clinically to a rapid onset of therapeutic activity and a larger magnitude treatment effect. Many of the diseases which we target are deep in the skin or the dermis, so we tune our formulations to deliver drug to that cytopathophysiology. Key to our diseases, many of which are genetically based and require long-term chronic administration, is also tolerability. So with each molecule that we bring into the platform, we tune that formulation to ensure low systemic absorption of that molecule. We're able to generate with Qutorin molecule-specific IP. This opens up an opportunity to have long-duration composition IP claims on the formulation, as well as method of use. Our first product candidate from the Qutorin platform is called Qutorin rapamycin. We refer to that as a breakthrough innovation because we've been granted FDA's breakthrough therapy designation. Over two years and over 80 prototypes, we landed on this final construct of cutorin, 3.9% rapamycin anhydrous gel. You can see the key innovations listed on the slide here. We're able to get high concentrations of the active into the anhydrous base. We've shown preclinically we get levels deep in the dermis, which exceed the IC90. And we've been able to show clinically and preclinically low systemic absorption of this, which is really key for patient tolerability. What's really held back rapamycin's potential in many of these mTOR-driven skin diseases and vascular anomalies is that it's today available orally, and it's not a viable therapeutic orally because of risks of immunosuppression and other acute mTOR-related toxicities. We hope to change that with our first FDA approval, anticipated first half of next year, and micro-LMs, but there is a much broader opportunity for our drug beyond microcystic lymphatic malformations. We believe Ketorin rapamycin can be a pipeline and a product. So when you look at our commercial markets, we're going to start with microcystic lymphatic malformations, but our goal is to continually expand the label in mTOR-driven diseases, and ultimately, we want to grow the pool of addressable patients by a factor of greater than 10x, as you can see represented on the slide here. Bottom of the slide are our estimated approval timelines. the way we'll do this from a regulatory perspective is through serial supplemental NDA submissions once that first NDA has been approved, which we anticipate in the first half of next year. Microcystic lymphatic malformations are driven by the PI3K pathway. They are monogenic somatic mutations where mTOR is upregulated. There are more than 30,000 diagnosed patients, we estimate, with this disease in the United States based on claims data, based on real-world occurrence studies. So we see this as a large, uncontested, total addressable market. Because of the PI3K mutation and the upregulation and hyperactivation of mTOR, you can see on the right side of the slide that you have genetically malformed lymphatic vessels protruding out through the skin. Clinically, this creates a significant burden for patients. They leak lymphatic fluid onto the skin, which puts them at persistent risk of infections, such as cellulitis. And this is a disease that is proliferative and progressive in nature. Today, nothing's approved. These patients are oftentimes treated with interventional approaches, such as laser surgery and sclerotherapy. We're grateful to the FDA for the designations we've been granted, which includes breakthrough, fast track, and orphan designation. Listed here is our phase three self-study. We completed a phase three study, which read out in Q1 of this year, we enrolled 51 patients into that study. We're grateful to the FDA for their financial support of that study through the FDA's non-dilutive FDA orphan drug grant program. The outcome of this study was positive. Our primary, key secondary, and all four key secondary endpoints were highly statistically significant. On our primary endpoint for patients six and above who completed the 24 weeks of treatment, 95% improved. On the primary endpoint, and 86% were rated by clinicians as much or very much improved. This was corroborated, the primary endpoint, by our blinded key secondary endpoint, which was a photo evaluation of the lesions, also demonstrated a highly statistically significant result. I'm going to show two of the patients who were in our phase three study. Here you can see a 10-year-old boy who had previously had multiple sclerotherapy procedures, had gone through rounds of antibiotics due to infection. after 24 weeks of therapy. Here you can see the height of the lesion has improved. The bleeding has improved. The vesicle appearance. And this patient continued on therapy after the 24-week efficacy evaluation period. Here's a seven-year-old girl who was in our phase three study. Also bottom of the slide, you can see had prior interventions such as laser as well as compounded topical rapamycin, which was discontinued. Very good result for this patient at 24 weeks. She also continued on therapy following that 24-week efficacy evaluation period. We just put out data a couple months ago at the International Society for the Study of Vascular Anomalies, or ISFA. This is the result of our blinded key secondary endpoint. You can see between day 56 and day 1, which was the pretreatment period, that the disease was largely stable, which you would anticipate. And then after patients at day 1 went on therapy, you can see numerically and statistically a very significant improvement. So great result on our key secondary endpoint, which corroborated our primary endpoint. We also presented data on the youngest patient population in our phase three study. That was the six to 11-year-old cohort. Two key takeaways here is that 100% of these patients were much or very much improved on the primary endpoint, and also 100% of these patients stayed on drug. We believe this data supports not only early intervention, but also the importance of chronic administration in a disease that has a genetic mutation that's constitutively active and the importance of counteracting that with a targeted topical