Krystal Biotech Inc (KRYS) 2024 Q3 法說會逐字稿

Thank you for standing by and welcome to Krystal Biotech's third-quarter earnings conference call. (Operator Instructions) As a reminder, today's conference is being recorded.

感謝您的耐心等待並歡迎參加 Krystal Biotech 第三季財報電話會議。（操作員指示）提醒一下，今天的會議正在錄製中。

I would now like to hand the conference over to your host, Stephane Paquette, Vice President of Corporate Development. Please begin.

現在我想將會議交給東道主企業發展副總裁史蒂芬‧帕克特 (Stephane Paquette)。請開始。

Good morning, and thank you all for joining today's call. Earlier today, we released our financial results for the third quarter of 2024. The press release is available on our website at www.krystalbio.com. We also filed our earnings 8-K and 10-Q with the SEC earlier today.

早安，感謝大家參加今天的電話會議。今天早些時候，我們發布了 2024 年第三季的財務表現。新聞稿可在我們的網站 www.krystalbio.com 上取得。今天早些時候，我們也向 SEC 提交了 8-K 和 10-Q 收益報告。

Joining me today will be Krish Krishnan, Chairman and Chief Executive Officer; Suma Krishnan, President of Research and Development; Jennifer McDonough, Senior Vice President of Patient Access Analytics and Operations; Christine Wilson, Senior Vice President and Head of US Sales and Marketing; and Kate Romano, Chief Accounting Officer.

今天與我一起出席的還有董事長兼執行長 Krish Krishnan； Suma Krishnan，研發總裁； Jennifer McDonough，病患訪問分析與營運資深副總裁； Christine Wilson，資深副總裁兼美國銷售與行銷主管；凱特‧羅馬諾 (Kate Romano)，首席會計官。

This conference call will and our responses to questions may contain forward-looking statements. You are cautioned not to rely on these forward-looking statements, which are based on current expectations using the information available as of the date of this call and are subject to certain risks and uncertainties that may cause the company's actual results to differ materially from those projected. A description of these risks, uncertainties, and other factors can be found in our SEC filings.

本次電話會議以及我們對問題的回答可能包含前瞻性陳述。請注意，不要依賴這些前瞻性陳述，這些陳述基於使用截至本次電話會議之日可用資訊的當前預期，並受到某些風險和不確定性的影響，可能導致公司的實際結果與這些結果存在重大差異預計。這些風險、不確定性和其他因素的描述可以在我們向 SEC 提交的文件中找到。

With that, I will turn the call over to Krish.

這樣，我會將電話轉給克里什。

Thank you, Stephane. Good morning, and welcome to the call.

謝謝你，史蒂芬。早安，歡迎您的來電。

Look, as I mentioned in my PR attribution, we're well on our way to achieving the two-year target that we set at the time of the launch. And by comparison to any other launch in orphan diseases or generic therapies, we believe our launch has exceeded all expectations to date. In my mind, there are two primary drivers for this success, the first obviously being the drug itself with all its attributes of efficacy, safety, patient convenience, et cetera, and the second being our assiduous focus on patient and physician experience. We've allowed the physician and the patient to drive demand at a pace they are comfortable with, and it has been rewarding especially in an indication where the expectation is that they will be on drug for a long time.

看，正如我在公關歸因中提到的，我們正在順利實現我們在發佈時設定的兩年目標。與任何其他孤兒疾病或非專利療法的推出相比，我們相信我們的推出已經超越了迄今為止的所有預期。在我看來，這項成功有兩個主要驅動因素，第一個顯然是藥物本身及其功效、安全性、患者便利性等所有屬性，第二個是我們對患者和醫生體驗的孜孜不倦的關注。我們允許醫生和患者以他們覺得舒服的速度推動需求，這是有回報的，特別是在預期他們將長期服用藥物的情況下。

On top of that, global opportunities for VYJUVEK come into focus. Ophthalmic formulation is progressing towards a registrational study in the next few months. And so we're starting to see increasing upside in the total market opportunity for the VYJUVEK franchise overall as we work toward treating DEB patients globally and comprehensively.

最重要的是，VYJUVEK 的全球機會成為焦點。眼科配方將在未來幾個月內進行註冊研究。因此，隨著我們致力於在全球範圍內全面治療 DEB 患者，我們開始看到 VYJUVEK 特許經營權的整體市場機會不斷增加。

In Europe, we're presently on track for a CHMP opinion before year end, and our recent breakthrough with HAS, granting early reimbursed access in France reflects the significant demand for VYJUVEK in Europe. And with our JNDA submitted last month, we're also on track for the 2025 launch in Japan. And so all preparations are underway for launching EU4, UK, and Japan, sequentially next year.

在歐洲，我們目前正計劃在年底前徵求 CHMP 意見，而我們最近與 HAS 的突破，在法國給予早期報銷准入權反映了歐洲對 VYJUVEK 的巨大需求。隨著我們上個月提交的 JNDA，我們也預計在 2025 年在日本推出。因此，明年依序推出 EU4、英國和日本的所有準備工作正在進行中。

Meanwhile, we had a positive readout for Jeune Aesthetics' KB301 in Q3, where we saw clear efficacy signals, and that propels us forward to a Phase 2 study expected to start next year and also continue to work on the Jeune Aesthetics' pipeline. That was the first of many data readouts upcoming from our deep clinical stage pipeline. We're looking forward to reporting on two more programs before year-end including our first data on HSV-1-based gene delivery to the lung, a tissue that has to date been hard to reach with other approaches. So both on the commercial and clinical fronts, we're excited and look forward to the rest of 2024 and 2025.

同時，我們在第三季度對Jeune Aesthetics 的KB301 進行了積極的解讀，我們看到了明確的功效信號，這推動我們推進預計將於明年開始的2 期研究，並繼續致力於Jeune Aesthetics 的管道工作。這是我們深度臨床階段管道即將讀出的眾多數據中的第一個。我們期待在年底前報告另外兩個項目，包括我們關於將基於 HSV-1 的基因傳遞到肺部的第一個數據，迄今為止，其他方法很難到達肺部組織。因此，無論是在商業還是臨床方面，我們都感到興奮並期待 2024 年和 2025 年的剩餘時間。

Finally, I'm happy to report that Krystal was again profitable this quarter at $0.95 per share, up sequentially from $0.54 per share in the second quarter of 2024. In Q3, we accrued $12.5 million in litigation expenses that once again mitigated our EPS as it did in our two prior quarters. This is the final accrual related to the litigation expense, and there will be no additional litigation accruals moving forward. With increasing profitability, a strong balance sheet, and upcoming expansion of our VYJUVEK franchise both in the US and through ex-US launches, and our eye drop formulation, we're super stoked about both the near term- and the long-term outlook for Krystal.

最後，我很高興地報告，Krystal 本季再次獲利，每股獲利 0.95 美元，高於 2024 年第二季每股 0.54 美元。第三季度，我們累積了 1250 萬美元的訴訟費用，這再次降低了我們的每股收益，就像前兩個季度一樣。這是與訴訟費用相關的最終應計費用，以後不會有額外的訴訟應計費用。隨著盈利能力的提高、強勁的資產負債表、即將在美國和美國以外地區推出 VYJUVEK 特許經營權以及我們的滴眼劑配方，我們對近期和長期前景感到非常興奮為了克里斯塔爾。

Moving now to our results. Net VYJUVEK revenue for the Q came in at $83.8 million, while gross margins in GTN continue to behave as expected. Thanks to the strong growth we achieved this quarter, total net VYJUVEK revenue since launch in August 2023 has already surpassed $250 million. Achieving this milestone only a little over a year after our first sale is a tremendous achievement for our organization and a testament to the value VYJUVEK is providing to patients suffering from DEB. Also, please note that net VYJUVEK revenue reported today again includes accrual for patients on contracted commercial plans who are projected to potentially hit the cap of $900,000 gross per patient per calendar year in 2024.

