BioCryst Pharmaceuticals Inc (BCRX) 2022 Q2 法說會逐字稿

Welcome to the BioCryst Second Quarter 2022 Earnings Conference Call. My name is Vanessa, and I will be your operator for today's call. At this time, (Operator Instructions) I will now turn the call over to your host, Mr. John Bluth at BioCryst.

歡迎來到 BioCryst 2022 年第二季度收益電話會議。我的名字是 Vanessa，今天我將擔任您的接線員。此時，（操作員說明）我現在將把電話轉給您的主持人，BioCryst 的 John Bluth 先生。

Thanks very much, Vanessa. Good morning, and welcome to BioCryst's Second Quarter 2022 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; CFO, Anthony Doyle; Chief Commercial Officer, Charlie Gayer; Chief Medical Officer, Dr. Bill Sheridan; and Chief R&D Officer, Dr. Helen Thackray.

非常感謝，凡妮莎。早上好，歡迎參加 BioCryst 2022 年第二季度公司更新和財務業績電話會議。今天的新聞稿和隨附的幻燈片可在我們的網站上找到。今天和我一起參加的還有首席執行官喬恩·斯通豪斯（Jon Stonehouse）；首席財務官安東尼·道爾；首席商務官查理·蓋爾；首席醫療官 Bill Sheridan 博士；和首席研發官 Helen Thackray 博士。

Following our remarks, we will answer your questions. Before we begin, please note that 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.

根據我們的評論，我們將回答您的問題。在我們開始之前，請注意今天的電話會議將包含前瞻性陳述，包括有關未來業績、未經審計和前瞻性財務信息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風險和不確定性的影響，可能導致我們的實際結果、業績或成就與本演示文稿中明示或暗示的任何未來結果或業績存在重大差異。您不應過分依賴這些前瞻性陳述。

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.

有關其他信息，包括對我們風險因素的詳細討論，請參閱公司向證券交易委員會提交的文件，該文件可在我們的網站上訪問。

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

我現在想把電話轉給 Jon Stonehouse。

Thanks, John. The ORLADEYO launch continues to be very strong. Revenue is on track to exceed $250 million this year. New patient starts remain consistently strong now for 6 quarters in a row. The prescriber base is expanding and deepening, the 96-week data we've begun promoting is resonating with our customers, and the switch data shows ORLADEYO is maintaining disease control of decreasing disease burden.

謝謝，約翰。 ORLADEYO 的推出繼續非常強勁。今年的收入有望超過 2.5 億美元。新患者開始連續 6 個季度保持強勁勢頭。處方藥基數正在擴大和深化，我們已經開始推廣的 96 週數據正在引起我們的客戶的共鳴，而轉換數據顯示 ORLADEYO 正在保持疾病控制以減少疾病負擔。

While the vast majority of our revenue is still from the U.S., sales from Europe are starting to grow, and all of this is good news for HAE patients. This is even more exciting when you realize there's so much more opportunity ahead of us, which leads us to refine our guidance for this year to between $255 million and $265 million and continue to track towards $1 billion at peak.

雖然我們的大部分收入仍來自美國，但來自歐洲的銷售額開始增長，所有這些對 HAE 患者來說都是好消息。當您意識到我們面前還有更多機會時，這更加令人興奮，這導致我們將今年的指導細化至 2.55 億美元至 2.65 億美元之間，並繼續朝著 10 億美元的峰值目標邁進。

Why is this important? Having a meaningful product in the market growing quarter after quarter with very long [IP] creates an amazing base to build on. In this challenging financial environment, having significant and steady revenue growth is rare, and critically important to creating greater value.

為什麼這很重要？擁有一個在市場上一個又一個季度增長且具有非常長 [IP] 的有意義的產品，為構建一個驚人的基礎。在這個充滿挑戰的金融環境中，收入實現顯著而穩定的增長是罕見的，而且對於創造更大的價值至關重要。

Our plan is to repeat this ORLADEYO success with our pipeline molecules for other patients suffering from rare diseases. Few companies can get one successful product to market, but if you're able to do it again and again, you can compound value. Key elements to gain there are having a strategy to bring therapies forward that patients truly want, and being disciplined by following the data and insights gathered objectively to make informed business decisions about when to invest and when not to.

我們的計劃是用我們的管道分子為其他患有罕見疾病的患者重複 ORLADEYO 的成功。很少有公司可以將一種成功的產品推向市場，但如果你能夠一次又一次地做到這一點，你就可以增加價值。獲得成功的關鍵要素是製定一項戰略，以推進患者真正想要的治療，並通過遵循客觀收集的數據和見解來進行紀律處分，以便就何時投資和何時不投資做出明智的商業決策。

ORLADEYO's success is a great example of this. Wouldn't it have been nice back in the early days of the program if clinical trials and market research pointed to a clear and straight path to success? But that's not how it played out. There were clear challenges and things that went differently than planned along the way. And we were disciplined in objectively following the data, studying the switch market carefully and quickly leverage those insights to make the investment decisions that ultimately are paying off today with our successful launch.

ORLADEYO 的成功就是一個很好的例子。如果臨床試驗和市場研究指出了一條清晰而直接的成功之路，在項目的早期階段不是很好嗎？但這不是它的結果。在此過程中，存在明顯的挑戰和與計劃不同的事情。我們在客觀地跟踪數據、仔細研究交換機市場并快速利用這些洞察力做出投資決策時受到紀律處分，這些投資決策最終在我們今天成功推出時獲得了回報。

We use this approach in all our capital allocation decisions, including our pipeline. This disciplined approach is especially important in the current environment. We see the complement area and the ability to bring oral drugs to fill large unmet needs for these rare disease patients as a massive opportunity that includes Factor D and extends even more broadly to include other targets. Our immediate decision is to allocate capital in the REDEEM and RENEW studies to see if we're able to achieve our goal of finding a safe and effective dose with BCX9930.

我們在所有資本分配決策中都使用這種方法，包括我們的管道。這種有紀律的方法在當前環境中尤其重要。我們將補充領域和為這些罕見病患者帶來大量未滿足需求的口服藥物的能力視為一個巨大的機會，其中包括因子 D，並更廣泛地擴展到包括其他目標。我們的直接決定是在 REDEEM 和 RENEW 研究中分配資金，看看我們是否能夠實現使用 BCX9930 找到安全有效劑量的目標。

If the data from the first small group of patients enrolled supports this goal, we'll continue to allocate capital to the 9930 program. If not, we'll stop its development but still pursue Factor D inhibitors as we've already invested in next-generation backups and molecules that we hope will be improvements. With the partial clinical hold now removed, preparations to restart enrollment have begun, and Helen will share more with you on what we know now and how we plan to proceed.

如果第一批入組患者的數據支持這一目標，我們將繼續為 9930 計劃分配資金。如果不是這樣，我們將停止其開發，但仍會繼續使用因子 D 抑製劑，因為我們已經投資於下一代備份和分子，我們希望它們會有所改進。隨著部分臨床暫停的取消，重新開始註冊的準備工作已經開始，Helen 將與您分享我們現在所知道的以及我們計劃如何進行的更多信息。

We have a successful rare disease launch with ORLADEYO growing into a global blockbuster. We have an exciting pipeline of compounds, some you know about and some you don't yet.

隨著 ORLADEYO 成長為全球重磅炸彈，我們成功推出了罕見病。我們有一個令人興奮的化合物管道，有些你知道，有些你還不知道。

And lastly, we have substantial capital to make thoughtful capital allocation decisions. This is a unique and very good spot to be in, in the current environment, and that brings me back to where I started, the tremendous market success of ORLADEYO. The steady and consistent revenue growth, disciplined and objective decision-making on capital allocation and alternative financing sources like the additional debt from Athyrium recently drew down are the things that give us confidence we can repeat the ORLADEYO success with other molecules and create much greater value in the process.

最後，我們擁有大量資金來做出深思熟慮的資本分配決策。在當前的環境中，這是一個獨特且非常好的地方，這讓我回到了我開始的地方，ORLADEYO 取得了巨大的市場成功。穩定和持續的收入增長、嚴格和客觀的資本分配決策以及替代融資來源（例如最近從 Athyrium 提取的額外債務）讓我們有信心在其他分子上重複 ORLADEYO 的成功並創造更大的價值進行中。

Now I'll turn the call over to Charlie to share additional details on another strong quarter of growth of ORLADEYO. Charlie?

現在我將把電話轉給查理，分享有關奧拉德約另一個強勁增長季度的更多細節。查理？

Thanks, Jon. The consistent pattern of patient growth that we have seen since launch continued without interruption in the second quarter. New patient prescriptions in Q2 were the best since the first quarter of the launch driven by continued broadening and deepening of the ORLADEYO prescriber base. There is no sign this launch is slowing.

謝謝，喬恩。自推出以來，我們看到的患者增長的一致模式在第二季度繼續沒有中斷。在 ORLADEYO 處方藥基礎的不斷擴大和深化的推動下，第二季度的新患者處方是自推出第一季度以來最好的。沒有跡象表明這次發射正在放緩。

Our market research with HAE treaters predicted this expansion and the 96-week data that we started promoting late last year is convincing physicians to prescribe. When they see the sustained median monthly attack rate of 0, they know that their patients can expect great efficacy.

我們對 HAE 治療師的市場研究預測了這種擴張，我們去年底開始推廣的 96 週數據正在說服醫生開處方。當他們看到持續的中位月發病率為 0 時，他們知道他們的患者可以期待很好的療效。

When they see patients doing really well on ORLADEYO in the real world, in particular, those patients who switched after being controlled on injectable prophylaxis. They are encouraged to increase prescribing. Our prescriber data in Q2 reflect this pattern. We added the most first-time prescribers since the third quarter of last year.

