Palvella Therapeutics Inc (PVLA) 2025 Q4 法說會逐字稿

Good day and thank you for standing by. Welcome to the Palvella Therapeutics full year 2025 financial results conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

各位好，感謝您稍候。歡迎參加 Palvella Therapeutics 2025 全年財務業績電話會議。(接線員指示) 請注意，今天的會議將被錄音。

I'd now like to hand the conference over to Bohan Wei, Vice President of Corporate Development. Please go ahead.

現在我想把會議交給企業發展副總裁 Bohan Wei。請開始。

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 Investors section of our website at www.palvellatx.com.

謝謝，接線員。各位早安，感謝您參加 Palvella Therapeutics 2025 全年財務業績與公司最新進展電話會議。提醒各位，詳述今日公告的新聞稿可於我們網站 www.palvellatx.com 的「投資人」專區查閱。

On today's call, you will first hear from Wes Kaupinen, 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 line for Q&A.

今天的會議將先由我們的創辦人兼執行長 Wes Kaupinen 發言；接著是我們的首席科學官 Jeff Martini 博士；以及我們的財務長 Matt Korenberg。在開放問答之前，Wes 將回來做結語。

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.

在開始之前，請注意今天的發言可能包含前瞻性陳述，涉及我們的研發計畫、法規策略、商業化規劃以及財務展望。這些陳述係基於目前的假設，並受各項風險與不確定性影響，可能導致實際結果與所述內容出現重大差異。關於這些風險因素的完整討論，請參閱我們向 SEC 提交的文件。

And now, I will turn the call over to Wes.

現在，我把電話交給 Wes。

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.

謝謝你，Bohan。2025 年是 Palvella Therapeutics 的里程碑之年，使我們更接近實現願景：打造領先的罕見疾病生物製藥公司，專注於研發並商業化用於嚴重罕見皮膚疾病與血管畸形的「疾病首創」療法。

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.

這要歸功於 Palvella 團隊、我們的科學與臨床合作夥伴、病友倡議夥伴，以及我們所服務的罕見疾病患者。我們達成多項創造價值的里程碑，包括第一，公布皮膚靜脈畸形（cutaneous venous malformations）的正向第二期數據；該數據支持我們推進此計畫，近期向 FDA 提交突破性療法（Breakthrough Therapy）認定申請，並展開關鍵性第三期研究。

Number two, surpassing our targeted 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.

第二，基於醫師與患者需求，以及我們臨床營運團隊的強力執行，我們在微囊性淋巴管畸形（microcystic lymphatic malformations）的第三期 SELVA 研究中，入組人數超越原先目標。

Number three, expanding our rare disease pipeline with the addition of two new programs, QTORIN rapamycin for clinically significant angiokeratomas and QTORIN pitavastatin for porokeratosis.

第三，新增兩項新計畫，擴充我們的罕見疾病產品線：用於具臨床意義血管角化瘤（clinically significant angiokeratomas）的 QTORIN 雷帕黴素（rapamycin），以及用於汗孔角化症（porokeratosis）的 QTORIN 匹伐他汀（pitavastatin）。

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 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.

第四，延攬頂尖人才加入高階管理團隊，包括任命 David Osborne 博士為首席創新官，以及 Ashley Kline 為首席商務官。第五，延續我們與 FDA 的合作，特別是 FDA 的孤兒產品發展辦公室（Office of Orphan Products Development）；該單位於 2025 年以額外的非稀釋性資金支持我們的 SELVA 第三期研究。第六，擴充我們的智慧財產權組合，取得兩項 QTORIN 雷帕黴素的美國專利，強化我們多層次的專屬性策略；第七，為 2025 年畫下句點的是，我們在具臨床意義血管角化瘤適應症上取得 FDA 的快速通道（Fast-Track）認定，這是 Palvella 第三個獲得快速通道認定的計畫。

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.

這股動能——來自 Palvella 團隊專注且紀律化的執行——延續到 2026 年。我們在今年稍早公布了微囊性淋巴管畸形之 SELVA 第三期研究的正向數據；我們相信，若 QTORIN 雷帕黴素獲准，將有望成為微囊性淋巴管畸形患者的一線標準治療（standard-of-care）療法。

With a significantly strengthened balance sheet as the result of a USD230 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 stand‑alone US launch, and concurrently advance the rest of our rare disease pipeline.

由於本季稍早宣布完成 2.30 億美元融資，我們的資產負債表已顯著強化；Palvella 現已具備良好條件，推進 QTORIN 雷帕黴素在微囊性淋巴管畸形的近期 FDA 核准、推動在美國的獨立上市（stand-alone US launch），並同時推進其餘罕見疾病產品線。

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. 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.

Palvella 有別於其他公司的關鍵，首先在於我們的公司策略：在尚無 FDA 核准療法的嚴重罕見疾病領域，同時推進研發與商業化。我們相信，這些疾病具有明確且高度未被滿足的醫療需求。我們刻意聚焦於我們能作為先驅、推進目標為「疾病首創」的療法之疾病，為受這些罕見疾病所苦的患者與家庭帶來希望。

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.

我們的目標是運用專有的 QTORIN 平台——這是我們內部的產品開發引擎，用於在一個聚焦的罕見皮膚疾病與血管畸形子領域中，可重複地開發新型外用（topical）候選產品；這些疾病具備清楚的生物學機制，且已有人體概念驗證（proof-of-concept）數據，可用以驗證特定的分子作用途徑。

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 and growing foundation of real‑world human clinical evidence upon which Palvella can build.

此研發策略的例證之一是微囊性淋巴管畸形：這是一種由 PI3K 突變所致、定義明確的疾病，其中 mTOR 的過度活化推動疾病進展；而雷帕黴素在真實世界的人體臨床證據方面已具備龐大且持續成長的基礎，Palvella 可在此基礎上進一步發展。

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.

我們在皮膚靜脈畸形、血管角化瘤，以及播散性淺表性日光性汗孔角化症（disseminated superficial actinic porokeratosis）上採取類似做法；並預期在年底前再新增兩個疾病至產品線，使我們目標治療的疾病數量達到六個。

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‑plus months.

整體而言，透過本投影片所概述的方法，我們的目標是在進入競爭較少、相較傳統且更競爭市場具有更有利商業動態的市場同時，降低取得 FDA 核准所需的時間與資本。約有 600 種罕見皮膚疾病，其中 98% 連一項核准療法都沒有；我們看見充足機會擴大產品線，並複製我們聚焦的罕見疾病研發模式。接下來我想說明，我們近期的執行如何在未來 12 個月以上轉化為多項預期的高影響力里程碑。

We entered 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 the second half of 2026 with a potential FDA approval targeted for the first half of 2027. 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.

我們在 2026 年初，無論在主力計畫或持續擴張的產品線方面，都處於極佳位置。先從微囊性淋巴管畸形開始，我們已取得正向第三期數據，並按計畫於 2026 年下半年提交 NDA（新藥申請），目標在 2027 年上半年取得 FDA 可能的核准。在皮膚靜脈畸形方面，繼正向第二期數據之後，我們預期在今年第二季取得突破性療法認定的決定，並計畫於今年下半年啟動第三期研究。

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 second half 2026. In DSAP, we have developed our QTORIN pitavastatin formulation, filed IP, and we expect to initiate a Phase 2 study in the second half of 2026. More broadly, we continue to expand the QTORIN pipeline, with a fourth indication for QTORIN rapamycin expected to be announced in the second half of this year, and a new QTORIN product candidate, our third, also expected to be announced in the second half of this year.

在具臨床意義血管角化瘤方面，我們已取得 FDA 的快速通道認定，並正提前推進至第二期研究啟動；目前預期第二期將於今年第二季啟動，較我們先前指引的 2026 年下半年更早。在 DSAP 方面，我們已完成 QTORIN 匹伐他汀配方開發、提交 IP，並預期於 2026 年下半年啟動第二期研究。更廣泛而言，我們持續擴充 QTORIN 產品線；預期今年下半年將公布 QTORIN 雷帕黴素的第四個適應症，並同樣預期於今年下半年公布一項新的 QTORIN 候選產品——也就是我們的第三個產品候選。

It 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. 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.

這使 Palvella 得以進入一個催化劑密集的時期，其中包括我們可能獲得首個 FDA 核准；我們相信，這可透過規劃中的補充 NDA 申請，為適應症擴展至其他由 mTOR 驅動的皮膚疾病建立一條精簡且高效率的途徑。接下來我想談談我們的主力計畫：用於微囊性淋巴管畸形的 QTORIN 雷帕黴素。根據理賠分析與已發表文獻，在美國估計有超過 30,000 名已確診患者；我們相信微囊性淋巴管畸形代表一個重大的、數十億美元規模的商業機會。

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.

基於第 3 期 SELVA 試驗結果、我們第 2 期研究的結果，以及我們所進行的市場調查，我們相信 QTORIN 雷帕黴素在可能獲得 FDA 核准後，有望成為微囊性淋巴管畸形的一線與標準治療，透過抑制致病的 mTOR 路徑直接針對疾病的根本生物學機制，並且在相關的致病皮膚組織中發揮作用。在臨床上，我們已在兩項前瞻性試驗中證實具強勁的治療效果，並呈現良好的安全性與耐受性，支持在此患者族群中的療效與長期使用的潛力。

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. 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.

