PTC Therapeutics Inc (PTCT) 2025 Q2 法說會逐字稿

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

女士們、先生們，感謝你們的支持。歡迎參加 PTC Therapeutics 2025 年第二季財報電話會議。（操作員指示）今天的通話正在錄音。

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

現在我想將電話轉給投資者關係主管 Ellen Cavaleri。請繼續。

Good afternoon, and thank you for joining us to discuss PTC Therapeutics' second-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 年第二季的公司更新與財務表現。今天與我一同出席的還有我們的執行長 Matthew Klein 博士、商務長 Eric Pauwels 和財務長 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。請在電話會議上同時查看我們投資者關係網站上發布的幻燈片，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適用的結果

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. I'm pleased to share results from another strong quarter, highlighted by the first approvals for Sephience for the treatment of children and adults with PKU. We expect Sephience to be the foundational product for PTC's sustainable growth and path to profitability.

感謝大家今天的參與。我很高興與大家分享另一個強勁季度的業績，其中最突出的是 Sephience 首次獲得批准用於治療患有 PKU 的兒童和成人。我們預計 Sephience 將成為 PTC 永續成長和獲利之路的基礎產品。

In the second quarter, we again had solid revenue performance with total revenue of $179 million, with continued contributions from our DMD franchise, including in Europe. Following the nonrenewal of the Translarna conditional marketing authorization, we have reached agreements with about half of European countries based on the unprecedented use of Article 117 to provide paid Translarna product.

在第二季度，我們的營收表現再次穩健，總收入達到 1.79 億美元，這得益於我們包括歐洲在內的 DMD 特許經營權的持續貢獻。在Translarna有條件上市許可不再續期後，我們根據史無前例的第117條規定，與大約一半的歐洲國家達成協議，提供付費的Translarna產品。

For the remainder of 2025, we expect to be able to maintain approximately 25% of European revenue from prior to authorization nonrenewal. The highlight of the quarter was the EU approval of Sephience in late June with a broad label inclusive of all disease subtypes and age groups. And last week, we announced FDA approval of Sephience with similar broad labeling for patients aged one month and above.

對於 2025 年剩餘時間，我們預計能夠維持授權未續約之前約 25% 的歐洲收入。本季的亮點是歐盟於 6 月底批准了 Sephience，其廣泛的適應症涵蓋所有疾病亞型和年齡層。上週，我們宣布 FDA 批准 Sephience，其類似廣泛標籤適用於一個月及以上的患者。

Based on the strong Sephience data package and the significant unmet need for PKU patients, Sephience is positioned to become the new standard of care for children and adults living with PKU. As we have discussed, we believe the Sephience revenue opportunity in the US exceeds $1 billion, and our global customer-facing teams are excited to bring this therapy to all those that could benefit.

基於強大的 Sephience 資料包和 PKU 患者的巨大未滿足需求，Sephience 有望成為 PKU 兒童和成人護理的新標準。正如我們所討論的，我們相信 Sephience 在美國的營收機會超過 10 億美元，我們面向全球客戶的團隊很高興將這種療法帶給所有可能受益的人。

We initiated the European launch in Germany in mid-July and are leveraging early access mechanisms in other European countries while formal pricing and reimbursement discussions proceed. In the US, we plan to ship the first commercial drug to patients within the next two weeks and look forward to a robust early launch. Eric will provide further details on the Sephience launches shortly.

我們於 7 月中旬在德國啟動了歐洲市場的發布，並在進行正式的定價和報銷討論的同時，利用其他歐洲國家的早期訪問機制。在美國，我們計劃在未來兩週內將首批商業藥物運送給患者，並期待早日強勁上市。Eric 很快就會提供有關 Sephience 發布的更多詳細資訊。

Given the potential significant revenue opportunity for Sephience, PTC has reached an agreement to purchase the annual global net sales payment obligation of 8% to 12% that was part of the acquisition of Censa Pharmaceuticals in 2020.

鑑於 Sephience 潛在的龐大收入機會，PTC 已達成協議，購買 2020 年收購 Censa Pharmaceuticals 時承擔的 8% 至 12% 的年度全球淨銷售額支付義務。

PTC will pay the participating Censa rights holders approximately $225 million upfront and additional future sales milestones for approximately 90% of our net sales payment obligation. We view this transaction as a constructive use of our cash reserves given the expected value creation based on the transaction terms.

PTC 將向參與的 Censa 權利持有者支付約 2.25 億美元的預付款以及約占我們淨銷售額支付義務 90% 的未來額外銷售里程碑款項。鑑於交易條款所預期的價值創造，我們認為這筆交易是對我們現金儲備的建設性利用。

Now with the FDA approval of Sephience, we have two NDAs that remain under FDA review for vatiquinone and Translarna. For the vatiquinone NDA for Friedreich's ataxia, a late cycle meeting was held in July. At that meeting, FDA shared that the application is still under active review and confirmed they do not plan to hold an advisory committee meeting.

現在，隨著 FDA 對 Sephience 的批准，我們還有兩項 NDA 仍在等待 FDA 審查，分別是 vatiquinone 和 Translarna。對於弗里德賴希共濟失調症的 vatiquinone NDA，7 月舉行了一次後期週期會議。在該會議上，FDA 表示該申請仍在積極審查中，並確認他們不打算召開諮詢委員會會議。

Turning to the PTC518 or votoplam Huntington's disease program. Following the positive Phase 2 PIVOT-HD study results, we continue to collaborate with Novartis on next steps for votoplam and aim to meet with FDA in the fourth quarter to discuss the Phase 3 trial study design and potential accelerated approval pathway.

轉向 PTC518 或 votoplam 亨廷頓氏症計劃。在第 2 階段 PIVOT-HD 研究取得積極成果之後，我們將繼續與諾華合作，共同研究 votoplam 的下一步進展，併計劃在第四季度與 FDA 會面，討論第 3 階段試驗研究設計和潛在的加速審批途徑。

Finally, we remain in a very strong financial position, closing the quarter with approximately $1.99 billion in cash, allowing us to fully support all planned commercial and R&D initiatives, engage in strategic business development activities and achieve cash flow breakeven without the need for additional capital.

最後，我們的財務狀況仍然非常強勁，本季末現金約為 19.9 億美元，這使我們能夠全力支持所有計劃中的商業和研發計劃，參與戰略業務發展活動，並在無需額外資本的情況下實現現金流收支平衡。

I will now turn the call over to Eric to discuss our commercial performance and our Sephience global launch. Eric?

現在我將把電話轉給 Eric，討論我們的商業表現和 Sephience 的全球發布。艾瑞克？

Thanks, Matt. Our global customer-facing teams performed well again this quarter, achieving $118 million in second quarter revenue from our marketed products, and we are excited to have initiated the global launch of Sephience following approvals in both Europe and the US We will review details of our Sephience launch efforts shortly.

謝謝，馬特。我們的全球客戶團隊本季再次表現出色，第二季我們行銷的產品收入達到 1.18 億美元，我們很高興在歐洲和美國獲得批准後啟動 Sephience 的全球上市，我們將很快審查 Sephience 上市工作的細節。

We generated $96 million revenue in the second quarter from our global DMD franchise. As Matt mentioned, despite the nonrenewal of the EU conditional license, we have continued supplying paid Translarna to several European countries, leveraging mechanisms specific to each country in accordance with Article 117.

我們第二季從全球 DMD 特許經營中獲得了 9,600 萬美元的收入。正如馬特所提到的，儘管歐盟有條件許可證沒有續簽，但我們仍繼續向幾個歐洲國家提供付費的 Translarna，並根據第 117 條利用每個國家特有的機制。

Outside of Europe, we continue to generate Translarna revenue, including in Latin America, the Commonwealth of Independent States, the Middle East and North Africa. Our experienced US neurology team is ready to bring Translarna to nonsense mutation DMD patients following potential FDA approval. Now turning to Emflaza. As expected, with additional generic entrants, we have seen continued market erosion.

在歐洲以外，我們繼續為 Translarna 創造收入，包括拉丁美洲、獨立國家聯合體、中東和北非。在獲得 FDA 批准後，我們經驗豐富的美國神經病學團隊已準備好將 Translarna 帶給無義突變 DMD 患者。現在轉向 Emflaza。正如預期的那樣，隨著更多仿製藥企業的進入，我們看到市場持續受到侵蝕。

However, we continue to see meaningful revenue and our PTC Cares team has done an outstanding job ensuring new patient starts and maintaining high levels of brand loyalty for Emflaza with the DMD community. Shifting to Tegsedi and Waylivra in Latin America. We continue to identify and treat new patients in the region and have received group purchase orders in Brazil.

然而，我們繼續看到可觀的收入，我們的 PTC Cares 團隊在確保新患者開始治療和維持 DMD 社群對 Emflaza 的高品牌忠誠度方面做得非常出色。轉向拉丁美洲的 Tegsedi 和 Waylivra。我們繼續在該地區發現和治療新患者，並已收到巴西的團購訂單。

For Upstaza and KEBILIDI, we are pleased that new AADC patients have been treated across multiple regions and our commercial efforts remain focused on where patients are identified, including those countries with AADC deficiency founder effects. We expect a steady cadence of AADC patients to be treated in the US, Europe, Asia Pacific and Latin America throughout 2025.

對於 Upstaza 和 KEBILIDI，我們很高興看到新的 AADC 患者已在多個地區得到治療，我們的商業努力仍然集中在確定患者的地方，包括那些存在 AADC 缺乏症創始效應的國家。我們預計，2025 年全年美國、歐洲、亞太地區和拉丁美洲將有穩定數量的 AADC 患者接受治療。

Turning now to Sephience for PKU. Our world-class commercial team is in place to successfully launch Sephience following the US and European approvals. We are well positioned to leverage our core launch capabilities in rare disease with more than a decade of commercial experience to drive early and rapid Sephience adoption. We initiated the first launch in Germany in mid-July and engaged key PKU centers in the country.