當他們在現實世界中看到患者在 ORLADEYO 上表現非常好時，特別是那些在註射預防控制後轉換的患者。鼓勵他們增加處方。我們在第二季度的處方數據反映了這種模式。自去年第三季度以來，我們增加了最多的首次處方者。

And we also had an identical number of repeat prescribers. We saw an uptick in prescribing among the top 500 physicians that treat 50% of HAE patients, 60% of those Tier 1 physicians have now prescribed ORLADEYO, and they accounted for 2/3 of new prescriptions in the quarter.

我們也有相同數量的重複處方者。我們看到在治療 50% HAE 患者的前 500 位醫生中開處方有所增加，其中 60% 的一級醫生現在開了 ORLADEYO，他們佔本季度新處方的 2/3。

Our source of business is also very balanced with overall patient potential. There are roughly 120 physicians in the top 3 deciles accounting for 30% of the HAE market opportunity. And they prescribed 32% of the new ORLADEYO prescriptions in Q2. Roughly 1,400 physicians represent the next 40% of the opportunity, and that group accounted for 48% of prescriptions.

我們的業務來源也與整體患者潛力非常平衡。前 3 個十分位數中大約有 120 名醫生，佔 HAE 市場機會的 30%。他們在第二季度開出了 32% 的新奧拉迪奧處方。大約 1,400 名醫生代表了接下來 40% 的機會，而這組醫生佔了 48% 的處方。

We also saw an improvement in patient retention. Although it is too soon to call this a trend, we had the fewest number of discontinuations since Q3 of last year, even as the overall number of patients on ORLADEYO has grown substantially. Our metrics on access and reimbursement, which were already good also continued to improve. The median time to shipment of reimbursed product for a new prescription is now under 3 weeks as our team helps patients move quickly through the prior authorizations.

我們還看到了患者保留率的提高。儘管現在稱這是一種趨勢還為時過早，但我們的停藥數量是自去年第三季度以來最少的，儘管 ORLADEYO 的患者總數已大幅增長。我們已經很好的訪問和報銷指標也繼續改善。現在，由於我們的團隊幫助患者快速通過事先授權，新處方的報銷產品發貨的中位時間不到 3 週。

Health care providers worry about the burdens of the access process for HAE treatments. So the success of our patient service model adds to their confidence in prescribing ORLADEYO. We made more progress toward the globalization of ORLADEYO in Q2 with regulatory approvals in Canada and Switzerland and final price agreements in Germany, France as well as Switzerland.

醫療保健提供者擔心 HAE 治療的獲取過程的負擔。因此，我們患者服務模式的成功增加了他們對 ORLADEYO 處方的信心。我們在第二季度在 ORLADEYO 的全球化方面取得了更大的進展，加拿大和瑞士的監管部門獲得了批准，德國、法國和瑞士也達成了最終價格協議。

We also entered a commercial distribution agreement with Pint Pharma for Latin America, and we expect to file for market authorization in multiple Latin American countries before the end of 2022. While the ex U.S. contribution to 2022 sales will be small, the progress we are seeing in Europe and other regions gives us confidence that ex U.S. sales for ORLADEYO will reach at least $200 million at peak.

我們還與 Pint Pharma 簽訂了拉丁美洲的商業分銷協議，我們預計將在 2022 年底之前在多個拉丁美洲國家申請市場授權。雖然前美國對 2022 年銷售額的貢獻很小，但我們正在看到的進展在歐洲和其他地區，我們相信 ORLADEYO 在美國的銷售額在峰值時將至少達到 2 億美元。

The prescribing dynamics and the patient trends that we saw in Q2 confirm to us that we are still in the early stages of the ORLADEYO launch trajectory. The trends that we see tell us that ORLADEYO is on track, not only for between $255 million and $265 million in sales in 2022, but also future market leadership and $1 billion in peak sales.

我們在第二季度看到的處方動態和患者趨勢向我們證實，我們仍處於 ORLADEYO 推出軌蹟的早期階段。我們看到的趨勢告訴我們，ORLADEYO 正步入正軌，不僅在 2022 年的銷售額在 2.55 億美元至 2.65 億美元之間，而且未來的市場領導地位和 10 億美元的峰值銷售額。

Now I'd like to turn the call over to Anthony.

現在我想把電話轉給安東尼。

Thanks, Charlie. ORLADEYO revenue performance for Q2 was really strong and takes our trailing 12-month revenue to short of $200 million. With the consistency of new patient growth in the U.S. and continued expansion globally, we're really well positioned to achieve our updated revenue guidance of $255 million to $265 million for 2022 and on from there to peak sales of $1 billion. You can find our detailed second quarter financials in today's earnings press release, and I'd like to call your attention to a few items.

謝謝，查理。 ORLADEYO 第二季度的收入表現非常強勁，使我們過去 12 個月的收入低於 2 億美元。隨著美國新患者增長的一致性和全球範圍內的持續擴張，我們確實有能力在 2022 年實現 2.55 億美元至 2.65 億美元的最新收入指導，並從那里達到 10 億美元的峰值銷售額。您可以在今天的收益新聞稿中找到我們詳細的第二季度財務數據，我想提請您注意一些項目。

Revenue for the quarter was $65.5 million, of which $65.2 million came from net sales of ORLADEYO. We had around $2.2 million of nonrepeating reimbursement-related accrual releases in the quarter and saw ORLADEYO net revenue specifically related to Q2 was $63 million. Having seen Q1 gross to net impacted by reauthorizations, co-pay assistance, resets and the government donut hole, Q2 reimbursement rates and gross to net adjustments have normalized and should continue at current rates through year-end.

本季度收入為 6550 萬美元，其中 6520 萬美元來自 ORLADEYO 的淨銷售額。我們在本季度有大約 220 萬美元的非重複報銷相關應計發布，並且與第二季度特別相關的 ORLADEYO 淨收入為 6300 萬美元。在看到第一季度的總淨額受到重新授權、共同支付援助、重置和政府甜甜圈洞的影響後，第二季度的報銷率和總淨額調整已經正常化，並且應該在年底之前繼續保持目前的水平。

Operating expenses, not including noncash stock compensation for the quarter was [$90 million.] This was lower than we previously forecasted as the team worked hard to manage cost during the 9930 enrollment hold period. With the program now moving forward, we've lowered our OpEx forecast for 2022 to $390 million to $400 million. Cash at the end of the quarter was at $419 million, having achieved and maintained the required revenue thresholds to draw the additional 75 million debt tranches from Athyrium, pro forma cash is at approximately $492 million.

本季度的運營費用（不包括非現金股票薪酬）為 [9000 萬美元]。這低於我們之前的預測，因為團隊在 9930 註冊期間努力管理成本。隨著該計劃的推進，我們已將 2022 年的運營支出預測下調至 3.9 億至 4 億美元。本季度末的現金為 4.19 億美元，已達到並維持從 Athyrium 提取額外 7500 萬筆債務所需的收入門檻，備考現金約為 4.92 億美元。

We have always been and will continue to be responsible and disciplined allocators of capital. This is especially true as we recommence enrollment in the 9930 program. We have taken into consideration the delay to the program, applied the reduced probability of success and reduce their assumptions for peak penetration.

我們一直並將繼續成為負責任和紀律嚴明的資本分配者。當我們重新開始註冊 9930 計劃時尤其如此。我們已經考慮到該計劃的延遲，應用了降低的成功概率並降低了他們對峰值滲透的假設。

Despite that, there's still significant value potential to support investment in the program. There are numerous markets that we can go into with 9930, not just PNH. These markets are big, especially in renal indications. And this is a drug that patients want. All of that results in a revenue potential for 9930 that is larger than that of ORLADEYO.

儘管如此，支持對該計劃的投資仍然具有巨大的價值潛力。我們可以使用 9930 進入許多市場，而不僅僅是 PNH。這些市場很大，尤其是在腎臟適應症方面。這是患者想要的藥物。所有這些都導致 9930 的收入潛力大於 ORLADEYO。

Our intent is to progress as quickly as possible, limit the additional investment and get to the point where we have confidence that we have a safe and effective drug. If we can achieve this, then we will continue to invest in moving the program forward. If we cannot, then we will terminate the program and allocate capital elsewhere. This data-driven objective unemotional approach has been a key factor in the successful launch of ORLADEYO and will continue to guide us in all of the programs that we have going forward.

我們的意圖是盡快取得進展，限制額外投資，並達到我們有信心擁有安全有效藥物的程度。如果我們能做到這一點，那麼我們將繼續投資推動該計劃的發展。如果我們不能，那麼我們將終止該計劃並將資金分配到其他地方。這種數據驅動的客觀冷靜方法一直是 ORLADEYO 成功推出的關鍵因素，並將繼續指導我們開展的所有項目。

Now I'll pass it over to Helen.

現在我會把它交給海倫。

Thanks, Anthony. As we announced today, the FDA has lifted their partial clinical hold on the BCX9930 program, and our pivotal trials in PNH can resume enrollment, along with our proof-of-concept trial in renal indications. This is an important step forward toward our goal of bringing a safe and effective Factor D inhibitor to patients with PNH and complement-mediated renal diseases.

