Krystal Biotech Inc (KRYS) 2025 Q2 法說會逐字稿

Thank you for standing by, and welcome to the Krystal Biotech Q2 2025 earnings call. (Operator Instructions) As a reminder, today's conference is being recorded.

感謝您的支持，歡迎參加 Krystal Biotech 2025 年第二季財報電話會議。（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，我想將會議交給主持人、企業發展副總裁 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 second quarter of 2025. 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 2025 年第二季的財務表現。新聞稿可在我們的網站 www.krystalbio.com 上查閱。我們今天稍早也向美國證券交易委員會 (SEC) 提交了 8-K 和 10-Q 財報。

Joining me today will be Krish Krishnan, Chairman and Chief Executive Officer; Suma Krishnan, President of Research and Development; Laurent Goux, Senior Vice President and General Manager for Europe, and Kate Romano, Chief Accounting Officer.

今天與我一起出席的還有董事長兼首席執行官克里什·克里希南 (Krish Krishnan)、研發總裁蘇瑪·克里希南 (Suma Krishnan)、歐洲高級副總裁兼總經理洛朗·古克斯 (Laurent Goux) 和首席會計官凱特·羅馬諾 (Kate Romano)。

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。這些陳述是基於使用截至本次電話會議之日可用資訊得出的當前預期，並受某些風險和不確定性的影響，這些風險和不確定性可能導致公司的實際結果與預測結果有重大差異。這些風險、不確定性和其他因素的描述可以在我們的美國證券交易委員會文件中找到。

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

說完這些，我將把電話轉給克里什 (Krish)。

Stephane, thank you. Good morning, everyone, and welcome to the Krystal earnings call. We'd like to touch on four topics in this call. First, the VYJUVEK launch, which is progressing well, and the upcoming launches in Europe and Japan are expected to significantly add to what is already a top-tier trajectory in the US.

史蒂芬，謝謝你。大家早安，歡迎參加 Krystal 財報電話會議。我們想在這次電話會議中談四個話題。首先，VYJUVEK 的上市進展順利，而即將在歐洲和日本上市的藥物預計將大大增強其在美國已經處於頂級水平的勢頭。

Second, we're expecting several clinical readouts in the upcoming months for diseases in lung and the eye, which could propel Krystal into its next stage of growth and dramatically increase our ability to deliver benefits to patients. We'll talk briefly on our recent KB304 readout, which we believe validates the platform and the opportunity that exists for our subsidiaries, Jeune in aesthetics.

其次，我們預計未來幾個月將有幾份關於肺部和眼部疾病的臨床報告，這可能會推動 Krystal 進入下一階段的成長，並大大提高我們為患者帶來益處的能力。我們將簡要討論我們最近的 KB304 讀數，我們相信它驗證了該平台以及我們的子公司 Jeune in aesthetics 所存在的機會。

Finally, I'm proud to report that we've been able to achieve these milestones while maintaining operational discipline. We were again profitable this quarter and a $1.29 per share fully diluted, marking now two years of consistently positive EPS for the company.

最後，我很自豪地報告，我們在保持營運紀律的同時已經實現了這些里程碑。本季我們再次實現獲利，每股收益為 1.29 美元，這標誌著該公司每股收益已連續兩年為正。

Moving on to our 2Q results. Q2 net VYJUVEK revenue was $96 million. This brings total net VYJUVEK revenue since launch to over $525 million. The return to growth in Q2 was due to patients who paused earlier getting back on drug, and the additional impact of our ongoing sales team expansion. It's important to note that sales force hiring is still underway. We expect the full impact of our new hires will only be felt over the next few quarters as hiring is completed, reps are trained to be fully operational in the field.

繼續討論我們的第二季業績。VYJUVEK 第二季度淨收入為 9,600 萬美元。這使得 VYJUVEK 自推出以來的總淨收入超過 5.25 億美元。第二季恢復成長是由於先前暫停用藥的患者重新開始用藥，以及我們持續的銷售團隊擴張的額外影響。值得注意的是，銷售人員的招募仍在進行中。我們預計，隨著招募的完成，新員工的全面影響將在未來幾季內顯現，銷售代表將接受培訓，並能夠在現場全面開展工作。

Gross margins and GTN were largely consistent with prior quarters. I'm also happy to report that we saw an increase of reimbursement approvals over the course of 2Q and we have secured over 575 reimbursement approvals for patients in the US. Compliance while on drug as of the end of the second quarter came in at 82%. However, we do expect compliance to trend down in the coming quarters as severe patients who started early are now achieving durable wound closure on VYJUVEK and as the percentage of moderate- and mild patients increase in the overall patient mix.

毛利率和 GTN 與前幾季基本一致。我也很高興地報告，我們在第二季度看到報銷批准增加，並且我們已經為美國患者獲得了超過 575 份報銷批准。截至第二季末，服藥期間的依從性達到 82%。然而，我們確實預計未來幾季依從性將呈下降趨勢，因為早期開始使用 VYJUVEK 的重症患者現在正在透過 VYJUVEK 實現持久的傷口閉合，並且中度和輕度患者在整體患者組合中所佔比例不斷增加。

But as we discussed last quarter, complete wound closure and treatment pauses are fantastic outcomes for patients and exactly what we set out to do when founding this company.

但正如我們上個季度所討論的那樣，完全閉合傷口和暫停治療對患者來說是極好的結果，這正是我們創立這家公司時所要做的。

It's also been rewarding to see patients grow increasingly comfortable with the pausing and restarting dynamic and gaining confidence in the fact that when wounds do open, they can easily access VYJUVEK and again achieve durable wound closure.

看到患者對暫停和重新啟動的動態越來越適應，並且越來越有信心，當傷口裂開時，他們可以輕鬆使用 VYJUVEK 並再次實現持久的傷口閉合，這也是令人欣慰的。

These treatment successes, together with the tireless commitment of our Krystal Connect Patient Support team are what allow us to build strong trust-based patient relationships for the long term. They also help activate new patients, and together with our recent publications and digital tools, they raise awareness of what is achievable with regular VYJUVEK therapy.

這些治療的成功，加上我們 Krystal Connect 患者支持團隊的不懈承諾，使我們能夠長期建立牢固的基於信任的患者關係。它們還有助於激活新患者，並結合我們最近的出版物和數位工具，提高人們對常規 VYJUVEK 療法可達到的效果的認識。

This also means that we remain in a period with inherent unpredictability quarter-to-quarter. Consistent with VYJUVEK mechanism of action and skin turnover, we are seeing a growing number of patient restarts but the exact cadence at the individual patient level is highly variable and still difficult to predict.

這也意味著我們仍處於一個季度與季度之間固有不可預測性的時期。與 VYJUVEK 的作用機制和皮膚更新一致，我們看到越來越多的患者重新開始使用，但個別患者層面的確切節奏差異很大，仍然難以預測。

Based on the summer pausing trends, we're seeing over the first few weeks of 3Q. Our current expectation is that 3Q revenues will come in below what we're reporting here today, with a return to growth in 4Q, driven by a growing patient funnel, restarts and sales expansion efforts.

根據夏季暫停趨勢，我們看到了第三季前幾週的情況。我們目前的預期是，第三季的收入將低於我們今天報告的水平，而第四季度的收入將恢復成長，這得益於患者數量的增加、重啟和銷售擴張的努力。

However, as usage patterns stabilized in the US, we expect this waviness to subside with transformative patient outcomes, driving long-term sustainable growth, penetration of the identified patient pool, and bringing new patients to therapy.

然而，隨著美國使用模式的穩定，我們預計這種波動將會消退，患者治療結果將發生轉變，從而推動長期可持續增長、滲透到已確定的患者群體並帶來新的患者接受治療。

The growth trajectory for VYJUVEK will also benefit from global expansion and our launch overseas. Laurent Goux, our GM for Europe, will touch on the European launch dynamics and near-term activities in a moment. But before getting into the European opportunity, I want to highlight another fantastic milestone for our team.

