Full Year 2025 Palvella Therapeutics Inc Earnings Call

March 31, 2026

Operator: Good day, and thank you for standing by. Welcome to the Palvella Therapeutics Full Year 2025 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to Bohan Wei, Vice President of Corporate Development. Please go ahead.

Speaker #2: Good day, and thank you for standing by. Welcome to the Palvella Therapeutics full-year 2025 financial results conference call. At this time, all participants are in a listen-only mode.

Speaker #2: After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you'll need to press *11 on your telephone.

Speaker #2: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded.

Speaker #2: I'd now like to hand the conference over to Bohan Way, Vice President of Corporate Development. Please go ahead.

Speaker #3: Thank you, Operator. Good morning, and thank you for joining the Palvella Therapeutics full-year 2025 financial results and corporate update call. As a reminder, our press release detailing today's announcements can be found in the Investor section of our website, at www.palvellatx.com.

Bohan Wei: Thank you, operator. Good morning, and thank you for joining the Palvella Therapeutics Full Year 2025 Financial Results and Corporate Update Call. As a reminder, our press release detailing today's announcements can be found in the investor section of our website at www.palvellatx.com. On today's call, you will first hear from Wes Kauppinen, our Founder and Chief Executive Officer, followed by Dr. Jeff Martini, our Chief Scientific Officer, and Matt Korenberg, our Chief Financial Officer. Wes will return for closing remarks before we open the lines for Q&A. 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.

Speaker #3: On today's call, you will first hear from Wes Kaufmann, our Founder and Chief Executive Officer, followed by Dr. Jeff Martini, our Chief Scientific Officer, and Matt Korenberg, our Chief Financial Officer.

Speaker #3: Wes will return for closing remarks before we open the line for Q&A. 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.

Speaker #3: 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.

Speaker #3: And now, I will turn the call over to Wes.

Bohan Wei: Now, I will turn the call over to Wes.

Speaker #4: Thanks, Bohan. 2025 was a landmark year for Palvella Therapeutics. One, that brings us closer to recognizing our vision, of building the leading rare disease biopharmaceutical company, focused on developing and commercializing first-in-disease therapies for serious rare skin diseases and vascular malformations.

Wesley H. Kaupinen: Thanks, Bohan. 2025 was a landmark year for Palvella Therapeutics. One that brings us closer to recognizing our vision of building the leading rare disease biopharmaceutical company focused on developing and commercializing first-in-disease therapies for serious rare skin diseases and vascular malformations. Thanks to the efforts of the Palvella team, our scientific and clinical collaborators, our patient advocacy partners, and the rare disease patients we serve, we achieved several value-creating milestones, including number one, announcing positive Phase 2 data in cutaneous venous malformations, data which support the advancement of that program toward a near-term Breakthrough Therapy designation submission to FDA and a pivotal Phase 3 study. Number two, surpassing our target enrollment in our Phase 3 SELVA study in microcystic lymphatic malformations, this based on physician and patient demand as well as strong execution from our clinical operations team.

Wesley Kaupinen: Thanks, Bohan. 2025 was a landmark year for Palvella Therapeutics. One that brings us closer to recognizing our vision of building the leading rare disease biopharmaceutical company focused on developing and commercializing first-in-disease therapies for serious rare skin diseases and vascular malformations. Thanks to the efforts of the Palvella team, our scientific and clinical collaborators, our patient advocacy partners, and the rare disease patients we serve, we achieved several value-creating milestones, including number one, announcing positive Phase II data in cutaneous venous malformations, data which support the advancement of that program toward a near-term Breakthrough Therapy designation submission to FDA and a pivotal Phase 3 study. Number two, surpassing our target enrollment in our Phase 3 SELVA study in microcystic lymphatic malformations, this based on physician and patient demand as well as strong execution from our clinical operations team.

Speaker #4: Thanks to the efforts of the Palvella team, our scientific and clinical collaborators, our patient advocacy partners, and the rare disease patients we serve, we achieved several value-creating milestones.

Speaker #4: Including, number one, announcing positive Phase 2 data in cutaneous venous malformations. Data which support the advancement of that program toward a near-term breakthrough therapy designation submission to FDA, and a pivotal Phase 3 study.

Speaker #4: Number two, surpassing our target enrollment in our Phase 3 SELVA study in microcystic lymphatic malformations—this based on physician and patient demand, as well as strong execution from our clinical operations team.

Wesley H. Kaupinen: Number three, expanding our rare disease pipeline with the addition of two new programs, QTORIN and rapamycin for clinically significant angiokeratomas, and QTORIN and pitavastatin for porokeratosis. Number four, adding top talent to our senior leadership team, including Dr. David Osborne as our Chief Innovation Officer and Ashley Kline as our Chief Commercial Officer. Number five, extending our collaboration with the FDA and specifically FDA's Office of Orphan Products Development, who in 2025 supported our SELVA Phase 3 study with additional non-dilutive funding. Number six, expanding our IP portfolio with two US patents for QTORIN and rapamycin, strengthening our multilayered exclusivity strategy. Number seven, capping 2025 by securing FDA's Fast Track designation in clinically significant angiokeratomas. The third Palvella program, which has been granted Fast Track designation.

Wesley Kaupinen: Number three, expanding our rare disease pipeline with the addition of two new programs, QTORIN and rapamycin for clinically significant angiokeratomas, and QTORIN and pitavastatin for porokeratosis. Number four, adding top talent to our senior leadership team, including Dr. David Osborne as our Chief Innovation Officer and Ashley Kline as our Chief Commercial Officer. Number five, extending our collaboration with the FDA and specifically FDA's Office of Orphan Products Development, who in 2025 supported our SELVA Phase 3 study with additional non-dilutive funding. Number six, expanding our IP portfolio with two US patents for QTORIN and rapamycin, strengthening our multilayered exclusivity strategy. Number seven, capping 2025 by securing FDA's Fast Track designation in clinically significant angiokeratomas. The third Palvella program, which has been granted Fast Track designation.

Speaker #4: Number three, expanding our rare disease pipeline with the addition of two new programs, Ketor and Rapamycin for clinically significant angiokeratomas, and Ketor and Pitavastatin for porokeratosis.

Speaker #4: Number four, adding top talent to our senior leadership team, including Dr. David Osborne, as our Chief Innovation Officer and Ashley Kline as our Chief Commercial Officer.

Speaker #4: Number five, extending our collaboration with the FDA and specifically FDA's Office of Orphan Products Development, who in 2025 supported our SELVA Phase 3 study with additional non-dilutive funding; number six, expanding our IP portfolio with two U.S.

Speaker #4: patents for Ketor and Rapamycin, strengthening our multi-layered exclusivity strategy; and number seven, capping 2025 by securing FDA's Fast-Track designation in clinically significant angiokeratomas. The third Palvella program, which has been granted Fast-Track designation.

Wesley H. Kaupinen: This momentum, the results of focus and disciplined execution by the Palvella team, has carried into 2026, where earlier this year we announced positive Phase 3 data from our SELVA study in microcystic lymphatic malformations. Results, which we believe position QTORIN rapamycin, if approved, to be a first-line standard of care therapy for individuals with microcystic lymphatic malformations. With a significantly strengthened balance sheet as the result of a $230 million financing announced earlier this quarter, Palvella is now well-positioned to pursue a near-term FDA approval of QTORIN rapamycin in microcystic lymphatic malformations, drive a successful standalone US launch, and concurrently advance the rest of our rare disease pipeline. What makes Palvella stand apart from other companies begins with our corporate strategy of pursuing development and commercialization in serious rare diseases with no FDA-approved therapies.

Wesley Kaupinen: This momentum, the results of focus and disciplined execution by the Palvella team, has carried into 2026, where earlier this year we announced positive Phase 3 data from our SELVA study in microcystic lymphatic malformations. Results, which we believe position QTORIN rapamycin, if approved, to be a first-line standard of care therapy for individuals with microcystic lymphatic malformations. With a significantly strengthened balance sheet as the result of a $230 million financing announced earlier this quarter, Palvella is now well-positioned to pursue a near-term FDA approval of QTORIN rapamycin in microcystic lymphatic malformations, drive a successful standalone US launch, and concurrently advance the rest of our rare disease pipeline. What makes Palvella stand apart from other companies begins with our corporate strategy of pursuing development and commercialization in serious rare diseases with no FDA-approved therapies.

Speaker #4: This momentum, the results of focus and disciplined execution by the Palvella team, has carried into 2026, where earlier this year we announced positive Phase 3 data from our SELVA study in microcystic lymphatic malformations, results which we believe position Ketor and Rapamycin if approved to be a first-line standard-of-care therapy for individuals with microcystic lymphatic malformations.

Speaker #4: With a significantly strengthened balance sheet as the result of a $230 million financing announced earlier this quarter, Palvella is now well positioned to pursue a near-term FDA approval of Ketor and Rapamycin in microcystic lymphatic malformations drive a successful standalone U.S.

Speaker #4: Launch and concurrently advance the rest of our rare disease pipeline. What makes Palvella stand apart from other companies begins with our corporate strategy of pursuing development and commercialization in serious rare diseases with no FDA-approved therapies.

Speaker #4: We believe that these diseases are unambiguously high unmet medical need. We intentionally focus on diseases where we are the pioneers in advancing therapies targeted to be first-in-disease for patients and families suffering from these rare diseases.

Wesley H. Kaupinen: We believe that these diseases are unambiguously high unmet medical need. We intentionally focus on diseases where we are the pioneers in advancing therapies targeted to be first in disease for patients and families suffering from these rare diseases. Our goal is to apply our proprietary QTORIN platform, our internal product development engine for reproducibly developing novel topical product candidates in a focused subset of rare skin diseases and vascular malformations which have clear biology and also the existence of human proof-of-concept data which serves to validate a specific molecular approach. Evidence of this development strategy is microcystic lymphatic malformations, a well-defined disease caused by PI3K mutation, where mTOR hyperactivation is driving the disease progression, and in which rapamycin has a large, growing foundation of real-world human clinical evidence upon which Palvella can build.

Wesley Kaupinen: We believe that these diseases are unambiguously high unmet medical need. We intentionally focus on diseases where we are the pioneers in advancing therapies targeted to be first in disease for patients and families suffering from these rare diseases. Our goal is to apply our proprietary QTORIN platform, our internal product development engine for reproducibly developing novel topical product candidates in a focused subset of rare skin diseases and vascular malformations which have clear biology and also the existence of human proof-of-concept data which serves to validate a specific molecular approach. Evidence of this development strategy is microcystic lymphatic malformations, a well-defined disease caused by PI3K mutation, where mTOR hyperactivation is driving the disease progression, and in which rapamycin has a large, growing foundation of real-world human clinical evidence upon which Palvella can build.

Speaker #4: Our goal is to apply our proprietary Ketor and platform, our internal product development engine for reproducibly developing novel topical product candidates, in a focused subset of rare skin diseases and vascular malformations which have clear biology and also the existence of human proof-of-concept data, which serves to validate a specific molecular approach.

Speaker #4: Evidence of this development strategy is microcystic lymphatic malformations, a well-defined disease caused by PI3K mutation, where mTOR hyperactivation is driving the disease progression and in which Rapamycin has a large, growing foundation of real-world human clinical evidence upon which Palvella can build.

Speaker #4: We are taking a similar approach in cutaneous venous malformations, angiokeratomas, and disseminated superficial actinic porokeratosis, and we anticipate by year-end the addition of two new diseases to our pipeline, bringing the number of diseases we aim to treat to six.

Wesley H. Kaupinen: We are taking a similar approach in cutaneous venous malformations, angiokeratomas, and disseminated superficial actinic porokeratosis, and we anticipate by year-end the addition of 2 new diseases to our pipeline, bringing the number of diseases we aim to treat to 6. Overall, by taking the approach outlined on this slide, our aim is to reduce the time and capital required to achieve FDA approvals while entering uncontested markets that have more favorable commercial dynamics when compared to more traditional and more competitive markets. With approximately 600 rare skin diseases, 98% of which do not have a single approved therapy, we see ample opportunity to grow our pipeline and repeat our focused rare disease development model. I want to take you through how our recent execution translates into multiple anticipated high-impact milestones over the next 12+ months.

Wesley Kaupinen: We are taking a similar approach in cutaneous venous malformations, angiokeratomas, and disseminated superficial actinic porokeratosis, and we anticipate by year-end the addition of 2 new diseases to our pipeline, bringing the number of diseases we aim to treat to 6. Overall, by taking the approach outlined on this slide, our aim is to reduce the time and capital required to achieve FDA approvals while entering uncontested markets that have more favorable commercial dynamics when compared to more traditional and more competitive markets. With approximately 600 rare skin diseases, 98% of which do not have a single approved therapy, we see ample opportunity to grow our pipeline and repeat our focused rare disease development model. I want to take you through how our recent execution translates into multiple anticipated high-impact milestones over the next 12+ months.

Speaker #4: Overall, by taking the approach outlined on this slide, our aim is to reduce the time and capital required to achieve FDA approvals while entering uncontested markets.

Speaker #4: That have more favorable commercial dynamics when compared to more traditional and more competitive markets. With approximately 600 rare skin diseases, 98% of which do not have a single approved therapy, we see ample opportunity to grow our pipeline and repeat our focused rare disease development model.

Speaker #4: I want to take you through how our recent execution translates into multiple anticipated high-impact milestones over the next 12-plus months. We entered 2026 exceptionally well positioned across both our lead program and our expanding pipeline.

Wesley H. Kaupinen: We enter 2026 exceptionally well-positioned across both our lead program and our expanding pipeline. Starting with microcystic lymphatic malformations, we have positive Phase 3 data in hand and are on track for NDA submission in H2 2026, with a potential FDA approval targeted for H1 2027. In cutaneous venous malformations, following positive Phase 2 data, we expect a breakthrough therapy designation decision in Q2 this year and plan to initiate a Phase 3 study in H2 this year. For clinically significant angiokeratomas, we have received FDA's Fast Track designation and are advancing towards initiation of our Phase 2 study ahead of schedule, with the Phase 2 initiation now expected in Q2 this year versus our previous guidance of H2 2026.

Wesley Kaupinen: We enter 2026 exceptionally well-positioned across both our lead program and our expanding pipeline. Starting with microcystic lymphatic malformations, we have positive Phase 3 data in hand and are on track for NDA submission in H2 2026, with a potential FDA approval targeted for H1 2027. In cutaneous venous malformations, following positive Phase II data, we expect a breakthrough therapy designation decision in Q2 this year and plan to initiate a Phase 3 study in H2 this year. For clinically significant angiokeratomas, we have received FDA's Fast Track designation and are advancing towards initiation of our Phase II study ahead of schedule, with the Phase II initiation now expected in Q2 this year versus our previous guidance of H2 2026.

Speaker #4: Starting with microcystic lymphatic malformations, we have positive Phase 3 data in hand and are on track through NDA submission in the second half of 2026, with a potential FDA approval targeted for the first half of 2027.

Speaker #4: In cutaneous venous malformations following positive Phase 2 data, we expect a breakthrough therapy designation decision in the second quarter of this year and plan to initiate a Phase 3 study in the second half of this year.

Speaker #4: For clinically significant angiokeratomas, we have received FDA's Fast Track designation and are advancing towards initiation of our Phase 2 study ahead of schedule. With the Phase 2 initiation now expected in the second quarter of this year, versus our previous guidance of the second half of 2026.

Speaker #4: In DSAP, we have developed our Ketor and Pitavastatin formulation, filed IP, and we expect to initiate a Phase 2 study in the second half of 2026.

Wesley H. Kaupinen: In DSAP, we have developed our QTORIN pitavastatin formulation, filed IP, and we expect to initiate a Phase 2 study in H2 2026. More broadly, we continue to expand the QTORIN pipeline with a fourth indication for QTORIN rapamycin expected to be announced in H2 this year, and a new QTORIN product candidate, our third, also expected to be announced in H2 this year. This positions Palvella for a catalyst-rich period, including the potential for our first FDA approval, which we believe could create a streamlined and efficient pathway for indication expansion into other mTOR-driven skin diseases through planned supplemental NDA submissions. Let me now turn to our lead program, QTORIN rapamycin for microcystic lymphatic malformations.

Wesley Kaupinen: In DSAP, we have developed our QTORIN pitavastatin formulation, filed IP, and we expect to initiate a Phase II study in H2 2026. More broadly, we continue to expand the QTORIN pipeline with a fourth indication for QTORIN rapamycin expected to be announced in H2 this year, and a new QTORIN product candidate, our third, also expected to be announced in H2 this year. This positions Palvella for a catalyst-rich period, including the potential for our first FDA approval, which we believe could create a streamlined and efficient pathway for indication expansion into other mTOR-driven skin diseases through planned supplemental NDA submissions. Let me now turn to our lead program, QTORIN rapamycin for microcystic lymphatic malformations.

Speaker #4: And more broadly, we continue to expand the Ketor and pipeline. With a fourth indication for Ketor and Rapamycin expected to be announced in the second half of this year, and a new Ketor and product candidate, our third, also expected to be announced in the second half of this year.

Speaker #4: This positions Palvella for a catalyst-rich period, including the potential for our first FDA approval—which we believe could create a streamlined and efficient pathway for indication expansion into other mTOR-driven skin diseases through planned supplemental NDA submissions.

Speaker #4: Let me now turn to our lead program, Ketor and Rapamycin, for microcystic lymphatic malformations. We believe microcystic lymphatic malformations represent a significant multi-billion dollar commercial opportunity, based on an estimated population of more than 30,000 diagnosed patients in the U.S.

Wesley H. Kaupinen: We believe microcystic lymphatic malformations represent a significant multibillion-dollar commercial opportunity based on an estimated population of more than 30,000 diagnosed patients in the US according to claims analysis and published literature. Based on the Phase 3 SELVA results, the results from our Phase 2 study, and the market research we've conducted, we believe QTORIN rapamycin, upon achieving potential FDA approval, is positioned to be first line and standard of care therapy for microcystic lymphatic malformations, directly targeting the underlying disease biology through inhibition of the causative mTOR pathway, and doing so in the pathogenic skin tissue of interest. Clinically, we have demonstrated a robust treatment effect across two prospective trials, along with a favorable safety and tolerability profile supporting efficacy and potential for long-term use in this patient population.

