PTC Therapeutics Inc (PTCT) 2025 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to PTC Therapeutics's third-quarter 2025 earnings conference call.

女士們、先生們，感謝各位的耐心等待。歡迎參加PTC Therapeutics 2025年第三季財報電話會議。

(Operator Instructions) Today's call is being recorded.

（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.

現在我將把電話交給投資者關係主管艾倫·卡瓦萊里女士。請開始吧。

Good afternoon and thank you for joining us to discuss PTC Therapeutics's third-quarter 2025 corporate update and financial results.

下午好，感謝各位參加本次 PTC Therapeutics 2025 年第三季公司最新動態與財務業績討論會。

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.

今天與我一同出席的有我們的執行長馬修·克萊因博士；首席商務官埃里克·保爾斯；以及首席財務官皮埃爾·格拉維耶。

Today's call will include forward-looking statements, based on our current expectations. These statements are subject to certain risks and uncertainties. Actual results may differ materially.

今天的電話會議將包含基於我們目前預期的一些前瞻性陳述。這些陳述受某些風險和不確定性因素的影響。實際結果可能與這些陳述有重大差異。

Please review the slide posted on our Investor Relations website in conjunction with the call, which contains information about our forward-looking statements, 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.

請查閱我們投資者關係網站上發布的與本次電話會議相關的幻燈片，其中包含有關我們前瞻性聲明、我們最近向美國證券交易委員會提交的 10-Q 表格季度報告和 10-K 表格年度報告以及我們向美國證券交易委員會提交的其他文件的信息，以詳細了解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不確定的內容和重大性差異。

Additionally, we will disclose certain non-GAAP information during this call. Information regarding our use of GAAP to non-GAAP financial measures and the 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GAAP資訊。有關我們使用GAAP和非GAAP財務指標以及GAAP與非GAAP調節表的信息，請參閱今天的盈利報告。

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

現在我將把電話轉交給我們的執行長馬修·克萊因博士。

Thank you, all, for joining the call today. I'm excited to share our outstanding third-quarter results.

感謝各位今天參加電話會議。我很高興與大家分享我們出色的第三季業績。

The highlight of the quarter was the initiation of the Sephience global launch in Europe and the United States. As we have discussed, we expect Sephience to be the foundational product for PTC's sustainable growth and near-term path to profitability.

本季最引人注目的是Sephience在歐洲和美國的全球發行。正如我們之前討論過的，我們預計Sephience將成為PTC可持續成長和近期實現盈利的基礎產品。

Overall, third-quarter revenue totaled $211 million, which includes the first revenue from the Sephience launch, as well as continued contributions from our DMD franchise. With this strong quarter performance, we are narrowing our 2025 full-year revenue guidance to $750 million to $800 million. the upper end of the initial revenue guidance range.

第三季總營收達2.11億美元，其中包括Sephience上市帶來的首筆營收，以及DMD產品線的持續貢獻。鑑於本季強勁的業績表現，我們將2025年全年營收預期調整為7.5億美元至8億美元，即先前預期範圍的上限。

The Sephience launch is off to a great start. As of September 30, Sephience generated $19.6 million in revenue. This includes $14.4 million in the US; and $5.2 million, ex-US. We have seen a great deal of enthusiasm upon launch, with 521 patient start forms received from US centers, as of September 30. We have received start forms for patients of all ages, including adults; all disease severities, including classical PKU; and various treatment histories, including patient switches, previous treatment failures, and treatment-naïve patients.

Sephience 的上市取得了良好的開端。截至 9 月 30 日，Sephience 的收入已達 1,960 萬美元，其中美國收入為 1,440 萬美元，美國以外地區收入為 520 萬美元。自上市以來，我們看到了極大的熱情，截至 9 月 30 日，我們已收到來自美國各中心的 521 份患者啟動表格。這些表格涵蓋了各個年齡層的患者（包括成人）、各種疾病嚴重程度的患者（包括經典型苯酮尿症患者）以及不同的治療史，包括患者更換治療方案、既往治療失敗以及初治患者。

While these are still early days, the fact that we are seeing demand from all key patient segments underscores the significant unmet need for PKU patients and the potential for Sephience to become the standard of care, providing a safe and effective therapy for both classical and non-classical PKU patients.

雖然目前還處於早期階段，但我們看到所有主要患者群體都有需求，這凸顯了苯酮尿症患者的巨大未滿足需求，以及 Sephience 有可能成為標準療法，為經典型和非經典型苯酮尿症患者提供安全有效的治療。

While we are presenting results today through September 30, the results for the month of October show sustained momentum.

雖然我們今天公佈的是截至 9 月 30 日的業績，但 10 月份的業績顯示出持續的成長勢頭。

We are encouraged by the strong initial numbers and broad interest from the physician and patient communities. To sustain broad uptake, our teams are continuing to gather data to help reinforce the highly differentiated Sephience profile.

我們對初期取得的強勁數據以及醫生和患者群體的廣泛關注感到鼓舞。為了保持廣泛的應用，我們的團隊正在繼續收集數據，以進一步強化Sephience的獨特優勢。

At the International Metabolism Meeting in September, we presented the results from the [AMPLIFY] head-to-head study comparing phenylalanine lowering between Sephience and BH4. In this crossover study, Sephience treatment resulted in an average 70% greater reduction in phenylalanine levels compared to BH4, demonstrating, once again, the robust and clinically differentiated benefits Sephience can provide.

在9月的國際代謝會議上，我們發表了[AMPLIFY]頭對頭研究的結果，該研究比較了Sephience和BH4降低苯丙胺酸水平的效果。在這項交叉研究中，Sephience治療使苯丙胺酸水平平均降低了70%，與BH4相比，再次證明了Sephience能夠提供的顯著且具有臨床差異化的益處。

Additional presentations at the conference highlighted Sephience benefits on cognitive function and diet liberalization, including in the most severe patients with classical PKU or BH4 non-responsive mutations.

會議上的其他報告重點介紹了 Sephience 對認知功能和飲食自由化的益處，包括對患有經典 PKU 或 BH4 無反應突變的最嚴重患者。

We are also finalizing a publication on the Sephience mechanism of action, including in vitro, in vivo, and clinical efficacy data in the most severe PKU mutations, supporting the potential ability of Sephience to provide a safe, well-tolerated, and efficacious therapy for the full spectrum of PKU patients.

我們也正在最終確定 Sephience 的作用機制的出版物，其中包括針對最嚴重的 PKU 突變的體外、體內和臨床療效數據，以支持 Sephience 為所有 PKU 患者提供安全、耐受性良好且有效的治療的潛在能力。

Eric will provide additional details on the launch.

埃里克將提供有關此次發布會的更多細節。

I will now briefly provide an update on the development and regulatory status of our other programs.

接下來，我將簡要介紹我們其他項目的進度和監管狀況。

Starting with the Votoplam Huntington's Disease Program, a meeting with FDA is planned for the fourth quarter to align on the study design for the next efficacy study, as well as to discuss the data package that could potentially support and Accelerated Approval Application.

從 Votoplam 亨廷頓病計畫開始，計劃在第四季度與 FDA 舉行會議，以就下一個療效研究的研究設計達成一致，並討論可能支持加速批准申請的資料包。

For the Vatiquinone Friedreich’s Ataxia Program, we are planning to meet with FDA this quarter to discuss potential next steps for the program.

對於 Vatiquinone Friedreich 共濟失調項目，我們計劃在本季度與 FDA 會面，討論該項目的潛在下一步措施。

For Translarna, the NDA remains under FDA review.

Translarna 的新藥申請仍在 FDA 審查中。

Finally, we remain in a very strong financial position, ending the third quarter with approximately $1.68 billion in cash. As we have discussed, this enables us to reach cash flow breakeven, as well as participate in strategic business development activities to complement our R&D and commercial portfolios.

最後，我們依然保持著非常穩健的財務狀況，第三季末現金儲備約16.8億美元。正如我們之前討論的，這使我們能夠實現現金流收支平衡，並參與策略性業務發展活動，以完善我們的研發和商業產品組合。

Additionally, as the company continues to build for future success, we will be hosting an R&D Day on Tuesday, December 2, to share progress on our research programs, including those from our splicing platform.

此外，隨著公司繼續為未來的成功而努力，我們將於 12 月 2 日星期二舉辦研發日活動，分享我們研究計畫的進展情況，包括我們拼接平台的研究進展。

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

現在我將把電話交給艾瑞克，讓他來討論Sephience的發布細節和我們的商業表現。艾瑞克？

Thanks, Matt.

謝謝你，馬特。

We are very pleased with the early momentum of the Sephience global launch. Our seasoned customer-facing teams are off to a strong start, leveraging their years of preparation and experience and delivering across all fronts.

我們對Sephience全球發布初期取得的良好動能感到非常滿意。我們經驗豐富的客戶服務團隊開局強勁，憑藉著多年的準備和經驗，在各方面都表現出色。

We are excited to simultaneously launch Sephience in the US and Europe, following regulatory approvals. We are actively preparing for the upcoming launch in Japan, following MAA approval, anticipated in Q4.

