BioCryst Pharmaceuticals Inc (BCRX) 2024 Q4 法說會逐字稿

Good day and welcome to the BioCryst fourth Quarter 2024 Earnings Call. All participants will be in listen-only mode. (Operator Instructions) Please note this event is being recorded.

大家好，歡迎參加 BioCryst 2024 年第四季財報電話會議。所有參與者將處於只聽模式。（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, at BioCryst. Please go ahead.

現在我想將會議交給 BioCryst 的 John Bluth。請繼續。

Thanks, Drave. Good morning and welcome to BioCryst's fourth quarter 2024 corporate update and financial results conference call. Today's press release and accompanying slides are available on our website. Participating with me today are CEO, Jon Stonehouse; CFO, Anthony Doyle; Chief Commercial Officer, Charlie Gayer; and Chief R&D Officer, Dr. Helen Thackray. Following our remarks, we'll answer your questions.

謝謝，德雷夫。早安，歡迎參加 BioCryst 2024 年第四季公司更新與財務績效電話會議。今天的新聞稿和隨附的幻燈片可在我們的網站上查閱。今天與我一起參加的還有首席執行官喬恩·斯通豪斯 (Jon Stonehouse)；首席財務官，Anthony Doyle；首席商務官 Charlie Gayer；以及首席研發官 Helen Thackray 博士。在我們發言之後，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. These statements are subject to known and unknown risks and uncertainties, which may cause their actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward-looking statements.

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。這些陳述受已知和未知的風險和不確定性的影響，這可能導致其實際結果、表現或成就與本簡報中表達或暗示的任何未來結果或表現有重大差異。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 documents followed with the Securities and Exchange Commission, which can be accessed on our website. In addition, today's conference call includes non-GAAO financial measures for reconciliation of these non-gap measures against the most directly comparable GAAP financial measure, please refer to the earnings release posted in the press releases section of our investor relations website at www.bioCryst.com.

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，該文件可在我們的網站上查閱。此外，今天的電話會議包括非 GAAO 財務指標，以便將這些非差距指標與最直接可比較的 GAAP 財務指標進行調節，請參閱我們投資者關係網站 www.bioCryst.com 的新聞稿部分發布的收益報告。

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

現在我想把電話轉給喬恩‧斯通豪斯。

Thank you, John. We ended 2024 with the strongest execution and performance in the company's history. What's even more exciting is it happened across the company. For the full year 2024, ORLADEYO revenue year-over-year grew by 34%, and we added as many patients as we did in the first year of launch. This is an amazing result for a rare disease medicine, especially considering it came in the fourth year on the market and reflects excellent execution by the commercial team.

謝謝你，約翰。我們以公司歷史上最強勁的執行力和業績結束了 2024 年。更令人興奮的是，這件事發生在整個公司。2024 年全年，ORLADEYO 收入年增 34%，新增病患數量與推出第一年一樣多。對於一種罕見疾病藥物來說，這是一個令人驚嘆的結果，特別是考慮到它上市已四年，並且體現了商業團隊的出色執行力。

Next, on the clinical front, we now have the data from our pediatric clinical trial with ORLADEYO to put us in a position to file the NDA this year. We also advanced BCX17725 for Netherton Syndrome into the clinic and made progress with the world stat for DME that will enable us. To put that program into the clinic this year. All of these advancing programs represent an opportunity to serve patients and provide them something meaningfully better than is currently available to them, a chance to really change their life.

接下來，在臨床方面，我們現在擁有與 ORLADEYO 合作進行的兒科臨床試驗的數據，可以讓我們在今年提交 NDA。我們還將用於治療 Netherton 綜合徵的 BCX17725 推進到臨床階段，並在 DME 的世界統計方面取得了進展，這將使我們能夠。今年將該計劃投入臨床。所有這些進步的項目都代表著為患者服務的機會，並為他們提供比目前更好的服務，一個真正改變他們生活的機會。

Whether it's no longer having to inject your toddler with their medicine for HAE, finally having a treatment to change the underlying cause of Netherton Syndrome or giving DME patients hope of a new therapy that may work for more patients and be given with fewer injections. The execution of our teams last year has put us in a great position to get data and answers on these programs later this year.

無論是不再需要為您的孩子注射治療 HAE 的藥物，還是最終透過治療改變 Netherton 症候群的根本原因，還是為 DME 患者帶來可能對更多患者有效且注射次數更少的新療法的希望。我們團隊去年的執行情況使我們在今年稍後能夠獲得有關這些計劃的數據和答案。

And finally we executed so well last year that we not only generated a non-GAAP operating profit, but this profit was over $60 million which is 3 times larger than what we had planned. The magnitude of the free cash flow we now expect over the next three years will likely further transform our company. The place we find ourselves in today, was intentional, as the execution by the employees at BioCryst has never been better, and the momentum we have is carrying over to this year and likely many years to come.

最後，我們去年的表現非常好，我們不僅創造了非公認會計準則營業利潤，而且這個利潤超過 6000 萬美元，是我們計劃的三倍。我們現在預計未來三年的自由現金流規模可能會進一步改變我們的公司。我們今天所處的位置是有意為之，因為 BioCryst 員工的執行力從未如此出色，我們的勢頭將延續到今年，甚至可能持續到未來的許多年。

I'll now turn it over to Charlie.

現在我將把發言權交給查理。

Thanks, John. ORLADEYO gained momentum in 2024 with over 34% growth in the fourth year on the market. And that increasing momentum is carrying into 2025. Demand in early 2025 has continued at the same strong pace we saw in 2024, but an even bigger source of early strength has been the impact of the Inflation Reduction Act for Medicare patients.

謝謝，約翰。ORLADEYO 在 2024 年發展勢頭強勁，上市第四年成長率超過 34%。這種成長勢頭將持續到 2025 年。2025 年初的需求將繼續保持與 2024 年相同的強勁速度，但早期強勁的更大來源是《通貨膨脹削減法案》對醫療保險患者的影響。

We are seeing that a much higher percentage of Medicare patients on ORLADEYO can afford their copayments, and this is happening at a rate ahead of our prior expectations. As a result, we are raising our ORLADEYO revenue guidance for the year to $535 million to $550 million. The full reauthorization season will run for at least two more months, and most [reoffs] within our large commercially insured patient base are still in process.

我們發現，奧拉迪亞縣的醫療保險患者中，能夠負擔共同支付費用的比例大大提高，而且這一增長速度超出了我們先前的預期。因此，我們將 ORLADEYO 今年的營收預期上調至 5.35 億美元至 5.5 億美元。完整的重新授權季節將持續至少兩個月，並且我們龐大的商業保險患者群體中的大多數[重新授權]仍在進行中。

The outcome of those cases will dictate where the revenue ends up relative to the increased guidance range. We've described previously how HAE traders are gaining enthusiasm for ORLADEYO. And we have four new posters of real-world evidence being presented this coming weekend at the QAD AI conference in San Diego that help explain why.

這些案件的結果將決定收入相對於增加的指導範圍的最終水準。我們之前曾描述 HAE 交易者如何對 ORLADEYO 產生熱情。我們將於本週末在聖地牙哥舉行的 QAD AI 會議上展示四張新的現實世界證據海報，以幫助解釋其中的原因。

Two of the posters stratify patient reported outcomes by baseline attack rate in type one and two patients, as well as HA patients with normal C1 inhibitor. And then examine long-term outcomes at 12 and 18 months. These analyses include hundreds of patients each, which we believe are much larger volumes of evidence than have been reported for any other HAE prophylactic medication.

其中兩張海報根據一型和二型患者以及 C1 抑制劑正常的 HA 患者的基線發生率對患者報告的結果進行了分層。然後檢查 12 個月和 18 個月的長期結果。這些分析均涉及數百名患者，我們認為其證據量比任何其他 HAE 預防藥物報告的證據量大得多。

The posters show that ORLADEYO dramatically reduces attack rates for patients with very high baseline rates and helps patients who are attack-free maintain zero attacks while benefiting from oral administration. In other words, this is a treatment that works well for all types of HAE patients, not just patients with so-called mild disease.

海報顯示，ORLADEYO 可顯著降低基線發病率非常高的患者的發病率，並幫助未發作過發作的患者在受益於口服給藥的同時保持零發作。換句話說，這是一種對所有類型的 HAE 患者都有效的治療方法，而不僅僅是所謂的輕度疾病患者。

Our latest market tracking study completed in December underscored the momentum building among prescribers. Slide 8 shows that 97% of the 60 US HAE treaters surveyed are considering prescribing . Among those who have prescribed, 59% say they are extremely likely to prescribe ORLADEYO to more patients, a metric that is up from just 26%, just 18 months prior.