Wesley Kaupinen: We believe microcystic lymphatic malformations represent a significant multibillion-dollar commercial opportunity based on an estimated population of more than 30,000 diagnosed patients in the US according to claims analysis and published literature. Based on the Phase 3 SELVA results, the results from our Phase II study, and the market research we've conducted, we believe QTORIN rapamycin, upon achieving potential FDA approval, is positioned to be first line and standard of care therapy for microcystic lymphatic malformations, directly targeting the underlying disease biology through inhibition of the causative mTOR pathway, and doing so in the pathogenic skin tissue of interest. Clinically, we have demonstrated a robust treatment effect across two prospective trials, along with a favorable safety and tolerability profile supporting efficacy and potential for long-term use in this patient population.

Speaker #4: according to claims analysis and published literature. Based on the Phase 3 SELVA results, the results from our Phase 2 study and the market research we've conducted, we believe Ketor and Rapamycin upon achieving potential FDA approval is positioned to be first-line and standard-of-care therapy for microcystic lymphatic malformations.

Speaker #4: Directly targeting the underlying disease biology through inhibition of the causative mTOR pathway, and doing so in the pathogenic skin tissue of interest. Clinically, we have demonstrated a robust treatment effect across two prospective trials, along with a favorable safety and tolerability profile supporting efficacy and potential for long-term use in this patient population.

Speaker #4: With positive Phase 3 data now in hand, we are on track for an NDA submission in the second half of 2026, and if approved, potential FDA approval in the first half of 2027.

Wesley H. Kaupinen: With positive Phase 3 data now in hand, we are on track for an NDA submission in H2 2026 and, if approved, potential FDA approval in H1 2027. I'd like to highlight our Phase 3 SELVA data, which we announced last month. Our team established base and upside cases grounded in what clinical study results could translate to meaningful improvement in patients' lives while supporting an attractive commercial opportunity. SELVA exceeded our predefined upside case across every dimension. On the primary endpoint, the Microcystic Lymphatic Malformation Investigator Global Assessment, we observed a highly statistically significant outcome well above our upside case. Importantly, 95% of patients completing the efficacy evaluation period improved, and 86% were much improved or very much improved. The blinded key secondary endpoint, the mLM-MCSS, was also highly statistically significant.

Wesley Kaupinen: With positive Phase 3 data now in hand, we are on track for an NDA submission in H2 2026 and, if approved, potential FDA approval in H1 2027. I'd like to highlight our Phase 3 SELVA data, which we announced last month. Our team established base and upside cases grounded in what clinical study results could translate to meaningful improvement in patients' lives while supporting an attractive commercial opportunity. SELVA exceeded our predefined upside case across every dimension. On the primary endpoint, the Microcystic Lymphatic Malformation Investigator Global Assessment, we observed a highly statistically significant outcome well above our upside case. Importantly, 95% of patients completing the efficacy evaluation period improved, and 86% were much improved or very much improved. The blinded key secondary endpoint, the mLM-MCSS, was also highly statistically significant.

Speaker #4: I'd like to highlight our Phase 3 SELVA data, which we announced last month. Our team established base and upside cases grounded in what clinical study results could translate to meaningful improvement in patients' lives, while supporting an attractive commercial opportunity.

Speaker #4: SELVA exceeded our predefined upside case across every dimension. On the primary endpoint, the microcystic lymphatic malformation investigator global assessment, we observed a highly statistically significant outcome, well above our upside case.

Speaker #4: Importantly, 95% of patients completing the efficacy evaluation period improved and 86% were much improved or very much improved. The blinded key secondary endpoint, the MLM/MCSS, was also highly statistically significant.

Speaker #4: From a safety perspective, Ketor and Rapamycin were well tolerated in both children and adults, supporting potential for chronic dosing across all ages. Importantly, retention in the study was exceptionally strong, with 98% of week 24 completers electing to roll into the extension period, supporting durability and continued treatment benefit.

Wesley H. Kaupinen: From a safety perspective, QTORIN rapamycin was well-tolerated in both children and adults, supporting potential for chronic dosing across all ages. Importantly, retention in the study was exceptionally strong, with 98% of week 24 completers electing to roll into the extension period, supporting durability and continued treatment benefit. SELVA exceeded what we at Palvella had hoped to see, not just on efficacy, but on durability and safety. Ultimately, these results, we believe, translate into meaningful impact for patients of all ages diagnosed with microcystic lymphatic malformations. Turning to our regulatory progress, our planned NDA submission is on track. We recently submitted our pre-NDA meeting request to FDA's Division of Dermatology and Dentistry, with the pre-NDA meeting anticipated in Q2 2026.

Wesley Kaupinen: From a safety perspective, QTORIN rapamycin was well-tolerated in both children and adults, supporting potential for chronic dosing across all ages. Importantly, retention in the study was exceptionally strong, with 98% of week 24 completers electing to roll into the extension period, supporting durability and continued treatment benefit. SELVA exceeded what we at Palvella had hoped to see, not just on efficacy, but on durability and safety. Ultimately, these results, we believe, translate into meaningful impact for patients of all ages diagnosed with microcystic lymphatic malformations. Turning to our regulatory progress, our planned NDA submission is on track. We recently submitted our pre-NDA meeting request to FDA's Division of Dermatology and Dentistry, with the pre-NDA meeting anticipated in Q2 2026.

Speaker #4: SELVA exceeded what we at Palvella had hoped to see, not just on efficacy, but on durability and safety. And ultimately, these results we believe translate into meaningful impact for patients of all ages diagnosed with microcystic lymphatic malformations.

Speaker #4: Referring to our regulatory progress, our planned NDA submission is on track. We recently submitted our pre-NDA meeting request to FDA's Division of Dermatology and Dentistry.

Speaker #4: With the pre-NDA meeting anticipated in the second quarter of 2026, notably we are pursuing a traditional full FDA approval based on clinical endpoints, which differs from an accelerated approval, which relies upon surrogate biomarkers that are likely to reasonably predict clinical outcomes.

Wesley H. Kaupinen: Notably, we are pursuing a traditional full FDA approval based on clinical endpoints, which differs from an accelerated approval, which relies upon surrogate biomarkers that are likely to reasonably predict clinical outcomes. Providing a strong foundation for our NDA submission is both our Phase 3 SELVA data, which were highly statistically significant and clinically meaningful, as well as the results from our Phase 2 study. Our interactions with physician key opinion leaders in this disease and our understanding of the progressive nature of the disease suggest that early therapeutic intervention could alter the natural history of the disease. Therefore, it is our intent to pursue a label which includes patients aged 3 and above.

Wesley Kaupinen: Notably, we are pursuing a traditional full FDA approval based on clinical endpoints, which differs from an accelerated approval, which relies upon surrogate biomarkers that are likely to reasonably predict clinical outcomes. Providing a strong foundation for our NDA submission is both our Phase 3 SELVA data, which were highly statistically significant and clinically meaningful, as well as the results from our Phase II study. Our interactions with physician key opinion leaders in this disease and our understanding of the progressive nature of the disease suggest that early therapeutic intervention could alter the natural history of the disease. Therefore, it is our intent to pursue a label which includes patients aged 3 and above.

Speaker #4: Providing a strong foundation for our NDA submission is both our Phase 3 SELVA data, which were highly statistically significant and clinically meaningful, as well as the results from our Phase 2 study.

Speaker #4: Our interactions with physician key opinion leaders in this disease, and our understanding of the progressive nature of the disease, suggest that early therapeutic intervention could alter the natural history of the disease.

Speaker #4: Therefore, it is our intent to pursue a label which includes patients aged three and above. We have previously been granted Breakthrough Therapy, Fast-Track, and Orphan Drug designations, and we plan to pursue a 505(b)(2) pathway.

Wesley H. Kaupinen: We have previously been granted Breakthrough Therapy, Fast Track, and Orphan Drug designations, and we plan to pursue a 505(b)(2) pathway, which may enable us to leverage existing FDA findings and the established body of evidence for rapamycin as part of a more streamlined development and regulatory strategy. We continue to collaborate closely with the FDA's Office of Orphan Products Development, which in addition to providing non-dilutive funding, intend to participate in our anticipated pre-NDA meeting with the review division in Q2 of this year. These elements support a path towards NDA submission in H2 2026 and potential for FDA approval in H1 2027. Turning to the commercial opportunity, we believe QTORIN rapamycin is well-positioned for a highly attractive orphan launch.

Wesley Kaupinen: We have previously been granted Breakthrough Therapy, Fast Track, and Orphan Drug designations, and we plan to pursue a 505(b)(2) pathway, which may enable us to leverage existing FDA findings and the established body of evidence for rapamycin as part of a more streamlined development and regulatory strategy. We continue to collaborate closely with the FDA's Office of Orphan Products Development, which in addition to providing non-dilutive funding, intend to participate in our anticipated pre-NDA meeting with the review division in Q2 of this year. These elements support a path towards NDA submission in H2 2026 and potential for FDA approval in H1 2027. Turning to the commercial opportunity, we believe QTORIN rapamycin is well-positioned for a highly attractive orphan launch.

Speaker #4: Which may enable us to leverage existing FDA findings and the established body of evidence for Rapamycin as part of a more streamlined development and regulatory strategy.

Speaker #4: We continue to collaborate closely with the FDA's Office of Orphan Products Development, which in addition to providing non-dilutive funding, intend to participate in our anticipated pre-NDA meeting with the review division in the second quarter of this year.

Speaker #4: These elements support a path towards NDA submission in the second half of 2026 and potential for FDA approval in first half of 2027. Turning to the commercial opportunity, we believe Ketor and Rapamycin is well positioned for a highly attractive orphan launch.

Wesley H. Kaupinen: Microcystic lymphatic malformations represent a serious rare disease with high unmet medical need and currently no FDA-approved therapies available to physicians and patients. There is already a large diagnosed patient population with a meaningful percentage of patients concentrated in specialized vascular anomaly centers. We have also consistently experienced strong enthusiasm from key opinion leaders about the potential for QTORIN rapamycin, many of whom participated in our Phase 3 and Phase 2 studies, and we believe this enthusiasm could contribute to a strong uptake curve following potential FDA approval. From a pricing and reimbursement perspective, we anticipate orphan pricing consistent with our previous guidance of $100,000 to $200,000 per patient per year.

Wesley Kaupinen: Microcystic lymphatic malformations represent a serious rare disease with high unmet medical need and currently no FDA-approved therapies available to physicians and patients. There is already a large diagnosed patient population with a meaningful percentage of patients concentrated in specialized vascular anomaly centers. We have also consistently experienced strong enthusiasm from key opinion leaders about the potential for QTORIN rapamycin, many of whom participated in our Phase 3 and Phase II studies, and we believe this enthusiasm could contribute to a strong uptake curve following potential FDA approval. From a pricing and reimbursement perspective, we anticipate orphan pricing consistent with our previous guidance of $100,000 to $200,000 per patient per year.

Speaker #4: Microcystic lymphatic malformations represent a serious rare disease with high unmet medical need and currently no FDA-approved therapies available to physicians and patients. There is already a large diagnosed patient population with a meaningful percentage of patients concentrated in specialized vascular anomaly centers.

Speaker #4: We have also consistently experienced strong enthusiasm from key opinion leaders about the potential for Ketor and Rapamycin. Many of whom participated in our Phase 3 and Phase 2 studies and we believe this enthusiasm could contribute to a strong uptake curve following potential FDA approval.

Speaker #4: From a pricing and reimbursement perspective, we anticipate orphan pricing consistent with our previous guidance of $100,000 to $200,000 per patient per year. All of this is supported by positive Phase 3 data, which indicate a favorable risk-benefit profile, particularly compared to the scarcity of therapeutic options available to these patients today.

Wesley H. Kaupinen: All of this is supported by positive Phase 3 data, which indicate a favorable risk-benefit profile, particularly compared to the scarcity of therapeutic options available to these patients today, reinforcing the potential for QTORIN rapamycin to become a first-line standard of care therapy for individuals with microcystic lymphatic malformations. We have made significant progress in building the foundation for a potential H1 2027 commercial launch. Starting with leadership, we have assembled a highly experienced commercial team. Last year, Ashley Kline joined Palvella as Chief Commercial Officer, and we recently added Jennifer McDonough to lead market access and patient services. Ashley is a commercial veteran in the rare disease space, having previously led the launch of OXERVATE, a novel topical therapy for neurotrophic keratitis and a therapy which now generates greater than $1 billion in US sales a few short years after launch.

Wesley Kaupinen: All of this is supported by positive Phase 3 data, which indicate a favorable risk-benefit profile, particularly compared to the scarcity of therapeutic options available to these patients today, reinforcing the potential for QTORIN rapamycin to become a first-line standard of care therapy for individuals with microcystic lymphatic malformations. We have made significant progress in building the foundation for a potential H1 2027 commercial launch. Starting with leadership, we have assembled a highly experienced commercial team. Last year, Ashley Kline joined Palvella as Chief Commercial Officer, and we recently added Jennifer McDonough to lead market access and patient services. Ashley is a commercial veteran in the rare disease space, having previously led the launch of OXERVATE, a novel topical therapy for neurotrophic keratitis and a therapy which now generates greater than $1 billion in US sales a few short years after launch.

Speaker #4: Reinforcing the potential for Ketor and Rapamycin to become a first-line standard of care therapy for individuals with microcystic lymphatic malformations. We have made significant progress in building the foundation for a potential first-half 2027 commercial launch.

Speaker #4: Starting with leadership, we have assembled a highly experienced commercial team. Last year, Ashley Kline joined Palvella as chief commercial officer and we recently added Jennifer McDonough to lead.

Speaker #4: Market access and patient services. Ashley is a commercial veteran in the rare disease space, having previously led the launch of Oxervate, a novel topical therapy for neurotrophic keratitis, and a therapy which now generates greater than $1 billion in U.S. sales a few short years after launch.

Speaker #4: Last week, we welcomed Jennifer McDonough to the Palvella team. Jennifer is widely regarded as a leading executive in rare disease market access and patient services.

Wesley H. Kaupinen: Last week, we welcomed Jennifer McDonough to the Palvella team. Jennifer is widely regarded as a leading executive in rare disease market access and patient services. Her contributions were critical to the success of the launch of VYJUVEK from Krystal Biotech, a first-in-disease topical therapy for dystrophic epidermolysis bullosa, a serious rare genetic skin disease. In parallel, we are building out our medical affairs capabilities with the hiring of medical science liaisons already underway and active participation across the key medical meetings you see listed on the slide here. Importantly, we are also taking a robust approach to patient identification and market development. We estimate more than 30,000 diagnosed patients in the US and importantly, approximately 1,500 new patients diagnosed each year.

Wesley Kaupinen: Last week, we welcomed Jennifer McDonough to the Palvella team. Jennifer is widely regarded as a leading executive in rare disease market access and patient services. Her contributions were critical to the success of the launch of VYJUVEK from Krystal Biotech, a first-in-disease topical therapy for dystrophic epidermolysis bullosa, a serious rare genetic skin disease. In parallel, we are building out our medical affairs capabilities with the hiring of medical science liaisons already underway and active participation across the key medical meetings you see listed on the slide here. Importantly, we are also taking a robust approach to patient identification and market development. We estimate more than 30,000 diagnosed patients in the US and importantly, approximately 1,500 new patients diagnosed each year.

Speaker #4: Her contributions were critical to the success of the launch of Vyjuvec from Crystal Biotech, a first-in-disease topical therapy for dystrophic epidermolysis bullosa a serious rare genetic skin disease.

Speaker #4: In parallel, we are building out our medical affairs capabilities, with the hiring of medical science liaisons already underway and active participation across the key medical meetings you see listed on the slide here.

Speaker #4: Importantly, we are also taking a robust approach to patient identification and market development. We estimate more than 30,000 diagnosed patients in the US and importantly, approximately 1,500 new patients diagnosed each year.

Speaker #4: We are concentrating our initial efforts on the highest value centers in treating physicians with a specific focus on approximately 400 high-volume centers that we estimate represent approximately 50% of the diagnosed population in the US.

Wesley H. Kaupinen: We are concentrating our initial efforts on the highest value centers and treating physicians with a specific focus on approximately 400 high volume centers that we estimate represent approximately 50% of the diagnosed population in the US. Overall, we've recruited top talent and are making significant investments to ensure we are well-positioned for a successful US launch of QTORIN rapamycin in microcystic lymphatic malformations. Moving now to our QTORIN rapamycin for cutaneous venous malformations program. Let me begin with some comments on the commercial opportunity in this disease. Venous malformations are the most common type of vascular malformation, and cutaneous venous malformations represent a large and underappreciated market opportunity, with an estimated more than 75,000 diagnosed patients in the US and currently no FDA-approved therapies.

Wesley Kaupinen: We are concentrating our initial efforts on the highest value centers and treating physicians with a specific focus on approximately 400 high volume centers that we estimate represent approximately 50% of the diagnosed population in the US. Overall, we've recruited top talent and are making significant investments to ensure we are well-positioned for a successful US launch of QTORIN rapamycin in microcystic lymphatic malformations. Moving now to our QTORIN rapamycin for cutaneous venous malformations program. Let me begin with some comments on the commercial opportunity in this disease. Venous malformations are the most common type of vascular malformation, and cutaneous venous malformations represent a large and underappreciated market opportunity, with an estimated more than 75,000 diagnosed patients in the US and currently no FDA-approved therapies.

Speaker #4: Overall, we've recruited top talent and are making significant investments to assure we are well positioned for a successful US launch of Ketor and Rapamycin in microcystic lymphatic malformations.

Speaker #4: Moving now to our Ketor and Rapamycin for cutaneous venous malformations program. Let me begin with some comments on the commercial opportunity in this disease.

Speaker #4: Venous malformations are the most common type of vascular malformation and cutaneous venous malformations represent a large and underappreciated market opportunity. With an estimated more than 75,000 diagnosed patients in the US and currently no FDA-approved therapies.

Speaker #4: We reported positive Phase 2 data in December of 2025 with statistically significant results. Across several clinician and patient-reported outcomes, specifically 73% of patients demonstrated improvement on the CVM investigator's global assessment with 67% rated as much improved or very much improved at week 12.

Wesley H. Kaupinen: We reported positive Phase 2 data in December 2025, with statistically significant results across several clinician- and patient-reported outcomes. Specifically, 73% of patients demonstrated improvement on the CVM Investigators' Global Assessment, with 67% rated as much improved or very much improved at week 12. This suggests both a high responder rate and a large magnitude treatment benefit in this initial Phase 2 study. We are now swiftly advancing towards a Phase 3 study, with study design alignment expected mid-2026 and trial initiation planned for H2. In parallel, we are finalizing a Breakthrough Therapy designation application. This following a constructive preliminary advice meeting with the FDA earlier this quarter, in which our collaborator, Dr.

