BioCryst Pharmaceuticals Inc (BCRX) 2023 Q1 法說會逐字稿

Good morning, and welcome to the BioCryst Q1 2023 Earnings Conference Call. (Operator Instructions) Please note this event is being recorded.

早上好，歡迎參加 BioCryst 2023 年第一季度收益電話會議。 （操作員說明）請注意此事件正在被記錄。

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

我現在想把會議交給 BioCryst 的 John Bluth。請繼續。

Thank you very much. Good morning, and welcome to BioCryst's First Quarter 2023 Corporate Update and Financial Results Conference Call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO, Jon Stonehouse; CFO, Anthony Doyle; Chief Commercial Officer, Charlie Gayer; and Chief R&D Officer, Dr. Helen Thackray. Following our remarks, we'll answer your questions.

非常感謝。早上好，歡迎參加 BioCryst 2023 年第一季度公司更新和財務業績電話會議。今天的新聞稿和隨附的幻燈片可在我們的網站上獲取。今天和我一起參加的是首席執行官喬恩·斯通豪斯 (Jon Stonehouse)；首席財務官安東尼·道爾；首席商務官查理·蓋爾；首席研發官 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 statements regarding future results, unaudited and forward-looking financial information as well as the company's future performance and/or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward-looking statements. For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

在我們開始之前，請注意，今天的電話會議將包含前瞻性聲明，包括有關未來業績、未經審計和前瞻性財務信息以及公司未來業績和/或成就的聲明。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、業績或成就與本演示文稿中明示或暗示的任何未來結果或業績存在重大差異。您不應過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。

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.

謝謝，約翰。

The launch of ORLADEYO remains very strong, now entering the third year. Charlie will share the details. And when you hear the total number of patients on therapy and the growth rates of adding new patients, both year-over-year and quarter-over-quarter. You should understand why we remain very confident in our guidance of no less than $320 million this year and $1 billion at peak. The large base of patients on therapy and the consistent number of new patient starts each quarter reflect a steady upward trajectory and this is just the beginning as there's so many more patients yet to try ORLADEYO. We have a once-a-day therapy in an injectable marketplace. It makes sense that more and more patients are wanting to try it and many see great benefit and tell us it's changed their lives.

ORLADEYO 的推出仍然非常強勁，現已進入第三個年頭。查理將分享細節。當您聽到接受治療的患者總數以及新增患者的增長率（同比和季度環比）時。你應該明白為什麼我們對今年不少於 3.2 億美元和峰值 10 億美元的指導仍然非常有信心。接受治療的患者基數龐大，並且每個季度開始治療的新患者數量穩定，反映出穩定的上升軌跡，這只是一個開始，因為還有更多的患者尚未嘗試 ORLADEYO。我們在註射劑市場上有一種每日一次的療法。越來越多的患者想要嘗試它，許多人看到了巨大的好處並告訴我們它改變了他們的生活，這是有道理的。

Beyond this, we will continue to invest in ORLADEYO R&D to reach more patients and create even greater value. We will do this by adding more countries around the world where patients gain access to ORLADEYO and by expanding the label like we're doing with the pediatric program. We will also continue to invest wisely and find the next ORLADEYO through our pipeline and discovery efforts. Our goal is to find another rare disease target where we're able to bring a best-in-class medicine to patients while balancing the risk inherent in drug development.

除此之外，我們將繼續投資 ORLADEYO 研發，以惠及更多患者並創造更大價值。我們將通過在世界上更多國家/地區增加患者獲得 ORLADEYO 的機會，並像我們在兒科項目中所做的那樣擴大標籤來實現這一目標。我們還將繼續明智地投資，並通過我們的管道和發現工作尋找下一個 ORLADEYO。我們的目標是找到另一種罕見疾病靶點，為患者提供一流的藥物，同時平衡藥物開發固有的風險。

Lastly, we have improved our already strong financial position by the recent refinancing. This was hard to do in the current environment, but Anthony and team got us better terms on our debt and push the repayment out to a time where we should be much closer to peak sales. This dramatically reduces our dependence on the capital markets and allows us to focus on the execution of our plan by growing ORLADEYO and finding another molecule where we can repeat the ORLADEYO success. That will lead to adding real value today and even more value in the future for patients and shareholders.

最後，我們通過最近的再融資改善了本已強勁的財務狀況。在當前環境下這很難做到，但安東尼和團隊為我們提供了更好的債務條件，並將還款時間推遲到我們應該更接近銷售峰值的時間。這極大地減少了我們對資本市場的依賴，使我們能夠通過發展 ORLADEYO 並找到另一個可以重複 ORLADEYO 成功的分子來專注於執行我們的計劃。這將為患者和股東帶來今天的實際價值，甚至未來的更多價值。

Now I'll turn the call over to Anthony.

現在我將把電話轉給安東尼。

Thanks, Jon.

謝謝，喬恩。

Q1 was a great quarter for ORLADEYO, with revenue of $18.7 million plus 38% compared to Q1 of last year. Additionally, for us to see the kind of underlying patient growth that Jon mentioned, and to overcome the reauthorization headwinds with revenue just slightly below the prior quarter, gives us a lot of confidence as we move forward to what we believe will be a strong Q2 and onwards to our full year goal of no less than $320 million. 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.

第一季度對於 ORLADEYO 來說是一個出色的季度，收入為 1,870 萬美元，比去年第一季度增長了 38%。此外，對於我們來說，看到喬恩提到的那種潛在的患者增長，並克服重新授權的阻力，收入略低於上一季度，這給了我們很大的信心，因為我們相信第二季度將是強勁的並繼續實現不低於 3.2 億美元的全年目標。您可以在今天的收益新聞稿中找到我們詳細的第一季度財務數據，我想提請您注意一些項目。

Total revenue for the quarter came in at $68.8 million, $68.4 million of which came from ORLADEYO, putting our trailing 12-month revenue at over $270 million. We expect Q2 revenue to be strong, and we should see our 2023 quarterly rhythm play out similarly to prior year. We are making a change to our approach to revenue segmentation. Moving forward, we will segment our revenue into ORLADEYO and non-ORLADEYO revenue. And for ORLADEYO revenue, we will be segmenting into U.S. and ex-U.S. to that end of the $68.4 million of Global ORLADEYO revenue, $60.8 million came from U.S. sales with the remaining $7.6 million coming from ex-U.S. This ex-U.S. revenue represents approximately 11% of global sales for the quarter. And while this percentage for ex-U.S. is higher in Q1 than we expect for the remaining quarters of the year because of the gross to net headwinds in Q1 for the U.S. We do expect ex-U.S. revenues for 2023 to come in at or above 10% of the global total.

該季度的總收入為 6880 萬美元，其中 6840 萬美元來自 ORLADEYO，使我們過去 12 個月的收入超過 2.7 億美元。我們預計第二季度收入將強勁，並且我們應該會看到 2023 年的季度節奏與去年類似。我們正在改變收入細分的方法。展望未來，我們將把收入分為 ORLADEYO 和非 ORLADEYO 收入。對於 ORLADEYO 的收入，我們將分為美國和美國以外地區。到此結束，ORLADEYO 全球 6840 萬美元收入中，6080 萬美元來自美國銷售，其餘 760 萬美元來自美國以外地區。這個前美國收入約佔該季度全球銷售額的 11%。雖然這個百分比對於美國以外的地區來說由於美國第一季度的總淨值逆風，第一季度的增長率高於我們對今年剩餘季度的預期。到2023年，收入將達到或超過全球總收入的10%。

Operating expenses, not including noncash stock compensation for the quarter were approximately $83 million. This is a decrease of $7 million from Q1 of 2022 and down $27 million compared to Q4 of '22, most of which is in the R&D area due to reduced clinical investment following the termination and ongoing closeout of the 9930 program. We reiterate our full year OpEx guidance at $375 million, flat to prior year, as we continue to invest in maximizing the ORLADEYO launch globally and continuing to invest in R&D.

本季度的運營支出（不包括非現金股票補償）約為 8,300 萬美元。這比 2022 年第一季度減少了 700 萬美元，比 22 年第四季度減少了 2700 萬美元，其中大部分用於研發領域，因為 9930 項目終止和持續收尾後臨床投資減少。我們重申全年運營支出指引為 3.75 億美元，與上年持平，因為我們將繼續投資以最大限度地擴大 ORLADEYO 在全球的推出，並繼續投資於研發。

For R&D, we are investing mainly in 3 key areas: continuing to develop ORLADEYO by identifying opportunities to expand the label, such as the pediatric trial, while also continuing to invest in real-world evidence generation. Our oral Factor D program, 10013 continues to move forward to determine if we can get to a safe and effective dose with a potential once-daily best-in-class profile. And lastly, we continue to invest our discovery and early development capabilities with the goal of developing differentiated treatments in selected rare diseases.

在研發方面，我們主要投資於 3 個關鍵領域：通過尋找擴大標籤的機會（例如兒科試驗）來繼續開發 ORLADEYO，同時繼續投資於現實世界的證據生成。我們的口服因子 D 項目 10013 繼續向前推進，以確定我們是否能夠獲得安全有效的劑量，並具有潛在的每日一次最佳水平。最後，我們繼續投資我們的發現和早期開發能力，目標是針對選定的罕見疾病開發差異化治療方法。

Cash at the end of the first quarter was up $403 million following the debt refinance deal that we closed last month with Pharmakon, net proceeds of that deal bring pro forma cash up to $429 million.

在我們上個月與 Pharmakon 完成債務再融資交易後，第一季度末的現金增加了 4.03 億美元，該交易的淨收益使預計現金達到 4.29 億美元。

I think it's helpful to add some extra color around that deal and process. It was a very competitive process with more interested parties than any deal that we have done before. The strength of our execution throughout the launch of ORLADEYO [to date] and the belief in our plans to get to $1 billion at peak was the main driver for that interest, and it was great to secure such a strong deal and a lender of the caliber of Pharmakon.

我認為在交易和流程中添加一些額外的色彩是有幫助的。這是一個競爭非常激烈的過程，感興趣的各方比我們以前做過的任何交易都多。 [迄今為止]我們在 ORLADEYO 推出過程中的執行力以及對我們計劃在峰值時達到 10 億美元的信心是這種興趣的主要驅動力，能夠獲得如此強有力的交易並成為該項目的貸款人真是太棒了Pharmakon 的口徑。

This deal helped us to achieve a number of goals that we have set out in advance of the process. Firstly, and for me, most importantly, it enabled us to delay the bullet payment from 2025 to 2028, at which point we'll be much closer to ORLADEYO peaks out.

