PTC Therapeutics Inc (PTCT) 2025 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics first-quarter 2025 earnings conference call. (Operator Instructions) Today's conference is being recorded.

女士們、先生們，感謝你們的支持。歡迎參加 PTC Therapeutics 2025 年第一季財報電話會議。（操作員指示）今天的會議正在錄製。

I would now like to turn the conference over to Ellen Cavaleri, Head of Investor Relations. Please go ahead.

現在，我想將會議交給投資者關係主管 Ellen Cavaleri。請繼續。

Good afternoon, and thank you for joining us to discuss PTC Therapeutics' first-quarter 2025 corporate update and financial results. I'm joined today by our Chief Executive Officer, Dr. Matthew Klein; our Chief Business Officer, Eric Pauwels; and our Chief Financial Officer, Pierre Gravier.

下午好，感謝您加入我們討論 PTC Therapeutics 2025 年第一季的公司更新和財務業績。今天和我一起出席的還有我們的執行長 Matthew Klein 博士；我們的商務長 Eric Pauwels；以及我們的財務長 Pierre Gravier。

Today's call will include forward-looking statements based on our current expectations. These statements are subject to certain risks and uncertainties, and actual results may differ materially. Please review the slide posted on our investor relations website in conjunction with the call, which contains information about our forward-looking statements and our most recent quarterly report on Form 10-Q and annual report on Form 10-K filed with the SEC, as well as our other SEC filings for a detailed description of applicable risks and uncertainties that could cause our actual performance and results to differ materially from those expressed or implied in these forward-looking statements.

今天的電話會議將包括基於我們目前預期的前瞻性陳述。這些聲明受一定風險和不確定性的影響，實際結果可能有重大差異。請查看我們投資者關係網站上與電話會議一起發布的幻燈片，其中包含有關我們的前瞻性聲明和我們向美國證券交易委員會提交的最新 10-Q 表季度報告和 10-K 表年度報告的信息，以及我們向美國證券交易委員會提交的其他文件，其中詳細說明了可能導致我們的實際業績和結果與這些前瞻性聲明中明示或暗示的結果不確定性。

Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and a reconciliation of GAAP to non-GAAP are available in today's earnings release.

此外，我們將在本次電話會議中揭露某些非公認會計準則資訊。有關我們使用 GAAP 與非 GAAP 財務指標以及 GAAP 與非 GAAP 調整的信息，請參閱今天的收益報告。

I will now pass the call over to our CEO, Dr. Matthew Klein.

現在我將把電話轉給我們的執行長馬修·克萊因博士。

Thank you all for joining today. Following a year of outstanding execution across every part of the company, we're off to a great start in 2025. We achieved $190 million of revenue in the first quarter, made great progress on our preparations for the anticipated global launch of Sephience, and continue to work with regulatory authorities on our several pending approval applications.

感謝大家今天的參與。經過公司各部門一年來的出色表現，我們在 2025 年迎來了良好的開端。我們在第一季實現了 1.9 億美元的收入，在 Sephience 預期的全球上市準備工作上取得了重大進展，並繼續與監管機構就幾項待審批的申請進行合作。

In addition, we closed the quarter with over $2 billion in cash, providing us the necessary resources to support all key commercial and R&D efforts as we continue to move towards becoming cash flow breakeven. Let me begin with our revenue performance.

此外，本季結束時我們擁有超過 20 億美元的現金，這為我們支持所有關鍵商業和研發工作提供了必要的資源，使我們繼續朝著現金流收支平衡的目標邁進。讓我先從我們的收入表現開始。

We closed the quarter with $190 million in total product and royalty revenue with continued strong contributions from the DMD franchise. With this revenue performance, we are narrowing our 2025 full-year revenue guidance to $650 million to $800 million. We expect to further narrow guidance pending regulatory actions and additional clarity on Emflaza performance for the remainder of 2025.

本季結束時，我們的產品和特許權使用費總收入為 1.9 億美元，DMD 特許經營權持續貢獻強勁。鑑於這項營收表現，我們將 2025 年全年營收預期縮小至 6.5 億美元至 8 億美元。我們預計將在監管行動和 2025 年剩餘時間內對 Emflaza 表現的進一步澄清下進一步縮小指導範圍。

We recently announced a positive CHMP opinion on the marketing authorization of Sephience with an expected broad label, including the full spectrum of PKU patients of all ages. As we await European Commission adoption of the opinion, which is expected in June, we are preparing for our European launch.

我們最近宣布了 CHMP 對 Sephience 上市許可的積極評價，預計其適用範圍將非常廣泛，包括所有年齡層的 PKU 患者。我們正在等待歐盟委員會於 6 月採納該意見，為在歐洲的推出做準備。

In terms of launch sequence, we are prioritizing Germany and other countries where we can achieve early access through named patient programs. Eric will provide more details on the Sephience launch plan in Europe as well as in the US ahead of the anticipated FDA decision.

在啟動順序方面，我們優先考慮德國和其他可以透過指定患者計畫來實現早期使用的國家。在 FDA 做出預期決定之前，Eric 將提供有關 Sephience 在歐洲和美國的上市計劃的更多細節。

In the first quarter, we shared updated data from the ongoing Sephience long-term studies that continue to support the ability of Sephience to address all key patient market segments and provide patients the ability to liberalize their diet. The most recent analysis of APHENITY long-term extension data demonstrates that 97% of participants in the Phe tolerance study were able to increase their dietary Phe intake with two-thirds of patients reaching or exceeding the recommended daily allowance of protein intake for an individual without PKU.

在第一季度，我們分享了正在進行的 Sephience 長期研究的最新數據，這些數據繼續支持 Sephience 滿足所有關鍵患者細分市場的能力，並為患者提供自由飲食的能力。APHENITY 長期擴展數據的最新分析表明，97% 的 Phe 耐受性研究參與者能夠增加其飲食 Phe 攝取量，其中三分之二的患者達到或超過了非 PKU 患者的每日建議蛋白質攝取量。

Notably, these effects were also observed in classical PKU patients. We also shared results of the genetic variant analysis of the Phase 3 APHENITY trial, which demonstrated meaningful treatment effect in classical PKU subjects with non-BH4 responsive genotypes, providing further evidence that Sephience can provide benefit to all disease subtypes. Discussions with the FDA on the Sephience NDA are progressing well.

值得注意的是，在經典 PKU 患者中也觀察到了這些影響。我們也分享了 3 期 APHENITY 試驗的基因變異分析結果，該結果證明了對非 BH4 反應基因型的經典 PKU 受試者俱有顯著的治療效果，進一步證明 Sephience 可以為所有疾病亞型帶來益處。與 FDA 就 Sephience NDA 的討論進展順利。

We are far along in labeling discussions, and I want to emphasize that we have seen no impact of recent FDA changes on the Sephience NDA review. As we have discussed, we believe we can achieve over $1 billion in revenue from Sephience, a significant revenue opportunity that will provide the foundation for PTC's future growth.

我們在標籤討論方面已經取得了很大進展，我想強調的是，我們沒有看到 FDA 最近的變化對 Sephience NDA 審查產生任何影響。正如我們所討論的，我們相信我們可以從 Sephience 獲得超過 10 億美元的收入，這是一個重要的收入機會，將為 PTC 的未來成長奠定基礎。

Similar to the Sephience NDA review, we have not seen any impact of recent FDA changes on our other approval applications. FDA review of the vatiquinone NDA for the treatment of children and adults with Friedreich's ataxia is progressing at the typical cadence for an application under priority review. The FDA is in the process of conducting inspections, and we have been told that FDA does not plan to hold an AdCom meeting. For the Translarna NDA, we have been receiving information requests and clinical site inspections have already been conducted. Turning to the PTC518 Huntington's disease program.

與 Sephience NDA 審查類似，我們沒有看到 FDA 最近的變更對我們的其他批准申請產生任何影響。FDA 對用於治療弗里德賴希共濟失調兒童和成人的 vatiquinone NDA 的審查正在按照優先審查申請的典型節奏進行。FDA 正在進行檢查，我們被告知 FDA 不打算召開 AdCom 會議。對於 Translarna NDA，我們一直在接收資訊請求，並且已經進行了臨床現場檢查。轉向 PTC518 亨廷頓氏症計劃。

Yesterday, we announced positive top line results for the PIVOT-HD Phase 2 study. The study met its primary endpoints of blood HTT lowering and safety and the results on the full study population are consistent with the previously reported evidence of dose-dependent HTT lowering, favorable safety profile and early signals of dose-dependent clinical effect at 12 months in Stage 2 patients.

昨天，我們宣布了 PIVOT-HD 第二階段研究的正面頂線結果。該研究達到了血液 HTT 降低和安全性的主要終點，並且對整個研究人群的結果與先前報告的劑量依賴性 HTT 降低、良好的安全性和第 2 期患者 12 個月劑量依賴性臨床效果的早期信號的證據一致。

In addition, after 24 months of treatment, there were continued trends of dose-dependent favorable clinical effect relative to a propensity matched natural history cohort as well as dose-dependent NFL lowering, supporting that over a longer treatment period, we are seeing effects of HTT lowering on multiple aspects of disease. We plan to complete additional analyses and look forward to discussing next development and regulatory steps, including the potential for accelerated approval.

此外，經過 24 個月的治療，與傾向匹配的自然史隊列相比，劑量依賴性良好臨床效果的趨勢以及劑量依賴性 NFL 降低的趨勢持續存在，這支持了在較長的治療期內，我們看到 HTT 降低對疾病的多個方面的影響。我們計劃完成額外的分析，並期待討論下一步的開發和監管步驟，包括加速批准的可能性。

Finally, I want to highlight our strong cash position. We closed Q1 with over $2 billion on our balance sheet. As we have discussed, this cash position enables us to support all planned commercial and R&D activities, participate in strategic business development activities and reach cash flow breakeven without the need to access additional capital.

