BioCryst Pharmaceuticals Inc (BCRX) 2025 Q3 法說會逐字稿

Good day, and welcome to BioCryst third quarter 2025 earnings conference call. (Operator Instructions) Please note this event is being recorded.

各位來賓，歡迎參加BioCryst 2025年第三季財報電話會議。 （操作說明）請注意，本次會議正在錄音。

I would now like to turn the conference over to Nick Wilder. Please go ahead.

現在我把會議交給尼克·懷爾德。請開始吧。

Good morning, and welcome to BioCryst's third quarter 2025 corporate update and financial results conference call. Participating with me today are CEO, Jon Stonehouse; President and Chief Commercial Officer, Charlie Gayer; Chief Development Officer, Dr. Bill Sheridan; and Chief Financial Officer, Babar Ghias. A press release and slide presentation about today's news are available on our investor relations website.

早安，歡迎參加BioCryst公司2025年第三季公司最新動態及財務業績電話會議。今天與我一同出席會議的有：執行長Jon Stonehouse；總裁兼商務長Charlie Gayer；首席開發長Bill Sheridan博士；以及財務長Babar Ghias。有關今天新聞的新聞稿和幻燈片簡報已發佈在我們的投資者關係網站上。

Today's call may contain forward-looking statements, including statements regarding future financial 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.

今天的電話會議可能包含前瞻性陳述，包括有關未來財務業績、未經審計的前瞻性財務資訊以及公司未來表現和/或成就的陳述。這些陳述受已知和未知風險及不確定性的影響，可能導致我們的實際業績、表現或成就與本次演示中明示或暗示的任何未來業績或表現存在重大差異。

For additional information, including a detailed discussion of these risks, please refer to slide 2 of the presentation. In addition, today's conference call includes non-GAAP financial measures. For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release.

如需了解更多信息，包括對這些風險的詳細討論，請參閱簡報第2頁。此外，今天的電話會議包含非GAAP財務指標。如需了解這些非GAAP指標與最直接可比較的GAAP財務指標的調節表，請參閱獲利新聞稿。

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

現在我想把電話交給喬恩‧斯通豪斯。

Thank you, Nick. We are very pleased to report yet another strong quarter for the year. Starting with ORLADEYO, we continue to see strong revenue growth year-over-year on a growing revenue base, well on our way to $1 billion at peak. Charlie will share the details as this was the first quarter with new competition, and we continue to see strong underlying growth and a growing prescriber base as we predicted.

謝謝尼克。我們非常高興地宣布，今年又一個季度業績強勁。首先是ORLADEYO，我們持續看到營收年增，且營收基數不斷擴大，正朝著10億美元的高峰穩步邁進。查理將詳細介紹情況，因為這是新競爭對手出現後的第一個季度，正如我們預測的那樣，我們繼續看到強勁的潛在成長和不斷擴大的處方醫生群體。

Next, we closed the sale of our European business and paid off our Pharmakon debt. And this not only cleaned up our balance sheet, but put us in a very strong financial position, generating operating profit and positive cash flow. Babar will share more details regarding our financial position. We are also making progress with our pipeline and expect early data that should give an initial view on activity and dose from our DME program, and we plan to share this early next year.

接下來，我們完成了歐洲業務的出售，並償還了Pharmakon的債務。這不僅改善了我們的資產負債表，也使我們的財務狀況非常穩健，實現了營業利潤和正現金流。 Babar將分享更多關於我們財務狀況的細節。我們的研發管線也正在取得進展，預計將獲得早期數據，這些數據將初步反映DME專案的活性和劑量情況，我們計劃在明年初公佈這些數據。

If these data are encouraging, we have also made a decision that given the program is outside our rare disease area of focus, we will look to spin out or partner this program to put it in the hands of someone better suited to advance it further. Regarding BCX17725, Bill will share encouraging data from our healthy volunteer study showing evidence that the drug does get to the skin following IV administration.

如果這些數據令人鼓舞，鑑於該計畫不在我們關注的罕見疾病領域，我們已決定將其剝離或與其他機構合作，交給更適合推進該計畫的人員。關於 BCX17725，Bill 將分享我們健康志願者研究中令人鼓舞的數據，這些數據表明該藥物在靜脈注射後確實能到達皮膚。

This is important as this is where the target for Netherton syndrome is and with a very potent inhibitor in BCX17725, we are excited to see in Netherton syndrome patients what effect it has on the disease. Enrollment is taking a little bit longer than planned, and we now expect early data in a small number of Netherton syndrome patients later in Q1 next year.

這一點至關重要，因為這正是內瑟頓症候群的治療標靶所在。 BCX17725 是一種非常有效的抑制劑，我們很期待看到它對內瑟頓症候群患者的療效。目前患者招募工作進展比預期稍慢，我們預計將於明年第一季稍後獲得少量內瑟頓症候群患者的早期數據。

Lastly, having announced the proposed acquisition of Astria last month and the expected close in Q1 next year, we are extremely excited to add a late-stage asset, navenibart, to our pipeline to leverage our expertise in HAE and bring patients a new treatment option with a low burden of administration. So clearly, we have been busy since last reporting quarterly earnings, and this is shaping up to be another outstanding year of performance for our company.

最後，繼上個月宣布擬收購Astria公司並預計將於明年第一季完成交易後，我們非常高興能將後期研發項目navenibart納入我們的產品線，以充分利用我們在遺傳性血管性水腫（HAE）領域的專業知識，為患者帶來一種給藥負擔輕的新治療方案。顯然，自從上次發布季度財報以來，我們一直忙於各項工作，而今年預計將成為公司業績又一個輝煌的年份。

With that, I will turn it over to Charlie.

接下來，我將把麥克風交給查理。

Thanks, Jon. We entered the final quarter of 2025 with continued momentum. We are raising our ORLADEYO revenue guidance to between $590 million and $600 million for the year, even after closing the sale of our European operations on October 1. And the exciting possibilities of the ORLADEYO granules launch for kids with HAE and the acquisition of Astria are just ahead.

謝謝，Jon。我們帶著持續的成長勢頭進入了2025年的最後一個季度。即使在10月1日完成了歐洲業務的出售之後，我們仍然將ORLADEYO全年的營收預期上調至5.9億美元至6億美元之間。此外，ORLADEYO顆粒劑即將上市，用於治療患有遺傳性血管性水腫（HAE）的兒童，以及收購Astria，這些都令人振奮。

ORLADEYO continues to be the most differentiated prophylaxis therapy for patients with HAE. Most HAE patients would rather prevent their attacks with an oral therapy. Physicians know this, and they trust ORLADEYO. Even as two new prophylaxis products launched recently, offering patients the potential of once monthly injectable dosing, new prescriptions for ORLADEYO continued at the same strong pace we have seen over the past two years.

ORLADEYO 仍是目前針對 HAE 患者最具差異化的預防性治療方案。大多數 HAE 患者更傾向於使用口服藥物來預防發作。醫生們深知這一點，並且信賴 ORLADEYO。儘管近期推出了兩種新的預防性產品，為患者提供了每月一次注射給藥的可能性，但 ORLADEYO 的新處方量仍然保持著過去兩年來強勁的增長勢頭。

In fact, we slightly exceeded the new patient prescription total from the third quarter a year ago. We also continue to expand the number of ORLADEYO prescribers with 64 new prescribers in the US, exceeding the average of the past eight quarters. The well-established trends in patient retention remained unchanged, and we ended the quarter with a paid patient rate of 82%, right in line with the typical second half pattern compared with the first half of the year.