謝謝，安東尼。正如我們今天宣布的那樣，FDA 已經解除了對 BCX9930 項目的部分臨床控制，我們在 PNH 的關鍵試驗以及我們在腎臟適應症方面的概念驗證試驗可以恢復註冊。這是朝著我們為 PNH 和補體介導的腎臟疾病患者提供安全有效的 D 因子抑製劑這一目標邁出的重要一步。

We will reinitiate enrollment using a step-up approach and a dose level of 400 milligrams twice daily, together with encouraging hydration and more frequent safety testing for the first few months in each patient. After review of the data and investigating the elevations in serum creatinine we reported in April, we've arrived at the hypothesis for the mechanism contributing to these observations and our proposal for how to address it. The hypothesis is that crystals are forming in the kidney when the concentration of the drug is highest in the urine, and that this can be mitigated by lowering drug levels in the urine.

我們將使用逐步增加的方法和每天兩次 400 毫克的劑量水平重新開始招募，同時鼓勵每位患者在最初幾個月內進行補水和更頻繁的安全測試。在審查了數據並調查了我們在 4 月報告的血清肌酐升高後，我們得出了促成這些觀察的機制的假設以及我們關於如何解決它的建議。假設是，當尿液中藥物濃度最高時，腎臟中會形成晶體，這可以通過降低尿液中的藥物濃度來緩解。

We will test this by lowering the dose from 500 milligrams twice daily to 400 milligrams twice daily and encouraging adequate fluid intake to achieve dilution of the drug as it is excreted in the kidney. If we are correct in our hypothesis and these steps successfully address the problem, this will mitigate the risk of elevated serum creatinine in patients receiving BCX9930.

我們將通過將劑量從每天兩次的 500 毫克降低到每天兩次的 400 毫克來測試這一點，並鼓勵攝入足夠的液體以實現藥物在腎臟中排泄時的稀釋。如果我們的假設是正確的並且這些步驟成功地解決了這個問題，這將降低接受 BCX9930 的患者血清肌酐升高的風險。

The evidence in support of this hypothesis comes from clinical observations and laboratory studies. As we shared in May, the clinical evidence suggested that the serum creatinine elevations occurred only at the 500-milligram dose level and were likely dose related. In addition, our recent clinical pharmacology studies have shown that a large fraction of the administered dose of BCX9930 is excreted by the kidney.

支持這一假設的證據來自臨床觀察和實驗室研究。正如我們在 5 月所分享的，臨床證據表明血清肌酐升高僅發生在 500 毫克劑量水平，並且可能與劑量有關。此外，我們最近的臨床藥理學研究表明，大部分 BCX9930 的給藥劑量由腎臟排泄。

Importantly, New laboratory studies have found BCX9930 drug solubility is lowered over the typical pH range of human urine, and recent nonclinical studies have also demonstrated dose-related crystal deposition in the renal tract in kidneys in animals. Understanding that, suggests a mechanism contributing to the rise in serum creatinine. It is likely to be a physical one, where crystals form in the urine, in the kidney, when urine concentration of the drug reaches a threshold level.

重要的是，新的實驗室研究發現 BCX9930 藥物溶解度在人類尿液的典型 pH 值範圍內降低，最近的非臨床研究也證明了動物腎臟腎道中與劑量相關的晶體沉積。了解這一點，表明了導致血清肌酐升高的機制。它很可能是一種物理性的，當藥物的尿液濃度達到閾值水平時，尿液和腎臟中會形成晶體。

The crystals cause an inflammatory response with resulting damage to the kidney cells. This would explain how kidney function is affected, and why a rise in serum creatinine is observed with BCX9930 at 500 milligrams. It could further explain why it is happening only in some patients and at the 500-milligram dose level, when intrarenal drug levels exceed a threshold for crystal formation.

這些晶體會引起炎症反應，從而對腎細胞造成損害。這可以解釋腎功能如何受到影響，以及為什麼在 500 毫克 BCX9930 中觀察到血清肌酐升高。它可以進一步解釋為什麼當腎內藥物水平超過晶體形成的閾值時，它只發生在某些患者和 500 毫克劑量水平。

This mechanism of injury is avoidable. We believe that the key is to avoiding risk of adverse kidney effects are to reduce the load of drug excretion by lowering the dose and to maintain more dilute urine to further lower the concentration of excreted drug by encouraging adequate fluid intake, especially at the time of drug administration. That dose reduction, together with the dilution effect of hydration, is designed to maintain adequate levels of the drug circulating in the blood for efficacy while reducing the concentration on elimination in the kidney to avoid crystal formation.

這種傷害機制是可以避免的。我們認為，避免腎臟不良反應風險的關鍵是通過降低劑量來減少藥物排泄的負荷，並通過鼓勵充足的液體攝入來保持更稀的尿液以進一步降低排泄藥物的濃度，尤其是在藥物管理。該劑量減少以及水合作用的稀釋效應旨在維持足夠的藥物在血液中循環以達到療效，同時降低腎臟中消除時的濃度以避免晶體形成。

Of course, we also need to maintain strong clinical efficacy. As a reminder, the data from our Phase I PNH program supports studying 400 milligram twice daily. When C5 inhibitor-naive patients were taking this dose 400 milligrams in the Phase I program, the hemoglobin rose from baseline by a robust amount, a mean of 4.3 grams per deciliter, and no transfusions were required. This clinical observation was consistent with our PK/PD work showing that 400 milligrams twice daily provided plasma levels above the exposure needed to achieve near complete inhibition of the alternative pathway of complement.

當然，我們還需要保持強大的臨床療效。提醒一下，我們的第一階段 PNH 計劃的數據支持每天兩次研究 400 毫克。當 C5 抑製劑初治患者在 I 期項目中服用 400 毫克這一劑量時，血紅蛋白從基線上升了一個強勁的量，平均為 4.3 克/分升，並且不需要輸血。這一臨床觀察與我們的 PK/PD 工作一致，表明每天兩次 400 毫克提供的血漿水平高於實現幾乎完全抑制補體替代途徑所需的暴露水平。

Given that evidence, we believe that 400 milligrams twice daily will achieve similar efficacy results to those we saw in Phase I.

鑑於這些證據，我們相信每天兩次 400 毫克將達到與我們在第一階段看到的相似的功效結果。

So what comes next? If we are correct in our hypothesis, and if the steps we are taking are the right ones to resolve the elevation in serum creatinine while maintaining strong clinical efficacy, we will be able to confirm this in the clinic.

那麼接下來會發生什麼？如果我們的假設是正確的，並且如果我們採取的步驟是解決血清肌酐升高同時保持強大的臨床療效的正確步驟，我們將能夠在臨床上證實這一點。

Our next steps are to lower the dose for patients already on study. While in parallel, we reopened the studies to enrollment. To do this, we will proceed with regulatory submissions for the amended protocols in the REDEEM clinical trials. We've included simple hydration instructions for all patients. And for new patients, we've included a revised regimen to get the 400-milligram dose level with a short initial step up in dose.

我們的下一步是降低已經在研究中的患者的劑量。與此同時，我們重新開放了研究招生。為此，我們將繼續為 REDEEM 臨床試驗中的修訂方案提交監管文件。我們為所有患者提供了簡單的補水說明。對於新患者，我們已經包括了一個修改後的方案，以獲得 400 毫克的劑量水平，並且初始劑量增加很短。

We are also amending the RENEW trial with similar measures and initiating the steps to reopen to enrollment at the 400-milligram dose in that trial. In terms of testing our hypothesis, we will assess patients in the first months of reopening enrollment in the REDEEM and RENEW trials. And we will observe patient outcomes closely to determine if the data on safety at 400 milligrams supports continuing to invest through the completion of the pivotal studies, provided we can recruit patients in a timely manner and the initial data are supportive of safety and efficacy we'll proceed. If the data are not supportive, we will discontinue the 9930 program and redirect our efforts and investment elsewhere in our pipeline.

我們還在用類似的措施修改 RENEW 試驗，並開始採取步驟在該試驗中以 400 毫克的劑量重新開始招募。在檢驗我們的假設方面，我們將在 REDEEM 和 RENEW 試驗重新開始招募的頭幾個月評估患者。我們將密切觀察患者的結果，以確定 400 毫克的安全性數據是否支持通過完成關鍵研究繼續投資，前提是我們可以及時招募患者並且初始數據支持我們的安全性和有效性。會繼續。如果數據不支持，我們將停止 9930 計劃，並將我們的努力和投資轉向我們管道的其他地方。

So how will we know this? As we resume enrollment at 400 milligrams, we'll look for absence of the early rise in serum creatinine in new patients enrolling in the study. You will recall that over the first few months of enrollment in REDEEM-1 and REDEEM-2 and in about 1/3 of the first 15 patients, we saw a rapid rise in serum creatinine at 500 milligrams. As we enroll patients at 400 milligrams, this will give us a good basis for comparison to inform our next step.

那麼我們怎麼知道呢？隨著我們以 400 毫克的劑量恢復入組，我們將在新入組的研究中尋找血清肌酐早期升高的情況。您會記得，在註冊 REDEEM-1 和 REDEEM-2 的最初幾個月以及前 15 名患者中的大約 1/3 中，我們看到血清肌酐在 500 毫克時迅速上升。當我們招募 400 毫克的患者時，這將為我們提供一個很好的比較基礎，以便為我們的下一步提供信息。

Let's look at it like this. If about the same small number of patients are treated without similar observations, this will build confidence that the hypothesis is correct and the protocol adjustments are sufficient to address it. By monitoring for serum creatinine at more frequent intervals in the first 3 months, we will gather the information we need to determine if our hypothesis is correct and if our revised amendments sufficiently resolve the problem.

