Amicus Therapeutics Inc (FOLD) 2025 Q1 法說會逐字稿

Good morning, ladies and gentlemen and welcome to the Amicus Therapeutics first quarter 2025 financial results conference call and webcast. At this time, participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded.

女士們、先生們，早安，歡迎參加 Amicus Therapeutics 2025 年第一季財務業績電話會議和網路廣播。此時，參與者處於僅聆聽模式。稍後我們將進行問答環節，屆時將提供說明。提醒一下，本次電話會議正在錄音。

I would now like to turn the conference call over to your host, mister Andrew Faughnan, Vice President of Investor Relations. You may now begin.

現在，我想將電話會議交給主持人、投資者關係副總裁 Andrew Faughnan 先生。現在你可以開始了。

Thank you, Travis. Good morning. Thank you for joining our conference call to discuss Amicus Therapeutics first quarter 2025 financial results and corporate highlights. Leading today’s call, we have Bradley Campbell, President and Chief Executive Officer; Sebastien Martell, Chief Business Officer; Dr.Jeff Castelli, Chief Development Officer; and Simon Harford, Chief Financial Officer. Joining for Q&A is Ellen Rosenberg, Chief Legal Officer.

謝謝你，崔維斯。早安.感謝您參加我們的電話會議，討論 Amicus Therapeutics 2025 年第一季的財務表現和公司亮點。主持今天電話會議的是總裁兼首席執行官布拉德利·坎貝爾 (Bradley Campbell)； Sebastien Martell，首席商務官； Jeff Castelli 博士，首席開發官；以及首席財務官西蒙·哈福德 (Simon Harford)。首席法律官 Ellen Rosenberg 也參與了問答環節。

As referenced on Slide 2 of the presentation, I would like to remind you that we will be making forward looking statements on today’s call. I encourage you to read the disclaimers in our slide presentation, the press release we issued this morning and the disclosures in our SEC filings which are all available on the IR portion of our corporate website.

正如簡報第 2 張投影片中所提到的，我想提醒您，我們將在今天的電話會議上做出前瞻性陳述。我鼓勵您閱讀我們幻燈片簡報中的免責聲明、我們今天早上發布的新聞稿以及我們向美國證券交易委員會提交的文件中披露的內容，這些都可以在我們公司網站的 IR 部分找到。

Forward looking statements are subject to substantial risks and uncertainties, speak only as of the call’s original date and then we undertake no obligation to update or revise any of the statements. Additionally, you are cautioned not to place undue reliance on any forward looking statements.

前瞻性陳述受重大風險和不確定性的影響，僅代表截至通話原始日期的觀點，我們不承擔更新或修改任何陳述的義務。此外，請注意不要過度依賴任何前瞻性陳述。

At this time, it is my pleasure to turn the call over to Bradley Campbell, President and Chief Executive Officer. Bradley?

現在，我很高興將電話轉給總裁兼執行長布拉德利坎貝爾。布拉德利？

Great. Thank you, Andrew and welcome everyone to our first quarter conference call. Before we get into the details with the backdrop of what has certainly been a tumultuous quarter in biotech, I thought it’d be valuable for me to frame the incredibly positive outlook we see for Amicus going forward.

偉大的。謝謝安德魯，歡迎大家參加我們的第一季電話會議。在我們深入探討生物技術領域動盪的一個季度的背景之前，我認為有必要先概括一下我們對 Amicus 未來發展的極其樂觀的展望。

First of all, I’m very pleased to share that we have delivered yet another quarter of strong double digit revenue growth on our core business in Pompe and Fabry. This is now our eleventh consecutive quarter with double digit sales growth and we see that trend continuing for years to come.

首先，我很高興地告訴大家，我們在龐貝和法布里的核心業務上又一個季度實現了強勁的兩位數營收成長。這是我們連續第十一個季度實現兩位數的銷售成長，我們預計這一趨勢將在未來幾年持續下去。

Second, we were thrilled to have entered into a strategic collaboration with Dimerix that for a modest upfront brings into our pipeline, the US commercialization rights to a first in class compound in late Phase III development for a rare fatal kidney disease with blockbuster market potential. Third, we continue to strengthen and diversify our supply chain. Through prudent operations and planning, we were able to effectively neutralize exposure to any potential tariffs this year.

其次，我們很高興與 Dimerix 達成策略合作，只需支付少量前期費用，我們就能獲得美國同類一流化合物的商業化權利，該化合物正處於 III 期後期開發階段，用於治療一種罕見的致命腎病，具有巨大的市場潛力。第三，我們繼續加強和多樣化我們的供應鏈。透過審慎的營運和規劃，我們能夠有效地抵消今年任何潛在關稅帶來的風險。

We also announced today that we are onshoring a portion of our drug product manufacturing from Pombiliti to enhance our diversification strategy even further. Fourth, while quarterly revenues for the Galafold and Pom-Op were impacted by some unexpected factors, we are highly confident in the acceleration in sales we’ll see through the remainder of the year, resulting in combined revenue projections within 2% of our original guidance and yet another year of double digit growth. Fifth, we reiterated our confidence that these two products, each with potential blockbuster sales at peak will reach combined sales of $1 billion by the end of 2028.

我們今天也宣布，我們將把部分藥品生產業務從龐比利蒂轉移至國內，以進一步加強我們的多元化策略。第四，雖然 Galafold 和 Pom-Op 的季度收入受到一些意外因素的影響，但我們對今年剩餘時間的銷售加速增長充滿信心，預計合併收入將與我們最初的預期相差 2% 以內，並再次實現兩位數增長。第五，我們重申我們的信心，這兩款產品在巔峰時期都具有巨大的銷售潛力，到 2028 年底，它們的總銷售額將達到 10 億美元。

And finally, as we maintain our financial discipline, we reiterated that we are on track to achieve GAAP profitability in the second half this year. Taken together, we are confident that what we have achieved this quarter leaves Anikas uniquely well positioned to create substantial value for shareholders and deliver on our mission for patients.

最後，在我們保持財務紀律的同時，我們重申我們預計今年下半年將實現 GAAP 盈利。總而言之，我們相信本季所取得的成就將使 Anikas 處於獨特的有利地位，能夠為股東創造巨大價值並履行我們為患者服務的使命。

With that, let me hand the call over to Sebastien to dive into the business in more detail. Sebastien?

說完這些，讓我把電話交給賽巴斯蒂安，讓他更詳細地談談這項業務。塞巴斯蒂安？

Thank you, Bradley and good morning to everyone. For Galafold on Slide 5, you see that revenue reached $104.2 million, up 6% at constant exchange rates. The underlying growth of this product remains very positive, with a number of new patient starts globally up 14% in the quarter. This puts us on track to deliver the highest level of patient starts this year.

謝謝你，布拉德利，大家早安。對於幻燈片 5 上的 Galafold，您可以看到其收入達到 1.042 億美元，以固定匯率計算成長 6%。該產品的潛在成長仍然非常積極，本季全球新患者數量增加了 14%。這使我們有望在今年實現最高水準的患者就診。

We ended the quarter with more than 69% of the global market share of treated Fabry patients with amenable mutations. Garasold is clearly positioned as the treatment amongst prescribers and there’s still many more potential patients eligible for our therapy.

截至本季度，我們佔據了接受治療的具有可耐受突變的法布瑞氏症患者的全球市場份額的 69% 以上。Garasold 顯然是處方醫師所青睞的治療方法，並且有更多潛在患者適合接受我們的治療。

Turning to Slide 6, our leading markets continue to be the biggest driver of strong patient demand. The US contributed significantly to growth and we reached a record number of patients on Galafold in Australia following the first line listing.

轉到幻燈片 6，我們的主要市場繼續成為強勁患者需求的最大驅動力。美國對我們業務的成長做出了巨大貢獻，在澳大利亞，Galafold 首次上市後，患者數量達到了創紀錄的水平。

When we look at the global mix which is about 65% naive and 35% switch, we’re seeing stronger uptake in naive populations. We continue to achieve high market shares in countries where we’ve been approved the longest but there’s still plenty of opportunity to switch patients over to GAFLD and to keep growing the market as we penetrate the Diagnosed Untreated and newly diagnosed segments.

當我們觀察全球的組成時，大約有 65% 是未受感染者，35% 是已轉換者，我們發現未受感染者的接受度更高。我們在獲批時間最長的國家繼續取得較高的市場份額，但隨著我們滲透到確診未治療和新診斷領域，仍然有大量機會將患者轉向GAFLD，並繼續擴大市場。

Turning to the revenue impacts in the quarter. While the US grew at 18% this quarter, we observed nonlinear order patterns ex-US. And Q1 sales in The UK were impacted by the higher VPAG rebates than prior industry guidance had assumed. With underlying growth in patient demand at 14%, our projection of a record level of new patient starts this year, we remain highly confident in our full year 2025 growth guidance for Galafold.

談談本季的營收影響。儘管本季美國經濟成長了 18%，但我們觀察到美國以外的訂單模式呈現非線性。英國第一季的銷售受到 VPAG 回扣的影響，高於先前行業指導的預期。由於患者需求的潛在成長率為 14%，我們預測今年新患者數量將創歷史新高，我們對 Galafold 2025 年全年的成長指引仍充滿信心。

The key drivers behind the growing demand for Galafold which we expect to continue well beyond 2025 are the following. First, finding new patients and reaching the diagnosed untreated population, including shortening the pathway to diagnosis. Second, expanding Galafold into new markets and extending the label. Third, driving Galafold’s share of treated amenable patients.

我們預計 Galafold 需求將持續成長，主要驅動因素如下，並且這種成長將持續到 2025 年以後。首先，尋找新患者並接觸未接受治療的確診族群，包括縮短診斷途徑。其次，將 Galafold 拓展到新市場並延長品牌。第三，推動 Galafold 接受治療的患者份額。

We’re actually seeing in our most mature markets that we can reach up to 85%, 90% share. So we know that there’s the potential to reach those levels globally. And fourth, sustaining compliance and adherence above 90% rates so that patients who go on Galafold predominantly stay on Galafold. So with our strong IP protection, we think Galafold is a long runway well into the next decade and a clear path to surpassing $1 billion in revenue in the next 12 years.

