BioCryst Pharmaceuticals Inc (BCRX) 2024 Q1 法說會逐字稿

Good morning and welcome to the BioCryst first quarter 2024 earnings 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.

早安，歡迎參加 BioCryst 2024 年第一季財報電話會議。 （操作員說明）請注意，正在記錄此事件。我現在想把會議交給 BioCryst 的 John Bluth。請繼續。

Thanks, Drew. Good morning and welcome to BioCryst's first quarter 2024 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 will answer your questions.

謝謝，德魯。早安，歡迎參加 BioCryst 2024 年第一季公司更新與財務績效電話會議。今天的新聞稿和隨附的幻燈片可在我們的網站上取得。今天和我一起參加的是執行長喬恩‧斯通豪斯 (Jon Stonehouse)；財務長安東尼·道爾；首席商務官查理·蓋爾；首席研發長 Helen Thackray 博士。接下來，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.

在開始之前，請注意，今天的電話會議將包含前瞻性聲明，包括有關未來業績、未經審計和前瞻性財務資訊以及公司未來業績和/或成就的聲明。這些陳述受到已知和未知的風險和不確定性的影響，這可能導致我們的實際結果、業績或成就與本簡報中明示或暗示的任何未來結果或業績存在重大差異。

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.

您不應過度依賴這些前瞻性陳述。如需了解更多信息，包括對我們風險因素的詳細討論，請參閱公司向美國證券交易委員會提交的文件，這些文件可在我們的網站上訪問。

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

此外，今天的電話會議還包括非公認會計準則預計財務指標。如需將這些非 GAAP 指標與最直接可比較的 GAAP 財務指標進行核對，請參閱我們投資者關係網站 www.biocryst.com 的新聞稿部分中發布的收益新聞稿。

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

我現在想把電話轉給喬恩·斯通豪斯。

Thanks, John. We are off to a fantastic start to the year with growing ORLADEYO revenue and our pipeline advancing on schedule. ORLADEYO revenue in Q1 exceeded our expectations as the commercial team in the US did a great job successfully navigating the reauthorization process faster than previous years. Charlie will share more detail, but now in the fourth year since approval, the steady and consistent growth of new patients shows no signs of letting up and we are even more confident we are on track to reach our goal of $1 billion in global revenue at peak.

謝謝，約翰。隨著 ORLADEYO 收入的不斷增長以及我們的管道按計劃推進，我們今年迎來了一個美好的開始。 ORLADEYO 第一季的收入超出了我們的預期，因為美國的商業團隊做得很好，比往年更快地成功完成了重新授權流程。 Charlie 將分享更多細節，但現在已經是批准後的第四年了，新患者的穩定持續成長沒有任何放緩的跡象，我們更有信心實現全球收入 10 億美元的目標。

We continue to make great progress with our prioritized pipeline too. Our ORLADEYO pediatric program is on schedule to file for approval next year. We continue to make progress with BCX10013 and expect we will be able to decide on whether to partner or discontinue the program later this year. In addition, our other pipeline programs, including BCX17725 for Netherton and avoralstat for DME are advancing toward the clinic with first or best-in-class profiles.

我們的優先管道也持續取得巨大進展。我們的 ORLADEYO 兒科計畫按計劃將於明年申請批准。我們繼續在 BCX10013 方面取得進展，預計我們將能夠在今年稍後決定是否合作或終止該計劃。此外，我們的其他管道項目，包括 Netherton 的 BCX17725 和用於 DME 的 avoralstat 正在以一流或一流的性能向臨床邁進。

Over the next 12 months, ORLADEYO will be approaching the midway point of our global peak revenue goal. We'll be preparing to file for approval for ORLADEYO use in pediatric patients and we'll be starting to move multiple pipeline programs into patient studies. And last but not least, we will be approaching profitability.

在接下來的 12 個月中，ORLADEYO 將接近我們全球高峰收入目標的中點。我們將準備申請批准 ORLADEYO 在兒科患者中使用，並將開始將多個管道項目轉移到患者研究中。最後但並非最不重要的一點是，我們將接近盈利。

The year is off to a strong start with exceptional progress in all of these areas, and we are focused on continuing this momentum throughout the year.

今年是一個良好的開端，所有這些領域都取得了非凡的進展，我們致力於全年保持這一勢頭。

With that, I'll turn it over to Charlie to share the outstanding performance of ORLADEYO for the quarter.

接下來，我將把它交給 Charlie 來分享 ORLADEYO 本季的出色表現。

Thanks, Jon. During the quarter, we continued to execute our global plan for ORLADEYO very effectively. Revenue of $88.9 million exceeded our expectations because of the efficient handling of prescription reauthorizations in the United States, combined with the continued strong demand as health care providers gained confidence in ORLADEYO. Based on these improvements and trends, we are raising our 2024 ORLADEYO revenue guidance to the top half of our prior range and now forecast $390 million to $400 million for the year. I'll describe these improvements and trends more specifically.

謝謝，喬恩。本季度，我們繼續非常有效地執行 ORLADEYO 的全球計畫。由於美國處方重新授權的高效處理，加上醫療保健提供者對 ORLADEYO 的信心持續強勁，收入 8890 萬美元超出了我們的預期。基於這些改進和趨勢，我們將 2024 年 ORLADEYO 收入指引提高到先前範圍的上半部分，現在預測今年的收入為 3.9 億美元至 4 億美元。我將更具體地描述這些改進和趨勢。

Last year, we invested in our patient services and market access teams with the goal of improving efficiency and effectiveness of patients to paid therapy. The first quarter shows that these investments are working. Two facts stand out in this improvement. First, our patient services team completed more benefits investigations in January than we did in the entire first quarter of 2023, resulting in patients getting back to paid therapy quicker than in previous years.

去年，我們對患者服務和市場准入團隊進行了投資，目標是提高患者付費治療的效率和效果。第一季顯示這些投資正在發揮作用。這項改進有兩個突出的事實。首先，我們的病患服務團隊 1 月完成的福利調查比 2023 年整個第一季還要多，導致病患比往年更快恢復付費治療。

Completing these investigations early in the first quarter gives our better understanding of the ease or difficulty of the reauthorization process. If it's easy, we get to paid shipments quickly. If it's going to be difficult, the team can act faster with better information to solve any issues. And second, even though we still provided temporary free product for many patients during the first quarter reauthorizations, the faster actions in the quarter meant that paid shipments were within 1% of fourth quarter 2023 paid shipments. This was above our expectations.

在第一季初期完成這些調查可以讓我們更了解重新授權過程的難易程度。如果很容易，我們就能很快收到付款。如果遇到困難，團隊可以利用更好的資訊更快採取行動來解決任何問題。其次，儘管我們在第一季重新授權期間仍然為許多患者提供了臨時免費產品，但本季更快的行動意味著付費出貨量僅佔 2023 年第四季付費出貨量的 1% 以內。這超出了我們的預期。

As for customer demand, we had another very strong quarter for new patient prescriptions. In fact, the last two quarters have been the best consecutive quarters for demand since the six months of the launch in 2021. Patients and health care providers continue to understand and gain confidence that they can get great efficacy and convenience with ORLADEYO, all with just one capsule once a day to prevent HAE attacks.