VYJUVEK 的成長軌跡也將受益於全球擴張和海外市場推廣。我們的歐洲總經理 Laurent Goux 稍後將談及歐洲的發布動態和近期活動。但在談到歐洲機會之前，我想先強調一下我們團隊的另一個重要里程碑。

Late last month, we announced the approval of VYJUVEK by Japan's Ministry of Health, Labor and Welfare. We received a broad label from the Japanese authorities similar to the one approved in Europe earlier this year that includes all DEB patients from birth with the option of home, self-or-family administration.

上個月底，我們宣布日本厚生勞動省批准了 VYJUVEK。我們從日本當局獲得了類似於今年早些時候在歐洲批准的標籤，該標籤涵蓋所有從出生起的 DEB 患者，可選擇在家中、自行或家人進行管理。

The label also provides clinicians flexibility with how to diagnose DEB patients and does not require a genetic test facilitating onboarding and initiation of treatment. Japan is another attractive market into which Krystal can launch directly with hundreds of DEB patients in urgent need of a safe and an effective therapy.

該標籤還為臨床醫生診斷 DEB 患者提供了靈活性，並且不需要進行基因測試，從而促進入院和開始治療。日本是另一個具有吸引力的市場，Krystal 可以直接進入該市場，為數百名急需安全有效治療的 DEB 患者提供治療。

We already have our core team in place to secure a pricing decision in the upcoming months and launch before year-end. Thanks to the recently completed and published Japanese open-label extension data, key opinion leaders in Japan already have initial experience with VYJUVEK, which is a tailwind for our launch.

我們的核心團隊已經到位，以確保在未來幾個月內做出定價決策並在年底前推出產品。由於最近完成並發布的日本開放標籤擴展數據，日本的關鍵意見領袖已經對 VYJUVEK 有了初步體驗，這對我們的推出來說是一個順風。

I'll now turn it to Laurent to share more detail on our European launch plans and latest timelines. Laurent?

現在我將請 Laurent 分享有關我們的歐洲發布計劃和最新時間表的更多細節。洛朗？

Thank you, Krish. I'm pleased to present an update on the upcoming European launch of VYJUVEK. After receiving approval earlier this year, we are on track for our European launch this quarter. In the second half of 2025, we will bring this important therapy to patients in Germany and then in France.

謝謝你，克里什。我很高興向大家介紹即將在歐洲推出的 VYJUVEK 的最新情況。在今年稍早獲得批准後，我們將按計劃於本季在歐洲推出該產品。2025 年下半年，我們將把這種重要的療法帶給德國患者，然後是法國患者。

Based on our latest analysis, the identified pool of patients in each country exceeds 500 patients. These patients are supported by four expert centers in both Germany and France, but also 20- to 30 additional sites, usually university hospitals. Please note that the launch in France is subject to the continuity of the Acces Precoce of early access program. We are working closely with local authorities to ensure that eligible patients can benefit from this pathway.

根據我們最新的分析，每個國家已確定的患者數量超過 500 名。這些患者得到了德國和法國四個專家中心的支持，此外還有 20 到 30 個額外站點（通常是大學醫院）的支持。請注意，在法國的發布取決於早期訪問計劃 Acces Precoce 的連續性。我們正在與地方政府密切合作，以確保符合條件的患者能夠從這一途徑中受益。

We have already established dedicated commercial teams in both countries with roughly eight team members on the ground in each market, supported by an additional eight colleagues at our European headquarter and leveraging US back-office resources. In Germany, we anticipate for our first commercial patient to be treated in August, making an important milestone in our efforts to bring meaningful solutions to the DEB patients and the health care professionals.

我們已經在兩個國家建立了專門的商業團隊，每個市場大約有 8 名團隊成員，並由我們歐洲總部的另外 8 名同事提供支持，並利用美國後台資源。在德國，我們預計將於 8 月迎來第一位商業患者，這是我們為 DEB 患者和醫療保健專業人員提供有意義的解決方案的努力中的一個重要里程碑。

To facilitate rapid and effective access, we have established comprehensive patient service and education programs. These initiatives are designed to support home administration of the therapy as well as administration by caregivers, ensuring that patients can benefit from our treatment regardless of their health care settings.

為了方便快速有效地就醫，我們建立了全面的病患服務和教育計畫。這些措施旨在支持家庭治療以及照護者的治療管理，確保患者無論在何種醫療環境下都能從我們的治療中受益。

These different possibilities are allowed by the very strong label approved by EMA. Since approval, the team has worked on identifying the key centers and preparing them to enroll patients. Our focus is to ensure successful launch, driving uptake at key centers and ensuring an efficient patient experience. This launch is a significant step for Krystal, reflecting both our commitment to rare disease patients and strategic execution of our international commercial plant.

EMA 批准的非常強大的標籤允許這些不同的可能性。自獲得批准以來，該團隊一直致力於確定重點中心並準備招募患者。我們的重點是確保成功啟動、推動主要中心的採用並確保高效的患者體驗。此次發布對於 Krystal 來說具有重要意義，體現了我們對罕見疾病患者的承諾以及我們國際商業工廠的策略執行。

I will now hand the call back over to Krish.

我現在將把電話交還給克里什。

Thank you, Laurent. With VYJUVEK delivering transformational clinical outcome for patients, we remain as confident as ever in the blockbuster trajectory for our first approved genetic medicine. In the US, we're already starting to see the benefits of our sales force expansion, which we expect to drive significant penetration of the remaining identified patient pool.

謝謝你，洛朗。隨著 VYJUVEK 為患者帶來變革性的臨床結果，我們對我們首個核准的基因藥物的轟動性軌跡仍然充滿信心。在美國，我們已經開始看到銷售團隊擴張帶來的好處，我們預計這將推動剩餘已確定患者群體的顯著滲透。

In Europe, with a broad label, flexible dosing options, and a large identified patient pool, we see a path for steady, multi-year growth as we work with key centers and launched sequentially in major markets. The broad label in Japan adds another high-value launch market which is start adding meaningfully to our top line in 2026.

在歐洲，憑藉廣泛的標籤、靈活的劑量選擇和龐大的已確定患者群體，隨著我們與主要中心合作並在主要市場陸續推出產品，我們看到了一條穩定的多年增長之路。日本的廣泛品牌增加了另一個高價值的發布市場，該市場將在 2026 年開始為我們的收入帶來有意義的成長。

And increasingly, we're pursuing meaningful opportunities in rest of the world markets, accessible through distributors and partners. Altogether, these put VYJUVEK on an exciting trajectory and provide a strong financial foundation and significant optionality for the company.

我們正在透過經銷商和合作夥伴，不斷尋求世界其他市場的有意義的機會。總而言之，這些因素使 VYJUVEK 走上了令人興奮的發展軌跡，並為公司提供了強大的財務基礎和重要的選擇權。

I'll now hand it off to Suma to touch on recent pipeline development at Krystal.

現在我將把話題交給 Suma，讓他談談 Krystal 最近的管道開發情況。

Thank you, Krish. Our R&D team has had another productive quarter as we work diligently to build a true portfolio of high-value genetic medicines. Today, I will touch on key accomplishments, including clinical data updates for oncology and aesthetic programs, progression of KB408 into repeat dosing for AATD as well as two new study starts that set us up for multiple near-term readouts in both the lung and eyes.

謝謝你，克里什。我們的研發團隊又度過了一個有成效的季度，我們努力打造真正的高價值基因藥物組合。今天，我將談及主要成就，包括腫瘤學和美容項目的臨床數據更新、KB408 對 AATD 重複給藥的進展以及兩項新研究的開始，這些研究為我們在肺部和眼睛的多個近期讀數奠定了基礎。

I would like to start with a few highlights on inhaled KB707. Earlier this summer, at ASCO, we shared an update on our Phase I/II study, KYANITE-1, evaluating inhaled KB707 for solid tumors of the lung. This update included safety data from 39 subjects treated with inhaled KB707 as monotherapy as well as an efficacy data update for the 11 KB707 treated patients with late line and NSCLC.