我們實際上看到，在最成熟的市場中，我們的份額可以達到 85% 到 90%。因此我們知道，在全球範圍內，我們有可能達到這些水準。第四，維持 90% 以上的依從性和堅持性，以便使用 Galafold 的患者主要繼續使用 Galafold。因此，憑藉我們強大的智慧財產權保護，我們認為 Galafold 將在未來十年擁有廣闊的發展前景，並有望在未來 12 年內實現收入超過 10 億美元的目標。

Turning now to Pompe disease on Slide 8, we outline our global launch progress with Pombiliti and Opfolda. In the first quarter, revenue reached $21 million up 92% at constant exchange rates.

現在轉到幻燈片 8 上的龐貝病，我們概述了與 Pombiliti 和 Opfolda 合作的全球發布進展。第一季度，營收達到 2,100 萬美元，以固定匯率計算成長 92%。

The majority of growth was driven by three of our initial launch countries, The US, Germany and Spain. The US represented approximately 45% of revenue and contributed to 65% of Prometheus and Opfolda growth in the quarter.

大部分的成長是由我們最初推出的三個國家推動的，即美國、德國和西班牙。美國約佔本季營收的 45%，並貢獻了 Prometheus 和 Opfolda 本季成長的 65%。

Outside of the US, revenue growth was largely driven by Germany and Spain, with UK sales impacted by the VBAC clawback. We continue to see patients switching proportionally based on market share, as well as broadening and deepening of prescriptions with more sites coming online and multiple new prescriptions from physicians. We expect the benefit of patient starts in new launch markets to be weighted towards the second half of the year.

在美國以外，收入成長主要受到德國和西班牙的推動，英國的銷售受到 VBAC 回扣的影響。我們繼續看到患者根據市場份額按比例轉換，同時隨著更多網站上線和醫生開出更多新處方，處方範圍也在不斷擴大和深化。我們預計，新上市市場患者開始受益的現象將在今年下半年顯現。

Additionally, The US, we anticipate sales to accelerate over the remainder of 2025 as the pool of patients eligible continues to expand. We’re already seeing some of this acceleration in the month of April, with the largest number of net new commercial patients globally driven by The US, as well as the largest number of countries with new prescriptions since launch.

此外，在美國，隨著符合資格的患者群體不斷擴大，我們預計 2025 年剩餘時間內的銷售額將會加速成長。我們已經在四月看到了這種加速的跡象，美國是全球新增商業患者數量最多的國家，同時也是自推出以來新增處方的國家數量最多的國家。

Despite this momentum, we do not expect that we’ll be able to fully catch up with our prior 2025 guidance. And so that’s why we’re adjusting our full year 2025 revenue growth guidance for Pombiliti and Opfolda from 65% to 85% to 50% to 65% at constant exchange rates. Our revised revenue guidance implies a healthy exit rate heading into next year.

儘管勢頭強勁，但我們預計無法完全實現我們先前對 2025 年的預期。因此，我們將龐比利蒂和奧普福爾達 2025 年全年營收成長預期從 65% 至 85% 調整為 50% 至 65%（以固定匯率計算）。我們修訂後的收入指引意味著明年的退出率將保持健康。

We remain highly confident in the long term outlook of this therapy. We expect Pombiliti and Opfolda to be a major contributor to multi-year growth for Amicus based on key growth drivers, namely continuing to increase the number of net new patients, increasing the depth and breadth of prescribers, launching in new countries, including up to 10 in 2025, differentiating our therapy through evidence generation and real world evidence and maintaining 90% plus compliance and adherence rates.

我們對這種療法的長期前景仍然充滿信心。我們預計，Pombiliti 和 Opfolda 將成為 Amicus 多年增長的主要貢獻者，其主要增長動力包括繼續增加淨新患者數量、增加處方醫生的深度和廣度、在新的國家推出產品（到 2025 年將達到 10 個）、通過證據生成和真實世界證據使我們的治療方法與眾不同，並保持 90% 以上從率的依從性和從性。

Moving to Slide 9, looking at the geographic expansion of Prometheus and Opfolda. We recorded revenue in Q1 in 7 countries, The US, Germany, Austria, Spain, The UK, as well as Switzerland and Sweden.

移至投影片 9，查看 Prometheus 和 Opfolda 的地理擴張。我們在第一季在美國、德國、奧地利、西班牙、英國以及瑞士和瑞典 7 個國家取得了收入。

Of the five recently reimbursed countries, two markets, namely Sweden and Switzerland, had a first patient start during the quarter. In Q2, we anticipate first patients in four more countries, namely Italy, The Czech Republic, Portugal and The Netherlands.

在最近獲得報銷的五個國家中，瑞典和瑞士兩個市場在本季迎來了第一位患者。預計第二季將有另外四個國家迎來首批患者，分別是義大利、捷克共和國、葡萄牙和荷蘭。

We’re very pleased to share that Pombiliti and Opfolda that was recently selected as preferred treatment for adults with LLPD in The Netherlands. This is a five year agreement enabling broad and sustained access for adults with LLPD currently on enzyme replacement therapy. We also recently received regulatory approvals in Australia and Canada and in Japan, our DCA is under review and we anticipate approval later this year. We’re also securing broad patient access throughout the EU.

我們非常高興地告訴大家，Pombiliti 和 Opfolda 最近被選為荷蘭 LLPD 成年人的首選治療方法。這是一項為期五年的協議，為目前正在接受酵素替代療法的 LLPD 成年人提供廣泛且持續的治療機會。我們最近也獲得了澳洲、加拿大和日本監管部門的批准，我們的 DCA 正在接受審查，預計今年稍後獲得批准。我們也確保整個歐盟範圍內的患者能夠廣泛獲得治療。

Moving to Slide 10, I’d like to take a few moments to provide additional color on the actions we’ve taken to further strengthen our global supply chain and access to our medicines. Firstly, regarding tariffs which we recognize are still evolving, we do not expect a material impact to our business operations this year due to our proactive supply chain planning and careful management of expenses. We already have our 2025 sales inventory inside the US We’ve also been proactive in diversifying our global supply chain.

現在轉到第 10 張投影片，我想花一點時間進一步介紹我們為進一步加強全球供應鏈和藥品獲取管道所採取的行動。首先，關於我們認識到仍在變化的關稅，由於我們積極主動的供應鏈規劃和謹慎的費用管理，我們預計今年的業務運營不會受到重大影響。我們在美國境內已經擁有了 2025 年的銷售庫存，我們也積極主動地實現全球供應鏈的多樣化。

In addition to our second source of Pombiliti drug substance manufacturing in Ireland, we’re announcing today a manufacturing and supply services agreement with Sharp Sterile Manufacturing. This agreement will bring a portion of Pombiliti drug product manufacturing to the US

除了我們在愛爾蘭的第二個 Pombiliti 藥物物質製造來源之外，我們今天還宣布與 Sharp Sterile Manufacturing 達成製造和供應服務協議。該協議將使部分 Pombiliti 藥品生產業務轉移到美國

And with that, I will now hand over the call to Jeff to highlight the work we do to further differentiate Pombiliti and Opfolda.

現在，我將把電話交給傑夫，以強調我們為進一步區分龐比利蒂和奧普福爾達所做的工作。

Thank you, Sebastien and good morning, everyone. On Slide 11, we highlight a few examples from the rapidly expanding and diverse body of evidence supporting the differentiation of Pombiliti and Opfolda in Pompe.

謝謝你，賽巴斯蒂安，大家早安。在投影片 11 上，我們重點介紹了一些來自迅速擴展和多樣化的證據的例子，這些證據支持龐貝氏症中的 Pombiliti 和 Opfolda 的區別。

First on clinical trials and long term data, we continue to see differentiated durability of effect in our ongoing clinical studies, including long term data from our Phase II and Phase III open label extensions which reinforce the sustained efficacy and safety profile of Pombiliti and Opfolda.

首先，在臨床試驗和長期數據方面，我們在正在進行的臨床研究中繼續看到效果的差異化持久性，包括來自我們 II 期和 III 期開放標籤擴展的長期數據，這些數據強化了 Pombiliti 和 Opfolda 的持續療效和安全性。

Second, mechanistic and translational insights, emerging data continues to support the unique dual mechanism of action of our therapy. This includes not only the benefits of the upholstery stabilizer but also the differentiated design of the pump building enzyme alone which offers increased BISM6P for greater cell uptake together with retained proteolytic and N glycan processing for maximal enzyme activity. These mechanistic features are increasingly recognized as key drivers of clinical outcomes.

其次，機械和轉化見解，新興數據繼續支持我們療法獨特的雙重作用機制。這不僅包括室內裝潢穩定劑的優點，還包括單獨的泵構建酶的差異化設計，其提供增加的 BISM6P 以實現更大的細胞吸收，同時保留蛋白水解和 N 聚醣加工以實現最大的酶活性。這些機械特徵越來越被認可為臨床結果的關鍵驅動因素。

Third, on comparative and real-world evidence, real world data from early access programs and treatment registries are showing consistent effects that mirror what we’ve seen in clinical trials, supporting both the efficacy and safety of Pombiliti and Opfolda in broader real-world settings.

第三，根據比較證據和現實世界證據，來自早期訪問計劃和治療登記冊的現實世界數據顯示出與我們在臨床試驗中看到的情況一致的效果，支持 Pombiliti 和 Opfolda 在更廣泛的現實世界環境中的有效性和安全性。

Comparative analyses continue to also add important context for how our therapy performs relative to other ERTs. And finally, we’re seeing a growing number of powerful and illustrative real world patient stories. This includes individual switching to Pombiliti and Opfolda from high dose, high frequency Lumizyme, as well as dose switching from Nexviazyme. These real world transitions further reinforce the clinical value and differentiation of Pom-Op as perceived by both physicians and patients.

比較分析也持續為我們的療法相對於其他 ERT 的表現增添重要背景。最後，我們看到越來越多強大且富有啟發性的真實世界患者故事。這包括從高劑量、高頻率的 Lumizyme 轉換為 Pombiliti 和 Opfolda，以及從 Nexviazyme 轉換劑量。這些現實世界的轉變進一步強化了醫生和病人對 Pom-Op 的臨床價值和差異化的看法。

Importantly, beyond what’s shown here, we continue to actively enroll into our pediatric clinical trials and enrollment continues to accelerate in the Amicus Pompe registry which will generate invaluable additional real-world data on the long-term use of Pom-Op across broader populations and geographies. Altogether, the strength and consistency of our data continue to give us great confidence that Pom-Op will continue to deliver meaningful and lasting impact for people living with Pompe.

