BioCryst Pharmaceuticals Inc (BCRX) 2025 Q2 法說會逐字稿

Good day, and welcome to the BioCryst second-quarter 2025 earnings conference call. (Operator Instructions) Please note this event is being recorded.

大家好，歡迎參加 BioCryst 2025 年第二季財報電話會議。 （操作員指示）請注意，本次會議正在錄製中。

I would now like to turn the conference over to John Bluth. Please go ahead.

現在我想把會議交給John Bluth。請發言。

Thank you very much. Good morning, and welcome to BioCryst's second-quarter 2025 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO, Jon Stonehouse; President and Chief Commercial Officer, Charlie Gayer; Chief R&D Officer, Dr. Helen Thackray; Chief Medical Officer, Dr. Donald Fong; and our new Chief Financial Officer, Babar Ghias. Following our remarks, we will answer your questions.

非常感謝。早安，歡迎參加 BioCryst 2025 年第二季公司更新及財務業績電話會議。今天的新聞稿及相關投影片可在我們的網站上取得。今天與我一起參加電話會議的嘉賓包括首席執行官 Jon Stonehouse、總裁兼首席商務官 Charlie Gayer、首席研發官 Helen Thackray 博士、首席醫療官 Donald Fong 博士以及我們新任首席財務官 Babar Ghias。發言結束後，我們將回答大家的提問。

Today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information as well as the company's future performance and/or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

今天的電話會議將包含前瞻性陳述，包括關於未來業績、未經審計的前瞻性財務資訊以及公司未來業績和/或成就的陳述。這些陳述受已知和未知的風險和不確定性的影響，可能導致我們的實際業績、業績或成就與本簡報中明示或暗示的任何未來業績或成就存在重大差異。您不應過度依賴這些前瞻性陳述。如需了解更多信息，包括對我們風險因素的詳細討論，請參閱公司向美國證券交易委員會提交的文件，該文件可在我們的網站上查閱。

In addition, today's conference call includes non-GAAP financial measures. For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the Press Releases section of our Investor Relations website at www.biocryst.com.

此外，今天的電話會議還包含非公認會計準則 (Non-GAAP) 財務指標。如需查看這些非公認會計準則 (Non-GAAP) 指標與最直接可比較的公認會計準則 (GAAP) 財務指標的對帳表，請參閱我們投資者關係網站 www.biocryst.com 新聞稿版塊發布的獲利新聞稿。

I'd now like to turn the call over to Jon Stonehouse.

現在我想把電話轉給喬恩‧斯通豪斯。

Thanks, John. Q2 was another outstanding quarter of performance for BioCryst. For ORLADEYO, it was the best quarter since approval, both from a revenue and underlying new patient demand perspective. To be in the fifth year of the launch and growing so sustainably quarter-after-quarter is a result of great execution by the team and continued growing confidence in the product.

謝謝，約翰。 BioCryst 第二季的表現再創佳績。對於 ORLADEYO 來說，無論是從收入或新增患者需求來看，這都是自獲批准以來最好的季度。產品上市至今已五年，並且保持著如此持續的季度成長，這得益於團隊的出色執行力以及對產品持續成長的信心。

The commercial team at BioCryst has learned so much in the marketplace and made adjustments along the way that has kept this growth sustainable. Our recipe for success has been combining talented, motivated people, data and insights to very acutely understand the market and our customers and focused execution.

BioCryst 的商業團隊在市場中累積了豐富的經驗，並不斷調整，從而保持了可持續的成長。我們的成功秘訣在於將才華橫溢、積極進取的員工、數據和洞察力相結合，從而深刻理解市場和客戶，並專注於執行。

We show up differently than our competition. I know this as I saw it recently at the US HAE Patient Summit, a gathering of over a thousand patients and their families and many leading KOLs. They shared with me and other members of our team the growing confidence they have in our product. Many made the effort to seek us out and describe how ORLADEYO has changed their lives.

我們與競爭對手截然不同。這一點我深有體會，因為我最近在美國心臟病學會 (HAE) 患者高峰會上就親眼見證了這一點。此次高峰會聚集了超過一千名患者及其家屬，以及許多業界領先的意見領袖。他們與我和團隊其他成員分享了他們對我們產品日益增長的信心。許多人特意找到我們，並向我們講述了 ORLADEYO 如何改變了他們的生活。

This underscores when the product works for a patient, it works very well, and the number of patients experiencing both efficacy and convenience continues to grow steadily. There is little doubt that we are on a path to $1 billion at peak and market leadership with ORLADEYO. But to create even greater value, we need to do it again with another product. It's clear that we must source our pipeline through both internal research and BD. Our Netherton syndrome and DME pipeline programs remain on track to have some data by the end of the year.

這凸顯了當產品對患者有效時，它的效果會非常好，並且體驗到療效和便利性的患者數量持續穩定成長。毫無疑問，憑藉奧拉迪約，我們正朝著10億美元的高峰目標邁進，並成為市場領導者。但為了創造更大的價值，我們需要在另一款產品上再次做到這一點。顯然，我們必須透過內部研究和業務拓展來拓展我們的產品線。我們的內瑟頓症候群和糖尿病性腦膜炎（DME）產品線計畫進展順利，預計在年底前獲得一些數據。

We also signed a definitive agreement to sell our European business to Neopharmed Gentili or NG, and we are working hard to complete all the necessary steps to close the deal in early October. This deal puts us in such a strong financial position, enabling us to pay off our term debt while generating an increasing operating profit margin. We believe it puts us on a path to generate more and more cash flow and that we will remain on this path through the rest of the decade and beyond.

我們也簽署了最終協議，將我們的歐洲業務出售給Neopharmed Gentili（簡稱NG），我們正在努力完成所有必要步驟，以便在10月初完成交易。這筆交易使我們的財務狀況非常強勁，使我們能夠償還定期債務，同時提高營業利潤率。我們相信，這將使我們走上創造更多現金流的道路，並在未來十年及以後繼續保持這一勢頭。

Pipeline progress and financial flexibility enable us to continue to advance our pipeline while looking for assets from other rare disease companies. We have built an outstanding commercial capability at BioCryst, and we plan to leverage it over time by bringing multiple products to the market to create greater and greater value. Before I turn the call over to Charlie, I want to say how excited I am to see the company move to the next stage of growth, call it BioCryst 2.0.

研發管線的進度和財務彈性使我們能夠繼續推進研發管線，同時尋找其他罕見疾病公司的資產。 BioCryst 已經建立了卓越的商業能力，我們計劃隨著時間的推移，將多種產品推向市場，創造更大的價值。在將電話轉給 Charlie 之前，我想說，我非常高興看到公司進入下一個成長階段，我們稱之為 BioCryst 2.0。

Charlie has built one of the most successful rare disease commercial engines ever, and now we are able to leverage this engine to become the consolidator of rare disease assets. We have built a great reputation through a track record of success, and now we have the financial strength to execute this strategy. So it's time to change the leadership to execute the strategy and take the company to the next phase.

Charlie 打造了迄今為止最成功的罕見疾病商業引擎之一，現在我們能夠利用這個引擎成為罕見疾病資產的整合者。我們憑藉過往的成功經驗建立了良好的聲譽，現在我們擁有執行這項策略的雄厚財力。因此，現在是時候更換領導階層來執行這項策略，帶領公司邁入下一階段了。

After an extensive succession planning process assessing both internal and external candidates, it's great to have our Board unanimously choose Charlie as our next CEO. I've seen Charlie grow as a leader for almost a decade now, and he has earned the job as the next CEO, and he is ready to lead the company.

經過對內部和外部候選人進行全面評估的繼任計劃流程後，我們董事會一致推選查理為下一任首席執行官，這令人欣喜。近十年來，我見證了查理作為領導者的成長，他已贏得下一任執行長的職位，並已準備好領導公司。

I look forward to working with Charlie and the team in these remaining months to make this a smooth transition into the new year. With that, I will turn it over to Charlie.

