Palvella Therapeutics (PVLA) 2026年第三季度业绩电话会：QTORIN FDA审评与上市计划

核心要点

• 美国FDA已受理Palvella Therapeutics关于QTORIN雷帕霉素用于治疗微囊型淋巴管畸形的新药申请（NDA），并授予优先审评资格，PDUFA目标行动日期为2027年2月28日。
• 截至2026年第三季度末，Palvella持有的现金、现金等价物及短期投资为2.367亿美元，而2026年第二季度末约为2.5亿美元。
• 第三季度净亏损从上年同期的1130万美元（合每股亏损1.03美元）扩大至2460万美元（合每股亏损1.70美元）。该季度计入了与Ligand特许权使用费协议相关的450万美元非现金费用。
• 管理层正着手准备美国市场的独立商业化上市，计划部署70多名商业和医学事务一线人员，其中包括约40名前线销售代表。该团队预计将在PDUFA日期前约两个月就位。
• 该公司估计美国有超过3万名已确诊的微囊型淋巴管畸形患者。管理层认为，若QTORIN雷帕霉素获批，该适应症在美国的年销售额峰值有望突破10亿美元。
• Palvella还计划推进QTORIN在皮肤静脉畸形、具有临床意义的血管角化瘤以及播散型浅表性日光性汗孔角化症等管线项目，这些疾病目前均无FDA批准的疗法。

核心财务数据

业务与经营表现

QTORIN雷帕霉素迎来FDA审评决议关键节点

FDA受理微囊型淋巴管畸形NDA标志着QTORIN雷帕霉素进入为期六个月的优先审评期。若获批准，该药将成为首款获FDA批准治疗该疾病的药物。

Palvella预计该药物有望用于不同严重程度的儿童及成人患者（以最终说明书标签为准）。管理层计划将该产品定位为一线疗法，并预计将通过长期用药来控制病情。

在针对150多名医生的市场调研中，超过70%的受访者表示若获批将处方QTORIN雷帕霉素。超70%的人预计在获批后三个月内开出处方，许多医生还计划在多名患者中启动治疗。

该公司估计美国确诊患者超过3万人。公司提及每位患者的潜在年罕见病定价区间为10万至20万美元，同时表示即便渗透率不高，也足以支撑美国年销售额峰值突破10亿美元。

上市前商业化基础设施加速铺设

Palvella预计在上市时将有70多名商业和医学事务人员驻扎一线，其中包括约40名前线销售代表。其余人员包括销售管理层、医学总监、患者用药联络员、一线市场人员及内部销售人员。

公司正在组建内部患者服务团队，以支持诊断、医保准入及持续治疗。其疾病认知普及和医生触达策略结合了一线互动、医学会议以及包括Meta、Reddit和Google在内的数字渠道。

管理层表示，约400家治疗中心覆盖了约1.5万名患者，这为罕见病药物上市创造了罕见的高度集中机遇。公司目前不打算扩大既定的一线团队规模，去覆盖大语言模型分析所发现的额外患者和处方医生。

研发管线拓展

Palvella计划在本季度启动QTORIN雷帕霉素治疗皮肤静脉畸形的3期临床试验。试验开始时，公司将公布最终方案设计、样本量、研究终点及试验周期。管理层估计美国有超7.5万名确诊患者，该项目已获得FDA快速通道资格认定。

在2期TOIVA研究中，73%的患者在第12周时的皮肤静脉畸形研究者整体评估（IGA）中实现改善。管理层表示，24周数据在多个终点上显示出进一步改善，且儿科患者的疾病严重程度及出血症状有所减轻。

针对具有临床意义的血管角化瘤，Palvella预计将于2027年下半年公布2期LOTUS研究的顶线数据。这项为期12周的研究正在约15名患者中评估每日一次局部外用雷帕霉素的效果。公司估计美国有超5万名确诊患者，该项目于2025年12月获得快速通道资格认定。

Palvella亦按计划将于本季度启动QTORIN匹伐他汀治疗播散型浅表性日光性汗孔角化症的临床研究。10月公布的一项医保理赔数据分析显示，美国约有15.5万名确诊患者。公司已完成剂型开发及多项支持IND申请的毒理学研究，并收到了90多名患者关于该试验的主动咨询。

管理层业绩指引

管理层表示，2026年全年的现金支出可能低于此前预期。然而，随着招聘、商业化前筹备及上市库存备货支出的加速，第四季度预计将成为公司迄今为止季度投资规模最大的一季。

由于Palvella正在搭建商业化基础设施并启动针对皮肤静脉畸形与播散型浅表性日光性汗孔角化症的研究，从2026年末延后的任何支出通常预计将顺延至2027年初。

基于目前的经营规划、2027年上半年获批并上市的假设以及当前市场一致预期的收入预测，管理层预计现有现金足以支持公司深入推进商业化上市。该规划包括在美国进行独立商业化推广，并继续推进皮肤静脉畸形、血管角化瘤及DSAP项目的研发。

Palvella不打算提供具体的2027年收入指引。管理层计划在临近商业化时再公布上市相关指标及测算模型输入参数。

风险与关注要点

• 商业化进程仍取决于能否在2027年2月28日的PDUFA日期前获得FDA批准，且最终获批的说明书标签可能与管理层的预期存在出入。
• 管理层提醒称，由于支付方制定报销政策、推行预先授权流程以及治疗中心将QTORIN雷帕霉素纳入其诊疗路径都需要时间，上市初期的需求与确认的收入之间可能存在脱节。
• 联邦医疗补助（Medicaid）的报销准入可能需要至少一个季度甚至数个季度的时间，尽管存在处方需求，但这可能会推迟初期收入的确认。
• 皮肤静脉畸形项目的最终3期设计细节仍取决于与监管机构正在进行的沟通。
• 获批前发生的产品成本已计入研发费用，因此上市初期的销售成本（COGS）将低于预期的长期水平。Ligand的特许权使用费费用将列于营业利润线下方，而非计入销售成本。