重要的是，除了這裡顯示的內容之外，我們還將繼續積極招募兒科臨床試驗，並且 Amicus Pompe 註冊中心的招募速度也在不斷加快，這將為在更廣泛的人群和地區長期使用 Pom-Op 提供寶貴的額外真實世界數據。總而言之，我們數據的強度和一致性繼續讓我們充滿信心，Pom-Op 將繼續為龐貝氏症患者帶來有意義和持久的影響。

I’ll now hand the call back to Sebastien.

我現在將電話交還給塞巴斯蒂安。

Thank you, Jeff. So moving to Slide 13. As we announced last evening, we took a major step forward in our strategy to strengthen our portfolio through a successful US licensing agreement with Dimerix to commercialize DMX-200, a first in class treatment in late stage development for FSGS, a rare and potentially fatal kidney disease.

謝謝你，傑夫。現在轉到投影片 13。正如我們昨晚宣布的那樣，我們透過與 Dimerix 成功達成美國許可協議將 DMX-200 商業化，在加強我們產品組合的策略上邁出了重要一步，DMX-200 是針對罕見且可能致命的腎臟疾病 FSGS 的後期開發中的一流治療方法。

This collaboration expands our late stage pipeline with a potential best in class treatment and brings significant opportunities to leverage our regulatory, commercial, medical and patient advocacy capabilities. As a promising late stage rare disease investigational medicine with blockbuster market potential, we believe this asset adds significant value to Amicus today and will create value for patients and shareholders.

此次合作將擴大我們的後期研發管線，為我們帶來潛在的最佳治療方案，並為發揮我們的監管、商業、醫療和病患權益保護能力帶來重大機會。作為一種具有巨大市場潛力的有前景的後期罕見疾病研究藥物，我們相信這項資產將為 Amicus 帶來巨大的價值，並將為患者和股東創造價值。

Slide 14 summarizes the transaction details. Dimerix will receive an upfront of $30 million paid from Amicus cash on hand. The deal is heavily weighted to success based milestones, of which the next potential milestone payments would be for positive readouts from the Phase III study.

投影片 14 總結了交易細節。Dimerix 將收到 Amicus 現金支付的 3000 萬美元預付款。該交易非常重視基於成功的里程碑，其中下一個潛在的里程碑付款將用於第三階段研究的積極讀數。

Dimerix would receive tiered royalties of US sales of DMX-200 that starts in the low teens up to the low 20s. Dimerix will fund and execute the Phase III study and Amicus will be responsible for submission and maintenance of the regulatory dossier in The United States, as well as all costs of commercialization activities.

Dimerix 將獲得美國 DMX-200 銷售的分級版稅，從十幾到二十幾不等。Dimerix 將資助並執行第三階段研究，而 Amicus 將負責在美國提交和維護監管檔案，以及商業化活動的所有費用。

Let me hand over the call to Jeff to give you more insights on FSGS and the ongoing Phase III study.

讓我把電話交給傑夫，以便他能為您提供有關 FSGS 和正在進行的 III 期研究的更多見解。

Thanks, Sebastien. First, I would like to again just reiterate how extremely excited we are to work with Dimerix on the further development of DMX-200 to bring this potentially transformative treatment to patients suffering from FSGS.

謝謝，塞巴斯蒂安。首先，我想再次重申，我們非常高興能與 Dimerix 合作進一步開發 DMX-200，為患有 FSGS 的患者帶來這種具有變革意義的治療方法。

So starting here on Slide 15, focal segmental glomerulosclerosis or FSGS is a rare and serious kidney disorder characterized by segmental scarring of the glomeruli which are the filtering units of the kidney proteinuria which is the leakage of protein out of the kidney into the urine and a progressive decline in kidney function often culminating in end stage renal disease.

從幻燈片 15 開始，局部節段性腎小球硬化症或 FSGS 是一種罕見且嚴重的腎臟疾病，其特徵是腎小球節段性瘢痕形成，腎小球是腎臟的過濾單位，蛋白尿是蛋白質從腎臟洩漏到尿液中，腎功能逐漸衰退，通常最終導致終末期腎病。

The underlying causes of FSGS are various including immune factors, genetic viruses, adaptive factors but the key is that all of these converge on on some podocyte injury that triggers then a pathogenic feedback loop of hemodynamic stress and inflammation that drives further fibrosis and progressive kidney damage. The average time from diagnosis to onset of complete kidney failure is typically in the 5-year to 10-year range.

FSGS 的根本原因多種多樣，包括免疫因素、遺傳病毒、適應性因素，但關鍵在於所有這些因素都集中在某種足細胞損傷上，從而引發血流動力學壓力和發炎的致病反饋迴路，導致進一步的纖維化和進行性腎臟損傷。從診斷到完全性腎衰竭發生的平均時間通常為 5 年至 10 年。

In The US, FSGS affects more than forty thousand people with about five thousand new cases diagnosed each year. There are currently no FDA approved therapies and standard of care includes nonspecific therapies like corticosteroids, calcineurin inhibitors and angiotensin receptor blockers, none of which adequately address the monocyte driven inflammatory component of FSGS.

在美國，FSGS 影響超過四萬人，每年診斷出的新病例約五千例。目前尚無 FDA 批准的治療方法，標準治療包括皮質類固醇、鈣調神經磷酸酶抑制劑和血管緊張素受體阻斷劑等非特異性療法，但這些療法均無法充分解決 FSGS 中單核細胞驅動的發炎成分。

DMX-200 is an oral small molecule taken in combination with ARBs to target the monocyte driven inflammatory component of the disease by specifically inhibiting the inflammatory signaling from angiotensin one receptor and chemokine receptor type two heteromers that are on inflamed kidney cells.

DMX-200 是一種口服小分子，與 ARB 聯合使用，透過特異性抑制發炎腎細胞上的血管緊張素一受體和趨化因子受體二異聚體的發炎訊號，針對單核細胞驅動的疾病發炎成分。

Moving on to Slide 16, we’re impressed by the strong momentum Dimerix has built and the growing body of evidence supporting DMX-200 and FSGS. Mechanistic data show that DMX-200 is a precision therapy targeting the monocyte driven inflammatory feedback loop without broadly suppressing immune function. This is reinforced by compelling preclinical proof of concept data.

繼續看幻燈片 16，Dimerix 所建立的強勁勢頭以及支持 DMX-200 和 FSGS 的越來越多的證據給我們留下了深刻的印象。機制數據表明，DMX-200 是一種針對單核細胞驅動的發炎反饋迴路的精準療法，不會廣泛抑制免疫功能。令人信服的臨床前概念驗證數據進一步證實了這一點。

Phase II studies across 80 patients have demonstrated encouraging efficacy and safety signals with meaningful reductions in both proteinuria and inflammation shown in FSGS patients. The pivotal Phase three ACTION three trial is progressing very well with one hundred and eighty five of the target two eighty six patients enrolled. The study is very robustly designed and strongly powered.

針對 80 名患者進行的 II 期研究已顯示出令人鼓舞的療效和安全性訊號，FSGS 患者的蛋白尿和發炎均顯著減少。關鍵的第三階段 ACTION 三期試驗進展順利，目前已招募患者 286 名，而目標患者人數為 185 名。這項研究設計非常嚴謹，證據充分。

Importantly, there is also now FDA alignment on proteinuria as the primary endpoint for approval. Notably, the first interim analysis conducted by Dimerix last year after thirty six weeks of treatment showed DMX-200 outperforming placebo in reducing proteinuria. Taken together, we believe these results strongly position DMX-200 to be a truly meaningful advance in the treatment of FSGS.

重要的是，FDA 現在也將蛋白尿作為核准的主要終點。值得注意的是，Dimerix 去年在經過三十六週的治療後進行的首次中期分析顯示，DMX-200 在減少蛋白尿方面優於安慰劑。綜合起來，我們相信這些結果有力地證明了 DMX-200 將成為 FSGS 治療領域真正有意義的進步。

Turning to Slide 17, as I mentioned, action three is well underway. This is a global randomized double blind placebo controlled study of DMX-200 versus placebo in patients receiving ARBs. And they are followed for one hundred and four weeks.

翻到投影片 17，如我所提到的，第三項行動正在順利進行中。這是一項針對接受 ARB 治療的患者進行 DMX-200 與安慰劑比較的全球隨機雙盲安慰劑對照研究。他們被追蹤了一百零四個星期。

Based on a successful meeting as I mentioned with the FDA just here in March, the primary endpoint of the study will be a change in proteinuria measured as urine protein to creatinine ratio with eGFR slope serving as a secondary endpoint. Subject to recruitment rates which is going very well, full enrollment of Action three is expected around the end of the calendar year. An additional blinded interim analysis is also planned to occur once additional interactions have happened with Parasol and with the FDA to align on the final primary and secondary endpoint parameters.

正如我剛才提到的，基於 3 月與 FDA 的成功會談，該研究的主要終點是蛋白尿的變化，以尿蛋白與肌酸酐的比率來衡量，eGFR 斜率作為次要終點。如果招募率進展順利，預計第三項行動將在今年年底前全面招募人才。一旦與 Parasol 和 FDA 有更多互動，也計劃進行額外的盲法中期分析，以確定最終的主要和次要終點參數。

With that, let me now hand the call back over to Simon, or sorry, to Simon to review our financial results and outlook. Simon?

說完這些，現在讓我把電話交還給西蒙，或者抱歉，交給西蒙回顧我們的財務表現和前景。西蒙？

Thank you, Jeff. Our financial summary begins on Slide 19 with our income statement for the first quarter ending March 31, 2025. For Q1, we achieved total revenue of $125.2 million which is a 13% increase over the same period last year.

謝謝你，傑夫。我們的財務摘要從第 19 張投影片開始，其中包含截至 2025 年 3 月 31 日的第一季損益表。第一季度，我們的總營收達到 1.252 億美元，比去年同期成長 13%。

At constant exchange rates, revenue grew 15%. The global geographic breakdown of total revenue in the quarter consisted of $75.2 million or 60% of revenue generated outside The United States and the remaining $50 million or 40% coming from within the US cost of goods sold as a percentage of net sales was 9.3% for the first quarter as compared to 12.3% for the prior year period.