Wesley Kaupinen: We reported positive Phase II data in December 2025, with statistically significant results across several clinician- and patient-reported outcomes. Specifically, 73% of patients demonstrated improvement on the CVM Investigators' Global Assessment, with 67% rated as much improved or very much improved at week 12. This suggests both a high responder rate and a large magnitude treatment benefit in this initial Phase II study. We are now swiftly advancing towards a Phase 3 study, with study design alignment expected mid-2026 and trial initiation planned for H2. In parallel, we are finalizing a Breakthrough Therapy designation application. This following a constructive preliminary advice meeting with the FDA earlier this quarter, in which our collaborator, Dr.

Speaker #4: This suggests both a high responder rate and a large magnitude treatment benefit in this initial Phase 2 study. We are now swiftly advancing towards a Phase 3 study, with study design alignment expected mid-2026 and trial initiation planned for the second half of the year.

Speaker #4: In parallel, we are finalizing a breakthrough therapy designation application. This following a constructive preliminary advice meeting with the FDA earlier this quarter in which our collaborator, Dr. Denise Adams, a prominent pediatric hematologist-oncologist from Children's Hospital of Philadelphia, described the unmet need in cutaneous venous malformations as well as her experience in the Phase 2 study.

Wesley H. Kaupinen: Denise Adams, a prominent pediatric hematologist-oncologist from Children's Hospital of Philadelphia, described the unmet need in cutaneous venous malformations, as well as her experience in the Phase 2 study. In addition to the Phase 2 data, our breakthrough application will include both patient qualitative interviews capturing the meaningfulness of the therapy to their daily lives and a letter of support from the investigators who participated in the Phase 2 study. We also importantly continue to generate additional data through the ongoing Phase 2 treatment extension period, with plans to present that data set at a medical meeting later this year. Overall, our QTORIN rapamycin program in cutaneous venous malformations represents a compelling opportunity to expand into a larger second clinical indication for QTORIN rapamycin. Assuming initial approval in microcystic lymphatic malformations, potentially advance through a streamlined supplemental NDA pathway.

Wesley Kaupinen: Denise Adams, a prominent pediatric hematologist-oncologist from Children's Hospital of Philadelphia, described the unmet need in cutaneous venous malformations, as well as her experience in the Phase II study. In addition to the Phase II data, our breakthrough application will include both patient qualitative interviews capturing the meaningfulness of the therapy to their daily lives and a letter of support from the investigators who participated in the Phase II study. We also importantly continue to generate additional data through the ongoing Phase II treatment extension period, with plans to present that data set at a medical meeting later this year. Overall, our QTORIN rapamycin program in cutaneous venous malformations represents a compelling opportunity to expand into a larger second clinical indication for QTORIN rapamycin. Assuming initial approval in microcystic lymphatic malformations, potentially advance through a streamlined supplemental NDA pathway.

Speaker #4: In addition to the Phase 2 data, our breakthrough application will include both patient qualitative interviews capturing the meaningfulness of the therapy to their daily lives and a letter of support from the investigators who participated in the Phase 2 study.

Speaker #4: We also, importantly, continue to generate additional data through the ongoing Phase 2 treatment extension period, with plans to present that data set at a medical meeting later this year.

Speaker #4: Overall, our Ketor and Rapamycin program in cutaneous venous malformations represents a compelling opportunity to expand into a larger second clinical indication for Ketor and Rapamycin.

Speaker #4: And assuming initial approval in microcystic lymphatic malformations, potentially advance through a streamlined supplemental NDA pathway. I will now hand the call over to Jeff, who will talk about our additional pipeline programs.

Wesley H. Kaupinen: I will now hand the call over to Jeff, who will talk about our additional pipeline programs. Jeff?

Wesley Kaupinen: I will now hand the call over to Jeff, who will talk about our additional pipeline programs. Jeff?

Jeff Martini: Thank you, Wes. Our clinically significant angiokeratomas program represents our third clinical indication for the QTORIN and rapamycin program. Our Phase 2 trial is ahead of schedule, with initiation anticipated in Q2. Angiokeratomas are a superficial lymphatic malformation and share overlapping clinical and pathological features with microcystic lymphatic malformations, including similar lesion morphology, superficial vascular involvement, and aberrant lymphatic biology. These lesions are associated with increased mTOR signaling and do not spontaneously regress. This provides a strong mechanistic and clinical rationale for targeting this indication with QTORIN and rapamycin. As Wes mentioned earlier in the presentation, and consistent with our strategy of leveraging existing human data, we are able to build on published proof of concept data, including multiple case reports demonstrating preliminary clinical benefit from off-label rapamycin use.

Jeff Martini: Thank you, Wes. Our clinically significant angiokeratomas program represents our third clinical indication for the QTORIN and rapamycin program. Our Phase II trial is ahead of schedule, with initiation anticipated in Q2. Angiokeratomas are a superficial lymphatic malformation and share overlapping clinical and pathological features with microcystic lymphatic malformations, including similar lesion morphology, superficial vascular involvement, and aberrant lymphatic biology. These lesions are associated with increased mTOR signaling and do not spontaneously regress. This provides a strong mechanistic and clinical rationale for targeting this indication with QTORIN and rapamycin. As Wes mentioned earlier in the presentation, and consistent with our strategy of leveraging existing human data, we are able to build on published proof of concept data, including multiple case reports demonstrating preliminary clinical benefit from off-label rapamycin use.

Speaker #4: Jeff?

Speaker #2: Thank you, Ash. Our clinically significant angiokeratomas program represents our third clinical indication for the Ketor and Rapamycin program. Our Phase 2 trial is ahead of schedule with initiation anticipated in the second quarter.

Speaker #2: Angiokeratomas are a superficial lymphatic malformation and share overlapping clinical and pathological features with microcystic lymphatic malformations, including similar lesion morphology, superficial vascular involvement, and aberrant lymphatic biology.

Speaker #2: These lesions are associated with increased mTOR signaling and do not spontaneously regress. This provides a strong mechanistic and clinical rationale for targeting this indication with Ketor and Rapamycin.

Speaker #2: As last mentioned earlier in the presentation, and consistent with our strategy of leveraging existing human data, we are able to build on published proof-of-concept data, including multiple case reports demonstrating preliminary clinical benefit from off-label Rapamycin use.

Jeff Martini: Clinically significant angiokeratomas represents a large underserved indication with more than 50,000 diagnosed patients in the US, no FDA-approved therapies, and the potential to expand QTORIN rapamycin into this indication through an sNDA. QTORIN rapamycin is a pipeline in a product, with our lead program in microcystic lymphatic malformations preparing for NDA submission and launch, our cutaneous venous malformations program advancing towards phase 3, and our clinically significant angiokeratomas program with a phase 2 study planned and ahead of schedule. Across these initial three indications, we are already addressing a meaningful patient population in the United States, but there is a significant opportunity for expansion. We are actively evaluating additional mTOR-driven diseases that meet our highly selective criteria and expect to continue to expand our addressable patient population over time.

Jeff Martini: Clinically significant angiokeratomas represents a large underserved indication with more than 50,000 diagnosed patients in the US, no FDA-approved therapies, and the potential to expand QTORIN rapamycin into this indication through an sNDA. QTORIN rapamycin is a pipeline in a product, with our lead program in microcystic lymphatic malformations preparing for NDA submission and launch, our cutaneous venous malformations program advancing towards phase 3, and our clinically significant angiokeratomas program with a Phase II study planned and ahead of schedule. Across these initial three indications, we are already addressing a meaningful patient population in the United States, but there is a significant opportunity for expansion. We are actively evaluating additional mTOR-driven diseases that meet our highly selective criteria and expect to continue to expand our addressable patient population over time.

Speaker #2: Clinically significant angiokeratomas represent a large, underserved indication, with more than 50,000 diagnosed patients in the US, no FDA-approved therapies, and the potential to expand Ketor and Rapamycin into this indication through a supplemental NDA.

Speaker #2: Ketor and rapamycin is a pipeline in a product with our lead program in microcystic lymphatic malformations preparing for NDA submission and launch. Our cutaneous venous malformations program is advancing towards Phase 3, and our clinically significant angiokeratomas program has a Phase 2 study planned and is ahead of schedule.

Speaker #2: Across these initial three indications, we are already addressing a meaningful patient population in the United States, but there is a significant opportunity for expansion.

Speaker #2: We are actively evaluating additional mTOR-driven diseases that meet our highly selective criteria and expect to continue to expand our addressable patient population over time.

Jeff Martini: This strategy enables efficient development by leveraging the same molecule and platform and targeting shared disease-driving biology across multiple indications. We are expanding our pipeline beyond rapamycin with QTORIN pitavastatin in disseminated superficial actinic porokeratosis or DSAP, which represents our second QTORIN program. DSAP is a chronic, progressive, and precancerous skin disease that presents with numerous expanding lesions on sun-exposed areas, causing significant symptoms including burning, itching, and discomfort, and carrying a risk of malignant transformation. Despite this, there are no FDA-approved therapies, and existing treatment approaches are invasive, temporary, and do not address the underlying disease biology. QTORIN pitavastatin is a pathogenesis-directed therapy targeting the mevalonate pathway with the potential to become first-line and standard of care for patients with DSAP.

Speaker #2: This strategy enables efficient development by leveraging the same molecule and platform, and targeting shared disease-driven biology across multiple indications. We are expanding our pipeline beyond Rapamycin with Ketor and Patavistatin in disseminated superficial actinic porokeratosis, or DSAP, which represents our second Ketorin program.

Speaker #2: DSAP is a chronic progressive and precancerous skin disease that presents with numerous expanding lesions on sun-exposed areas, causing significant symptoms including burning, itching, and discomfort, and carrying a risk of malignant transformation.

Speaker #2: Despite this, there are no FDA-approved therapies, and existing treatment approaches are invasive, temporary, and do not address the underlying disease biology. Ketor and Patavistatin is a pathogenesis-directed therapy targeting the mevalonate pathway, with the potential to become first-line in standard of care for patients with DSAP.

Jeff Martini: Our approach is supported by emerging scientific evidence, including our recent publication in Experimental Dermatology, highlighting real-world statin use and treatment gaps, and our presentation at the American Academy of Dermatology demonstrating the burden of disease. Following our public announcement of the program, we are seeing strong inbound patient interest as we prepare for our phase 2 study, which remains on track for initiation in H2 2026. QTORIN pitavastatin for DSAP highlights our disciplined approach to selecting diseases that meet our highly selective criteria, combined with the QTORIN platform's ability to efficiently develop pathogenesis-directed therapies. Before turning the call over to Matt, I'd like to briefly highlight the strength of the QTORIN platform as a new product development engine. We follow a disease-first R&D strategy, spending significant time identifying diseases that meet our highly selective criteria and are well suited for targeted topical therapies.

Jeff Martini: Our approach is supported by emerging scientific evidence, including our recent publication in Experimental Dermatology, highlighting real-world statin use and treatment gaps, and our presentation at the American Academy of Dermatology demonstrating the burden of disease. Following our public announcement of the program, we are seeing strong inbound patient interest as we prepare for our Phase II study, which remains on track for initiation in H2 2026. QTORIN pitavastatin for DSAP highlights our disciplined approach to selecting diseases that meet our highly selective criteria, combined with the QTORIN platform's ability to efficiently develop pathogenesis-directed therapies. Before turning the call over to Matt, I'd like to briefly highlight the strength of the QTORIN platform as a new product development engine. We follow a disease-first R&D strategy, spending significant time identifying diseases that meet our highly selective criteria and are well suited for targeted topical therapies.

Speaker #2: Our approach is supported by emerging scientific evidence, including our recent publication in experimental dermatology, highlighting real-world statin use in treatment gaps, and our presentation at the American Academy of Dermatology demonstrating the burden of disease.

Speaker #2: Following our public announcement of the program, we are seeing strong inbound patient interest as we prepare for Phase 2 study, which remains on track for initiation in the second half of 2026.

Speaker #2: Ketor and Patavistatin for DSAP highlights our disciplined approach to selecting diseases that meet our highly selective criteria combined with the Ketorin platform's ability to efficiently develop pathogenesis-directed therapies.

Speaker #2: Before turning the call over to Matt, I'd like to briefly highlight the strength of the Ketorin platform as a new product development engine. We follow a disease-first R&D strategy, spending significant time identifying diseases that meet our highly selective criteria and are well suited for targeted topical therapies.

Jeff Martini: We have now validated the platform with two positive clinical readouts, including our Phase 3 SELVA trial and our Phase 2 TOIVA results. We are leveraging QTORIN to scale our pipeline, rapidly advancing and testing multiple molecules in a time and capital efficient manner. We also plan to pursue FDA Platform Technology Designation following the anticipated approval of QTORIN and rapamycin. We look ahead, we expect to announce one new QTORIN program and one additional QTORIN and rapamycin indication later this year. QTORIN represents a validated and scalable engine to deliver first-in-disease therapies that we believe can make a meaningful difference for patients and create long-term value for shareholders. With that, I'll turn the call over to Matt to review our financial results.

Jeff Martini: We have now validated the platform with two positive clinical readouts, including our Phase 3 SELVA trial and our Phase II TOIVA results. We are leveraging QTORIN to scale our pipeline, rapidly advancing and testing multiple molecules in a time and capital efficient manner. We also plan to pursue FDA Platform Technology Designation following the anticipated approval of QTORIN and rapamycin. We look ahead, we expect to announce one new QTORIN program and one additional QTORIN and rapamycin indication later this year. QTORIN represents a validated and scalable engine to deliver first-in-disease therapies that we believe can make a meaningful difference for patients and create long-term value for shareholders. With that, I'll turn the call over to Matt to review our financial results.

Speaker #2: We have now validated the platform with two positive clinical readouts, including our Phase 3 SELVA trial and a Phase 2 TOILA results. We are leveraging Ketorin to scale our pipeline, rapidly advancing and testing multiple molecules in a time and capital-efficient manner.

Speaker #2: We also plan to pursue FDA platform technology designation following the anticipated approval of Ketor and Rapamycin. As we look ahead, we expect to announce one new Ketorin program and one additional Ketor and Rapamycin indication later this year.

Speaker #2: Ketorin represents a validated and scalable engine to deliver first-in-disease therapies that we believe can make a meaningful difference for patients and create long-term value for shareholders.

Speaker #2: With that, I'll turn the call over to Matt to review our financial results.

Matthew E. Korenberg: Thanks, Jeff. Turning to the financials, Palvella ended Q4 with $58 million in cash and cash equivalents as of December 31, 2025. Following our positive phase 3 SELVA data, we completed an oversubscribed $230 million public offering in February 2026, bringing in $215.8 million in net proceeds. I wanna emphasize what this financing means for the company. With pro forma cash of $274 million, this financing fundamentally strengthens our balance sheet and eliminates financing overhang as we enter the most important execution period in Palvella's history. With this cash, even before considering any potential revenue, we're now fully funded to advance our microcystic lymphatic malformations program through an NDA filing, an FDA approval, and if approved, a US commercial launch.

Matthew Korenberg: Thanks, Jeff. Turning to the financials, Palvella ended Q4 with $58 million in cash and cash equivalents as of December 31, 2025. Following our positive phase 3 SELVA data, we completed an oversubscribed $230 million public offering in February 2026, bringing in $215.8 million in net proceeds. I wanna emphasize what this financing means for the company. With pro forma cash of $274 million, this financing fundamentally strengthens our balance sheet and eliminates financing overhang as we enter the most important execution period in Palvella's history. With this cash, even before considering any potential revenue, we're now fully funded to advance our microcystic lymphatic malformations program through an NDA filing, an FDA approval, and if approved, a US commercial launch.

Speaker #3: Thanks, Jeff. Turning to the financials, Palvella ended Q4 with $58 million in cash and cash equivalents as of December 31, 2025. Following our positive Phase 3 SELVA data, we completed an oversubscribed $230 million public offering in February of 2026, bringing in $215.8 million in net proceeds.

Speaker #3: I want to emphasize what this financing means for the company. With pro forma cash of 274 million dollars, this financing fundamentally strengthens our balance sheet and eliminates financing overhang as we enter the most important execution period in Palvella's history.

Speaker #3: With this cash, even before considering any potential revenue, we're now fully funded to advance our microcystic lymphatic malformations program through an NDA filing and FDA approval, and, if approved, a US commercial launch.

Matthew E. Korenberg: For QTORIN rapamycin cutaneous venous malformations, our runway allows us to execute a phase three program and subsequently complete an NDA filing. For our QTORIN pipeline, we have the runway to support multiple phase two data reads from our existing and future pipeline programs. The quality of investor participation in this financing was exceptional, and we believe it reflects the growing institutional conviction in both the SELVA data and our broader pipeline strategy. With this capital base and our innovative operating model that prioritizes capital efficiency, the Palvella team can now focus entirely on execution without the distraction of the near-term financing needs. I'll now turn the call back over to Wes for closing remarks and to open the line for questions. Wes?

Matthew Korenberg: For QTORIN rapamycin cutaneous venous malformations, our runway allows us to execute a Phase III program and subsequently complete an NDA filing. For our QTORIN pipeline, we have the runway to support multiple Phase II data reads from our existing and future pipeline programs. The quality of investor participation in this financing was exceptional, and we believe it reflects the growing institutional conviction in both the SELVA data and our broader pipeline strategy. With this capital base and our innovative operating model that prioritizes capital efficiency, the Palvella team can now focus entirely on execution without the distraction of the near-term financing needs. I'll now turn the call back over to Wes for closing remarks and to open the line for questions. Wes?

Speaker #3: For Ketor and Rapamycin in cutaneous venous malformations, our runway allows us to execute a Phase 3 program and subsequently complete an NDA filing. And for our Ketorin pipeline, we have the runway to support multiple Phase 2 data readouts from our existing and future pipeline programs.

Speaker #3: The quality of investor participation in this financing was exceptional, and we believe it reflects the growing institutional conviction in both the SELVA data and our broader pipeline strategy.

Speaker #3: With this capital base and our innovative operating model that prioritizes capital efficiency, the Palvella team can now focus entirely on execution without the distraction of near-term financing needs.

Speaker #3: I'll now turn the call back over to Wes for closing remarks and to open the line for questions. Wes?