分析师问答要点

管理层表示，早期治疗的科普教育将由医学事务团队牵头，通过疾病遗传学机制、临床发表文献及药代动力学数据，解释为何在病变组织进一步浸润前进行干预有助于改善预后。

在资金使用效率方面，高管提到了505(b)(2)监管途径、已知分子带来的较低药理学风险以及QTORIN平台产生的可复用剂型技术。在推进关键性临床试验之前，Palvella通常通过约10至15名患者的小型2期研究来评估疗效信号。

管理层预计QTORIN雷帕霉素上市初期不会出现一次性集中放量，而是呈现平稳的环比增长；虽然医生底层处方意愿强烈，但建立医保报销及治疗中心工作流程所需的时间会对其放量速度形成一定制约。

在患病率方面，管理层表示，美国确诊微囊型淋巴管畸形患者超过3万人的估计是刻意保持保守的。此前公司的分析得出了更高的区间，但Palvella将商业规划锚定在区间低位，同时承认随着疾病认知度的提升，确诊人数可能会进一步增加。

财报电话会议完整实录

完整财报电话会议逐字稿

管理层陈述

Operator

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 a session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Bo Han Wei, Vice President of Corporate Development and New Product Planning. Please go ahead.

Unknown Speaker

Thank you, operator. Good morning and thank you for joining the Palvela Therapeutics third quarter, 2026 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.palvelatx.com. today's call, you will first hear from Wes Kaupinen, our Founder and Chief Executive Officer, followed by Ashley Klein, our Chief Commercial Officer, Dr. Jeff Martini, our Chief Scientific Officer, and Matt Korenberg, our Chief Financial Officer. 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. And now, I'll turn the call over to Wes.

Wesley Kaupinen

Thanks, Bo. Good morning, everyone. And thank you all for joining us on the Polvella Therapeutics third quarter earnings call and corporate update. For children and adults living with microcystic lymphatic malformations, every day counts. Microcystic lymphatic malformations are a serious, rare, and chronically debilitating genetic disease. Starting at a young age, daily life can be impacted by persistent leaking and bleeding from their lymphatic lesions, functional impairment, infections, disfigurement, and a physical and psychological burden of living with a lifelong infiltrative disease that progressively worsens over time. Despite this profound burden of disease, there are currently no FDA-approved therapies for microcystic lymphatic malformations. Last Wednesday, October 28th, a major milestone was achieved that could soon change the treatment paradigm for individuals living with microcystic lymphatic malformations. Our team at Palvella Therapeutics announced that the FDA has accepted our new drug application for Qtorin Rapamycin for the treatment of microcystic LMs and furthermore that the program has been granted FDA's priority review, a designation for medicines that if approved significant improvements in the safety or effectiveness of treating serious conditions, and which sets a six-month FDA review goal rather than the standard 10-month review.

In light of this milestone, I want to take a moment to recognize the patients and families who have participated in our clinical studies, our clinical investigators, our patient advocacy collaborators, our highly dedicated employees, and everyone who helped us reach this important point. Thank you. Furthermore, 116 days from today, on February 28, 2027, the Palvella team, working in conjunction with our physician and patient advocacy collaborators, will have the potential opportunity to begin transforming the lives of these patients through the commercialization of of ketorin rapamycin if approved. Our goal isn't simply to bring another medicine to market. Our goal is to establish ketorin rapamycin as the first line treatment and standard of care for microcystic lymphatic malformations. Recently, I was in Fort Lauderdale, Florida with newly recruited members of our commercial and medical affairs teams. We've recruited an exceptional group of leaders who have helped build and launch some of the most successful products in both rare diseases and dermatology, including individuals like Phil Hazel, Wiesel, Marnie Telkamp, Nick Kerr, Matt Giordano, Erica Lucchesi-Johnson, and many others. What struck me was the depth of their experience in launching novel products, their boundless positive energy, and most of all, the shared commitment to delivering on the potential for a highly successful launch for the microcystic lymphatic malformation community.

Longer term, an FDA approval in microcystic lymphatic malformations may open the door to many other potential clinical indications where topical rapamycin can make a meaningful impact to patients. The vision for ketorin rapamycin is a pipeline and a product, one drug that can eventually address many rare skin diseases and vascular anomalies in which the mTOR pathway has been identified to be a key driver of those diseases. At Palvella, we are striving to realize the full patient impact that Keturin Rapamycin can have. And as you'll hear today, we're actively advancing Keturin Rapamycin for multiple additional indications, two of which are in advanced clinical stages in cutaneous venous malformations and clinically significant angiokeratomas with the goal of delivering multiple first-in-disease therapy to these deserving rare disease patient populations. While we believe ketorin rapamycin for microcystic lymphatic malformations will represent our first FDA approval and an attractive peak annual US sales opportunity exceeding $1 billion, we believe what truly sets Paul Vela apart is our ability to repeatedly unlock multi-billion dollar dollar markets in orphan diseases previously thought to be untreatable. The repeatability of our approach is enabled by two elements that are core to Palvela. Number one, our discipline first in disease strategy.

We aim to go from 0-1 in serious rare diseases that currently have no FDA approved therapies. Rather than pursue incremental differentiation in crowded markets, our focus is on pioneering the first approved therapy in diseases where patients have oftentimes been left behind. Number two, our proprietary QTORIN platform, which enables us to reproducibly generate novel IP-protected topical product candidates to address these serious rare skin diseases and vascular malformations. Importantly, at Palvella, we often focus on selecting diseases where there is already human proof of concept data supporting the therapeutic approach, frequently from real-world clinical evidence. This provides early but important mechanistic and clinical validation that modulating a has the potential to deliver meaningful benefit to patients. We then apply our QTORN platform to optimize localized drug targeting, tissue exposure, and tolerability with the goal of translating that early evidence into compelling clinical outcomes demonstrated in rigorous, well-conducted clinical trials. clinical trials while using endpoints specifically designed to support FDA approvals. Our overarching goal is to bring first-in-disease therapies to FDA approval as quickly and efficiently as possible, recognizing that time matters to rare disease patients while capital efficiency and the probability of achieving FDA approvals matter to our shareholders, who have entrusted us to translate their investment into high clinical impact, commercially available, FDA approved therapies.