這筆交易幫助我們實現了在此過程之前設定的許多目標。首先，對我來說，最重要的是，它使我們能夠將一次性付款從 2025 年推遲到 2028 年，屆時我們將更接近 ORLADEYO 的頂峰。

Next, in a very tough environment, we were able to secure significantly reduced margins spread on the loan to much more competitive rates. Then we're able to pay interest in kind for 50% of the interest for the first 6 quarters, which preserves cash as that option had expired in our prior agreement with Athyrium. We also have the ability to draw an additional $150 million up to September of 2024. These funds are committed and the decision to draw them or not is ours. We will only draw the funds if we can generate value by doing so, but access to it gives us additional flexibility and continued optionality.

接下來，在非常艱難的環境中，我們能夠確保貸款利差大幅降低，利率更具競爭力。然後，我們能夠以實物形式支付前 6 個季度利息的 50%，這可以保留現金，因為我們之前與 Athyrium 達成的協議中該選項已到期。截至 2024 年 9 月，我們還有能力額外提取 1.5 億美元。這些資金已承諾，是否提取由我們決定。只有當我們能夠通過這樣做產生價值時，我們才會提取資金，但獲得資金給我們帶來了額外的靈活性和持續的選擇性。

Lastly, it significantly reduces our reliance on the capital equity markets. This is our third refinancing -- or third financing event in a row, not to be centered around equity. At current prices, the equity markets do not reflect what we believe to be the true value for risk. A company with a product on its way to $1 billion in peak sales, a discovery and development engine capable of bringing additional drugs to market behind it and a strong balance sheet. And so being able to use nonequity instruments is the best option for us.

最後，它大大減少了我們對資本股權市場的依賴。這是我們的第三次再融資，或者說是連續第三次融資活動，但不以股權為中心。按照目前的價格，股票市場並未反映我們認為的真實風險價值。該公司的產品銷售額即將達到 10 億美元峰值，其發現和開發引擎能夠將更多藥物推向市場，並且資產負債表強勁。因此，能夠使用非股權工具對我們來說是最好的選擇。

With this refinancing, growing ORLADEYO revenues and our continued disciplined approach to capital allocation, all moving us closer to profitability, we have the financial strength to allow us to unlock greater value for the company and for our shareholders.

通過這次再融資、不斷增長的 ORLADEYO 收入以及我們持續嚴格的資本配置方法，所有這些都使我們更接近盈利，我們擁有財務實力，可以為公司和股東釋放更大的價值。

And now I'll pass it over to Helen.

現在我將把它交給海倫。

Thanks, Anthony.

謝謝，安東尼。

The ORLADEYO launch is succeeding because we have delivered to patients a best-in-class oral once-daily medicine that is differentiated in the marketplace. We are making R&D investments both to reach more patients with ORLADEYO and to deliver our next best-in-class molecule to the market. This is the standard we have set with ORLADEYO, and our goal is to develop and commercialize more highly differentiated products for the treatment of rare disease.

ORLADEYO 的推出取得了成功，因為我們為患者提供了一種在市場上與眾不同的一流口服每日一次藥物。我們正在進行研發投資，既是為了接觸更多 ORLADEYO 患者，也是為了向市場提供我們的下一個同類最佳分子。這是我們與 ORLADEYO 制定的標準，我們的目標是開發和商業化更多高度差異化的產品，用於治療罕見疾病。

As we shared before, we are studying use ORLADEYO in children with HAE under the age of 12. We have initiated dosing in the pediatric registration trial. And in fact, we've had tremendous support and excitement for this pediatric program in the medical and patient communities. Enrollment is off to an excellent start in the initial dose groups, and we are pleased to be on our way to building the data set for the evaluation of ORLADEYO in children under 12 with HAE.

正如我們之前分享的，我們正在研究在 12 歲以下患有 HAE 的兒童中使用 ORLADEYO。我們已經在兒科註冊試驗中開始給藥。事實上，我們在醫療界和患者界對這個兒科項目給予了巨大的支持和興奮。初始劑量組的入組工作有一個良好的開端，我們很高興能夠建立數據集，用於評估 ORLADEYO 對 12 歲以下患有 HAE 的兒童的療效。

In complement-mediated disease, our once daily oral Factor D inhibitor, BCX10013 has an opportunity to be our next differentiated best-in-class molecule. While this program is still early and therefore has risk, if we succeed, it would bring a unique therapy with substantial benefit to patients. Also, in the complement system, we are investigating both single target and combined target approaches to address diseases mediated by any of the pathways, the classical, lectin alternative and terminal pathways of complement. This includes our oral C2 inhibitor program currently in lead optimization.

在補體介導的疾病中，我們每日一次的口服 D 因子抑製劑 BCX10013 有機會成為我們下一個差異化的同類最佳分子。雖然這個項目還處於早期階段，因此存在風險，但如果我們成功，它將帶來一種獨特的療法，給患者帶來巨大的好處。此外，在補體系統中，我們正在研究單靶點和組合靶點方法，以解決由補體的任何途徑、經典途徑、凝集素替代途徑和末端途徑介導的疾病。這包括我們目前正在進行先導化合物優化的口服 C2 抑製劑項目。

As we look at -- we are investing so we can deliver additional best-in-class medicines in the future for targets within the complement system as well as for other select rare diseases outside the complement system. Our approach is to bring multiple candidates and programs forward through discovery, spreading risk across an early pipeline with a variety of targets, modes of therapy and diseases. We are focusing our efforts where we believe our structural biology-based discovery capability provides an advantage so we can do what we do best: develop potent, selective and bioavailable molecules against difficult targets.

正如我們所看到的，我們正在進行投資，以便將來能夠為補體系統內的靶標以及補體系統外的其他特定罕見疾病提供更多一流的藥物。我們的方法是通過發現來推進多個候選者和項目，通過各種目標、治療模式和疾病在早期管道中分散風險。我們將重點放在我們相信基於結構生物學的發現能力提供優勢的領域，以便我們可以做我們最擅長的事情：開發針對困難目標的有效、選擇性和生物可利用的分子。

We look forward to sharing more detail on these additional programs at an R&D Day later this year or early next year. In the meantime, we continue to make disciplined investments in the compounds we believe can offer best-in-class differentiation just as we have done with ORLADEYO.

我們期待在今年晚些時候或明年初的研發日上分享有關這些附加項目的更多細節。與此同時，我們繼續對我們認為能夠提供一流差異化的化合物進行嚴格的投資，就像我們對 ORLADEYO 所做的那樣。

Now I'll turn the call over to Charlie.

現在我會把電話轉給查理。

Thanks, Helen.

謝謝，海倫。

The trajectory of the launch continued in Q1, keeping us on track for no less than $320 million in revenue this year. I'll provide more specific patient metrics today than I will in most updates because ORLADEYO has reached a significant milestone.

第一季度的推出繼續保持軌跡，使我們今年的收入有望不少於 3.2 億美元。今天我將提供比大多數更新中更具體的患者指標，因為 ORLADEYO 已經達到了一個重要的里程碑。

We recently surpassed 1,000 patients on active therapy in the U.S. after just over 2 years on the market. The number of U.S. patients taking ORLADEYO at the end of Q1 was up 46% over the same point in 2022 and up over 8% since the end of Q4. There's even more opportunity in front of us because most of the 7,500 U.S. patients have not yet tried ORLADEYO. The strong and steady growth that we are seeing gives us confidence that the majority of those remaining patients will try ORLADEYO by the time we reach peak sales.

上市僅兩年多後，我們最近在美國接受積極治療的患者數量已超過 1,000 名。第一季度末服用 ORLADEYO 的美國患者人數比 2022 年同期增加了 46%，自第四季度末以來增加了 8% 以上。我們面前還有更多機會，因為 7,500 名美國患者中的大多數尚未嘗試過 ORLADEYO。我們看到的強勁而穩定的增長讓我們相信，當我們達到銷售高峰時，大多數剩餘患者將嘗試 ORLADEYO。

Continued customer demand also supports our confidence. Our U.S. team got off to a great start this year with new prescriptions in Q1, up 20% year-over-year. We generally expect new starts in the first quarter to be softer because there is so much focus on payer reauthorizations, but Q1 starts were greater than 3 of the 4 quarters in 2022. Prescribing was again balanced across all deciles with about 50% of new starts coming from the top 500 physicians and patient retention remained consistent. We retain 60% of patients through their first year on treatment and lose very few patients after that.

客戶的持續需求也支撐著我們的信心。我們的美國團隊今年取得了良好的開端，第一季度的新處方數量同比增長 20%。我們通常預計第一季度的新開工量會較疲軟，因為人們非常關注付款人重新授權，但第一季度的開工量超過 2022 年 4 個季度中的 3 個季度。所有十分位數的處方數量再次達到平衡，新開工量的比例約為 50%來自排名前 500 名的醫生和患者保留率保持一致。我們在治療的第一年留住了 60% 的患者，之後流失的患者很少。

What this means is that we add many more patients than we lose each quarter, and we see this consistent growth pattern continuing for years to come.

這意味著我們每個季度新增的患者數量遠多於失去的患者數量，並且我們看到這種持續的增長模式將在未來幾年持續下去。

As expected, revenue was down slightly from Q4 because many patients moved temporarily to free product during Q1 reauthorizations and commercial patient copayment assistance and Medicare donut hole obligations are always larger in the first quarter of the year. I've commented before that the percentage of patients on free product, particularly long term, with our patient assistance program crept up in the second half of 2022. We are starting to reverse this trend through increased focus on high-quality prior authorization and appeal submissions, and we exceeded our Q1 goal for moving commercially insured patients who had been on long-term free product over to paid therapy.

正如預期的那樣，收入較第四季度略有下降，因為許多患者在第一季度重新授權期間暫時轉向免費產品，而商業患者共付援助和醫療保險甜甜圈義務在今年第一季度總是較大。我之前曾評論過，隨著我們的患者援助計劃在 2022 年下半年，使用免費產品的患者比例（尤其是長期患者的比例）逐漸上升。我們開始通過更加註重高質量的事先授權和上訴來扭轉這一趨勢我們超出了第一季度的目標，將長期使用免費產品的商業保險患者轉為付費治療。

As you've seen, we are reporting ex-U.S. revenues for the first time. The great majority of these sales in Q1 were from Europe where our initial launches are progressing well as physicians continue to move toward modern prophylaxis as the standard of care for patients with HAE. Once ORLADEYO gains access in international markets, we are seeing steady, consistent growth in patients on therapy, similar to the pattern in the U.S. We expect international markets will drive slightly over 10% of sales this year, and this early growth gives us confidence that ex-U.S. markets will account for about 20% of peak revenue.