現在轉向 PKU 的 Sephience。我們擁有世界一流的商業團隊，致力於在獲得美國和歐洲批准後成功推出 Sephience。我們完全有能力利用我們在罕見疾病領域的核心發布能力以及十多年的商業經驗來推動 Sephience 的早期和快速採用。我們於 7 月中旬在德國啟動了首次發布活動，並與該國主要的北大中心進行了合作。

We are very pleased with the initial feedback from health care providers and the first patients have already received commercial therapy. Our teams in Europe have identified other key markets where paid early access programs are available for Sephience, and we'll leverage them as soon as possible.

我們對醫療保健提供者的初步回饋感到非常滿意，第一批患者已經接受了商業治療。我們在歐洲的團隊已經確定了其他可以為 Sephience 提供付費搶先體驗計畫的關鍵市場，我們將盡快利用這些市場。

We are thrilled with the recent FDA approval of Sephience, which we believe is well positioned to redefine the standard of care for PKU. In the US, our dedicated team is already calling on health care providers in 104 PKU centers of excellence who account for more than 80% of PKU claims and treat the highest concentration of US patients, including those diagnosed at birth, children, adolescents and adults.

我們對 FDA 最近批准 Sephience 感到非常興奮，我們相信它有能力重新定義 PKU 的治療標準。在美國，我們的專業團隊已聯繫了 104 個 PKU 卓越中心的醫療保健提供者，這些中心處理了超過 80% 的 PKU 索賠，並且治療了美國最多的患者，包括出生時確診的患者、兒童、青少年和成人。

The clinical data support the ability of Sephience to address the full spectrum of the approximately 17,000 patients in the US. In terms of sequencing, our initial focus is on the patients who recently failed or are not well controlled on existing therapies, and those who could be switched from existing oral therapies who are seeking greater Phe reduction.

臨床數據證明 Sephience 能夠全面治療美國約 17,000 名患者。在排序方面，我們最初的重點是那些近期療法失敗或控制不佳的患者，以及那些可以從現有口服療法轉換並尋求更大程度降低 Phe 的患者。

We will then progress to treatment-naive patients who could benefit from a new effective treatment. Our payer meetings continue to be productive following presentations of the clinical data and the value proposition of Sephience from our market access and medical affairs teams. We have actively engaged with key commercial, Medicaid and Medicare payers covering over 220 million lives and have received positive feedback on access and coverage of Sephience with minimal restrictions.

然後，我們將針對那些從未接受過治療但可以從新的有效治療中受益的患者。在我們的市場准入和醫療事務團隊介紹了 Sephience 的臨床數據和價值主張之後，我們的付款人會議繼續富有成效。我們積極與主要的商業、醫療補助和醫療保險支付機構合作，覆蓋超過 2.2 億人的生活，並收到了關於以最少的限制訪問和覆蓋 Sephience 的積極反饋。

We are equally excited about the anticipated regulatory approvals of Sephience in Japan and Brazil before the end of the year, building on the launch momentum that has already begun in the US and Europe. Initial feedback from health care providers worldwide is highly positive, and we look forward to continuing to provide updates on the Sephience global trajectory in the next several quarters.

我們同樣對 Sephience 預計今年年底前在日本和巴西獲得監管部門的批准感到興奮，這將鞏固 Sephience 在美國和歐洲已經開始的上市勢頭。來自全球醫療保健提供者的初步回饋非常積極，我們期待在接下來的幾個季度繼續提供有關 Sephience 全球發展軌蹟的最新資訊。

In addition to our team's focus on the Sephience launch, we have also been preparing for the potential launch of vatiquinone in the US. Our experienced teams in neurology are ready to launch the product and address the significant unmet need for both children under 16 who currently have no approved therapy, as well as adults with FA who may benefit from a well-tolerated and effective therapy.

除了我們的團隊專注於 Sephience 的發布之外，我們還一直在為在美國可能推出的 vatiquinone 做準備。我們經驗豐富的神經病學團隊已準備好推出該產品，並滿足目前尚未獲得批准的療法的 16 歲以下兒童以及可能受益於耐受性良好且有效的療法的 FA 成人的重大未滿足需求。

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？

Thanks, Eric. I will begin by reiterating our excitement for the approval of Sephience, a pivotal milestone both for patients and for PTC. As we discussed, Sephience has the potential to become the standard of care for PKU and will serve as the cornerstone product driving our path to profitability.

謝謝，埃里克。首先，我要重申我們對 Sephience 核准的興奮之情，這對患者和 PTC 來說都是一個關鍵的里程碑。正如我們所討論的，Sephience 有可能成為 PKU 的治療標準，並將成為推動我們獲利的基石產品。

Today, we announced the purchase of Sephience' annual global net sales payment obligation owed to Censa. This strategic transaction is accretive based on the terms we negotiated and underscores our confidence in the market opportunity.

今天，我們宣布購買 Sephience 欠 Censa 的年度全球淨銷售付款義務。這項策略交易根據我們協商的條款具有增值性，並強調了我們對市場機會的信心。

I'll now share the financial highlights of our second quarter of 2025. Beginning with top line results. Total product, collaboration and royalty revenue for the second quarter was $179 million, including DMD franchise revenue of $96 million. Starting with the DMD franchise. Translarna net product revenue in the quarter was $59 million and Emflaza net product revenue was $36 million.

現在我將分享我們 2025 年第二季的財務亮點。從頂線結果開始。第二季的產品、合作和特許權使用費總收入為 1.79 億美元，其中包括 9,600 萬美元的 DMD 特許經營收入。從 DMD 特許經營開始。Translarna 本季淨產品收入為 5,900 萬美元，Emflaza 淨產品收入為 3,600 萬美元。

For Evrysdi, Roche achieved second quarter global revenue of approximately USD 559 million, resulting in royalty revenue of $58 million for PTC.

就 Evrysdi 而言，羅氏第二季全球營收約為 5.59 億美元，為 PTC 帶來 5,800 萬美元的專利費收入。

For the second quarter of 2025, non-GAAP R&D expense was $104 million, excluding $9 million in noncash stock-based compensation expense compared to $123 million for the second quarter of 2024, excluding $9 million in noncash stock-based compensation expense.

2025 年第二季度，非 GAAP 研發費用為 1.04 億美元，不包括 900 萬美元的非現金股票薪酬費用，而 2024 年第二季為 1.23 億美元，不包括 900 萬美元的非現金股票薪酬費用。

Non-GAAP SG&A expense was $76 million for the second quarter of 2025, excluding $10 million in noncash stock-based compensation expense compared to $60 million for the second quarter of 2024, excluding $10 million in noncash stock-based compensation expense.

2025 年第二季的非 GAAP 銷售、一般及行政費用為 7,600 萬美元，不包括 1,000 萬美元的非現金股票薪酬費用，而 2024 年第二季的非 GAAP 銷售、一般及行政費用為 6,000 萬美元，不包括 1,000 萬美元的非現金股票費用。

Cash, cash equivalents and marketable securities totaled $1,989 million as of June 30, 2025, compared to $1,140 million as of December 31, 2024. Our strong financial position provides us with the necessary resources to seamlessly execute on our strategy, successfully launch all our new commercial products globally, achieve all our anticipated milestones, as well as advance our novel R&D efforts and accelerate our trajectory towards cash flow breakeven and profitability.

截至 2025 年 6 月 30 日，現金、現金等價物及有價證券總額為 19.89 億美元，而截至 2024 年 12 月 31 日為 11.4 億美元。我們強大的財務狀況為我們提供了必要的資源，以無縫執行我們的策略，在全球範圍內成功推出我們所有的新商業產品，實現我們所有預期的里程碑，以及推進我們的新穎的研發工作並加速我們實現現金流收支平衡和盈利的軌跡。

Furthermore, this strong foundation provides us with the ability to explore business development opportunities to enhance our commercial portfolio and pipeline for long-term growth. I will now turn the call over to the operator for Q&A. Operator?

此外，這堅實的基礎使我們能夠探索業務發展機會，以增強我們的商業組合和管道，以實現長期成長。我現在將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. I have two. The first is just on Huntington's. What is going to be on your wish list related to the trial design you and your partners' talk with the FDA? And will you have any additional data to share with them at that time?

恭喜本季取得優異成績。我有兩個。第一個是關於亨廷頓的。您和您的合作夥伴與 FDA 討論的試驗設計方面您的願望清單上有哪些內容？到時候您還有什麼其他數據可以跟他們分享嗎？

And then for Translarna in Europe, under this Article 117, which I'm less familiar with, do you have to renew this every year? Should we be expecting this 25% revenues on a go-forward basis?

那麼對於歐洲的 Translarna 來說，根據我不太熟悉的第 117 條，是否必須每年更新？我們是否應該預期未來會有這 25% 的收入？

Thank you very much for the questions, Kristen. On the first question, so look, I think this is exactly as we said we hope to be doing with our partner, Novartis, which is once we completed the readout of PIVOT-HD, engage with the FDA to discuss two things: one, the design of the efficacy trial based on some of the key learnings that we talked about from PIVOT-HD, as well as discuss pathways to accelerated approval, whether that's on the existing data we've shared thus far with PIVOT-HD or the additional data that we could continue to collect as the open-label extension is ongoing.

非常感謝你的提問，克里斯汀。關於第一個問題，所以看，我認為這正如我們所說的，我們希望與我們的合作夥伴諾華公司一起做的那樣，一旦我們完成 PIVOT-HD 的讀數，就與 FDA 討論兩件事：第一，基於我們從 PIVOT-HD 中談到的一些關鍵經驗來設計療效試驗，並討論加速批准的途徑，無論是基於我們迄今為止與 PIV-HD 的額外標籤

As we talked about, we would fully expect the efficacy trial to be a large trial as has been done previously with Huntington's disease. And as you know, there's a fairly finite universe of endpoints and certain factors that could go into discussion. So I would say our wish list is to come away with alignment for what the key elements of that efficacy trial will be.