至於客戶需求，我們在新患者處方方面又經歷了一個非常強勁的季度。事實上，過去兩個季度是自2021 年推出六個月以來需求連續最好的季度。需每天一次，一粒膠囊，以預防 HAE 發作。

We also continued to strengthen the brand by presenting new evidence showing the real-world impact of ORLADEYO. At AAAAI in February, we showed how well ORLADEYO is controlling HAE attacks, regardless of prior therapies or baseline attack rates.

我們也透過提供新的​​證據來展示 ORLADEYO 的現實世界影響力，繼續強化品牌。在 2 月的 AAAAI 上，我們展示了 ORLADEYO 在控制 HAE 發作方面的表現，無論先前的治療或基線發作率如何。

Patients switching to ORLADEYO from other HAE prophylaxis therapies, for example, maintain and even improve long-term attack control, reaching a median rate of half an attack per month. Patients attack-free at baseline remained attack-free on ORLADEYO. Later this week, we will present new data at the ISPOR conference in Atlanta, demonstrating that patients initiating ORLADEYO experienced significant reductions in overall health care resource utilization, a finding that will be very meaningful to payers.

例如，從其他 HAE 預防療法轉向 ORLADEYO 的患者可以維持甚至改善長期發作控制，達到每月一半發作的中位數。基線時無發作的患者在 ORLADEYO 治療後仍保持無發作。本週晚些時候，我們將在亞特蘭大舉行的 ISPOR 會議上公佈新數據，表明開始使用 ORLADEYO 的患者整體醫療保健資源利用率顯著降低，這一發現對付款人來說非常有意義。

We are well positioned to provide frequent health economics -- health outcomes and economics updates with large and growing cohorts that already include hundreds of patients. These new data will further support the growth in customer demand for ORLADEYO for many years to come.

我們處於有利地位，可以經常提供健康經濟學——健康結果和經濟學更新，涉及規模龐大且不斷增長的人群，其中已經包括數百名患者。這些新數據將進一步支持 ORLADEYO 未來許多年客戶需求的成長。

The increasing customer confidence that we're seeing in the US is also happening in the rest of the world. Patient growth in Europe was strong and consistent in the first quarter and recent launches in Spain and Italy are already adding to this trend. Finally, our BioCryst Japan team is now fully in place from the start of 2024, and we are encouraged by the early signs of their impact.

我們在美國看到的客戶信心的增強也在世界其他地區發生。第一季歐洲的患者成長強勁且持續，最近在西班牙和義大利的推出已經加劇了這一趨勢。最後，我們的 BioCryst Japan 團隊現在從 2024 年初全面到位，他們的影響的早期跡象讓我們感到鼓舞。

The overall trends in real-world evidence, customer confidence in patient growth continue to point to $800 million in peak US revenue with sustained peak global revenue of $1 billion.

現實世界證據的總體趨勢、客戶對患者成長的信心繼續表明美國收入高峰為 8 億美元，全球收入高峰持續為 10 億美元。

I'll now hand over to Helen to provide an update on our pipeline.

我現在將交給 Helen 提供有關我們管道的最新資訊。

Thanks, Charlie. Our research and development teams are busier than ever as we are rapidly approaching our next major pipeline milestones, which include advancing multiple programs into the clinic starting later this year and filing for pediatric approval with ORLADEYO. Let's start there.

謝謝，查理。我們的研發團隊比以往任何時候都更加忙碌，因為我們正在迅速接近下一個主要管道里程碑，其中包括從今年稍後開始將多個項目推進臨床，並向 ORLADEYO 申請兒科批准。讓我們從這裡開始。

I'm pleased to share that we've completed enrollment in the pediatric trial with ORLADEYO, which includes extending dosing in children down to two years of age. This means we are on track to submit for pediatric registration as planned in 2025. It also means we are even closer to providing the first oral prophylactic therapy to children with HAE.

我很高興地告訴大家，我們已經完成了 ORLADEYO 兒科試驗的入組工作，其中包括將兒童用藥劑量延長至兩歲。這意味著我們預計將在 2025 年按計劃提交兒科註冊申請。

It's been remarkable how quickly our pediatric has enrolled. We believe this reflects the demand for an oral therapy as prophylaxis of HAE attacks in children. It has the potential for this to be a transformative option for both children and their parents. A pediatric formulation made of granules that can be sprinkled on soft foods or taken with a glass of water. We are excited to be so close to achieving this goal of bringing ORLADEYO to children under 12, and we look forward to submitting for registration next year.

我們的兒科入組速度之快令人矚目。我們認為這反映了對口服療法作為預防兒童 HAE 發作的需求。這有可能成為兒童及其父母的變革性選擇。一種由顆粒製成的兒科配方，可撒在軟食物上或與一杯水一起服用。我們很高興能夠如此接近實現將 ORLADEYO 帶給 12 歲以下兒童的目標，我們期待明年提交註冊。

Turning to our next clinical program, our Factor D inhibitor, BCX10013, we continue to progress the ongoing proof of concept trial, and we expect to either partner or discontinue the program later this year as planned.

談到我們的下一個臨床項目，我們的 D 因子抑制劑 BCX10013，我們將繼續推進正在進行的概念驗證試驗，我們預計在今年稍後按計劃合作或終止該項目。

Up next, we have two pipeline programs that will enter the clinic within 18 months. These are BCX17725 for Netherton syndrome and avoralstat for diabetic macular edema or DME. We are on track to begin a clinical trial with BCX17725 by the end of this year. This is a fusion protein with very high potency inhibition for KLK5 and has the potential to be a best-in-class product, providing disease-altering treatment for people with Netherton syndrome.

接下來，我們有兩個管道項目將在 18 個月內進入臨床。這些是 Netherton 綜合徵的 BCX17725 和用於糖尿病黃斑水腫或 DME 的 avoralstat。我們預計在今年年底開始 BCX17725 的臨床試驗。這是一種對 KLK5 具有非常高效抑製作用的融合蛋白，有潛力成為同類最佳產品，為 Netherton 症候群患者提供改變疾病的治療。

Netherton syndrome is a rare, lifelong genetic disorder that often presents in infancy with red, scaly, and inflamed skin. Patients require chronic care to protect the skin and monitor for lifelong susceptibility to inflammatory and atopic conditions. Netherton syndrome can be life-threatening, especially during infancy when neonates are vulnerable to dehydration and recurrent infections. Currently, there is no approved treatment for Netherton syndrome, and it's our goal to deliver a targeted therapy for these patients.

內瑟頓症候群是一種罕見的終生遺傳性疾病，通常在嬰兒期出現皮膚發紅、鱗狀和發炎。患者需要長期照護以保護皮膚並監測終生對發炎和特異性疾病的易感性。內瑟頓症候群可能會危及生命，尤其是在嬰兒期，此時新生兒很容易脫水和反覆感染。目前，還沒有批准的治療 Netherton 綜合徵的方法，我們的目標是為這些患者提供標靶治療。

Next into the clinic will be avoralstat, our plasma kallikrein inhibitor, in development for the treatment of diabetic macular edema or DME, which is on track to initiate a trial in patients next year. Our goal here is to improve vision in patients with persistent DME despite the use of VEGF inhibitors. At least a third of patients with DME have continuing symptoms and even worsening vision loss when treated with VEGF inhibitors, which may be because plasma kallikrein is a contributing cause of disease. The need for additional therapeutic options is real.

