BioCryst Pharmaceuticals Inc (BCRX) 2024 Q3 法說會逐字稿

Good day and Welcome to the BioCryst Third Quarter 2024 Earnings Call.

大家好，歡迎參加 BioCryst 2024 年第三季財報電話會議。

All participants will be in listen-only mode.

所有參與者將處於只聽模式。

(Operator Instructions) Please note this event is being recorded.

（操作員指示）請注意，此事件正在被記錄。

I would now like to turn the conference over to John Bluth, Chief Communications Officer.

現在，我想將會議交給首席通訊官約翰·布魯斯 (John Bluth)。

Please go ahead.

請繼續。

Thanks, Dave.

謝謝，戴夫。

Good morning and welcome to BioCryst Third Quarter 2024 Corporate Update and Financial Results Conference Call.

早安，歡迎參加 BioCryst 2024 年第三季公司更新與財務業績電話會議。

Today's press release and accompanying slides are available on our website.

今天的新聞稿和隨附的幻燈片可在我們的網站上查閱。

Participating with me today are CEO, Jon Stonehouse; CFO, Anthony Doyle; Chief Commercial Officer, Charlie Gayer; and Chief R&D Officer, Dr. Helen Thackray; and Chief Data and Insights Officer, Jinky Rosselli.

今天與我一起參加的有執行長喬恩‧斯通豪斯 (Jon Stonehouse)；財務官，Anthony Doyle；首席商務官 Charlie Gayer；首席研發長 Helen Thackray 博士；以及首席數據和洞察官 Jinky Rosselli。

Following our remarks, we'll answer your questions.

在我們發表評論之後，我們將回答您的問題。

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.

今天的電話會議將包含前瞻性陳述，包括有關未來業績、未經審計和前瞻性財務資訊以及公司未來業績和/或成就的陳述。

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.

這些陳述受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、績效或成就與本報告中表達或暗示的任何未來結果或績效有重大差異。

You should not place undue reliance on these forward-looking statements.

您不應過度依賴這些前瞻性陳述。

For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website.

如需更多信息，包括我們的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，可在我們的網站上查閱。

In addition, today's conference call includes non-GAAP financial measures.

此外，今天的電話會議還包括非公認會計準則財務指標。

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 www.biocryst.com.

有關這些非 GAAP 指標與最直接可比較的 GAAP 財務指標的對照表，請參閱我們投資者關係網站 www.biocryst.com 新聞稿部分發布的收益新聞稿。

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

現在我想將電話轉給喬恩·斯通豪斯。

Thanks, John.

謝謝，約翰。

Our third quarter performance is remarkable on multiple fronts.

我們第三季的表現在多個方面都非常出色。

First, growing ORLADEYO quarterly revenue year-over-year by nearly 36% now four years in from approval is amazing.

首先，ORLADEYO 在獲得批准四年後，季度營收年增近 36%，這是令人驚訝的。

This is a result of growing confidence in our therapy where physicians are seeing that ORLADEYO offers many of their patients both outstanding efficacy and convenience.

這是因為醫生們對我們的療法越來越有信心，他們看到 ORLADEYO 為他們的許多患者提供了出色的療效和便利性。

Next, advancing BCX17725 for Netherton syndrome into the clinic is exciting, especially considering there is nothing to treat the underlying cause of this disease.

接下來，將用於治療 Netherton 綜合徵的 BCX17725 推進到臨床是令人興奮的，尤其是考慮到目前沒有可以治療這種疾病的根本原因。

And Finally, being able to do all of this and move closer to sustainable profitability supports that we are building a company with the potential for durable growth.

最後，能夠做到這一切並更接近可持續盈利，支持了我們正在建立一家具有持久成長潛力的公司。

That's been our goal, and it's great to see it coming together quarter after quarter after quarter.

這正是我們的目標，我們很高興看到我們一個季度又一個季度地實現這一目標。

So, today Charlie will share more about our performance with ORLADEYO and how it continues to reinforce and grow our confidence in the path to $1 billion at peak, even in an increasingly crowded market.

因此，今天 Charlie 將更多地分享我們在 ORLADEYO 的表現，以及它如何在日益擁擠的市場中繼續增強和增強我們邁向 10 億美元巔峰的信心。

Helen will share how there is more potential with ORLADEYO by expanding the label to younger children and starting a Phase 4 study to help physicians and patients learn more about the best ways to switch therapies.

Helen 將分享 ORLADEYO 如何透過擴大適應症範圍至年齡較小的兒童並啟動第 4 階段研究來發揮其更多潛力，以幫助醫生和患者更多地了解轉換療法的最佳方法。

She will also share the importance of moving into the clinic with BCX17725 for patients living with Netherton syndrome.

她還將分享 BCX17725 進入臨床對於 Netherton 綜合徵患者的重要性。

And Anthony will wrap up by sharing how our financial position gets stronger and stronger and we are well on our way to our commitment of achieving sustained profitability.

最後，安東尼將分享我們的財務狀況如何變得越來越強大，以及我們正在順利實現持續盈利的承諾。

With that, I'll turn it over to Charlie.

說完這些，我會把話題交給查理。

Thanks John.

謝謝約翰。

We had another great quarter for ORLADEYO with $116.3 million in global revenue and nearly 36% year-over-year growth in year four.

ORLADEYO 又度過了一個出色的季度，全球收入達 1.163 億美元，第四年同比增長近 36%。

Prescribers and patients are increasingly convinced that ORLADEYO delivers outstanding efficacy, as well as convenience.

醫生和病人越來越相信 ORLADEYO 不僅具有出色的療效，而且非常方便。

We added 67 new US Prescribers in the quarter, one of our best quarters in the last two years.

我們在本季增加了 67 名新的美國處方人員，這是過去兩年來最好的季度之一。

And new prescriptions came in at the same elevated rate we have now seen for 12 months straight.

我們看到，新處方的數量已經連續 12 個月保持高速成長。

In fact, US start forms over the past 12 months are up almost 15% compared to the prior 12 months.

事實上，過去 12 個月美國的出生人數與前 12 個月相比增加了近 15%。

As far as improving paid therapy, we are ahead of plan.

至於改善付費治療，我們已經提前做好了規劃。

I've described before that our goal is to hold the paid rate steady in the second half of the year while advancing in the first half.

我以前講過，我們的目標是下半年薪資水準保持穩定，上半年薪資水準提高。

So it's great news that we improved the paid rate by almost 0.5% to 74.8% compared to a drop of 2% in the third quarter last year.

因此，我們將工資率提高了近 0.5% 至 74.8%，而去年第三季的降幅為 2%，這是一個好消息。

The commercial paid rate held steady at 82% and the Medicare rate ticked up 3% to 55%.

商業支付率維持穩定在 82%，醫療保險支付率上漲 3% 至 55%。

This progress increases our confidence that we will reach our goal of 85% paid overall, and we expect to take another big step in that direction in the first half of 2025.

這項進展增強了我們實現整體支付率 85% 的目標的信心，我們預計在 2025 年上半年朝著這個方向邁出一大步。

With a strong demand and improved paid rate, we are tightening our revenue guidance for 2024 to $430 million to $435 million, the upper end of our prior range.

由於需求強勁和付費率提高，我們將 2024 年的營收預期收緊至 4.3 億美元至 4.35 億美元，也就是我們先前預期的上限。

ORLADEYO has been on the market for almost four years, and we have accumulated a large and growing body of real-world evidence that is reinforcing prescribers' views about the product while driving growth.

ORLADEYO 已上市近四年，我們累積了大量且不斷增長的真實世界證據，這些證據在推動成長的同時強化了處方人員對該產品的看法。

Last week at the ACAAI conference, we presented two posters showing significant and sustained real-world attack reductions in over 450 patients with Type 1 or Type 2 HAE and over 350 patients with HAE with C1 normal inhibitor.

上週在 ACAAI 會議上，我們展示了兩張海報，展示了超過 450 名 1 型或 2 型 HAE 患者和超過 350 名具有 C1 正常抑制劑的 HAE 患者在現實世界中的發病率顯著且持續下降。

These are unprecedented patient numbers for evidence reported on any HAE prophy therapy.