我們在 12 月完成的最新市場追蹤研究強調了處方者之間的勢頭正在增強。投影片 8 顯示，受訪的 60 位美國 HAE 治療者中，97% 的人正在考慮開處方。在已開立處方的患者中，59% 的人表示他們極有可能為更多患者開出 ORLADEYO，而 18 個月前這一數字僅為 26%。

That prescribing momentum showed up in 2024 as the number of new prescriptions was exactly the same as in 2021, the first year of the launch. Slide 9 shows that HAE treaters expect to continue the momentum by prescribing ORLADEYO to 17% more of their current patients in 2025, with an emphasis on prescribing to current injectable prophy patients.

這種處方勢頭在 2024 年顯現，因為新處方的數量與推出的第一年 2021 年完全相同。投影片 9 顯示，HAE 治療人員預計將保持這一勢頭，到 2025 年將為 17% 以上的現有患者開出 ORLADEYO，重點是為當前的注射預防患者開出處方。

Over the first four years of the launch, this forward view of the coming year from positions has been very predictive of the ORLADEYO growth trajectory. And physician intent is aligning with patient preference. Slide 10 shows that over half of injectable prophy patients would prefer an oral route of administration, while only one in 5 prefers an injectable. Over 1,200 US HAE treaters have prescribed ORLADEYO to over 3,000 patients through the end of 2024. And both patients and physicians are telling us to expect a lot more growth ahead.

在推出後的前四年裡，從各個地點對來年的前瞻性展望非常能預測 ORLADEYO 的成長軌跡。醫生的意圖與病人的偏好是一致的。幻燈片 10 顯示，超過一半的注射預防疾病患者喜歡口服給藥，而只有五分之一的患者喜歡注射。截至 2024 年底，超過 1,200 名美國 HAE 治療醫生已為超過 3,000 名患者開設了 ORLADEYO。患者和醫生都告訴我們未來還會有更大的成長。

I'll turn it over to Helen, to describe other exciting sources of future growth.

我將把這個交給海倫，來描述未來成長的其他令人興奮的來源。

Thanks, Charlie. In our pipeline we're making great progress already this year, advancing both BCX17725 and Netherton Syndrome and Avoralstat in Diabetic Macular Edema towards meaningful clinical data readouts and submitting our NDA this year to expand the range for ORLADEYO to kids ages 2 to 11.

謝謝，查理。我們的研發管線今年已取得巨大進展，BCX17725 和 Netherton 綜合徵以及糖尿病性黃斑水腫的 Avoralstat 均獲得了有意義的臨床數據讀數，並在今年提交了 NDA，將 ORLADEYO 的範圍擴大到 2 至 11 歲的兒童。

I'll start with Netherton Syndrome, a severe disease that has no approved treatments and for which we will have initial clinical data later this year as we evaluate BCX1775 for the potential to deliver a functional cure. Patients with Netherton Syndrome have a genetic mutation causing abnormal skin turnover and inflammation with premature separation and peeling of the outer layers of skin.

我首先要介紹的是內瑟頓綜合徵，這是一種嚴重的疾病，目前尚無核准的治療方法，我們將在今年稍後獲得初步臨床數據，以評估 BCX1775 實現功能性治癒的潛力。患有 Netherton 綜合徵的患者存在基因突變，導致皮膚更新異常和炎症，並導致皮膚外層​​過早分離和剝落。

They experience intense chronic itching and redness along with severe atopic symptoms like asthma and food allergies, which means that patients live with a disease that involves much more than red peeling skin. The effect on their health and well-being is profound. One patient I spoke with described the constant battle she faces to keep her skin in good condition, spending hours a day applying ointments and lotions all over her body.

他們會經歷劇烈的慢性搔癢和發紅，以及氣喘和食物過敏等嚴重的過敏症狀，這意味著患者所患的疾病不僅僅是皮膚發紅脫皮。這對他們的健康和福祉的影響是深遠的。與我交談過的一位患者描述了她為了保持皮膚良好狀態所面臨的持續鬥爭，每天要花幾個小時在全身塗抹藥膏和乳液。

Everyday life for her means having itchy, fragile skin and being unable to prevent it from peeling off in big pieces. Even with her best efforts, she's still been in the hospital multiple times for infections as a child and also as an adult. There are no disease modifying options for a patient like her even though she has a confirmed diagnosis and sees specialists for her care. Our goal is to change this.

對她來說，日常生活意味著皮膚發癢、脆弱，無法防止大塊皮膚脫落。即使她盡了最大努力，她在小時候和成年後仍然因感染而多次住院。對於像她這樣的患者，儘管已經確診，並請專科醫生進行治療，但沒有任何可以改變病情的治療方案。我們的目標是改變這種狀況。

We've engineered BCX1775 to replace the missing protein function and to deliver this with very high potency for subcutaneous delivery potential and high affinity, the ability to stick to the target for a long time and have a lasting effect. We are aiming for a long dosing interval every two weeks or longer, which we believe could deliver a differentiated therapy for Netherton Syndrome.

我們設計了 BCX1775 來取代缺失的蛋白質功能，並以極高的效力實現皮下輸送潛力和高親和力，能夠長時間黏附於目標並產生持久的效果。我們的目標是每兩週或更長時間進行一次給藥間隔，我們相信這可以為 Netherton 症候群提供差異化治療。

Today, BCX1775 is in a Phase 1 trial with dose escalation underway and healthy volunteers. Next, we will start dosing patients, and we plan to have data this year to confirm that the drug gets to the skin in patients and that the drug has the intended biomarker activity on the target, KLK5 in the skin. These patients will receive multiple doses of the drug, so we can assess for healing of the skin using known endpoints for chronic skin disease.

目前，BCX1775 正處於第一階段試驗，正在進行劑量遞增並招募健康志願者。接下來，我們將開始對患者進行給藥，我們計劃今年獲得數據來確認該藥物能夠到達患者的皮膚，並且該藥物對皮膚中的標靶 KLK5 具有預期的生物標記活性。這些患者將接受多劑量的藥物，因此我們可以使用已知的慢性皮膚病終點來評估皮膚的癒合情況。

Because there is no cure for physicians to offer patients, we believe Nethergen syndrome is underdiagnosed. What we know today is that Nethergen Syndrome is an ultra-rare disease, and our studies estimate about 1,600 patients in the US based on the reporting of a known feature called bamboo hair. We also know that patients with a diagnosis of severe ichthyosis or inflamed scaly skin may not be tested for the genetic mutation, and yet many may in fact have it.

由於醫生無法為患者提供治癒方法，我們認為 Nethergen 症候群未被充分診斷​​。我們今天所知道的是，內瑟根症候群是一種極為罕見的疾病，我們的研究根據已知特徵竹毛的報告估計美國約有 1,600 名患者。我們也知道，被診斷為嚴重魚鱗病或鱗狀皮膚發炎的患者可能不會接受基因突變檢測，但實際上許多人可能患有這種疾病。

We've seen how diagnosis rates change once a disease targeting treatment becomes available for a rare disease. Not too long ago, HAE was thought to affect only about 2000 patients in the US, but today, changes in therapy have led to a known market more than 5 times the initial estimate, about 11,000 patients in the US. It is possible Netherton Syndrome will follow this pattern, making it an even more attractive opportunity for a drug like BCX17725.

我們已經看到，一旦針對罕見疾病的治療問世，診斷率就會發生怎樣的變化。不久前，HAE 被認為僅影響美國約 2,000 名患者，但如今，治療方法的改變已使已知市場規模達到最初估計的 5 倍以上，影響到美國約 11,000 名患者。內瑟頓症候群很可能會遵循這種模式，這使得 BCX17725 之類的藥物更具吸引力。

Next, in the pipeline, rural staff will be moving into the clinic in patients with Diabetic Macular Edema this year. We've had a lot of interest from physicians in pursuing an alternative mechanism to treat DME because VEGF inhibitors are effective only for a little over half of all patients. This [gap] in treatment leaves many with continuing loss of visual acuity, making independent living more and more difficult.

接下來，鄉村醫護人員今年將進駐糖尿病黃斑水腫患者的診所。許多醫生對尋找治療 DME 的替代機制很感興趣，因為 VEGF 抑制劑只對一半多一點的患者有效。治療中的這種差距導致許多人的視力持續下降，獨立生活變得越來越困難。

Earlier this year we presented images from a pre-clinical model that showed the cessation of vascular leakage after a supraroidal injection of aorostat, a plasma alacrine inhibitor. The images, which you can see on slide 19, are from an animal model of retinal vascular leakage and show the change in that vascular leakage in the retina before and six days after treatment with the boostat.