我想先介紹一下吸入式 KB707 的一些亮點。今年夏初，在 ASCO 上，我們分享了 I/II 期研究 KYANITE-1 的最新進展，該研究評估了吸入式 KB707 對肺實體瘤的療效。此次更新包括 39 名接受吸入 KB707 單一療法治療的受試者的安全性數據，以及 11 名接受 KB707 治療的晚期 NSCLC 患者的療效數據更新。

With an extended follow-up and new data cut of April 15, 2025, we saw deepening of the responses in the NSCLC Cohort with an improved objective response rate of 36%. Median duration of response and progression-free survival were not yet reached.

隨著 2025 年 4 月 15 日的延長追蹤和新數據截斷，我們看到 NSCLC 隊列的反應不斷加深，客觀反應率提高​​到 36%。中位反應持續時間和無惡化存活期尚未達到。

Just as importantly, inhaled KB707 continue to be safe and generally well tolerated and amenable to administration in outpatient setting. We are increasingly excited about the profile of inhaled KB707 monotherapy in the clinic.

同樣重要的是，吸入式 KB707 仍然是安全的，通常耐受性良好，並且適合在門診環境中使用。我們對吸入式 KB707 單一療法在臨床上的表現越來越感到興奮。

In addition, combination therapy cohorts have been opened in KYANITE-1 and enrollment is ongoing. We have also made exciting progress with KB408 for the treatment of AATD lung disease. We recently completed dosing and bronchoscopy of a third AATD patient dosed with KB408 in Cohort 2. As shown on this slide, we again saw robust airway transduction, resulting in functional AATD expression as demonstrated by neutrophil elastase binding in the ELF.

此外，KYANITE-1 中已開放聯合治療隊列，目前正在進行招募。我們在 KB408 治療 AATD 肺病方面也取得了令人興奮的進展。我們最近完成了第 2 組第三位使用 KB408 的 AATD 患者的給藥和支氣管鏡檢查。如本幻燈片所示，我們再次看到了強大的氣道轉導，導致功能性 AATD 表達，如 ELF 中的中性粒細胞彈性蛋白酶結合所證明的那樣。

Please note that this patient was a background IV augmentation and yet we still detected a reduction of three neutrophil elastases following KB408 dosing. Across all three bronchoscopy patients, we have seen transaction rates in the 30% to 40% range after a single dose. The safety profile of KB408 continues to be attractive across all five patients dosed in Cohort 2.

請注意，該患者是背景靜脈增強，但我們仍檢測到 KB408 給藥後三種中性粒細胞彈性蛋白酶的減少。在所有三名接受支氣管鏡檢查的患者中，我們發現單次給藥後的交易率在 30% 到 40% 之間。對於第 2 組接受治療的所有五名患者來說，KB408 的安全性仍然具有吸引力。

Based on these data, we recently amended the SERPENTINE-1 protocol and started dosing in a newly opened Cohort 2b to investigate repeat dosing in Cohort 2 dose levels. Our study objectives with this new cohort are to evaluate safety and tolerability of repeat dosing as well as assess additive efficacy of repeat dosing and explore optimal dosing timing based on durability of effect.

基於這些數據，我們最近修改了 SERPENTINE-1 方案，並開始在新開設的 Cohort 2b 中進行給藥，以研究 Cohort 2 劑量水平的重複給藥。我們對這個新隊列的研究目標是評估重複給藥的安全性和耐受性以及評估重複給藥的附加功效，並根據效果的持久性探索最佳給藥時間。

Design details are summarized on the slide. Patients will undergo a baseline bronchoscopy, receive four weekly doses of KB408, and then receive a bronchoscopy, either one or two weeks after the final dose to assess expression and durability. We expect the data generated from Cohort 2b to dictate our approach with respect to the advanced clinical development of KB408, including potential accelerated approval approaches.

投影片上總結了設計細節。患者將接受基線支氣管鏡檢查，每週接受四次 KB408 劑量治療，然後在最後一次服藥後一周或兩週接受支氣管鏡檢查，以評估表達和持久性。我們預計，第 2b 組產生的數據將決定我們針對 KB408 的高級臨床開發的方法，包括潛在的加速審批方法。

We are also making steady progress on KB407 with TDN sanctioning and the additional of new network sites providing expanded access to CF patients, including those that are currently ineligible for modulators. We now have our fourth patient enrolled in Cohort 3 and expect to soon have five TDN sites up and running to support completion of both Cohort 3 as well as subsequent repeat dosing studies.

我們也在 KB407 方面取得穩定進展，獲得了 TDN 批准並增加了新的網路站點，為 CF 患者（包括目前沒有資格使用調節劑的患者）提供了更廣泛的治療途徑。現在，我們已經有第四名患者加入了第 3 組，並且預計很快將有五個 TDN 站點投入運行，以支持完成第 3 組以及後續的重複給藥研究。

Based on the latest patient screening and enrollment timelines, we expect to be able to share molecular data later this year. Finally, we have our recent clinical data in aesthetics, where we reported positive results from our 2:1 randomized, double-blind and placebo-controlled study evaluating our second aesthetic candidate, KB304.

根據最新的患者篩檢和入組時間表，我們預計今年稍後能夠共享分子數據。最後，我們有最近在美學領域的臨床數據，我們報告了評估我們的第二個美學候選藥物 KB304 的 2：1 隨機、雙盲和安慰劑對照研究的積極結果。

KB304 is a combination Aesthetic therapy encoding both collagen 3 and elastin, to drive aesthetic improvement in the skin. As the Jeune's team shared a few weeks ago, investigators and subjects alike reported meaningful aesthetic improvements across multiple attributes, including wrinkles and elasticity with clear and statistical significant advantages over placebo.

KB304 是一種編碼膠原蛋白 3 和彈性蛋白的組合美容療法，可促進皮膚的美觀改善。正如 Jeune 團隊幾週前分享的那樣，研究人員和受試者都報告了多種屬性的顯著美觀改善，包括皺紋和彈性，與安慰劑相比具有明顯且具有統計意義的優勢。

The images shown on right highlight the improvement achieved by some of our KB304-treated subjects. The safety profile of KB304 was also in line with expectations. All adverse events were mild to moderate and transient. Based on the broad aesthetic improvement observed with KB304, in PEARL-2, we have decided to progress KB304 into Phase II study for the treatment of wrinkles of the decollete.

右側顯示的影像突顯了我們一些接受 KB304 治療的受試者所取得的改善。KB304 的安全性也符合預期。所有不良事件均為輕度至中度且短暫的。基於在 PEARL-2 中觀察到的 KB304 的廣泛美學改善，我們決定將 KB304 推進到治療頸部皺紋的 II 期研究。

In support of this goal, we also recently completed development and validation of a decollete-specific photonumeric scale, we intend to align on the Phase II protocol later this year, enabling a potential Phase II study start in the first half of 2026.

為了實現這一目標，我們最近也完成了針對胸部的光數字量表的開發和驗證，我們打算在今年稍後完成第二階段的協議，以便在 2026 年上半年開始第二階段的研究。

Finally, I would like to add that we started two ophthalmology clinical trials in the last two months. IOLITE, a Phase III study evaluating KB803 for the treatment and prevention of corneal liberations in DEB patients and EMERALD-1, a Phase I/II study evaluating KB801 for the treatment of neurotropic keratitis. Both of these programs leverage the unique attributes of our platform and showcase what is achievable with our HSV-1 based platform in the front of the eye.

最後，我想補充一點，我們在過去兩個月啟動了兩項眼科臨床試驗。IOLITE 是一項 III 期研究，評估 KB803 對 DEB 患者角膜解放的治療和預防作用；EMERALD-1 是一項 I/II 期研究，評估 KB801 對神經性角膜炎的治療效果。這兩個專案都利用了我們平台的獨特屬性，並展示了我們基於 HSV-1 的平台在眼前所能實現的目標。

We are looking forward to sharing data progress, updates on those programs as they progress. Altogether, this steady execution sets up for many near-term readouts in CF, AATD, MK and DEB, that we expect will validate the breadth of opportunity that exists with our HSV-1 based platform.

