Good day, and thank you for standing by. Welcome to the Palvella Therapeutics conference call to discuss expansion of QTORIN™ rapamycin 3.9% anhydrous gel pipeline to include clinically significant angiokeratomas. You may begin. I would now like to hand the call over to Bohan Wei.
Thank you, operator. Good morning, and thank you for joining the Palvella Therapeutics QTORIN™ rapamycin indication expansion conference call. As a reminder, our press release detailing today's announcements 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 programs, 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. The format of today's conference call will be presentation only. Additionally, as a reminder, we will not be discussing or commenting on our ongoing clinical trials with QTORIN™ rapamycin. On today's call, we are joined by Wes Kaupinen, Palvella's Chief Executive Officer, Dr. Jeff Martini, our Chief Scientific Officer, and Matt Korenberg, our Chief Financial Officer, along with Dr. Jim Treat from the Children's Hospital of Philadelphia. I'd like to hand the call over to Wes.
Thanks, Bohan. Good morning, everyone, and thank you all for joining us on today's call to discuss our QTORIN™ rapamycin 3.9% anhydrous gel pipeline expansion into clinically significant angiokeratomas, a rare, chronically debilitating lymphatic disease that currently has no FDA-approved therapies. Let me begin by saying that it's an honor to have Dr. Jim Treat with us here today at Palvella Therapeutics headquarters and on this call. By background, Dr. Treat is a Pediatric Dermatologist at the Children's Hospital of Philadelphia, where he also serves as Professor of Clinical Pediatrics and Dermatology at the Perelman School of Medicine, University of Pennsylvania. At Children's Hospital of Philadelphia, Dr. Treat is training the next generation of physicians while advancing new therapies for patients with significant unmet needs. Dr. Treat is also a Clinical Dermatologist at the Comprehensive Vascular Anomalies Program at Children's Hospital of Philadelphia.
He is internationally recognized for his expertise in vascular anomalies and complex skin diseases. Dr. Treat will provide us with his clinical perspective on the unmet medical need in clinically significant angiokeratomas, Palvella Therapeutics' third target clinical indication for QTORIN™ rapamycin 3.9% anhydrous gel. It's an exciting time to be at Palvella Therapeutics with two high-impact new pipeline program announcements planned, followed by two major clinical readouts. The common theme across all four programs listed on the slide here is Palvella Therapeutics' relentless pursuit of developing targeted therapies for serious, rare, high-unmet-need diseases which currently have no FDA-approved therapies. In each of these diseases, we believe we have a clear opportunity to develop a targeted therapy that has the potential to be first-line and standard-of-care therapy for deserving rare disease patient populations that have historically been neglected and underserved.
This morning, we announced the first of these four planned milestones between now and the end of Q1 2026, our plans to pursue the development and potential commercialization, if approved, of QTORIN™ rapamycin 3.9% anhydrous gel for the treatment of clinically significant angiokeratomas, a rare, chronically debilitating lymphatic disease that currently has no FDA-approved therapies. In Q4, we will further expand the Palvella Therapeutics rare disease pipeline with milestone number two, our planned announcement of the next QTORIN™ platform program, an announcement which I'm pleased to share remains on track for later this year. Moving to milestone number three, our Phase 2 TOIVA study of QTORIN™ rapamycin 3.9% anhydrous gel for the treatment of cutaneous venous malformations, a program which has been granted FDA's FastTrack designation.
That study, thanks to our clinical operations team, recently achieved full enrollment with 16 patients with a planned top-line readout in mid-December of this year. Finally, we will read out top-line results from our ongoing SELVA Phase 3 study of QTORIN™ rapamycin 3.9% anhydrous gel for the treatment of microcystic lymphatic malformations, a program which has been granted FDA's breakthrough therapy, FastTrack, and orphan designations in Q1 of 2026. These four high-impact milestones establish a steady cadence of new pipeline and clinical readouts between now and the end of Q1 of 2026, setting the stage for a transformative period for Palvella Therapeutics. Moving to clinically significant angiokeratomas, clinically significant angiokeratomas are superficial vascular malformations of lymphatic origin and impact an estimated more than 50,000 diagnosed patients in the United States.