今年早些時候，我們展示了臨床前模型的圖像，該模型顯示在子宮上註射血漿阿拉克林抑製劑 aorostat 後血管滲漏停止。您可以在幻燈片 19 上看到的圖像來自視網膜血管滲漏的動物模型，顯示了使用 boostat 治療之前和治療六天后視網膜血管滲漏的變化。

This effect lasted through 21 days before leaking started to return by the next time point at day 36. This is a clear effect, and we believe it demonstrates the involvement of the Kallikrein and pathway in retinal leakage and importantly provides strong evidence that plasma Kallikrein inhibition may be an alternative pathway for reducing retinal vascular leakage.

這種影響持續了 21 天，直到第 36 天的下一個時間點洩漏才開始再次出現。這是一個明顯的效果，我們相信它證明了激肽釋放酶和通路參與了視網膜滲漏，重要的是提供了強有力的證據，表明血漿激肽釋放酶抑制可能是減少視網膜血管滲漏的替代途徑。

Of course, the real assessment of potential for both efficacy and durability and treating DME can only be made in patients. So we look forward to moving the program into the clinic. Later this year, we plan to enroll patients with newly diagnosed DME and including patients who received a few injections of anti-VEGF therapy. Our goal is that by the end of the year we may be evaluating for activity such as measurable changes in edema in the first few patients on the trial.

當然，只有在患者身上才能真正評估其療效和持久性以及治療 DME 的潛力。因此我們期待將該項目推廣到臨床。今年晚些時候，我們計劃招募新診斷的 DME 患者，其中包括接受過幾次抗 VEGF 治療注射的患者。我們的目標是，到今年年底，我們可能會對試驗中最初幾名患者的水腫可測量變化等情況進行評估。

And last, following Charlie's, description of the robust real-world evidence we're presenting this coming weekend at QAD AI, I'm really excited to report that the first data from our Apex P trial with the pediatric oral granule formulation of Kallikrein in children under 12 with HAE will be highlighted in a late breaking abstract on Sunday. This is the largest trial to date evaluating prophylactic therapy for HAE in this age group, and we are thrilled with the results. I want to thank all the children and their families and our investigators who made this trial possible.

最後，繼 Charlie 描述了我們即將於本週末在 QAD AI 上展示的強有力的真實世界證據之後，我很高興地報告，我們在 Apex P 試驗中使用兒童口服顆粒劑型激肽釋放酶治療 12 歲以下 HAE 兒童的首批數據將在周日的最新摘要中重點介紹。這是迄今為止針對該年齡層進行 HAE 預防性治療評估的最大規模試驗，我們對結果感到非常興奮。我要感謝所有讓這次試驗成為可能的孩子、他們的家人和我們的研究人員。

There is an urgent medical need for an oral therapy to prevent HAE attacks in children. As both a pediatrician and a mom, I am truly excited that we are getting closer to making or available for children with HAE. In the AXP trial, we saw that the granules were safe and well tolerated in this pediatric population. And children achieved early and sustained reduction in monthly HAE attack rates. In fact, 25 out of 29 children remain on the study.

目前迫切需要一種口服療法來預防兒童發生 HAE 發作。身為兒科醫生和母親，我由衷地感到高興，我們離為患有 HAE 的兒童提供治療越來越近了。在 AXP 試驗中，我們發現這些顆粒對於兒科族群來說是安全的且耐受性良好。兒童的每月 HAE 發生率早期就持續降低了。事實上，29名兒童中仍有25名繼續接受研究。

These results for safety and efficacy are consistent with the adolescent and adult experience, and we are on track to file our NDA this year. We also learned that children with HAE are experiencing severe swelling attacks at a very young age, with a median age of onset at two years. These findings support an earlier age of symptom onset and need for HAE prophylaxis then has generally been understood.

這些安全性和有效性的結果與青少年和成年人的經驗一致，我們預計今年將提交 NDA。我們也了解到，患有 HAE 的兒童在很小的時候就會出現嚴重的腫脹症狀，平均發病年齡為兩歲。這些發現支持了人們普遍認為的更早出現症狀的年齡和進行 HAE 預防的必要性。

And we've learned that the oral granule formulation for ORLADEYO also allows simple prophylaxis with great attack control to be provided for the youngest children. These outstanding data will be included in our NDA submission, which is on track for later this year. So we have a very exciting 2025 ahead with the pediatric NDA [inaudible] and our initial clinical data coming from both our Netherton Syndrome and DME programs.

我們了解到，ORLADEYO 的口服顆粒劑型還可以為最小的兒童提供簡單的預防和良好的發病控制。這些未完成的數據將包含在我們的 NDA 提交中，預計將於今年稍後提交。因此，我們迎來了令人興奮的 2025 年，我們將獲得兒科 NDA [聽不清楚] 以及來自 Netherton 綜合徵和 DME 項目的初步臨床數據。

And now, I'll turn the call over to Anthony.

現在，我將把電話轉給安東尼。

Thanks, Helen. At the beginning of last year, we laid out our goals for strong commercial growth for ORLADEYO, advancing our early pipeline into the clinic and moving towards sustainable and meaningful profitability in the short term. And as we shared earlier, it's great to see that we've exceeded even our own expectations in achieving these goals.

謝謝，海倫。去年年初，我們制定了 ORLADEYO 強勁商業成長的目標，將我們的早期產品線推進到臨床階段，並在短期內實現可持續且有意義的盈利。正如我們之前所分享的，我們很高興地看到，我們在實現這些目標方面甚至超出了我們自己的預期。

You can find our detailed fourth quarter financials in today's earnings press release, and I'd like to call your attention to a few items. Total revenue for the quarter came in at $131.5 million 124.2 million dollars of which came from ORLADEYO. For full year 2024, total revenue was $450.7 million, with ORLADEYO contributing $437.7 million of that.

您可以在今天的收益新聞稿中找到我們第四季度的詳細財務狀況，我想提請您注意以下幾點。本季總營收為 1.315 億美元，其中 1.242 億美元來自 ORLADEYO。2024 年全年總收入為 4.507 億美元，其中 ORLADEYO 貢獻了 4.377 億美元。

For quarter 4 $17.2 million or 13.9% of the $124.2 million total for ORLADEYO came from ex US. Well for a full year it was $51.7 million or 11.8% of the $437.7 million total. Operating expenses, not including non-cash stock compensation for the quarter were approximately $115 million.

第四季度，ORLADEYO 1.242 億美元總額中有 1,720 萬美元（即 13.9%）來自美國以外地區。全年而言，這一數字為 5,170 萬美元，佔總數 4.377 億美元的 11.8%。本季營運費用（不包括非現金股票補償）約為 1.15 億美元。

Operating expenses, not including non-cash, non-stock-based compensation for full year 2024, came in at $388 million, an increase of just $8 million versus 2023. With revenue increasing $119 million year over year and this small increase in OpEx, this resulted in an operating profit, not including stock-based comp, of $62.9 million. That's an increase of $111 million versus the non-GAAP operating loss of $48.1 million from 2023, a remarkable achievement that sets us up for 2025 and beyond.

2024 年全年營運費用（不含非現金、非股票薪酬）為 3.88 億美元，較 2023 年僅增加 800 萬美元。由於營收年增 1.19 億美元，且營運支出略有增加，因此營業利潤（不包括股票補償）達到 6,290 萬美元。與 2023 年的非 GAAP 營業虧損 4,810 萬美元相比，這一數字增加了 1.11 億美元，這是一項了不起的成就，為我們在 2025 年及以後的發展奠定了基礎。

Cash at the end of the year was approximately $343 million and net cash utilization for the quarter was $8.4 million. Charlie shared the increase in guidance for all the revenue for this year of between $535 million and $550 million based on the progress that we've seen thus far in Q1 around reauthorization and Medicare reimbursement. The total revenue, we're adjusting guidance upwards in line with the ORLADEYO increase to between $560 million and $575 million.