With our NDA now accepted and our PDUFA date set for next quarter, I'd like to introduce you to our Chief Commercial Officer, Ashley Klein, who will be leading the launch of QTORIN Rapamycin in microcystic lymphatic malformations. Ashley began working with Palvella more than two years ago, and we formally announced her appointment as Chief Commercial Officer. commercial officer in May of last year. What makes Ashley particularly valuable to Palvella is that she's not preparing for her first successful rare disease launch, she's preparing for her next one, bringing lessons learned from her previous successful launches directly into our preparations for ketoran rapamycin. While General Manager of Dompe's U.S. business, Ashley led the highly successful launch of Oxervate, a first in disease topical therapy for a rare disease with no previously FDA approved treatments. Under her leadership, Oxervate grew to more than $500 million in annual U.S. sales while achieving profitability in the U.S. in its first year. What impresses me most about Ashley is her combination of strategic thinking, relentless execution, and a genuine commitment to patients. With our potential first approval approaching, I couldn't be more excited about the team that Ashley has recruited, the progress of our launch preparations, thanks to Ashley and her entire team, and our shared determination to deliver for the microcystic LM community.

Ashley, over to you.

Unknown Speaker

Thanks, Wes. As Wes mentioned, I've been working with Palvella for a couple of years. Prior to that, I led the launch of Oxervate, a topical eye drop for the rare eye disease neurotrophic keratitis. Seven years after launch, Oxirvate has grown to more than $1 billion in U.S. sales. I bring that up because the NK market in 2018 looked a lot like what we see today in microcystic lymphatic malformation. Some of the parallels with the launch of Qtorin rapamycin include the lack of an FDA approved therapy and potential upside from patients who were undiagnosed. I want to spend a few minutes on how we expect this launch to unfold, assuming approval. Well, I'm proud of what I've achieved previously.

What's very exciting about the opportunity at Palvella is the large number of existing diagnosed patients and the organic maturation of vascular anomaly clinics with large numbers of patients receiving specialist care. Some keys for a successful orphan launch are strong prescribing intent, a pathway to coverage with non-clinical barriers addressed and removed, and a patient finding effort that allows resources and capital to be deployed efficiently. Here's the headline. We expect strong physician demand for QTORIN rapamycin to be there from day one. In our market research with more than 150 physicians, more than 70% said that they would expect to prescribe if approved. On the payer side, we know that payers see value in the product. We've had initial conversations with some plans and those conversations have been constructive and I'll share more on that in a minute. Next, a word on the market opportunity and patient identification.

We had a lot of confidence in our claims analysis and traditional market research. But at Povella, we have a culture of refusing to be satisfied, and we continue to invest in refining our view of this market. One recent investment was using a large language model to analyze anonymized chart notes, which unearthed novel treaters and ICD-10 coding patterns. group that was invisible in traditional claims analysis, indicating potential upside on our internal estimates. We are deploying this novel algorithm now in the largest US database of dermatology encounters, and we look forward to those results. The underlying opportunity is clear. With more than 30,000 diagnosed US patients at 100,000 to $200,000 per patient per year, reaching $1 billion at peak requires modest penetration. Our team is laser focused on bringing these patients the first FDA approved therapy for their disease if we receive approval next year. When we received the SELDA data in February, the results of the clinical study exceeded all of our tested scenarios.

So we went out to both physicians and payers to do additional market research. The data that I'm sharing with you here has not been shared before. This research bolsters our confidence in early uptake. More than 70% of physicians surveyed expect to begin prescribing within three months of approval and most plan to start several patients at once. Our market access testing confirmed that payers agree MLM is a serious genetic vascular anomaly with unmet need, and they found the Selva data to provide a compelling clinical evidence package. Payers agree that clinical diagnosis is appropriate in MLM and noted that there will not be step-through therapy given the lack of FDA-approved treatment options. We also anticipate favorable coverage in the orphan pricing corridor.

We also have a team of MSLs, field marketers, and patient assistance liaisons in the field. and what they are reporting back is consistent with what we heard in market research. I'd like to take a minute to discuss the how behind our execution. I'm fortunate to work with an exceptional leadership team here at Pulvella, and we continue to add outperformers every week, Each of us bring different perspectives from prior roles, including deep expertise in both dermatology and rare disease. And that breadth makes us a very powerful group. In the prelaunch setting, we are reinforcing the urgency to treat that we have heard from our KOLs and investigators. By launch, we will have about 70 people in the field, all custom-built to serve the Netherton community. Importantly, we are building our own patient services organization in-house at Pulvella because we believe that owning the patient experience directly from diagnosis through access and ongoing support is critical in a rare disease like MLM.

That decision is informed by the experience of many of our team who join us from rare disease launches, including Krystal Biotech, Incyte, Horizon, Ascendis, and others. We are very deep into recruiting and we expect most of the team to be on board and trained prior to our PDUFA date in late February. I also want to touch on a precision digital marketing effort led by our VP of Marketing, Peter Finlayson. Just as we deploy innovative trial designs and formulation science, there is a great deal of innovation on the marketing side. Alvella is using cutting-edge physician-targeting technology to efficiently deploy dollars against top treaters of MLM in the U.S., expanding our reach far beyond what could be accomplished alone via a field organization. This is already in place for our Beyond MLM disease education campaign. I want to sum up with how we expect this launch to unfold, assuming approval.

We have the opportunity to be the first FDA-approved therapy for an estimated more than 30,000 microcystic LM patients in the U.S. We have confirmed that there is strong physician demand, and we will position Cutorin rapamycin as first line and establish it as the new standard of care for appropriate patients if approved. There is no approved therapy for these patients today, and we have a sense of urgency to deliver this drug to patients. We expect a broad label that covers both pediatric and adult use for patients with all severities, including those that are treatment naive and those who have tried off-label drugs and procedures. and we anticipate long-term administration to keep the disease in check. Now I will hand it over to Dr. Jeff Martini, who will provide an update on our pipeline.