我們很高興在獲得監管部門批准後，Sephience 將在美國和歐洲同步上市。我們正積極籌備在日本上市，預計將於第四季獲得日本藥品管理局 (MAA) 的批准。

As of September 30, Sephience global revenue reached $19.6 million and 341 patients on commercial therapy, driven by robust performances in both the US and Germany. Following FDA approval on July 28, our US team made the first Sephience shipments to patients, approximately two weeks afterwards.

截至9月30日，Sephience全球營收達1,960萬美元，共有341名患者接受了商業化治療，主要得益於美國和德國市場的強勁表現。在7月28日獲得FDA批准後，我們的美國團隊在大約兩週後向患者交付了首批Sephience產品。

Through the end of the third quarter, our PTC Cares teams received 521 patient start forms from 141 unique prescribers. The response, thus far, from US healthcare providers has been overwhelmingly positive, with a high willingness to prescribe Sephience to a wide range of PKU patients, including switches, poorly controlled or failed, and treatment-naïve individuals, as well as to children and adults.

截至第三季末，我們的PTC Cares團隊已收到來自141位不同處方醫生的521份病患用藥申請表。迄今為止，美國醫療保健提供者的回饋非常積極，他們非常願意為各類苯酮尿症（PKU）患者開立Sephience處方，包括轉換治療方案的患者、病情控制不佳或治療失敗的患者、初治患者，以及兒童和成人患者。

Many of these healthcare providers have shared their observations of the rapid benefits of fee lowering and improved patient outcomes; and indicated their intent to continue to prescribe Sephience to a broad spectrum of PKU patients.

許多醫療保健提供者分享了他們觀察到的降低費用和改善患者療效帶來的快速益處；並表示他們打算繼續為廣泛的苯酮尿症患者開立 Sephience 處方。

US payer engagement continues to be positive. Our market access and medical affairs teams have met with more than 35 payers, covering approximately 250 million lives. US payers continue to recognize the highly differentiated profile and strong value proposition of Sephience.

美國支付方的參與度持續保持積極態勢。我們的市場准入和醫學事務團隊已與超過35家支付方進行了會面，涵蓋約2.5億人口。美國支付方繼續認可Sephience高度差異化的產品特性和強大的價值主張。

We have seen initially favorable payer policies that maintain broad access, with coverage that includes prior authorizations to the label, no or limited step edits, and refills for 6 to 12 months. Although we are still in the early stages of the launch, we have seen a favorably higher commercial payer ratio and expect this payer mix to stabilize at 65-35, as Medicaid and Medicare plans finalize their policies in Q4.

我們初步觀察到一些有利的支付方政策，這些政策維持了廣泛的市場准入，涵蓋範圍包括事先獲得藥品標籤授權、無需或僅有有限的處方修改，以及6至12個月的續藥期限。儘管我們仍處於產品上市的早期階段，但商業支付方的比例已顯著提高，預計隨著醫療補助計劃和醫療保險計劃在第四季度最終確定其政策，這一支付方比例將穩定在65:35。

Likewise, the launch in Germany is off to a great start, as we quickly converted compassionate use program patients that were on Sephience prior to (inaudible) approval onto commercial therapy. We have also received prescriptions for new patients from Germany and additional EU countries on a name-patient basis; and are preparing health technology assessment dossiers to secure pricing and reimbursement across many international markets with early access programs.

同樣，我們在德國的上市也取得了良好的開端，我們迅速將先前透過同情用藥計畫使用Sephience的患者（在（聽不清楚）獲批之前）轉為商業治療。我們還收到了來自德國和其他歐盟國家的指定患者處方；並且正在準備衛生技術評估文件，以確保在許多國際市場透過早期准入計畫獲得定價和報銷。

Throughout Europe and other key markets, we see similar dynamics with healthcare providers prescribing Sephience to a broad range of PKU patients. Along with the positive feedback from healthcare providers, we've also seen a highly engaged response from the PKU patient community, worldwide.

在歐洲和其他主要市場，我們看到類似的趨勢，醫療服務提供者正在為眾多苯酮尿症（PKU）患者開立 Sephience 處方。除了來自醫療服務提供者的正面回饋外，我們還看到了全球 PKU 患者群體的高度參與。

Social media serves as a powerful platform to see, firsthand, patients' experience with Sephience and is also a strong channel for patient-to-patient communication: Instagram and other channels, including Stories and Posts from patients who have started Sephience. Some are even tasting new foods for the first time.

社群媒體是一個強大的平台，讓我們能夠第一時間了解患者使用Sephience的體驗，同時也是患者之間交流的重要管道：Instagram和其他平台，包括Sephience患者的Stories和帖子，都提供了豐富的資訊。有些患者甚至第一次嘗試了新的食物。

The excitement for Sephience is equally tangible at PKU community events, such as NPKUA's annual gathering in September, where many PKU patients share their desire for new treatment options.

在 PKU 社區活動中，人們對 Sephience 的熱情同樣顯而易見，例如 NPKUA 在 9 月的年度聚會，許多 PKU 患者在聚會上表達了他們對新治療方案的渴望。

Our customer-facing teams continue to lead medical education programs at key congresses, such as ICIEM and E.SP.KU in September, featuring roundtables, scientific exchanges, and investigator meetings in the US, Europe, and Japan, highlighting the strong clinical data of Sephience.

我們的客戶團隊繼續在重要的醫學教育大會上進行醫學教育項目，例如 9 月的 ICIEM 和 E.SP.KU，這些項目包括在美國、歐洲和日本舉行的圓桌會議、科學交流和研究人員會議，重點介紹了 Sephience 的強大臨床數據。

As Matt mentioned, these activities featured new Sephience data, including long-term results from the [AFFINITY] extension study and new data from the head-to-head study, further supporting the differentiated efficacy of Sephience. Additionally, data were presented in Japanese patients showing robust fee lowering and safety results, consistent with the global PKU population.

正如Matt所提到的，這些活動展示了Sephience的最新數據，包括[AFFINITY]擴展研究的長期結果和頭對頭研究的新數據，進一步證實了Sephience的差異化療效。此外，還展示了日本患者的數據，顯示出顯著的費用降低和安全性結果，與全球PKU人群的結果一致。

We continue to expand the global launch with our experienced teams in key international markets. We recently received approval for Sephience in Canada. We anticipate regulatory approval in Japan and Brazil, later this year.

我們正與經驗豐富的團隊攜手，持續拓展全球市場，涵蓋關鍵國際市場。 Sephience 近期已獲得加拿大監管機構的批准。我們預計今年稍後獲得日本和巴西的監管部門批准。

As we have previously discussed, we will continue to maintain a narrow pricing corridor throughout this early stage of the launch.

正如我們之前討論過的，在產品上市初期，我們將繼續保持較窄的價格區間。

Now, turning to our established portfolio, we continue to defend our DMD franchise by maintaining patients on Translarna. across the majority of European markets, leveraging Article 117 and fostering brand loyalty for EMFLAZA with targeted programs for healthcare providers and DMD patients in the US, despite multiple generic entries.

現在，讓我們來看看我們已有的產品組合，我們將繼續捍衛我們的 DMD 產品線，在大多數歐洲市場繼續為患者提供 Translarna，利用第 117 條規定，並透過針對美國醫療保健提供者和 DMD 患者的定向項目，培養 EMFLAZA 的品牌忠誠度，儘管有多個仿製藥進入市場。

In summary, the early global rollout of Sephience is off to a great start. We are very pleased with the early results in the quarter, with the US being our main engine for product growth, supplemented by other key international markets that we expect to bring on board over the next 12 months.

總而言之，Sephience 的全球早期推廣取得了良好的開端。我們對本季的早期業績非常滿意，美國市場是我們產品成長的主要引擎，其他重要的國際市場也將在未來 12 個月內陸續加入。

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

那麼，我現在將電話轉給皮埃爾，請他報告財務狀況。皮埃爾？

Thanks, Eric. I'll now share the financial highlights of our third quarter of 2025.

謝謝，埃里克。接下來我將分享我們2025年第三季的財務亮點。

Beginning with top-line results, total revenue for the third quarter was $211 million. Starting with Sephience, net product revenue in the quarter was $19.6 million, as of September 30. DMD franchise revenue for the quarter was $86 million, with Translarna net product revenue of $51 million and EMFLAZA net product revenue of $35 million.

首先來看營收方面，第三季總營收為2.11億美元。截至9月30日，Sephience產品當季淨營收為1,960萬美元。 DMD產品線當季營收為8,600萬美元，其中Translarna淨營收為5,100萬美元，EMFLAZA淨營收為3,500萬美元。

For EBITDA, Roche achieved third -quarter global revenue of approximately $532 million, resulting in royalty revenue of $71 million for PTC.

羅氏第三季全球 EBITDA 營收約為 5.32 億美元，為 PTC 帶來 7,100 萬美元的特許權使用費收入。

For the third quarter of 2025, non-GAAP R&D expense was $91 million, excluding $9 million in non-cash stock-based compensation expense, compared to $152 million for the third quarter of 2024, excluding $9 million in non-cash stock-based compensation expense.

