BioCryst Pharmaceuticals Inc (BCRX) 2022 Q4 法說會逐字稿

Good morning, and welcome to the BioCryst Fourth Quarter 2022 Earnings Conference Call. (Operator Instructions) Please note this event is being recorded. I would now like to turn the conference over to John Bluth at BioCryst. Please go ahead.

早上好，歡迎來到 BioCryst 2022 年第四季度收益電話會議。 （操作員說明）請注意正在記錄此事件。我現在想將會議轉交給 BioCryst 的 John Bluth。請繼續。

Thanks, Andrea. Good morning, and welcome to BioCryst's Fourth Quarter and Year-end 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; and Chief R&D Officer, Dr. Helen Thackray. Following our remarks, we'll answer your questions.

謝謝，安德里亞。早上好，歡迎來到 BioCryst 的第四季度和年底 2022 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獲取。今天和我一起參加的有首席執行官 Jon Stonehouse；首席財務官安東尼道爾；首席商務官 Charlie Gayer；和首席研發官 Helen Thackray 博士。在我們的評論之後，我們將回答您的問題。

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. 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.

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。這些陳述受到已知和未知的風險和不確定性的影響，這些風險和不確定性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。如需更多信息，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備案的文件，這些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. 2022 was another outstanding year for ORLADEYO as we doubled sales in our second full year of launch on top of the fantastic start we had in the first year. It shouldn't be surprising given the excellent safety, efficacy and once-daily oral profile. We are consistently hearing from patients that ORLADEYO is changing their lives. As you will hear from Charlie, in the U.S., our prescriber base continues to grow both in breadth and depth. In addition, ORLADEYO is already commercially available to HAE patients in 15 countries around the world. The ability of ORLADEYO to deliver meaningful results for patients is driving the steady patient growth we are seeing quarter after quarter.

謝謝，約翰。 2022 年是 ORLADEYO 又一個出色的一年，因為在第一年取得了出色的開端之後，我們在推出第二個完整年度的銷售額翻了一番。鑑於出色的安全性、有效性和每日一次的口服概況，這不足為奇。我們不斷聽到患者說 ORLADEYO 正在改變他們的生活。正如您將從查理那裡聽到的那樣，在美國，我們的處方醫生群體在廣度和深度上都在持續增長。此外，ORLADEYO 已經在全球 15 個國家上市，供 HAE 患者使用。 ORLADEYO 為患者提供有意義的結果的能力正在推動我們每個季度看到的患者穩定增長。

And in 2023, we expect this strong steady demand to continue, leading to the global sales of no less than $320 million. Our goal with this guidance is very simple to be accurate. Accurate guidance has been our track record since launch because we're the only ones with access to the prescription data through our sole source specialty firms. With our sales performance in 2021 and 2022 and our guidance in 2023, you now have three data points to get a sense of the slope of the ORLADEYO launch. We are on a trajectory to achieve peak global sales of $1 billion, and our IP for ORLADEYO extends out to 2039. So we expect to be at peak sales for many, many years. While our revenues continue to grow, we expect our operating expenses to be flat year-over-year as we have made and will continue to make thoughtful capital allocation decisions on our pipeline investment. This reduction in net cash use has strengthened our financial position moved us closer to profitability. You will hear more detail on this from Anthony shortly.

到 2023 年，我們預計這種強勁穩定的需求將持續下去，導致全球銷售額不少於 3.2 億美元。我們在本指南中的目標很簡單，就是要準確。自推出以來，準確的指導一直是我們的跟踪記錄，因為我們是唯一可以通過我們的唯一來源專業公司訪問處方數據的人。根據我們在 2021 年和 2022 年的銷售業績以及我們在 2023 年的指導，您現在可以通過三個數據點來了解 ORLADEYO 發布的斜率。我們有望實現 10 億美元的全球銷售額峰值，而我們的 ORLADEYO 知識產權將延伸至 2039 年。因此，我們預計將在很多年內保持銷售額峰值。在我們的收入繼續增長的同時，我們預計我們的運營費用將與去年同期持平，因為我們已經並將繼續對我們的管道投資做出深思熟慮的資本分配決策。淨現金使用量的減少增強了我們的財務狀況，使我們更接近盈利。您很快就會從 Anthony 那裡聽到更多詳細信息。

Now I'll turn the call over to Charlie to review ORLADEYO performance in more detail.

現在，我將把電話轉給查理，以更詳細地審查 ORLADEYO 的表現。

Thanks, Jon. The base of patients treated with ORLADEYO in the United States continued to grow as expected in the fourth quarter, as new patients start and patient retention remains consistent with the trends we have seen over the last 2 years. The prescriber base expanded strongly again, and existing prescribers continue to add new prescriptions. New starts on ORLADEYO were also distributed evenly with just over 50% coming from the top tier of health care providers who treat half of all HAE patients.

謝謝，喬恩。在美國接受 ORLADEYO 治療的患者基數在第四季度繼續如預期增長，因為新患者的開始和患者保留與我們在過去兩年中看到的趨勢保持一致。處方者基數再次強勁擴張，現有處方者繼續增加新處方。 ORLADEYO 的新開始也分佈均勻，超過 50% 來自頂級醫療保健提供者，他們治療了一半的 HAE 患者。

As we begin 2023, we have confidence that we will achieve no less than $320 million in global revenue this year. Our U.S. field team expansion is in place and patient growth trends are on track. Our European growth is also gaining momentum, and we continue to lay the foundation for ORLADEYO expansion globally. And this weekend, we will present more long-term clinical and real-world evidence at the Quad AI meeting, adding to the growing body of evidence showing how ORLADEYO can improve the lives of patients living with HAE. We have noted before that typical U.S. payer reauthorization dynamics for rare disease products like ORLADEYO will soften Q1 revenue growth as many patients shift temporarily to free product. What we are seeing so far this year tells us that ORLADEYO revenue is likely to be flat to slightly down compared to Q4, even as our patient base continues to grow. We ended 2022 with a total number of patients on ORLADEYO that we expected and the patient growth trends we see in the U.S. and around the world give us confidence not only in our 2023 trajectory, but also that ORLADEYO peak revenue will reach $1 billion.

