Palvella Therapeutics Inc (PVLA) 2025 Q1 法說會逐字稿

Good day and thank you for standing by. Welcome to Palvella's first quarter 2025 Financial results and corporate Update conference call. (Operator Instructions) I would like to turn the conference over to your speaker today. Bohan way, please go ahead.

您好，感謝您的支持。歡迎參加 Palvella 2025 年第一季財務業績和公司更新電話會議。（操作員指示）今天我想將會議交給您的發言人。博漢路，請繼續。

Thank you, operator. Good morning and thank you for joining the Palvella Therapeutics Q1 2025 Financial Results and corporate update call. As a reminder, our press release summarizing today's updates is available under the investor section of our website at www.palvellatx.com. On today's call, we are joined by Wes Kaupinen, our Chief Executive Officer, Jeff Martini, our Chief Scientific Officer, and Matt Kornberg, our Chief Financial Officer.

謝謝您，接線生。早安，感謝您參加 Palvella Therapeutics 2025 年第一季財務業績和公司最新情況電話會議。提醒一下，我們總結今日更新的新聞稿可在我們網站 www.palvellatx.com 的投資者專區查閱。今天的電話會議由我們的執行長 Wes Kaupinen、財務長 Jeff Martini 和財務長 Matt Kornberg 共同出席。

Before we begin, please note that today's remarks may include forward-looking statements regarding our development programs, regulatory plans, commercial outlook, and financial performance. These statements are based on current assumptions and subject to risks and uncertainties that may cause actual results to differ. Please refer to our filings with the SEC for more information.

在我們開始之前，請注意，今天的評論可能包括有關我們的開發計劃、監管計劃、商業前景和財務業績的前瞻性陳述。這些聲明是基於目前的假設，並受可能導致實際結果不同的風險和不確定性的影響。請參閱我們向美國證券交易委員會提交的文件以了解更多資訊。

And now I'll turn the call over to West.

現在我將把電話轉給韋斯特。

Thank you, Bohan. Good morning, everyone, and thank you all for joining us today. This past Monday morning, the Palvella team, including our Scientific and Clinical Collaborators, Investors, Senior Advisors, Board Members, and family members, converged on New York City for the ringing of NASDAQ's opening bell.

謝謝你，博漢。大家早安，感謝大家今天的參加。上週一早上，Palvella 團隊，包括我們的科學和臨床合作者、投資者、高級顧問、董事會成員和家庭成員，齊聚紐約市，聆聽納斯達克的開市鐘聲。

Palvella becoming a publicly traded company approximately five months ago is an important milestone for the company, and it is a testament to Palvella's vision of building the leading rare disease biotech company focused on serious genetic skin diseases with no FDA approved therapies. It is also a testament to our mission, which is to relentlessly serve those rare disease patient populations who have historically been neglected.

大約五個月前，Palvella 成為一家上市公司，這是該公司的一個重要里程碑，也證明了 Palvella 的願景，即打造一家專注於治療未經 FDA 批准的嚴重遺傳性皮膚病的領先罕見疾病生物技術公司。這也證明了我們的使命，那就是堅持不懈地為那些歷史上被忽視的罕見疾病患者群體提供服務。

And to our strategy, which is to focus our therapeutic development efforts and eventually our commercial efforts exclusively on those diseases with no FDA approved therapies. We want to be first for patients. Becoming public is furthermore a testament to the Palvella management team, who have turned mere concepts into breakthrough designated medicines while turning the challenges of drug development and rare complex diseases into triumphs.

我們的策略是將我們的治療開發工作以及最終的商業努力集中在那些尚未獲得 FDA 批准的治療方法的疾病。我們希望以患者為先。上市進一步證明了 Palvella 管理團隊的實力，他們將單純的概念變成了突破性的指定藥物，同時將藥物開發和罕見複雜疾病的挑戰變成了勝利。

The collective sentiment at NASDAQ that day was that our substantial progress to date, including both developing a late-stage pipeline with QTORIN and rapamycin, and a compelling platform with QTORIN is truly only the beginning for Pulvella.

當天納斯達克的集體情緒是，我們迄今為止的實質進展，包括開發 QTORIN 和雷帕黴素的後期管道，以及 QTORIN 的引人注目的平台，對於 Pulvella 來說這才僅僅是一個開始。

Our hope is to return to NASDAQ one day in the near future to celebrate the first regulatory approval of QTORIN 3.9% Rapamycin hydrous gel, a milestone we believe we're even closer to achieving. Based on today's exciting update that we have exceeded our enrollment target of 40 patients in the landmark Selva phase 3 study of QTORIN rapamycin for the treatment of microcystic lymphatic malformations.

我們希望在不久的將來有一天重返納斯達克，慶祝 QTORIN 3.9% 雷帕黴素水凝膠首次獲得監管部門的批准，我們相信我們距離實現這一里程碑已經更近了一步。根據今天令人興奮的最新消息，我們在具有里程碑意義的 Selva 第 3 階段研究中已經超過了 40 名患者的招募目標，該研究旨在研究 QTORIN 雷帕黴素用於治療微囊淋巴管畸形。

Four quarters, four anticipated high-impact milestones, moving left to right, microcystic lymphatic malformations are a serious, rare, chronically debilitating, and lifelong monogenic disease. The genetics, disease biology, target skin tissue, and natural history of microcystic lymphatic malformations have all been well characterized.

四個季度，四個預期的高影響里程碑，從左到右，微囊淋巴畸形是一種嚴重的、罕見的、慢性衰弱的、終身單基因疾病。微囊淋巴畸形的遺傳學、疾病生物學、目標皮膚組織和自然史都已被很好的描述。

Genetically they're caused by PI3K mutations. Biologically, the PI3K mutation results in the hyperactivation of the [M4] pathway, which ultimately produces malformed vessels that protrude through the skin, as you can see from the picture here on the slide.

從基因上來說，它們是由 PI3K 突變引起的。從生物學角度來看，PI3K 突變會導致 [M4] 通路過度活躍，最終產生從皮膚突出的畸形血管，正如您從幻燈片上的圖片中看到的那樣。

The target skin tissue is the dermis, which is the site of disease origin cystic lymphatic malformations. From a natural history perspective, the disease is present at birth, has no spontaneous regression, and is proliferative and progressive.

目標皮膚組織是真皮，這是囊性淋巴管畸形的病因部位。從自然史角度來看，該疾病在出生時就存在，沒有自然消退，並且具有增殖性和進行性。

The major clinical burden to these patients is referred to as lymphorhea, which is the leaking or discharge of internal lymphatic fluid onto the skin or into the soft tissues. The result of this is that these patients are at persistent risk of serious infections, including acute cellulitis, which can cause repeated hospitalizations.

這些患者的主要臨床負擔是淋巴溢漏，即內部淋巴液洩漏或排放到皮膚或軟組織中。結果是，這些患者持續面臨嚴重感染的風險，包括急性蜂窩性組織炎，可能導致反覆住院。

There are unfortunately no FDA approved therapies for these patients. We'll provide an update today on our phase 3 Selva study of QTORIN and rapamycin, which has received FDA's breakthrough therapy, fast track, and orphan drug designations. We anticipate top line results from the study in Q1 2026.

不幸的是，目前還沒有 FDA 批准針對這些患者的治療方法。今天，我們將提供有關 QTORIN 和雷帕黴素的 3 期 Selva 研究的最新進展，該研究已獲得 FDA 的突破性療法、快速通道和孤兒藥稱號。我們預計該研究將於 2026 年第一季公佈最終結果。

Moving to cutaneous venous malformations, the disease pathology of cutaneous venous malformations is similarly driven by the [MTOR] pathway caused by mutations in either PI3K or TI 2, which leads to overactivated MTOR signaling. Cutaneous venous malformations are a serious disease, and they're characterized by dysregulated growth of malformed veins in the skin, which can cause functional impairment and bleed.

對於皮膚靜脈畸形，皮膚靜脈畸形的疾病病理同樣是由 PI3K 或 TI 2 突變引起的 [MTOR] 路徑驅動的，這會導致 MTOR 訊號過度活化。皮膚靜脈畸形是一種嚴重的疾病，其特徵是皮膚畸形靜脈生長失調，可導致功能障礙和出血。

Because of the genetic driver of the disease, cutaneous venous malformations continue to grow over time and do not spontaneously regress. There are unfortunately no FDA approved therapies for patients afflicted with cutaneous venous malformations. We'll update today on our phase 2 to study of QTORIN and rapamycin, which has received FDA's fast track designation, and we anticipate the study will report top line results in Q4 of 2025.