在目前已取得正向第 3 期數據的情況下，我們正按計畫於 2026 年下半年提交 NDA，並在獲核准的前提下，可能於 2027 年上半年取得 FDA 核准。我想重點說明我們上個月公布的第 3 期 SELVA 數據。我們的團隊建立了基準情境與上行情境，並以臨床研究結果可如何轉化為對患者生活具有意義的改善、同時支持具吸引力的商業機會為依據。SELVA 在各個面向都超越了我們預先設定的上行情境。

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. 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.

在主要終點——微囊性淋巴管畸形研究者整體評估（investigator global assessment）——我們觀察到高度具統計顯著性的結果，遠高於我們的上行情境。重要的是，在完成療效評估期的患者中，95% 有所改善，且 86% 為「大幅改善」或「非常大幅改善」。盲態的關鍵次要終點 MLM‑MCSS 亦達到高度統計顯著。就安全性而言，QTORIN 雷帕黴素在兒童與成人中皆具良好耐受性，支持各年齡層進行慢性給藥的潛力。同樣重要的是，研究留存率異常強勁：完成第 24 週的受試者中有 98% 選擇進入延伸期，支持療效持久性與持續治療效益。

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. 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, with the pre‑NDA meeting anticipated in the second quarter of 2026.

SELVA 的結果超出我們 Palvella 的期待，不僅在療效上，也在持久性與安全性上。最終，我們相信這些結果可為所有年齡層、被診斷為微囊性淋巴管畸形的患者帶來具意義的影響。就法規進展而言，我們規劃的 NDA 提交正按計畫推進。我們近期已向 FDA 皮膚科與牙科處（Division of Dermatology and Dentistry）提交 pre‑NDA 會議申請，預計 pre‑NDA 會議將於 2026 年第二季舉行。

Notably, we are pursuing a traditional full FDA approval based on clinical endpoints, which differs from an accelerated approval, which relies upon surrogate biomarkers 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.

值得注意的是，我們正以臨床終點為基礎，尋求傳統的完整 FDA 核准；這不同於加速核准（accelerated approval），後者依賴可合理預測臨床結果的替代性生物標記（surrogate biomarkers）。為我們 NDA 申請提供堅實基礎的，包含我們具高度統計顯著且具臨床意義的第 3 期 SELVA 數據，以及第 2 期研究結果。

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 age 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, 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.

我們與此疾病領域的醫師關鍵意見領袖（KOL）的互動，以及對疾病進展特性的理解，顯示及早治療介入可能改變疾病的自然病程。因此，我們的目標是爭取標籤（label）涵蓋 3 歲以上患者。我們先前已獲授予突破性療法（Breakthrough Therapy）、快速通道（Fast‑Track）與孤兒藥（Orphan Drug）資格認定；我們也計畫採取 505(b)(2) 途徑，這可能使我們得以利用 FDA 既有的審查結論與雷帕黴素既有的證據體系，作為更精簡的開發與法規策略的一部分。

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

我們持續與 FDA 孤兒產品開發辦公室（Office of Orphan Products Development）密切合作；該辦公室除提供非稀釋性資金外，也預計將參與我們預期於今年第二季與審查部門（Review Division）舉行的 pre‑NDA 會議。這些要素支持我們在 2026 年下半年提交 NDA，並在 2027 年上半年取得 FDA 核准的可能性。談到商業機會，我們相信 QTORIN 雷帕黴素已為一個極具吸引力的孤兒藥上市（orphan launch）做好良好布局。

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.

微囊性淋巴管畸形是一種嚴重的罕見疾病，存在高度未被滿足的醫療需求，目前醫師與患者尚無任何 FDA 核准的治療可用。目前已存在龐大的已確診患者族群，且相當比例的患者集中於專門的血管異常中心。我們也持續感受到關鍵意見領袖對 QTORIN 雷帕黴素潛力的高度熱忱，其中許多人參與了我們的第 3 期與第 2 期研究；我們相信這份熱忱可在可能獲得 FDA 核准後，促成強勁的採用曲線。

From a pricing and reimbursement perspective, we anticipate orphan pricing consistent with our previous guidance of USD100,000 to USD200,000 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, reinforcing the potential for QTORIN rapamycin to become a first‑line standard‑of‑care therapy for individuals with microcystic lymphatic malformations.

在定價與給付（reimbursement）方面，我們預期採用與先前指引一致的孤兒藥定價，即每位患者每年 100,000 至 200,000 美元。這一切均由正向的第 3 期數據所支持；數據顯示具良好的風險—效益概況，特別是相較於目前這些患者可用治療選項的稀缺性，進一步強化 QTORIN 雷帕黴素成為微囊性淋巴管畸形患者一線標準治療的潛力。

We have made significant progress in building the foundation for a potential first‑half 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 USD1 billion in US sales a few short years after launch.

我們在建立 2027 年上半年可能商業上市的基礎方面已取得重大進展。首先在領導團隊方面，我們已組建一支經驗非常豐富的商業團隊。去年，Ashley Kline 加入 Palvella 擔任商務長（Chief Commercial Officer），而我們近期也延攬 Jennifer McDonough 領導市場准入（market access）與患者服務。Ashley 是罕見疾病領域的商業資深人士，曾主導 Oxervate 的上市——這是一種用於神經營養性角膜炎的創新外用療法，且在上市後短短數年內，其美國銷售額已超過 10 億美元。

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 key medical meetings.

上週，我們歡迎 Jennifer McDonough 加入 Palvella 團隊。Jennifer 被廣泛視為罕見疾病市場准入與患者服務領域的頂尖主管之一。她的貢獻對 Krystal Biotech 推出 Vyjuvek 的成功至關重要；Vyjuvek 是首個針對營養不良型表皮分解性水皰症（dystrophic epidermolysis bullosa）這一嚴重罕見遺傳性皮膚疾病的同病種首創（first‑in‑disease）外用療法。同時，我們也在擴建醫學事務（medical affairs）能力，醫學科學聯絡員（medical science liaisons）的招募已在進行中，並積極參與各項關鍵醫學會議。

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 approximately 1,500 new patients diagnosed each year. We're 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 roughly 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.

重要的是，我們也正以強而有力的方法推動病患辨識與市場開發。我們估計美國有超過30,000名已確診病患，且每年約有1,500名新確診病患。我們將初期資源聚焦於價值最高的中心與治療醫師，特別鎖定約400家高量中心；我們估計這些中心約代表美國已確診族群的50%。整體而言，我們已招募頂尖人才並進行重大投資，以確保我們已為QTORIN rapamycin在微囊性淋巴管畸形（microcystic lymphatic malformations）的美國成功上市做好充分準備。

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. We reported positive Phase 2 data in December of 2025 with statistically significant results across several clinician and patient‑reported outcomes.

接下來談我們用於皮膚性靜脈畸形（cutaneous venous malformations）的QTORIN rapamycin計畫，我先就此疾病的商業機會做一些說明。靜脈畸形是最常見的血管畸形類型，而皮膚性靜脈畸形代表一個龐大且長期被低估的市場機會；美國估計有超過75,000名已確診病患，且目前沒有任何FDA核准的療法。我們已於2025年12月公布正向的第二期數據，在多項臨床醫師與病患回報的結果指標上皆達到具統計顯著性的結果。

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. 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. In parallel, we're finalizing a Breakthrough Therapy designation application following a constructive preliminary advice meeting with the FDA earlier this quarter, in which our collaborator Dr. Denise Adams described the unmet need in cutaneous venous malformations and her experience in the Phase 2 study.

具體而言，73%的病患在CVM研究者整體評估（Investigator’s Global Assessment）上呈現改善，其中67%在第12週被評為「明顯改善」或「非常明顯改善」。這顯示在這項初步的第二期研究中，回應者比例高，且治療效益幅度大。我們目前正迅速推進至第三期研究，預期於2026年年中完成研究設計一致性對齊，並計畫於下半年啟動試驗。同時，我們也在完成突破性療法（Breakthrough Therapy）認定申請；本季稍早我們與FDA進行了具建設性的初步諮詢會議，會中我們的合作夥伴Denise Adams醫師說明了皮膚性靜脈畸形的未被滿足需求，以及她在第二期研究中的經驗。

In addition to the Phase 2 data, our Breakthrough application will include 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 continue to generate additional data through the ongoing Phase 2 treatment extension period with plans to present that dataset 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 and, assuming initial approval in microcystic lymphatic malformations, potentially advance through a streamlined supplemental NDA pathway.

除第二期數據外，我們的突破性療法申請也將納入病患質性訪談，以呈現該療法對其日常生活意義之重大性，並包含參與第二期研究之研究者的支持函。我們也持續透過正在進行的第二期治療延伸期產出更多數據，並計畫於今年稍晚在醫學會議上發表該資料集。整體而言，我們在皮膚性靜脈畸形的QTORIN rapamycin計畫，提供一個極具吸引力的機會，可擴展至更大的第二個臨床適應症；並且在微囊性淋巴管畸形獲得初始核准的前提下，可能透過更精簡的補充新藥申請（supplemental NDA）途徑推進。

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

接下來我把電話交給Jeff，他將介紹我們其他的研發管線計畫。Jeff。

Thank you, Wes. Our clinically significant angiokeratomas program represents our third clinical indication for the QTORIN rapamycin program. Our Phase 2 trial is ahead of schedule, with initiation anticipated in the second quarter. 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 rapamycin.