現在來看我們的結果。VYJUVEK Q 的淨收入為 8,380 萬美元，而 GTN 的毛利率繼續符合預期。由於我們本季實現的強勁成長，自 2023 年 8 月推出以來，VYJUVEK 總淨收入已超過 2.5 億美元。在我們首次銷售僅一年多一點的時間裡就實現了這一里程碑，這對我們的組織來說是一項巨大的成就，也證明了 VYJUVEK 為 DEB 患者提供的價值。另請注意，今天報告的 VYJUVEK 淨收入再次包括合約商業計劃患者的應計費用，預計到 2024 年，這些患者每日曆年的總收入可能會達到 900,000 美元的上限。

With that, I'll hand it off to Jen and Christine to share more detail on our recent accomplishments and strong fundamentals, which we expect will sustain our launch for years to come. Jen?

接下來，我將把它交給 Jen 和 Christine，讓他們分享更多關於我們最近的成就和強大的基礎知識的細節，我們預計這將在未來幾年維持我們的發布。珍？

Thank you, Krish. I am pleased to report another quarter of strong VYJUVEK access growth across the US in sspite of summer seasonality headwinds as our team works tirelessly to help more and more patients gain control over this terrible disease. As of October, the number of patients with reimbursement approvals is up to over 460. Reimbursement approvals were modestly impacted by transient summer seasonality effects in this quarter. These scheduling disruptions are now behind us. More importantly, and thanks to our flexible support infrastructure that adapts to patient schedules and timelines, we have been able to keep patients and their applications for reimbursement on track to achieve positive access outcomes.

謝謝你，克里什。我很高興地報告，儘管存在夏季季節性逆風，但 VYJUVEK 在美國各地的使用量又實現了強勁增長，因為我們的團隊孜孜不倦地努力幫助越來越多的患者控制這種可怕的疾病。截至10月，獲批報銷的患者人數已達460餘人。本季短暫的夏季季節性影響對報銷審批產生了輕微影響。這些日程安排中斷現在已經成為過去。更重要的是，由於我們適應患者日程和時間表的靈活支援基礎設施，我們能夠讓患者及其報銷申請步入正軌，以實現積極的訪問結果。

Reimbursement approval splits are largely in line with recent quarters and roughly evenly split between commercial and government plans. Approvals continue to come across the entire DEB patient population, including patients of all ages and with either dominant or recessive forms of the disease. With near-complete coverage for commercial and Medicaid live nationwide, the access for VYJUVEK is strong. This has enabled us to achieve 100% success rate on reauthorizations, all have either been approved or are in process and sets us up well for sustained success in the US. Our Krystal Connect team works closely with the home healthcare providers, employing a patient-centric approach that focuses on patient needs and preferences.

報銷審批比例與最近幾季基本一致，商業計劃和政府計劃之間的比例大致相等。整個 DEB 患者群體繼續獲得批准，包括所有年齡層以及患有顯性或隱性疾病的患者。VYJUVEK 幾乎完全覆蓋全國範圍內的商業和醫療補助，因此其訪問範圍很廣。這使我們能夠實現 100% 的再授權成功率，所有授權均已獲得批准或正在進行中，並為我們在美國的持續成功奠定了良好的基礎。我們的 Krystal Connect 團隊與家庭醫療保健提供者密切合作，採用以患者為中心的方法，重點關注患者的需求和偏好。

The team navigates things such as summer vacations, family activities, working back-to-school schedules to successfully integrate weekly treatment into the family's normal routine. Patient preference for at-home administration is effectively unchanged, and currently, 97% of the weekly treatments occur in the home setting. With now over one year of real-world experience, the team is developing and implementing strategies to ensure patients receive the best possible experience starting and staying on VYJUVEK. This includes developing enhanced education, tools, and other resources for patients and nurses.

團隊負責處理暑假、家庭活動、返校工作時間表等事宜，成功地將每週治療融入家庭的日常生活中。患者對在家治療的偏好實際上並沒有改變，目前，97% 的每週治療是在家庭環境中進行的。憑藉一年多的實際經驗，該團隊正在製定和實施策略，以確保患者在開始和留在 VYJUVEK 時獲得盡可能最佳的體驗。這包括為患者和護理人員開發強化教育、工具和其他資源。

We focus on topics such as preparing for treatment, practical considerations for wound selection, and options for hydrophobic dressings. We recognize that every patient has unique needs, and the impact of the disease varies for each patient. Our program and resources include regular touchpoints to support monitoring treatment progress and identifying potential issues early and addressing them promptly. While we continue to see a high compliance to weekly treatment at 87% across our DEB patient population, including new starts for both recessive and dominant dystrophic EB, please note that for some patients that have been on VYJUVEK for over an extended period of time, in particular, who have been participated in our OLE study, we are seeing maintenance treatment patterns emerge.

我們重點討論治療準備、傷口選擇的實際考慮因素以及疏水性敷料的選擇等主題。我們認識到每位患者都有獨特的需求，疾病對每位患者的影響也各不相同。我們的計劃和資源包括定期接觸點，以支持監測治療進展並及早發現潛在問題並及時解決。雖然我們繼續看到我們的DEB 患者群體對每週治療的依從性很高，高達87%，包括隱性和顯性營養不良EB 的新開始，但請注意，對於一些已經使用VYJUVEK 較長時間的患者，特別是對於參與我們的 OLE 研究的人，我們看到維持治療模式的出現。

This includes cycling between periods of treatment pauses due to wound closure. While it's early, and we believe it would be premature to estimate the frequency or the duration of treatment pauses, we can expect reported compliance to weekly treatment across the entire patient base to trend down in upcoming quarters. As we continue our launch, the Krystal Connect team is fully focused on ensuring patients have a smooth experience starting and staying on therapy. We are developing and investing in strategies that lead to better treatment outcomes and overall satisfaction. We are building long-term patient relationships and are committed to providing sustained worry-free access to corrective therapy where and when they need it.

這包括由於傷口閉合而導致治療暫停期間的循環。雖然現在還為時過早，而且我們認為現在估計治療暫停的頻率或持續時間還為時過早，但我們預計整個患者群每週治療的依從性在未來幾個季度將呈下降趨勢。隨著我們繼續推出產品，Krystal Connect 團隊完全專注於確保患者在開始和持續治療時擁有順利的體驗。我們正在製定和投資能夠帶來更好治療結果和整體滿意度的策略。我們正在與患者建立長期關係，並致力於在他們需要的時間和地點提供持續、無憂的矯正治療。

I will now hand it off to Christine to discuss recent sales and marketing activities which have us on track to hit our most ambitious prelaunch penetration targets. Christine.

我現在將把它交給克里斯汀討論最近的銷售和行銷活動，這些活動使我們有望實現最雄心勃勃的發布前滲透目標。克里斯汀.

Thank you, Jen. As Jen just mentioned, at launch, we set an ambitious target for the commercial organization. We established a goal of 60% penetration of the identified patient pool, equating to roughly 720 reimbursement approvals within two years of launch. I'm happy to say that based on our progress to date, our ongoing sales and marketing efforts and the sustained demand we are seeing in the field, we remain on track to achieve this goal. Our core commercial strategy focused on the three pillars of claims analytics, medical education, and patient activation is paying off.

謝謝你，珍。正如 Jen 剛才提到的，在啟動時，我們為商業組織設定了一個雄心勃勃的目標。我們設定的目標是使已確定的患者庫滲透率達到 60%，相當於在推出後兩年內獲得約 720 項報銷批准。我很高興地說，根據我們迄今為止的進展、我們持續的銷售和行銷努力以及我們在該領域看到的持續需求，我們仍然有望實現這一目標。我們專注於理賠分析、醫學教育和患者激活三大支柱的核心商業策略正在取得回報。

We are seeing strong demand across both key centers and in the community as we continue to drive awareness of VYJUVEK and the real-world impact to healthcare professionals, patients, and caregivers. Healthcare professional education remains a major focus. We continue to educate physicians and their support staff on how VYJUVEK is the only FDA-approved therapy that treats the genetic cause of death sharing the clinical data that supports long-term use in wound healing for all patients from localized to severe disease and showing the stunning real-world results patients are seeing at home.