2025 年第三季度，非 GAAP 研發費用為 9,100 萬美元，不包括 900 萬美元的非現金股票選擇權費用；而 2024 年第三季度，非 GAAP 研發費用為 1.52 億美元，不包括 900 萬美元的非現金股票選擇權費用。

Non-GAAP SG&A expense was $74 million for the third quarter of 2025, excluding $10 million in non-cash stock-based compensation expense, compared to $63 million for the third quarter of 2024, excluding $10 million in non-cash stock-based compensation expense.

2025 年第三季非 GAAP 銷售、一般及行政費用為 7,400 萬美元，不包括 1,000 萬美元的非現金股票選擇權費用；而 2024 年第三季為 6,300 萬美元，不包括 1,000 萬美元的非現金股票選擇權費用。

Cash, cash equivalents, and marketable securities total [$1,688 million], as of September 30, 2025, compared to [$1,140] million as of December 31, 2024. The third-quarter cash balance reflects the previously announced purchase of 90% of our Sephience annual global net sales payment obligation of 8% to 12% owed to former Censa shareholders for approximately $225 million upfront and future sales-based milestone payments.

截至 2025 年 9 月 30 日，現金、現金等價物及有價證券總額為 16.88 億美元，而截至 2024 年 12 月 31 日為 11.4 億美元。第三季現金餘額反映了先前宣布的收購 Sephience 90% 的年度全球淨銷售額付款義務（該義務為 8% 至 12%，原欠 Censa 股東），收購款項約為 2.25 億美元，以及未來基於銷售額的里程碑付款。

Given the significant Sephience revenue opportunity, we expect meaningful value creation, based on the transaction terms. We remain well-capitalized to reach cash flow breakeven and profitability, as well as pursue business development opportunities that will further enhance our commercial portfolio and expand our innovative pipeline.

鑑於 Sephience 蘊藏著巨大的營收潛力，我們預期根據交易條款，此次收購將創造可觀的價值。我們資金充足，足以實現現金流量收支平衡和獲利，並能積極尋求業務拓展機會，進一步豐富我們的商業產品組合，拓展創新產品線。

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

現在我將把電話轉交給接線生進行問答環節。接線生？

(Operator Instructions)

（操作說明）

Kristen Kluska, Cantor Fitzgerald.

克里斯汀·克魯斯卡，坎托·費茲傑拉。

Hi. Good afternoon. Congrats on an amazing start for Sephience. Really exciting to see that.

您好，下午好。恭喜Sephience取得如此驚人的開局，真是令人興奮！

Wanted to ask what's going to give you confidence that beyond this really strong out-of-the-gate launch, you're going to see maintained durability and that patients will be on therapy for a while?

我想問一下，除了這次強勁的開局之外，是什麼讓您有信心看到療效能夠持續下去，並且患者能夠長期接受治療？

Kristen, thanks so much for the question. We, too, are quite excited with the start and seeing a lot of what we believed we would see, which is given the highly differentiated profile of Sephience; uptake in all segments, including those who've been on previous therapies, therapy-naïve patients -- we're getting adults who are therapy-naïve, who people thought were so remote that'd be hard to get. I should add also classical, non-classical, full spectrum of severity.

克里斯汀，非常感謝你的提問。我們也對目前的進展感到非常興奮，並且看到了很多我們預期會出現的情況，這與Sephience高度差異化的特性相符：各個群體都接受了Sephience，包括接受過其他療法的患者和初次接受治療的患者——我們甚至獲得了之前認為很難接觸到的成年初次接受治療患者。我還想補充一點，Sephience也適用於各種嚴重程度的典型和非典型癌症。

What we're continuing to hear from physicians and from the patient community is great response. We're seeing on social media patients being able to eat food for the first time that they couldn't eat before, like hamburgers and pizza. And then, a lot of physician feedback that some of the more severe patients that they wanted to try first are responding and are responding really well.

我們不斷從醫生和患者群體那裡聽到正面的回饋。我們在社群媒體上看到，有些患者第一次能夠吃到以前無法食用的食物，例如漢堡和披薩。此外，許多醫生也回饋說，他們首先嘗試的一些病情較重的患者也出現了良好的反應。

We even heard from one of the early skeptics, one of the physicians who was a bit skeptical at first of whether or not Sephience could have a place for the classical and more severe patients -- and we heard, recently, she said, I'm converted and I'm ready to try all my patients on Sephience, which is something we're hearing again and again from a number of physicians.

我們甚至聽到了早期一位懷疑論者的聲音，這位醫生起初對 Sephience 是否能用於治療經典型和更嚴重的患者持懷疑態度——而最近，我們聽說，她說：“我已經改變了看法，我準備讓我的所有患者都嘗試使用 Sephience。” 我們從許多醫生那裡反复聽到類似的說法。

So we've got this broad interest in trying patients. We're getting initial feedback that patients are responding; responding in terms of lowering fee, as well as being able to start to liberalize their diet.

因此，我們對嘗試這種療法的患者群體表現出了廣泛的興趣。我們得到的初步回饋是，患者對此反應良好；他們的反應體現在費用降低以及飲食習慣的放寬等。

Look, it's early days. We're only a few weeks into the launch. But what we're seeing early looks good. We'll see. We'll see as things continue to unfold.

現在還處於早期階段，產品發布才幾週時間。但目前來看，情況不錯。讓我們拭目以待，看看後續發展如何。

We keep in mind that in our clinical studies, we saw up to 75% response rate in patients of the full spectrum, which, again, suggests that we can deliver benefit to the broad spectrum of patients. Of course, as you've talked about a lot in some of the research notes that you've written, patients really want to have lower fee and also, see the diet liberalization. That's really going to be a key factor in adherence.

我們始終銘記，在臨床研究中，我們觀察到所有類型患者的回應率高達75%，這再次表明我們能夠使廣泛的患者群體受益。當然，正如您在一些研究報告中多次提到的，患者確實希望降低費用，飲食方面也能更加靈活。這確實是影響患者依從性的關鍵因素。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Good evening. Congrats from me, as well, on a really strong launch out of the gates.

大家好，晚上好。我也要祝賀你們，開局非常順利。

Matt, maybe I wanted to ask you a couple of questions. Can you just talk to me about what magnitude of fee reduction are doctors and payers looking for in order to keep a patient on treatment beyond the trial period? Maybe related to that as well, what's your expectation for percentage of patients that are going to stay on treatment, following this initial trial? How are you thinking about guiding the Street in that particular dynamic, as well?

馬特，我想問你幾個問題。你能跟我說說醫生和支付方希望在試驗期結束後，病人繼續接受治療的費用降低幅度是多少嗎？另外，你預計在初步試驗結束後，有多少患者會繼續接受治療？你打算如何引導市場應對這種情況？

Absolutely. Thanks for the questions, Tazeen. I'll give initial responses. I'll also ask Eric to provide a little bit of color.

當然。謝謝你的提問，塔津。我會先給出初步回答。我也會請艾瑞克補充一些細節。

On your first question of magnitude of response, we're hearing different things from different folks, right? We're hearing that for some patients, certainly ones that are more severe, they've never had a therapy that they could tolerate or respond to that 15% fee reduction could be meaningful for them; 20% fee reduction. Others say we're going to look for maybe 30% fee reduction, which is what we used in the trial. Others say, it's not really a number. Are patients feeling better?

關於您提出的第一個問題，即療效的程度，我們從不同的人那裡聽到了不同的說法，對吧？我們了解到，對於某些患者，尤其是病情較重的患者，他們之前從未接受過任何能夠耐受或有效的治療，因此15%的費用減免對他們來說可能意義重大；20%的費用減免也可能意義重大。其他人則表示，我們可能會考慮30%的費用減免，這正是我們在試驗中使用的比例。還有人說，這並非一個具體的數字。關鍵在於患者是否感覺好轉。

One of the exciting pieces of data we reported at the International Metabolism Meeting in Japan is that we're able to see in the clinical study that patients' cognitive function, executive function, and mood are improving. That's another aspect of benefit that is not as easy to quantify but it's another example of the things that physicians would be looking for, in addition to quantifiable reductions in phenylalanine. Patients report that they can liberalize their diet in this overall sense that they're feeling better.

我們在日本舉行的國際代謝會議上發表的一項令人振奮的數據是，臨床研究顯示患者的認知功能、執行功能和情緒均有所改善。這是療效的另一個方面，雖然難以量化，但除了苯丙胺酸水平的可量化降低之外，這也是醫生們關注的指標之一。患者表示，由於整體感覺較好，他們可以放寬飲食限制。

So I think it's going to be a combination of factors.

所以我認為這是多種因素共同作用的結果。

Again, I'll ask Eric to comment a little bit on what we're hearing, in terms of the dynamics in terms of payer, payer requests, and things like that.

我再次邀請艾瑞克就我們聽到的內容，特別是付款方動態、付款方要求等方面，發表一些評論。

In terms of expectations for patients to stay on it, look, it's early. It's also too early --n to your third question -- to provide specific guidance. As we get further into the launch, we'll be able to do that.

