BioCryst Pharmaceuticals Inc (BCRX) 2023 Q2 法說會逐字稿

Good day, and welcome to the BioCryst Second Quarter 2023 Earnings Call.

美好的一天，歡迎參加 BioCryst 2023 年第二季財報電話會議。

(Operator Instructions)

（操作員說明）

Please note, this event is being recorded.

請注意，此事件正在被記錄。

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

我現在想將會議轉交給 BioCryst 的 John Bluth 先生。請繼續。

Thank you very much. Good morning, and welcome to BioCryst's Second Quarter 2023 Corporate Update and Financial Results Conference Call. Today's press release and accompanying slides are available on our website.

非常感謝。早安，歡迎參加 BioCryst 2023 年第二季公司最新動態與財務業績電話會議。今天的新聞稿和隨附的幻燈片可在我們的網站上取得。

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.

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。在我們的發言之後，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 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。您不應過度依賴這些前瞻性陳述。有關更多信息，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，這些文件可以在我們的網站上訪問。

In addition, today's conference call includes non-GAAP pro forma financial measures. For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the Press Release section of our Investor Relations website at 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。有關這些非 GAAP 指標與最直接可比較的 GAAP 財務指標的調節，請參閱我們投資者關係網站 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. The strong step-up in revenue that we expected and achieved in the second quarter and the consistent steady growth we continue to see in patients on treatment, positions us well to achieve no less than $320 million in ORLADEYO revenue for the year and $1 billion at peak. Charlie will share more of the details, but I want to point out the success Charlie and his commercial team have had in a rare market where there are many treatment options for patients, and yet, they're still switching to ORLADEYO, that is great execution by the entire team.

謝謝，約翰。我們預期並在第二季度實現的收入強勁增長，以及我們繼續看到接受治療的患者持續穩定增長，使我們有能力在ORLADEYO 實現今年不少於3.2 億美元的收入，在奧拉德約實現10億美元的收入。頂峰。查理將分享更多細節，但我想指出查理和他的商業團隊在一個罕見的市場中取得的成功，該市場為患者提供了多種治療選擇，但他們仍然轉向奧拉德約，這很棒由整個團隊執行。

Charlie and I also recently attended the U.S. HAEA Patient Summit in Orlando, Florida. This was the first major gathering of U.S. HAE patients since 2019, which was before the approval of ORLADEYO. A record 1,200 HAE patients and their families were in attendance, and it was an amazing opportunity for us to showcase our company and make connections with this community. Patient activation is a major part of our strategy, and this event was a fantastic launching pad for that.

查理和我最近也參加了在佛羅裡達州奧蘭多舉行的美國 HAEA 患者高峰會。這是自 2019 年以來美國 HAE 患者的首次大型聚會，當時是在 ORLADEYO 獲得批准之前。創紀錄的 1,200 名 HAE 患者及其家人出席了會議，這對我們來說是一個絕佳的機會來展示我們的公司並與這個社區建立聯繫。患者活化是我們策略的重要組成部分，這次活動是一個極好的啟動平台。

Lastly, we're very excited about the progress we're making with our pipeline. We will host an R&D Day on November 3 at our labs in Birmingham, Alabama. We plan to show you much more about additional assets and programs we haven't discussed previously. Our hope is you will see more clearly how our structure-based drug design platform focused on pursuing first-in-class or best-in-class medicines for patients with rare disease, allows us to spread inherent risk of drug discovery across multiple programs, targets and diseases and increases our probability to get at least one of them to the market to follow the success of ORLADEYO. We look forward to sharing more with you in November.

最後，我們對管道取得的進展感到非常興奮。我們將於 11 月 3 日在阿拉巴馬州伯明罕的實驗室舉辦研發日。我們計劃向您展示更多有關我們之前未討論過的其他資產和計劃的資訊。我們希望您能更清楚地看到我們基於結構的藥物設計平台如何專注於為罕見疾病患者尋求一流或一流的藥物，使我們能夠在多個項目中分散藥物發現的固有風險，目標和疾病，並增加了我們將其中至少一種推向市場以跟隨ORLADEYO 的成功的可能性。我們期待在 11 月與您分享更多資訊。

Now I'll hand it over to Charlie.

現在我把它交給查理。

Thanks, Jon. Second quarter results for ORLADEYO rolled out as we expected. The long-term linear growth in patients on therapy continued and revenue jumped following the first quarter prescription reauthorization process. I'll provide more color on both. Growth in patients treated with ORLADEYO continued at the same consistent pace we've seen over the past 2 years. After a strong first quarter in the United States for net patients added to therapy, we added about the same number of patients again in the second quarter. I noted at the last earnings call that we had crossed 1,000 patients on therapy in the U.S. As you would expect, we are above that number -- that total now. This is what linear growth looks like.

謝謝，喬恩。奧拉德約第二季業績符合我們的預期。在第一季的處方重新授權流程之後，接受治療的患者數量繼續保持長期線性增長，收入大幅增長。我將為兩者提供更多顏色。接受 ORLADEYO 治療的患者數量繼續以與過去兩年相同的一致速度增長。在美國第一季新增治療的淨患者數量強勁之後，我們在第二季度再次增加了大約相同數量的患者。我在上次財報電話會議上指出，我們在美國接受治療的患者人數已超過 1,000 名。正如您所料，我們已經超過了這個數字——現在的總數。這就是線性成長的樣子。

We also made great progress in getting patients to paid therapy, adding the most net paid patients in a quarter since Q2 of last year. In fact, we added the exact same number of net paid patients as a year ago. We also had a very similar number of discontinuations as in the second quarter last year, even though our current patient base is significantly larger, so the discontinuation rate continues to go down. Again, linear growth. As we forecasted, revenue took a substantial jump in Q2 over Q1, just like it did a year ago. The biggest driver was the continued growth in our patient base, but we are also improving our ability to get patients to paid therapy.

我們在讓患者接受付費治療方面也取得了巨大進展，自去年第二季以來增加了淨付費患者數量最多的一個季度。事實上，我們增加的淨付費患者數量與一年前完全相同。儘管我們目前的患者基數明顯較大，但我們的停藥數量也與去年第二季非常相似，因此停藥率持續下降。再次，線性成長。正如我們預測的那樣，第二季度的收入比第一季大幅成長，就像一年前一樣。最大的推動力是我們患者群體的持續成長，但我們也在提高讓患者接受付費治療的能力。

In January and February, for example, roughly 34% of patients were on free product during the heavy reauthorization period. That fell to about 32% by the end of March. By the end of Q2, the percentage of patients on free product fell to 30%. So we made a lot more progress after reauthorizations were completed. Every percentage point of our current patient base that we move to paid therapy is worth about $4 million in annual revenue. So these improvements are very meaningful.

例如，在一月和二月，大約 34% 的患者在重度重新授權期間使用免費產品。到 3 月底，這一比例降至 32% 左右。到第二季末，使用免費產品的患者比例下降至 30%。因此，重新授權完成後，我們取得了更多進展。我們目前轉向付費治療的患者基數每增加一個百分點，年收入就價值約 400 萬美元。所以這些改進是非常有意義的。

Based on the trends we see and the work our team is doing, we expect to see continued steady improvements in that percentage over the next few years. We are confident we will reach our long-term goal of getting over 80% of U.S. patients on ORLADEYO to paid status.

根據我們看到的趨勢和我們團隊正在做的工作，我們預計未來幾年將持續穩定提高。我們有信心實現長期目標，讓 ORLADEYO 超過 80% 的美國患者獲得付費狀態。

The bottom line in the U.S. is this. We are growing total patients on therapy at a very consistent rate every quarter just as we have done since launch, and we're getting even better at moving patients to paid therapy. For the rest of 2023, we expect revenue to track along with steady patient growth to reach no less than $320 million in global revenue for the year. In future years, you can expect the same pattern based on patient growth trends and insurance seasonality. Q1 revenue being slightly down based on reauthorizations, Q2 being a larger bump in revenue and steady growth in Q3 and Q4.