隨著我們不斷提高 VYJUVEK 的認識以及對醫療保健專業人員、患者和照護者的現實影響，我們看到了主要中心和社區的強勁需求。醫療保健專業教育仍然是主要焦點。我們繼續向醫生及其支持人員介紹 VYJUVEK 如何成為 FDA 批准的唯一治療遺傳性死亡原因的療法，並分享臨床數據，支持從局部到嚴重疾病的所有患者長期使用傷口癒合，並顯示患者在家中就能看到令人驚嘆的真實結果。

In addition, we are working with physicians, particularly those in the community who may not regularly see these patients to educate them on the streamlined process for getting their patients started on VYJUVEK. This is a high-touch, customer-centric model that delivers a positive onboard experience for both the prescriber and the patients. The prescriber base is expanding.

此外，我們正在與醫生合作，特別是那些可能不定期拜訪這些患者的社區醫生，教育他們如何讓患者開始使用 VYJUVEK 的簡化流程。這是一種高接觸度、以客戶為中心的模式，為處方者和患者提供積極的機上體驗。處方者基礎正在擴大。

Over 70% of the prescribers in 3Q were new writers. This demonstrates that our targeting efforts are effective and that both KOLs and community physicians see the value of VYJUVEK and ease of prescribing. We have also made significant progress recently in our direct-to-consumer outreach. We are now live on all planned social media channels, showcasing real-world experiences for both pediatric and adult patients, some of whom have been on therapy since 2020. Since January of this year, our paid social direct-to-consumer advertising has served over 31.3 million impressions, connecting prospective patients and caregivers with VYJUVEK. The 3Q launch into new social platforms, along with lead generation advertising on social media, will continue to drive user engagement and expand our reach.

第三季超過 70% 的處方者是新作家。這表明我們的針對性努力是有效的，KOL 和社區醫生都看到了 VYJUVEK 的價值和處方的便利性。最近，我們在直接面向消費者的推廣方面也取得了重大進展。我們現在在所有計劃的社交媒體頻道上直播，展示兒科和成人患者的真實體驗，其中一些患者自 2020 年以來一直在接受治療。自今年 1 月以來，我們的付費社交直接面向消費者的廣告已提供超過 3,130 萬次展示，將潛在患者和照護者與 VYJUVEK 連接起來。第三季推出新的社群平台，以及社群媒體上的潛在客戶開發廣告，將繼續推動用戶參與度並擴大我們的覆蓋範圍。

Finally, as part of our annual recognition and support of EB Awareness Week, which took place just last week, the Krystal team hosted educational webinars for our target physician audience as well as sponsor a patient and caregiver webinar in conjunction with one of our EB advocacy partners. These live webinars feature dermatologists with real-world DEB and VYJUVEK experience as well as VYJUVEK-treated patients showing their personal experience of the positive impact that VYJUVEK has brought to their conditions. Members of the Krystal team also attended the debra of America benefit during EB Awareness Week, which honors those in the EB community and champions our ongoing mission to advance EB research and patient care.

最後，作為我們上週舉行的EB 意識週年度表彰和支持的一部分，Krystal 團隊為我們的目標醫生受眾舉辦了教育網絡研討會，並與我們的EB 倡導者之一聯合贊助了一場患者和護理人員網路研討會合作夥伴。這些現場網路研討會邀請了具有實際 DEB 和 VYJUVEK 經驗的皮膚科醫生以及接受 VYJUVEK 治療的患者，展示了他們對 VYJUVEK 給他們的病情帶來的積極影響的個人經驗。Krystal 團隊的成員也參與了 EB 意識週期間的 debra of America 慈善活動，該活動旨在表彰 EB 社區的人們，並支持我們不斷推進 EB 研究和患者護理的使命。

These are just a few highlights from our ongoing commercial efforts to drive awareness, streamline the physician experience, and help more patients get on treatment faster. It has been deeply rewarding to see these efforts translate into reimbursement approvals, and with continued education, we are optimistic that we can achieve not only the near-term targets we have set but ultimately grow well past them in later years.

這些只是我們持續不斷的商業努力的一些亮點，這些努力旨在提高人們的認識、簡化醫生的體驗並幫助更多的患者更快地接受治療。看到這些努力轉化為報銷批准，我們感到非常高興，並且透過繼續教育，我們樂觀地認為，我們不僅可以實現我們設定的近期目標，而且最終在以後的幾年中遠遠超過這些目標。

Now I will hand it off to Suma to share pipeline results.

現在我將把它交給 Suma 來分享管道結果。

Thank you, Christine. Our development team continues to execute at a high level. And over the past few months, we have achieved key milestones to not only broaden DEB patient access but also advance our diverse pipeline of redosable genetic medicines. Leading off with an update on the global development of PVAC, steady progress has poised for commercial launches in both Europe and Japan next year. In Europe, EMA's review of our marketing authorization application is progressing well.

謝謝你，克里斯汀。我們的開發團隊繼續保持高水準執行。在過去的幾個月裡，我們實現了重要的里程碑，不僅擴大了 DEB 患者的可及性，而且推進了我們可重複使用基因藥物的多樣化管道。以 PVAC 全球發展的最新情況為開端，穩步進展已為明年在歐洲和日本的商業推出做好了準備。在歐洲，EMA 對我們行銷授權申請的審查進展順利。

EU GMP certification was granted for our commercial manufacturing facility, Ancoris, earlier this year. And our latest interactions with the EMA suggest support for home dosing and a broad label, including DEB patients from birth.

今年早些時候，我們的商業生產工廠 Ancoris 獲得了歐盟 GMP 認證。我們與 EMA 的最新互動表明支持家庭給藥和廣泛的標籤，包括從出生起的 DEB 患者。

Based on the current pace of discussions, we expect a CHMP decision before the end of the year and a first launch in Germany in the first half of 2025. In interim, we also achieved an access breakthrough in France. In September, Haute Autorité de Santé in France approved premarketing early reimbursed access to B-VEC under the Accès Précoce program. DEB patient access to B-VEC under AP1 is expected to start later this year. AP1 allows for early access to innovative therapies in France prior to European regulatory approval and is a reflection of the strongly positive benefit/risk ratio provided by B-VEC in a patient population with high unmet need. In addition to rapidly broadening patient access in France, this approval will also provide physicians with an opportunity to build clinical experience with B-VEC even in advance of commercial launch.

根據目前的討論進度，我們預計 CHMP 將在年底前做出決定，並於 2025 年上半年在德國首次推出。在此期間，我們還在法國實現了進入突破。9 月，法國 Haute Autorité de Santé 批准了 Accès Précoce 計劃下的 B-VEC 上市前早期報銷。DEB 患者預計將於今年稍後開始根據 AP1 獲得 B-VEC。AP1 允許在歐洲監管機構批准之前在法國儘早獲得創新療法，這反映了 B-VEC 在需求未滿足的患者群體中提供的強烈的積極效益/風險比。除了迅速擴大法國患者的使用範圍之外，此次批准還將為醫生提供在 B-VEC 商業推出之前積累臨床經驗的機會。

In Japan, we also achieved a major milestone with the recent submission of our Japan new drug application. Our application to the Japanese authorities include the results of our open-label extension study in Japanese patients in which overall results closely mirror those from our registrational Phase 3 trial. Having previously received orphan drug designation by Japan's Pharmaceuticals and Medical Device Agency, we expect a priority review putting us on track for both the decision by Japanese authorities as well as launch in 2025.

在日本，我們最近提交了日本新藥申請，也實現了一個重要的里程碑。我們向日本當局提出的申請包括我們在日本患者中進行的開放標籤擴展研究的結果，其中總體結果與我們的註冊 3 期試驗的結果非常接近。我們先前已獲得日本藥品和醫療器材管理局的孤兒藥指定，預計優先審查將使我們走上日本當局的決定以及 2025 年上市的軌道。

Shifting focus to our broader pipeline. We are very excited to report the first of many upcoming data readouts last quarter. In the data readout for Jeune Aesthetics' KB301, we reported clear and clinically significant improvements in not only wrinkles but many other skin attributes including radiance, hydration, and creepiness. This robust efficacy signal taken together with our previous reports of durable benefit positions KB301 as a potentially transformational product in the field of regenerative aesthetics. We look forward to progressing KB301 into Phase 2 next year. This is just the beginning. Before the end of the year, we expect to disclose interim updates on the KB408 and KB707 programs.