年末現金約 3.43 億美元，本季淨現金利用率為 840 萬美元。根據我們在第一季迄今看到的重新授權和醫療保險報銷方面的進展，查理將今年所有收入的預期增長定為 5.35 億美元至 5.5 億美元。在總收入方面，我們根據 ORLADEYO 的成長上調預期，至 5.6 億美元至 5.75 億美元之間。

While there's some increased uncertainty around future government funding for RAPIVAB, we're also seeing strong commercial demand for the product, given the prevalence of flu at the moment. For OpEx, the improved ORLADEYO of commercial performance will result in increased expenses around COGS, distribution fees, and incentive compensation, but should remain bound by the upper end of the $425 million to $435 million guidance that we provided previously.

儘管未來政府對 RAPIVAB 的資助存在一些不確定性，但鑑於目前流感的流行，我們也看到對該產品的強勁商業需求。對於營運支出 (OpEx)，商業績效的提高將導致 ORLADEYO 的 COGS、分銷費和激勵薪酬等費用增加，但仍應受我們先前提供的 4.25 億美元至 4.35 億美元指導上限的約束。

That puts us in a great position to achieve our 2025 goals of positive and sustainable quarterly cash flow and EPS in the second half of the year. Longer term, earlier in the year, we provided guidance for revenue with a three-year CAGR of 20%. So north of $750 million by 2027 and also reiterated our belief of getting to $1 billion in global revenue by 2029.

這使我們處於有利地位，可以在下半年實現 2025 年的正向且可持續的季度現金流和每股盈餘目標。從長遠來看，今年早些時候，我們給出了三年複合年增長率為 20% 的收入預期。因此，到 2027 年，全球收入將超過 7.5 億美元，同時我們也重申了 2029 年實現 10 億美元全球收入的信念。

We also provided a CAGR for OpEx, not including stock Bascom of 5%, so closer to $450 million by 2027. With positive quarterly cash flow this year, annual positive cash flow generation next year, and the cash flow that we will generate in 2027 when revenue was greater than OpEx by more than $300 million. We expect to have more than $600 million of cash on hand at that time, allowing us to reduce our debt and our cost of capital and reinforcing our position that we are capital markets independent.

我們也提供了營運支出的複合年增長率（不包括 Bascom 股票），即 5%，因此到 2027 年將接近 4.5 億美元。今年季度現金流為正，明年年度現金流為正，2027 年我們將產生現金流，屆時收入將超過營運支出超過 3 億美元。我們預計屆時手頭上將有超過 6 億美元的現金，這使我們能夠減少債務和資本成本，並鞏固我們獨立於資本市場的地位。

Operator, we can open it up for Q&A.

接線員，我們可以開放問答環節了。

(Operator Instructions) Tazeen Ahmad, Bank of America.

（操作員指示） Tazeen Ahmad，美國銀行。

Thanks guys. Good morning. Thanks for all of the color. I wanted to start maybe with a question on Netherton. You're expecting data from patients later this year. Can you potentially narrow down when this year those patient data could come in? And then secondly, can you talk about what would be positive data in your view?

謝謝大家。早安.感謝所有的色彩。我想先問一個關於 Netherton 的問題。您將在今年稍後收到患者的數據。您能否縮小今年可以獲得這些患者數據的時間範圍？其次，您能談談您認為哪些是正面的數據嗎？

Do you think the amount of patients that you've enrolled would allow for a sense of efficacy in a clinical setting beyond the biomarker data that you've talked about releasing? And if that data is encouraging, what do you think the path forward could be for Netherton just given that there's nothing approved in patients right now and it is an area of unmet need. Thanks.

您是否認為，除了您談到發布的生物標記數據之外，您招募的患者數量是否能夠在臨床環境中讓您感受到療效？如果這些數據令人鼓舞，考慮到目前還沒有任何藥物獲準用於治療患者，而且這是一個尚未滿足需求的領域，您認為 Netherton 的前進之路會是怎樣的？謝謝。

Helen you want to take that?

海倫你想拿走那個嗎？

Thanks to, Tazeen. So first of all, we have, we will have data this year, and that's the guidance we're giving at the moment. In terms of what we expect to see. So how many patients, one thing about this disease is a genetically driven disease is that we really only need to see data in a very small number of patients to have confidence that we're hitting. The mechanism we're looking to make a functional replacement of the missing protein, and we may see that with single digit patients.

感謝 Tazeen。首先，我們有，今年也會有數據，這就是我們目前給的指引。就我們期望看到的情況而言。那麼有多少患者，這種疾病是一種遺傳性疾病，我們實際上只需要查看極少數患者的數據就可以確信我們正在治癒它。我們正在尋找一種機制來取代缺失的蛋白質，我們可能會在個位數患者身上看到這一點。

In terms of what we're looking for then, we're looking at the first of all, as I said, the activity in the skin. But with that specifically we're looking for the drug's effect on KLK5 activity in the skin, the suppression of KLK5 activity. What that will lead to then is healing in the skin. And so we're looking for a graded observation of the skin and is it actually demonstrating signs of healing.

就我們所尋找的內容而言，正如我所說，我們首先關注的是皮膚的活動。但我們具體是在尋找藥物對皮膚中 KLK5 活性的影響，即對 KLK5 活性的抑制。這將導致皮膚癒合。因此，我們希望對皮膚進行分級觀察，看看它是否真的顯示出癒合的跡象。

So that we would be able to see later this year, possibly and early next year as well for healing of the skin. In terms of the development path forward, the data we'll get this year is very important to us, because that few patient's worth of data showing activity in the skin, that the drug is getting to the skin and having its activity.

這樣我們就能在今年晚些時候，甚至明年年初看到皮膚癒合的情況。就未來的發展道路而言，我們今年獲得的數據對我們來說非常重要，因為少數患者的數據顯示了藥物在皮膚中的活性，表明藥物到達皮膚並發揮其活性。

We would then expect to see some degree of healing following from there, and we would move pretty quickly into assessing that in a the next study. This is an ultra-rare population with a serious outcome and a pretty clear response that we're looking for. So it could be a very short path to pivotal studies. As we have a dose which I'd expect to have at some point next year, then we'll move into a pivotal program that would be the registration program. And it probably is a single pivotal trial program supported by the data that we'll be collecting this year and next.

然後，我們期望看到一定程度的治愈，並且我們將很快在下一項研究中對此進行評估。這是一個極為罕見的群體，其結果很嚴重，我們期待得到非常明確的反應。因此，這可能是一條通往關鍵研究的捷徑。由於我們預計明年某個時候會有劑量，因此我們將進入一個關鍵計劃，即註冊計劃。這可能是我們今年和明年收集的數據支持的關鍵試驗計劃。

And Helen, the profile we're shooting for is a functional cure. So the magnitude of effect will drive what the pivotal program looks like and the number of patients necessary. So the bigger the effect, the faster we probably can go and the fewer patients we need. Is that a fair assessment?

海倫，我們追求的目標是功能性治癒。因此，效果的大小將決定關鍵計劃的具體內容以及所需的患者數量。因此，效果越大，我們可能就能越快取得進展，需要的患者就越少。這是一個公平的評價嗎？

Yes

是的

Thank you.

謝謝。

Jessica Fye, JP Morgan Securities.

摩根大通證券的傑西卡費伊 (Jessica Fye)。

Hey guys, good morning. Thanks for taking my questions. One on ORLADEYO and one just following up on the prior question for Netherton. First on ORLADEYO, where are you tracking towards for the proportion of paid patients overall and within Medicare specifically? And what is the current ORLADEYO guidance embed there?

大家好，早安。感謝您回答我的問題。一個是關於 ORLADEYO 的，另一個只是對 Netherton 先前的問題的跟進。首先關於 ORLADEYO，您追蹤的付費病患整體比例以及醫療保險內付費病患的具體比例是多少？目前 ORLADEYO 的指導內容是什麼？

And then second, how quickly could we expect to see this mechanism result in skin healing in Netherton, just thinking about the mechanism and the underlying disease pathology.

其次，僅考慮機制和潛在的疾病病理，我們可以多快看到這種機制導致 Netherton 的皮膚癒合。

I'll take the ORLADEYO question. Thanks, Jess. As far as the proportion of paid patients, we ended last year at 73.5% paid across our whole patient base. I can't give you an exact number yet because we're literally right in the middle of the reauthorization season. So what that means is a lot of our patients who were previously on long-term free products or even paid product have moved temporarily into quick Start product.

我來回答一下 ORLADEYO 的問題。謝謝，傑西。就付費患者的比例而言，去年我們整個患者群的付費患者比例為 73.5%。我還不能給你一個確切的數字，因為我們實際上正處於重新授權季節的中期。這意味著，許多先前使用長期免費產品甚至付費產品的患者已經暫時轉而使用快速啟動產品。

So any number that I would give you now would not be accurate. I have said though before that with a swing back in Medicare paid patients that could push us toward 80%. And so by the end of the quarter we'll be able to see where we are. So I would expect to report that in the next earnings.