最後，我想強調一下我們強大的現金狀況。我們第一季的資產負債表上有超過 20 億美元的餘額。正如我們所討論的，這種現金狀況使我們能夠支持所有計劃的商業和研發活動，參與策略性業務發展活動，並實現現金流收支平衡，而無需獲取額外資本。

The timing of cash flow breakeven will be determined by the ramp of PKU commercial sales as well as the outcome of FDA approval applications for vatiquinone and Translarna. In addition, this cash position provides us with insulation from global macro uncertainties.

現金流損益平衡的時間將取決於 PKU 商業銷售的成長以及 FDA 對 vatiquinone 和 Translarna 的核准申請結果。此外，這種現金狀況使我們免受全球宏觀不確定性的影響。

In summary, PTC is off to a strong start in 2025. I look forward to our team's continued execution as we build PTC for successful 2025 and beyond.

總而言之，PTC 在 2025 年將迎來強勁開局。我期待我們的團隊繼續努力，為 PTC 在 2025 年及以後的成功而努力。

I will now turn the call over to Eric to discuss our commercial performance. Eric?

現在我將把電話轉給 Eric 來討論我們的商業表現。艾瑞克？

Thanks, Matt. Our global customer-facing teams have kicked off the first quarter of 2025 on a strong footing, delivering $153 million in revenue for our five marketed products. Our team is focused on the continued defense of our DMD franchise and diversification within our current commercial portfolio and executing on new product launch preparations globally this year.

謝謝，馬特。我們的全球客戶服務團隊在 2025 年第一季取得了良好的開端，為我們行銷的五種產品創造了 1.53 億美元的收入。我們的團隊專注於繼續捍衛我們的 DMD 特許經營權和當前商業組合的多樣化，並在今年在全球範圍內執行新產品的發布準備。

We delivered strong first-quarter revenue of $134 million for our global DMD franchise, which resulted from our defense strategies to maximize Translarna revenue in Europe and to successfully protect the Emflaza business in the US.

我們在第一季為全球 DMD 特許經營業務實現了 1.34 億美元的強勁收入，這得益於我們為最大化歐洲的 Translarna 收入而採取的防禦策略以及成功保護美國 Emflaza 業務而採取的策略。

While we remain disappointed with the EC decision to withdraw Translarna's marketing authorization in Europe, we have planned for this scenario for many months by working at a country level in Europe to identify pathways to continue to commercialize Translarna. In fact, we already have confirmation from many countries in the EU seeking continued access to Translarna via local reimbursement mechanisms and have already shipped product to multiple countries the first few weeks following the EC decision at the end of March, leveraging Article 117 of the EU directive.

雖然我們對歐盟委員會撤銷 Translarna 在歐洲的營銷授權的決定感到失望，但我們已經為這種情況籌劃了數月，在歐洲國家層面開展工作，以確定繼續將 Translarna 商業化的途徑。事實上，我們已經得到歐盟許多國家的確認，尋求透過當地的報銷機制繼續使用 Translarna，並且在 3 月底歐盟委員會做出決定後的前幾週，已經根據歐盟指令第 117 條將產品運送到多個國家。

In markets outside of Europe, we continue to receive orders in Latin America, Commonwealth of Independent States and the Middle East and North Africa regions. And we expect to see continued access to Translarna therapy moving forward for both new and existing nonsense mutation DMD patients.

在歐洲以外的市場，我們繼續接獲拉丁美洲、獨聯體以及中東和北非地區的訂單。我們期望看到新的和現有的無義突變 DMD 患者能夠繼續接受 Translarna 療法。

As Matt mentioned, the Translarna NDA is currently under review by the FDA. And if approved, our experienced US team is prepared for a rapid and effective launch. As for Emflaza, quarterly net revenue remained strong, demonstrating ongoing brand loyalty from health care providers and patients despite generic entries. While we have seen new additional generic approvals, the impact was not significant on Q1 revenues.

正如馬特所提到的，Translarna NDA 目前正在接受 FDA 的審查。如果獲得批准，我們經驗豐富的美國團隊將準備快速有效地啟動。至於 Emflaza，季度淨收入依然強勁，顯示儘管有仿製藥存在，醫療保健提供者和患者仍然對品牌保持忠誠。雖然我們看到了新的仿製藥獲批，但對第一季營收的影響並不大。

Moving to Tegsedi and Waylivra. We continue to grow these franchises in Latin America through patient identification efforts as well as geographic expansion in the region. For Upstaza and Kebilidi, we continue to focus our commercial efforts in countries where patients are identified, including those countries with AADC deficiency founder effects.

搬到 Tegsedi 和 Waylivra。我們透過患者識別工作以及該地區的地理擴張，繼續在拉丁美洲發展這些特許經營業務。對於 Upstaza 和 Kebilidi，我們將繼續把商業努力重點放在已確定患者的國家，包括那些有 AADC 缺乏症創始效應的國家。

Now turning to Sephience. We continue to accelerate our global launch plans. We are pleased with the recent CHMP positive opinion and are prepared to launch in key European markets as soon as EC ratification occurs. We implemented an early access program in Germany that will enable us to convert patients rapidly to commercial product and we are exploring other early access mechanisms in parallel with health technology assessments in Europe.

現在轉向 Sephience。我們將繼續加快全球發布計劃。我們對 CHMP 最近給予的正面評價感到高興，並準備在歐盟委員會批准後立即進入歐洲主要市場。我們在德國實施了一項早期使用計劃，這將使我們能夠快速將患者轉化為商業產品，並且我們正在與歐洲的健康技術評估同時探索其他早期使用機制。

Worldwide, there are approximately 58,000 addressable patients with PKU in markets where Sephience could be reimbursed. We expect to roll out the global launches in 25 markets over the next 12 months, prioritizing the launches in Germany, the US, and Japan. Sephience is a highly differentiated therapy that we believe will deliver transformative outcomes for patients living with PKU. Our data have consistently demonstrated the significant and meaningful efficacy of Sephience in both classical and nonclassical PKU patients, underscoring its broad commercial potential across the full spectrum of patients.

在全球範圍內，在 Sephience 可以獲得報銷的市場中，大約有 58,000 名可治療的 PKU 患者。我們預計在未來 12 個月內在全球 25 個市場推出產品，並優先在德國、美國和日本推出。Sephience 是一種高度差異化的治療方法，我們相信它將為苯酮尿症患者帶來變革性的結果。我們的數據一致證明了 Sephience 對經典和非經典 PKU 患者均具有顯著且有意義的療效，凸顯了其在所有患者群體中的廣泛商業潛力。

Our research and in-person meetings with key health care providers indicate their understanding of the potential of Sephience to help more patients reach their dietary goals. Diet liberalization is a critical factor for PKU patients, physicians and payers and is expected to drive early adoption of Sephience. Patients with PKU are often connected through social media, where we see posts suggesting they are well informed about the benefits of Sephience. We have heard from many key opinion leaders that patients have been reaching out to their treatment centers in advance of our anticipated launch and enrolling in our disease awareness programs.

我們的研究以及與主要醫療保健提供者的面對面會談表明，他們了解 Sephience 幫助更多患者實現飲食目標的潛力。飲食自由化對於苯酮尿症患者、醫生和付款人來說是一個關鍵因素，預計將推動 Sephience 的早期採用。苯酮尿症患者經常透過社群媒體進行聯繫，我們在社群媒體上看到的貼文表明他們充分了解 Sephience 的益處。我們從許多關鍵意見領袖那裡聽說，患者在我們預期推出的疾病意識計劃之前就已經聯繫了他們的治療中心並報名參加我們的疾病意識計劃。

Now moving to vatiquinone for Friedreich's ataxia. There remains a significant unmet need for children as well as adults with FA. Vatiquinone's differentiated mechanism of action and strong safety record and evidence of clinical benefit in both children and adult patients support a broad potential commercial opportunity for those under 16 for whom there is no approved therapy as well as for FA patients of all age groups. In preparation for a potential launch, our team has worked to understand the different dynamics of the pediatric and adult patient markets.

現在轉向使用 vatiquinone 來治療弗里德賴希共濟失調。對於患有 FA 的兒童和成人來說，仍然存在大量未滿足的需求。Vatiquinone 的差異化作用機制、強大的安全記錄以及對兒童和成人患者的臨床益處證據，為尚未獲得批准的治療方法的 16 歲以下患者以及所有年齡段的 FA 患者提供了廣泛的潛在商業機會。為了準備潛在的發布，我們的團隊致力於了解兒科和成人患者市場的不同動態。

In the US, the estimated prevalence is approximately 6,000 patients with Friedreich's ataxia, about one-third of whom are children typically treated in small numbers of children's hospitals with whom PTC has established long-term relationships. Many other centers of excellence in the US also treat adult FA patients, and our customer-facing teams are actively profiling these neurology centers to identify unmet needs and prepare for a successful launch following the potential FDA approval this summer.

在美國，估計弗里德賴希共濟失調症的患病人數約為 6,000 人，其中約三分之一是通常在少數與 PTC 建立了長期合作關係的兒童醫院接受治療的兒童。美國的許多其他卓越中心也為成年 FA 患者提供治療，我們面向客戶的團隊正在積極分析這些神經病學中心，以確定未滿足的需求，並為在今年夏天獲得 FDA 批准後成功上市做好準備。

With that, I will now turn the call over to Pierre for a financial update. Pierre?

說完這些，我現在將電話轉給皮埃爾，讓他報告財務最新情況。皮埃爾？

Thank you, Eric. I'll now share the financial highlights of our first quarter of 2025. Beginning with top-line results. Total products and royalty revenue for the first quarter was $190 million, including DMD franchise revenue of $134 million.