就任何 HAE 預防治療的證據而言，這些患者數量都是前所未有的。

The Type 1 and 2 patients reported experiencing a median rate of just one-third of an attack per month.

據報告，1 型和 2 型患者每月發病的平均機率僅為三分之一。

That's only four attacks per year.

也就是說，每年僅有四起攻擊事件。

For patients, this is what great attack control looks like.

對患者來說，這才是良好的發作控制。

And as we described last quarter, three out of four patients in our market research studies report their attacks are less severe on ORLADEYO.

正如我們上個季度所描述的，在我們的市場調查中，四分之三的患者報告稱，使用 ORLADEYO 後，他們的病情減輕了。

The C1 normal inhibitor patients reported median rates of less than an attack per month, down from over three per month before starting ORLADEYO.

C1 正常抑制劑患者報告的平均發生率為每月不到一次，低於開始使用 ORLADEYO 之前每月三次以上。

C1 normal patients typically have struggled for years to find an effective therapy, and we're glad that so many are benefiting from ORLADEYO.

C1 正常患者通常要努力多年才能找到有效的治療方法，我們很高興看到如此多的患者從 ORLADEYO 中受益。

We also presented a poster last week confirming high patient retention on ORLADEYO.

我們上週也展示了一張海報，證實了 ORLADEYO 的高病患保留率。

The analysis of payer claims showed that patients starting ORLADEYO, Takhzyro, or Haegarda have similar one-year adherence around 60%.

付款人索賠分析顯示，開始使用 ORLADEYO、Takhzyro 或 Haegarda 的患者的一年依從性相似，約為 60%。

The analysis also showed that for patients with at least two fills of their prescription, one-year adherence was 71% for ORLADEYO and 63% for the other two products.

分析也顯示，對於至少服用過兩次處方藥的患者，ORLADEYO 的一年依從率為 71%，而其他兩種產品的一年依從率為 63%。

No HAE therapy is perfect for every patient, but these data make sense.

沒有一種 HAE 療法適合所有患者，但這些數據是有意義的。

If patients are experiencing just a few attacks per year on an oral once-daily therapy.

如果患者每天口服一次藥物，每年只發作幾次。

Why wouldn't they remain on ORLADEYO long-term?

他們為什麼不能長期留在奧拉德約？

That long-term stickiness is what our market research and predictive modeling show, even when accounting for the launch of several new HAE therapies in the coming years.

我們的市場研究和預測模型表明，即使考慮到未來幾年將推出幾種新的 HAE 療法，這種長期黏性仍然會存在。

As described on slide 9, we conduct a comprehensive annual exercise, including a conjoint preference study of 175 HAE treaters, 100 HAE patients, and over 50 payers, followed by running a Monte Carlo model with 6,000 simulated interactions between patients, physicians, and payers.

如投影片 9 所述，我們每年都會進行一項全面的活動，包括對 175 名 HAE 治療者、100 名 HAE 患者和 50 多名付款人的聯合偏好研究，然後運行蒙特卡洛模型，模擬患者、醫生和付款人之間的 6,000 次互動。

That's a really big number for a market that had about 8,500 diagnosed and treated patients in 2023.

對於 2023 年確診並接受治療的患者的市場而言，這是一個非常大的數字。

Those 6,000 simulations account for the many dynamics that affect treatment choice, such as product preference, frequency of visits to physicians, and future product launch dates.

這 6,000 次模擬考慮了影響治療選擇的許多動態因素，例如產品偏好、就診頻率以及未來產品的發布日期。

To assess treatment preference, we show respondents the best-case product profiles for potential new competitors but are conservative about the profile we show for ORLADEYO, despite the real-world attack control that we are seeing.

為了評估治療偏好，我們向受訪者展示了潛在新競爭對手的最佳產品概況，但對 ORLADEYO 的概況持保守態度，儘管我們看到了現實世界的攻擊控制。

The results of this exercise have been consistent over the past three years, even as we add information about potential competitors and include new cohorts of physicians and patients in the market research every year.

儘管我們每年都會添加有關潛在競爭對手的資訊並在市場研究中納入新的醫生和患者群體，但過去三年來，這項工作的結果一直保持一致。

Our most recent run, showed on slide 10, reinforced what we have seen before.

我們最近的運行結果（如幻燈片 10 所示）證實了我們之前所看到的情況。

This comprehensive research and modeling predicts that ORLADEYO will reach and maintain a steady state of over 2,000 patients after 2028, even as newly-laudux are predicted to gain share in the overall market.

這項全面的研究和建模預測，即使新型 laudux 預計將在整個市場中獲得份額，ORLADEYO 也將在 2028 年後達到並維持超過 2,000 名患者的穩定狀態。

We are very confident in what we see now and for the future of ORLADEYO.

我們對 ORLADEYO 的現況和未來充滿信心。

That confidence comes from the huge volume of evidence that we've collected and will continue to collect.

這種信心來自於我們已經收集並將繼續收集的大量證據。

What we see is compound annual global revenue growth of nearly 20% through 2029, when we expect to reach $1 billion in annual revenue, followed by up to a decade of stable and significant cash flow that will help fund our innovative pipeline.

我們預計，到 2029 年，全球年複合收入成長率將接近 20%，屆時我們預計年收入將達到 10 億美元，隨後十年內將出現穩定且可觀的現金流，這將有助於資助我們的創新管道。

I'll turn it over to Helen to describe the recent and upcoming advances in that pipeline.

我將讓海倫來描述該管道最近和即將取得的進展。

Thanks, Charlie.

謝謝，查理。

As both a pediatrician and a parent, I'm incredibly proud that we're on track for regulatory submissions for the first oral prophylactic therapy for children with HAE in 2025.

身為兒科醫生和家長，我感到非常自豪，我們預計在 2025 年提交首個針對 HAE 兒童的口服預防性治療的監管申請。

This is an incredibly important therapy that will change the lives of these children.

這是一種非常重要的治療方法，它將改變這些孩子的生活。

We know that this disease manifests in childhood and can be seen beginning at very young ages.

我們知道這種疾病在兒童時期就表現出來，從很小的時候就開始出現。

In toddlers and school-age children, recurrent swelling and unexplained pain not only need urgent medical attention, such as an emergency room visit or hospitalization, but also interrupt a child's ability to learn, play, make friends, and experience a normal childhood.

對於幼兒和學齡兒童來說，反覆出現的腫脹和不明原因的疼痛不僅需要緊急醫療救治，如急診室就診或住院治療，還會影響孩子學習、玩耍、交朋友和體驗正常童年的能力。

Frequent, unpredictable interruptions in family life and school are unfortunately, what's normal for these children, making the burden of disease a real problem for them and their caregivers.

不幸的是，家庭生活和學業頻繁且不可預測的中斷對這些孩子來說是正常的，這使得疾病負擔成為他們及其照顧者的真正問題。

Treatment availability for children with HAE has lagged behind that of adults.

患有 HAE 的兒童的治療機會落後於成人。

The only prophylaxis is by injection, and parents have to inject their child at home multiple times a month, every month, just to prevent acute attacks.

唯一的預防措施是注射，父母必須每個月在家中給孩子注射多次，以防止急性發作。

Imagine the burden this puts on the whole family.

想像一下這給整個家庭帶來多大的負擔。

Parents face the dilemma of giving their child injections or exposing them to HAE attacks.

父母面臨著給孩子注射藥物或讓其遭受 HAE 攻擊的困境。

We plan to change this completely with the new ORLADEYO granules.

我們計劃利用新的 ORLADEYO 顆粒徹底改變現狀。

They're about the size of sprinkles, so they provide lots of options.

它們的大小與糖粒差不多，所以有很多選擇。

For younger children, these can be mixed in soft foods such as chocolate pudding for easy dosing.

對於較小的兒童，可以將它們混合在巧克力布丁等軟食物中，以方便服用。

Older kids can put the granules into a glass of water or even directly in their mouth and wash it down with a drink.

大一點的孩子可以將顆粒放入一杯水中，甚至直接放入嘴裡，然後用飲料吞下去。

That ease-of-use alone will be transformative for many families.

光是這種易用性就能夠改變許多家庭。

So what comes next with the ORLADEYO pediatric program?