在 2023 年伊始，我們有信心今年的全球收入將不少於 3.2 億美元。我們的美國現場團隊擴張已經到位，患者增長趨勢步入正軌。我們在歐洲的增長勢頭也越來越強勁，我們繼續為 ORLADEYO 的全球擴張奠定基礎。本週末，我們將在 Quad AI 會議上展示更多長期臨床和真實世界的證據，增加越來越多的證據表明 ORLADEYO 如何改善 HAE 患者的生活。我們之前已經註意到，由於許多患者暫時轉向免費產品，典型的美國付款人對 ORLADEYO 等罕見疾病產品的重新授權動態將減緩第一季度的收入增長。我們今年到目前為止所看到的情況告訴我們，與第四季度相比，ORLADEYO 的收入可能持平或略有下降，即使我們的患者群繼續增長。到 2022 年，我們預計使用 ORLADEYO 的患者總數以及我們在美國和世界各地看到的患者增長趨勢使我們不僅對我們 2023 年的軌跡充滿信心，而且 ORLADEYO 的峰值收入將達到 10 億美元。

Helen, I'll turn the call over to you.

海倫，我會把電話轉給你。

Thanks, Charlie. Today, I'd like to provide some additional updates on the next step for (inaudible) our potential once-daily Factor B inhibitor for complement data to (inaudible) We shared last month, initial data from our Phase I single ascending dose and multiple ascending dose trials in healthy volunteers showed rapid, sustained and greater than 97% suppression of the alternative pathway of complement system, 24 hours following a single 110 mg dose, and that BCX10013 has been safe and generally well tolerated at all doses study state in the clinic. These data provide early support of the development and (inaudible) leave the product has the potential to differentiate once daily oral vac inhibitor for multiple (inaudible). The next key staff in clinical development in those ranges work in patients with the goal of confirming optimal dosing in digital set. Nonclinical program helps us to assess the safe dosing range we can evaluate in human. Recently, in emerging dose-related observations early in an ongoing chronic nonclinical studies, which were not seen at the same time period in a separate already completed study. We need to understand the full picture of these differences as they complete the currently ongoing study.

謝謝，查理。今天，我想提供一些關於（聽不清）我們潛在的每日一次因子 B 抑製劑的下一步的額外更新，以補充數據（聽不清）我們上個月分享了我們第一階段單次遞增劑量和多次遞增劑量的初始數據在健康志願者中進行的遞增劑量試驗顯示，在單次 110 mg 劑量後 24 小時內，補體系統旁路途徑得到快速、持續和超過 97% 的抑制，並且 BCX10013 在所有劑量研究狀態下都是安全且普遍耐受性良好的診所。這些數據為開發提供了早期支持，並且（聽不清）使該產品有可能將每日一次口服 vac 抑製劑區分為多種（聽不清）。這些範圍內臨床開發的下一個關鍵人員在患者中工作，目標是在數字集中確認最佳劑量。非臨床項目幫助我們評估我們可以在人體中評估的安全劑量範圍。最近，在一項正在進行的慢性非臨床研究的早期出現了與劑量相關的觀察結果，這在同一時間段內未在另一項已經完成的研究中觀察到。在完成當前正在進行的研究時，我們需要了解這些差異的全貌。

At the same time, as a result of these observations, the pace at which we can evaluate higher doses human to assess efficacy will be slower, and we expect to related delay in the timeline. So in order to grasp towards clinical selection, we'll continue working to understand what we're seeing in the ongoing nonclinical program and we'll keep you posted on our progress. In addition, (inaudible) we are making progress with our research program to identify oral medicines directly other targets across the classical, lectin and terminal pathways of the complement system, including C2, which is a critical upstream serine protease enzyme for activation of the classical and lectin pathways. As we reported in January, we developed potent, selective molecules targeting C2, and these are currently in the lead optimization stage. Our long-term goal is [to bring] multiple novel orally delivered products forward, treat any (inaudible). Now I'll pass to Anthony.

同時，由於這些觀察結果，我們評估更高劑量人體以評估療效的速度將變慢，我們預計時間線會有所延遲。因此，為了掌握臨床選擇，我們將繼續努力了解我們在正在進行的非臨床項目中看到的內容，我們會及時向您通報我們的進展情況。此外，（聽不清）我們正在通過我們的研究計劃取得進展，以確定口服藥物直接跨越補體系統的經典、凝集素和末端途徑的其他目標，包括 C2，它是激活經典補體的關鍵上游絲氨酸蛋白酶。和凝集素途徑。正如我們在 1 月份報導的那樣，我們開發了針對 C2 的強效選擇性分子，這些分子目前處於先導優化階段。我們的長期目標是[推出]多種新型口服產品，治療任何（聽不清）。現在我將交給安東尼。

Thanks, Helen. You can find our detailed fourth quarter and year-end financials in today's earnings press release, and I'd like to call your attention to a few items. Total revenue for the year came in at $271 million, over $250 million of which came from ORLADEYO in just its second year since launch, more than doubling net revenue from the prior year. Revenue for the fourth quarter was $79.5 million, of which $70.7 million came from net sales of ORLADEYO, with the remainder coming from sales of RAPIVAB, including the fulfillment of the last of our contract equipment (inaudible). Operating expenses, not including noncash stock compensation for the quarter were $110.6 million. This puts full year OpEx of $374.6 million, the increase compared to prior guidance was driven by almost $10 million of accelerated costs related to closeout activities for the termination of 9930 and 9250 programs. Cash at the end of the year, was at $444 million.

謝謝，海倫。您可以在今天的收益新聞稿中找到我們詳細的第四季度和年終財務數據，我想提請您注意一些事項。今年的總收入為 2.71 億美元，其中超過 2.5 億美元來自 ORLADEYO 自推出以來的第二年，淨收入比前一年增加了一倍多。第四季度的收入為 7,950 萬美元，其中 7,070 萬美元來自 ORLADEYO 的淨銷售額，其餘來自 RAPIVAB 的銷售，包括履行我們最後的合同設備（聽不清）。本季度不包括非現金股票補償的運營費用為 1.106 億美元。這使得全年運營支出為 3.746 億美元，與之前的指導相比有所增加，這是由於與終止 9930 和 9250 計劃的收尾活動相關的近 1000 萬美元加速成本推動的。年底現金為 4.44 億美元。

Earlier in the year, we provided guidance for 2023 ORLADEYO revenue of no less than $320 million. For OpEx, we expect 2023 to be flat the prior year at around $375 million. We previously stated that 2023 R&D investment would be in line with prior year. We're now forecasting that R&D expenses will decrease year-over-year following the discontinuation of the 9930 and 9250 program and the delay in the 10013 clinical program that Helen described. This will be offset by additional commercial investments that we're making both here in the U.S. and as we continue our international expansion. As our revenue and OpEx curves continue to converge, we expect net cash utilization in 2023 to decrease compared to 2022, even when factoring with the (inaudible). The combination of our strong balance sheet increasing revenue and our disciplined approach, capital allocation puts us in an outstanding financial position with an ever-decreasing reliance on the capital markets [for funding].