正如我們所說的，我們完全希望療效試驗能成為一項大規模試驗，就像之前對亨廷頓舞蹈症所做的那樣。如您所知，可供討論的端點和某些因素的數量是相當有限的。所以我想說，我們的願望是就療效試驗的關鍵要素達成一致。

And obviously, we have confidence that, that should happen as well as clarity on the data that we'll need, whether it's the data we have at hand now, showing long-term cUHDRS changes NfL, some of the other biomarker changes to support accelerated approval or whether there are going to be additional data that we could use once we get further into the open-label extension.

顯然，我們有信心，這應該會發生，而且我們所需的數據也很清楚，無論是我們現在掌握的數據，顯示長期 cUHDRS 變化 NfL，一些其他生物標誌物變化以支持加速批准，還是一旦我們進一步進入開放標籤擴展，我們就可以獲得更多數據。

On your second question, I would -- ARC-117 is something that was referenced in the European Commission's adoption of the CHMP opinion. And actually, there's 2 articles. There's Article 117 and Article 5, which together -- which referenced specific things in the European Commission doctrines. And what they allowed together is individual countries to allow Translarna to still be commercially available despite the fact that the license has not been renewed.

關於您的第二個問題，我想說—ARC-117 是歐盟委員會在採納 CHMP 意見時提到的內容。實際上，有兩篇文章。第 117 條和第 5 條共同引用了歐盟委員會原則中的具體內容。他們共同允許的是，儘管許可證尚未續期，但各國仍允許 Translarna 進行商業銷售。

So it's basically an umbrella or a directive that each individual country can elect to leverage or not based on individual country-by-country mechanisms that they have. And as we said, we've seen about half the countries look -- leverage that availability.

因此，它基本上是一個保護傘或指令，每個國家都可以根據其國家現有的機制選擇是否要利用它。正如我們所說，我們已經看到大約一半的國家正在利用這種可用性。

And that's, again, based on a lot of the feedback we've gotten from patients and physicians who have clearly communicated the benefits they've observed with Translarna as well as the lack of alternative therapies. And so, in countries where possible, we've been able to provide paid drug. Other countries have elected not to do it.

再一次，這是基於我們從患者和醫生那裡得到的大量回饋，他們清楚地傳達了他們觀察到的 Translarna 的好處以及缺乏替代療法的缺點。因此，在可能的國家，我們能夠提供付費藥物。其他國家選擇不這樣做。

And so we're about half now. We've said that we expect to be able to maintain about 25% revenue through the rest of 2025. And I think it's going to -- we're going to see how different countries, different contracts and things play out over time. 117 doesn't need to be renewed. It will be at the discretion of individual countries about renewing and in some countries, for example, Italy has publicized they're allowing for 6 months and then it will be revisited.

現在我們已經完成了大約一半。我們曾表示，預計在 2025 年剩餘時間內能夠維持約 25% 的收入。我認為我們會——我們會看到不同的國家、不同的合約和事情隨著時間的推移如何發展。 117 不需要續簽。是否續約將由各國自行決定，例如，義大利等一些國家已宣布允許續簽 6 個月，之後將重新考慮。

Other countries have not given a time line. So it's going to be very variable, which is why we've said we expect the 25% for the remainder of the year. But look, this is all an incredible upside given the context of the situation when you consider that the license wasn't renewed. And again, this is really based on a lot of the feedback from the patients and the physicians about the clear perceived benefits of Translarna. And we're, one, happy to be able to still harvest revenue from Europe, but two, really happy to be able to still provide this therapy to patients who really need it.

其他國家尚未給出時間表。所以它會非常多變，這就是為什麼我們說我們預計今年剩餘時間的成長率將達到 25%。但是，當你考慮到許可證沒有續期時，考慮到當時的情況，這一切都是一個令人難以置信的好處。再次強調，這實際上是基於大量患者和醫生對 Translarna 明顯益處的回饋。而且，首先，我們很高興能夠仍然從歐洲獲得收入，其次，我們真的很高興能夠仍然為真正需要的患者提供這種療法。

Tazeen Ahmad, Bank of America Securities.

Tazeen Ahmad，美國銀行證券。

For Sephience, Matt, can you give us clarity on the metrics that we should expect to see in the early innings of the launch, presumably on the 3Q call? And then can you clarify if you've already started receiving scripts? And if so, do you have any kind of sense on what types of patients are receiving scripts first?

對於 Sephience，Matt，您能否向我們明確一下在發布初期（大概是在第三季度電話會議上）我們應該看到的指標？然後能否澄清一下是否已經開始接收腳本了？如果是這樣，您是否知道哪些類型的患者會先收到處方？

Thank you for the question, Tazeen. I think it's early days, as you say, and I think we're happy with how things have gone, and in particular, what we've seen in the public, a lot of social media and a lot of patients talking about how happy they are. This is data that they wish for and hoped for.

謝謝你的提問，Tazeen。正如您所說，我認為現在還處於早期階段，我們對事情的進展感到滿意，特別是我們在公眾、社交媒體和許多患者身上看到的，他們都在談論他們有多高興。這是他們希望得到和期待的數據。

And just a lot of positive feedback, which, one, is incredibly gratifying and two, is really consistent with our understanding of the significant unmet need that Sephience can fill. Eric, do you want to go into a little more detail on Tazeen 's two questions on the early -- on the metrics we plan to share in early dynamics?

而且有很多正面的回饋，首先，這令人難以置信地欣慰，其次，這與我們對 Sephience 可以滿足的重大未滿足需求的理解一致。艾瑞克，你想更詳細地談談 Tazeen 關於我們計劃在早期動態中分享的指標的兩個問題嗎？

Yes. Thanks for the question, Tazeen. I mean, as we said earlier, the metrics we're going to continually provide on a quarterly basis will be prescriptions, patient start forms, the number of commercial patients that are currently available on treatment. We'll also provide information regarding health care provider, as well as payer sort of prescribing dynamics and coverage dynamics. We'll also provide you some color on the rollout and the international flavor of Sephience, where we -- which countries we will actually be bringing on board.

是的。謝謝你的提問，Tazeen。我的意思是，正如我們之前所說，我們將按季度持續提供的指標是處方、患者開始表格以及目前可接受治療的商業患者數量。我們還將提供有關醫療保健提供者以及付款人的處方動態和覆蓋動態的資訊。我們還將向您介紹 Sephience 的推出和國際特色，包括我們將在哪些國家推出該產品。

So there's a number of key metrics here. But more importantly, I think you're going to see this as -- it's still early days, but you're going to see the metrics really centered around the number of prescriptions and the number of health care providers who have prescribed.

這裡有許多關鍵指標。但更重要的是，我認為你會看到這一點——現在還為時過早，但你會看到指標真正集中在處方數量和開處方的醫療保健提供者數量上。

On the scripts received so far, if any?

關於目前收到的腳本（如果有）？

Yes. And just to provide you some -- we're thrilled that we've already gotten prescriptions in the US We have patient start forms that came in on the very first day. And we -- the feedback from health care providers has been excellent so far. As I mentioned, we also have our first patients on commercial therapy in Europe already.

是的。只向您提供一些資訊 - 我們很高興我們已經在美國獲得了處方，我們在第一天就收到了患者的開始表格。到目前為止，我們收到的醫療保健提供者的回饋非常好。正如我所提到的，我們在歐洲已經迎來了第一批接受商業治療的患者。

The feedback from physicians has been very positive. Our teams have been promoting the benefits of Sephience immediately. The characteristics that we've seen, and again, it's very early days, it kind of matches up very closely to what we've seen. Physicians are looking to bring in patients who are poorly controlled or have failed. Many of them have interest in switching patients to get better feed control, and we've also seen prescriptions for naive patients.

醫生們的回饋非常正面。我們的團隊一直在推廣 Sephience 的優勢。我們所看到的特徵，而且，現在還處於早期階段，它與我們所看到的非常接近。醫生們正在尋求接收那些治療控制不佳或失敗的患者。他們中的許多人都對更換病人以獲得更好的進食控制感興趣，我們也看到了針對初治患者的處方。

Brian Cheng, JPMorgan.

摩根大通的 Brian Cheng。

Two from us. It's probably still in the early days to understand how contracting and the eventual net pricing for Sephience is. But I know that you already have been in touch with a sizable portion of commercial payers out there. So just curious if you had some feedback that can help us to think through the level of contracting. And then I have a quick follow-up.

我們有兩個。現在可能還處於早期階段，無法了解 Sephience 的承包情況和最終淨定價如何。但我知道您已經與相當一部分商業付款人取得了聯繫。所以我很好奇您是否有一些回饋可以幫助我們思考合約的水平。然後我有一個快速的跟進。

Yes. Thanks, Brian, for the question. We've been having really good meetings with payers so far. As I mentioned, it's been really dozens of payers and quite a good mix between both commercial, Medicaid and Medicare. We continue to have these meetings now post launch.

是的。謝謝 Brian 提出的問題。到目前為止，我們與付款人的會面一直非常順利。正如我所提到的，實際上有幾十個付款人，並且商業、醫療補助和醫療保險之間有相當好的組合。發布後我們也會繼續舉行這些會議。

And I think really more than anything else, it's going as well as what we expected. We see right now that the clinical profile of Sephience is being very well received. Payers already see that it's highly differentiated, and there's a high willingness to cover the product. Importantly, very minimal restrictions, prior authorizations to the label and only a few have said that we would implement step edits. So overall, minimal restrictions.

我認為最重要的是，一切進展順利，正如我們所預期的。我們現在看到，Sephience 的臨床特徵受到了廣泛好評。付款人已經看到它的高度差異化，並且有很高的意願來支付該產品。重要的是，限制非常少，事先授權給標籤，只有少數人表示我們會實施逐步編輯。總體而言，限制很少。

Regarding your question around contracting, we haven't gotten -- it's still early days. We haven't gotten into that at this point in time. We don't necessarily see the need at this point in time either to contract with payers. And as I said, we will be providing metrics around gross to net further down the line as we get the payer mix, which we anticipate at this point in time to be 65% commercial and approximately 35% to be Medicaid or Medicare. So at this point in time, it's a bit early.