以固定匯率計算，營收成長了15%。本季全球總收入的地理分佈包括 7,520 萬美元或 60% 的收入來自美國以外，其餘 5,000 萬美元或 40% 的收入來自美國境內，第一季銷售成本佔淨銷售額的百分比為 9.3%，而去年同期為 12.3%。

Total GAAP operating expenses decreased to $121.5 million for the first quarter as compared to $124.6 million in the first quarter of 2024, a decrease of 2%. On a non-GAAP basis, total operating expenses increased to $94.5 million for the first quarter as compared to $85.6 million in the same period last year, an increase of 10%.

第一季 GAAP 總營運費用下降至 1.215 億美元，而 2024 年第一季為 1.246 億美元，降幅為 2%。以非美國通用會計準則計算，第一季總營運費用增至 9,450 萬美元，而去年同期為 8,560 萬美元，增幅為 10%。

We define non-GAAP operating expenses, research and development and SG and A expenses, excluding stock based compensation expense, loss on impairment of assets, changes in fair value of contingent consideration, restructuring charges and depreciation and amortization.

我們定義非公認會計準則營運費用、研發費用及銷售及行政費用，不包括股票薪酬費用、資產減損損失、或有對價公允價值變動、重組費用及折舊及攤提。

On a GAAP basis, net loss in the first quarter of 2025 was $21.7 million or $0.07 per share compared to a net loss of $48.4 million or $0.16 per share for the first quarter of 2024. In the first quarter of this year, non-GAAP net income was $9 million or a profit of $0.03 per share compared to non-GAAP net loss of $4.6 million or a loss of $0.02 per share in the same period last year. Cash, cash equivalents and marketable securities were two fifty one million dollars at March 31, 2025 compared to $25 million at December 31, 2024.

以 GAAP 計算，2025 年第一季淨虧損為 2,170 萬美元，即每股 0.07 美元，而 2024 年第一季淨虧損為 4,840 萬美元，即每股 0.16 美元。今年第一季度，非公認會計準則淨收入為 900 萬美元，即每股獲利 0.03 美元，而去年同期非公認會計準則淨虧損為 460 萬美元，即每股虧損 0.02 美元。2025 年 3 月 31 日的現金、現金等價物及有價證券為 2.51 億美元，而 2024 年 12 月 31 日為 2,500 萬美元。

On Slide 20, we outline our full year financial guidance for 2025. Total revenue growth guidance is updated to 15% to 22% from the previous 17% to 24%. We are reiterating Galafold revenue growth guidance of 10% to 15%. We are revising Pombiliti and Opfolda revenue growth guidance to 50% to 65% from the previous 65% to 85%. All growth rates are at CER.

在第 20 張投影片上，我們概述了 2025 年全年財務指引。總營收成長預期從先前的17%至24%更新為15%至22%。我們重申 Galafold 10% 至 15% 的營收成長預期。我們正在將 Pombiliti 和 Opfolda 的收入成長預期從先前的 65% 至 85% 修改為 50% 至 65%。所有成長率均以 CER 計算。

Gross margin is still expected to be in the mid-80s. We are updating our non-GAAP operating guidance to include the $30 million upfront license payment for the DMX-200 licensing. Non-GAAP operating expense guidance is therefore expected to be $380 million to $400 million. We anticipate positive GAAP net income during the second half of 2025.

預計毛利率仍將在80%左右。我們正在更新非公認會計準則營運指南，以包括 DMX-200 許可的 3000 萬美元預付許可費用。因此，非公認會計準則營運費用預計為 3.8 億美元至 4 億美元。我們預計 2025 年下半年 GAAP 淨收入將為正值。

As mentioned earlier this year, we anticipate 2025 to be a hybrid year for Pombiliti and Opfolda COGS as we expect to work through the previously expensed inventory during the first half of the year. As a result, we expect our gross margin to be in the mid-80s for the full year as we begin to recognize Pombiliti and Opfolda.

正如今年早些時候提到的，我們預計 2025 年將是 Pombiliti 和 Opfolda COGS 的混合年，因為我們預計將在上半年處理掉之前已計入費用的庫存。因此，隨著我們開始認可 Pombiliti 和 Opfolda，我們預計全年毛利率將達到 85% 左右。

COGS through the P&L later this year. In terms of operating expense, as a reminder, we continue to have R&D commitments, including registry studies in both, Fabry and Pompe, the ongoing Pompe Phase III study in countries not yet reimbursed, next generation manufacturing process development for Pombiliti, as well as the DMX-200 upfront licensing fee.

今年晚些時候，我們將透過損益表來計算 COGS。在營運費用方面，需要提醒的是，我們繼續進行研發承諾，包括在法布瑞氏症和龐貝氏症的註冊研究、在尚未報銷的國家進行的龐貝氏症 III 期研究、龐比利蒂的下一代製造工藝開發，以及 DMX-200 的前期許可費。

And with that, let me turn the call back over to Bradley for our closing remarks.

最後，請允許我將電話轉回給布拉德利，請他做最後發言。

Great. Thank you, Simon, Jeff, Sebastien. As we come to the end of our presentation, here is a reminder of the strategic priorities for the year reflecting the updates from today’s call. And before I conclude the discussion, I do want to take a moment to acknowledge Mike Cavany , who was our President of The US business at Amicus and retired at the end of Q1.

偉大的。謝謝你，西蒙、傑夫、賽巴斯蒂安。在我們的簡報即將結束之際，我們來回顧今年的策略重點，這些重點反映了今天電話會議的最新進展。在結束討論之前，我想花點時間感謝一下 Mike Cavany，他曾擔任 Amicus 美國業務總裁，並於第一季末退休。

Mike is a great friend and colleague who joined Amicus in 2018 to lead the US commercial team and he’s been a critical part of our success with Galafold and Pombiliti and Opfolda. Want to thank Mike for his contribution, for our mission and wish him so well in his retirement.

Mike 是我的好朋友和同事，他於 2018 年加入 Amicus，領導美國商業團隊，他是我們在 Galafold、Pombiliti 和 Opfolda 取得成功的關鍵人物。感謝麥克為我們的使命所做的貢獻，並祝他退休後一切順利。

By the same token, I also want to give a warm welcome to Gwen Whitney, who has succeeded Mike in this role. Gwen is an energetic and accomplished leader in the rare disease space and I very much look forward to her help in driving the US business in the next phase of our growth.

同樣，我也要熱烈歡迎接替麥克擔任這一職務的格溫·惠特尼 (Gwen Whitney)。格溫是罕見疾病領域一位精力充沛、成就卓越的領導者，我非常期待她能幫助我們推動美國業務在下一階段的成長。

Finally, on the last slide, let me leave you the way I started. We are very pleased with the growing demand for both of our therapies and are extremely excited to bring in a promising Phase three asset to our portfolio and an indication of significant unmet need. I remain highly confident in our growth projections for the remainder of 2025 and for many years ahead, as well as our ability to deliver significant value for shareholders and for people living with rare diseases.

最後，在最後一張投影片上，讓我回到我開始的方式。我們對我們的兩種療法的需求不斷增長感到非常高興，並且非常高興為我們的產品組合引入有前景的第三階段資產，並表明存在大量未滿足的需求。我對我們在 2025 年剩餘時間和未來許多年的成長預測以及我們為股東和罕見疾病患者創造重大價值的能力仍然充滿信心。

With that, operator, we can now open the call to questions.

接線員，現在我們可以開始提問了。

(Operator Instructions)

（操作員指示）

Anupam Rama from JPMorgan.

摩根大通的 Anupam Rama。

Hey guys, thanks so much for taking the question. Just one from me. Was there something particular noted assessments for both Galafold and Pombiliti-Opfolda that led to the rebate being a little bit higher than anticipated for both products? Thanks so much.

嘿夥計們，非常感謝你們回答這個問題。我只有一個。Galafold 和 Pombiliti-Opfolda 的評估中是否存在一些特別值得注意的問題，導致這兩種產品的折扣都比預期的要高一點？非常感謝。

Yeah. thanks Anupam. It’s really frustrating. That’s a negotiated rebate by industry association in The UK and they give guidance to industry of what to expect for the year. And so our guidance was between 1215%. And we assume the maximum of that rate 15% to be conservative. In the end, they came back with a negotiated rate of 22%.

是的。謝謝 Anupam。這真是令人沮喪。這是英國行業協會協商後的回扣，他們為業界提供全年預期的指導。因此我們的指導價位在 1215% 之間。我們假設該利率的最高值為 15%，這是比較保守的。最終，他們協商的利率為22%。

So almost a 50% increase in what we had anticipated. The challenge is of course, that hits you in the quarter and then throughout the year which is frustrating but it is what it is. It’s a one-time thing and it’s reflective of just a negotiated settlement with the government for all of industry. There’s a lot of coverage of that in The UK press, as you might imagine.

因此比我們預期增加了近 50%。當然，挑戰會在本季度甚至全年給你帶來困擾，這令人沮喪，但事實就是如此。這是一次性的事情，它反映了所有產業與政府達成的談判解決方案。正如您可能想像的那樣，英國媒體對此進行了大量報導。

Now I think we can confidently say with Galafold, we can make up for that based on the patient growth. And then you saw the revised guidance for Pombiliti and Opfolda.

現在，我認為我們可以自信地說，有了 Galafold，我們可以根據患者的成長來彌補這一點。然後你看到了針對龐比利蒂和奧普福爾達的修訂指南。

Thanks so much for taking our question

非常感謝您回答我們的問題

Eli Merrill of UBS.

瑞銀的 Eli Merrill。

This is [Tejas] on for Eli. I guess just in terms of the cadence of ex-US launches and patient starts, what has changed on your expectations there? And how much of that contributed to you guys taking down the Pom-Op guidance?

這是 [Tejas] 為 Eli 準備的。我想，就美國以外地區的發射節奏和耐心啟動而言，您的預期發生了哪些變化？這在多大程度上促使你們取消 Pom-Op 指導？

Yeah. thanks for the question. I think there’s really two big elements there. The first is exactly as you said, you saw in previous slides as we came into the year and then we reiterated here, we reached a number of reimbursement settlements at the end of last year in the early part of the quarter.