美國的底線就是這樣。正如我們自推出以來所做的那樣，每季接受治療的患者總數都以非常穩定的速度成長，而且我們在讓患者接受付費治療方面做得更好。在 2023 年剩餘時間內，我們預計營收將隨著患者的穩定成長而成長，全年全球營收將達到不少於 3.2 億美元。在未來幾年，您可以根據患者成長趨勢和保險季節性預期相同的模式。第一季營收因重新授權而略有下降，第二季營收大幅成長，第三季和第四季穩定成長。

The U.S. currently accounts for about 90% of global sales, but this may overshadow how well we are doing in Europe and the rest of the world. What we are seeing right now in Europe is very similar to the U.S., steady quarterly growth in patients on therapy. We are laying the groundwork for similar patient growth trajectories as we launch in more and more countries around the world, on the way to 20% of peak global sales coming from markets beyond the U.S.

美國目前約佔全球銷售額的 90%，但這可能會掩蓋我們在歐洲和世界其他地區的表現。我們目前在歐洲看到的情況與美國非常相似，接受治療的患者數量逐季度穩定成長。隨著我們在全球越來越多的國家推出產品，我們正在為類似的患者成長軌跡奠定基礎，力爭達到全球銷售額高峰的 20% 來自美國以外的市場。

As John said earlier, we recently attended the U.S. HAEA Summit in Orlando, along with 1,200 patients and their family members. Their interest and enthusiasm showed us how much demand there is for an oral once-daily prophylaxis therapy. We are seeing the same thing around the world. Our teams and our partners in North America, Europe, Latin America and the Middle East are doing phenomenal work to bring ORLADEYO to patients who need it. We keep growing and we keep improving. I'm so proud of our global teams and how they're bringing this transformative therapy to patients living with HAE all over the world.

正如約翰之前所說，我們最近與 1,200 名患者及其家屬一起參加了在奧蘭多舉行的美國 HAEA 高峰會。他們的興趣和熱情向我們展示了對每日一次口服預防療法的需求有多大。我們在世界各地都看到同樣的事情。我們在北美、歐洲、拉丁美洲和中東的團隊和合作夥伴正在做出色的工作，將 ORLADEYO 帶給有需要的患者。我們不斷成長，不斷進步。我為我們的全球團隊以及他們如何為世界各地的 HAE 患者帶來這種變革性療法感到非常自豪。

Helen, I'll turn it over to you.

海倫，我把它交給你了。

Thanks, Charlie. It was exciting to hear from so many patients at the HAEA Summit about how ORLADEYO has controlled their attacks and changed their lives. HAE is a hereditary disease passed down from parents to children, and we spoke with many parents who wanted to know what progress we are making towards bringing ORLADEYO to the pediatric population. The burden of HAE and in particular, the burden of injectable therapy is especially difficult for children. That is why we are focused on a future pediatric indication with oral once-daily ORLADEYO in the APeX-P trial, including evaluation of a new formulation using granules to best meet the needs of children with HAE. APeX-P is up and running at multiple sites, and I'm pleased to note that enrollment is proceeding as expected.

謝謝，查理。在 HAEA 高峰會上聽到這麼多患者講述 ORLADEYO 如何控制他們的發作並改變他們的生活，真是令人興奮。 HAE 是一種從父母傳給孩子的遺傳性疾病，我們採訪了許多家長，他們想知道我們在將 ORLADEYO 帶給兒科族群方面取得了哪些進展。 HAE 的負擔，特別是注射治療的負擔對兒童來說尤其困難。這就是為什麼我們在 APeX-P 試驗中將重點放在每日口服一次 ORLADEYO 的未來兒科適應症上，包括評估使用顆粒的新配方，以最好地滿足 HAE 兒童的需求。 APeX-P 已在多個站點啟動並運行，我很高興地註意到註冊正在按預期進行。

Turning now to the Pipeline. We're looking forward to our R&D Day in November, where we'll share with you details on new programs and molecules that you haven't seen before. Our goal with our pipeline is to bring first-in-class or best-in-class molecules to patients with rare diseases and to have a second product and more following that, which we bring to market as we did with ORLADEYO.

現在轉向管道。我們期待 11 月的研發日，屆時我們將與您分享您以前從未見過的新程序和分子的詳細資訊。我們管道的目標是為罕見疾病患者帶來一流或一流的分子，並推出第二種產品以及更多後續產品，就像我們將 ORLADEYO 推向市場一樣。

As we focus our investments across multiple molecules, targets and rare diseases that meet our criteria, we are diversifying risk by adding to our options in discovery and early development. Adding these options then increases our overall chances for success in achieving that goal of bringing additional products through registration and to patients.

當我們將投資集中在符合我們標準的多個分子、目標和罕見疾病時，我們會透過增加發現和早期開發的選擇來分散風險。添加這些選項可以增加我們成功實現透過註冊向患者提供更多產品這一目標的整體機會。

As you've seen, we are also disciplined about decisions to invest in later-stage products, which are proportionately more expensive. We won't accelerate R&D spending for pivotal program until we have clear data that we are likely to have a first-in-class or best-in-class molecule. This is our approach with BCX10013. We want to see data that shows BCX10013 is an oral Factor D inhibitor with once daily dosing, excellent safety and efficacy if it is as good or better than the other options for patients. If the data show BCX10013 has this profile, this is the profile of a best-in-class molecule, and we will invest to run pivotal trials and bring it to market. If the data show, we don't have a best-in-class molecule here, we'll stop development. It is early and there's still plenty of unknowns with BCX10013 program, but we do have 2 updates to share with you today.

正如您所看到的，我們對投資後期產品的決策也很嚴格，這些產品的成本相對較高。在我們有明確的數據表明我們可能擁有一流或一流的分子之前，我們不會加速關鍵項目的研發支出。這是我們使用 BCX10013 的方法。我們希望看到數據顯示 BCX10013 是一種口服 D 因子抑制劑，每天給藥一次，如果它與患者的其他選擇一樣好或更好，則具有出色的安全性和有效性。如果數據顯示 BCX10013 具有這種特徵，那麼這就是同類最佳分子的特徵，我們將投資進行關鍵試驗並將其推向市場。如果數據顯示我們沒有一流的分子，我們將停止開發。現在還為時過早，BCX10013 計畫仍有許多未知因素，但今天我們確實有 2 個更新要與您分享。

We have restarted dosing in our multiple ascending dose trial in healthy volunteers to add another dose level. We have previously evaluated multiple doses up to 80 milligrams and also single doses of up to 110 milligrams where we saw excellent durable control of the alternative pathway at 24 hours post dose. These data support proceeding with evaluation of patients. Now we'll take our healthy volunteer dosing higher to refine our model -- our PK model data set with daily dosing at 160 milligrams for 14 days. This is in parallel to the work we'll do in patients to obtain more robust information for our PK model and eventually inform pivotal -- final pivotal dose selection.

我們已在健康志願者中重新開始多次劑量遞增試驗，以增加另一個劑量水平。我們之前評估過高達 80 毫克的多劑量以及高達 110 毫克的單一劑量，我們發現在給藥後 24 小時對替代途徑具有出色的持久控制。這些數據支持對患者進行評估。現在，我們將提高健康志願者的劑量來完善我們的模型——我們的 PK 模型資料集，每日劑量為 160 毫克，持續 14 天。這與我們將在患者身上所做的工作同時進行，以便為我們的 PK 模型獲得更可靠的信息，並最終為關鍵的最終關鍵劑量選擇提供資訊。

We are now also proceeding with our dose-ranging trial, BCX10013 in patients. We expect to begin enrolling patients by the end of the year with initial data available next year. We are conducting this trial in patients, and we have chosen to work in PNH for evaluation of both alternative pathway activity and clinical outcomes. To determine if we have a safe, effective, once-daily dose that meets our criteria to move forward into a pivotal program in renal complement-mediated diseases like IgAN. Beyond BCX10013, we continue to build and advance our early pipeline as we invest in discovery for new targets. We're now ready to share our exciting progress with a growing pipeline of molecules, and we look forward to doing this at our R&D Day in November at the BioCryst Discovery Center of Excellence in Birmingham, Alabama.