關於您提出的有關簽約的問題，我們還沒有得到答案——現在還為時過早。目前我們還沒有討論這個問題。我們目前也未必認為有必要與付款人簽訂合約。正如我所說的，隨著我們獲得付款人組合，我們將進一步提供有關總額到淨額的指標，我們預計目前該組合將為 65％ 商業，約 35％ 為醫療補助或醫療保險。所以現在還為時過早。

But overall, I think it's going as well as we expect it to go.

但總體而言，我認為一切進展順利，正如我們預期的那樣。

Great. And then maybe one for Pierre. Is there any meaningful inventory build that we should think through? And also, how should we also think about any changes in terms of the SG&A line that we should expect for the Sephience launch?

偉大的。然後也許給皮埃爾一個。是否存在值得我們深思的有意義的庫存建設？此外，我們還應該如何看待 Sephience 發佈時預計的銷售、一般和行政費用 (SG&A) 方面的變化？

Yes. Thanks for the question, Brian. As we mentioned, we are leveraging our existing infrastructure. So there will be no additional OpEx. And then in terms of inventory, everything is ready, right, just to be clear.

是的。謝謝你的提問，布萊恩。正如我們所提到的，我們正在利用現有的基礎設施。因此不會有額外的營運支出。然後就庫存而言，一切都準備好了，對的，只是為了清楚起見。

So all the patients have what they need.

因此所有患者都得到了他們需要的東西。

Yes. And I would just add -- I can add a little more color to that, Pierre. In the context of inventory, we plan to ship to patients sometime around mid-August. And clearly, we were working with 2 specialty pharmacies that will carry just-in-time inventory levels. So it's not really something that we're looking at in terms of building.

是的。我只想補充一點——皮埃爾，我可以對此添加更多色彩。在庫存方面，我們計劃在八月中旬左右發貨給患者。顯然，我們正在與兩家提供即時庫存水準的專業藥局合作。所以這並不是我們真正在考慮的建設問題。

But what we are doing right now is anticipating that demand based on the number of start forms that we've already started to accumulate. As we've mentioned, there has been incredible excitement around the launch of Sephience and the community now is really poised to begin that. So we'll be monitoring that very closely. But again, Brian, we're not really going to be building inventory at all. We're just going to be managing accordingly with our specialty pharmacies.

但我們目前正在做的是根據已經開始累積的開始表格的數量來預測需求。正如我們所提到的，Sephience 的推出引起了令人難以置信的興奮，社區現在已經準備好開始這項工作。因此我們將密切關注此事。但是，布萊恩，我們實際上根本不會建立庫存。我們將對我們的專業藥局進行相應的管理。

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Congrats on the update. I guess, can you provide a little more color on the decision to allocate capital to these prior Censa shareholders? Is there anything you can share in terms of kind of hurdles for your decisions to do that on kind of a returns basis relative to maybe allocating that capital somewhere else, business development on potentially earlier-stage assets or just investing further in your pipeline?

恭喜更新。我想，您能否更詳細地說明一下向這些 Censa 前股東分配資本的決定？您能否分享一下，在做出這項決定時，您面臨哪些障礙？這些障礙與將資本分配到其他地方、在潛在的早期資產上進行業務開發或只是進一步投資於您的管道有關，從回報角度來看，您面臨哪些障礙？

Thanks for the question, Judah. As we talked about, we have accumulated and built significant cash reserves. We closed the second quarter with almost $2 billion still in cash on the balance sheet. And what we said we're going to use that for. We're going to deploy it strategically.

謝謝你的提問，猶大。正如我們所說，我們已經累積並建立了大量現金儲備。截至第二季末，我們的資產負債表上仍有近 20 億美元現金。我們說過我們會用它來做這件事。我們將戰略性地部署它。

We're going to support our commercial programs, our R&D program -- pipeline programs as well as be thoughtful about business development and corporate developments. And I would put this under the heading of a strategic deployment of our capital. Pierre, do you want to give a little bit more detail on the thinking around this and why it was a strategic deployment of capital?

我們將支持我們的商業計劃、我們的研發計劃—管道計劃，並認真考慮業務發展和企業發展。我將把這歸結為我們資本的策略部署。皮埃爾，您能否更詳細地介紹一下您對此的想法以及為什麼這是一個資本的策略部署？

Yes, absolutely. Look, given the revenue potential of Sephience and our ability to achieve $1 billion plus of revenues in the US alone, this is a thoughtful use of our cash. We said that we will be disciplined. We will focus on creative value transaction, and that's exactly how we thought about it.

是的，絕對是。瞧，考慮到 Sephience 的收入潛力以及我們僅在美國就能實現 10 億美元以上收入的能力，這是對我們現金的深思熟慮的使用。我們說過我們會遵守紀律。我們將專注於創意價值交易，這正是我們的想法。

And this is a very high return on capital. So that's how we thought about it. Furthermore, as Matt mentioned, we have a very strong financial position that will not preclude us for additional opportunity for BD or pipeline investments or own R&D efforts. We have a lot of firepower remaining.

這是非常高的資本報酬率。這就是我們的想法。此外，正如馬特所提到的，我們的財務狀況非常強勁，這不會妨礙我們在 BD 或管道投資或自主研發方面獲得更多機會。我們還剩下很多火力。

Okay. Great. And then just on Huntington's, is there anything you can share on interactions you've had with Novartis since providing the update?

好的。偉大的。然後就亨廷頓舞蹈症而言，自從提供最新消息以來，您能否分享一下您與諾華公司的互動？

Judah, I would say that the teams have worked very well together. There's a clear shared sense of urgency in getting this program forward and getting a therapy to patients that could be beneficial. There's a shared enthusiasm for the mechanism of Huntington lowering and the positive attributes of votoplam or PTC518 being an oral small molecule splicing agent. And I think what we've done in the past few weeks is really take 2 very aligned teams, work together and make sure that we take the next necessary important step, which is meeting with the FDA to align on the efficacy trial design as well as understanding with the data we have at hand and what additional data we could have, what the potential pathway for accelerated approval looks like.

猶大，我想說這兩個團隊合作得非常好。大家顯然都迫切希望推進這個項目，並為患者提供可能有益的治療方法。人們對亨廷頓降低的機制以及沃托普拉姆或 PTC518 作為口服小分子剪接劑的正面特性有著共同的熱情。我認為我們在過去幾週所做的實際上是讓兩個非常一致的團隊共同努力，確保我們採取下一個必要的重要步驟，即與 FDA 會面，以協調療效試驗設計，並了解我們手頭上的數據以及我們可以擁有的額外數據，加速批准的潛在途徑是什麼樣的。

Kelly Shi, Jefferies.

傑富瑞 (Jefferies) 的凱莉施 (Kelly Shi)。

Congrats on the progress. Maybe first on PKU launch, specifically on how to timely capture those who are under care and recently failed other therapies, how soon could they get Sephience? And will there be some wait time between -- for logistical reasons? Also, on the sales guidance for full year '25 remain the same from Q1 from $650 million to $800 million. Curious if this number include any revenues from PKU launch?

恭喜你取得進展。也許首先在 PKU 推出時，具體是如何及時捕捉那些正在接受治療並且最近其他療法失敗的人，他們多久可以得到 Sephience？由於後勤原因，中間是否會有一些等待時間？此外，25 年全年的銷售預期與第一季保持不變，從 6.5 億美元增至 8 億美元。好奇這個數字是否包含了 PKU 發射的收入？

And also, I have a follow-up.

此外，我還有一個後續行動。

Thank you for the questions, Kelly. I'll start and then pass to Eric and Pierre. First, we've talked about the ability to provide benefit to the full spectrum of PKU patients. But in terms of sequencing that there are a relatively large number of patients who are at these specialty centers, 104 specialty centers that we talked about, who are either on existing therapy -- oral therapies and can certainly benefit from one that could provide greater lowering and Phe greater diet liberalization, others who've recently tried and failed and others who may be in recent contact with the centers and therapy naive. So it's that group of patients that we've talked about that we see as the first that we would be targeting in terms of sequence.

謝謝你的提問，凱利。我先開始，然後交給 Eric 和 Pierre。首先，我們討論了為所有 PKU 患者提供益處的能力。但就排序而言，這些專科中心的患者數量相對較多，我們討論過的 104 個專科中心，他們要么正在接受現有療法 - 口服療法，並且肯定可以從一種可以提供更大降低和更大飲食自由度的療法中受益，其他人最近嘗試過但失敗了，其他人可能最近才與中心接觸並且沒有接受過治療。因此，我們認為我們討論過的這群患者是我們按照序列優先考慮的第一批患者。

And then, of course, those who may be in less contact with the center as time goes on. But there's a large number, as we shared on the call last week, somewhere around 7,000 patients fit into that first wave of the sequence. Eric, do you want to talk a little bit about wait times and how quickly patients can get therapy?

當然，隨著時間的推移，這些人與中心的連結可能會減少。但數量很大，正如我們上週在電話會議上分享的那樣，大約有 7,000 名患者屬於第一波病例。艾瑞克，你想談談等待時間以及病人多快能得到治療嗎？

Yes, Kelly, thanks for the question. I think really, that's going to depend. Again, it's very early days, and part of that is going to be based on the patient's profile. If they've already been controlled on current therapies and would like to switch to Sephience, then it may take a little bit longer. However, most of these patients that Matt described are either poorly controlled or they failed.

是的，凱利，謝謝你的提問。我認為這確實要視情況而定。再次強調，現在還處於早期階段，部分研究將基於患者的狀況。如果他們已經透過目前的療法得到控制並希望改用 Sephience，那麼可能需要更長的時間。然而，馬特描述的大多數患者要么控制不佳，要么治療失敗。

And some of them are looking for better Phe control. If there's documentation, usually, that will go much quicker through the payer. So for us, we anticipate that, that first wave will already have previous documentation, and we will be able to, if you will, address many of the prior authorizations and if required, some of the step edits very quickly. We have a lot of experience with that over the last 8.5 years. Our teams have been dealing with that with prednisone and Emflaza.