謝謝你，埃里克。現在我將分享我們 2025 年第一季的財務亮點。從頂線結果開始。第一季產品和特許權使用費總收入為 1.9 億美元，其中包括 1.34 億美元的 DMD 特許經營收入。

Starting with the DMD franchise. Translarna net product revenue in the quarter was $86 million and Emflaza net product revenue was $48 million. For Evrysdi, Roche achieved first quarter global revenue of approximately USD 470 million, resulting in royalty revenue of $36 million for PTC.

從 DMD 特許經營開始。Translarna 本季淨產品收入為 8,600 萬美元，Emflaza 淨產品收入為 4,800 萬美元。對於 Evrysdi，羅氏第一季的全球收入約為 4.7 億美元，為 PTC 帶來了 3,600 萬美元的專利費收入。

For the first quarter of 2025, non-GAAP R&D expense was $100 million, excluding $9 million in non-cash stock-based compensation expense compared to $107 million for the first quarter of 2024, excluding $9 million in noncash stock-based compensation expense. Non-GAAP SG&A expense was $72 million for the first quarter of 2025, excluding $9 million in non-cash stock-based compensation expense compared to $64 million for the first quarter of 2024, excluding $9 million in non-cash stock-based compensation expense.

2025 年第一季度，非 GAAP 研發費用為 1 億美元，不包括 900 萬美元的非現金股票薪酬費用，而 2024 年第一季為 1.07 億美元，不包括 900 萬美元的非現金股票薪酬費用。2025 年第一季的非 GAAP 銷售、一般及行政費用為 7,200 萬美元，不包括 900 萬美元的非現金股票薪酬費用，而 2024 年第一季為 6,400 萬美元，不包括 900 萬美元的非現金股票薪酬費用。

Cash, cash equivalents and marketable securities totaled $2,027 million as of March 31, 2025, compared to $1,140 million as of December 31, 2024. This strong financial position provides us with the resources to execute on our strategy and to achieve all our anticipated milestones as well as advance and expand our R&D efforts and explore business development opportunities to augment our commercial portfolio and pipeline.

截至 2025 年 3 月 31 日，現金、現金等價物及有價證券總額為 20.27 億美元，而截至 2024 年 12 月 31 日為 11.4 億美元。強大的財務狀況為我們提供了執行策略和實現所有預期里程碑的資源，同時推進和擴大我們的研發工作並探索業務發展機會以擴充我們的商業組合和管道。

And I will now turn the call over to the operator for Q&A. Operator?

現在我將把電話轉給接線員進行問答。操作員？

(Operator Instructions) Kristen Kluska, Cantor Fitzgerald.

（操作員說明）Kristen Kluska、Cantor Fitzgerald。

Congrats on a great quarter. So on Sephience, you noted that you're far along in discussions with the FDA. I don't know what you're able to discuss there, but a bit of a positive surprise given we're still a couple of months away from the PDUFA.

恭喜本季取得優異成績。關於 Sephience，您指出您與 FDA 的討論已經取得了很大進展。我不知道您能在那裡討論什麼，但考慮到我們距離 PDUFA 仍有幾個月的時間，這是一個積極的驚喜。

And then you also noted that you're hearing that patients are reaching out to doctors requesting information ahead of a potential launch. Are you able to comment on what the dynamic is? Are these mostly patient-naive patients? Are these patients that have tried other therapies and either failed or couldn't tolerate? And then is there a particular reason that's driving all of the inbound traffic to the doctors?

然後您還注意到，您聽說患者正在聯繫醫生，在可能推出之前請求提供資訊。您能評論一下這種動態嗎？這些患者大多都是初次接受治療的患者嗎？這些患者是否嘗試過其他療法但失敗或無法忍受？那麼，是否有一個特定的原因導致所有的訪問流量都流向醫生呢？

Thank you for the questions, Kristen. I'll take the first one, and I'll pass it over to Eric to handle the second question. So we are through several rounds of label negotiations. We believe we're near the end. We've gone through package insert discussions, carton create patient information.

謝謝你的提問，克里斯汀。我先回答第一個問題，然後交給 Eric 處理第二個問題。因此，我們經過了幾輪標籤談判。我們相信我們已經接近尾聲了。我們已經討論過包裝說明書，紙盒上創建了患者資訊。

So as you pointed out, things that are pretty far along in the review process. So that gives us a great deal of confidence that, one, the review is on track. I know there's been a lot of concerns with changes in FDA that there could be an impact to upcoming decisions. We've seen none of that impact. If anything, as you alluded to, we feel like things may be a little bit ahead of schedule.

正如您所指出的，審查過程已經進展到相當階段了。因此，這給了我們很大的信心，首先，審查正在按計劃進行。我知道很多人擔心 FDA 的變化可能會對即將做出的決定產生影響。我們沒有看到任何影響。如果有的話，正如您所提到的，我們覺得事情可能會稍微提前一點。

We still have a late cycle meeting to go that's scheduled for this month as would typically be done based on the PDUFA date, but we remain confident that, one, of the approval; and two, there not being any delays or any impact from any of the changes at FDA.

我們本月仍需參加一次後期週期會議，這通常是根據 PDUFA 日期進行的，但我們仍然相信，第一，批准；二是 FDA 的任何變更均不會造成任何延誤或影響。

I'll point out given the recent news of an hour ago that all of our applications are in SEDAR and the teams that we've been working with for all of our NDAs have appeared to be intact. We have the contact people are saying the teams do the same. So overall, no impact on the Sephience NDA nor any of other applications nor do we anticipate any.

我要指出的是，根據一小時前的最新消息，我們所有的申請都在 SEDAR 中，而且我們為所有 NDA 合作的團隊似乎都完好無損。我們的聯絡人說，各個團隊也做了同樣的事情。因此總體而言，這對 Sephience NDA 或任何其他應用程式均沒有影響，我們預計也不會有任何影響。

In terms of the second question before I turn it over to Eric, I'll just say this has just been the -- what we've seen, and I think you alluded to this in the note that you had put out a few months back, right, social media, patients communicating from all different types. Those are on therapies, those are therapy naive, sharing their experience and a lot of social media activity that I think is driving a lot of the interest, but I'll let Eric give a little bit more detail.

關於第二個問題，在我把它交給 Eric 之前，我只想說，這就是我們所看到的，我想您在幾個月前發布的說明中提到了這一點，對吧，社交媒體，來自各種不同類型的患者進行交流。這些都是關於治療方法的，這些都是不熟悉治療方法的，他們分享自己的經驗，並且有很多社交媒體活動，我認為這引起了人們的極大興趣，但我會讓 Eric 提供更多細節。

Yes. Thanks, Kristen, for the question. I mean our activities are really a lot engaged with a number of the key centers as well as health care providers, but a lot of patient activity.

是的。謝謝克里斯汀提出的問題。我的意思是，我們的活動確實與許多主要中心以及醫療保健提供者密切相關，但也有很多是針對患者的活動。

We have a disease awareness website, PTC Reimagines PKU. It's basically a disease website where a lot of the patients, healthcare providers, families are engaging. They'll enroll in the program. And we see a very steady cadence of every week, every month, that number increasing.

我們有一個疾病意識網站，PTC Reimagines PKU。它基本上是一個疾病網站，許多患者、醫療保健提供者和家庭都參與其中。他們將參加該計劃。我們看到，每週、每月，這個數字都在穩定成長。

And as Matt said, there's really been no specific patient type. It has been all patients. There have been younger patients. There's been healthcare providers with a bolus of patients that are ready to go. And some of them are just really interested not only sharing the information, but getting updates about the status of Sephience ultimately when it will be approved.

正如馬特所說，實際上並沒有特定的患者類型。都是病人。還有一些較年輕的患者。已經有醫療服務提供者為患者準備了一批藥物。他們中的一些人不僅真的有興趣分享訊息，而且還想了解 Sephience 最終獲得批准時的狀態更新。

So, I mean, we're very pleased right now that a lot of the activity is going through social media and then channeling that through our disease awareness site. So we anticipate that that will continue. And of course, publication, scientific information and all of that is shared widely as well.

所以，我的意思是，我們現在非常高興，很多活動都是透過社群媒體進行的，然後透過我們的疾病意識網站傳播。因此我們預計這種情況將會持續下去。當然，出版品、科學資訊等也都被廣泛分享。

Eric Joseph, JPMorgan.

摩根大通的艾瑞克‧約瑟夫。

Just on Sephience in Europe, I'm wondering if whether it's reasonable to expect any contribution to top line, any sales performance in 2025 and that you might actually see some pull-through through named patient access programs beginning in Germany?

就歐洲的 Sephience 而言，我想知道是否可以合理地預期它會對 2025 年的營收和銷售業績做出貢獻，以及您是否可能實際上看到透過從德國開始的指定患者訪問計劃實現一些突破？

And then secondly, I know that you obviously have lots going on with multiple new product launches and a focus on cash flow breakeven. That said, just given the balance sheet, I'm wondering whether you can talk a little bit about sort of your appetite from a business development perspective, areas that you might be focused in and whether sort of the broader pressure that we're seeing on valuations might kind of spur that activity or that interest a little bit further.

其次，我知道您顯然有很多事情要做，包括推出多款新產品並專注於現金流損益兩平。話雖如此，僅從資產負債表來看，我想知道您是否可以從業務發展的角度談談您的興趣，您可能關注的領域，以及我們在估值方面看到的更廣泛的壓力是否可能會進一步刺激這種活動或興趣。

Thank you for the questions, Eric. On the first one, yes, we absolutely expect revenue in 2025 from Europe. As Eric alluded to, we'll be ready to launch in Germany once we have the adoption of the opinion, and then we'll also be leveraging other early access programs to garner revenue in '25 and as soon as possible.