我期待在接下來的幾個月與查理和團隊攜手合作，確保一切順利過渡到新的一年。接下來，我將把工作交給查理。

Thank you, Jon. It's an incredible honor to be chosen to lead this company, and it is not lost on me that I would not be in this position nor would BioCryst have reached this exciting point without your leadership. And thanks to all our colleagues who work so hard every day to bring transformative therapies like ORLADEYO to patients. You are making a big difference, and we are just getting started.

謝謝你，喬恩。能夠被選中領導這家公司，我深感榮幸。我深知，如果沒有你的領導，我就不會擁有今天的成就，BioCryst 也不會達到如今的輝煌。感謝我們所有同事，你們每天都在努力工作，為患者帶來像 ORLADEYO 這樣的變革性療法。你們正在創造巨大的改變，而我們才剛起步。

And what a start it has been for ORLADEYO. We are halfway through year five since launch, and ORLADEYO continues to build momentum that is reaching a new level. The second quarter was the best ever for the US with new patient prescriptions up over 10% above the first quarter of the launch in 2021 and over 15% above Q1 this year.

ORLADEYO 的開局真是太棒了！上市至今已過去五年，ORLADEYO 持續保持強勁勢頭，並達到了新的高度。第二季度是美國市場有史以來最好的季度，新增患者處方量較 2021 年第一季成長超過 10%，較今年第一季成長超過 15%。

ORLADEYO revenue greatly exceeded our expectations, over $22 million above Q1 and 45% growth year-over-year, and it did so for several reasons. The spike in new patient demand, further efficiency in getting paid shipments, lower discontinuations during the first half of 2025 compared to last year, gross to net improvements and strong international results all contributed in roughly equal parts to generate the overperformance. Each of these factors was a direct result of our team's continued focus on execution.

ORLADEYO 的營收遠超我們的預期，比第一季高出 2,200 多萬美元，較去年同期成長 45%。這得益於以下幾個方面：新病患需求的激增、付費出貨效率的提升、2025 年上半年停藥率較去年同期下降、毛利與淨利的改善以及強勁的國際業績，這些因素對業績超預期貢獻了大致相同的比例。所有這些因素都直接源自於我們團隊對執行力的持續關注。

With this strong second quarter, we are confident that we will reach the upper half of our revenue guidance of $580 million to $600 million for the full year, even after removing fourth quarter European revenue after closing the sale of our European business, which we anticipate in early October. We expect to provide more detailed guidance on the go-forward BioCryst business at our third quarter earnings call in November.

憑藉著強勁的第二季業績，我們有信心實現全年營收預期（5.8億至6億美元）的上半部分，即便在10月初完成歐洲業務出售後剔除第四季度歐洲業務營收後，我們仍有信心實現這一目標。我們預計將在11月的第三季財報電話會議上，就BioCryst業務的未來發展提供更詳細的指引。

The spike in demand was only one component of the surge in revenue in Q2, but the prescription trend bodes particularly well for long-term growth. We saw an uptick in new US prescribers with 69 compared to 59 in Q1, and existing prescribers continue to prescribe ORLADEYO to more of their patients. A big factor in the jump is the confidence physicians gain when they see our large volume of real-world evidence.

需求激增只是第二季營收激增的因素，但處方趨勢對長期成長尤其有利。我們看到美國新增處方醫生數量上升，從第一季的59名增加到69名，現有處方醫生繼續為更多患者開立奧拉迪舒。這一增長的一個重要因素是，醫生們看到我們大量的真實世界證據後，信心倍增。

For example, we recently released data showing that a large cohort of HAE patients with normal C1 inhibitor experienced substantial reduction in attack rates after starting ORLADEYO. This analysis of over 350 patients tracked for up to 18 months is helping physicians offer new hope for a segment of the HAE community that has struggled to get effective care for years.

例如，我們最近發布的數據顯示，大量C1抑制劑水平正常的HAE患者在開始使用奧拉迪尤後，其發生率顯著降低。這項針對350多名患者長達18個月的追蹤分析，正在幫助醫生為多年來一直難以獲得有效治療的HAE族群帶來新的希望。

There was a lot of excitement at the recent HAEA Summit because diagnosis and treatment of HAE with normal C1 inhibitor was a major part of the agenda as presenters described new consensus guidelines that were created in partnership with the patient community. US payers reimburse ORLADEYO for normal C1 at a rate about 10% less than for Type 1 and 2 patients, but our evidence generation and the expert consensus statements are helping to close that gap.

在近期舉行的HAEA高峰會上，大家興奮不已，因為C1抑制劑正常的HAE的診斷和治療是會議議程的重點，演講者介紹了與患者群體合作制定的新共識指南。美國保險公司對奧拉迪沃治療C1抑制劑正常的患者的報銷比例比1型和2型患者低約10%，但我們的證據產生和專家共識聲明正在幫助縮小這一差距。

Strong and consistent demand from Type 1 and 2 patients, the increasing demand from patients with normal C1 inhibitor and the future pediatric demand from the anticipated FDA approval of ORLADEYO granules in December set us up to continue revenue growth momentum into 2026 and beyond.

1 型和 2 型患者的強勁而持續的需求、C1 抑制劑正常的患者不斷增長的需求以及 FDA 預計 12 月批准 ORLADEYO 顆粒所帶來的未來兒科需求，使我們的收入增長勢頭延續到 2026 年及以後。

I'll turn it back to Jon in his role as acting CFO for the second quarter to review the financials.

我將把這個任務交給第二季代理財務長喬恩來審查財務狀況。

Thank you, Charlie. To make such positive and significant strides commercially while advancing our pipeline during the quarter is great to see. To be able to achieve all of that while continuing to improve our already strong financial position makes it even better. So let me walk you through the financials.

謝謝你，查理。本季度，我們在商業上取得瞭如此積極和顯著的進展，同時推進了我們的產品線，這真是令人欣喜。能夠取得所有這些成就，同時繼續改善我們本已強勁的財務狀況，這真是再好不過了。那麼，讓我來向你介紹一下財務狀況。

While you can find the detailed second quarter financials in today's press release, I'd like to draw your attention to a few items. Total revenue for the quarter came in at $163.4 million, $156.8 million of which came from ORLADEYO. Of that ORLADEYO revenue, $140.3 million or almost 90% was generated in the US.

雖然您可以在今天的新聞稿中找到第二季的詳細財務數據，但我想提請您注意以下幾點。本季總收入為1.634億美元，其中1.568億美元來自ORLADEYO。在ORLADEYO的收入中，有1.403億美元（近90%）來自美國。

For ORLADEYO revenue, that represents 45% growth in quarterly revenue over the same quarter last year. Non-GAAP operating expenses, excluding stock-based comp and deal-related costs were $106.4 million for the second quarter of 2025, up from $87.4 million in Q2 of 2024. Based on the investments we've made in the past, we've started to see strong operating leverage in our business.

ORLADEYO 的營收年增了 45%。 2025 年第二季度，非公認會計準則營運費用（不包括股票補償和交易相關成本）為 1.064 億美元，高於 2024 年第二季的 8,740 萬美元。基於我們過去的投資，我們已開始在業務中看到強勁的營運槓桿。

As you would expect, some of this increase was driven by continued investment in our R&D programs and details on expense drivers can be found in our press release. Non-GAAP operating profit for the quarter, excluding stock comp and deal-related costs, was $57 million, and our non-GAAP net income for the quarter was $32.3 million, resulting in a non-GAAP EPS of $0.15.

如您所料，部分成長得益於我們對研發專案的持續投入，具體費用驅動因素詳情請參閱我們的新聞稿。本季非公認會計準則 (Non-GAAP) 營業利潤（不包括股票補償和交易相關成本）為 5,700 萬美元，本季度非公認會計準則淨利潤為 3,230 萬美元，非公認會計準則每股收益為 0.15 美元。

We generated $45 million of cash in the second quarter before any debt prepayment. Based on the continued strength in our cash position, we paid down $75 million in principal from our term loan in April and an additional $50 million in July.

我們在第二季產生了4500萬美元的現金（未計任何債務預付）。鑑於我們持續強勁的現金狀況，我們在4月份償還了7500萬美元的定期貸款本金，並在7月份額外償還了5000萬美元。

This reduces the balance of our term debt to $199 million, and our intent is to pay it off in full upon closing the sale of the European business in early October. The cumulative effect of these prepayments enables approximately $90 million of net interest savings over the life of the loan. Our accelerating cash flow generation enables us to reach an expected $700 million in cash by 2027.