那麼 ORLADEYO 兒科計畫下一步會做什麼呢？

We reported earlier this year that enrollment in the APeX-P study completed, and now we've also completed the observations for the primary outcome, which is evaluation of exposure to the drug in these young patients.

我們在今年稍早報告稱，APeX-P 研究的招募已經完成，現在我們也完成了主要結果的觀察，即對這些年輕患者接觸藥物情況的評估。

They'll continue on drug as the analysis and upcoming regulatory submissions are underway.

他們將繼續對藥物進行研究，因為分析和即將進行的監管提交正在進行中。

Now I'll turn to the transition study to build more post-market evidence for ORLADEYO.

現在我將轉向過渡研究，為 ORLADEYO 建立更多的上市後證據。

As Charlie described, 52% of patients initiating ORLADEYO have switched from another prophylactic therapy and the evidence shows they do very well.

正如查理所描述的，52% 開始使用 ORLADEYO 的患者已經從其他預防療法轉換而來，而且證據表明他們的效果非常好。

Physicians often ask us about the best strategy for making the transition.

醫生經常向我們詢問實現轉變的最佳策略。

And to answer this, we've opened the Phase 4 APeX-P study APeX-T study, to collect data on the transition, enrolling patients who've decided to switch.

為了回答這個問題，我們啟動了第 4 階段 APeX-P 研究（APeX-T 研究），收集有關轉換的數據，招募決定轉換的患者。

The physician will determine how to manage the transition over a defined time period, and this could involve switching immediately or having some overlap between the injectable prophylaxis and ORLADEYO.

醫生將確定如何在規定的時間段內管理轉變，這可能涉及立即切換或在註射預防和 ORLADEYO 之間進行一些重疊。

The goal is to understand how physicians are approaching the transition and to describe the post-transition experience for patients.

目標是了解醫生如何應對轉變並描述患者轉變後的體驗。

We're confident this Phase 4 study will provide more knowledge and experience supporting the decision for future patients to switch as well.

我們相信，這項第 4 階段研究將提供更多的知識和經驗，為未來患者的轉換決策提供支援。

We are excited to get this started.

我們很高興能開始這個工作。

Now let's turn to the pipeline.

現在讓我們轉向管道。

I recently met a patient who described what it was like living with Netherton syndrome with skin that shed and peeled-off in big pieces from fingers, arms and legs every day at school, work and social events.

我最近遇到一位患者，他描述了患有 Netherton 綜合徵的生活狀況，這種疾病的症狀是，每天在學校、工作和社交活動中，手指、手臂和腿上的皮膚都會大塊脫落。

This patient described the shame of being a young child on the first day at school, when no one else in the class, not even the teacher, felt comfortable holding hands.

這位病人描述了自己第一天上學時感到的羞恥，當時班上沒有其他人，甚至連老師都不願意牽手。

Today, there is no disease-altering therapy available for Netherton syndrome.

目前，尚無可以改變病情的療法可以治療 Netherton 症候群。

Treatment is limited to supportive care involving topical treatment of the skin with cumbersome and messy ointments and creams to suit the skin and decrease the scaling.

療程僅限於支持性護理，包括使用繁瑣且麻煩的軟膏和乳霜進行皮膚局部治療以適合皮膚並減少脫屑。

The patient I met has learned to build this into a lifelong daily routine and even so continue to have such profound peeling and shedding of skin that it was hard to face new social interactions.

我遇到的病人已經學會將此作為終生的日常生活，但即使如此，皮膚仍然嚴重脫落，以至於很難面對新的社交互動。

I realized how much of a burden this disease is every day, starting with early childhood and continuing through life.

我意識到這種疾病從幼兒期開始，一直持續到一生，每天都會帶給我多大的負擔。

As reported in October, we recently initiated dosing in a Phase I healthy volunteer study for BCX17725, our potent KLK5 inhibitor for the treatment of Netherton syndrome.

正如 10 月報告的那樣，我們最近啟動了一項 I 期健康志願者試驗，對 BCX17725 進行給藥，BCX17725 是我們用於治療 Netherton 綜合徵的強效 KLK5 抑製劑。

I'm proud to say that this is a huge milestone for patients and for BioCryst.

我很自豪地說，這對患者和 BioCryst 來說都是一個巨大的里程碑。

This marks the successful rapid delivery of our first protein therapeutic into the clinic using our new protein platform technology to diversify and expand our pipeline capabilities.

這標誌著我們利用新的蛋白質平台技術成功地將第一種蛋白質療法藥物快速送入臨床，從而實現了產品線的多樣化和拓展。

And we are evaluating BCX17725 as a functional replacement to correct for the missing protein right at the source for Netherton syndrome.

我們正在評估 BCX17725 作為功能性替代品的可行性，以從源頭上修正 Netherton 症候群缺失的蛋白質。

We are looking for a dramatic reduction in the symptoms of itchiness, flaking and peeling skin.

我們希望顯著減少皮膚搔癢、脫皮和剝落的症狀。

We plan to move quickly next year to patients to evaluate for exposure in the skin and ultimately to assess improvement and healing of the skin.

我們計劃明年迅速對患者進行皮膚暴露評估，並最終評估皮膚的改善和癒合。

Finally, I'll turn to our next drug coming to the clinic avoralstat being evaluated for treatment of diabetic macular edema.

最後，我將介紹下一種即將進入臨床的藥物阿沃拉司他，該藥物正在用於治療糖尿病性黃斑水腫。

What is the effect of this disease?

這個病有什麼影響？

Patients with diabetic macular edema progressively lose their vision, as a result of the effect of diabetes, which causes leakiness in the blood vessels of the retina, resulting in accumulation of fluid known as edema, in the microscopic layers of the retina.

患有糖尿病性黃斑水腫的患者的視力會逐漸喪失，這是由於糖尿病的影響，導致視網膜血管滲漏，從而導致視網膜微觀層中積聚了稱為水腫的液體。

A patient might not recognize it as anything more than fuzziness in the vision at first, with difficulty reading or focusing on small things.

患者一開始可能只會感到視力模糊，無法意識到其他症狀，難以閱讀或專注於看清小事。

Over time, however visual acuity is impaired and patients lose the ability to read, drive and do routine tasks.

然而，隨著時間的推移，視力會受損，患者會失去閱讀、駕駛和執行日常任務的能力。

Current treatment includes VEGF inhibitors that slow the leakiness of the retinal blood vessels and slow or decrease accumulating edema.

目前的治療包括使用 VEGF 抑制劑，以減緩視網膜血管的滲漏以及減緩或減少積聚的水腫。

At some point, this therapy stops working, patients lose their vision.

某種程度上，這種療法會失效，患者會失去視力。

Recently, plasma kallikrein has been shown to contribute to the leaking of the retinal blood vessels in DME and we also know that getting adequate durable exposure to a drug at the retina is a critical step for efficacy.

最近，血漿激肽釋放酶已被證明是導致糖尿病性黃斑水腫（DME）視網膜血管滲漏的原因之一，我們也知道，讓藥物在視網膜上充分且持久地暴露是取得療效的關鍵步驟。

We believe avoralstat and plasma kallikrein inhibitor is the right drug to achieve this.

我們相信阿沃拉司他和血漿激肽釋放酶抑制劑是實現這一目標的正確藥物。

Our goal is to deliver avoralstat continuously by placing it adjacent to the retina, where it will slowly diffuse providing steady exposure lasting months.

我們的目標是透過將阿沃拉司他放置在視網膜旁邊來持續輸送它，它會在視網膜上緩慢擴散，提供持續數月的穩定暴露。

We'll know we've been successful if we see the macular edema decrease in the near-term and ultimately, visual acuity improves.

如果我們看到近期黃斑水腫減少並且最終視力改善，我們就知道我們已經成功了。

We look forward to initiating our first study of avoralstat in patients with DME in 2025.

我們期待在 2025 年啟動針對 DME 患者的第一項阿沃拉司他研究。

So in summary, in 2025, we'll have two new programs dosing in patients in Netherton syndrome and DME with initial data by the end of the year.

總而言之，到 2025 年，我們將推出兩個新的治療項目，分別針對 Netherton 症候群和 DME 患者，並在年底前提供初步數據。

And now I'll turn the call to Anthony.