是的。謝謝你的提問。我認為這裡面有兩個重要因素。首先正如您所說的，您在先前的幻燈片中看到，當我們進入今年時，我們在這裡重申，我們在去年年底本季初達成了多項報銷協議。

And we had assumed that those patients would start on therapy in the first quarter. Unfortunately, of them started, only a handful started in the first quarter and many of them are starting to start in the second quarter. So really that’s a timing thing. So it’s kind of just pushes the curve to the right.

我們曾假設這些患者將在第一季開始接受治療。不幸的是，其中只有少數是在第一季開始的，而許多是在第二季開始的。所以這其實就是一個時間問題。所以它只是將曲線向右推。

And then unfortunately, we do have that impact of VPAG. And as a reminder, The UK is one of our top three revenue markets for both Pom-Op and for Galafold. And so that ends up being a hit for the rest of the year.

不幸的是，我們確實受到了 VPAG 的影響。提醒一下，英國是 Pom-Op 和 Galafold 的三大收入市場之一。因此，這成為了今年剩餘時間的熱門話題。

I would think of it mostly just based on what we’re seeing in that acceleration that we’ve already started to see in April and that we expect to see in the back half of the year, just a shifting to the right. And we have some great positives that we’re seeing. We’ve already started patients now in Italy and Sweden and some other markets, Switzerland as well. And that Netherlands First position, think will be a big growth driver for us in the second half of the year as well.

我主要根據我們在四月就已經開始看到的加速情況來考慮這個問題，我們預計今年下半年也會看到這種加速，只是向右移動。我們看到了一些非常積極的進展。目前，我們已經在義大利、瑞典和其他一些市場以及瑞士開始接待患者。而荷蘭第一的地位，我認為這也將成為我們下半年的一大成長動力。

Yes, I guess just a quick on The Netherlands, how much of that impact is just coming from Netherlands? I know you mentioned it in the first quarter shifting to the right a little bit.

是的，我想簡單談談荷蘭，其中有多少影響只是來自荷蘭？我知道您在第一季提到它稍微向右移動。

Well, our 150 plus patients, LLPD patients in The Netherlands and they are, as we mentioned, we have now been awarded first position there. So that’s a significant opportunity. One of the challenges is that it’s only one center in The Netherlands that is treating the majority of those patients. And so there’s a bit of a bottleneck there that is taking a little bit longer to get started. Again, we very much look forward to seeing that play out over the back half of the year and beyond.

嗯，我們在荷蘭有 150 多名 LLPD 患者，正如我們所提到的，我們現在已經在那裡獲得了第一名。所以這是一個重要的機會。其中一個挑戰是，荷蘭只有一家中心負責治療大多數患者。因此，那裡存在一些瓶頸，需要更長的時間才能啟動。再次，我們非常期待看到這一情況在今年下半年及以後的進展。

I would orient you also to Sweden, much smaller patient population, however, similar outcome where we were awarded first position and we’re getting 80% or 90% of the patients there. So I think in the medium term, it’s going to be a huge opportunity for us. But because of some of that kind of bottlenecking and getting started, those patients will fall into the second and third and fourth quarter.

我還想向您介紹瑞典，那裡的患者人數少得多，但結果卻相似，我們都獲得了第一名，並且在那裡接收了 80% 或 90% 的患者。所以我認為從中期來看，這對我們來說將是一個巨大的機會。但由於一些瓶頸和起步階段的問題，這些患者將落入第二、第三和第四季。

Joseph Schwartz from Leerink.

Leerink 的 Joseph Schwartz。

This is [Will] on for Joe. So I'll pick it up and ask about DMX-200. So I guess on the licensing agreement here, it would be a bit helpful to hear some more color on the diligence process and how you ultimately ended up settling on an asset in a rare renal disease? And what provided you with the confidence of the asset's differentiation versus late-stage competition? And maybe how do you see this kind of fitting into the overall treatment paradigm if approved? Thank you.

這是喬的[威爾]。所以我會拿起它並詢問有關 DMX-200 的問題。因此，我想，就此處的許可協議而言，如果能聽到有關盡職調查過程的更多細節以及您最終如何確定罕見腎病資產，將會有所幫助？是什麼讓您對該資產與後期競爭的差異化充滿信心？如果獲得批准，您認為它如何適應整體治療模式？謝謝。

So I think you talked a little bit about the strategy, little bit about the diligence and then about the differentiation of the molecule. I’ll start with maybe the first two and ask Jeff and Sebastien to add any color, especially on the differentiation, Jeff.

所以我認為你談了一點策略、一點關於勤奮以及一點關於分子的差異化。我可能會從前兩個開始，然後請 Jeff 和 Sebastien 添加一些顏色，特別是關於區分，Jeff。

So first and foremost, might remember as we came into finished last year and came into this year, what we described as our strategy was bringing into Amicus late stage de risked assets that we believed could meet a significant unmet medical need. We also talked about sort of how we would think about disease areas and of course Fabry Pompe remain center to our focus going forward. But we also talked about disease areas that could bring significant synergies.

因此，首先，大家可能還記得，當我們在去年年底進入今年時，我們所描述的策略是將我們認為可以滿足重大未滿足醫療需求的後期去風險資產引入 Amicus。我們也討論瞭如何看待疾病領域，當然法布瑞龐貝氏症仍然是我們未來關注的重點。但我們也討論了可以帶來顯著協同效應的疾病領域。

And if you think about FSGS as a rare kidney disease, the endpoints proteinuria, GFR, the call points nephrologists, specialty medical centers, etcetera, very much synergistic with our capabilities and our team today. So we really felt like both the structure of the deal which was a modest upfront and then really success based milestones going forward, as well as the strategic fit was sort of perfect for what we were looking for as our first deal to expand the portfolio. In terms of diligence, of course, we looked very carefully through the data that was provided. We did a lot of market research, talked to physicians, worked very closely with Dimerix. It was a very, I think collaborative process.

如果您將 FSGS 視為一種罕見的腎臟疾病，那麼終點蛋白尿、GFR、呼叫點腎病專家、專科醫療中心等與我們今天的能力和團隊具有很大的協同作用。因此，我們真的覺得這筆交易的結構是適度的前期付款，然後是真正基於成功的里程碑，以及戰略契合度，這對於我們作為擴大投資組合的第一筆交易所尋求的來說是完美的。當然，在盡職調查方面，我們非常仔細地查看了所提供的數據。我們做了大量的市場調查，與醫生交談，並與 Dimerix 密切合作。我認為這是一個非常協作的過程。

What gave us particular conviction here from a diligence perspective was, of course, the Phase II data very compelling, the unmet need very compelling. Then also the interim analysis that Dimerix had previously shown that showed statistical favorability for proteinuria in that blinded analysis, that was a planned interim analysis that had already been conducted.

當然，從盡職調查的角度來看，讓我們特別有信心的是第二階段的數據非常有說服力，未滿足的需求非常有說服力。然後，Dimerix 先前進行的中期分析也表明，在盲法分析中蛋白尿具有統計上的優勢，這是已經進行的計劃中期分析。

And then if you combine that with the very recent FDA meeting and meeting minutes that we saw confirming proteinuria as the primary endpoint, I think that’d give us great confidence that this is again, a highly de risked asset and likely to succeed.

然後，如果將其與我們看到的最新 FDA 會議和會議記錄結合起來，確認蛋白尿是主要終點，我認為這會讓我們非常有信心，這又是一項高風險資產，而且很可能會成功。

And maybe Jeff just hit quickly the differentiation point on the molecule itself in FSGS.

也許 Jeff 只是迅速抓住了 FSGS 分子本身的分化點。

Yes, thanks Brad. You know, think one of the things we’re really excited about here is the mechanism of action of DMX-two hundred and how differentiated it is. So when you look at standard of care, when you look at some of the other development compounds, none of them are targeting this monocyte driven inflammatory component of the feedback loop.

是的，謝謝布拉德。您知道，讓我們真正興奮的事情之一是 DMX-200 的作用機制以及它的差異化程度。因此，當您查看護理標準時，當您查看其他一些開發化合物時，您會發現它們都沒有針對反饋迴路中單核細胞驅動的發炎成分。

A lot of them are focused more on controlling the hemodynamic side of things through A1TR or through endothelin. And really what DMX-200 is specifically targeting the inflammatory signaling in the damaged kidney.

他們中的許多人更注重透過 A1TR 或內皮素來控制血液動力學方面。DMX-200 的真正作用是專門針對受損腎臟中的發炎訊號。

So FSGS, it’s a very diverse disease, lots of underlying causes, lots of drivers of the ongoing damage. And I think what we’re going to see is some patients are going to respond better if it’s mainly a hemodynamic driven challenge to ARBs or to new drugs like sparsentan that are targeting that side of things.

因此，FSGS 是一種非常多樣化的疾病，有許多潛在原因，有許多持續損害的驅動因素。我認為，我們將會看到，如果主要對 ARB 或針對該方面的新藥（如 sparsentan）提出血流動力學驅動的挑戰，一些患者的反應會更好。

And then patients that were really it’s that ongoing monocyte macrophage driven inflammation that’s really driving things, they might respond better to TMX200. And then down the line obviously I think there’s room for complimentary approaches here because all of the drugs are targeting different aspects of the disease. And you might see that actually in some patients combination of these approaches might work best ultimately.

而那些真正由持續的單核細胞巨噬細胞驅動的發炎所致的患者，他們可能對 TMX200 有更好的反應。然後顯然我認為這裡存在互補方法的空間，因為所有藥物都針對疾病的不同方面。您可能會發現，實際上對於某些患者來說，這些方法的組合最終可能會產生最佳效果。

But really that sort of also feeds into how we see this fitting There’s going to be some set of patients that respond better to one treatment than the other. And I think you’re going to see physicians sort of trying to figure out how to identify which patients are most likely to benefit from which treatment.

但實際上這也影響了我們如何看待這種治療方法，有些患者對一種治療方法的反應會比另一種更好。我認為你會看到醫生們試圖弄清楚如何確定哪些病人最有可能從哪種治療中受益。

And really with DMX two hundred, there are ways you can sort of look at the how much the inflammatory component is driving things. And those would be the patients that I think docs would those are going to be the patients we’re going to see respond best in the trials. And those are going to be the patients that I think doctors will want to focus on.

實際上，透過 DMX 200，您可以透過多種方式了解發炎成分對事物的影響程度。我認為醫生會認為這些患者是我們在試驗中看到反應最好的患者。我認為這些是醫生想要重點關注的病人。

And maybe, Seb, anything on the other strategy? No, okay.