所以我現在給你的任何數字都不準確。我之前曾說過，隨著醫療保險支付患者人數的回升，我們有可能達到 80% 的目標。因此，到本季末，我們將能夠看到我們所處的狀況。因此我希望在下次收益報告中報告這一點。

We do think because of all of the reauthorization season, revenue for the first quarter is still going to be flat to slightly down versus Q4 just because of all the free product that we have to give away as well as the impact to gross to net from the co-payment assistance that we provide to commercial patients.

我們確實認為，由於整個重新授權季節，第一季的收入仍將與第四季度持平或略有下降，這是因為我們必須贈送所有免費產品，以及我們向商業患者提供的共同支付援助對毛收入和淨收入的影響。

There is also a little bit of a headwind as it relates to foreign exchange. So included in Charlie's increased guidance, there is, a headwind of probably around $5 million give or take in the EU. So it makes the number that we're achieving in terms of the increased guidance for here in the US, all the more impressive.

在外匯方面也存在一些阻力。因此，在查理增加的指導中，歐盟可能面臨約 500 萬美元的逆風。因此，就美國增加的指導而言，我們取得的數字更加令人印象深刻。

Hey, Charlie. Our assumption prior to getting into the new year was that it would, the Medicare thing would happen over a couple two-year, three-year period. That's not what you're seeing the pace of it is significantly faster, and that's the reason for the guide.

嘿，查理。在進入新的一年之前，我們的假設是，醫療保險制度將在兩年或三年內實現。這不是你所看到的，它的速度明顯更快，這就是指南的原因。

That's correct. We assume that we would get back to. A high paid rate in Medicare by 2027. It's looking like we'll get much more of that back this year, but we won't know the final results until after the quarter.

沒錯。我們假設我們會回到。到 2027 年，醫療保險的支付率將達到高水準。看起來我們今年會獲得更多的回報，但我們直到本季結束後才能知道最終結果。

Helen, you want to take the Netherton.

海倫，你想佔領內瑟頓。

So Jess, on your question about Netherton Syndrome and how quickly we'd expect to see. Healing in the skin. The short answer is we don't know, but what we do know is that we'll see the activity on target activity first. And it could be just a very few months after that that we're seeing healing of the skin. We'll be looking at four weeks, eight weeks, twelve weeks, et cetera.

那麼傑西，關於你關於內瑟頓症候群的問題以及我們預計多久會看到結果。皮膚癒合。簡短的回答是我們不知道，但我們知道的是，我們將首先看到目標活動的活動。可能只需要幾個月的時間，我們就能看到皮膚的癒合。我們將關註四週、八週、十二週等等。

And once we see that. A target-on-target activity, the biomarker, we'll know that we're at the dose and then we'll just continue treating longer term and following for that those first few months to assess for healing of the skin.

一旦我們看到了這一點。透過靶向活性和生物標記，我們可以知道我們達到了劑量，然後我們將繼續進行長期治療，並在最初幾個月內評估皮膚的癒合情況。

And Helen, can you talk about skin turnover and it's not like it's years to see an effect that talk a little bit about that.

海倫，您能談談皮膚更新嗎？並不是說要過幾年才能看到效果，請稍微談談這個。

So skin turnover is actually pretty fast and normal skin expects the skin layers to turn over about every two weeks or so. And so with this drug, when I talk about seeing activity on target, that KLK5 activity, then we would expect that activity to be there for the duration of that skin layer being present.

因此，皮膚更新速度實際上非常快，正常皮膚的皮膚層大約每兩週更新一次。因此，對於這種藥物，當我談到看到目標活性，即 KLK5 活性時，我們預計該活性會在皮膚層存在期間一直存在。

So it's going to be two weeks and longer that we'd expect to see the effect of the drug for each dose and then we're looking to see what happens with that skin over time. So that's why I look back to it could be very few months, our weeks, eight weeks, twelve weeks follow up.

因此，我們預計需要兩週甚至更長時間才能看到每次劑量的藥物效果，然後我們觀察隨著時間的推移皮膚會發生什麼變化。所以這就是為什麼我回顧它可能是幾個月、幾週、八週、十二週的後續。

And given what we see in terms of potency and affinity of this molecule, the treatment effect that we're expecting is pretty significant, and it should come pretty quickly. In general, in terms of the results that we see from this early study.

鑑於我們對這種分子的效力和親和力的了解，我們預期的治療效果非常顯著，而且應該很快就會顯現出來。總的來說，就我們從這項早期研究中看到的結果而言。

Yes, we're looking for a pretty big effect here, and this is a very potent drug. It is very sticky. That's that high affinity. And we're looking for a really obvious effect. So that's why we think it's something that we might see pretty quickly.

是的，我們期待它能產生相當大的效果，這是一種非常有效的藥物。它很粘。就是親和力那麼高。我們正在尋找真正明顯的效果。所以我們認為這是我們可能很快就會看到的事情。

And is it safe to say that de-risking event is the drug getting to the skin in patients?

是否可以肯定地說，降低風險的事件是藥物到達患者的皮膚？

Yes.

是的。

Okay, thanks.

好的，謝謝。

And was there a follow up, Ms. Fye?

還有後續消息嗎，Fye 女士？

That's it. Thank you.

就是這樣。謝謝。

Stacy Ku, TD Cowen.

史黛西·庫（Stacy Ku），考恩公司（Cowen）TD。

Okay, well, thank you so much for taking our questions and congratulations on the results. So first, quick follow up on Netherton? We might have missed this. Have you talked about specifically when you plan on kind of dosing other temptations. So just some, specific timing on that. And then again on this. So now to ORLADEYO. Almost every result. Are you kind of finding that the tax-free rates are similar to other prophylaxis therapies?

好的，非常感謝您回答我們的問題，並對所取得的成果表示祝賀。那麼首先，您能快速跟進一下 Netherton 的情況嗎？我們可能錯過了這一點。您是否具體談過何時計劃抑制其他誘惑。因此，這只是一些具體的時間安排。然後再談這一點。現在去奧拉代約。幾乎每一個結果。您是否發現免稅稅率與其他預防療法相似？

Kind of curious your takeaway as it relates to kind of the patients that are well controlled on oral versus patients that are well controlled on conductible therapies. And then the last question is kind of another follow-up on the guidance. What exactly are you seeing kind of in the last month and a half that kind of gives you conviction and a new updated guidance? Is it kind of the charities? Is it really just that Medicare, kind of update and remind us kind of every 1% that you're converting is that $5 million in sales? Thank you so much.

有點好奇您的看法，因為它與口服療法控制良好的患者和傳導療法控制良好的患者有關。最後一個問題是對該指導的另一個後續問題。在過去一個半月裡，您究竟看到了什麼事情，讓您更堅定了信念，並獲得了新的指導？這算是慈善事業嗎？這真的只是醫療保險的一種更新，並提醒我們您轉換的每 1% 都是 500 萬美元的銷售額嗎？太感謝了。

So Netherton Syndrome in terms of when we'd be dosing. So we haven't said exactly. However, what I can say is we are dosing in healthy volunteers now and we're moving towards dosing patients with Netherton Syndrome soon. So it will be sometime around the middle of the year, third quarter. That's what would give us then the opportunity to assess the activity in the skin and be looking at healing by the end of the year.

因此，就我們何時服藥而言，內瑟頓症候群是可以治癒的。所以我們還沒有確切地說。然而，我可以說的是，我們現在正在對健康志願者進行給藥，並且很快就會對患有 Netherton 綜合症的患者進行給藥。所以大概是在今年年中，也就是第三季左右。這將使我們有機會評估皮膚活動，並在年底前觀察癒合情況。

And then Stacy, as far as the attack free or sorry, -- the attack rate reduction that we're seeing in the real world. I think we see that patients on ORLADEYO are getting to really low rates of attacks. If they don't, they move on. So what we've said before is no drug is perfect for every patient. But this is related to a really strong retention rate for ORLADEYO of patients of 60% in a year.

然後史泰西，就攻擊自由或抱歉而言——我們在現實世界中看到的攻擊率降低。我認為我們看到 ORLADEYO 患者的發生率確實很低。如果他們不這樣做，他們就會繼續前進。所以我們之前說過，沒有一種藥物適合所有病人。但這與 ORLADEYO 一年內 60% 的病患保留率非常高有關。

Patients are staying on because they're doing really well. That's what you'll see in the posters that we present at QAD AI this coming weekend, that patients, whether they started at a baseline attack rate that was really high over five attacks a month, or whether they started at zero attacks at baseline. They're doing really well over time. So we think they're getting a very competitive efficacy rate.