現在我將電話轉給安東尼。

Thanks, Helen.

謝謝，海倫。

It's great to see that in addition to ORLADEYO having another really impressive quarter, we are also making significant progress on the development side, all while continuing along our path to profitability.

我們很高興地看到，ORLADEYO 除了度過了一個令人印象深刻的季度之外，我們在開發方面也取得了重大進展，同時繼續沿著盈利的道路前進。

You can find our detailed third quarter financials in today's earnings press release, and I'd like to call your attention to a few items for the quarter before reviewing year-end guidance.

您可以在今天的收益新聞稿中找到我們第三季的詳細財務狀況，在審查年終指引之前，我想提請您注意本季度的幾個項目。

Total revenue for the quarter was $117.1 million with $116.3 million of that coming from ORLADEYO.

本季總營收為 1.171 億美元，其中 1.163 億美元來自 ORLADEYO。

That's an almost 36% growth in ORLADEYO quarterly revenue over the same quarter last year, a 33% increase in ORLADEYO revenue on a year-to-date basis over last year, and ORLADEYO revenues in the past 12 months are now over $404 million.

ORLADEYO 的季度營收比去年同期成長了近 36%，ORLADEYO 的年初至今營收比去年同期成長了 33%，過去 12 個月 ORLADEYO 的營收現已超過 4.04 億美元。

Of the $116.3 million of global ORLADEYO revenue $103.1 million came from US sales with the remaining $13.2 million or 11.3% coming from ex-US sales.

ORLADEYO 全球營收 1.163 億美元中，1.031 億美元來自美國銷售，剩餘 1,320 萬美元（11.3%）來自美國以外的銷售。

Operating expenses, not including non-cash stock compensation for the quarter were $92.2 million.

本季營業費用（不含非現金股票補償）為 9,220 萬美元。

Stock compensation for the quarter was $17.2 million and so GAAP operating expenses came in at $109.4 million.

本季的股票補償為 1,720 萬美元，因此 GAAP 營運費用為 1.094 億美元。

We achieved an operating profit for the quarter of $24.9 million, excluding non-cash stock comp and even when including non-cash stock comp, we made an operating profit of $7.7 million.

本季度，我們實現了 2,490 萬美元的營業利潤，不包括非現金股票補償，即使包括非現金股票補償，我們的營業利潤也達到了 770 萬美元。

Cash at the end of the quarter was up $351.7 million and we had positive net cash flow for the quarter of over $13 million.

本季末的現金增加了 3.517 億美元，本季我們的淨現金流為正，超過 1,300 萬美元。

Continuing strong revenue growth combined with disciplined capital allocation were the main drivers.

持續強勁的收入成長和嚴格的資本配置是主要驅動力。

Also worthy of note, is that we chose not to elect to pick the 50% interest option in Q3, meaning that we paid out an extra $5 million of cash versus prior periods.

同樣值得注意的是，我們選擇在第三季不選擇 50% 的利息選項，這意味著我們比前幾期多支付了 500 萬美元的現金。

So being able to achieve that level of cash positivity is a great achievement.

因此，能夠達到這種現金正值水準是一項偉大的成就。

Not electing to exercise the pick option in Q3, and also not electing to draw the additional $150 million in debt tranches, both of which have now expired, is due to the strong cash position and outlook for the company and our independence from capital markets.

沒有選擇在第三季行使選擇權，也沒有選擇提取額外的 1.5 億美元債務部分（這兩項債務現在都已到期），是因為公司現金狀況強勁、前景光明，而且我們不受資本市場的獨立性。

While Q4 and Q1 will likely be cash flow negative, we expect that later next year, we will see sustainably positive quarterly cash flow.

雖然第四季和第一季的現金流可能為負，但我們預計明年晚些時候，我們將看到持續的正季現金流。

Charlie gave updated 2024 revenue guidance for ORLADEYO earlier, and we are now planning to achieve between $430 million and $435 million.

Charlie 早些時候給出了 ORLADEYO 2024 年最新收入指引，目前我們計劃實現 4.3 億美元至 4.35 億美元的收入。

Given that year-to-date ORLADEYO revenues are at $313.5 million, this means that even more of the revenue that we generate in Q4, will fall into the lower royalty tier as we move above $350 million in annual sales during Q4 and could therefore result in an almost $8 million reduction in royalties for Q3 versus Q4 versus Q3.

鑑於 ORLADEYO 年初至今的收入為 3.135 億美元，這意味著，隨著第四季度的年銷售額超過 3.5 億美元，我們在第四季度產生的更多收入將落入較低的特許權使用費層級，因此可能導致第三季度的特許權使用費與第三季度相比減少近 800 萬美元。

In addition to that, we expect significant near-term revenues for RAPIVAB.

除此之外，我們預期 RAPIVAB 近期將帶來可觀的收入。

First, we have API orders for our Southeast Asia partners for Q4 totaling almost $7 million.

首先，我們與東南亞合作夥伴簽訂了第四季度的 API 訂單，總額近 700 萬美元。

Additionally, with the announcement of the new five-year $69 million US government stockpile contract for RAPIVAB so around $14 million per option.

此外，美國政府宣布簽署新的五年期 6,900 萬美元 RAPIVAB 儲備合同，因此每種藥物的價格約為 1,400 萬美元。

We now expect to be able to ship a significant portion of the first option for this order in either late Q4 or in the first half of 2025.

我們現在預計能夠在第四季度末或 2025 年上半年發運該訂單的第一選擇的大部分產品。

And the revenue associated with that shipment should be $10 million with the remaining $4 million shipment likely later in the first half of 2025.

該批貨物的相關收入應為 1,000 萬美元，剩餘的 400 萬美元貨物可能在 2025 年上半年稍後交付。

Conservatively, for RAPIVAB for full year, we expect to have revenue of around $13 million and therefore total company revenue should be in the range of $443 million to $448 million.

保守地說，我們預計 RAPIVAB 全年的收入約為 1,300 萬美元，因此公司總收入應在 4.43 億美元至 4.48 億美元之間。

If we deliver the first part of the stockpile order in Q4 that would result in an upside to this guidance.

如果我們在第四季度交付第一批庫存訂單，那麼該預期將有所上行。

For OpEx, we are now guiding at between $380 million and $390 million.

對於營運支出，我們目前的指導金額在 3.8 億至 3.9 億美元之間。

The main drivers for the increase are increased cost of goods sold related to the RAPIVAB sales, especially the API sales which are at lower margins.

成長的主要原因是與 RAPIVAB 銷售相關的銷售成本增加，尤其是利潤率較低的 API 銷售。

Increased variable costs like incentive compensation and distribution costs related to the continued strong revenue performance for ORLADEYO, and increased expenses that are seasonally booked in Q4 related to our support for the HAE community, including charitable donations.

與 ORLADEYO 持續強勁的收入表現相關的激勵性薪酬和分銷成本等變動成本增加，以及與我們對 HAE 社區的支持（包括慈善捐款）相關的第四季度季節性預訂的費用增加。

I know we said this before, but the company really is in the best financial position that we've ever been in.

我知道我們之前說過這個，但公司目前的財務狀況確實處於有史以來最好的水平。

Advancing past this milepost of achieving a quarter with such significant cash positivity is a great step on our path to profitability, the path that we feel more confident than ever of achieving, while maintaining financial independence from the capital markets.

實現如此顯著的現金正收益這一里程碑，是我們在盈利道路上邁出的一大步，我們比以往任何時候都更有信心實現這一目標，同時保持對資本市場的財務獨立。

Having generated a significant operating profit in each of the past two quarters now, we will generate an operating profit for full year 2024, not including non-cash stock comp and be close to an operating profit even when incorporating non-cash stock comp.

我們已經在過去兩個季度中每個季度都創造了可觀的營業利潤，2024 年全年我們將實現營業利潤（不包括非現金股票補償），即使納入非現金股票補償也接近營業利潤。

Next year, we remain confident that we can achieve quarterly cash flow positivity and be approaching quarterly EPS positivity in the second half of the year and in 2026, we can achieve positivity in both of these metrics on a full year basis.