這將使我們的定期債務餘額降至1.99億美元，我們計劃在10月初完成歐洲業務出售後全額還清。這些預付款的累積效應使我們在貸款期限內節省了約9000萬美元的淨利息。我們不斷加速的現金流產生使我們預計到2027年將達到7億美元的現金。

However, we don't plan to sit on the cash, but to actively deploy it into value-creating opportunities. This strong financial performance alone represents great progress for the company. But to pair it with the commercial team firing on all cylinders and the great progress that we have made advancing our pipeline, it's even more remarkable.

然而，我們並不是打算坐擁現金，而是積極將其投入創造價值的機會。單憑強勁的財務表現就足以證明公司取得了巨大的進步。而再加上我們全力以赴的商業團隊以及我們在產品線推進方面取得的巨大進展，這一切就更加令人矚目了。

This was a great quarter to conclude my brief stint as acting CFO, and I'm delighted to welcome Babar Ghias to the team as our new CFO. Babar's extensive deal-making and operational experience in addition to his previous roles as CFO at rare disease companies are exactly what we need at this time as we look to deploy capital and accelerate our path to sustainable growth and increasing value.

本季我擔任代理財務長的短暫任期圓滿結束，這是一個美好的季度。我很高興歡迎Babar Ghias加入我們團隊，擔任新任財務長。 Babar豐富的交易和營運經驗，加上他之前在罕見疾病公司擔任財務長的經歷，正是我們目前急需的人才，因為我們正尋求資本配置，加速實現永續成長和價值提升。

I've been impressed with how quickly he's gotten up to speed and integrated with the team. The growing financial strength of the business and the inorganic opportunities available present exciting prospects for BioCryst 2.0.

他上手速度之快、融入團隊之快令我印象深刻。該公司財務實力的不斷增強以及豐富的外部投資機會，為 BioCryst 2.0 帶來了令人振奮的前景。

With that, I will turn it over to Babar.

說完這些，我就把麥克風交給巴巴爾。

Thank you, Jon. To have achieved such a strong quarter and great progress in the last few months during your tenure as Interim CFO is a testament to the amazing finance team that we have here at BioCryst. Their positive attitude and desire to make this company better have been evident to me immediately, and I'm excited to work with them.

謝謝你，喬恩。在你擔任臨時財務長的幾個月裡，BioCryst 取得瞭如此強勁的季度業績和顯著的進步，這充分證明了我們 BioCryst 擁有一支出色的財務團隊。他們積極的態度和讓公司更上一層樓的願望讓我立刻感受到了，我很高興能與他們共事。

I am honored to be joining the BioCryst team at such a pivotal point for the company. The continued strength of ORLADEYO and the recently announced European business sale creates several value-enhancing options for BioCryst. It enables us to streamline our operating structure upon completion, improving our overall profit margins.

我很榮幸能夠在公司如此關鍵的時刻加入 BioCryst 團隊。 ORLADEYO 的持續強勁表現以及近期宣布的歐洲業務出售，為 BioCryst 創造了多項增值方案。這使我們能夠在收購完成後精簡營運結構，從而提高整體利潤率。

Our plan to pay down our outstanding debt will further boost earnings from future interest expense savings. And most importantly, our strong cash flow profile, combined with an unlevered balance sheet going forward, provides us the ability to deploy capital in building sustainable shareholder value, whether it's in-licensing pipeline programs, product or company acquisitions or even return of capital to shareholders in the future. This next journey of BioCryst is going to be a very exciting one, and it's great to be here. Operator, we'll now open the call for Q&A.

我們償還未償債務的計畫將進一步提升未來利息支出節省所帶來的收益。最重要的是，我們強勁的現金流狀況，加上未來無槓桿的資產負債表，使我們能夠將資本用於建立可持續的股東價值，無論是授權通路項目、產品或公司收購，或是未來向股東返還資本。 BioCryst 的下一個旅程將會非常令人興奮，很高興能來到這裡。主持人，現在開始問答。

(Operator Instructions)

（操作員指示）

Jessica Fye, JPMorgan.

潔西卡費伊，摩根大通。

Hi, this is [Abdul] on for Jess. Congrats, Jon, on your upcoming retirement, Charlie and Barbara on the new roles. I just have two quick questions. So first, of the 45% year-over-year ORLADEYO net rev growth, how much of that was volume and how much was better paid rate or net price?

大家好，我是[Abdul]，取代Jess。祝賀Jon即將退休，也祝賀Charlie和Barbara就任新職位。我有兩個簡短的問題。首先，ORLADEYO淨收入年增45%，其中有多少是銷售成長，有多少是更好的薪資率或淨價格成長？

And then you mentioned an improved discontinuation rate for first half '25 than first half '24. What are the numbers you're seeing there? And what do you think is driving that? And should we expect the trend to continue and why? Thanks.

然後您提到2025年上半年的停藥率比2024年上半年有所改善。您看到的具體數字是多少？您認為是什麼推動了這個趨勢？我們應該預期這種趨勢會持續下去嗎？為什麼？謝謝。

Yes. So for the growth in Q2, as I said in my prepared comments, it was a mix of everything from volume. There was some gross to net improvement. We were also just more efficient in squeezing out more paid shipments during the quarter. So it was a big mix of everything.

是的。正如我在準備好的評論中所說，第二季的成長是各方面因素共同作用的結果。總收入和淨收入都有所改善。我們也在本季更有效率地完成了更多付費出貨。所以，這是一個綜合因素綜合作用的結果。

But what I'm really excited about is the fact that the demand was so high because that's what's going to drive the long-term growth. And it's -- it was better than ever. And sorry, the second part of the question, can you repeat that part?

但我真正興奮的是需求如此之高，因為這將推動長期成長。而且——情況比以往任何時候都好。抱歉，關於問題的第二部分，您能重複嗎？

The second question or the second part of the first question?

第二個問題還是第一個問題的第二部分？

Sorry, the second question.

抱歉，第二個問題。

Yeah. So you mentioned an improved discontinuation rate for the first half of '25. What numbers are driving that there? And do you expect to continue that?

是的。您提到2025年上半年停藥率有改善。是什麼因素推動了這股趨勢？您預計這種情況會持續下去嗎？

So what we've seen over the last several years, and it's true in the first half of this year as well is that the one-year discontinuation rate has been rock solid. So 60% of patients who start make it to a year. That really hasn't shifted. Where I think we've seen a little bit of an improvement as our patient base grows, the overall discontinuation rate is trending slightly down because patients who make it to a year, they're doing really well, they stay on therapy.

過去幾年，以及今年上半年，我們看到的都是一年期停藥率一直非常穩定。 60%的患者在開始治療後堅持了一年。這個比例幾乎沒有變化。我認為，隨著患者群體的成長，情況略有改善，但整體停藥率略有下降，因為堅持了一年的患者病情都很好，他們會繼續接受治療。

And so it's exactly what you want to see, and I would expect to see this kind of same solid discontinuation or retention rate going forward.

這正是您想要看到的，我希望看到未來同樣穩定的停產率或保留率。

Thank you.

謝謝。

Laura Chico, Wedbush Securities.

勞拉‧奇科 (Laura Chico)，韋德布希證券公司。

Good morning. Thanks so much for taking the questions. My congrats to Jon, Charlie, Babar. Thank you. So I guess I had just one -- your comments on discontinuation rates made us a little curious here. Could you speak a little bit to persistency rates in relationship to other injectable prophylactic regimens?

早安.非常感謝你們回答這些問題。祝賀喬恩、查理和巴巴爾。謝謝。我想我只有一個問題——你們關於停藥率的評論讓我們有點好奇。能否談談與其他注射預防方案相比，持續率的相關性？

And I realize there's probably no direct head-to-head studies, but wondering if you can comment here on any real-world data just that puts into context the persistency you're now seeing with ORLADEYO versus the injectable products. Thank you.