由於疾病的遺傳驅動因素，皮膚靜脈畸形會隨著時間的推移而不斷生長，並且不會自行消退。不幸的是，目前還沒有 FDA 批准針對皮膚靜脈畸形患者的治療方法。今天我們將更新 QTORIN 和雷帕黴素的第 2 階段研究，該研究已獲得 FDA 的快速通道資格，我們預計該研究將在 2025 年第四季度報告頂線結果。

Importantly, if approved, we believe based on market research that QTORIN and rapamycin has the potential to be first line therapy and standard of care for patients with both microcystic lymphatic malformations and cutaneous venous malformations.

重要的是，如果獲得批准，我們根據市場研究相信 QTORIN 和雷帕黴素有可能成為微囊淋巴畸形和皮膚靜脈畸形患者的第一線治療和標準護理。

Our pipeline beyond our two lead programs and microcystic LMs and cutaneous venous malformations continues to make tangible progress under the strong leadership of our Chief Scientific Officer, Dr. Jeff Martini. In the third panel on this slide, we truly believe QTORIN rapamycin can represent a pipeline and a product with clinical and commercial potential that extends well beyond microcystic lymphatic malformations and cutaneous venous malformations.

在我們首席科學官 Jeff Martini 博士的強有力領導下，除了我們的兩個主要項目以及微囊性 LM 和皮膚靜脈畸形之外，我們的研發管線繼續取得切實進展。在這張投影片的第三個面板中，我們堅信 QTORIN 雷帕黴素可以代表一種具有臨床和商業潛力的管道和產品，其範圍遠遠超出微囊淋巴管畸形和皮膚靜脈畸形。

We anticipate unveiling our third target clinical indication for QTORIN rapamycin in the second half of this year. Moving to the fourth panel, we also anticipate unveiling our next QTORIN program in the second half of this year, which would be our second product candidate from the QTORIN platform after QTORIN and rapamycin.

我們預計在今年下半年公佈 QTORIN 雷帕黴素的第三個目標臨床適應症。進入第四個小組，我們也預計將在今年下半年推出我們的下一個 QTORIN 項目，這將是繼 QTORIN 和雷帕黴素之後我們 QTORIN 平台的第二個候選產品。

We see both our next QTORIN rapamycin indication and our next QTORIN platform program as key near-term value drivers for Paul Bell. Dr. Martini will provide updates on our progress on both programs on this call.

我們認為我們的下一個 QTORIN 雷帕黴素適應症和我們的下一個 QTORIN 平台計劃是 Paul Bell 近期的關鍵價值驅動因素。馬蒂尼博士將在本次電話會議上介紹我們這兩個計畫的進展。

Our strong momentum at alvella is highlighted first by what's presented at the top of the slides. We have now exceeded our enrollment goal of 40 patients in our landmark phase 3 study evaluating QTORIN and rapamycin for the treatment of microcystic LMs.

幻燈片頂部所呈現的內容首先突出了我們在阿爾維拉的強勁發展勢頭。在具有里程碑意義的 3 期研究中，我們評估了 QTORIN 和雷帕黴素對微囊性 LM 的治療效果，目前已超過 40 名患者的招募目標。

On our phase 2 (toyva) study of QTORIN and rapamycin for the treatment of cutaneous VMs, we now have six sites open and enrolling, and top line readout is anticipated in Q4 2025.

在我們針對 QTORIN 和雷帕黴素治療皮膚 VM 的 2 期（toyva）研究中，我們目前有 6 個站點開放並正在招募患者，預計將於 2025 年第四季度獲得頂線讀數。

We recently participated in the Society of Investigative Dermatology. And the International Society for the Study of Vascular Anomalies meetings where we gathered new insights and deepened our relationships with scientific and clinical leaders in the field.

我們最近參加了皮膚病學研究協會。在國際血管異常研究學會會議上，我們收集了新的見解並加深了與該領域科學和臨床領導者的關係。

From an organizational standpoint, We've added Jason Burdett to our executive team as SVP of CMC and technical operations. Jason brings 30 years of experience in global pharmaceutical development, technical operations, and supply chain to Pulvella, and we're thrilled to have him on our senior team as we approach planned NDA submission next year and if approved, stand-alone US commercialization in 2027.

從組織的角度來看，我們已將 Jason Burdett 加入我們的執行團隊中，擔任 CMC 和技術營運資深副總裁。Jason 為 Pulvella 帶來了 30 年的全球醫藥開發、技術營運和供應鏈經驗，我們很高興他能加入我們的高級團隊，我們計劃明年提交 NDA，如果獲得批准，將於 2027 年在美國獨立商業化。

We also continue to make progress on our search for an exceptional Chief Commercial Officer with that higher plan for the second half of this year. For this position, we're seeking a proven leader with experience launching novel therapies that were first to market in serious rare diseases.

我們也將繼續尋找一位出色的首席商務官，並在今年下半年制定更高的計畫。對於這個職位，我們正在尋找一位經驗豐富的領導者，他具有推出首次上市的治療嚴重罕見疾病的新療法的經驗。

In addition to the proven experience commercializing in rare diseases consistent with Palvella's historical and current model of operating with capital efficiency, we are seeking to recruit a leader who can lead a launch in a thoughtful and capital efficient manner.

除了符合 Palvella 歷史和當前資本效率運營模式的罕見疾病商業化經驗外，我們還在尋求招募一位能夠以深思熟慮和資本高效的方式領導產品發布的領導者。

We look forward to keeping everyone updated on our progress, and we've also expanded our intellectual property portfolio with the issuance of our fifth US patent with anticipated claims from that patent into 2038.

我們期待讓每個人都了解我們的進展，同時我們也擴大了我們的智慧財產權組合，獲得了第五項美國專利，預計該專利的有效期將持續到 2038 年。

Moving to our lead program, QTORIN and rapamycin for the treatment of microcystic lymphatic malformations, I'm pleased to share thanks to the dedicated efforts of our phase 3 investigators and the research coordinators at clinical trial sites, our patient advocacy collaborators, the highly committed Paulvella clinical operations team, and most of all the patients living with microcystic lymphatic malformations.

談到我們的主導項目，QTORIN 和雷帕黴素用於治療微囊淋巴畸形，我很高興地感謝我們 3 期研究人員和臨床試驗地點的研究協調員、我們的患者權益合作者、高度敬業的 Paulvella 臨床運營團隊以及大多數患有微囊淋巴畸形的患者的辛勤努力。

That we have exceeded enrollment of 40 patients and our pivotal phase 3 trial evaluating QTORIN and rapamycin in patients with microcystic LMs. The study has generated strong interest with all 13 sites, including institutions such as Stanford University, the Cleveland Clinic, Children's Hospital of Philadelphia, the Mayo Clinic, to name a few, all enrolling patients into the study.

我們已經招募了超過 40 名患者，我們的關鍵 3 期試驗正在評估 QTORIN 和雷帕黴素對微囊性 LM 患者的作用。這項研究引起了 13 個機構的強烈興趣，包括史丹佛大學、克利夫蘭診所、費城兒童醫院、梅奧診所等機構，它們都招募患者參與了這項研究。

In terms of concluding enrollment, we're anticipating closing study enrollment in June after all pending enrolled patients have completed screening. As a result of the diligent efforts and commitment from investigators and sites beyond these pending enrolled patients, there is additional potential for more patients to enter the study.

在結束招募方面，我們預計將在所有待招募患者完成篩檢後於 6 月結束研究招募。除了這些待入組的患者之外，由於研究人員和研究中心的辛勤努力和承諾，還有更多患者參與研究的可能性。

We believe that it is in Palvella's best interests to honor the site's work and their relationships with patients and accommodate additional patients into the study in a timely manner.

我們相信，尊重研究中心的工作及其與患者的關係並及時接納更多患者參與研究符合 Palvella 的最大利益。

At the same time, now that we've exceeded our enrollment target of 40 patients, our goal is to bring the phase 3 trial to an orderly close while communicating closely and clearly with our study investigators and sites on defined study closure timelines.

同時，現在我們已經超過了 40 名患者的招募目標，我們的目標是有序地結束第 3 階段試驗，同時與我們的研究人員和研究中心就確定的研究結束時間表進行密切、清晰的溝通。

As you can see from the graphic at the bottom of the slide, if patients meet study eligibility criteria, they are then enrolled into the study. Patients first move through an eight-week baseline period before moving to the efficacy evaluation period of 24 weeks, followed by the treatment extension period of 24 weeks.

從投影片底部的圖形可以看出，如果患者符合研究資格標準，就會被納入研究。患者先經歷八週的基線期，然後進入24週的療效評估期，接著是24週的治療延長期。

We look forward to providing more detail on final patient enrollment numbers at the time of achieving full enrollment in the near future. Overall, we are pleased that we've been able to accomplish our phase 3 study enrollment goals while remaining on track to report top line data in the first quarter of 2026.