接下來進入臨床的將是 avoralstat，我們的血漿激肽釋放酶抑制劑，正在開發用於治療糖尿病黃斑水腫或 DME，預計將於明年在患者中啟動試驗。我們的目標是在使用 VEGF 抑制劑的情況下改善持續性 DME 患者的視力。至少三分之一的 DME 患者在接受 VEGF 抑制劑治療時會出現持續症狀，甚至視力喪失惡化，這可能是因為血漿激肽釋放酶是疾病的原因之一。確實需要額外的治療選擇。

We're working with Clearside to deliver avoralstat to the suprachoroidal space in the eye in order to achieve sufficient exposure in the right location to interrupt the pathophysiology of DME in the retina and stop swelling in the back of the eye. Based on the preclinical and safety data we accumulated with avoralstat when we studied it in the HAE program, we are in a position to move quickly into patients with DME with our first clinical trial next year, so we can evaluate for proof of concept directly in patients.

我們正在與 Clearside 合作，將 avoralstat 輸送到眼睛的脈絡膜上腔，以便在正確的位置實現足夠的暴露，從而中斷視網膜 DME 的病理生理學並阻止眼睛後部的腫脹。根據我們在 HAE 計畫中研究 avoralstat 時累積的臨床前和安全性數據，我們能夠在明年的首次臨床試驗中快速進入 DME 患者，因此我們可以直接評估概念驗證患者。

Right behind these two programs, our discovery programs for targets across the complement system are also advancing. The three programs underway include our protein therapeutic complement inhibitor targeting all three pathways: the classical, lectin, and alternative pathways complement; and our oral C5 and oral C2 inhibitor small molecules. We are on track to have both the oral C5 inhibitor and the protein therapeutic multifunctional complement inhibitor advance into IND-enabling studies later this year.

在這兩個項目之後，我們針對補體系統標靶的發現項目也正在取得進展。正在進行的三個項目包括我們針對所有三種途徑的蛋白質治療補體抑制劑：經典補體、凝集素和替代途徑補體；以及我們的口服 C5 和口服 C2 抑制劑小分子。我們預計在今年稍後將口服 C5 抑制劑和蛋白質治療多功能補體抑制劑推進 IND 研究。

So in summary, we continue to progress well towards our goal of delivering inhibitors for every pathway in the complement system. Overall, the depth and breadth of our pipeline provides balance and great potential with a diversified set of molecules moving forward. This allows us to increase the likelihood that our pipeline today will produce our next drug in the market tomorrow. We are excited the pipeline is now advancing into the clinic with multiple programs.

總而言之，我們繼續朝著為補體系統中的每個途徑提供抑制劑的目標取得良好進展。總體而言，我們管道的深度和廣度為多元化的分子向前發展提供了平衡和巨大的潛力。這使我們能夠增加今天的管道明天在市場上生產下一種藥物的可能性。我們很高興該管道現在正透過多個項目進入臨床。

Next, I'll turn it to Anthony for a financial update.

接下來，我將向安東尼詢問最新的財務狀況。

Thanks, Helen. You can find our detailed first quarter financials in today's earnings press release, and I'd like to call your attention to a few items.

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一季財務數據，我想提請您注意一些項目。

Total revenue for the quarter was $92.8 million, $88.9 million of which came from ORLADEYO with the remaining $3.9 million coming from RAPIVAB sales. That puts ORLADEYO trailing 12-month revenues at $346.4 million, with Q1 revenue increasing 30% over Q1 of 2023. Of the $88.9 million of global ORLADEYO revenue sales, $80 million came from US sales with the remaining $8.9 million or 10% coming from ex-US sales.

該季度總收入為 9,280 萬美元，其中 8,890 萬美元來自 ORLADEYO，其餘 390 萬美元來自 RAPIVAB 銷售。這使得ORLADEYO 過去12 個月的收入為3.464 億美元，第一季營收比2023 年第一季成長30%。或10% 來自前銷售-美國銷售。

The 30% year-over-year increase in sales was primarily driven by the strong underlying patient growth that we have continued to see quarter-over-quarter. The $4 million improvement in Q1 performance versus our previous guidance of $85 million was primarily driven by the efforts of the commercial team to improve and accelerate the reauthorization process. That's $4 million that last year we would not have been able to capture until Q2, but this year, the team managed to accelerate the timing and achieve it from quarter one.

銷售額年增 30%，主要是由我們持續看到的逐季強勁的潛在患者成長所推動的。第一季業績比我們之前指導的 8,500 萬美元提高了 400 萬美元，這主要是由於商業團隊為改進和加速重新授權流程所做的努力。去年我們要到第二季才能獲得 400 萬美元，但今年，團隊設法加快了時間安排，從第一季就實現了這一目標。

For Q2, we expect to achieve revenues of approximately $97 million, and as Charlie said, we've revised our full year revenue guidance to the higher end of the range between $390 million and $400 million. Operating expenses, not including noncash stock compensation, for the quarter were $93.6 million, an increase of $10.4 million over Q1 of 2023. Included in this are $1.3 million of onetime expenses related to the R&D structuring at the beginning of the year.

對於第二季度，我們預計將實現約 9,700 萬美元的收入，正如 Charlie 所說，我們已將全年收入指引修訂為 3.9 億美元至 4 億美元之間的較高區間。該季度的營運費用（不包括非現金股票補償）為 9,360 萬美元，比 2023 年第一季增加 1,040 萬美元。

Full year 2024 guidance for OpEx is unchanged, up between $365 million and $375 million. With revenue up $24 million year-over-year at $92.8 million and OpEx up $10.4 million year-over-year at $93.6 million, we continue to see improved margin accretion and our operating loss for the quarter, not including noncash stock comp was less than $1 million.

2024 年全年營運支出指引維持不變，增加 3.65 億美元至 3.75 億美元之間。營收年增 2,400 萬美元，達到 9,280 萬美元，營運支出年增 1,040 萬美元，達到 9,360 萬美元，我們繼續看到利潤成長有所改善，本季的營運虧損（不包括非現金股票補償）低於100萬美元。

Cash at the end of the quarter was up $338.4 million, and net cash utilization for the quarter was $52.4 million. Q1 is historically our largest quarter of the year for cash utilization. For context, last year's Q1 was responsible for over 50% of total cash utilization for the entire year. Included in Q1, this year we had $3.2 million related to the R&D restructuring and $6.9 million related to royalty payments to OMERS. This is our first quarter of making such cash payments to OMERS, and as a reminder, while the royalties are considered a debt instrument for GAAP purposes that cannot be called and ultimately should be considered more the long-time liability than true debt.

本季末現金增加 3.384 億美元，本季淨現金利用率為 5,240 萬美元。從歷史上看，第一季是我們一年中現金利用率最高的季度。就背景而言，去年第一季的現金使用量佔全年總現金使用量的 50% 以上。包括第一季在內，今年我們有 320 萬美元與研發重組相關，690 萬美元與向 OMERS 支付的特許權使用費相關。這是我們向 OMERS 支付此類現金的第一個季度，提醒一下，雖然特許權使用費被視為 GAAP 目的的債務工具，但不能調用，最終應被視為長期負債，而不是真正的債務。

Additionally, with the revised guidance for full year ORLADEYO revenue, this will result in an improved blended royalty rate as more revenue will fall into the above $350 million tier where royalties are at a reduced rate of 7.5%. Cash utilization will decline in the remaining quarters of the year as it did last year, closer to an average of $10 million to $12 million per quarter, and we expect to end the year with above $300 million in cash.