將重點轉移到更廣泛的管道。我們非常高興地報告上季即將公佈的眾多數據中的第一個。在 Jeune Aesthetics 的 KB301 的數據讀出中，我們報告了不僅在皺紋方面而且在許多其他皮膚屬性（包括光澤、水合作用和令人毛骨悚然）方面都有明顯且具有臨床意義的改善。這種強大的功效訊號與我們先前的持久效益報告相結合，使 KB301 成為再生美學領域潛在的變革性產品。我們期待明年將 KB301 推進到第二階段。這只是開始。年底前，我們預計將揭露 KB408 和 KB707 計畫的中期更新。

KB408 is our redosable inhaled therapy for alpha-1 antitrypsin deficiency which is currently being evaluated in a Phase 1 Serpentine-1 study. Serpentine-1 is an open-label, single-dose escalation study in adult patients with AATD to allow assessment of safety, tolerability, alpha-1 antitrypsin levels, and key pharmacodynamic biomarkers. With strong enrollment and a recent protocol amendment to include bronchoscopies in Cohort 2, we hope to provide interim molecular data before the end of the year.

KB408 是我們針對 alpha-1 抗胰蛋白酶缺乏症的可重複吸入療法，目前正在 1 期 Serpentine-1 研究中進行評估。Serpentine-1 是一項針對 AATD 成年患者的開放標籤、單劑量遞增研究，旨在評估安全性、耐受性、α-1 抗胰蛋白酶水平和關鍵藥效生物標記。隨著入組人數的增加以及最近的方案修訂將支氣管鏡檢查納入第 2 組，我們希望在今年年底之前提供臨時分子數據。

On readout, we expect to showcase the significant potential of HSV-1 for gene delivery through the lung. KB707 is our modified HSV-1 vector designed to deliver genes encoding both human IL-12 and IL-2 to the tumor microenvironment and promote systemic immune-mediated tumor clearance. Two formulations, one, for the intratumoral injection and the other for delivery by inhalation are being evaluated in Phase 1 dose escalation and expansion studies. Both studies are enrolling well. And with this pace, we expect to share an interim data update focused on safety and early immune profiling data before end of the year.

在讀出時，我們希望展示 HSV-1 透過肺部進行基因傳遞的巨大潛力。KB707 是我們改良的 HSV-1 載體，旨在將編碼人類 IL-12 和 IL-2 的基因遞送到腫瘤微環境並促進全身免疫介導的腫瘤清除。兩種製劑，一種用於腫瘤內注射，另一種用於吸入給藥，正在第一階段劑量遞增和擴展研究中進行評估。這兩項研究的招生情況都很好。按照這個速度，我們預計將在年底前分享專注於安全性和早期免疫分析數據的中期數據更新。

I'm also happy to share that intratumoral KB707 was granted a rare pediatric disease designation for the treatment of rhabdomyosarcoma. Both inhaled and intratumoral KB707 has now been granted rare pediatric disease designation and Fast Tack designation by the FDA.

我還很高興地告訴大家，腫瘤內 KB707 被授予治療橫紋肌肉瘤的罕見兒科疾病資格。吸入型和瘤內注射型 KB707 現已獲得 FDA 的罕見兒科疾病認定和 Fast Tack 認定。

We expect additional data updates in 2025, including follow-on updates on our oncology program as well as initial data from an ongoing Phase 1 study evaluating inhaled KB407 for cystic fibrosis. We recently activated two additional clinical sites in our Phase 1 CORAL-1 study, evaluating KB407 and are now on a path to report intermolecular data for KB407 in the first half of 2025.

我們預計 2025 年會有更多數據更新，包括我們的腫瘤學計劃的後續更新，以及正在進行的評估吸入 KB407 治療囊性纖維化的 1 期研究的初始數據。我們最近在 1 期 CORAL-1 研究中啟動了另外兩個臨床中心，評估 KB407，目前正準備在 2025 年上半年報告 KB407 的分子間數據。

Finally, we are on track to both start and report interim data from our registrational trial, IOLITE, next year. IOLITE will be a single-arm, open-label study designed to evaluate KB803, our newly developed ophthalmic formulation of B-VEC, for the treatment of ocular complications in DEB patients. In the interim, we continue to enroll in our natural history study to prospectively collect data on the frequency of corneal abrasions in patients with DEB. This study will also serve as a run-in period for patients who may be eligible to participate in IOLITE and should enable us to accelerate enrollment in this registrational study.

最後，我們預計在明年啟動並報告註冊試驗 IOLITE 的中期數據。IOLITE 將是一項單臂、開放標籤研究，旨在評估 KB803（我們新開發的 B-VEC 眼科製劑）用於治療 DEB 患者眼部併發症的效果。在此期間，我們繼續參與自然史研究，前瞻性地收集 DEB 患者角膜擦傷頻率的數據。這項研究也將作為可能有資格參加 IOLITE 的患者的磨合期，並使我們能夠加快這項註冊研究的入組速度。

We have entered an exciting period for Krystal as we unveil trial results that we expect will highlight the visibility of our gene delivery program. We look forward to sharing these updates as they unfold and advancing our pipeline of uniquely differentiated genetic therapies.

對於 Krystal 來說，我們已經進入了一個令人興奮的時期，我們公佈了試驗結果，我們預計這些結果將突出我們的基因傳遞計劃的可見性。我們期待分享這些最新進展，並推進我們獨特差異化基因療法的研發管線。

With that, I would like to turn the call to Kate.

說到這裡，我想把電話轉給凱特。

Thank you, Suma. In the third quarter, Krystal saw continued VYJUVEK revenue growth with net product revenue of $83.8 million, representing an increase of approximately $75.3 million over the third quarter of 2023 which was the first quarter that we had revenue after our approval in May of 2023. Cost of goods sold was $6.7 million for the quarter or about 8% of net product revenue, resulting in a gross margin of 92%. In the third quarter of 2023, cost of goods sold was artificially low at $223,000 as a result of a significant portion of the cost to manufacture being previously expensed to research and development expense prior to product approval.

謝謝你，蘇瑪。第三季度，Krystal 的 VYJUVEK 收入持續成長，產品淨收入為 8,380 萬美元，比 2023 年第三季增加約 7,530 萬美元，這是我們在 2023 年 5 月獲得批准後第一個有收入的季度。該季度的銷售成本為 670 萬美元，約佔產品淨收入的 8%，毛利率為 92%。2023 年第三季度，銷售成本被人為壓低至 223,000 美元，因為在產品批准之前，很大一部分製造成本已計入研發費用。

Research and development expenses for the quarter were $13.5 million, inclusive of stock-based compensation of $2.3 million compared to $10.6 million for the prior year's third quarter inclusive of $2.3 million of stock-based compensation. Higher research and development expenses in the third quarter of 2024 were due to increased clinical development costs, increased R&D-related manufacturing costs for our pipeline candidates, and increased R&D facilities and equipment costs this quarter. These increases were partially offset by capitalization of direct and indirect over cost to manufacture VYJUVEK being charged to inventory following our FDA approval.

本季的研發費用為 1,350 萬美元，其中包括 230 萬美元的股票薪酬，而去年第三季的研發費用為 1,060 萬美元，其中包括 230 萬美元的股票薪酬。2024年第三季的研發費用增加是由於臨床開發成本增加、我們的候選產品研發相關製造成本增加以及本季研發設施和設備成本增加。這些成長被 FDA 批准後計入庫存的直接和間接生產 VYJUVEK 成本資本化部分抵消。

Selling, general, and administrative expenses for the quarter were $28.7 million, inclusive of stock-based compensation of $11 million compared to $23.7 million for the prior year's third quarter, inclusive of stock-based compensation of $6 million. Higher selling, general, and administrative expenses in the third quarter of 2024 compared to the prior year's third quarter were primarily the result of increased commercial-related professional service fees and VYJUVEK marketing costs. The most significant increase in SG&A is related to the increase in stock compensation expense of $5 million quarter over quarter. We again recorded litigation settlement expense this quarter of $12.5 million due to our anticipation of reaching the third and final milestone payment in the PeriphaGen settlement which is triggered at $300 million in cumulative sales payable within 30 days following the filing of our Form 10-K in which the $300 million milestone is achieved.