今年早些時候，我們為 2023 年 ORLADEYO 的收入提供了不少於 3.2 億美元的指導。對於運營支出，我們預計 2023 年將與上年持平，約為 3.75 億美元。我們之前曾表示，2023 年的研發投資將與上一年持平。我們現在預測，隨著 9930 和 9250 計劃的終止以及 Helen 描述的 10013 臨床計劃的延遲，研發費用將同比下降。這將被我們在美國和我們繼續進行國際擴張時進行的額外商業投資所抵消。隨著我們的收入和運營支出曲線繼續趨同，我們預計 2023 年的淨現金利用率將比 2022 年有所下降，即使考慮到（聽不清）也是如此。我們強勁的資產負債表增加了收入，加上我們嚴格的資本配置方法，使我們處於出色的財務狀況，並且對資本市場的依賴性不斷降低 [for funding]。

Now operator, we'll be happy to open up to Q&A.

現在是接線員，我們很樂意開放問答環節。

(Operator Instructions) And our first question comes from Jessica Fye of JPMorgan.

（操作員說明）我們的第一個問題來自摩根大通的 Jessica Fye。

Great. Two for me. I guess first, what else can you share with us about the dose-dependent finding with 10013? And second, maybe a nuance here, but if I recall at the healthcare conference, you indicated that 1Q revenue would be roughly flat with 4Q, I think now you're saying flat to slightly down. Does that just mean we should think of 4Q revenue as being even higher than it would have been otherwise? Or does that take a little bit of the buffer out of whatever might have been in your full year guidance?

偉大的。兩個給我。我想首先，關於 10013 的劑量依賴性發現，您還能與我們分享什麼？其次，這裡可能有細微差別，但如果我記得在醫療保健會議上，你表示第一季度收入將與第四季度大致持平，我想你現在說的是持平或略有下降。這是否僅僅意味著我們應該認為第四季度的收入比其他情況下的收入還要高？或者這是否會從您全年指導中的任何內容中扣除一點緩衝？

Do you want to take the first one?

你想拿第一個嗎？

Yes. Sure. So we -- in the nonclinical findings, what we're saying is that we are seeing something at a time point that is not (inaudible) at a time point in our other (inaudible) studies. And the impact then is that we want to learn more about the safe branch exposure and we understand the difference.

是的。當然。所以我們——在非臨床研究結果中，我們所說的是我們在某個時間點看到的東西在我們其他（聽不清）研究的某個時間點不是（聽不清）。然後的影響是我們想了解更多關於安全分支暴露的信息，我們了解其中的區別。

And Jess, as far as the Q4 and Q1 revenue, so this is not a Q4 being bigger than it should be. It's really based on what we're seeing out there with Q1 reauthorization. It's always a challenge every year. And what we're seeing is that this year, it's just -- this isn't an ORLADEYO specific thing just broadly the reauthorization process is just more work than ever. And so that's why we think it could be a little bit down or flat to Q4, but patient growth trends are on track and no less than $320 million is very much on track.

而 Jess，就第四季度和第一季度的收入而言，這並不是第四季度比應有的更大。這實際上是基於我們在 Q1 重新授權中看到的情況。每年都是一個挑戰。我們看到的是，今年，這只是——這不是 ORLADEYO 的具體事情，只是從廣義上講，重新授權過程比以往任何時候都更加工作。因此，這就是為什麼我們認為第四季度可能會略有下降或持平，但患者的增長趨勢正在步入正軌，而且不少於 3.2 億美元的收入已經步入正軌。

Yes. And that part is really important to remember that patient numbers are going up each quarter, but the reason revenue was flat to slightly down is because we have more patients on free drug going to the reauthorization.

是的。這部分非常重要，要記住患者數量每個季度都在上升，但收入持平或略有下降的原因是因為我們有更多的免費藥物患者去重新授權。

Next question comes from Tazeen Ahmad of Bank of America.

下一個問題來自美國銀行的 Tazeen Ahmad。

On ORLADEYO, Jon, I'm just wondering what do you think could change in order for sales to be above the minimum that you have just guided to for this year. So outside of negotiating with payers, where else would you see a potential for upside relative to how you're looking at the market right now?

關於 ORLADEYO，喬恩，我只是想知道你認為可以改變什麼才能使銷售額高於你剛剛指導的今年的最低水平。因此，除了與付款人談判之外，相對於您目前對市場的看法，您還會在哪裡看到上漲的潛力？

Yes. I think for right now, we believe $320 million is the number, and that's the number of people should put in their model. But in terms of what could be a tailwind, I think Charlie's team is more successful than we had planned around getting patients from free drug to pay drug. You've got this expansion -- many expansion that they went through late last year. Maybe that has more of an uptick on revenue as well. Those could be things that could be a lift.

是的。我認為就目前而言，我們認為 3.2 億美元是這個數字，這是應該投入他們的模型的人數。但就順風而言，我認為查理的團隊比我們計劃的讓患者從免費藥物到付費藥物更成功。你有這種擴張——他們在去年年底經歷了許多擴張。也許這對收入也有更多的增長。這些可能是一種提升。

Okay. Great. And then maybe one question on your 10013. I think you have previously highlighted that there was no facilitation talk seen before in your frequent models. Is that still the case?

好的。偉大的。然後可能有一個關於您的 10013 的問題。我想您之前已經強調過，在您的常用模型中之前沒有看到過引導談話。現在還是這樣嗎？

Yes, this is very different than the 99 -- your question is around 9930 in comparison to 10013 of that, yes, this is very different from that.

是的，這與 99 有很大不同——你的問題是 9930 左右，而 10013 與 9930 相比，是的，這與那個有很大不同。

The next question comes from Chris Raymond of Piper Sandler.

下一個問題來自 Piper Sandler 的 Chris Raymond。

And if you don't mind me beating the dead horse here. It sounds like you guys are -- I don't want to answer a ton of questions on exactly what you saw, but I guess I'll just ask on 10013, when would you be in a position to tell us exactly what you found? And what's the path forward and the next steps for when the issues will be resolved? And then on the C2 program, I know you described this as a program has in development, but can you maybe give a little bit more color maybe on the timeline pathway to be in the clinic on that program?