明年，我們仍然有信心實現季度現金流為正，並在下半年接近季度每股收益為正，到 2026 年，我們可以在全年實現這兩個指標的正增長。

With growing ORLADEYO revenues, plans to submit an NDA for ORLADEYO in children aged 2 to 12 and also generating clinical data in both Netherton syndrome and DME patients during that time frame.

隨著 ORLADEYO 收入的不斷增長，計劃為 2 至 12 歲的兒童提交 ORLADEYO 的 NDA，並在此期間為 Netherton 綜合徵和 DME 患者生成臨床數據。

I'm very excited for the future of the company in the coming months and years.

我對公司未來幾個月和幾年的前景感到非常興奮。

Operator, we can now open for Q&A.

接線員，我們現在可以開始問答環節。

(Operator Instructions)

（操作員指令）

Jessica Fye with JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

Hi, this is Nick on for Jeff.

大家好，我是尼克，代表傑夫。

Thanks for taking our questions.

感謝您回答我們的問題。

The first, on patient growth for ORLADEYO, out of the prophy experience switch patient population, patients moving to prophy from on-demand and those naive to treatment.

首先，關於 ORLADEYO 的患者成長情況，從預防性治療經驗轉換的患者群體，從按需治療轉向預防性治療的患者和未接受過治療的患者。

Can you talk a little bit more about which you think will drive more growth in the near-term and maybe which population represents a long-term opportunity?

您能否進一步談談您認為哪些因素將在短期內推動更多成長，以及哪些人群代表著長期機會？

And then also thinking about your guidance of approaching quarterly positive EPS and positive cash flows in the second half of '25.

然後也考慮您對 25 年下半年實現季度正每股收益和正現金流的指導。

Can you just help provide a little bit more framework on how you're thinking about capital allocation and spend management, especially as your pipeline begins to enter the clinic?

您能否提供更多有關您如何考慮資本分配和支出管理的框架，尤其是當您的管道開始進入診所時？

Charlie, you want to take that?

查理，你想拿走那個嗎？

Sure.

當然。

So Nick, on your first question about whether prophy switches or patients moving from acute-only to ORLADEYO drives a bigger portion.

所以 Nick，關於你的第一個問題，預防性治療的轉變或病人從單純急性治療轉到 ORLADEYO 是否佔了更大的比重。

What we've seen since the start of the launch and this continues is a really even split between the two.

自發布會開始以來，我們看到的是兩者之間勢均力敵的局面，而且這種情況仍在持續。

Over the longer-term, as we kind of get out to that peak of $1 billion, we would expect that prophy switch will drive a larger portion of it.

從長遠來看，隨著我們達到 10 億美元的峰值，我們預計預防性治療轉換將佔更大比重。

But in the next year or so, we expect that kind of even split between the two.

但在未來一年左右的時間裡，我們預期兩者的比例將達到平等。

And then Anthony, do you want to?

那麼安東尼，你想嗎？

In terms of capital allocation, not just for next year, but kind of near-term years through 2026 that we provided guidance for revenues will outpace the OpEx growth that we have we feel very comfortable with that.

在資本配置方面，不只是針對明年，而且到 2026 年的近期，我們提供的指導是收入將超過我們的營運支出成長，我們對此感到非常滿意。

So in terms of capital allocation, our focus will remain on kind of two, three things.

因此，在資本配置方面，我們的重點仍將放在兩三件事上。

One, continuing to secure additional growth for ORLADEYO both here and internationally, continuing to fund the advancement of both Netherton syndrome and DME trials into the clinic into patients and then continuing to advance the early phase pipeline that we have high hopes for.

一是繼續確保 ORLADEYO 在國內和國際上的額外增長，繼續資助 Netherton 綜合徵和 DME 試驗進入臨床並應用於患者，然後繼續推進我們寄予厚望的早期階段的研發管線。

During that period, we will expect to see margin accretion.

在此期間，我們預計利潤率將會增加。

And again we feel very comfortable that we'll get to EPS and cash flow positivity or approaching at tail-end of next year but 2026, we expect to -- we fully expect to hit both of them for a full year.

我們再次感到非常有信心，我們將在明年年底實現每股收益和現金流為正，但我們預計到 2026 年——我們完全預計全年都能實現這兩個目標。

Great.

偉大的。

Thank you.

謝謝。

You’re welcome.

別客氣。

Tazeen Ahmad with Bank of America.

美國銀行的 Tazeen Ahmad。

Hi guys good morning.

大家早安。

Thanks for taking my questions.

感謝您回答我的問題。

The first is on Netherton.

第一個是在 Netherton。

You've now guided to presenting some initial data next year.

現在您已得到指導以便在明年呈現一些初步數據。

What exactly should we be expecting to see?

我們到底該期待看到什麼？

And what kind of data are you looking for?

您正在尋找什麼類型的資料？

Is it biomarker data?

它是生物標誌物數據嗎？

Is it signs of efficacy?

這是療效的跡象嗎？

Are you just looking for any kind of signal of activity, as well as safety.

您是否只是在尋找任何類型的活動以及安全訊號。

It would be helpful to kind of frame that expectation and then just to clarify, as far as OpEx goes, how should we be thinking about that heading into next year?

建構這種預期會很有幫助，然後澄清一下，就營運支出而言，我們應該如何考慮明年的營運支出？

You are investing into moving other programs into clinic and so relative to where you end this year, just directionally, how should we be thinking about OpEx?

您正在投資將其他項目轉移到診所，因此相對於今年年底的目標，從方向上看，我們應該如何考慮營運支出？

Thanks.

謝謝。

So, Helen, why don't you take the Netherton question and Anthony, you can take the OpEx?

那麼，海倫，為什麼不回答 Netherton 的問題，而安東尼，你可以回答 OpEx 的問題呢？

Yeah.

是的。

So, on the Netherton syndrome program, we'll be moving into patients next year.

因此，關於 Netherton 綜合徵項目，我們將於明年開始投入患者治療。

We'll be looking for data that will be a progression of finding.

我們將不斷尋找數據，以期找到進步。

So first, we are looking for penetration of skin exposure at the site of the target.

因此首先，我們要尋找目標部位皮膚暴露的滲透性。

Second, we'll be looking for markers of activity in the skin.

其次，我們要尋找皮膚中的活動標記。

And third, then we'll be looking for recovery in the skin.

第三，我們會關注皮膚的恢復情況。

That will be longer-term.

這將是長期的。

And so that will be, I think, later.

所以我認為，那將是以後的事了。

And Helen, maybe just talk about what we are trying to do with this drug.

海倫，也許我們只是談論一下我們打算用這種藥物做什麼。

It's not just the creams and addressing the symptoms, it's changing the disease.

這不僅僅是使用藥膏和治療症狀，而是改變疾病。

Can you talk about that?

你能談談這個嗎？

Yeah.

是的。

So, what's great about this approach is that it's a disease it's a targeted therapy for the disease.

所以，這種方法的優點在於它是一種針對疾病的針對性治療方法。

So where the standard-of-care is topical and supportive treatment at the moment.

因此，目前的標準治療方法是局部治療和支持性治療。

This would affect the target at the site of disease action in the skin and correct for that missing activity of the protein.

這會影響皮膚中疾病部位的目標並糾正蛋白質缺失的活性。

Like a functional cure.

就像功能性治療一樣。

It's a functional cure.

這是一種功能性治療。

And what we're looking for then is the evidence first of all, that the drug is getting to the point in the skin where it needs to act and then second, that it is having the effect it needs to have, and we'll be looking at the healing of the skin and prevention of itching and scaling.

我們尋找的證據首先是藥物到達皮膚需要起作用的部位，其次是藥物發揮了應有的效果，我們將觀察皮膚的癒合情況以及搔癢和脫屑的預防情況。

Yeah.

是的。

In terms of OpEx, so quarters one, two and three relatively consistent, give or take a few million dollars in terms of our numbers.

就營運支出而言，第一、二和第三季相對一致，就我們的數字而言，上下浮動數百萬美元。

Q4 seasonally, we usually see increased OpEx for that period.

作為季節性因素，我們通常會看到第四季度的營運支出增加。

But going into next year, we'll probably give guidance at the start of the year on a much more specific basis.

但進入明年，我們可能會在年初提供更具體的指導。

But what I would say is for next year, in terms of looking at revenue versus OpEx, revenue growth on an absolute basis will significantly outpace the OpEx growth.