我們期待在不久的將來實現全面入組時提供有關最終患者入組人數的更多詳細資訊。整體而言，我們很高興能夠完成第三階段研究的招生目標，同時繼續按計畫在 2026 年第一季報告頂線數據。

In addition, as you'll hear from our CFO Matt Kornberg later in this call, we are also staying on track for our 2025 cash expenses and long-term cash runway forecast. Moving to our regulatory overview, we've all been carefully monitoring the recent and ongoing changes at FDA, and the Palvella management team will continue to remain vigilant in doing so along with our regulatory advisors. For Palvella's QTORIN and rapamycin, we wanted to provide additional clarity that our program is regulated by the division of Dermatology and Dentistry.

此外，正如您將在本次電話會議稍後聽到我們的財務長 Matt Kornberg 所說，我們還將繼續按計劃執行 2025 年的現金支出和長期現金流預測。轉到我們的監管概述，我們一直在密切關注 FDA 近期和正在進行的變化，Palvella 管理團隊將與我們的監管顧問一起繼續保持警惕。對於 Palvella 的 QTORIN 和雷帕黴素，我們希望進一步明確我們的計畫受皮膚病學和牙科部門的監管。

Which is within the Center for Drug Evaluation Research, or CEDA, which you can see listed at the top of this slide. Importantly, the division of dermatology and dentistry continues to be led by Dr. Jill Lindstrom, a dermatologist and the division director who began as director of the division in late 2023 and continues in that role today.

該部門隸屬於藥物評估研究中心（CEDA），您可以在此幻燈片頂部看到其清單。重要的是，皮膚病學和牙科部門繼續由皮膚科醫生兼部門主任吉爾·林德斯特羅姆博士領導，她於 2023 年底開始擔任該部門主任，並一直擔任該職位至今。

Due to our plan 505B2 pathway for our NDA submission, we anticipate division level leadership. In this case, Dr. Lindstrom, would be responsible for the NDA review and approval decision. So, while there have been many changes across the FDA that we've all read about and that we continue to track, there has by contrast been consistency for Palvella in terms of number one, the division regulating Palvella 's program. Dermatology and dentistry and number two, the leadership of that division in this case, Dr. Lindstrom.

由於我們的 NDA 提交計劃採用 505B2 途徑，因此我們預計會有部門級領導。在這種情況下，Lindstrom 博士將負責 NDA 審查和批准決定。因此，儘管我們已經讀到並持續追蹤了 FDA 內部發生的許多變化，但相比之下，Palvella 在第一大部門（監管 Palvella 專案的部門）方面卻保持一致。皮膚科和牙科，第二位，本案中該部門的負責人是林斯特羅姆博士。

As a reminder, assuming positive phase 3 data, we anticipate that our program could potentially be expedited as a result of some of the designations we've achieved over the years. In Q4 of 2023, we were awarded FDA's breakthrough therapy designation based on the results from our phase 2 baseline controlled single arm study of 12 patients.

提醒一下，假設第三階段的數據是正面的，我們預期我們的計劃可能會因我們多年來取得的一些指定而加快。2023 年第四季度，我們根據對 12 名患者進行的 2 期基線對照單臂研究的結果獲得了 FDA 的突破性治療稱號。

Breakthrough therapy designation was added to our previously granted fast track and orphan drug designations. Additionally, out of 51 applications received by FDA's Orphan Products grants program in fiscal year 2024, Paulvella's Phase 3 Selva trial was one of just seven clinical programs and the only phase 3 study to be named an awardee of a non-dilutive FDA grant.

我們先前授予的快速通道和孤兒藥稱號又增加了突破性療法稱號。此外，在 FDA 2024 財政年度孤兒產品資助計畫收到的 51 份申請中，Paulvella 的 3 期 Selva 試驗是僅有的 7 個臨床計畫之一，也是唯一一項獲得非稀釋性 FDA 資助的 3 期研究。

In our case, we anticipate up to $2.6 million from the FDA over multiple years in non-dilutive funding to support the Phase 3 study.

就我們而言，我們預計 FDA 將在多年內提供高達 260 萬美元的非稀釋性資金來支持第 3 階段研究。

Moving to the bottom of the slide in terms of the regulatory environment for our other planned pipeline programs, the Paulvella team is closely monitoring emerging regulatory frameworks, including a newly proposed plausible mechanism accelerated approval pathway for certain rare diseases that has been publicly highlighted at a conceptual level by Commissioner Dr. Marty Mcery.

就我們其他計劃中的管道項目的監管環境而言，Paulvella 團隊正在密切關注新興的監管框架，包括新提出的針對某些罕見疾病的合理機制加速審批途徑，該途徑已由局長 Marty Mcery 博士在概念層面公開強調。

We were encouraged by the comments about the need to expedite therapies to patients living with rare, ultra rare, and oftentimes serious diseases, and we will continue to follow updates from FDA on these new pathways and their potential relevance to our earlier stage programs.

我們對需要加快對患有罕見、極罕見和通常嚴重的疾病的患者的治療的評論感到鼓舞，我們將繼續關注 FDA 對這些新途徑的更新及其與我們早期計劃的潛在相關性。

I'd like to now turn to the commercial opportunity we see ahead for QTORIN and rapamycin. As a reminder, at a high level, Palvella firmly believes that the opportunity to develop and commercialize in serious rare diseases where Palvella can introduce the first FDA approved therapy can represent very attractive commercial opportunities, especially considering the lower competitive intensity dynamics in these markets compared to more conventional and competitive rare disease markets which are already well served.

現在我想談談我們所看到的 QTORIN 和雷帕黴素的商業機會。需要提醒的是，Palvella 堅信，在嚴重罕見疾病領域進行開發和商業化的機會（Palvella 可以推出首個 FDA 批准的療法）可以代表非常有吸引力的商業機會，特別是考慮到這些市場與已經得到充分服務的更傳統、競爭更激烈的罕見病市場相比競爭強度較低。

As a function of having existing approved therapies in most cases, as this slide shows for microcystic lymphatic malformations, a recent epidemiology study conducted by a multidisciplinary team that leveraged an extensive medical claims database resulted in the following estimates.

正如這張幻燈片顯示的微囊淋巴管畸形一樣，由於大多數情況下都有現有的批准療法，最近由一個多學科團隊利用廣泛的醫療索賠數據庫進行的一項流行病學研究得出了以下估計結果。

In terms of estimated diagnosed US prevalence of microcystic LMs, the study indicated. That there could be greater than 44,000 diagnosed US patients, figures that are largely in line with Paul Della's previous estimates. In terms of estimated annual incidence of microcystic LMs, the study indicated that there could be 1,500 or more new microcystic LM cases per year.

研究表明，就美國微囊性 LM 的診斷盛行率而言。美國確診患者人數可能超過 44,000 人，這一數字與保羅·德拉先前的估計基本一致。就微囊性 LM 的年估計發病率而言，研究表明每年可能有 1,500 例或更多新的微囊性 LM 病例。

When taking these prevalence and incidence estimates and overlaying them with anticipated orphan pricing levels, the data supports that microcystic lymphatic malformations could be a multi-billion-dollar total addressable market in the United States.

當這些盛行率和發病率估計值與預期的孤兒藥定價水準疊加時，數據顯示微囊淋巴管畸形在美國可能是一個總價值數十億美元的可尋址市場。

Importantly, the posts are also indicated that about one third of diagnosed patients are currently managed at vascular anomaly centers, which are already established centers of excellence for diagnosing and treating microcystic lymphatic malformations and other vascular malformations.

重要的是，貼文還指出，目前約有三分之一的確診患者在血管異常中心接受治療，這些中心已經是診斷和治療微囊淋巴管畸形和其他血管畸形的卓越中心。

We look forward to providing more information related to the commercial opportunity and Palvella's commercial planning as we on board a Chief Commercial Officer in the coming months. With that, I'll turn it over to our Chief Scientific Officer, Dr. Jeff Martini.

我們期待在未來幾個月內任命首席商務官，並提供更多與商業機會和 Palvella 商業規劃相關的資訊。接下來，我將把發言權交給我們的首席科學官 Jeff Martini 博士。

Thank you, Wes. In April, I had the opportunity to represent Palvella at the International Society for the Study of Vascular Anomalies, or ISSFA conference in Paris. The leading global scientific and medical forum focused on vascular malformations, including microcystic lymphatic malformations and cutaneous venous malformations.

謝謝你，韋斯。四月份，我有機會代表 Palvella 參加在巴黎舉行的國際血管異常研究學會 (ISSFA) 會議。全球領先的科學和醫學論壇重點關注血管畸形，包括微囊淋巴管畸形和皮膚靜脈畸形。

While there, I met with many of the field's foremost clinicians to discuss our two lead indications, MLMs and CBMs, as well as other serious rare skin diseases that may be strong candidates for QTORIN rapamycin and future QTORIN-based therapies.