如果你不介意我在這裡打死馬。聽起來你們是——我不想就你們所看到的確切回答一大堆問題，但我想我會在 10013 上問一下，你們什麼時候可以準確地告訴我們你們發現了什麼？解決問題的前進道路和後續步驟是什麼？然後在 C2 程序上，我知道你將其描述為一個正在開發中的程序，但你能否在時間表路徑上提供更多顏色，以便在該程序的診所中使用？

Yes, I'll take those. Second one, you can take, Helen, you can take the first one. So what we said in January is the C2 programs in lead optimization. And it's hard to predict when it will get into [toxin] Phase I studies, but it's just lead optimization now once we pick a lead, we'll go into talk and move forward from there, but we can't give timing on that right now. Then the first question is around (inaudible)

是的，我會拿那些。第二個，你可以拿，海倫，你可以拿第一個。所以我們在 1 月份所說的是領先優化中的 C2 程序。很難預測它什麼時候會進入 [毒素] 第一階段研究，但現在只是先導優化，一旦我們選擇了先導，我們就會開始討論並從那裡向前推進，但我們不能給出時間現在。然後第一個問題是（聽不清）

Yes. So on 10013, what we're seeing is that we're seeing something that is different. We're seeing it at the same time point where we did see it before. What that means is that we need to learn more, we need to learn more about that difference more about the nature of what we're seeing. The goal here is to understand the safe range of exposures, and that's the point of the nonclinical work at this point. The goal in the clinic is then to understand the effective dose in patients. So our next steps [starts] to sweep the nonclinical side and a stance there also to go into the study patients that we've been planning and assess the patients they get to an understanding both of what is the same range and what's the effective range for the (inaudible). So if we can define those accordance to the program.

是的。所以在 10013 上，我們看到的是一些不同的東西。我們在之前看到它的同一時間點看到它。這意味著我們需要了解更多，我們需要更多地了解這種差異，更多地了解我們所見事物的本質。這裡的目標是了解安全的暴露範圍，這就是此時非臨床工作的重點。臨床的目標是了解患者的有效劑量。因此，我們接下來的步驟 [開始] 掃除非臨床方面，並採取立場進入我們一直在計劃的研究患者，並評估他們獲得的患者，以了解什麼是相同範圍和什麼是有效範圍對於（聽不清）。因此，如果我們可以根據程序定義那些。

Yes. Chris, it's an ongoing chronic [tox] study right now. And so until we've completed that, it's hard to give you some sense of when we'll have a better picture.

是的。克里斯，這是一項正在進行的慢性 [毒性] 研究。因此，在我們完成之前，很難讓您知道我們什麼時候會有更好的畫面。

The next question comes from Liisa Bayko of Evercore ISI.

下一個問題來自 Evercore ISI 的 Liisa Bayko。

Can you give us a sense of the degree of free drug and sort of gross to net -- and where you're at for the beginning of 2023?

你能告訴我們免費藥物的程度和淨收入的多少——以及你在 2023 年初的進展情況嗎？

Sure. Liisa, overall, what we've said is that based on our contract status, we expected at least 80% of patients to be paid drug, 20% on free. In recent quarters, we've seen that pick up above 20%. And then in Q1, it's just a larger portion that will temporarily -- pretty much all the patients are going through the authorization in Q1. And so a lot of them step back temporary -- temporarily to free product. So I think overall, that plus the fact that we also have the impact of commercial co-pay assistance is the greatest in Q1 Medicare donut hole payments you're going to see the lowest -- the worst gross to net in the first quarter. And then it will normalize back up once we get into Q2, 3, 4, when we were in Q4, Liisa, we saw gross to net nonreimbursed products at around [15 to 20]

當然。 Liisa，總的來說，我們所說的是，根據我們的合同狀態，我們預計至少 80% 的患者將獲得付費藥物，20% 的患者免費。在最近幾個季度，我們看到這一比例上升了 20% 以上。然後在第一季度，它只是暫時的更大一部分——幾乎所有患者都在第一季度獲得授權。所以他們中的很多人暫時退後一步——暫時免費產品。所以我認為總的來說，加上我們也有商業共同支付援助的影響，這是第一季度醫療保險甜甜圈支付中最大的，你會看到最低的 - 第一季度最差的毛淨值。然後，一旦我們進入第 2、3、4 季度，它就會恢復正常，當我們在第 4 季度時，Liisa，我們看到非報銷產品的毛額與淨額在 [15 到 20] 左右

Okay. And can you tell us a little bit more -- give us a little more color on the mini expansion that you described, what you want this business.

好的。你能告訴我們更多一點——給我們更多關於你描述的迷你擴展的顏色，你想要這個業務嗎？

Yes. So the basic -- the essence of that was we expanded the number of sales regions. It was not a major sales force expansion, but we made our regions smaller. So added more regional managers so that they can work closely with their teams as well as some of the top KOLs. Then simultaneously, we also added more to our market access team and our patient access specialist team so that we can do more to work with customers and particularly patients who help to get paid therapy.

是的。所以最基本的 - 其本質是我們擴大了銷售區域的數量。這不是主要的銷售人員擴張，但我們縮小了我們的區域。所以增加了更多的區域經理，以便他們可以與他們的團隊以及一些頂級 KOL 密切合作。同時，我們還增加了更多的市場准入團隊和患者准入專家團隊，以便我們可以做更多的工作來與客戶合作，尤其是幫助獲得付費治療的患者。

Okay. And then just a follow-up to Chris' question. Are you -- when will you get -- when are you going to complete this preclinical tox study?

好的。然後只是克里斯的問題的後續行動。你——你什麼時候——你打算什麼時候完成這項臨床前毒理學研究？

It will be sometime this year.

這將是今年的某個時候。

Okay. And any sense do you think this might be something specific to the species and like what species have you been looking at?

好的。從某種意義上說，您認為這可能是該物種特有的東西，例如您一直在觀察什麼物種？

That's a really good question that we don't have an answer to.

這是一個非常好的問題，我們沒有答案。

Okay. Can you mention the species just for...

好的。你能提到這個物種只是為了......

Yes. Not at this time, no.

是的。不是現在，不是。

Okay. Okay. And then just final question for me. Are you able to get clinically into what you think is an efficacious dose range -- or as you described going more slowly now in kind of your dose escalation, are you going to be kind of capped below what you think is the target efficacious dose?

好的。好的。然後是我的最後一個問題。您是否能夠在臨床上達到您認為有效的劑量範圍——或者正如您描述的現在劑量增加得更慢，您是否會被限制在您認為的目標有效劑量以下？

Our hope is that we get to an effective dose in the safe range. I don't think we can answer that question today, given what we're seeing, but that's the whole.

我們希望能達到安全範圍內的有效劑量。鑑於我們所看到的，我認為我們今天無法回答這個問題，但僅此而已。

And I would add, we already know from the data that we presented in January (inaudible) excellent pressure of the alternative pathway complement of 24 hours already with the dose has been evaluating [health] volunteers. So we have more to learn about the range (inaudible) that information.