此外，根據修訂後的 ORLADEYO 全年收入指引，混合特許權使用費率將得到改善，因為更多收入將落入 3.5 億美元以上的層級，其中特許權使用費將降低 7.5%。今年剩餘季度的現金利用率將像去年一樣下降，接近每季平均 1,000 萬至 1,200 萬美元，我們預計年底現金利用率將超過 3 億美元。

It's great to see the continuing strong performance of ORLADEYO. The commercial team did an outstanding job to improve our performance during the reauthorization process, an improvement that we'd hope to continue and build upon in next year's quarter one. This strength in revenue performance, supported by continued strong underlying patient demand, is what drives the revised full year revenue guide between $390 million and $400 million.

很高興看到 ORLADEYO 持續強勁的表現。商業團隊在重新授權過程中出色地提高了我們的績效，我們希望在明年的第一季繼續並在此基礎上繼續改進。這種強勁的收入表現，加上持續強勁的潛在患者需求的支持，推動修訂後的全年收入指南在 3.9 億美元至 4 億美元之間。

And with full year OpEx remaining consistent for our guidance, we are in an even stronger position to deliver an operating profit this year when excluding noncash stock comp. We will continue on our planned path to near-term profitability that we shared earlier in the year, approaching quarterly cash flow and EPS positivity late next (technical difficulty) with full year cash flow and EPS positivity in 2026, all while continuing to advance our pipeline at full pace without the need to raise additional capital to get there.

由於全年營運支出與我們的指導保持一致，因此在排除非現金股票補償後，我們今年在實現營業利潤方面處於更有利的地位。我們將繼續沿著今年稍早分享的實現近期盈利的計劃道路前進，在接下來的晚些時候（技術難度）接近季度現金流和EPS 正值，並在2026 年實現全年現金流和EPS正值，同時繼續推進我們的業務管道全速推進，無需籌集額外資金即可實現這一目標。

Operator, we'll now open it up for questions.

接線員，我們現在開始提問。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作員指示）Jessica Fye，摩根大通。

Hey. This is Nick on for Jess. Congrats on the quarter and thanks for taking our questions. Two from us. You mentioned that the past two quarters have the most new prescription in the US since the first two quarters of the launch. Can you maybe provide some additional details on how that trend is looking so far in 2Q? And then maybe one on ex-US revenues. I know they came in at 10% this Q. You've talked about them being lumpier than the US. How should we expect that growth in the ex-US business this year? And at what point could that become less lumpy?

嘿。這是尼克替傑西發言。恭喜本季度，感謝您提出我們的問題。我們兩個。您提到，自從前兩個季度推出以來，過去兩個季度在美國有最新的處方。您能否提供一些有關第二季度迄今為止趨勢的更多詳細資訊？然後也許是關於美國以外的收入。我知道他們這個季度的表現是 10%。我們該如何預期今年美國以外的業務成長？什麼時候它會變得不那麼笨拙？

Charlie, why don't you take the first one and Anthony take the second one?

查理，為什麼你不拿第一個，安東尼拿第二個？

Sure. I'm not going to comment yet on Q2, but other than two consecutive quarters of really great prescriptions, we've talked more -- we've talked before about all the market research that we do with physicians. They continue to expect to grow ORLADEYO prescriptions by about 30% over the next year. So we would expect this kind of demand to continue.

當然。我還不打算對第二季發表評論，但除了連續兩個季度提供非常好的處方外，我們已經討論了更多——我們之前已經討論過我們與醫生一起進行的所有市場研究。他們預計明年 ORLADEYO 處方量將成長約 30%。因此，我們預計這種需求將會持續下去。

Charlie, is it worth spending a little bit of time talking about the confidence that you're seeing in physicians and patients at this stage since the approval?

查理，值得花一點時間談論自批准以來現階段醫生和患者的信心嗎？

Sure. Yeah. Like I said in my prepared remarks, as physicians have gained more and more experience in patients as well, they see that this drug is much more than just a convenient oral therapy. They see that ORLADEYO is a really effective therapy. And once they know that they can expect the high efficacy and the convenience together, it just gives them more confidence in prescribing. Physicians know that the majority of patients would prefer an oral therapy. And if they can get a really effective oral therapy, that makes them want to prescribe more. And I think that's what we're seeing now three-plus years into this launch.

當然。是的。正如我在準備好的演講中所說，隨著醫生在病人身上獲得越來越多的經驗，他們發現這種藥物不僅僅是一種方便的口服療法。他們認為 ORLADEYO 是一種非常有效的療法。一旦他們知道他們可以同時期待高效和便利，這只會讓他們對處方更有信心。醫生知道大多數患者更喜歡口服治療。如果他們能得到真正有效的口服療法，他們就會想要開更多的藥。我認為這就是我們在推出三年多後所看到的情況。

So Nick, with that confidence, we just don't see it letting up. Anthony?

所以尼克，帶著這種信心，我們不會看到它放鬆。安東尼？

Yeah. So for ex-US, yeah. By the nature of how we sell into the ex-US markets, there's always going to be some lumpiness. Last year, we had about 11.5% of our total revenue coming from ex-US. I would expect something similar this year. I mean, if it's not there, it will be due to US overperformance as opposed to ex-US not being where we expect it to be. Ultimately, we would expect ex-US sales to continue to increase year-over-year until we hit peak.

是的。所以對前美國來說，是的。根據我們向美國以外市場銷售的方式的性質，總是會出現一些波動。去年，我們總收入的 11.5% 左右來自美國以外地區。我預計今年會出現類似的情況。我的意思是，如果它不存在，那將是由於美國表現出色，而不是美國以外的國家沒有達到我們預期的水平。最終，我們預計美國以外的銷售額將繼續同比增長，直到達到高峰。

And then just to add to on the lumpiness. That really is -- it's just based on how we distribute. It has nothing to do with customer demand. What we're seeing is physicians are gaining the same kind of confidence that I described in the US, and we expect that to continue.

然後只是增加塊狀。這確實是——這只是基於我們的分配方式。與客戶需求無關。我們看到的是，醫生們正在獲得我在美國描述的相同的信心，我們預計這種情況會持續下去。

Great. Thank you.

偉大的。謝謝。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Hi. Congrats on the quarter and thanks for taking my question. In your prepared remarks, you talked about your patient services team and investigations early in the first quarter that led to categorizing reauthorizations that's easy versus difficult. Can you talk more about what makes the reauthorizations easy versus difficult? And how you plan on building upon your learnings for the rest of the year with that?

你好。恭喜本季度，感謝您提出我的問題。在您準備好的演講中，您談到了您的患者服務團隊和第一季初期的調查，這些調查導致了重新授權的簡單與困難的分類。您能否詳細談談是什麼讓重新授權變得容易和困難？你計劃如何在今年剩下的時間裡鞏固你所學到的知識？

Sure, Maury. With this kind of rare disease therapy, payors are always trying to make things a little bit difficult, but it's the kind of thing that I've described before, which is, they want a full patient history. They want lab tests. They want all the information they can get. And sometimes, when the payors already have this information, they can make it pretty quick to get to the reauthorization, but it's kind of in the payor's interest to throw as many speed bumps as possible. And so even if we've provided it before, sometimes they'll ask for it to be provided again.