在那裡，我會見了該領域的許多頂尖臨床醫生，討論了我們的兩種主要適應症，MLM 和 CBM，以及其他可能成為 QTORIN 雷帕黴素和未來基於 QTORIN 的療法的有力候選者的嚴重罕見皮膚病。

Several themes emerged that reinforce the direction we're headed. First, the field is clearly moving towards targeted therapeutic approaches based on the underlying genetic drivers of each vascular anomaly.

出現的幾個主題強化了我們前進的方向。首先，該領域顯然正朝著基於每种血管異常的潛在遺傳驅動因素的針對性治療方法發展。

Second, there's a real need for therapies that can improve efficacy while reducing the systemic side effects associated with current treatments, many of which were originally developed for internal infiltrative diseases rather than localized cutaneous lesions.

其次，我們確實需要能夠提高療效同時減少目前治療方法所帶來的全身副作用的治療方法，其中許多治療方法最初是針對內部浸潤性疾病而不是局部皮膚病變而開發的。

And third, there's a significant opportunity to expand treatment options across a broader spectrum of cutaneous vascular malformations both within and outside the MTOR pathway, which we are actively pursuing as part of our pipeline expansion activities. These insights continue to support the potential of the QTORIN platform and help guide how we prioritize future indications within our development strategy.

第三，我們有很大機會擴大針對 MTOR 通路內外更廣泛的皮膚血管畸形的治療選擇，我們正在積極尋求這一機會，並將其作為我們管道擴展活動的一部分。這些見解繼續支持 QTORIN 平台的潛力，並幫助指導我們如何在發展策略中確定未來適應症的優先順序。

Moving on to our clinical trial of cutaneous venous malformations, or our toy study in CVMs is actively enrolling. This single arm baseline control trial includes patients aged six and over and evaluates both clinician and patient reported outcomes. The purpose of the study is to one, evaluate safety and tolerability, and two, determine which endpoints are most sensitive to change with QTORIN rapamycin.

我們正在進行皮膚靜脈畸形的臨床試驗，或者說我們的 CVM 玩具研究正在積極招募參與者。這項單組基線對照試驗包括六歲及以上的患者，並評估臨床醫生和患者報告的結果。研究的目的一是評估安全性和耐受性，二是確定哪些終點對 QTORIN 雷帕黴素的變化最敏感。

We currently have six sites open, five of which came online in the past two months. Topline data from Tuiba are expected in the fourth quarter of this year.

我們目前開放了六個站點，其中五個是在過去兩個月內上線的。預計推吧將於今年第四季公佈主要數據。

As we continue to build momentum behind our lead programs, we're very focused on expanding our QTORIN platform through two distinct development tracks. First, we are advancing additional indications for QTORIN rapamycin itself.

隨著我們繼續為我們的領先項目積累動力，我們非常注重透過兩個不同的發展軌道來擴展我們的 QTORIN 平台。首先，我們正在推動 QTORIN 雷帕黴素本身的更多適應症。

Based on what we've seen in the clinic and through ongoing dialogue with experts in the field, we view QTORIN rapamycin as a pipeline in a product. We've identified several diseases that fit the stringent Pavella criteria of serious rare skin diseases that lack FDA approved therapies and where MTR dysregulation is a key driver of the disease pathology.

根據我們在臨床上看到的情況以及透過與該領域專家的持續對話，我們將 QTORIN 雷帕黴素視為產品中的一條管道。我們已經確定了幾種符合嚴格的帕維拉 (Pavella) 標準的疾病，這些疾病屬於嚴重罕見皮膚病，缺乏 FDA 批准的療法，而 MTR 失調是疾病病理學的主要驅動因素。

These opportunities fit directly within Pavella's development strategy and offer the potential to further extend the impact of our lead asset.

這些機會直接符合 Pavella 的發展策略，並有可能進一步擴大我們領先資產的影響力。

Second, we're progressing a novel QTORIN-based program that delivers a different therapeutic agent or API. This effort is being guided by our close collaboration with many of the world's leading rare skin disease experts, clinicians who frequently see the limitations of current therapies and who help us identify promising targets both based on both biology and real-world treatment experiencing experience, including off-label use of systemic drugs.

其次，我們正在推動一項基於 QTORIN 的新型計劃，該計劃可提供不同的治療劑或 API。這項工作由我們與許多世界領先的罕見皮膚病專家和臨床醫生密切合作指導，他們經常看到當前療法的局限性，並幫助我們根據生物學和現實世界的治療經驗（包括全身藥物的標籤外使用）確定有希望的目標。

Internally, each candidate is rigorously evaluated through our disease selection process, which links biological rationale with commercial viability and alignment with Palvella's mission. Both programs, our next QTORIN and rapamycin indication and our novel QTORIN asset have identified lead diseases, and the latter has progressed to defined target molecules.

在內部，我們透過疾病選擇流程對每個候選人進行嚴格評估，該流程將生物學原則與商業可行性以及與 Palvella 使命的一致性聯繫起來。這兩個項目，我們的下一個 QTORIN 和雷帕黴素適應症以及我們的新型 QTORIN 資產都已確定了主要疾病，後者已進展到確定目標分子。

Importantly, both are tracking towards potential fast track and breakthrough therapy designation eligibility. And remain on schedule to be announced in the second half of this year. With that, I'll turn it over to Matt to provide a financial update.

重要的是，兩者都正在朝著潛在的快速通道和突破性療法認定資格邁進。並仍按計畫於今年下半年公佈。說完這些，我將把麥克風交給馬特來提供財務更新。

Thanks, Jeff. Before I turn to my financial comments, I first wanted to touch on one last point on Jeff's slide. In addition to all the key criteria that Jeff mentioned for choosing new products to develop, we also focus on diseases and programs that align with our capital efficient approach.

謝謝，傑夫。在我開始發表財務評論之前，我首先想談談傑夫幻燈片上的最後一點。除了 Jeff 提到的選擇新產品開發的所有關鍵標準之外，我們還專注於符合我們資本高效方法的疾病和專案。

For our next QTORIN molecule, we're targeting generating phase 2 proof of concept data within 2.5 years and for less than $10 million of clinical spend. We believe this approach allows Palvella to deliver maximum benefit for both patients and value for investors.

對於我們的下一個 QTORIN 分子，我們的目標是在 2.5 年內產生第 2 階段概念驗證數據，臨床支出不超過 1000 萬美元。我們相信這種方法可以讓 Palvella 為患者帶來最大利益，並為投資者帶來最大價值。

Turning now to the financials, Palvella remains in a strong financial position, allowing us to continue confidently on our path to successfully developing and commercializing drugs to treat rare diseases. Cash and cash equivalents as of March 31, 2025 or $75.6 million.

現在談談財務狀況，Palvella 仍然保持著強勁的財務狀況，這使我們能夠繼續充滿信心地成功開發和商業化治療罕見疾病的藥物。截至 2025 年 3 月 31 日的現金及現金等價物為 7,560 萬美元。

We're fortunate to have two years of cash runway remaining following the oversubscribed pipe financing we completed in connection with our reverse merger at the end of 2024.

我們很幸運，在 2024 年底反向合併中完成超額認購的管道融資後，我們還有兩年的現金儲備。

Led by BVF Partners and Frasier Life Sciences and with participation from our major existing investors plus a roster of new investors, the financing combined with existing cash, provided Palvella with a clear cash runway into the second half of 2027.

在 BVF Partners 和 Frasier Life Sciences 的領投下，以及我們現有主要投資者和一群新投資者的參與下，這筆融資加上現有現金，為 Palvella 到 2027 年下半年提供了清晰的現金流。

Our current funding covers our major upcoming milestones including the completion of our phase 3 microcystic LM trial, completion of our phase 2 cutaneous venous malformations trial, submission of the microcystic LM NDA filing, and pre-commercialization efforts, as well as the addition of two new programs to the pipeline.

我們目前的資金涵蓋了我們即將到來的主要里程碑，包括完成我們的 3 期微囊 LM 試驗、完成我們的 2 期皮膚靜脈畸形試驗、提交微囊 LM NDA 文件和商業化前期工作，以及在管道中增加兩個新項目。

Our cash spend and financial results for Q1 2025 were in line with our expectations, and I'll briefly review the results reported in this morning's press release.

我們 2025 年第一季的現金支出和財務表現符合我們的預期，我將簡要回顧一下今天上午的新聞稿中報告的結果。

Research and development expenses were $4.1 million for Q1 2025 as compared to just under $1 million for the comparable period in 2024, with the increase driven primarily by the expenses associated with our microcystic LM and cutaneous VM clinical trials.