至於預期患者能否堅持服用，現在下結論還為時過早。同樣，對於你的第三個問題，現在提供具體指導也為時過早。隨著產品上市的深入，我們將能夠提供這方面的資訊。

Again, we've fallen back a bit on the clinical trial data, which shows that we have anywhere between a 66% to 75% response rate, looking at 15% or 30% as a threshold for fee reduction with very good adherence, given the safety, the tolerability, the ease of administration of the drug.

我們再次參考了臨床試驗數據，數據顯示，該藥物的回應率在 66% 到 75% 之間。考慮到該藥物的安全性、耐受性和易用性，我們將 15% 或 30% 作為費用減免的閾值，前提是患者依從性非常好。

Again, that's why we're so excited about being able to see early starts from all segments of the population because our experience has been that patients, regardless of their age, regardless of their severity or previous treatment history, once they get on the therapy, it's a low burden to take and the vast majority of patients report having some benefit.

再次強調，正因如此，我們才對能夠看到各個階層的人群儘早開始接受治療感到如此興奮，因為我們的經驗表明，無論患者的年齡、病情嚴重程度或既往治療史如何，一旦他們開始接受治療，治療負擔都很輕，而且絕大多數患者都表示從中受益。

Eric, do you want to provide a little bit more color on what we're hearing, in terms of defining responses and staying on therapy?

艾瑞克，你能否就我們聽到的內容，例如對治療反應的定義以及堅持治療等方面，再補充一些細節？

Yeah. Thanks, Matt. Thanks, Tazeen, for the question.

是的。謝謝你，馬特。也謝謝塔津的提問。

Clearly, what we're seeing is a very, very quick and rapid response from these Centers of Excellence. It's very early days but we're really pleased, not only with the interactions that we've had with the payers but also the way the physicians have adopted Sephience.

顯然，我們看到這些卓越中心的反應非常迅速。雖然現在還處於初期階段，但我們非常滿意，不僅對我們與支付方的互動感到滿意，也對醫生接受 Sephience 的方式感到滿意。

The clinical data that has been highlighted that we provided, including the AFFINITY long-term extension and the AMPLIFY data, has been leveraged not only with physicians but also with payers.

我們重點介紹的臨床數據，包括 AFFINITY 長期擴展數據和 AMPLIFY 數據，不僅被醫生所利用，也被支付方所利用。

The things we see right away is that the robust efficacy is seen within day; days and weeks. It's rapid-acting. I think that's something that patients and physicians look at.

我們最先看到的是，它的顯著療效能在幾天、幾週內顯現。它起效迅速。我認為這是患者和醫生都非常關注的一點。

The safety profile has been excellent. It's an ease of administration with once-daily oral administration. Physicians like that.

該藥安全性極佳，每日一次口服，服用方便，醫生們很喜歡這一點。

The value proposition to payers, right now, we have seen no major obstacles. No significant restrictions at all, right now, for access to Sephience.

就目前而言，我們尚未發現對支付方而言有任何重大障礙。目前，Sephience 的取得也沒有任何重大限制。

The teams have been really working very closely and productively with these payers, now covering more than 250 million lives.

這些團隊與這些支付方進行了非常密切且富有成效的合作，目前已覆蓋超過 2.5 億人。

The clinical data and the value proposition is clearly what has been driving some of these policies.

臨床數據和價值主張顯然是推動其中一些政策推出的因素。

It's early days now but these policies are very favorable. We're seeing physicians who are not only writing their first prescriptions but also we're seeing good momentum in October with refills.

現在還處於初期階段，但這些政策非常有利。我們看到醫生們不僅開始開出首張處方，而且10月的續方數量也呈現良好的成長動能。

Brian Abrahams, RBC Capital Markets.

Brian Abrahams，加拿大皇家銀行資本市場。

Hi. Good afternoon. Thanks for taking my question. Congrats on the launch.

您好，下午好。感謝您回答我的問題。祝賀產品發布成功。

I'm wondering if you could talk a little bit about just what the timeline is like from a new start form to a patient receiving a prescription and actually getting the drug, getting access? And then, how should we be thinking about the patients for whom there are start forms, new start forms, who are not yet on Sephience? Should we expect those patients to roll onto treatment in the fourth quarter? Thanks.

我想請您簡要介紹一下，從提交新的用藥申請表到患者收到處方並實際獲得藥物，整個流程的時間線是怎樣的？另外，對於那些已經提交了用藥申請表（新申請表）但尚未開始使用Sephience的患者，我們該如何看待？我們是否應該預期這些患者會在第四季開始接受治療？謝謝。

Thanks for the question, Brian. I think, again, so far, things have been moving through quite well. I can give a little bit more detail but I just want to give a particular mention to our PTC Cares team, which is our team of case managers who are incredibly experienced and provide a white-blood service.

謝謝你的提問，布萊恩。我想，到目前為止，一切進展都很順利。我可以提供更多細節，但我想特別提及我們的PTC關懷團隊，他們是由一群經驗極其豐富、服務一流的個案經理組成的團隊。

Again, they've with us through all the EMFLAZA days. They're battle-tested through that and are really at the front lines now of working with the patients, working with the physician's offices, working with the nurse practitioners who are writing a lot of the prescriptions to really get the start forms; and then, quickly get those start forms processed; and shepherd them through the system so we can get these patients on drugs as quickly as possible.

他們和我們一起經歷了EMFLAZA專案的所有階段。他們經受住了考驗，現在真正站在與患者、醫生辦公室以及開具大量處方的執業護士合作的第一線，以便盡快獲得起始表格；然後，快速處理這些起始表格；並引導他們完成整個流程，以便我們能夠讓這些患者盡快開始用藥。

Eric, do you want to provide some detail on the timeline?

艾瑞克，你能詳細說明一下時間安排嗎？

Yeah. Again, Brian, keep in mind, it's early days. It's only been a few weeks here. But we're really surprised to see that there's already a number of commercial payers that have written policies, highly favorable ones. This has really helped in terms of the speed from the time of [PSF] to actual fill.

是的。布萊恩，再次提醒你，現在還處於初期階段。我們才來幾週而已。但我們確實很驚訝地發現，已經有不少商業保險公司製定了非常有利的保單。這大大加快了從[PSF]到實際生效的整個流程。

The one thing we have to look at is, have there been denials or restrictions? We haven't seen that. In the case, it's very limited. If there are denials, there are no hard denials. Of course, we're working through those through medical necessity documentation.

我們必須關注的一點是，是否有拒付或限制？目前還沒有發現這種情況。就此案例而言，拒付的情況非常有限。即使有拒付，也沒有硬性拒付。當然，我們會透過醫療必要性證明文件來解決這些問題。

As Matt said, our PTC Cares team, very experienced at managing this for the last eight-and-a-half years in DMD. We're working through all of these very, very quickly.

正如馬特所說，我們的PTC關懷團隊在過去八年半的時間裡，在DMD（杜氏肌肉營養不良症）領域積累了非常豐富的管理經驗。我們正在非常迅速地處理所有這些問題。

I would say that, right now, we're seeing somewhere -- depending on the plan, whether it's a commercial plan, it could actually be from the time of PSF to fill, could be days. On average, we're somewhere between two to four weeks. That's really depending on the plan.

我認為，目前來看，具體時間取決於方案，如果是商業方案，從每平方英尺報價到最終成交可能只需要幾天。平均而言，大約需要兩到四周。這確實取決於方案的具體情況。

We would anticipate that many of the government plans Medicare, Medicaid -- it's probably going to take a little longer for them to write and finalize their policies. But, even then, we're seeing patients on Medicare, Medicaid, and TRICARE being reimbursed.

我們預計，許多政府計劃，例如聯邦醫療保險（Medicare）和醫療補助（Medicaid），可能需要更長時間才能製定和最終確定其政策。但即便如此，我們也看到參加聯邦醫療保險、醫療補助和TRICARE計畫的患者已經獲得了報銷。

Brian Cheng, J.P. Morgan.

Brian Cheng，摩根大通。

Hey, guys. I just want to pass on my congrats here, as well. Thanks for taking our question.

嘿，各位。我也想在這裡表達我的祝賀。感謝你們回答我們的問題。

Just on the [521] start form number, how should we think about the rate of start form that is coming in? I think earlier you said that October, you're seeing sustained momentum. Can you provide just more color on that comment? Is that specifically referring to the pace of uptake in start form or access with payers? What is the momentum specifically based on? Thank you.

僅就[521]份起始表格的數量而言，我們該如何看待起始表格的提交速度？我記得您之前提到過，10月份的成長勢頭持續強勁。您能否就此做進一步說明？這具體是指起始表格的提交速度，還是指與支付方的對接速度？這種成長勢頭具體基於哪些因素？謝謝。

Thanks for the question, Brian.

謝謝你的提問，布萊恩。

There's not much more color we can provide because we are still in very much early days, other than say we've seen pretty consistent rates in the start forms and patients getting on to drug. We'll continue to watch this as we head to the rest of the fourth quarter.

由於目前仍處於早期階段，我們無法提供更多信息，只能說我們看到起始治療申請和患者用藥率都相當穩定。我們將繼續密切關注第四季度的進展。

Of course, there's Thanksgiving; there's Christmas; there's holidays; and things which may or may not affect the dynamics. But, again, for now, things seem to be, from the start until now, pretty consistent.