謝謝你，Wes。我們的具臨床意義血管角化瘤（angiokeratomas）計畫，是QTORIN rapamycin計畫的第三個臨床適應症。我們的第二期試驗進度超前，預計於第二季啟動。血管角化瘤是一種表淺性淋巴管畸形，並與微囊性淋巴管畸形在臨床與病理特徵上有重疊，包括相似的病灶形態、表淺血管受累，以及異常的淋巴生物學。這些病灶與mTOR訊號增強相關，且不會自發性消退。因此，使用QTORIN rapamycin鎖定此適應症具有強而有力的機轉與臨床合理性。

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. 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 QTORIN rapamycin into this indication through a supplemental NDA.

如同Wes先前在簡報中提到，且符合我們利用既有人體數據的策略，我們得以建立在已發表的概念驗證（proof-of-concept）資料之上，包括多篇病例報告顯示以適應症外（off-label）使用rapamycin可帶來初步臨床效益。具臨床意義的血管角化瘤是一個龐大且服務不足的適應症，美國已確診病患超過50,000人、沒有FDA核准療法，並且有機會透過補充新藥申請（supplemental NDA）將QTORIN rapamycin擴展至此適應症。

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.

QTORIN rapamycin可說是「一個產品中的一條管線」：我們的領先計畫—微囊性淋巴管畸形—正準備提交NDA並上市；皮膚性靜脈畸形計畫正推進至第三期；而具臨床意義血管角化瘤計畫的第二期研究已規劃且進度超前。在這三個初始適應症上，我們已在美國觸及一個具意義的病患族群，但仍有顯著的擴張機會。我們正積極評估其他由mTOR驅動、且符合我們高度嚴格篩選標準的疾病，並預期將隨時間持續擴大我們可服務的病患族群。

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.

此策略可透過運用相同分子與平台，並在多個適應症中鎖定共同的致病生物學，來實現高效率的開發。我們也正將管線擴展至rapamycin之外，推出用於播散性表淺日光性汗孔角化症（disseminated superficial actinic porokeratosis，DSAP）的QTORIN pitavastatin，這是我們第二個QTORIN計畫。DSAP是一種慢性、進行性且具癌前性質的皮膚疾病，表現為在日曬部位出現多發且逐漸擴大的病灶，造成顯著症狀，包括灼熱、搔癢與不適，並帶有惡性轉化風險。儘管如此，目前沒有FDA核准療法，而既有治療方式具侵入性、效果短暫，且無法處理疾病的根本生物學機制。

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. 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 the second half of 2026.

QTORIN pitavastatin是一種以致病機轉為導向（pathogenesis-directed）的療法，鎖定甲羥戊酸（mevalonate）途徑，具潛力成為DSAP病患的一線治療與標準照護。我們的方法有新興科學證據支持，包括我們近期在《Experimental Dermatology》發表的論文，強調真實世界的statin使用情況與治療缺口，以及我們在美國皮膚科醫學會（American Academy of Dermatology）的發表，展示疾病負擔。在我們公開宣布該計畫後，隨著我們準備第二期研究，我們看到病患主動洽詢的強烈興趣；該研究仍按計畫於2026年下半年啟動。

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.

用於DSAP的QTORIN pitavastatin凸顯我們在選擇符合高度嚴格標準之疾病上的紀律性做法，並結合QTORIN平台高效率開發以致病機轉為導向療法的能力。在把電話交給Matt之前，我想簡要強調QTORIN平台作為新產品開發引擎的優勢。我們採取以疾病為先（disease-first）的研發策略，投入大量時間辨識符合我們高度嚴格標準、且適合以標靶外用療法治療的疾病。

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 rapamycin.

我們目前已透過兩項正向的臨床讀出驗證該平台，包括我們的第三期SELVA試驗與第二期TOIVA結果。我們正運用QTORIN來擴大管線，以時間與資本效率高的方式，快速推進並測試多個分子。在QTORIN rapamycin預期獲准後，我們也計畫申請FDA平台技術（platform technology）認定。

As we look ahead, we expect to announce one new QTORIN program and one additional QTORIN 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.

展望未來，我們預期將於今年稍晚宣布一項新的 QTORIN 計畫，以及一項額外的 QTORIN 雷帕黴素適應症。QTORIN 代表一個已獲驗證且可擴展的引擎，用以提供「疾病領先（first-in-disease）」療法；我們相信這些療法能為患者帶來有意義的改變，並為股東創造長期價值。

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

接下來，我把電話交給 Matt，請他回顧我們的財務結果。

Thanks, Jeff.

謝謝你，Jeff。

Turning to the financials, Palvella ended Q4 with USD58 million in cash and cash equivalents as of December 31, 2025. Following our positive Phase 3 SELVA data, we completed an oversubscribed USD230 million public offering in February of 2026, bringing in USD215.8 million in net proceeds. With pro forma cash of USD274 million, this financing fundamentally strengthens our balance sheet and eliminates financing overhang as we enter the most important execution period in Palvella’s history.

接著談財務面，Palvella 於 2025 年 12 月 31 日止的第四季末，現金及約當現金為 5,800 萬美元。在我們公布正向的第三期 SELVA 數據後，我們於 2026 年 2 月完成一項超額認購的 2.30 億美元公開發行，帶來 2.158 億美元的淨募資款。以備考（pro forma）現金 2.74 億美元計，這次融資從根本上強化了我們的資產負債表，並在 Palvella 歷史上最重要的執行期到來之際，消除了融資不確定性（financing overhang）。

With this cash, and even before considering any potential revenue, we are now fully funded to advance our microcystic lymphatic malformations program through an NDA filing, an FDA approval, and, if approved, a US commercial launch. For QTORIN rapamycin in cutaneous venous malformations, our runway allows us to execute a Phase 3 program and subsequently complete an NDA filing. And for our QTORIN pipeline, we have the runway to support multiple Phase 2 data readouts from our existing and future pipeline programs.

憑藉這筆現金，即使在尚未考慮任何潛在營收之前，我們現在也已具備充足資金，得以推進我們的微囊性淋巴管畸形（microcystic lymphatic malformations）計畫，直至 NDA 申請遞交、FDA 核准，以及若獲核准後的美國商業上市。針對皮膚靜脈畸形（cutaneous venous malformations）的 QTORIN 雷帕黴素，我們的資金續航期足以執行第三期計畫，並隨後完成 NDA 申請遞交。而就我們的 QTORIN 產品線而言，我們的資金續航期也足以支持現有與未來多個管線計畫的第二期數據讀出。

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 near‑term financing needs.

本次融資的投資人參與品質非常出色，我們相信這反映出機構投資人對 SELVA 數據以及我們更廣泛的管線策略之信心正在提升。在這樣的資本基礎，以及我們以資本效率為優先的創新營運模式之下，Palvella 團隊如今可以完全專注於執行，而不必分心於短期融資需求。

I'll now turn the call back over to Wes for closing remarks and to open the line for questions. Wes.

我現在把電話交回給 Wes，請他做結語並開放提問。Wes。

Thanks, Matt.

謝謝你，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.

2025 年對 Palvella 而言是非常卓越的一年。現在，我們的重點完全放在推進我們深厚的罕見疾病管線計畫之執行。我們距離首次獲得 FDA 核准比以往任何時候都更近，而 Palvella 全體團隊都致力於讓這件事成真，為那些一直在等待的患者與家庭帶來希望。

For that, operator, we will open the line for questions.

因此，接下來請接線員開放提問。

(Operator Instructions)

（接線員指示）

Josh Schimmer, Cantor.

Josh Schimmer，Cantor。

Great. Thanks so much for taking the questions. For the Ketorin rapamycin platform, what are the gating steps for each new indication that you choose to pursue? 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? Thank you.

太好了。非常感謝讓我提問。關於 Ketorin 雷帕黴素平台，對於你們選擇要推進的每一個新適應症，其關鍵門檻步驟（gating steps）是什麼？另外，考量到外用雷帕黴素在許多情境下其實已有數據，你們最終預期標籤上可能會有多少個不同適應症？謝謝。

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.

很好，Josh。謝謝你參與，也謝謝你的問題。就平台而言，也就是你第一個問題，我們確實是從疾病本身出發。

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.

我們會篩選疾病：第一，沒有任何 FDA 核准療法的疾病。第二，我們會尋找在研發管線中競爭強度較低的疾病。這讓我們有機會成為第一個。目標就是走在能夠取得首個核准療法的軌道上。

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...

我們也會從科學角度仔細評估，該疾病是否具有清楚的生物學機制、明確的生物學基礎；而且我們確實偏好進入那些——我想 Jeff 先前也很清楚地提到——已有既有……

Human proof-of-concept data, sometimes that can be from off-label use, like we've seen with the use of rapamycin and lymphatic malformations.

人體概念驗證（proof-of-concept）數據的疾病；有時這些數據可能來自適應症外使用（off-label），例如我們看到雷帕黴素用於淋巴管畸形的情況。

We think that having some of that data in hand, human proof-of-concept data, helped 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 ketorin 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.

我們認為手上若有一些這類人體概念驗證數據，有助於驗證特定的分子策略。接著我們當然會套用 QTorin 平台，目標是——在這些局部皮膚疾病中，做到命中靶點並在組織中達到有效暴露。至於你的第二個問題，關於 ketorin 雷帕黴素最終能有多少個適應症，清單很長。我認為有三篇文獻很好地總結了 mTOR 路徑牽涉的各種不同皮膚疾病。

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.