病人之所以留下來，是因為他們的情況非常好。這就是您將在即將到來的這個週末我們在 QAD AI 上展示的海報中看到的內容，患者無論開始時的基線發病率是每月超過五次發病，還是基線發病率為零。隨著時間的推移，他們做得非常好。因此我們認為他們獲得了非常有競爭力的功效。

And the things that give us confidence so far in the year. The number one thing is the Medicare patients moving to paid therapy. We think that this is really because the IRA is making it more affordable, probably makes it more affordable for the charities, but what we're just seeing is patients are getting approved by their plans they're able to afford their copayments and so they're staying on paid therapy.

今年到目前為止，這些事情給了我們信心。最重要的是醫療保險患者轉向付費治療。我們認為，這實際上是因為 IRA 使其變得更實惠，也可能使慈善機構更能負擔得起，但我們所看到的是，患者得到了計劃的批准，他們能夠負擔得起共同支付的費用，因此他們繼續接受付費治療。

So that gives us confidence and then the continued demand that we're seeing in the first half of the first quarter is very consistent to what we saw last year. And so those two things together give us confidence to raise guidance at this point.

這給了我們信心，而且我們在第一季上半年看到的持續需求與去年的情況非常一致。因此，這兩件事讓我們有信心在此時提高指導。

Hey, Charlie, just one more piece on the control with the real-world data that we see, do you really see it when you're controlled on ORLADEYO? Is there a difference in the control versus the therapies on the market are the ones that are coming in the data that we see in the future.

嘿，查理，關於我們看到的真實世界數據的控制，還有一點，當你在 ORLADEYO 上受到控制時，你真的看到它了嗎？從我們未來看到的數據來看，對照組和市面上的療法之間是否有差異？

Not based on what we've seen in our market research. So the patients, -- very few patients across the board regardless of what product you're on are truly attack free. The goal for patients is to have very infrequent attacks, have those attacks be very manageable. So they tend to be more mild on prophylaxis. That's what we're seeing on ORLADEYO. That's what we're seeing on injectable products. And we think it's consistent to what we'll see with future products that reach the market as well.

這並不是基於我們在市場調查中看到的情況。因此，無論患者使用什麼產品，很少有患者能夠真正擺脫疾病的困擾。患者的目標是盡量減少發作頻率，並讓發作變得容易控制。因此他們在預防方面往往採取較為溫和的措施。這就是我們在 ORLADEYO 上看到的。這就是我們在註射產品上看到的。我們認為這與我們未來進入市場的產品的情況一致。

As physicians see that data or they have that experience with their own patients, that's what's driving that excitement about prescribing more of it in the future.

當醫生看到這些數據或他們在自己的病人身上獲得這樣的經驗時，這就是他們在未來開出更多這種藥物的興奮之情的驅動力。

Yes. That's what's exactly. So not only are they saying physicians telling us as of December. That they will prescribe to 17% more of their patients. They expect over 60% of those prescriptions to come from injectable prophylaxis switches. It's because they have confidence in what they're seeing with ORLADEYO.

是的。確實如此。因此，他們不僅說醫生告訴我們截至 12 月的情況。他們將為17%以上的患者開出處方。他們預計其中 60% 以上的處方將來自註射預防藥物。這是因為他們對 ORLADEYO 的表現充滿信心。

So Stacy, I think the bottom line is that there's control with ORLADEYO and any incremental, anybody that's saying that there's incremental control with a future product or a current product really isn't true. It either works or it doesn't work.

所以 Stacy，我認為底線是 ORLADEYO 和任何增量都有控制權，任何人說未來產品或當前產品有增量控制權都是不正確的。它要么有效，要么無效。

Okay, understood. Thank you so much.

好的，明白了。太感謝了。

You're welcome.

不客氣。

Brian Abrahams, RBC Capital Markets.

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

Hey, good morning. Thanks for taking my questions and congrats on all the progress. Two for me, I guess, first on the pediatric study, can you talk about how tolerability compared to the adult experience and maybe just remind us your expectations for the regulatory bar, in the US as you prepare the NDA filing there and then kind of what you're planning for the for international approvals and filings.

嘿，早安。感謝您回答我的問題，並祝賀您取得的所有進展。我想有兩個問題，首先是關於兒科研究，您能否談談與成人體驗相比的耐受性，也許可以提醒我們您對美國監管標準的期望，因為您在美國準備提交 NDA 文件，然後您對國際批准和文件有何計劃。

And then secondly, I guess speaking of international for or the day or commercially in fourth quarter it looks like you saw an uptick in the contribution from Europe. I know that can be variable and sometimes higher in the fourth quarter. And of course we'll need to think about the FX headwind for next year, but where do you see that demand outside the US tracking in 2025. Thanks.

其次，我想就第四季度的國際業務或當日業務或商業業務而言，您似乎看到來自歐洲的貢獻上升。我知道第四季的情況可能會有所變化，有時甚至會更高。當然，我們需要考慮明年的外匯逆風，但您認為 2025 年美國以外的需求將會如何發展。謝謝。

So in pediatrics. So this is the new formulation for pediatrics is oral granules. They are what we know from the study is that those are delivering well. Patients are able to use them easily. We're seeing good exposure levels, which means that they're compliant with receiving them. And we're seeing very good tolerability with the oral granules as well.

在兒科也是如此。這是兒科的新劑型，即口服顆粒。我們從研究中得知，這些措施的成效良好。患者可以輕鬆使用它們。我們看到了良好的曝光水平，這意味著他們願意接受這些內容。我們也發現口服顆粒的耐受性非常好。

It's very similar to what we'd expect in terms of efficacy and safety for the adults and for the adolescents, and so this is a formulation that we're very a -- very pleased with how it's doing in pediatric patients. In terms of the regulatory bar for approval, this is actually a pediatric extrapolation is what it's called it means we're matching safety and exposure for the pediatric population to extend labeling from adults and adolescents down to the younger children.

就對成人和青少年的療效和安全性而言，它與我們預期的非常相似，因此我們對它在兒科患者中的表現非常滿意。就審批的監管標準而言，這實際上是一種兒科推斷，即所謂的兒科推斷，這意味著我們正在為兒科人群匹配安全性和暴露量，將標籤從成人和青少年擴展到年幼的兒童。

That means the primary outcomes are safety and pharmacokinetics. We have that data, and we've already discussed that with regulators in the US. This is a fairly straightforward approach with something called a written request with FDA in Europe. It's under a pediatric investigative plan with EMA.

這意味著主要結果是安全性和藥物動力學。我們擁有這些數據，並且已經與美國監管機構討論過。這是一種相當直接的方法，即向歐洲 FDA 提出書面請求。這是與 EMA 合作的兒科研究計劃。

Both of those are predefined the path to approval in the US and Europe, and we're on track to submit the data that meets those requirements. So we think we're in a really great place with this data set and looking forward to bring this, bringing this to children.

這兩項技術都預先定義了在美國和歐洲獲得批准的途徑，我們正在按計劃提交符合這些要求的資料。因此，我們認為我們擁有這個數據集，並期待將它帶給孩子們。

And we've had convert go ahead. You we had conversations with the Japanese authorities as well. And so we have agreement on what the path forward for that is as well. So we expect that filings will occur in multiple countries either all this year or into the you know early part of next year.

我們已經轉換了前進的方向。我們也與日本當局進行了對話。因此，我們對未來發展方向也達成了一致。因此，我們預計今年全年或明年年初將在多個國家進行申請。

And then maybe as far as ex US demand, I'll cover the demand, and Anthony, can talk about kind of the cadence of the revenue. What we're seeing in Europe, in Canada, and Japan is the same type of growing confidence in ORLADEYO that we're seeing in the US.

然後也許就美國以外地區的需求而言，我會介紹需求，安東尼可以談談收入的節奏。我們在歐洲、加拿大和日本看到的對 ORLADEYO 的信心增長與我們在美國看到的一樣。

Different markets are at a different place depending on where the launch was. So if for example, we're seeing really transformative confidence with ORLADEYO in the United Kingdom, which has been on the market for several years now. We're seeing great early confidence in Italy that just launched last year as examples, but what they're seeing is ORLADEYO is a really effective drug

根據產品的發布地點不同，不同的市場處於不同的位置。舉例來說，我們看到英國市場對 ORLADEYO 的信心發生了真正的轉變，該產品已在市場上銷售了好幾年。我們看到義大利對去年剛上市的藥物表現出了極大的信心，但他們看到的是 ORLADEYO 是一種非常有效的藥物

And we're also very excited in Europe. That countries that historically have used more androgen steroids are going away from that. And patients are being switched over new patients are not being prescribed androgens anymore. And so I think we're still seeing a transformation of how prophylaxis is understood around the world and ORLADEYO playing a big part of that.