但我想說的是，對於明年而言，從收入與營運支出的角度來看，絕對收入成長將大大超過營運支出成長。

So while I’d expect there to be OpEx growth, especially as we move to of our assets into the clinic, significantly outpaced by revenue and therefore, continuing to see margin accretion during that period.

因此，儘管我預計營運支出將會成長，特別是當我們將資產轉移到診所時，但成長速度將大大超過收入，因此，在此期間利潤率將繼續成長。

Yes.

是的。

So even when we get to pivotal studies, the revenue will be so high with ORLADEYO that it will outpace the spend.

因此，即使我們進行關鍵研究，ORLADEYO 的收入將非常高，以至於超過支出。

Brian Abrahams with RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Brian Abrahams。

Hi guys good morning.

大家早安。

Thanks for taking my questions and congrats on the quarter and the continued progress.

感謝您回答我的問題，並對本季度和持續的進步表示祝賀。

Two for me.

對我來說是兩個。

First off, your 2024 ORLADEYO revenue guidance suggests a slight slowdown in quarter-over-quarter sales growth for fourth quarter.

首先，您對 2024 年 ORLADEYO 收入的預測顯示第四季度的環比銷售成長略有放緩。

I'm just wondering if that just reflects less expected benefit from the paid drug uptick that you saw in third quarter or anything else embedded in there?

我只是想知道，這是否反映了您在第三季度看到的付費藥品上漲帶來的預期收益減少，還是其中的其他任何影響？

And then secondarily, just looking at 2025 consensus numbers, those do suggest a slight slowdown in the quarterly ORLADEYO sales growth rate as well.

其次，僅查看 2025 年的一致數據，這些數據也確實顯示 ORLADEYO 季度銷售成長率略有放緩。

And I realize it is too early for specific guidance for next year, but just wondering if there's anything we should be thinking about that you may be observing or respecting with respect to demand or gross to net trends that might support this expectation, as we get into next year.

我知道現在就為明年提供具體指引還為時過早，但我只是想了解，在進入明年之際，在需求或總淨趨勢方面，是否有任何我們應該考慮的、可能支持這一預期的事情？

Thanks.

謝謝。

Charlie, you got both of those.

查理，你做到了這兩點。

Yeah, I got it.

是的，我明白了。

So yes, Brian, for Q4 a couple of things.

是的，布萊恩，對於第四季有幾件事。

One, we do typically see the paid rate slowing down in the latter part of the year.

首先，我們通常會看到下半年支付率會放緩。

And that's really because as new patients come on to therapy, it's harder to get them approved for paid therapy at the end of the year.

這是因為，隨著新病人開始接受治療，年底獲得付費治療的批准變得更加困難。

And so that's a contributor to why we have the bump up in the first half of next year as we're able to convert those patients to paid.

所以這就是為什麼我們明年上半年的收入會增加，因為我們能夠將這些患者轉為付費患者。

The other piece is just around the holidays and the holidays don't set up particularly well this year, the way Christmas falls, but what we've reported, the $430 million to $435 million, that's what we see in our models right now.

另一件事是在假期前後，今年的假期安排並不是特別好，就像聖誕節一樣，但我們報告的 4.3 億美元到 4.35 億美元，是我們目前在模型中看到的。

As far as the growth rate slowing next year, we are certainly not seeing any slowing in demand as I noted.

至於明年成長率放緩，正如我所說，我們肯定沒有看到需求放緩。

So clearly, the percentage growth over time will go down as the revenue keeps going up, but we're really confident in what we see for next year, continued demand, continued patient switching.

因此顯然，隨著收入的不斷增加，百分比成長率將會下降，但我們對明年的持續需求和持續的患者轉換充滿信心。

So next year should be a very good year for us.

所以明年對我們來說將會是非常好的一個年頭。

Yeah, Brian, I'd just restate what Charlie said earlier, which is 20% compound annual growth rate through 2029.

是的，布萊恩，我只是想重申查理之前所說的話，即到 2029 年的複合年增長率為 20%。

That's a nice clip, but nice growth.

這是一個很棒的剪輯，也反映了很好的成長。

Thanks Jon, thanks Charlie really helpful.

謝謝喬恩，謝謝查理，真的很有幫助。

Maury Raycroft with Jefferies.

莫里·雷克羅夫特 (Maury Raycroft) 和傑富瑞 (Jefferies) 在一起。

Hi, good morning.

嗨，早安。

Congrats on the quarter and thanks for taking my questions.

恭喜本季取得佳績，感謝您回答我的問題。

I was wondering for the 67 new US prescribers added this quarter, was that better than expected or as expected?

我想知道本季美國新增的 67 名處方人員是否比預期好或達到預期？

And can you say how many of them are from Tier 1 versus Tier 2 and how this could contribute fourth quarter and going forward?

您能否說出其中有多少來自 Tier 1 和 Tier 2，以及這對第四季及未來的貢獻如何？

Sure, Maury.

當然，莫里。

The 67 was, as I noted it was one of our better quarters in the last two years.

正如我所說，67 是我們過去兩年表現較好的季度之一。

But all that said, the last eight quarters have been really strong.

但總而言之，過去八個季度的表現確實非常強勁。

We've averaged about 62 new prescribers per quarter.

我們平均每季新增處方人員約 62 名。

So, this was very much in-line with that consistent growth we've seen.

所以，這與我們所看到的持續成長非常一致。

We in the quarter, we had another very even split between Tier 1 and Tier 2 physicians, as we have in recent quarters, and we expect that to continue.

在本季度，我們再次看到了一級和二級醫師之間的均衡分佈，就像最近幾季一樣，我們預計這種情況將持續下去。

So I think it is just a sign of how much demand there is for this drug and also how much opportunity we still have in front of us.

所以我認為這只是顯示這種藥物的需求有多大，以及我們面前還有多少機會。

Got it.

知道了。

And maybe a follow-up, just for the Phase IV study.

或許還會進行後續研究，僅針對第四階段研究。

What are some of your expectations for what the results could show in respect to switching dynamics?

您對轉換動力學結果有何期望？

And what are some of the strategies for how you will leverage those data?

您將採用哪些策略來利用這些數據？

Helen?

海倫？

So, in terms of the results, and this is an observational study, it's a Phase 4.

因此，就結果而言，這是一項觀察性研究，目前處於第 4 階段。

So we are looking at how physicians are actually managing that transition.

因此，我們正在觀察醫生實際上是如何管理這種轉變的。

As I said in the remarks, they have a choice how they manage it, whether they transition the patient immediately.

正如我在評論中所說，他們可以選擇如何處理，是否立即轉移患者。

ORLADEYO whether they do it over time, and we'll be looking for how that experience goes and then how patients are doing after the switch to ORLADEYO.

ORLADEYO 是否會隨著時間的推移而這樣做，我們會觀察這種體驗如何，以及患者轉換到 ORLADEYO 後的情況如何。

Got it.

知道了。

Okay, thanks for taking my questions.

好的，感謝您回答我的問題。

Stacy Ku with TD Cowen.

Stacy Ku 的 TD Cowen。

Hi, thanks for taking my questions.

你好，謝謝你回答我的問題。

First for Charlie, a quick follow-up.

首先對查理來說，這是一個快速的後續行動。

As we think about these clinician additions for 2025, can you talk about your goals and potential additions for next year, just specific numbers around how many clinicians you aim to kind of add on.

當我們考慮 2025 年臨床醫生的增加時，您能談談您明年的目標和潛在的增加嗎，只是關於您計劃增加的臨床醫生的具體數字。

And then the next question is also for next year, what are your expectations in terms of the transition to paid just because we've seen such nice progress this year?

下一個問題也是針對明年的，由於我們今年看到瞭如此好的進展，您對付費過渡有何期望？

And then last for Helen, can you speak further to this transition study.

最後，海倫，您能進一步談談這項過渡研究嗎？

With these results, who you trying to target?

透過這些結果，您想針對誰？

Is it more for community clinicians?

它是否更適合社區臨床醫師？

Or is it just to give more feedback for patients that are thinking about switching?

或者只是為了向正在考慮轉換的患者提供更多回饋？

Thank so much.