2025 年第一季的研發費用為 410 萬美元，而 2024 年同期則略低於 100 萬美元，成長主要源自於與微囊 LM 和皮膚 VM 臨床試驗相關的費用。

General and administrative expenses were $3.8 million for Q1 2025 as compared to $800,000 for the comparable period in 2024. The increase here was driven by public company costs and the cost associated with our increased headcount.

2025 年第一季的一般及行政費用為 380 萬美元，而 2024 年同期為 80 萬美元。這裡的成長是由上市公司成本和員工人數增加相關的成本所推動的。

Our net loss was $8.2 million or $0.74 per diluted share for Q1 2025 compared to a net loss of $2.7 million or $1.54 per diluted share for the comparable period in 2024. We remain on track to end the year with at least $55 million in cash and cash equivalents based on our current strategic operating plan.

2025 年第一季度，我們的淨虧損為 820 萬美元，即每股攤薄虧損 0.74 美元，而 2024 年同期的淨虧損為 270 萬美元，即每股攤薄虧損 1.54 美元。根據我們目前的策略營運計劃，我們仍有望在年底前擁有至少 5,500 萬美元的現金和現金等價物。

Our cash spend for 2025 remains on track for approximately $30 million in total cash spend. With that, I'll turn the call back over to West for some closing remarks before we open up the call for questions.

我們 2025 年的現金支出仍將維持在約 3,000 萬美元的水準。說完這些，在我們開始提問之前，我將把電話轉回給韋斯特，讓他做一些結束語。

Great, thank you, Matt. Looking ahead, Palvella has a clear set of four high impact milestones. We expect top line data from our phase 3 SELVA study in Q1 2026. We expect top line data from our phase 2 toIVA study in Q4 2025. And we have planned to announce two new QTORIN programs in the second half of this year, an additional QTORIN rapamycin indication and a novel product from our QTORIN platform.

太好了，謝謝你，馬特。展望未來，Palvella 有四個明確的高影響力里程碑。我們預計 2026 年第一季將獲得第三階段 SELVA 研究的頂線數據。我們預計 2025 年第四季將獲得第 2 階段 IVA 研究的頂線資料。我們計劃在今年下半年宣布兩個新的 QTORIN 項目、一個額外的 QTORIN 雷帕黴素適應症以及來自我們 QTORIN 平台的一款新產品。

NDA preparation is underway, and we're actively building towards commercialization if approved, including the planned addition of a Chief Commercial Officer later this year. In closing, Paul Vella is positioned for a transformative year ahead, and we want to thank everyone for attending today's call. We'll now open the line for questions.

NDA 準備工作正在進行中，如果獲得批准，我們將積極推動商業化，包括計劃在今年稍後增設一名首席商務官。最後，保羅·維拉 (Paul Vella) 已為未來的變革之年做好了準備，我們要感謝大家參加今天的電話會議。我們現在開放問答熱線。

Thank you, ladies and gentlemen. (Operator Instructions) Our first question comes from Ritu Barra with TDC and your line is open.

謝謝各位，女士們、先生們。（操作員指示）我們的第一個問題來自 TDC 的 Ritu Barra，您的線路已開通。

Good morning guys. Thanks for taking the question. Wes, I wanted to ask you about target enrollment for Phase 3 MLM. Is there a soft target enrollment you have in mind beyond the 40? I know you mentioned keeping the relationship. With the KOLs and patients, which is very important, but I'm wondering if there may be some additional powering targets or important subpopulations worth exploring with a bigger N.

大家早安。感謝您回答這個問題。韋斯，我想問你關於第三階段 MLM 的目標招生狀況。除了 40 名學生以外，您還考慮過其他軟性招生目標嗎？我知道你曾提到維持這段關係。有了 KOL 和患者，這非常重要，但我想知道是否有一些額外的動力目標或重要的亞群值得用更大的 N 來探索。

And then I have a manufacturing related follow up.

然後我有一個與製造相關的後續工作。

Great. Hey, thanks for being on today's call. To answer your first question, the target enrollment has always been 40 patients enrolled into this study, so we were really pleased with the demand that we saw from all of our clinical study sites, all13 have enrolled patients.

偉大的。嘿，感謝您參加今天的電話會議。回答您的第一個問題，研究的目標招募人數一直是 40 名患者，因此，我們對所有臨床研究地點的需求感到非常高興，所有 13 個地點都已招募患者。

I'll ask Jeff to briefly comment as it relates to your question around powering and subpopulations.

我會請傑夫就您關於供電和亞群的問題做簡短的評論。

Yeah, so, thanks for the question. This is Jeff. So we designed the study based on the efficacy results that we observed in phase two.

是的，謝謝你的提問。這是傑夫。因此，我們根據第二階段觀察到的療效結果設計了這項研究。

In that study, all12 patients were in the top two categories of that 7 point change scale, much improved or very much improved, and based on the results, with 40 patients or more, we're greater than 99% powered into the phase 3 study, and those assumptions remain on track.

在該研究中，所有 12 名患者均處於 7 分變化量表的前兩類，即有很大改善或非常大改善，並且根據結果，在 40 名或更多患者的情況下，我們進入第 3 階段研究的動力超過 99%，並且這些假設仍然正確。

Got it. And you know what, I changed my mind. My follow-up question is going to be on something different. How does your poster impact the way that the company is looking at the TAM for MLM? Like if the incidence of MLM is higher than expected, how will this is this, I mean, I know you don't have a Chief Commercial Officer yet, but Wes, given your background, how is this changing your plan in your head on how to target these patients and those, I believe 142 or 150 ish vascular anomaly centers? Thanks.

知道了。你知道嗎，我改變主意了。我的後續問題將涉及一些不同的事情。您的海報如何影響公司看待 MLM 的 TAM 的方式？例如，如果 MLM 的發病率高於預期，這將如何發生，我的意思是，我知道您還沒有首席商務官，但是 Wes，考慮到您的背景，這會如何改變您心中的計劃，即如何針對這些患者和那些，我相信是 142 或 150 個血管異常中心？謝謝。

Well, thanks for two.

嗯，謝謝兩位。

As you well know, and others on this call on these rare diseases where there's no approved therapies. There's really an obligation by the innovator in the space, in this case, Paul Bella, to do prospective methodical work to try to really understand what the prevalence and incidents are of these patient populations.

眾所周知，其他人也都呼籲關注這些尚無獲批療法的罕見疾病。這個領域的創新者，在這個例子中是保羅·貝拉，確實有義務進行前瞻性的系統性工作，試圖真正了解這些患者群體的盛行率和發病率。

From our perspective or just a little bit of history. We had done a real-world occurrence study that's published in an orphaned Journal of Rare Diseases that estimated that there could be upwards of 80,000 microcystic or mixed patients. We followed that with a claims analysis last year which suggested that there's around 40,000 diagnosed patients in the US.

從我們的角度來看或只是一點點歷史。我們曾進行過一項真實世界發生率研究，該研究發表在《罕見疾病雜誌》上，估計可能有多達 80,000 名微囊病或混合性患者。我們去年進行了索賠分析，結果顯示美國約有 4 萬名確診患者。

So to answer your question on the prevalent side. We think the numbers from the poster are largely in line with what we've been guiding on US diagnosed prevalence. We've been guiding greater than 30,000 diagnosed US patients. What is new, and I'm glad you asked the question, is there hadn't been any rigorous work done around estimated annual incidence of microcystic lymphatic malformations.

因此，我要從普遍的角度來回答你的問題。我們認為海報上的數字與我們對美國確診盛行率的指導基本一致。我們已經指導了超過 30,000 名確診的美國患者。我很高興你問了這個問題，新的一點是，目前還沒有對微囊淋巴畸形的年發生率進行任何嚴格的研究。

So Matt and the team are working with our commercial consultants to really closely evaluate our market model to reflect that there could be 1,500 or more new patients coming into that eventual total addressable pool of patients that can be addressed with QTORIN and rapamycin.

因此，馬特和他的團隊正在與我們的商業顧問合作，非常仔細地評估我們的市場模式，以反映最終可以使用 QTORIN 和雷帕黴素治療的患者總數中可能會有 1,500 名或更多的新患者。

On the on the targeting question, we've certainly wanted to understand, given that there are established centers of excellence, these vascular anomaly centers, we think that that's favorable as we think about commercial dynamics is that these centers of excellence in place.

關於目標問題，我們當然想了解，鑑於已經建立了卓越中心，這些血管異常中心，我們認為，當我們考慮商業動態時，這些卓越中心的建立是有利的。

So we want to understand from this analysis approximately how many patients with diagnosed microcystic LMs are currently within those about 150 centers. We estimate, as you see from the poster, that about a third of those, so greater than 10,000, somewhere perhaps between 10,000 and 15,000 are in these vascular anomaly centers.