我們對歐洲也感到非常興奮。歷史上使用較多雄性激素類固醇的國家正逐漸放棄使用這種藥物。且患者被轉換了，新患者不再被開立雄性激素藥。因此，我認為我們仍然看到世界各地對預防治療的理解正在轉變，而 ORLADEYO 在其中發揮了重要作用。

Specifically, as it relates to Q4

具體來說，與第四季相關

Yes. So the percentage for Q4 ex US was higher than the total for the year, so 13.9% versus what, 11.8% for a full year. Some of the drivers are, yeah, Europe, it helps in that regard, but also some of the Q4 dynamics, distributors that we have, whether it's, in Latin America, whether it's in Eastern Europe, whether it's in the Middle East, some of their annual distribution shipments go out in that Q4 time period.

是的。因此，第四季（美國除外）的百分比高於全年的百分比，即 13.9%，而全年的百分比為 11.8%。其中一些驅動因素是歐洲，它在這方面有所幫助，但也有一些第四季度的動態，我們擁有的分銷商，無論是在拉丁美洲，還是在東歐，還是在中東，他們的一些年度分銷出貨量都在第四季度期間發出。

So that that can be a small driver. The other one is we renegotiated and kind of refocused on the Japan side of the house. In the year we were able to renegotiate a revised term around flipping the economics for performance over a certain number. We achieved that number in Q4 and we're able to get a higher share therefore of the licensing revenue for that territory.

這樣就可以成為一個小小的驅動力。另一個是我們重新談判並重新關注日本方面。今年，我們能夠重新協商修改條款，圍繞在一定數量上扭轉經濟表現。我們在第四季度實現了這一數字，因此我們能夠在該地區獲得更高的許可收入份額。

In terms of how that plays out into 2025, listen, for Q1, we'll probably get to the point where, flat to lower, on the total revenue for the rest of the year, the same dynamic would play out, including this Q4 dynamic that I just described. In terms of the percentage of ex-US compared to the total for ORLADEYO.

至於到 2025 年將如何發展，聽著，對於第一季度，我們可能會達到這樣的一個水平：在今年剩餘時間的總收入中，持平或下降，同樣的動態將會出現，包括我剛才描述的第四季度的動態。就美國以外地區佔奧拉迪約 (ORLADEYO) 總數的百分比而言。

This year might be a little bit different. We, we'd normally say that you'd get about a percentage increase or uptick on your way to that 20%. With the significant increase that we're seeing here in the US. That might be slightly deflated, but that has nothing to do with the continued growth that we would expect to see ex-US. It's just the counterpoint of the significant strength that we'll see on the US side.

今年可能會有些不同。我們通常會說，在達到 20% 的過程中，您會獲得大約百分比的成長或上升。我們在美國看到了顯著的成長。這可能略有下降，但這與我們預期美國以外地區持續成長無關。這只是我們將在美國方面看到的強大實力的對比。

That's super, helpful. Thanks so much.

這太有幫助了。非常感謝。

Hey Brian, just one more to the tolerability, the retention rate in the pediatric study, I can't remember the exact numbers, but it was pretty high.

嘿，布萊恩，關於耐受性，我再問一個問題，兒科研究中的保留率，我不記得確切的數字，但它相當高。

There was 25 patients out of 29 who stayed on drug also using that formulation and having the effect that they a lot of.

29 名繼續服用該藥物的患者中，有 25 名也使用該配方，並獲得了顯著的效果。

Times that can reflect some of the tolerability, Brian.

時代可以反映出一些容忍度，布萊恩。

Got it. That's really helpful. Thank you.

知道了。這真的很有幫助。謝謝。

Gena Wang, Barclays Capital Inc.

Gena Wang，巴克萊資本公司

Thank you for taking my questions. I have one also regarding ORLADEYO, so maybe like, you did mention the Medicare patient, the benefit from the low copay. Can you share with us what percentage of patients or Medicare patients? And I assume those Medicare patients in 2024 Q24, paid, percentage is 73.5%. And you are expecting this will go up, right?

感謝您回答我的問題。我還有一個關於奧拉迪約 (ORLADEYO) 的問題，所以也許就像您提到的那樣，醫療保險患者從低自付費用中受益。您能否與我們分享病患或醫療保險病患的百分比？我假設 2024 年 Q24 的醫療保險患者付費比例為 73.5%。您預計這個數字會上升，對嗎？

And the second question is regarding the Netherton Syndrome, and you did mention that it would start with healthy volunteer and then switch to patient. So maybe can you give us a little bit more color regarding what kind of how many dose escalation you were tested in a healthy volunteer. And what KLK5 activity you'll be looking for to switch to patient and can you give us the benchmark of what are you looking for regarding the KLK5 activity?

第二個問題是關於 Netherton 綜合症的，您確實提到過，研究會從健康的志願者開始，然後轉移到患者身上。那麼，您能否向我們提供更多詳細信息，說明您在健康志願者身上進行了多少劑量遞增的測試。您希望尋找哪種 KLK5 活性來轉換到患者身上，您能否給我們關於 KLK5 活性您所尋找的基準？

Hey Gena, I'll take the question about Medicare. Medicare is about 20% of the patients on ORLADEYO are covered by Medicare. The 73.5% paid rate was across our entire book of business. In Medicare, it was actually lower. So we finished last year at about a 55%, 56% paid rate. Historically, the Medicare plans tend to say yes, that they will cover ORLADEYO at 80% or more.

嘿，吉娜，我來回答有關醫療保險的問題。奧拉迪約 (ORLADEYO) 約有 20% 的患者享有醫療保險。我們整個業務的支付率達到 73.5%。在醫療保險方面，這一比例實際上更低。因此，我們去年的支付率約為 55% 至 56%。從歷史上看，醫療保險計劃往往會回答“是”，即覆蓋奧拉迪約 80% 或更多。

The problem has just been the affordability. And so what we're seeing in Q1 is the plans are still saying yes. The affordability seems to be there for the patients. And so they're able to move to pay therapy. And this is a big part getting that that proportion of our Medicare patients over to paid therapy is a big part of our path to 85% paid over the long-term, which represents by 2029 that that will represent about $100 million in increased revenue towards our $800 million future view of revenue in the US.

問題只是在於能否負擔得起。因此，我們在第一季看到計劃仍然順利進行。患者似乎能夠負擔得起。這樣他們就能支付治療費用了。讓這部分醫療保險患者接受付費治療是實現長期付費率達到 85% 的重要途徑，這意味著到 2029 年，這將為美國帶來約 1 億美元的收入成長，而我們未來在美國的收入目標是 8 億美元。

So what Seeing is this year that may be accelerating a bit and we'll know the final answer after the reauthorization season is complete.

因此，今年的情況可能會加速，我們將在重新授權季節結束後知道最終答案。

And Helen, maybe just describe the design of going from sad to mad to then patience and the differences between what you can see in healthy versus what you can see in patients.

海倫，也許你只是描述一下從悲傷到瘋狂再到耐心的設計，以及你在健康人和病人身上看到的差異。

So Netherton Syndrome, Gena, we are in a Phase 1 study that Phase 1 is in healthy volunteers and will include patients. In healthy volunteers we're doing single ascending dose. We will proceed also with multiple ascending dose. And what we're looking for there is simple safety and pharmacokinetics exposure levels so that we can identify a dose that is likely to have activity and goes to patients from there.

因此，對於 Netherton 綜合徵，Gena，我們目前處於第一階段研究，第一階段是在健康志願者中進行的，並將包括患者。對於健康志願者，我們進行單次遞增劑量。我們也將繼續進行多次遞增劑量。我們正在尋找簡單的安全性和藥物動力學暴露水平，以便我們能夠確定可能具有活性的劑量並從那裡提供給患者。

We would expect to include patients in the study while continuing with the dose escalation in healthy volunteers. So it's not in serious and dependent on that. And there's an interesting aspect of this disease, which is that KLK5 activity is normal in healthy volunteers, which means we can't really look for activity there, and we want to get to patients as quickly as possible.