塞布，您還有其他策略嗎？不，好吧。

Ritu Baral from TD Cowen.

Ritu Baral 的 TD Cowen。

This is Joshua Fleishman on the line for Ritu. Thanks for taking our question. Hi, Josh. On DMX-200, even if qPCR is a fully approvable primary endpoint, what is any benefit in eGFR is FDA looking for besides the primary? Two, what timeline should we expect for the next interim analysis which is gated by Parasol and FDA? Does nine months sound reasonable? And three, what have you seen to justify acceleration of US switches for Pom-Op in 2HAP-25.

我是 Joshua Fleishman，代表 Ritu 連線。感謝您回答我們的問題。你好，喬希。在 DMX-200 上，即使 qPCR 是完全可批准的主要終點，除了主要終點之外，FDA 還在尋求 eGFR 的什麼好處？二、我們應該期待下一次由 Parasol 和 FDA 控制的中期分析的時間表是怎樣的？九個月聽起來合理嗎？第三，您看到了什麼來證明美國在 2HAP-25 中加速轉向 Pom-Op 是合理的。

Great. So maybe I’ll start with Palm Up first and then Jeff, you can speak to those other points. So, look, I think as Sebastien shared with you on the call, we’re already seeing a significant acceleration in switches in Pombiliti and Opfolda in The United States and around the world just in the month April.

偉大的。因此，也許我會先從 Palm Up 開始，然後 Jeff，你可以談談其他要點。所以，我認為，正如塞巴斯蒂安在電話會議上與您分享的那樣，僅在四月份，我們就已經看到美國和世界各地的龐比利蒂和奧普福爾達的轉換速度顯著加快。

So it was really it was actually our best month for new commercial starts, so not clinical trial conversions but new commercial starts since we’ve launched. So that’s really exciting. Why are we seeing that? Part of it for sure is just the dynamic we had already talked about which is more and more Nexviazyme patients entering into that two year period. And I’ll mention again that we saw in that period, majority of the switchers coming from Nexviazyme. So we’re winning that game.

因此，這實際上是我們自推出以來新商業啟動最好的一個月，不是臨床試驗轉換，而是新商業啟動。這真是令人興奮。我們為什麼會看到這種情況？部分原因肯定是我們已經討論過的動態，越來越多的 Nexviazyme 患者進入這兩年期。我還要再提到，我們看到在那段時期，大多數轉換者來自 Nexviazyme。所以我們贏了這場比賽。

I think also part of it is what Jeff talked about which is the growing body of real world evidence. We presented for the first time, or one of our thought leaders did at a medical congress, case studies supporting the switch from Nexviazyme for the first time.

我認為其中一部分也是傑夫所說的，越來越多的現實世界證據。我們第一次提出，或者我們的一位思想領袖在醫學會議上第一次提出，支持從 Nexviazyme 轉換的案例研究。

So that’s, I think really important real world evidence that will continue to grow. And I do think too, we’ve talked about this before, we’ve always seen Q1 as a sort of nonlinear quarter in Fabry. And I think you may start to see that in Pompe as well. So this could be a reflection of that.

所以，我認為這是真正重要的現實世界證據，並且會繼續增長。我也確實認為，我們之前已經討論過這個問題，我們一直將第一季視為法布里的一個非線性季度。我想你可能也會在龐貝古城看到這種情況。這可能反映了這一點。

And then if you add in those kind of onetime factors we talked about ex-US, I think that kind of explains the quarter. Jeff, do you want to talk about FSGS and both the proteinuria GFR feedback from the FDA which is fantastic from the Type C meeting and then also some of the early timelines that we have line of sight to.

如果你加上我們談到的那些美國以外的一次性因素，我認為這可以解釋這個季度的情況。傑夫，你想談談 FSGS 和 FDA 對蛋白尿 GFR 的回饋嗎？這些回饋來自 C 型會議，非常棒，此外還有一些我們所關注的早期時間表。

Yes, thanks. And so, importantly, the alignment with FDA was proteinuria as a primary endpoint for full approval, not accelerated approval within some other TBD endpoint like GFR for confirmatory which we’ve seen now in other kidney diseases. I think what’s really exciting is we’re seeing FDA now move more and more towards recognizing proteinuria is so strongly tied to GFR decline and ultimate kidney progression that they’re moving now more and more towards qPCR as the provable full endpoint.

是的，謝謝。因此，重要的是，與 FDA 的一致性是將蛋白尿作為完全批准的主要終點，而不是在某些其他 TBD 終點（如 GFR 確認終點）內的加速批准，我們現在已在其他腎臟疾病中看到這種情況。我認為真正令人興奮的是，我們看到 FDA 現在越來越多地認識到蛋白尿與 GFR 下降和最終腎臟進展密切相關，因此他們現在越來越多地將 qPCR 作為可證明的完整終點。

And that’s really driven by data in FSGS from the Parasol Initiative, that’s 50 different researchers that have 1,600-plus FSGS patients and they’ve really been key in helping to show that tight association between changes in proteinuria and changes in GFR. So in terms of what we need to see on GFR, it’s really not any specific set statistical test at this point.

這實際上是由 Parasol Initiative 的 FSGS 數據推動的，該倡議由 50 位不同的研究人員組成，他們研究了 1,600 多名 FSGS 患者，他們在幫助證明蛋白尿變化和 GFR 變化之間的緊密關聯方面發揮了關鍵作用。因此，就我們需要了解的 GFR 而言，目前它實際上並不是任何特定的統計測試。

It just looks like we need to have a secondary endpoint on GFR that’s showing supportive data which we believe the design of the study is well designed to show. In terms of the interim analysis, so the main discussion with FDA that Dimerix had was alignment on proteinuria as that single primary endpoint.

看起來我們需要一個關於 GFR 的次要終點來顯示支持性數據，我們相信這項研究的設計很好地證明了這一點。就中期分析而言，Dimerix 與 FDA 的主要討論是以蛋白尿為單一主要終點。

There also was some talk about potentially an interim analysis to support accelerated approval that will require additional analysis of that Parasol dataset collaborating with Parasol which will take about three to six months to conduct that work, then go back and meet with FDA, make sure there’s alignment on all of the potential interim or accelerated endpoints, the full endpoints and then conduct that interim analysis.

還有一些關於潛在中期分析以支持加速批准的討論，這將需要與 Parasol 合作對 Parasol 數據集進行額外分析，這項工作大約需要三到六個月的時間，然後回去與 FDA 會面，確保所有潛在的中期或加速終點、完整終點都保持一致，然後進行中期分析。

So I think nine months, as you said, could be in that ballpark. But really, after we get through this three to six months, we can start to get more timing specifically about the next FDA interaction and when that interim might occur.

所以我認為，正如你所說，九個月大概就可以達到這個水準。但實際上，在我們度過這三到六個月之後，我們就可以開始更具體地了解下一次 FDA 互動的時間以及該過渡期可能發生的時間。

Great. Thanks Jeff.

偉大的。謝謝傑夫。

Dennis Ding from Jefferies.

傑富瑞 (Jefferies) 的丹尼斯丁 (Dennis Ding)。

Hi, good morning. Thanks for taking our question. I had one on FSGS specifically on the CCR2 mechanism. You know, I appreciate that Dimerix had already had positive Phase II and Phase three interim but hemosynchronous failed the Phase II a few years ago in FSGS with the, the same mechanism. Can you comment on what happened there? If there was a drug target or trial design issue and how may the drugs be different at this time?

嗨，早安。感謝您回答我們的問題。我有一個關於 FSGS 的具體關於 CCR2 機制的研究。您知道，我很欣賞 Dimerix 已經取得了積極的 II 期和 III 期中期成果，但幾年前血液同步療法在 FSGS 中由於同樣的機製而未能通過 II 期研究。您能評論一下那裡發生的事情嗎？如果有藥物標靶或試驗設計問題，那麼此時藥物可能會有何不同？

Yes, it’s a great question. I think it’s important that Jeff highlighted this, although maybe Jeff, you can provide just a little bit more color there. This molecule DMX-200 is a differentiated CCR2 inhibitor molecule. And so I think it’s very important to highlight those differences. And so Jeff, maybe share a little bit more of that color specifically how it acts within the kidney.

是的，這是一個很好的問題。我認為 Jeff 強調這一點很重要，儘管 Jeff，也許你可以提供更多一些說明。此分子DMX-200是一種分化的CCR2抑制劑分子。因此我認為強調這些差異非常重要。因此，傑夫，也許您可以分享更多關於這種顏色的知識，特別是它在腎臟中的作用。

Yes, thanks. That’s a great question. So there have been CCR2 inhibitors historically that have been tried by several companies and different diseases, mostly to try to knock down monocyte driven inflammation. The difference with DMX-200 is it’s not a direct inhibitor of the binding of the MCP1 which is sort of the inflammatory signal to the CCR2 receptor. Instead DMX-200 specifically acts downstream and blocks the signaling coming out of the A1TR CCR2 heteromer that’s on and damaged kidney tissue that acts as the amplification for inflammation.

是的，謝謝。這是一個很好的問題。因此，歷史上已經有多家公司針對不同疾病嘗試過 CCR2 抑制劑，主要是為了嘗試抑制單核細胞驅動的發炎。DMX-200 的不同之處在於它不是 MCP1 結合的直接抑制劑，而 MCP1 是向 CCR2 受體發出的一種發炎訊號。相反，DMX-200 專門作用於下游並阻斷來自 A1TR CCR2 異聚體的訊號，該訊號會破壞腎臟組織，從而起到發炎放大的作用。

So what happened with traditional binding inhibitors is MCP-one couldn’t dock and it actually led to a rebound effect where MCP-one levels dramatically increase which then would compete with the inhibitor and kind of lead to a muting of effect.

因此，傳統結合抑制劑所發生的情況是 MCP-one 無法對接，這實際上導致了反彈效應，即 MCP-one 水平急劇升高，然後會與抑制劑競爭，並導致效果減弱。

So the beauty of the downstream blocking is that MCP-one can still dock that leads to actually MCP-one degradation, the signal is stopped. So we’re actually seeing MCP-one levels come down with DMX-two hundred versus increase which is really sort of the benefit of having that downstream targeting. We think that will really maximize the ability to shut down the monocyte inflammation.