讓我們這樣看。如果在沒有類似觀察的情況下對大約相同數量的患者進行治療，這將建立對假設正確並且方案調整足以解決它的信心。通過在前 3 個月更頻繁地監測血清肌酐，我們將收集我們需要的信息，以確定我們的假設是否正確，以及我們的修訂是否足以解決問題。

On an individual patient level, more frequent monitoring will allow us to identify any changes in the near term and react swiftly if warranted, both for each individual safety on trial and for any appropriate decision on continuing the program. It's clear to us that the need for better treatment options in these diseases is significant. Throughout our investigation, we have received unwavering encouragement from our investigators and patient organizations in both the hematology and nephrology communities to find a path forward for BCX9930 if there is one.

在個體患者層面，更頻繁的監測將使我們能夠識別短期內的任何變化，並在必要時迅速做出反應，無論是對每個個體的試驗安全性還是對繼續該計劃的任何適當決定。我們很清楚，這些疾病需要更好的治療方案是非常重要的。在我們的整個調查過程中，我們從血液學和腎病學界的研究人員和患者組織那裡得到了堅定不移的鼓勵，如果有的話，我們會為 BCX9930 找到前進的道路。

We are pleased that the FDA has removed the partial clinical hold following their review of our data, our investigation findings and our proposed protocol adjustments. Because of this high unmet need in PNH and other complement-mediated diseases and because we believe making a limited additional investment now to test this hypothesis is warranted by the potential value if the program is successful.

我們很高興 FDA 在審查了我們的數據、我們的調查結果和我們提議的方案調整後取消了部分臨床暫停。由於在 PNH 和其他補體介導的疾病中存在這種高度未滿足的需求，而且我們相信，如果該計劃成功，現在進行有限的額外投資來檢驗這一假設是有必要的，因為它的潛在價值是必要的。

We continue to pursue our goal of bringing a safe and effective Factor D inhibitor to the market for these patients. We are working hard to achieve this goal, and we will make the decisions on where to invest in our pipeline based on sound evidence and where we can create the most value.

我們繼續追求我們的目標，即為這些患者將安全有效的 D 因子抑製劑推向市場。我們正在努力實現這一目標，我們將根據可靠的證據決定在哪裡投資我們的管道以及我們可以在哪裡創造最大價值。

Now I'll hand the call back to Jon.

現在我會把電話轉回給喬恩。

Thanks, Helen. Let me conclude by summarizing where we are. The ORLADEYO launch through 6 quarters continues to be strong with no signs of slowing down, and we are on our way to global peak sales of $1 billion. We have a testable hypothesis with 9930 that we believe we can answer in relatively short order. And if 400 milligrams BID is a safe and effective dose, we have an asset potentially more valuable than ORLADEYO. If not, we move on to the rest of our pipeline to find the next ORLADEYO.

謝謝，海倫。最後，讓我總結一下我們所處的位置。 ORLADEYO 推出的 6 個季度繼續保持強勁勢頭，沒有放緩的跡象，我們正朝著 10 億美元的全球銷售高峰邁進。我們有一個 9930 的可檢驗假設，我們相信我們可以在相對較短的時間內回答。如果 400 毫克 BID 是一種安全有效的劑量，那麼我們擁有的資產可能比 ORLADEYO 更有價值。如果沒有，我們將繼續進行其餘的管道以尋找下一個奧拉德約。

We have a very solid balance sheet. And when the capital markets are challenging like they have been for a while now, we can access other sources of capital. Add this all up, and you can see we are creating meaningful value now, and we have the potential for much greater value in the future.

我們有一個非常穩固的資產負債表。當資本市場像現在這樣充滿挑戰時，我們可以獲取其他資金來源。把這一切加起來，你可以看到我們現在正在創造有意義的價值，而且我們有潛力在未來創造更大的價值。

That concludes our remarks, and we'll now open up the call to your questions.

我們的發言到此結束，我們現在將向您提出問題。

(Operator Instructions) We have our first question from Stacy Ku with Cowen and Company.

（操作員說明）我們收到了來自 Cowen and Company 的 Stacy Ku 的第一個問題。

Congratulations on a ORLADEYO quarter. So we have a few questions. First, on the 9930 update, can you speak about the patients that have stayed on the REDEEM trials. Are there any safety measures that are being monitored? Any updates there? It sounds like they are on 500 milligrams and that will be adjusted to 400 milligrams. That's the first question, those patients.

祝賀奧拉德約季度。所以我們有幾個問題。首先，在 9930 更新中，您能談談留在 REDEEM 試驗中的患者嗎？是否有任何正在監控的安全措施？那裡有更新嗎？聽起來他們的劑量為 500 毫克，並將調整為 400 毫克。這是第一個問題，那些病人。

And then for the second, can you talk about kind of that FDA decision a little bit earlier than expected. So should we look into that as any read through? Kind of it's clearly an overhang to the street. So any details would be appreciated there.

然後第二個，你能比預期早一點談談 FDA 的決定嗎？那麼我們是否應該在通讀時進行調查？很明顯，它是街道的懸垂部分。所以任何細節都會在那裡受到讚賞。

So Helen, do you want to take the first one, I'll take the second one?

那麼海倫，你要不要拿第一個，我要第二個？

Sure. Thanks for the question. So with regard to patients on the REDEEM trials, we have continued to monitor them. Patients who remain on drug are doing so because per the partial clinical hold, they were continuing to drive benefits. They continue on drug. Their results have supported that, and we're reducing the dose in all patients.

當然。謝謝你的問題。因此，對於 REDEEM 試驗中的患者，我們繼續對其進行監測。繼續服藥的患者之所以這樣做，是因為根據部分臨床試驗，他們繼續推動獲益。他們繼續吸毒。他們的結果支持了這一點，我們正在減少所有患者的劑量。

And then on the FDA question, we said the end of third quarter because we didn't know how many rounds we'd go back and forth with the FDA. And when we send in the complete response to their hold, they reviewed it and we got off clinical hold. So we got off faster than we originally planned.

然後關於 FDA 的問題，我們說第三季度末，因為我們不知道我們將與 FDA 來回進行多少輪。當我們發送對他們暫停的完整回复時，他們對其進行了審查，我們就退出了臨床暫停。所以我們下車的速度比我們原先計劃的要快。

We have our next question from Jon Wolleben with JMP Securities.

我們有來自 JMP 證券公司的 Jon Wolleben 的下一個問題。

Thanks for all the color on the 9930 update. Just wanted to ask, previously, you discussed 2 different patterns of the creatinine elevations, some patients seeing it early and then some developing over time. These mitigation steps seem to affect the latter, but wondering if you could talk about the potential of this cropping up over time in some patients as they stay on 9930 long term.

感謝 9930 更新中的所有顏色。只是想問一下，之前，您討論了肌酐升高的 2 種不同模式，一些患者很早就看到了，然後一些患者隨著時間的推移而發展。這些緩解措施似乎會影響後者，但想知道您是否可以談論隨著時間的推移在某些患者中出現這種情況的可能性，因為他們長期使用 9930。

Let me start and then you and Bill can jump in. So I think the important thing is a small number of patients, like we saw in the early start of the enrollment of the REDEEM study is going to give us a sense of the first pattern, which was that acute rise. And those same patients we're going to continue to track over time, and we'll get a sense of what happens over time with the same small group of patients. So I think we get the benefit from both patterns with this early group of patients.

讓我開始，然後你和比爾可以加入。所以我認為重要的是少數患者，就像我們在註冊 REDEEM 研究的早期開始時看到的那樣，這將使我們對第一種模式有所了解，這是急劇上升。隨著時間的推移，我們將繼續跟踪這些相同的患者，我們將了解隨著時間的推移，同一小組患者會發生什麼。所以我認為我們可以從這兩種模式中受益於這批早期患者。

And I can answer on the -- another point on the early rise and the slow trend. We think this is a threshold effect. We think it's threshold of the drug concentration in the urine. That could explain both the early rise findings and the slow later findings. We expect to be able to answer each of those questions in the first small group of patients who were enrolled.

我可以回答 - 關於早起和緩慢趨勢的另一點。我們認為這是一個門檻效應。我們認為它是尿液中藥物濃度的閾值。這可以解釋早起的發現和緩慢的後期發現。我們希望能夠在第一批入組的患者中回答這些問題。

That's helpful. And then maybe a couple of follow-ups. Helen, you discussed a few different procedural steps to get -- take new patients in. Wondering, when do you think you could start dosing new patients in REDEEM and RENEW. And then also when you're thinking about this early evaluation, what is the bar that's acceptable? Do you have to see a complete absence of serum creatinine, or is there any discussion with FDA about what can you see that's tolerable and what is intolerable here?

這很有幫助。然後可能會有一些後續行動。海倫，你討論了幾個不同的程序步驟來獲得 - 接受新患者。想知道，你認為什麼時候可以開始在 REDEEM 和 RENEW 中給新患者給藥。然後當你考慮這個早期評估時，可以接受的標準是多少？您是否必須看到完全沒有血清肌酐，或者是否與 FDA 討論過您認為哪些是可以容忍的，哪些是不能容忍的？

So maybe on that second one, the stopping rule and on the first one's pretty straightforward.

所以也許在第二個，停止規則和第一個非常簡單。

Yes. So we have some work to do initially, which is to get the protocols up and running. We have to submit countries and sites that will take a few months, and then we will be enrolling from there. We expect that within the first few months of experience with the first [track] patients will have the opportunity to see data. So this is an incremental approach. First is get to the readiness for start-up, then get to enrollment and then get to the data.