我知道可能沒有直接的頭對頭研究，但我想知道您是否可以在這裡評論任何真實世界的數據，這些數據可以解釋您目前觀察到的奧拉迪優（ORLADEYO）相對於注射產品的持久性。謝謝。

Yes. Thanks, Laura. We actually put out some data at a recent conference. I think it was last fall at the college meeting. We looked at health care claims data for both ORLADEYO for TAKHZYRO and HAEGARDA and looked at patients starting any of those three products.

是的。謝謝，勞拉。我們最近在一次會議上公佈了一些數據。我記得是去年秋天的大學會議上。我們查看了ORLADEYO的TAKHZYRO和HAEGARDA的醫療保健理賠數據，並研究了開始使用這三種產品的患者。

and looked at the one-year persistence rate. And the one-year rate is statistically identical for all of them, around 60%. Numerically, actually, ORLADEYO was a little bit better than the other two. And so I think what that shows to us is no single HAE therapy is perfect for every patient. And we know that about 70% of patients would prefer to treat with an oral prophy product. So it shows that ORLADEYO has got the profile that patients want and performs really well in the real world.

並觀察了一年的持續率。從統計學角度來看，所有藥物的一年持續率都相同，約60%。實際上，從數值上看，ORLADEYO略優於其他兩種藥物。我認為這說明，沒有一種HAE療法能夠完美適用於所有患者。我們知道，大約70%的患者更傾向於使用口服預防產品來治療。這表明，ORLADEYO滿足了患者的需求，並且在實際治療中表現出色。

Thanks very much.

非常感謝。

Steve Seedhouse, Cantor.

史蒂夫‧西德豪斯 (Steve Seedhouse)，領唱。

Good morning. Thank you. Congratulations, Jon, Charlie, Babar, really everyone on the quarter as well. Two questions. First, any early indications of how the June and July approvals in HAE, so garadacimab and Ekterly are affecting ORLADEYO demand over the past month? And also, any additional color you can provide on the pediatric PDUFA delay just to give us comfort there. Thank you.

早安.謝謝。恭喜Jon、Charlie、Babar，也恭喜本季的各位。兩個問題。首先，有沒有早期跡象表明，HAE（加拉達昔單抗）和Ekterly在6月和7月的批准對過去一個月ORLADEYO的需求有何影響？此外，您能否就兒科PDUFA（處方藥使用者付費法案）的延期提供一些補充信息，讓我們安心一些？謝謝。

Sure. On the new approvals, we just had by a substantial margin, the most new patient prescriptions ever. So what it shows is physicians aren't waiting for any of these new products, which is exactly what our long-term market research has shown. ORLADEYO is the most differentiated prophy in the market, and I expect our demand to continue.

當然。就新獲批准的藥物而言，我們剛剛獲得了大幅增長，創下了患者處方數量的歷史新高。這顯示醫師們對這些新產品並不急於求成，這正是我們長期市場調查的成果。奧拉迪尤是市場上最具差異化的預防藥物，我預期我們的需求將持續成長。

Yeah. I think it's important, too, to remember that we've told you patients don't see their doctor much more than once or twice a year. So if they were going to have that conversation, they would have it set up, and we're not seeing that. So I think that's at least an early good sign for us. Do you want to take the pediatric?

是的。我認為同樣重要的是，要記住我們說過，病人一年看醫生的次數不會超過一兩次。所以，如果他們要進行這種談話，他們肯定會提前安排，但我們沒有看到這種情況。所以我認為這至少對我們來說是一個早期的好兆頭。你想去兒科嗎？

Yeah. And the question on the pediatric and the PDUFA date. So the FDA upon receiving some final reports and some responses that we gave them decided that they needed a little more time to review. So that's a major amendment to the NDA, and that leads us to the PDUFA date of December 12. So we're on track for that.

是的。關於兒科和PDUFA日期的問題。 FDA在收到我們提交的一些最終報告和回覆後，決定需要更多時間進行審查。這是對NDA的一項重大修訂，因此PDUFA的日期定在12月12日。我們正在按計劃進行。

Yeah. And we knew when we submitted the original filing that we had these reports that we had to get in. If we had waited for those, we would have virtually the same PDUFA date. So we thought we would take a shot at that. And we're excited. The key is we're going to get approval this year, and we're excited about that. So --

是的。我們在提交原始申請時就知道，我們必須提交這些報告。如果我們等到這些報告提交，PDUFA 的日期幾乎會一樣。所以我們想試試看。我們很興奮。關鍵是我們今年就能獲得批准，我們對此感到很興奮。所以——

Thanks so much.

非常感謝。

Tazeen Ahmad, Bank of America.

美國銀行的塔津·艾哈邁德（Tazeen Ahmad）。

Hi, good morning. Congrats on a great quarter once again. I just wanted to maybe get a little bit of color on what you think your penetration rate is into the addressable market today? And where are you seeing most of your use? Is it more from doctors who've tried ORLADEYO, like the results and keep prescribing it? Or are you seeing an acceleration of new doctors coming on board to write scripts for the first time? Thanks.

大家早安。再次恭喜您本季取得如此佳績。我想稍微解釋一下，您認為目前奧拉西坦在潛在市場的滲透率是多少？您認為奧拉西坦的主要應用場景是哪些？更多的是來自那些嘗試過奧拉西坦、喜歡其效果並繼續開處方的醫生嗎？還是說，您是否看到越來越多的新醫生首次加入並開立處方？謝謝。

Charlie, you might want to talk too about pace because I think that's an important piece that people might not understand.

查理，你可能也想談談節奏，因為我認為這是一個人們可能不理解的重要部分。

Yeah. Tazeen, from a penetration rate perspective, we've noted before at the end of 2024, about 3,000 patients had already tried ORLADEYO, roughly half of those are still on therapy. And recall that we've also put out data that there are about 11,000 diagnosed patients in the market. So we still have a lot of upside growth remaining. As far as health care providers, I was really thrilled that we had 69 new prescribers in Q2 this late in the launch.

是的。 Tazeen，從滲透率的角度來看，我們之前就注意到，到2024年底，大約有3000名患者已經嘗試過ORLADEYO，其中大約一半仍在接受治療。記得，我們​​也公佈了數據顯示，市場上大約有1.1萬名確診患者。所以我們仍然有很大的成長空間。至於醫療保健提供者，我很高興看到我們在第二季如此快速地推出了ORLADEYO，就新增了69名處方醫生。

It shows that we keep finding and convincing more doctors. And the overall split of prescriptions tends to still be about 50-50 with about half of them being from Tier 1 physicians, the top 600 roughly that treat half the patients in the market. And then the other half comes from the wider base of other physicians who have just a few patients.

這表明我們一直在尋找並說服更多醫生。處方的整體分配仍然趨於五五開，其中約一半來自一級醫生，也就是大約600名頂尖醫生，他們治療著市場上一半的患者。另一半則來自更廣泛的其他醫生群體，他們只有少數患者。

And what we're seeing overall, and Jon mentioned this in his comments, I alluded to this as well is there's just more confidence amongst physicians in the long-term data that they're seeing the data that we present to them and then also what they experience themselves.

總體而言，我們看到的是，喬恩在他的評論中提到了這一點，我也提到了這一點，醫生對長期數據更有信心，他們看到了我們向他們提供的數據，以及他們自己的經歷。

And so they're really thinking about ORLADEYO very differently than they were a few years ago, and they have confidence in putting -- switching patients, which is still roughly 50% of the patients. They're confident in putting acute-only patients having them come over to prophy, start with ORLADEYO. And then patients naive to therapy as well. When they start on a prophy, ORLADEYO is the natural place. So we're capturing all the segments.

所以，他們對奧拉迪約 (ORLADEYO) 的理解與幾年前截然不同，他們有信心將患者轉診至奧拉迪約，目前約佔患者的 50%。他們有信心讓僅接受急性治療的患者先接受預防性治療，然後再從奧拉迪約開始。對於初次接受治療的患者，他們也同樣有信心。當他們開始進行預防性治療時，奧拉迪約是最佳選擇。因此，我們正在涵蓋所有細分市場。

Charlie spent a bit of time in his prepared remarks talking about normal C1 patients, and that is a real opportunity for us, a place that historically physicians have not had great success in either diagnosing or treating. And we've generated data, meaningful data, 350 patients worth of real-world evidence showing pretty amazing reductions in baseline attack rates on ORLADEYO with these patients. So those are examples of areas that the team just keeps scouring and finding, and that's why you keep seeing this sustainable growth.