Jeffrey Martini

Thank you, Ashley. Before I provide details on our programs, I want to spend a minute highlighting the FDA's new Rare Disease Framework Initiative. Isabella recently attended the FDA's public meeting on the initiative held on October 28th in partnership with the Reagan Udall Foundation. One of the key themes was that the framework starts from the position that rare disease drug development should no longer be measured against precedents set by drugs for more common conditions. Rare diseases are fundamentally different, and they should be treated differently. This quote captures why that matters in our space. I spoke with Dr. Zerwas this week about the opportunity in rare diseases, and this is the comment he provided to FDA at the public meeting. that dermatology has more rare diseases than any other specialty and that he is taking care of more rare disease patients than he could ever count. It's another third-party view that rare skin disease is a corridor of high unmet need, and we will continue to be the leader in this space.

Turning to our pipeline, we set out to build the leading pipeline in serious, rare skin diseases and vascular anomalies, and we are doing exactly that. Every program on this slide targets a serious, rare, and commercially attractive disease with no FDA-approved therapy. What makes this possible is Qtoran, our platform and the engine behind the programs you see here. Qtorrent delivers drugs directly into the skin where the disease manifests while limiting systemic exposure. It is a repeatable engine. We pair it with molecules that have strong biological rationale, and we can move from one rare disease to the next with speed and capital efficiency. Today, that engine has produced a lead program approaching its PDUFA date in February, several more programs advancing behind it, and new cuturin programs on the way. Later this year, we expect to announce a new cuturin rapamycin indication and a third cuturin program.

We are just getting started and we look forward to sharing more as this pipeline grows. One of the questions I get asked most often by investors is, when should patients be treated? My answer starts with three things, genetics, biology, and the course of the disease. All three point the same way, and they're why clinicians who treat lymphatic malformations recommend treating early before the malformation infiltrates multiple tissue planes. planes. Starting with genetics, researchers at Boston Children's discovered that lymphatic malformations are driven by somatic PIK3CA mutations that keep the mTOR pathway switched on. That drives the biology. Because the growth pathway is always on, a microcystic lymphatic malformation is proliferative and progressive with no spontaneous regression. mTOR signaling drives the disease, and that is the scientific basis for ketoran rapamycin for this disease. So, the longer a patient waits, the deeper and wider the disease can spread, and the harder it becomes to treat. As the Boston Children's authors put it, early intervention should be considered because of their tendency to progress.

Treating early gives us a chance to change the course of this disease. Moving to our programs in development, cutaneous venous malformations is our next pivotal program. It is the most common vascular malformation with more than 75,000 estimated diagnosed patients in the U.S. and no FDA approved therapies. And ketoran rapamycin has the potential to be the first approved therapy. We remain on track to initiate our phase three study this quarter. We are currently in the midst of our regulatory interactions, and we plan to announce study initiation and the final study design once the study starts. The FDA has been a collaborative partner throughout our work in rare disease, and we value its engagement as we advance ketoran rapamycin for patients who have no approved therapies.

The program has fast track designation and there is significant overlap with the physicians who treat microcystic lymphatic malformations. We plan to pursue a supplemental NDA building on our planned launch in microcystic LMs. As a reminder, in our positive phase 2 TOIBA study, 73% of patients improved on the CVM IgA at week 12. The 24-week data, presented at PEDRA in October, showed additional improvement between week 12 and week 24 on multiple endpoints and a reduction in disease severity and bleeding in pediatric patients after treatment. Our next program is clinically significant angiokeratomas, which we see as an under-recognized market opportunity. I spoke earlier this week with Dr. Jim Treat, the senior pediatric dermatologist at Children's Hospital Philadelphia, and our incoming chief medical officer, who commented on how these patients are highly symptomatic, and how this is an under-recognized disease.

The lesions bleed with minor friction and because the dilated vessels sit at the top layer of the skin, the bleeding can be startling and lead to firm, painful clots. On the genitalia, lesions can bleed during sexual activity, which carries real stigma. That sensitive location also limits today's destructive options. treatments. Angiokeratomas are a type of superficial lymphatic malformation, and these patients are often seen in the same vascular anomaly clinics that treat microcystic lymphatic malformations and venous malformations. There are no FDA-approved therapies for the more than 50,000 estimated diagnosed U.S. patients, and the FDA granted fast-track designation in December 2025. We expect top line results from our phase two LOTUS study in the second half of 2027. LOTUS is a 12-week baseline controlled study of once-daily topical rapamycin in about 15 patients.

And we are seeing strong enrollment momentum and site engagement. Thank you to our incredible clinical and clinical operations team. for leading this. Validating our view of this opportunity, market research with 50 physicians found that if approved, 96% would incorporate topical rapamycin into their practice. Turning to our second Keturin product candidate, Keturin-Petavastatin for disseminated superficial actinic porokeratosis, or DSAP. DSAP is a chronic, progressive, and precancerous skin disease with no FDA-approved therapies. Ketoran Pitavastatin directly targets the Mevalonate pathway that causes DSAP, making it the first potential pathogenesis-directed therapy for this disease. We continue to make strong progress.

Working with Dr. Keith Choate, who will serve as the study PI, and Dr. Leahy Atsumoni at Yale, we established pharmacodynamic proof of principle, showing that pitavastatin reversed hyperproliferation in a human porokeratosis cell model, and we plan to publish these findings in a future manuscript. We have completed formulation development and multiple IND enabling toxicology studies, and we have licensed a US patent from Yale and filed additional IP. We remain on track to initiate the phase three study this quarter, and interest is already strong, with more than 90 unsolicited patient requests about this trial. The market is also larger than we expected. A new claims analysis presented at Fall Clinical Dermatology in October identified approximately 155,000 diagnosed U.S. DSAP patients. And torim-pitavastatin has the potential to become the first FDA-approved therapy and standard of care for these patients.