Wesley H. Kaupinen: Thanks, Matt. 2025 was an exceptional year for Palvella. Now our focus is squarely on execution across our deep pipeline of rare disease programs. We are closer to our first FDA approval than we have ever been, and the entire Palvella team is committed to making that a reality for the patients and families who have been waiting. With that, operator, we will open the line for questions.

Wesley Kaupinen: Thanks, Matt. 2025 was an exceptional year for Palvella. Now our focus is squarely on execution across our deep pipeline of rare disease programs. We are closer to our first FDA approval than we have ever been, and the entire Palvella team is committed to making that a reality for the patients and families who have been waiting. With that, operator, we will open the line for questions.

Speaker #1: Thanks, Matt. 2025 was an exceptional year for Palvella. Now our focus is squarely on execution across our deep pipeline of rare disease programs. We are closer to our first FDA approval than we have ever been, and the entire Palvella team is committed to making that a reality for the patients and families who have been waiting.

Speaker #1: With that, operator, we will open the line for questions.

Operator: Our first question comes from Josh Schimmer with Cantor.

Speaker #4: As a reminder, if you'd like to ask a question at this time, please press *11 on your telephone and wait for your name to be announced.

Speaker #4: To withdraw your question, please press *11 again. Our first question comes from Josh Shimmer with Cantor.

Operator: Our first question comes from Josh Schimmer with Cantor.

Josh Schimmer: Great. Thanks so much for taking the questions. For the QTORIN rapamycin platform, what are the gating steps for each new indication that you choose to pursue? Given the broad number of settings where there is actual data for topical rapamycin, how many different indications do you ultimately expect you might have on the label? Thank you.

Speaker #5: Great, thanks so much for taking the questions. For the Ketor and Rapamycin platform, what are the gating steps for each new indication that you choose to pursue?

Speaker #5: And given the broad number of settings where there is actual data for topical Rapamycin, how many different indications do you ultimately expect you might have on the label?

Speaker #5: Thank you.

Wesley H. Kaupinen: Great, Josh. Thank you for being on, and thanks for the question. For the platform, which was your first question, we really start with the disease. We profile diseases that, one, have no FDA-approved therapies. Number two, we look for diseases where there's low competitive intensity in the development pipeline. That allows us to be first. That's the goal, to be on a trajectory to having that first approved therapy. We also carefully evaluate, from a scientific perspective, whether there is clear biology in that particular disease, well-defined biology, and we do prefer to go in diseases, I think as Jeff nicely highlighted earlier, where there is existing human proof of concept data. Sometimes that can be from off-label use, like we've seen with the use of rapamycin in lymphatic malformations.

Wesley Kaupinen: Great, Josh. Thank you for being on, and thanks for the question. For the platform, which was your first question, we really start with the disease. We profile diseases that, one, have no FDA-approved therapies. Number two, we look for diseases where there's low competitive intensity in the development pipeline. That allows us to be first. That's the goal, to be on a trajectory to having that first approved therapy. We also carefully evaluate, from a scientific perspective, whether there is clear biology in that particular disease, well-defined biology, and we do prefer to go in diseases, I think as Jeff nicely highlighted earlier, where there is existing human proof of concept data. Sometimes that can be from off-label use, like we've seen with the use of rapamycin in lymphatic malformations.

Speaker #1: Great, Josh. Thank you for being on, and thanks for the question. For the platform, which was your first question, we really start with the disease.

Speaker #1: We profile diseases that, one, have no FDA-approved therapies. Number two, we look for diseases where there's low competitive intensity in the development pipeline. That allows us to be first.

Speaker #1: That's the goal, to be on a trajectory to having that first approved therapy. We also carefully evaluate, from a scientific perspective, whether there is clear biology in that particular disease—well-defined biology—and we do prefer to go in diseases, I think, as Jeff nicely highlighted earlier, where there is existing human proof of concept data.

Speaker #1: Sometimes that can be from off-label use, like we've seen with the use of Rapamycin in lymphatic malformations. We think that having some of that data in hand, human proof of concept data, helped to validate a particular molecular approach.

Wesley H. Kaupinen: We think that having some of that data in hand, human proof of concept data, help to validate a particular, molecular approach. We then apply the QTORIN platform, of course, the goal being, to be on target and in tissue for these localized, skin diseases. On your second question, in terms of how many indications, we can eventually have for, QTORIN rapamycin, there's a long list. There's three publications that, I think nicely summarize all the different diseases, skin diseases, where the mTOR pathway, is implicated. Jeff can speak to some of those diseases, but, there's well over, a dozen diseases where, scientists, clinicians, researchers, geneticists, have implicated a strong role for, the mTOR pathway. Jeff?

Wesley Kaupinen: We think that having some of that data in hand, human proof of concept data, help to validate a particular, molecular approach. We then apply the QTORIN platform, of course, the goal being, to be on target and in tissue for these localized, skin diseases. On your second question, in terms of how many indications, we can eventually have for, QTORIN rapamycin, there's a long list. There's three publications that, I think nicely summarize all the different diseases, skin diseases, where the mTOR pathway, is implicated. Jeff can speak to some of those diseases, but, there's well over, a dozen diseases where, scientists, clinicians, researchers, geneticists, have implicated a strong role for, the mTOR pathway. Jeff?

Speaker #1: We then apply the Ketorin platform—of course, the goal being to be on target and in tissue for these localized skin diseases. On your second question, in terms of how many indications we can eventually have for Ketorin and Rapamycin, there's a long list.

Speaker #1: There are three publications that I think nicely summarize all of the different diseases—skin diseases—where the mTOR pathway is implicated. Jeff can speak to some of those diseases, but there are well over a dozen diseases where scientists, clinicians, researchers, and geneticists have implicated a strong role for the mTOR pathway.

Jeff Martini: Hey, Josh. Thanks for the question. You know, just to kind of reiterate what Wes said, you know, we take a really disease-first approach, rely heavily on our medical and scientific advisory board, both for understanding the disease unmet need as well as the biological rationale, and then find experts in the diseases. Because these are rare diseases, we have a lot of good collaboration with experts in these fields, which typically haven't seen much scientific or medical research. So we collaborate very closely with the KOLs and then ultimately pick the diseases that have the highest probability of success, biggest unmet need, and also we do have a commercial evaluation as well.

Speaker #1: Jeff?

Speaker #3: Yeah, Josh, thanks for the question. Just to kind of reiterate what Wes said, we take a really disease-first approach and rely heavily on our medical and scientific advisory board.

Speaker #3: Both for understanding the disease unmet need, as well as the biological rationale. And then find experts in the diseases. Because these are rare diseases, we have a lot of good collaboration with experts in these fields, which typically haven't seen much scientific or medical research.

Speaker #3: So we collaborate very closely with the KOLs and then ultimately pick the diseases that have the highest probability of success, biggest unmet need, and also we do have a commercial evaluation as well.

Wesley H. Kaupinen: Maybe just to round that out, Josh, the three papers that I referenced, the authors are Swarbrick, Fogel, and Tatiana Lappa, which look at the involvement of the mTOR pathway in skin diseases to maybe quantify your question. In terms of size of population, we think the addressable size of the patient population to be treated with QTORIN rapamycin once you add microcystic lymphatic malformations, CVM, angiokeratomas, and several of the other diseases that we've identified is in the hundreds of thousands.

Wesley Kaupinen: Maybe just to round that out, Josh, the three papers that I referenced, the authors are Swarbrick, Fogel, and Tatiana Lappa, which look at the involvement of the mTOR pathway in skin diseases to maybe quantify your question. In terms of size of population, we think the addressable size of the patient population to be treated with QTORIN rapamycin once you add microcystic lymphatic malformations, CVM, angiokeratomas, and several of the other diseases that we've identified is in the hundreds of thousands.

Speaker #5: And maybe just to round that out, Josh, the three papers that I referenced—the authors are Swarbrick, Fogel, and Tatiana Lapa—which look at the involvement of the mTOR pathway in skin diseases, to maybe quantify your question.

Speaker #5: In terms of size of population, we think the addressable size of the patient population to be treated with Ketor and Rapamycin, once you add microLM, CVM, angiokeratomas, and several of the other diseases that we've identified, is in the hundreds of thousands.

Josh Schimmer: Thanks very much.

Speaker #3: Thanks very much.

Operator: Our next question comes from Ritu Baral with TD Cowen.

Speaker #4: Our next question comes from Ritu Baral with TD Cowen.

Ritu Baral: Good morning, everyone. Thanks for taking my question. Wes, will the phase 2 extension data or at least some of the phase 2 extension data from the CVM study be part of your breakthrough application for that indication to FDA? Can you give us any more detail as to when that extension data will be presented and sort of like the parameters of that extension data? I've got a follow-up on commercial.

Ritu Baral: Good morning, everyone. Thanks for taking my question. Wes, will the Phase II extension data or at least some of the Phase II extension data from the CVM study be part of your breakthrough application for that indication to FDA? Can you give us any more detail as to when that extension data will be presented and sort of like the parameters of that extension data? I've got a follow-up on commercial.

Speaker #6: Good morning, everyone. Thanks for taking my question. Wes, will the Phase 2 extension data, or at least some of the Phase 2 extension data, from the CVM study be part of your breakthrough application for that indication to the FDA?

Speaker #6: And can you give us any more detail as to when that extension data will be presented and sort of the parameters of that extension data?

Speaker #6: And then I've got a follow-up on commercial.

Wesley H. Kaupinen: Great. Hey, Ritu, good morning. Thanks for the questions. The Phase 2 extension data is not yet finalized, and we are proceeding with our Breakthrough Therapy designation application. Our Breakthrough Therapy designation application will include the Phase 2 data, where we saw 67% of patients either achieve the ratings of much improved or very much improved. We're also gonna include interviews, patient qualitative interviews, where the patients, in their own words as part of a qualitative interview sub-study that we incorporated, describe their experience in the trial. We think that that's really important to augment the statistically significant data with data that supports clinical meaningfulness. Finally, our investigators have really rallied here to put together a letter of support for the Breakthrough Therapy designation application.

Wesley Kaupinen: Great. Hey, Ritu, good morning. Thanks for the questions. The Phase II extension data is not yet finalized, and we are proceeding with our Breakthrough Therapy designation application. Our Breakthrough Therapy designation application will include the Phase II data, where we saw 67% of patients either achieve the ratings of much improved or very much improved. We're also gonna include interviews, patient qualitative interviews, where the patients, in their own words as part of a qualitative interview sub-study that we incorporated, describe their experience in the trial. We think that that's really important to augment the statistically significant data with data that supports clinical meaningfulness. Finally, our investigators have really rallied here to put together a letter of support for the Breakthrough Therapy designation application.

Speaker #3: Great. Hey, Ritu. Good morning, and thanks for the questions. The Phase 2 extension data is not yet finalized, and we are proceeding with our Breakthrough Therapy Designation application.

Speaker #3: Our Breakthrough Therapy designation application will include the Phase 2 data, where we saw 67% of patients either achieve the ratings of 'much improved' or 'very much improved.'

Speaker #3: We are also going to include interviews, patient qualitative interviews, where the patients in their own words, as part of a qualitative interview sub-study that we incorporated, describe their experience in the trial.

Speaker #3: We think that that's really important to augment the statistically significant data with data that supports clinical meaningfulness. And finally, our investigators have really rallied here to put together a letter of support for the breakthrough therapy designation application.

Wesley H. Kaupinen: This is something that our Chief Operating Officer, Kathy Goin, has spearheaded with Denise Adams and several others. That's gonna be a key part of the breakthrough application. That letter will cover not only their view about the preliminary clinical evidence package, but also their view around future study designs, which is gonna be part of our discussion with the FDA after the breakthrough decision.

Wesley Kaupinen: This is something that our Chief Operating Officer, Kathy Goin, has spearheaded with Denise Adams and several others. That's gonna be a key part of the breakthrough application. That letter will cover not only their view about the preliminary clinical evidence package, but also their view around future study designs, which is gonna be part of our discussion with the FDA after the breakthrough decision.

Speaker #3: This is something that our Chief Operating Officer, Kathy Goen, has spearheaded with Denise Adams and several others. So that's going to be a key part of the breakthrough application.

Speaker #3: That letter will cover not only their view about the preliminary clinical evidence package, but also their view around future study designs, which is going to be part of our discussion with the FDA after the breakthrough decision.

Ritu Baral: Understood. Then on the commercial side for MLM, Wes, you mentioned, and this is an Ashley question I too, I guess. You mentioned there's the diagnosed pool for MLM. What are your up-to-the-minute estimates for that? Then you mentioned that those patients were under care in a concentrated way at vascular anomaly clinics. Do you have the number of those clinics and what percentage of the diagnosed pool they cover? Then right now, maybe more high level, what are your plans as far as patient support services, coverage support services, for, you know, adjunct to the price range that you mentioned? Thanks.

Speaker #6: Understood. And then on the commercial side for MLM, Wes, you mentioned—and this is an Ashley question too, I guess—you mentioned there's the diagnosed pool for MLM.

Speaker #6: What are your up-to-the-minute estimates for that? And then, you mentioned that those patients were under care in a concentrated way at vascular anomaly clinics.

Speaker #6: Do you have the number of those clinics, and what percentage of the diagnosed pool they cover? And then right now, maybe more high-level, what are your plans as far as patient support services and coverage support services, for adjunct to the price range that you mentioned?

Wesley H. Kaupinen: Yeah, thanks, Ritu. Our latest estimates, and this is based on convergence of evidence from a real-world occurrence study that was published by Jack Gallagher, that's available in Orphanet, which projects that there's approximately 80,000 patients in the United States with a cutaneous manifestation of their microcystic lymphatic malformations. We've also done claims work, which suggests a range around 45,000 to 95,000 diagnosed patients that are within clinical medicine in the US. We look at all that evidence. This is a dynamic process at Palvella. You're always evaluating claims data. We estimate, perhaps conservatively, that there's greater than 30,000 diagnosed patients in the United States with microcystic lymphatic malformations that could be addressable, if approved, with QTORIN rapamycin.

Wesley Kaupinen: Yeah, thanks, Ritu. Our latest estimates, and this is based on convergence of evidence from a real-world occurrence study that was published by Jack Gallagher, that's available in Orphanet, which projects that there's approximately 80,000 patients in the United States with a cutaneous manifestation of their microcystic lymphatic malformations. We've also done claims work, which suggests a range around 45,000 to 95,000 diagnosed patients that are within clinical medicine in the US. We look at all that evidence. This is a dynamic process at Palvella. You're always evaluating claims data. We estimate, perhaps conservatively, that there's greater than 30,000 diagnosed patients in the United States with microcystic lymphatic malformations that could be addressable, if approved, with QTORIN rapamycin.

Speaker #6: Thanks.

Speaker #3: Yeah, thanks, Ritu. So, our latest estimates—and this is based on convergence of evidence from a real-world occurrence study that was published by Jack Gallagher.

Speaker #3: That's available in Orphanet, which projects that there are approximately 80,000 patients in the United States with a cutaneous manifestation of their microcystic lymphatic malformations. We've also done claims work, which suggests a range of around 45,000 to 95,000 diagnosed patients that are within clinical medicine in the US.

Speaker #3: So, our—we look at all that evidence. This is a dynamic process at Palvella. You're always evaluating claims data. We estimate, perhaps conservatively, that there's greater than 30,000 diagnosed patients in the United States with microcystic lymphatic malformations that could be addressable, if approved, with Ketor and Rapamycin.

Wesley H. Kaupinen: When you break down the claims data, we break it down into high volume centers, many of which, Ritu, are these vascular anomaly centers. If you take the 400 highest volume centers, that constitutes about 15,000 patients in the United States. That really is our primary focus. We fortunately have great relationships with many of these vascular anomaly centers as a result of work by our clinical operations teams and the Phase II and Phase III studies that we've run. In terms of patient services for our US launch, Ashley has a lot of experience in this area, having launched OXERVATE, one of the most successful orphan drug launches of the past decade. We're also thrilled to have recruited Jennifer McDonough.

Wesley Kaupinen: When you break down the claims data, we break it down into high volume centers, many of which, Ritu, are these vascular anomaly centers. If you take the 400 highest volume centers, that constitutes about 15,000 patients in the United States. That really is our primary focus. We fortunately have great relationships with many of these vascular anomaly centers as a result of work by our clinical operations teams and the Phase II and Phase III studies that we've run. In terms of patient services for our US launch, Ashley has a lot of experience in this area, having launched OXERVATE, one of the most successful orphan drug launches of the past decade. We're also thrilled to have recruited Jennifer McDonough.

Speaker #3: When you break down the claims data, we break it down into high-volume centers, many of which, Ritu, are these vascular anomaly centers. If you take the 400 highest volume centers, that constitutes about 15,000 patients in the United States.

Speaker #3: So that really is our primary focus. We fortunately have great relationships with many of these vascular anomaly centers as a result of work by our clinical operations teams and the Phase 2 and Phase 3 studies that we've run.

Speaker #3: In terms of patient services for our US launch, Ashley has a lot of experience in this area, having launched OxfordVait, one of the most successful orphan drug launches of the past decade.

Speaker #3: We're also thrilled to have recruited Jennifer McDonough. We've closely followed and rooted on Vyjuvex's success from Krista Biotech in a really rare and devastating disease there.

Wesley H. Kaupinen: We've closely followed and rooted for VYJUVEK's success from Krystal Biotech in a really rare and devastating disease there. What we wanna do is work with a specialty pharmacy and a patient services hub that have a proven track record in the rare disease space, particularly when you think about microcystic LMs, where you're very likely to see chronic dosing with QTORIN rapamycin, so that we're not only treating the existing clinical signs, but that we're also preventing that disease recurrence, which is a major issue with the disease today.

Wesley Kaupinen: We've closely followed and rooted for VYJUVEK's success from Krystal Biotech in a really rare and devastating disease there. What we wanna do is work with a specialty pharmacy and a patient services hub that have a proven track record in the rare disease space, particularly when you think about microcystic LMs, where you're very likely to see chronic dosing with QTORIN rapamycin, so that we're not only treating the existing clinical signs, but that we're also preventing that disease recurrence, which is a major issue with the disease today.

Speaker #3: So what we want to do is work with specialty pharmacy and a patient services hub that have a proven track record in the rare disease space, particularly when you think about microcystic LMs, where you're very likely to see chronic dosing with ketor and rapamycin.

Speaker #3: So that we're not only treating the existing clinical signs, but that we're also preventing that disease recurrence, which is a major issue with the disease today.