查理在準備好的發言中花了一些時間談論普通的C1患者，這對我們來說是一個真正的機會，因為過去醫生在診斷和治療方面都不太成功。我們已經產生了數據，有意義的數據，350名患者的真實世界證據表明，這些患者在ORLADEYO的基線發病率顯著降低。這些都是團隊不斷探索和發現的領域的例子，這也是我們持續看到這種永續成長的原因。

Thanks for the color, guys. And then just maybe to follow up, are you expecting that stickiness topic that has come up on several calls to continue as you add new patients, how reliable do you think they'll be to stay on therapy if new potential -- new oral competitors come online. Thanks.

謝謝大家的關注。接下來我想問一下，隨著新患者的增加，您是否預計在幾次電話會議中提到的「患者黏性」問題會持續下去？如果出現新的口服藥物競爭對手，您認為這些患者繼續接受治療的可靠性如何？謝謝。

Sure. No, I think extremely sticky. You either do great on ORLADEYO and you stay on or you don't, and you move off. So I don't think patients are not waiting for some hypothetical future oral product. They'll switch today. They've got a lot of good injectable options. If they don't get what they need from ORLADEYO, they'll switch. And so I think the patients that stay are very sticky.

當然。不，我認為非常粘性。要嘛奧拉迪尤效果很好，繼續使用，要嘛效果不好，就停藥。所以我認為患者不會在等待未來可能出現的口服產品。他們現在就會換藥。他們有很多不錯的注射產品可供選擇。如果奧拉迪尤沒有達到他們想要的效果，他們就會換藥。所以我認為留下來的患者黏性非常強。

Yeah. And the last thing I'd say is what would be better than a once-a-day highly effective drug, right? Like what behind us is coming that is better. There really isn't a profile that's better. So we expect it to be very sticky, as Charlie said.

是的。最後想說的是，還有什麼比每天一次的高效藥物更好呢？就像我們即將推出的更好的藥物一樣。真的沒有比它更好的了。所以我們預計它會非常持久，就像查理說的。

Gena Wang, Barclays.

巴克萊銀行的 Gena Wang。

Thank you for taking my questions. Also, congrats on the strong quarter. So maybe Charlie and the team, if you can give a little bit more color regarding the launch metrics in 2Q regarding the reimbursement product rate, I think the last quarter was at 84%. And retention rate, I just want to confirm, is that consistent, stay at 60%? And if you can provide any other metrics regarding the patient segment.

感謝您回答我的問題。另外，恭喜您本季表現強勁。 Charlie 和團隊，能否請您詳細介紹第二季的上市指標，例如報銷產品費率。我認為上一季的報銷產品率是 84%。至於留存率，我想確認一下，這個數字是否穩定在 60% 左右？您能否提供一些關於患者細分市場的其他指標？

And then second question is regarding the timing for the two pipeline assets. I know you said that by the end of -- by year-end '25 for two pipeline assets. Maybe any additional color you can share regarding the patient enrollment and expectation for the data.

第二個問題是關於這兩項在研藥物的上市時間。我知道您說過，到2025年底，兩項在研藥物都會上市。您能否分享一些關於患者入組情況和數據預期的更多資訊？

Lastly, very quickly, I just wanted to ask, Jon, I know it's -- it has been great working with you. And I'm just wondering what's the reason regarding the timing for transition to the next journey of your life?

最後，我想快速問一下，喬恩，我知道和你合作很愉快。我只是想知道，你選擇在這個時候開啟人生的下一個旅程，原因是什麼？

Great. Charlie, do you want to take the first one?

太好了。查理，你想坐第一個嗎？

Sure, Gena. As far as the launch metrics, I mentioned in my prepared remarks that we were able to -- part of the overperformance in the quarter is we got more paid shipments out of our patient population than we have historically on a trend rate. So that was part of the overperformance. The actual paid rate is doing exactly what I predicted last quarter, which is we reached a high watermark around the April, May timeframe when we come off of the reimbursement -- sorry, the reauthorization season. And then for the rest of the year, the paid rate tends to be dominated by new patients coming in.

當然，Gena。就上市指標而言，我在準備好的發言中提到過，我們本季業績超預期，部分原因是我們從患者群體中獲得的付費發貨量超過了歷史趨勢水平。所以，這也是業績超預期的原因之一。實際付費率與我上個季度的預測完全一致，也就是在4月和5月左右達到最高點，那時我們剛結束報銷期——抱歉，是重新授權期。而在今年剩餘時間裡，付費率往往由新入院的患者決定。

What that means is it drifts down slightly over the course of the year by -- we would expect it to go a percentage or 2 down by the end of the year, and we're on that trend. So we feel really good about where we are. Then next year, we'll recover that and probably take the reimbursement rate to a new high. As far as retention, as I mentioned in the last question, it's been really solid. So that one-year 60% retention rate has been consistent for the last roughly three years.

這意味著它會在一年內略有下降——我們預計到年底會下降一到兩個百分點，而且我們正處於這個趨勢之中。所以我們對目前的狀況非常滿意。明年，我們將恢復這一水平，並可能將報銷率推向新的高度。至於留存率，正如我在上一個問題中提到的，它一直非常穩固。所以，過去大約三年來，60% 的一年留存率一直保持穩定。

And it's because patients they -- as I said, they either do really well, and they stay on or they move on to a different product.

這是因為患者——正如我所說，他們要么表現得很好，繼續使用，要么轉向其他產品。

And then with regard to the pipeline question, so we have two programs in the pipeline, both in the clinic that we're progressing with data anticipated by the end of the year. They're both progressing well on track for Netherton syndrome, our program is 17725, for which data this year will be both on exposure, the penetration of the drug in the skin and on potential efficacy endpoints, including itching and healing of the skin. So we anticipate having initial data for that drug for those endpoints by the end of the year.

關於研發管線問題，我們目前有兩個項目正在研發中，目前都處於臨床階段，預計年底前可以取得數據。這兩個項目在治療內瑟頓症候群方面進展順利，我們的計畫是17725，今年的數據將涵蓋藥物的暴露量、藥物在皮膚中的滲透性以及潛在的療效終點，包括搔癢和皮膚癒合。因此，我們預計年底前將獲得該藥物在這些終點的初步數據。

For avoralstat this is a trial in patients where one dose will give sustained exposure. We expect to have exposure over months. And so what we'll be looking for is how patients do once they've had that single dose. This is treating for DME. So we'll be looking for effect on the retina and the potential for reducing the swelling in the retina. And as I said, its exposure over months, but we'll be looking at 4 weeks, 8 weeks, 12 weeks in.

對於阿沃拉司他，這是一項針對單一劑量即可產生持續性作用的患者試驗。我們預計作用時間將持續數月。因此，我們關注的是患者在單一劑量給藥後的表現。該藥物用於治療糖尿病性黃斑水腫 (DME)。因此，我們將觀察其對視網膜的影響以及減輕視網膜腫脹的可能性。正如我所說，其作用時間持續數月，但我們將觀察4週、8週或12週後的情況。

So that initial data will be coming this year, too.

因此初始數據也將於今年公佈。

Great. And then in terms of timing for me, Gena, thank you, by the way. It's been great working with you as well. It's time. I don't know how else to say it. I turned 65 this year. I've been in the company. It will be nearly 19 years when I leave. The company is in great shape. The Board and I have been working on this succession for over a couple of years, and Charlie is a great choice. So it all just kind of lined up, and it's just perfect timing. So that's my answer.

太好了。至於時機，吉娜，順便說一句，謝謝你。和你一起工作也很愉快。是時候了。我不知道該怎麼說。我今年65歲了。我已經在公司工作了。到我離開的時候，已經快19年了。公司狀況很好。董事會和我為繼任者的工作已經進行了幾年，查理是個很棒的人選。所以一切都安排好了，時機也剛剛好。這就是我的答案。

Stacy Ku, TD Cowen.