我要補充的是，我們已經從 1 月份提供的數據中得知（聽不清）替代途徑的極佳壓力已經補充了 24 小時的劑量，一直在評估 [健康] 志願者。所以我們有更多關於範圍（聽不清）的信息。

The next question comes from Jon Wolleben of JMP Securities.

下一個問題來自 JMP Securities 的 Jon Wolleben。

Just a couple on ORLADEYO. I wonder if you could tell us what the quarter-over-quarter patient growth was in fourth quarter. And then with regards to the $320 million guidance. What's the breakdown between U.S. and ex U.S. contribution there?

ORLADEYO 上只有一對。我想知道您能否告訴我們第四季度患者的環比增長情況。然後是關於 3.2 億美元的指導。美國和前美國貢獻之間的細分是什麼？

Sure, Jon. We haven't specified the growth. What I can say is we are on the same trends, both in terms of new patient acquisition that we've seen over the last many quarters. And also our discontinuation rate has been very stable. So what that means is that every quarter, we're growing nicely, and that would that's what gives us so much confidence in the $320 million this year and the long-term projection to $1 billion. And -- you want to add something?

當然，喬恩。我們沒有具體說明增長。我可以說的是，我們在過去幾個季度看到的新患者獲取方面處於相同的趨勢。而且我們的停產率也非常穩定。所以這意味著每個季度，我們都在很好地增長，這就是讓我們對今年的 3.2 億美元和 10 億美元的長期預測充滿信心的原因。並且 - 你想添加一些東西嗎？

Yes, I think in terms of contribution from -- the way I think about it, John, is U.S. continues to be the majority of revenue. When we get to a point, and we will get to a point, hopefully, where we'll split out U.S. and ex U.S. That will be when ex U.S. accounts for around 10% of total revenue. When that will be will be. But at the moment, I think we're doing really well in both the U.S. and from a global expansion.

是的，我認為就貢獻而言——約翰，我認為美國仍然是收入的主要來源。當我們達到一個點時，我們將達到一個點，希望我們將美國和美國以外地區分開，屆時美國以外地區將佔總收入的 10% 左右。什麼時候會是。但目前，我認為我們在美國和全球擴張方面都做得很好。

The next question comes from Ken Cacciatore of Cowen & Company.

下一個問題來自 Cowen & Company 的 Ken Cacciatore。

Obviously, it's been a fantastic launch of ORLADEYO, you set up a great U.S. commercial infrastructure that would seemingly be attractive to many companies either don't have a U.S. infrastructure would want some further leverage I'm guessing, just looking at the P&L, the product is now profitable, which is a credit to the organization, excluding R&D, and you did it fast. So just -- we often -- we rarely, I should say, see such a gap between a profitable product and kind of pipeline replenishment. Just wondering how you all think about maximizing the value of this [dichotomy] going to grow a little bit now, unfortunately, over time here, kind of an organization, a little bit in two separate worlds. Can you just talk about that, how you think about maximizing that value and maybe kind of just strategically what you all are thinking?

顯然，這是 ORLADEYO 的一次精彩發布，你建立了一個偉大的美國商業基礎設施，這對許多公司來說似乎很有吸引力，要么沒有美國的基礎設施，要么需要一些進一步的影響力，我猜，只要看看損益表，產品現在盈利了，這是組織的功勞，不包括研發，而且你做得很快。因此，我應該說，我們經常——我們很少看到盈利產品和某種管道補貨之間存在這樣的差距。只是想知道你們是如何考慮最大化這種[二分法]的價值的，不幸的是，隨著時間的推移，這裡有點像一個組織，有點處於兩個不同的世界。你能談談這個，你如何考慮最大化這個價值，也許只是戰略上你們都在想什麼？

Yes. Thanks, Ken. We agree with you that it's off to a fantastic launch and have a real high degree of confidence that we're getting to the $1 billion in peak sales, and we're on that trajectory. So and that it's -- on a stand-alone basis, it's profitable today. And I even said in my prepared remarks that with the investments that we're making, we're getting closer to profitability because revenue is growing faster than expense basically. So anyway, I think we're always looking -- the goal here is to have a second product that's as big or bigger than ORLADEYO. That may take us longer with our pipeline. And so we're also evaluating BD activities as well. We brought Clayton Fletcher on board recently, who's a very experienced biotech BD person. And we're probably getting more inbound stuff than we ever have in the history of BioCryst. So we'll continue to evaluate that stuff you want to make sure that if you're bringing something in, it's something that can create real value. And so we're constantly looking at that as well.

是的。謝謝，肯。我們同意你的看法，它即將推出，並且非常有信心我們將達到 10 億美元的峰值銷售額，並且我們正處於這一軌道上。所以它是 - 在獨立的基礎上，它今天是有利可圖的。我什至在準備好的發言中說，通過我們正在進行的投資，我們越來越接近盈利能力，因為收入增長速度基本上快於支出增長速度。所以無論如何，我認為我們一直在尋找——這裡的目標是擁有第二個與 ORLADEYO 一樣大或更大的產品。這可能會花費我們更長的時間來處理我們的管道。因此，我們也在評估 BD 活動。我們最近聘請了 Clayton Fletcher，他是一位非常有經驗的生物技術 BD 人員。我們收到的東西可能比 BioCryst 歷史上的任何時候都多。因此，我們將繼續評估你想要的東西，以確保如果你帶來了一些東西，它是可以創造真正價值的東西。因此，我們也一直在關注這一點。

The next question comes from Justin Kim of Oppenheimer.

下一個問題來自奧本海默的賈斯汀金。

Just with the upcoming Quad AI meeting and based on the recent commercial progress, is there anything that needs to be better clarified with the prescriber base in attendance. Just wondering sort of what your goals are? And any changes in the dynamic of where new scripts are coming from, either from a patient perspective or a clinician.

就在即將召開的 Quad AI 會議上，根據最近的商業進展，是否有任何需要與出席的處方者基礎更好地澄清的事情。只是想知道你的目標是什麼？以及新腳本來源動態的任何變化，無論是從患者的角度還是從臨床醫生的角度。

Justin. So I think as far as clarify, we're just continuing the messages that we've been delivering about how well ORLADEYO is working in patients particularly over the long term, you look at our long-term data or 96-week data where patients were getting down to 16 out of 17 months attack-free. What we'll see at Quad AI is more data of the same coming out from our clinical trials that confirm that. And so it's really just about getting to all these physicians and showing them how well or day at work posting clinical trials and then now how well is working in the real world. And then how well it works regardless of where patients are coming from. So some of the patients who do absolutely the best in ORLADEYO are those who switch from other prophylaxis products that were already stable on those other products to switch to ORLADEYO, and they continue to do really well with very good, continued control. So that's -- it's sort of a long-term building of that. And there are lots of doctors who already get that. And then there are others who just haven't absorbed that message yet, and we're confident that we're going to get to them as well.