事實上，我們本季新增病患處方總量略高於去年同期。同時，我們繼續擴大 ORLADEYO 處方醫生的數量，在美國新增 64 位處方醫生，超過了過去八個季度的平均值。患者留存率保持穩定，本季末付費患者比例達 82%，與往年下半年相比，這一比例基本上符合預期。

As always, we're very pleased with the great results, but not surprised. Our deep insight and market simulation works consistently predicted that the growth of ORLADEYO would not be affected by new competition. We updated that work over the summer, and the 2025 results were nearly identical to the 2024 results, as you can see on slide 8 in today's presentation.

和以往一樣，我們對取得的優異成績感到非常滿意，但也在意料之中。我們深入的市場洞察和模擬分析一直預測，ORLADEYO 的成長不會受到新競爭的影響。我們在夏季更新了相關分析，2025 年的預測結果與 2024 年的預測結果幾乎完全一致，正如您在今天簡報的第 8 頁投影片中所見。

With the expected addition of ORLADEYO granules on top of the existing strong growth trends for ORLADEYO capsules, our market simulation continues to predict $1 billion in peak revenue for BioCryst in 2029, even after the sale of our European business. The analysis demonstrates that new injectable therapies primarily compete with existing injectable therapies.

鑑於 ORLADEYO 顆粒劑的預期銷售成長，以及 ORLADEYO 膠囊劑目前強勁的成長勢頭，我們的市場模擬預測，即使在出售歐洲業務後，BioCryst 的峰值收入仍將在 2029 年達到 10 億美元。分析表明，新型注射療法的主要競爭對手是現有的注射療法。

This is why we are so enthusiastic about the prospect of adding navenibart to our portfolio. With navenibart, we could have the lowest burden, most differentiated injectable prophylactic therapy, along with a long-time leading oral therapy, significantly expanding our ability to help patients in the HAE community. We expect navenibart to drive double-digit HAE revenue growth well into the 2030s after ORLADEYO revenue reaches a steady plateau.

正因如此，我們對將navenibart納入產品組合的前景感到無比興奮。有了navenibart，我們就能擁有負擔最輕、差異化程度最高的注射預防性療法，以及長期領先的口服療法，從而顯著提升我們幫助HAE患者的能力。我們預計，在ORLADEYO收入趨於穩定後，navenibart將推動HAE業務在2030年代實現兩位數的收入成長。

And we expect to manage costs by using the same rare disease commercialization engine that has made ORLADEYO so successful. Today, I'm also very pleased to announce that Ron Dullinger will succeed me as Chief Commercial Officer when I move to the CEO role on January 1. Ron led the sales team at ViroPharma during the early days of CINRYZE commercialization.

我們計劃沿用ORLADEYO取得巨大成功的罕見疾病商業化模式來控製成本。今天，我也非常高興地宣布，我將於1月1日昇任首席執行官，屆時Ron Dullinger將接替我擔任首席商務官。 Ron曾在CINRYZE商業化初期領導ViroPharma的銷售團隊。

While that drug changed the HAE treatment paradigm at the time, Ron always knew that an oral therapy was what many patients really wanted, and he wanted to be part of making that possible. Ron joined us in 2019 to build and lead the US team -- US sales team for the launch of ORLADEYO. And since 2022, he has served as General Manager of our US and Americas business, fostering a team culture that is deeply caring and authentically focused on serving patients while also being relentlessly driven to improve.

雖然那款藥物在當時改變了遺傳性血管性水腫（HAE）的治療模式，但羅恩始終認為，許多患者真正渴望的是口服療法，而他希望能夠參與實現這一目標。羅恩於2019年加入我們，負責組建並領導美國團隊——也就是ORLADEYO上市的美國銷售團隊。自2022年以來，他一直擔任我們美國及美洲業務的總經理，致力於打造一種充滿關懷、真正以服務患者為中心，並不斷追求卓越的團隊文化。

That's a rare combination, and it has produced amazing results. I look forward to what our commercial team will achieve under Ron's leadership. As we look forward to helping a growing number of HAE patients, our excitement about the potential to help patients with Netherton syndrome is also growing.

這是一種難得的組合，並且已經取得了驚人的成果。我非常期待我們的商業團隊在羅恩的領導下能夠取得怎樣的成就。在我們期待幫助越來越多的遺傳性血管性水腫（HAE）患者的同時，我們也對幫助內瑟頓症候群（Netherton syndrome）患者的潛力感到無比興奮。

I'll turn it over to Bill to describe our progress with BCX17725.

接下來由比爾來介紹我們在 BCX17725 方面的進展。

Thanks, Charlie. I'm very pleased to be able to share some findings from our ongoing Phase I study of BCX17725, our novel investigational KLK5 inhibitor designed to replace functions of the natural inhibitor that are deficient in individuals living with Netherton syndrome. This trial is designed with multiple goals in mind: number one, understanding the preliminary safety profile of BCX17725.

謝謝查理。我很高興能與大家分享我們正在進行的 I 期臨床試驗 BCX17725 的一些結果。 BCX17725 是一種新型的在研 KLK5 抑制劑，旨在取代內瑟頓症候群患者體內天然抑制劑的功能缺陷。這項試驗的設計目標有很多：首先，了解 BCX17725 的初步安全性。

Number two, quantitating its systemic exposure with serum drug levels. Number three, evaluating the distribution of the drug into the epidermis. This is very important because the target enzyme, KLK5 is expressed in that location. Number four, assessing its potential early treatment effects on signs and symptoms of Netherton syndrome.

第二，透過血清藥物濃度量化其全身暴露量。第三，評估藥物在表皮的分佈。這一點非常重要，因為標靶酶KLK5在該部位表達。第四，評估其對內瑟頓症候群徵兆和症狀的潛在早期治療效果。

We are planning to first do this in a few individuals living with NS in Part 3 of the trial. The trial has so far progressed through multiple cohorts in healthy volunteers with different cohorts administered single or multiple doses of study drug. This gives us a handle on the first three goals. The dose level of BCX17725 has been progressively increased with up to 12 milligrams per kilogram administered by IV infusion.

我們計劃首先在試驗的第三部分中，對幾名患有腎病綜合徵（NS）的患者進行這項研究。目前，該試驗已在多個健康志願者隊列中取得進展，不同隊列分別接受了單次或多次研究藥物給藥。這使我們能夠更好地掌握前三個目標。 BCX17725 的劑量水準已逐漸增加，最高劑量為每公斤體重 12 毫克，透過靜脈輸注給藥。

In the multiple ascending dose portion, three doses were given on a Q2-week schedule. In this trial, administration of BCX17725 has been safe and well tolerated with no safety signals seen and preliminary assessment of systemic exposure profiles supports continued testing of up to every two weeks dosing regimens.