Jeff 可以談談其中一些疾病，但遠遠超過……有十幾種疾病，科學家、臨床醫師、研究人員與遺傳學家都指出 mTOR 路徑扮演重要角色。Jeff。

Hey, Josh, thanks for the question. Just to kind of reiterate what Wes said, 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.

嗨，Josh，謝謝你的問題。再重申一下 Wes 所說的，我們採取非常以疾病為先的方法。我們高度倚重醫學與科學顧問委員會，既用於理解疾病未被滿足的需求，也用於評估生物學理據。接著我們會找到該疾病領域的專家。由於這些是罕見疾病，我們與這些領域的專家有很多良好合作，而這些領域通常過去並未受到太多科學或醫學研究關注。因此我們與關鍵意見領袖（KOL）非常緊密合作，最終選擇成功機率最高、未滿足需求最大，同時我們也會做商業面……的評估。

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 NTOR 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 QTOR and rapamycin once you add microLM, CVM, angioperatomas, and several of the other diseases that we've identified. Is in the hundreds of thousands.

另外也補充一下，Josh，我剛提到的三篇論文作者分別是 Swarbrick、Fogel，以及 Tatiana Lapa；這些論文探討 NTOR 路徑在皮膚疾病中的參與情形，或許也能用來量化你對族群規模的問題。我們認為，一旦把 microLM、CVM、angioperatomas，以及我們已辨識的其他幾種疾病納入後，可用 QTOR 與雷帕黴素治療的可觸及患者族群規模……將達到數十萬人。

Thanks very much.

非常感謝。

Ritu Baral with TD Cowen.

TD Cowen 的 Ritu Baral。

Good morning, everyone. Thanks for taking my question.

各位早安。謝謝讓我提問。

Wes, will the Phase 2 extension data, or at least some of the Phase 2 extension data from the CBM study, be part of your breakthrough application for that indication to FDA? And can you give us any more detail as to when that extension data will be presented and sort of like the.

Wes，CBM 研究的第二期延伸數據（Phase 2 extension data），或至少其中一部分，是否會納入你們就該適應症向 FDA 提出的突破性療法認定（breakthrough）申請？另外，你能否再提供一些細節，說明該延伸數據何時會公布，以及大概像是……

Of that extension data. And then I've got a follow-up on commercial.

該延伸數據的……內容概況。然後我還有一個關於商業化的追問。

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.

很好。嗨，Ritu，早安，謝謝你的問題。第二期延伸數據目前尚未定稿，而我們正持續推進突破性療法認定申請。

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.

我們的突破性療法認定（Breakthrough Therapy designation）申請將納入第2期數據；在該研究中，我們看到67%的患者達到「明顯改善」或「非常明顯改善」的評分。

We are also going to include interviews, patient qualitative interviews, where the patients, in their own words as part of.

我們也將納入訪談、患者質性訪談，讓患者以自己的話語作為其中的一部分。

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.

我們納入的一項質性訪談子研究，描述他們在試驗中的經驗。我們認為，使用能支持的數據來補強具統計顯著性的數據，這點非常重要。

Clinical meaningfulness. And finally, our investigators have really rallied here to put together a letter of support for the Breakthrough Therapy designation application. 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. That letter will cover not only their view about the preliminary clinical evidence package, but also their view.

臨床意義。最後，我們的研究者在此確實齊心協力，為突破性療法認定申請整理一封支持函。這項工作由我們的營運長Kathy Goen在Denise Adams及其他幾位人士的協助下主導。因此，這將成為突破性申請的關鍵部分。該支持函不僅會涵蓋他們對初步臨床證據資料包的看法，也會涵蓋他們的觀點。

Future study designs, which is going to be part of our discussion with the FDA after the breakthrough decision.

未來研究設計，這將成為在突破性療法認定決定之後，我們與FDA討論的一部分。

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 diagnosis pool for MLM. 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?

了解。接著在MLM的商業面，Wes，你提到——我想這也是Ashley的問題——你提到MLM的診斷患者池。你們對此最新的估計是多少？另外你提到這些患者正在接受照護。而且是以相對集中的方式在血管異常門診（vascular anomaly clinics）？

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, coverage support services for, adjunct to the price range that you mentioned? Thanks.

你們有這些門診的數量，以及它們涵蓋已診斷患者池的百分比嗎？另外就目前而言，可能更高層次地問，你們在患者支持服務、給付/保險覆蓋支持服務方面有什麼計畫，以配合你提到的價格區間？謝謝。

Yeah, thanks for two. So, 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 of around 45,000.

好的，謝謝這兩個問題。我們最新的估計是基於多項證據的匯聚：一項由Jack Gallagher發表、可在Orphanet查到的真實世界發生率研究，推估美國約有80,000名患者具有微囊性淋巴管畸形（microcystic lymphatic malformations）的皮膚表現。我們也做了理賠（claims）分析，顯示約45,000的範圍。

To 95,000 diagnosed patients that are within clinical medicine in the U.S. So we look at all that evidence, this is a dynamic process at Palvell, you're always evaluating claims data.

到95,000名在美國臨床醫療體系中已被診斷的患者。因此我們綜合所有證據來看——在Palvell這是一個動態的過程，你會持續評估理賠數據。

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 Q2 and rapamycin. When you break down the claims data, we break it down into.

我們估計（或許偏保守）美國有超過30,000名已診斷的微囊性淋巴管畸形患者；若Q2與雷帕黴素（rapamycin）獲批，這些患者可能是可觸及的對象。當你拆解理賠數據時，我們會把它拆分成。

High volume centers, many of which are two are these vascular anomaly centers. If you take the 400 highest volume centers, that constitutes about 15,000 patients in the United States. So that really is our primary focus.

高量中心，其中許多是血管異常中心。如果你看前400家最高量中心，合計約涵蓋美國15,000名患者。因此那確實是我們的主要重點。

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 two and phase three studies that we've run. In terms of. Patient services for our US Launch.

幸運的是，因為我們臨床營運團隊的工作，以及我們執行的第2期與第3期研究，我們與許多血管異常中心建立了很好的關係。至於。我們在美國上市（US Launch）的患者服務。

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.

Ashley在這方面經驗豐富，曾推出Oxervate，這是過去十年最成功的孤兒藥上市案例之一。我們也很高興延攬Jennifer McDonough。

We've closely followed and rooted on Vigevec's success from Crystal Biotech and a really rare and devastating disease there. 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.

我們一直密切關注並為Crystal Biotech的Vigevec成功喝采，該藥用於一種非常罕見且具毀滅性的疾病。因此我們希望與專科藥局（specialty pharmacy）以及患者服務中心（patient services hub）合作，這些合作夥伴在罕病領域有經證實的實績；特別是考量到微囊性LM，你很可能會看到。

Chronic dosing with cutor and 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.

使用cutor與雷帕黴素的長期用藥（chronic dosing），使我們不僅治療現有的臨床徵象，也能預防疾病復發——而這在當前該疾病中是一個重大問題。

Great. Thank you.

很好。謝謝你。

Annabelle Samimy, Stifel.

Annabelle Samimy，Stifel。

Hi. Thanks for taking my question. Great progress. I just want 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.

嗨。謝謝讓我提問。進展很棒。我只是想說，我們一直收到投資人對FDA不可預測性的提問。這顯然不是加速核准（accelerated approval），而且你們也非常明確指出這不是替代終點（surrogate endpoints），而是臨床終點（clinical endpoints）。

But there is still some concern about a one-armed study. How have these interactions been with FDA?

但對於單臂研究（one-armed study）仍然有些疑慮。你們與FDA的互動情況如何？

Are you still comfortable with that design? And I guess looking at CVM, what are you planning as far as phase three design, and how might that change with breakthrough designation? And should we have any read-through to the MLM receptivity to one-armed trials? So it's, I guess, a multi-layered question, but really it's about FDA unpredictability these days.

你們仍對這個設計有信心嗎？另外看CVM，你們對第3期設計有什麼規劃？突破性療法認定可能會如何改變它？我們是否可以由此推論MLM對單臂試驗的接受度？所以我想這是一個多層次的問題，但核心其實是近來FDA的不可預測性。

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. 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.

當然。謝謝你，Annabelle，提出這些問題。在第3期研究開始之前，我們相信我們與FDA在該單臂、第3期、以基線為對照（baseline-controlled）的研究設計上已達成一致，且目前仍保持一致；也就是由患者作為自身對照。我認為這裡有幾點很重要。第一，這是一種已有文獻記載不會自發性消退（no spontaneous regression）的疾病。

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. We shared several photos in our Phase 3 silver release.

因此，這可使單臂設計在療效評估上成為可靠的設計，特別是當你採用像我們這樣的臨床結局時；我們認為其本質上是客觀的——醫師在治療結束時對患者病灶進行評分，並與基線照片比較。我們在第3期SELVA新聞稿中分享了數張照片。

And we think they clearly indicate clinical improvement in lesions that would otherwise progress to a worsened state. 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 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 Phase 2.