謝謝你的提問，艾瑞克。關於第一個問題，是的，我們絕對預期 2025 年的收入將來自歐洲。正如 Eric 所提到的，一旦意見獲得通過，我們就會準備好在德國推出該產品，然後我們還將利用其他早期訪問計劃，在 2025 年及以後盡快獲得收入。

I think for us, we have a well-established global commercial infrastructure, including in Europe. Our teams are very well versed in launching products, launching rare disease products and also understanding the country-by-country nuances and the country-by-country programs that enable us to accelerate revenue opportunities in cases where we can ahead of formal pricing and reimbursement discussions.

我認為我們擁有完善的全球商業基礎設施，包括歐洲。我們的團隊非常精通產品上市、罕見疾病產品的上市，同時也了解各國的細微差別和各國的計劃，這使我們能夠在正式定價和報銷討論之前盡可能地加速收入機會。

In terms of business development, let me turn it over to Pierre to talk a little bit how we're thinking about potential opportunities as we turn some cards over the rest of the year.

在業務發展方面，讓我將話題交給皮埃爾，讓他稍微談談我們在今年剩餘時間內如何看待潛在的機會。

Yes. First of all, we're very happy with our strong financial position over $2 billion in this environment. Obviously, it gives us a lot of flexibility to continue all our activities and not worry about cash anytime soon. Furthermore, in terms of BD, we're absolutely looking at business development opportunities, both commercial and pipeline assets as PTC has done historically. And obviously, we'll haul in one way or the other as we get further clarity on our portfolio.

是的。首先，我們對當前環境下超過 20 億美元的強勁財務狀況感到非常滿意。顯然，它為我們提供了極大的靈活性，可以繼續進行所有活動，而不必擔心近期的現金問題。此外，就 BD 而言，我們絕對會尋找業務發展機會，包括商業和管道資產，就像 PTC 過去所做的那樣。顯然，隨著我們的投資組合變得更加清晰，我們會採取某種方式來應對。

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Maybe just following up on Sephience. Is there any indication you can give us of, I guess, relatively recent interest from the nutritionist community? And then are you able to delineate between commercialization efforts and ramp in Europe versus in the US and what's being done differently in each?

也許只是跟進 Sephience。我想，您能否向我們透露一下營養學家群體最近對此有何興趣？然後，您能否區分歐洲和美國的商業化努力和成長，以及兩者之間的差異？

Thank you for the questions, Judah. Let me just start by saying that our entire launch plan has had nutritionists and dietitians intimately involved. We appreciate that patient -- centers of excellence have physicians who play a clearly important role for patient management, but so do nurse practitioners, nurses and dietitians. They're often the frontline of contact with patients who are on the therapy as diet management is such a key part of the PKU patient daily life.

謝謝你的提問，猶大。首先我要說的是，我們的整個發布計劃都得到了營養師和營養師的密切參與。我們讚賞患者卓越中心擁有在患者管理中發揮重要作用的醫生，但執業護士、護士和營養師也同樣如此。他們通常是與接受治療的患者接觸的第一線人員，因為飲食管理是苯酮尿症患者日常生活中非常重要的一部分。

So we have done a lot of work to make sure that we understand the needs of nutritionists, hear from them, and we've bolstered our own medical team with nutritionists and dietitians so we can provide appropriate peer-to-peer support.

因此，我們做了很多工作來確保我們了解營養師的需求，聽取他們的意見，並且我們還透過營養師和營養師加強了我們自己的醫療團隊，以便我們能夠提供適當的點對點支援。

Let me turn it over to Eric to give a little bit more detail on that as well as talk about how we're thinking about relative ramps in the commercialization of Sephience.

讓我把這個問題交給 Eric 更詳細地介紹一下，並談談我們如何看待 Sephience 商業化的相對提升。

Yes. Interestingly enough, we will be launching both in Germany and the US in a very similar time frame. And the ramps are going to be very interesting in the context that we've been doing a lot of work in the premarketing area.

是的。有趣的是，我們將在非常相似的時間內在德國和美國推出該產品。鑑於我們在預行銷領域已經做了大量工作，這些坡道將會非常有趣。

As I mentioned earlier, in the US, we've had a number of patients that have come up, two centers have opted into our disease website. These will be the very first ones that are being targeted clinical trial patients as well. In Germany, we implemented a compassionate use program. That program actually had more than half of the sites in Germany that treat patients that are enrolling patients now before. And these patients will be available at commercial launch immediately once we end up launching and pricing the product in Germany.

正如我之前提到的，在美國，我們已經接待了許多患者，有兩個中心選擇加入我們的疾病網站。這些也將是首批被作為臨床試驗目標的患者。在德國，我們實施了一項同情用藥計畫。事實上，該計畫在德國擁有超過一半的治療點，這些治療點之前都在招募患者。一旦我們最終在德國推出該產品並確定其價格，這些患者將立即獲得商業上市許可。

So we believe that the US and Germany will be very significant contributors to revenue in the second half of 2025.

因此，我們相信美國和德國將成為 2025 年下半年收入的重要貢獻者。

Brian Abrahams, RBC.

布萊恩·亞伯拉罕斯，RBC。

This is Joe on for Brian. I just wanted to ask on Huntington's. So you've had a little more time to look at the data. Do you have any updated thoughts on how to best balance accelerating potential approval time line and maximizing the chance of demonstrating drug benefits more clearly. Any thoughts on how you could potentially shorten approval timeline, like interim read data at a certain percentage of patients would be very helpful.

這是喬 (Joe) 取代布萊恩 (Brian)。我只是想問一下亨廷頓的情況。因此您有更多的時間來查看數據。您對如何最好地平衡加快潛在審批時間表和最大限度地更清楚地展示藥物益處的機會有什麼最新的想法嗎？關於如何縮短審批時間的任何想法，例如對一定比例的患者的臨時讀取數據，都將非常有幫助。

Yes. Thanks, Joe, for the questions. Hasn't been that much time. We've been a little busy, but I will say that our impressions of the data from yesterday remain very similar.

是的。謝謝喬提出的問題。還沒那麼久。我們有點忙，但我要說的是，我們對昨天的數據的印象仍然非常相似。

We were very pleased with the results when you look at this in terms of the Phase 2 trial in a neurodegenerative disease to be able to demonstrate that the drug does what it's supposed to do in terms of target engagement and the dose-dependent huntingtin lowering we observed. It goes where it's supposed to go, getting not only adequate CNS exposure, but we have higher exposure in the CSF than -- free drug exposure in the CSF than the plasma. The drug is demonstrating itself to be safe and well tolerated, and we're seeing signals both of important clinical and biomarker effect at 12 months and at 24 months that confirm that things are moving in the exact direction they need to.

從神經退化性疾病的 2 期試驗的角度來看，我們對結果非常滿意，因為能夠證明該藥物在靶向作用和我們觀察到的劑量依賴性亨廷頓蛋白降低方面發揮了應有的作用。它會到達它應該去的地方，不僅獲得足夠的中樞神經系統暴露，而且我們在腦脊髓液中的暴露量比血漿中的遊離藥物暴露量更高。該藥物被證明是安全且耐受性良好的，我們在 12 個月和 24 個月時看到了重要的臨床和生物標記效應信號，證實事情正在朝著正確的方向發展。

And finally, I'll add, I know we got a lot of questions about the Stage 3 patients and what does that do to our thoughts about the program. It was an incredibly important learning to make. One of the important hypotheses of the PIVOT-HD trial was that Stage 2 patients may be the optimal clinical trial population.

最後，我要補充一點，我知道我們收到了很多關於 3 期患者的問題，以及這對我們對該計劃的看法有何影響。這是一個極為重要的學習。PIVOT-HD 試驗的一個重要假設是，第 2 階段患者可能是最佳臨床試驗族群。

So let me just make clear, clinical trial population is different than a patient population in whom the drug may ultimately have benefit. It's a population in whom over the typical length of a clinical trial, you're well positioned to show that you're modifying disease progression in a strong enough way that you can meet an efficacy endpoint.

因此，讓我明確一點，臨床試驗族群與藥物最終可能受益的患者族群不同。對於這一人群，在典型的臨床試驗期間，您可以很好地證明自己正在以足夠強大的方式改變病情進展，從而達到療效終點。

And we've talked a lot about being concerned that the Stage 2 patients may be so advanced that it's going to be very difficult to capture modification in that population. That was our hypothesis going into PIVOT-HD, and that was proven out. So that's a very important learning as we think about the next stage in development to know that, that Stage 2 population is likely the optimal one in whom we can establish efficacy.

我們已經多次討論過，我們擔心 2 期患者的病情可能已經非常嚴重，因此很難捕捉到該族群的改變。這是我們進入 PIVOT-HD 的假設，並且已經得到證實。因此，當我們考慮下一階段的發展時，這是一個非常重要的認識，即知道第 2 階段的人群可能是我們能夠確定療效的最佳人群。

In terms of accelerated the path, we continue to believe that we've demonstrated that we are lowering HTT levels and our discussions with the agency indicated that they are aligned scientifically that HTT lowering is likely to predict clinical benefit. And we believe that we have additional evidence that huntingtin lowering is associated with favorable things. At 12 months, we see dose-dependent lowering on the disease rating scale driven by the things in Stage 2 that they should be driven by PMS and SDMT.

在加速路徑方面，我們仍然相信我們已經證明我們正在降低 HTT 水平，並且我們與該機構的討論表明，他們在科學上是一致的，即 HTT 降低可能預測臨床益處。我們相信，我們有更多證據表明亨廷頓蛋白的降低與有利的事情有關。在 12 個月時，我們看到疾病評定量表呈現劑量依賴性降低，這是由第 2 階段的因素引起的，而這些因素應該是由 PMS 和 SDMT 引起的。

And as we move out to 24 months, we're now able to show additional associations with significant effect relative to natural history on the disease rating scale and the dose-dependent lowering of NFL, which now provides biological evidence of potential neuroprotection, which really, again, supplements this concept that HTT lowering is associated with favorable things that in the long term can result in efficacy and an efficacious therapy for all Huntington's disease patients. So again, we're very much where we were yesterday in our view of the data and look forward to discussions with Novartis as we chart additional steps.