在多劑量遞增方案部分，每兩週給藥一次，共給藥三次。本試驗中，BCX17725 的給藥安全且耐受性良好，未觀察到任何安全訊號，初步的全身暴露評估支持繼續進行每兩週一次的給藥方案試驗。

Some representative images from skin biopsies taken before and after dosing in healthy subjects are shown on the accompanying slide. These small punch biopsies are taken under local anesthetic and processed for imaging. The images shown use a technique called immunofluorescence microscopy. Antibodies are applied that specifically bind to the protein you want to detect, in this case, the drug, BCX17725.

隨附的幻燈片展示了健康受試者給藥前後皮膚活檢的一些代表性圖像。這些小的穿刺活檢樣本在局部麻醉下採集，並進行影像處理。所示影像採用免疫螢光顯微鏡技術。此技術使用特異性結合目標蛋白（在本例中為藥物 BCX17725）的抗體。

These complexes are then detected with secondary antibodies, covalently tagged with a fluorochrome, which is a chemical that fluorescence typically under ultraviolet or near ultraviolet light. That means we can see a specific color based on the fluorochrome used wherever the drug is located in the tissue specimen and the more drug there is, the brighter the signal.

這些複合物隨後用二抗體進行檢測，二抗共價標記有螢光染料，這種化學物質通常在紫外光或近紫外光下發出螢光。這意味著，無論藥物位於組織樣本的哪個位置，我們都可以根據所使用的螢光染料觀察到特定的顏色，藥物濃度越高，訊號越強。

We can also use other differently colored fluorochromes to pick out structures such as cell nuclei. Although minimally invasive, we are limited in the number of biopsies we can take. So we decided to obtain a baseline biopsy prior to the first dose as a control sample and a post-dose biopsy five hours after the last dose of drug.

我們也可以使用其他不同顏色的螢光染料來辨識細胞核等結構。雖然這種方法屬於微創手術，但我們能採集的切片樣本數量有限。因此，我們決定在首次給藥前採集一份基線活檢樣本作為對照樣本，並在末次給藥後五小時採集一份給藥後活檢樣本。

The displayed biopsy sample images from a representative healthy volunteer in the 12-milligram per kilogram multiple dose cohort show the DNA located in cell nuclei in blue and the drug located in the extracellular matrix in green. The pre-dose sample shows the loose dermis with widely spaced bright blue nuclei, and the dense epidermis with tightly packed nuclei with a very faint green signal due to nonspecific binding of the assay reagents.

圖中展示的來自12毫克/公斤劑量多劑量組中一名健康志願者的活檢樣本圖像顯示，細胞核內的DNA呈藍色，細胞外基質中的藥物呈綠色。給藥前樣本顯示，真皮層疏鬆，細胞核呈亮藍色且間距較大；表皮層緻密，細胞核緊密排列，由於檢測試劑的非特異性結合，綠色訊號非常微弱。

In the post-dose sample, there is an obvious difference with much brighter green fluorescence. You can use the blue nuclei as a benchmark. In the post-dose image, drug has flooded the loose connective tissue in the dermis and distributed throughout the epidermis. These are important findings. The drug was able to diffuse across the epidermal basement membrane into the extracellular matrix of all the layers of the epidermis.

給藥後樣本中，綠色螢光明顯增強，差異顯著。可將藍色細胞核作為基準。給藥後影像顯示，藥物已滲入真皮的疏鬆結締組織，並分佈於整個表皮。這些都是重要的發現。藥物能夠穿過表皮基底膜，擴散到表皮各層的細胞外基質。

Drug getting to the epidermis will allow its access to the target enzyme KLK5 in patients with Netherton syndrome. Our investigators are quite excited by these results as are we, and we look forward to enrolling patients with NS into the trial in coming months.

藥物到達表皮後，即可作用於內瑟頓症候群患者的標靶酶KLK5。我們的研究人員和我們一樣，對這些結果感到非常興奮，並期待在未來幾個月內招募內瑟頓症候群患者參與試驗。

I'd now like to turn the call to Babar to walk you through the financial progress.

現在我想把電話交給巴伯，讓他為大家介紹一下財務進度。

Thanks, Will. My first full quarter as CFO of BioCryst was extremely eventful and was marked by several significant achievements, which I believe position us well for future growth and profitability. On October 1, we successfully closed the sale of our European business, providing an immediate boost to our financial position, enabling us to fully repay our Pharmakon debt.

謝謝威爾。我擔任BioCryst財務長的第一個完整季度可謂精彩紛呈，取得了多項重大成就，我相信這些成就為我們未來的成長和獲利奠定了堅實的基礎。 10月1日，我們成功完成了歐洲業務的出售，這立即提振了我們的財務狀況，使我們能夠全額償還Pharmakon的債務。

During Q3, we worked diligently on a highly strategic and transformative acquisition of Astria Therapeutics, which we announced last month, an acquisition which is expected to strengthen our presence in HAE and solidify double-digit growth trajectory for our portfolio over the next decade. As part of this proposed transaction, we also worked on securing a strategic financing partnership with Blackstone at a highly attractive cost of capital.

第三季度，我們積極推動了對Astria Therapeutics的策略性收購，並於上月正式宣布了這項收購。此次收購預計將增強我們在HAE領域的地位，並鞏固我們產品組合在未來十年內兩位數的成長動能。作為此次擬議交易的一部分，我們也與黑石集團達成了一項策略性融資合作，獲得了極具吸引力的融資成本。

Upon closing of the Astria acquisition, which is expected in Q1 2026, we will access up to $400 million of cash from this facility. But all of this was only made possible due to the continued strength of ORLADEYO and our improving operating performance. Please refer to our third quarter financials in today's press release.

預計在2026年第一季完成對Astria的收購後，我們將從該項融資安排中獲得至多4億美元的現金。但這一切都得益於ORLADEYO的持續強勁表現以及我們不斷提升的營運績效。請參閱今天新聞稿中的第三季財務數據。

However, I would like to take a moment to elaborate on some of these accomplishments and their impact on our trajectory. Total ORLADEYO revenue was $159.1 million, representing 37% year-over-year growth. Of that ORLADEYO revenue, $141.6 million or 89% came from the US. As you heard in Charlie's remarks, we continue to see strong momentum in our business despite the recently announced approvals.

不過，我想花點時間詳細闡述這些成就及其對我們發展軌跡的影響。 ORLADEYO 的總收入為 1.591 億美元，較去年同期成長 37%。其中，1.416 億美元（佔 89%）來自美國。正如您在 Charlie 的演講中所聽到的，儘管近期宣布了一些審批結果，但我們的業務依然保持強勁增長勢頭。

Non-GAAP operating expenses, excluding stock-based comp and transaction-related costs were approximately $108 million for the third quarter of 2025, up from approximately $92 million in the third quarter of 2024. Some of this increase was driven by continued investment in R&D, which continues to be a priority for us.

2025年第三季度，不計股權激勵和交易相關成本的非GAAP營運費用約為1.08億美元，高於2024年第三季的約9,200萬美元。部分成長是由於對研發的持續投入，研發仍然是我們的優先事項。

As you heard from Bill, we are very excited about the promise of these programs. We have also made a strategic decision to seek partners for our DME program after we evaluate initial patient data, in light of sharpening our focus on rare diseases and focusing our capital allocation on programs where we can create most value.