我們現在也在患者中進行劑量範圍試驗 BCX10013。我們預計在今年年底前開始招募患者，並在明年提供初步數據。我們正在患者中進行這項試驗，並選擇在 PNH 工作，以評估替代途徑活性和臨床結果。確定我們是否有安全、有效、每日一次的劑量，符合我們的標準，以推進 IgAN 等腎補體介導疾病的關鍵計劃。除了 BCX10013 之外，我們還在投資新標靶的發現過程中繼續建造和推進我們的早期產品線。我們現在已準備好與不斷增長的分子管線分享我們令人興奮的進展，我們期待在 11 月份位於阿拉巴馬州伯明翰 BioCryst 卓越發現中心的研發日上分享這一成果。

Now I'll turn the call over to Anthony.

現在我將把電話轉給安東尼。

Thanks, Helen. With Global ORLADEYO revenue for Q2 coming in at $81 million, we saw the step-up that we anticipated from Q1. Based on the strong second quarter revenue performance and continuing underlying patient growth. And similar to last year's quarterly cadence, we anticipate that revenues will increase slightly in the third and then again in the fourth quarter.

謝謝，海倫。隨著第二季 ORLADEYO 全球營收達到 8,100 萬美元，我們看到了第一季預期的成長。基於第二季度強勁的收入表現和持續的潛在患者成長。與去年的季度節奏類似，我們預計第三季營收將小幅成長，然後第四季再次成長。

Year-to-date, ORLADEYO revenue is at over $149 million. We expect revenue in the second half to come in at approximately $171 million or an average of $85.5 million over the next 2 quarters, and we're confident that we will achieve our revenue guidance of no less than $320 million for the year. You can find our detailed second quarter financials in today's earnings press release, and I'd like to call your attention to a few items.

今年迄今為止，ORLADEYO 的收入超過 1.49 億美元。我們預計下半年的收入約為 1.71 億美元，或未來 2 個季度的平均收入為 8,550 萬美元，我們有信心實現全年不低於 3.2 億美元的收入指引。您可以在今天的收益新聞稿中找到我們詳細的第二季財務數據，我想提請您注意一些項目。

Total revenue for the quarter came in at $82.5 million, $81 million of which came from ORLADEYO. Of that $81 million of global ORLADEYO revenue, $72.8 million came from U.S. sales with the remaining $8.2 million coming from ex U.S., increases of 24% and 26% over Q2 of 2022, respectively.

該季度總收入為 8,250 萬美元，其中 8,100 萬美元來自奧拉德約。在 ORLADEYO 的 8,100 萬美元全球收入中，7,280 萬美元來自美國銷售，其餘 820 萬美元來自美國以外地區，分別比 2022 年第二季增長 24% 和 26%。

Operating expenses, not including noncash stock compensation for the quarter were $90.4 million, flat to Q2 of 2022. R&D investment for the first half of 2023 reduced significantly compared to the same period in 2022, and we expect that trend to continue and that R&D investment in the second half of '23 will be lower than in the second half of 2022, even as we factor in the additional trials for BCX10013 that Helen discussed, and continued investment in our pipeline that we will share more about at the R&D Day in November. We reiterate our full year OpEx guidance of $375 million for the year, flat to prior year.

該季度的營運費用（不包括非現金股票補償）為9,040 萬美元，與2022 年第二季持平。2023 年上半年的研發投資與2022 年同期相比大幅減少，我們預計這一趨勢將持續下去，研發投資將繼續下降即使我們考慮到Helen 討論過的BCX10013 的額外試驗，以及我們將在11 月的研發日分享更多有關我們管道的持續投資，23 年下半年的銷售額將低於2022 年下半年。我們重申全年營運支出指引為 3.75 億美元，與前一年持平。

Cash at the end of the second quarter was at $415.7 million, that includes net proceeds of $26 million from the Pharmakon refinancing that we closed in April, a deal that moved our debt repayment date out into 2028, gave us greater access to capital and improved our terms. Net operating cash utilization for the quarter improved from $28 million in Q2 of 2022 to approximately $13 million last quarter, primarily driven by our increased revenues.

第二季末的現金為4.157 億美元，其中包括我們4 月份完成的Pharmakon 再融資的2,600 萬美元淨收益，該交易將我們的債務償還日期推遲到2028 年，使我們能夠更容易地獲得資本並改善我們的條款。本季的淨營運現金利用率從 2022 年第二季的 2,800 萬美元增加到上季的約 1,300 萬美元，這主要是由於我們的收入增加所致。

GAAP earnings per share for the quarter were negative $0.40. That includes the impact of an approximately $29 million debt extinguishment charge following the refi with Pharmakon. Adjusting this onetime charge out on a pro forma basis, earnings per share came in at approximately negative $0.24 for the quarter.

該季度 GAAP 每股收益為負 0.40 美元。其中包括與 Pharmakon 進行再融資後約 2,900 萬美元債務清償費用的影響。根據預估調整這筆一次性費用後，本季每股收益約為負 0.24 美元。

With the continuing strong performance of ORLADEYO, as we move towards our 2023 no less than $320 million and onwards to peak sales of $1 billion, OpEx flat to prior year, while continuing to invest in advancing our pipeline, all combined with our strong capital position, we're in great financial shape to generate value as we move the company forward.

隨著ORLADEYO 持續強勁的業績，隨著我們向2023 年不低於3.2 億美元的目標邁進，並進一步達到10 億美元的峰值銷售額，營運支出與上一年持平，同時繼續投資推進我們的管道，所有這些都與我們強大的資本狀況相結合，我們的財務狀況良好，可以在推動公司前進的過程中創造價值。

Now I'll pass it back to Jon.

現在我會把它傳回給喬恩。

Thanks, Anthony. So we had a great quarter, whether it's the ORLADEYO performance or the advancing of the pipeline, and that is a direct result of great execution. And so I want to thank the BioCryst employees for that. We plan to report Q3 earnings on November 2 from Birmingham the day before our R&D Day. And we are very excited to host some of you at our labs in Birmingham, Alabama. We've got limited space, so the rest of you will be able to participate via webcast.

謝謝，安東尼。因此，我們度過了一個出色的季度，無論是 ORLADEYO 的表現還是管道的推進，這是出色執行的直接結果。因此，我要為此感謝 BioCryst 的員工。我們計劃於 11 月 2 日研發日的前一天從伯明罕報告第三季財報。我們非常高興能夠在我們位於阿拉巴馬州伯明罕的實驗室接待你們中的一些人。我們的空間有限，所以其他人可以透過網路廣播參與。

Some of you may be asking why are we holding this on a Friday afternoon in Alabama. And there's 2 main reasons. One, we found that when you're there and have hands on seen what we do and how we do it and meeting our scientists, you have a better appreciation for what we're capable of doing. And the second reason is Saturday, the next day after, for those of you who are college football fans or not, there's a pretty important game down the road in Tuscaloosa where LSU is coming to play Alabama. So we look forward to hosting our R&D Day on November 3 in Birmingham, Alabama.

你們中的一些人可能會問為什麼我們要在周五下午在阿拉巴馬州舉行這個會議。有兩個主要原因。第一，我們發現，當您親臨現場親眼目睹我們所做的事情以及我們如何做並會見我們的科學家時，您會對我們的能力有更好的認識。第二個原因是星期六，也就是第二天，對於那些是否是大學橄欖球迷的人來說，接下來在塔斯卡盧薩有一場非常重要的比賽，路易斯安那州立大學將對陣阿拉巴馬州。因此，我們期待 11 月 3 日在阿拉巴馬州伯明罕舉辦研發日活動。

And that's it for our prepared remarks. We're now going to open it up for your questions.

這就是我們準備好的發言。我們現在將打開它來回答您的問題。

(Operator Instructions)

（操作員說明）

Our first question comes from Tazeen Ahmad with Bank of America.

我們的第一個問題來自美國銀行的 Tazeen Ahmad。

And I'll start looking for flights to Alabama. I wanted to maybe get a little bit of color on how you're thinking about the second half of the year for ORLADEYO trends. Now you were specific about saying that you expect to see some growth in the third and fourth quarter. I think people will be interested in knowing how your growth, which is very strong, could turn into outsized growth in coming years? And where do you see your areas of real unmet need now that you're fairly matured into this launch, what are your focus areas for your marketing team, for example? And where do you think most of the upside is going to be coming from?