隨著研究時間延長至 24 個月，我們現在能夠證明，與疾病評估量表的自然病程和 NFL 的劑量依賴性降低相比，存在更多具有顯著影響的關聯，這為潛在的神經保護作用提供了生物學證據，這再次補充了以下概念：HTT 降低與有利因素相關，從長遠來看，可以為所有亨廷頓舞蹈症患者帶來療效和有效的治療。因此，我們再次重申，從數據來看，我們與昨天的情況基本一致，並期待與諾華進行討論，並制定進一步的措施。

In terms of regulatory discussions and further development plans. I'd say the only thing that's come between yesterday and today is a lot of outreach from patients and KOLs hearing their enthusiasm for the data, including experts like Dr. Ed Wild, who is probably one of the main experts and biomarkers of HD disease who is incredibly enthusiastic about the NFL data and HTT lowering and the safety and tolerability. So if anything, what we've heard from outside has increased our belief of the strength of this data set for this disease.

在監管討論和進一步發展計劃方面。我想說，昨天和今天之間唯一發生的事情是大量患者和關鍵意見領袖的關注，聽到他們對數據的熱情，包括像 Ed Wild 博士這樣的專家，他可能是亨廷頓氏病的主要專家和生物標誌物之一，他對 NFL 數據和 HTT 降低以及安全性和耐受性非常熱情。因此，無論怎樣，我們從外界聽到的消息都增強了我們對這種疾病的資料集的可信度。

Kelly Shi, Jefferies.

傑富瑞 (Jefferies) 的凱莉施 (Kelly Shi)。

This is Jose for Kelly. I have a question about PKU, specifically on diet liberalization for Sephience. Wonder if you could please remind us how you can leverage your findings for payer reimbursement purposes, especially for patients who respond to generic standard of care. In other words, what's the clinical utility in your view of even higher diet liberalization that could support reimbursement in this segment with minimal payer pushback?

我是凱利的何塞。我有一個關於 PKU 的問題，特別是關於 Sephience 的飲食自由化。想知道您是否可以提醒我們如何利用您的研究結果來實現付款人報銷目的，特別是對於對通用護理標準有反應的患者。換句話說，您認為更高程度的飲食自由化在臨床上有何實用價值，可以支持這一領域的報銷，同時最大程度減少付款人的阻力？

Thank you very much for the question, Jose. Let me just give an overview -- one quick overview, and then I'll let Eric go into detail a bit about the payer dynamics and the importance of Phe tolerance data. I think Phe tolerance is something that's very important to patients, incredibly important for patient uptake, physician uptake and as you pointed out, has a role in payers.

非常感謝你的提問，何塞。讓我先做一個概述——一個快速的概述，然後我會讓 Eric 詳細介紹一下付款人動態和 Phe 耐受性數據的重要性。我認為 Phe 耐受性對於患者來說非常重要，對於患者接受度、醫生接受度都極為重要，並且正如您所指出的，對於付款人也起著一定的作用。

I think one of the things to point out is that our data has shown in the clinical studies, and it's also based on mechanism that patients who may be enjoying benefits of sapropterin BH4 therapy branded or generic have shown to have a greater amount of lowering with sepiapterin. That's something we saw in our clinical trial with the 27 subjects who came into the trial on sapropterin. And again, it makes sense mechanistically when you consider that we're able to get much greater intracellular concentrations of BH4 through sepiapterin administration and sapropterin administration.

我認為需要指出的一點是，我們的數據已在臨床研究中得到證實，並且它還基於這樣的機制：可能享受到沙丙蝶呤 BH4 療法（品牌或仿製藥）益處的患者在使用墨蝶呤後，血壓降低幅度更大。我們在對 27 名參加沙丙蝶呤試驗的受試者進行的臨床試驗中看到了這一點。再次，當您考慮到我們能夠透過墨蝶呤給藥和沙丙蝶呤給藥獲得更高的細胞內 BH4 濃度時，這在機制上是有意義的。

And then, of course, for those who are not considered to be BH4 responsive or have mutations that are considered to be not BH4 responsive, we've been able to show that we've been able to have a significant effect, not only in terms of phenylalanine lowering, but also in terms of the ability to allow patients to have diet liberalization. And that includes the more severe classical PKU patients and a lot of the patients who are in that therapy-naive bucket. Eric, do you want to talk a little bit how we're thinking about the Phe tolerance data in terms of the payer discussions and dossiers.

當然，對於那些被認為對 BH4 沒有反應或具有被認為對 BH4 沒有反應的突變的人，我們已經能夠證明我們已經能夠產生顯著的效果，不僅在降低苯丙胺酸方面，而且在允許患者進行飲食自由化的能力方面。其中包括病情較為嚴重的典型苯酮尿症患者和許多未接受過治療的患者。艾瑞克，你想談談我們如何從付款人討論和檔案的角度來考慮 Phe 耐受性數據嗎？

Yes. Thanks for the question. In fact, we actually have presented -- we have the AMCP dossier, but we have presented all the data live, and we've also tested market research with a number of key US payers, both commercial and government.

是的。謝謝你的提問。事實上，我們確實已經提交了——我們有 AMCP 檔案，但我們已經在現場提交了所有數據，我們也與一些主要的美國付款人（包括商業和政府）進行了市場研究測試。

The first thing they do see is an incredibly differentiated profile. And to Matt's point, they see Phe reductions that are substantially better and different than anything that we currently have in terms of standards of care. Their reaction to the number of patients reaching goals is impressive. And in addition to that, the diet liberalization is one of the things that really triggers their appetite, if you will, to say that the product is highly differentiated and superior to Kuvan as it stands.

他們首先看到的是一個極其差異化的形象。正如馬特所說，他們發現 Phe 的減少比我們目前的任何護理標準都要好得多，而且有所不同。他們對達到目標的患者數量的反應令人印象深刻。除此之外，飲食自由化是真正激發他們食慾的因素之一，如果你願意的話，可以說該產品具有很高的差異化，並且優於現有的 Kuvan。

When we've actually pressed and looked at the various things in terms of potential steps or prior authorizations, we believe there will be prior authorizations to the label. And only naive patients might be going through steps because the vast majority of patients and 90% of the patients in the US are not on any kind of current medical treatment, which means more than half or more have actually tried and failed.

當我們真正從潛在步驟或事先授權的角度考慮和審視各種事物時，我們相信該標籤將會事先獲得授權。而且只有未成熟的患者才可能需要採取這些措施，因為絕大多數患者以及美國 90% 的患者目前都沒有接受任何醫療治療，這意味著超過一半或更多的患者實際上已經嘗試過但失敗了。

So we'll be able to avoid many of those because the prior authorizations will allow for clinical information on the patient. And if we have to go through step edits, they're very short. So, so far, the payers -- the dynamics have been very favorable, and we will continue to test that as we engage and become closer to the launch.

因此，我們將能夠避免其中的許多問題，因為事先的授權將允許獲取患者的臨床資訊。如果我們必須進行逐步編輯，那麼它們就非常短。所以，到目前為止，付款人的動態一直非常有利，我們將在參與和接近發佈時繼續測試這一點。

Eliana Merle, UBS.

瑞銀的 Eliana Merle。

This is Jasmine on for Ellie. Congratulations on the progress. We have one on Emflaza. So what have you been seeing in terms of volumes and gross to net generic approvals? And what do you expect to see here going forward this year?

這是 Jasmine 為 Ellie 演唱的。恭喜你取得進展。我們在 Emflaza 有一個。那麼，就彷製藥批准數量和總額與淨額而言，您看到了什麼？您期望今年看到什麼進展？

And can you talk about some of your strategies to defend the brand against generic erosion?

您能談談保護品牌免受通用產品侵蝕的一些策略嗎？

Thanks for the question, Jasmine. Let me turn it over to Eric. And obviously, we're very proud of the continued Emflaza performance through the first quarter and really a testament to terrific efforts by our teams. Eric?

謝謝你的提問，Jasmine。讓我把它交給艾瑞克。顯然，我們對 Emflaza 在第一季的持續表現感到非常自豪，這確實證明了我們團隊的出色努力。艾瑞克？

Yes. The teams have continued to, if you will, garner brand loyalty from the Duchenne community. I mean I think the secret sauce is we've been with them for the last eight years, and we've been providing them exceptional services. Our teams have actually focused on dispenses written and co-pay assistance, but also have strong relationships with each one of these Duchenne patients.

是的。如果你願意的話，這些球隊將繼續贏得杜氏肌肉營養不良症患者群體的品牌忠誠度。我的意思是，我認為秘訣在於我們過去八年來一直與他們合作，並一直為他們提供卓越的服務。我們的團隊實際上專注於提供書面處方和共同支付援助，同時也與每位杜氏肌肉營養不良症患者建立了牢固的關係。

Now while we have seen some generics come in, the pricing happens to be very similar. So your question around gross to net, we haven't seen that much change at all with our gross to net because it's unclear for us whether the generics are rebating at a higher rate. Now we do expect some erosion. We'll continue to expect erosion as more generic entrants come in.

現在，雖然我們已經看到一些仿製藥的出現，但定價卻非常相似。因此，您關於毛利與淨利比率的問題，我們並沒有看到毛利與淨利比率有太大變化，因為我們不清楚仿製藥的回扣率是否更高。現在我們確實預期會出現一些侵蝕。隨著更多通用產品的進入，我們將繼續預期市場下滑的趨勢。

But one thing we've been able to do is every single month in the quarter, we've been able to add new patients, and we've been able to maintain a number of the existing patients with minimal disruption. So I think all in all, I have to say that our US team is really dedicated in terms of managing and giving that sort of white-glove service to every single Duchenne patient, and that's been the secret sauce.