賈斯汀。因此，我認為就澄清而言，我們只是繼續傳達我們一直在傳達的信息，即 ORLADEYO 在患者身上的效果如何，特別是從長期來看，你看看我們的長期數據或 96 週的數據，患者17 個月中有 16 個月沒有受到攻擊。我們將在 Quad AI 上看到更多來自我們臨床試驗的相同數據，這些數據證實了這一點。因此，這實際上只是與所有這些醫生接觸，並向他們展示發布臨床試驗後的工作情況或一天的工作情況，以及現在在現實世界中的工作情況。然後不管病人來自哪裡，它的效果如何。因此，一些在 ORLADEYO 中表現絕對最好的患者是那些從其他產品已經穩定的預防產品轉向 ORLADEYO 的患者，他們在非常好的、持續的控制下繼續做得很好。這就是——這是一種長期的建設。而且有很多醫生已經明白了這一點。然後還有其他人還沒有吸收該信息，我們相信我們也會得到他們的幫助。

Yes. I think the other thing, Justin, is that there are docs out there that they're patients controlled, and that's good enough for them. And so what we've got to be able to do is say, no, a patient could do a whole lot better in terms of burden of therapy if they want to a once-daily oral and to dip away at that. And I think part of Charlie's expansion, where we're having the regional business directors focus on KOLs is to get those potential high prescribers to start to break through even further, get the ones that haven't prescribing the ones that have to prescribe more.

是的。我認為另一件事，賈斯汀，那裡有醫生說他們是病人控制的，這對他們來說已經足夠了。所以我們必須能夠做的是說，不，如果患者想要每天口服一次並減少治療負擔，他們可以在治療負擔方面做得更好。我認為 Charlie 擴張的一部分，我們讓區域業務總監專注於 KOLs 是為了讓那些潛在的高處方者開始進一步突破，讓那些沒有開處方的人必須開更多的處方.

I guess, I'm just curious in terms of your views on the long-term growth trajectory, is that mix of where the strip is coming from expected to change, whether between the 500 and non-500 base? I mean just trying to understand if that split of 50-50 is expected to continue and then for how long?

我想，就您對長期增長軌蹟的看法而言，我只是好奇，無論是在 500 點還是非 500 點之間，地帶的來源組合是否會發生變化？我的意思是只是想了解 50-50 的分裂是否預計會持續，然後會持續多長時間？

I think it's a good question. First of all, I'm really happy with that balance because what it shows is that we're reaching all parts of the market, and we're growing in both segments. So we're constantly expanding the number of top 500 doctors who are new ORLADEYO prescribers, and then we're seeing them once they do, go deeper into their list. And then that next 1,000 or so doctors were expanding it to them as well. So there's -- what it tells me is there is a lot of opportunity left in front of us, both amongst what HCPs can do and then the number of patients that can -- that still haven't experienced the benefit of ORLADEYO and our goal long term is to give every patient who needs to be on prophylaxis, a chance to try ORLADEYO because most of them are going to do really well.

我認為這是一個很好的問題。首先，我對這種平衡感到非常滿意，因為它表明我們正在觸及市場的所有部分，並且我們在這兩個領域都在增長。因此，我們不斷擴大 ORLADEYO 新開處方者的前 500 名醫生的數量，一旦他們這樣做，我們就會看到他們，深入了解他們的名單。然後接下來的 1,000 名左右醫生也將其擴展到他們身上。所以 - 它告訴我，我們面前還有很多機會，無論是 HCP 可以做什麼，還是可以做的患者數量 - 仍然沒有體驗到 ORLADEYO 的好處和我們的目標長期是給每個需要預防的患者一個嘗試 ORLADEYO 的機會，因為他們中的大多數人都會做得很好。

Yes. I think there's two really interesting pieces of evidence that we're going in that direction to: one is quarter-to-quarter, we're expanding the prescriber base; and the second is the market research, quarter after quarter after quarter says that docs are going to prescribe more in 12 months than they're currently prescribing. And that's a combination of people who have not yet prescribed that will in the future or those that are prescribing that will prescribe more. So those we think are two really encouraging pieces of data that give us a lot of confidence it's going to keep growing.

是的。我認為有兩個非常有趣的證據表明我們正朝著這個方向努力：一個是季度環比，我們正在擴大處方者基礎；第二個是市場研究，一個季度又一個季度地表明，醫生將在 12 個月內開出比目前開出的處方更多的處方。這是尚未開處方的人或將來會開處方的人的組合。因此，我們認為這是兩個非常令人鼓舞的數據，它們讓我們對它會繼續增長充滿信心。

The next question comes from Brian Abrahams of RBC Capital Markets.

下一個問題來自 RBC Capital Markets 的 Brian Abrahams。

You guys have talked about a recent slower conversion from free drug to pay commercial drug in fourth quarter (inaudible) And I just want to better understand this trend. Do you think this is reflecting just expanding to new physicians who may be less used to prescribing ORLADEYO? And are there ways to help educate those physicians about how to process the necessary paperwork? Or is there anything different about these patients, either they have milder disease or more on prior prophylaxis or have different types of insurance plans that may be contributing to this greater lag time? And then just real quick on 10013, were the preclinical findings you observed shared with relevant regulators? And is there any need to, I guess, pause dosing? Or should we just expect you'll be looking at shorter durations and/or lower dose levels as the clinical studies proceed.

你們談到了最近第四季度從免費藥物到付費商業藥物的轉變速度較慢（聽不清），我只是想更好地了解這一趨勢。您認為這是否反映了擴大到可能不太習慣開 ORLADEYO 處方的新醫生？有沒有辦法幫助教育這些醫生如何處理必要的文書工作？或者這些患者有什麼不同，他們患有較輕的疾病或更早接受預防，或者有不同類型的保險計劃可能會導致這種更大的滯後時間？然後很快在 10013 上，您觀察到的臨床前發現是否與相關監管機構共享？我猜是否需要暫停給藥？或者我們是否應該期望隨著臨床研究的進行，您會看到更短的持續時間和/或更低的劑量水平。

I'll take the first question, Brian. Yes. So it's really much more of the first thing you said. So as we're expanding to less experienced prescribers within the HAE space. It worked to get any drug, whether it's ORLADEYO any other HAE therapy approved by insurers. It's not a contracting issue. It's really about providing all the information, the lab test, the clinical history, the complete information that payers want to see before approving any treatment or HAE. And so that's a big part of the team expansion that we've described. We have more people out there to help with this process to get patients to paid therapy. And it's really about having a very complete prior authorization and reauthorization to make sure that we help them give all the information that the payers need. So I'm actually with what I'm seeing, I'm confident that we are going to make great improvement in this ratio of paid to free product, it's not all going to be in Q1. It is going to be a year-long process. But I think we are very much on the right track.