本季的銷售、一般和管理費用為 2,870 萬美元，其中包括 1,100 萬美元的股票薪酬，而去年第三季的銷售、一般和管理費用為 2,370 萬美元，包括 600 萬美元的股票薪酬。與去年第三季相比，2024 年第三季的銷售、一般和管理費用增加，主要是由於商業相關的專業服務費和 VYJUVEK 行銷成本增加。SG&A 最顯著的成長與股票薪資費用較上季增加 500 萬美元有關。我們本季再次記錄了1250 萬美元的訴訟和解費用，因為我們預計將達到PeriphaGen 和解中的第三筆也是最後一筆里程碑付款，該付款是在我們提交10-K 表格後30 天內應付的累計銷售額達到3 億美元時觸發的。

We now have fully accrued for the entirety of this matter and, if achieved, anticipate making the final related payments in early 2025. Net income for the quarter was $27.2 million, which represented $0.95 per basic and $0.91 per diluted share. We have reduced and narrowed the range of our non-GAAP R&D and SG&A expense guidance which is now expected to be between $115 million and $125 million for the full year ending December 31, 2024. As a reminder, this guidance excludes the noncash impact of stock-based compensation.

我們現在已經為整個此事全額提列了費用，如果實現的話，預計將在 2025 年初支付最終的相關付款。本季淨利為 2,720 萬美元，相當於每股基本收益 0.95 美元，每股稀釋收益 0.91 美元。我們減少並縮小了非 GAAP 研發和 SG&A 費用指南的範圍，目前預計截至 2024 年 12 月 31 日的全年將在 1.15 億美元至 1.25 億美元之間。提醒一下，本指南不包括股票薪酬的非現金影響。

Finally, we ended the third quarter with $374 million in cash on hand and $694.2 million in total cash plus short-term and long-term investments, marking continued quarterly growth in our overall cash and investment position with an increase over our second quarter of 2024 cash and investments balance by about $65 million.

最後，截至第三季末，我們的手頭現金為3.74 億美元，加上短期和長期投資的現金總額為6.942 億美元，這標誌著我們的整體現金和投資頭寸持續季度增長，較2024 年第二季度有所增長現金和投資餘額約 6500 萬美元。

And now I will turn the call back over to Krish.

現在我將把電話轉回給克里什。

Thanks, Kate. So in closing, I'd like to highlight the significant potential for value creation in the years ahead to be driven both by VYJUVEK and our deep clinical stage pipeline. Our VYJUVEK launch, having already achieved over $250 million in net revenue is progressing very well. However, as we saw in Q4 of last year, we do anticipate some disruption over the holiday season as life gets in the way for many families. That said, our conviction in the overall trajectory of our launch remains unchanged. More importantly, this is only the beginning of the opportunity we see for the VYJUVEK franchise.

謝謝，凱特。因此，最後，我想強調在 VYJUVEK 和我們深入的臨床階段管道的推動下，未來幾年價值創造的巨大潛力。我們的 VYJUVEK 推出已取得超過 2.5 億美元的淨收入，進展順利。然而，正如我們在去年第四季看到的那樣，我們確實預計假期期間會出現一些幹擾，因為許多家庭的生活會受到影響。也就是說，我們對發布整體軌蹟的信念保持不變。更重要的是，這只是我們為 VYJUVEK 特許經營權看到的機會的開始。

In the coming years, we expect ex-US expansion, development and launch of our eye drop formulation for KB803, both driving significant revenue growth. Meanwhile, our KB301 readout is a reminder of the significant, yet-to-be tapped potential that we see in our pipeline. With multiple readouts coming up, we think we're on the verge of demonstrating the true potential of our HSV-1-based gene therapy platform. And with the benefit of commercial scale in-house GMP manufacturing infrastructure, growing revenues, five quarters of positive EPS, we have the necessary resources to pursue these opportunities efficiently and in such a way to maximize value for our shareholders.

未來幾年，我們預計 KB803 眼藥水配方將在美國以外地區擴張、開發和推出，推動收入顯著成長。同時，我們的 KB301 讀數提醒我們，我們在管道中看到了巨大的、尚未開發的潛力。隨著多個讀數的出現，我們認為我們即將展示基於 HSV-1 的基因治療平台的真正潛力。憑藉商業規模的內部 GMP 製造基礎設施、不斷增長的收入、五個季度的正 EPS，我們擁有必要的資源來有效地抓住這些機會，並以這種方式為我們的股東實現價值最大化。

Thanks for listening. I'd like to open the call for Q&A.

感謝您的聆聽。我想打開問答電話。

(Operator Instructions)

（操作員說明）

Alec Stranahan, BOA.

亞歷克·斯特拉納漢，BOA。

Just two from us. First, could you give us a sense of how many patients are at or near their annual cap currently? Is this something we should be looking for when we model sales into year-end? Or should the new patient adds throughout the year sort of offset this?

離我們只有兩個人。首先，您能否讓我們了解目前有多少患者達到或接近年度上限？當我們對年底的銷售進行建模時，這是我們應該尋找的東西嗎？或者全年增加的新患者是否應該抵消這項影響？

And second, I appreciate this data is probably still evolving, but on the duration of wound closures over time, curious if there's any trends coming out of your clinical studies you could point to for duration of wound closure. Just trying to get a sense of how long a pause due to wound closure could last before a patient would need to receive therapy again?

其次，我知道這些數據可能仍在不斷發展，但隨著時間的推移，傷口閉合的持續時間，我想知道您的臨床研究中是否有任何趨勢可以指出傷口閉合的持續時間。只是想了解在患者需要再次接受治療之前，因傷口閉合而導致的暫停會持續多久？

On your first question on how many patients are going to hit the cap. We're not particularly disclosing that aspect of it. You can glean the cap is in the GTM, and the whole point of growing was to make sure there's no volatility with respect to net revenues in any of the quarters. That's the whole point. And I think we're on track to make sure that the net revenue growth is pretty smooth over Q1, Q2, Q3, and Q4. We'll have a much better sense as we go further into the launch of that point.

關於你的第一個問題，有多少患者將達到上限。我們並沒有特別揭露這方面的內容。您可以了解 GTM 中的上限，而成長的全部目的是確保任何季度的淨收入都沒有波動。這就是重點。我認為我們有望確保第一季、第二季、第三季和第四季的淨收入成長相當穩定。當我們進一步推出這一點時，我們會有更好的感覺。

With respect to duration of wound closure, a couple of things I want to mention. Look, there are -- depending on the location of the wound and the nature of the activity, this can be pretty varied across individuals. Our thesis is still to stick on -- even though we've seen much larger durations of wound closure in some patients, we still stick to the science behind it, which is, given the half-life of collagen, we expect the average wound to be durable for about 90 days.

關於傷口閉合的時間，我想提幾件事。看，根據傷口的位置和活動的性質，這可能因人而異。我們的論點仍然堅持下去——儘管我們已經看到一些患者的傷口閉合時間更長，但我們仍然堅持其背後的科學，即考慮到膠原蛋白的半衰期，我們預計傷口的平均癒合時間耐用約90天。

And then, I mean, can I add? Also agree, I mean, we are seeing very good clinical benefits. The wounds are closing, and they are staying durable. But also what happens is these patients are now increasing their activity. We hear from patients now they can go out and do more physical activities. They can work.

然後，我的意思是，我可以添加嗎？我也同意，我的意思是，我們看到了非常好的臨床效益。傷口正在癒合，而且很持久。但同時發生的事情是這些患者現在正在增加他們的活動。我們聽說患者現在可以出去做更多的體能活動。他們可以工作。

As a result, they see breakdown in the skin, but now they're very -- I mean, they want the wound to be treated because they see the benefit of treating VYJUVEK. So the patients are being extra cautious. So even if the wounds are closed and if they [ripe] open, they want the drug back on. So that's the trend that we see in the commercial setting.

結果，他們看到皮膚破裂，但現在他們非常——我的意思是，他們希望傷口得到治療，因為他們看到了治療 VYJUVEK 的好處。所以患者要格外小心。因此，即使傷口已經閉合並且傷口[成熟]，他們也希望重新使用藥物。這就是我們在商業環境中看到的趨勢。

Yigal Nochomovitz, Citi Group.