他們中的一些人正在尋求更好的 Phe 控制。如果有文件，通常付款人會更快處理。因此，對於我們來說，我們預計第一波已經有先前的文件，並且我們將能夠（如果願意的話）非常快速地處理許多先前的授權，如果需要的話，還可以處理一些步驟編輯。在過去的 8.5 年裡，我們在這方面累積了豐富的經驗。我們的團隊一直在使用潑尼松和 Emflaza 來解決這個問題。

And the good news here is Sephience and the activity of Sephience and Phe can be measured very quickly. So we can get to the point of prescription and dispense relatively quickly, particularly in that group that Matt mentioned, that initial wave of close to 7,000 patients.

好消息是，Sephience 以及 Sephience 和 Phe 的活動可以很快被測量。因此，我們可以相對快速地開出處方並配藥，特別是對於馬特提到的那組患者，即最初接近 7,000 名的患者。

Maybe just quickly on FA, could you share any comments on your latest engagements with the regulatory agency and also, your confidence level for the PDUFA given it's only 12 days away?

也許只是快速地談論 FA，您能否分享一下您與監管機構的最新合作情況，以及考慮到距離 PDUFA 僅剩 12 天，您對 PDUFA 的信心程度如何？

Yes. Thanks, Kelly. I can answer that and then I can pass it to Pierre to answer your question about guidance because I don't think we got to that one. So on assay, we had a late cycle meeting a few weeks ago. It was a very constructive meeting.

是的。謝謝，凱利。我可以回答這個問題，然後我可以把它傳遞給皮埃爾來回答你關於指導的問題，因為我認為我們還沒有討論這個問題。因此，在分析方面，我們幾週前舉行了一次後期週期會議。這是一次非常有建設性的會議。

We were told by the agency that they're still actively reviewing the application. And so, we're just waiting for any additional information and questions that we can address as they continue their review despite it being so close to PDUFA. Pierre, did you just want to comment on guidance and the inputs?

該機構告訴我們，他們仍在積極審查該申請。因此，儘管距離 PDUFA 已經很近，我們仍在等待任何額外的資訊和問題，以便他們可以繼續審查。皮埃爾，你只是想對指導和意見發表評論嗎？

Yes. Guidance, $650 million to $800 million, as we discussed, the bulk of it is our existing product portfolio and obviously includes new product launch as well. There are still some uncertainties, as you can imagine, on Emflaza, for instance, that's probably how you derive the $650 million at the bottom end and the $800 million will be dependent on how fast we ramp up and the upside potential there as well.

是的。指導金額為 6.5 億美元至 8 億美元，正如我們所討論的，其中大部分是我們現有的產品組合，顯然也包括新產品的推出。你可以想像，Emflaza 仍然存在一些不確定性，例如，這可能是你如何獲得底端 6.5 億美元的，而 8 億美元將取決於我們的成長速度和那裡的上行潛力。

Brian Abrahams, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

This is Kevin on for Brian. I just had a couple on Sephience in the EU. Just maybe can you talk about what uptake is expected in other EU countries with early access that you've identified? And sort of more generally, how we should think about the EU opportunity? And then I believe you mentioned no G&A impact given these launches.

我是凱文，取代布萊恩。我剛剛在歐盟的 Sephience 上見過幾次面。您能否談談您所發現的其他歐盟早期准入國家預計的採用情況？更廣泛地說，我們該如何看待歐盟的機會？然後我相信您提到了這些發布不會對 G&A 產生影響。

Does that -- I'm assuming that also applies to the EU as well?

這是否——我假設這也適用於歐盟？

Kevin, thanks for the questions. I'll just tackle the second one first and let Eric talk about European dynamics. No, we don't expect any OpEx changes for Sephience. It's all currently covered. As Pierre said, we're leveraging our existing infrastructure.

凱文，謝謝你的提問。我將首先解決第二個問題，然後讓 Eric 談談歐洲的動態。不，我們預計 Sephience 的營運支出不會發生任何變化。目前已全部涵蓋。正如皮埃爾所說，我們正在利用現有的基礎設施。

Similarly, for vatiquinone, if approved and launch there, the OpEx is already baked in as we'll be leveraging our existing neurology commercial infrastructure in the US Eric, do you want to talk a little bit about what we're seeing or expecting in Europe beyond the Germany early access program?

同樣，對於 vatiquinone，如果在那裡獲得批准並推出，運營成本已經考慮在內，因為我們將利用我們在美國現有的神經病學商業基礎設施。 Eric，你想談談除了德國早期使用計畫之外，我們在歐洲看到或期待的情況嗎？

Yes. Thanks for the question, Kevin. The European opportunity will be very significant. And of course, Germany is the second largest market in the world. So for us, it's incredibly important to get off to a really good start and establish, if you will, the pricing corridor.

是的。謝謝你的提問，凱文。歐洲的機會將非常重要。當然，德國是世界第二大市場。因此，對我們來說，有一個良好的開始並建立定價區間非常重要。

We're going to be leveraging a number of key markets in Europe that have early access programs and then patient programs. Those are typically the Southern European markets as well as Central and Eastern European markets, and there are some in the North. We would anticipate somewhere between 5 to about up to 10 markets that could potentially contribute during the course of this year and through the first half of next year. And the European opportunity will be incredibly important if we can maintain and we will maintain a very narrow pricing corridor. But in addition to that, we also expect approval in Japan and Brazil and coming on board there, we will also add some of the momentum that we've built from the US

我們將利用歐洲一些擁有早期訪問計劃和患者計劃的關鍵市場。這些通常是南歐市場以及中歐和東歐市場，北歐也有一些。我們預計今年和明年上半年大約有 5 到 10 個市場可能會做出貢獻。如果我們能夠維持並且將繼續維持一個非常狹窄的價格區間，那麼歐洲的機會將非常重要。但除此之外，我們還期待日本和巴西的批准，加入這些國家後，我們還將增加我們在美國建立的一些動力

and Europe. So these are two also incredibly important markets to our growth in the future.

和歐洲。因此，這兩個市場對於我們未來的發展也非常重要。

Ellie Merle, UBS.

瑞銀的艾莉·梅爾（Ellie Merle）。

This is Tejas on for Ellie. I know you mentioned you had some scripts coming in. Have you guys seen any approvals yet for coverage? I know it's ahead of any drug getting shipped, but just anything anecdotal? And then a little bit on the ex-US opportunity. How does the distribution of patients work in some of these countries? Are they concentrated at major centers? Or are they a bit more spread out through these countries?

這是為 Ellie 而設的 Tejas。我知道你提到你有一些劇本即將面世。你們有看過任何關於報道的批准嗎？我知道這比任何藥物的運輸都要早，但這只是傳聞嗎？然後稍微談談美國以外地區的機會。這些國家的患者分佈如何？它們集中在主要中心嗎？或者它們在這些國家分佈得更廣一些？

Thanks for the questions, Tejas. On the first one, it's still early days to answer that question. So it's nothing more to add on that. But Eric, do you want to talk a little bit about distribution of patients in Europe?

謝謝你的提問，Tejas。對於第一個問題，現在回答還為時過早。因此，對此沒有什麼可補充的。但是艾瑞克，你想談談歐洲患者的分佈嗎？

Yes. And just going back on the insurance, we're in the process. We're just in a few days. And so, as you can understand, we're going through the process of insurance verification in the US That process price was lifted, insurance verification and then co-pay assistance, that takes a few days for all that to happen.

是的。回到保險問題上，我們正在處理中。我們還有幾天就到了。因此，正如您所理解的，我們正在美國進行保險驗證流程，該流程的價格已經提高，保險驗證和共同支付援助，所有這些需要幾天的時間才能完成。

But as we progress, we'll be providing a little bit more color there. In terms of major centers of excellence, in fact, I think Germany is a great example where we were able through our compassionate use program to target more than half of the centers in Germany that actually oversee close to 8,000 patients. And with that, our compassionate use program was actually rolled out and has been incredibly important in converting some of those patients immediately. Most of these patients are seen in centers of excellence, very much like the US where you have a patient that's diagnosed at birth.

但隨著我們的進步，我們將提供更多的色彩。就主要卓越中心而言，事實上，我認為德國就是一個很好的例子，我們能夠透過我們的同情用藥計畫瞄準德國一半以上的中心，這些中心實際上負責管理近 8,000 名患者。同時，我們的同情用藥計畫正式啟動，並且對於立即轉化部分患者發揮了極其重要的作用。大多數此類患者都在卓越醫療中心接受治療，與美國的情況非常相似，在美國，患者在出生時就被診斷出患有這種疾病。

So they're actually moved immediately into that center and followed throughout adolescents and then their adulthood. So we see in Europe a very high concentration in the major cities, and it's really not as diffuse. It's actually far more centralized.

因此，他們實際上會立即被轉移到該中心，並在青少年時期和成年期接受追蹤。因此，我們看到歐洲主要城市的集中度非常高，但實際上並沒有那麼分散。它實際上更加集中化。

I guess just with those compassionate use programs, just around the world, how many patients are on them, including in the US? And how fast do you think you could convert those?

我猜想，光是這些同情用藥計畫中，全世界就有多少患者參與其中，包括美國？您認為您能多快實現這些轉變？

Yes, Tejas, this was a very specific early access program in Germany that we launched because for 2 reasons. One, with the pricing -- with listing of the price initiating the German launch, those patients pretty quickly turn right over to commercial and also was an opportunity for us to get the drug in the hands of those physicians at the concentrated centers. So we did not institute a global early access program. This was a specific decision made in Germany or a global compassionate use program. This is a specific decision made in Germany due to the dynamics of the launch, listing of the price and the 6 months of free pricing you get as soon as you initiate the launch.