我們認為這些照片清楚顯示病灶的臨床改善；若非治療，病灶原本會進展至更惡化的狀態。自第3期SELVA研究結束以來，我們已與審查部門（review division）、皮膚科部門（derm division），以及孤兒產品開發辦公室（Office of Orphan Products Development）都有互動。我們向他們呈報了數據。我會將這些互動形容為具建設性；我們正朝向已提出申請的pre-NDA會議推進，並預期該會議將在第2季舉行。

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. McCary advocating for a common-sense approach, describing that the new default approach to generating substantial evidence of effectiveness is one trial, not two.

我認為FDA有一些面向。在宏觀層面上讓我們非常受到鼓舞。我想大家都在關注McCary博士倡議以常識為本的方法，並指出產生「充分有效性證據」（substantial evidence of effectiveness）的新預設做法是一項試驗，而不是兩項。

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. And from Paul Vella's perspective, we believe the FDA much prefers approved drugs to off-label or compounded drugs. So we think all of those.

而且他一直主張加速將療法提供給罕病患者。FDA在去年第4季也談到會接納真實世界證據（real-world evidence）以協助監管決策。從Paul Vella的角度來看，我們相信FDA更偏好已核准藥物，而非適應症外用藥（off-label）或調劑配製藥（compounded drugs）。因此我們認為所有這些。

Sort of macro trends certainly work in our favor. 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. That application is going to go in imminently with the various elements that I mentioned earlier.

某種程度上，宏觀趨勢確實對我們有利。從 CVM 的角度來看，最終確定研究設計將會是兩步驟的流程。第一步是判定我們是否會被授予突破性療法認定。該申請將會在近期立即遞交，並包含我先前提到的各項要素。

Whether or not we're granted breakthrough, we're going to meet with the FDA on the other side of that decision.

不論我們是否獲得突破性認定，在該決定出爐後，我們都會與 FDA 會面。

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.

而我認為我們的 KOL 會強力主張第三期研究設計應具備彈性。這裡可能出現的結果範圍很廣。

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. Malformation. So there could be issues around clinical equipoids or ethics as well that we have to work through collaboratively with the FDA.

在我們與 CHOP 的 Denise Adams 等人的互動中，我認為他們會更希望所有病人都有機會用藥，因為大家普遍接受西羅莫司確實對血管畸形具有活性，且特別是。畸形。因此，在臨床均衡（equipoise）或倫理方面也可能會有一些議題，需要我們與 FDA 協作共同解決。

That said, there is also the potential for a placebo-controlled design. Our strategy is to first determine whether or not we're breakthrough-designated, and then on the other side of that, aligned with the FDA on a study design that works for patients, physicians, FDA, and for Paul Bell as well.

話雖如此，也存在採用安慰劑對照設計的可能性。我們的策略是先確認是否獲得突破性療法認定，之後再與 FDA 對齊一個能同時符合病人、醫師、FDA，以及 Paul Bell 需求的研究設計。

Okay, great. Thank you.

好的，很棒。謝謝。

Ryan Deschner with Mizuho.

Mizuho 的 Ryan Deschner。

Hi, this is Ryan for today.I'm just wondering if you guys could talk a little bit about the plans for the commercial launch beyond some of the key new hires, like any organizational changes, upgrades.

嗨，我是今天代打的 Ryan。我想請問你們是否可以多談一些商業化上市的規劃，除了幾位關鍵新聘人員之外，例如任何組織調整、系統升級等。

Timelines on Salesforce, any plans for upcoming, any kind of you're sort of prepping?

Salesforce 的時程如何？接下來是否有任何計畫，或你們正在做哪些準備？

Thank you. Yeah, thanks Ryan for those questions. I'm a firm believer in trying to recruit the best talent in the world to Paul Vella. Ultimately, I think that's going to help dictate our success for patients and shareholders. 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.

謝謝。好的，謝謝 Ryan 的問題。我一直堅信要為 Paul Vella 招募全世界最優秀的人才。最終我認為這將有助於決定我們對病人與股東的成功。我也認為我們已經集結了非常出色的人才，包括商務長 Ashley Klein、Jennifer McDonough，以及我們醫療事務團隊的建置。

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.

Ryan，關於你問到的變更或升級，我會將我們目前的狀態描述為。我們正在進行的增補與投資。因此，我們正在擴編醫學科學聯絡員（MSL）團隊。

We expect that to be somewhere between five and 10 MSLs. They will be very active with these Top 400 targets that I mentioned earlier. They will also have a major presence at medical meetings.

我們預期規模大約在 5 到 10 位 MSL 之間。他們會非常積極地與我先前提到的前 400 個目標對象互動。他們也會在醫學會議上有很高的能見度。

We expect to hire, and it was noted in our corporate deck.

我們預期會進行招募，這也在我們的公司簡報中提到。

Ahead of sales in the near term, we're going to bring that higher on a bit early to start to really think through how to shape an attractive uptake curve for Ketorin rapamycin, similar to what we saw with companies like the ones I've been involved with, such as Inzmed, Ashley with Oxervate and Jen McDonough. Crystal Biotech. So that's going to be really key. We put forward a provisional range of 20 to 40 sales reps.

在短期內、在銷售團隊到位之前，我們會稍微提前把這個職能招進來，開始深入思考如何為 Ketorin 雷帕黴素打造具吸引力的採用曲線（uptake curve），類似我曾參與的公司所看到的情況，例如 Inzmed、Ashley 在 Oxervate 的經驗，以及 Jen McDonough 在。Crystal Biotech。因此這會非常關鍵。我們提出了一個暫定區間：20 到 40 位業務代表。

I think with the capital raise having been completed, and we're very grateful to the investors who participated for their support.

我認為隨著增資已完成，我們也非常感謝參與的投資人給予支持。

We're more likely to go to the upper end of that 20 to 40 range versus the lower end of that range.

我們更可能採用 20 到 40 這個區間的上緣，而不是下緣。

Key in all this will be quality, Ryan. 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. 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，這一切的關鍵在於品質。因此，我們在此導入的一項招募流程是：高階管理團隊會深度參與招募。在各個層級。我們希望確保引進的是正確的人才、是高績效者。我們是一個以績效驅動的文化，但同時也要是真正以病人為中心、並且真心渴望服務罕見疾病病人的人。

Great. Thanks, Wes.

很好。謝謝，Wes。

Sam Soski with LifeSci Capital.

LifeSci Capital 的 Sam Soski。

Hey, good morning. Thanks for taking the questions.

嗨，早安。謝謝讓我提問。

So obviously great to see the angio keratoma phase two 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 will be deemed clinically relevant? 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? Thanks.

很高興看到血管角化瘤第二期試驗的啟動提前到第二季，但能否請你們提醒一下，這裡會觀察哪些關鍵終點，以及多大的效果幅度會被視為具有臨床意義？另外，隨著你們準備商業化上市與擴充產品線，能否就未來一年現金消耗（cash burn）的預期提供更細的資訊？謝謝。

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 going to be similar to what we did in MLM and CVM and that there's going to be no.

嗨，Sam，非常感謝這兩個問題。我先請 Jeff 說明我們在第二期血管角化瘤研究中所關注的終點。這會與我們在 MLM 與 CVM 的做法類似，也就是不會有。

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.

預先指定的統計階層（statistical hierarchy），也沒有主要終點（primary endpoint）。我們認為在罕見疾病領域採取這樣的方式是審慎的：在沒有 FDA 核准療法的情況下，你真正要做的是先判定哪些終點對治療效果的偵測最敏感，之後再在第三期建立那個統計階層。

So, Jeff will comment on that, and then we'll pass it over to Matt Korenberg to address the second part of your question. Jeff.

所以 Jeff 會就此評論，接著我們會請 Matt Korenberg 回答你問題的第二部分。Jeff。

Thanks for the question, Sam. So, we're going to follow. We're calling the Paul Vella 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. 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. We started out by.

Sam，謝謝你的問題。所以，我們會遵循。我們稱之為 Paul Vella 的作戰手冊（playbook），也就是重複我們在其他從未做過臨床試驗的罕見疾病上所採用的整體策略。如 Wes 所提，沒有統計階層。本研究的目的在於了解哪些終點對變化敏感。我們一開始先。

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

與病人以及臨床醫師討論，以辨識關鍵徵象有哪些。因此我們會觀察個別徵象，也會用整體性終點來評估全局變化。我們會同時採用動態與靜態量表。也會同時納入臨床醫師與病人的觀點。此外，和我們所有試驗一樣，捕捉病人的聲音非常重要。因此我們會在基線與治療結束時進行質性訪談，最終把所有資料整合，並用以指引未來。

Yeah, Sam, on the cash burn, appreciate the question. It's, as I said in my prepared comments, it's the cash that we have today is sufficient to get us through.

是的，Sam，關於現金消耗，謝謝你的提問。如同我在事先準備的發言中所說，我們目前持有的現金足以讓我們撐過。

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.

基本上在未來幾年推進我們所有的計畫。換算到 2026 年，大約是 8,000 萬美元的現金消耗。所以 2026 年的數字大約就是 8,000 萬美元左右。

Thanks, Sam.

謝謝，Sam。

Whitney Ijem with Kinecornuity.

我是來自 Kinecornuity 的 Whitney Ijem。

Hey guys, thanks for taking the question. Just kind of to the FDA regulatory, or sorry, the FDA flexibility and macro tailwinds with, 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.