正如您所看到的，我們正在報告美國以外的地區。首次實現收入。第一季度的大部分銷售額來自歐洲，我們的首次推出進展順利，醫生們繼續將現代預防作為 HAE 患者的護理標準。一旦 ORLADEYO 進入國際市場，我們就會看到接受治療的患者數量穩定、持續增長，與美國的模式類似。我們預計國際市場今年的銷售額將略高於 10%，這種早期增長讓我們有信心：美國以外市場收入將占峰值收入的20%左右。

Based on the strong demand and consistent growth we are seeing in the U.S. and globally, we remain confident that peak revenue for ORLADEYO will reach $1 billion.

基於我們在美國和全球看到的強勁需求和持續增長，我們仍然有信心 ORLADEYO 的峰值收入將達到 10 億美元。

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

現在，操作員，我們很高興開始問答。

(Operator Instructions) Our first question will come from Chris Raymond with Piper Sandler.

（操作員說明）我們的第一個問題將來自 Chris Raymond 和 Piper Sandler。

This is Ally Bratzel on for Chris. So first, just on the pipeline. Apologies if I missed this in the prepared remarks, but just what is the current status on the BCX10013 program? I think the latest update was chronic tox work is underway and should complete this year. But just curious if you had any other visibility on time lines or next steps towards the clinic?

我是艾麗·布拉澤爾 (Ally Bratzel) 替克里斯發言。首先，就在管道上。如果我在準備好的發言中遺漏了這一點，我深表歉意，但 BCX10013 計劃的當前狀態是什麼？我認為最新的更新是慢性毒物工作正在進行中，應該在今年完成。但只是好奇您是否對時間線或診所的後續步驟有任何其他了解？

Helen, do you want to take that?

海倫，你想接受這個嗎？

Yes, sure. Thanks for the question. There's not much to update at the moment. We are preparing to initiate a trial in patients with PNH and that's just as the ability to dose once-daily. So we're currently working through the regulatory process, and we'll have more on this later in the year.

是的，當然。謝謝你的提問。目前沒有太多可更新的內容。我們正準備在 PNH 患者中啟動一項試驗，即每天給藥一次的能力。因此，我們目前正在完成監管流程，今年晚些時候我們將有更多相關信息。

Great. And then I think you had discussed the opportunity for ORLADEYO in pediatric patients. Could you just remind us on the development path there? And just how we should think about the pace of enrollment and potential time line to sNDA's filing? I think clinical trials -- what's the primary completion date for that trial in mid-'25. But just curious if that's accurate or what your expectations are there?

偉大的。然後我想您已經討論了 ORLADEYO 在兒科患者中的機會。您能否介紹一下那裡的發展歷程？我們應該如何考慮註冊速度和 sNDA 提交的潛在時間表？我認為臨床試驗——該試驗的主要完成日期是 25 年中期。但只是好奇這是否準確或者您的期望是什麼？

So that's -- our pediatric trial is, as we said, is enrolling. We've had good interest and excitement amongst patients and investigators. It's too soon to predict the pace of enrollment there and the timing for that. So we'll update as we have more as the trial proceeds.

正如我們所說，我們的兒科試驗正在招募。患者和研究人員對我們產生了濃厚的興趣和興奮。現在預測那裡的入學速度和時間還為時過早。因此，隨著審判的進行，我們將更新更多信息。

But this is a really important unmet need. I mean think about it, kids and injecting them with therapy. We have a formulation that's granules that you can sprinkle on yogurt or apple sauce and so patients are -- and their parents in particular, are really excited about this program and so are we.

但這是一個非常重要的未滿足的需求。我的意思是，孩子們，想一想，給他們注射治療。我們有一種顆粒配方，您可以將其撒在酸奶或蘋果醬上，因此患者，尤其是他們的父母，對這個計劃感到非常興奮，我們也是如此。

Our next question will come from Jessica Fye with JPMorgan.

我們的下一個問題將來自摩根大通的傑西卡·菲伊。

This is (inaudible) for Jess. So we have a couple of questions. First, is there any update on the percentage of patient of free drug in 1Q that you can provide to us? And how should we think about the percentage of free drug patients for the remainder of the year?

這是（聽不清）傑西的。所以我們有幾個問題。首先，您能否向我們提供第一季度免費藥物患者比例的最新情況？我們應該如何考慮今年剩餘時間內免費吸毒患者的比例？

And then secondly, is there anything regarding the reauthorization process you can share with us, for example, does the reauthorization process require the same or similar lab test, right, that required for the start forms?

其次，您可以與我們分享有關重新授權過程的任何內容嗎？例如，重新授權過程是否需要與啟動表格所需的相同或相似的實驗室測試，對吧？

And then lastly, regarding your full year guidance. Does it imply a substantial step-up in terms of revenues for 2Q and beyond? And can you explain -- or can you kind of elaborate on your conviction over there?

最後，關於您的全年指導。這是否意味著第二季度及以後的收入將大幅增長？你能解釋一下嗎——或者你能詳細闡述一下你的信念嗎？

Charlie, can you take this?

查理，你能接受這個嗎？

Yes, I'll start with the first 2 questions and have Anthony cover the third one.

是的，我將從前兩個問題開始，然後讓安東尼回答第三個問題。

So on the percentage of free drug, I mentioned, in our last update, we were trending up towards 30% of patients on free drug. And we think long term, we can bring this down into the lower 20s and eventually down into the teens. So we actually -- in the first quarter, as I mentioned in my prepared remarks, we're ahead of the game in terms of converting patients from commercially insured patients who are on long-term free product over to paid. So we're doing well on that. We are a little bit over 30% of total patients on free drug. And the reason for that is that we had an unanticipated headwind in the quarter, which was the external charities that help Medicare patients afford their copayments for drugs like ORLADEYO ran short of funding. And so they had -- so some patients who otherwise would have been on paid therapy, were not able to afford their copayment insurance. And thus, we've made the decision to convert those patients over to patient assistance because that's something that we can control.

關於免費藥物的百分比，我在上次更新中提到，我們有 30% 的患者接受免費藥物的趨勢。我們認為，從長遠來看，我們可以將這一數字降低到 20 多歲，並最終降低到十幾歲。因此，實際上，正如我在準備好的發言中提到的那樣，在第一季度，我們在將患者從使用長期免費產品的商業保險患者轉變為付費患者方面處於領先地位。所以我們在這方面做得很好。我們有略高於 30% 的患者接受免費藥物。原因是我們在本季度遇到了意想不到的阻力，即幫助醫療保險患者支付奧拉德約等藥物自付款的外部慈善機構資金短缺。因此，一些本來可以接受付費治療的患者卻無力承擔自付費用保險。因此，我們決定將這些患者轉為患者援助，因為這是我們可以控制的。

So what that means is those patients will be on free product for the rest of this year but they're doing great on ORLADEYO, and we expect that in 2024, we'll be able to convert many of these patients back over to paid therapy. So right now, we're a little over 30% of patients on free drug, but we expect that percentage to come down over the year because the team is making really good progress with getting people to paid therapy overall.

因此，這意味著這些患者將在今年剩餘時間裡使用免費產品，但他們在 ORLADEYO 上表現良好，我們預計到 2024 年，我們將能夠將其中許多患者轉回付費治療。目前，我們有超過 30% 的患者在接受免費藥物，但我們預計這一比例在一年內會下降，因為該團隊在讓人們整體接受付費治療方面取得了非常好的進展。

Yes. Charlie, just to add, I mean, this was a real crisis in the first quarter for these patients because you can imagine a senior and all of a sudden, they don't have access to their medicine anymore. And so with our free drug program, we were able to step in very quickly and take care of a good number of patients. We even got some switches as a result of that.

是的。查理，我想補充一點，我的意思是，對於這些患者來說，第一季度這是一場真正的危機，因為你可以想像一個老年人，突然之間，他們再也無法獲得藥物了。因此，通過我們的免費藥物計劃，我們能夠非常迅速地介入並照顧大量患者。因此我們甚至得到了一些轉變。

But this is an investment by our company because as many of you know, with the Inflation Reduction Act, the co-pays are capped at Charlie help me again, $3,200 or something like that next year and then $2,000 I think, in 2025. And so we believe that we're going to get these patients back to paid. And in fact, Medicare are some of our best paid patients in the population of paid patients. So it was a move that we thought was a smart one for patients and a good one for our business long term.

但這是我們公司的一項投資，因為你們很多人都知道，根據《通貨膨脹削減法案》，自付費用的上限是查理再次幫助我，明年為 3,200 美元或類似的金額，然後我想，到 2025 年為 2,000 美元。所以我們相信我們會讓這些患者收回費用。事實上，醫療保險是我們付費患者群體中付費最高的患者之一。因此，我們認為這一舉措對患者來說是明智之舉，對我們業務的長期發展也是有利的。

So Jay had this Medicare issue not been there, we would be under 30% of patients on co-pay at this or a free product at this point.

因此，如果傑伊不存在醫療保險問題，那麼此時我們將有不到 30% 的患者使用自付費用或免費產品。

Your second question on just the re-auth process. Yes, there's nothing new there. It's just the standard reauthorization for patients. Sometimes this means confirming lab tests, sometimes it's just reviewing clinical history, but it's standard stuff, nothing new there. It always is a time-consuming process. And so that's why across our overall patient base, a lot of patients step back to free product temporarily while we were helping them through that process.

您的第二個問題是關於重新驗證過程的。是的，那裡沒有什麼新鮮事。這只是患者的標準重新授權。有時這意味著確認實驗室測試，有時只是回顧臨床病史，但這是標準的東西，沒什麼新鮮的。這始終是一個耗時的過程。因此，這就是為什麼在我們的整個患者群體中，許多患者在我們幫助他們完成這一過程時暫時退回到免費產品。

And Charlie, because we had a bigger base, we had more people switched to Quick Start as a result of that in the first quarter.

查理，因為我們有更大的基礎，所以第一季度有更多的人轉向快速啟動。

Correct. That's right. And it was a busy quarter overall. So the impact of free product definitely depressed Q1 revenue.

正確的。這是正確的。總體而言，這是一個繁忙的季度。因此，免費產品的影響肯定會壓低第一季度的收入。

And so maybe, Anthony, turning over to the pace?

那麼，安東尼，也許會轉向節奏？

Yes. I think Jay had use 2022 as a surrogate for how we'd expect the curve to play out. So there will be a step-up in revenue in Q2 and then in Q3 and Q4, I would expect revenue to continue to increase. So I wouldn't just take the remaining year divided by 3. I think the step-up in Q2 will be a healthy step-up and then Q3 and Q4, I'll see steady growth from there on out.