但我們能夠做到的一件事是，在本季度的每個月，我們都能夠增加新患者，並且能夠以最小的干擾維持一定數量的現有患者。所以我認為總的來說，我不得不說我們的美國團隊確實致力於管理並為每位杜氏肌肉營養不良症患者提供這種白手套服務，這就是我們的秘訣。

Geoff Meacham, Citigroup.

花旗集團的傑夫‧米查姆。

I just had another one on diet liberalization in PKU. I guess more of a commercial one, though. The question is how rapidly do you think real-world use could reflect this? I wasn't sure what success looks like in the US. And then are there differences when you think commercially between the European and Japanese market just on this topic?

我剛剛又聽了一篇關於北大飲食自由化的報導。不過，我猜這更多的是商業性的。問題是您認為現實世界的使用能多快反映這一點？我不確定在美國成功是什麼樣子的。那麼，就這個主題而言，您從商業角度考慮歐洲和日本市場是否存在差異？

Thanks very much for the question. I mean when you think about -- I guess, by commercially, you mean in sort of real life when the drug is out there and being taken by people. I think one very good indicator we have of that is what we -- the feedback we've gotten and things we see on social media, which is patients being incredibly enthusiastic about the ability to liberalize their diet, whether it's a small amount of liberalization or complete liberalization away from the diet.

非常感謝您的提問。我的意思是，當你考慮——我猜，從商業角度來說，你指的是現實生活中，當藥物存在並被人們服用時。我認為，我們得到的回饋和在社群媒體上看到的情況是一個很好的指標，表明患者對於放開飲食的能力非常熱情，無論是少量的放開還是完全遠離飲食的放開。

And this has not only benefits to them in terms of daily life, but also can have other important benefits especially the kids in school in terms of socialization and peer interactions. So I think this plays out very well. It's not something that is actively monitored in the commercial setting, but it is something that we know that is going to be important for patients to try.

這不僅對他們的日常生活有益，而且還能帶來其他重要益處，尤其是對學校裡的孩子在社交和同儕互動方面有益。所以我認為這會起到很好的效果。它不是在商業環境中受到主動監控的東西，但我們知道它對病人來說值得嘗試。

And this is part of the reason for the earlier question, we've been working so closely with the dietitians and nutritional therapists to help manage things appropriately so patients can liberalize their diet in a very thoughtful, rational way, so they're set up for success and can gradually do so. So those that can get to full liberalization, we're able to get there. Those that can get some liberalization can do that and help understand if it's a kid that they can have their lunch at school now and stay with the other kids and have a typical lunch and maybe have less protein in other meals.

這也是前面提出問題的部分原因，我們一直與營養師和營養治療師密切合作，幫助他們妥善管理，以便患者能夠以非常周到、合理的方式放寬飲食，從而為成功做好準備，並可以逐步實現。因此，那些能夠實現全面自由化的國家，我們也能實現。那些可以獲得一些自由化的人可以這樣做，並幫助理解，如果是孩子，他們現在可以在學校吃午飯，與其他孩子呆在一起，吃一頓典型的午餐，也許在其他餐食中攝入較少的蛋白質。

So all of that are things that will play out in the commercial setting. It's why we've staffed our medical team and are working so closely with the nutritionists and the expert centers. I don't know if you have any additional comment on differences in Japan or Europe.

所以所有這些都將在商業環境中發揮作用。這就是我們配備醫療團隊並與營養師和專家中心密切合作的原因。我不知道您對日本或歐洲的差異是否有其他評論。

No, we haven't actually seen any differences. And in fact, I think diet liberalization has been well embraced by our healthcare providers. Obviously, Europe and Japan, there's patient information that is out there on PKU, but the physicians really drive a lot of that education. They're incredibly impressed with diet liberalization and the dieticians have embraced it as one of the reasons to really revolutionize or really transform the way patients not only socialize and live, but importantly, they have to change their diet for greater increases in protein intake.

不，我們實際上沒有看到任何差異。事實上，我認為飲食自由化已經得到了我們的醫療保健提供者的廣泛接受。顯然，歐洲和日本都有關於苯酮尿症的患者訊息，但醫生才是真正推動這類教育的主要力量。他們對飲食自由化印象深刻，營養師也將其視為真正革新或改變患者社交和生活方式的原因之一，重要的是，他們必須改變飲食習慣以增加蛋白質的攝取。

So it has been a really important catalyst, not just at the patient level, but at the physician level. It's a piece of data that really is impressive.

因此，它是一個非常重要的催化劑，不僅在病人層面，而且在醫生層面。這確實是一個令人印象深刻的數據。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

For me, I just wanted to ask another question on Friedreich's. Can you just clarify for us what doctor feedback is on the under met need? So if you are able to get approved in this indication, what would prevent, let's say, every patient from being put on it?

對我來說，我只是想問另一個關於弗里德賴希的問題。您能否為我們澄清一下醫生對於未滿足需求的回饋是什麼？那麼，如果您能夠獲得該適應症的批准，那麼什麼會阻止每個患者都使用該藥物？

And then secondly, on your comments about FDA coming back and saying that you should not expect to have an AdCom. Is that based on discussions you've had specifically with the agency and the agency feels that the data itself is clear enough? Or is there a different reason why at this time, they are not planning on holding an AdCom?

其次，關於您對 FDA 的評價，FDA 表示您不應該期望有一個 AdCom。這是基於您與該機構進行的專門討論，並且該機構認為數據本身足夠清晰嗎？或者他們此時不打算召開 AdCom 還有其他原因嗎？

Tazeen, thank you very much for the questions. Let me start with the second one. The communication about not having an AdCom was something that was raised by the agency at our mid-cycle meeting that was held last month. They said at this point in the review, they don't see a need and don't expect to hold an AdCom meeting. They didn't give any further detail on that.

Tazeen，非常感謝您提出這些問題。我先從第二個開始。關於沒有 AdCom 的問題是我們機構在上個月舉行的中期會議上提出的。他們表示，在審查的這個階段，他們認為沒有必要召開 AdCom 會議，也不打算召開。他們沒有透露有關此事的更多細節。

And as we said all along, we believe the agency understands the disease, understands the endpoints, both from their experience with the SKYCLARYS review as well as a number of other future protective therapies in development. So I think they're very involving conversations.

正如我們一直所說的那樣，我們相信該機構了解這種疾病，了解終點，這既來自他們對 SKYCLARYS 審查的經驗，也來自正在開發的其​​他一些未來保護療法的經驗。所以我認為他們的對話非常引人入勝。

And in our discussions regarding the vatiquinone package, it has become very clear that they understand the mFARS endpoint. They understand the dynamics involved with upright stability. They understand the long-term registry that was an important part of our confirmatory evidence.

在我們關於 vatiquinone 方案的討論中，很明顯他們了解 mFARS 終點。他們了解與直立穩定性有關的動力學。他們了解長期登記是我們確認證據的重要部分。

So we were not surprised by the decision to not hold the AdCom. In terms of accessing populations, I think, look, there's nothing available for patients under the age of 16, and that's certainly a population where we've been able to show benefit as well as safety in the trials. We have safety data with vatiquinone going down to children less than one year of age, and we have experience in adult populations as well. And so I believe that we have the opportunity to be a therapy not only for children who don't have alternatives now, but also to be a safe -- an additional potential safe and well-tolerated and effective therapy for adults.

因此，我們對不舉行 AdCom 的決定並不感到驚訝。在人群獲取方面，我認為，目前還沒有針對 16 歲以下患者的治療方法，而我們在試驗中已經能夠證明該治療方法對這一人群的益處和安全性。我們擁有關於瓦替奎酮對一歲以下兒童的安全性數據，我們也有針對成年人的經驗。因此我相信，我們不僅為目前沒有其他選擇的兒童提供一種治療方法，而且還為成年人提供一種安全、耐受性良好且有效的額外潛在治療方法。

Eric, I don't know if you want to provide any more color on what we've been -- the work that your team has been doing in terms of understanding the landscape.

艾瑞克，我不知道您是否想進一步介紹我們一直在做的事情——您的團隊在了解情況方面所做的工作。

Yes. Thanks for the question, Tazeen. I mean our teams have been very active. We've been in pediatric neurology now for over eight years. We understand and know the dynamics in these children's hospitals.

是的。謝謝你的提問，Tazeen。我的意思是我們的團隊一直都非常活躍。我們從事小兒神經病學已有八年多了。我們了解並知道這些兒童醫院的動態。

where the vast majority of patients are either diagnosed or treated. The feedback is obviously a great -- a very high unmet need. The burden of illness, the disability, the comorbidities in children is very, very high. There's no approved therapy.

絕大多數患者都在這裡得到診斷或治療。回饋顯然是一個巨大的未滿足需求。兒童的疾病、殘障和合併症負擔非常非常重。目前尚無核准的療法。

And when physicians, particularly the pediatric neurologists see the profile, they're very convinced, and we believe there will be a rapid uptake. But in addition, a lot of them are treating adults. And as Matt said, we believe that this is going to be a broad use, especially for patients who are naive and not have been on Omav therapy or those who are poorly controlled or dropped out.

當醫生，特別是兒科神經科醫生看到這份資料時，他們非常相信，我們也相信它會迅速普及。但除此之外，他們中的許多人都在治療成年人。正如馬特所說，我們相信這將得到廣泛的應用，特別是對於那些未接受過 Omav 治療的患者或控制不佳或退出治療的患者。

So the opportunity is very large. And the first thing that our healthcare providers see is the efficacy, an efficacy that is at least as good or currently with the current treatment available. But the safety profile is a big winner here because it's very safe and there's very limited or no monitoring involved, particularly for children.

所以機會非常大。我們的醫療保健提供者首先看到的是療效，這種療效至少與目前可用的治療方法一樣好。但其安全性是一大優勢，因為它非常安全，監控非常有限甚至不需要，特別是對於兒童而言。

And they all recognize that there's a very differentiated mechanism of action, something that's unique and different. So they see that value. And what we're doing is obviously working in those centers that we have a ton of experience in over the last eight years or so to put out disease awareness and ensure that we can focus on a lot of the unmet needs and prepare the market for the launch of vatiquinone.