當然，還有感恩節、聖誕節、各種節日，這些都可能影響也可能不影響現狀。但總的來說，從一開始到現在，情況似乎都相當穩定。

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Hi, guys. Thanks for taking the questions. Let me say congrats, too. A couple on Sephience.

大家好。感謝你們回答問題。也請容許我祝賀一下。其中有幾位在Sephience上取得了成功。

First, just can you help us with the narrowing of the full-year guide? Is that solely tied to Sephience? Any other moving pieces you'd call out, like the legacy portfolio coming in ahead this quarter?

首先，您能否幫我們縮小一下全年業績指引的範圍？這是否完全取決於 Sephience？還有其他需要注意的因素嗎？例如，本季可能會優先考慮的傳統業務組合？

Second, just for those Centers of Excellence, I think you called out 104 of them, can you talk maybe in numbers how far you've penetrated those centers; what the opportunities left are within those? Thanks.

其次，就您所提到的104個卓越中心而言，能否用數字說明您目前在這些中心的滲透程度，以及這些中心還有哪些發展機會？謝謝。

Absolutely, Judah. Thanks so much for the questions.

當然可以，猶大。非常感謝你的提問。

Pierre, do you want to talk first, briefly, about guidance and what went into that? And then, Eric, if you want to talk a little bit about the Centers of Excellence and the high penetration rate we've seen?

皮埃爾，你想先簡單談談指導原則以及其中的緣由嗎？然後，埃里克，你想稍微談談卓越中心以及我們看到的高滲透率嗎？

Yes. On the guidance, I would say this is the upper end of our initial guidance, which highlights our confidence in our ability to execute on our launch and all our products.

是的。關於業績預期，我認為這是我們最初預期範圍的上限，這凸顯了我們對產品上市及所有產品執行能力的信心。

The delta is with the EMFLAZA. We always talked about the delta being EMFLAZA. That's the main delta from the 750 to the 800.

差別在於EMFLAZA。我們一直都說差別在於EMFLAZA。這是750到800的主要差異。

Eric, do you want to talk about PKU?

艾瑞克，你想談談苯酮尿症嗎？

Yeah. Let me just add in there because when we started the year, we were [600] to [800], thinking that we could have (inaudible). EMFLAZA, last year, came in at [$208 million].

是的。我補充一下，因為年初的時候，我們估計可以達到 6 億到 8 億美元，當時覺得我們能做到（聽不清楚）。去年，EMFLAZA 的營收是 2.08 億美元。

The question was, with all the generic entrants, where would that be? Would we see a rapid decline? And so a lot of that wide gap was around in EMFLAZA. Now that we've come through three quarters, we're seeing despite there being six generics, we're still seeing consistent performance from EMFLAZA, which gives us the confidence, along with the early Sephience numbers, as well as the remaining portfolio continuing to do well to narrow to that upper end of the guidance of [750] to [800].

問題是，隨著眾多仿製藥的湧入，市場會如何改變？我們會看到市場快速下滑嗎？因此，市場與原廠藥之間的巨大差距很大。現在，三個季度過去了，儘管有六款仿製藥上市，EMFLAZA 的表現依然穩定，這讓我們更有信心，再加上 Sephience 早期公佈的數據，以及其他產品組合的持續良好表現，最終將市場規模縮小到此前預期的上限 [750] 至 [800]。

To answer your question regarding the Centers of Excellence, we have called on every Center of Excellence. There's 100% awareness of Sephience in each one of these centers. We've received prescriptions from all of them.

關於您提出的卓越中心的問題，我們已經聯繫了所有卓越中心。每個中心都100%了解Sephience。我們也收到了所有中心開立的處方。

However, what we're really interested in is how many of these centers have actually prescribed more than one. We've seen about two-thirds of these centers actually prescribe more than one prescription.

然而，我們真正感興趣的是，這些中心中有多少家實際上開出了不止一張處方。我們發現，大約三分之二的中心實際上開出了不只一張處方。

Of course, there are some that are a little higher concentration than others. But, overall, I think the Centers of Excellence are really bringing in patients at a nice cadence. We're working with each one of them to increase the volume of patients to get on Sephience.

當然，有些中心的患者濃度略高於其他中心。但整體而言，我認為卓越中心接收患者的速度相當不錯。我們正在與每個中心合作，以增加接受 Sephience 治療的患者數量。

Clara Dong, Jefferies.

克拉拉‧董，傑富瑞。

Hi. Thanks for taking our question. Really, congratulations on a great launch.

您好。感謝您回答我們的問題。真的，恭喜你們發表會圓滿成功。

Can you share a little bit more details on the patient profile for new prescribers and, specifically, are you seeing any initial uptake more concentrated in one group than the other?

您能否詳細介紹一下新處方醫生的患者概況，特別是，您是否發現某個群體比其他群體更容易接受新處方？

I also just want to get your updated thoughts on the size of the overall opportunity, given such a very strong early launch movement to really ensure the atmosphere? Thank you.

我還想了解您對整體市場機會規模的最新看法，鑑於早期階段的強勁勢頭，能否真正營造出良好的市場氛圍？謝謝。

Clara, thanks so much for the questions.

克拉拉，非常感謝你的提問。

Look, again, it's early days so it's really hard to give specific numbers on the breakout of how many from each segment but I think what we're seeing, importantly, is contributions from all segments. Again, as we said, we're seeing treatment-naïve patients; we're seeing switches from other therapies, including (inaudible). We have a full age range. I think we have patients down as young two to three months of age. We have a patient as old as 79 years of age, who's been prescribed.

再次強調，現在還處於早期階段，所以很難給出每個細分群體具體人數的統計數據，但我認為重要的是，我們看到所有細分群體都有所貢獻。正如我們所說，我們看到既有初治患者，也有從其他療法轉而來的患者，包括（聽不清楚）。我們的患者年齡跨度很大。我記得最小的患者只有兩三個月大，最大的患者已經79歲了，他也接受了這種治療。

So I think what we're seeing is this full spectrum of patients getting put on therapy. As we get further into the launch, I think we'll be able to give more concrete metrics on penetration into each segment. But, again, the important point is we're seeing that we are getting patients from every possible segment.

所以我認為我們目前看到的是各階層的患者都在接受治療。隨著產品上市的深入，我們將能夠提供更具體的指標，衡量產品在各個細分市場的滲透率。但再次強調，重點是我們看到患者來自各個可能的群體。

And so the start has been great. I think it's still a little too soon for us to give revenue projections. What we've said all along is we've always thought of Sephience as a highly differentiated rare disease therapy and, therefore, as we think about the market opportunity with 17,000 patients in the US, we think of it, again, very much like how you would think about with a new, highly differentiated, safe, and well-tolerated therapy with a strong data package that can provide potential benefit to the full spectrum of that 17,000 patients.

所以，開局非常順利。我認為現在給出營收預測還為時過早。我們一直以來都強調，Sephience 是一種高度差異化的罕見疾病療法。因此，當我們考慮美國17,000名患者的市場機會時，我們的想法與看待一種全新的、高度差異化的、安全且耐受性良好的療法非常相似，這種療法擁有強大的數據支持，能夠為這17000名患者帶來潛在的益處。

Paul Choi, Goldman Sachs.

Paul Choi，高盛。

Hi. Thank you. Congrats on the early progress with the Sephience launch.

您好。謝謝。恭喜Sephience發布初期進展順利。

I want to ask with regard to Europe, any additional coverage updates you could provide for both Germany and the other major markets there?

我想問一下關於歐洲方面，您能否提供德國及其他主要市場的最新報道資訊？

My second question is, as you think about the outlook for '26, it looks like you guys are in a position to start generating leverage maybe ahead of Street expectations, can you maybe just comment on the trajectory of OpEx and just how you're thinking about it, perhaps, versus where consensus estimates are?

我的第二個問題是，在展望 2026 年時，你們似乎已經具備了開始創造槓桿效應的能力，或許比華爾街的預期還要早。你們能否談談營運支出的軌跡以及你們是如何看待它的，並與普遍預期進行比較？

Thank you for taking the questions.

感謝您回答這些問題。

Thanks for the questions, Paul. Eric, do you want to take the first, just about how dynamics are playing in Europe? And then, Pierre, do you want to talk a little bit about how we're thinking about the balance sheet?

謝謝你的提問，保羅。艾瑞克，你想先回答第一個問題嗎？就談談歐洲當前的經濟動態吧。然後，皮埃爾，你想簡單談談我們是如何看待資產負債表的嗎？

Yeah. Thanks for the question, Paul.

是的。謝謝你的提問，保羅。

With Germany, we're still in the free pricing period at this point in time. Obviously, we'll be looking at benefit assessment and going through the (inaudible) process, which will take it for approximately another six months into 2026. That process, right now, will keep going.

目前，德國仍處於免費定價期。顯然，我們將進行效益評估並完成相關流程，這將需要大約六個月的時間，直到2026年。目前，該流程仍在進行中。

We have, in addition to that, actually submitted (inaudible) dossiers in most of the countries in southern Europe. We're working in parallel there with a number of their mechanisms for early access and name-patient programs that are being paid at prices which are equivalent to the German price.