Yigal Nochomovitz，花旗集團。

I was just curious about your broader marketing campaign. So I think you mentioned something about the very broad footprint on the social media platforms, 31.3 impression. Can you comment to what extent that's actually helping identify patients? Or obviously, it's a low conversion rate given the market size, but I'm just curious how that's working as far as identifying patients? And if any of that effort has translated to new starts?

我只是對你們更廣泛的行銷活動感到好奇。所以我想你提到了社交媒體平台上非常廣泛的足跡，31.3 的印象。您能否評論一下這在多大程度上真正有助於識別患者？或者顯然，考慮到市場規模，轉換率很低，但我只是好奇這在識別患者方面是如何發揮作用的？這些努力是否已轉化為新的開始？

Christine?

克里斯汀？

Sure. Yeah, we're excited about -- our goal is to receive patients wherever they may be, and our social media campaigns are allowing us to do that. We are seeing benefit of finding some patients that are not yet engaged or haven't been engaged for some period of time with the healthcare system that is allowing to reach them, educate them, and engage them in accessing their HCPs. So we are pleased, as you mentioned, the volumes will, right, from a patient base to begin with, right, as were in the ultrarare space. But our opportunity to reach every patient is ultimately our goal, and one by one, we're getting there.

當然。是的，我們很興奮——我們的目標是接收無論身在何處的患者，而我們的社群媒體活動使我們能夠做到這一點。我們發現，找到一些尚未參與或在一段時間內未參與醫療保健系統的患者是有好處的，該系統允許接觸他們、教育他們並讓他們接觸他們的 HCP。因此，正如您所提到的，我們很高興這些卷將從患者群體開始，對，就像在極其罕見的空間中一樣。但我們最終的目標是有機會接觸到每位患者，我們正在一個接一個地實現這一目標。

And then I think, Krish, on the last call, you mentioned that you identified about 10% more patients from the 1,200 base that was forecast at the launch. I'm just curious if you had any updated thoughts in terms of that number or you're comfortable with that statement now?

然後我想，Krish，在上次電話會議中，您提到您從啟動時預測的 1,200 名患者中確定了大約 10% 的患者。我只是好奇您對這個數字是否有任何更新的想法，或者您現在對這個說法感到滿意嗎？

In terms of comfortable, yeah, we were comfortable when we reported the number. The trend continues to go up. And if we hit a significant milestone moving forward, we'll report again. But more and more patients as VYJUVEK tends to be well used and the volume of patients increases, the awareness goes up, we are starting to see the market expand beyond the original estimate.

就舒適度而言，是的，當我們報告這個數字時，我們感到很舒服。趨勢持續上升。如果我們向前邁進了一個重要的里程碑，我們將再次報告。但隨著越來越多的患者使用VYJUVEK，且患者數量增加，認知度提高，我們開始看到市場擴大超出最初的估計。

Ritu Baral, TD Cowen.

裡圖·巴拉爾，TD·考恩。

I'm going to focus on Europe with my two questions today. Have you guys received the 180-day questions? And if so, can you comment on the topics and whether you've responded and whether at this point, you're expecting oral arguments. And then I think it was Suma to your point on label expectations. You mentioned that -- it sounded like you could go down to DEB patients from birth literally, but you didn't comment on recessive versus dominant. Is that a question in Europe?

今天我將重點放在歐洲的兩個問題。你們收到180天的問題了嗎？如果是這樣，您能否對這些主題發表評論，以及您是否已做出回應以及此時您是否期待口頭辯論。然後我認為這是蘇瑪對你的標籤期望的觀點。你提到過——聽起來你可以從字面上看DEB患者從出生開始，但你沒有評論隱性與顯性。這是歐洲的問題嗎？

And then the follow-up question is for Krish on pricing in Europe. What can you say on how we should be thinking about European pricing versus US pricing and how to best model that?

接下來的問題是克里什關於歐洲定價的問題。您對我們應該如何考慮歐洲定價與美國定價以及如何最好地建模有何看法？

Thanks, Ritu for the question. Yes, we did receive the 180 questions. And in fact, today is our response date to the 180-day question. Yes, I mean, most of the -- all the issues are resolved. There doesn't seem to be an oral meeting at the point set with the EMA at the moment. So that's where we stand.

謝謝瑞圖的提問。是的，我們確實收到了 180 個問題。事實上，今天是我們對 180 天問題的答覆日期。是的，我的意思是，大多數——所有問題都得到了解決。目前似乎沒有與 EMA 舉行口頭會議。這就是我們的立場。

With regarding to the label, the label right now as the way it goes based on our 180-day comment on the SMBC, it's going to be from birth in the EV patients. That includes both dominant and representations for the SMBC.

關於標籤，目前的標籤是基於我們對 SMBC 的 180 天評論，它將從 EV 患者出生起就開始使用。這包括 SMBC 的主導地位和代表性。

On pricing, Ritu, we're going to do our very best to get the maximum price possible. We're starting -- excuse me, when you think about pricing, in Germany, for example, we get to launch with the US price for the first six months as we start to begin negotiations in Germany, the first country of launch. At the end of six months, will start accruing, expecting a certain price that we land with at the end of 12 months. So the actual pricing in Europe in the first country doesn't really get set until 1Q of, say, 2026 at this moment.

關於定價，Ritu，我們將盡最大努力獲得盡可能高的價格。我們正在開始——對不起，當你考慮定價時，例如在德國，我們將在前六個月以美國價格推出，因為我們開始在第一個發布國家德國開始談判。六個月末，將開始累積，預計我們在 12 個月末達到一定的價格。因此，歐洲第一個國家的實際定價要到 2026 年第一季才會真正確定。

We will have an [unknown] price given the NPP. So what will be public is the US and the unknown price. But overall expectations for us, if you combine all of Europe, look, at the conservative end, about 50% of the US price. And we'll do our very best given all the product differentiators for VYJUVEK to make a strong case in an ultra-rare disease to land somewhere between the 50% and the US (inaudible)

考慮到核電站，我們將得到一個[未知]的價格。所以將公開的是美國和未知的價格。但我們的整體預期是，如果將整個歐洲結合起來，保守地說，約為美國價格的 50%。考慮到 VYJUVEK 的所有產品差異化因素，我們將盡最大努力，為超罕見疾病提供有力的支持，使其登陸 50% 和美國之間的某個地區（聽不清楚）

I just want to add one more thing is we are still on track to get home dosing in euro. So based on the 180 days. So that's something very positive for us.

我只想補充一件事，我們仍在按計劃以歐元進行國內給藥。所以基於180天。所以這對我們來說是非常正面的事情。

Sami Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

How do you expect declining compliance to impact revenue? And do you plan on giving any revenue guidance for 2025? And then just as a follow-up, you kind of pointed us to reimbursement approvals as a measure of the VYJUVEK launch in the US. What metrics are we looking for for the launch as it progresses in Europe and Japan next year?

您預計合規性下降會對收入產生什麼影響？您是否打算給予 2025 年的收入指引？然後，作為後續行動，您向我們指出了報銷批准作為 VYJUVEK 在美國推出的衡量標準。隨著明年在歐洲和日本的推出，我們會尋找哪些指標？

Hey, Sami. I missed the first half of your first question ahead of the guidance. What were you saying?

嘿，薩米。我在指導之前錯過了你的第一個問題的前半部分。你說什麼？

How you expect the decline in compliance to impact revenue?

您預計合規性下降將如何影響收入？

In the US, you mean?

你是說在美國？

Yes, yeah.

是的，是的。

Look, when we launched -- at the time of the launch, our expectation was that patients would be utilizing four vials a month, and our expectation was that it would get to about two vials a month, 18 months post launch. That was the expectation we had at the time of launch. We seem to be much ahead with respect to compliance because the overwhelming proportion of patients in the study were recessive and potentially more severe in the early days of launch. So we're tracking a little bit higher of that.