當然，莫里。對於這種罕見疾病的治療，付款人總是試圖讓事情變得有點困難，但這是我之前描述過的事情，也就是說，他們想要完整的病患病史。他們想要實驗室測試。他們想要獲得所有可以得到的資訊。有時，當付款人已經掌握了這些資訊時，他們可以很快地獲得重新授權，但盡可能地設置減速帶也符合付款人的利益。因此，即使我們以前提供過，有時他們也會要求再次提供。

And then there are some patients who just have more complicated histories, and those are the bigger challenges, but our teams had great success in getting all types of patients approved. So sometimes it's quick and sometimes it just takes a little bit of time. Everything that I see, though, gives me confidence about the 85% paid rate at peak, it's just going to take us a few years to get there.

還有一些患者有更複雜的病史，這些都是更大的挑戰，但我們的團隊在讓所有類型的患者獲得批准方面取得了巨大成功。所以有時它很快，有時只需要一點時間。不過，我所看到的一切都讓我對高峰時 85% 的付費率充滿信心，我們只需要幾年時間就能實現這一目標。

I think the other piece is Charlie made a decision a little over a year ago to change the model and improve this reimbursement and the support services around it, starting to see the fruit of that. And I think we'll continue to see that as this year progresses in future years. So it's a great, great signal. Great signal.

我認為另一件事是查理一年多前做出了一個決定，改變模式並改善報銷及其周圍的支援服務，並開始看到其成果。我認為隨著今年的進展，我們將在未來幾年繼續看到這一點。所以這是一個非常非常好的訊號。信號很好。

Got it. And maybe just a quick question. If you can comment on the way to say you're seeing with gross to net. And with the price increase that you took in January, is that something that we should expect going forward for the next couple of years?

知道了。也許只是一個簡單的問題。如果你可以評論說你看到的淨值是多少。隨著一月份的價格上漲，我們應該預期未來幾年會出現這種情況嗎？

The first one, you take the second.

第一個，你拿第二個。

Yeah. On the GTN side, so for reimbursed product, we've historically at 15% to 20%. And much like last year, Q1 is at the higher end of that range, closer to 20%. For the remainder of the year, based on the speed at which Charlie's team got through the (inaudible) process, we'd expect it to come down and be at the lower end.

是的。在 GTN 方面，對於報銷產品，我們歷史上的稅率為 15% 到 20%。與去年非常相似，第一季處於該範圍的高端，接近 20%。在今年剩餘的時間裡，根據查理的團隊完成（聽不清楚）過程的速度，我們預計它會下降並處於較低水平。

And Maury, this year we did -- at the beginning of the year, we had a 5% price increase, and we expect to net about 3.5% of that. And as far as growth to the $800 million at peak in the US, all we would expect is very modest price increases as part of that build towards the $800 million.

莫里，今年我們做到了——年初，我們的價格上漲了 5%，我們預計淨收益約為 3.5%。至於在美國達到 8 億美元高峰的成長，我們所期望的只是價格的小幅上漲，作為邁向 8 億美元目標的一部分。

Got it. Thanks for taking my questions.

知道了。感謝您回答我的問題。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Good morning and thanks for taking my questions. Can I ask about 1013. Any more color on when you expect to make a final decision on that asset? And are you going to be presenting any more data if you do intend to move forward with that? And then I just wanted to ask a question about guidance. And based on where you are still early in the year, is it possible that you could revise the upper end of guidance higher as the year progresses just based on trends that you're seeing so far? Thanks.

嗨，大家好。早安，感謝您提出我的問題。我可以詢問有關 1013 的情況嗎？如果您確實打算繼續推進的話，您會提供更多數據嗎？然後我只是想問一個關於指導的問題。根據今年年初的情況，隨著今年的進展，您是否有可能僅根據迄今為止所看到的趨勢，將指導上限修改得更高？謝謝。

Yeah, on 10013, as we said at the beginning of the year, the goal is either to partner it or if we can't, then we'll stop the program. And so, the next thing that you'll likely hear is whether or not we've decided to partner the drug. And then on guidance, we've adjusted the bottom up in the range. And when we're confident to adjust it further, we'll let you know. But for right now, it's moving the bottom up.

是的，在 10013 年上，正如我們在年初所說，目標是要么與其合作，要么如果我們不能，那麼我們將停止該計劃。因此，您可能會聽到的下一件事是我們是否決定與該藥物合作。然後根據指導，我們調整了該範圍的底部。當我們有信心進一步調整時，我們會通知您。但就目前而言，它正在自下而上移動。

Okay. Was there a follow-up to your question?

好的。您的問題有後續嗎？

I think both were answered. Thanks.

我想兩者都得到了答案。謝謝。

Serge Belanger, Needham & Company.

謝爾蓋貝蘭格 (Serge Belanger)，李約瑟公司。

Good morning. Thanks for taking my questions. Nice ORLADEYO quarter. I guess for Charlie, you mentioned two strong quarters of patient growth, exceeding the first two quarters of the launch. Can you give us just a little more color on that and maybe how it compares on a year-over-year basis? And then with the success of the reauthorization process, it sounds like we're not going to see the usual seasonality trends, but curious how you think about your long-term target of 85% paid scripts? Is that still the target? And does that move up the timeline to hit that target? Thanks.

早安.感謝您回答我的問題。不錯的奧拉德約季度。我想對於查理來說，您提到了患者成長的兩個強勁季度，超過了發布的前兩個季度。您能給我們更多資訊嗎？然後，隨著重新授權過程的成功，聽起來我們不會看到通常的季節性趨勢，但很好奇您如何看待 85% 付費腳本的長期目標？這還是目標嗎？這是否會提前實現該目標的時間表？謝謝。

Thanks, Serge. So just to clarify one thing. The last two quarters were the best two quarters since the first two quarters of launch. So the first two quarters were just slightly better. But I think what it shows is that there was no just -- there's no bolus of patients early that we got and then demand falls. Demand is actually building over time as customers gain more confidence, like I was saying in one of my previous responses.

謝謝，塞爾日。所以只是為了澄清一件事。過去兩個季度是自前兩個季度推出以來最好的兩個季度。所以前兩季只是稍微好一點。但我認為這表明我們早期沒有大量患者，然後需求下降。正如我在先前的回覆中所說，隨著客戶信心的增強，需求實際上是隨著時間的推移而增加的。

And then the 30% growth in revenue year-over-year, I think, kind of speaks for itself at this point in launch, to be growing that strongly is impressive. As far as the Q2 seasonality, as Anthony was saying, we would not expect as big a jump this year. We're guiding to $97 million in Q2, and we would expect that same trend, I think, in the future, where we're going to get more revenue in the first quarter just through more effective reauthorization processes.

我認為，營收年增 30% 在發佈時就已經說明了一切，如此強勁的成長令人印象深刻。就第二季的季節性而言，正如安東尼所說，我們預計今年不會有這麼大的跳躍。我們預計第二季的營收將達到 9,700 萬美元，我認為未來我們預計也會出現同樣的趨勢，透過更有效的重新授權流程，我們將在第一季獲得更多收入。

And then as far as the growth to 85%, that underlying improvement in the rate of paid, as I commented before, it's going to take us some years to get there. All of these improvements that we're making with adding to the team, getting better and better each year going through this process, tells me we're going to get there. And the bigger jump, the bigger opportunity would be next year with the IRA rolling in and hopefully, that helps us get more Medicare patients to paid therapy as the maximum out-of-pocket goes to $2,000. But the overall growth to 85% is going to be a multiyear process.