On the far right side of this slide, you can see the clinical impact to patients who are afflicted with angiokeratomas, which Dr. Jim Treat will discuss in detail. Overall, these chronically debilitating skin lesions can contribute to a significantly diminished quality of life. Since this disease does not spontaneously regress, disease presentation can be persistent, with potential to increase in size, number, and extent over time. Unfortunately for these patients, there are no FDA-approved therapies, and patients are therefore relegated to invasive interventional procedures such as laser therapy, electrosurgery, cryotherapy, and surgical incisions, which have several limitations which Dr. Jim Treat will discuss. Work by leading researchers in the field has recently revealed that angiokeratomas are lymphatic-derived skin lesions, and furthermore, that increased VEGF signaling is driving the vessel dilation and hyperkeratosis.
These scientific discoveries, along with preliminary case studies exploring the potential of off-label rapamycin, have opened up the potential to address this disease with a targeted therapy such as QTORIN™ rapamycin 3.9% anhydrous gel. Palvella's development will initially be focused on the subset of patients with, number one, clinically significant angiokeratomas that necessitate medical intervention, and number two, the four angiokeratoma subtypes you see listed at the top of the slide here: fordyce, solitary, mobile, and circumscriptum. For today's presentation, number one, Dr. Treat will present an overview of the unmet medical need that exists for clinically significant angiokeratomas as well as the recent classification of angiokeratomas as superficial vascular malformations of lymphatic origin. Number two, our Chief Scientific Officer, Dr. Jeff Martini, will provide a scientific overview of the disease and review some of the clinical similarities between clinically significant angiokeratomas and microcystic lymphatic malformations, another indication in which we're evaluating the potential of QTORIN™ rapamycin 3.9% anhydrous gel. Number three, our Chief Financial Officer, Matt Korenberg, will summarize initial work completed by Matt and his team as well as Ashley Klein, our Chief Commercial Officer. This work strongly supports that clinically significant angiokeratomas are an attractive commercial opportunity for Palvella and QTORIN™ rapamycin 3.9% anhydrous gel. Finally, we'll review the envisioned streamlined development plan for QTORIN™ rapamycin 3.9% anhydrous gel for clinically significant angiokeratomas, including our plan to initiate a Phase 2 study in the second half of 2026. It is now my pleasure to hand the call over to Dr. Treat.
Thank you, Wes. I'm pleased to be here today to share my clinical perspective on angiokeratomas. These are a type of superficial vascular malformation with lymphatic origin and can be quite bothersome to the patient. They can be large in size or located on very sensitive areas such as the genitalia and are associated with symptoms such as bleeding and irritation. For some patients with angiokeratomas, these lesions are less symptomatic and do not require medical intervention. On the other hand, it's important to recognize that there is a significant percentage of patients with angiokeratomas who face an especially difficult course. Those are often referred to as clinically significant. These lesions are chronic, debilitating, hyperkeratotic, and prone to bleeding with minor trauma. They are susceptible to infection and have a significant impact on patients' quality of life.
This population represents a truly underserved group of patients with no FDA-approved therapy today. When we look at the current treatment paradigm for how angiokeratomas are managed today, it is important to note that there are no FDA-approved medical therapies to treat this disease. For clinically significant angiokeratomas, existing approaches are often inadequate and destructive. The most commonly used interventions include laser therapy, electrocautery, and other destructive techniques. The patients face significant risks of pain, scarring, and importantly, recurrence of lesions. It is also important and worth noting, despite the unmet need, that there are currently no ongoing clinical trials investigating pharmacotherapies for angiokeratomas. This underscores the stagnant treatment landscape and highlights the unmet medical need. On this slide, I want to highlight where angiokeratomas now fit within the classification system of ISSVA or the International Society for the Study of Vascular Anomalies.