各位好，謝謝讓我提問。想就 FDA 監管——抱歉，是關於 FDA 的彈性以及你們提到的宏觀順風——想請問你們是否有機會與主管機關就「合理機轉（plausible mechanism）」途徑進行交流。我知道你們在去年 12 月曾談到這點。

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 that that might be a potential path forward to shorten the timeline to some of those things?

對，就是想確認你們是否已經有過這些對話；另外，當我們思考所有那些外用雷帕黴素已有某種臨床驗證的適應症時，這是否可能成為一條潛在的前進路徑，讓其中一些項目的時程得以縮短？

Thanks, Wendy, 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.

謝謝你，Wendy，提出這些問題。關於「合理機轉」途徑，在目前這個階段，我們尚未就我們的一個或多個專案是否符合該途徑，與 FDA 進行正式互動。

Qualify for the plausible mechanism pathway.

符合「合理機轉」途徑的資格。

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. 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 microLMs could qualify for the plausible mechanism pathway. 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.

從我們的產品線來看，我們確實有數個分子與數個疾病領域，我們認為其機轉更接近「已驗證（validated）」而非僅屬「合理推定（plausible）」。因此，我們正密切觀察 FDA 如何落實新的「合理機轉」途徑計畫；我們也打算進一步了解，除了 microLMs 之外，我們是否有一個或多個專案可符合「合理機轉」途徑。至於 microLMs，我們目前不認為需要走這條途徑來推進 NDA 送件與 FDA 核准；但「合理機轉」可能適用於 CVM、可能也適用於 angiokeratomas，以及 porokeratosis。

Great. Thanks.

很好。謝謝。

Ryan Deschner with Raymond James.

我是來自 Raymond James 的 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?

謝謝讓我提問。FDA 的書面回饋中，是否有特定驅動因素促使你們加速 angiokeratomas 的臨床啟動時程？

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? Thanks.

另外，以目前的現金跑道來看，你們預期在新專案的臨床開發上，能推進到什麼程度？謝謝。

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.

很好。謝謝你，Ryan，兩個問題都很重要。我先回答第一個問題，接著 Matt 會談談我們打算達成的關鍵里程碑。

With the cash on hand.

在現有現金的支持下。

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.

Ryan，FDA 在去年年底時授予我們 angiokeratomas 的快速通道（Fast-Track）資格。我們把這視為公司的一個重大里程碑。這是我們第三個獲得快速通道資格的專案。

We placed in front of the FDA a Phase 2 design on angiokeratomas of about 10 or 20 patients.

我們向 FDA 提交了一個針對 angiokeratomas 的第二期試驗設計，約 10 到 20 名病患。

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. 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 Ketorin 3.9% rapamycin and hydrogel.

這個設計的目的主要是做訊號探索（signal-finding）研究。FDA 了解我們正在評估此疾病中多個不同的終點，而目前該疾病尚無任何 FDA 核准的療法。我認為讓我們能夠快速推進的原因之一——也呼應我們先前闡述的商業模式核心——是我們在 FDA 那邊已經有一個針對 Ketorin 3.9% 雷帕黴素與水凝膠的開放式 IND。

They're very familiar with the tox package.

他們對毒理（tox）資料包非常熟悉。

All the safety data that we've presented over the years, we're leveraging our existing manufacturing process, so our ability to jumpstart new indications on Q2 and rapamycin, while preserving that same formulation IND manufacturing processes.

我們多年來提交的所有安全性資料，他們都看過；我們也在沿用既有的製造流程，因此我們能夠在維持相同配方、IND 與製造流程的前提下，快速啟動新的適應症、以 Q2 與雷帕黴素為基礎推進。

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 lymptotic malformation.

我們認為其中一項優勢——也將使我們在取得第一個核准適應症後，能隨時間進行連續性的 SNDA 送件——而我們預期第一個核准適應症會是微囊性淋巴管畸形（microcystic lymphatic malformation）。

Matt, do you want to tackle the second part of the question?

Matt，你要不要回答第二部分的問題？

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 in the 2028 period.

好，謝謝，Wes。Ryan，如我所說，現有現金即使不考慮任何營收，也足以支撐我們在 2026、2027 以及 2028 年期間的一系列催化事件（catalysts）。

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 two trials this year.

在主力專案 MLM 上，我們可以一路推進到潛在核准與上市。在 CVMs 上，我們認為我們可以推進到 DSAP 與 angiokeratoma 的申報（filing）；這兩個專案都將在今年啟動第二期試驗。

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 and those indications as well.

我們也能順利取得這兩項試驗的數據。然後。至於我們今年提到將宣布的兩個新適應症，我們相信現金也足以支撐到這些適應症的數據讀出（data readouts）。

Importantly, my prepared comments were caveated by a lack of any revenue adjustment for that cash runway. I think if we consider potential cash.

重要的是，我在事先準備的發言中已註明：這個現金跑道的估算並未納入任何營收調整。我認為如果我們把潛在現金

Generation through revenue and launch, there's a potential that we can get to cash flow break even depending on how aggressively revenue ramps and depending on how aggressively we build out the pipeline. So we feel like we have all the cash we need.

透過營收與上市所帶來的現金創造納入考量，那麼我們有可能達到現金流損益兩平（cash flow break even），取決於營收爬坡的速度，以及我們擴建產品線的積極程度。所以我們覺得我們擁有所需的全部現金。

For the foreseeable future to really just focus on execution and generating data and eventually commercial products across the pipeline.

在可預見的未來，我們可以專注於執行、產出數據，並最終在整個產品線上推出商業化產品。

All right. Thank you very much.

好的。非常感謝。

Danielle Brill with Truth Securities.

我是來自 Truth Securities 的 Danielle Brill。

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

嗨，早安。這題是問 Danielle 的。謝謝回答我們的問題。我想問關於 microcystic 的給藥劑量。你們先前提到，部分病灶較大的病患，每日一次給藥可能需要超過一個按壓（pump）。根據你們近期的醫學事務外展（medical affair outreach），我們想了解在不同病灶大小的病患之間，平均每日劑量與年度營收應該如何建模？謝謝。

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. Mike Kelly from the Cleveland Clinic.

好的，謝謝你的問題。我們認為平均病患會是每天一個按壓（pump），而且我們預期這會是以慢性治療（chronic therapy）的方式給藥。我想這是我們從 KOL 那裡蒐集到的資訊，包括像克里夫蘭診所（Cleveland Clinic）的 Mike Kelly 醫師等人。

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. And so averaging that out across.

我們的建模方式——Matt 也可以補充——是把定價落在每位病患每年 10 萬到 20 萬美元的區間。因此把這個在

Patients, some of whom will consume more than one pump per day, some patients who probably will consume less than one pump per day. And so Matt can comment on any further specificity that he'd like to add.

病患之間做平均：有些人每天會用超過一個按壓，有些病患可能每天用不到一個按壓。Matt 可以就他想補充的更具體部分再說明。

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 and MLM doing is taking pretty conservative assumptions across the board, including for patient numbers, penetration, and then to your specific question on any.

好的，謝謝，Wes。我認為重點在於，當我們最近開始談到：峰值銷售機會（peak sales opportunity）對應的是數十億美元規模的 TAM，以及 MLM 的峰值銷售可達 10 億美元或以上時，我們在各方面都採取了相當保守的假設，包括病患人數、滲透率，以及針對你具體問題中提到的任何……

Patient compliance assumptions as you move out in years for patients on drugs. 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. But we've been very conservative about that. As we get to that billion-dollar peak sales number. So I think that's probably the most level of specificity that we've given so far.

隨著年限往後推進，針對用藥患者的患者依從性假設。因此，我們認為相較於標準的每日一次按壓（one pump per day），任何依從性變動都會被每年新增超過1,500名新患者的新增發病人群所大幅抵銷。但我們在這方面一直非常保守。當我們推估到十億美元的峰值銷售額時。所以我想，這大概是我們迄今所提供的最具體的程度了。

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 recognizing, did the data generate more buy-in from those doctors?

謝謝，這非常有幫助。我們還有一個問題，關於近期AAD會議上醫師的回饋。具體來說，對於那些過去一直依賴、或對於不再使用配製藥（compounded）而有所猶豫的皮膚科醫師而言，這些數據是否讓那些醫師更願意買單（buy-in）？

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 SELVA Phase 3 data release.

是的，謝謝這個問題。我們已就這個問題與我們的醫師合作夥伴進行了廣泛的討論。我們許多第二期與第三期的研究者都曾使用配製的適應症外（off-label）治療。我想你也聽到了，Jenny，這可能是你從Mike Kelly醫師在SELVA第三期數據發布時提到的。

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.

我們非常一致地聽到的是，醫師們。更偏好一個已獲FDA核准、且在前瞻性研究並在FDA IND之下證實其安全性、品質與療效的治療，而不是任何未經那套嚴謹且嚴格的FDA核准流程的治療。

That's very consistent feedback, and I think as we look at FDA activity around compounders.

這是非常一致的回饋；而且我認為，當我們觀察FDA對配製業者（compounders）的動作時。

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. So that's been consistent feedback that we've received from folks like Mike Kelly, Jim Tree at CHOP.

可以確定的是，在已有FDA核准藥物存在的情況下，FDA正在加強對配製藥品的執法，最明顯的例子就是GLP-1。因此，這一直是我們從像Mike Kelly、CHOP的Jim Tree等人那裡收到的一致回饋。

And others and 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. Strong uptake from patients and physicians, and we're looking forward to that day of having cutorin-rapamycin be made available to those folks.