是的。我認為 Jay 使用 2022 年作為我們預期曲線如何發展的替代指標。因此，第二季度的收入將會增加，然後在第三季度和第四季度，我預計收入將繼續增加。因此，我不會只將剩餘年份除以 3。我認為第二季度的增長將是一個健康的增長，然後是第三季度和第四季度，我將看到從那時起的穩定增長。

And our conviction is that these -- the reauthorization process is going fine and that these patients will be switched to paid in the second quarter. That's why we're very positive around the $320 million.

我們堅信，重新授權過程進展順利，這些患者將在第二季度轉為付費。這就是為什麼我們對 3.2 億美元非常樂觀。

Our next question will come from Jon Wolleben with JMP Securities.

我們的下一個問題將由 JMP 證券公司的 Jon Wolleben 提出。

Congrats on the progress. A couple for me. Very helpful to have the number of patients on ORLADEYO today. Wondering if you could tell us what number of patients have started ORLADEYO in total? And then also, as we're looking throughout the year with the step-up in SG&A spending, where do you think that additional investment needs to go to continue the growth you're seeing today?

祝賀取得的進展。給我一對。今天了解奧拉德約的患者數量非常有幫助。想知道您能否告訴我們總共有多少患者開始使用 ORLADEYO？另外，當我們展望全年銷售管理及行政費用支出的增加時，您認為需要額外的投資去哪裡才能繼續您今天所看到的增長？

Sorry, Jon, I missed the last. Can you repeat the last part of your question?

抱歉，喬恩，我錯過了最後一次。你能重複一下你問題的最後部分嗎？

Yes. If you guys are spending additional SG&A this year to maintain the growth, where are you investing that capital?

是的。如果你們今年要花費額外的銷售及管理費用來維持增長，那麼你們會把這些資金投資到哪裡？

Okay. So the -- on the total, we have -- haven't disclosed the latest number, but in the fourth quarter of last year, actually, it's something we use in our promotion, and we disclosed that the allergy -- the College of Allergy Meeting in November. At that point, we had over 1,500 prescriptions. And so with the 1,000 patients roughly at this point, it's consistent with what we've talked about with patients. We retained 60% of patients at a year and then a year on therapy, and then very few drop off after that. And so that's why we're growing so consistently quarter after quarter.

好的。因此，總的來說，我們還沒有披露最新的數字，但實際上，在去年第四季度，我們在促銷中使用了這個數字，我們披露了過敏學院十一月過敏會議。那時，我們有超過 1,500 個處方。因此，目前大約有 1,000 名患者，這與我們與患者討論的情況一致。我們在一年後保留了 60% 的患者，然後繼續治療一年，之後很少有人退出。這就是我們每個季度持續增長的原因。

And as far as SG&A, I can start on that and Anthony can add color. So the investments on the ORLADEYO side commercially that we've made this year, we've talked about before, we made some expansions into our U.S. field team just to add more regions, in particular, just a couple of new territories and then supporting team to help with market access and patient services. And so that's something we do to just improve our efficiency and our ability to reach customers and we may make incremental investments like that in the future. And then, of course, international expansion, we're building out our Wave 2 countries like Italy and Spain and Europe, and we'll continue to make those kind of international investments.

至於SG&A，我可以從這個開始，安東尼可以添加色彩。因此，我們今年在奧拉德約方面進行的商業投資，我們之前已經討論過，我們對我們的美國現場團隊進行了一些擴展，只是為了增加更多的區域，特別是幾個新的區域，然後支持團隊幫助市場准入和患者服務。因此，我們這樣做只是為了提高我們的效率和接觸客戶的能力，我們可能會在未來進行類似的增量投資。當然，還有國際擴張，我們正在建設第二波國家，如意大利、西班牙和歐洲，我們將繼續進行此類國際投資。

Before we go to Anthony, Charlie, you said in your comments that -- and one of the biggest challenges we have is switching patients from long-term free drug to paid and you said that we exceeded the progress of our goal for the quarter. Can you just talk about that's an investment that we made. Can you talk a little bit about what you're seeing and why you're confident?

在我們去找安東尼之前，查理，您在評論中說，我們面臨的最大挑戰之一是將患者從長期免費藥物轉變為付費藥物，您說我們超出了本季度目標的進度。您能談談我們所做的一項投資嗎？您能談談您所看到的情況以及您為何如此自信嗎？

Yes. So the main thing that I've talked about in this is just focusing on really making sure that the healthcare practices and the patients provide all the information that the insurance companies want. And so as we've expanded our market access and patient services team, that's allowing us to put a greater focus on educating our customers and making sure that all that information is collected and then helping them in the case of writing the right prior authorization or appeals letters and making the proper case to the insurance companies, we've got the team there ready to help with that process. And so that is -- the investments we've made there in the people is directly correlated to the improvement that we're seeing in moving people from free product to paid product, and we expect to keep getting better as the year goes on.

是的。因此，我在此討論的主要內容是真正確保醫療保健實踐和患者提供保險公司想要的所有信息。因此，隨著我們擴大市場准入和患者服務團隊，這使我們能夠更加專注於教育我們的客戶並確保收集所有信息，然後幫助他們編寫正確的事先授權或上訴信並向保險公司提出適當的理由後，我們的團隊已準備好幫助完成這一過程。因此，我們在人員方面所做的投資與我們在將人員從免費產品轉向付費產品方面所看到的改進直接相關，並且隨著時間的推移，我們預計會繼續變得更好。

Okay. Yes, I think the only thing I'd add to Charlie's comment is increase in investment that we'll see in the SG&A side will be incremental, right? It will be mostly driven by the areas Charlie talked about and international growth. The step type increase that we have between Q3 and Q4 of last year, predominantly driven by the larger investment that Charlie made -- Charlie's team made here in the U.S. But at the moment, I think it's just going to be incremental as (inaudible) to anything of kind of major significance like that.

好的。是的，我認為我在查理的評論中唯一要補充的是，我們將在SG&A方面看到的投資增加將是增量的，對吧？這將主要由查理談到的領域和國際增長推動。去年第三季度和第四季度之間的階梯式增長，主要是由查理所做的更大投資推動的——查理的團隊在美國進行的投資。但目前，我認為這只是增量（聽不清）任何具有重大意義的事情。

Got it. Very helpful. And one more for Anthony, if I may. Are you guys taking the option to pay that 50% of the interest on the Pharmakon facility?

知道了。很有幫助。如果可以的話，還有一個是給安東尼的。你們會選擇支付 Pharmakon 設施 50% 的利息嗎？

I'd say at the moment, it's highly likely. We did take advantage of it while we had it for the 8 quarters with Athyrium. It's something that we do have to select on a per quarter basis. But I think given what it does for us in terms of cash preservation as we have the opportunity to see that net cash utilization kind of start to converge between revenue and OpEx, I think it's safe to assume that at least in the short term, yes, we would likely take advantage of it.

目前我想說的是，可能性很大。當我們與 Athyrium 一起度過了 8 個季度時，我們確實利用了它。這是我們必須按季度選擇的東西。但我認為，考慮到它在現金保存方面對我們的作用，因為我們有機會看到淨現金利用率開始在收入和運營支出之間趨同，我認為可以安全地假設，至少在短期內，是的，我們可能會利用它。

Our next question will come from Tazeen Ahmad with Bank of America.

我們的下一個問題將來自美國銀行的 Tazeen Ahmad。

Just wanted to have a little bit more color maybe, Jon, about your long-term view of ORLADEYO sales. We've talked about that target of achieving about $1 billion in peak. What's your assessment, I guess, from where you stand today? You had a great initial launch from here on in, what do you really need to achieve in order to get to that target? Is it a matter of just having a lot of patients on drug like going through? Or is it also leading to have a certain amount of compliance and a certain dropout rate in order to achieve that target?

喬恩，我只是想對您對 ORLADEYO 銷售的長期看法有更多的了解。我們已經討論過峰值時實現約 10 億美元的目標。我想，從你今天的立場來看，你的評價是什麼？從現在開始，您的初始發布就非常順利，為了實現該目標，您真正需要實現什麼？難道只是讓很多病人接受藥物治療的問題嗎？或者它是否也導致有一定的合規性和一定的輟學率才能實現該目標？

Yes. I think on the discontinuation piece, I think we're getting really comfortable that the pattern and the rate have stabilized. And so just to remind you the pattern, 50% of the people that discontinue, discontinue in the first few months. And if you make it out to a year, we got you. I mean the discontinuation rate after that is really, really low. And the discontinuation rate drops from 3 months to 6 months and 6 months to 12. So that has not changed now, Charlie, for what, almost a year, maybe even more now. And so I think we feel very comfortable with that.

是的。我認為在停產方面，我認為我們對模式和利率已經穩定感到非常滿意。所以只是想提醒您一下這種模式，50% 停止使用的人會在最初幾個月內停止使用。如果你能堅持一年，我們就會抓住你。我的意思是，此後的停藥率非常非常低。停藥率從 3 個月下降到 6 個月，再從 6 個月下降到 12 個月。查理，所以現在情況沒有改變，差不多一年了，甚至可能更長了。所以我認為我們對此感到非常滿意。

So then it's about adding more patients. And I think a really important point is that we crossed this 1,000 patient threshold of patients on therapy and that we grew from last year, almost 50%, which is remarkable in a couple of years of launch. And so -- and the consistency of new patient adds quarter after quarter is just unbelievable. So there is no slowing down there. There's no low hanging fruit here. This is fighting it out in the marketplace. It's a very competitive market, but we have an oral drug where everything else is injectable. And so it's a steady upward trajectory.

那麼接下來就是增加更多的病人。我認為非常重要的一點是，我們已經突破了接受治療的 1,000 名患者的門檻，並且比去年增長了近 50%，這在推出的幾年中是引人注目的。因此，新患者逐季增加的一致性令人難以置信。所以那裡沒有放慢速度。這裡沒有唾手可得的果實。這就是市場上的鬥爭。這是一個競爭非常激烈的市場，但我們有口服藥物，而其他藥物都是注射藥物。所以這是一個穩定的上升軌跡。

The one problem we had was free drug to paid and we're seeing that change with the changes that Charlie made in the team. And so very confident in our ability to get to the $1 billion. And we think this is a fantastic molecule for patients and therapy for patients. So when you have that, your chances of doing well is high.

我們遇到的一個問題是免費藥物的支付，我們看到查理在團隊中所做的改變帶來了變化。我們對達到 10 億美元目標的能力非常有信心。我們認為這對於患者和患者的治療來說都是一種奇妙的分子。因此，當你擁有這一點時，你取得好成績的機會就很高。

Our next question will come from Stacy Ku with Cowen.

我們的下一個問題將由 Stacy Ku 和 Cowen 提出。

We did have a few. So first, you've kind of discussed the stabilization, but can you clarify where exactly you see the retention for ORLADEYO beyond 12 months? Is it very close to that 60%? Are you willing to provide some more details there? We're just hoping to get a sense of how sticky these patients might be for ORLADEYO, very long term since they can kind of be toggled on and off that free drug program. So that's the first question.