因此，下游阻斷的好處是 MCP-one 仍然可以對接，從而導致 MCP-one 降解，訊號被停止。因此，我們實際上看到 MCP-1 水平隨著 DMX-200 水平的上升而下降，這實際上是下游目標的優勢。我們認為這將真正最大限度地提高關閉單核細胞發炎的能力。

And the other great thing about that is it allows monocytes to continue their job elsewhere because we’re not directly blocking the MCP-one binding to monocyte, so they can still fight infections as they should outside of the kidney.

另一個好處是，它允許單核細胞在其他地方繼續工作，因為我們沒有直接阻止 MCP-one 與單核細胞的結合，所以它們仍然可以像在腎臟外一樣抵抗感染。

Thank you for the question.

謝謝你的提問。

Tazeen Ahmad from Bank of America Securities

美國銀行證券公司的 Tazeen Ahmad

This is [Yeung] on for Tazeen. So you mentioned that this VPAG rebate drag is a onetime thing. So I wonder like can you clarify on that? Can you make sure that this is not a recurring event?

這是 [Yeung] 為 Tazeen 主持的。所以你提到這個 VPAG 回扣拖累是一次性的事情。所以我想知道您能否澄清一下這一點？你能確保這不是重複發生的事件嗎？

Our second question is how do you plan to message the positioning of Pom-Op versus the traditional ERT in the new 10 countries you plan to launch? And what have you been heard so far from the payers and providers?

我們的第二個問題是，您計劃如何在您計劃推出的 10 個新國家中傳達 Pom-Op 與傳統 ERT 的定位？到目前為止，您從付款人和提供者那裡聽到了什麼消息？

And our third question is, can you elaborate whether that this in-license deal represent the beginning of the broader plan into nephrology or inflammation related rare disease?

我們的第三個問題是，您能否詳細說明這項授權協議是否代表腎臟科或發炎相關罕見疾病更廣泛計畫的開始？

Yes. So I think the first question was around VPAG. Just to be clear, we had anticipated based on the guidance from the industry association up to a 15% rebate and what was provided in fact was or what was decided and given to us was a 22% rebate. To be clear, that will impact revenue over the course of the year. And that’s part of why with Pom-Op, we’ve adjusted our guidance downwards.

是的。所以我認為第一個問題是關於 VPAG 的。需要明確的是，根據行業協會的指導，我們預計可以獲得高達 15% 的折扣，但實際上提供的或決定給予我們的折扣是 22%。需要明確的是，這將影響全年的收入。這就是為什麼我們針對 Pom-Op 下調了指導方針。

With Galafold, because again of strong patient growth, we believe we will be able make up for that over the course of the year which is great. VPAG is something that we’ve always had, in our estimation part of the arrangement between industry and the UK government.

有了 Galafold，由於患者數量再次強勁增長，我們相信我們將能夠在今年內彌補這一不足，這非常好。我們一直都有 VPAG，我們認為它是產業和英國政府之間協議的一部分。

And so it’s always part of our expectations and guidance. It’s just very unusual to have this kind of significant increase in the eventual rate versus what they guide us to. Hope that provides some clarity.

因此，它始終是我們期望和指導的一部分。與他們指引的數值相比，最終利率出現如此顯著的成長是非常不尋常的。希望這能提供一些清晰度。

As it relates to positioning, we’ve done an amazing job of working through the reimbursement process in Europe. We were the first ever product to get approval by NICE ahead of MHRA approval. We got first position in Sweden, First position in The Netherlands.

就定位而言，我們在歐洲的報銷流程方面做得非常出色。我們是首個在 MHRA 批准之前獲得 NICE 批准的產品。我們在瑞典獲得了第一名，在荷蘭獲得了第一名。

We had a very fast launch and a reimbursement process in Spain. So we’re very clearly demonstrating the value proposition of the product and the positioning from a competitive perspective, of course, is all about the data.

我們在西班牙的啟動和報銷流程非常快。因此，我們非常清楚地展示了產品的價值主張，從競爭的角度來看，定位當然都與數據有關。

And again, the differentiated data we’ve shown in terms of the only product in a controlled study showing that we can improve patients who switch from enzyme replacement therapy. And I think those are the data that are continuing to drive adoption of the product.

再次，我們在對照研究中展示的唯一產品的差異化數據表明，我們可以改善從酵素替代療法轉換而來的患者的治療效果。我認為這些數據將繼續推動產品的採用。

So hopefully that gives you a flavor there. Maybe Seb, just a quick reminder of the strategy around how we thought of this product and then what we think going forward from a PV perspective or portfolio perspective.

希望這能讓你對此有所體會。也許 Seb，只是想快速提醒我們如何看待這個產品的策略，以及我們從 PV 角度或投資組合角度對未來的看法。

Yes, Brad. So we did highlight in the past the areas of interest from a standpoint. Think we have shared that we tend to think for our framework in adjacencies to our existing businesses. Looking at neuromuscular and rare kidney or rare cardiology assets, more broadly speaking at rare metabolic diseases generally speaking. So these are clearly the areas of interest.

是的，布拉德。因此，我們過去確實從某個角度強調了感興趣的領域。我們認為我們已經分享過，我們傾向於從與現有業務相關的角度來思考我們的框架。考察神經肌肉和罕見腎臟或罕見心臟病資產，更廣泛地說，考察一般罕見代謝疾病。所以這些顯然是感興趣的領域。

This particular deal here is for US rights in FSGS as well as in other indications, by the way, given our excitement around the MRA. And so, you know, we think that there’s clearly an opportunity to expand in the rare kidney space with that specific asset in the US We’re also eager to continue to expand our portfolio on a global scale. So interested to also leverage our capabilities ex-US

順便說一句，鑑於我們對 MRA 的興奮，這項特別交易涉及美國在 FSGS 以及其他適應症方面的權利。所以，您知道，我們認為，利用美國的這一特定資產，顯然有機會在稀有腎臟領域擴張。我們也渴望繼續在全球擴大我們的投資組合。因此有興趣利用我們在美國以外的能力

Great thank you. And thanks for the question.

非常感謝。感謝您的提問。

Thank you.

謝謝。

Kristen Kluska from Cantor Fitzgerald.

坎托·菲茨杰拉德的克里斯汀·克魯斯卡。

Hey, guys. This is Rick Miller on for Kristen. Thanks for taking our question. Just one FSGS here. You talked about their potentially being kind of subsets of patients, maybe some that respond better from a hemodynamic driven mechanism versus inflammatory driven and FSGS. So to kind of get at this, is there any stat around what percentage of FSGS patients seem to be poor responders on ARBs or how should we be thinking about that?

嘿，大家好。我是里克米勒 (Rick Miller)，為克里斯汀 (Kristen) 表演。感謝您回答我們的問題。這裡只有一個 FSGS。您談到他們可能屬於患者的子集，也許有些人對血流動力學驅動機制的反應比對發炎驅動和 FSGS 的反應更好。那麼，為了弄清楚這一點，有沒有統計數據表明有多少比例的 FSGS 患者對 ARB 的反應不佳，或者我們應該如何看待這個問題？

Yes, just as a reminder, Jeff, I’ll turn it over to you from perspective. As a reminder, there are over forty thousand patients with primary FSGS, at least in The United States. And we think a fairly sizable subset of those patients would be prime candidates for this product. But Jeff, maybe talk a little bit about sort of how we see as kind of the most obvious, most likely to be responders and then some of the other opportunities as well.

是的，只是提醒一下，傑夫，我會從角度把它交給你。需要提醒的是，至少在美國，有超過四萬名原發性 FSGS 患者。我們認為這些患者中相當一部分人是該產品的主要候選人。但是傑夫，也許可以稍微談談我們如何看待最明顯、最有可能做出回應的人，以及其他一些機會。

Yes, it’s a great question. And so the focus of the patients for DMX-200 in the trial are primary FSGS which is sort of originally triggered by T cell, insults that then causes feedback loop and then also, genetic which is mainly driven by APOL1 patients.

是的，這是一個很好的問題。因此，DMX-200 在試驗中關注的患者重點是原發性 FSGS，這種疾病最初是由 T 細胞損傷引發的，然後引起回饋迴路，然後還有遺傳因素，主要由 APOL1 患者驅動。

So in that group, what we’re targeting there are patients despite ARBs, despite corticosteroids still have proteinuria which is greater than 1.5 gram per gram that are in the trial. Unfortunately, that’s actually a majority of FSGS patients, it’s still despite those treatments, have significantly elevated proteinuria. And in those patients, in particular, the higher the proteinuria levels, it’s more and more likely that they have an uncontrolled inflammatory component going on.

因此，在該組中，我們的目標是那些儘管使用了 ARB 和皮質類固醇，但蛋白尿水平仍然高於每克 1.5 克的患者，這些患者正在接受試驗。不幸的是，實際上大多數 FSGS 患者儘管接受了這些治療，但蛋白尿仍然顯著增加。尤其對於這些患者來說，蛋白尿水平越高，他們出現不受控制的發炎成分的可能性就越大。

So there’s not great numbers about how many patients in that group have significantly elevated MCP-one, for example. But through some of the work that Dimerix has done, what we’ll continue to learn through the Phase three, we think that is a significant percentage of those patients.

因此，關於該組中有多少患者的 MCP-one 顯著升高，目前還沒有確切的數字。但透過 Dimerix 所做的一些工作，我們將在第三階段繼續了解情況，我們認為這佔這些患者的很大比例。

And those are the ones in particular where we expect to see potentially a very robust response in terms of reduction in proteinuria. Also, you know, in others that might not be as elevated that are in the trial or out there that might be treated down the line. Inflammation does start to kick up in these patients.

我們尤其希望看到這些藥物在減少蛋白尿方面有非常強勁的效果。此外，您知道，在試驗中或在外面的其他可能不會升高的情況中，可能會在以後得到治療。這些患者體內確實開始出現發炎。

So you might actually prevent kind of a worsening in addition to actually driving some improvement in particular in those that are sort of have major ongoing inflammatory components. But I think we’re going to learn more and more with FSGS that there’s a lot of different mechanisms going on.

因此，您實際上可以防止病情惡化，並實際上推動一些改善，特別是對於那些具有主要持續發炎成分的病情。但我認為，我們將透過 FSGS 了解到很多不同的機制正在發生。

I think we’re going to start to really start to refine the different MOAs that are better for different types of patients. But we’re super excited that we think DMX-200 is going to address a significant percentage of those patients where it’s really that inflammation that’s driving things.