因此，我們想透過這項分析來了解目前大約 150 個中心內有多少被診斷為微囊性 LM 的患者。正如您從海報中看到的，我們估計其中約三分之一，即超過 10,000 人，大概在 10,000 到 15,000 人之間，位於這些血管異常中心。

We do think, and we've got a lot more work to do from a commercial planning perspective, but we do think that that concentration of patients should provide efficiencies for how we think about building out commercial and medical infrastructure in the United States. Thank you.

我們確實認為，從商業規劃的角度來看，我們還有很多工作要做，但我們確實認為，患者的集中應該為我們思考如何在美國建立商業和醫療基礎設施提供效率。謝謝。

One moment for our next question. Our next question comes from Annabelle Sammy with Stefo. Your line is open.

請稍等片刻，回答我們的下一個問題。下一個問題來自 Stefo 的 Annabelle Sammy。您的線路已開通。

Hi, thanks for taking my question. Actually just following on Rita's questions about the commercial side. And the infrastructure you might need. So clearly you've identified that 1/3 of the patients are sitting in these centers, but that, follows that 2/3 are not sitting at those centers.

你好，謝謝你回答我的問題。其實只是繼續回答麗塔關於商業方面的問題。以及您可能需要的基礎設施。因此很明顯你已經確定 1/3 的患者在這些中心就診，但這意味著 2/3 的患者並不在這些中心就診。

And so does that require a larger infrastructure than you may have anticipated or are you going to stick with just targeting the 142 centers and doing Separate outreach to bring people into those. And then if I can follow on the on the higher side, I guess you've said in the past that pricing is really going to depend on the results of the trial, and it's rare that you see 100% efficacy, no less carrying that into phase 3.

那麼這是否需要比您預期的更大的基礎設施，或者您是否會堅持只針對 142 個中心並進行單獨的外展以吸引人們加入這些中心。然後，如果我可以從更高的角度來理解，我想您過去曾說過，定價實際上將取決於試驗的結果，並且很少看到 100％ 的療效，更不用說將其帶入第 3 階段了。

But when you think about pricing, have you established thresholds of efficacy for various price ranges, like, say for example 70% reduction will get you X and 90% reduction will get you Y, or is it still kind of nebulous in that range? Like what do we need to see to see like really clear rare orphan pricing? Thanks.

但是當您考慮定價時，您是否為不同的價格範圍設定了功效閾值，例如，減少 70% 可獲得 X，減少 90% 可獲得 Y，還是在該範圍內仍然有點模糊？例如，我們需要看到什麼才能真正清楚地了解稀有孤兒藥的定價？謝謝。

Yeah, thanks for the question, Annabelle. So to answer your first question, we think that it's a very attractive commercial dynamic to have to have greater than an estimated 10,000 patients concentrated in about 150 centers. So right now, as we stand today, and this is all pending bringing in a Chief Commercial Officer who's going to refine our plan. We think that that's favorable.

是的，謝謝你的提問，安娜貝爾。因此，回答您的第一個問題，我們認為將超過 10,000 名患者集中在約 150 個中心是一個非常有吸引力的商業動態。所以現在，就我們今天的立場而言，這一切都有待於聘請一位首席商務官來完善我們的計劃。我們認為這是有利的。

The second area, and we're doing more digging on this with some of our consultants is that beyond those 150 vascular anomaly centers, there's a second wave of academic medical centers that do have a fairly significant patient load.

第二個領域，我們正在與一些顧問對此進行進一步的探討，那就是除了這 150 個血管異常中心之外，還有第二波學術醫療中心，這些中心的患者負擔確實相當大。

So we think that we can also efficiently go after not just the 150 established vascular anomaly centers, but that second wave of academic medical centers that has a higher concentration of patients, so that's going to be the second wave and then obviously from a targeting perspective those physicians and sites that maybe only have call it one patient that's diagnosed those, we will pursue those in a capital efficient and thoughtful manner, and there are some strategies that have been articulated by our commercial advisers in terms of how to go after that smaller percentage of the market.

因此，我們認為，我們不僅可以有效地爭取 150 個已建立的血管異常中心，還可以爭取第二波患者集中度更高的學術醫療中心，所以這將是第二波，然後顯然從目標角度來看，那些可能只診斷出一名患者的醫生和站點，我們將以資本高效和周到的方式追求他們，我們的商業顧問已經闡明了一些關於如何爭取份額的市場的策略。

On the payer front, we can share that we've engaged very experienced pricing and reimbursement advisors with deep experience in the rare disease space, having worked closely with companies like Crystal Biotech. There's a lot of things we believe that go into pricing, but most importantly, let's just talk about the fundamentals of microcystic LMs.

在付款人方面，我們可以分享的是，我們聘請了經驗豐富的定價和報銷顧問，他們在罕見疾病領域擁有豐富的經驗，並與 Crystal Biotech 等公司密切合作。我們認為有很多因素會影響定價，但最重要的是，讓我們來談談微囊 LM 的基本原理。

Number one, this is a serious rare genetic disease where when these patients have incidence of lymphorhea, they can be hospitalized. They can have acute cellulitis, sepsis. Talking about a very serious disease and one that we think payers should be motivated to see these patients do better.

首先，這是一種嚴重的罕見遺傳疾病，當這些患者出現淋巴溢血時，就需要住院治療。他們可能患有急性蜂窩性組織炎、敗血症。這是一種非常嚴重的疾病，我們認為付款人應該有動力看到這些患者的情況好轉。

Number two, there are no FDA approved therapies. I think precedents will show that companies that launch into diseases where there are no FDA approved therapies are able to command orphan pricing when you have those two dynamics. At this point in time, we have not established thresholds of efficacy and what the resulting price pricing range would be.

第二，沒有 FDA 核准的治療方法。我認為先例表明，當擁有這兩種動力時，那些針對沒有 FDA 批准療法的疾病進行研發的公司能夠獲得孤兒藥定價。目前，我們尚未確定療效閾值以及最終的價格定價範圍。

In my experience, typically what we would do is we would take the totality of the phase 3 data and then we would work closely with our pricing advisers and do some third-party sort of blinded payer work to help then establish what we think.

根據我的經驗，通常我們會做的是獲取第 3 階段的全部數據，然後與我們的定價顧問密切合作，並進行某種第三方盲付款人工作，以幫助我們確定我們的想法。

The price point would be for QTORIN and rapamycin in the US. So, as we sit here today in May of 2025, we're about two years away from commercialization. I think the most important factor on making sure that we have an exceptional commercial launch, if we're approved, is securing the right leader that's done this before, done it successfully, and can guide these really important decisions, Annabelle, that you're asking about on this call.

此價格點對應於美國的 QTORIN 和雷帕黴素。因此，當我們今天坐在這裡，也就是 2025 年 5 月，我們距離商業化還有大約兩年的時間。我認為，如果我們獲得批准，確保我們能夠順利進行商業發布最重要的因素是找到一位合適的領導者，他以前做過這件事，並且成功做過，並且可以指導這些真正重要的決定，安娜貝爾，你在這次電話會議上詢問過。

Great. Thank you so much.

偉大的。太感謝了。

One moment for our next question. Our next question comes from Louise Chan with Scotiabank, your eyes open.

請稍等片刻，回答我們的下一個問題。我們的下一個問題來自豐業銀行的 Louise Chan，請睜開你的眼睛。

Hi, thanks for taking my questions here and congratulations on all the progress this quarter. So I wanted to ask you how you think about the market size of the two assets that you will disclose later this year versus the MLM and CBM opportunity.

你好，感謝您在這裡回答我的問題，並祝賀您本季的所有進展。所以我想問您，您如何看待今年稍後將披露的兩種資產與 MLM 和 CBM 機會的市場規模。

And then do you plan to commercialize your pipeline on your own? I know there's only a few centers to target and the second wave of centers that you mentioned, but would you consider a global partner to help you in the US and outside the US? Thank you.

那麼，您計劃自行將管道商業化嗎？我知道只有幾個中心作為目標，還有您提到的第二波中心，但您會考慮在美國和美國以外尋找一個全球合作夥伴來幫助您嗎？謝謝。

Yeah, great. So, on your second question, Louise, and thanks for being on the call, on your second question, we are going to prioritize stand-alone US launch for all of our products in the rare genetic skin disease space. I think we've all seen there's been a number of successful rare disease launches where.

是的，很棒。因此，關於您的第二個問題，路易絲，感謝您接聽電話。關於您的第二個問題，我們將優先考慮在美國獨立推出我們在罕見遺傳皮膚病領域的所有產品。我想我們都已經看到了許多成功治療罕見疾病的案例。

To do everything we can to learn from those launches. What are the best practices and incorporate them into our launch in terms of outside the United States, those are valuable markets we believe for QTORIN and Rapamycin as well.