我們確實有一些。首先，您已經討論了穩定性問題，但是您能澄清一下您認為 ORLADEYO 超過 12 個月後的保留率到底在哪裡嗎？是不是非常接近那個60%？您願意在那裡提供更多細節嗎？我們只是希望了解這些患者對 ORLADEYO 的粘性有多大，從長遠來看，因為他們可以切換免費藥物計劃。這是第一個問題。

The second question is your guidance for Q2, is that you expect to see a step up. Will it be similar quarter-over-quarter in terms of the percentage growth from last year? Which would imply Q2 could be closer or even exceed that consensus number around $80 million? So curious to get your thoughts there.

第二個問題是您對第二季度的指導，您期望看到進步。與去年相比，季度環比增長百分比是否會類似？這是否意味著第二季度可能更接近甚至超過 8000 萬美元左右的共識數字？很想知道你的想法。

And then the last question. Helen, it sounds like the timing for any pipeline update is going to be around year-end or early 2024. Is that correct? And if you could are you having -- are you planning on having any discussions with the FDA around the nonclinical tox [linings] for 10013? And if so, were the major factors that you'd like to have covered higher doses, duration treatment? Any additional color would be appreciated.

然後是最後一個問題。海倫，聽起來任何管道更新的時間都將在年底或 2024 年初左右。這是正確的嗎？如果可以的話，您是否計劃與 FDA 就 10013 的非臨床毒性[襯裡]進行任何討論？如果是這樣，您希望涵蓋更高劑量、持續治療時間的主要因素是？任何額外的顏色將不勝感激。

Yes. So, let me start because I want to make sure that people get this point because this is really important that if you've been on our drug for a year, there's not a 60% fallout post a year. It's like 1% or 2% post a year. And so if we -- that's why I say if we got you to a year, we've got you, so that base just keeps getting bigger and bigger and bigger. And that is a really important point for people to remember.

是的。那麼，讓我開始吧，因為我想確保人們明白這一點，因為這非常重要，如果您服用我們的藥物一年，一年後就不會出現 60% 的副作用。相當於每年1%或2%。因此，如果我們——這就是為什麼我說，如果我們讓你到了一年，我們就得到了你，所以這個基礎就會變得越來越大。這是人們要記住的非常重要的一點。

Yes. Jon, I was going to make the same point and then just kind of add that you can do the math with the numbers we gave you today. We're at about 1,000 patients. We grew 46%. So what we're adding consistently on a 12-month basis because of the demand and that really stable retention is we're adding 300-plus patients every 12 months. And so that's where we on all of the signs that we see in the market, our forward-looking market research, the trends that we see, we are still in the early stages of growing demand in this market. And so we have a lot of confidence based on the demand and the retention that we're going to keep the same pace of growth towards the $1 billion.

是的。喬恩，我本來也想表達同樣的觀點，然後補充一點，你可以用我們今天給你的數字進行數學計算。我們大約有 1,000 名患者。我們增長了 46%。因此，由於需求和真正穩定的保留，我們每 12 個月持續增加患者數量，每 12 個月增加 300 多名患者。因此，從我們在市場上看到的所有跡象、我們的前瞻性市場研究、我們看到的趨勢來看，我們仍處於這個市場需求增長的早期階段。因此，基於需求和保留率，我們非常有信心，我們將保持同樣的增長速度，邁向 10 億美元。

Yes. I guess yes (inaudible) in terms of Q2, we're not going to give specific guidance. We've talked about how we looked at last year. Bear in mind, last year, there were some different dynamics, right? We were still in the last [throws] of figuring out the contracting on the PBMs and the insurers and getting all of that in. I think in terms of last year also, Charlie talked about the significant growth that we have seen. So with the base significantly higher now than it was at that point in time. I wouldn't assume that the percentage will be as high as it was last year.

是的。我想是的（聽不清）就第二季度而言，我們不會給出具體的指導。我們已經討論了去年的情況。請記住，去年有一些不同的動態，對吧？我們仍處於最後階段，弄清楚 PBM 和保險公司的合同並將所有內容納入其中。我認為就去年而言，查理也談到了我們所看到的顯著增長。因此，現在的基數明顯高於當時的基數。我不認為這個百分比會像去年一樣高。

What I will say is what I said in the remarks, we expect for Q2 to be a step up, and we do expect Q3 and Q4 to grow on top of what we'll see in Q2 or within the confines of metering exceeding the $320 million guidance for the year.

我要說的是我在評論中所說的，我們預計第二季度將取得進步，並且我們確實預計第三季度和第四季度將在我們將在第二季度看到的基礎上或在計量超過 320 美元的範圍內實現增長全年指導額 100 萬元。

And then Helen on timing.

然后海倫負責計時。

Stacy, thanks for the question. So on R&D Day and an update on the pipeline, we think we'll be talking about something late in the year or early next year. We'll certainly have more color on what's going on in the discovery part of our pipeline then.

史黛西，謝謝你的提問。因此，在研發日和管道更新時，我們認為我們將在今年年底或明年初討論一些事情。屆時我們肯定會對我們管道的發現部分所發生的事情有更多的了解。

In terms of 10013 and any discussions, so we are always in discussions with regulators around the program that it's coming in from the program. With this nonclinical program and study that's ongoing. And so for that, we need to complete the study to understand what we would conclude from it. The focus at the moment in our regulatory process and discussions is going through the regulatory process to start the PNH study. And so we have what we need for this in terms of the data set to get started, but that's the focus of where we're looking at for our regulatory interactions with the goal of moving into patients to assess if this drug can be safe and effective with once-daily dosing.

就 10013 和任何討論而言，我們始終圍繞該計劃與監管機構進行討論，該計劃來自該計劃。這項非臨床計劃和研究正在進行中。因此，為此，我們需要完成這項研究，以了解我們會從中得出什麼結論。目前我們監管流程和討論的重點是通過監管流程啟動 PNH 研究。因此，我們已經擁有了開始所需的數據集，但這是我們關注監管相互作用的重點，目標是進入患者體內，評估這種藥物是否安全和可靠。每日一次給藥有效。

Our next question will come from Justin Kim with Oppenheimer & Company.

我們的下一個問題將來自奧本海默公司的賈斯汀·金 (Justin Kim)。

Maybe just on the $320 million guidance. In terms of reaching at least that number, how much of the assumptions rely on conversion of patients who are on free drug beyond sort of the seasonality of Q1 to Q2?

也許只是 3.2 億美元的指導。就達到至少這個數字而言，有多少假設依賴於超出第一季度到第二季度季節性的免費藥物患者的轉化？

Yes. So Justin, there's some of that built into our assumptions, but the major part of this is just organic growth in our patient base. So it's the continued demand and then the constant gradual improvement. We always expect to make the biggest improvement in getting people to paid therapy in the first quarter just through the re-auths, but then we'll make incremental improvements over the years. So we expect the percentage of paid patients to drop into the 20s as the year goes on. But the biggest part, again, is new patients coming in and then that base constantly growing that Jon described.

是的。賈斯汀，我們的假設中有一些內容，但其中主要部分只是我們患者群體的有機增長。所以這是持續的需求，然後是不斷的逐步改進。我們總是期望通過重新授權在第一季度讓人們接受付費治療方面取得最大的進步，但隨後我們將在接下來的幾年中做出漸進的改進。因此，我們預計隨著時間的推移，付費患者的比例將下降到 20 多歲。但最重要的部分還是新患者的到來，然後喬恩描述的這個基礎不斷增長。

Okay. And could you provide any color on the background of these new patient adds, whether they are switch patients, prophylaxis naive or coming from community versus epidemic, low prescriber, low volume versus high-volume prescribers?

好的。您能否提供有關這些新患者背景的任何信息，無論他們是轉換患者、未經預防治療還是來自社區與流行病、低處方者、低劑量與高劑量處方者？

So really, I'll sound very repetitive here, but it's great to see the consistency. So it's -- it's -- we're still getting about 50% of the patients were prophy switches, 50% -- the other 50%, mostly from acute only. And then the mix of prescribers I mentioned we're getting half the prescriptions from top 500 docs. Those are the bigger treaters that cover about half the patients in the marketplace. And so the other half is coming from the not so much the community doctors but the smaller HAE treaters. So the ones who have 1, 2, 3 patients in their practice.

所以說真的，我在這裡聽起來很重複，但很高興看到一致性。所以，我們仍然發現大約 50% 的患者進行了預防性轉換，50%——另外 50%，大部分只是急性發作。然後是我提到的處方醫生組合，我們從前 500 名醫生那裡獲得了一半的處方。這些是較大的治療儀，覆蓋了市場上大約一半的患者。因此，另一半不是來自社區醫生，而是來自規模較小的 HAE 治療人員。因此，那些在實踐中擁有 1、2、3 個患者的人。

Our team is able to reach both those segments and even more effectively with some of our team increases this year. And so we've seen this pattern continue over the last couple of years, and we expect those same patterns to continue going forward.

我們的團隊能夠覆蓋這兩個細分市場，並且隨著今年我們團隊的一些成員的增加，甚至可以更有效地實現這一目標。因此，我們看到這種模式在過去幾年中持續存在，並且我們預計這些模式將繼續向前發展。

Yes. And I think another piece that's really important that we haven't fully tapped into is the patient word-of-mouth spread, and Charlie said this a bunch of times before, but the patient summit that takes place in the U.S. every 2 years hasn't taken place into 2019 due to COVID and occurs in July. And we're really excited. This will be the first time, we actually have a booth with the product that's on the market. And it's just a great place where patients are talking to each other and an opportunity for that word of mouth to spread. So we're looking forward to that.

是的。我認為我們還沒有充分利用的另一個非常重要的部分是患者的口碑傳播，查理之前已經說過很多次了，但是每兩年在美國舉行的患者峰會並沒有由於新冠疫情，該活動沒有在 2019 年舉行，而是在 7 月舉行。我們真的很興奮。這將是我們第一次在展位上展示市場上的產品。這是一個患者互相交談的好地方，也是傳播口碑的機會。所以我們對此充滿期待。

Okay. Great. Maybe just a final one. As you think about breaking out the ex-U.S. numbers, I'm sort of curious, should we expect the ex-U.S. sort of growth rate to outpace on a percentage basis the U.S.? And so I'm just wondering whether we might see that line item reach sort of the peak potential before U.S.?