正如比爾所說，我們對這些項目的前景感到非常興奮。鑑於我們將更加專注於罕見疾病領域，並將資金投入到能夠創造最大價值的專案中，我們已做出策略決策，在評估初步病患資料後，為我們的耐用醫療設備（DME）專案尋找合作夥伴。

Non-GAAP operating profit, excluding stock-based compensation expense and transaction-related costs was $51.7 million for the third quarter of 2025 an increase of 107% year-over-year as we continue to benefit from significant operating leverage. Our non-GAAP net income for the quarter was $35.6 million, resulting in non-GAAP EPS of $0.17 per share.

2025年第三季度，不計股權激勵費用和交易相關成本的非GAAP營業利潤為5170萬美元，年增107%，這主要得益於我們持續受益於顯著的經營槓桿效應。該季度非GAAP淨利為3560萬美元，非GAAP每股收益為0.17美元。

We finished the quarter strong with $269 million in cash, which included cash held for sale by European entities. Our strong cash flow profile enabled us to make a $50 million prepayment on our Pharmakon term loan during Q3. And with the closing of the sale of European business, we also paid off the outstanding amount under the term loan of approximately $200 million.

本季末，我們現金儲備強勁，達到2.69億美元，其中包括歐洲實體持有的待售現金。強勁的現金流使我們能夠在第三季提前償還Pharmakon定期貸款的5000萬美元。隨著歐洲業務出售的完成，我們也償還了該定期貸款剩餘的約2億美元。

Our pro forma cash balance giving effect to these adjustments is approximately $294 million and zero term debt. Due to the strong expected cash flow generation, we anticipate reaching $1 billion in cash during 2029. However, we will continue to evaluate various capital allocation opportunities to generate value for our stockholders, much like our recently announced proposed acquisition of Astria Therapeutics.

經過上述調整後，我們的備考現金餘額約為2.94億美元，且無長期債務。由於預期現金流強勁，我們預計2029年現金儲備將達到10億美元。然而，我們將繼續評估各種資本配置機會，以期為股東創造價值，例如我們近期宣布的擬收購Astria Therapeutics的計劃。

We will also explore upon closing of the transaction, a European license of navenibart and strategic opportunities for the STAR-0310 program, which may yield further upsides. Moving on to guidance. Charlie already alluded to the revenue guidance, and at the same time, we are lowering our non-GAAP OpEx guidance to $430 million to $440 million from our original guidance of $440 million to $450 million.

交易完成後，我們也將探討navenibart的歐洲許可事宜以及STAR-0310專案的策略機遇，這些機會可能帶來更多收益。接下來談談業績指引。 Charlie已經提到了營收指引，同時，我們將非GAAP營運支出指引從原先的4.4億美元至4.5億美元下調至4.3億美元至4.4億美元。

The European divestiture allows us the opportunity to continue to streamline our base business cost structure. We remain on track to deliver non-GAAP net income and positive cash flows for full year 2025. As previously stated in our acquisition press release, we are expecting to stay profitable on a non-GAAP basis as well as cash flow positive even during the development period of navenibart.

此次歐洲業務剝離使我們有機會繼續精簡基礎業務成本結構。我們仍有望在2025年全年實現非GAAP淨利和正現金流。正如我們先前在收購新聞稿中所述，即使在navenibart的開發階段，我們也預計能夠維持非GAAP獲利和正現金流。

In closing, I'm proud of our team's continued focus and execution as we work to drive sustainable growth and deliver meaningful improvements in patients' lives. Our strong results and disciplined operational and financial strategies position us to capitalize on future growth opportunities, strengthen our leadership in rare diseases and continue delivering value for our stockholders.

最後，我為我們團隊在推動永續成長和實際改善患者生活方面所展現出的專注和執行力感到自豪。我們強勁的業績和嚴謹的營運及財務策略使我們能夠把握未來的成長機會，鞏固我們在罕見疾病領域的領先地位，並持續為股東創造價值。

Operator, we are now ready for your questions.

操作員，我們現在可以回答您的問題了。

(Operator Instructions) Jessica Fye, JPMorgan.

（操作說明）潔西卡費伊，摩根大通。

This is [Jose] for Jessica. Of the 37% year-over-year ORLADEYO net revenue growth, how much of that was volume? And how much of that was better paid rate or net price? And on that front, how should we think about gross to net this quarter and going into 2026? And very quickly, how confident are you that you can maintain steady patient retention rates given the increasingly competitive landscape?

我是[Jose]，問Jessica。 ORLADEYO的淨收入年增37%，其中有多少是銷售成長？又有多少是較高的支付費率或淨價所帶來的成長？就此而言，我們該如何看待本季以及展望2026年的毛利與淨利比率？另外，鑑於競爭日益激烈的市場環境，您對維持穩定的病患留存率有多大信心？

I can start with that question. So of the 37% year-over-year, we had really steady -- we've had very steady volume growth over time, but there was a big portion of it that was price based on the improvement in paid rate that we described earlier this year, particularly in the Medicare segment. So the volume is growing at the pace that we expect and at the pace that we need to get to the $1 billion in peak revenue in 2029.

我可以先回答這個問題。在同比增長37%的業績中，銷售增長一直非常穩定，但其中很大一部分增長是基於價格因素，這主要得益於我們今年早些時候提到的支付率的提高，尤其是在聯邦醫療保險（Medicare）領域。因此，銷售成長速度符合我們的預期，也符合我們實現2029年營收高峰10億美元目標所需的速度。

As far as the patient retention with new competition coming in, as I mentioned in the remarks, our patient retention has been identical to our ongoing trend, not affected at all by the new products coming in the market, and we expect that to continue.

至於隨著新競爭的出現，患者留存率如何，正如我在發言中提到的，我們的患者留存率與我們目前的趨勢一致，完全沒有受到市場上新產品的影響，我們預計這種情況將繼續下去。

Yes. And I'd just add, the logic behind that is these patients are really well controlled. They're getting similar control to injectable drugs, and they're on a once a day pill. And so what on earth would they switch to that could be better than that.

是的。我還要補充一點，背後的邏輯是這些患者的病情控制得非常好。他們每天只需服用一次藥片，就能達到與注射藥物類似的控制效果。所以，他們還能換用什麼藥物，才能比這更好呢？

And then gross to net is still about 15%, as we've announced earlier this year.

正如我們今年稍早宣布的那樣，毛利淨利比率仍然在 15% 左右。

And next year in that 15% to 20% --

明年這15%到20%的比例——

Yes. Next year, it will still be in the 15% to 20%, probably a little closer to the 15%.

是的。明年應該還在15%到20%之間，可能更接近15%。

Laura Chico, Wedbush Securities.

Laura Chico，Wedbush Securities。

One question with respect to the new prescriber numbers. I think this is the second quarter in a row you've been over 60. Just curious if you have any feedback, market research that can help us understand why they're deciding to prescribe now? What has been kind of the motivating factor more recently to accelerate the adds here?

關於新增處方醫生數量，我有一個問題。我想這已經是連續第二季超過60位數了。我很好奇您是否有任何回饋或市場研究數據，可以幫助我們了解他們為什麼選擇現在開處方？最近促使他們加快新增處方醫師數量的因素是什麼？

And then I guess, if you could share a little bit more color on what would the expected blended royalty rate look like in '26? I know you're projecting a step down over time here, but just kind of curious how we should be thinking about it directionally from '25 to '26.