Ritu Baral: Great. Thank you.

Speaker #6: Great. Thank you.

Operator: Our next question comes from Annabel Samimy with Stifel.

Speaker #4: Our next question comes from Annabelle Simini with Stifel.

Annabel Samimy: Hi. Thanks for taking my question. Great progress. I just want, you know, we've been getting questions from investors about FDA unpredictability. This is not an accelerated approval, clearly, and you've noted very specifically that it's not surrogate endpoints, but clinical endpoints. But there is still some concern about a one-arm study. How have these interactions been with FDA? Are you still comfortable with that design? And I guess looking at CVM, what are you planning as far as Phase 3 design, and how might that change with breakthrough designation? And should we have any read-through to the MLM receptivity to one-arm trials? I guess it's a multilayered question, but really it's about FDA unpredictability these days.

Speaker #6: Hi. Thanks for taking my question. Great progress. I just want to mention that we've been getting questions from investors about FDA unpredictability. This is not an accelerated approval, clearly, and you've noted very specifically that it's not surrogate.

Speaker #6: Endpoints, but clinical endpoints. But there is still some concern about a one-armed study. How have these interactions been with the FDA? Are you still comfortable with that design?

Speaker #6: And I guess, looking at CVM, what are you planning as far as Phase 3 design, and how might that change with breakthrough designation? And should we have any read-through to the MLM receptivity to one-armed trials?

Speaker #6: So it's, I guess, a multi-layered question, but really it's about FDA unpredictability these days.

Wesley H. Kaupinen: Sure. Thanks, Annabel, for the questions. Prior to the commencement of the phase 3 study, we believe we were aligned and continue to be aligned with the FDA on that single-arm, phase 3 baseline controlled study where the patient serves as their own control. I think it's important to note here a couple things. Number one, this is a disease where there is documented no spontaneous regression of the disease. Therefore, that can enable a single arm design to serve as a reliable design for the purposes of an efficacy assessment, particularly, when you employ clinical outcomes like we have, which we think are objective in nature, where the physician is scoring the patient's lesion at the end of treatment and comparing that to a baseline photo.

Wesley Kaupinen: Sure. Thanks, Annabel, for the questions. Prior to the commencement of the phase 3 study, we believe we were aligned and continue to be aligned with the FDA on that single-arm, phase 3 baseline controlled study where the patient serves as their own control. I think it's important to note here a couple things. Number one, this is a disease where there is documented no spontaneous regression of the disease. Therefore, that can enable a single arm design to serve as a reliable design for the purposes of an efficacy assessment, particularly, when you employ clinical outcomes like we have, which we think are objective in nature, where the physician is scoring the patient's lesion at the end of treatment and comparing that to a baseline photo.

Speaker #3: Sure. Thanks, Annabelle, for the questions. Prior to the commencement of the Phase 3 study, we believe we were aligned—and continue to be aligned—with the FDA on that single-arm, Phase 3 baseline-controlled study where the patient serves as their own control.

Speaker #3: I think it's important to note here a couple of things. Number one, this is a disease where there is documented no spontaneous regression of the disease.

Speaker #3: Therefore, that can enable a single-arm design to serve as a reliable design for the purposes of an efficacy assessment, particularly when you employ clinical outcomes like we have, which we think are objective in nature, where the physician is scoring the patient's lesion at the end of treatment and comparing that to a baseline photo.

Wesley H. Kaupinen: We shared several photos in our Phase 3 SELVA release, and we think they clearly indicate clinical improvement in lesions that would otherwise progress to a worsened state. Our interactions, we've had interactions with both the review division, the Dermatology division, as well as the Office of Orphan Products Development. Since the Phase 3 SELVA study concluded, we presented them with the data. I would describe those interactions as constructive, and we are proceeding towards a pre-NDA meeting that's been requested at this point in time, and we expect that to occur in Q2. I think there are certain elements of the FDA at a macro level that we're really encouraged by. I think we've all been following Dr.

Wesley Kaupinen: We shared several photos in our Phase 3 SELVA release, and we think they clearly indicate clinical improvement in lesions that would otherwise progress to a worsened state. Our interactions, we've had interactions with both the review division, the Dermatology division, as well as the Office of Orphan Products Development. Since the Phase 3 SELVA study concluded, we presented them with the data. I would describe those interactions as constructive, and we are proceeding towards a pre-NDA meeting that's been requested at this point in time, and we expect that to occur in Q2. I think there are certain elements of the FDA at a macro level that we're really encouraged by. I think we've all been following Dr.

Speaker #3: We shared several photos in our Phase 3 silver release, and we think they clearly indicate clinical improvement in lesions that would otherwise progress to a worsened state.

Speaker #3: So, our interactions—we've had interactions with both the Review Division, the Derm Division, as well as the Office of Orphan Products Development since the Phase 3 SILO study.

Speaker #3: Concluded, we presented them with the data. I would describe those interactions as constructive, and we are proceeding towards a pre-NDA meeting. That's been requested at this point in time.

Speaker #3: And we expect that to occur in Phase 2. I think there are certain elements of the FDA at a macro level that we're really encouraged by.

Wesley H. Kaupinen: Makary advocating for a common sense approach, describing that the new default approach to generating substantial evidence of effectiveness is one trial, not two. He's consistently been advocating for expediting therapies to patients with rare diseases. FDA came out in Q4 of last year talking about accommodating real-world evidence to help inform regulatory decision-making. From Palvella's perspective, we believe the FDA much prefers approved drugs to off-label or compounded drugs. We think all of those sort of macro trends certainly work in our favor. From a CMC perspective, it's gonna be a two-step process to land on a study design. Step one is gonna be determining whether or not we are breakthrough designated.

Wesley Kaupinen: Makary advocating for a common sense approach, describing that the new default approach to generating substantial evidence of effectiveness is one trial, not two. He's consistently been advocating for expediting therapies to patients with rare diseases. FDA came out in Q4 of last year talking about accommodating real-world evidence to help inform regulatory decision-making. From Palvella's perspective, we believe the FDA much prefers approved drugs to off-label or compounded drugs. We think all of those sort of macro trends certainly work in our favor. From a CMC perspective, it's gonna be a two-step process to land on a study design. Step one is gonna be determining whether or not we are breakthrough designated.

Speaker #3: I think we've all been following Dr. McCary, advocating for a common-sense approach. He described that the new default approach to generating substantial evidence of effectiveness is one trial, not two.

Speaker #3: And he's consistently been advocating for expediting therapies to patients with rare diseases. FDA came out in Q4 of last year talking about accommodating real-world evidence to help inform regulatory decision-making.

Speaker #3: And from Palvella's perspective, we believe the FDA much prefers approved drugs to off-label or compounded drugs. So we think all of those sort of macro trends certainly work in our favor.

Speaker #3: From a CVM perspective, it's going to be a two-step process to land on a study design. Step one is going to be determining whether or not we are breakthrough designated.

Wesley H. Kaupinen: That application is gonna go in imminently with the various elements that I mentioned earlier. Whether or not we're granted breakthrough, we're gonna meet with the FDA on the other side of that decision. I think our KOLs will be strongly advocating for flexibility for the phase 3 study design. There's a range of potential outcomes here. In our interactions with folks like Denise Adams at CHOP, I think they would much prefer all patients having the opportunity to go on drug, given that it's well accepted that sirolimus does have activity in vascular malformations and specifically venous malformations. So there could be issues around clinical equipoise, or ethics as well that we have to work through collaboratively with the FDA. That said, there is also the potential for a placebo-controlled design.

Wesley Kaupinen: That application is gonna go in imminently with the various elements that I mentioned earlier. Whether or not we're granted breakthrough, we're gonna meet with the FDA on the other side of that decision. I think our KOLs will be strongly advocating for flexibility for the phase 3 study design. There's a range of potential outcomes here. In our interactions with folks like Denise Adams at CHOP, I think they would much prefer all patients having the opportunity to go on drug, given that it's well accepted that sirolimus does have activity in vascular malformations and specifically venous malformations. So there could be issues around clinical equipoise, or ethics as well that we have to work through collaboratively with the FDA. That said, there is also the potential for a placebo-controlled design.

Speaker #3: That application is going to go in imminently, with the various elements that I mentioned earlier. Whether or not we're granted breakthrough, we're going to meet with the FDA.

Speaker #3: On the other side of that decision, and I think our KOLs will be strongly advocating for flexibility for the Phase 3 study design. There's a range of potential outcomes here.

Speaker #3: In our interactions with folks like Denise Adams at CHOP, I think they would much prefer all patients having the opportunity to go on drug, given that it's well accepted that serolimus does have activity in vascular malformations and specifically venous malformations.

Speaker #3: So there could be issues around clinical equipoise or ethics as well that we have to work through collaboratively with the FDA. That said, there is also the potential for a placebo-controlled design.

Wesley H. Kaupinen: Our strategy is to first determine whether or not we're breakthrough designated, and then on the other side of that, align with the FDA on a study design that works for patients, physicians, FDA, and for Palvella as well.

Wesley Kaupinen: Our strategy is to first determine whether or not we're breakthrough designated, and then on the other side of that, align with the FDA on a study design that works for patients, physicians, FDA, and for Palvella as well.

Speaker #3: Our strategy is to first determine whether or not we're breakthrough designated. And then, on the other side of that, align with the FDA on a study design that works for patients, physicians, the FDA, and for Palvella as well.

Annabel Samimy: Okay, great. Thank you.

Speaker #6: Okay. Great. Thank you.

Operator: Our next question comes from Ryan Reeves with Mizuho.

Speaker #4: Our next question comes from Ryan Reese with Mizuho.

Ryan Reeves: Hi, this is Ryan on for today. I was just wondering if you guys could talk a little bit about the plans for the commercial launch of QTORIN rapamycin and MLMs beyond some of the key new hires, like any organizational changes, upgrades, or timelines on Salesforce or expanding KOL. Any plans for upcoming meetings? Any kind of prep you're sort of prepping. Thank you.

Speaker #3: Hi, this is Ryan for today. I was just wondering if you guys could talk a little bit about the plans for the commercial launch of Ketor and Rapamycin MLMs, beyond some of the key new hires.

Speaker #3: Any organizational changes, upgrades, or timelines on Salesforce? Any plans for upcoming? Any sort of prepping? Thank you.

Wesley H. Kaupinen: Yeah. Thanks, Ryan, for those questions. Yeah, I'm a firm believer in trying to recruit the best talent in the world to Palvella. Ultimately, I think that's gonna help dictate our success for patients and shareholders. I think we've really assembled incredible talent between Ashley Kline as Chief Commercial Officer, Jennifer McDonough, and our build-out of our medical affairs team. Ryan, in terms of your questions of changes or upgrades, I would characterize where we are as additions and investments that we're making. We are building out a medical science liaison team. We expect that to be somewhere between 5 and 10 MSLs. They will be very active with these top 400 targets that I mentioned earlier.

Wesley Kaupinen: Yeah. Thanks, Ryan, for those questions. Yeah, I'm a firm believer in trying to recruit the best talent in the world to Palvella. Ultimately, I think that's gonna help dictate our success for patients and shareholders. I think we've really assembled incredible talent between Ashley Kline as Chief Commercial Officer, Jennifer McDonough, and our build-out of our medical affairs team. Ryan, in terms of your questions of changes or upgrades, I would characterize where we are as additions and investments that we're making. We are building out a medical science liaison team. We expect that to be somewhere between 5 and 10 MSLs. They will be very active with these top 400 targets that I mentioned earlier.

Speaker #5: Yeah, thanks, Ryan, for those questions. I'm a firm believer in trying to recruit the best talent in the world to Palvella. Ultimately, I think that's going to help dictate our success for patients and shareholders.

Speaker #5: And I think we've really assembled incredible talent between Ashley, Klein as Chief Commercial Officer, Jennifer McDonough, and our build-out of our medical affairs team.

Speaker #5: Ryan, in terms of your questions of changes or upgrades, I would characterize where we are as additions and investments that we're making. So, we are building out a medical science liaison team.

Speaker #5: We expect that to be somewhere between 5 and 10 MSLs that will be very active with these top 400 targets that I mentioned earlier.

Wesley H. Kaupinen: They will also have a major presence at medical meetings. We expect to hire, and it was noted in our corporate deck, a head of sales in the near term. We're gonna bring that hire on a bit early to start to really think through how to shape an attractive uptake curve for QTORIN, similar to what we saw with companies like the ones I've been involved with, such as Enzyvant, Ashley with Oxervate, and Jen McDonough with Krystal Biotech. That's gonna be really key. We've put forward a provisional range of 20 to 40 sales reps.

Wesley Kaupinen: They will also have a major presence at medical meetings. We expect to hire, and it was noted in our corporate deck, a head of sales in the near term. We're gonna bring that hire on a bit early to start to really think through how to shape an attractive uptake curve for QTORIN, similar to what we saw with companies like the ones I've been involved with, such as Enzyvant, Ashley with Oxervate, and Jen McDonough with Krystal Biotech. That's gonna be really key. We've put forward a provisional range of 20 to 40 sales reps.

Speaker #5: They will also have a major presence at medical meetings. We expect to hire, and it was noted in our corporate deck, a head of sales in the near term.

Speaker #5: We're going to bring that hire on a bit early to start to really think through how to shape an attractive uptake curve for Ketor and Rapamycin, similar to what we saw with companies like the ones I've been involved with, such as InzMed, Ashley with OxfordVait, and Jen McDonough.

Speaker #5: With Crystal Biotech, so that's going to be really key. We've put forward a provisional range of 20 to 40 sales reps. I think with the capital raise having been completed—and we're very grateful to the investors who participated for their support—

Wesley H. Kaupinen: I think with the capital raise having been completed, and we're very grateful to the investors who participated for their support, we're more likely to go to the upper end of that 20 to 40 range versus the lower end of that range. Key in all this will be quality, Ryan. One of the hiring processes that we've implemented here is that the senior executive team is very involved in the hiring at all levels. We wanna make sure we bring in the right people that are high performers. We're a performance-driven culture here, but also ones who are authentically patient-oriented and really feel a strong desire to serve patients with rare diseases.

Wesley Kaupinen: I think with the capital raise having been completed, and we're very grateful to the investors who participated for their support, we're more likely to go to the upper end of that 20 to 40 range versus the lower end of that range. Key in all this will be quality, Ryan. One of the hiring processes that we've implemented here is that the senior executive team is very involved in the hiring at all levels. We wanna make sure we bring in the right people that are high performers. We're a performance-driven culture here, but also ones who are authentically patient-oriented and really feel a strong desire to serve patients with rare diseases.

Speaker #5: We're more likely to go to the upper end of that 20 to 40 range, versus the lower end of that range. Key in all this will be quality, Ryan.

Speaker #5: So, one of the hiring processes that we've implemented here is that the senior executive team is very involved in the hiring at all levels.

Speaker #5: We want to make sure we bring in the right people that are high performers. We're a performance-driven culture here, but also ones who are authentically patient-oriented and really feel a strong desire to serve patients with rare diseases.

Ryan Reeves: Great. Thanks, Wes.

Speaker #3: Great. Thanks, Wes.

Operator: Our next question comes from Sam Slutsky with LifeSci Capital.

Speaker #4: Our next question comes from Sam Sotke with LifeSci Capital.

Sam Slutsky: Hey, good morning. Thanks for taking the questions. Obviously great to see the angiokeratoma phase 2 initiation moves up to Q2, but could you just remind us on the key endpoints that you'll be looking at here and the magnitude of effect that would be deemed clinically relevant? As you prepare for commercial launch and pipeline expansion, any additional granularity that you're able to give on cash burn expectations over this next year? Thanks.

Sam Slutsky: Hey, good morning. Thanks for taking the questions. Obviously great to see the angiokeratoma Phase II initiation moves up to Q2, but could you just remind us on the key endpoints that you'll be looking at here and the magnitude of effect that would be deemed clinically relevant? As you prepare for commercial launch and pipeline expansion, any additional granularity that you're able to give on cash burn expectations over this next year? Thanks.

Speaker #1: Hey, good morning. Thanks for taking the questions. So, obviously, great to see that Angiokeratoma Phase 2 initiation moved up to Q2. But could you just remind us of the key endpoints that you'll be looking at here, and the magnitude of effect that would be deemed clinically relevant?

Speaker #1: And then, just as you prepare for commercial launch and pipeline expansion, any additional granularity that you're able to give on cash burn expectations over this next year?

Wesley H. Kaupinen: Hey, Sam. Thanks a lot for both questions. I'll pass it over to Jeff to discuss the endpoints that we're looking at in the Phase 2 angiokeratoma study. That's gonna be similar to what we did in MLM and CVM, and that there's gonna be no pre-specified statistical hierarchy, no primary endpoint. We think that's a thoughtful approach to take in rare diseases where there's no FDA-approved therapies and really where you're trying to determine which endpoints are sensitive to detecting a treatment effect before putting together that statistical hierarchy in Phase 3. Jeff will comment on that, and then we'll pass it over to Matt Korenberg to address the second part of your question. Jeff?

Wesley Kaupinen: Hey, Sam. Thanks a lot for both questions. I'll pass it over to Jeff to discuss the endpoints that we're looking at in the Phase II angiokeratoma study. That's gonna be similar to what we did in MLM and CVM, and that there's gonna be no pre-specified statistical hierarchy, no primary endpoint. We think that's a thoughtful approach to take in rare diseases where there's no FDA-approved therapies and really where you're trying to determine which endpoints are sensitive to detecting a treatment effect before putting together that statistical hierarchy in Phase 3. Jeff will comment on that, and then we'll pass it over to Matt Korenberg to address the second part of your question. Jeff?

Speaker #1: Thanks.

Speaker #5: Hey, Sam. Thanks a lot for both questions. I'll pass it over to Jeff to discuss the endpoints that we're looking at in the Phase 2 Angiokeratoma study.

Speaker #5: That's going to be similar to what we did in MLM and CVM, in that there's going to be no pre-specified statistical hierarchy, no primary endpoint.

Speaker #5: We think that's a thoughtful approach to take in rare diseases, where there are no FDA-approved therapies and really where you're trying to determine which endpoints are sensitive to detecting a treatment effect before putting together that statistical hierarchy in Phase 3.

Speaker #5: So Jeff will comment on that, and then we'll pass it over to Matt Kornberg to address the second part of your question. Jeff?