therapy like cutorin rapamycin. Very good safety tolerability profile from our perspective. There were no severe or serious treatment-related adverse events. Bottom of the slide shows very low levels of systemic absorption, which was the design goal with cutorin rapamycin is have the drug in the skin, pharmacologically active in the skin, but not getting levels that would create issues around immunosuppression and acute toxicities. As I mentioned at the outset, pleased to report that our NDA has now been submitted. We'll be seeking a broad label from the agency. We submitted under a 505 B2 pathway. Our efficacy submission was supported by both phase three and phase two evidence, as well as real-world studies as supportive evidence. Our innovations are protected by a three-layer approach. Patents, trade secrets, as well as regulatory exclusivities. We now have six issued patents in the United States, cumulatively over 100 claims. Those claims are broad, ranging from 0.1 to 20 percent and hydrogel compositions. Some of our most significant innovations are held as trade secrets, and we also have FDA's orphan drug exclusivity. At Paul Vela, we talk a lot about our people. We were thrilled to be able to recruit David Osborne to be our chief innovation officer over his 30-plus year career in dermatology. He's developed about three dozen drugs that have been approved, primarily topical drugs. David has led our patent work since joining. We've made some additional patent filings that have issued extend into the mid-2040s. Launch planning is well underway. You can see our key strategies listed here. We always begin with people. We have proactively sought out an experienced commercial leadership team with experience in both rare disease as well as dermatology. We are positioning our drug as a potential first approved therapy, first line and standard of care. There's about 400 centers that manage about half the patients with this disease. We are actively meeting with those centers every week. We've built an internal patient services team, and we've raised significant capital in Q1 of this year, a $230 million raise, and a lot of those resources will be invested to support a strong commercial launch. Listed here is our senior commercial team. This team is assembled. This team is actively recruiting their teams. They're in the field meeting with physicians. I'll just highlight here what we think is a combination of deep rare disease launch experience and dermatology experience. These are proven product launchers who have hit impressive revenue numbers, and we all look forward to working together to make this the best launch that we've all been a part of. We're going to support the launch with 40 sales reps, which we expect to be hired in advance of the launch. We had previously guided on a range of 20 to 40. We think 40 is the right number to make sure physician education, and promotion that we get that right from day one. Our market research supports that 98% of physicians would consider this a first-line therapy, and they would consider prescribing the drug to three-quarters of their patients. Top right of the slide, close to 100% of physicians in our market research saw advantages to a targeted topical approach for a localized disease compared to using systemic therapies such as oral mTOR inhibitors or PI3K inhibitors. What's different about this orphan launch than a lot of orphan launches is that there's been organic market development at the academic centers over the last 20 years. These centers have come together to form vascular anomaly centers, and today they manage about 15,000 patients across 400 centers. So our sales force will promote to all three tiers. We'll also have non-personal promotion to all three tiers, but there is a high concentration of existing diagnosed patients that are at these vascular anomaly centers, and we look forward to further engagement with those centers. We've met with over 200 of our top 400 targets, and we'll continue to invest our balance sheet from a pricing perspective. We estimate pricing the drug somewhere between $100,000 to $200,000 per patient per year. That's supported by first-in-disease analogs, recent topical orphan launches, as well as payer testing that we've recently completed following our phase 3 study. Moving to cutaneous venous malformations, this is a larger commercial population. There are more than 75,000 patients we estimate that have cutaneous venous malformations. It's the most common type of vascular malformation, and the genetics and the biology here are also well characterized. Either TIE2 or PI3K mutations can cause hyperactivation of the mTOR pathway. Nothing is approved. So this is a great Paul Vella disease where we have the opportunity to bring forward that first approved therapy. We also presented data at ISFA showing that height and engorgement and appearance improved between week 12 and week 24, so longer time on therapy resulted in greater effect sizes for patients. We're meeting with the FDA soon for our end of phase two meeting, and we anticipate starting our phase three pivotal trial before the end of the year. We're grateful to the agency for fast-track designation, and we look forward to moving this forward with great urgency. A lot of data to support that rapamycin as an active demonstrates clinical benefit in this disease. In the middle panel there is a published real-world evidence study of oral rapamycin for patients with internal venous malformations. So we're building on a large base of human proof-of-concept data to take our construct, cutorin 3.9% rapamycin, into those subset of patients that have cutaneous venous malformations. Our phase two study, which was completed and announced in Q4 of last year, 16 patients, single arm study, we showed 73% of patients on a clinician change scale called the CVM Investigator Global Assessment. 