是的，Tejas，這是我們在德國推出的一個非常具體的早期訪問計劃，原因有二。首先，隨著定價的公佈，隨著藥物在德國上市，那些患者很快就轉向商業化，這也是我們讓藥物到達集中中心的醫生手中的機會。因此我們沒有製定全球早期訪問計劃。這是德國或全球同情用藥計畫做出的具體決定。這是德國根據發布的動態、價格清單以及啟動發布後立即獲得的 6 個月免費定價做出的具體決定。

Geoff Meacham, Citigroup.

花旗集團的傑夫‧米查姆。

This is Jarwei on for Geoff. Two questions. Just to your earlier comment on the early scripts coming in, could you provide some color on the cadence and types of patients coming in? Have these patients lined up more with their scheduled visits? Or have these early patients been coming in voluntarily for a medication switch?

這是 Jarwei 代替 Geoff 上場。兩個問題。就您先前對早期處方情況的評論而言，您能否提供一些有關患者入院節奏和類型的信息？這些患者是否已經按照預定的就診時間排起了長隊？還是這些早期患者是自願來換藥的？

And then second question, based on your latest conversations with FDA on vatiquinone, what has been your sense on the agency stance on a broad label for all age groups? And is there a possibility that the agency could perceive demonstration of benefit on certain mFAR subgroups to be more appropriate for certain portions of the patient population? And on that topic of labeling, have those discussions begun?

第二個問題，根據您最近與 FDA 就 vatiquinone 的對話，您認為該機構對於所有年齡層的廣泛標籤的立場如何？並且，該機構是否有可能認為，對某些 mFAR 亞群展示益處更適合特定部分患者群體？關於標籤的話題，討論已經開始了嗎？

Thanks for the question, Jarwei. On the first question, look, it's still early days. And what we can tell you is that, there's no rules or patterns we see other than we know there are a lot of patients who are really interested in getting on drug really quickly. We're seeing a lot in social media patients saying we're writing our doctors right away. We're trying to -- we're going to get in as quickly as possible.

謝謝你的提問，Jarwei。關於第一個問題，現在還為時過早。我們可以告訴您的是，我們沒有發現任何規則或模式，只是我們知道有很多患者確實對快速服藥感興趣。我們在社群媒體上看到很多患者說我們正在立即寫信給醫生。我們正在努力——我們將盡快進入。

And again, a lot of the prescription decisions and prescription writing at these centers can be MDs, could be the doctors, could be nurse practitioners. And so, it's really kind of a mix. We've also talked about a lot of centers, particularly in the US having waitlist of patients. So there's -- they can be working off that as well.

再次強調，這些中心的許多處方決定和處方書寫工作可以由醫學博士、醫生或執業護理師負責。所以，這確實是一種混合。我們也討論了很多中心，特別是美國的中心，都有病人等候名單。所以——他們也可以從中獲益。

So there's no clear rules, but exactly as we expected, you're seeing a broad swath of patients wanting to get access to drug and physicians wanting to provide a drug for all those different segments, as Eric has talked about. On vatiquinone, we would expect, based on our conversations that the label will be inclusive of all age groups, while the MOVE-FA study was focused in pediatric and adolescent patients for whom there's an unmet need without approved therapies now.

因此沒有明確的規則，但正如我們所預料的那樣，你會看到大批患者希望獲得藥物，醫生希望為所有不同群體提供藥物，正如 Eric 所說的那樣。對於瓦替奎寧，根據我們的談話，我們預計標籤將涵蓋所有年齡段，而 MOVE-FA 研究則集中於兒科和青少年患者，目前這些患者尚無核准的療法，存在未滿足的需求。

We have data in adults in that study as well that are consistent with what we've seen in the younger patients as well as data from our longer-term extension studies that were provided in terms of confirmatory evidence, including data from an earlier study where we see in adults, both ambulatory and non-ambulatory, significant effect in terms of slowing of disease progression over years.

我們在該研究中得到的成年人數據與我們在年輕患者中看到的結果一致，並且我們長期擴展研究提供的數據也提供了確認證據，包括來自早期研究的數據，我們發現成年人（包括可行走和不可行走的）在多年來減緩疾病進展方面均有顯著效果。

So taken together, the data package clearly supports benefit and certainly safety in the full age spectrum and full spectrum of disease severity for FA. We have not gone formally into labeling negotiations yet at this point.

因此，綜合起來，數據包清楚地支持了 FA 在整個年齡和整個疾病嚴重程度範圍內的益處和安全性。目前我們尚未正式進入標籤談判階段。

Joon Lee, Truist.

Joon Lee，Truist。

When you talk to the FDA for the Huntington's, my guess is that it will be with CDER, but CBER is also looking at AMT-130 for Huntington's and is expected to run their decision on accelerated approval path this quarter. So given the same disease indication with the decision by CBER, is that any sort of regulatory precedent that may impact CDER and your program? And also quickly, do you still owe royalties to Shiratori?

當您與 FDA 談論亨廷頓舞蹈症時，我猜測它將與 CDER 合作，但 CBER 也在研究亨廷頓舞蹈症的 AMT-130，並預計將於本季度就加速審批路徑做出決定。那麼，鑑於 CBER 的決定與疾病指徵相同，這是否會成為可能影響 CDER 和您的計劃的監管先例？還有快說，你還欠白鳥的版稅嗎？

Thanks for the questions, Joon. On the first question, we're obviously watching with great interest on the FDA interactions that CBER is having around the gene therapy. Look, we've talked a lot about there's potential benefits of the gene therapy administered to one part of the brain through direct administration to lower HTT.

謝謝你的提問，Joon。關於第一個問題，我們顯然非常感興趣地關注 FDA 和 CBER 在基因治療方面的互動。你看，我們已經討論了很多關於透過直接給藥對大腦某個部位進行基因治療以降低 HTT 的潛在益處。

If there's benefits there, we think that reads through incredibly well to lowering Huntington protein throughout the whole brain and to be able to do that in a durable way and also allowing for dose titration and monitoring peripherally of HTT lowering. We've always thought from a development standpoint, there are very good read-throughs.

如果這樣做有好處，我們認為這可以非常好地降低整個大腦的亨廷頓蛋白，並且能夠以持久的方式做到這一點，同時還允許劑量滴定和監測 HTT 降低的外圍情況。我們一直認為，從開發的角度來看，有非常好的通讀效果。

And certainly on the regulatory side, I think there has been increasing desire by the agency to have alignment, particularly when it comes to their views on rare disease, whether it's in CBER or CDER. Obviously, there have been a lot of changes in FDA recently. But I think that concept and that desire to have alignment remains.

當然，在監管方面，我認為各機構越來越希望達成一致，特別是在涉及罕見疾病的觀點時，無論是在 CBER 還是 CDER。顯然，FDA 最近發生了很多變化。但我認為，這種觀念和保持一致的願望仍然存在。

So with that in mind, we're clearly very interested in understanding what the pathway could look like as we shared at the PIVOT-HD readout in May, we were very happy to demonstrate the statistically significant benefit after two years relative to a well-matched natural history cohort from the ENROLL-HD database, as well as the signals of dose-dependent longer NfL after 24 months.

因此，考慮到這一點，我們顯然非常有興趣了解該途徑可能會是什麼樣子，正如我們在 5 月份的 PIVOT-HD 讀數中所分享的那樣，我們很高興地證明了相對於來自 ENROLL-HD 數據庫的匹配良好的自然歷史隊列，兩年後具有統計學上的顯著優勢，以及 24 個月後依賴性劑量更長 NfL 的信號。

So, obviously, we're going to be very keen to see the FDA's position with regard to using the natural history comparator with [CH] to address. Obviously, we have the additional benefit of being able to provide the peripheral Huntington lowering biomarker data as well, which is clearly an important piece of evidence that we're having a favorable effect on what matters most of the disease that toxic Huntington protein.

因此，顯然，我們非常希望看到 FDA 在使用自然歷史比較器和 [CH] 來解決問題方面的立場。顯然，我們還有額外的好處，那就是能夠提供外周亨廷頓降低生物標記的數據，這顯然是一個重要的證據，表明我們對最重要的疾病——毒性亨廷頓蛋白——產生了有利的影響。

And then, Pierre, do you want to comment on remaining royalties for Shiratori?

那麼，皮埃爾，你想評論一下白鳥剩餘的版稅嗎？

Yes, we still owe low single-digit royalty to Shiratori.

是的，我們仍然欠 Shiratori 幾千元的版稅。

Sami Corwin, William Blair.

薩米·科溫、威廉·布萊爾。

Congrats on the progress. I was curious if you could provide an update on the Translarna review in the US I think the last we heard there have been some clinical site inspections. And then given your strong balance sheet and revenue projections, what are your thoughts on additional BD opportunities or early pipeline investments?

恭喜你取得進展。我很好奇您是否可以提供有關美國 Translarna 審查的最新情況，我想我們上次聽說已經進行了一些臨床現場檢查。然後，鑑於您強勁的資產負債表和收入預測，您對額外的 BD 機會或早期管道投資有何看法？

Thanks for the question, Sami. On Translarna, that NDA remains under active review, as we mentioned that we had had the clinical site inspections completed in the spring. We have got IRs in the early part of the summer that we were able to easily address.

謝謝你的提問，薩米。關於 Translarna，該 NDA 仍在積極審查中，正如我們所提到的，我們已經在春季完成了臨床現場檢查。我們在夏初就遇到了 IR，並且能夠輕鬆解決。

And so, now obviously, without the PDUFA date, it's hard to know exactly when the agency will reach an action, but we have had back and forth in terms of IRs in addition to the inspections as we previously talked about. In terms of the balance sheet, clearly, we still remain with significant firepower and look to do strategic BDs.

因此，現在顯然，如果沒有 PDUFA 日期，就很難確切知道該機構何時會採取行動，但正如我們之前談到的，除了檢查之外，我們在 IR 方面也一直在反覆溝通。就資產負債表而言，顯然我們仍然擁有強大的火力並希望進行策略性業務拓展。

Pierre, do you want to just talk a little bit how we've been thinking about the potential BD opportunities and timing?