我將開始尋找飛往阿拉巴馬州的航班。我想了解您對今年下半年 ORLADEYO 趨勢的看法。現在您具體說您預計第三季和第四季會出現一些成長。我認為人們會有興趣了解你們的強勁成長如何在未來幾年轉變為超額成長？既然您在這次發布中已經相當成熟，那麼您在哪裡看到真正未滿足需求的領域，例如，您的行銷團隊的重點領域是什麼？您認為大部分上漲空間將來自哪裡？

Sure. Tazeen, I can take that. So first of all, the question about the second half of this year, so we expect the revenue to go up at the pace of our -- the additions of patients on therapy. So as I've talked about, we've had really consistent growth in patients on therapy. So that's what's going to drive the growth in Q3 and Q4 just as it does since launch. And as far as your question about the unmet need, the opportunity, what we know is that the -- all things being equal, the great majority of HAE patients would rather treat their disease with one pill once a day. And so the unmet need is to get all the people who haven't tried yet to try ORLADEYO. And a lot of those are patients who are taking other prophylaxis therapies, injectable prophylaxis. So we're going to keep focusing as a #1 priority on giving them the chance to switch over and try ORLADEYO, and seeing how much more they can benefit by treating their disease with an oral drug.

當然。塔津，我可以接受。首先，關於今年下半年的問題，我們預計收入將隨著接受治療的患者數量的增加而增加。正如我所說，接受治療的患者數量確實持續增加。因此，這將推動第三季和第四季的成長，就像它自推出以來一樣。至於你關於未滿足的需求、機會的問題，我們知道，在所有條件相同的情況下，絕大多數 HAE 患者寧願每天服用一粒藥來治療他們的疾病。因此，尚未滿足的需求是讓所有尚未嘗試過的人嘗試 ORLADEYO。其中許多是正在接受其他預防療法、注射預防療法的患者。因此，我們將繼續將重點放在讓他們有機會轉換並嘗試 ORLADEYO 上，看看他們透過口服藥物治療疾病能獲得多少益處。

Charlie, I'd add, when we were at the Patient Summit in Orlando, One of the things that we had a challenge with at the launch was patient activation because of COVID. And what we heard from patients is this is the first time they were aware that it was approved and available to them. And I think the more that we get go into, Tazeen, I think that's a potential for continued growth. But the bottom line is, there's a lot of good drugs out there that are people are controlled on. And so it's tackling it doctor by doctor, patient by patient to get them to want to try it because if they work for them, it's way better than being injecting yourself.

查理，我想補充一點，當我們參加奧蘭多患者高峰會時，我們在啟動時遇到的挑戰之一是由於新冠肺炎而激活患者。我們從患者那裡聽到的是，這是他們第一次知道該藥物已獲得批准並可供他們使用。我認為，塔澤恩，我們投入得越多，我認為這就是持續成長的潛力。但最重要的是，有許多好的藥物可供人控制。因此，我們正在逐個醫生、逐個患者地解決這個問題，讓他們願意嘗試，因為如果他們為他們工作，這比自己注射要好得多。

Okay, Jon. And you have reiterated your confidence in reaching $1 billion in peak. You have a sense of how long it would take from where you are now to reach that goal?

好吧，喬恩。您也重申了您對達到 10 億美元高峰的信心。您知道從現在的位置到實現該目標需要多長時間嗎？

So I think what we've said before, we'll say again on this, Tazeen. You can draw a line between our year 1 revenue of about $122 million, $250 million last year, and $320 million this year. And that will give you a pretty good sense of when we expect to get $1 billion -- to $1 billion. It will take some more years based on what Jon was just talking about. It's -- moving this market takes a while. But everything we see in our forward-looking market research as well as our -- the results that we're putting on the board, gives us great confidence that we're going to get there.

所以我想我們之前說過的話，我們會再說一遍，塔津。您可以在我們第一年約 1.22 億美元的收入、去年的 2.5 億美元和今年的 3.2 億美元之間劃清界線。這會讓你對我們預計何時獲得 10 億美元到 10 億美元有一個很好的了解。根據喬恩剛才所說的，還需要幾年的時間。推動這個市場需要一段時間。但我們在前瞻性市場研究中看到的一切以及我們在董事會上公佈的結果，都讓我們對實現這一目標充滿信心。

Yes, that line crosses $1 billion around the turn of the decade. And remember, we have patent protection out to 2039. So we've got almost another 10 years of protection at peak, so that's real value.

是的，這個界限在本世紀初就突破了 10 億美元。請記住，我們的專利保護期到 2039 年。因此，我們在高峰期也獲得了近 10 年的保護期，因此這是真正的價值。

Our next question comes from Chris Raymond with Piper Sandler.

我們的下一個問題來自克里斯·雷蒙德和派珀·桑德勒。

This is Nicole Gabreski on for Chris. Maybe just around the 10013 program, I know you guys are going to evaluate a higher dose in healthy volunteers. I guess, just any color around maybe how that translates to the dose in preclinical models where you observe the chronic tox in all? And then just to clarify, I guess, have the chronic tox experiments been completed at this point?

我是克里斯的妮可·加布雷斯基。也許就在 10013 計畫前後，我知道你們將在健康志工中評估更高的劑量。我想，任何顏色都可能如何轉化為臨床前模型中觀察慢性毒性的劑量？然後我想澄清一下，慢性毒性實驗現在已經完成了嗎？

Yes. So I'm going to take those in reverse order. In terms of the chronic tox, we had a chronic tox program. It's still ongoing, and we don't expect that to complete until later in the year. In terms of the information and translating that to effect, what we really -- what we know is from healthy volunteers where we see that the clinical -- the complement pathway is inhibited to greater than 97% at 110 milligrams, and we need to go into patients. We'll do that with our patient trial in PNH to assess further information around complement inhibition at that in dose escalating as well as then how that translates into clinical outcomes so that we can confirm the dose.

是的。所以我將以相反的順序處理。就慢性毒素而言，我們有一個慢性毒素計劃。它仍在進行中，我們預計要到今年晚些時候才能完成。就資訊並將其轉化為效果而言，我們真正知道的是來自健康志願者，我們在臨床上看到補體途徑在 110 毫克時被抑製到 97% 以上，我們需要去進入患者體內。我們將透過 PNH 中的患者試驗來評估有關劑量遞增時補體抑制的進一步信息，以及如何將其轉化為臨床結果，以便我們可以確認劑量。

But I think -- at the end of the day, Nicole, it's all about what do we see in humans. And do we have a safe and effective dose that's once a day. So that's the whole point behind that trial.

但我認為，妮可，歸根結底，這一切都與我們在人類身上看到的東西有關。我們是否有安全有效的每天一次的劑量？這就是該審判背後的全部意義。

Yes. Got it. And then just really quick. I know last quarter, there were some unanticipated headwinds with the lack of funding from some of the external charities helping to provide co-pay for patients on ORLADEYO. I guess where does that situation stand currently?

是的。知道了。然後很快。我知道上個季度，由於一些外部慈善機構缺乏資金來幫助為 ORLADEYO 患者提供自付費用，因此出現了一些意想不到的阻力。我想目前的情況是怎麼樣的呢？

So the situation has stabilized. So we are not losing more patients or having patients having to drop back to free product since the first quarter. Those that we did put on long-term free product in the first quarter have to stay on it for the rest of this year. But for now, the situation is stabilized.

於是局勢就穩定下來了。因此，自第一季以來，我們並沒有失去更多患者，也沒有讓患者不得不重新使用免費產品。那些我們在第一季提供長期免費產品的產品必須在今年剩餘時間內繼續使用。但目前，局勢已經穩定。

Yes. And I'd just make one big for Charlie and his team. Despite that, they're making great traction -- having great traction and converting patients from free product to paid. As he said, it was at 34%, and now it's down to 30%. And my expectation, I think Charlie's as well is that, that's going to continue to go down.

是的。我只想為查理和他的團隊做一件大事。儘管如此，它們還是產生了巨大的吸引力——具有巨大的吸引力，並將患者從免費產品轉變為付費產品。正如他所說，之前是34%，現在已經下降到30%了。我的期望，我想查理也是如此，這將繼續下降。

Our next question comes from Stacy Ku with TD Cowen.