盡一切努力從這些發射中吸取教訓。就美國以外而言，最佳實踐是什麼？並將它們納入我們的產品發布中，我們相信這些市場對於 QTORIN 和雷帕黴素來說也是很有價值的。

We'll look, as any thorough company would do at both stand-alone launches in Europe and Japan. We'll also look at partnering, I think, where we stand today. We want to stick with our core competencies, which is really focusing on resources on the US, so it's most likely that we'll prioritize partnering those those markets.

我們會進行觀察，就像任何一家細緻的公司都會在歐洲和日本的獨立發表會上所做的那樣。我認為，我們還將考慮目前的合作關係。我們希望堅持我們的核心競爭力，即真正專注於美國的資源，因此我們很可能會優先考慮與這些市場合作。

But again, I think if we're doing this in a thorough way, we'll look at both launching alone and partnering, albeit with the bias, to leverage others' footprint in places like Europe and Japan to launch.

但我再次認為，如果我們要徹底地做到這一點，我們會考慮單獨推出和合作推出，儘管帶有偏見，但會利用其他人在歐洲和日本等地的足跡來推出。

In terms of how we think about our next indications for QTORIN and Rapamycin, as well as our next QTORIN platform, maybe we'll just start with the criteria of serious, rare. And nothing approved. We really want to be first.

關於我們如何考慮 QTORIN 和雷帕黴素的下一個適應症以及我們的下一個 QTORIN 平台，也許我們將從嚴重、罕見的標準開始。沒有任何一項得到批准。我們確實想成為第一名。

That is part of the fiber of this company and the entire management team is being first for these patients. We also think that has the benefit of by definition, being commercially attractive just to give a little bit of guidance, so we're answering your question. Typically we prioritize those diseases that are rare, not ultra rare. So it's unlikely that you'll see us in, these ultra rare indications with less than 2000 patients.

這是該公司精神的一部分，整個管理團隊都首先為這些患者服務。我們還認為，從定義上講，這具有商業吸引力，可以提供一點指導，所以我們正在回答您的問題。通常我們優先考慮那些罕見的疾病，而不是極為罕見的疾病。因此，您不太可能看到我們治療這些極為罕見的疾病，患者人數不到 2000 人。

We tend to gravitate towards those diseases that have, 10,000 or more patients. We think that those are commercially attractive in nature and look forward to providing you and everyone else with more detail when Jeff makes his big reveal later this year.

我們傾向於關注那些擁有 10,000 名或更多患者的疾病。我們認為這些本質上具有商業吸引力，並期待在今年稍後 Jeff 公佈重大消息時為您和其他人提供更多細節。

Thank you.

謝謝。

One moment for our next question. Our next question comes from Angela rang with Canaccord Genuity. Your line is open.

請稍等片刻，回答我們的下一個問題。我們的下一個問題來自 Canaccord Genuity 的 Angela。您的線路已開通。

Congrats on the quarter. This is actually Juan Kim. I'm for Whitney. Thanks for taking our question. Maybe just a quick one from us on phase 3. It was very encouraging to see that enrollment had completed so quickly. And so any additional color on how many of those patients are between the 3 year to 5 year old range and as a follow up, can you remind us how you intend to use that data, whether you'll be submitting a cut of that data concurrently with the initial filing, or do you expect that they will be submitted at a later date for potential label expansion? Thanks so much.

恭喜本季取得佳績。這實際上是 Juan Kim。我支持惠特妮。感謝您回答我們的問題。也許我們只是對第三階段做一個簡短的介紹。看到報名這麼快就完成，真是令人鼓舞。因此，您能否進一步說明這些患者中有多少人年齡在 3 歲至 5 歲之間？作為後續行動，您能否提醒我們您打算如何使用這些數據，您是否會在首次提交的同時提交這些數據的一部分，或者您是否預計他們會在稍後提交這些數據以進行潛在的標籤擴展？非常感謝。

Juan, thanks for your comments about the efforts of our clinical operations team and sites and investigators. We're similarly encouraged to have exceeded our enrollment target. We look forward to providing much more information at the point of full enrollment and beyond in terms of the breakout of the patients who are greater than six, as well as this additional cohort of 3- to 5-year-olds.

胡安，感謝您對我們的臨床營運團隊、站點和研究人員的努力的評價。我們同樣很高興能夠超額完成招生目標。我們期待在全面招募時及之後提供更多關於 6 歲以上患者以及 3 至 5 歲兒童群體的資訊。

To answer your question from a regulatory perspective. We are going to concurrently include data from 3- to 5-year-olds in our NDA submission. We think that that's the best strategy, assuming that we're seeing a consistent safety and efficacy profile between those two cohorts, the 3- to 5-year-olds and then the six and above.

從監管角度回答您的問題。我們將在 NDA 提交中同時納入 3 至 5 歲兒童的數據。我們認為這是最好的策略，假設我們看到這兩組人群（3 至 5 歲兒童和 6 歲以上兒童）之間具有一致的安全性和有效性。

And so the strategy there would be to concurrently submit that data, keep our NDA timelines on track, and obviously the goal here is to one, be able to serve patients.

因此，我們的策略是同時提交數據，確保我們的 NDA 時間表按計劃進行，顯然，我們的目標是能夠為患者提供服務。

With this disease down to the age of 3, but 2, getting that broader label should enrich the commercial opportunity because we're able to do patients from 3 to 5, and as we've seen from the poster at SID, there's about 1,500 new patients coming into the pool per year.

由於這種疾病的發病年齡在 3 歲到 2 歲時，獲得更廣泛的標籤應該會豐富商業機會，因為我們能夠為 3 至 5 歲的患者提供治療，而且正如我們從 SID 的海報上看到的那樣，每年大約有 1,500 名新患者加入治療池。

Great, thanks so much.

太好了，非常感謝。

One moment for our next question. Our next question comes from Ananda Gos with AC Wainwright. Your line is open.

請稍等片刻，回答我們的下一個問題。我們的下一個問題來自 AC Wainwright 的 Ananda Gos。您的線路已開通。

Hey, hi, good morning. Maybe switching gears. I just wanted to get, both MLMs and CBMs have been notoriously defined as, like the patient with, a lot of heterogeneity in terms of, the disease pathogenesis as well as in terms of the drugs.

嘿，你好，早安。或許可以換個方式。我只是想了解，MLM 和 CBM 都被錯誤地定義為患者，在疾病發病機制和藥物方面存在很大的異質性。

So how you know if you can if you can shed light on the recruitment, the patient recruitment aspect in terms of, what were the screening techniques you have used to maximize the utility of the phase 3, that would be very helpful as well as for the.

那麼，您如何知道如果您可以闡明招募情況，就患者招募方面而言，您使用了哪些篩選技術來最大限度地提高第 3 階段的效用，這將非常有幫助。

Yeah, thanks for the question. In terms of patient screening for the phase 3 study, we've enriched that study for patients that are that are determined to be moderate to severe at baseline. That's important.

是的，謝謝你的提問。在第 3 階段研究的患者篩選方面，我們豐富了針對基線時確定為中度至重度患者的研究。這很重要。

Having patients in the trial that are that are less severe, it can be hard to show a delta or separation, show a treatment effect. So that's one point of enrichment. We also have a number of techniques or controls in our protocol to make sure that we're getting the right patients into the study, and these rare disease studies where you have, sample size like our Selva study of 40 or more patients, every patient counts.

對於試驗中病情較輕的患者，很難顯示出差異或分離，也很難顯示治療效果。這是豐富的一點。我們的方案中也採用了多種技術或控制措施，以確保將合適的患者納入研究，這些罕見疾病研究的樣本量很大，例如我們的 Selva 研究有 40 名或更多患者，因此每位患者都很重要。

So, we go to great lengths in all of our rare disease studies to have strict criteria, as Jeff mentioned as it relates to patient inclusion exclusion. On the phase 2 study, I'll pass it over to Jeff to talk about how we're optimizing for the right patient population for that trial.

因此，正如 Jeff 所提到的，我們在所有罕見疾病研究中都竭盡全力製定嚴格的標準，因為這與患者納入排除有關。關於第二階段的研究，我將交給傑夫討論我們如何針對該試驗的合適患者群體進行最佳化。

Yeah. Thank you. So as a reminder, the phase 2 TIVA study is our first study in this disease. We'll be looking at safety and efficacy and then looking at a number of different end points to see how the patients potentially respond to treatment.

是的。謝謝。因此提醒一下，第 2 階段 TIVA 研究是我們對這種疾病的首次研究。我們將研究安全性和有效性，然後觀察一些不同的終點，以了解患者對治療的潛在反應。

We're repeating a lot of what we did in MLM, which was successful, which was number one, training all the clinicians as they as they start the study. I'm involved in training all those clinicians.