以及其他人；而且最重要的是，再次強調，我們的SELVA第三期數據顯示，在完成療效評估期的患者中，有95%在用藥期間有所改善，其中86%屬於「改善很多」或「改善非常多」。我們認為如果獲得FDA核准，將會帶來。患者與醫師的強勁採用（uptake）；我們也期待有一天能讓cutorin-rapamycin提供給這些人使用。

Kaveri Pullman with ClearStreet.

ClearStreet的Kaveri Pullman。

Yeah, 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, and and were there any patients in the phase three or prior phase two trial who needed to pass the treatment due to adverse events or any other factors? And overall, also for MLM out of 30,000 patients, can you share like what proportion.

是的，早安。謝謝更新，也謝謝回答我的問題。我想追問一下，是否可以提供更多關於治療依從性的細節，通常會是什麼樣子；另外，在第三期或先前第二期試驗中，是否有任何患者因不良事件或其他因素而需要暫停治療？此外，整體而言，對於MLM的3萬名患者，你們能否分享大概有多少比例。

Considered truly like moderate to severe and therefore more appropriate for the treatment? And I have a follow-up.

被認為是真正的中度到重度，因此更適合接受治療？我還有一個追問。

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 ketorin-rapamycin. I think part of that goes to the underlying biology of the disease.

好的，謝謝這些問題，Kaveri。我先從最後一個問題開始。我們認為，任何在臨床醫療體系內的患者，而我們的數據顯示目前在臨床醫療體系內被診斷為微囊性LMs的患者超過30,000名。我們認為任何符合該特徵的患者都是ketorin-rapamycin的良好候選人。我想其中一部分原因與該疾病的基礎生物學機制有關。

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.

這是一種增生性且進展性的疾病。因此若疾病未接受治療，患者狀況會惡化。我們在臨床上知道，這很可能導致滲漏或淋巴漏（lymphorrhea）、出血、其他對生活品質的影響，當然也包括感染風險。

Cellulitis and other infections, some of which can even be life-threatening. 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.

蜂窩性組織炎與其他感染，其中有些甚至可能危及生命。因此我們認為最佳做法是，即便對於那些可能屬於較中度的患者，也應治療病灶，並以希望能緩解臨床徵象、同時也能預防疾病進展的方式來治療。

From a treatment compliant perspective, 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 Kutorin 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.

就治療依從性而言，我們的目標是與——Ritu先前也問到——我們的專科藥局以及患者服務中心（hub）合作，鼓勵患者遵從用藥。我們認為Kutorin rapamycin的設計方式能讓患者對藥物具有高度依從性。我的意思是什麼？它是每日一次給藥。

We've also selected excipients in the formulation that are designed to be non-irritating. We do not have any traditional penetration enhancers, 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.

我們也在配方中選用了設計為不刺激的賦形劑（excipients）。我們沒有任何傳統的滲透促進劑（penetration enhancers），因此我們預期相較於其他治療（可能需要更頻繁的每日給藥，且可能有更顯著的安全性或耐受性影響），本品的依從性會更高。Jeff。

Yeah, Barry, thanks for the question on adverse events. So we've completed 2 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.

是的，Barry，謝謝關於不良事件的問題。我們已完成兩項臨床試驗。第一項是第二期試驗，為期12週。在該研究中，沒有患者因不良事件而退出。在第三期試驗中，為期24週，共納入50名患者。

We did have six patients who discontinued treatment. Five of those six 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.

我們確實有6名患者停止治療。其中6人中的5人被判定與研究用藥無關。其中1名患者被認為可能與研究用藥相關。這名患者有淋巴漏（lymphorrhea）病史，並因淋巴漏而退出。

Yes, I'm sorry, I just wanted to know if any patient had to pause the treatment in between and they restarted the treatment during that period.

是的，不好意思，我只是想知道是否有任何患者在期間需要中途暫停治療，之後又在那段期間重新開始治療。

No, we did not have that situation.

沒有，我們沒有出現那種情況。

Got it. That's helpful. And maybe, 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 the majority of patients. Is that your expectation for ketorin 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? Thank.

了解。這很有幫助。另外，最近有一篇出版物指出，雷帕黴素連續使用兩年，之後再採取更客製化的間歇性使用，能為多數患者帶來長期效益。這也是你們對ketorin rapamycin的預期嗎？或者你們認為，若有正式標籤與核准，提升認知度並提供清楚指引，可能會改變對治療期間長短的這些估計？謝謝。

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. What we've observed in our clinical trial is that over 24 weeks with continued treatment is that you continue to have clinical benefit, and we observed. Patients, 98% rolled over to the treatment extension. So they were, at least in our perspective, were 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.

是的，謝謝這個問題。那是一篇很好的科學出版物，顯示長期使用雷帕黴素可以帶來相當不錯的臨床效益。我們在臨床試驗中觀察到的是，在24週的持續治療下，臨床效益會持續累積；而且我們觀察到。有98%的患者進入延伸治療（treatment extension）。因此至少在我們看來，他們認為其風險效益比是正向的。我們目前沒有超過那個時間點的額外數據，但我們會在延伸治療期間持續追蹤這些患者。

Catherine Novak with Jones Trading.

Jones Trading 的 Catherine Novak。

Hi, thanks for taking my question.

嗨，謝謝讓我提問。

Just curious of, what's still up for discussion at the pre-NDA meeting? Do you think you'll get clarity on the three plus age range at this time, or would this be something that would take place down the line during labeling discussions? And then just remind us of the enrollment dynamics that led to exclusions of three to five age patients from the ITT in phase three. Thanks.

我只是好奇，在 NDA 前會議（pre-NDA meeting）上，還有哪些事項仍在討論中？你們認為這次就能釐清「三歲以上」的年齡範圍嗎？還是這會在後續標示（labeling）討論時才會處理？另外，也請提醒我們第三期試驗中，導致 3 到 5 歲患者被排除在 ITT（意向治療）分析之外的入組動態（enrollment dynamics）。謝謝。

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.

很好。謝謝你，Katherine。關於 pre-NDA 會議，基本上你們是在提出你們預期用來支持「具實質證據的有效性」（substantial evidence of effectiveness）的申報資料組合。

As well as what will constitute your safety package as well. 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.

以及同時也會構成你們安全性資料組合（safety package）的內容。所以我不確定這些是否算是「仍待討論」的事項。我認為 FDA 很早就已經了解我們的藥物開發計畫，以及我們進行過第二期研究這件事。

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.

回想一下，他們就是基於那項第二期研究授予突破性療法認定（breakthrough therapy designation），這代表已有初步臨床證據（preliminary clinical evidence）。接著在第三期以非常相似的設計、只是樣本數大得多的情況下，我們在主要終點、關鍵次要終點以及所有次要終點上，都展示了高度統計顯著的結果。

So it's a matter of presenting that data to the FDA.

所以重點在於把這些數據呈交給 FDA。

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 Paul Vella to advocate that younger patients might have this therapy available to them, of course, pending FDA review and approval. Steph, do you want to speak to why the three to five-year-old cohort was not a part of the primary endpoint?

至於你問到的年齡範圍，這通常會在 NDA 討論的較後期才會發生。我們覺得在這通電話上分享這點很重要：根據我們從研究者那裡得到的回饋，大家希望 Paul Vella 能倡議讓更年幼的患者也可能取得這項治療，當然前提是仍需經 FDA 審查與核准。Steph，你要不要談談為什麼 3 到 5 歲的族群沒有納入第三期主要終點的主要分析？

Yes, thanks. So, Catherine, for what we did in phase two is we had patients six and up in that trial where we had 100%. Patients respond. And so for phase three, 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. 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. And just did post-hoc analysis on the patient in the three to five-year-old category.

好的，謝謝。所以，Catherine，在第二期我們納入的是 6 歲以上的患者，而在那個試驗中我們看到 100% 的。患者有反應。因此在第三期，我們的意圖是重複那個成功的研究，我們最初入組的是 6 歲以上的患者。研究者對於把年齡擴大到 3 到 5 歲有很高的興趣。我們把這件事與 FDA 討論。他們同意，並允許我們在試驗進行中擴大納入。基本上，因為我們尚未在 3 到 5 歲族群中研究療效，所以我們維持主要終點的主要分析不變（6 歲以上），然後。並且僅對 3 到 5 歲類別的患者做事後（post-hoc）分析。

Got it. That's very helpful. Thanks.

了解。這非常有幫助。謝謝。

Thanks, Catherine.

謝謝你，Catherine。

Albert Lowe with Craig-Hallum.

Craig-Hallum 的 Albert Lowe。

Hi. I was wondering, what are the steps for platform technology designation after the initial approval, and when can you potentially receive the designation?

嗨。我想請問，初次核准之後，取得平台技術認定（platform technology designation）的步驟是什麼？以及你們可能在什麼時點獲得該認定？

How would this change the Pavela playbook?

這會如何改變 Pavela 的作戰手冊（playbook）？

Yeah, thanks for that question, Albert.

好的，謝謝這個問題，Albert。

The goal is to secure approval of ketorin rapamycin first. That's going to be the first product from the platform, we believe, to achieve that FDA approval.

目標是先取得 ketorin rapamycin 的核准。我們相信這會是該平台的第一個產品，能夠取得 FDA 核准。

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. So our strategy for achieving the platform technology designation would be to indicate or 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 Pavela playbook? I think that's. An important question. 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. So we see a lot of value in. 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. 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. And we think the platform technology designation would help us achieve that.