我們的下一個問題來自 Stacy Ku 和 TD Cowen。

We have a few follow-ups. So first, regarding 10013 additional cohort. Was this a request from the FDA or just the next natural step in your development for this program? And then regarding the potential range of doses for the global PNH study, willing to provide some details there. And I know you've discussed data next year, but their potential to get a sense of the safety profile any earlier? So those are our questions on kind of the pipeline. And then, regarding ORLADEYO, I know you've in the past not discussed exactly the size of the sales force, but now that you've increased it in Q4. Could you just talk about the relative sizing versus other competitors like Takeda as you think about expanding potential efforts in maybe community settings and clinicians that really only treat the patients?

我們有一些後續行動。首先，關於 10013 個額外隊列。這是 FDA 的要求還是只是您開發該專案的下一個自然步驟？然後關於全球 PNH 研究的潛在劑量範圍，願意提供一些細節。我知道你們已經討論了明年的數據，但它們是否有可能更早地了解安全狀況？這些是我們關於管道類型的問題。然後，關於 ORLADEYO，我知道您過去沒有具體討論過銷售團隊的規模，但現在您在第四季度增加了銷售隊伍的規模。當您考慮在社區環境和真正只治療患者的臨床醫生中擴大潛在努力時，您能否談談與武田等其他競爭對手相比的相對規模？

So Helen, do you want to take the 10013 and Charlie, you can take the sales force.

海倫，你想接 10013 嗎？查理，你可以接銷售人員。

Yes. So 10013, the dose that we're adding -- the healthy volunteer trial, the 160 milligrams, that is for our own purposes, that is -- so that we can assess, mostly PK from that dose level and build it into our PK model. We'll need that once we have our patient data in order to confirm the final dose for pivotal trial initiation. And so that's why we're adding that dose level. In terms of the range of doses then that we're looking in the PNH trial, we'll be starting at 80 milligrams and dosing up from there. What we're looking for is complement activity. We're looking for that to be -- looking at that for multiple doses and in the disease state. We're also looking then for clinical outcomes, and we're trying to assess then for safety, but more importantly, for efficacy that in the PNH, in the population setting will be in clinical outcomes like looking at hemoglobin and LDH.

是的。所以 10013，我們添加的劑量 - 健康志願者試驗，160 毫克，這是為了我們自己的目的 - 這樣我們就可以評估該劑量水平的主要 PK 並將其納入我們的 PK模型。一旦我們獲得了患者數據，我們就需要它來確認關鍵試驗啟動的最終劑量。這就是我們增加劑量水平的原因。就我們在 PNH 試驗中研究的劑量範圍而言，我們將從 80 毫克開始，然後逐漸增加劑量。我們正在尋找的是補體活動。我們正在尋找這一點——研究多次劑量和疾病狀態的情況。然後我們也在尋找臨床結果，我們正在嘗試評估安全性，但更重要的是，在 PNH 中、在人群環境中的功效將在臨床結果中，例如觀察血紅蛋白和 LDH。

And Helen, it might be good to just talk about roughly how many patients do you think we need for that study to get a sense of that? And how long do we need to follow those patients to get a sense of the safety, at least, in this initial study.

海倫，最好談談您認為這項研究需要多少患者才能了解這一點？至少在這項初步研究中，我們需要追蹤這些患者多長時間才能了解安全性。

Yes. So that's a small study, and we don't need many patients, and that's one of the reasons to assess complement inhibitor in patients with PNH. You can dose escalate and we will be doing that within individual patients, and each one will be giving us information on then how that patient's complement system is affected and their own clinical outcomes and dose escalating with that information. So not very many patients, small trial. In terms of the safety information, we'll be looking at that as we dose up as well. And so we'll have, again, in individual patients the ability to observe safety across a range of doses.

是的。所以這是一項小型研究，我們不需要很多患者，這也是評估 PNH 患者補體抑制劑的原因之一。您可以增加劑量，我們將在個別患者中進行這種操作，每個患者都會向我們提供有關該患者的補體系統如何受到影響的信息以及他們自己的臨床結果和使用該信息進行劑量升級的信息。所以患者不是很多，小規模試驗。就安全資訊而言，我們也會在劑量增加時關注這一點。因此，我們將再次能夠在個別患者中觀察一系列劑量的安全性。

In 3 months, 6 months, 10 to 15 patients, roughly.

3個月、6個月，大概有10到15名患者。

Yes. That's pretty small, and it's 4 to 12 weeks to have a first outcome.

是的。這個時間很小，需要 4 到 12 週才能得到第一個結果。

Great.

偉大的。

And then on the sizing of the sales force, what I've said before is that our teams between kind of right in the midpoint between 30 and 50 people. I've never said the exact number. But at the beginning of the year, we did add a few sales territories. The biggest thing, though, that we did is double the number of our regions. So it gave our regional managers or regional directors more time to spend with their teams and with key customers. When we build our sales force, the #1 thing we look at is the market potential in terms of HAE prescribers out there. And so we build it on a workload basis for each sales reps so they can be efficient. But we also do look at what best we can tell what the competition is doing, and we think that our team is sized very comparably to them.

然後關於銷售團隊的規模，我之前說過我們的團隊人數介於 30 到 50 人之間。我從來沒有說過確切的數字。但在今年年初，我們確實增加了一些銷售區域。不過，我們所做的最重要的事情是將我們的區域數量增加了一倍。因此，這讓我們的區域經理或區域總監有更多的時間與他們的團隊和主要客戶相處。當我們建立銷售團隊時，我們首先關注的是 HAE 處方者的市場潛力。因此，我們根據每個銷售代表的工作量來建立它，以便他們能夠有效地工作。但我們也會考慮我們能最好地了解競爭對手在做什麼，我們認為我們的團隊規模與他們非常相似。

And Charlie, it's not just the rep, right? What we hear from docs is that they see somebody from BioCryst every week. And so you might want to just talk about the whole team that.

查理，這不僅僅是代表，對吧？我們從醫生那裡聽到的是，他們每週都會見到來自 BioCryst 的人。所以你可能只想談論整個團隊。

So simultaneously, what we do is we have a market access team out in the field. So we've built up that team. We've expanded our patient services team, so that they work closely with patients, but also with the practices. And then, of course, on our medical side, we've got a very excellent medical team out there working to educate physicians. So we look at the whole package. And as we do our...

因此，同時，我們所做的就是在現場建立一個市場准入團隊。所以我們已經建立了這個團隊。我們擴大了患者服務團隊，以便他們與患者以及診所密切合作。當然，在我們的醫療方面，我們擁有一支非常優秀的醫療團隊，致力於教育醫生。所以我們看看整個包。當我們做我們的...

Market research.

市場調查。

Yes, we get feedback that they're seeing BioCryst people the most frequently.

是的，我們得到的回饋是他們最常見到 BioCryst 人員。

Our next question comes from Brian Abrahams with RBC.

我們的下一個問題來自加拿大皇家銀行 (RBC) 的布萊恩亞伯拉罕 (Brian Abrahams)。

This is Nevin on for Brian. Congrats again on a good quarter. So I have a couple of questions about how the efforts that you guys are taking to convert free drug patients to pay drug. Can you talk about some of the efforts there in regards to patient education, simplification of some of the paperwork that's been mentioned on previous calls. And then also if you could speak to some of the gross to net trends in the quarter and some of the recovery into future quarters as well.

這是布萊恩的內文。再次恭喜季度表現良好。所以我有幾個問題，關於你們如何努力將免費吸毒患者轉變為付費藥物。您能否談談在患者教育、簡化先前電話中提到的一些文書工作方面所做的一些努力。然後，您是否可以談談本季的一些毛淨趨勢以及未來幾季的一些復甦。

Sure. Yes. On the conversion from free drug to paid drug, the place where we've made the most progress is within the commercially insured market, which is the largest portion of our business, a little over 60%. And the #1 thing as you're alluding to is, is making sure that we are working with customers to get all the complete paperwork. So what that means is for a new prescription coming in, that the start form is complete. We've got the lab test. We've got the clinical background and justification. If we get that all complete upfront, the insurer is much more likely to approve the claim.

當然。是的。在從免費藥品轉變為付費藥品的過程中，我們取得最大進展的是商業保險市場，這是我們業務的最大部分，略高於60%。正如您所提到的，第一件事是確保我們與客戶合作以獲得所有完整的文書工作。因此，這意味著對於新處方的到來，起始表格已完成。我們已經進行了實驗室測試。我們已經掌握了臨床背景和理由。如果我們預先完成所有這些工作，保險公司就更有可能批准索賠。

Likewise, anyone who has been on free drug going back and doing a comprehensive appeal, letter of medical necessity, putting in the whole patient and family history is critical to the insurers changing their mind. And as our team is more and more focused on this and helping educate health care providers, in particular, we're seeing more success in getting people moved over to paid product.