我來回答第一個問題，布賴恩。是的。所以這實際上更像是你說的第一件事。因此，當我們擴展到 HAE 領域內經驗不足的處方者時。它適用於獲得任何藥物，無論是 ORLADEYO 還是保險公司批准的任何其他 HAE 療法。這不是合同問題。這實際上是關於提供所有信息、實驗室測試、臨床病史以及付款人在批准任何治療或 HAE 之前希望看到的完整信息。因此，這是我們所描述的團隊擴張的重要組成部分。我們有更多的人在那裡幫助完成這個過程，讓患者接受付費治療。這實際上是關於獲得非常完整的事先授權和再授權，以確保我們幫助他們提供付款人需要的所有信息。所以我實際上和我所看到的一樣，我相信我們將在付費產品與免費產品的比例上做出很大的改進，這不會全部出現在第一季度。這將是一個長達一年的過程。但我認為我們走在正確的軌道上。

Helen, do you want to take the 10013?

海倫，你要坐 10013 嗎？

Yes. So on your question on 10013. So this is -- the nonclinical information we're reporting today, this is an ongoing study, and so we still have more to learn here. We always are in so such with regulators over what's going in -- on what data comes in programs that's not on full and clinical, we have deferred the higher dose levels in our healthy volunteer study, and so we learn more about this information, but we do still plan to go forward in patients that take the drug therapeutic range in patients understand there. What we're saying is that as the nonclinical data informs your understanding of the range of exposures we expect it will have some delay in how high we go to the fast for dose sorry, how fast we go to the higher doses in patients [that we] study.

是的。所以關於你關於 10013 的問題。所以這是——我們今天報告的非臨床信息，這是一項正在進行的研究，所以我們在這裡還有更多的東西要學習。我們總是與監管機構就正在發生的事情保持聯繫——關於哪些數據來自不完整和臨床的項目，我們已經推遲了我們健康志願者研究中的更高劑量水平，因此我們了解了更多關於這些信息的信息，但是我們仍然計劃在那些了解那裡的患者服用藥物治療範圍的患者中繼續前進。我們要說的是，由於非臨床數據告知您對暴露範圍的理解，我們預計它會延遲我們達到多高的禁食劑量抱歉，我們多快達到患者的更高劑量 [that我們學習。

And Brian, if I could just come back, I realize that probably didn't answer part of your question, which is just on patient mix. It doesn't have anything to do with the patient mix. It's all about the other things that I described just giving the doctors -- or sorry, giving the plans or the information that they needed. Remember, half of our patients since launch have been patients switching from other prophy product. So it's really -- it's not about the patient.

布萊恩，如果我能回來，我意識到這可能沒有回答你的部分問題，這只是關於病人的問題。它與患者組合沒有任何關係。這都是關於我描述的其他事情，只是給醫生——或者抱歉，給他們需要的計劃或信息。請記住，自推出以來我們的患者中有一半是從其他預防產品轉換過來的患者。所以這真的——這與病人無關。

The next question comes from Maurice Raycroft of Jefferies.

下一個問題來自 Jefferies 的 Maurice Raycroft。

I was wondering for Quad AI later this week. If you can provide some preview around observed similarities or differences in treating pediatric HAE patients and remind what the sNDA timeline could look like? And how does the pediatric opportunity fit into your $1 billion in peak sales estimate.

本週晚些時候我想知道 Quad AI。您是否可以圍繞觀察到的治療兒科 HAE 患者的異同提供一些預覽，並提醒 sNDA 時間表可能是什麼樣子？以及兒科機會如何符合您 10 億美元的銷售峰值估算。

Sure. So -- where we are with our pediatric clinical trial, it's open, it's been rolling. And so it's -- it will take a little time to get that fully enrolled until we get to the sNDA, but what we're seeing and one thing that we'll present this week at Quad AI is just the overall burden of treatment and of HAE identified by both caregivers, parents and patients. And one thing we hear over and over again is when a kid has symptomatically (inaudible), the -- sometimes the treatment is injectable can be worse than -- almost worse than the attack themselves. It could be really traumatic for kids to have regular injections or infusions. And so there's just real demand for an oral therapy to help these kids. And so we have -- long term, we think that this is going to be -- it's not so much about the number of patients treated. It's about the fact that we're going to be able to make the lives better for a lot of these kids, and then, of course, it's a genetic disease. So we see typically families will often use the same types of product. So it gives us an opportunity to kind of tell the ORLADEYO story to a complete family, which we're really looking forward to.

當然。所以——我們的兒科臨床試驗是開放的，它一直在滾動。所以它——在我們進入 sNDA 之前要完全註冊需要一些時間，但我們所看到的以及我們本週將在 Quad AI 上展示的一件事只是治療的總體負擔和由護理人員、父母和患者確定的 HAE。我們一遍又一遍地聽到的一件事是，當一個孩子有症狀（聽不清）時，——有時注射治療可能比——幾乎比攻擊本身更糟糕。定期注射或輸液對孩子來說可能真的很痛苦。因此，真正需要口服療法來幫助這些孩子。所以我們 - 從長遠來看，我們認為這將是 - 這與接受治療的患者數量無關。這是關於這樣一個事實，即我們將能夠讓這些孩子中的許多人過上更好的生活，當然，這是一種遺傳病。所以我們看到通常家庭會經常使用相同類型的產品。因此，它讓我們有機會向整個家庭講述 ORLADEYO 的故事，我們非常期待。

I think the other thing, Maurice, is the formulation that we have for this is -- we used to call it many tabs, what do we call granules but it's like sprinkles that you put on a cake almost at that size. And so asking a little kid to take a capsule is a difficult thing, too. So we've come up with a formulation that you could put on Apple sauce on yogurt and just make it way less traumatic along the lines of what Charlie was describing, and that will be huge. And then this is a patient for life, right? And so it's not a huge market, but we think it's an important one, and we think these are customers that we could have for a very long time.

莫里斯，我想另一件事是我們為此制定的公式是——我們過去稱它為許多標籤，我們稱之為顆粒，但它就像灑在幾乎那個大小的蛋糕上。因此，讓小孩服用膠囊也是一件困難的事情。所以我們想出了一個配方，你可以把蘋果醬放在酸奶上，然後按照查理所描述的那樣減少創傷，這將是巨大的。然後這是終身病人，對吧？所以這不是一個巨大的市場，但我們認為這是一個重要的市場，我們認為這些是我們可以長期擁有的客戶。

Got it. That's helpful. It makes sense. And maybe one other quick question. just for the 10013 delays, is that factored into the $375 million OpEx assumptions for next year? Can you talk more about OpEx assumptions in general for next year -- for this year?