然後，就成長到 85% 而言，即支付率的根本改善，正如我之前評論的那樣，我們將需要幾年的時間才能實現這一目標。我們透過增加團隊所做的所有這些改進，在這個過程中每年都變得越來越好，告訴我我們將會實現這一目標。隨著 IRA 的加入，明年的跳躍幅度越大，機會就越大，希望這能幫助我們讓更多的 Medicare 患者接受付費治療，因為最高自付費用將達到 2,000 美元。但整體成長到 85% 將是一個多年的過程。

Thank you.

謝謝。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hi everyone. This is [Nevin] on for Brian. Congrats on a good quarter. I just had a couple of questions on SG&A and some of your strategic initiatives to maybe accelerate some of that. Can you speak to some of those, whether you have any sales acceleration initiatives planned to drive any increased uptake either in the US or ex-US as well with some of the expansions in some of the geographies ex-US?

大家好。這是布萊恩的[內文]。恭喜季度表現良好。我只是有幾個關於 SG&A 的問題，以及你們的一些策略舉措，也許可以加速其中的一些進程。您能否談談其中的一些問題，您是否計劃採取任何銷售加速舉措來推動美國或美國以外地區的銷售成長，以及在美國以外的某些地區進行擴張？

And then are you -- in fourth quarter, you had guided towards increase in SG&A of about $20 million. Is that still the case for 2024? And could we expect the patient services team to be in place throughout the year? Or would this be something that you would add to the team seasonally as well near the end of the year, maybe add to the team to help with the rep at the beginning?

然後是 - 在第四季度，您指導 SG&A 增加約 2000 萬美元。 2024年還是這樣嗎？我們能否期望病患服務團隊全年都到位？或者，您是否會在年底時將其添加到團隊中，或者在開始時添加到團隊中以幫助代表？

Charlie, maybe just talk just talk in general about where you're at with the build of your team and then Anthony can talk directly on some of these things.

查理，也許只是簡單地談談你在團隊建立方面的進展，然後安東尼可以直接談論其中的一些事情。

Sure. And I'll also talk about some of those specific initiatives that Nevin asked about. So the investments we made last year were to, like I said, just to improve the efficiency and effectiveness. We're always looking to make improvements at the margin. If we see an opportunity, we'll add a little bit. We don't expect any major adds to our team at this point. It will just be kind of marginal additions, particularly as our patient base grows.

當然。我也會討論內文詢問的一些具體舉措。因此，正如我所說，我們去年所做的投資只是為了提高效率和效果。我們一直在尋求邊際上的改進。如果我們看到機會，我們會添加一點。目前我們預計我們的團隊不會有任何重大補充。這只是一種邊際補充，特別是隨著我們患者群體的成長。

Our patient services team will grow slightly as the patient base grows. But that's not a seasonal growth. That's kind of long-term investment in the team. And then we're always looking to strengthen the brand with additional data and additional initiatives. So we'll continue to look for those opportunities, like the real-world evidence that I described in my prepared remarks.

隨著患者群體的擴大，我們的患者服務團隊將略有成長。但這不是季節性成長。這是對團隊的長期投資。然後，我們一直尋求透過額外的數據和額外的舉措來加強品牌。因此，我們將繼續尋找這些機會，就像我在準備好的發言中所描述的現實世界的證據一樣。

In terms of where we are versus what we had talked about previously, I'd expect about a 20% increase in SG&A year-over-year. But again, most of that is broken down into kind of the full-year impact for the increases that Charlie's team did where you had partial impact last year. And then for the ex-US side, yeah, there'll be smaller increases. But I would think about it far more in terms of how the team is focusing on the idea of margin accretion.

就我們目前的情況與之前討論的情況而言，我預計 SG&A 同比增長 20% 左右。但同樣，其中大部分都被分解為查理團隊在去年產生部分影響的情況下所做的成長的全年影響。然後對於前美國方面，是的，會有較小的成長。但我會更考慮團隊如何關注利潤成長的想法。

So the investments that we are making, the investments that we continue to make, are going to be significantly less than the revenues that are generated as we get towards peak. And so, I'm really excited to start to see that margin accretion and its role in getting us to and through profitability.

因此，我們正在進行的投資，我們繼續進行的投資，將大大低於我們達到頂峰時產生的收入。因此，我真的很高興開始看到利潤的增加及其在使我們實現盈利方面的作用。

Got it. Thank you. Just wanted to clarify, you mentioned 20% increase year-over-year in SG&A --

知道了。謝謝。只是想澄清一下，您提到 SG&A 年成長 20% --

Sorry. $20 million.

對不起。 2000萬美元。

$20 million? Okay. Thank you.

2000萬美元？好的。謝謝。

Liisa Bayko, Evercore ISI.

莉莎·貝科，Evercore ISI。

Hi. Congrats on a good quarter. Just a couple of points of clarification. For your outside like OUS revenue, and you said it was about 10%, does that include the Japanese royalty or no?

你好。恭喜季度表現良好。只需澄清幾點。對於你的外部收入，例如OUS收入，你說大約是10%，這是否包括日本特許權使用費？

Yeah, it does include the Japanese royalty.

是的，它確實包括日本皇室。

Okay. And then what were gross to net in the quarter? And maybe you can comment on how they'll evolve over the course of this year?

好的。那麼本季的毛淨額是多少？也許您可以評論一下它們在今年將如何發展？

Yeah. So gross to net on the reimbursed side here in the US closer to 20%. So again, historically guiding to 15% to 20%. That includes the reauthorization impact, the co-pay assistance impacts, the reset of that and then moving towards the latter part of the year, it will normalize closer into that 15% range, but it will average us out for the year in the 15% to 20%.

是的。因此，美國報銷方面的毛額與淨額接近 20%。再次強調，歷史指引值為 15% 至 20%。這包括重新授權的影響、共同支付援助的影響、其重置，然後到今年下半年，它將正常化，接近 15% 的範圍，但它將使我們在 15 年的平均水平下降% 至20% 。

Okay. And then other revenue, does that -- how much of that is Japanese revenue and how much of that is Rapivab or other stuff? Could you clarify.

好的。然後其他收入，有多少是日本收入，有多少是 Rapivab 或其他東西？你能澄清一下嗎？

Yeah, revenue is all Rapivab.

是的，收入全是 Rapivab。

Yeah. So $88.9 million of it is ORLADEYO and then #3.9 million is Rapivab. If you're asking for a specific split of product versus other revenue, we don't generally give that. But, listen, Rapivab revenue for the most part is inconsequential, especially as ORLADEYO revenue's getting to the point where it's almost $100 million a quarter.

是的。因此，其中 8890 萬美元是 ORLADEYO，然後#390 萬是 Rapivab。如果您要求產品與其他收入的具體分配，我們通常不會提供。但是，聽著，Rapivab 的收入在很大程度上是無關緊要的，特別是當 ORLADEYO 的收入達到每季近 1 億美元的水平時。

Okay. But that doesn't include Japanese revenue in that line, yeah?

好的。但這不包括日本的收入，對嗎？

The $88.9 million does. Japanese.

8890 萬美元確實如此。日本人。

The $88.9 million does include ORLADEYO -- sorry, Japanese ORLADEYO revenue.

8890 萬美元確實包括 ORLADEYO——抱歉，是日本 ORLADEYO 的收入。

Okay. Got it. And then any inventory changes in the quarter?

好的。知道了。那麼該季度的庫存有變化嗎？

No. We continue to be laser focused on ensuring that we have significant quantities. The cost of sales is really, really low. And so, our team does a great job of making sure that we have enough for all of our territories.