Matthew Korenberg

Matt will now provide an update on the finances. Matt? Thanks, Jeff, and good morning, everyone. The third quarter marked a transition.

Unknown Speaker

point for Palvela. We completed our NDA submission at the end of August, and last week, FDA accepted the application, granted priority review, and set a PDUFA target action date of February 28, 2027. The.

Matthew Korenberg

Team's focus and my remarks this morning center on one thing, making sure we're ready financially and operationally to launch Keturin Rapamycin in the first half of 2027, if approved. As of the end of Q3, Pelvela had 236.7 million in cash, cash equivalents, and short-term investments, compared with approximately 250 million at the end of Q2 2026. The lower cash balance reflects over 16 million of cash expenditures offset by 2.6 million of interest income and the proceeds received from our FDA Orphan Products Grant. Research and development expenses for the third quarter were 10.8 million compared to 6.5 million in the third quarter of 2025. The increase was primarily a result of CMC activities, completion of our NDA submission, our Phase II LO2 trial in angiokeratomas, and increased headcount. G&A expenses were 11.9 million compared to 3.6 million a year ago, reflecting increased headcount overall, with commercial and medical affairs hiring being by far the largest portion of that spend, and an increase in other pre-launch activities and general expenses associated with public company activities. That loss was 24.6 million, or $1.70 per share, compared to a net loss of 11.3 million, or $1.03 per share, in the third quarter of 2025.

The Q3 2026 net loss includes 4.5 million of non-cash charges related to our Ligand royalty agreement. Our cash expenses for 2026 have been below our previous expectations, and it's likely that the full year will come in below our previous guidance. That said, we do expect the fourth quarter to be our largest investment to date as we ramp up hiring and pre-commercial activities. Within the 70 overall commercial and medical affairs team members that Ashley mentioned, we continue to plan for approximately 40 frontline sales reps, and we expect to have the team in place about two months ahead of the PDUFA date. We're also spending to build launch inventory. As we get our commercial infrastructure built across the organization and we begin trials in CVM and DSAP this quarter, any spend savings in late 2026 versus previous guidance will generally be pushed into early 2027. Our view of cash runway is unchanged.

Based on our current operating plan, our assumption of an approval and launch in the first half of 2027, and current consensus revenue estimates, we expect our existing cash to fund Pelvela deep into the commercial launch. That includes a fully funded standalone U.S. launch, the Phase III C-20. CVM program, our angiokeratoma and DSAP programs, and continued expansion of the Keturin platform this year and beyond. If Keturin rapamycin is approved, our cash balance provides our team the ideal environment to focus exclusively on executing a successful launch. Lastly, I wanted to offer a few points that may help with modeling as we approach a potential commercialization. First, closer to commercialization, we'll provide specific cost of goods guidance, but I wanted to mention two related points to consider now. Product costs incurred before approval will be expensed in R&D, translating to cost of goods sold levels running below our long-term rate for an initial period after launch.

In addition, please note that royalties owed to Ligand will not run through the cost of goods line. Expenses associated with the Ligand royalty payments will appear below the operating line. Second, the first few quarters in any first in disease launch are about wiring the system with revenue and underlying demand frequently decoupled. Each step takes time, including payers writing coverage policies, prior authorization pathways settling in, treatment centers building Qtorin rapamycin into their workflows and our patient services team moving patients from prescription to first fill. Commercial plans vary in how quickly they move, and Medicaid access can take at least a quarter, if not multiple quarters, to get in place. We expect early demand to be strong, with revenue realization in line with other first in disease launches reflecting the wiring period before revenue uptake accelerates. Third, we will share key launch metrics that we think are most informative and helpful once we're closer to being commercial.

We do not intend to provide specific 2027 revenue guidance, but we hope to provide the building blocks and metrics that will allow investors to model and track our progress. To sum up, we enter the final months before our PDUFA date with 236 million on the balance sheet, a launch plan that is fully funded, and a commercial and medical team that will be in place well ahead of our PDUFA date. With that, I'll turn the call back to Wes for additional comments prior to our Q&A. Thank you, Matt.

Wesley Kaupinen

I want to take a moment to summarize the potential market opportunities, anticipated market position, and potential for uptake in Palvella's four target clinical indications. The punchline summary is that each may represent a multibillion-dollar total addressable market in the U.S., This based on estimated diagnosed US prevalence in each disease and the expectation for orphan pricing upon approval. Importantly, our data-driven epidemiologic work indicates an estimated more than 30,000 diagnosed U.S. patients with microcystic LMs, more than 75,000 diagnosed patients with cutaneous venous malformations, more than 50,000 diagnosed U.S. patients with clinically significant angiokeratomas, and greater than 50,000 diagnosed U.S. patients with malformations. greater than 50,000 diagnosed U.S. patients with disseminated superficial actinic porokeratosis. Furthermore, for each of the diseases you see listed here, we believe, assuming continued clinical and regulatory execution by our team, that we're on a trajectory to potentially introduce the first FDA-approved therapy for each of these diseases. A first and only market position we believe has favorable uptake implications when compared to a more conventional biotech company strategy of pursuing incremental differentiation in competitive markets with well resourced entrenched incumbents. Specifically across all four indications, our supports that more than 80% of physicians surveyed indicated they would consider the Keturin product candidate targeted for that indication as a first-line therapy if approved. As Jeff highlighted earlier on this call, this slide will soon expand from four diseases to six.

We believe both new programs will reflect the hallmark characteristics of Paul Vela's approach. The potential to pioneer the first FDA-approved therapy in a serious rare disease combined prevalence and orphan pricing potential that make each opportunity unambiguously commercially attractive. In closing, at Paul Vela, our mission to serve patients, our vision to build a leading company addressing rare skin diseases and vascular anomalies, and our strategy of pioneering first in disease therapies have never been stronger. They're the foundation of what we will become multiple first-in-disease FDA-approved therapies for patients who today have no approved treatment options. We stand today on the cusp of our first potential FDA approval next quarter with a compelling late-stage rare disease pipeline extending well beyond MLM. an internal product development engine powered by QTORIN that we believe can generate novel therapies for many years to come. We believe this upcoming potential FDA approval will be a defining achievement for Palvella and demonstrate the potential of our Q-Torrent platform to deliver many more first in disease therapies in the years ahead. Thank you. Operator, you may now open the call for questions.