Historically, angiokeratomas were considered a provisionally unclassified vascular anomaly. However, in the 2025 ISSVA classification update, they were formally reclassified within the lymphatic malformation subcategory, the same subcategory as microcystic lymphatic malformations. This reclassification reflects our improved understanding of angiokeratoma cellular origin. With that, I'd like to turn the call over to Dr. Jeff Martini, Palvella Therapeutics' Chief Scientific Officer.
Thank you, Jim. I'm very excited about this new third indication for QTORIN™ rapamycin 3.9% anhydrous gel, which aligns well with our R&D strategy of being first in serious, rare diseases for which there are no FDA-approved therapies. Before getting into the clinical and molecular overlap with microcystic lymphatic malformations, I want to spend a moment on the endothelial cell lineage of angiokeratomas. Historically, these lesions were thought to be simple vascular malformations. However, two key studies, Wang and Trindade, use immunohistochemical markers to demonstrate angiokeratomas are actually of lymphatic endothelial lineage. This means the dilated dermal vessels you see in angiokeratomas express lymphatic markers including D240 and Prox1, placing them within the category of isolated lymphatic malformations. That's critical because it reframes angiokeratomas as having a lymphatic origin and provides the first plausible mechanistic rationale for targeting VEGF signaling and mTOR.
Now that we've established the lymphatic lineage of angiokeratomas, it's important to place them in context with microcystic lymphatic malformations with which angiokeratomas share several features. First, both angiokeratomas and microcystic LMs arise from lymphatic endothelial cells, placing them both as a type of isolated lymphatic malformation. Second, there is a strong scientific rationale for targeting VEGF signaling and mTOR inhibition, as well as real-world evidence supporting rapamycin as a targeted therapeutic approach. From a pharmacokinetic perspective, both conditions are located in the superficial dermis, making them particularly well-suited for a topical therapy like QTORIN™ rapamycin 3.9% anhydrous gel. The clinical burden is significant in both diseases and are associated with bleeding, risk of infection, and where patients may experience a significant daily impact to quality of life. In both cases, these are chronic conditions with no regression and no FDA-approved therapies.
I will now hand it off to Matt Korenberg, our Chief Financial Officer, to address the commercial opportunity.
Thanks, Jeff. Before I dive deeper into the clinically significant angiokeratoma market, I wanted to remind investors about our pipeline and a product strategy for QTORIN™ rapamycin. Clinically significant angiokeratomas will be our third active clinical indication using QTORIN™ rapamycin. Like microcystic lymphatic malformations and cutaneous venous malformations, clinically significant angiokeratomas are a rare but not ultra-rare indication in terms of estimated prevalence. By leveraging the same QTORIN™ rapamycin 3.9% anhydrous gel drug product across all three programs, as well as any potential future programs, we can save significant time and cost in development while continuing to add significant pools of patients to our addressable market with QTORIN™ rapamycin. If we are successful in obtaining regulatory approval in microcystic lymphatic malformations or cutaneous venous malformations, it is our plan to pursue additional approvals through the supplemental NDA or SNDA pathway.
From a timing perspective, we've spaced the programs out such that we would expect the approvals to be achieved every couple of years. Taken together, MLM, CVM, and clinically significant angiokeratomas would represent a patient pool of over 150,000 individuals in a multibillion-dollar total addressable market. We believe that clinically significant angiokeratomas represent not just a significant clinical need, but also a very compelling market opportunity. QTORIN™ rapamycin has the potential to be the first targeted therapy for the disease, addressing a population of more than 50,000 patients in the U.S. alone. As we were considering which disease to pursue for our third clinical indication with QTORIN™ rapamycin, we took the same initial steps we did with microcystic lymphatic malformations and cutaneous venous malformations, and we conducted a real-world evidence study.