皮埃爾，您能否簡單談談我們對潛在 BD 機會和時機的看法？

Yes. As Matt mentioned, we have a significant financial position, and we're actively looking at BD opportunities. We have a global infrastructure. We know how to get drug approved globally, and we know how to obviously commercialize this drug worldwide. And so, these are -- so we're looking at assets that we could cast it in our existing infrastructure.

是的。正如馬特所提到的，我們的財務狀況良好，並且正在積極尋找 BD 機會。我們擁有全球基礎設施。我們知道如何讓藥物獲得全球批准，我們也知道如何在全球範圍內實現這種藥物的商業化。所以，這些是——所以我們正在尋找可以在我們現有基礎設施中投入的資產。

Furthermore, we're also looking at pipeline assets that will complement our R&D portfolio, and that's how we're thinking about BD opportunities. And we demonstrated today that we will be disciplined and that we will do transactions that create value for our shareholders.

此外，我們也正在尋找可以補充我們研發組合的管道資產，這就是我們對 BD 機會的看法。今天我們表明，我們將嚴守紀律，並將進行為股東創造價值的交易。

A kind of follow-up question on the BD. Is there a sweet spot in terms of the stage of clinical development that you're looking at?

關於 BD 的一種後續問題。就您所關注的臨床開發階段而言，是否存在一個最佳點？

Yes. I think we're looking pretty broadly, Sami. I think a lot -- certainly on the commercial side, we'll see what we have in terms of all the regulatory decisions, and that will dictate whether we're busy doing multiple launches or whether we'll have capacity -- commercial capacity with our existing infrastructure to bring something and to continue to develop -- to drive top line revenue. We have a number of things coming from our research platforms coming into the clinic. So it's going to be a matter of looking for an opportunity that can complement what we have already very nicely.

是的。我認為我們的視野非常開闊，薩米。我認為有很多——當然在商業方面，我們將看到我們在所有監管決策方面的情況，這將決定我們是否忙於進行多次發布，或者我們是否有能力——利用我們現有的基礎設施的商業能力來帶來一些東西並繼續發展——來推動營收。我們的研究平台已將許多成果應用於臨床。因此，我們要尋找一個機會來補充我們已經擁有的東西。

But clearly, it will be in our sweet spot of rare disease, could be CNS, could be non-CNS. I think it's going to be something that would have to be the right opportunity that we felt could complement our existing programs and expertise.

但顯然，它將是我們罕見疾病的最佳治療點，可能是中樞神經系統疾病，也可能是非中樞神經系統疾病。我認為這將是一個合適的機會，我們認為它可以補充我們現有的專案和專業知識。

Joseph Thome, TD Cowen.

約瑟夫·托米（Joseph Thome），考恩（Cowen）TD。

This is Peyton on for Joe. So kind of asking a little bit about the vatiquinone scenarios. Saying that it is approved around the PDUFA date, how quickly could you launch therapy? And is there a particular population that you would go after? And then kind of along with that, would you then move it to try and get a registration in Europe?

我是佩頓，代替喬回答問題。我想問一下關於瓦替奎寧的情況。假設它在 PDUFA 日期左右獲得批准，您多快可以推出治療？您想要針對的特定族群是哪些？那麼，您是否會嘗試將其轉移到歐洲進行註冊？

And then in the case that you do not get it approved, would you be open to running another trial? If you can walk us through that as well, that would be great.

那麼，如果未獲得批准，您是否願意進行另一次試驗？如果您能向我們介紹一下這一點，那就太好了。

So, Peyton, our focus right now is on potential success. So I would say that our teams are in position and ready and the infrastructure is built and we'd be ready to launch this right away. As we talked about with there out being any approved drugs for patients under 16, we clearly see that as the first place that we would go. We are proud of having a long-standing collaboration with the Friedreich's ataxia centers in the US, many that treat pediatric patients and treat pediatric and adult patients. So I think it will be relatively -- it will be a very exciting opportunity for us, and we'd be ready to go day one.

所以，佩頓，我們現在的重點是潛在的成功。所以我想說，我們的團隊已經準備就緒，基礎設施也已經建成，我們準備好立即啟動這項工作。正如我們所討論的，目前沒有任何針對 16 歲以下患者的核准藥物，我們顯然認為這是我們首先要考慮的問題。我們很自豪能夠與美國弗里德賴希共濟失調中心建立長期合作關係，其中許多中心為兒科患者提供治療，也為兒科和成人患者提供治療。所以我認為這對我們來說是一個非常令人興奮的機會，我們已經準備好從第一天開始。

And then if there wasn't success, would you consider running another trial? Or would you shelter the program?

如果沒有成功，您會考慮進行另一次試驗嗎？或者你會保護這個計畫嗎？

Yes. As I said, we're thinking about success right now. We believe that this is a -- we believe that vatiquinone provides as the data show, an effective therapy, not only for children who need a safe and effective therapy, but also for adults who would benefit from having a safe, well-tolerated and effective treatment option. That's what we believe the data show, and which is what supported the NDA submission. And we can expect that we have a commitment to patients that we will always look to try to support.

是的。正如我所說，我們現在正在考慮成功。我們相信，正如數據所示，vatiquinone 不僅為需要安全有效治療的兒童提供了一種有效的治療方法，而且也為能從安全、耐受性良好且有效的治療方案中受益的成年人提供了一種有效的治療方法。我們相信數據表明了這一點，這也是支持 NDA 提交的證據。我們可以期待我們對患者做出承諾，我們將始終盡力提供支持。

And it comes from the line of Luke Herrmann from Baird.

它來自貝爾德的盧克·赫爾曼 (Luke Herrmann) 家族。

Just 2 quick regulatory ones for me. First, a follow-up on the vatiquinone review. Has FDA given you any sort of indication around when labeling discussions could potentially get underway? And then second, on Translarna, again, has FDA given you sort of runway or time line for when an action date could be put in place?

對我來說，只有 2 個快速監管要求。首先，對 vatiquinone 的評論進行跟進。FDA 是否曾向您透露過標籤討論可能何時開始？其次，關於 Translarna，FDA 是否再次為您提供了可以製定行動日期的時間表或時間表？

Yes. So, Luke, on your first question, there was no formal timetable as we said, the late cycle meeting was just a few weeks ago, and there are still some questions about that we were talking to them about at the time and no specific time line for next steps was given.

是的。所以，盧克，關於你的第一個問題，正如我們所說，沒有正式的時間表，後期週期會議就在幾週前，當時我們與他們討論了一些問題，但沒有給出下一步的具體時間表。

As you know, I think things are quite busy at FDA these days. And in terms of the Translarna, and there will not be a PDUFA date issued just given the particulars of that application that it was a resubmission of an NDA that was received the CRL following a submission following an RTF. Anyway, just the legacy of this going back many, many years, it is not going to be as part of the PDUFA program.

如您所知，我認為 FDA 最近非常忙碌。就 Translarna 而言，不會發布 PDUFA 日期，只是考慮到該申請的具體情況，它是在 RTF 提交後收到 CRL 的 NDA 的重新提交。無論如何，這只是許多年前遺留下來的遺留問題，它不會成為 PDUFA 計劃的一部分。

So PDUFA date will not be given.

因此不會給出 PDUFA 日期。

Paul Choi, Goldman Sachs.

高盛的保羅·崔（Paul Choi）。

This is Daniel on for Paul. We're curious about like what's the pricing assumption after the 6-month free drug program ends in Germany?

這是丹尼爾代替保羅。我們很好奇，德國 6 個月免費藥物計畫結束後的定價假設是怎麼樣的？

Thanks for the question, Daniel. Eric, do you want to talk about our global pricing strategy?

謝謝你的提問，丹尼爾。艾瑞克，你想談談我們的全球定價策略嗎？

Yes. Thanks for the question, Daniel. Look, right now, we're working to provide a very narrow pricing corridor. We've already announced the price in the US and in Germany.

是的。謝謝你的提問，丹尼爾。你看，現在，我們正在努力提供一個非常狹窄的定價範圍。我們已經公佈了美國和德國的價格。

They're very close to each other. In fact, we anticipate with the launch of Japan and other European markets to maintain that very narrow pricing corridor. Regarding your specific question, it's a process in Germany. The AMNOG process provides you free pricing.

他們彼此非常親近。事實上，我們預計隨著日本和其他歐洲市場的推出，價格區間將保持非常狹窄。關於您的具體問題，這是德國的一個流程。AMNOG 流程為您提供免費定價。

And then after that six months later, we will be in negotiations following a medical benefit assessment, and we'll be supporting that with all of the clinical data to help differentiate for all the same reasons why patients in Germany should actually obtain Sephience, particularly those who are poorly controlled who have failed.

六個月後，我們將根據醫療福利評估進行談判，並將提供所有臨床數據作為支持，以幫助區分為什麼德國患者應該真正接受 Sephience，特別是那些控制不佳且治療失敗的患者。

And I think the real-world data over the next 6 months and the support from our key opinion leaders and centers are going to help us with that benefit assessment. So stay tuned. This is a process that will take at least 12 months during the whole process for us to work. And I think we're very optimistic about maintaining a very close and narrow pricing corridor.

我認為未來 6 個月的真實數據以及我們關鍵意見領袖和中心的支持將幫助我們進行效益評估。敬請關注。這是我們整個工作過程中至少需要12個月的時間。我認為我們對維持非常緊密和狹窄的定價區間非常樂觀。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

I have one regarding Sephience. Just want to confirm that there is no IP protection and it will be rely on the orphan designation market exclusivity in US, Europe and Japan. And I missed the beginning part of the call, just apologize if already asked. So should we start to see revenue contribution in 3Q '25? And then second question is very quickly regarding the vatiquinone in FAE (sic - "FA").