非常感謝。

Hi, Stacy.

你好，史黛西。

So goals for adding new physicians, I think generally, our goal is to continue the same progress that we've been making.

因此，我認為，增加新醫生的目標總體上是，我們的目標是繼續取得我們已經取得的相同進展。

So continue to reach both Tier 1s and Tier 2 physicians.

因此，請繼續接觸一級和二級醫生。

At this point, a little over 70% of Tier 1 physicians have prescribed ORLADEYO.

目前，已有超過 70% 的一級醫師開出了 ORLADEYO。

So we have more room to grow there in that group.

因此我們在該群體中還有更大的成長空間。

And also that in Tier 1, there is a lot more opportunity within current prescribers to do more.

而且，在第 1 層，目前的處方人員有更多的機會做更多的事情。

So we'll keep the focus there.

因此，我們會繼續集中精力在那裡。

But as I always say, if there is an HAE patient out there, if there is a physician treating an HAE patient, we will find that position, and we will talk to them about ORLADEYO and the team has done a great job with that.

但正如我常說的那樣，如果有 HAE 患者，如果有醫生正在治療 HAE 患者，我們就會找到那個位置，我們會與他們討論 ORLADEYO，而團隊在這方面做得很好。

As far as the paid rate, we expect to make continued progress towards 85%.

就支付率而言，我們預計將繼續朝85%邁進。

And one thing that we've talked a lot about is how the Medicare paid rate has stepped back we'll look to see in the first part of that next year, whether that corrects itself, whether patients are able to afford their copayments as the IRA rolls in.

我們經常討論的一件事是，聯邦醫療保險支付率如何回落，我們將在明年上半年觀察這種情況是否會自行糾正，以及隨著 IRA 的推出，患者是否有能力負擔共同支付的費用。

But we'll have more to report on that in the first quarter.

但我們將在第一季發布更多相關報告。

And then with regard to the transition study.

然後是關於過渡研究。

So first, we know that patients are doing well transitioning in the real world.

首先，我們知道患者在現實世界中的轉變過程進展良好。

We've seen that in the real-world evidence.

我們已經在現實世界的證據中看到了這一點。

We are getting questions as more and more physicians are prescribing ORLADEYO and those questions are how do I manage this?

隨著越來越多的醫生開出奧拉迪約的處方，我們收到了很多問題，這些問題包括我該如何處理？

How does the patient transition do you start immediately?

您如何立即開始患者轉變？

Or do you overlap therapies.

或者你們的治療方法有重疊。

So this study is to capture that experience in the real world and then use that information to describe it for physicians who are less experienced with managing patients with HAE through that transition.

因此，本研究旨在捕捉現實世界中的經歷，然後利用這些資訊向那些在治療 HAE 患者方面經驗較少的醫生描述這種轉變。

Okay.

好的。

Really helpful.

真的很有幫助。

Thank you.

謝謝。

Liisa Bayko with Evercore ISI.

Liisa Bayko 與 Evercore ISI 合作。

Please go ahead.

請繼續。

Hi, there.

你好呀。

Can you talk a little bit more about your transition away from free drug on to commercial sort of the shape of that when we should get to that 85%.

您能否再多談一下從免費藥物轉變為商業藥物的轉變，以及當我們應該達到 85% 時的具體情況。

And then also how to think about the first quarter, I know that's been a little lumpy, especially with the unknowns around the Medicare portion of that?

然後還有如何看待第一季度，我知道這有點不穩定，尤其是醫療保險部分周圍的未知因素？

Have you sorted through that, if you could give us any color, that would be great.

你已經整理好了嗎？

Thank you.

謝謝。

Sure.

當然。

Again, the 85% is a long-term goal.

再說一遍，85%是一個長期目標。

We are making really good progress.

我們正在取得非常好的進展。

As I noted, we're already at 82% for the commercial segment.

正如我所說，我們的商業領域覆蓋率已經達到 82%。

And commercial is about 60% of our patients overall.

商業患者約占我們患者的 60%。

So it just -- it shows where we are headed.

所以這只是——它顯示了我們前進的方向。

We would expect it to get to the 85% over the next three years or so.

我們預計未來三年左右這一比例將達到 85%。

But the big wild card is, as I was just saying, is what happens with the Medicare patients, as we go to the transition to the IRA and the MAX $2,000 out of pocket.

但正如我剛才所說，最大的不確定因素是，當我們轉向 IRA 和最高 2,000 美元的自付費用時，醫療保險患者會發生什麼情況。

Thank you.

謝謝。

Yeah, And I'd just add Liisa, in the first quarter, we'll have a better sense of that.

是的，我只想補充一下 Liisa，在第一季度，我們會對此有更好的了解。

That's where that you get a really good idea of who's covered who's not with Medicare in the first quarter.

這樣，您就能真正了解第一季誰享有了醫療保險，誰沒有享有醫療保險。

So we should have a better idea in.

所以我們應該有一個更好的想法。

What factors there are under your control, if any?

如果有的話，哪些因素是您可以控制的？

What's under our control is the relationships that we have with patients and all the investments that I've described before to build up our team so that we have really the best-in-class patient services organization.

我們所掌控的是我們與患者之間的關係以及我之前描述的為建立我們的團隊而進行的所有投資，以便我們擁有真正一流的患者服務組織。

And so we get ready for that Q1 reauthorization season.

所以，我們要為第一季的重新授權季做好準備。

We learned a lot in the last couple of years.

過去幾年我們學到了很多。

We're going to put all those learnings into practice at the beginning of 2025.

我們將在 2025 年初將所有這些學習成果付諸實現。

Our goal is to get better and better every year.

我們的目標是每年都變得越來越好。

Yeah, And I would say, while we can't control this, the burden on the patient in Medicare is going down dramatically from last year to this year and from this year to next year.

是的，我想說，雖然我們無法控制這一點，但從去年到今年，從今年到明年，醫療保險患者的負擔正在大幅下降。

And then what we can't control is timing, right?

那我們無法控制的是時間，對嗎？

And how when that effect?

以及效果如何？

So could it come all in the first quarter?

那麼這一切都能在第一季實現嗎？

Possibly.

有可能。

Could it be spread out over a couple of years, possibly.

有可能，這個進程會持續幾年嗎？

We don't know the answer to that.

我們不知道答案。

Great.

偉大的。

Okay, thanks.

好的，謝謝。

Gena Wang with Barclays.

巴克萊銀行的 Gena Wang。

Thank you.

謝謝。

I have two questions.

我有兩個問題。

Maybe just follow up Liisa question.

也許只是跟進 Liisa 的問題。

First question, also noncommercial setting.

第一個問題，也是非商業設定。

So I know there's not too much you can do, but if there is unfavorable to you, what could be actual steps you can do regarding try to get additional improvement regarding the revenue and maybe also from the commercial side to reach the total $800 million revenue guidance in the US?

所以我知道您能做的並不太多，但如果對您不利，您可以採取哪些實際措施來嘗試進一步提高收入，也許還可以從商業方面努力達到美國 8 億美元的總收入預期？

And the second question is regarding your new assets.

第二個問題是關於您的新資產。

So the question for the 7725 Phase I data in 2025.

所以問題是關於 2025 年的 7725 第一階段資料。

How would you do you need to do a biopsy the skin biopsy and to measure the protein expression.

您需要怎麼做才能進行皮膚活檢並測量蛋白質表現。

And I think that the heating part seems pretty straightforward.

我認為加熱部分看起來相當簡單。

And then regarding the biomarker, could you give a little more color regarding what kind of protein expression you are looking for?

然後關於生物標誌物，您能否詳細說明您正在尋找哪種蛋白質表現？

And how do you measure that?

那你如何衡量呢？

Okay.

好的。

So Charlie, do you want to take question one and Helen, number two?

那麼查理，你想回答第一個問題嗎？

Hi, Gena, as far as what we can do, I think going to say something pretty similar to the last couple of answers that we gave.

你好，Gena，就我們能做的事情而言，我想說的與我們之前給出的幾個答案非常相似。

We do what we can to help patients get ready, but there's a lot that's outside of our control.