好的。偉大的。也許只是最後一張。當你考慮突破前美國時數字，我有點好奇，我們是否應該期待美國以外的國家按百分比計算，增長率會超過美國嗎？所以我只是想知道我們是否會看到該訂單項在美國之前達到峰值潛力？

Yes. No. So I think for kind of an indefinite period of time, more of our growth is still going to come from the U.S. It's the bigger market. But ex-U.S. is a little above. As Anthony said, it's about 11% now. We expect it to be in just a little over 10% for the year. At peak, it will get to 20%, but it's going to evolve more slowly because it's all about launching in new markets, getting market access and building in those markets. But what we're seeing in the places we've launched in Europe, in particular, is the same kind of steady growth. Once we're launched, we're adding more patients and growing steadily just as we're doing in the U.S. But U.S. is going to dominate in both pace and sales for the next few years.

是的。不會。所以我認為，在一段不確定的時間內，我們的增長的更多部分仍將來自美國，這是更大的市場。但除美國外就是上面一點。正如安東尼所說，現在大約是11%。我們預計今年的增長率將略高於 10%。在高峰期，這一比例將達到 20%，但發展速度會更慢，因為一切都與開拓新市場、獲得市場准入以及在這些市場中進行建設有關。但我們在歐洲推出的地方尤其看到了同樣的穩定增長。一旦我們推出，我們就會增加更多的患者並穩步增長，就像我們在美國所做的那樣。但美國將在未來幾年的速度和銷售方面佔據主導地位。

Yes. And the other dynamic is it takes 3 to 4 patients outside of the U.S. to make up the value of a patient inside the U.S. And we haven't -- for example, in Europe, we haven't gotten to Spain, Italy, Benelux, Portugal, and we expect to start to launch next year in those countries. But it just rolls out slower. But at peak, we're really confident that we'll get to the 20%. And we're really pleased with how Europe has performed even if it isn't a big chunk of the business yet. It's still important.

是的。另一個動態是，美國境外的患者需要 3 到 4 名患者才能彌補美國境內患者的價值，而我們還沒有——例如，在歐洲，我們還沒有到達西班牙、意大利、比荷盧經濟聯盟、葡萄牙，我們預計明年開始在這些國家推出。但它只是推出得更慢。但在高峰期，我們確實有信心達到 20%。我們對歐洲的表現感到非常滿意，儘管它還不是業務的一大塊。這仍然很重要。

Our next question will come from Serge Belanger with Needham & Company.

我們的下一個問題將來自 Needham & Company 的 Serge Belanger。

A couple of questions, I guess, for Charlie. First one, was the impact of patients on free drug in the first quarter larger than it was in 2022? Just trying to reconcile the difference between the 38% year-over-year increase in sales. I think you had a 46% increase in of patients on drug and a 5% price increase starting in January.

我想有幾個問題要問查理。第一，第一季度患者對免費藥物的影響是否比2022年更大？只是想彌補銷售額同比增長 38% 之間的差異。我認為從 1 月份開始，接受藥物治療的患者數量增加了 46%，價格上漲了 5%。

And then secondly, it looks like you had a stronger level -- new patient starts in the first quarter of '23 at 20%. Is that a significant uptick from prior quarters in 2022? And do you think that's sustainable for the rest of the year?

其次，看起來您的水平更高 - 新患者在 23 年第一季度開始為 20%。與 2022 年前幾個季度相比，這是否顯著上升？您認為這種情況在今年剩餘時間裡可持續嗎？

Sure. Thanks, Serge. So on your first question in the free product in the quarter, yes, the overall impact of free product was greater this first quarter than in 2022, even considering the relative size of the patient basis. And so that was for 2 reasons. One is as our base was bigger, and the reauthorization process is just -- it's always a complicated time-consuming process. And so patients on average were on free drug, just a little bit longer as we were doing the free or the reauthorization. So that's the first factor.

當然。謝謝，塞爾吉。因此，關於本季度免費產品的第一個問題，是的，即使考慮到患者基礎的相對規模，第一季度免費產品的總體影響也比 2022 年更大。這是有兩個原因。一是我們的基礎更大，而重新授權過程總是一個複雜且耗時的過程。因此，患者平均獲得免費藥物，只是比我們免費或重新授權的時間長一點。這是第一個因素。

The second factor is what I mentioned earlier around the Medicare patients not being able to afford their copayments and not having as much access to outside help doing so. And so that was something new that happened this year that did not happen last year.

第二個因素是我之前提到的醫療保險患者無法負擔自付費用並且無法獲得足夠的外部幫助。所以這是今年發生的去年沒有發生的新事情。

So you put those 2 things together, if the Medicare had not happened, our revenue growth would have been comparable to the patient growth at about 46%. And then the price increase, we expect the net for the price increase. We took a 5% price increase at the start of the year. We expect to, over the course of the year to net out at about a 4% improvement in ASP. That just doesn't all show up in Q1.

所以你把這兩件事放在一起，如果醫療保險沒有發生，我們的收入增長將與患者的增長相當，約為 46%。然後價格上漲，我們預計淨價格上漲。我們在年初將價格上漲了 5%。我們預計，在這一年中，平均售價將提高約 4%。這並沒有全部出現在第一季度。

And then as far as the new starts, yes, we were really pleased to have the 20% growth over last year in Q1 because, as I mentioned, this re-auth process is -- keeps everyone particularly the health care providers busy. And so the fact that they prescribe that much in Q1 is a great sign. I don't think it necessarily means we're going to be 20% up for the rest of the year, but we will do our best to try that. But with many new members of the team as we went through our expansions. I'm just -- I'm really pleased with how the team is doing and how well they started in Q1.

就新的啟動而言，是的，我們真的很高興第一季度比去年增長了 20%，因為正如我提到的，這個重新授權過程讓每個人，尤其是醫療保健提供者都很忙。因此，他們在第一季度開出這麼多處方是一個很好的跡象。我認為這並不一定意味著我們今年剩餘時間的增長率會達到 20%，但我們會盡力嘗試。但隨著我們的擴張，團隊中出現了許多新成員。我只是——我對團隊的表現以及他們在第一季度的開局感到非常滿意。

And just one last one on the pediatric ongoing pediatric clinical trial. So is the goal here to expand ORLADEYO's IP with this pediatric label expansion or it's really just an additional market opportunity for ORLADEYO?

這只是正在進行的兒科臨床試驗的最後一項。那麼，我們的目標是通過兒科標籤擴展來擴展 ORLADEYO 的知識產權，還是這實際上只是 ORLADEYO 的一個額外市場機會？

Yes. I mean we have incredibly long IP. So the pediatric piece is not critical to that in our opinion. I mean, this is a high unmet need. When you think about kids 6, 7 years old, having to get injections for their therapy, instead, you can sprinkle something on an oral sprinkles on yogurt or apple sauce. It's just -- and Bill shared, I mean going way back when he and I would attend these patient summits, we had parents just like when is the pediatric formulation coming. And so there's a pent-up demand there. It's not a huge market, but it's a patient for life, right? And we think it's an important segment of the market to serve. So -- but this was really all about high unmet need and serving that high unmet need.

是的。我的意思是我們有非常長的IP。因此，我們認為兒科部分對此並不重要。我的意思是，這是一個未滿足的高度需求。當您想到 6、7 歲的孩子必須接受注射治療時，您可以在口腔灑上撒一些酸奶或蘋果醬。只是 - 比爾分享道，我的意思是，早在他和我參加這些患者峰會時，我們就有父母，就像兒科配方什麼時候出現一樣。因此，存在被壓抑的需求。這不是一個巨大的市場，但它是一個終生的病人，對嗎？我們認為這是一個需要服務的重要市場部分。所以，但這實際上都是關於未滿足的高需求以及服務於未滿足的高需求。

(Operator Instructions) Our next question will go from Liisa Bayko with Evercore ISI.

（操作員說明）我們的下一個問題將由 Evercore ISI 的 Liisa Bayko 提出。

Aside from the free drug, can you -- what was the gross to net on the rest of beyond -- ex-free drug?

除了免費毒品之外，您能否——除此之外——前免費毒品的總淨收入是多少？

Yes. So in Q1 is always going to be the highest from a growth perspective as it relates to the reimbursed part of it. So we've previously guided to 15% to 20% for the year. I would say that Q1 is right at the top end of that range, and then we continue to get better as we move through the year to get towards that 15% to 20%. But again, driven by reauthorizations, co-pay assistance, a lot of the things that by the time you hit the end of Q1, you're starting to normalize and they'll have a minimal effect in Q2 and then as you go through the year even less again.

是的。因此，從增長的角度來看，第一季度總是最高的，因為它與報銷部分相關。因此，我們之前預計今年的增長率為 15% 至 20%。我想說，第一季度正好處於該範圍的頂端，然後隨著我們全年的發展，我們會繼續變得更好，以達到 15% 到 20% 的目標。但同樣，在重新授權、共同支付援助的推動下，到第一季度末時，很多事情都開始正常化，它們在第二季度的影響微乎其微，然後隨著你經歷今年就更少了。

Okay. That's helpful. And why -- for the Medicare issue you're facing (inaudible) that will rest of the year, these patients will be on free drug, viable next year, they no longer be on free drug? I guess I'm trying to understand what changes?

好的。這很有幫助。為什麼 - 對於您面臨的醫療保險問題（聽不清），今年剩餘時間，這些患者將獲得免費藥物，明年可行，他們不再獲得免費藥物？我想我想了解什麼變化？

Give us some sense of the co-pay now versus co-pay in the future.

讓我們對現在的自付費用與未來的自付費用有一些了解。

So based on the way Medicare Part D is right now for a rare disease product like ORLADEYO, depending on the person's plan, their copayment responsibility for the year is going to be north of $10,000 off in north of $20,000. So for a senior citizen, that very few can actually afford to pay that out of pocket. So these outside charities help them afford this because we, as manufacturers by law, are not allowed to do that.

因此，根據 Medicare D 部分目前針對像 ORLADEYO 這樣的罕見疾病產品的方式，根據個人的計劃，他們今年的共付責任將減少 10,000 美元到 20,000 美元以上。因此，對於老年人來說，實際上很少有人能夠自掏腰包支付這筆費用。因此，這些外部慈善機構幫助他們負擔得起這筆費用，因為法律不允許我們作為製造商這樣做。

When the Inflation Reduction Act rolls in, part of it recognizes this challenge for patients. So next year, the maximum that a Part D patient will pay is around $3,200 across all the drugs that they take, not just individual drugs. And then in 2025, that number is capped at $2,000. And so what it means is the overall copayment burden goes down which means more patients will be able to afford out of pocket. And also, it may mean that these outside charities will be able to help more patients because the average assistance that they provide will be much lower. And so that's why we're optimistic and we're very much supporters of that part of the IRA.