他們都認識到存在一種非常差異化的作用機制，一種獨特且不同的機制。所以他們看到了這個價值。顯然，我們正在這些中心開展工作，我們在過去八年左右的時間裡積累了豐富的經驗，以提高人們對疾病的認識，確保我們能夠專注於許多未滿足的需求，並為推出 vatiquinone 做好市場準備。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

This is Hang Hu for Gena Wang. So I have a question for Translarna. We know that you have agreements with ex-EU countries based on the EU approvals. So in light of the EC withdrawal decision in EU, could you share with us the status and expectation in ex-EU countries and how sustainable the revenue would be?

這是 Hang Hu 為 Gena Wang 所做。所以我有一個問題想問 Translarna。我們知道您與前歐盟國家簽訂了基於歐盟批准的協議。那麼，鑑於歐盟退出歐盟的決定，您能否與我們分享歐盟以外國家的現狀和期望，以及收入的可持續性如何？

Hang, thank you very much for the question. As Eric pointed out, we're even in EU, through the European Commission's directive of the ability to use Articles 117 and Article 5 for individual countries in Europe to continue to make commercial products available. We are still able to generate revenue within Europe. So I just want to emphasize that, as Eric said in his presentation.

Hang，非常感謝您的提問。正如艾瑞克所指出的那樣，我們甚至在歐盟，透過歐盟委員會的指令，歐洲各國都可以使用第 117 條和第 5 條繼續提供商業產品。我們仍然能夠在歐洲創造收入。所以我只想強調這一點，正如 Eric 在演講中所說的那樣。

And then, Eric, do you want to talk about what we're seeing outside Europe, which has been virtually no impact.

然後，艾瑞克，你想談談我們在歐洲以外看到的情況嗎？幾乎沒有任何影響。

Yes. There's been actually no disruption, especially in Latin America. We've already negotiated a contract with Brazil. We've begun shipping product in Brazil. These are group purchase orders that we'll be shipping the natural cadence over the course of the year.

是的。實際上並沒有發生任何中斷，特別是在拉丁美洲。我們已經與巴西談妥了合約。我們已經開始向巴西運送產品。這些是團購訂單，我們將在一年內以自然節奏出貨。

In other smaller Latin American markets as well, we see that the UK license is still in place, and we can continue to work through that. And we've had orders in the Middle East and Northern Africa. So very little disruption outside of Europe. And as Matt said, we are working country by country and to find the right mechanisms for reimbursed Translarna within Europe.

在其他較小的拉丁美洲市場，我們也看到英國許可證仍然有效，我們可以繼續努力。我們已經接到中東和北非的訂單了。因此，歐洲以外地區的干擾很小。正如馬特所說，我們正在逐一開展工作，尋找在歐洲範圍內報銷 Translarna 費用的正確機制。

Yes. Really helpful. And the last one, we also want to go back to Huntington's disease data you reported yesterday. So in 24-month data, you compared the results with the natural history controls, but we noticed that you used the two different references. So in the functional outcome, you compared your data with enroll HD disease registry.

是的。真的很有幫助。最後，我們也想回顧一下您昨天報告的亨廷頓舞蹈症數據。因此，在 24 個月的數據中，您將結果與自然歷史對照進行了比較，但我們注意到您使用了兩個不同的參考。因此，在功能結果中，您將自己的數據與登記的亨丁頓舞蹈症疾病登記處進行了比較。

But for FL, neurofilament light, you compared the data with a Lancet publication. So could you share with us what's the rationale when selecting the natural history controls? And why do you use different reference data sets?

但是對於 FL（神經絲輕鏈），您將數據與《柳葉刀》出版物進行了比較。那麼，您能否與我們分享一下選擇自然史對照的理由呢？為什麼要使用不同的參考資料集？

Yes, let me clarify that. The only comparative analysis performed that we reported yesterday was a comparison of the treated patients for 24 months on functional measures with a large enroll registry, which has over 20,000 entrants and allowed us to get a robust propensity matched comparator population so that we could really understand the benefit we were observing with PTC518 treatment on those different scales.

是的，讓我澄清一下。我們昨天報告的唯一一項比較分析是，對接受治療的患者 24 個月的功能指標與大型登記庫進行了比較，該登記庫有超過 20,000 名參與者，使我們能夠獲得強大的傾向匹配比較人群，以便我們能夠真正了解我們在不同規模上觀察到的 PTC518 治療益處。

We did not perform a comparative analysis of the NFL data. What we did show was that we have the dose-dependent lowering of NFL and made reference to the most recent natural history publication from Parkin and the group in London showing that in Stage 2 patients, there tends to be an increase in NFL of about 12.5% per year.

我們沒有對 NFL 數據進行比較分析。我們確實表明，NFL 具有劑量依賴性降低，並參考了 Parkin 和倫敦研究小組最新的自然史出版物，該出版物表明，在第 2 期患者中，NFL 每年往往增加約 12.5%。

There are registries that have NFL data such as TRACK-HD and others, and we'll go ahead and look at that. But we wanted to just communicate the concept, which has been consistently shown in every study that over the course of time, NFL increases in HD patients, and we wanted to give a reference to the magnitude that's most recently reported for the stage-specific patients. But the only direct match comparison was done for the functional outcomes that generated the comparative values and the p-value showing the evidence of significant effect relative to that matched natural history on the cUHDRS, the TFC as well as the SDMT scales.

有一些註冊中心擁有 NFL 數據，例如 TRACK-HD 等，我們將繼續查看這些數據。但我們只是想傳達這個概念，每項研究都一致表明，隨著時間的推移，亨廷頓氏病患者的 NFL 會增加，我們想為最近報告的特定階段患者的幅度提供一個參考。但僅對功能結果進行了直接匹配比較，產生了比較值和 p 值，證明了相對於 cUHDRS、TFC 以及 SDMT 量表上匹配的自然史存在顯著影響。

Peyton Bohnsack, TD Cowen.

佩頓·博恩薩克 (Peyton Bohnsack)，TD Cowen。

I guess kind of in a more broad sense, can you talk about any impact some of the global macro factors we've been seeing over the past couple of weeks would influence your financial guidance that maybe such as things like tariffs with the manufacturing Executive Order yesterday or Most Favored Nation. And then how that would impact your decision to conduct business development going forward?

我想從更廣泛的意義上講，您能否談談過去幾週我們看到的一些全球宏觀因素會對您的財務指導產生什麼影響，例如昨天製造業行政命令中的關稅或最惠國待遇。那麼這會對您未來開展業務發展的決策產生什麼影響呢？

Thanks for the questions, Peyton. Look, well, none of us have a crystal ball to predict exactly what's going to happen in terms of tariffs, what's going to happen in terms of Most Favored Nation and the discussions so far have been around maybe Medicaid, there's a bill that Holly and others are putting through the clients.

謝謝你的提問，佩頓。你看，好吧，我們誰都沒有水晶球來準確預測關稅方面會發生什麼，最惠國待遇方面會發生什麼，到目前為止的討論可能都圍繞著醫療補助，還有一項法案是霍莉和其他人正在向客戶提出的。

So we don't have a crystal ball, but let's just start with the tariffs. We expect to have minimal impact on our business for a number of reasons, particularly for our US products, the IP is domiciled in the US. So there's no transfer pricing as the product remains US-owned throughout. So any potential tariff would be on cost of goods and would be quite minimal impact to our business.

因此，我們沒有水晶球，但我們先從關稅開始。由於多種原因，我們預計我們的業務將受到最小的影響，特別是對於我們的美國產品，其智慧財產權位於美國。因此不存在轉讓定價，因為該產品始終歸美國所有。因此，任何潛在的關稅都將影響商品成本，對我們的業務的影響微乎其微。

Similarly, on Most Favored Nation, as Eric alluded to, we're very thoughtful about establishing our pricing corridor. That's something we do independent of an MFN situation to ensure that we're getting the maximum value for our products. So again, I think we'd be very well positioned.

同樣，關於最惠國待遇，正如艾瑞克所提到的，我們非常認真地建立我們的定價區間。這是我們獨立於最惠國待遇情況而採取的措施，以確保我們的產品獲得最大價值。所以，我再次認為我們處於非常有利的位置。

And then in terms of other macro things going on, as I mentioned, that the recent changes in CBER, all of our applications are in CDER, all of our pending applications are relying on clinical efficacy from clinical trials, both placebo-controlled as well as in each case, longer-term studies that confirm the benefit we saw in the placebo-controlled study. So I think we're sitting in a position that is not -- would not be affected good or bad by any of the changes going on in CBER.

然後就正在發生的其他宏觀事情而言，正如我所提到的，CBER 最近發生了變化，我們所有的申請都在 CDER，我們所有待決的申請都依賴於臨床試驗的臨床療效，包括安慰劑對照研究以及在每種情況下的長期研究，以證實我們在安慰劑對照研究中看到的益處。所以我認為我們現在的處境不會受到 CBER 發生的任何變化的好壞影響。

And as I mentioned, despite all the changes in FDA, everything remains on schedule for us, and we've observed no impact. So I would say there have been a great deal of macro things, a great deal of anxiety and uncertainties, but we believe we're pretty well insulated from each of them.

正如我所提到的，儘管 FDA 發生了許多變化，但一切仍按計劃進行，我們沒有觀察到任何影響。所以我想說，有很多宏觀因素、很多焦慮和不確定性，但我們相信，我們已經很好地避開了它們。

Maybe if I could just ask a quick follow-up on that on the sepiapterin, has your pricing strategy changed at all due to any macro updates? Or has everything stayed about the same?