除此之外，我們實際上已向南歐大多數國家提交了（聽不清楚）申請文件。我們正在與這些國家的多個早期准入機制和指定患者項目合作，這些項目的支付價格與德國的價格相當。

We've also opened up other markets in Central and Eastern Europe, as well. Those countries also have mechanisms. We've received prescriptions, as well, in the Middle East; as well as in Latin America.

我們也開拓了中歐和東歐的其他市場。這些國家也有相應的機制。此外，我們也獲得了中東和拉丁美洲市場的許可。

Again, we are working through all the main patient programs country by country, as they have specific rules. But we're very pleased so far with the progress.

我們正在逐一研究所有主要的患者項目，因為每個國家都有各自的規定。但到目前為止，我們對進展非常滿意。

Keep in mind that Europe is usually a relative -- southern Europe, particularly, is a long-term process: somewhere between 6 to 12 months between (inaudible) assessment and then, final price negotiations.

請記住，歐洲通常是一個相對的概念——尤其是南歐，這是一個長期的過程：從（聽不清楚）評估到最終價格談判，大約需要 6 到 12 個月。

In terms of OpEx trajectory, I will say a few things.

關於營運支出軌跡，我想說幾點。

Number one, as usual, we will provide 2026 guidance at J.P. Morgan. It's a bit early. However, you should expect OpEx to decline.

首先，和往常一樣，摩根大通將提供2026年的業績指引。現在下結論還為時過早。不過，預計營運支出將會下降。

Jon Lee, Truist Securities.

Jon Lee，Truist Securities。

Really, congrats on the Toronto launch. Thanks for taking our questions.

真的，恭喜多倫多發表會圓滿成功！感謝你們回答我們的問題。

I was a little bit surprised to hear that you're seeing switches, even from (inaudible). Is that an outlier or is there any reason why someone on (inaudible) would consider a BH4 or even Sephience? Or are there people who are on Sephience who really should be on Sephience?

聽到你看到有人換耳機，甚至來自（聽不清楚）的用戶，我有點驚訝。這只是個例嗎？還是說（聽不清楚）的用戶有什麼理由會考慮BH4甚至Sephience？或者說，Sephience用戶中有些人其實比較適合Sephience？

A quick follow-up on how quickly could you launch in Japan, post-approval, by year end; and where would you put the peak opportunity in Japan vis-à-vis US versus EU? I think you said that at least [$1 billion] in US and [$500 million] in EU. I'm just curious where you would put that in Japan in that spectrum. Thank you.

請問，產品核准後，您預計多久能在年底前在日本上市？另外，您認為日本的市場潛力與美國和歐盟相比如何？我記得您說過美國至少有10億美元的市場規模，歐盟至少要5億美元。我很好奇，您認為日本的市場規模在這個範圍內處於什麼位置？謝謝。

Joon, thanks so much for the questions.

Joon，非常感謝你的提問。

On your first question, regarding (inaudible) switches, look, we're just reporting what we're seeing and hearing from the field. Again, it's early days to say what's going to be a trend or not a trend.

關於你的第一個問題，關於（聽不清楚）開關，我們只是把從現場看到和聽到的情況如實報告。再說一遍，現在斷言什麼會成為趨勢還為時過早。

But what we have heard from KOLs -- and I think several folks who've done KOL calls have shared similarly -- the realization that the physicians and nurse practitioners and care teams have that Sephience can provide significant benefit to patients with severe mutations, including patients with (inaudible), are zero, which is the most severe genotypes, classical PKU patients.

但我們從 KOL 那裡聽到的——而且我認為一些進行過 KOL 電話會議的人也表達了類似的觀點——醫生、執業護士和護理團隊意識到 Sephience 可以為患有嚴重突變的患者帶來顯著益處，包括患有（聽不清）0 的患者，這是最嚴重的基因型，即經典 PKU 患者。

For them, it's the question of, can we, given, once a day, well-tolerated oral therapy that can deliver significant reductions in phenylalanine the ability to liberalize diet -- and when you consider that opportunity with Sephience, that is something that physicians want to try, certainly considering the potential tolerability profile of (inaudible).

對他們來說，問題是，如果每天一次，口服藥物耐受性良好，能夠顯著降低苯丙胺酸水平，我們能否放寬飲食限制——考慮到 Sephience 的這種可能性，醫生們當然想要嘗試，尤其考慮到其潛在的耐受性（聽不清楚）。

But, again, this is what we're hearing; also, again, emphasizing that we're hearing that a number of physicians are saying their intent is to try all patients on Sephience, knowing that, of course, not every patient's going to respond but certainly given the fact that the severe patients, classical BKU patients, can respond, can have feed-lowering, can liberalize their diet, and the once-a-day oral, well-tolerated profile of Sephience really makes that the attractive place to start.

但是，我們再次強調，我們聽到的是這樣的；此外，我們再次強調，我們聽到許多醫生表示，他們打算讓所有患者都嘗試使用 Sephience，當然，他們也知道並非每個患者都會有反應，但考慮到重症患者，即典型的 BKU 患者，可能會有反應，可以減少餵養量，可以放寬每天一次飲食，使其耐受性良好，這一點確實使其成為一個有吸引力的起點。

And then, Eric, do you want to talk a little bit about the timing of Japan launch and the dynamics there and pricing?

那麼，艾瑞克，你想稍微談談日本市場的上市時間、市場動態和定價嗎？

Sure. Yeah. Absolutely. Yeah. Japan, for us, is an important market; a key market. This will be our first approval. We're anticipating that before the end of the year. Sephience -- we're anticipating, like the US and Europe, a very broad label.

當然。沒錯。絕對的。是的。日本對我們來說是一個重要的市場，一個關鍵市場。這將是我們首次獲得日本市場的批准。我們預計在年底前獲得批准。 Sephience－我們預計，就像在美國和歐洲一樣，日本的藥品標籤會非常廣泛。

Prevalence, right now, for PKU patients is approximately 1,000 patients. However, while it's a smaller market in terms of overall prevalence, it's very high value. Both (inaudible), as well as (inaudible), are approved.

目前，苯酮尿症患者的盛行率約為1000人。雖然從整體盛行率來看，這是一個較小的市場，但其價值卻非常高。兩種藥物（聽不清楚）以及（聽不清楚）均已獲批准。

We anticipate the price of Sephience to be at a premium to that, given our clinical data. which would make that higher price than in Germany and higher than the US.

根據我們的臨床數據，我們預計Sephience的價格會高於這個水平，這將使其價格高於德國和美國。

We have a full team that is experienced and that is already on the ground, right now, ready to promote Sephience once it is approved. We will likely be in discussions for the next few months to finalize the price.

我們擁有一支經驗豐富的完整團隊，他們目前已在現場待命，一旦 Sephience 獲得批准，我們將立即展開推廣工作。未來幾個月，我們可能會就價格進行最終商討。

There will be one discussion. It should probably be done through that period of negotiation by the first quarter. At that point in time, we'll be able to launch, fully reimbursed.

會有一次討論。應該會在第一季透過談判完成。屆時，我們就可以啟動項目，並獲得全額報銷。

So Japan is incredibly important to the overall sequence. We anticipate approvals in other markets, as well. But we'd be maintaining a very narrow pricing corridor, which makes Japan very attractive.

因此，日本市場在整個審批流程中至關重要。我們預計其他市場也會獲得批准。但我們會維持非常窄的價格區間，這使得日本市場極具吸引力。

Gina Wang, Barclays.

吉娜·王，巴克萊銀行。

Thank you for taking my questions. I also wanted to -- congrats on the super impressive first quarter.

感謝您回答我的問題。另外，我還想祝賀貴公司第一季取得了非常優異的成績。

Regarding of -- since we are talking about price, I did my quick math. You deliver $19.6 million, you treated 341 patients. So this is two months of the full quarter. If my math correct, net price is about $350,000. Is that the right calculation? Should we think about the net price? Is at the right benchmark. This is the first question.

關於價格——既然我們在討論價格，我簡單算了一下。你們的營業額是1960萬美元，治療了341位病患。這是前兩個月的季度數據。如果我的計算沒錯，淨價大約是35萬美元。這個計算對嗎？我們應該考慮淨價嗎？它是否處於合適的基準水平？這是第一個問題。

And then, second question is, what is the average time for a patient on drug, right now? Have you seen the retention of the patient so far? I know it's due very early but have you seen any, like, so far, are all the patient doing very well on the drug?

第二個問題是，目前患者服用藥物的平均時間是多久？您目前觀察到患者的用藥依從性如何？我知道現在問這個問題還為時過早，但您目前觀察到的情況是，所有患者服用藥物後都進展順利嗎？

And then, lastly, very quickly, how do you book the revenue? Is that the monthly review? And then, every month, one patient review, you will book the revenue?

最後，快速問一下，你們如何確認收入？是透過月度審核嗎？然後，每個月根據一位病患的審核結果來確認收入？

Great, Gina. Thank you very much for your questions.