當《降低通貨膨脹法案》出台時，其中的一部分就認識到了患者面臨的這一挑戰。因此，明年，D 部分患者為他們服用的所有藥物（而不僅僅是個別藥物）支付的最高費用約為 3,200 美元。到 2025 年，這個數字上限為 2,000 美元。因此，這意味著總體共付負擔下降，這意味著更多的患者將能夠自付費用。而且，這可能意味著這些外部慈善機構將能夠幫助更多的患者，因為他們提供的平均援助會低得多。這就是為什麼我們持樂觀態度，並且我們非常支持愛爾蘭共和軍的這一部分。

Okay. And so why then would that Medicare piece, why will they be on free drug for the rest of this year? Because why don't they kick in above?

好的。那麼為什麼醫療保險會在今年剩下的時間裡提供免費藥物呢？因為他們為什麼不在上面踢呢？

That's just by law that once we put a patient on long-term patient assistance. For the rest of the calendar year, we have to keep them on it. And so it's all part of kind of the complicated rules around government insurance.

根據法律規定，一旦我們為患者提供長期患者援助。在今年剩下的時間裡，我們必須讓它們繼續下去。因此，這都是圍繞政府保險的複雜規則的一部分。

That's helpful. And then just like more broadly, what percentage of the 7,500 patients are now on prophylaxis? Like what does your market research tell you?

這很有幫助。更廣泛地說，7,500 名患者中目前正在接受預防治療的患者所佔的比例是多少？比如你的市場調查告訴你什麼？

North of 70% in the U.S. and we see -- we still see that growing to 80%, maybe even 90% over time.

在美國，這一比例超過了 70%，而且隨著時間的推移，我們仍然看到這一比例會增長到 80%，甚至可能達到 90%。

Yes. And one of the reasons for that is you've got 3 companies now promoting it as each new entrant of injectable prophy comes out, you're going to have more companies. We think that will go to 80% or even higher when everybody is talking about why would you put somebody on prophylactic therapy.

是的。原因之一是現在有 3 家公司在推廣它，隨著注射預防劑的每一個新產品的出現，你將會有更多的公司。我們認為，當每個人都在談論為什麼要讓某人接受預防性治療時，這一比例將會達到 80% 甚至更高。

Okay. Any inventory changes for the quarter?

好的。本季度庫存有變化嗎？

No. And we -- again, inventory is really not an issue for us because of the sole-source pharmacy. Every patient shipment is -- every sale is a direct flash sale to patients. So we don't have an inventory factor.

不。我們再次強調，由於我們是獨家藥房，所以庫存對我們來說確實不是問題。每一次向患者發貨都是——每一次銷售都是對患者的直接閃購。所以我們沒有庫存因素。

Strong coverage from an inventory perspective, up and down the channel with dual supply to make sure we're...

從庫存角度來看，渠道上下游的雙重供應提供了強大的覆蓋，以確保我們......

Plenty of supply. Yes.

貨源充足。是的。

Okay. And what kind of compliance are you seeing these days? What's the general rate?

好的。如今您看到了什麼樣的合規性？一般費率是多少？

Yes. So overall compliance remains strong. It's 90% plus. Is there always or it's going to be some smaller percentage of patients that struggle a little bit more. But with some of the team expansions that I described, part of their job too on the patient services side will be to help identify patients who are having compliance challenges and help educate them and make sure that they do their best to take one pill once a day. But overall, we see compliance very high, 90% plus.

是的。因此，總體合規性仍然很強。這是90%以上。是否總是有或將會有一小部分患者的情況會更加困難？但是，隨著我所描述的一些團隊擴張，他們在患者服務方面的部分工作也將是幫助識別面臨合規挑戰的患者，並幫助教育他們，並確保他們盡力每次服用一粒藥。天。但總體而言，我們認為合規性非常高，超過 90%。

Okay. Great. And then just one point of clarification on the PNH study. Are you clear to start Phase II in PNH? Or you're just kind of having a conversation with FDA now? What's exactly the stand?

好的。偉大的。然後對 PNH 研究做一點澄清。您準備好開始 PNH 的第二階段了嗎？或者您現在只是在與 FDA 進行對話？究竟什麼是立場？

So again, we're looking at countries where the benefit risk, where patients don't have access to other therapies. And so the U.S. -- plenty of other therapies for patients to have access to. So we're looking outside the U.S. and we're working through the process. We can't give you more of an update than that. Our goal is to start a study, and we will announce that when we do and if we do, but at this point, I can't give you an update.

因此，我們再次關注那些存在獲益風險、患者無法獲得其他療法的國家。因此，在美國，患者可以獲得許多其他療法。因此，我們正在將目光投向美國以外的地區，並正在完成整個過程。我們無法為您提供更多更新信息。我們的目標是開始一項研究，我們將宣布何時進行以及是否進行，但目前我無法向您提供最新消息。

And Helen, you might want to clarify again why PNH, why we're going there first?

海倫，你可能想再次澄清為什麼 PNH，為什麼我們要先去那裡？

So we're pursuing PNH as the fastest path to be able to assess the drug to understand if we have a safe and effective drug that can achieve once daily dosing. And that's an opportunity to do that first before we then move into the renal diseases.

因此，我們將 PNH 作為評估藥物的最快途徑，以了解我們是否有一種安全有效的藥物可以實現每日一次給藥。在我們進入腎臟疾病之前，這是一個先這樣做的機會。

Our next question will come from Brian Abrahams with RBC Capital Markets.

我們的下一個問題將來自加拿大皇家銀行資本市場部的布萊恩·亞伯拉罕斯 (Brian Abrahams)。

Two for me. First off, as you've been able to gather more and more longitudinal data here, anything you can take from the learnings around this really high retention rate after patients are through a year and apply it to potentially reducing the dropout rate within that initial year?

給我兩個。首先，由於您已經能夠在這裡收集越來越多的縱向數據，因此您可以從患者一年後的這種非常高的保留率中學到任何東西，並將其應用於潛在地降低第一年的退出率？

And then secondly, it sounds like the newer patients being added are quite consistent in terms of the switchers versus naive and where they're coming from with regards to prescribers. But I guess I'm curious, those who are starting ORLADEYO at this point in the launch, is there anything different about them versus those who started earlier just in terms of region, insurance coverage, time on existing therapy that might make it more or less challenged going through the free drug process on to paid drug or more or less likely for them to stay on therapy longer term?

其次，聽起來新加入的患者在切換者與天真者以及他們來自處方者方面非常一致。但我想我很好奇，那些在推出時開始 ORLADEYO 的人，與那些較早開始的人相比，在地區、保險範圍、現有治療的時間方面有什麼不同，這可能會使其更多或更好通過免費藥物過程轉向付費藥物的挑戰較少，或者他們或多或少不太可能繼續長期接受治療？

Sure. Good questions, Brian. So first on the long-term data, yes, I mean we collect a ton of data. And I think the biggest learning and this isn't really surprising in HAE, but the biggest learning is it's about patient confidence and physician confidence. They've -- fortunately, patients have so many more therapies today than they did a decade or more ago. So they want to know now that they get access to these therapies that their drug is really working for them. And so switching is something that stress is a trigger for HAE attacks and switching can be stressful. So what we've learned is the biggest thing to do is set expectations of this is how the drug works. Here are things that could happen, side effects or breakthrough attacks, that's normal, but you need to give this a period of time, 3 to 6 months to really figure out if this drug is working for you. So that's a big part of our promotion and educational message and that just -- we just have to keep repeating. And we're seeing over time that, that's that is improving and stabilizing our retention rate.

當然。好問題，布萊恩。首先是長期數據，是的，我的意思是我們收集了大量數據。我認為最大的學習，這在 HAE 中並不令人驚訝，但最大的學習是關於患者信心和醫生信心。幸運的是，今天的患者比十年或更長時間前接受了更多的治療。因此，他們現在想知道，當他們獲得這些療法時，他們的藥物確實對他們有效。因此，切換是壓力是 HAE 攻擊的觸發因素，而切換可能會帶來壓力。所以我們了解到最重要的事情就是設定對藥物作用的期望。以下是可能發生的事情，副作用或突破性發作，這很正常，但你需要給它一段時間，3到6個月，才能真正弄清楚這種藥物是否對你有效。因此，這是我們促銷和教育信息的重要組成部分，我們必須不斷重複。隨著時間的推移，我們看到，我們的保留率正在提高和穩定。

Yes. And I would just add, Charlie. You asked the question, Brian, why is the retention rate so high after a year? Because they're doing great. right? I mean they're taking one capsule once a day. It's controlling their disease, and they're tolerating it really well. And so it's almost the ideal therapy, right? So that's why.

是的。我想補充一點，查理。你問過這個問題，Brian，為什麼一年後保留率這麼高？因為他們做得很好。正確的？我的意思是他們每天服用一粒膠囊。它正在控制他們的疾病，而且他們對它的耐受性非常好。所以這幾乎是理想的療法，對吧？所以這就是為什麼。

And we're absolutely learning from our data that when patients who are doing well, low attack rates rarely with breakthrough attacks on other injectable therapies when they switch over to ORLADEYO they're having the same kind of outcomes on ORLADEYO. And so making sure that patients and physicians understand that is part of the education.

我們絕對從我們的數據中了解到，當表現良好、低發病率的患者在改用 ORLADEYO 時，其他注射療法很少出現突破性發作，他們在 ORLADEYO 上會獲得相同的結果。因此，確保患者和醫生理解這一點是教育的一部分。

Then your question on just the types of patients. I mentioned the mix of switching has been similar. I think the difference -- there's really no difference from getting patients to insurance. That's been consistent. Probably the biggest difference is these are -- as we're getting further into the market, there are patients who have been taking more of a wait-and-see approach. They've been welcome on other therapies as we were just describing. So we need to just keep pushing and educating and sharing data. And Jon mentioned word-of-mouth, driving word-of-mouth before. The biggest challenge is getting someone who's doing well on another product to take the chance of switching. And we see that happening, but we haven't gotten to everyone. We haven't convinced everyone but we will convince them over time, and that's what's leading to the steady growth of this product.

那麼你的問題只是關於患者的類型。我提到過切換的組合是相似的。我認為區別在於——讓患者獲得保險實際上沒有什麼區別。這是一致的。也許最大的區別是——隨著我們進一步進入市場，有些患者採取了更多的觀望態度。正如我們剛才所描述的，他們在其他療法中受到了歡迎。因此，我們需要繼續推動、教育和共享數據。喬恩之前也提到過口碑，帶動口碑。最大的挑戰是讓在另一種產品上表現出色的人抓住機會轉換。我們看到這種情況正在發生，但我們還沒有覆蓋到所有人。我們還沒有說服所有人，但隨著時間的推移我們會說服他們，這就是導致該產品穩定增長的原因。

Our next question will come from Gena Wang with Barclays.