同樣，任何接受過免費藥物的人都可以回去提交一份全面的上訴、醫療必要性信函、輸入整個患者和家族史，這對於保險公司改變主意至關重要。隨著我們的團隊越來越關注這一點，特別是幫助教育醫療保健提供者，我們看到在讓人們轉向付費產品方面取得了更多成功。

On the gross to net, gross to net, that's a part of what happens in the first quarter where revenue goes down a bit. One of those factors is that we take on our commercial side with our co-payment assistance program, the biggest hit happens in Q1, where many patients get up to the point of their out-of-pocket maximums are exhausted and then that normalizes in Q2 and for the rest of the year. So gross to net was, was as bad as it's ever going to be in Q1, and then it normalizes for the rest of the quarters.

就總淨額而言，總淨額而言，這是第一季收入略有下降的情況的一部分。其中一個因素是，我們透過共同支付援助計劃來承擔商業方面的責任，最大的打擊發生在第一季度，許多患者的自付費用已經耗盡，然後這種情況在第一季度恢復正常。第二季度以及今年剩餘時間。因此，毛淨值是第一季有史以來最糟糕的，然後在剩下的季度中恢復正常。

Yes. And to (inaudible), what we said in Q1 that it was at the higher end of that 15% to 20% range, and we had expected that in Q2, it would come into the lower end of that range and then maintain that throughout the year, and that's exactly what we saw happen.

是的。對於（聽不清楚），我們在第一季度說過，它處於 15% 到 20% 範圍的高端，我們預計在第二季度，它將進入該範圍的下端，然後在整個過程中保持這一水平那一年，這正是我們所看到的情況。

Okay. And then if I could also ask about the retention rate of patients who are on the drug. You had mentioned that the same number of patients who dropped up despite the higher, I guess, the higher denominator there. And so what do -- are those retention rates? And in regards to the retention rates, are they kind of the same in the U.S. and ex U.S.? Or are you seeing any difference within what those rates look like in those geographies?

好的。然後我是否還可以詢問服用該藥物的患者的保留率。你曾提到，儘管分母較高，但放棄治療的患者數量相同。那麼，這些保留率是什麼呢？至於保留率，美國和美國以外的地區是否相同？或者您發現這些地區的費率有任何差異？

Yes. Great question. So what we're seeing at this point, we've got a lot of history now that gives us confidence in saying this is that the pattern of discontinuation is very consistent. So when a patient starts in the U.S., a patient starts on therapy, about 60% of them make it to 1 year, and then we lose very few people after a year. And so what that means in the U.S. market is every month as we're getting a consistent number of patients coming on to product, we can predict how many people are going to drop off and our base is growing. So the absolute discontinuation rate as a proportion of our base keeps going down.

是的。很好的問題。因此，我們目前所看到的，我們現在有很多歷史記錄，這讓我們有信心地說，停產模式是非常一致的。因此，當患者在美國開始接受治療時，大約 60% 的患者能堅持到 1 年，一年後我們就失去了少數的患者。因此，這在美國市場意味著，隨著每個月都有一定數量的患者開始使用產品，我們可以預測有多少人會放棄，而我們的基數正在成長。因此，絕對停藥率占我們基數的比例不斷下降。

Ex U.S., we're seeing the same pattern of when people discontinue, but actually, the overall retention rate is -- has been better. And we think a lot of that has to do with just the -- in Europe, you tend to have larger HAE treatment centers where the health care providers are very focused on their patients and may be just generally providing better education.

在美國，我們看到了人們停止使用的相同模式，但實際上，整體保留率更好。我們認為這很大程度上與歐洲有較大的 HAE 治療中心有關，那裡的醫療保健提供者非常關注他們的患者，並且可能只是提供更好的教育。

Overall, the key to retention is, and we're very focused on this, is setting expectations with patients so that they know what to expect in those first few months of therapy. And if they hit any bumps, then they don't panic and drop off therapy. And we've seen that, that has been very effective. And I think that's why we've got the stable pattern that we're seeing now.

總的來說，保留的關鍵是，我們非常關注這一點，是為患者設定期望，以便他們知道在治療的最初幾個月會發生什麼。如果他們遇到任何障礙，他們不會驚慌並放棄治療。我們已經看到，這非常有效。我認為這就是我們現在看到的穩定模式的原因。

Our next question comes from Jon Wolleben with JMP Securities.

我們的下一個問題來自 JMP 證券的 Jon Wolleben。

On the free truck dynamic, Charlie, you mentioned the goal to get to at least 20% or less on free drug. Wondering when you think that could happen. And then with the guidance for the second half of the year, with steady revenues between 3Q, 4Q, should we expect any movement on the free drug status in the back half of the year, if you're seeing steady patient adds in steady revenue, it seems like that should be stable? But Wondering if you could talk a little bit about those 2 points.

關於免費卡車的動態，查理，您提到了免費毒品至少達到 20% 或更少的目標。想知道您何時認為這可能發生。然後根據下半年的指導，在第三季、第四季之間收入穩定，如果您看到穩定的患者增加了穩定的收入，我們是否應該預期下半年免費藥物狀態會出現任何變化，看起來應該是穩定的吧？但想知道您是否可以談談這兩點。

Sure. Yes. So kind of the second question. Yes, we expect to make just continued incremental progress in the second half of the year, getting people to paid drug, it will contribute, but I think the patient growth is really what's going to drive our sales growth the second half of the year. As far as when do we expect to get to the 20% or better, it's going to take a few years to get there. But the early -- we guys are really focused on this, what we're seeing in the last few months is new patients starting on therapy are already getting to an 80% plus paid rate. And so that gives us that confidence that over time, we're going to be able to get everyone there. So I think it's the team focused, our patient services team, our market access team, our sales team working to educate patients and health care providers about this and to continue to work with payers, that's -- all of that together is what's making the difference.

當然。是的。這是第二個問題。是的，我們預計下半年將取得持續的漸進進展，讓人們支付藥物費用，這將做出貢獻，但我認為患者的成長確實將推動我們下半年的銷售成長。至於我們預計什麼時候能達到 20% 或更好，需要幾年時間才能實現。但早期——我們真的很關注這一點，我們在過去幾個月看到的是，開始接受治療的新患者的付費率已經達到 80% 以上。這讓我們有信心，隨著時間的推移，我們將能夠讓每個人都到達那裡。因此，我認為這是以團隊為中心的，我們的患者服務團隊、我們的市場准入團隊、我們的銷售團隊致力於向患者和醫療保健提供者提供有關此方面的教育，並繼續與付款人合作，所有這些共同構成了不同之處。

Got it. And ex-U.S., you mentioned things are going well. Wondering if we should expect to see an acceleration at any point if there is a tipping point? Or is this going to be grind higher as well there? And maybe a little bit about if it's going to be certain countries contributing the most? Or is this going to be consistent geographic expansion driving the revenue ex-U.S.?

知道了。在美國以外，你提到事情進展順利。想知道如果存在臨界點，我們是否應該期望在任何時候都會看到加速？或者這也會在那裡磨得更高？也許還有一點關於是否某些國家會做出最大的貢獻？或者這會是持續的地域擴張推動美國以外地區的收入？

Yes. I wouldn't expect a tipping point or acceleration. We're really seeing the same pattern of patient growth. As we've talked about, it takes a good 4 patients ex-U.S. to add up to 1 U.S. patient just from a revenue perspective. We will keep add -- so the steady patient growth is the #1 thing we'll keep adding countries. So we expect next year to launch in our Wave 2 of Europe, so countries like Italy and Spain and Benelux. So we'll have those continued additions to our revenue stream, but I wouldn't expect a big inflection point. Steady growth.

是的。我預計不會出現臨界點或加速。我們確實看到了相同的患者成長模式。正如我們所討論的，需要 4 名來自美國以外的患者。僅從收入角度來看，就增加了 1 名美國患者。我們將繼續增加——因此，患者的穩定成長是我們將繼續增加國家的第一件事。因此，我們預計明年將在歐洲第二波市場推出，例如義大利、西班牙和比荷盧經濟聯盟等國家。因此，我們的收入流將持續增加，但我預計不會出現大的拐點。穩定的成長。

Our next question comes from Justin Kim with Oppenheimer & Co.