那麼，您能否更詳細地介紹一下2026年的預期混合版稅率？我知道您預計版稅率會隨著時間推移而下降，但我只是好奇從2025年到2026年，我們應該如何看待版稅率的發展方向。

I'll start with -- thanks, Laura. I'll start with the prescriber data and then hand it over to Babar on the royalties. So the motivating factors, and we've described this before, is just physicians getting more and more comfortable with the long-term evidence, the real-world evidence for how well ORLADEYO works. What they understand now is that ORLADEYO works very well, equally well to injectable products in most patients. It either works or it doesn't.

我先說——謝謝勞拉。我會先從處方醫師的資料入手，然後再把版稅方面的事情交給巴伯。所以，推動這項措施的因素，我們之前也提到過，就是醫生們越來越認同ORLADEYO的長期療效，也就是真實世界的數據。他們現在明白，ORLADEYO的療效非常好，對大多數患者來說，其療效與注射劑不相上下。要嘛有效，要嘛無效。

And if the patients don't have the benefit that they need, they move on. So physicians are really understanding that. That's the first part. The second part is our ability to find prescribers in this market and accurately target means that we are able to find physicians who have a smaller number of patients. So if you have one HAE patient, we will find you and ORLADEYO is becoming the treatment of choice for those doctors.

如果患者無法獲得所需的療效，他們就會放棄。醫生們對此深有體會。這是第一點。第二點是我們能夠在這個市場中找到處方醫生並進行精準定位，這意味著我們能夠找到患者數量較少的醫生。所以，即使您只有一位 HAE 患者，我們也能找到您，而 ORLADEYO 正在成為這些醫生的首選治療方案。

Overall, as we grow the number of physicians, we consistently see a pretty equal balance between those smaller prescribers as well as the top 600 or so doctors that treat 50% of the market. So we keep chipping away at those top prescribers and launch to date over 80% of those doctors have prescribed. So we're really thrilled to show this consistent progress expanding the number of prescribers.

總體而言，隨著醫生數量的增加，我們發現，小型處方醫生和占據50%市場份額的約600名頂級醫生之間的比例基本上保持平衡。因此，我們不斷爭取這些頂級處方醫生的支持，迄今為止，已有超過80%的頂級醫生開立了處方。我們很高興看到處方醫生數量持續成長並取得如此顯著的進展。

And just one other thing I'd like to add, Charlie is, there's still physicians out there even in the top prescribers that haven't written for ORLADEYO. And one of the things we're extremely excited about next year is the pediatric approval because these docs have pediatric patients, many of them, and there is no reason that they should use anything but ORLADEYO for prophylaxis for these patients. So we think that's going to open up even more new prescribers next year.

查理，我還有一點要補充，即使是那些處方量最大的醫生中，也仍然有一些沒有開過ORLADEYO的處方。我們非常期待明年ORLADEYO能獲得兒科批准，因為這些醫生有很多兒科患者，他們沒有理由不給這些患者使用ORLADEYO進行預防性治療。所以我們認為，這將為明年更多的新醫生打開處方管道。

Yes. And on the royalty section, we are pleased to share that this quarter, we are tripping over the lower threshold, and it will continue to come down. As you can see in our slides, prepared slides, the rate is in the early -- the blended rate is in early teens. And while we have not given 2026 guidance, I can assure you that rate continues to come down because there's a cap on some of those royalties when you hit the $550 million.

是的。關於特許權使用費部分，我們很高興地告訴大家，本季我們的特許權使用費已突破下限，並且還會繼續下降。正如您在我們準備的幻燈片中看到的，綜合費率目前處於十幾個百分點的水平。雖然我們尚未給出2026年的業績指引，但我可以向您保證，費率會繼續下降，因為當特許權使用費達到5.5億美元時，部分特許權使用費的上限就會被設定。

But as you can imagine, when we are out to provide you guidance, when you do the math, it will be -- it will continue to decline. And as we've said, over time, it will be in single-digits as we pay off the OMERS liability altogether.

但正如您所想，當我們向您提供指導時，如果您進行計算，您會發現——它會繼續下降。正如我們所說，隨著時間的推移，當我們完全償還OMERS債務後，它將降至個位數。

Yes. So as revenue goes up, profitability gets better and better and cash flow continues to flow. So it's a very bright financial future.

是的。隨著營收成長，獲利能力越來越好，現金流也持續充裕。所以，財務前景非常光明。

Stacy Ku, TD Cowen.

Stacy Ku，TD Cowen。

Congrats on the progress. So we have a couple of questions. First, on the new entrants, our KOLs do indicate there are a couple of patients switching from ORLADEYO to injectables, but the same clinicians are also saying that they expect ORLADEYO's share to stay stable. So beyond this anecdotal feedback and obviously, you all have highlighted the one-year 60% retention.

恭喜取得的進展。我們有幾個問題。首先，關於新用戶，我們的關鍵意見領袖（KOL）確實提到有幾位患者從使用ORLADEYO轉而使用注射劑，但這些臨床醫生也表示，他們預計ORLADEYO的市場份額將保持穩定。除了這些零星的回饋之外，顯然，你們都強調了60%的一年留存率。

Are you able to share any recent metrics to suggest ORLADEYO is unlikely to be impacted by these injectable entrants? That's the first question. And then the second is on that pediatric HAE approval. As we approach the PDUFA date, maybe help us understand your views on the opportunity and what commercial strategy and preparation is ongoing to really make sure you all maximize that pediatric expansion?

您能否分享一些近期數據，以表明 ORLADEYO 不太可能受到這些注射劑競爭者的影響？這是第一個問題。第二個問題是關於兒科 HAE 的批准。隨著 PDUFA 日期的臨近，能否請您談談您對此機會的看法，以及目前正在進行的商業策略和準備工作，以確保最大限度地拓展兒科市場？

Are many of these patients already identified? Just help us understand as we get to the new year, any type of expectations around maybe some latent patient demand.

這些患者中有多少已經確診？在新的一年到來之際，能否幫助我們了解一下，對於可能的潛在患者需求，我們有哪些預期？

Sure. Thanks, Stacy. As far as the new entrants, yes, of course, some patients are switching from ORLADEYO because 40% of new patient starts on ORLADEYO drop off within the year. And in the past, they might have dropped off to TAKHZYRO and HAEGARDA, now maybe they're more likely to switch to some of the new entrants. So that's exactly what we expected.

當然。謝謝，Stacy。至於新上市的藥物，是的，當然，有些患者會從ORLADEYO轉用其他藥物，因為40%的新患者在開始使用ORLADEYO後會在一年內停止治療。過去，他們可能會轉而使用TAKHZYRO或HAEGARDA，現在他們更有可能轉而使用一些新上市的藥物。這完全符合我們的預期。

What we're not seeing, though, is a change in our new patient prescribing patterns or a change in our overall retention rate. And as far as the data that give us confidence in this, as I mentioned, slide 8, we redid our market research. We redid our big conjoint analysis and market simulation with all the new information about new and future competitors.