Jeff Martini: Yeah. Thanks for the question, Sam. We're gonna follow what we're calling the Palvella playbook, and it's really repeating the overall strategy that we've used for these other rare diseases that have never had a clinical trial done with them before. As Wes mentioned, there is no statistical hierarchy. The purpose of the study is to understand what are the endpoints that are sensitive to change. We started out by talking with patients as well as clinicians to identify what are the key signs. We'll look at individual signs as well as global endpoints to look at global changes. We'll look at both dynamic and static scales. We'll also look at both clinician and patient's perspective.

Speaker #2: Yeah, thanks for the question, Sam. So we're going to follow what we're calling the Palvella playbook. And it's really repeating the overall strategy that we've used for these other rare diseases that have never had a clinical trial done with them before.

Speaker #2: So, as Wes mentioned, there is no statistical hierarchy. The purpose of the study is to understand what are the endpoints that are sensitive to change.

Speaker #2: We started out by talking with patients as well as clinicians to identify what are the key signs. So we'll look at individual signs, as well as global endpoints, to look at global changes.

Speaker #2: We'll look at both dynamic and static scales. We'll also look at both the clinician's and patient's perspective. And then, importantly, like all of our trials, it's really important to capture the voice of the patient.

Jeff Martini: Importantly, like all of our trials, it's really important to capture the voice of the patient, so we'll be conducting qualitative interviews both at baseline and end of treatment. Ultimately, we'll package all that data, and that will inform future plans.

Speaker #2: So we'll be conducting qualitative interviews both at baseline and end of treatment, and ultimately we'll package all that data, and that will inform future plans.

Wesley H. Kaupinen: Yeah. Sam, on the cash-

Matthew Korenberg: Yeah. Sam, on the cash-

Jeff Martini: Bring it back.

Matthew E. Korenberg: Yep. On the cash burn, appreciate the question. It's, as I said in my prepared comments, the cash we have today is sufficient to get us through, you know, basically advancing all of our programs over the next several years. What that translates to for 2026 is somewhere around $80 million of cash burn. So, that's the number for 2026, just around $80 million.

Matthew Korenberg: Yep. On the cash burn, appreciate the question. It's, as I said in my prepared comments, the cash we have today is sufficient to get us through, you know, basically advancing all of our programs over the next several years. What that translates to for 2026 is somewhere around $80 million of cash burn. So, that's the number for 2026, just around $80 million.

Speaker #1: Yeah. And Sam, on the cash—yep, on the cash burn, appreciate the question. As I said in my prepared comments, the cash that we have today is sufficient to get us through basically advancing all of our programs over the next several years.

Speaker #1: What that translates to for 2026 is somewhere around $80 million of cash burned. So that's the number for 2026, just around $80 million.

Sam Slutsky: All right.

Wesley H. Kaupinen: Thanks, Sam.

Wesley Kaupinen: Thanks, Sam.

Operator: Our next question comes from Whitney Ijem with Canaccord Genuity.

Speaker #4: All right.

Speaker #5: Thanks, Sam.

Speaker #4: Our next question comes from Whitney Ijem with Clinical Genuity.

Whitney Ijem: Hey, guys. Thanks for taking the question. Just kind of to the FDA regulatory or sorry, the FDA flexibility, and macro tailwinds, Wes, I think you said there. Just curious if you've had a chance to speak with the agency on the Plausible Mechanism Pathway. I know that was something you talked about back in December. Yeah, just curious if you've had those conversations and just as we think about kind of all of the indications, where there is sort of clinical validation for topical rapamycin, just if that might be a potential path forward to shorten the timeline to some of those. Thanks.

Speaker #6: Hey, guys. Thanks for taking the question. Just kind of to the FDA regulatory—or, sorry, the FDA flexibility and macro tailwinds, Wes, I think you said there.

Speaker #6: Just curious if you've had a chance to speak with the agency on the plausible mechanism pathway. I know that was something you talked about back in December.

Speaker #6: Yeah, just curious if you've had those conversations, and just as we think about kind of all of the indications where there is clinical validation for topical rapamycin, that might be a potential path forward to shorten the timeline to some of those things.

Wesley H. Kaupinen: Thanks, Whitney, for those questions. On the Plausible Mechanism Pathway, at this juncture, we have not had formal interactions with FDA as to whether one or more of our programs qualify for the Plausible Mechanism Pathway. Looking across our pipeline, we do have several molecules and several diseases that we believe represent closer to a validated mechanism than one that is plausible in nature. We're carefully monitoring how the FDA is implementing the new Plausible Mechanism Pathway program. It is our intention to better understand whether one or more of our programs, other than microLMs, could qualify for the Plausible Mechanism Pathway.

Wesley Kaupinen: Thanks, Whitney, for those questions. On the Plausible Mechanism Pathway, at this juncture, we have not had formal interactions with FDA as to whether one or more of our programs qualify for the Plausible Mechanism Pathway. Looking across our pipeline, we do have several molecules and several diseases that we believe represent closer to a validated mechanism than one that is plausible in nature. We're carefully monitoring how the FDA is implementing the new Plausible Mechanism Pathway program. It is our intention to better understand whether one or more of our programs, other than microLMs, could qualify for the Plausible Mechanism Pathway.

Speaker #5: Thanks, Whitney, for those questions. On the plausible mechanism pathway, at this juncture we have not had formal interactions with the FDA as to whether one or more of our programs qualify for the plausible mechanism pathway.

Speaker #5: Looking across our pipeline, we do have several molecules and several diseases that we believe represent closer to a validated mechanism than one that is plausible in nature.

Speaker #5: So, we're carefully monitoring how the FDA is implementing the new Plausible Mechanism Pathway program. And it is our intention to better understand whether one or more of our programs, other than micro LMs, could qualify for the Plausible Mechanism Pathway.

Wesley H. Kaupinen: On microLMs, we don't think that's a pathway at this point in time that we need to march towards an NDA submission and FDA approval, but plausible mechanism could apply to CVM, potentially angiokeratomas, as well as porokeratosis.

Wesley Kaupinen: On microLMs, we don't think that's a pathway at this point in time that we need to march towards an NDA submission and FDA approval, but plausible mechanism could apply to CVM, potentially angiokeratomas, as well as porokeratosis.

Speaker #5: On micro LMs, we don't think that's a pathway at this point in time that we need to march towards an NDA submission and FDA approval.

Speaker #5: But a plausible mechanism could apply to CVM, potentially angiokeratomas, as well as porokeratosis.

Whitney Ijem: Great. Thanks.

Speaker #6: Great. Thanks.

Operator: Our next question comes from Ryan Deschner with Raymond James.

Speaker #4: Our next question comes from Ryan Deshner with Raymond James.

Ryan Deschner: Thanks for the question. Were there specific drivers in the written feedback from FDA that drove the acceleration in the angiokeratomas clinical initiation timeline? What are your expectations for how far along in the clinical development of your new programs you can get with the current cash runway at this point? Thanks.

Speaker #3: Thanks for the question. Were there specific drivers in the written feedback from the FDA that drove the acceleration in the Angiokeratomas clinical initiation timeline? And also, what are your expectations for how far along in the clinical development of your new programs you can get with the current cash runway at this point?

Speaker #3: Thanks.

Wesley H. Kaupinen: Great. Thanks, Ryan, for both questions. I'll take the first question, and then Matt can speak to the key milestones that we intend to achieve with the cash on hand. FDA granted us, Ryan, Fast Track designation in angiokeratomas at the conclusion of last year. We look at that as a major milestone for the company. It's our third Fast Track designated program. We placed in front of the FDA a phase 2 design on angiokeratomas of about 10 or 20 patients. That design is intended to really be a signal finding study. The FDA understands that we're evaluating a number of different endpoints in this disease, which currently has no FDA-approved therapies.

Wesley Kaupinen: Great. Thanks, Ryan, for both questions. I'll take the first question, and then Matt can speak to the key milestones that we intend to achieve with the cash on hand. FDA granted us, Ryan, Fast Track designation in angiokeratomas at the conclusion of last year. We look at that as a major milestone for the company. It's our third Fast Track designated program. We placed in front of the FDA a Phase II design on angiokeratomas of about 10 or 20 patients. That design is intended to really be a signal finding study. The FDA understands that we're evaluating a number of different endpoints in this disease, which currently has no FDA-approved therapies.

Speaker #5: Great. Thanks, Ryan, for both questions. I'll take the first question, and then Matt can speak to the key milestones that we intend to achieve with the cash on hand.

Speaker #5: The FDA granted us, Ryan, fast-track designation in Angiokeratomas at the conclusion of last year. We look at that as a major milestone for the company.

Speaker #5: It's our third fast-tracked designated program. We place in front of the FDA a Phase 2 design on angiokeratomas of about 10 or 20 patients.

Speaker #5: That design is intended to really be a signal-finding study. The FDA understands that we're evaluating a number of different endpoints in this disease, which currently has no FDA-approved therapies.

Wesley H. Kaupinen: I think, what enables us to move quickly there, and it's core to the business model that we articulated earlier, is we do have an open IND at the FDA around QT ORIN and 3.9% rapamycin in hydrogel. They're very familiar with the tox package, all the safety data that we've presented over the years. We're leveraging our existing manufacturing process. Our ability to jumpstart new indications on QT ORIN and rapamycin while preserving that same formulation, IND, manufacturing process is, we think, one of the advantages and what will allow us to do serial and sNDA submissions over time once we have that first approved indication, which we expect to be microcystic lymphatic malformation. Matt, do you wanna tackle the second part of the question?

Wesley Kaupinen: I think, what enables us to move quickly there, and it's core to the business model that we articulated earlier, is we do have an open IND at the FDA around QT ORIN and 3.9% rapamycin in hydrogel. They're very familiar with the tox package, all the safety data that we've presented over the years. We're leveraging our existing manufacturing process. Our ability to jumpstart new indications on QT ORIN and rapamycin while preserving that same formulation, IND, manufacturing process is, we think, one of the advantages and what will allow us to do serial and sNDA submissions over time once we have that first approved indication, which we expect to be microcystic lymphatic malformation. Matt, do you wanna tackle the second part of the question?

Speaker #5: I think what enables us to move quickly there, and it's core to the business model that we articulated earlier, is we do have an open IND at the FDA around Keytorin 3.9% rapamycin in hydrogel.

Speaker #5: They're very familiar with the tox package, all of the safety data that we've presented over the years. We're leveraging our existing manufacturing process, so our ability to jump-start new indications on Keytorin (rapamycin) while preserving that same formulation, IND, and manufacturing process is, we think, one of the advantages and what will allow us to do serial and sNDA submissions over time once we have that first approved indication, which we expect to be microcystic lymphatic malformations.

Speaker #5: Matt, do you want to tackle the second part of the question?

Matthew E. Korenberg: Yeah. Thanks, Wes. Ryan, the existing cash, as I said, even without considering any revenue, fuels a whole number of catalysts for us over the 2026 and 2027 and into 2028 period. On the lead program MLM, we can get all the way through a potential approval and launch. On CVMs, we think we can get through a filing. For DSAP and angiokeratoma, the two programs launching Phase 2 trials this year, we can easily get through data on those two trials. Then, for the two new indications that we've talked about, announcing this year, we believe we have sufficient cash to get through data readouts in those indications as well.

Matthew Korenberg: Yeah. Thanks, Wes. Ryan, the existing cash, as I said, even without considering any revenue, fuels a whole number of catalysts for us over the 2026 and 2027 and into 2028 period. On the lead program MLM, we can get all the way through a potential approval and launch. On CVMs, we think we can get through a filing. For DSAP and angiokeratoma, the two programs launching Phase II trials this year, we can easily get through data on those two trials. Then, for the two new indications that we've talked about, announcing this year, we believe we have sufficient cash to get through data readouts in those indications as well.

Speaker #1: Yeah, thanks, Wes. Ryan, the existing cash, as I said, even without considering any revenue, fuels a whole number of catalysts for us over the 2026 and 2027 and into 2028 period.

Speaker #1: On the lead program, MLM, we can get all the way through a potential approval and launch. On CVMs, we think we can get through a filing.

Speaker #1: For DSAP and angiokeratoma, the two programs launching Phase 2 trials this year, we can easily get through data on those two trials. And then for the two new indications that we've talked about announcing this year, we believe we have sufficient cash to get through data readouts in those indications as well.

Matthew E. Korenberg: Importantly, my prepared comments were caveated by lack of any revenue adjustment for that cash runway. I think if we consider potential cash generation through revenue and launch, there's a potential that we can get to cash flow breakeven depending on how aggressively revenue ramps and depending on how aggressively we build out the pipeline. We feel like we have all the cash we need for the foreseeable future to really just focus on execution and generating data and eventually commercial products across the pipeline.

Matthew Korenberg: Importantly, my prepared comments were caveated by lack of any revenue adjustment for that cash runway. I think if we consider potential cash generation through revenue and launch, there's a potential that we can get to cash flow breakeven depending on how aggressively revenue ramps and depending on how aggressively we build out the pipeline. We feel like we have all the cash we need for the foreseeable future to really just focus on execution and generating data and eventually commercial products across the pipeline.

Speaker #1: Importantly, my prepared comments were caveated by the lack of any revenue adjustment for that cash runway. I think if we consider potential cash generation through revenue and launch, there's a potential that we can get to cash flow breakeven depending on how aggressively revenue ramps, and depending on how aggressively we build out the pipeline.

Speaker #1: So, we feel like we have all the cash we need for the foreseeable future to really just focus on execution and generating data, and eventually commercial products across the pipeline.

Wesley H. Kaupinen: All right. Thank you very much.

Wesley Kaupinen: All right. Thank you very much.

Speaker #3: All right. Thank you very much.

Operator: Our next question comes from Danielle Brill with Truist Securities.

Speaker #4: Our next question comes from Danielle Brill with Truist Securities.

Jenny Yang: Hey, good morning. This is Jenny Yang for Danielle. Thanks for taking our questions. So I have a question about the microcystic LM dosing. You previously mentioned that some patients with larger lesions may require more than one pump per daily dose based on your recent medical affairs outreach. We're just wondering, how should we think about modeling the average daily dose and, the annual revenue per patient across different lesion sizes? Thank you.

Jenny Wang: Hey, good morning. This is Jenny Yang for Danielle. Thanks for taking our questions. So I have a question about the microcystic LM dosing. You previously mentioned that some patients with larger lesions may require more than one pump per daily dose based on your recent medical affairs outreach. We're just wondering, how should we think about modeling the average daily dose and, the annual revenue per patient across different lesion sizes? Thank you.

Speaker #6: Hey, good morning. This is Cheney Alford, Danielle. Thanks for taking our questions. So, I have a question about the microcystic LM dosing. You previously mentioned that some patients with larger lesions may require more than one pump per daily dose.

Speaker #6: Based on your recent medical fair outreach, we're just wondering how we should think about modeling the average daily dose and the annual revenue per patient across different lesion sizes.

Speaker #6: Thank you.

Wesley H. Kaupinen: Yeah. Thanks for the question. We think the average patient will be one pump per day, and we expect this to be dosed in a manner that will be chronic therapy. I think that's something that we've gathered from our KOLs, including folks like Dr. Michael Kelly from the Cleveland Clinic. The way we're modeling that, and Matt can comment further, is looking at that in the pricing range of $100 to 200 thousand per patient per year. Averaging that out across patients, some of whom will consume more than one pump per day, some patients who probably will consume less than one pump per day. Matt can comment on any further specificity that he'd like to add.

Wesley Kaupinen: Yeah. Thanks for the question. We think the average patient will be one pump per day, and we expect this to be dosed in a manner that will be chronic therapy. I think that's something that we've gathered from our KOLs, including folks like Dr. Michael Kelly from the Cleveland Clinic. The way we're modeling that, and Matt can comment further, is looking at that in the pricing range of $100 to 200 thousand per patient per year. Averaging that out across patients, some of whom will consume more than one pump per day, some patients who probably will consume less than one pump per day. Matt can comment on any further specificity that he'd like to add.

Speaker #5: Yeah, thanks for the question. We think the average patient will use one pump per day, and we expect this to be dosed in a manner that will be chronic therapy.

Speaker #5: I think that's something that we've gathered from our KOLs, including folks like Dr. Mike Kelly from the Cleveland Clinic. The way we're modeling that—and Matt can comment further—is looking at that in the pricing range of $100,000 to $200,000 per patient per year.

Speaker #5: And so, averaging that out across patients—some of whom will consume more than one pump per day, some patients who probably will consume less than one pump per day.

Speaker #5: And so, Matt can comment on any further specificity that he'd like to add.

Matthew E. Korenberg: Yeah. Thanks, Wes. I think it's important when we have recently started talking about a peak sales opportunity of multi-billion-dollar TAM and $1 billion or more as peak sales and MLM doing is taking pretty conservative assumptions across the board, including for patient numbers, penetration, and then to your specific question on any patient compliance assumptions as you move out in years per patients on drug. We see any kind of compliance variations from a standard 1 pump per day as being more than offset by the new incident population of more than 1,500 new patients coming in per year.

Matthew Korenberg: Yeah. Thanks, Wes. I think it's important when we have recently started talking about a peak sales opportunity of multi-billion-dollar TAM and $1 billion or more as peak sales and MLM doing is taking pretty conservative assumptions across the board, including for patient numbers, penetration, and then to your specific question on any patient compliance assumptions as you move out in years per patients on drug. We see any kind of compliance variations from a standard 1 pump per day as being more than offset by the new incident population of more than 1,500 new patients coming in per year.

Speaker #1: Yeah, thanks, Wes. I think it's important when we have recently started talking about a peak sales opportunity of multi-billion dollar TAM and a billion dollars or more as peak sales in MLM. What I'm doing is taking pretty conservative assumptions.

Speaker #1: Across the board, including for patient numbers, penetration, and then to your specific question on any patient compliance assumptions as you move out in years for patients on drugs.

Speaker #1: So, we see any kind of compliance variations from a standard one pump per day as being more than offset by the new incident population of more than 1,500 new patients coming in per year.

Matthew E. Korenberg: We've been very conservative about that, as we get to that billion-dollar peak sales number. I think that's probably the most level of specificity that we've given so far.

Matthew Korenberg: We've been very conservative about that, as we get to that billion-dollar peak sales number. I think that's probably the most level of specificity that we've given so far.

Speaker #1: But we've been very conservative about that as we get to that $1 billion peak sales number. So I think that's probably the most level of specificity that we've given so far.

Jenny Yang: Thanks. That's very helpful. We have another question on the doctor feedback from the recent AAD conference. Specifically, you know, for the dermatologists who have historically relied on or were hesitant to move away from compounded rapamycin, did the data generate more buy-in from those doctors?