太好了，吉娜。非常感謝你的提問。

On the first one, respectfully said, I think your math is a bit off, just because it may be that the patients -- you have to consider when we actually were able to ship the first that shift the first drug, which wasn't from the start of the -- it wasn't from approval. It's when we were able to do launch. And then, also, of course, different patients are coming on at different times.

關於第一個問題，恕我直言，我認為您的計算可能有點偏差，因為患者的情況可能有所不同——您需要考慮我們實際能夠交付第一批藥物的時間，這會影響到第一種藥物的上市時間，而這並非從藥物獲批之初就開始計算，而是從我們能夠正式上市之時開始計算。此外，當然，不同患者的用藥時間也各不相同。

I'll let Eric give more color on how we're thinking about gross-to-net at this point. But we've talked about the (inaudible) being somewhere around [$490,000], with an expectation that the average patient is approximately 45 kilograms.

我會讓艾瑞克更詳細地解釋我們目前是如何考慮毛利和淨利的。但我們之前討論過，（聽不清楚）大概在49萬美元左右，預計患者的平均體重約為45公斤。

What we're seeing is that we are, in fact, in that ballpark at this point, which, again, is not surprising. But it's also early days.

我們現在看到的是，我們實際上已經處於那個大致範圍內，這並不令人意外。但現在還處於早期階段。

Do you want to talk a bit, Eric, just any clarity you want to give about how we're thinking about gross-to-net over time, booking revenue, and such?

艾瑞克，你想稍微談談嗎？你想就我們如何看待毛利潤到淨利潤的變化、預訂收入等等方面做些澄清嗎？

Yeah. Sure. First of all, we book revenue and we recognize revenue and we ship to our specialty pharmacies. We book our revenues immediately in Germany because we ship directly to pharmacies immediately after a prescription is written. There's very little inventory that's actually kept. It's usually just on demand as needed. So that's one thing.

是的，當然。首先，我們會確認收入，然後向我們的專科藥房發貨。在德國，我們會在處方開出後立即確認收入，因為我們會立即將藥品運送給藥房。實際上，我們幾乎不保留庫存，通常都是按需發貨。這是其中一點。

But, importantly, around the gross-to-net, I think it'll be important -- what drives that is, of course, in the US, our payer mix. The payer mix, right now, is slightly more favorable commercial. We anticipated that. That's generally the case with most orphan launches, anyway because commercial plans tend to write their policies quicker and we've had very favorable policies in the beginning.

但更重要的是，就毛利與淨利的比率而言，我認為關鍵在於——當然，在美國，影響這一比率的因素是我們的支付方結構。目前的支付方結構略微偏向商業保險。我們預料到了這一點。無論如何，大多數孤兒藥上市都會出現這種情況，因為商業保險的保單製定速度往往更快，而且我們一開始就獲得了非常有利的保單。

Now, it's still early stages. We're seeing that PKU patients, in general -- and the PKU population -- is more skewed to commercial anyway. And so that's what's helping in terms of the favorability of gross-to-net.

目前還處於早期階段。我們發現，總體而言，苯酮尿症患者——以及苯酮尿症患者群體——本身就更傾向於商業用途。因此，這有助於提高毛利潤與淨利潤的比值。

However, you also know that Medicare, Medicaid, will be writing their plans; and TRICARE and a number of other government plans will be finalizing them over the next few weeks. We've guided that ultimately when this stabilizes, this will be about a 65 to 35 patient mix; meaning, 65% is commercial. We're tracking a little higher than that right now but that's as expected.

不過，您也知道聯邦醫療保險（Medicare）和醫療補助（Medicaid）正在製定各自的計劃；而TRICARE和其他一些政府計劃也將在未來幾週內最終確定方案。我們預計，最終當情況穩定下來時，商業保險和醫療保險的患者比例將約為65:35，也就是說，65%的患者是商業保險參保者。目前我們追蹤到的比例略高於這個數字，但這也在預期中。

And then, Eric, do you want to also comment on what we're seeing in terms of refill dynamics? As Gena -- as you said, it is early days so it's really hard to see that.

那麼，艾瑞克，你能否也談談我們目前看到的補貨情況？正如吉娜所說，現在還處於早期階段，所以很難看出這一點。

This is very early days. Interestingly enough, the vast majority of patients that we've seen, both in Germany as well as in the US, the ones that were put on prescriptions in August or early September, we're seeing refills, the vast majority of them.

現在還處於非常早期的階段。有趣的是，我們看到的絕大多數患者，無論是在德國還是在美國，那些在8月或9月初獲得處方的患者，絕大多數都在續藥。

It's interesting, more than not, that is that these physicians and the healthcare providers who have prescribed Sephience, for the vast majority of them, these have been patients who have been the most challenging. So they're the ones who are poorly controlled; the ones who have failed on previous therapies.

有趣的是，這些開立賽芬寧處方的醫生和醫療保健人員，絕大多數都是在治療最棘手的病人。這些患者病情控制不佳，先前的治療也都失敗了。

And so when we look at that patient population and we see the results and fairly good momentum in terms of refill rates, that gives us some real good confidence moving forward.

因此，當我們觀察該患者群體，看到結果以及續藥率方面相當良好的勢頭時，這給了我們很大的信心去向前邁進。

Sami Corwin, William Blair.

薩米·科溫，威廉·布萊爾。

Hey, there. I want to share my congrats, as well, on a strong launch.

嗨，大家好。我也想祝賀你們取得了巨大的成功。

Matt, I know you said that the average weight is falling within the ballpark of 45 kilograms but can you provide a bit more granularity on if you're seeing these initial patients as skewing more towards pediatric or adult?

馬特，我知道你說過平均體重在 45 公斤左右，但你能否更具體地說明一下，你看到的這些早期患者更偏向兒童還是成人？

And then, switching gears a little bit, given the recent news from a competitor, how are you and Novartis thinking about the registrational trial for Huntington's disease? What are you hoping to get out of that meeting with FDA? Thank you.

然後，稍微換個話題，鑑於競爭對手最近發布的消息，您和諾華公司對亨廷頓舞蹈症的註冊試驗有何看法？您希望從與FDA的會面中獲得什麼？謝謝。

Yeah. Thanks so much for the question, Sami.

是的。非常感謝你的提問，薩米。

On your first question, we're seeing a good mix. As we said, we're seeing this full age spectrum. We've had infants all the way up to septuagenarians, which is pretty interesting. Also, I'd say, on average, we're -- late adolescent. 17 years old, I think, is probably where we are, in terms of an average. Again, things that we pretty much expected. Again, still early days. We'll know better as time moves on.

關於你的第一個問題，我們看到的人群組成很均衡。正如我們所說，我們涵蓋了各個年齡層。從嬰兒到七十多歲的老人都有，這很有趣。另外，平均而言，我認為我們的人群正處於青春期後期。 17歲左右，我想，這大概是我們的平均年齡。這些都和我們預期的差不多。當然，現在還處於初期階段。隨著時間的推移，我們會了解更多情況。

In terms of HD, I mean, look, we all saw the news yesterday. Look, we have a very different therapy and a very different program. Votoplam is an oral -- small molecule. We've conducted a placebo-controlled study that has over 140 patients. We've been able to provide proof-of-target engagement and methods of action, dose-dependent effects, consistent safety profile in that large population, and a protocol for long-term extension that pre-specified that we'll be doing a natural history comparison to determine treatment benefit over the long term.

就亨廷頓舞蹈症而言，我的意思是，大家都看到了昨天的新聞。我們採用的療法和方案截然不同。 Votoplam 是一種口服小分子藥物。我們進行了一項安慰劑對照研究，納入了超過 140 名患者。我們已經證實了藥物標靶結合和作用機制、劑量依賴性效應、在如此龐大的人群中具有一致的安全性，並且制定了長期擴展方案，其中預先規定我們將進行自然病程比較，以確定長期治療獲益。

So we think we're in a different context here. We expect that all patients across 24 months in the spring will analyze those data. And then, with Novartis, (inaudible) make a plan to go to FDA to talk about the potential for accelerated approval based on those data.

所以我們認為現在的情況有所不同。我們預計春季將對過去24個月內所有患者的數據進行分析。然後，我們將與諾華公司（聽不清楚）共同製定計劃，向FDA提交申請，探討基於這些數據獲得加速審批的可能性。

The fourth-quarter meeting that we talked about has two objectives, right? One is to talk about what a path to accelerated approval could look like but then, also to align on what that efficacy trial would look like, whether that's a Phase 3 approval trial or whether that would be done as a confirmatory study in the context of potential accelerated approval.

我們之前提到的第四季會議有兩個目標，對吧？一是討論加速審批的途徑，二是確定療效試驗的具體形式，是進行三期審批試驗，還是在潛在加速審批的背景下進行驗證性研究。

But again, I think we're in a very different framework with Votoplam.

但我認為，我們與 Votoplam 的合作框架截然不同。

Joe Schwartz, Leerink Partners.

Joe Schwartz，Leerink Partners。

Great. Thanks for taking my question. Congrats on a strong launch, so far.