然而，我們並未觀察到新病患處方模式或整體留存率的變化。至於支撐我們這一觀點的依據，正如我在第8張幻燈片中提到的，我們重新進行了市場調查，並利用所有關於新競爭對手和未來競爭對手的新信息，重新進行了大型聯合分析和市場模擬。

And what you see is no change to our prior versions of this market research. It shows that ORLADEYO remains -- ORLADEYO patients remain very sticky, and we expect that to continue. As far as the pediatric approval, we see that there are about 500 patients today diagnosed with HAE under age 12. And only about 40% of those patients today are on or kind of in the prophylaxis space have tried prophylaxis.

本次市場調查結果與我們先前的版本並無變化。數據顯示，ORLADEYO 的患者遵從性依然很高，我們預期這種情況將持續下去。關於兒科用藥審批方面，目前約有 500 名 12 歲以下的 HAE 患者確診。而這些患者中，只有約 40% 的人正在接受或嘗試預防性治療。

So we think that there's an opportunity both to grow the use of prophylaxis within pediatrics as well as for switching because an oral therapy is important to a lot of patients, but it's particularly important to kids with HAE. So as far as our strategy, and Jon mentioned earlier, the doctors that treat kids with HAE tend to be the same physicians that are treating patients over age 12. So we're already calling on these physicians.

所以我們認為，兒科預防性用藥的推廣以及治療方案的轉換都存在機會，因為口服藥物對許多患者來說都很重要，尤其對患有遺傳性血管性水腫（HAE）的兒童來說更是如此。至於我們的策略，正如Jon之前提到的，治療HAE患兒的醫生往往也是治療12歲以上患者的醫生。因此，我們已經在聯絡這些醫生了。

We know who is treating kids, and the team will be ready to go with the launch shortly after approval.

我們知道誰在為孩子們治療，團隊將在獲得批准後不久做好啟動準備。

Steve Seedhouse, Cantor.

史蒂夫·西德豪斯，領唱。

I was hoping you could expand on the decision to deemphasize, I guess, avoralstat for DME. Have you had an early look at the Phase I data there? And then looking at the updated pipeline slide, the undisclosed programs listed for rare diseases, at least that are preclinical. Can you give us some insights into what you're working on there preclinically and how close it might be to the clinic?

我希望您能詳細解釋一下關於降低avoralstat在DME治療中的優先順序的決定。您是否已經看過該藥物的I期臨床試驗數據？另外，從更新後的研發管線幻燈片來看，其中列出了一些針對罕見疾病的未公開項目，至少是處於臨床前階段的項目。您能否介紹一下您目前在臨床前階段的研究進展，以及距離臨床試驗還有多遠？

Yes, I'll take that one. So regarding avoralstat, no, we haven't seen any of the data. We just enrolled the first cohort. And so this is a decision based on focus and expense. And by bringing a late-stage product like navenibart into our pipeline, we need to create space to be able to fund and bring that to the finish line. And these DME programs get really expensive the further on you go in clinical development.

是的，我接受這個方案。至於avoralstat，不，我們還沒有看到任何數據。我們剛剛招募了第一批患者。所以，這是一個基於重點和成本的決定。將像navenibart這樣處於後期研發階段的產品引入我們的產品線，我們需要騰出資金來支持並完成它的研發。而且，隨著臨床開發的深入，這些DME計畫的成本會越來越高。

And quite honestly, we don't have the expertise there we do in rare disease. And so we just think it's better in the hands of somebody who has that expertise. And then on the undisclosed, we're not going to disclose what it is. It's early. It's exciting. But when it's ready to be shared, we'll have more information to share with you.

坦白說，我們在罕見疾病領域沒有這方面的專業知識。所以我們認為，交給有這方面專業知識的人來處理會更好。至於尚未公開的內容，我們暫時不會透露。現在還處於早期階段，令人興奮。但當一切準備就緒，可以分享時，我們會提供更多資訊。

Okay. And just quick on Netherton. Have you had any dialogue with regulators there and forming an understanding of what a pivotal program requirement might be?

好的。關於內瑟頓項目，我只想簡單提一下。您是否與當地監管機構進行任何對話，並了解了關鍵專案要求可能是什麼？

Yes, we have. Not enough to share with you the design of the pivotal program at this point. I think the biggest thing, and Bill, you can correct me if I get this wrong, is the bigger the treatment effect, the better options we have to move fast with this program. And we'll figure that out once we start getting data. But too early to predict kind of the design of the pivotal program. Is that fair, Bill?

是的，我們已經有了。但目前還不足以和您分享關鍵方案的設計。我認為最重要的是（比爾，如果我說錯了請指正），治療效果越好，我們就能越快推進這個計畫。一旦開始收集數據，我們就能弄清楚這一點。但現在預測關鍵方案的設計還為時過早。比爾，這樣說您懂嗎？

That's very fair. I think once we have evidence of the effects of the drug in patients with NS and the safety of the drug in NS, then we'll have complete conversations with regulators about how to get it approved.

這很合理。我認為，一旦我們掌握了該藥物對腎病綜合徵患者的療效和安全性證據，我們就會與監管機構全面討論如何獲得批准。

Maurice Raycroft, Jefferies.

莫里斯‧雷克羅夫特，傑富瑞集團。

Congrats on the progress. I'll just ask a couple of quick ones on Netherton. Wondering if you could just talk more about the slower enrollment there and how many patients you'll have in the first quarter data update next year? And do you anticipate dosing higher than the 12 mg per kg? And I'm wondering if you're still exploring the subcu dose? Or is it going to be an IV dosing going forward?

恭喜取得進展。關於內瑟頓（Netherton）的情況，我只想問幾個問題。您能否詳細談談該地病患招募速度較慢的原因，以及明年第一季數據更新時預計會有多少患者？您預計劑量會高於每公斤12毫克嗎？另外，您是否仍在探索皮下注射給藥方案？還是未來會採用靜脈注射給藥？

Yes, I'll take the first part of it. You want to take the second. We're only off by a quarter. So it's a very slight delay in the program. And the enthusiasm, as Bill said, by investigators is really high, especially when they see the healthy volunteer data. We didn't expect to see the drug get to the target in healthy volunteers. And so that has been really encouraging data.

是的，我負責第一部分。你想負責第二部分。我們只差了四分之一。所以這只是專案進度上一個很小的延遲。正如比爾所說，研究人員的熱情非常高漲，尤其是在他們看到健康志願者的數據之後。我們原本沒期待這種藥物能在健康志願者身上達到標靶。所以這些數據確實令人鼓舞。

And then, Bill, do you want to take the second part of the question?

那麼，比爾，你想回答問題的第二部分嗎？

Sure. Yes, we're exploring both subcutaneous and intravenous administration. We'll continue to do that. And we may explore higher doses, that option is open.

當然。是的，我們正在研究皮下注射和靜脈注射兩種給藥途徑。我們會繼續進行這項研究。我們可能還會探索更高的劑量，這個選項是開放的。

Brian Abrahams, RBC.

Brian Abrahams，RBC。

Congrats on the continued progress in the quarter. Maybe just continuing on Netherton. Can you elaborate a little bit more on, I guess, what you're seeing from a PK/PD standpoint in those first couple of parts of the ongoing study? And I'm also curious what the trigger was for starting that Part 4, which I know you started in recent weeks.