Operator

question and answer session. As a reminder, to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. Our first question comes from Josh Shimmer at Cantor Fitzgerald. Great. Thanks so much for taking the questions.

分析师问答

Joshua Schimmer

Very quick ones. First, you noted the importance of initiating therapy early for MLMs. How are you going to be able to educate the field about the importance of doing so? Number two, the CVM trial for ketor and rapamycin should be starting soon, but I think we're still waiting to hear on a final design. Where are you in terms of aligning that on that with the FDA? And then the last question is around the capital efficiency that you've shown. And just wondering how much of that is a function of the unique space that you're in? the ability to leverage 505B2 applications and fundamentally lower costs of dermatologic clinical development compared to perhaps the frugality of the company in light of what is still a somewhat higher cost of capital, since that will ultimately determine how the expense structure evolves over time. Thank you.

Wesley Kaupinen

Hey, Josh, thanks for being on this morning and thanks for your three questions. We'll go through each of those now. On number one, how are we going to educate the field in terms of early intervention? That's going to be a medical and scientific-led initiative from Paul Vela. We've hired Vabosa. Vimal Patel as our head of medical affairs. We now have a medical affairs team under Vimal and that team day in and day out is already in the field. working with those 400 centers that represent about half the market, as well as working with the additional Tier 2 and Tier 3 parts of the market. We've also recruited, Jeff highlighted, Dr. Jim Treat. Dr. Treat has been the Senior Pediatric Dermatologist at Children's Hospital Philadelphia and really has led their efforts on the dermatology side of their vascular anomalies clinic.

So we're making sure that we bring in this top talent. We have a scientific and medical discussion that's being led with of the market and then at approval course that's going to be augmented by the incredible commercial team that Ashley has recruited. Jeff will speak out here momentarily but also we have a steady flow of publications and science that we put out even recently to demonstrate large effect sizes and our young populations in the Selva study. Those posters are publicly available on our website and credit to our ClinOps, ClinDev, and MedAffairs team for the great work they've done there. On cutaneous venous malformations, we're in the midst of those regulatory interactions now and we plan to announce the study initiation, the final study design. Once the study starts, we expect that to be this quarter. When we announce, we expect to share things like the study design, the sample size, the trial endpoints, and and the duration of that clinical study.

And again, we're appreciative, as Jeff mentioned, of the collaborative dialogue that we've had with the FDA, including the fast track designation that they've granted for this program. On capital efficiency, I think that starts with a management philosophy above all, which is, you know, our goal is to flush out and mitigate as much risk as we can on the smallest amounts of capital. That's always been the goal. We view that the capital we have should be deployed towards our R&D and commercial engine. We run lean, our facilities are lean here in Wayne. Feel free to come visit us. We've got two to three people piled into each office here. It's a startup entrepreneurial culture and it's one that's being replicated by the commercial and medical teams that we've hired.

There are also, and I appreciate you calling them out, advantages we believe to the market 505(b)(2) program. That's a program I'm very familiar with from my time at Insmed and clearly our first program here with ketor and rapamycin is leveraging that program as well. Jeff, I want to open it up to you and Ashley to comment on the first part of Josh's question around early intervention.

Jeffrey Martini

Yes, so for early intervention, you know, it's really about disease education, and we're going to take a strong medical affairs approach. So, we find that clinicians really respond well to data. So, showing them the publications, explaining the genetics, explaining the pharmacokinetics of ketor and rapamycin, how we're able to deliver high concentrations. at the site of pathophysiology, and then if you can turn off this over-activated pathway, you can really change the clinical disease course. That'll be a key initiative, both medical affairs and attending medical conferences next year and throughout the launch.

Unknown Speaker

Thanks, Jeff. I'll just add that in speaking with clinicians who treat a lot of microcystic lymphatic malformation, especially patients who are older, including adults, they see the effects of the lifelong impact of the disease and the way that it can ravage a patient's tissue. So, there's a lot of. alignment already from the physician community on the importance of treating early. Josh, I want to add one point to your third question on capital efficiency.

Jeffrey Martini

about what we do and I really think that this the 505 b2 pathway has some efficiencies when we take the molecules we don't have the same pharmacology risk of a new chemical entity so in our early stages clinical trials because no one's ever run these studies before well really what we're looking at is what is clinically meaningful differences what are the right endpoints what are these endpoints that change to try out to interaction with the Ketoran product but we don't need to de-risk to see if the molecule is working or not so that really saves us a lot of time in our early stage.

Matthew Korenberg

clinical development. Matt here. The last point on capital efficiency, really the only thing I'd add is our QTORUM platform really allows us to operate in a much more capital efficient manner. We can leverage all the historic knowledge and expertise and know-how we have. from our QTORUM platform as we develop each new program. So developing the next program is far more capital efficient than others' typical development.

Joshua Schimmer

Thanks for those comprehensive answers.

Operator

Our next question comes from Ritu Baral at TD Cowen.

Ritu Baral

Good morning guys, thanks for taking the question. I have a couple, they're all commercial because there's a lot to ask about. One, the field force, Ashley you mentioned that you had 70 people ready at launch and then I think later this year Matt, you mentioned there were 40 frontline reps. Can you break out sort of that delta of 30? Are those MSLs? Are they reimbursement support? How many of them are in-house hub and going to be devoted to reimbursement support. And then my second question was about the shape of the launch and what your learnings in the field force are telling you. Do they support the slides, I'm sorry, the numbers on slide 20 because our calls with doctors suggest the MLM numbers could go up. with education, are you expecting like a bolus or at least a bolus of interest? And do you have ideas on the cadence that patients come in to see their doctors and if that could change with a new therapy?.