看，當我們推出時，我們的預期是患者每月會使用四瓶，我們的預期是每月大約使用兩瓶，即推出後 18 個月。這是我們在發佈時的期望。我們在依從性方面似乎遙遙領先，因為研究中絕大多數患者都是隱性的，在啟動初期可能會更加嚴重。所以我們追蹤的數字會更高一些。

We're already at like 15 months, and we don't expect to get to 50% over the next three months. So we're ahead. And that, as I mentioned before, is primarily because the percentage of RDEB patients is much higher than the dominant patients in the study. With respect to revenue guidance next year, we're still thinking and internally talking about it. We have put ourselves in a position where we're actually expecting an EU launch early in 1Q, and we have to get closer to figure out the rate at which the German launch progresses.

我們已經有大約 15 個月的時間了，我們預計在接下來的三個月內不會達到 50%。所以我們領先了。正如我之前提到的，這主要是因為 RDEB 患者的比例遠高於研究中的主要患者。關於明年的收入指導，我們仍在思考和內部討論。我們實際上預計在第一季初在歐盟推出，並且我們必須進一步了解德國推出的進度。

And then we're up in France under the AP2 or the AP1 program. So a lot of moving parts next year to be extremely definitive about guidance at this point. But hopefully, by the time the next Q comes around, we'll have more clarity on what we're going to talk about with respect to guidance in 2025.

然後我們在法國參加 AP2 或 AP1 計劃。因此，明年的許多活動部件在這一點上都將非常明確地給予指導。但希望在下一個問題出現時，我們能夠更清楚地了解我們將要討論的 2025 年指導內容。

With respect to your last question, in the US, we had reimbursement approvals. In the EU, everything is a bit different. Germany is a bit different than France. It's a bit different than Japan. And so we haven't made a decision at this point in time. And as we get closer to the CHMP opinion, we'll sit down and talk about what makes the best sense in terms of expecting what net revenues for 2025 will end up being.

關於你的最後一個問題，在美國，我們獲得了報銷批准。在歐盟，一切都有點不同。德國與法國略有不同。這和日本有點不一樣。所以我們目前還沒有做出決定。隨著我們越來越接近 CHMP 的意見，我們將坐下來討論什麼對於預期 2025 年淨收入最終是最有意義的。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

I just wanted to focus in on AATD and the data coming later this year. A first question here, can you just level set on the amount of data that we'll be getting? Like how many patients per cohort, which patients can be on augmentation therapy, and also remind us which cohorts the lavages are done in and at what time point?

我只是想關注 AATD 和今年稍後發布的數據。第一個問題是，您能否對我們將獲得的資料量進行水平設定？例如每個隊列有多少患者，哪些患者可以接受增強治療，並提醒我們在哪些隊列中進行灌洗以及在什麼時間點進行？

Yeah. Right now, we are in the process of enrolling Cohort 2. We happen in enrolling three patients. We are going to enroll additional patients in Cohort 2, and based on our animal study and our NHP study, we feel this is a cohort that we really need to evaluate molecular correction for this dose because we did see nice expression at this equaling dose in the NHP animal model.

是的。目前，我們正在招募第二組。我們碰巧招募了三名患者。我們將在隊列 2 中招募更多患者，根據我們的動物研究和 NHP 研究，我們認為這是我們確實需要評估該劑量的分子校正的隊列，因為我們確實在該相等劑量下看到了良好的表達NHP動物模型。

So we have additional patients. They are basically ZZ patients. The combinations -- right now, we have patients that are not on augmentation and on augmentation. So we will do -- evaluate them before and after for molecular correction in their lung lavage.

所以我們有更多的病人。他們基本上都是ZZ患者。組合－現在，我們有未接受增強治療和正在接受增強治療的患者。因此，我們將在肺部灌洗中對他們進行分子校正之前和之後進行評估。

So we hope to have couple of patients enrolled before end of the year and hope to have data on that cohort by end of the year with regards to levels of expression, multiple biomarkers, A180 expression, neutrophil elastase, binding of neutrophil elastase, so we'll understand and have a complete picture of what the inhaled molecule is doing.

因此，我們希望在今年年底前招募幾名患者，並希望在年底前獲得該隊列的表達水平、多種生物標記、A180 表達、中性粒細胞彈性蛋白酶、中性粒細胞彈性蛋白酶結合的數據，所以我們將理解並全面了解吸入分子的作用。

That's helpful. And do you believe that the bronchoalveolar lavages or the bronchoscopies will be more informative. And what's the bar on either of those measures?

這很有幫助。您認為支氣管肺泡灌洗或支氣管鏡檢查會提供更多資訊嗎？這些措施的門檻是什麼？

So we are looking at everything. I mean, obviously, these patients were subjected to bronchoscopy, so we have their baseline bronchoscopy done. We now just -- we have -- we collected the lavage. We did biopsies. So we have both brushing of the lung. So all three was taken at the baseline and after dosing, so we will look at all of that in completeness to understand what it looks like.

所以我們正在考慮一切。我的意思是，顯然，這些患者接受了支氣管鏡檢查，所以我們完成了他們的基線支氣管鏡檢查。我們現在只是──我們已經──收集了灌洗液。我們做了活檢。所以我們都刷肺部。因此，這三項都是在基線和給藥後進行的，因此我們將完整地查看所有這些，以了解它的樣子。

As far as levels, I mean, again, we are hoping -- I mean, again, hoping we -- I mean, these patients will not have A180, so we're going to hope to see good expression levels of A180, at least 1 micromole in the lung lavage.

就水平而言，我的意思是，我們再次希望——我的意思是，再次希望我們——我的意思是，這些患者不會有 A180，所以我們希望看到 A180 的良好表達水平，肺灌洗液中至少有1 微摩爾。

Gavin, I do want to add one point. We are a redosing mechanism, right? So -- and one of our objectives following a good readout in AATD is to go into a redosing type situation. So while one is kind of like a target we've set for ourselves, if you look at the complete package and we get close enough to it, we will look to redosing to move the program forward. But I do want to be clear, at this point, we do not have any sense of what the levels are in any of these patients.

加文，我確實想補充一點。我們是一個重劑量機制，對吧？因此，在 AATD 良好讀數後，我們的目標之一是進入重劑量類型的情況。因此，雖然一個目標有點像我們為自己設定的目標，但如果您查看完整的計劃並且我們已經足夠接近它，我們將尋求重做以推動該計劃向前發展。但我確實想澄清，目前我們對這些患者中的水平沒有任何了解。

I mean, also keep in mind, we are looking at the entirety, right? You're looking at neutrophil elastase, the binding of A180 to neutrophil elastase. So it's not just the expression of A180. You want to make sure you're seeing wild type A with A180, and it's functional. So that's critical.

我的意思是，也要記住，我們正在關注整體，對吧？您正在觀察嗜中性球彈性蛋白酶，即 A180 與嗜中性球彈性蛋白酶的結合。所以這不僅僅是A180的表達。您需要確保看到的是帶有 A180 的野生 A 型，並且它具有功能性。所以這很關鍵。

So we're going to -- those are -- that's the kind of data that's going to be critical for us. And hopefully, that's what will lead to see clinical benefit.

因此，我們將——這些數據——對我們來說至關重要。希望這將帶來臨床效益。

Dae Gon Ha, Stifel.

大貢河，斯蒂菲爾。

Two from us as well. Going back to the VYJUVEK launch metric, you mentioned 460 being reimbursed. I was kind of curious if you can maybe give us a little bit more color around how that distribution is between centers of excellence and the primary care, I guess, the community dots. Just kind of curious what kind of growth we should be expecting going into Q4 and the future.

我們也有兩個。回到 VYJUVEK 啟動指標，您提到了 460 美元的報銷。我很好奇你能否給我們更多關於卓越中心和初級保健中心（我想是社區點）之間的分佈的信息。只是有點好奇我們應該期待第四季和未來的成長。

And secondly, on the AATD, just to kind of level set and clarify here. Suma, is it the expectation that the year-end update is Cohort 1 and 2, and therefore, you will make a go-forward decision as well as the protocol amendment for redosing after the Cohort 2? Or will you still go through Cohort 3A and 3B, which I recall was the IV augmentation or without IV augmentation?