知道了。這很有幫助。這說得通。也許還有另一個快速問題。僅針對 10013 次延誤，是否將其計入明年 3.75 億美元的 OpEx 假設中？你能談談明年——今年的 OpEx 總體假設嗎？

Yes. So it's fact. The way to think about OpEx for the year, so flat year-over-year, but what we've said is that commercial expenditure is going to increase based on -- the additions that Charlie has talked about predominantly here in the U.S. as well as expansion from a global perspective, given that we're now in 15 countries and we'll be doing more. For R&D, the delay is factored in, depending on what we see on an ongoing basis, that may change when we get more information, and we'll update that later in the year. But yes, it is currently factored in. And what we said about R&D is, it's going to decrease year-over-year anyway. When we we're talking about this about a quarter ago, we said it was going to be flat, but now we're saying, it's going to be down but offset by the commercial investment that we've seen.

是的。所以這是事實。考慮今年運營支出的方式，同比持平，但我們所說的是，商業支出將增加——查理主要在美國也談到了這些增加作為全球範圍內的擴張，鑑於我們現在已經在 15 個國家/地區開展業務，而且我們會做得更多。對於研發，延遲被考慮在內，這取決於我們在持續的基礎上看到的情況，當我們獲得更多信息時，這可能會改變，我們將在今年晚些時候更新。但是，是的，它目前已被考慮在內。我們所說的研發是，它無論如何都會逐年減少。大約一個季度前，當我們談論這個問題時，我們說它會持平，但現在我們說，它會下降，但會被我們看到的商業投資所抵消。

And then most importantly, with revenues increasing and then seeing that flattening of the OpEx line and the convergence of those two lines, the net cash utilization and what that means as we move towards profitability, I think, has a lot of value for the company.

然後最重要的是，隨著收入的增加，然後看到 OpEx 線的扁平化和這兩條線的融合，淨現金利用率以及這對我們走向盈利意味著什麼，我認為，對公司有很大的價值.

The next question comes from Gena Wang of Barclays.

下一個問題來自巴克萊銀行的 Gena Wang。

The first one is regarding 10013. So just want to confirm, is it fair to say that we should not expect the FDA clinical hold regarding this program? And then my second question is regarding the ORLADEYO, in early January, you mentioned that the retention rate is about 60%. Can you clarify if that is 1 year or 3 months retention rate? And also, do you expect the similar retention rate maintaining in 2023?

第一個是關於 10013。所以只是想確認一下，我們不應該期望 FDA 對這個項目進行臨床試驗是否公平？然後我的第二個問題是關於 ORLADEYO，在 1 月初，您提到保留率約為 60%。您能否說明這是 1 年還是 3 個月的保留率？而且，您預計 2023 年會保持類似的保留率嗎？

So the first question on 10013, we're not on clinical [hold] with this program. There's it's a little difficult to say what will happen in the future. So -- that's where we are today.

所以關於 10013 的第一個問題，我們不在這個項目的臨床 [hold] 中。很難說未來會發生什麼。所以 - 這就是我們今天所處的位置。

And as far as the patient retention, Gena, yes, 60% of that 1 year -- and we would expect -- what we're seeing in the overall retention rate is really stabilizing out. And so that's part of our confidence, no less than $320 million this year. And so we'd expect the same retention trend overall in 2023.

就患者保留率而言，Gena，是的，1 年的 60%——我們預計——我們在總體保留率中看到的情況確實穩定下來。所以這是我們信心的一部分，今年不少於 3.2 億美元。因此，我們預計 2023 年總體保留趨勢相同。

Our last question comes from Rohit Bhasin of Needham & Co.

我們的最後一個問題來自 Needham & Co 的 Rohit Bhasin。

This is Rohit on for [Serge]. Just in terms of peak sale estimates, do you still expect about 20% to 25% to come from ex U.S. territories -- and can you talk about your expectations for the long-term competitive landscape for ORLADEYO.

這是 [Serge] 的 Rohit。就銷售峰值估計而言，您是否仍預計約有 20% 至 25% 來自美國以外地區——您能否談談您對 ORLADEYO 長期競爭格局的預期。

Sure. Rohit. Absolutely. So when we talk about the $1 billion, we still see about 20% of that is coming from Europe and the rest of the world and all the trends in those -- in the 15 countries where we've launched so far, give us confidence that we will get to that 20% at the (inaudible)

當然。羅希特。絕對地。因此，當我們談論這 10 億美元時，我們仍然看到其中約 20% 來自歐洲和世界其他地區，以及這些方面的所有趨勢——在我們迄今為止推出的 15 個國家中，給了我們信心我們將在（聽不清）達到那 20%

And then with regard to the competitors, it's a pretty crowded space, but with regard to oral specifically, it's been challenging for some to advance their programs. And so what that means for us is we have more time to get people to try our drug and see if it works for them. And what we've learned in the marketplace is to get people to switch, there's got to be some meaningful benefit that they're not seen with the drug that they're on. And it can't be efficacy because if you're on our drug, you're controlled, if you're not controlled, you're not staying on our drug. So -- and so that goes for injectables as well. And I think a tailwind that we're curious, Charlie, has pointed this multiple times, but we'll be curious to see is as new products come to market, if a physician is saying, "hey! maybe I'll switch from one injectable to another", why wouldn't they try an oral first? And then if it didn't work for that patient, switch to the new injectables. So it could be a tailwind.

然後關於競爭對手，這是一個非常擁擠的空間，但特別是關於口語，對於一些人來說，推進他們的項目一直是一個挑戰。所以這對我們來說意味著我們有更多時間讓人們嘗試我們的藥物，看看它是否對他們有效。我們在市場上學到的是讓人們改變，必須有一些有意義的好處，他們沒有看到他們使用的藥物。它不可能有效，因為如果你服用我們的藥物，你就會受到控制，如果你不受控制，你就不會繼續服用我們的藥物。所以——注射劑也是如此。而且我認為我們很好奇的順風，查理，已經多次指出這一點，但我們很想看到隨著新產品進入市場，如果醫生說，“嘿！也許我會從一個可以注射到另一個”，他們為什麼不先嘗試口服呢？然後，如果它對那個病人不起作用，就換成新的注射劑。所以這可能是順風。

This concludes the question-and-answer session. The conference has now also concluded. Thank you for attending today's presentation, and you may now disconnect.

問答環節到此結束。會議現已結束。感謝您參加今天的演講，您現在可以斷開連接了。