Wesley Kaupinen

Thanks for those questions, Ritu. On the field force, the slide notes the more than 70 that we expect to be in place at the time of launch. Matt mentioned it. Forty of those will be frontline field sales reps. The remaining 30 are going to be our sales leaders, which are now in place, and we're at the meeting in Fort Lauderdale that I mentioned. That includes area vice presidents, as well as rare disease directors that are across the country. We also, as part of that 30, have a MedAffairs team. team of medical directors as well as Vimal who's leading that group, patient access liaisons, field marketers, as well as inside sales. So I appreciate you asking the question because hopefully you get a sense of the resources that we're putting against the launch and all that is in the spirit of Bill building a world-class service organization to pair with what we think is a product that demonstrated 95% efficacy on the primary endpoint in our Phase 3 study. I'll let Ashley speak to the cadence of the launch.

We don't anticipate a bolus. We think this will be a steady growth. quarter over quarter. It's a large market, different than some of the recent orphan launches, which have more of an ultra-orphan profile, but pass it over to Ashley to add any color. Thanks, Les, and thanks, Ritu. Good morning.

Unknown Speaker

I have spent a lot of time in the field at medical meetings and meeting with he and dermatologists over the last month. I was in Vienna at the EADV meeting. I was in Las Vegas at Fall Clinical Dermatology, and I was in Florida at the LEARN Lymphatic Education and Research Network meeting last month. So I've had a lot of face time with clinicians over the last few weeks. My takeaway from that is that clinicians are, they find our clinical profile to be very compelling. They have confirmed that there is an unmet need and they do not plan to watch and wait once our product is available. So there's that urgency to treat that we represented on the slide. earlier.

The other point that has really come through in those meetings is how much they find the Cutora technology to be a major differentiator. So, there's a lot of excitement about how the Cutora technology has created a profile that has efficacy but also seems seems to have a great safety profile and they're excited about how we could use the Q-Torrent platform in other diseases and with other APIs. So, there's a lot of clinician excitement there. I don't know if that answers your question about supporting the numbers. It does. And I know you also had a question. Yes, go ahead.

Ritu Baral

Oh, I was going to say, if I could sneak in one last question about what you're learning as far as the reimbursement split of the MLM market, public-private.

Wesley Kaupinen

Yes, thanks for that question. We'll have some more of that data available over to you as we get closer to launch. This is a payer mix that we expect to be heavily weighted towards commercial and also Medicaid as well.

Operator

Our next question comes from Greg Suvenive at Mizuho.

Ryan Ries

Good morning, everyone. This is Ryan Reese on today for Greg. Just wanted to ask a little bit about driving awareness among physicians and patients in your early outreach efforts, especially your digital awareness campaign. Can you tell us about the channels that you'll be using to reach out to both of those groups and what can you tell me about those efforts so far and how do you see those efforts steering patients and physicians towards Valturna and Tekturna HCT?.

Wesley Kaupinen

Thank you. Great. Hey, Ryan, thanks for being on and appreciate the question. So, Those channels are going to be field-based. They're going to be digital, which Ashley will speak to. We've also had a significant presence at recent medical congresses. That's only going to intensify as we move closer to launch. And through the launch, I was fortunate enough to be able to attend and the Pediatric Derm Research Alliance meeting in my hometown of Alexandria, Virginia last month. first hand our team educating physicians with our Beyond MLM disease state awareness campaign. Really proud of what we've accomplished here in terms of partnering with several patient advocacy groups to launch that campaign.

We've been pleased with the opt-in rates that we're seeing thus far to that, which has exceeded our internal forecast. And Ashley will provide additional color around our efforts to do so. drive awareness in advance of launch.

Unknown Speaker

Thanks Vasan, and thanks for the question. I'll just add that in terms of interacting with patients, we've had the great opportunity to attend Arkansas Children's Vascular Anomalies Family Day. Recently, the vascular birthmarks foundation had an event in New York that they invited us to partner with them. and there are many other vascular anomaly family days that we're planning to participate in and that's a nice way for us to support the community and And then in terms of digital outreach, we have a robust digital plan focused on educating patients about the disease and encouraging them to seek care from a clinician. And we're advertising on all of the places you would expect, including Meta, Reddit, Google, and others.

Operator

experienced team in marketing that's leading that effort. Great. Thank you. Our next question comes from Annabel Samimi at Stiefel.

Annabel Samimy

Hi, all. Thanks for taking my questions and congrats on the progress. So just going back to the launch, you had talked about, you know, thanks for the color around the reception from physicians and the identifying, identification of new prescribers through your LLM model. I guess, if from that perspective, this LLM model that identified these new prescribers, how does that change the breadth of physicians that you could be potentially targeting over time? I know you talked about 450, and change physicians. Could this potentially expand the breadth of your infrastructure and in terms of identifying also not only just physicians but more patients? And are there any new orphan disease analogs that you would point to that you feel comfortable using as a good benchmark? And then separately on CVM, um, I know that you're still talking to the FDA about the study design. Um, maybe you can provide some color around how FDA views CVM differently from MLM that it continues to be an ongoing discussion and how this trial proceeds. Thanks.

Wesley Kaupinen

Yes, good morning, Annabelle, and thanks for your questions. Before I pass it over to Ashley, I just want to answer the first part of your question, which is we believe that infrastructure we highlighted on the call earlier today of more than 70 is the existing infrastructure that we'll need. We will not need to expand. And in the early part of the launch, even with some of the new patients and new treaters we think we're identifying outside of those claims analysis, that can be handled by this infrastructure that is largely in place and will be fully in place, as Matt mentioned, about two months before the launch. to promote at approval to all three segments of the market. There's So it's about 400 centers that we believe manage about 15,000 patients. So this is an unusual level of patient concentration for a rare disease that exists because of this inorganic, this organic market development that's occurred at the vascular anomaly centers here over the last two decades. Before I pass it over to Ashley to give more color, we've talked about launch analogs in the past, certainly Aracase from Insmed, a drug I have experience with on a pre-market basis, Ashley's experience with Oxervate.