我們的下一個問題將來自巴克萊銀行的 Gena Wang。

I have 3 quick questions. The first one is regarding the new prescribers. You mentioned that 50% from Tier 1 and 50% from the other parts and also for the switcher, you said 50% switch from other prophy and 50% from acute or naive patient. So does this apply to the 1,000 patients that currently on ORLADEYO? That was the first question.

我有 3 個簡單的問題。第一個是關於新的處方者。您提到 50% 來自第 1 層，50% 來自其他部分，對於切換器，您說 50% 來自其他預防措施，50% 來自急性或幼稚患者。那麼這是否適用於目前在奧拉德約接受治療的 1,000 名患者呢？這是第一個問題。

My second question is the guidance. Regarding guidance of a $320 million. Now you expect 10%, 11% is from ex-U.S. was that consistent with your prior assumption when you initially gave the guidance beginning of this year?

我的第二個問題是指導。關於 3.2 億美元的指導。現在你預計 10%、11% 來自美國以外地區。這與您在今年年初最初提供指導時的先前假設一致嗎？

And then lastly, any plan to achieve profitability (inaudible)?

最後，是否有實現盈利的計劃（聽不清）？

Sure. I can do the first one and then I'll turn it over to Anthony.

當然。我可以做第一個，然後我會把它交給安東尼。

So the 50-50, the 2 50-50, so half of the prescribers big top 500, half being lower tier and then half -- roughly half the patients be prophy switches have from acute only and then how that relates to the 1,000 patients. So of the 1,000 patients, it's all very consistent all around. So retention amongst our patients is very similar, whether they came from another prophy therapy or whether they came from acute only, whether they were prescribed by a top KOL or whether they were prescribed by a smaller HAE treater. So across the board, it's really, really consistent in all of these different segments no matter how you slice it.

所以 50-50，2 50-50，所以一半的處方者是前 500 名，一半是較低級別的，然後是一半——大約一半的患者是預防性轉換的，只有急性的，然後這與 1,000 名患者有什麼關係。因此，在 1,000 名患者中，情況非常一致。因此，我們的患者的保留率非常相似，無論他們是來自另一種預防治療還是僅來自急性治療，無論他們是由頂級 KOL 開出處方還是由較小的 HAE 治療師開出處方。因此，總的來說，無論你如何劃分，它在所有這些不同的細分市場中都非常非常一致。

And as far as the $320 million guidance, I think it's consistent -- the ex-U.S. split. -- ex-U.S. has been growing, and we've -- this year we've consistent with our plans. And so we see it being consistently above 10%, and that's why we're splitting it out at this point.

至於 3.2 億美元的指導，我認為它是一致的——不包括美國在內。分裂。 -- 前美國一直在增長，今年我們與我們的計劃保持一致。因此我們看到它始終高於 10%，這就是我們此時將其分開的原因。

Yes. And it's in line now with when we initially put out the $320 million guidance, kind of same assumptions.

是的。現在這與我們最初提出 3.2 億美元的指導時的情況是一致的，類似的假設。

For your question on profitability, I mean we're in a much better spot than we have been previously, right? So the combination of revenue growth on our way to $320 million and then up to $1 billion. I think, flash guidance that we gave for OpEx and the control that we've put in place there. And then the deal that we signed with Pharmakon last month, I think, puts us in a great spot to be able to achieve it. I think our focus continues to be on not just the speed that we get there both the longer-term level of profitability. And so making sure that we continue to invest in ORLADEYO, in the label, in real-world evidence generation and then in the pipeline just when we get there, it's as significant as we can make it be. I think we're financially in a great spot to be able to achieve profitability when it will come will depend on those variables. But this is the best financial position the company has been in.

對於你關於盈利能力的問題，我的意思是我們現在的處境比以前好得多，對吧？因此，我們的收入增長將達到 3.2 億美元，然後達到 10 億美元。我認為，我們為運營支出提供了快速指導以及我們在那裡實施的控制。我認為，我們上個月與 Pharmakon 簽署的協議使我們處於實現這一目標的有利位置。我認為我們的重點不僅在於我們實現目標的速度，還在於長期的盈利水平。因此，確保我們繼續投資 ORLADEYO、品牌、現實世界的證據生成以及當我們到達那裡時的管道，這是我們所能做到的最重要的。我認為我們在財務上處於有利地位，能夠實現盈利，具體時間取決於這些變量。但這是該公司有史以來最好的財務狀況。

Yes. It's so different from the past. I mean our reliance on the capital markets has dropped dramatically. And what that allows us to do is execute our plan and not worry about "oh, God, when is the next rate?" Where are we getting the money from? And we're in such a strong spot now compared to where we were before. And we can make smart investments and have growing revenue. I mean it's like night and day compared to where we were.

是的。這與過去有很大不同。我的意思是我們對資本市場的依賴急劇下降。這讓我們能夠執行我們的計劃，而不必擔心“哦，上帝，下一個利率是什麼時候？”我們從哪裡得到錢？與以前相比，我們現在處於如此有利的位置。我們可以進行明智的投資並獲得不斷增長的收入。我的意思是，與我們所在的地方相比，這就像白天和黑夜。

Our last question will come from Maury Raycroft with Jefferies.

我們的最後一個問題將由莫里·雷克羅夫特和杰弗里斯提出。

I was going to ask about the new loan optionality to draw another $150 million. Can you provide perspective on your decision tree and what would trigger pulling down more of the loan? And talk about some potential ways you can create value with the additional capital?

我本來想詢問是否有新的貸款選項可以再提取 1.5 億美元。您能否提供您對決策樹的看法以及什麼會導致減少更多貸款？並談談您可以利用額外資本創造價值的一些潛在方式？

Sure. So we have up until September of 2024. So the goods of 1.5 years, give or take. I think during that time period, we'll obviously expect revenue to continue to lease. We'll have, I think, additional clarity as to where we are for 10013, we'll also continue, like we've talked about previously to invest in the pipeline. We've talked about that there's C2 and then other areas that we're investing in.

當然。所以我們的截止日期是 2024 年 9 月。所以 1.5 年的貨物，無論給予還是接受。我認為在此期間，我們顯然預計收入將繼續增長。我認為，我們將進一步明確 10013 的進展情況，我們還將繼續，就像我們之前討論過的那樣，投資管道。我們已經討論過 C2 以及我們正在投資的其他領域。

I think it gives us that time to see those dynamics play out as and when we get there, if we see value and where would we create value, we're constantly creating value in ORLADEYO. So if there's something that we could do to accelerate growth, whether it's here in the U.S. or international, if there's something that we could do to accelerate one of the clinical trials that we think will continue to generate value, then that's another area that we could use it or if it was to bridge ourselves to profitability. I think that would be another value creation opportunity for the company. So it's fully at our option as to whether we do it. It's committed funds. So I think the optionality and the flexibility that it gives us, Maury, is huge for us. And only if we -- only if we can kind of meet some of those targets, will we draw those funds.

我認為這讓我們有時間看到這些動態的發揮，當我們到達那裡時，如果我們看到價值以及我們將在哪裡創造價值，我們就會在奧拉德約不斷創造價值。因此，如果我們可以做些什麼來加速增長，無論是在美國還是在國際上，如果我們可以做些什麼來加速我們認為將繼續產生價值的一項臨床試驗，那麼這就是我們的另一個領域可以利用它，或者它是否可以幫助我們實現盈利。我認為這將是公司的另一個價值創造機會。因此，我們完全可以選擇是否這樣做。這是承諾資金。所以我認為它給我們帶來的選擇性和靈活性，莫里，對我們來說是巨大的。只有當我們能夠實現其中一些目標時，我們才會提取這些資金。

Yes. And remember, too, I said that we're investing in R&D for ORLADEYO and the pediatric trial is just one thing that we're investing and there's other ideas that we have that are too early to share with you. But we're looking at ways of expanding the label, getting more patients on therapy. And as Anthony said, and then the pipeline and those things can create real value. There's a real return on investment there. So that's how we look at it.

是的。還要記住，我說過我們正在投資 ORLADEYO 的研發，兒科試驗只是我們投資的一件事，我們還有其他想法，但現在與您分享還為時過早。但我們正在尋找擴大標籤的方法，讓更多的患者接受治療。正如安東尼所說，然後管道和那些東西可以創造真正的價值。那裡有真正的投資回報。這就是我們的看法。

Got it. That makes sense. Maybe just one quick clarification question. For the patients going back to free product temporarily for the re-auth process. Charlie, you mentioned they were on drug a little bit longer in first quarter '23 versus first quarter '22. Are you providing more specifics on whether it was 1, 2 or 3 months of the quarter on free drug? And should we expect the metrics around this to change or stay the same in future calendar cycles?

知道了。這就說得通了。也許只是一個快速澄清的問題。對於暫時返回免費產品以進行重新授權過程的患者。查理，你提到他們在 23 年第一季度的吸毒時間比 22 年第一季度要長一些。您能否提供更多關於該季度的 1、2 或 3 個月免費藥物的具體信息？我們是否應該期望圍繞此的指標在未來的日曆週期中發生變化或保持不變？

Yes. No, I'm not providing specifics, just on average, there was just more use of free product, but the vast majority of those patients -- the patients are through the re-auth process now and -- as I mentioned, we were actually ahead of our plan in the commercial segment of the market, which is over 60% of our patients. And so those patients will be on paid therapy for the rest of the year. So as -- and then as we go through the year, we'll just keep making incremental improvements in getting people to paid therapy.

是的。不，我沒有提供具體細節，只是平均而言，免費產品的使用更多了，但絕大多數患者 - 患者現在正在經歷重新授權過程 - 正如我提到的，我們是實際上，在商業市場領域（占我們患者的 60% 以上）提前了我們的計劃。因此，這些患者將在今年剩餘時間內接受付費治療。因此，在這一年中，我們將不斷改進，讓人們接受付費治療。

So we -- with the patient base that we have, with the continued demand and the retention and then doing better and better on paid getting people at paid therapy. We're just really confident in the year and particularly the long term based on what we see now.

因此，我們憑藉現有的患者基礎、持續的需求和保留率，然後在讓人們接受付費治療方面做得越來越好。根據我們現在所看到的情況，我們對今年尤其是長期充滿信心。

Yes, when you have a bigger base of patients that have to go through the re-auth process, it can take longer. So next year, it might take longer as well, right, with a bigger base next year. So...

是的，當您有更多的患者需要經歷重新驗證過程時，可能需要更長的時間。所以明年可能也需要更長的時間，對吧，明年的基數更大。所以...

This concludes our question-and-answer session as well as the conference. Thank you for attending today's presentation. You may now disconnect.

我們的問答環節和會議到此結束。感謝您參加今天的演講。您現在可以斷開連接。