史黛西·庫 (Stacy Ku)，考恩 (Cowen) TD。

Hey, good morning. A quick congratulations to both Jon and Charlie on the announcements. You both have done amazing things together with the BioCryst team. So a few questions. One quick follow-up. Just longer term, maybe remind us how you're thinking about the on-demand launch of oral Ekterly as we think about -- as we always had thought that would be a benefit for you all.

早安.恭喜 Jon 和 Charlie 兩位宣布了這一消息。你們和 BioCryst 團隊一起做出了許多了不起的成就。所以，我有幾個問題。接下來是一個簡單的跟進。從長遠來看，或許可以談談你們對按需推出口服 Ekterly 的看法，我們一直認為這對你們所有人都有益處。

So just help us understand, is the sales force able to maybe re-grab share with patients that had to go back on injectables with ORLADEYO? Is that low-hanging fruit? And then from a payer perspective, how are they going to handle all this? So just maybe some more details there as we've been getting some investor questions.

所以請您幫我們理解一下，銷售團隊能否從那些不得不重新使用奧拉迪舒注射劑的患者手中重新搶佔市場份額？這很容易實現嗎？然後從付款人的角度來看，他們將如何處理這一切？鑑於我們最近收到了一些投資者的提問，我想再提供一些細節。

And then second, a little bit of just a double checking here. As we think about the paid shipments in Q2, just want to understand, is there any implications on a quarterly basis, something that has come up with other companies. I just want to make sure there's no changes to the normal quarterly cadence?

其次，這裡需要再確認一下。我們考慮一下第二季的付費出貨量，想了解這是否會對季度產生影響，其他公司也遇到類似的情況。我只是想確保正常的季度節奏沒有變化。

And then last, we see the IND approval by the FDA for Netherton. So congratulations there. As we await data, just remind us the current competitive landscape there and what kind of learnings you are taking? Thanks so much.

最後，我們見證了FDA對Netherton的IND批准。恭喜！在等待數據期間，能否介紹一下目前的競爭格局以及你們正在學習哪些經驗？非常感謝。

Sure. Thanks, Stacy. As far as the role of Ekterly, yeah, we think patients are really excited. The ability to ultimately have an all-oral combination where you take an oral prophy and then when you have an occasional breakthrough attack, be able to treat it with an oral as well. It just adds to the convenience and for patients just being able to worry less and kind of forget that they have HAE.

當然。謝謝，Stacy。說到Ekterly的作用，是的，我們認為患者們非常興奮。最終能夠實現全口服合併治療，即患者服用口服預防藥物，當病情偶爾出現突破性發作時，也可以口服藥物進行治療。這不僅增加了便利性，也讓患者減少擔憂，幾乎忘記自己患有HAE。

We saw that excitement at the HAE Summit last month. And so we do think it has -- there's a potential positive upside both in terms of attracting patients to ORLADEYO and for patient retention if they're also taking -- or using an oral on demand.

我們在上個月的HAE峰會上看到了這種興奮。因此，我們確實認為，無論是在吸引患者到奧拉迪尤治療方面，還是在患者同時服用或使用按需口服藥物的情況下，奧拉迪尤都具有潛在的積極作用。

What we definitely know from speaking to patients and physicians in large numbers is prophy is still the backbone of therapy that they're looking for and in particular, oral prophy. As far as paid ships in Q2, no, nothing that we're seeing out of the ordinary. The improvements that we're seeing is just about our team's execution.

透過與大量患者和醫生的交流，我們確信預防性治療仍然是他們尋求的治療手段的支柱，尤其是口服預防性治療。至於第二季的付費出貨量，我們並沒有發現任何異常。我們看到的改進僅僅源自於我們團隊的執行力。

And then I would expect for the rest of the year a similar quarterly cadence to what we saw last year, where the revenue growth slows down a bit relative to Q2 because we're out of the reauthorization season. And so I would expect it to look quite similar with Q3 and Q4 growing according to our new patient demand.

我預計今年剩餘時間的季度節奏將與去年類似，由於已度過重新授權期，營收成長相對於第二季會略有放緩。因此，我預計第三季和第四季的情況會與去年類似，會根據新患者的需求而成長。

And then with regard to the competitive landscape, I mean, it's always hard to say stuff with any certainty. But Daiichi, we haven't heard boo from their program in almost two years. And so that's probably not a good sign. And we've heard that for business reasons, they've terminated. We don't know if that's true or not, we've heard that.

至於競爭格局，我的意思是，總是很難確切地說出任何事。但對於大一核電站，我們近兩年來沒有聽過對他們計畫的批評。所以這可能不是一個好兆頭。我們聽說他們出於商業原因終止了該專案。我們不知道這是不是真的，但我們確實聽說過。

And then BI had a program that I think they out-licensed or sold to a company. Usually, you don't sell an asset if you have a lot of value and confidence in an asset. So that probably doesn't bode well. So we -- I mean, we could be the first therapy, which would be amazing because I think we were third or fourth even when we were first looking at this. But -- and this is a place where the unmet need is huge, right?

然後，BI 有一個項目，我認為他們授權給了其他公司或出售給了其他公司。通常情況下，如果你對某項資產很有價值且很有信心，你就不會賣掉它。所以這可能不是一個好兆頭。所以我們——我的意思是，我們可能會成為第一個療法，這很棒，因為我認為即使在我們最初研究這個療法的時候，我們也排在第三或第四位。但是——這是一個未滿足需求龐大的領域，對吧？

So -- we're really excited about it and eager to get the data to have a sense of dose and is it getting to the skin and is it having an effect. So stay tuned.

所以——我們對此感到非常興奮，並渴望獲得相關數據，以了解劑量、它是否到達皮膚以及是否產生了效果。敬請期待。

Thank you so much.

太感謝了。

Brian Abrahams, RBC Capital Markets.

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

Hey, guys. Thanks for taking my questions. Jon, congrats on all your career achievements, and congratulations as well to Charlie and Babar on your new and upcoming roles. Two bigger picture questions for me. I guess, first, for most favored nation policy, how do you guys model that playing out and potentially affecting you guys, if at all, particularly with European pricing that's no longer going to be under your control? Maybe remind us of your overall Medicaid exposure.

大家好。感謝你們回答我的問題。喬恩，祝賀你職業生涯的所有成就，也祝賀查理和巴巴爾即將就任的新職位。我有兩個更重要的問題。我想，首先，關於最惠國政策，你們如何模擬它如何運作，以及它對你們的潛在影響（如果有的話），尤其是在歐洲定價不再受你們控制的情況下？或許可以談談你們在醫療補助方面的整體風險。

And then secondly, you talked a lot on the -- earlier in the call on deployment of capital. And I'm just I'm curious how you're viewing the market for buyers here, how competitive it is, the types of opportunities that you might be interested in, in terms of stage and segment and your optimal timelines for executing on that? Thanks.

其次，您在先前的電話會議上談了很多關於資本配置的問題。我很好奇您如何看待這裡的買家市場？競爭如何？您可能感興趣的機會類型是什麼？在階段和細分領域，以及您執行這些機會的最佳時間表是什麼？謝謝。

Sure. So Charlie, do you want to take the first one and Babar will take the second.

當然。那麼查理，你想拿第一個，巴巴爾拿第二個嗎？

So Brian, as far as MFN, obviously, like others, we're watching this, but I don't think we've seen anything specific that would apply to us. And so we'll just keep executing and watching that space. Medicaid for us is a relatively small segment. It actually is sort of between 10% and 15% of our patients. So we'll just watch. But right now, we don't see an immediate impact.

布萊恩，就最惠國待遇（MFN）而言，顯然，和其他人一樣，我們正在關注此事，但我認為目前還沒有看到任何具體適用於我們的情況。所以我們會繼續執行並關注這個領域。醫療補助（Medicaid）對我們來說是一個相對較小的領域。它實際上只占我們患者的10%到15%。所以我們會繼續觀察。但目前，我們還沒有看到立竿見影的效果。

And Brian, your next question, the market couldn't be better for -- if you're a buyer at the moment and you don't need to tap -- raise more capital. And I think that's what we -- you heard from the remarks that we are in an enviable position of having sustainable cash flow. But let me give you a little bit more color. We will be broadly looking at the rare disease space. We want to be a consolidator of rare disease assets. So assets where we can -- where there's high unmet needs and we can leverage our operational infrastructure.