我們期待分享這些項目的數據進展和最新進展。總而言之，這種穩定的執行為 CF、AATD、MK 和 DEB 中的許多近期讀數奠定了基礎，我們預計這將驗證基於 HSV-1 的平台所存在的廣泛機會。

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, and good morning, everyone. I'd like to provide some highlights from our second quarter financial results that were reported in our press release and filing this morning. As Krish mentioned earlier, our net product revenue for VYJUVEK was $96 million for the second quarter of 2025. This marks continued growth as compared to the second quarter of 2024, as well as 9% growth over the recent first quarter of 2025.

謝謝你，蘇瑪，大家早安。我想提供一些我們在今天早上的新聞稿和文件中報告的第二季度財務業績的亮點。正如 Krish 之前提到的，2025 年第二季 VYJUVEK 的淨產品收入為 9,600 萬美元。與 2024 年第二季相比，這標誌著持續成長，並且與最近的 2025 年第一季相比成長了 9%。

Gross to net revenues remained consistent with prior quarters. Cost of goods sold was $7.2 million compared to $6 million in the prior year second quarter, and gross margin remained relatively consistent at 93% in 2Q 25.

總收入與淨收入之比與前幾季保持一致。銷售成本為 720 萬美元，而去年同期第二季為 600 萬美元，毛利率保持相對穩定，為 2025 年第二季的 93%。

Research and development expense was $14.4 million compared to $15.6 million in the prior year. The decrease quarter-over-quarter is primarily due to the timing of our various research and development manufacturing runs, offset slightly by increased clinical development costs across many of our product candidates.

研發費用為 1,440 萬美元，而去年同期為 1,560 萬美元。環比下降主要是由於我們各項研發生產運作的時間安排，但被許多候選產品的臨床開發成本增加所略微抵銷。

General and administrative expenses were $35.2 million compared to $27.6 million in the prior year second quarter, primarily due to increased professional services fees, including marketing services, consulting and legal. We also saw increased personnel-related costs compared to last year, due mainly to growth in our head count to support global commercialization and this was inclusive of increased stock-based compensation costs from new grants.

一般及行政開支為 3,520 萬美元，而去年同期第二季為 2,760 萬美元，主要由於專業服務費用增加，包括行銷服務、諮詢和法律服務。與去年相比，我們還發現與人員相關的成本有所增加，這主要是由於我們為支持全球商業化而增加了員工人數，其中包括新贈款增加的股票薪酬成本。

Operating expenses for the quarter included non-cash stock-based compensation of $14.1 million as compared to $13.2 million in the second quarter of 2024. You'll note that our non-GAAP R&D and SG&A guidance remains unchanged on slide 14.

本季營運費用包括 1,410 萬美元的非現金股票薪酬，而 2024 年第二季為 1,320 萬美元。您會注意到，第 14 張投影片上的非 GAAP 研發和銷售、一般及行政費用指南保持不變。

Net income for the quarter was $38.3 million which represented $1.33 per basic and $1.29 per diluted share. This is compared to $15.6 million in the prior year second quarter at $0.54 per basic and $0.53 per diluted share.

本季淨收入為 3,830 萬美元，相當於每股基本收入 1.33 美元，每股稀釋收入 1.29 美元。相比之下，去年同期第二季每股收益為 1,560 萬美元，基本每股收益為 0.54 美元，稀釋每股收益為 0.53 美元。

Finally, I am happy to comment on the sustained strength of our balance sheet. We closed the quarter with over $820 million in combined cash and investments with continued growth in our net cash provided by operating activities over previous quarters. We believe this puts us in a great position ahead of our upcoming Europe and Japan launches as well as for the significant number of research and development objectives we have set forth for the remainder of 2025 and into 2026.

最後，我很高興評論我們資產負債表的持續強勁。本季結束時，我們的現金和投資總額超過 8.2 億美元，且我們的營運活動所提供的淨現金較前幾季持續成長。我們相信，這將使我們在即將在歐洲和日本推出的產品以及我們為 2025 年剩餘時間和 2026 年制定的大量研發目標方面處於有利地位。

With that, I'll now turn the call back over to Krish.

說完這些，我現在將電話轉回給克里什。

Thanks, Kate. With clear growth drivers for VYJUVEK in the US and abroad, plus the additional upside of a potential KB803 launch for corneal abrasions over the next few years, we're excited about the path ahead for VYJUVEK and for Krystal.

謝謝，凱特。由於 VYJUVEK 在美國和國外擁有明顯的成長動力，再加上未來幾年可能推出用於治療角膜擦傷的 KB803 的額外優勢，我們對 VYJUVEK 和 Krystal 的未來發展感到興奮。

It's important to understand that this upward trajectory will not necessarily be linear, but looking beyond the short term, this is a multiyear growth story that has only just begun. Add a rich and a growing pipeline of clinical stage programs targeting clear unmet needs with step jump implications for Krystal, we see opportunities to build significant shareholder value in the years ahead.

重要的是要明白，這種上升軌跡不一定是線性的，但從短期來看，這是一個才剛開始的多年成長故事。增加豐富且不斷成長的臨床階段項目，這些項目針對明確的未滿足需求，對 Krystal 具有階梯意義，我們看到了在未來幾年創造重大股東價值的機會。

In the months ahead, lung readouts in CF and AATD, together with ophthalmology readouts in NK and DEB will make clear the potential of our platform across multiple tissues and open up blockbuster product opportunities. Finally, our inhaled 707 program for NSCLC continues to progress well and stay tuned for readouts in 2026.

在未來的幾個月裡，CF 和 AATD 中的肺部讀數以及 NK 和 DEB 中的眼科讀數將明確我們的平台在多種組織中的潛力，並開闢重磅產品機會。最後，我們針對 NSCLC 的吸入式 707 計畫持續進展順利，敬請期待 2026 年的讀數。

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

感謝您的聆聽，現在我想開始問答環節。

(Operator Instructions)

（操作員指示）

Rogers Haung, Jefferies.

羅傑斯·黃（Rogers Haung），傑富瑞（Jefferies）。

This is Fiona on for Roger. Congrats on the quarter. My first question is just to clarify, the revenue growth for this Q is not impacted by the sales force expansion. And if you think the volatility for the next quarters will be offset by the sales force expansion kicking in and the EU launch?

這是 Fiona 代替 Roger 上場的。恭喜本季取得佳績。我的第一個問題只是為了澄清，本季的營收成長不受銷售隊伍擴張的影響。您是否認為下一季的波動性將被銷售隊伍的擴張和歐盟的推出所抵消？

No. As I alluded to in my script, part of the increase in Q2 was driven by people -- patients who are causing getting back on drug and start -- and we have been hiring reps since the tail end of Q1. And so there was an incremental effect. I think the point I was trying to make is the full impact of all the hires will be felt over the next couple of quarters as they come on board, get trained and are fully functional in the field.

不。正如我在腳本中提到的那樣，第二季度的成長部分是由人們推動的——那些重新開始吸毒的患者——而且我們從第一季末就開始招募銷售代表了。因此產生了漸進效應。我想我要表達的觀點是，所有新員工的全面影響將在接下來的幾個季度內顯現出來，因為他們將加入公司、接受培訓並在該領域全面發揮作用。

Gavin Clark-Gartner, Evercore ISI.

Gavin Clark-Gartner，Evercore ISI。

Could you just give us a little more quantitative commentary on the magnitude of how much slower the first few weeks of the quarter have been versus Q1? Just any rough way to think about that.

您能否給我們一些更定量的評論，說明本季前幾週與第一季相比成長放緩的程度？只需粗略地思考一下即可。

No, we're not going to get to that level of detail, Gavin. And it is early in the quarter. I was just trying to set expectations that in the summer, people take vacation and the summer holidays always has an impact on pauses. But beyond that, it's tough for me to quantify because it's such a variable thing. The quarter is just maybe one-third of its way in. But I just wanted to point out that summer is usually filled with more pauses than usual.