Jenny Wang: Thanks. That's very helpful. We have another question on the doctor feedback from the recent AAD conference. Specifically, you know, for the dermatologists who have historically relied on or were hesitant to move away from compounded rapamycin, did the data generate more buy-in from those doctors?

Speaker #6: Thanks, that's very helpful. We have another question on the doctor feedback from the recent AAD conference. So, specifically, for the dermatologists who have historically relied on, or were hesitant to move away from, compounded rapamycin, did the data generate more buy-in from those doctors?

Wesley H. Kaupinen: Yeah. Thanks for that question. We've had extensive conversations with our physician collaborators around that question. Many of our phase 2 and phase 3 investigators have utilized compounded off-label therapies. I think you heard that, Jenny, likely from Dr. Michael Kelly on the SELVA phase 3 data release. Very consistently, what we hear is that physicians much prefer an FDA-approved therapy that has proven safety, quality, and efficacy, and done so in prospective studies under an FDA IND to any therapy which has not gone through that rigorous and stringent FDA-approved process. That's very consistent feedback, and I think, as we look at FDA activity around compounders, certainly the FDA is ramping up their enforcement of compounded medications in the presence of drugs that are FDA-approved, most notably from the GLP-1.

Wesley Kaupinen: Yeah. Thanks for that question. We've had extensive conversations with our physician collaborators around that question. Many of our Phase II and phase 3 investigators have utilized compounded off-label therapies. I think you heard that, Jenny, likely from Dr. Michael Kelly on the SELVA phase 3 data release. Very consistently, what we hear is that physicians much prefer an FDA-approved therapy that has proven safety, quality, and efficacy, and done so in prospective studies under an FDA IND to any therapy which has not gone through that rigorous and stringent FDA-approved process. That's very consistent feedback, and I think, as we look at FDA activity around compounders, certainly the FDA is ramping up their enforcement of compounded medications in the presence of drugs that are FDA-approved, most notably from the GLP-1.

Speaker #5: Yeah, thanks for that question. We've had extensive conversations with our physician collaborators around that question. Many of our Phase 2 and Phase 3 investigators have utilized compounded off-label therapies. I think you heard that, Jenny, likely from Dr. Mike Kelly on the Silva Phase 3 data release.

Speaker #5: Very consistently, what we hear is that physicians much prefer an FDA-approved therapy that has proven safety, quality, and efficacy, and has done so in prospective studies under an FDA IND, to any therapy which has not gone through that rigorous and stringent FDA-approved process.

Speaker #5: That's very consistent feedback. And I think as we look at FDA activity around compounders, certainly the FDA is ramping up their enforcement of compounded medications in the presence of drugs that are FDA-approved.

Wesley H. Kaupinen: That's been consistent feedback that we have received from folks like Michael Kelly, Joyce Teng at CHOP, and others. Most importantly, just to reiterate our SELVA phase 3 data, we saw 95% of patients who completed the efficacy evaluation period improve while on drug, and 86% of those were much or very much improved. We think that if we're FDA approved, we think that will result in a strong uptake from patients and physicians, and we're looking forward to that day of having QTORIN rapamycin be made available to those folks.

Speaker #5: Most notably from the GLP-1, so that's been consistent feedback that we've received from folks like Mike Kelly, Jim Tree at CHOP, and others. And most importantly, just to reiterate, our SILVA Phase 3 data showed that 95% of patients who completed the efficacy evaluation period improved while on drug, and 86% of those were much or very much improved.

Wesley Kaupinen: That's been consistent feedback that we have received from folks like Michael Kelly, Joyce Teng at CHOP, and others. Most importantly, just to reiterate our SELVA phase 3 data, we saw 95% of patients who completed the efficacy evaluation period improve while on drug, and 86% of those were much or very much improved. We think that if we're FDA approved, we think that will result in a strong uptake from patients and physicians, and we're looking forward to that day of having QTORIN rapamycin be made available to those folks.

Speaker #5: We think that if we're FDA-approved, we think that will result in strong uptake from patients and physicians. And we're looking forward to that day of having Q4 and rapamycin be made available to those folks.

Operator: Our next question comes from Kaveri Pohlman with Clear Street.

Speaker #4: Our next question comes from Kaveri Pullman with ClearStreet.

Kaveri Pohlman: Yes. Good morning. Thanks for the updates, and thanks for taking my questions. I would like to follow up on, maybe if you can provide more details on treatment compliance, what it would look like typically. You know, were there any patients in the phase 3 or prior phase 2 trial who needed to pause the treatment due to adverse events or any other factors? Overall, also for MLM, out of 30,000 patients, can you share, like, what proportion you know consider truly, like, moderate to severe and therefore more appropriate for the treatment? I have a follow-up.

Kaveri Pohlman: Yes. Good morning. Thanks for the updates, and thanks for taking my questions. I would like to follow up on, maybe if you can provide more details on treatment compliance, what it would look like typically. You know, were there any patients in the phase 3 or prior Phase II trial who needed to pause the treatment due to adverse events or any other factors? Overall, also for MLM, out of 30,000 patients, can you share, like, what proportion you know consider truly, like, moderate to severe and therefore more appropriate for the treatment? I have a follow-up.

Speaker #6: Oh, yes. Good morning. Thanks for the updates, and thanks for taking my questions. I would like to follow up by asking if you can provide more details on treatment compliance—what it would typically look like, and whether there were any patients in the Phase 3 or prior Phase 2 trial who needed to pause the treatment due to adverse events or any other factors?

Speaker #6: And overall, also for MLM, out of 30,000 patients, can you share what proportion you now consider truly moderate to severe, and therefore more appropriate for the treatment?

Wesley H. Kaupinen: Yeah. Thanks for those questions, Kaveri. I'll start with the last one. We think that any patient who is within clinical medicine, and our data indicates that there's greater than 30,000 patients that are currently within clinical medicine that are diagnosed with microcystic LM. We think any patient with that profile is a good candidate for QTORIN and rapamycin. I think part of that goes to the underlying biology of the disease. This is a proliferative and progressive disease, so if the disease is left untreated, the patient will worsen. What we know clinically is that's likely to result in leaking or lymphorrhea, bleeding, other impact on quality of life and, of course, risk of infection, cellulitis, and other infections, some of which can even be life-threatening.

Wesley Kaupinen: Yeah. Thanks for those questions, Kaveri. I'll start with the last one. We think that any patient who is within clinical medicine, and our data indicates that there's greater than 30,000 patients that are currently within clinical medicine that are diagnosed with microcystic LM. We think any patient with that profile is a good candidate for QTORIN and rapamycin. I think part of that goes to the underlying biology of the disease. This is a proliferative and progressive disease, so if the disease is left untreated, the patient will worsen. What we know clinically is that's likely to result in leaking or lymphorrhea, bleeding, other impact on quality of life and, of course, risk of infection, cellulitis, and other infections, some of which can even be life-threatening.

Speaker #6: And I have a follow-up.

Speaker #5: Yeah, thanks for those questions, Kaveri. I'll start with the last one. We think that any patient who is within clinical medicine—and our data indicates that there's greater than 30,000 patients that are currently within clinical medicine that are diagnosed with microcystic LMs—we think any patient with that profile is a good candidate for Q4 and rapamycin.

Speaker #5: I think part of that goes to the underlying biology of the disease. This is a proliferative and progressive disease, so if the disease is left untreated, the patient will worsen.

Speaker #5: What we know clinically is that it's likely to result in leaking or lymphuria, bleeding, other impact on quality of life, and, of course, risk of infection—cellulitis and other infections, some of which can even be life-threatening.

Wesley H. Kaupinen: We think the best approach, even for those patients who may be more moderate in nature, is to treat the lesion and treat it in a manner that hopefully alleviates the clinical signs but also prevents the progression of the disease. From a treatment compliance perspective, you know, our goal will be to work with, and Ritu asked the question earlier, our specialty pharmacy and our patient services hub to encourage patients to be compliant. We think that compliance with QTORIN rapamycin is set up in a manner for patients to be highly compliant with the drug. What do I mean by that? It is once daily dosing. We've also selected excipients in the formulation that are designed to be non-irritating. We do not have any traditional penetration enhancers.

Wesley Kaupinen: We think the best approach, even for those patients who may be more moderate in nature, is to treat the lesion and treat it in a manner that hopefully alleviates the clinical signs but also prevents the progression of the disease. From a treatment compliance perspective, you know, our goal will be to work with, and Ritu asked the question earlier, our specialty pharmacy and our patient services hub to encourage patients to be compliant. We think that compliance with QTORIN rapamycin is set up in a manner for patients to be highly compliant with the drug. What do I mean by that? It is once daily dosing. We've also selected excipients in the formulation that are designed to be non-irritating. We do not have any traditional penetration enhancers.

Speaker #5: So we think the best approach, even for those patients who may be more moderate in nature, is to treat the lesion and treat it in a manner that hopefully alleviates the clinical signs, but also prevents the progression of the disease.

Speaker #5: From a treatment compliance perspective, our goal will be to work with number two, ask the question earlier, our specialty pharmacy, and our patient services hub to encourage patients to be compliant.

Speaker #5: We think that compliance with Q4 and rapamycin is set up in a manner for patients to be highly compliant with the drug. What do I mean by that?

Speaker #5: It is once-daily dosing. We've also selected excipients in the formulation that are designed to be non-irritating. We do not have any traditional penetration enhancers.

Wesley H. Kaupinen: For that reason, we would expect to see high compliance relative to other therapies which may require more frequent daily dosing and which may have more significant safety or tolerability effects. Jeff?

Wesley Kaupinen: For that reason, we would expect to see high compliance relative to other therapies which may require more frequent daily dosing and which may have more significant safety or tolerability effects. Jeff?

Speaker #5: And for that reason, we would expect to see high compliance relative to other therapies, which may require more frequent daily dosing and which may have more significant safety or tolerability effects.

Jeff Martini: Yeah. Kaveri, thanks for the question on adverse events. You know, we've completed two clinical trials. The first was the phase 2 trial, which was 12 weeks. In that study, no patients withdrew due to adverse events. In the phase 3 trial, which was 24 weeks in duration, we had 50 patients enrolled. We did have 6 patients who discontinued treatment. Five of those 6 were deemed unrelated to study drug. One of the patients was related as possibly related to study drug. This is a patient who had a history of lymphorrhea and withdrew for lymphorrhea.

Jeff Martini: Yeah. Kaveri, thanks for the question on adverse events. You know, we've completed two clinical trials. The first was the Phase II trial, which was 12 weeks. In that study, no patients withdrew due to adverse events. In the phase 3 trial, which was 24 weeks in duration, we had 50 patients enrolled. We did have 6 patients who discontinued treatment. Five of those 6 were deemed unrelated to study drug. One of the patients was related as possibly related to study drug. This is a patient who had a history of lymphorrhea and withdrew for lymphorrhea.

Speaker #5: Jeff?

Speaker #3: Yeah, Kaveri, thanks for the question on adverse events. So we've completed two clinical trials. The first was the Phase 2 trial, which was 12 weeks.

Speaker #3: In that study, no patients withdrew due to adverse events. In the Phase 3 trial, which was 24 weeks in duration, we had 50 patients enrolled.

Speaker #3: We did have six patients who discontinued treatment. Five of those six were deemed unrelated to the study drug. One of the patients was deemed possibly related to the study drug.

Speaker #3: This is a patient who had a history of lymphuria and withdrew for lymphuria.

Kaveri Pohlman: Oh, yes. Sorry. I just wanted to know if any patient had to pause the treatment in between and they restarted the treatment during that period.

Speaker #6: Oh, yes. Sorry. I just wanted to know if any patient had to pause the treatment in between, and if they restarted the treatment during that period.

Jeff Martini: No. We did not have that situation.

Kaveri Pohlman: Got it. That's helpful. Maybe, you know, there was a recent publication suggesting that rapamycin's two years of continuous use followed by more like customized intermittent use can provide long-term benefit to majority of patients. Is that your expectation for Keytruda and rapamycin as well? Do you think having an official label and approval would increase awareness, and clear guidance could change these estimates around duration of treatment? Thank you.

Speaker #3: No, we did not have that situation.

Speaker #6: Got it. That's helpful. And maybe there was a recent publication suggesting that rapamycin—two years of continuous use followed by more customized intermittent use—can provide long-term benefit to the majority of patients.

Speaker #6: Is that your expectation for Q4 and rapamycin as well, or do you think having an official label and approval would increase awareness and clear guidance could change these estimates around duration of treatment?

Jeff Martini: Yeah. Thanks for the question. It's a really nice scientific publication that came out just showing that, you know, long-term use of rapamycin can have a really nice clinical benefit. What we've observed in our clinical trial is that over 24 weeks with continued treatment you continue to have clinical benefit. That we observed 98% of patients roll over to the treatment extension. They were, at least in our perspective, perceiving a positive risk-benefit profile. We don't have additional data beyond that point, but we'll continue to monitor those patients in the treatment extension period.

Speaker #6: Thank you.

Speaker #3: Yeah, thanks for the question. It's a really nice scientific publication that came out just showing that long-term use of rapamycin can have a really nice clinical benefit.

Speaker #3: What we've observed in our clinical trial is that over 24 weeks with continued treatment, you continue to have clinical benefit. And we observed patients—98%—roll over to the treatment extension.

Speaker #3: So they were, at least in our perspective, perceiving a positive risk-benefit profile. We don't have additional data beyond that point, but we'll continue to monitor those patients in the treatment extension period.

Operator: Our next question comes from Catherine Novack with JonesTrading.

Speaker #4: Our next question comes from Katherine Novak with Jones Trading.

Catherine Novack: Hi. Thanks for taking my question. Just curious of, you know, what's still up for discussion at the pre-NDA meeting? Do you think you'll get clarity on the 3+ age range at this time, or would this be something that would take place down the line during labeling discussions? Just remind us of the enrollment dynamics that led to exclusion of the 3 to 5 age patients from the ITT in phase 3. Thanks.

Speaker #7: Hi, thanks for taking my question. Just curious about what's still up for discussion at the pre-NDA meeting. Do you think you'll get clarity on the 3-plus age range at this time, or would this be something that would take place down the line during labeling discussions?

Speaker #7: And then, just remind us of the enrollment dynamics that led to exclusion of the three- to five-age patients from the ITT in Phase 3.

Wesley H. Kaupinen: Great. Thanks, Catherine. On the pre-NDA meeting, essentially what you're doing is putting forth what you anticipate being your package to support substantial evidence of effectiveness, as well as what will constitute your safety package as well. I'm not sure those are up for discussion. I think the FDA has known for a long time about our drug development program, the fact that we ran a phase 2 study. Recall that they granted Breakthrough Therapy designation on that phase 2 study, so that's demonstration of preliminary clinical evidence. With a very similar design in phase 3, albeit with a much larger sample size, we demonstrated highly statistically significant results on our primary, key secondary, and all secondary endpoints. It's a matter of presenting that data to the FDA.

Wesley Kaupinen: Great. Thanks, Catherine. On the pre-NDA meeting, essentially what you're doing is putting forth what you anticipate being your package to support substantial evidence of effectiveness, as well as what will constitute your safety package as well. I'm not sure those are up for discussion. I think the FDA has known for a long time about our drug development program, the fact that we ran a Phase II study. Recall that they granted Breakthrough Therapy designation on that Phase II study, so that's demonstration of preliminary clinical evidence. With a very similar design in phase 3, albeit with a much larger sample size, we demonstrated highly statistically significant results on our primary, key secondary, and all secondary endpoints. It's a matter of presenting that data to the FDA.

Speaker #7: Thanks.

Speaker #5: Great, thanks, Katherine. On the pre-NDA meeting, essentially what you're doing is you're putting forth what you anticipate being your package to support substantial evidence of effectiveness, as well as what will constitute your safety package as well.

Speaker #5: So, I'm not sure those are up for discussion. I think the FDA has known for a long time about our drug development program, the fact that we ran a Phase 2 study.

Speaker #5: Recall that they granted Breakthrough Therapy designation on that Phase 2 study. So that's demonstration of preliminary clinical evidence. And then, with a very similar design in Phase 3—albeit with a much larger sample size—we demonstrated highly statistically significant results on our primary, key secondary, and all secondary endpoints.

Wesley H. Kaupinen: To your question regarding age range, that typically does occur later on in the NDA discussions. We felt like it was important on this call to share that based on our feedback from investigators, that there is a desire for Palvella to advocate that younger patients might have this therapy available to them, of course, pending FDA review and approval. Jeff, do you wanna speak to why the 3- to 5-year-old cohort was not a part of the primary endpoint?

Wesley Kaupinen: To your question regarding age range, that typically does occur later on in the NDA discussions. We felt like it was important on this call to share that based on our feedback from investigators, that there is a desire for Palvella to advocate that younger patients might have this therapy available to them, of course, pending FDA review and approval. Jeff, do you wanna speak to why the 3- to 5-year-old cohort was not a part of the primary endpoint?

Speaker #5: So, it's a matter of presenting that data to the FDA. To your question regarding age range, that typically does occur later on in the NDA discussions.

Speaker #5: We felt like it was important on this call to share that, based on our feedback from investigators, there is a desire for Palvella to advocate that younger patients might have this therapy available to them—of course, pending FDA review and approval.

Speaker #5: Jeff, do you want to speak to why the three- to five-year-old cohort was not a part of the primary endpoint?

Jeff Martini: Yep. Thanks. So Catherine, what we did in phase 2 is we had patients 6 and up in that trial where we had 100% of patients respond. For phase 3, our intention was to repeat that successful study. We originally enrolled patients age 6 and up. We had a lot of interest from investigators to increase the age to 3 to 5. We ran that by the FDA, they agreed, and they allowed us to expand while that trial was ongoing. Essentially because we haven't studied the efficacy in the 3- to 5-year-old population, we kept the primary analysis of the primary endpoint the same, age 6 and up, and then just did post hoc analysis on the patient in the 3- to 5-year-old category.

Jeff Martini: Yep. Thanks. So Catherine, what we did in Phase II is we had patients 6 and up in that trial where we had 100% of patients respond. For phase 3, our intention was to repeat that successful study. We originally enrolled patients age 6 and up. We had a lot of interest from investigators to increase the age to 3 to 5. We ran that by the FDA, they agreed, and they allowed us to expand while that trial was ongoing. Essentially because we haven't studied the efficacy in the 3- to 5-year-old population, we kept the primary analysis of the primary endpoint the same, age 6 and up, and then just did post hoc analysis on the patient in the 3- to 5-year-old category.