恭喜本季取得持續進展。或許可以繼續推進Netherton的研究。能否詳細談談，從藥物動力學/藥效學（PK/PD）的角度來看，您在目前這項研究的前幾個階段觀察到了哪些現象？另外，我很好奇是什麼促使您啟動了第四部分的研究，我知道您最近幾週才開始。

And then just secondarily, separately on ORLADEYO, just wondering what you're seeing in terms of demand from the normal C1 inhibitor population. I think that was a growth driver you cited in the past.

其次，關於ORLADEYO，我想單獨問一下，您觀察到的來自普通C1抑制劑患者群體的需求情況如何？我記得您之前提到這是推動成長的一個因素。

Bill, do you want to take the Netherton and Charlie can take the ORLADEYO?

比爾，你想走內瑟頓線嗎？查理可以走奧拉德約線嗎？

Sure. So Netherton is a fascinating disease. So it's all about what's happening in the epidermis. There aren't any plasma or serum biomarkers to measure. Secondly, we have a very tight binding, very potent inhibitor. And you have to think about what relationship the plasma concentration is going to have to the effects in the epidermis.

當然。內瑟頓病是一種非常有趣的疾病。它的關鍵在於表皮的病變。目前沒有任何血漿或血清生物標記可以檢測。其次，我們有一種結合力很強、效力極強的抑制劑。你必須考慮血漿濃度與表皮病變之間的關聯。

And there could, in fact, be a disconnect between how long the drug sits in the epidermis after binding to the target compared to how long it circulates in the plasma. That being said, of course, we're measuring the blood concentrations of the drug, nothing unexpected there. Solely on that basis, we think that it's worth continuing to explore up to every two weeks dosing.

事實上，藥物與靶點結合後在表皮中停留的時間與在血漿中循環的時間可能存在差異。當然，我們測量的是藥物的血中濃度，這並不出乎意料。光是這一點，我們就認為值得繼續探索每兩週給藥一次的方案。

But really, it's going to be looking at the effects on the disease. There aren't any pharmacodynamic markers to measure. It's the effects on the disease in patients with Netherton and when we get into that. Just a clarification, we have not disclosed whether we've started Part 3 or Part 4. Part 3 is just a few subjects with short-term dosing.

但實際上，我們將著重研究藥物對疾病的影響。目前沒有藥效學指標可供測量。我們將關注藥物對患有內瑟頓症候群患者的疾病影響，以及我們稍後將深入探討的內容。需要澄清的是，我們尚未透露是否已啟動第三部分或第四部分。第三部分僅針對少數受試者進行短期給藥。

That's the design. Part 4 enables longer-term dosing, and we look forward to stepping through both of those.

這就是設計方案。第四部分將實現更長期的給藥方案，我們期待逐步完成這兩項工作。

Yes. And the expectation is that the data we'll have in the first quarter is Part 3. Charlie?

是的。預計第一季的數據將是第三部分。查理？

Yes. Brian, on C1 normal patients, launch to date, that's been about 1/3 of the patients on ORLADEYO, and that's what we saw in Q3. Q2, you might recall, we had an exceptional best ever quarter for new patient starts. There was an additional bolus of C1 normal patients in Q2 because we released some new data. Q3 looked like the steady high demand that we've seen over the last two years with about 1/3 of the patients being C1 normal.

是的。布萊恩，就目前而言，在C1正常患者中，大約有三分之一的患者正在接受ORLADEYO治療，這與我們在第三季度觀察到的情況一致。您可能還記得，第二季我們新增病患數量創歷史新高。由於我們發布了一些新數據，第二季新增了一批C1正常患者。第三季度，市場需求持續旺盛，與過去兩年的情況類似，C1正常患者約佔三分之一。

Jon Wolleben, Citizens.

Jon Wolleben，市民。

Just looking at sales so far this year in your guidance, it's implying that we're going to see a drop in quarter-over-quarter sales for the first time. We haven't seen that seasonality before. So hoping you could talk a little bit about your expectations, what's driving that? And if that's something we should expect moving forward or if this is going to be a one-time seasonality effect?

從您今年迄今為止的銷售業績來看，似乎意味著我們將首次看到季度環比銷售額下降。我們以前從未遇到過這種季節性波動。所以，希望您能談談您的預期，是什麼因素導致了這種情況？我們是否應該預期這種情況會持續下去，還是這只是一次性的季節性影響？

Yes, Jon, it's going to be a one-time seasonality because we just sold our European business. So we're losing the sort of $10 million to $15 million of revenue that otherwise would have occurred. So next year, you will not see a drop in Q4.

是的，喬恩，這只是暫時的季節性因素，因為我們剛剛出售了歐洲業務。所以我們損失了大約1000萬到1500萬美元的收入，而這些收入原本是會獲得的。因此，明年第四季不會出現下滑。

Mr. Jon, does that answer your question?

喬恩先生，這樣回答您的問題了嗎？

Yes.

是的。

John Todaro, Needham & Co.

John Todaro，Needham & Co.

This is John on for Serge today. Just wanted to touch on pediatric ORLADEYO with the ongoing review and the PDUFA in mid-December. Just curious if you guys have seen any impacts from the government shutdown, whether you've had continuous feedback from the FDA and whether you expect them to still meet that PDUFA.

我是John，今天替Serge主持節目。我想談談兒科藥物ORLADEYO，它目前正在接受審查，而且PDUFA（處方藥用戶付費法案）將於12月中旬生效。我很好奇你們是否感受到政府停擺的影響，是否持續收到FDA的回饋，以及你們是否預期他們還能準時完成PDUFA的審核。

And then pending product availability, do you have any expectations for how the payer landscape will look in this segment? And whether or not you could expect a bolus of patients to come on board early upon product launch?

那麼，在產品上市之前，您對該領域的支付方格局有何預期？您能否預期產品上市初期會有大量病患加入？

So I'll take the first part. Charlie, you take the second. So with regard to the interactions with FDA, we're getting closer to the PDUFA date, and we're going through the things you think you would be going through at this point, late-stage in the review process. So there's nothing that we see that gives us concern about the government shutdown, that could change, but at least where we sit today, nothing that we see.

那我先回答第一部分，查理，你回答第二部分。關於與FDA的溝通，我們距離PDUFA截止日期越來越近了，我們正在經歷你認為在這個階段——審查流程的後期——應該經歷的那些事情。所以目前來看，政府停擺並沒有給我們帶來任何擔憂，雖然情況可能會有所變化，但至少就目前而言，我們還沒有看到任何影響。

And John, as far as payer landscape, we are in a really great spot with payers with ORLADEYO, and we expect the peds indication to slide right into that. So nothing special on the payer front. As far as the bolus of patients, we know that there's a lot of anticipation for this product. I'm sure we'll update you after we launch and get product into the market, we'll update you in 2026 as to the pace of patient growth.

約翰，就支付方而言，我們與支付方的關係非常融洽，ORLADEYO 的支付方合作非常順利，我們預計兒科適應症也會順利納入其中。所以支付方方面面沒有什麼特別之處。至於患者數量，我們知道大家對這款產品充滿期待。產品上市後，我們會及時向您報告，並在 2026 年向您介紹患者成長速度。

Gena Wang, Barclays.