也許我可以就 sepiapterin 的問題快速詢問一下，您的定價策略是否由於宏觀更新而發生了變化？還是一切都保持不變？

No, we have no changes in our strategy. Again, our strategy anticipates a lot of these things prior to even the introduction of discussion of legislation or orders or anything like that.

不，我們的戰略沒有改變。再次強調，我們的策略在立法或命令或類似事項開始討論之前就已經預見了很多這樣的事情。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

This is Chris on for Joel. Regarding vatiquinone, just getting maybe a little deeper into the patient breakdown, are you able to provide some general color on the percentage of patients you're anticipating will come from that pediatric 16 and under population versus adults?

這是克里斯代替喬爾。關於 vatiquinone，如果我們稍微深入了解一下患者的細分情況，您能否大致說明一下您預計來自 16 歲及以下兒童患者與來自成年人患者的百分比？

Yes. Thanks for the questions, Chris. I think we've talked about that we -- there's about 6,000 patients in the US with Friedreich's ataxia, and we said about a third of them, we believe would be in that pediatric bucket.

是的。謝謝你的提問，克里斯。我想我們已經討論過了——美國大約有 6,000 名弗里德賴希共濟失調患者，我們認為其中大約三分之一屬於兒科患者。

Joseph Schwartz, Leerink Partners.

Leerink Partners 的 Joseph Schwartz。

This is Jenny on for Joe. The majority of your products and candidates are either approved or at the regulatory approval stage of development with the exception of PTC518. This leaves a bit of a pipeline gap with a little less going on in terms of earlier stage development, at least for what's been publicly disclosed. Is there anything exciting that you're working on internally that you might highlight too?

我是珍妮，為喬轉達。除 PTC518 外，您的大多數產品和候選藥物已獲得批准或處於監管部門批准的開發階段。這就留下了一些通路缺口，早期開發的進展較少，至少就已公開揭露的情況而言。您內部正在進行什麼令人興奮的工作，可以強調一下嗎？

Additionally, this market environment could be advantageous for companies like you guys who have cash on hand that could be deployed for BD. Are there any opportunities that you're actively pursuing or general areas you might be interested in?

此外，這種市場環境對於像你們這樣手頭上有現金可以用於 BD 的公司來說可能是有利的。您是否正在積極尋求機會或對某些領域感興趣？

Thanks for the question, Jenny. So the answer to both is yes. We do have pipeline programs that we've been working on. We disclosed some of them at the JPMorgan discussion. And we've put a lot of effort just as we focused a lot of our development and commercial efforts, we've also done a lot of work to focus our earlier programs to ensure that we're leveraging our unique scientific platforms, including splicing and our ferroptosis inflammation platform.

謝謝你的提問，珍妮。所以這兩個問題的答案都是肯定的。我們確實有一些正在努力的管道計劃。我們在摩根大通的討論中披露了其中一些內容。我們付出了很多努力，就像我們集中大量開發和商業努力一樣，我們也做了很多工作來集中我們早期的項目，以確保我們能夠利用我們獨特的科學平台，包括剪接和我們的鐵死亡發炎平台。

I think the experience of PTC518 following on the heels of Evrysdi is really a testament to our unique ability to get small molecule splicing therapies into the clinic, into patients and moving forward through development and being able to show that we can favorably affect splicing and do so safely. So we have a number of splicing programs that we're working on that are at various stages of preclinical development that we look forward to moving into the clinic very soon, and we'll be detailing them soon.

我認為 PTC518 緊隨 Evrysdi 之後的經驗確實證明了我們獨特的能力，即將小分子剪接療法帶入臨床，帶入患者體內，並通過開發不斷推進，並能夠證明我們可以對剪接產生有利影響，並且安全地做到這一點。因此，我們正在研究多個處於臨床前開發不同階段的剪接程序，我們期待很快進入臨床階段，我們很快就會詳細介紹它們。

We shared it at the JPMorgan conference that we have a program with a DHODH inhibitor that we expect to be Phase 2 ready by the end of the year that we're looking at for a number of different neuroinflammatory indications given the importance of DHODH to immuno-inflammatory response. And we also have -- we shared an NLRP3 inhibitor program that's peripherally based that we're looking at for a number of potential indications where the NLRP3 inflammasome has been intimately linked to disease pathology. But more to come on all of that.

我們在摩根大通會議上分享了我們有一個 DHODH 抑制劑項目，預計該項目將在年底前進入第二階段，鑑於 DHODH 對免疫發炎反應的重要性，我們正在研究多種不同的神經發炎適應症。我們也分享了一個基於週邊的 NLRP3 抑制劑項目，我們正在研究 NLRP3 發炎小體與疾病病理密切相關的多種潛在適應症。但關於這一切，還有更多內容。

In addition, we are looking, as Pierre said, in business development opportunities and things that we think that can complement our existing R&D portfolio. And as you know, business development is not -- is sort of a long-term proposition. So we've been working on it for a while.

此外，正如皮埃爾所說，我們正在尋找業務發展機會以及我們認為可以補充我們現有研發組合的事物。如您所知，業務發展並不是一項長期任務。因此我們已經為此努力了一段時間。

We have a number of different potential things that we're looking at that some are earlier stage, some are even commercial stage, some are geographic licenses, all different opportunities that we continue to look at. And as we understand better our commercial portfolio later this year, pending the regulatory decisions for Translarna, for vatiquinone in the US, that will also help direct where we might move.

我們正在研究許多不同的潛在事物，有些處於早期階段，有些甚至處於商業階段，有些是地理許可，我們正在繼續研究所有不同的機會。隨著我們在今年稍後對我們的商業組合有更好的了解，等待美國對 Translarna 和 vatiquinone 的監管決定，這也將有助於指導我們可能採取的行動。

But the key part is we're looking at a number of different opportunities. And as we always have, we'll continue to be very strategic in how we think about utilizing business development to supplement the R&D and/or commercial portfolios.

但關鍵是我們正在尋找許多不同的機會。像往常一樣，我們將繼續非常有策略地思考如何利用業務發展來補充研發和/或商業組合。

Paul Choi, GS.

Paul Choi，GS。

This is Daniel on for Paul. Thank you for clarifying that you're mainly working with CDER, but we still have a question regarding vatiquinone. Could you share any color or feedback from the agency regarding the utilization for natural history for the approval, especially the long-term open-label part for MOVE-FA?

這是丹尼爾代替保羅。感謝您澄清您主要與 CDER 合作，但我們對 vatiquinone 仍有疑問。您能否分享該機構關於批准自然歷史應用的任何細節或回饋，特別是 MOVE-FA 的長期開放標籤部分？

Thanks for the question, Daniel. So as we've talked about, the comparison of our long-term data following MOVE-FA with the robust FA-COMS or FACOMS natural history database is an important part of our confirmatory evidence. We, in fact, provided a comparison with the MOVE-FA data -- long-term data to the FACOMS database where we were able to show a 50% slowing in disease progression over three years.

謝謝你的提問，丹尼爾。正如我們所討論的，將 MOVE-FA 之後的長期數據與強大的 FA-COMS 或 FACOMS 自然史資料庫進行比較是我們確認證據的重要組成部分。事實上，我們將 MOVE-FA 數據（長期數據）與 FACOMS 資料庫進行了比較，結果顯示三年內病情進展減緩了 50%。

And then we did a similar comparative analysis from the long-term study of a previously conducted placebo-controlled study in adults, both ambulatory and non-ambulatory, where again, we've demonstrated a significant multipoint slowing in disease progression in that case, over 24 months.

然後，我們對先前針對可行走和不可行走的成年人進行的安慰劑對照研究的長期研究進行了類似的比較分析，結果再次證明，在 24 個月內，病情進展在多個點上顯著減緩。

I'll point out that the FACOMS registry is probably one of the most robust rare disease registries. This has been established by FARA, and they've done an incredible job of ensuring a reliable network of centers that contribute high-quality data to this registry with frequent assessments that allow for a granular comparison with data that we would collect in a clinical study.

我要指出的是，FACOMS 註冊中心可能是最強大的罕見疾病註冊中心之一。這是由 FARA 建立的，他們做了出色的工作，確保了可靠的中心網絡為該註冊中心提供高品質的數據，並透過頻繁的評估進行與我們在臨床研究中收集的數據進行細緻的比較。

The FDA, of course, is familiar with the FACOMS registry because that was used as the confirmatory evidence in the SKYCLARYS authorization back in 2023. So it's something they know well and it's something that I think many have called out the FACOMS registry as the type of natural history database that can support regulatory decision-making. So we're happy to -- we're grateful to the FARA and the FA community and the patients who have contributed their data to that registry because it really allows us to inform a really important data point, which is the long-term benefit we see with vatiquinone in both children and adults with Friedreich's ataxia.

當然，FDA 熟悉 FACOMS 註冊，因為早在 2023 年，它就被用作 SKYCLARYS 授權的確認證據。所以這是他們很了解的事情，我認為很多人都將 FACOMS 註冊表稱為可以支援監管決策的自然歷史資料庫類型。因此，我們很高興——我們感謝 FARA 和 FA 社區以及向該註冊中心貢獻數據的患者，因為它確實使我們能夠告知一個非常重要的數據點，即我們看到的 vatiquinone 對患有弗里德賴希共濟失調的兒童和成人的長期益處。

This concludes the question-and-answer session. I would now like to turn it back to Dr. Matthew Klein for closing remarks.

問答環節到此結束。現在我想請馬修·克萊恩博士作最後發言。

Thank you all again for joining the call today. We're very excited about our excellent progress we made in the first quarter and look forward to continued successes in 2025 and beyond. Thank you again.

再次感謝大家今天參加電話會議。我們對第一季的出色進展感到非常興奮，並期待在 2025 年及以後繼續取得成功。再次感謝您。

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

感謝大家參加今天的會議。該計劃確實就此結束。您現在可以斷開連線。