我們的下一個問題來自奧本海默公司的賈斯汀金 (Justin Kim)。

Maybe just a quick one first on the commercial. As you think about the additional data being accrued for PNH, can you just discuss how those results may inform IgAN? And whether you think the clinical bar might be lower in terms of the alternative pathway inhibition required perhaps due to the nature of the disease or competitive bar there? And then maybe on the commercial front, for Charlie, could you just update us on the mix of growth you're observing? Whether those patients being added are naive to prophylaxis or experience as well as coming from high prescribers for low-volume prescribers?

也許只是在廣告上先快速介紹一下。當您考慮 PNH 累積的額外數據時，您能否討論一下這些結果如何為 IgAN 提供資訊？您是否認為在所需的旁路途徑抑制方面臨床標準可能會較低，這可能是由於疾病的性質或那裡的競爭標準？然後，也許在商業方面，查理，您能否向我們介紹一下您觀察到的成長組合的最新情況？這些被加入的患者是否對預防或經驗缺乏了解，以及來自高處方量的低處方量患者？

Sure. So on the PNH question, what we need to understand next is the dose that gets us to efficacy. So we're looking for a safe dose that is effective, and that's measured by both the effect on the complement pathway and then the clinical outcomes. We're looking at that in PNH because that is an excellent opportunity to understand very quickly with a small number of patients, whether we're getting to rigorous complement inhibition and the clinical outcomes that translate. And we know what we need to see to demonstrate a dose that is achieving both.

當然。因此，關於 PNH 問題，我們接下來需要了解的是讓我們發揮功效的劑量。因此，我們正在尋找有效的安全劑量，並透過對補體途徑的影響和臨床結果來衡量。我們正在 PNH 中關注這一點，因為這是一個極好的機會，可以快速了解少數患者是否達到嚴格的補體抑制以及所轉化的臨床結果。我們知道我們需要看到什麼來證明劑量能夠同時實現這兩個目標。

We would expect that dose tend to translate to other diseases. And we're treating the PNH opportunity as one that we would assign. We would sort of achieve and understand the pivotal dose and then take that into IgAN and in other diseases. And we are -- as a reminder, we're looking for a differentiated drug to take forward. We're looking for safety and efficacy that's as good or better from what we're seeing in the field of complement inhibition and we're looking at that with once-daily dosing.

我們預期該劑量往往會轉化為其他疾病。我們將 PNH 機會視為我們將分配的機會。我們將獲得並了解關鍵劑量，然後將其應用於 IgAN 和其他疾病。提醒一下，我們正在尋找一種差異化藥物來前進。我們正在尋找與我們在補體抑制領域所看到的一樣好或更好的安全性和有效性，我們正在透過每日一次給藥來研究這一點。

And that's what others have done in the field with alternative pathway inhibitors. So this is a new ground.

這就是其他人在替代途徑抑制劑領域所做的事情。所以這是一個新天地。

And then on the patient and prescriber mix, Justin, again, the story is consistent patterns. So still about 50% of the patients are coming from other prophylaxis products. And the other 50%, at least best we can tell, we're not recently on a prophylaxis product or were completely prophy-naive. So it's great to see that consistency. And then on the prescriber mix, we get a little more than half of our prescriptions from those top 500 doctors that I've talked about, the ones who treat about 50% of the market, and then we get a little less than half from the larger group of other physicians. And what's great is that every quarter, we're seeing a very consistent number of new ORLADEYO prescribers being added. So we continue to go broader into the prescriber market and then deeper within existing prescribers.

然後，關於患者和處方者的混合，賈斯汀再次強調，故事的模式是一致的。因此仍有約 50% 的患者來自其他預防產品。而另外 50%，至少我們可以說，我們最近沒有使用預防產品，或完全沒有預防過。所以很高興看到這種一致性。然後在處方者組合方面，我們的處方有一半以上來自我談到的前 500 名醫生，他們治療了大約 50% 的市場，然後我們從較大的其他醫生群體。令人高興的是，每季我們都會看到新增的奧拉德約處方者數量非常穩定。因此，我們繼續更廣泛地進入處方者市場，然後深入現有處方者。

(Operator Instructions)

（操作員說明）

Our next question comes from Serge Belanger with Needham Co.

我們的下一個問題來自 Needham Co. 的 Serge Belanger。

A lot of questions have been asked at this point. So maybe a couple around the HAEA summit that was held recently. Maybe just talk about the level of awareness of ORLADEYO within the patients that you met there. And whether you've seen you've experienced any tailwinds from attending the meeting, maybe some additional enrollment in the Quick Start program.

此時已經提出了許多問題。也許是最近舉行的 HAEA 峰會上的一對夫婦。也許只是談談您在那裡遇到的患者對 ORLADEYO 的認識程度。無論您是否因參加會議而經歷任何順風順水，也許在快速啟動計劃中獲得了一些額外的註冊。

Yes, Serge. As Jon said earlier, we did -- first of all, we had a big presence there, and this is our first time attending since we've launched ORLADEYO. And we had a booth there, we actually had 2 booths, both a branded and an unbranded booth. A lot of patient traffic coming through our booth, a lot of great conversations. And it's always a little frustrated what a patient says, "Oh, is this drug launched?" But we did hear that. And so it's great. Now they know ORLADEYO is on the market. And as we said, 1,200 patients and family members they all left knowing that ORLADEYO is on the market. So what we're telling are health care providers out there is that this conference just happened, and they may be getting patients coming in and asking different questions about their therapy and that ORLADEYO is -- they may have questions about ORLADEYO. So we'll see if we get a tailwind, but it was definitely an important milestone, and it was great to see the community again and just to see their excitement of just them getting together. Again, it was a really great meeting.

是的，塞爾日。正如喬恩之前所說，我們做到了——首先，我們在那裡有很大的影響力，這是我們自推出 ORLADEYO 以來第一次參加。我們在那裡有一個展位，實際上我們有 2 個展位，一個是品牌展位，一個是非品牌展位。很多病人湧入我們的展位，進行了許多精彩的對話。當病人說「哦，這個藥上市了嗎？」時，總是有點沮喪。但我們確實聽到了。所以這很棒。現在他們知道 ORLADEYO 已上市。正如我們所說，1,200 名患者及其家屬都知道 ORLADEYO 已上市。因此，我們告訴醫療保健提供者的是，這次會議剛剛召開，他們可能會讓患者進來並詢問有關他們的治療的不同問題，而奧拉德約 - 他們可能對奧拉德約有疑問。所以我們會看看是否能順風順水，但這絕對是一個重要的里程碑，很高興再次見到社區，看到他們聚在一起的興奮。再說一次，這真是一次很棒的會議。

I think, too, it's like the first of what I hope will be a bunch of patient meetings regionally, all that stuff stopped with COVID. And so a certain state or certain part of the country, they gather. And I think the other thing is people reconnected it's like watching a family reunion, honestly, and the word of mouth spread. Because we got an equal number of people that came up to and I was like, "Oh my God, ORLADEYO has changed my life." And let me explain to you why. And so when they're talking to other patients about that. I think that's going to be helpful too. And then the last piece was the KOLs are there as well. And it's just a different dynamic at a patient meeting than when you go to the college meeting or (inaudible) and so we're able to show up in a way that differentiates us maybe from our competition. And I think it's a chance to really reinforce and connect with the KOLs in a way that maybe is harder in other settings. So it was fantastic.

我也認為，這就像我所希望的第一次區域性耐心會議，所有這些事情都隨著新冠疫情而停止了。因此，他們聚集在某個州或國家的某個地區。我認為另一件事是人們重新建立了聯繫，老實說，就像觀看家庭聚會一樣，並且口碑傳播。因為我們有同樣數量的人過來，我當時想，“天哪，奧拉德約改變了我的生活。”讓我向您解釋原因。所以當他們與其他患者談論這個問題時。我認為這也會有幫助。最後一點是 KOL 也在那裡。這只是病人會議上的動態與你去大學會議或（聽不清楚）時的動態不同，因此我們能夠以一種可能使我們從競爭對手中脫穎而出的方式出現。我認為這是一個真正加強與 KOL 聯繫的機會，而這種方式在其他環境中可能更難。所以這太棒了。

Our next question comes from [Gena Huidong Wang] with Barclays.