This initial epidemiology study was led by our new Chief Commercial Officer, Ashley Klein, and was an excellent example of the important work we need to do to validate new rare disease markets. Ashley's experience at Dompé launching Oxervate in the neurotrophic keratitis market was key to designing this study and will be critical in executing our commercial efforts across all of our programs. The study conducted with Clarity Pharma included 643 physicians surveyed earlier this summer. The results of the survey show that there are more than 50,000 patients with clinically significant angiokeratomas. From a pricing perspective, we plan to use the same QTORIN™ rapamycin drug product we are using for microcystic lymphatic malformations and cutaneous venous malformations, and we therefore anticipate similar pricing.
To further understand the unmet need and potential market adoption, we conducted separate market research with physicians to give us detailed insights into real-world practice patterns and treatment attitudes. In a survey of 50 physicians across the United States, 96% would incorporate a topical 3.9% rapamycin gel into their practice for clinically significant angiokeratomas. Given that the only current options are destructive procedures like laser and electrocautery, and clinicians are frustrated by the lack of alternatives, 85% of physicians surveyed say there is a clear unmet need for a topical novel therapy. In summary, clinically significant angiokeratomas represent a large underserved market with strong clinician demand and a clear path for rapid adoption. This positions a product with the target profile of QTORIN™ rapamycin to transform the treatment landscape for this serious, rare, and debilitating disease.
Wes will now wrap up with some comments about our anticipated clinical development plan and then a summary of today's comments.
Thank you, Matt, for QTORIN™ rapamycin's development for clinically significant angiokeratomas. We are planning to leverage many established aspects of the QTORIN™ 3.9% rapamycin anhydrous gel program, including, as seen on the slide here, number one, using our existing 3.9% anhydrous formulation, number two, drug supply, which has already been manufactured and is ready to deploy to the clinic for trial purposes, number three, our open IND and non-clinical data package with FDA's Division of Dermatology and Dentistry, and number four, our existing granted intellectual property, which we believe covers the potential commercial use of QTORIN™ rapamycin in clinically significant angiokeratomas, if approved.
By leveraging years of innovation and investment in QTORIN™ rapamycin to expand into a new clinical indication, we believe this presents potentially significant time and cost advantages when compared to a more traditional biotech pipeline build involving a de novo preclinical program. From a regulatory perspective, our plan is to conduct an FDA meeting in the first half of 2026, followed by a Phase 2 study of approximately 10 to 20 patients with initiation of that study currently planned for the second half of 2026. The program is likely to mimic the microcystic lymphatic malformation development program, including many similar efficacy endpoints and initially a single-arm baseline controlled study design. In summary, clinically significant angiokeratomas represent a compelling Palvella rare disease program with shared characteristics to our other QTORIN™ rapamycin target indications, microcystic lymphatic malformations, and cutaneous venous malformations.
Clinically significant angiokeratomas meet Palvella's disease selection criteria in terms of the serious, chronically debilitating nature of the disease, the rarity of the disease, and the absence of even a single FDA-approved therapy, meaning we can potentially be first for patients and for physicians like Dr. Jim Treat. Furthermore, we believe, as you heard today, that a strong scientific and biological rationale exists, which is further supported by published case studies and real-world use of off-label rapamycin at academic centers, which together optimizes our likelihood of clinical success with QTORIN™ rapamycin. Finally, the opportunity to be first in disease and standard of care for the estimated more than 50,000 clinically significant angiokeratoma patients meets our threshold for a commercially compelling opportunity.
In closing, we would like to thank everyone who has passionately contributed to informing Palvella's decision to accelerate the development of QTORIN™ rapamycin to patients with clinically significant angiokeratomas, especially Dr. Jim Treat and our other medical and scientific collaborators, including Doctors Joyce Teng, Amy Paller, John Du, Vishal Patel, Megha Tollison, Misha Rosenbach, and Maria Beuth, all of whom have supported our evaluation of multiple opportunities and helped shape this strategy. Looking ahead, we are excited to continue to expand our pipeline and announce our new QTORIN™ platform program later this year, which will be in another serious, rare, commercially attractive disease with no FDA-approved therapies. Our thanks to everyone for attending this morning's call. This now concludes our presentation.
This concludes today's conference call. Thank you for participating. You may now disconnect.