不會。銷售成本真的非常非常低。因此，我們的團隊在確保我們所有地區都有足夠的資源方面做得非常出色。

Okay. Great. And then just finally, can you maybe just talk about the pediatric expansion opportunity and just kind of qualify that in terms of potential upside?

好的。偉大的。最後，您能否談談兒科擴張機會，並從潛在的上行空間方面對其進行限定？

Sure. I think the first point is, as Helen pointed out, there's just a huge need amongst kids to have an oral therapy. It's not just the kids, it's the parents. So I think that this is a very highly anticipated product launch when it comes from the market. We think there are about -- in the US, about 500 kids who may be in the consideration for prophylactic therapy. It's an evolving space because there haven't been prophy therapies available for kids before and then to have the first oral, it will change.

當然。我認為第一點是，正如海倫所指出的那樣，孩子們非常需要口腔治療。不只是孩子，還有父母。所以我認為這是一個市場非常期待的產品發布。我們認為，在美國，大約有 500 名兒童可能需要考慮接受預防性治療。這是一個不斷發展的領域，因為之前還沒有針對兒童的預防療法，然後第一次口服，它會改變。

So it's up to 500 patients for prophylaxis. And then the other piece is just the halo effect, which is another way to introduce ORLADEYO to physicians and the families to patients. And so, we expect it to be important for us.

因此，需要對多達 500 名患者進行預防治療。另一個部分就是光環效應，這是向醫生介紹 ORLADEYO、向病人介紹家屬的另一種方式。因此，我們希望它對我們很重要。

And as Helen said in her remarks, when you enroll faster than you thought, that's usually a really good sign that you've got something that people want, and that's exactly what happened.

正如海倫在她的演講中所說，當你註冊的速度比你想像的要快時，這通常是一個非常好的跡象，表明你已經得到了人們想要的東西，而這正是發生的事情。

Okay. Great. Thanks.

好的。偉大的。謝謝。

Stacy Ku, TD Cowen.

史黛西·庫，TD·考恩。

Hey. Thanks so much for taking our questions and congratulations on the progress. So we have a few follow-ups. So first, regarding your Q1 outperformance. What do you think is contributing to this new prescription growth, just characterize these patients a bit more? Is it coming from new prescribers versus current prescribers, just from kind of your patient activation and activities? That's the first question.

嘿。非常感謝您提出我們的問題並祝賀我們的進展。所以我們有一些後續行動。首先，關於您第一季的優異表現。您認為是什麼促成了這種新處方的成長？它是否來自新的處方者與當前的處方者，僅來自於您的患者的激活和活動？這是第一個問題。

And then the second is around your long-term expectations for the Japanese launch of ORLADEYO. Can you just speak a little bit more about what you're seeing so far in early days and how you feel comfortable kind of long term for that opportunity?

第二個是圍繞您對 ORLADEYO 在日本上市的長期期望。您能否多談談到目前為止您在早期所看到的情況以及您對這個機會的長期感覺如何？

And then last, just on 10013. For the partnership, is the team waiting for the full 24-week results before engaging in discussions? And just to confirm, you all would still be getting those results in the middle of 2024, but you do not anticipate disclosing data to the Street? Thanks so much.

最後，就在 10013 上。順便確認一下，你們仍然會在 2024 年中期得到這些結果，但你們預計不會向華爾街披露數據？非常感謝。

Hi, Stacy. So the first question, just in terms of the color on the new growth. It's very similar to what we've seen before. So we're getting prescriptions from existing prescribers. We're always adding new prescribers, as more become aware of ORLADEYO and gain confidence. The mix of patients is also very similar. The roughly 50% switching from other prophy and the other 50% best we can tell being naive to prophylactic therapy. So very consistent and, as I mentioned earlier, consistent to what physicians expect to do in the future. They see a lot more growth coming over the next year.

嗨，史黛西。所以第一個問題，就新生長的顏色而言。這與我們之前看到的非常相似。所以我們從現有的處方醫生那裡獲得處方。隨著越來越多的人了解 ORLADEYO 並獲得信心，我們一直在增加新的處方醫生。患者的組成也非常相似。大約 50% 的人放棄了其他預防性治療，而另外 50% 的人則認為他們對預防性治療很幼稚。非常一致，正如我之前提到的，與醫生未來的期望一致。他們預計明年會有更多成長。

As far as Japan, we think still that there are fewer than 1,000 patients who have been identified in a market that could be 2,500 to even 3,000 HAE patients. So what the team is focused on right now is driving use of prophylaxis and oral prophylaxis within the diagnosed patient community and just building awareness about ORLADEYO.

就日本而言，我們認為在可能有 2,500 甚至 3,000 名 HAE 患者的市場中，確診的患者還不到 1,000 名。因此，該團隊目前的重點是在確診患者群體中推動預防和口服預防的使用，並提高人們對 ORLADEYO 的認識。

Longer term, we think that as we're there with ORLADEYO, other manufacturers are there with other prophylaxis products, there will be more patient diagnosis. And so, we expect this to be a growing market for the next 5 or 10 years. We're very, very enthusiastic about the opportunity in Japan.

從長遠來看，我們認為，隨著我們推出 ORLADEYO，其他製造商也推出其他預防產品，將會有更多的患者得到診斷。因此，我們預計這將在未來 5 到 10 年內成為一個不斷成長的市場。我們對日本的機會非常非常熱情。

And then, Stacy, on 10013, yes, we expect the data in the middle of this year. But what matters since we're not advancing it, we're seeking a partner to advance. It's what do they think about the data at the end of the day. And so, that's where we'll focus our attention.

然後，史黛西，在 10013 上，是的，我們預計今年年中會出現數據。但重要的是，我們不是在推動它，而是在尋找合作夥伴來推進它。這就是他們最終對數據的看法。因此，這就是我們重點關注的地方。

Understood. Thank you so much.

明白了。太感謝了。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Thank you. Maybe just one regarding the Japan since we have quite a few questions on Japan market. What is the price there? Is that also a 30% to 50% discount of the US price relative -- like similar to Europe price? And the second question is regarding the pediatric trial. I noticed it is a single-arm study. What data could be approvable based on FDA feedback?

謝謝。也許只是一個關於日本的問題，因為我們對日本市場有很多問題。那裡的價格是多少？這是否也是美國價格相對價格的 30% 到 50% 折扣——類似於歐洲價格？第二個問題是關於兒科試驗的。我注意到這是一項單臂研究。根據 FDA 的回饋，哪些數據可以被批准？

Charlie, you take Japan price and Helen take the --

查理，你選擇日本價格，海倫選擇——

Gena, the Japanese price is actually the second highest price -- ORLADEYO price in the world. So at the moment -- and then, of course, it's subject to exchange rate variation. But at the moment, it's close to $200,000 per year. So it's higher than our European prices.

Gena，日本的價格其實是全球第二高的價格－ORLADEYO價格。所以目前——當然，它會受到匯率變動的影響。但目前，每年接近 20 萬美元。所以它比我們歐洲的價格還要高。

And then, Helen.

然後，海倫。

Question on the pediatric trial. It is a single arm, and that's fairly standard now for what's called extrapolation of the data. The point is to match exposures in the pediatric population with the exposures that are known to be effective in the adult population. So it's safety and PK, and that's what we'll really be submitted to the agency.