布萊恩，你的下一個問題是，如果你現在是買家，而且不需要進一步融資，那麼現在的市場環境再好不過了。我想這就是我們——你剛才說的，我們擁有令人羨慕的可持續現金流。不過，讓我再跟你講一次。我們將廣泛關注罕見疾病領域。我們希望成為罕見疾病資產的整合者。也就是說，我們會整合那些存在大量未滿足需求的資產，並充分利用我們的營運基礎設施。

We have a very promising early pipeline. So we will look to balance our portfolio with more later-stage assets post proof of concept, soon to be commercial and even commercial assets. So I think the next couple of months will be very interesting from that vantage point, and we'll have some more developments over the next coming months.

我們擁有非常有前景的早期產品線。因此，我們將尋求透過更多概念驗證後的後期資產、即將投入商業化甚至商業化的資產來平衡我們的投資組合。因此，我認為從這個角度來看，接下來的幾個月將會非常有趣，我們在接下來的幾個月裡還會有更多進展。

Yeah. And Brian, you know firsthand that companies are really struggling to find capital to fund their operations, whether it's clinical development or launching a product. So it's just a tough spot for people to be in and an opportunity for us.

是的。布萊恩，你親身經歷過，很多公司都很難找到資金來維持運營，無論是臨床開發還是產品發布。所以，這對人們來說是一個艱難的處境，而對我們來說卻是個機會。

Congrats on the strong quarter that put you in that position. And thanks again for taking our questions.

恭喜您在這個季度取得如此出色的成績，並最終獲得這一職位。再次感謝您回答我們的問題。

John Wolleben, Citizens.

約翰‧沃勒本，《公民報》。

Hey. Thanks for taking the question and sharing our congrats to Jon and Charlie as well. I was hoping you guys could talk a little bit about typical second half push and pulls with like about $290 million in first half revenue. Not much has to go right for you guys to hit that lower end of your guidance. So wondering if you think kind of all the positive dynamics here in 2Q are going to continue or just a little bit about what you see typically second half and what you're seeing so far this year. Thanks.

嘿。感謝您回答這個問題，也感謝你們向喬恩和查理表示祝賀。希望你們能談談下半年的典型情況，例如上半年營收約2.9億美元。你們不需要做太多準備就能達到預期的下限。所以，我想知道您是否認為第二季的所有積極勢頭會持續下去，或者您能簡單談談下半年的典型情況以及今年迄今為止的情況。謝謝。

Sure, Jon. Second half, as I've said, tends to be -- it's driven by new patients coming in. And it takes a little bit longer to get a new patient or the new patient population to the same paid rate as our overall population. And so therefore, number one, the overall paid rate tends to go down or will probably go down 1 percentage point or 2 in the second half.

當然，喬恩。正如我之前所說，下半年的趨勢往往是由新病人的到來所推動的。而讓一位新病人或新病人群體達到與我們總人口相同的付費率需要更長的時間。因此，首先，下半年的整體付費率往往會下降，或者可能會下降1到2個百分點。

We don't have the opportunity to bring a big bolus of patients from new prescription or from long-term free product over to paid the way that we do in the first quarter into early the second quarter. And so we expect those same dynamics for the second part of this year. And all signs show that our demand is going to continue to be really strong.

我們沒有機會像第一季一樣，將大量新處方藥或長期免費產品的患者轉為付費患者，這種情況持續到第二季​​初。因此，我們預計今年下半年的情況將與去年相同。所有跡像都表明，我們的需求將持續強勁。

And the last thing that I'd say in terms of the dynamics is remember that the fourth quarter, we will not have European revenue. And we've guided you to what the trailing 12 months was in terms of the revenue that was being generated when we announced the deal. So you can add a little bit of extra for the fourth quarter because it's usually a little bit higher. But that will give you some sense of what to deduct out of the fourth quarter revenue.

關於動態，我最後要說的是，請記住，第四季我們將沒有歐洲收入。我們已經向您介紹了我們宣布交易時過去12個月的收入情況。因此，您可以為第四季度增加一些額外收入，因為它通常會更高一些。但這會讓您大致了解應該從第四季度收入中扣除哪些部分。

Yeah. And Jon, you may have heard me say, but I did say in my comments, I expect us to be in the upper half of our $580 million to $600 million after subtracting European revenues in Q4.

是的。喬恩，你可能聽我說過，但我在評論中確實說過，我預計扣除第四季度歐洲收入後，我們的營收將達到 5.8 億至 6 億美元的上半部分。

Got it. Thanks, guys. That's helpful.

明白了。謝謝大家。這很有幫助。

Serge Belanger, Needham & Company.

塞爾日·貝朗格（Serge Belanger），Needham & Company。

Hi, good morning and congrats on another strong quarter. Charlie, you mentioned a couple of factors behind the strength of ORLADEYO this quarter. You did mention an improvement in gross to net. So just curious if it's still within that prior 15% to 20% range.

大家早安，恭喜您又一個強勁的季度。 Charlie，您提到了ORLADEYO本季業績強勁的幾個因素。您確實提到了毛利潤與淨利潤的比率有所提高。所以，我很好奇它是否仍在之前的15%到20%的範圍內。

And you also mentioned you hit a new high watermark in new patient adds. How does that compare to 2024 levels when I believe you added about 300 patients for the year? And then lastly, just given the overall expansion of the prescriber base and the strong patient add, is there a case here to add on to the current sales force to take advantage of the strength? Thanks.

您也提到，新病人新增數量創歷史新高。與2024年的水準相比如何？我認為2024年您新增了大約300名病人。最後，考慮到處方醫生群體的整體擴張和強勁的病人新增量，是否有理由在現有銷售隊伍的基礎上進一步擴充，以充分利用這一優勢？謝謝。

Sure. Thanks, Serge. As far as gross to net, yes, we've been really efficient this year. And some of that is just the mix with Medicare patients getting up to a higher paid rate as we talked about last quarter, and there's a bunch of other factors as the team manages it. So I think we're in the lower portion.

當然。謝謝，Serge。就毛收入與淨收入之比而言，是的，我們今年的效率確實很高。這部分是由於我們上個季度討論過的醫保患者支付率上升，以及團隊管理過程中的許多其他因素。所以我認為我們的收入佔比較低。

We're still in the 15% to 20%, but closer to 15% off of net price. And then as far as new patient adds compared to 2024, at the end of Q1, I did mention Q1 was a really good quarter this year, and it was last year was the best year we had since the first year of launch. Q1 was just a little bit better than the best quarter of last year. And then Q2 this year blew away Q1. So we're doing really well on the new patient adds. And then as far as the prescriber base and do we need more reps? No, we don't. We have a fantastic team out there.

我們仍然在15%到20%的範圍內，但接近淨價的15%。至於新增患者數量，與2024年相比，在第一季末，我提到今年第一季表現非常好，去年也是我們自推出產品以來最好的一年。第一季比去年最好的季度略好。然後，今年第二季的表現又超過了第一季。所以我們在新增患者數量方面做得非常好。至於處方藥基數，我們需要更多銷售代表嗎？不，我們不需要。我們擁有一支非常優秀的團隊。

They are able to cover the population. They're able to expand the number of prescribers quarter-after-quarter. And actually, if we added more people, it would decrease our efficiency and probably just tick off our customers. So we're not going to do that. And one thing that's been great is we've been growing our revenue, but our actual direct commercial spends are hardly going up at all. And that's because we've got the right data, the right message, the right team and they're executing in a phenomenal way.