73% of patients improved. Two-thirds of those patients were much or very much improved. You can see one case study here of a 17-year-old girl with a tech mutation. This patient was a plus three treated at Children's Hospital of Philadelphia by Dr. Denise Adams. I think it's really important to pay attention here to the patient qualitative interview. We really want to understand the effect of our drug on patients and their quality of life. You can see the quote here, which I'll read. I've definitely noticed some improvements. It's definitely had a positive effect. It's more comfortable to wear a bra now. I've had less pain in that specific area. So we're in the process of collecting all that patient experience data, those patient qualitative interviews, and submitting that to the FDA. Consistent with our other trials of cutorin rapamycin, we show good safety and tolerability, very low levels of systemic absorption. And our market research indicates here we also have the opportunity to potentially introduce a first-line therapy. 86% of physicians that we surveyed indicated that they would consider cutorin rapamycin as a potential first-line therapy. So we look forward to getting this Phase III study initiated, enrolled, and ultimately our approval timeline here is 2029. Our third indication is also a type of lymphatic malformation. This is called clinically significant angiokeratomas. We have already been granted FDA's fast-track designation here. We started our phase two study earlier than anticipated. Here, we're going to enroll up to 15 patients and read out that study in the second half of next year. This is also a chronically debilitating lymphatic-derived skin lesion. These patients can bleed a lot. Recent biological findings have implicated the mTOR and VEGF pathways are involved. There are some case studies that show the use of rapamycin in this disease that we're building on. We look forward to announcing a phase two study in the second half of next year, and there's more than 50,000 patients in the United States, we estimate, with this disease. Bottom of the slide here shows that 96% of physicians surveyed would incorporate a drug such as cutorin rapamycin into their practice in 85% seen unmet need across the various subtypes of angiokeratomas. Our second product from the cutorin platform is called cutorin patavastatin. We're moving that forward in a disease called disseminated superficial actinic porokeratosis. This is a genetic disease. It is pre-malignant in nature, where if there is malignant transformation, patients can have squamous cell carcinoma, so there is an urgency to treat. We estimate more than 50,000 patients in the United States that have DSAP, no approved therapies, very little in the way of development activity. This is a great Paul Vella disease. This disease does not improve on its own, and we expect to announce our initiation of our phase two study later this year. With all Paul Vella diseases, we try to leverage existing human proof of concept data, usually from off-label use of a drug that shows some clinical validation, where we can bring forward our Cutorin platform to design a Cutorin product that can deliver transformational efficacy for patients. Here, what we have is we have off-label use of statins applied topically with some evidence of efficacy. However, there is a lot of access issues. There's issues with variability in these formulations, and all of our market research indicates a significant need for an FDA-approved product. That's what we've developed with Ketorin Ptavastatin. We've developed a product that is designed to be on target, so it's inhibiting the causal mevalonate pathway. It's doing upstream of the genetic defect, so it's pathogenesis-directed, and it's doing that in the causal tissue of interest or the pathogenic tissue of interest. We took a very methodical approach to formulating. We tested seven different statins for potency, skin PK, and stability. The one that rose to the top was patavastatin. As you can see here, we've achieved a payload greater than 2%. We've shown in preclinical studies that we get levels in the skin greater than the IC90. So we're excited to bring this forward. It is a very close strategic fit to our other programs, high on met need. We think we've optimized for likelihood of clinical success based on the known biology, based on the human proof of concept data. And most importantly, at the bottom, this is a multi-billion dollar US TAM right now that is uncontested and where we have the opportunity to be first. Thanks to our investors, when we went public in our recent capital raise, we had the ability to continue to invest in the platform. So the future of Paul Vela and the Paul Vela platform is an internal product development engine where we can reproducibly bring in APIs, create molecule-specific IP, and bring those forward to be first in disease therapies. Our team leading this is David Osborne, as well as our chief scientific officer, Dr. Jeff Martini, and we're grateful for the significant contributions that they're making right now on preclinical products, which we hope to soon bring into the clinic. From a finance perspective, we ended last quarter with more than $250 million in cash. That is enough capital to get us through all of our key value inflection points, including deep into the commercial launch. We are well-funded for not only the NDA submission, but the build-out and expansion of our commercial and medical teams, as well as our major Qtorn pipeline and platform value drivers. So I'll wrap up here to say that the team and I at Paul Vela are very energized to have the opportunity, really once-in-a-career opportunity, to build the enduring leader in areas that have long been underserved, where we have a lead, we see uncontested markets that are multi-billion dollar markets, and we have a platform that allows us to continue to deepen that pipeline on an internal basis. We're excited to be a commercial company. We expect that in the first half of next year. Ketorin Rapamycin will be a pipeline and a product, and we look forward to bringing forward additional Ketorin programs. Most of all, we want to deliver for patients. It's in the name Paul Vela to serve. So everyone shares that mission, and we look forward to being successful in delivering on that mission. Thank you very much.