我有一個關於 Sephience 的。只是想確認沒有智慧財產權保護，並且將依賴美國、歐洲和日本的孤兒藥指定市場獨佔權。我錯過了通話的開始部分，如果已經問過了，請原諒。那麼我們是否應該在 2025 年第三季開始看到營收貢獻？然後第二個問題很快就涉及到 FAE（原文如此 - “FA”）中的 vatiquinone。

I know you mentioned that late cycle review was discussed a few weeks ago. And just wondering if you can provide a little bit more color what was discussed during that late cycle review. And then any label discussion come up during the discussion or afterwards?

我知道您提到過幾週前討論過後期週期審查。我只是想知道您是否可以提供一些更多關於後期週期審查中討論的內容的資訊。然後在討論期間或之後會出現任何標籤討論嗎？

Thank you, Gena. Let me correct the first question. We have guided IP to 2039. We have a polymorph patent that goes out to 2038 that we believe will provide -- it's a combination of matter of polymorph that we believe can support protection through 2038 and then conservatively estimating at least a year of patent term extension beyond that to 2039. And of course, we're continuing to work to expand, as we always do, the IP portfolio to see if we can take protection even further beyond 2039.

謝謝你，吉娜。讓我糾正一下第一個問題。我們已將 IP 引導至 2039 年。我們擁有一項有效期至 2038 年的多晶型物專利，我們相信它將提供 - 它是多晶型物的組合，我們相信它可以支持到 2038 年的保護，然後保守估計專利期限至少延長一年至 2039 年。當然，我們將一如既往地繼續努力擴大智慧財產權組合，看看能否在 2039 年後進一步提供保護。

And that applies, not only to the US, the 2039 guidance, but to the key markets globally. We have -- we will expect there to be revenue in Q3 from Sephience as we have already begun delivering commercial product in Germany, and we've gotten patient start forms in the US and expect to be able to ship Sephience to patients in the next couple of weeks.

這不僅適用於美國、2039 年指導方針，也適用於全球主要市場。我們——我們預計 Sephience 將在第三季度產生收入，因為我們已經開始在德國交付商業產品，並且我們已經在美國獲得了患者的開始表格，並預計能夠在未來幾週內將 Sephience 運送給患者。

We've said that there's -- in the wide guidance that there is some new product revenue baked in there and that upper end of the guidance that stays $800 million is allowing for the potential of upside from new products. In terms of vatiquinone in the late cycle meeting was a relatively brief meeting that -- where we discussed the -- mainly focused on discussion of the evidence where they are in their review and their assurances that they're actually still working through the review.

我們已經說過，在廣泛的指導中，包含了一些新產品的收入，而指導的上限保持在 8 億美元，這考慮到了新產品的上升潛力。就 vatiquinone 而言，後期週期會議是一次相對簡短的會議，我們在會議上討論了 - 主要集中討論了他們審查中的證據以及他們實際上仍在進行審查的保證。

Not surprisingly, one of the main questions of the review is the fact that upright stability wasn't prespecified as a primary endpoint, would that support persuasiveness of evidence of effect, which along with the confirmatory evidence could support approval.

毫不奇怪，審查的主要問題之一是，直立穩定性並未被預先指定為主要終點，這是否支持效果證據的說服力，而這與確認證據一起可以支持批准。

Of course, they acknowledged and we're all aware of their recent guidance that others have received that upright stability can itself be an efficacy endpoint and has -- it will be used as a primary endpoint, for example, in the SKYCLARYS pediatric trial, which I think supports the FDA's evolving understanding that upright stability is the most relevant measurement of efficacy in ambulatory pediatric and adolescent patients. As we said, we've not had any labeling discussions beyond anything that was discussed in the late cycle meeting at this time.

當然，他們承認，而且我們都知道他們最近向其他人提供的指導，即直立穩定性本身可以作為療效終點，並且它將被用作主要終點，例如在 SKYCLARYS 兒科試驗中，我認為這支持了 FDA 不斷發展的理解，即直立穩定性是衡量兒科和青少年門診患者療效的最相關指標。正如我們所說，除了本次後期週期會議上討論的內容之外，我們還沒有進行任何標籤討論。

Joseph Schwartz, Leerink Partners.

Leerink Partners 的 Joseph Schwartz。

This is Jenny on for Joe. I just have a few follow-ups on vatiquinone. First, has the FDA given any indication that the review has been delayed and/or may be delayed due to staffing issues? We know it's kind of crazy over there. And then if approved, should we be looking at the SKYCLARYS launch as a template?

我是珍妮，為喬轉達。我有一些關於瓦替奎寧的後續問題。首先，FDA 是否有任何跡象表明審查因人員配備問題而被推遲和/或可能被推遲？我們知道那裡的情況有點瘋狂。如果獲得批准，我們是否應該將 SKYCLARYS 的發布視為模板？

And if not, how should we be thinking about that? And do you see any potential for combinations of SKYCLARYS and vatiquinone in FA patients?

如果不是，我們該如何考慮這個問題？您是否認為 SKYCLARYS 和 vatiquinone 合併使用對 FA 患者有治療潛力？

Thanks for the question, Jenny. There was no discussion of not meeting time lines. I'm not sure there would be one even if there was a chance that could happen. I think we all understand that there has been a lot of changes over at FDA and a lot of work. And certainly, we've seen examples as recently as this week of programs from the neurology division, maybe not getting -- meeting certain time lines.

謝謝你的提問，珍妮。沒有討論未能滿足時間表的問題。即使有可能發生這種情況，我也不確定是否會有。我想我們都明白 FDA 已經發生了很多變化，也做了很多工作。當然，就在本週，我們看到一些神經病學部門的計畫可能沒有達到特定的時間表。

But look, we look forward to continuing to work collaboratively with the division and getting to what we hope will be a positive outcome on time and if not on time, when the time can be. As we talked about, we see the launch dynamics being quite different for a number of reasons. I can let Eric go into that. Do you want to talk a bit about...

但是，我們期待繼續與該部門合作，並按時取得我們希望的積極成果，如果不能按時，那麼在適當的時候。正如我們所討論的，我們發現由於多種原因，發布動態有很大不同。我可以讓埃里克去參與其中。你想談談嗎？

Yes. I think we have an experienced team already that have been calling for the last 8.5 years in pediatric neurology. So we've already profiled all the key centers specific to FA. And we know the prescribers. We know through claims data where they are and the high unmet needs plus the clinical differentiation.

是的。我認為我們已經擁有一支經驗豐富的團隊，他們在兒科神經病學領域工作了 8.5 年。因此，我們已經對所有特定於 FA 的關鍵中心進行了概述。我們知道開處方的人。我們透過索賠數據了解他們的情況、未滿足的需求以及臨床差異。

So we're already very well poised to launch and begin the process like we have with Sephience to get patient start forms on day 1. Our teams, not only are experienced in this, but we're looking at a number of different things, which include, not only the pediatric, but a number of those patients who are adults who have failed on SKYCLARYS and some of them are poorly controlled, and there's still quite a bit of naive patients. So all in all, I think the opportunity is very significant, and our team is experienced and ready to go on day one.

因此，我們已經做好了充分的準備，可以啟動並開始這一流程，就像我們與 Sephience 合作時那樣，在第一天就獲得患者的開始表格。我們的團隊不僅在這方面經驗豐富，而且我們正在研究許多不同的情況，不僅包括兒科患者，還包括許多使用 SKYCLARYS 治療失敗的成年患者，其中一些患者控制不佳，而且還有相當多的初治患者。總而言之，我認為這個機會非常重要，我們的團隊經驗豐富，準備在第一天就開始行動。

Yes. And then to your other -- just add to that also, we would see -- we wouldn't expect there to be any monitoring. And obviously, the pediatric patients have a much different dynamic than adults do. So I think we would see the launch dynamics quite different for that reason. And in terms of combination therapy, look, I think it's something that people talk about.

是的。然後對於你的另一個 - 只需添加到這一點，我們會看到 - 我們不希望有任何監控。顯然，兒科患者的情況與成人患者有很大不同。因此我認為，出於這個原因，我們會看到相當不同的發布動態。至於聯合療法，我認為這是人們談論的話題。

I think those close to the FA community have always believed rightfully so that Friedreich's ataxia is going to be optimally managed with the cocktail of therapies like any other complex disorder. So we certainly imagine that they'd be interested in looking at combining both vatiquinone and SKYCLARYS.

我認為 FA 社區的親信們一直都正確地相信，弗里德賴希共濟失調症將像任何其他複雜疾病一樣通過混合療法得到最佳控制。因此，我們當然可以想像他們有興趣研究將 vatiquinone 與 SKYCLARYS 結合起來。

Excuse me, Jenny, any further questions?

打擾一下，珍妮，還有其他問題嗎？

No, that's it.

不，就是這樣。

Dear speakers, there are no further questions. I would now like to hand the conference over to your speaker, Chief Executive Officer, Dr. Matthew Klein. Please go ahead.

尊敬的發言者，沒有其他問題了。現在，我想將會議交給發言人、執行長馬修·克萊因博士。請繼續。

Thank you all again for joining the call today. We're excited to have had another strong quarter. We're still seeing continued contributions, meaningful contributions from our DMD franchise, which is great because we now can have that in hand as we now embark on the future, which is the launch of Sephience, and we're incredibly excited how things are going in the early days and all indicators we're seeing from everywhere in the world that this will meet our expectations of being our foundational product for building PTC going forward. So thank you all again, and have a great evening.

再次感謝大家今天參加電話會議。我們很高興又迎來了強勁的季度。我們仍然看到來自 DMD 特許經營權的持續貢獻，有意義的貢獻，這很棒，因為我們現在可以掌握它，因為我們現在著手未來，即推出 Sephience，我們對早期的進展感到非常興奮，我們從世界各地看到的所有指標都表明，這將滿足我們的期望，成為未來構建 PTC 的基礎產品。再次感謝大家，祝大家有個愉快的夜晚。

This concludes today's conference call. Thank you for participating. You may now all disconnect. Have a nice day.

今天的電話會議到此結束。感謝您的參與。你們現在都可以斷開連結了。祝你今天過得愉快。