是的。所以我們最初有一些工作要做，那就是讓協議啟動並運行。我們必須提交需要幾個月時間的國家和網站，然後我們將從那裡註冊。我們預計，在第一批 [track] 患者體驗的最初幾個月內，將有機會查看數據。所以這是一種漸進的方法。首先是為啟動做好準備，然後是註冊，然後是數據。

And in terms of what we're looking for then, we think that this is a threshold effect, as I said. The goal is to avoid that. And so what we're looking for is the patient to be dosed at the 400-milligram dose level and for us to be seeing in those new patients that we're not observing these findings.

正如我所說，就我們當時正在尋找的東西而言，我們認為這是一個門檻效應。目標是避免這種情況。因此，我們正在尋找以 400 毫克劑量水平給藥的患者，並且讓我們在這些新患者中看到我們沒有觀察到這些發現。

Yes. If we have serum creatine major increases in serum creatinine, then we don't have a drug that's safe and effective, right? So it's pretty straightforward. And on the first point, we're going to go as fast as we can, right? It's hard to predict how quickly that will happen, but we're going to go as fast as we can.

是的。如果我們的血清肌酸顯著升高，那麼我們就沒有安全有效的藥物，對吧？所以這很簡單。在第一點上，我們會盡可能快，對吧？很難預測這會發生多快，但我們會盡可能快地進行。

We have our next question from Chris Raymond with Piper Sandler.

我們有來自 Chris Raymond 和 Piper Sandler 的下一個問題。

Two questions. I guess, first on 9930. Maybe could you provide a little bit more color on the sort of hydration protocol, I guess you're describing? I'm just trying to understand what specifically you're -- you submitted to FDA in terms of that -- what patients need to do. Is it more the hydration or the lower dose, I guess, that you're hypothesizing can alleviate this issue. And maybe just give us a sense of how this sort of translates into the real world, if in fact, you keep going with this hydration protocol and it's approved and then there's this requirement for patients to hydrate.

兩個問題。我想，首先是 9930。也許你能提供更多關於水合協議的顏色，我猜你正在描述？我只是想了解你具體是什麼——你提交給 FDA——患者需要做什麼。我猜，你假設的水合作用或低劑量可以緩解這個問題。也許只是讓我們了解這種情況如何轉化為現實世界，如果事實上，你繼續使用這種水合協議並且它被批准，然後對患者進行水合的要求。

And then the second question on ORLADEYO. We've done some KOL checks. I'm kind of curious what you guys are seeing in the larger market. The feedback we've gotten is that overall prophy share is relatively growing steadily. But share of new patients is really where the bolus of use is like 80% or more of new patients, at least from one of our KOLs. So I guess I'm just kind of curious, what are you seeing in the broader market? And if you're seeing a similar sort of proportion there, what kind of lag do you anticipate before this really starts to accelerate total share?

然後是關於 ORLADEYO 的第二個問題。我們已經做了一些 KOL 檢查。我有點好奇你們在更大的市場上看到了什麼。我們得到的反饋是，整體預防份額相對穩定增長。但是，新患者的份額實際上是 80% 或更多新患者的使用量，至少來自我們的一位 KOL。所以我想我只是有點好奇，你在大盤中看到了什麼？如果你在那裡看到類似的比例，你預計在這真正開始加速總份額之前會有什麼樣的滯後？

Do you want to take the first one on hydration?

你想第一個補水嗎？

Yes. So with 9930, the hydration protocol is actually really simple. It's simply to encourage hydration while on the drug. That could be as simple as taking the drug with a glass of water. We've not prescribed specifically what it should be, but it's encouraging hydration. The reasoning behind that is that we're taking a two-pronged approach to be able to get the urine concentration below the threshold for formation of any crystals.

是的。因此，對於 9930，補水協議實際上非常簡單。這只是為了在服藥時促進水合作用。這可能就像用一杯水服用藥物一樣簡單。我們沒有具體規定它應該是什麼，但它鼓勵水合作用。其背後的原因是，我們正在採取雙管齊下的方法，以使尿液濃度低於任何晶體形成的閾值。

And that's both with the dose reduced within the effective dosing range and the addition of hydration in order to get to that sustained level below the threshold for crystal formation. In terms of where this would go in the sort of next, if you use this in the real world, it's really quite simple. This is as simple as take your medicine with a glass of water. And so we think that this is very achievable.

這既要在有效劑量範圍內減少劑量，又要增加水合作用，以達到低於晶體形成閾值的持續水平。就下一步的發展方向而言，如果你在現實世界中使用它，它真的很簡單。這就像用一杯水服藥一樣簡單。所以我們認為這是可以實現的。

Great. Charlie, do you want to take the ORLADEYO?

偉大的。查理，你想參加奧拉德約嗎？

Chris, thanks for the question. So first of all, overall, 50% -- about 50% of the patients that are on ORLADEYO today, have switched from another prophylaxis product. And that's really in proportion to what we think is the market share. So about half of those switches -- prophy switches are coming from Takhzyro, Haegarda and so on. As I talked about the prescriber base, we've got a really big prescriber base. And so I think we're still early in this process of getting all the different KOLs to fully understand this.

克里斯，謝謝你的問題。因此，首先，總體而言，今天使用 ORLADEYO 的患者中有 50% - 約 50% 已從另一種預防產品轉換。這與我們認為的市場份額成正比。所以這些開關中大約有一半——prophy 開關來自 Takhzyro、Haegarda 等。正如我談到開藥者基礎時，我們有一個非常大的開藥者基礎。所以我認為我們還處於讓所有不同 KOL 充分理解這一點的過程的早期階段。

And I think in the future, they will switch more patients. But across the overall market, there's been a lot of switching. And as more and more doctors get familiar with our data, and see the real-world efficacy that those prophy switchers are having, I expect that the trend will continue.

而且我認為在未來，他們會轉換更多的病人。但在整個市場上，發生了很多轉變。隨著越來越多的醫生熟悉我們的數據，並看到這些預防轉換者在現實世界中的療效，我預計這種趨勢將繼續下去。

We have our next question from Jessica Fye with JPMorgan.

我們有來自摩根大通的 Jessica Fye 的下一個問題。

So a couple more for you on 9930. When you talk about a reasonable time frame and a relatively small number of patients needed to find a safe and effective dose, can you just elaborate on how you define 2 things? First, is a reasonable time frame, the 3 months you talked about in the prepared remarks? And is that 3 months from today? Or is that once you get 3 months of follow-up on a small number of patients, and it could take a few months to spool up enrollment again?

因此，請在 9930 上為您提供更多信息。當您談到合理的時間框架和相對較少的患者需要找到安全有效的劑量時，您能否詳細說明您如何定義兩件事？首先，是一個合理的時間框架，你在準備好的評論中提到的3個月？那是從今天開始的3個月嗎？還是說，一旦您對少數患者進行了 3 個月的隨訪，可能需要幾個月的時間才能重新啟動登記？

And then second, how do you define a small number of patients? Is that a dozen, a couple of dozen? I'm just trying to figure out when investors will have more clarity here.

其次，您如何定義少數患者？是十幾個，幾十個？我只是想弄清楚投資者何時會在這裡更加清晰。

Yes. So I think it's important to look at what we saw in the study that caused us to stop, right? So it was about 15 patients roughly in enrollment in the REDEEM studies that we saw this effect. And so we think similar number is roughly what will give us confidence that we're not seeing the effect where we are. And the time frame for that, as Helen said, it could take some months to get the revised protocols. These are major amendments. And so you got to go to the regulatory authorities.

是的。所以我認為看看我們在研究中看到的導致我們停下來的東西很重要，對吧？因此，大約有 15 名患者參加了 REDEEM 研究，我們看到了這種效果。所以我們認為類似的數字大致可以讓我們相信我們沒有看到我們現在的影響。正如海倫所說，時間框架可能需要幾個月的時間才能獲得修訂後的協議。這些都是重大修改。所以你必須去監管機構。

And then it took about 2 months to see the effect in these patients. So once we got it up and running and we're enrolling patients, it will be a couple of months before we see -- we feel like we're in a position where we know what we're seeing. So I hope that gives you a little bit more frame. It's really hard to predict, just because it takes time to get these things approved and then start enrollment. But we're going to work as fast as we can, and we'll keep you updated along the way.

然後花了大約 2 個月的時間在這些患者身上看到效果。因此，一旦我們啟動並運行它並且我們正在招募患者，我們將需要幾個月的時間才能看到 - 我們覺得我們處於一個我們知道我們所看到的位置的位置。所以我希望這能給你更多的框架。這真的很難預測，只是因為這些事情得到批准然後開始註冊需要時間。但我們會盡可能快地工作，並且會在此過程中隨時為您提供最新信息。

Got it. And I appreciate the kind of deliberate approach here. And I can understand how a small number of patients can rule in a safety issue, but how do you get comfortable that a small number of patients can rule out a safety issue?

知道了。我很欣賞這裡的那種深思熟慮的方法。而且我可以理解少數患者如何能夠排除安全問題，但是您如何對少數患者可以排除安全問題感到滿意？

Yes. Maybe I'll start and then you and Bill can jump in. The hypothesis is based on the data we've gathered to date, right, which is a combination of the clinical data and what we saw at [400 milligrams] and what we saw at [500 milligrams] and then what we saw in [Clinfarm] and what we saw in laboratory tests and some recent animal studies. And so we believe it's a threshold effect that causes the drug to go out of solution and causes a clogging of these tubules.