Speaker #3: Yep. Thanks, Katherine. What we did in Phase 2 is we had patients six and up in that trial, where we had 100% of patients respond.

Speaker #3: And so, for Phase 3, our intention was to repeat that successful study, and we originally enrolled patients age six and up. We had a lot of interest from investigators to increase the age to three to five.

Speaker #3: We ran that by the FDA. They agreed, and they allowed us to expand while that trial was ongoing. Essentially, because we haven't studied the efficacy in the three- to five-year-old population, we kept the primary analysis of the primary endpoint the same—age six and up—and then just did post-hoc analysis on the patients in the three- to five-year-old category.

Catherine Novack: Got it. That's very helpful. Thanks.

Wesley H. Kaupinen: Thanks, Catherine Novack.

Wesley Kaupinen: Thanks, Catherine Novack.

Speaker #7: Got it. That's very helpful. Thanks.

Operator: Our next question comes from Albert Lowe with Craig-Hallum.

Speaker #5: Thanks, Katherine.

Speaker #4: Our next question comes from Albert Lowe with Craig Hallam.

Albert Lowe: Hi. I was wondering, what are the steps for Platform Technology Designation after the initial approval? When can you potentially receive designation, and how would this change the Palvella playbook?

Speaker #8: Hi. I was wondering, what are the steps for platform technology designation after the initial approval? And when can you potentially receive the designation? And how would this change the Palvella playbook?

Wesley H. Kaupinen: Yeah. Thanks for that question, Albert. The goal is to secure approval of QTORIN rapamycin first. That's gonna be the first product from the platform, we believe to achieve that FDA approval. As noted on this call, we've had a constructive and collaborative relationship with multiple parts of the FDA, including the review division and the Office of Orphan Products. Our strategy for achieving the platform technology designation would be to indicate our interest in that designation to the review division of the FDA, but also involving other parts of the FDA, if relevant, before submitting a more formal application around that. How does that change the Palvella playbook? I think that's an important question.

Wesley Kaupinen: Yeah. Thanks for that question, Albert. The goal is to secure approval of QTORIN rapamycin first. That's gonna be the first product from the platform, we believe to achieve that FDA approval. As noted on this call, we've had a constructive and collaborative relationship with multiple parts of the FDA, including the review division and the Office of Orphan Products. Our strategy for achieving the platform technology designation would be to indicate our interest in that designation to the review division of the FDA, but also involving other parts of the FDA, if relevant, before submitting a more formal application around that. How does that change the Palvella playbook? I think that's an important question.

Speaker #3: Yeah, thanks for that question, Albert. The goal is to secure approval of Q4 and rapamycin first. That's going to be the first product from the platform we believe to achieve that FDA approval.

Speaker #3: As noted on this call, we've had a constructive and collaborative relationship with multiple parts of the FDA, including the review division and the Office of Orphan Products.

Speaker #3: So our strategy for achieving the platform technology designation would be to indicate our interest in that designation to the review division of the FDA, but also involving other parts of the FDA if relevant, before submitting a more formal application around that.

Speaker #3: How does that change the Palvella playbook? I think that's an important question. The platform technology designation, while relatively new, in many ways functions similar to other expedited programs.

Wesley H. Kaupinen: The Platform Technology Designation, while relatively new, in many ways, functions similar to other expedited programs in the sense that it's designed as a result of the FDA's review of a CMC package and an understanding of a technology platform to then create more expedited and streamlined pathways for future platform products. We see a lot of value in this, particularly given some of the similarities between QTORIN pitavastatin and QTORIN rapamycin. Dr. Osborne, David Osborne, and Jeff will be announcing a third QTORIN platform product later this year.

Wesley Kaupinen: The Platform Technology Designation, while relatively new, in many ways, functions similar to other expedited programs in the sense that it's designed as a result of the FDA's review of a CMC package and an understanding of a technology platform to then create more expedited and streamlined pathways for future platform products. We see a lot of value in this, particularly given some of the similarities between QTORIN pitavastatin and QTORIN rapamycin. Dr. Osborne, David Osborne, and Jeff will be announcing a third QTORIN platform product later this year.

Speaker #3: In the sense that it's designed as a result of the FDA's review of a CMC package, and an understanding of a technology platform, to then create more expedited and streamlined pathways for future platform products.

Speaker #3: So, we see a lot of value in this, particularly given some of the similarities between Q4 and pitavastatin, and Q4 and rapamycin. Dr. Osborne, David Osborne, and Jeff will be announcing a third Q4 and platform product later this year.

Wesley H. Kaupinen: Again, further to one of my initial slides that was presented today, we are consistently pursuing and advocating for ways to get drugs to patients sooner and do so on reduced time and reduced capital, and we think the Platform Technology Designation would help us achieve that.

Wesley Kaupinen: Again, further to one of my initial slides that was presented today, we are consistently pursuing and advocating for ways to get drugs to patients sooner and do so on reduced time and reduced capital, and we think the Platform Technology Designation would help us achieve that.

Speaker #3: And so again, further to one of my initial slides that was presented today, we are consistently pursuing and advocating for ways to get drugs to patients sooner and do so on reduced time and reduced capital.

Speaker #3: And we think the platform technology designation would help us achieve that.

Albert Lowe: Great. That's helpful. Thank you.

Speaker #8: Great, that's helpful. Thank you, Albert.

Wesley H. Kaupinen: Thanks, Albert.

Wesley Kaupinen: Thanks, Albert.

Operator: Our next question comes from Dev Prasad with Lucid Capital Markets.

Speaker #4: Our next question comes from Dev Prasad with Lucid Capital Markets.

Dev Prasad: Hi. Thank you for taking my question, and congrats on the update. I have a couple of questions. One is, can you talk about identification and recruitment of 10 to 20 angiokeratoma patient for phase 2. Are you leveraging the same clinical site network as SELVA and TOIVA, or does this require a distinct referral approach? The second is the QTORIN pitavastatin. It's the first directed therapy for DSAP for this pathway. Just can you remind the most significant translational data or preclinical evidence that support this mechanism and what gives you confidence in topical drug penetration for these layers? Thank you.

Dev Prasad: Hi. Thank you for taking my question, and congrats on the update. I have a couple of questions. One is, can you talk about identification and recruitment of 10 to 20 angiokeratoma patient for Phase II. Are you leveraging the same clinical site network as SELVA and TOIVA, or does this require a distinct referral approach? The second is the QTORIN pitavastatin. It's the first directed therapy for DSAP for this pathway. Just can you remind the most significant translational data or preclinical evidence that support this mechanism and what gives you confidence in topical drug penetration for these layers? Thank you.

Speaker #9: Hi. Thank you for taking my question, and congrats on the update. I have a couple of questions. One is, can you talk about identification and recruitment of 10 to 20 NGC keratoma patients for Phase 2?

Speaker #9: Are you leveraging the same clinical site network as Salva and Toiva, or does this require a distinct referral approach? And the second is the Q4 and Pitavastatin.

Speaker #9: It's the first directed therapy for DSAP for this pathway. Just, can you remind me of the most significant translational data or preclinical evidence that supports this mechanism?

Speaker #9: And what gives you confidence in topical drug penetration for these lesions? Thank you.

Wesley H. Kaupinen: Great. Thanks, Dev. I'll take your first question on the angiokeratoma phase 2 study, and then Jeff will take your second question around evidence of mevalonate pathway inhibitors in porokeratosis. Actually, there's a great paper that Jeff was involved with that we recently published on that, so he'll be able to go through the highlights of that paper. In terms of the sites for angiokeratomas, you're exactly right. We are going to leverage some of the same sites that we've worked with closely in microcystic lymphatic malformations and cutaneous venous malformations, and we have great relationships with these groups. We're also gonna leverage commercial sites that often have large volumes of patients with angiokeratomas. I'd say we've been pleasantly surprised.

Wesley Kaupinen: Great. Thanks, Dev. I'll take your first question on the angiokeratoma Phase II study, and then Jeff will take your second question around evidence of mevalonate pathway inhibitors in porokeratosis. Actually, there's a great paper that Jeff was involved with that we recently published on that, so he'll be able to go through the highlights of that paper. In terms of the sites for angiokeratomas, you're exactly right. We are going to leverage some of the same sites that we've worked with closely in microcystic lymphatic malformations and cutaneous venous malformations, and we have great relationships with these groups. We're also gonna leverage commercial sites that often have large volumes of patients with angiokeratomas. I'd say we've been pleasantly surprised.

Speaker #3: Great. Thanks, Dev. I'll take your first question on the NGO keratoma Phase 2 study, and then Jeff will take your second question around evidence of Mevalonate pathway inhibitors.

Speaker #3: In Porokeratosis, actually, there's a great paper that Jeff was involved with that we recently published on that. So he'll be able to go through the highlights of that paper.

Speaker #3: In terms of the sites for NGO keratomas, you're exactly right. We are going to leverage some of the same sites that we've worked with closely.

Speaker #3: In microcystic lymphatic malformations and cutaneous venous malformations, we're also—and we have great relationships with these groups. We're also going to leverage commercial sites that often have large volumes of patients with angio keratomas.

Wesley H. Kaupinen: One of our feasibility efforts that we make on all of our clinical trials is understanding just how many patients a particular academic site or a commercial site have with this condition. I'd say consistently, we've heard from our clinical operations team that there are more angiokeratoma patients than there are microcystic LM, and maybe even as much as cutaneous venous malformation. A nice blend of both academic sites and commercial sites, as well as a nice blend of sites who have been involved in MLM CVM, but also some new sites that will leverage for angiokeratomas as well as additional studies from our QTORIN platform. Jeff?

Wesley Kaupinen: One of our feasibility efforts that we make on all of our clinical trials is understanding just how many patients a particular academic site or a commercial site have with this condition. I'd say consistently, we've heard from our clinical operations team that there are more angiokeratoma patients than there are microcystic LM, and maybe even as much as cutaneous venous malformation. A nice blend of both academic sites and commercial sites, as well as a nice blend of sites who have been involved in MLM CVM, but also some new sites that will leverage for angiokeratomas as well as additional studies from our QTORIN platform. Jeff?

Speaker #3: I'd say we've been pleasantly surprised. One of our feasibility efforts that we make on all of our clinical trials is understanding just how many patients a particular academic site or commercial site have with this condition.

Speaker #3: And I'd say, consistently, we've heard from our clinical operations team that there are more NCGO keratoma patients than there are microcystic LM, and maybe even as much as cutaneous venous malformations.

Speaker #3: So, a nice blend of both academic sites and commercial sites, as well as a nice blend of sites who have been involved in MLM/CVM, but also some new sites that we will leverage for NGO keratomas, as well as additional studies from our Q4 and platform.

Jeff Martini: Yeah, thanks for the question, Dev. With DSAP, the genetics here are very well characterized, and a lot of this work comes out of the lab of Dr. Keith Choate at Yale University, who's a close collaborator and also a member of our MSAB. Genetically, they're monogenic loss of function mutations in any of the five genes involved in the mevalonate pathway. Genetically, we know that this is the right pathway to involve a therapy. The idea mechanistically is if you can inhibit this pathway from being activated, you can have a clinical response because these intermediate metabolites can cause toxicity within the cells. This was first studied out of Keith Choate's lab. He did a really nice clinical study with topical lovastatin which showed clinical response.

Speaker #3: Jeff?

Speaker #5: Thanks for the question, Dev. So with DSAP, the genetics here are very well characterized. A lot of this work comes out of the lab of Dr. Keith Choate at Yale University, who's a close collaborator and also a member of our MSAB.

Speaker #5: Genetically, they're monogenic, loss-of-function mutations in any of the five genes involved in the mevalonate pathway. So genetically, we know that this is the right pathway to involve in a therapy.

Speaker #5: And the idea, mechanistically, is if you can inhibit this pathway from being activated, you can have a clinical response. Because these intermediate metabolites can cause toxicity within the cells.

Speaker #5: This was first studied out of Keith Choat's lab. He did a really nice clinical study with topical lovastatin, which showed clinical response. And since that time, there's been a number of studies—about 24 studies that we recently published on during a review—showing the potential proof-of-concept data with inhibiting this pathway in porokeratosis.

Jeff Martini: Since that time, there's been a number of studies, about 24 studies that we recently published on during a review showing, the potential proof of concept data with, inhibiting this pathway in porokeratosis. Importantly, what we've uncovered in our, formulation work, really led by David Osborne, was that many of these statins are chemically labile. They break down very, very quickly, which really translates to the inconsistent yield which we've heard during our market research. What we've done with QTORIN pitavastatin is optimize that for delivery, so we get a stable formulation and consistent delivery at therapeutic concentrations with low systemic absorption.

Speaker #5: Importantly, what we've uncovered in our formulation work, really led by David Osborne, was that many of these statins are chemically labile, so they break down very, very quickly.

Speaker #5: Which really translates to the inconsistent yield, which we've heard during our market research. What we've done with Q4 and pitavastatin is optimize that for delivery.

Speaker #5: So, we get a stable formulation and consistent delivery at therapeutic concentrations with low systemic absorption.

Dev Prasad: Great. Thank you.

Operator: Our next question comes from Jeet Mukerji with BTIG.

Speaker #9: Great. Thank you.

Speaker #4: Our next question comes from Jeet Mukerji with BTIG.

Jeet Mukherjee: Great. Thanks for taking the question. You shared some details about the phase 2 study for angiokeratomas in terms of number of patients and efficacy measures. I was hoping you could shed some light on the phase 2 study for DSAP as well, and when can we expect data from both these phase 2 programs? Thank you.

Jeet Mukherjee: Great. Thanks for taking the question. You shared some details about the Phase II study for angiokeratomas in terms of number of patients and efficacy measures. I was hoping you could shed some light on the Phase II study for DSAP as well, and when can we expect data from both these Phase II programs? Thank you.

Speaker #10: Great. Thanks for taking the question. So, you shared some details about the Phase 2 study for NGO keratomas in terms of number of patients and efficacy measures.

Speaker #10: I was hoping you could shed some light on the Phase 2 study for DSAP as well. And when can we expect data from both these Phase 2 programs?

Wesley H. Kaupinen: Great, Jeet. Thanks for being on. Thanks for the questions. Jeff can speak to the phase 2 study design in DSAP. At this point in time, we have not given specific guidance on trial readout timelines. We are really enthusiastic about the fact that the angiokeratoma study one is moving ahead of schedule with the first patient expected to be dosed this quarter, and also just the level of demand that we're seeing for the study. We look forward to providing guidance on those trial timeline readouts here in the near term for both angiokeratomas and porokeratosis as we get a little bit further along towards initiation and start to move up the enrollment curve. Jeff?

Wesley Kaupinen: Great, Jeet. Thanks for being on. Thanks for the questions. Jeff can speak to the Phase II study design in DSAP. At this point in time, we have not given specific guidance on trial readout timelines. We are really enthusiastic about the fact that the angiokeratoma study one is moving ahead of schedule with the first patient expected to be dosed this quarter, and also just the level of demand that we're seeing for the study. We look forward to providing guidance on those trial timeline readouts here in the near term for both angiokeratomas and porokeratosis as we get a little bit further along towards initiation and start to move up the enrollment curve. Jeff?

Speaker #10: Thank you.

Speaker #3: Great, Jeet. Thanks for being on. Thanks for the questions. Jeff can speak to the Phase 2 study design in DSAP. At this point in time, we have not given specific guidance on trial readout timelines.

Speaker #3: We are really enthusiastic about the fact that the NGO keratoma study one is moving ahead of schedule, with the first patient expected to be dosed this quarter.

Speaker #3: And also just the level of demand that we're seeing for the study. So we look forward to providing guidance on those trial timeline readouts here in the near term.

Speaker #3: For both NGO keratomas and porokeratosis, as we get a little bit further along towards initiation and start to move up the enrollment curve—Jeff?

Jeff Martini: Yeah, thanks for the question. The trial design for DSAP is not finalized yet, so we're still working through that. At a very high level, our approach is very similar. There's no spontaneous regression in this disease, and we know that inhibiting the mevalonate pathway is on target. What we've developed with QTORIN pitavastatin is an on target in tissue approach. We're looking at both individual signs of the disease and global changes in disease. We're working with both patients and KOLs to identify what are the right signs to measure and what we think we can have a clinical benefit on. We'll also, like all of our programs, incorporate baseline and exit interviews to help capture the voice of the patient.

Speaker #5: Yeah, thanks for the question. So, the trial design for DSAP is not finalized yet—we're still working through that. But at a very high level, our approach is very similar.

Speaker #5: There's no spontaneous regression in this disease. And we know that inhibiting the mevalonate pathway is on target. So what we've developed with Q4 and pitavastatin is an on-target, in-tissue approach.

Speaker #5: We're looking at both individual signs of the disease and global changes in disease. We're working with both patients and KOLs to identify what are the right signs to measure and what we think we can have a clinical benefit on.

Speaker #5: We'd also like all of our programs to incorporate baseline and exit interviews to help capture the voice of the patient.

Operator: That concludes today's question and answer session. I'd like to turn the call back to Wes Kaupinen for closing remarks.

Speaker #4: That concludes today's question-and-answer session. I'd like to turn the call back to Wes Coppenan for closing remarks.

Wesley H. Kaupinen: Thank you, operator. In closing, thank you to everyone who firmly believes in Palvella's mission to serve, our vision to lead, and our strategy of being first in disease. We remain relentlessly focused on execution and have an unwavering commitment to delivering on this mission, vision, and strategy. We deeply appreciate your continued support. With that, I'd like to conclude today's call. Thank you, everyone.

Wesley Kaupinen: Thank you, operator. In closing, thank you to everyone who firmly believes in Palvella's mission to serve, our vision to lead, and our strategy of being first in disease. We remain relentlessly focused on execution and have an unwavering commitment to delivering on this mission, vision, and strategy. We deeply appreciate your continued support. With that, I'd like to conclude today's call. Thank you, everyone.

Speaker #3: Thank you, operator. In closing, thank you to everyone who firmly believes in Paul Vella's mission to serve, our vision to lead, and our strategy of being first in disease.

Speaker #3: We remain relentlessly focused on execution and have an unwavering commitment to delivering on this mission, vision, and strategy. We deeply appreciate your continued support.

Speaker #3: And with that, I'd like to conclude today's call. Thank you, everyone.

Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.

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