如同本次電話會議所提到的，我們與 FDA 的多個部門一直維持具建設性且合作的關係，包括審查部門以及孤兒藥辦公室（Office of Orphan）。Products。因此，我們取得平台技術認定的策略，是先向 FDA 的審查部門表達我們對該認定的意向或興趣，並在相關情況下也讓 FDA 的其他部門參與，之後再就此提交更正式的申請。這會如何改變 Pavela 的 playbook？我認為那是。一個重要的問題。平台技術認定雖然相對較新，但在很多方面其運作方式類似其他加速計畫：它是基於 FDA 對 CMC 資料組合（CMC package）的審查，以及對技術平台的理解，進而為未來的平台產品建立更快速、更精簡的途徑。因此我們認為它具有很高的價值。特別是考量到 Qtorin pitavastatin 與 Qtorin rapamycin 之間的一些相似性，Osborne 醫師、David Osborne 與 Jeff 將會宣布第三個 Qtorin 平台產品。在今年稍晚。因此，再次呼應我今天簡報中最初的其中一張投影片，我們一直在持續追求並倡議各種方式，讓藥物能更快送達患者，同時縮短時間並降低資本投入。我們認為平台技術認定將有助於我們達成這點。

Great. That's helpful. Thank you.

很好。這很有幫助。謝謝。

Thanks, Albert.

謝謝你，Albert。

Dev Prasad with Lucid Capital Markets.

Lucid Capital Markets 的 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 patients for phase two? Are you leveraging the same clinical site network as Selva and Tiwa?

嗨，謝謝讓我提問，也恭喜這次更新。我有幾個問題。第一個是，你們能談談第二期試驗中 10 到 20 位血管角化瘤（angiokeratoma）患者的辨識與招募嗎？你們是否會沿用與 Selva 和 Tiwa 相同的臨床試驗中心網絡？

Or does this require a distinct referral approach? And the second is the ketorin 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 lay cells. Thank you.

還是這需要不同的轉介（referral）方式？第二個是關於 ketorin pitavastatin。它是針對此途徑、用於 DSAP 的第一個定向治療。能否請你們回顧一下，支持此作用機轉最重要的轉譯數據或臨床前證據是什麼？以及是什麼讓你們對外用。藥物能穿透到這些病灶細胞（lesion cells）有信心？謝謝。

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.

很好。謝謝你，Dev。我先回答你第一個關於血管角化瘤第二期研究的問題，接著 Jeff 會回答你第二個關於甲羥戊酸（mevalonate）途徑抑制劑證據的問題。

In porokeratosis. This actually is 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.

在毛孔角化症（porokeratosis）方面。這其實是一篇很棒的論文，Jeff 也有參與，我們最近已經發表了，因此他可以帶大家看一下那篇論文的重點。

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. 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 angiokeratomas.

至於血管角化瘤的試驗中心，你說得完全正確。我們會運用一些我們在微囊性淋巴管畸形（microcystic lymphatic malformations）與皮膚靜脈畸形（cutaneous venous malformations）方面密切合作過的相同中心。另外，我們也會（而且我們與這些團隊關係很好）運用商業型中心，這些中心往往有大量血管角化瘤患者。

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. Our particular academic site or commercial site have with this condition. And I'd say consistently, we've heard from our clinical operations team that there are more angiokeratoma patients than there are microcystic LM.

我想說，我們感到相當驚喜。我們在所有臨床試驗都會做的一項可行性工作，是了解到底有多少患者。我們特定的學術中心或商業中心在這個疾病上有多少患者。而我想我們的臨床營運團隊一直回報說，血管角化瘤患者比微囊性 LM 的患者還要多。

And maybe even as much as cutaneous venous malformation. 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 will leverage for angiokeratomas as well as additional studies from our Ketorin platform. Jeff.

甚至可能多到皮膚靜脈畸形。因此，這是一個很好的組合，涵蓋學術站點與商業站點，也涵蓋曾參與 MLM/CVM 的站點，同時也有一些新站點，將用於血管角化瘤，以及我們 Ketorin 平台的其他研究。Jeff。

Thanks for the question, Dave. So 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 RMSAB. 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 a therapy.

謝謝你的提問，Dave。關於 DSAP，這裡的遺傳學特徵已經非常清楚，其中很多工作來自耶魯大學 Keith Choate 醫師的實驗室；他是我們的密切合作夥伴，也是 RMSAB 的成員。從遺傳角度來看，這是單基因的功能缺失突變，發生在甲羥戊酸（mevalonate）途徑中涉及的五個基因之一。因此在遺傳學上，我們知道這是正確、應該以治療介入的途徑。

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. This was first studied out of Keith Chop's lab. He did a really nice clinical study with topical lovastatin who 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.

而在機制上的想法是，如果你能抑制這條途徑被活化，就可能產生臨床反應，因為這些中間代謝物會在細胞內造成毒性。這最早是在 Keith Choate 的實驗室中研究的。他做了一項非常出色的外用洛伐他汀（lovastatin）臨床研究，顯示出臨床反應。自那之後，已經有多項研究；我們最近在一篇回顧中發表並整理了約 24 項研究，顯示。

The potential proof-of-concept data with inhibiting this pathway in poor keratosis. Importantly, what we've uncovered in our formulation work, really led by David Osborne, was that many of these statins.

在毛孔角化症中，透過抑制這條途徑所得到的潛在概念驗證（proof-of-concept）資料。重要的是，我們在配方工作中所發現的內容——主要由 David Osborne 領導——是許多這些他汀類藥物。

Chemically labiles. They break down very quickly, which really translates to the inconsistent yield, which we've heard during our market research. What we've done with Kutorim and Pitavastatin is optimize that for delivery, so we get a stable formulation and consistent delivery at therapeutic concentrations with low systemic absorption.

在化學上不穩定。它們分解得非常快，這也直接導致產率不一致，而這正是我們在市場調研中聽到的。我們使用 Kutorim 與匹伐他汀（pitavastatin）所做的，是針對遞送進行最佳化，因此能在低全身吸收的情況下，得到穩定的配方，並以治療濃度進行一致的遞送。

Great. Thank you.

很好。謝謝你。

Jeet Mukherjee with BTIG.

BTIG 的 Jeet Mukherjee。

Great. Thanks for taking the question. So, you shared some details about the Phase 2 study for angiokeratomas in terms of number of patients and efficacy measures.

很好。謝謝讓我提問。你們分享了血管角化瘤第二期研究的一些細節，包括受試者人數與療效衡量指標。

I was hoping to shed some light on the Phase 2 study for DSAP as well. And when can we expect data from both these Phase 2 programs?

我也希望能請你們說明一下 DSAP 的第二期研究。以及我們何時可以期待這兩個第二期計畫的數據？

Thank you.

謝謝。

Great, G. Thanks for being on. Thanks for the questions. Jeff can speak to the Phase 2 study design in DSAP.

很好，Jeet，謝謝你在線上。謝謝你的問題。Jeff 可以談談 DSAP 的第二期研究設計。

At this point in time, we have not given specific guidance on trial readout timelines.

截至目前，我們尚未就試驗讀出（readout）時間點提供具體指引。

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. So we look forward to providing guidance on.

我們對血管角化瘤研究感到非常振奮：第一，它的進度超前，預計本季將為第一位患者給藥；第二，我們也看到該研究的需求程度。因此我們期待在。

Those trial timeline readouts here in the near term for both angiokeratomas and para keratosis as we get a little bit further along towards initiation and start to move up the enrollment curve. Jeff.

在近期，隨著我們在啟動方面再往前推進一些、並開始沿著入組曲線上升，我們將就血管角化瘤與毛孔角化症兩項試驗的時間線讀出提供指引。Jeff。

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

是的，謝謝你的提問。DSAP 的試驗設計目前尚未定案，所以我們仍在推進相關工作。但從非常高的層面來看，我們的方法非常相似。

There's no spontaneous progression in this disease, and we know that inhibiting the mevalonin pathway is on target. So what we've developed with 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.

這個疾病不會自發性進展，而我們也知道抑制甲羥戊酸（mevalonate）途徑是命中靶點（on target）的。因此，我們以匹伐他汀所開發的是一種在組織內、命中靶點的策略。我們會同時觀察疾病的個別徵象以及疾病整體的變化。我們正與患者及關鍵意見領袖（KOL）合作，確認哪些徵象是正確的量測指標，以及我們認為能在哪些方面帶來臨床效益。此外，如同我們所有的計畫，我們也會納入基線與結束訪談，以協助捕捉患者的聲音。

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

以上為今天的問答環節。我想把電話交回給 Wes Kaupinen 作結語。

Thank you, operator. In closing, thank you to everyone who firmly believes in Pallvella'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. And with that, I'd like to conclude today's call.

謝謝你，接線員。最後，感謝每一位堅定相信 Pallvella 使命——服務、願景——引領，以及我們「在疾病領域率先（first in disease）」策略的人。我們仍將不懈地專注於執行，並以堅定不移的承諾來落實這項使命、願景與策略。我們由衷感謝各位持續的支持。那麼，我想在此結束今天的電話會議。

Thank you, everyone.

謝謝大家。

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

今天的電話會議到此結束。感謝各位參與。您現在可以掛線。