是的。也許我會開始，然後你和比爾可以加入。這個假設是基於我們迄今為止收集的數據，對，這是臨床數據和我們在 [400 毫克] 看到的數據以及我們所看到的數據的組合。看到了 [500 毫克]，然後是我們在 [Clinfarm] 中看到的，以及我們在實驗室測試和最近的一些動物研究中看到的。所以我們認為這是一種閾值效應，導致藥物從溶液中消失並導致這些小管堵塞。

And so we think that if we don't see these elevations, we won't -- it's not something that will linger on over time. right? It's not -- this drug doesn't accumulate, so it's not something that will happen over time. It's not an exposure issue. It's a threshold issue. So that's why we think the small number of patients in the early phase of the study will give us much more confidence. Helen or Bill, anything else you want to say?

所以我們認為，如果我們看不到這些海拔，我們就不會——它不會隨著時間的推移而流連忘返。正確的？不是——這種藥物不會積累，所以它不會隨著時間的推移而發生。這不是曝光問題。這是一個門檻問題。所以這就是為什麼我們認為研究早期階段的少數患者會給我們更多的信心。海倫或比爾，你還有什麼想說的嗎？

I would only add that the findings in that first group of patients that -- for which we paused enrollment, those were pretty definitive. They were pretty early. And I think if we don't see that in the first group, it's about the same size, as you said, it would give us increasing confidence. This is going to be an incremental approach as well. We need that first step. We need to see that, and then we'll continue to follow them and add more patients.

我只想補充一點，在第一組患者中的發現——我們暫停了登記，這些發現是非常明確的。他們來得很早。而且我認為，如果我們在第一組中看不到它，它的大小大致相同，正如你所說，它會讓我們越來越有信心。這也將是一種漸進的方法。我們需要這第一步。我們需要看到這一點，然後我們將繼續關注他們並增加更多患者。

Yes. I would only add that it gives you confidence to complete enrollment in the studies.

是的。我只想補充一點，它讓你有信心完成學習。

Yes. That's right.

是的。這是正確的。

Our next question is from Maury Raycroft with Jefferies.

我們的下一個問題來自 Jefferies 的 Maury Raycroft。

For ORLADEYO, can you elaborate more on what the ideal patient is to switch and the ideal patient to benefit from ORLADEYO? I guess there are some observations that you're seeing from the front line on that, that you can talk about?

對於ORLADEYO，您能否詳細說明一下理想的患者是轉換什麼以及從ORLADEYO 中受益的理想患者？我想您可以從前線看到一些觀察結果，您可以談談嗎？

Yes. Maury, good question. And, yes, we're starting to get an increasing amount of evidence about the ideal patient. And it really is patients who were already well controlled on another prophy drug. If they had a very low attack rate coming in, most of those patients tend to stay at the same low attack rate on ORLADEYO. And so I think as more and more physicians start seeing that and as more and more patients start experiencing that, that's where we're going to see more -- the trend of switching continuing and maybe even increasing.

是的。莫里，好問題。而且，是的，我們開始獲得越來越多關於理想患者的證據。確實是患者已經在另一種預防藥物上得到了很好的控制。如果他們的發病率非常低，大多數患者傾向於在 ORLADEYO 上保持同樣的低發病率。所以我認為隨著越來越多的醫生開始看到這一點，隨著越來越多的患者開始體驗到這一點，這就是我們將看到更多的地方——轉換的趨勢繼續存在，甚至可能增加。

And Charlie, when you say low attack rate coming in, you mean on their prophy therapy?

查理，當你說低攻擊率進來時，你是指他們的預防治療？

Exactly. On their existing prophy therapy, and then they switch and keep the same low attack rate on ORLADEYO.

確切地。在他們現有的預防治療上，然後他們切換並在 ORLADEYO 上保持同樣的低攻擊率。

Got it. And -- any -- and thanks for providing all of the detail on 9930 as well. I'm just wondering for the actual molecule, do you have an understanding of why it's crystallizing? And is that something that is relevant as to why the molecule is actually crystallizing?

知道了。並且 - 任何 - 並感謝您提供有關 9930 的所有詳細信息。我只是想知道實際的分子，你知道它為什麼會結晶嗎？這是否與分子實際結晶的原因有關？

Helen, you or Bill?

海倫，你還是比爾？

Yes, I can take that. So we have -- since making these observations, as I said in the remarks, we've done further work in the laboratory, and we've been able to establish the solubility level at the pH range in the urine. It's simple crystal formation as a result of the molecules chemistry. So there's nothing really special about it. But now that we know that, we know where to look for.

是的，我可以接受。因此，正如我在評論中所說，自從進行這些觀察以來，我們已經在實驗室進行了進一步的工作，並且我們已經能夠確定尿液中 pH 值範圍內的溶解度水平。由於分子化學，這是簡單的晶體形成。所以它並沒有什麼特別之處。但是現在我們知道了，我們知道在哪裡尋找。

(Operator Instructions) We have our next question from Gena Wang at Barclays.

（操作員說明）我們有來自巴克萊的 Gena Wang 的下一個問題。

I have a few regarding the ORLADEYO. And so I hope I did not miss it. Just wondering, have you mentioned the patient retention rate, would they still maintain at 70%? And regarding the new patient percentage of patients that switched from other prophy, what was the number there? Was that still like 50%? And then quickly on the pricing. I know you finalized in Germany, France and Switzerland. What are the comparison -- the price compared to the U.S. price? And sorry, one last question regarding Factor D, how much initial capital allocation will you put for that program?

我有一些關於 ORLADEYO 的信息。所以我希望我沒有錯過它。只是想知道，你有沒有提到病人的保留率，他們還會保持在 70% 嗎？關於從其他預防轉換的患者的新患者百分比，那裡的數字是多少？那還是50%嗎？然後快速定價。我知道你在德國、法國和瑞士敲定了。比較是什麼 - 與美國價格相比的價格？抱歉，關於因子 D 的最後一個問題，您將為該計劃投入多少初始資本分配？

Yes, go ahead, Charlie.

是的，繼續，查理。

Great Gena. So on patient retention, what I did note is that we had a decrease in discontinuations in Q2. So retention, it's too soon to call a trend, but it appears to be getting better. It's been a real focus of the team, particularly in improving retention early in therapy so that patients don't give up too early. The overall retention rate since launch, I think, I've said before, was in the mid-60% retention since launch.

偉大的熱那。因此，在患者保留方面，我確實注意到我們在第二季度的停藥減少了。所以留存率，現在稱之為趨勢還為時過早，但它似乎正在變得更好。這是團隊真正關注的焦點，特別是在治療早期提高保留率，以便患者不會過早放棄。我認為，自發布以來的整體留存率，我之前說過，自發布以來的留存率在 60% 左右。

It's similar to that. But what's really important now is we see some signs that this is improving. And as far as the overall switch rate, I think I just mentioned a minute ago, but about 50% of the patients have switched from other prophy and then the other 50% is mostly switching from acute only, and then some patients who are naive to therapy, starting ORLADEYO as their first drug.

與此類似。但現在真正重要的是我們看到一些跡象表明這種情況正在改善。至於整體轉換率，我想我剛剛在一分鐘前提到過，但是大約 50% 的患者已經從其他預防轉換，然後另外 50% 主要是從急性轉換，然後是一些天真的患者開始治療，開始使用 ORLADEYO 作為他們的第一種藥物。

Yes, Charlie, I think part of your question was retention and those folks, it's actually better in the...

是的，查理，我認為您的部分問題是保留，而那些人，實際上在...中更好

Yes. Sorry, yes, right. That was the other part. Yes. So -- and I've mentioned this in previous calls that the retention of people switching from injectable prophy at 6 months for Takhzyro, Haegarda, Cinryze is in the high 70%, and that's based on the fact that they were well controlled before and they stay -- most of those patients stay well controlled on ORLADEYO.

是的。對不起，是的，對。那是另一部分。是的。所以——我在之前的電話會議中提到過，Takhzyro、Haegarda、Cinryze 的人在 6 個月時從注射預防轉換的保留率高達 70%，這是基於他們之前得到很好控制的事實，並且他們留下來——這些患者中的大多數在 ORLADEYO 上都得到了很好的控制。

And then you had a question about EU pricing. So our German list price is about EUR 156,000. The Swiss price is a little bit higher than that. So you get a sense for how that compares to U.S. where our WAC pricing is $499,000.

然後你有一個關於歐盟定價的問題。因此，我們的德國標價約為 156,000 歐元。瑞士的價格比這高一點。因此，您可以了解這與我們的 WAC 定價為 499,000 美元的美國相比如何。

And then, Anthony, you want to take the capital allocation question?

然後，安東尼，你想回答資本配置的問題嗎？

Yes, sure. So from a capital allocation perspective, it will depend on how quickly we can move through the trials. Our intent is to move as quickly as possible. Helen talked about it being incremental in terms of how we move forward with the program. One thing I will say is we've talked about it being a small number of patients that we need at the start. We've also said in the guidance that we've reduced our OpEx guidance down to $390 million to $400 million for the year.

是的，當然。因此，從資本配置的角度來看，這將取決於我們能夠以多快的速度通過試驗。我們的意圖是盡快行動。 Helen 談到它在我們如何推進該計劃方面是漸進的。我要說的一件事是，我們一開始就談到了我們需要的少數患者。我們還在指導中表示，我們已將今年的運營支出指導降低至 3.9 億美元至 4 億美元。

So that in combination with the revenue increase in the guidance means from a net cash burn perspective, we're definitely in a better spot now than we were previously. So listen, we'll be absolutely responsible and smart in terms of how we invest that capital. It is the right investment in capital at this point in time given the potential returns.