吉娜·王，巴克萊銀行。

Wanted to ask about the Netherton syndrome also regarding the 12-milligram per kg IV dosing, by the way, very impressive biomarker data. I'm wondering what kind of safety you see in the patient -- in the healthy volunteer data? And then also, regarding the first quarter, the Part 3 data. So maybe if you can lay out what we should expect from this 1Q '26 data update from Part 3?

我也想問一下關於內瑟頓症候群的問題，特別是關於12毫克/公斤靜脈注射劑量的情況。順便說一句，生物標記數據非常令人印象深刻。我想知道您在患者身上——以及在健康志願者數據中——觀察到的安全性如何？另外，關於第一季度，也就是第三部分的數據。您能否概述一下我們應該對2026年第一季第三部分的資料更新抱持什麼樣的預期？

And quickly, just housekeeping questions regarding ORLADEYO. I know you mentioned some of the comments, but I do wanted to double check with the actual numbers regarding the retention rate, are we still similar around 60% and the pay rate, I think last quarter, we talked about could be by year-end, 82% to 83%. Is that still the same? And then lastly is the patient segment, 50% switch from other prophy, is that still the same?

最後，關於ORLADEYO，還有一些日常事務上的問題。我知道您提到了一些評論，但我還是想再次確認實際數據，例如客戶留存率，是否仍然維持在60%左右？還有支付率，我記得上個季度我們討論過，到年底可能會達到82%到83%。現在還是這樣嗎？最後，患者族群方面，先前提到的50%是從其他預防性治療機構轉過來的，這個比例現在還一樣嗎？

All right. So Bill, why don't you take the safety and the design of the Part 3? And then Charlie, you can take the ORLADEYO.

好的。比爾，你負責第三部分的安全性和設計部分吧？查理，你負責奧拉德約（ORLADEYO）部分。

So there's -- really, the thing to say about safety in healthy subjects is that it's very safe so far, it's been very safe and well tolerated. So there have been no safety signals emerging with multiple doses of the drug through the dose that you mentioned. So that's really good news. I think that with regard to what you can expect from Part 3, this is very short-term administration of the drug in Part 3.

所以，關於健康受試者的安全性，實際上需要說明的是，到目前為止，藥物非常安全，耐受性也很好。正如您所提到的，多次給藥後，尚未出現任何安全性訊號。這確實是個好消息。至於第三部分的研究結果，我認為第三部分的研究對像是短期用藥。

We're at the cutting edge of clinical science and investigations into Netherton syndrome with a parenteral drug. So we'll be discovering how long it takes in order to get an effect. So I don't know that yet. Will that short-term administration be enough to see an effect? Don't know. If we do, that would be very encouraging. If we don't, we'll just give the drug for longer and maybe we'll increase the dose.

我們正處於臨床科學研究和內瑟頓症候群研究的前沿，使用一種腸外給藥的藥物。所以我們將探索藥物起效所需的時間。目前我還不清楚。短期給藥是否足以產生療效？我不知道。如果有效，那將非常令人鼓舞。如果無效，我們會延長給藥時間，或許還會增加劑量。

So I think I would temper expectations with regard to what we might see from short-term dosing in a few subjects with Netherton. Obviously, we'll be looking at safety. So we'll learn a lot and look forward to extending the dosing in Part 4 of the study. The sorts of things that you would measure are pretty obvious, itch, pain, skin redness and the like.

所以我認為，對於內瑟頓（Netherton）在少數受試者身上進行的短期給藥試驗，我們應該降低預期。顯然，我們會關注安全性。我們會從中學到很多，並期待在研究的第四部分延長給藥時間。需要測量的指標顯而易見，例如搔癢、疼痛、皮膚發紅等等。

And Bill, we're testing multiple doses in the Part 3. So we'll get that and start to zoom in on what we then want to look at Part 4. Is that right?

比爾，我們在第三部分測試了多種劑量。所以我們會拿到這些劑量，然後開始聚焦在我們第四部分想要研究的內容。是這樣嗎？

It's the first step for more extensive testing in Part 4.

這是第四部分更廣泛測試的第一步。

Great. Charlie?

太好了。查理？

And Gena, as far as the ORLADEYO numbers, so yes, the patient retention rate is in line with exactly what we've seen over the last several years. So 60% of patients who start ORLADEYO make it to a year. And everything that we saw in Q3 tells us we're right on track with that same number. The paid rate, we ended Q3 at 82%, which is right about where we thought we would be. In Q4, I wouldn't be surprised if we end closer to 81%, even 80%.

至於ORLADEYO的數據，Gena，是的，病人留存率與過去幾年的情況完全一致。也就是說，60%的ORLADEYO患者能夠堅持治療一年。第三季的所有數據都表明，我們正朝著這個目標穩步前進。付費率方面，第三季末達到了82%，這與我們的預期基本相符。第四季度，如果付費率接近81%，甚至達到80%，我不會感到驚訝。

Typically, in the second half of the year, the paid rate starts to decline because we have all these new patients coming in and less of an opportunity to switch people from long-term free product to paid product. That opportunity comes in Q1 into early Q2 of the new year. And so we're right on track for where we need to be, and we expect to have a lot of those patients then switching to paid therapy earlier in 2026.

通常情況下，下半年付費率會開始下降，因為大量新患者湧入，而將長期免費患者轉為付費患者的機會減少。這種機會會在新年第一季到第二季初出現。因此，我們目前正按計畫推進，預計到2026年初，將有許多患者轉為付費治療。

And then as far as the source of business for patients, yes, the same basic trends where we get close to 50% of the people switching from other prophy history with other prophy products and then other patients switching from acute only coming over to prophy. And then a good number of patients, best we can tell, are starting ORLADEYO as their first HAE treatment ever because more of those are newly diagnosed patients.

至於患者來源方面，基本趨勢依然存在：近 50% 的患者之前使用過其他預防性治療產品，後來轉而使用 ORLADEYO；還有一些患者之前只用於急性期治療。據我們觀察，相當一部分患者將 ORLADEYO 作為他們首次接受 HAE 治療，因為其中新確診的患者較多。

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

謝謝。問答環節到此結束。現在我把會議交還給喬恩‧斯通豪斯，請他作閉幕致詞。

Yes. We thought about ending the call with the rolling stones. This will be the last time, but thought different of it. But let me say this, it's been an honor to lead the employees of BioCryst for nearly the last two decades. Proud of what we built, what we've accomplished together and extremely excited and confident to see this team take the company into the future by delivering more and more innovative treatments for patients living with rare disease because in this industry, that's how you create real value. So thank you for your interest in our company and have a great day.

是的。我們本來想用滾石樂團的歌來結束這通通話。這將是最後一次了，但後來改變了主意。不過，我想說的是，在過去的近二十年裡，能夠領導BioCryst的員工是我的榮幸。我為我們共同建立的一切、我們共同取得的成就感到自豪，並且非常興奮和自信地看到這支團隊帶領公司走向未來，為罕見病患者提供更多創新療法，因為在這個行業，這才是創造真正價值的方式。所以，感謝您對我們公司的關注，祝您今天愉快。

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

謝謝。會議到此結束。感謝您參加今天的報告會。您可以斷開連線了。