我們正在重複在 MLM 中所做的很多事情，這些事情是成功的，這是最重要的，即在所有臨床醫生開始研究時對他們進行培訓。我參與了所有這些臨床醫生的培訓。

The patients that are of moderate or worse severity, so we've been rich for disease severity there, and then they go through as well an external third-party check just to confirm eligibility and make sure that these are the right patients for the trial.

對於病情嚴重程度為中度或更嚴重的患者，我們已經了解了他們的病情嚴重程度，然後他們還要經過外部第三方檢查，以確認其資格並確保他們是適合參加試驗的患者。

Great, thanks.

太好了，謝謝。

One moment for our next question. Our next question comes from Dev Prasad with Lucid Capital Markets. Your line is open.

請稍等片刻，回答我們的下一個問題。我們的下一個問題來自 Lucid Capital Markets 的 Dev Prasad。您的線路已開通。

Hi, thank you for taking my question. Could you talk about steps and timeline to NDA submission?

你好，謝謝你回答我的問題。您能談談提交 NDA 的步驟和時間表嗎？

Once top line data is released in first quarter of next year, additionally, do you need to do some additional work around 505B2 submission package? Thank you.

一旦明年第一季發布了頂線數據，此外，您是否需要圍繞 505B2 提交包做一些額外的工作？謝謝。

Yeah, hey, thanks, Deb, for those questions. So our goal after topline data in Q1 of 2026, that data will be presented on a top line basis to the FDA, and then we expect to submit the NDA in the second half of 2026 that puts us on an approval trajectory assuming those timelines are met or exceeded, which is our goal of having the drug approved in Q2 of 2027.

是的，嘿，謝謝 Deb 提出這些問題。因此，我們的目標是在 2026 年第一季獲得頂線數據後，以頂線方式向 FDA 提交該數據，然後我們預計將在 2026 年下半年提交 NDA，這將使我們走上批准軌道（假設這些時間表得到滿足或超過），我們的目標是在 2027 年第二季度批准該藥物。

So top line dev Q1 of next year and then. In half of next year to have that NDA submitted, we will, as we're modeling this out and looking at timelines, we will be eligible for priority review. That's as a function of both breakthrough designation and fast track designation.

因此，頂級開發者將於明年第一季及之後進行開發。我們將在明年上半年提交該保密協議，隨著我們對此進行建模並查看時間表，我們將有資格獲得優先審查。這是突破性指定和快速通道指定的功能。

So we expect potentially a six-month priority review based on having those designations in hand in terms of the 505B2 pathway. That's really a pathway that's designed to streamline the review process. We're able to reference existing data in our case, the reference listed drug.

因此，我們預計，在獲得 505B2 途徑的指定後，可能會進行為期六個月的優先審查。這確實是一條旨在簡化審查流程的途徑。在我們的案例中，我們可以參考現有數據，即參考所列的藥物。

Is oral rapamycin or oral (serolimus), so we've got to have the right advisors assembled who are familiar with 505b2 submissions. I've done those before many times and done them successfully, and we expect to work closely with those advisors so that we have a detailed list of every item that needs to be submitted in the 505B2 pathway. But overall we think that that having 5055B2 augment breakthrough, fast track, and orphan is favorable for the program.

是口服雷帕黴素還是口服（塞羅莫司），所以我們必須召集熟悉 505b2 提交的合適顧問。我之前已經做過很多次了，並且都成功了，我們希望與這些顧問密切合作，以便我們有一個詳細的清單，列出 505B2 途徑中需要提交的每一項內容。但總體而言，我們認為 5055B2 增強突破、快速通道和孤兒藥對該計劃有利。

Good, thank you.

好的，謝謝。

One moment for our next question. Next question comes from Catherine Novak with Jones trading. Your line is open.

請稍等片刻，回答我們的下一個問題。下一個問題來自瓊斯交易公司的凱瑟琳·諾瓦克。您的線路已開通。

Hi, morning. Thanks for taking my question. I just want to ask a little bit about the difference between the scales, phase 2, phase 3. The physicians not have to reference photos in phase 2. And as well, do you have confirmation from the FDA that this new scale satisfies the need for static measures of LMs as well as the improvement relative to baseline. Thanks.

嗨，早安。感謝您回答我的問題。我只是想問量表、第 2 階段、第 3 階段之間的差異。醫生在第二階段不需要參考照片。另外，您是否得到了 FDA 的確認，即這個新量表滿足了 LM 靜態測量的需求以及相對於基線的改進。謝謝。

Great. So, to answer your first question, in phase two, physicians were able to access the photos that were baseline photos, but they were not required to in the protocol. Given that we extended Catherine treatment duration from 12 weeks to 24 weeks, we felt that the addition to the protocol of requiring the physicians at that primary endpoint visit, which is a live clinician assessment.

偉大的。因此，回答您的第一個問題，在第二階段，醫生能夠訪問基線照片，但協議中並沒有要求他們這樣做。鑑於我們將凱瑟琳的治療時間從 12 週延長至 24 週，我們認為在方案中增加要求醫生進行主要終點訪問的條款，即現場臨床醫生評估。

At 24 weeks to reference back to that baseline photo, we think that that added an important layer of objectivity to that assessment. So that was the change that we supported, and we think strengthened the data. It also helps to mitigate recall bias when a physician is trying to recall what a patient's status was or lesion's severity was 24 weeks ago.

我們認為，在 24 週後回顧基線照片，可以為評估增添重要的客觀性。所以這是我們支持的改變，我們認為它強化了數據。當醫生試圖回想 24 週前患者的狀況或病變的嚴重程度時，它也有助於減輕回憶偏差。

Jeff, I'm going to pass it over to you to answer the second part of Katherine's question.

傑夫，我會把這個問題交給你來回答凱瑟琳問題的第二部分。

Yeah, thank you, Katherine Jeff. So we've had extensive, conversations with the FDA on the primary endpoints, starting with the breakthrough therapy designation, we presented the clinician interviews from the trial as well as clinician testimonies, and this was the most sensitive end points. Subsequent to that meeting, we did apply for the FDA breakthrough therapy designation. And that was or not, the FDA orphan drug grant which we were awarded, and overall, we are aligned on the end points with the FDA.

是的，謝謝你，凱瑟琳傑夫。因此，我們與 FDA 就主要終點進行了廣泛的對話，從突破性療法認定開始，我們提供了試驗中的臨床醫生訪談以及臨床醫生的證詞，這是最敏感的終點。在那次會議之後，我們確實申請了 FDA 突破性療法認定。不管這是否是我們獲得的 FDA 孤兒藥補助金，總的來說，我們在終點上與 FDA 保持一致。

Got it. And then, I think you just you had disclosed your power and assumptions that it could detect a 0.5 point change on the scale, is that correct? Is that is that meaningful? Or, what, to what extent would an improvement be considered meaningful to these patients?

知道了。然後，我認為您剛剛披露了您的能力和假設，即它可以檢測到規模上 0.5 個點的變化，對嗎？那有那麼有意義嗎？或者，對這些患者來說，什麼程度的改善才算有意義？

Yeah, so, Katherine, on that question, in rare diseases, typically you're not defining minimal clinically important differences on a pre-specified basis. I think what you're referencing on the 0.5 improvement.

是的，凱瑟琳，關於這個問題，在罕見疾病中，通常你不會在預先指定的基礎上定義最小的臨床重要差異。我認為您指的是 0.5 的改進。

Is what we would need to see to achieve the lower threshold of statistical significance. So, zero on our scale, which goes from negative three very much worse to plus three very much improved. Zero is no change with 40 patients in the study, if the mean change is 0.5, which would be significantly below what we saw in phase two, which was about a 2.42 average change. With a standard deviation that's higher than what we assumed in phase two, we'd still be at a threshold of achieving statistical significance according to our biostatistical assumptions.

是我們需要看到的，以達到統計顯著性的較低閾值。因此，我們的量表上的數值為零，從-3 級非常糟糕到+3 級非常改善。如果研究中的 40 名患者的平均變化量為 0.5，那麼零就表示沒有變化，這將大大低於我們在第二階段看到的變化量（平均變化量約為 2.42）。即使標準差高於我們在第二階段假設的標準差，根據我們的生物統計學假設，我們仍然處於實現統計顯著性的閾值。

Okay. Got it. Thanks, that's helpful.

好的。知道了。謝謝，這很有幫助。

And I'm not showing any further questions at this time, and as such, this does conclude today's presentation. You may now disconnect and have a wonderful day.

我現在沒有其他問題，今天的演講就到此結束。現在您可以斷開連接並享受美好的一天。