因此，從淨現金消耗的角度來看，與指引中的收入增長相結合，我們現在肯定比以前處於更好的位置。所以聽著，就我們如何投資這些資本而言，我們將絕對負責任和聰明。考慮到潛在的回報，此時這是對資本的正確投資。

We have our next question from Brian Abrahams with RBC Capital Markets.

我們有來自加拿大皇家銀行資本市場的 Brian Abrahams 的下一個問題。

Congratulations on the continued strong ORLADEYO launch. A few for me. I guess, on 9930, are there mechanistically different considerations with regards to this crystal formation for PNH patients versus those with underlying kidney disease?

祝賀 ORLADEYO 繼續強勁推出。幾個給我。我想，在 9930 上，對於 PNH 患者與患有潛在腎臟疾病的患者的這種晶體形成，是否存在機械上不同的考慮？

Secondly, on the interim assessment that you're going to be doing, will efficacy be a part of that? And will the FDA have any requirements that they'll need to sign off on before the trial is extended out?

其次，在你將要進行的中期評估中，功效會是其中的一部分嗎？在延長試驗之前，FDA 是否有任何要求他們需要簽署的要求？

And then lastly, on ORLADEYO, it sounds like you're reiterating your $1 billion peak sales estimate. I'm just wondering if there's any evolution in the parameters that form your confidence around that. It sounds like the U.S., ex U.S. breakdown is similar to what you had expected before, but just wondering if the improving retention, new patient starts, degree of overall market growth, how those factors are evolving to continue to shape that goal?

最後，在 ORLADEYO 上，聽起來您在重申您對 10 億美元的最高銷售額估計。我只是想知道參數是否有任何演變可以形成您對此的信心。聽起來美國，前美國的細分與您之前的預期相似，但只是想知道是否提高保留率、新患者開始、整體市場增長程度、這些因素如何演變以繼續塑造該目標？

So Helen, do you want to take the 9930 and then Charlie can take the ORLADEYO?

那麼海倫，你想拿 9930 然後查理可以拿 ORLADEYO 嗎？

Yes. So the first question was, is there any mechanistic difference in this -- in the patients with different diseases. And we don't think so. And the hypothesis says crystals forming when there's a high concentration of the drug excreted in the urine. That is a drug that's independent of disease. So once we have solved this for a dose that is safe and effective, in one disease, we would expect that to be relevant in all diseases.

是的。所以第一個問題是，這是否存在任何機制差異——在患有不同疾病的患者中。我們不這麼認為。假設說當尿液中排出高濃度的藥物時會形成晶體。那是一種獨立於疾病的藥物。因此，一旦我們在一種疾病中以安全有效的劑量解決了這個問題，我們希望這與所有疾病都相關。

The second question was in terms of what we are assessing on an interim basis in the study. This is a simple safety assessment. It's simple observation. If we see continued episodes of rise in creatinine in patients being dosed at 400 milligrams, and we'll know that we're seeing it, if we're not, then we won't be. And that's the extent of the interim view.

第二個問題是關於我們在研究中臨時評估的內容。這是一個簡單的安全評估。這是簡單的觀察。如果我們看到服用 400 毫克的患者肌酐持續升高，我們就會知道我們正在看到它，如果我們沒有看到，那麼我們就不會看到。這就是臨時觀點的範圍。

Yes. And his question too was around the FDA and efficacy. There were no requirements by the FDA. They they're always looking at a benefit risk. And clearly, they see some benefit in keeping the patients on the study and us continuing study. But from an efficacy perspective, if we have breakthrough hemolysis, we'll see that. And we're evaluating whether the DMC can look at the blinded data, our unblinded data as well from an efficacy perspective. So we're concerned about both, Brian. And those -- we said before, the goal is a safe and effective drug.

是的。他的問題也圍繞著 FDA 和療效。 FDA沒有要求。他們一直在關注利益風險。很明顯，他們看到了讓患者繼續參與研究和我們繼續研究的一些好處。但從療效的角度來看，如果我們有突破性的溶血，我們會看到的。我們正在評估 DMC 是否可以從功效的角度查看盲數據，我們的非盲數據。所以我們都擔心，布賴恩。而那些——我們之前說過，目標是一種安全有效的藥物。

Brian, the -- as far as the $1 billion. Nothing significant has changed. We do -- as you know, we do a lot of market research, a lot of planning. And as we see the real-world evidence, the real-world results matching up what we expected, we gain even more confidence and reiterate. So what we're seeing in Europe, the early uptake, the pricing that we've been able to achieve is in line with our expectations. And so that gives us great confidence in getting to at least $200 million in the rest of the world. And then the real-world evidence that I've talked about coming out of patients who are switching to ORLADEYO in the U.S. and the fact that most of those patients are staying on drug and having a great experience, gives us that much more confidence. And then what I said about our prescriber base expanding. All of this just gives us more confidence in where this drug is headed in.

布賴恩，最高達 10 億美元。沒有任何重大變化。我們做——如你所知，我們做了大量的市場調查和規劃。當我們看到真實世界的證據，真實世界的結果與我們的預期相匹配時，我們會獲得更多的信心並重申。因此，我們在歐洲看到的情況、早期採用率、我們能夠實現的定價符合我們的預期。這讓我們對在世界其他地方至少獲得 2 億美元充滿信心。然後，我談到的真實世界證據來自美國轉用 ORLADEYO 的患者，以及大多數患者繼續服藥並擁有豐富經驗的事實，讓我們更有信心。然後是我所說的關於我們的處方基礎擴大的內容。所有這些只是讓我們對這種藥物的發展方向更有信心。

Yes, and quarter after quarter, it keeps getting better. Right? We're growing sales. We're expanding, prescribing. We're getting more into the funnel in terms of new patients. Our confidence goes up every single quarter. There is no sign of slowing down.

是的，一個季度又一個季度，它不斷變得更好。正確的？我們正在增加銷售額。我們正在擴大，開處方。就新患者而言，我們正在更多地進入漏斗。我們的信心每個季度都在上升。沒有放緩的跡象。

We have our next question. Our next question comes from Serge Belanger with Needham & Company.

我們有下一個問題。我們的下一個問題來自 Needham & Company 的 Serge Belanger。

I guess, one on 9930 to start off. Did I hear correctly that you are evaluating some of the backup molecules to 9930. And if I did hear it correctly, how close are they to being ready for clinical evaluation? And then on ORLADEYO, a couple for Charlie. Can you talk about where you are with market share now? And in terms of new patient add cadence, how it progressed in the second quarter and maybe whether you expect summer seasonality impact on that cadence?

我猜，一個在 9930 上開始。我沒聽錯你正在評估一些 9930 的備用分子。如果我沒聽錯，他們離臨床評估準備還有多遠？然後是奧拉德約，查理的一對。你能談談你現在的市場份額嗎？就新患者添加節奏而言，它在第二季度的進展情況如何，也許您是否預計夏季季節性會對該節奏產生影響？

So I'll take the back up one, Charlie, and then you take the ORLADEYO new patient. Yes, we're always working on backups and we didn't slow down. We've always put full code advance -- I said in the remarks that we're investing fully in those. And so I can't tell you yet when it's ready to share more broadly. But there are multiple backups. And as we have more data, we'll share that with you. And I think the other piece is we're working to have improved molecules as well. And you saw that with the move from avoralstat to ORLADEYO. And so in this program, we're trying to do the same, whether or not we'll be successful is to be determined, but full speed ahead on the backups.

所以我會帶上一個，查理，然後你帶上 ORLADEYO 的新病人。是的，我們一直在做備份工作，我們並沒有放慢腳步。我們一直在推進完整的代碼——我在評論中說我們正在全力投資這些。所以我還不能告訴你什麼時候可以更廣泛地分享。但是有多個備份。隨著我們擁有更多數據，我們將與您分享。我認為另一部分是我們也在努力改進分子。從 avoralstat 到 ORLADEYO，你已經看到了這一點。所以在這個計劃中，我們也在嘗試做同樣的事情，我們是否會成功還有待確定，但要全速推進備份。

And then Serge, as far as market share, we've shared some of our market research in the past, I think most recently some data from earlier this year. We -- the survey showed ORLADEYO share of about 12%. That was probably a little ahead of where we actually were in the market at that time. But then we've grown since then. So it's -- and physicians see in our market research see this becoming their most prescribed drug in the future.

然後 Serge，就市場份額而言，我們過去分享了一些市場研究，我想最近是今年早些時候的一些數據。我們——調查顯示奧拉迪約的份額約為 12%。這可能比我們當時在市場上的實際情況要早一點。但是從那時起我們就長大了。所以它是 - 醫生在我們的市場研究中看到這將成為他們未來最多的處方藥。

And as we've said before, all we need is 25% to 30% market share in the U.S. to get to about $750 million, $800 million towards that $1 billion of peak sales. So it's growing all the time. We're doing well. And then as far as the new patient cadence, I mentioned in the remarks, that we had the most new patient prescriptions in Q2 since the very first quarter of the launch.

正如我們之前所說，我們只需要在美國獲得 25% 到 30% 的市場份額，就可以達到大約 7.5 億美元，達到 10 億美元的峰值銷售額需要 8 億美元。所以它一直在增長。我們做得很好。然後就新患者的節奏而言，我在評論中提到，自推出第一季度以來，我們在第二季度擁有最多的新患者處方。

And that's really significant now 6 quarters in. No signs of slowing down. And as far as the summer slowdown, any differences there? We'll see. We'll talk about that after Q3, but we ended Q2 in June really strongly. So I feel good about where we are.