其次，關於 AATD，只是為了在這裡設定和澄清。Suma，是否預計年終更新是隊列 1 和隊列 2，因此您將在隊列 2 之後做出前進的決定以及重做方案的修訂？或者您仍然會經歷隊列 3A 和 3B，我記得這是 IV 增強還是沒有 IV 增強？

So I'll take your question first, and then I think the commercial team will answer your question one. Yes, I think a Cohort 1 and -- I mean, if we see the expression we need to, I think we will stop at Cohort 2. If not, I mean, we have the option to move to Cohort 3 because, so far, we don't see any dose-limiting toxicity in our Cohort 2.

所以我先回答你的問題，然後我認為商業團隊會回答你的問題一。是的，我認為是第 1 組，而且——我的意思是，如果我們看到我們需要的表達，我認為我們將在第 2 組停止。如果沒有，我的意思是，我們可以選擇轉移到第 3 組，因為到目前為止，我們在第 2 組中沒有看到任何劑量限制性毒性。

So we have the option. But I think we are at a pretty good dose level right now with Cohort 2. And if we get -- you see what we see, then I think we will be ready to go into repeat dosing with Cohort 2 or the option to to go Cohort 3.

所以我們有選擇。但我認為我們現在第 2 組的劑量水平相當不錯。如果我們得到——你看到我們所看到的，那麼我認為我們將準備好與隊列 2 重複給藥或選擇進入隊列 3。

Hi. I'm happy to answer question number two. Our success has been built on the fact that we balanced growth in both the COEs and the community setting. Our KOLs continue to position VYJUVEK in a very healthy way. What we see in the COEs is either new patients that are coming in and where patients who maybe haven't yet seen the COE since the approval of VYJUVEK.

你好。我很高興回答第二個問題。我們的成功建立在我們平衡 COE 和社區環境成長的基礎上。我們的 KOL 繼續以非常健康的方式定位 VYJUVEK。我們在 COE 中看到的要么是新進來的患者，要么是自 VYJUVEK 批准以來尚未見過 COE 的患者。

In the community setting, as was mentioned, 70% of our prescribers in Q3 were new prescribers, and that's because we are successful in identifying where these patients are through our claims alert, but allowing us to find these patients all across the United States including in the community setting. So we need to do both in order for us to continue to see the growth trajectory that we see today.

如同前面所提到的，在社區環境中，我們在第三季的處方者中有70% 是新處方者，這是因為我們透過索賠警報成功地確定了這些患者的位置，而且使我們能夠在美國各地找到這些患者，包括在社區環境中。因此，我們需要同時做到這兩點，才能繼續看到今天的成長軌跡。

I guess, Suma, just to clarify, Cohort 1 and 2 data for the year-end update for AATD?

我想，Suma，只是為了澄清一下，AATD 年終更新的隊列 1 和隊列 2 數據？

You're right. That's what we're shooting for. I mean, we have patients enrolled in the bronchoscopy portion, and hopefully, we'll keep adding more patients to that.

你說得對。這就是我們拍攝的目的。我的意思是，我們有患者參加了支氣管鏡檢查部分，希望我們能繼續增加更多的患者。

(Operator Instructions) Debjit Chattopadhyay, Guggenheim Securities.

（操作員指令）Debjit Chattopadhyay，古根漢證券公司。

So as patients approach their reimbursement caps coupled with the holiday season, how should we think about 4Q? Do you expect a significant growth here, or is this going to be a sequentially flat quarter? And then on the 2025 guidance, I understand a lot of moving parts as far as Europe is concerned, but why not guide to the US market, especially now that you have trends both from the summer and the holiday season under your belt?

那麼隨著病患報銷上限的臨近以及假期的到來，我們該如何看待第四季？您預計該季度會顯著成長嗎？然後，關於 2025 年指導，就歐洲而言，我了解很多變化因素，但為什麼不指導美國市場，尤其是現在您掌握了夏季和假期季節的趨勢？

Yeah, look, on the first question, the only reason I made the comment, I remember some confusion last year after we came through Q4. And the only point I'm trying to make is Thanksgiving and Christmas. Those are at least two weeks where patients try to not have a dose due to life, family, vacations, or whatever, and also the nurses have their own schedules. So the only reason for making that comment was not to directionally point to some weakening or flattening.

是的，看，關於第一個問題，我發表評論的唯一原因，我記得去年我們經歷第四季後出現了一些混亂。我唯一想說的是感恩節和聖誕節。在這至少兩週的時間裡，患者因生活、家庭、假期或其他原因盡量不服藥，護士也有自己的時間表。因此，發表這項評論的唯一原因不是直接指出某種削弱或扁平化。

We're still on track for the 720 reimbursement approvals, as we said at the time of the launch. I just wanted to alleviate concerns post Q4 right now by saying, please think about the holidays, life gets in the way.

正如我們在發佈時所說，我們仍在順利獲得 720 項報銷批准。我現在只是想減輕第四季後的擔憂，我說，請考慮一下假期，生活會受到阻礙。

With respect to guidance for 2025, you are right. We will have a much better handle of the US We will not have a handle on Germany or France or some of the other ex-US countries. And so at the end of the year, we'll sit down and think about going into the Q4 if that's something that would be useful to shareholders as a way to model, fully realizing that it will be supplemented by revenues potentially in Germany and France and hopefully even Japan.

關於 2025 年的指導，你是對的。我們將更能應對美國。因此，在今年年底，我們將坐下來考慮進入第四季度，這是否對股東有用，作為一種建模方式，充分認識到它將得到德國和法國潛在收入的補充希望甚至是日本。

Andrea Newkirk, Goldman Sachs.

安德里亞·紐柯克，高盛。

Maybe one here on the European launch. Just curious if you could share what activities are currently underway as you prepare for this potential launch starting in Germany. And then as you do look to next year, what type of step-up in infrastructure do you believe is required to support the launch?

也許是歐洲發表會上的一個。只是好奇您是否可以分享當前正在進行的活動，因為您正在為在德國啟動的這一潛在發布做準備。然後，當您展望明年時，您認為需要哪種類型的基礎設施升級來支援發布？

Yeah, Thanks, Andrea. With respect to activities, Look, we're starting to work on the dossiers ahead of the pricing negotiations in several countries. The commercial team in Germany is in place and would probably -- and the commercial team in France is expected to be in place by the end of the year, the first two countries we're going to be launching in.

是的，謝謝，安德里亞。關於活動，您看，我們正在幾個國家的定價談判之前開始處理檔案。德國的商業團隊已經就位，並且很可能會就位，而法國的商業團隊預計將在今年年底前就位，這是我們將首先在兩個國家推出的產品。

In terms of infrastructure, look, we're not -- we're expecting somewhere about 10 employees per country at a high level. And that usually includes pretty much all aspects of commercial like medical affairs, reps, maybe somebody for access, et cetera. So a rough estimate would be less than 10 employees per country for each of the European countries.

在基礎設施方面，我們預計每個國家約有 10 名高水準員工。這通常包括商業的幾乎所有方面，如醫療事務、代表、也許是訪問人員等等。因此，粗略估計每個歐洲國家的員工人數將少於 10 名。

Got it. And should we expect those to be onboarded, I guess, maybe closer to the potential launch in each of those -- as those countries come online?

知道了。我想，隨著這些國家/地區上線，我們是否應該期望這些國家/地區能夠加入，也許更接近這些國家的潛在推出？

I think in Germany, most of them will be onboarded before the end of the year. In France, maybe some by the end of the year and some early next year. And we also have a team out in Japan. We have like six to eight employees in Japan today, and they'll be onboarded in the first half in anticipation of a two days launch in Japan.

我認為在德國，他們中的大多數人將在年底前入職。在法國，也許有些是今年底，有些則是明年初。我們在日本也有一個團隊。今天我們在日本有大約六到八名員工，他們將在上半年入職，預計在日本推出兩天。

There are no further questions in queue.

隊列中沒有其他問題。

So thank you all for joining the call. We look forward to answering any follow-on questions in the upcoming days. Thank you.

感謝大家加入此次通話。我們期待在未來幾天回答任何後續問題。謝謝。

Thank you for joining the Krystal Biotech's third-quarter earnings conference call. This concludes today's event. You may disconnect your phone lines at this time, and have a wonderful day. Thank you for your participation.

感謝您參加水晶生物科技第三季財報電話會議。今天的活動到此結束。此時您可以斷開電話線，度過美好的一天。感謝您的參與。