我們的下一個問題來自巴克萊銀行的[Gena Huidong Wang]。

Sorry, I think this is Tony on for Gena Wang. Another quick one question kind of on 10013. What initial data would warrant potentially for the development? And what could we maybe expect to see at R&D Day on this or even other new pipeline assets?

抱歉，我想這是托尼（Tony）為吉娜·王（Gena Wang）代言的。另一個關於 10013 的快速問題。哪些初始資料有可能為開發提供保證？我們可以期望在研發日看到這個甚至其他新管道資產的什麼？

Yes. Okay. So with 10013, we are looking for something that's really quite straightforward, and I think we'll be quite clear data to show that we're seeing the activity levels we need to see and the clinical outcomes that we're looking for in patients. And we're looking for that in a manner that's also safe. So it's fairly simple. We're looking for safety and efficacy that's as good or better than what is available to patients. And we're looking for that then with once daily dosing. Once we see that and have selected the dose per program, that's the point at which we would be making the decision to further invest in state pivotal trials.

是的。好的。因此，對於 10013，我們正在尋找非常簡單的東西，我認為我們將提供非常清晰的數據來表明我們正在看到我們需要看到的活動水平以及我們在患者中尋找的臨床結果。我們正在以一種安全的方式尋找這一點。所以相當簡單。我們正在尋找與患者可用的產品一樣好或更好的安全性和有效性。我們正在透過每天一次的給藥來尋找這一點。一旦我們看到這一點並選擇了每個項目的劑量，我們就會決定進一步投資州關鍵試驗。

In terms of R&D Day, we'll update across the pipeline there. We have a number of things that we've been working on, and I'm really excited and pleased with what's been happening in the discovery and early programs in Birmingham and within the company. So it's sort of breadth and depth of the pipeline that we'll be discussing there.

在研發日方面，我們將在那裡進行更新。我們一直在做很多事情，我對伯明翰和公司內部的發現和早期專案所發生的事情感到非常興奮和高興。因此，我們將在那裡討論管道的廣度和深度。

Yes. I thought there'll be any new information on 10013. At that point, this will be stuff you've not heard of before.

是的。我以為10013會有新的資訊。到那時，這將是你以前沒有聽說過的東西。

Okay. Got it. Very helpful. And then I guess another quick one on ORLADEYO launch. I know there's been a lot of questions already. What -- is there anything that could lead to sales kind of exceeding guidance for $320 million either in terms of the retention rate or new patients or patient switching?

好的。知道了。很有幫助。然後我猜想還有一個關於 ORLADEYO 發射的快速事件。我知道已經有很多問題了。就保留率、新患者或患者轉換而言，有什麼可能導致銷售額超過 3.2 億美元的指導嗎？

We're really confident in the $320 million number. And based on what we're seeing, I think that's what you should expect for this year. So consistent patient growth, incremental progress on getting patients over to paid therapy. And that same pattern that I described earlier about patient retention to get us to $310 million. And then the continued growth outside of the U.S., that's what will get us to the $320 million.

我們對 3.2 億美元的數字非常有信心。根據我們所看到的情況，我認為這就是您今年應該期待的情況。患者持續​​成長，在讓患者接受付費治療方面取得了漸進的進展。與我之前描述的關於患者保留的模式相同，我們的收入達到了 3.1 億美元。然後是美國以外地區的持續成長，這將使我們的銷售額達到 3.2 億美元。

Our final question comes from Maury Raycroft with Jefferies.

我們的最後一個問題來自傑弗里斯的莫里·雷克羅夫特。

This is Yan for Maury. Congrats on a good quarter. I guess our first question is on the Q2 revenue growth, you're saying for the rest of the year, the revenue growth is going to be more steady. From last year, we saw there was a bit of confounding factor from the 4th July holiday ordering that affected the relative growth rate of Q3 and Q4. How should we think about the effect this year?

這是 Maury 的 Yan。恭喜季度表現良好。我想我們的第一個問題是關於第二季的營收成長，你說今年剩餘時間裡，營收成長將更加穩定。從去年開始，我們發現 7 月 4 日假期訂單存在一些混雜因素，影響了第三季和第四季的相對成長率。我們該如何看待今年的影響？

Yes. So Q3 and Q4 will not be as big a jump in revenue as Q2. Because Q2 was driven by the patient growth, but also all the factors coming out of the Q1 reauthorization process. So as Anthony described in his comments, we should average about 85.5% for the -- a little bit less than that in Q3, a little bit more in Q4 to get to the $320 million. For the July 4. Yes, so July 4 was on a Tuesday this year. So there was a day or 2 of shipments that came into June, and that was part of our expectation this year. We saw that happen last year, and so we built that into our plan. And just as a reminder for everyone, in the U.S., we have a sole-source specialty pharmacy. So this is all based on individual patient demand. And there are a lot of those patients going away for the 4th of July holiday. And so around times like that, you will see a little bit of a pull forward, but it's usually just a day or 2 of shipments.

是的。所以第三季和第四季的營收增幅不會像第二季那麼大。因為第二季度是由患者成長推動的，也是第一季重新授權過程中產生的所有因素的推動因素。因此，正如安東尼在他的評論中所描述的那樣，我們應該平均為 85.5% 左右——比第三季度少一點，第四季度多一點，才能達到 3.2 億美元。 7 月 4 日。是的，所以今年 7 月 4 日是星期二。因此，六月有一兩天的出貨，這是我們今年預期的一部分。我們去年就看到了這種情況，所以我們將其納入我們的計劃中。提醒大家的是，在美國，我們有一家獨家專業藥局。所以這一切都是根據患者的個人需求而定。 7 月 4 日假期期間，有許多患者外出度假。因此，在這樣的時期，您會看到一點點的提前，但通常只是一兩天的發貨。

I see. Maybe just a quick one on C1 normal patients. We saw some data on ORLADEYO successfully managing C1 normal patients early this year in [Yachi]. I'm just wondering if you're sharing any insights into how you're seeing real-world how patients with C1 normal profile, like how many of them are on a therapy? If you see anything about retention rate and et cetera?

我懂了。也許只是針對 C1 正常患者的快速治療。今年年初，我們在[Yachi]看到了 ORLADEYO 成功治療 C1 正常患者的一些數據。我只是想知道您是否正在分享您如何看待現實世界中 C1 正常的患者的見解，例如其中有多少人正在接受治療？您是否看到有關保留率等的資訊？

Yes. We haven't shared the number other than what you saw in the [Yachi] poster in terms of the proportion of our business. But we do get C1 normal patients. I think all the prophylaxis products are seeing C1 normal patients. These are patients who have really struggled for a number of years. It's been -- their diagnosis isn't as clear cut as Type 1 and Type 2. And so they've looked for therapies that work and what we're seeing for a lot of them is that ORLADEYO is really helping them. And so we're seeing consistent reduction in attack rates in patient-reported attack rates. And then from a retention perspective, we're seeing just about as good retention with C1 normal patients as we are with Type 1 and Type 2 patients. And so we -- you can expect more data from us on this in the future. But right now, what we're seeing is we're very pleased and just glad that we can help these patients.

是的。除了您在[Yachi]海報中看到的關於我們業務的比例之外，我們還沒有分享過其他數字。但我們確實有 C1 正常的患者。我認為所有的預防產品都是針對 C1 正常患者的。這些患者多年來一直在與病魔作鬥爭。他們的診斷並不像 1 型和 2 型那樣明確。因此，他們一直在尋找有效的療法，而我們對他們中的許多人來說，ORLADEYO 確實在幫助他們。因此，我們看到患者報告的發病率持續下降。然後從保留的角度來看，我們發現 C1 正常患者的保留率與 1 型和 2 型患者的保留率幾乎一樣好。因此，您可以期待我們將來提供更多這方面的數據。但現在，我們看到的是我們非常高興並且很高興我們能夠幫助這些患者。

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

我們的問答環節到此結束，會議就此結束。感謝您參加今天的演講。您現在可以斷開連線。