現在已經有 6 個季度了，這真的很重要。沒有放緩的跡象。至於夏季放緩，那裡有什麼不同嗎？走著瞧。我們將在第三季度之後討論這個問題，但我們在 6 月份結束了第二季度的表現非常強勁。所以我對我們所處的位置感覺很好。

Thank you. We have our final question from Liisa Bayko with Evercore ISI.

謝謝你。我們收到了來自 Evercore ISI 的 Liisa Bayko 的最後一個問題。

I understand what you're saying about the threshold effect for 9930, yet you did have some patients that had these elevations and some that didn't any ability to decipher what that is? And what's your threshold I know you saw it in 15 patients. Like if you see one case, is that enough to stop what's your threshold for like seeing cases as you go into this next phase now?

我理解你所說的關於 9930 的閾值效應，但你確實有一些患者有這些升高，而一些患者沒有任何能力破譯那是什麼？你的閾值是多少 我知道你在 15 名患者身上看到過。就像如果您看到一個案例，這是否足以阻止您現在進入下一階段時看到案例的門檻是多少？

So I can take the question. So on the threshold, yes, we have seen this in some patients, not all. We do think this is a threshold effect. What that means is that in some patients under some circumstances, crystals could be forming. And we're pretty close to the edge of that threshold with the 500-milligram dose. That's what we infer.

所以我可以回答這個問題。所以在門檻上，是的，我們在一些患者身上看到了這種情況，而不是全部。我們確實認為這是一個門檻效應。這意味著在某些情況下，某些患者可能會形成晶體。我們非常接近 500 毫克劑量的閾值邊緣。這就是我們推斷的。

And that means that with the two-pronged approach, and that's part of why we're taking that two-pronged approach of reducing the dose and hydration. We could see that we get below the threshold for all patients all the time. And that's the goal is to avoid this.

這意味著採用雙管齊下的方法，這就是為什麼我們採取雙管齊下的方法來減少劑量和水合作用的部分原因。我們可以看到我們一直低於所有患者的閾值。這就是避免這種情況的目標。

So this is a hypothesis. We're still working on this. We need to observe in the clinical setting if we've addressed this with 400 milligram. But that's why we think it's happening, it's sporadically occurring because we're close to the threshold, some of the time, but not all the time.

所以這是一個假設。我們仍在努力。如果我們用 400 毫克解決了這個問題，我們需要在臨床環境中進行觀察。但這就是為什麼我們認為它正在發生，它是偶爾發生的，因為我們接近閾值，有時，但不是所有時間。

And then the stopping rule. And then what's the -- I think that's important for people to know.

然後是停止規則。然後是什麼——我認為這對人們來說很重要。

Yes. So -- and the question is one case enough. So what we think is that -- there are multiple things that can also occur in patients with these diseases that can cause rise in serum creatinine. We want to make sure that we are assessing any rise in serum creatinine in the context of where -- what's happening with patient and if it is likely to be related to the drug or something else.

是的。所以——問題是一個案例就足夠了。所以我們認為——在患有這些疾病的患者身上也會發生多種事情，這些事情會導致血清肌酐升高。我們希望確保我們正在評估血清肌酐的任何升高情況——患者發生了什麼，以及它是否可能與藥物或其他原因有關。

So we're assessing these. We will review them together with our DMC. We have a stopping rule in the studies that if we see 3 events that are serious events and that are considered to be related to the drug, that's the point in which we would stop the study.

所以我們正在評估這些。我們將與我們的 DMC 一起審查它們。我們在研究中有一個停止規則，如果我們看到 3 個事件是嚴重事件並且被認為與藥物有關，那就是我們停止研究的時間點。

Okay. So it's 3 cases. Okay. And then just this notion of inferring. So like what makes you believe that $400 milligram is sort of below that threshold?

好的。所以是3例。好的。然後就是這個推斷的概念。那麼，是什麼讓你相信 400 毫克低於這個門檻？

So it's a hypothesis, and it's based on what we see at this point in the data, we have not observed this at 400 milligrams. And we do have every patient in the Phase I went through the 400-milligram stage of dosing.

所以這是一個假設，它基於我們在數據中看到的這一點，我們沒有在 400 毫克觀察到這一點。我們確實讓第一階段的每位患者都經歷了 400 毫克的給藥階段。

Yes. It's a drug concentration thing. If you have less drug and you have more hydration, less chance of having it go out of solution, right? So there's logic there, too.

是的。這是藥物濃度的事情。如果你有更少的藥物並且你有更多的水合作用，那麼它失去溶液的機會就更少了，對吧？所以那裡也有邏輯。

Okay. Okay. And then sorry, I may have missed it, but did you break down sales like U.S., Japan, rest of world? Or could you do that?

好的。好的。然後對不起，我可能錯過了，但你有沒有像美國、日本、世界其他地方那樣分解銷售？或者你能做到嗎？

We have not broken that out yet, Liisa.

Liisa，我們還沒有解決這個問題。

Yes. And the reason we have it is the majority of it is U.S. So the other stuff isn't significant enough to report out. But it is growing. I mean I said that in the remarks that it's nice to see you're growing, and that's not surprising because now we've got pricing, now we've got promotion, now patients are getting on therapy. So over time, we will break it out. But at this point, it's vast, vast majority is U.S.

是的。我們擁有它的原因是其中大部分是美國。所以其他的東西不足以報告出來。但它正在增長。我的意思是我在評論中說很高興看到你在成長，這並不奇怪，因為現在我們有了定價，現在我們有了促銷，現在患者正在接受治療。所以隨著時間的推移，我們會打破它。但在這一點上，絕大多數是美國。

Okay. And then one quick question. I've been getting questions from clients lately about the types of patients who stay on ORLADEYO for longer than 6 months. And is there any relationship between sort of severity of disease and response. So if you could just kind of talk about the kind of patients who tend to be more sticky -- and then related question on severity and response to ORLADEYO.

好的。然後是一個快速的問題。我最近收到客戶關於在 ORLADEYO 停留超過 6 個月的患者類型的問題。疾病的嚴重程度與反應之間是否存在任何關係。因此，如果您可以談談傾向於更粘稠的患者類型 - 然後是有關嚴重程度和對 ORLADEYO 反應的相關問題。

Yes. The type of patient that tends to be the most sticky are again those patients who were well controlled on another drug and then switched over to ORLADEYO and remain well controlled. And so the fact that they were on prophylaxis prior suggested they needed their attacks controlled and then they maintain that same rate on ORLADEYO.

是的。往往最粘稠的患者類型再次是那些在另一種藥物上得到良好控制然後切換到 ORLADEYO 並保持良好控制的患者。所以他們之前接受預防的事實表明他們需要控制他們的攻擊，然後他們在 ORLADEYO 上保持同樣的速度。

Yes. This idea of attack severity or frequency of attack, people control their disease now. So that's like a -- that's a whole way of looking at it. Now the way you should look at it is where are we getting the business? We're getting it from people that are controlled on their injectable therapy, but don't want the burden of therapy, the injectable therapy. Those are the people we're getting and that will continue to grow, and we'll get more and more share of that.

是的。這種關於發作嚴重程度或發作頻率的想法，人們現在可以控制自己的疾病。所以這就像 - 這是一個完整的看待它的方式。現在你應該看待它的方式是我們從哪裡獲得業務？我們從那些控制他們的注射療法但不想要治療負擔的人那裡得到它，注射療法。這些是我們得到的人，並且會繼續增長，我們將獲得越來越多的份額。

This concludes our question-and-answer session. I will now turn the call over to Mr. Stonehouse for closing remarks.

我們的問答環節到此結束。我現在將把電話轉給斯通豪斯先生做閉幕詞。

Yes. Thank you. something I've learned, and I think, we've learned as a company over many years of working on many, many projects is the importance of objectivity and following the evidence and the data in our decision-making, whether it's clinical data that we're looking at to advance a program or market data, do we have the right profile that will be competitive in the marketplace. If you go into it, wanting to see a certain thing, you're not going to be objective and you could make the wrong decision. We don't do that at BioCryst. We look at the evidence and we make our decisions based on what we see.

是的。謝謝你。我學到的東西，而且我認為，作為一家公司，我們在多年從事許多項目的過程中學到了客觀性的重要性，並在我們的決策中遵循證據和數據，無論是臨床數據我們正在考慮推進項目或市場數據，我們是否擁有在市場上具有競爭力的正確配置文件。如果你進入它，想看到某件事，你就不會客觀，你可能會做出錯誤的決定。我們在 BioCryst 不這樣做。我們查看證據並根據我們所看到的做出決定。

And I think as a result of that, we're starting to create greater value and have more success and ORLADEYO is the case study for that. So if you're not familiar with our thinking, we encourage you to get to know us better, and we can share with you -- and listen, it's not the only part that's important in success -- people, good science is also about the decision-making on this stuff and the objectivity is critical and we think it affects value tremendously. So thanks for your interest in our company, and have a great day.

我認為因此，我們開始創造更大的價值並取得更大的成功，而 ORLADEYO 就是這方面的案例研究。所以如果你不熟悉我們的想法，我們鼓勵你更好地了解我們，我們可以和你分享——聽著，這不是成功的唯一重要部分——人，好的科學也是關於對這些東西的決策和客觀性至關重要，我們認為它會極大地影響價值。感謝您對我們公司的關注，祝您有美好的一天。

Thank you. Ladies and gentlemen, this concludes our conference. Thank you for participating. You may now disconnect.

謝謝你。女士們先生們，我們的會議到此結束。感謝您的參與。您現在可以斷開連接。