These drugs that are first in disease launching in new markets we think are very good analogs. In terms of your question as it relates to CVM, you know, there are some similarities between microcystic lymphatic malformations and cutaneous venous malformations. We think both of those diseases are serious, rare. There's no spontaneous regression. And the diseases are progressive. And really importantly, there's a nice base of real-world clinical evidence supporting the use of mTOR inhibition and rapamycin. In terms of where we are from a regulatory perspective, we're currently in the midst of those regulatory interactions. We expect those to conclude very soon here, at which point our goal is to urgently start We want to bring this drug to patients with the same urgency that we are with microcystic lymphatic malformations, and we expect to soon have that study design and be able to announce that to the market at the time of initiation.

Ashley.

Unknown Speaker

I'll just reiterate that the team size that we described with approximately 40 frontline salespeople and about 70 people in total in the field is sufficient to cover the opportunity that we believe we've identified, and that includes the group that we have worked on using the LLM model and some of the analogies. along with. Okay, great. Thank you.

Operator

Our next question comes from Alithea Young at William Blair. Thanks for taking my question, guys, and congrats on getting to the milestone of a very fast time, which also reiterates your pipeline and the progress there. So a couple questions. I don't know when that's a version of this, but I got I kind of wanted to just understand like when you think about there's numbers for MLM they're like 45 to 90 and then you know you're talking over 30 like, you know, can we get a little bit more granular in reconciling like kind of what what's the differential, um, like are these people, you know, just that they're just not found and they're in the community or something? That's my first question My next question is, when we think about, like, your pipeline and some of the bigger programs beyond MLM, like, how do we think about, like, in phase one, like, de-risking those programs? Do you think it requires bigger studies in a way to kind of get to, you know, potentially even faster answers in late-stage development? And then I'm always intrigued by... the topical stat and DSAP. So I just wanted to kind of get a little bit more on, you know, there seems to be like, JAMA papers out there about kind of development strategies. Is that how we should frame it and think about it? Thank you.

Wesley Kaupinen

Great. Hey, Alethea. Good morning. Thank you for being on. Jeff will address the question around the topical statins. In terms of your question on microcystic lymphatic malformations, I think you're I've been working for many years in rare disease epidemiology. And, you know, it's not a precise science. You really have to triangulate in these diseases where there's no approved therapies to estimate what the diagnosed prevalence is. So we invest in those methods. We've published on the results of those.

The first thing we did in microcystic lymphatic malformations is we ran a real-world occurrence study that's published in Orphanet, which projected 79,000 diagnosed patients with microcystic manifestations of their lymphatic malformations. That was the U.S. diagnosed prevalence number. You mentioned the claims work that Ashley has done. of 45,000 to slightly north of 90,000. Our 30,000 number reflects management philosophy, similar to what Josh was asking earlier, which is we think we should anchor on the lower end of our ranges, embed conservatism in those numbers. We may find when we go to launch and you know this from all of your orphan experience that when you have the first company step into a disease, oftentimes it can really elevate disease state awareness. It can improve diagnosis rates and those numbers can grow over time. we're going to stick with our greater than 30,000 number, knowing that there could be patients beyond that as Ashley has highlighted. In terms of how we de-risk, Q-Torin programs.

Thanks for that question. I'll point to the evidence of the Phase II microcystic LM study as well as the Phase II TOIVA study in cutaneous venous malformations. We're oftentimes going into our Phase II studies with some early real-world evidence that the do have clinical activities, and they have shown that in early proof-of-concept studies. So we're building on a human clinical base of evidence many times before we apply Q-Torin and run our Phase II studies. What we showed in our LM Phase II study, sample size of N equals 12, we had 100% of patients on the clinician global impression of change that were much or very much improved. And our TOIVA phase two study, we had 100% of patients on the clinician global impression phase two study, we had 73% of patients, again, in a disease where there are no FDA approved therapies, respond on our cutaneous venous malformations investigator global assessment. We have a similar strategy on angiokeratomas where we think we can really get that early answer on an efficacy signal and call it a 10 to 15 patient clinical strategy. So Jeff likes to refer to this as the Palvella playbook.

We think that's a reasonable sample size in a rare disease to make that go, no-go decision. for making that phase three investment moving into the later stages of development. On the topical statins, I'll pass it over to Jeff to address your questions there.

Jeffrey Martini

We're really excited about the Qtorin pitavastatin program for DSAP. The team here at Paul Vela is excited to get the study started later this quarter. We're hearing a lot from study investigators who are reiterating the unmet need. And as I mentioned in the video, earlier in the call, the patients are reaching out to us. They're unsolicited patients. We've had greater than 90 patients reach out to us inquiring about the trial and reiterating the unmet need. One of the things that we do with our development programs is start by talking to the patients. We've already conducted qualitative interviews to understand the burden patients, you know, What are the key signs that are critical to them? And in working with our clinicians, we design endpoints that we believe can move with the cuturin-petavastatin program.

Our phase two strategy will be testing a lot of different endpoints, and we'll see which ones are most sensitive to treatment change with cuturin-petavastatin And then ultimately, that design of that phase two will inform the design of a larger phase three trial, which in our Paul Vela playbook that Wes mentioned is our pivotal phase three.

Unknown Speaker

Great. Thank you, guys. I like that Paul Vela playbook. That was a good one.

Operator

This concludes the question and answer session. I would now like to turn it back to Wes Haubner for closing remarks.

Wesley Kaupinen

Great, thank you, Operator. And thank you all for your thoughtful questions and your strong interest in what we're building at Palvella Therapeutics. We are all eyes forward here to February 28th of 2027. That happens to serendipitously be Rare Disease Day. And we're all striving for that to be the day that we achieve our first of what we really want to be, many FDA approvals for these deserving patients that today are living with serious rare skin diseases and vascular anomalies. We look forward to updating all of you on our continued progress with both our launch planning. Thank you. Especially for being on today and the advancement of our deep rare disease pipeline. Operator, you may now conclude the call.

Have a great day, everyone.

Operator

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

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