我們盡力幫助患者做好準備，但有很多事情是我們無法控制的。

One thing also patients do is themselves is work closely with the HAEA, the Patient Association who also gives them a lot of education and information about getting to paid therapy.

患者自己做的一件事就是與 HAEA（患者協會）密切合作，該協會也為患者提供大量有關獲得付費治療的教育和資訊。

And that's true for patients who have Medicare and patients who have other insurance.

對於擁有醫療保險和擁有其他保險的患者來說，情況都是如此。

And so what we do is whatever we can do compliantly to help them educate them and put them in best position to get to paid.

因此，我們所做的就是盡我們所能合規地幫助他們教育他們並讓他們處於獲得報酬的最佳位置。

As Jon was just noting.

正如喬恩剛才指出的。

Sorry, Charlie.

對不起，查理。

Just one other thing you said what could negatively go wrong.

您剛才也說了可能會出現負面影響的事情。

It's actually trending in the positive we saw it go from under 50% now up to 55% this year.

事實上，我們看到它呈現積極的趨勢，從現在的不到 50% 上升到今年的 55%。

I'm certain that part of that is the changes in the cost of the patients, and we expect that to continue to improve.

我確信其中部分原因是患者費用的變化，我們預計這種情況會繼續改善。

So I don't think we see it negative, we see it moving in the positive direction.

因此，我認為我們並不認為它是負面的，而是認為它正朝著正面的方向發展。

What we can't predict is what I said before, the speed at which that changes.

正如我之前所說，我們無法預測變化的速度。

That's right.

這是正確的。

Yes.

是的。

And then on 17725, so we'll be enrolling in patients in 2025 with initial data coming in.

然後是 17725，所以我們將在 2025 年招募患者，並獲得初步數據。

It is common to do skin biopsy or to test the skin in this disease, and that's a very good way of understanding if you're getting penetration of the drug at the skin.

對於這種疾病，進行皮膚活檢或皮膚測試是很常見的，這是一種了解藥物是否滲透到皮膚的好方法。

So that's a critical first step is to demonstrate that the drug is getting to the skin, binding to the target in the skin -- and this drug is also -- has very high affinity, so we'll be looking for binding to the target and then maintenance of that binding.

因此，關鍵的第一步是證明藥物能夠到達皮膚，並與皮膚中的目標結合 - 而且這種藥物也具有非常高的親和力，因此我們將尋找與目標的結合，然後維持這種結合。

So once it's on the target, it doesn't come off.

因此一旦瞄準目標，就不會脫落。

So in terms of biomarkers then in the skin, we'll be looking, number one, as I said, for drug present in the skin, but number two, activity at target.

因此，就皮膚中的生物標記而言，正如我所說，我們首先要尋找的是皮膚中存在的藥物，其次要尋找的是目標的活性。

So this is activity of the drug in binding and preventing KLK5 activity.

這是藥物結合併阻止 KLK5 活性的作用。

It's possible downstream that we could also be looking at cytokine and cytokine release, that's a downstream cascade reaction to KLK5 activity.

有可能，下游我們也會觀察細胞激素和細胞激素的釋放，這是對 KLK5 活性的下游級聯反應。

That's the kind of thing that we'll define further as we move towards the clinical patients.

當我們走向臨床患者時，我們會進一步定義這種事情。

And Helen, is it safe to say with a potent drug like this, what dose we ultimately need and the frequency will be another important piece to learning.

海倫，對於這種強效藥物，我們可以肯定地說，我們最終需要的劑量和頻率是另一個需要學習的重要部分。

It will be.

這將是。

Yes.

是的。

So we're expecting to see that activity binding affinity sticking and activity.

因此，我們希望看到活性結合親和力黏附和活性。

But that means that we'll be looking at how long is it before you need another dose.

但這意味著我們要觀察您多久才需要服用另一劑。

This could be a very potent we expect to be delivering it potentially and subcutaneously, and it could be an extended interval time before a second dose is needed.

這可能非常有效，我們期望透過皮下注射的方式給藥，並且可能需要延長間隔時間才需要注射第二劑。

Thank you.

謝謝。

Serge Belanger with Needham & Company.

Needham & Company 的 Serge Belanger。

Good morning and thanks for squeezing me in.

早安，感謝您抽空給我。

I guess two for Charlie.

我想查理有兩個。

The first one on patient adds.

第一個關於病人的補充。

I think on slide 8 where you lay out the path to get to $800 million in sales you assume an annual rate of 200 new patients.

我認為在第 8 張投影片中您列出的實現 8 億美元銷售額的途徑是假設每年新增 200 名患者。

Just curious where you are tracking relative to that target given that you said that the rate is currently 14% or 15% above where you were 12 months ago?

我很好奇，鑑於您說目前的利率比 12 個月前高出 14% 或 15%，那麼您相對於該目標的追蹤情況如何？

And then secondly, on the competition front, I know one of the prophylactics was delayed a little bit recently, but I think we should assume one or two new approvals on the prophy front in 2025.

其次，在競爭方面，我知道其中一種預防措施最近有點延遲了，但我認為我們應該假設 2025 年在預防方面會有一兩種新的批准。

How do you think about the that could impact the switch opportunity for ORLADEYO once they're approved?

一旦獲得批准，您認為這會對 ORLADEYO 的轉換機會產生什麼影響？

Thanks.

謝謝。

Thanks, Serge.

謝謝，Serge。

Yes, on patient adds, we are very much on track.

是的，在增加患者方面，我們的進展非常順利。

As you can imagine, we're having a great year with ORLADEYO.

正如您所想像的，我們與 ORLADEYO 一起度過了美好的一年。

And so as I said in my prepared remarks, we are as confident as ever.

正如我在準備好的演講中所說，我們一如既往地充滿信心。

As far as the potential new competition yes, we expect two new injectable pro fees to launch sometime in the middle of next year.

就潛在的新競爭而言，是的，我們預計兩項新的可注射專業費用將在明年年中某個時候推出。

And what our all of our modeling and market research shows is that new injectables will really compete with existing injectables, not with us as an oral but it's an opportunity in that there will be more discussion about switching.

我們所有的建模和市場研究表明，新型注射劑將與現有註射劑真正競爭，而不是與我們的口服劑競爭，但這是一個機會，因為將會有更多關於轉換的討論。

And we have, we think the most differentiated product with once-daily oral, and so it creates an opportunity for us.

我們認為最具差異化的產品是每日一次的口服產品，因此這為我們創造了機會。

And we were ready for anything that might have come this quarter now that it's a little bit delayed, we will be ready at the middle of next year.

我們已經為本季可能發生的任何事情做好了準備，雖然有點延遲，但我們將在明年年中做好準備。

And Serge, I think about it this way, if a doc in a patient or at a point where they are open to switching from their current therapy.

塞爾吉，我是這樣想的，如果醫生在治療一個病人或他處於一個願意改變現有療法的階段。

Why on earth wouldn't they try the oil first, right?

他們為什麼不先嘗試石油呢？

And so we think that's a real opportunity.

因此我們認為這是一個真正的機會。

This concludes our question-and-answer session.

我們的問答環節到此結束。

I would like to turn the conference back over to Mr. Stonehouse for any closing remarks.

我想將會議交還給斯通豪斯先生，請他作最後發言。

Yes.

是的。

So it's great to see another outstanding quarter on multiple fronts.

因此，很高興看到本季在多個方面又取得了出色的成績。

And these quarters are the building blocks of building a growing company and a sustainable company.

這些部分是打造一家成長型公司和永續發展型公司的基石。

And that doesn't happen by accident.

這並不是偶然發生的。

That happens by dedicated employees that are working their butts-off to deliver on our goals and continue to help us execute quarter after quarter after quarter.

這是由那些盡心盡力、努力工作以實現我們的目標並持續幫助我們一個季度又一個季度地完成任務的員工實現的。

So, I want to say thank you to all the BioCryst employees for another great quarter and what's shaping up to be a fantastic year.

所以，我想向所有 BioCryst 員工說謝謝，感謝他們度過了另一個出色的季度，並有望迎來精彩的一年。

You guys have a great day.

祝你們有個愉快的一天。

The conference has now concluded.

會議現已結束。

Thank you for attending today's presentation.

感謝您參加今天的演講。

You may now disconnect.

您現在可以斷開連線。