不，我們不會達到那種程度的細節，加文。現在正值本季初。我只是想設定這樣的期望：在夏天，人們會休假，而暑假總是會對暫停產生影響。但除此之外，我很難量化，因為它是個改變很大的東西。本季可能只完成了三分之一。但我只是想指出，夏天通常比平常有更多的停頓。

Okay. Great. Just a quick follow-up. For US VYJUVEK, what's the mix of RDEB versus DDEB patients either in reimbursement approvals or in start forms that are coming on to therapy?

好的。偉大的。只是一個快速的跟進。對於美國 VYJUVEK，無論是在報銷批准中還是在開始治療的開始表格中，RDEB 和 DDEB 患者的比例是怎樣的？

That's a good question. I believe, as of the last quarter, that mix is more like 64%-36% in that range. But I ask Stephane, Stephane if you have a clearer number, can you jump in?

這是個好問題。我認為，截至上個季度，該比例更像是 64%-36%。但我問史蒂芬，史蒂芬，如果你有一個更明確的數字，你能加入嗎？

Yes, it's basically in line. We didn't see really much movement at all in the breakdowns for reimbursement approvals, either RDEB, DDEB, age, even the insurance plan. So one of the reasons we didn't really get into it this time around, but they're largely stable. Maybe shifting -- as always, and we're shifting. We're very gradually into DEB, so.

是的，基本上符合。我們在報銷審批的細目中並沒有看到太大的變化，無論是 RDEB、DDEB、年齡，甚至是保險計劃。所以我們這次沒有真正深入研究的原因之一是，它們基本上是穩定的。也許正在轉變——一如既往，我們正在轉變。我們正在逐步進入 DEB，所以。

Ritu Baral, TD Cowen.

Ritu Baral，TD Cowen。

This is Josh Fleishman on the line for Ritu. Congrats on the quarter. How do you expect for drug holidays to factor into the original guidance of 720 US patients initiating VYJUVEK. And on Europe, how should we think about pricing? And what's important to the country's health technology assessments?

我是 Josh Fleishman，負責 Ritu 的接線工作。恭喜本季。您認為藥物假期會對 720 名開始使用 VYJUVEK 的美國患者的原始指導產生什麼影響？那麼在歐洲，我們該如何考慮定價？那麼對於國家衛生技術評估來說什麼最重要呢？

With respect to 720, Joshua, as we mentioned last quarter, we're on track, but we're maybe a quarter or two behind. Sometime early next year is when we think we'll get to that number. Our original ambitious goal was to get there by September, October of this year. And so I think we're still very pleased with the track we're on, and we hope to get there pretty quickly. In terms of EU pricing, I'm going to let Laurent speak to it, and I'll come back to the last question when it's time. Laurent?

關於 720，約書亞，正如我們上個季度提到的那樣，我們正在按計劃進行，但可能落後了一兩個季度。我們認為明年年初就能達到這個數字。我們最初的雄心勃勃的目標是在今年九月、十月實現這一目標。所以我認為我們對目前的發展方向仍然非常滿意，並且我們希望很快就能實現目標。關於歐盟定價，我將讓 Laurent 來談談這個問題，到時候我會再回答最後一個問題。洛朗？

Thank you, Krish. Reimbursement application processes are proceeding as planned with the HTA bodies in the main countries in Europe. As you know, in Germany, we benefit from free pricing during the first 12 months post approval and then negotiation with GKV are about to start now. It's a bit premature to provide any feedback given that we have not received any feedback from the authorities with regard to our HTA dossier.

謝謝你，克里什。報銷申請流程正在按計劃與歐洲主要國家的 HTA 機構進行。如您所知，在德國，我們在批准後的前 12 個月內享受免費定價，然後與 GKV 的談判即將開始。由於我們尚未收到當局關於我們的 HTA 檔案的任何反饋，因此現在提供任何反饋還為時過早。

But the early engagement we had with the key authorities throughout Europe were very productive, and the unmet medical need in DEB is well recognized by the payers and the potential benefit, transformational benefit of VYJUVEK seems to be understood. Krish?

但是，我們與歐洲各地主要當局的早期合作非常富有成效，DEB 中未滿足的醫療需求得到了付款人的充分認可，並且 VYJUVEK 的潛在益處和轉型益處似乎也得到了理解。克里什？

Yeah, thanks, Laurent. And Joshua, your last question was something around technology used in salesforce.

是的，謝謝，勞倫特。約書亞，你的最後一個問題是關於銷售人員使用的技術。

It was on what's important to the country's health technology assessments.

這是關於國家衛生技術評估的重要內容。

Got you. So it's -- okay, great. Does that answer your question? Any follow up?

明白了。所以——好的，太好了。這回答了你的問題嗎？有後續嗎？

Sami Corwin, William Blair.

薩米·科溫、威廉·布萊爾。

Hey there, good morning. Congrats on the quarter. I have another couple of questions about the upcoming European launches. I know previously you mentioned that there might be a dynamic of onboarding patients based on their need to get treated in a physician office first. So I wonder if you could comment on that a little bit.

嘿，早安。恭喜本季。我對即將在歐洲推出的產品還有幾個問題。我知道您之前提到過，可能會根據患者首先在醫生辦公室接受治療的需求來動態地接收患者。所以我想知道您是否可以對此發表一些評論。

And then do you have any goal in terms of the reimbursement ramp like the 720 number that was initially applied for the US launch? Thank you.

那麼，對於報銷額度，您是否有什麼目標，例如最初在美國推出時申請的 720 號碼？謝謝。

Yes, Krish. Thanks for the question. I mean the requirement for an appointment at a specialty center is quite customary in practice in Europe to access a prescription in general and even more for specialty drugs. So it's not something unusual that you have to go through an appointment at a center.

是的，克里什。謝謝你的提問。我的意思是，在歐洲，通常需要預約專科中心才能獲得處方，尤其是專科藥物。因此，您必須在中心進行預約，這並不是什麼不尋常的事情。

I mean this is the reason why the team has dedicated the past three months in notifying the centers, understanding the potential bottlenecks and ensuring their readiness to enroll patients, either through education, advanced scheduling or addressing any other needs on a case-by-case basis.

我的意思是，這就是為什麼團隊在過去三個月裡致力於通知各中心、了解潛在的瓶頸並確保他們準備好接收患者，無論是透過教育、提前安排或根據具體情況解決任何其他需求。

So these are the main guidelines. Then with regard to the number of patients covered, in Europe, when a country grants reimbursement, it will be for the entire population that will be designated in the reimbursement approval. So there is no case-by-case request once the drug is approved by the payer body, the national insurance in most cases.

這些就是主要的指導方針。然後關於覆蓋的患者數量，在歐洲，當一個國家給予報銷時，它將針對報銷批准中指定的整個人口。因此，一旦藥物獲得付款機構（大多數情況下是國家保險）的批准，就不需要逐案處理。

Okay. If I could rephrase those questions slightly then. So is it possible for patients to do that initial appointment in a group? Or does it need to occur on a patient-by-patient basis? And then I guess, instead of a patient ramp, do you have a goal in terms of onboarding patients to drug over a particular period of time?

好的。如果我可以稍微重新表達一下這些問題的話。那麼患者可以集體進行初次預約嗎？還是需要根據每個患者的狀況進行？然後我想，除了患者人數增加之外，您是否有一個在特定時間內讓患者接受藥物治療的目標？

So I don't think we have communicated any guidance for patient on drugs. This will be a step-wise approach and that will depend on when the countries will be reimbursing the product. So we have the same goal as the US, which is to reach 60% of the patient pool, the eligible patient pool within the first two to three years, but we have not communicated more detailed numbers.

所以我認為我們沒有向患者傳達任何有關藥物的指導。這將是一個逐步的方法，取決於各國何時償還產品。因此，我們的目標與美國相同，即在前兩到三年內達到 60% 的患者群體，即符合條件的患者群體，但我們尚未公佈更詳細的數字。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey guys, this is Matthew Wong for Alec. Maybe on the pipeline, I noticed that the timeline for CF data was mid 2025, now by year ends. Anything to read into this or is this just enrollment timelines and then maybe you can remind us of sort of the number or type of patients we expect in that first readout?