我認為我們將開始真正完善適合不同類型患者的不同 MOA。但我們非常高興，我們認為 DMX-200 將解決很大一部分由發炎引起的疾病患者的問題。

Thanks guys.

謝謝大家。

Gil Blum, Needham & Company.

吉爾·布魯姆（Gil Blum），Needham & Company。

Good morning, everyone and thanks for taking our question. Just, maybe a couple of, macro items. So you mentioned very limited impact of tariffs in 2025 but, you know, looking into the future, is there going to be additional investment required in order to control potential for tariff impact in later years? What is the impact of the weakening dollar? Thank you.

大家早安，感謝您回答我們的問題。也許只是一些宏項目。所以您提到 2025 年關稅的影響非常有限，但是，展望未來，是否需要額外的投資來控制未來幾年關稅影響的可能性？美元疲軟有何影響？謝謝。

Yes. Thanks, Gil. On the manufacturing side of things, I don’t foresee significant additional investment to be made to navigate around the tariffs. You might remember that we’ve already are well underway in moving the majority of our manufacturing to Ireland.

是的。謝謝，吉爾。在製造方面，我預計不會有大規模的額外投資來規避關稅。您可能還記得，我們​​已經在將大部分製造業務轉移到愛爾蘭。

And that will I think help diversify and de risk the manufacturing both cost and geopolitical location. And then Sebastien and I mentioned on the call, we’re moving some of the drug product manufacturing here to The United States which again further diversifies. So I think we feel very good about our ability to manage that going forward, despite the uncertainty that’s out there.

我認為這將有助於分散製造成本和地緣政治位置的風險並降低製造風險。然後塞巴斯蒂安和我在電話中提到，我們正在將部分藥品生產轉移到美國，這又進一步實現了多樣化。因此，儘管存在不確定性，但我認為我們對未來管理這個問題的能力非常有信心。

As it relates to the second one, just as a reminder, a significant portion of our revenue comes from the pound, the euro and the yen. And so a weak dollar for us generally gives us some FX benefit. However, we’ve tried to, I think, show in some of our slides just an example of what changes in the value of the dollar could impact our revenue.

至於第二個，需要提醒的是，我們很大一部分的收入來自英鎊、歐元和日圓。因此，美元疲軟通常會為我們帶來一些外匯利益。然而，我認為，我們試圖在一些幻燈片中展示美元價值的變化可能對我們的收入產生的影響。

That’s also why we focus on growth from a constant exchange rate perspective. But hopefully, that gives you some flavor of, in our case, a weakening dollar tends to help on the top line based on the majority of revenues coming outside The United States.

這也是我們從固定匯率角度關注成長的原因。但希望這能讓您感受到，在我們的案例中，美元走弱往往有助於提高營收，因為大部分收入來自美國以外。

Thank you.

謝謝。

Salveen Richter, Goldman Sachs

薩爾文·里克特，高盛

This is Shunitra for Salveen. Thank you for taking our question. So regarding Pom-Op , could you maybe give some more color on the competitive dynamics in the US With a good portion of patients on XYZIM coming into that appropriate window for switching? And basically, how are physicians at this point deciding between the two products? And what sort of market feedback have you been getting?

這是 Salveen 的 Shunitra。感謝您回答我們的問題。那麼關於 Pom-Op，您能否更多地介紹美國的競爭動態，因為 XYZIM 上的大部分患者都進入了適當的轉換窗口？那麼，醫生目前如何在這兩種產品之間做出選擇呢？您得到了什麼樣的市場回饋？

Great questions. You know, one thing we would note actually and this is just public information, the global franchise for Sanofi and Pompe actually declined by 5% in the first quarter. So I think that shows that for the first time we are starting to meaningfully take share and impact their growth. And so you could see our 90% growth obviously in stark contrast with that.

很好的問題。您知道，我們實際上要注意的一件事，這只是公開訊息，賽諾菲和龐貝的全球特許經營權在第一季度實際上下降了 5%。所以我認為這表明我們第一次開始真正佔據市場份額並影響他們的成長。因此，您可以看到我們的 90% 的成長與此形成了鮮明的對比。

In terms of positioning, think it continues to be what we’ve shared which is in The United States in particular, once physicians start a patient on Nexviazyme and that was the only choice they had because we weren’t on the market yet, they want to give about two years of time before they’re ready to switch again.

在定位方面，我認為它將繼續是我們所分享的，特別是在美國，一旦醫生開始為患者使用 Nexviazyme，這是他們唯一的選擇，因為我們尚未上市，他們希望給大約兩年的時間，然後他們才准備再次轉換。

And so having just big numbers of Nexviazyme patients coming into that switch period is helpful. And I think if you look at the acceleration that Sebastien talked about and the proportion of patients coming majority from Nexviazyme that continues to say that we will and are switching those patients.

因此，讓大量 Nexviazyme 患者進入轉換期是有幫助的。我認為，如果您看看塞巴斯蒂安談到的加速和來自 Nexviazyme 的患者比例，這繼續表明我們將會並且正在轉換這些患者。

Most importantly, they’re looking at is decline in both six minute walk and forced vital capacity but also some other patient reported outcomes. And that’s where the data that Jeff mentioned, the growing body of evidence looking at long term impact, not just on those two endpoints but also PROs but then also these case studies and showing improvement showing the support for the switch from Nexviazyme to Pom-Op, I think is really important. So those are the things that we think are going to continue to drive the switch and support that acceleration over the course of the year.

最重要的是，他們正在關註六分鐘步行和用力肺活量的下降，以及一些其他患者報告的結果。這就是 Jeff 提到的數據，越來越多的證據著眼於長期影響，不僅針對這兩個終點，還針對 PRO，然後還有這些案例研究，並顯示出對從 Nexviazyme 轉向 Pom-Op 的支持改進，我認為這非常重要。因此，我們認為這些因素將繼續推動這一轉變，並支持這項加速發展。

Maxwell Skor from Morgan Stanley.

摩根士丹利的 Maxwell Skor。

Thank you for taking my questions. Could you elaborate a bit more on other potential indications amendable to DMX-200’s MOA? And also, given the evolving regulatory landscape, could you share any insights or potential changes you might like to see at the agency to improve rare disease drug development or review efficiencies? Thank you.

感謝您回答我的問題。您能否詳細說明一下可修改 DMX-200 的 MOA 的其他潛在指示？此外，鑑於監管環境的不斷發展，您能否分享任何見解或希望看到該機構做出的潛在改變，以改善罕見疾病藥物的開發或審查效率？謝謝。

Yes, I’ll start the second one. I will say that’s maybe the one bright spot and all the craziness out there as you are hearing from senior officials, including the new FDA director, a nod towards rare disease drug development.

是的，我將開始第二個。我想說，這也許是唯一的亮點，儘管大家聽到一些高級官員（包括新任 FDA 局長）表示對罕見疾病藥物研發表示贊同，但這只是冰山一角。

We would love to see more use of real world evidence. We’d love to see an acknowledgement that in rare diseases, you can’t always have a placebo control arm in a rare fatal rare disease. We would love to see some other incentives that would, I think appropriately recognize some of the modernization of regulatory ability and clinical trial design. So, I think there is maybe a silver lining there which we look forward to continuing to see that play out.

我們希望看到更多真實世界證據的使用。我們很高興看到人們認識到，在罕見疾病中，你不能總是在罕見的致命罕見疾病中設立安慰劑對照組。我們希望看到一些其他的激勵措施，我認為這些激勵措施能夠適當地認可監管能力和臨床試驗設計的現代化。所以，我認為這裡也許還有一線希望，我們期待繼續看到這一幕的發生。

And then, maybe Jeff quickly take the second one, of the at least maybe one of the indications we’re thinking about.

然後，也許傑夫會迅速採取第二個行動，至少這可能是我們正在考慮的跡象之一。

Yes. So I mean, with the mechanism of action and it’s been being very kidney specific, just looking across rare kidney diseases where monocyte macrophage inflammation seems to be playing a key part and it’s not well addressed. I think there’s a number of potential interesting areas, you know, diabetic nephropathy and IgA nephropathy have been looked at.

是的。所以我的意思是，由於其作用機制，它對腎臟具有很強的特異性，只需觀察罕見腎臟疾病，單核細胞巨噬細胞發炎似乎起著關鍵作用，但尚未得到很好的解決。我認為有很多潛在的有趣的領域，你知道，糖尿病腎病變和 IgA 腎病已經被研究過。

I think there’s a lot of potential players in those spaces. Know, there are ones like proliferative lupus nephritis that also looks like this could be a key mechanism to address. So I think we’re looking at sort of a number of different areas and saying where is really mechanistically the best fit and then what also sort of fits in terms of building off of our FSGS kind of learnings clinically as well as those physicians that we’ll call on.

我認為這些領域有許多潛在參與者。要知道，像增生性狼瘡性腎炎這樣的疾病看起來也可能是需要解決的關鍵機制。所以我認為我們正在研究一些不同的領域，並找出從機制上來說最適合的領域，以及從我們在 FSGS 方面的臨床學習以及我們將要諮詢的醫生的角度來看，什麼也是最適合的。

So I think there’s a few really good candidates there that we’re going to start to dig into. There already is proof of concept data for some of those with the general pathway of CCR2 being involved.

所以我認為那裡有幾個非常好的候選人，我們將開始深入研究。目前已經有了一些與 CCR2 一般途徑有關的理論數據。

Yes, I think that’s where, again, turning profitable in the back half of this year and then obviously that leads eventually to positive free cash flows. That gives us our own capabilities and resources to start to expand the portfolio even within the products that we have and now with the MX200 that should give us an opportunity there as well.

是的，我認為這就是今年下半年再次獲利的原因，顯然這最終會帶來正的自由現金流。這為我們提供了自己的能力和資源，可以開始擴展產品組合，甚至在我們現有的產品範圍內，現在有了 MX200，這也為我們提供了機會。

All right. Thank you. So that was the last question for today. So this does conclude today's conference call, and I do hope everyone has a great day. Thank you.

好的。謝謝。這是今天的最後一個問題。今天的電話會議到此結束，我希望大家能度過愉快的一天。謝謝。

Thanks very much. Thanks, everybody, for tuning in.

非常感謝。謝謝大家的收看。