他們能夠涵蓋所有人群，能夠逐季增加處方人員的數量。實際上，如果我們增加更多人手，反而會降低效率，甚至可能惹惱客戶。所以我們不會這麼做。值得慶幸的是，我們的收入一直在成長，但實際的直接商業支出幾乎沒有成長。這是因為我們擁有正確的數據、正確的資訊、合適的團隊，而且他們的執行力非常出色。

And kind of back to what Babar was saying about leveraging the existing infrastructure that we have. We have made investments in patient services and more data to be smarter about where we might find more physicians. But that we can use for any product in the future. And it's not direct salespeople that you have to add. So that's why we're so convinced that putting more products into this well-oiled commercial machine is going to create greater and greater value.

回到Babar所說的利用我們現有的基礎設施。我們在患者服務和更多數據方面進行了投資，以便更明智地找到更多醫生。這些數據未來可以用於任何產品，而且不需要增加直銷人員。也因為如此，我們堅信，將更多產品投入這台運作良好的商業機器中，將創造越來越大的價值。

Thank you.

謝謝。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特 (Maury Raycroft)，傑富瑞 (Jefferies)。

Hi, this is Amy, on for Maury. Thank you for taking our questions and congrats on the quarter. We have two questions on the pipeline programs, Netherton and DME. For the Netherton, what is your latest thoughts on the pivotal trial design and the regulatory timeline for this indication? Is there a defined pathway for accelerated approval either from precedents or clear KOL or FDA feedback?

大家好，我是艾米，代表莫里發言。感謝您回答我們的問題，並祝賀本季取得的成績。我們有兩個關於Netherton和DME的在研計畫的問題。關於Netherton，您對該適應症的關鍵試驗設計和監管時間表有何最新看法？是否有明確的加速審批途徑，無論是根據先例、明確的KOL或FDA的回饋？

And for the DME program, like what would the outcomes from the Phase 3 study contribute to the design of Phase 2 or even the pivotal? And for the retinal swelling reduction results that we are expecting to see at the end of this year, what is the bar that we need to beat here? Thank you.

對於DME項目，3期研究的結果會對2期甚至關鍵研究的設計有何貢獻？對於我們預計在今年年底看到的視網膜腫脹減輕結果，我們需要突破的標準是什麼？謝謝。

Okay. So Helen, do you want to take the first one? Don, take the second one?

好的。海倫，你想選第一個嗎？唐，你想選第二個嗎？

Yeah. So on Netherton syndrome, the pivotal trial, so this is a really interesting program because it is one in which there is an unmet need. And there is -- it's a very serious disease, which means that it's -- you don't need to see much effect and you don't need to see it in many patients to demonstrate that the drug is going to be beneficial for patients. What we expect with 17725 is a very large effect. This is a potent drug with high affinity.

是的。關於內瑟頓症候群的關鍵試驗，這是一個非常有趣的項目，因為它涉及一個尚未滿足的需求。而且，這是一種非常嚴重的疾病，這意味著，你不需要看到太多的效果，也不需要在許多患者身上看到效果，就能證明這種藥物對病人有益。我們預計17725會有非常顯著的效果。這是一種具有高親和力的強效藥物。

It's targeted drug and it's intended to essentially provide a replacement of the missing enzyme function. So the pivotal trial design will be looking at what is the effect that matters to patients. What is the effect on an approvable endpoint.

它是一種靶向藥物，其本質上旨在替代缺失的酶功能。因此，關鍵的試驗設計將著眼於對患者而言重要的效果。它對可批准終點的影響是什麼？

And we think that is changes in the skin, both how it's healing, the assessment of the skin and the patient experience, the itching. Those are relatively simple to measure. We'll be looking at those in our current trial. We'll be looking at those in a pivotal trial, and it's possible this could be a very short path to pivotal. It's possible also it could be then a short path to a registration endpoint and submission to the FDA.

我們認為這是皮膚的變化，包括癒合情況、皮膚評估、患者體驗以及搔癢感。這些都相對容易測量。我們將在目前的試驗中研究這些變化。我們將在關鍵試驗中研究這些變化，這可能是一條通往關鍵終點的捷徑。也可能是通往註冊終點並提交給FDA的捷徑。

What that looks like and when it is, we can't say at this point. We need to talk with FDA and get their input. We need to understand if they agree with us on the endpoints and the path. But we do think that this is a program that could warrant a smaller data set and a relatively simpler path to registration.

目前我們還無法確定具體情況和具體時間。我們需要與FDA溝通，聽取他們的意見。我們需要了解他們是否同意我們關於終點和路徑的意見。但我們確實認為，這個專案可能需要更小的資料集和相對更簡單的註冊路徑。

I think to the fact that, that competition question that came up earlier, if we're first, we may be able to go really fast depending on what kind of treatment effect we have. So we'll see. And then, Don, let me set up the DME and then you can hit the specifics. So just to remind you, what we're trying to do is get a sense of do we have activity and do we have some sense of dose? And does kallikrein, plasma kallikrein play a role in DME as an alternative pathway to VEGF.

我認為，就先前提到的競爭問題而言，如果我們是第一個，我們或許能夠快速推進，這取決於我們的治療效果。我們拭目以待。然後，Don，讓我先設定DME，然後你再說具體細節。提醒一下，我們試著了解我們是否有活性，以及​​劑量是否合適？還有，激肽釋放酶，血漿激肽釋放酶，作為VEGF的替代途徑，在DME中是否發揮作用。

Those are all questions we're hoping to answer with a small investment in a Phase I study with a single dose in a handful of patients roughly. From there, we would make the next investment, which would be a proof-of-concept study and then ultimately to get approval. But if we're able to prove that kallikrein plays an alternative role, and we have a drug that actually affects that, it's off to the races for us. But I'll let Don describe what we hope to see towards the end of this year.

我們希望透過少量投資，在一期臨床試驗中，對大約少數患者進行單劑量給藥，來解答這些問題。之後，我們將進行下一輪投資，即概念驗證研究，並最終獲得批准。但如果我們能夠證明激肽釋放酶發揮了另一種作用，並且我們確實研發出一種能夠影響這種作用的藥物，那麼我們就能一鳴驚人了。不過，我還是請唐來描述我們希望在今年底看到的結果吧。

Yeah. Thank you, Jon. I think that is correct. The kallikrein pathway is an independent pathway of the VEGF pathway. We just presented some preclinical evidence at the American Society of Retina Surgeons this last weekend, and there was a lot of excitement about a new pathway for our product. In answer to your specific question of what the pivotal study would look like, the path for approval of drugs for DME is best corrected visual acuity.

是的。謝謝你，喬恩。我認為你說得對。激肽釋放酶路徑是VEGF路徑的獨立路徑。上週末我們在美國視網膜外科醫師協會（ASR）上展示了一些臨床前證據，大家對我們產品的新通路感到非常興奮。關於你關於關鍵研究的具體問題，DME藥物的核准途徑是最佳矯正視力。

So we will be looking for a similarity or noninferiority to existing anti-VEGF products. In our Phase 2 design, we will be looking specifically at change in central subfield thickness that will give us indication that the avoralstat product is effective at reducing central subfield thickness and macular edema.

因此，我們將尋找與現有抗VEGF產品的相似性或非劣效性。在我們的第二期臨床試驗設計中，我們將特別關注中心亞區厚度的變化，這將為我們提供證據，證明avoralstat產品在降低中心亞區厚度和黃斑水腫方面有效。

Thank you. That's very helpful.

謝謝。這很有幫助。

(Operator Instructions)

（操作員指示）

We have no further questions at this time. I would now like to turn the conference back over to Jon Stonehouse for any closing remarks.

目前我們沒有其他問題。現在，我想將會議交還給喬恩·斯通豪斯，請他做最後總結發言。

Yeah, I don't think there's a whole lot more to say when you have a quarter like we did, where you have growing revenue, profit, great cash flow, the start of great cash flow and strong underlying demand continuing to increase. It doesn't get any better than that. And we're going to continue to execute and looking forward to how the rest of the year unfolds. So thank you for your interest. Have a great day.

是的，我認為，當你像我們這樣擁有一個季度，收入、利潤、現金流、強勁的現金流、強勁的現金流以及持續增長的強勁潛在需求時，沒有什麼可說的了。沒有比這更好的了。我們將繼續執行，並期待今年剩餘時間的進展。感謝您的關注。祝您有美好的一天。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您可以斷開連線了。