大家好，我是 Alec 的 Matthew Wong。也許在管道上，我注意到 CF 數據的時間線是 2025 年中期，現在是年底。有什麼可以解讀的嗎？或者這只是招生時間表，然後也許您可以提醒我們第一次讀數中我們預期的患者數量或類型？

Yeah, I can take this question. As you may be aware that we did announce that the TDN, we got endorsement from the TDN, so that opened up all the TDN sites. So we've been actively working with -- at the moment six TDN sites that we are in contract and budget phase.

是的，我可以回答這個問題。您可能知道，我們確實宣布了 TDN，我們得到了 TDN 的認可，因此開放了所有 TDN​​ 網站。因此，我們一直在積極合作——目前我們正與六個 TDN 站點進行合約和預算階段。

So unfortunately, with these academic sites, just the whole process and paperwork took more time than we anticipated. Our team really pushed, but we're getting close. So we believe once we can get these sites up and running, which we are pretty close, we should be able to enroll the patients. So that pushed out. But hopefully, we can enroll multiple patients across these sites once they are up and operational.

因此不幸的是，對於這些學術網站來說，整個過程和文書工作所花費的時間比我們預期的要多。我們的團隊確實很努力，但我們已經很接近了。因此我們相信，一旦這些站點能夠啟動並運行，我們就應該能夠招募患者。所以就推開了。但希望這些站點一旦投入運營，我們就能招募多名患者。

And with respect to the data announcement, look, you know Cohort 3 is essentially three patients on modulator and three now. And what we're looking to show is molecular data on three null mutation patients in (inaudible).

關於數據公告，您知道第 3 組基本上是三名使用調節劑的患者，現在有三名。我們希望展示的是三名無效突變患者的分子數據（聽不清楚）。

And again, keep in mind, now patients are harder to get by, but the TDN sites have them. So we have patients, but you also need patients that are willing to bronch, becuase -- not easy. But we are there. We're getting there.

再次提醒，請記住，現在患者越來越難找，但 TDN 站點仍有患者。所以我們有病人，但你也需要願意接受支氣管插管的病人，因為──這並不容易。但我們在那裡。我們即將到達那裡。

Andrea Newkirk, Goldman Sachs.

高盛的安德里亞紐柯克 (Andrea Newkirk)。

This is Morgan on for Andrea Newkirk. Following up on one of the previous questions. Do you anticipate a similar dynamic will be required in Japan such that patients will need to be seen by a health care practitioner before initiating VYJUVEK?

這是摩根 (Morgan) 為安德里亞紐柯克 (Andrea Newkirk) 拍攝的。繼續回答之前的一個問題。您是否預期日本也需要類似的動態，即患者在開始使用 VYJUVEK 之前需要接受醫療保健從業者的檢查？

And then also, can you share some details on the fifth patient dose in Cohort 2 for AATD in terms of the percent cells that were transduced and the level of AAT expression and distribution of 408 across the lungs?

另外，您能否分享有關第 2 組 AATD 第五名患者劑量的一些詳細信息，包括轉導的細胞百分比以及肺部 AAT 表達水平和 408 的分佈？

On the Japan question, yes, it's very similar to Europe. It's the way all drugs like the first visit is in a physician office. So no change there. In terms of the AAT, I'd ask somebody to go back to that slide -- I don't know, Stephane, if you can pull up that slide on AAT, just give us a minute. Yes. And as you --

關於日本問題，是的，它與歐洲非常相似。所有藥物都像第一次就診一樣在醫生辦公室進行。所以沒有變化。就 AAT 而言，我會請某人回到那張幻燈片 - 我不知道，Stephane，如果你能把 AAT 上的那張幻燈片拉出來，請給我們一點時間。是的。正如你--

So basically, all three patients we saw expression in the biopsy samples. We could clearly see expression from baseline increase. Are we seeing the [lavage]? One of the patients we had difficulty recovering the right amount of lavage because this whole procedure is pretty tricky. And it's because of some of the issues with recovery of the lavage, we were not able to get the levels.

所以基本上，我們在這三名患者的活檢樣本中都看到了表達。我們可以清楚地看到表達從基線開始增加。我們是否看到了[灌洗]？由於整個過程非常棘手，我們很難為其中一位患者恢復正確的灌洗量。由於灌洗液恢復過程中的一些問題，我們無法達到該水平。

But in two patients, we were able to show both expression of -- in the lavage, we were able to measure AAT and show neutrophil elastase and binding and reduction of the neutrophil elastase. But in all of the patients in the biopsies, we did see expression of AAT above the levels of baseline.

但在兩名患者中，我們能夠顯示兩種表達方式——在灌洗液中，我們能夠測量 AAT 並顯示中性粒細胞彈性蛋白酶以及中性粒細胞彈性蛋白酶的結合和減少。但在所有活檢患者中，我們確實看到 AAT 表達高於基線水平。

Joe Pantginis, HC Wainwright.

喬潘特吉尼斯、HC溫賴特。

Two topics, if you don't mind. So first on VYJUVEK, Krish, you talked about one topic. I know it might be too early and also might include a lot of patient variability. So I don't know if it really could be answered. How would you view based on the pausing and restarting and chronic wounds being closed versus mild to moderate, how would you define if you can steady state for a patient as around VYJUVEK over the long term with regard to starts and restarts and wound reopening?

如果你不介意的話，有兩個主題。首先，在 VYJUVEK 上，Krish，您談到了一個話題。我知道這可能為時過早，並且可能涉及許多患者的差異。所以我不知道是否真的可以回答這個問題。您如何看待基於暫停和重新開始以及慢性傷口閉合與輕度至中度傷口閉合之間的關係，您如何定義是否可以在開始和重新開始以及傷口重新開放方面長期保持患者圍繞 VYJUVEK 的穩定狀態？

We've said consistently even from -- at the prelaunch stage that steady state implies that the entire patient base, on average, consume about 26 vials a year and we're not there yet. And we believe we'll get to steady state when the ratio of our DEB [Adida] patients is about 50% each.

我們甚至從上市前階段就一直表示，穩定狀態意味著整個患者群體平均每年消耗約 26 瓶藥物，但我們尚未達到這一水平。我們相信，當我們的 DEB [Adida] 患者比例達到約 50% 時，我們就會達到穩定狀態。

So if you have an even split of recessive and dominant. And they've been on drug a while, we expect the average consumption across the patient base to be 26 vials a year. So that is how we define steady state. And if you look at the compliance, if you look at the RDEB, DDEB ratio, you look at the vials consumed, we're definitely months away from getting to that point.

因此，如果隱性和顯性基因均等分裂的話。他們已經服藥一段時間了，我們預計整個患者群體每年的平均消耗量為 26 瓶。這就是我們對穩定狀態的定義。如果你看一下依從性，如果你看一下 RDEB、DDEB 比率，如果你看一下消耗的小瓶，你就會知道，我們肯定還需要幾個月的時間才能達到這一點。

Okay. That's helpful. And then I just want to switch gears to Jeune right now. I'll start with the Phase II program. The prepared comments with regard to decollete Phase II, you talked about a photonumeric scale, I guess I wanted to discuss the novelty of that and what are the key aspects of the regulatory discussions around this end point.

好的。這很有幫助。然後我現在只想轉到 Jeune。我將從第二階段計劃開始。關於第二階段胸部手術的準備好的評論，您談到了光數字量表，我想討論一下它的新穎性以及圍繞這一終點的監管討論的關鍵方面。

I mean, obviously, as you know, with 304, it's a combination of collagen 3 and elastin, So I mean, with adding elastin and we clearly know that we can express elastin from animal models with our vector. The definition of elastin, obviously, it's not going to be -- it's going to be slightly different. You're going to see improvement in texture of the skin, skin quality et cetera, et cetera. And that's something that we captured in our 304 study.