關於兒科試驗的問題。它是一個單臂，現在對於所謂的資料外推來說這是相當標準的。關鍵是將兒科族群的暴露量與已知對成人有效的暴露量相匹配。所以這是安全性和 PK，這就是我們真正要提交給該機構的內容。

I noticed you do have, also, attack rate collection. Will FDA also consider that data point, any like, say, threshold that you have to achieve?

我注意到你也有攻擊率收集。 FDA 是否也會考慮該數據點，例如您必須達到的門檻？

So attack rate's always collected when you're following patients, and we know the patient is doing well. That will be submitted as part of the data set, but the decision will be based on safety and the exposure.

因此，當您追蹤患者時，總是會收集發病率，並且我們知道患者狀況良好。這將作為資料集的一部分提交，但決定將基於安全性和暴露程度。

Okay. Thank you.

好的。謝謝。

Francois Brisebois, Oppenheimer.

弗朗索瓦·布里斯布瓦，奧本海默。

Hi. Thanks. In terms of the pediatric importance here, you talked about up to 500 patients, but is there a scenario where you'd ever expect the patient to -- a pediatric to be on this and then turn into an adult and maybe change treatment option? Just wondering too if you can remind us all of the competition on the pediatric front.

你好。謝謝。就兒科的重要性而言，您談到了多達 500 名患者，但您是否曾期望患者——一名兒科患者接受此治療，然後變成成人，並可能改變治療選擇？我也想知道您能否提醒我們所有兒科領域的競爭。

I think we -- what we would see is that patients who -- kids that need to start on prophylaxis and oral is going to be the best option for them just for obvious reasons. And this is a lifelong disease. So we think there's an opportunity for these kids to be on ORLADEYO for a very long period of time. And then as I mentioned earlier, just the family aspect of it too as a genetic disease. Usually, there is a parent or often a sibling, other family members in the household. And so, it's an opportunity for whole families to become more aware of the benefits of ORLADEYO. So we would expect them to stay on for the long term.

我認為我們 - 我們會看到的是，出於顯而易見的原因，需要開始預防和口服藥物的孩子將成為他們的最佳選擇。而且這是一種終身疾病。所以我們認為這些孩子有機會在奧拉德約待很長一段時間。正如我之前提到的，家庭方面也是一種遺傳疾病。通常，家裡有父母或兄弟姊妹以及其他家庭成員。因此，這是一個讓整個家庭更加了解 ORLADEYO 好處的機會。因此，我們希望他們能夠長期留下來。

I understood. Thank you.

我明白了。謝謝。

Jon Wolleben, JMP Securities.

喬恩‧沃勒本 (Jon Wolleben)，JMP 證券。

Hey. Thanks for taking the question. One on your market research, which has been seemingly accurate in the past. When you ask about prescribing in the next 12 months, wondering if you actually ask longer term as well about ultimate usage how that factors into your growth projection? Then also, it seems to be reflective of the uptake we're seeing. Do you ever have to expand who you're asking and what you're asking about to get more insight into what the trajectory looks like three, four years down the line?

嘿。感謝您提出問題。一項關於您的市場研究，過去看起來似乎很準確。當您詢問未來 12 個月內的處方情況時，想知道您是否真的會詢問長期的最終使用情況，這如何影響您的成長預測？而且，這似乎也反映了我們所看到的情況。您是否需要擴展您的詢問對象和詢問內容，才能更深入地了解三、四年後的發展軌跡？

Yeah. Thanks for the question, Jon. We absolutely do look at that longer term and ask them about the longer term. The growth in the next 12 months, that's the quarterly survey that we do with 60 to 100 physicians every quarter. Then we use that information plus other studies once a year to build a much longer-term model where we also incorporate everything that might come in the future, and we ask physicians their opinions of those products, what they think they will use. And then that all goes into a much larger market forecasting model to predict the future. It was very accurate in our first year of launch. And every year, our team updates this model.

是的。謝謝你的提問，喬恩。我們絕對會著眼於更長期的目標，並詢問他們關於更長期的目標。未來 12 個月的成長，這是我們每個季度對 60 到 100 名醫生進行的季度調查。然後，我們每年一次使用這些資訊和其他研究來建立一個更長期的模型，其中我們還納入了未來可能出現的所有內容，並詢問醫生他們對這些產品的看法，他們認為他們會使用什麼。然後，所有這些都進入更大的市場預測模型來預測未來。在我們推出的第一年，它非常準確。我們的團隊每年都會更新這個模型。

And so we have a lot of confidence in our future predictions. And it is -- that is where our $1 billion peak revenue comes from. It comes from that model that incorporates all of the forward-looking market research.

因此，我們對未來的預測充滿信心。這就是我們 10 億美元高峰收入的來源。它來自包含所有前瞻性市場研究的模型。

And then when this year do you guys do that annual revamp? And do you -- will you guys let us know the results?

那麼今年你們什麼時候進行年度改造呢？你們會讓我們知道結果嗎？

We will let you know if anything changes. We do it once a year around the middle of the year. And yeah, our goal is to be accurate in all of our forecasting. So if we see anything different, we'll definitely let you know.

如果有任何變化，我們會通知您。我們每年在年中左右進行一次。是的，我們的目標是準確地進行所有預測。因此，如果我們發現任何不同的情況，我們一定會通知您。

Got it. Thanks, Charlie.

知道了。謝謝，查理。

Chris Raymond, Piper Sandler.

克里斯·雷蒙德，派珀·桑德勒。

Thanks for squeezing me in. Jon, you've been pretty open in the past when folks have asked you guys about strategic interest and sort of inbound interest. And I think it's pretty clear now, by now, that there's a lot of buoyancy here, if you will, for maybe lack of a better word to ORLADEYO's uptake. I guess any discernible change in terms of frequency or maybe tenor of the inbound calls that you guys have had from strategics? Thanks.

謝謝你讓我插話。我認為現在已經很清楚了，如果你願意的話，這裡有很大的活力，因為也許沒有更好的詞來形容奧拉德約的吸收。我想你們從戰略部門接到的呼入電話的頻率或基調方面有什麼明顯的變化嗎？謝謝。

Yeah, Chris, I mean, you know I can't talk about specifics and volume or changes. But the answer about our willingness to entertain those remains unchanged. We're a public company, and we have shareholder interest in our minds. And if someone is interested, we'll take the call. So no change there.

是的，克里斯，我的意思是，你知道我不能談論細節、數量或變化。但關於我們是否願意招待這些人的答案仍然沒有改變。我們是一家上市公司，我們關心股東利益。如果有人有興趣，我們會接聽電話。所以那裡沒有變化。

Thank you.

謝謝。

This concludes our question-and-answer session. I would like to turn the conference back over to Jon Stonehouse for any closing remarks.

我們的問答環節到此結束。我想將會議轉回喬恩·斯通豪斯（Jon Stonehouse）發表閉幕詞。

Yeah. Thanks again for your interest in our company. We are off to a really, really good start to this year, and we're super excited where this will lead us to in terms of ORLADEYO trajectory and advancing the pipeline. So we're focused on continuing this momentum throughout the year and look forward to updating you as we have new information. Have a great day.

是的。再次感謝您對我們公司的關注。今年我們有了一個非常非常好的開始，我們非常興奮，這將引導我們在奧拉德約的發展軌跡和推進管道方面取得進展。因此，我們致力於全年保持這一勢頭，並期待在獲得新資訊時向您通報最新情況。祝你有美好的一天。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。