太好了。謝謝你回答我的問題。祝賀你們目前為止的發布非常成功。

Can you quantify for us how the response rate for Sephience is tracking in the real world, based on refills or any other metrics you have? I heard Eric mention you have good momentum in October with refills. It would be helpful to hear how the response rate is tracking, relative to AFFINITY in the real world.

您能否根據續訂率或其他指標，量化 Sephience 在實際應用中的回應率？我聽 Eric 提到，10 月的續訂率成長勢頭良好。如果能了解 Sephience 的回應率與 AFFINITY 相比在實際應用中的表現，那就太好了。

Yeah. Joe, I think it's too early for us to give those numbers. Again, we've started with the first shipment of drug in August. It's really too soon now to give any granularity detail on that. I think, as we get further into the launch, we may have a better handle on that, other than the color we provided that we're hearing very good response rates and the commentary Eric gave on the refills thus far, though, again, with the caveat that it's all very early.

是的，喬，我覺得現在給出具體數字還為時過早。再說一遍，我們八月才開始發貨，現在提供任何細節資訊都為時過早。我想，隨著上市進程的推進，我們或許能更好地掌握情況，除了我們之前提到的反饋非常好，以及埃里克對目前續藥情況的評論之外，但同樣需要注意的是，這一切都還處於非常早期的階段。

Peyton Bohnsack, TD Cowen.

佩頓·博恩薩克，TD·考恩。

Thank you, guys. Congratulations on a strong launch.

謝謝各位。祝賀你們發布成功。

Talking, maybe, about the Sephience launch in Brazil, assuming it's approved, can you quantify the opportunity for us? And then, maybe talk about any difference in patient population in terms of history or disease severity. And then, what the steps are from a potential improvement to a launch. Thanks.

假設Sephience在巴西獲批上市，您能否量化一下它對我們的市場機會？另外，能否談談患者群體在病史或疾病嚴重程度方面是否有差異？還有，從潛在的療效提升到產品上市，具體需要哪些步驟？謝謝。

Sure, Peyton. As we said, we expect the Brazil authorization would come this quarter. We're still expecting it to come this quarter.

當然，佩頓。正如我們所說，我們預計巴西的授權會在本季到位。我們仍然預計會在本季到位。

I'll let Eric talk a little bit about the dynamics in Brazil and what happens between approval and how we get onto the market there.

我將讓艾瑞克談談巴西市場的動態，以及從獲得批准到我們如何進入巴西市場之間會發生什麼。

Yeah. Brazil will be an important market for us. I think there's a lot of differences in terms of how Brazil approaches PKU differently than, perhaps, the US and Europe and other markets. There are certain states that do newborn screening but not across the board.

是的，巴西對我們來說將會是一個重要的市場。我認為巴西在應對苯酮尿症方面與美國、歐洲和其他市場有許多不同之處。巴西有一些州會進行新生兒篩檢，但並非所有州都會這樣做。

Patients are going to be likely going to be diagnosed. They're going to be a little older in age. They're going to be adolescents, in some places.

患者很可能會確診。他們的年齡會稍大。在某些地方，他們甚至是青少年。

But, in terms of the process itself, we're first going to have registration. Obviously, we have a very experienced team in there that's been managing, right now, four rare disease products over the last 10 years. So we understand the dynamics, whether it's small molecules, DMD, metabolics with [STS], (inaudible), all of that.

但就流程本身而言，我們首先要進行註冊。顯然，我們擁有一支經驗豐富的團隊，他們在過去十年中一直負責管理四種罕見疾病產品。因此，我們了解其中的動態，無論是小分子藥物、杜氏肌肉營養不良症 (DMD) 藥物，還是伴隨[STS]的代謝性疾病藥物（聽不清楚），等等。

As we know, right now, the experience of that team is first going to get -- after the registration, will get pricing from (inaudible). That will be referenced to the prices that will be currently available at the time, which will be Germany, Japan, and the US, and other markets where we maintain a narrow pricing corridor.

我們知道，目前團隊的體驗首先取決於註冊後的價格（聽不清楚）。該價格將參考當時的市場價格，包括德國、日本、美國以及其他我們定價區間較窄的市場。

There will be a process afterwards by which, once the product is approved, we already will be working with many of the key centers to ensure that patients are diagnosed and onto therapy. Some of these processes may include some judicialization. But, for the most part, we believe that the opportunity will be very, very similar to other key markets.

產品獲批後，我們將與多家關鍵醫療中心合作，確保患者得到診斷並接受治療。其中一些流程可能涉及司法程序。但總的來說，我們相信，這項機會與其他主要市場非常相似。

Certainly, the number of patients -- well over 6,000 patients, right now -- means that there is a significant opportunity. And then, of course, diagnosing new patients at younger ages will be another key area.

當然，目前患者人數已超過6000人，這意味著存在巨大的發展機會。此外，對較年輕的患者進行診斷也將是另一個關鍵領域。

But I would go back and say that Brazil is a very important market. Our experience there with rare disease means that we will be working very closely to bring this on board in, likely, in revenue in 2026.

但我還是要說，巴西是一個非常重要的市場。我們在巴西罕見疾病領域的經驗意味著，我們將與巴西密切合作，爭取在2026年將巴西市場納入我們的商業版圖，並有望帶來相應的收入。

Luke Herman, Baird.

盧克·赫爾曼，貝爾德。

Hi, team. Congrats on the quarter and the supply and launch progress.

大家好，祝賀團隊。恭喜本季業績以及供應和產品發表的進展。

Just a follow-up on patient weight, thus far. Given the commentary around trying new foods, do you think diet liberalization can be a tailwind to patient weight over time, particularly for those starting with poorly controlled disease?

關於患者體重，我有個後續問題。考慮到大家對嘗試新食物的看法，您認為隨著時間的推移，飲食習慣的放寬是否會有利於患者體重的減輕，特別是對於那些病情控制不佳的患者？

Luke, thanks so much for the question.

盧克，非常感謝你的提問。

It's hard to say. I would say that not all PKU patients are -- many individuals with PKU have average typical weights for their height. They're not all underweight. In fact, we have patients who've had lifelong PKU who have much greater body weight than one would anticipate.

很難說。我認為並非所有苯酮尿症患者都是如此——許多苯酮尿症患者的體重與其身高相符，屬於正常範圍。他們並非都體重過輕。事實上，我們有一些終生患有苯酮尿症的患者，他們的體重遠超預期。

In terms of the diet liberalization, this is something we haven't thought about in terms of a tailwind. What we've been thinking a lot about with diet liberalization is making sure we're working very closely with the dietitians and nutritionists at the PKU centers so that we ensure that when patients do begin to liberalize their diet, they do so in a very steady, gradual way. And then, it's being done very thoughtfully in terms of the diets and the nutrition quality of the foods being introduced into an individual's diet.

就飲食放寬而言，我們並沒有將其視為順風之舉。我們一直在思考的是，如何與苯酮尿症中心的營養師和營養師緊密合作，確保患者在開始放寬飲食時，能夠以非常穩定、循序漸進的方式進行。此外，在飲食方案的選擇和引入食物的營養品質方面，我們也進行了非常周全的考慮。

So I think we're thinking of it more in terms of setting individuals up for success, the ability to liberalize their diet, doing so in a gradual fashion, which is not such an easy thing sometimes, right?

所以我覺得我們更多是從幫助個人獲得成功、逐步放寬飲食習慣的角度來考慮這個問題，這有時並不是一件容易的事，對吧？

If you have, an individual, a teenager who is going to have a hamburger for the first time, they may want to have a hamburger for lunch, a pizza for dinner. But this has to be done in a very thoughtful, managed way,

如果你有一個青少年，他/她第一次吃漢堡，他/她可能想午餐吃漢堡，晚餐吃披薩。但這必須以非常周全、有計劃的方式進行。

We've, again, worked very hard with the Centers of Excellence to ensure that there's protocols for diet liberalization so that we set all patients up for success so they can enjoy as much diet liberalization as possible and still maintain control of phenylalanine.

我們再次與卓越中心密切合作，確保制定飲食自由化的方案，以便讓所有患者都能成功，從而盡可能地享受飲食自由化，同時也能控制苯丙胺酸水平。

Great. Thank you.

太好了，謝謝。

That concludes today's question and answer session.

今天的問答環節到此結束。

I'd like to turn the call back to Dr. Klein for closing remarks.

我想把電話轉回給克萊恩博士，請他作總結發言。

Thank you, all, again for joining the call today.

再次感謝各位今天參加電話會議。

We're excited about the performance of the quarter and the strong start to the Sephience launch. This really reflects a lot of work by our team over the past two years to get ready for this launch and, really, a strong desire to ensure that we could provide what we view as a very efficacious, safe, and well-tolerated therapy to as many individuals with PKU as possible.

我們對本季的業績以及Sephience上市的強勁開局感到非常興奮。這充分體現了我們團隊過去兩年為此次上市所做的大量準備工作，以及我們渴望為盡可能多的苯酮尿症患者提供我們認為高效、安全且耐受性良好的療法的強烈願望。

Thank you, all, again. We look forward to keeping you updated on the launch as we progress.

再次感謝各位。我們將持續關注並及時向大家報告發布進度。

Have a good evening.

祝你晚上愉快。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您可以斷開連線了。