我的意思是，顯然，如你所知，304 是膠原蛋白 3 和彈性蛋白的組合，所以我的意思是，透過添加彈性蛋白，我們清楚地知道我們可以用我們的載體從動物模型中表達彈性蛋白。顯然，彈性蛋白的定義不會——它會略有不同。您會看到皮膚質地、皮膚品質等等的改善。這就是我們在 304 研究中發現的。

If you look at our patients' feedback, I mean or their rating, that's some of the consistent feedback that we got from consistently all the patients that were on the drug that they felt their skin was smoother. The texture just felt better. So obviously, some of that cannot be captured just by photonumeric scale. So we do want to talk to the agency about the novel mechanism, obviously, with this division, we know that we can express collagen 3 will express elastin.

如果你看一下我們患者的回饋，我的意思是他們的評價，這是我們從所有服用該藥物的患者那裡得到的一致反饋，他們感覺自己的皮膚更光滑了。質感感覺更好。顯然，其中一些無法僅透過光數字尺度來捕捉。因此，我們確實想與該機構討論新機制，顯然，透過這個部門，我們知道我們可以表達膠原蛋白 3 並表達彈性蛋白。

And we need to -- we're going to propose some sort of quality evaluation for the patient-reported outcome of skin quality and skin texture. So this is something we're going to sit down with the agency and have that discussion. We have developed a photonumeric scale at the moment for the decollete. So we have a scale that's developed and validated. So we want to do some sort of a combination and then just have that discussion with the agency.

我們需要—我們將針對患者報告的皮膚品質和皮膚紋理結果提出某種品質評估。因此，我們將與該機構坐下來討論這個問題。目前，我們已經開發出一種用於胸部的光數字量表。因此，我們有一個已經開發並驗證過的量表。因此，我們希望進行某種組合，然後與該機構進行討論。

Got it. And then just quickly on Jeune again. I know, Krish, you've talked about this in the past with regard to potential options of how Jeune corporate aspect might play out with regard to, say, keeping it a subsidiary, part of Krystal, spinning out or what have you. Do you have any potential thoughts on when we might see visibility on potential outcomes there?

知道了。然後很快又回到了 Jeune 身上。我知道，Krish，您過去曾談論過 Jeune 公司方面可能如何發揮作用的潛在選擇，例如將其保留為子公司、Krystal 的一部分、分拆出去或諸如此類。您對於我們何時可以看到潛在結果有何想法？

Yes. I think following the announcement on 304 and Suma is starting to have conversations with the FDA. From a development perspective, we expect to start Phase II in the upcoming months. And meanwhile Nishant, the CEO and the CFO of Jeune are actively pursuing or diligently working towards getting Jeune financed and spun out. And the broad timing on that is roughly before the end of Phase II. So our expectation is by the middle to the end of 2026, we're expecting Jeune to be a separate subsidiary of Krystal.

是的。我認為在 304 公告發布後，Suma 就開始與 FDA 進行對話。從發展角度來看，我們預計在未來幾個月內啟動第二階段。與此同時，Jeune 的執行長和財務長 Nishant 正在積極尋求或努力為 Jeune 籌集資金並進行分拆。大致時間是在第二階段結束前。因此，我們預計到 2026 年中期至年底，Jeune 將成為 Krystal 的獨立子公司。

Josh Schimmer, Cantor.

希默 (Josh Schimmer)，領唱。

Just two quick ones. Krish, can you clarify that when you suggest a decline in VYJUVEK revenue quarter-over-quarter in the third quarter, is that in the US only? Or does that encompass worldwide because you do have the offsetting launch in Europe?

只需簡單兩句話。Krish，您能否澄清一下，當您提到第三季度 VYJUVEK 收入環比下降時，這是否僅發生在美國？或者這是否涵蓋全球範圍，因為您確實在歐洲進行了抵消發射？

And then second question, your R&D expense allocation, at least in the 10-Q seems very heavily weighted to the oncology program, specifically. Just curious as to why that's the case and what trends do you expect to see going forward across the other programs?

然後是第二個問題，您的研發費用分配，至少在 10-Q 中似乎特別專注於腫瘤學課程。只是好奇為什麼會出現這種情況，以及您預計其他項目未來會出現什麼趨勢？

On the decline, that was on the US commentary, it was a completely 100% US-specific commentary taking into account like we saw last year that in the summer months, families gone vacation and there's more disruptions and pauses than usual. With respect to the R&D breakdown on cost, cancer trials are expensive --

關於下降，這是關於美國的評論，這是完全 100% 針對美國的評論，考慮到就像我們去年看到的那樣，在夏季，家庭外出度假，因此比平時有更多的干擾和停頓。就研發成本分攤而言，癌症試驗成本高昂--

I can surely chime in. Obviously, you guys saw the monotherapy data. We are now in the process -- the study has already started between the combination. KEYTRUDA is not cheap and it's expensive. And also given agencies recent disrupting and other stuff, we believe we have very strong data. So we want to position ourselves to meet with the agency and start talking about a controlled study.

我當然可以附和。顯然，你們看到了單一療法的數據。我們現在正處於這一過程中——組合之間的研究已經開始。KEYTRUDA 並不便宜，而且價格昂貴。而且考慮到各機構最近發生的混亂和其他事件，我們相信我們擁有非常強大的數據。因此，我們希望與該機構會面並開始討論一項對照研究。

So -- I mean, again, this is something we'll have based on our discussion with the agency, but we anticipated that into the cost. What it would take if you would go into a full-blown study.

所以——我的意思是，這是我們根據與該機構的討論而做出的決定，但我們已將其計入成本中。如果你要進行一項全面的研究，需要做些什麼呢？

Yigal Nochomovitz, Citigroup.

花旗集團的 Yigal Nochomovitz。

Two questions. Could you talk about -- you talked a lot about the 720, the 60%, as you pointed out. I'm curious about the other 40%, the 420 to get to the full 1,200. What have you said or what can you say today above the timelines to capture that aspect of the US market?

兩個問題。您能談談嗎——正如您所指出的，您談了很多關於 720 和 60% 的事情。我對剩下的 40% 感到好奇，即達到全部 1,200 所需的 420。您在時間線上說過什麼，或者您今天能說些什麼來了解美國市場的這個面向？

Look, the 720, it's a number -- like if you look at the past history of drugs that have been launched, the best of the launches have gotten to about 60% market share in two years. So this is more of an academic benchmark than anything related to -- oh, it has nothing to do with we're going to stop at 720. We fully believe that the entire 1,200 patient base is something that we need to target. But we had set a goal in terms of the rate of launch, trying to get to like a 60% market share and compete with the best of prior launches out there.

你看，720，這是一個數字——如果你看看過去推出的藥物的歷史，最好的藥物在兩年內就佔據了大約 60% 的市場份額。因此，這更多的是一個學術基準，而不是與之相關的任何東西——哦，這與我們將停在 720 無關。我們完全相信，我們需要以整個 1,200 名患者為目標。但我們在發布速度方面設定了一個目標，試圖佔據 60% 的市場份額，並與先前推出的最佳產品競爭。

The only point I'll make is as you get past 700, the profile of patients that we get will be much more moderate to mild, much more out in the community, probably higher on the age scale. And so -- but it does not mean every wound is important for VYJUVEK to be treated, and it's by no means are we trying to convey that once we get to 720, we're on some different mode of pathway.

我唯一要指出的是，當人數超過 700 人時，我們接收的患者情況將更加偏向中度至輕度，社區患者較多，年齡層可能也更高。所以 — — 但這並不意味著每個傷口都需要用 VYJUVEK 來治療，我們也絕不是想表達，一旦我們達到 720，我們就會走上某種不同的治療途徑。

We'll continue with the same level of diligence and effort to get to the remaining 1,200. And once we get to that point, we'll definitely start thinking about how to go after the gap between the 1,200 and the 3,000, which is a much more undiagnosed, difficult-to-find target population.

我們將繼續以同樣的勤奮和努力，爭取剩下的 1,200 個。一旦我們達到這一點，我們肯定會開始思考如何彌補 1,200 人和 3,000 人之間的差距，這是一個難以診斷、更難找到的目標群體。

Okay. That's helpful. And then I think you made a comment with respect to France, something about the continuity of the EAP. Can you just expand on that? Are there specific risks for continuity? Or why wouldn't there be continuity with the EAP that would impact the transition to the commercial. Can you just walk through that in more detail, please?

好的。這很有幫助。然後我認為您對法國發表了一些評論，涉及 EAP 的連續性。能詳細闡述嗎？是否存在特定的連續性風險？或者為什麼 EAP 不會保持連續性，從而影響向商業的過渡。能更詳細地介紹一下嗎？

Yes, Laurent?

是嗎，洛朗？

Yes. I mean this is a more formal aspect to it. We had the Acces Precoce pre-marketing authorization in France, and now we are waiting for the Acces Precoce post authorization. It does happen, even though it's very rare, but it does happen that some companies don't. So we respect the process that we have engaged with the authorities. But we are confident that, yes, the patients will be able to have access to the drug under the Acces Precoce in France.

是的。我的意思是這是一個更正式的方面。我們已獲得法國 Acces Precoce 的上市前授權，現在正在等待 Acces Precoce 的上市後授權。這種情況確實會發生，儘管非常罕見，但有些公司確實沒有這樣做。因此，我們尊重與當局接觸的進程。但我們相信，患者能夠根據法國的 Acces Precoce 獲得該藥物。

Debjit Chattopadhyay, Guggenheim Securities.

古根漢證券公司的 Debjit Chattopadhyay。

I have got a couple of clarifications. So on the 82% compliance, could you sort of clarify what percentage of patients are currently using four months of vials versus three-, two-, one-month et cetera? And how are you -- how have recessive patients evolved versus the dominant patients? And I have a follow-up.

我有幾個澄清。那麼，關於 82% 的依從性，您能否澄清一下，目前使用四個月劑量的藥瓶的患者比例是多少，以及使用三個月、兩個月、一個月等劑量的藥瓶的患者比例是多少？您好嗎－與顯性患者相比，隱性患者有何變化？我還有一個後續問題。

Yes, Debjit, I was following you along. Can you just repeat the first part of your question?

是的，Debjit，我一直在關注你。您能重複問題的第一部分嗎？

So the 82% compliance rate? What percentage of these patients are on four vials versus three-, two-, one-month et cetera? We're just trying to get a better feel for how to calculate that 82% or how to calculate in our models rather.

那麼合規率為 82% 嗎？在這些患者中，服用四瓶藥物的患者佔比是多少，服用三個月、兩個月、一個月等等的患者佔比是多少？我們只是想更了解如何計算這 82% 或如何在我們的模型中進行計算。

Look, the way we define compliance has always been consistent and the same since the time of the launch. I mean, the easiest way to think about compliance is if you are on drug for 10 weeks and you miss a week, you're at 90% compliance. That said, if somebody paused for an extended period and got back on drug, they kind of hurt compliance. And if you never came back on drug, you kind of helped compliance.

你看，自從發布以來，我們對合規性的定義一直是一致的、相同的。我的意思是，考慮依從性的最簡單方法是，如果你服藥 10 週，並且有一周沒有服藥，那麼你的依從性就是 90%。也就是說，如果有人在停藥一段時間後又重新開始吸毒，那麼他們的依從性就會受到影響。如果你不再吸毒，那麼你就在某種程度上幫助了遵守規定。

So it's just -- so that's why it's compliance while you're on drug as opposed to if you're not on drug. But that said, Debjit, irrespective of how one calculates compliance, whether on a quarterly basis or a six-month basis or an annual basis, we're talking a range somewhere between 76% and 84%. Like it's not that far off with respect to -- and there could be many ways to calculate and we try not to get into and it's not that material to the overall situation.

所以這只是——這就是為什麼當你吸毒時要遵守規定，而不是當你不吸毒時。但話雖如此，Debjit，無論如何計算合規性，無論是按季度、六個月還是按年度，我們討論的範圍都在 76% 到 84% 之間。就像它並不是那麼遙遠——而且可以有很多種計算方法，我們盡量不去深入探討，而且它對整體情況來說並不是那麼重要。

I appreciate the clarification. Then just a follow-up then on the utilization that you're seeing in the recessive patients versus the dominance I know you mentioned months, you get to 50-50, roughly 26 vials per patient. But right now, what are you seeing in the recession versus dominance?

我很感謝你的澄清。然後只是跟進您在隱性患者和顯性患者中看到的利用率，我知道您提到了幾個月，您得到了 50-50，每個患者大約 26 瓶。但是現在，您在經濟衰退和主導地位方面看到了什麼？

The recessive are definitely much more consistent and have been since the beginning of the launch. I mean we even look at what is the compliance of the people who came on the drug in Q3 of 2023? How are they doing today? All the pauses and stops and starts are heavily impacted by moderate- to mild patients typically adult moderate- to mild patients is who make this pause start difficult to figure out.

隱性肯定更加一致，並且自推出以來一直如此。我的意思是，我們甚至會看看 2023 年第三季服用該藥物的人的依從性如何？他們今天過得怎麼樣？所有的停頓、停止和開始都受到中度至輕度患者的嚴重影響，通常是成年中度至輕度患者，這使得這種停頓和開始難以弄清楚。

The RDEB is extremely consistent on track for the most part. Some of them now are approaching a point where the wounds are fully healed. And so there is an opportunity for them to take a break and get back on drug. But the entire conversation around stops and starts is on the moderate- to mild side.

RDEB 在大多數情況下都極為穩定地運作。其中一些人的傷口現在已經接近完全癒合的階段。這樣他們就有機會休息一下，然後再重新開始吸毒。但有關停止和啟動的整個討論都處於中等到溫和的水平。

Awesome. And then one last one. So based on the single-arm data, what kind of TPS scores are you enrolling in the combo program in non-small cell lung cancer?

驚人的。還有最後一個。那麼，基於單臂數據，您在非小細胞肺癌聯合治療計畫中招募了什麼樣的 TPS 分數？

TPS scores.

TPS 分數。

Okay. we are looking at -- obviously, we are agnostic, right? It doesn't matter what kind of PD-1 expression or PDL-1 expression, right? I mean we are looking for frontline failed patients. So either they failed PD-1 or PD-1 plus platinum therapy. So once they fail, we know -- we challenging with PD-1, the number of overall response goes down from 30% to 35% to 10%.

好的。我們正在看——顯然，我們是不可知論者，對吧？不管是PD-1表達或PDL-1表達，對吧？我的意思是我們正在尋找一線失敗的病人。因此，他們要么未能成功進行 PD-1 治療，要么未能成功進行 PD-1 加鉑類治療。因此，一旦它們失敗，我們就知道——我們用 PD-1 進行挑戰，整體反應數量會從 30% 下降到 35% 再到 10%。

So we are agnostic. We have seen -- we looked at our data with monotherapy with patients that have failed PD-1 or with they were mutation-specific, we still seem to have an impact when we work. We see stable disease or in some cases, we also see possible responses. So we feel we are pretty much agnostic.

所以我們是不可知論者。我們已經看到——我們查看了針對 PD-1 治療失敗或突變特異性患者的單一療法數據，我們發現，當我們進行治療時，似乎仍然會產生影響。我們看到病情穩定，或者在某些情況下，我們也看到了可能的反應。所以我們覺得自己幾乎是不可知論者。

So we are going to stratify our enrollment. Obviously, we look at PD-1 high patients and PD-1 zero. So we -- in our recruitment study and our analysis, we will try to stratify and collect that data and see the impact of whether you use in combination with pembro, are we seeing better impact with higher PD-1 expression versus negative PD-1 expression?

因此，我們將分層招生。顯然，我們關注的是 PD-1 高患者和 PD-1 零患者。因此，在我們的招募研究和分析中，我們將嘗試分層和收集這些數據，並觀察與 pembro 聯合使用的影響，我們是否看到較高的 PD-1 表達與陰性 PD-1 表達相比具有更好的影響？

Thank you. We have reached the end of the question-and-answer session and today's conference call. You may disconnect your phone lines at this time, and have a wonderful day. Thank you for your participation.

謝謝。問答環節和今天的電話會議已經結束。此時您可以斷開電話線，祝您有美好的一天。感謝您的參與。