我們希望將患者納入研究，同時繼續在健康志願者中增加劑量。因此，這並不嚴重，也不依賴於此。這種疾病有一個有趣的方面，那就是 KLK5 活性在健康志願者中是正常的，這意味著我們無法真正在那裡尋找活動，我們希望盡快找到患者。

That's why we've built the patient portion straight into the phase 1 study. That's why we're dose escalating sort of quickly healthy volunteers to get to the likely effective dose range. And then we're moving to patients within that study so that we can look at the activity of the drug in the skin where KLK5 activity is abnormal and look at whether the drug is inhibiting KLK5 activity at the dose levels there.

這就是我們將患者部分直接納入第一階段研究的原因。這就是為什麼我們要快速增加健康志願者的劑量以達到可能有效的劑量範圍。然後，我們將研究對象轉移到該研究中的患者，以便我們可以觀察藥物在 KLK5 活性異常的皮膚中的活性，並觀察藥物是否在那裡的劑量水平抑制 KLK5 活性。

And so we'll be looking at a range of doses, but we're expecting to be in an effective range in patients. And we'll be looking for that suppression of KLK5 activity to give us confidence that the drug's having the effect and to extend dosing then in those patients to assess for the healing we were talking about earlier in the call.

因此，我們將研究一系列劑量，但我們預期該劑量對患者有效。我們將尋找 KLK5 活性的抑制，以使我們相信該藥物具有效果，然後延長這些患者的用藥時間，以評估我們在早期的通話中談到的治療效果。

What percentage of the suppression you would think in KLK5 suppression that will lead to the clinical benefit.

您認為 KLK5 抑制中多大的百分比會帶來臨床益處。

So short answer, that's not known. But what we're looking for is this drug is very potent and we're talking about, it has this stickiness, this high affinity. What we're looking for is suppression. So that's nearly complete suppression of KLK5.

簡而言之，這是未知的。但我們正在尋找的是一種非常有效的藥物，它具有這種黏性，這種高親和力。我們所尋求的是壓制。所以這幾乎完全抑制了 KLK5。

And as we learn more about what's, whether that's actually required for healing activity, we'll learn more later on in the program, but in the near term we're looking for complete suppression of KLK5.

隨著我們更多地了解這是否真的是治療活動所必需的，我們將在以後的計劃中了解更多信息，但在短期內，我們尋求完全抑制 KLK5。

Okay thank you.

好的，謝謝。

Jonathan Wolleben, JMP Securities.

喬納森·沃勒本，JMP 證券。

Hey, good morning. Thanks for taking the questions. Just a couple for me, Charlie, wondering if you could talk a little bit about the historical reauthorization rates and what you guys have seen prior, first quarters and how it's tracking so far this year.

嘿，早安。感謝您回答這些問題。查理，我只想問幾個問題，想知道您是否可以談談歷史重新授權率以及之前第一季的情況，以及今年迄今為止的走勢如何。

And then for the pediatric opportunity wondering if you guys have thrown that in your market model what we should think about that opportunity if that's included in kind of your projections that you have on slide 12, in your deck.

然後，對於兒科機會，想知道你們是否已經將其納入了市場模型，如果將其包含在你們第 12 張幻燈片中的預測中，我們應該如何看待這個機會。

Sure, thanks, John. As far as the reauthorization, what we see is roughly half of our patients across all payers go through reauthorization in the first quarter. And it, -- but it's really more than just the first quarter. It tends to drift into the early part of the second quarter that's what we saw last year.

當然，謝謝，約翰。就重新授權而言，我們看到，所有付款人中大約有一半的患者在第一季經歷了重新授權。但實際上不僅僅是第一季。它往往會持續到第二季​​初，就像我們去年看到的那樣。

And so when I said earlier, we're right in the middle of it, it's because we are, we're right in the middle of it now. The last, as I've talked about previously, the last few years, our team has done a tremendous amount of work to be ready for this reauthorization. Every year we think we get better at it based on what we learned from the previous year.

所以當我之前說我們正處於其中時，那是因為我們現在正處於其中。最後，正如我之前提到的，過去幾年，我們的團隊為這次重新授權做了大量準備。每年我們都認為自己會根據前一年所學到的知識而做得更好。

And so I'm pleased with what we see so far, but we won't know the final results until we get through everything. As far as the pes opportunity, it is not baked into our billion dollars dollar peak global revenue forecast. At some point, particularly, obviously when we get the approval, we'll probably build that in. But what we have said is in the United States there are about 500 patients that we believe are under age 12 and diagnosed with HAE.

我對目前所看到的情況感到滿意，但只有完成所有工作後我們才能知道最終結果。就 PES 機會而言，它並未被納入我們十億美元的全球高峰收入預測中。在某個時候，特別是當我們獲得批准時，我們可能會將其納入其中。但我們所說的是，在美國，我們認為大約有 500 名年齡在 12 歲以下並被診斷出患有 HAE 的患者。

Historically we thought maybe 40% of them, 200 or so, were appropriate for a prophylaxis therapy based on what Helen, was describing earlier and the young age that we saw, the patients in our trial. The young age when they first had their attacks, we're rethinking this. We think that there may be more of an opportunity within that within that under age 12 population.

從歷史上看，根據海倫先前的描述以及我們在試驗中看到的患者年齡較小，我們認為其中約 40%（200 例左右）適合接受預防性治療。他們第一次發作時的年齡很小，我們正在重新思考這個問題。我們認為，12 歲以下的人口中可能有更多機會。

And again, we think ORLADEYO as an oral drug is going to be transformative for these kids. So we expect a lot of changes in how Kids with HAE are treated in the future.

而且，我們認為 ORLADEYO 作為一種口服藥物將會改變這些孩子的生活。因此，我們預期未來 HAE 兒童的治療方式將會發生很大變化。

And Charlie, is it safe to say that even with the increase in guidance and the tailwind that we're getting with free drug to pay drug that the first quarter dynamics still exist. There's still free drugs that were given to people going through [Riyadh] and there's still, as you said before, gross to net issues, so flat to slightly down?

查理，可以肯定地說，即使指導增加，並且我們獲得了免費藥物對付費藥物的順風，第一季的動態仍然存在。經過 [利雅德] 的人仍然可以免費獲得藥物，而且正如您之前所說，總額與淨額之間仍然存在問題，所以持平或略有下降？

Flat slightly down for Q1 just because of all of that, regardless of how well we do, that is a dynamic that we cannot defeat.

由於所有這些原因，第一季的業績略有下滑，無論我們做得多好，這都是我們無法戰勝的動力。

And Charlie, maybe just one quick follow up. What, -- how do you categorize a pediatric patient as appropriate for prophylactic therapy?

查理，也許我只想快速跟進。什麼－您如何將兒科病患歸類為適合預防性治療？

Well, that's John. I think that it's a great question. And I think that's what we're going to see changing over time. I think historically physician HAE treaters have not seen as many kids with attacks because they really didn't have options for treating them. Now they have some injectable options, which is great.

嗯，那是約翰。我認為這是一個很好的問題。我認為隨著時間的推移我們將會看到這種變化。我認為，從歷史上看，治療 HAE 的醫生並沒有見過那麼多患有此病的兒童，因為他們確實沒有其他治療方法。現在他們有一些可注射的選擇，這很好。

But what it led to is families just coping, physicians coping with this and treating kids acutely, but that puts a huge burden on the kids and the families. And so with an available oral therapy, we think it's going to have physicians, parents, obviously the kids rethink how to treat HAE.

但它導致的是家庭只能應對，醫生只能應對並對孩子進行緊急治療，但這給孩子和家庭帶來了巨大的負擔。因此，我們認為，有了口服療法，醫生、家長，當然還有孩子們都會重新思考如何治療 HAE。

And it could create an opportunity where kids grow up rarely having attacks, which could really change the trajectory of their whole childhood, their whole life, their whole relationship with HAE. So we're really excited about working with the community to make that happen for kids.

這可能會創造一個機會，讓孩子在成長過程中很少受到攻擊，這可能會真正改變他們的整個童年、整個生活以及他們與 HAE 的整個關係的軌跡。因此，我們非常高興能夠與社區合作，為孩子們實現這一目標。

I think too when we saw this data, I think we, many of us were surprised at how sick and how early kids got sick with this disease. That changes our view of the market a bit that there are younger kids that really need this drug and so that could increase the opportunity so.

我也認為，當我們看到這些數據時，我們中的許多人都對孩子們患上這種疾病的程度和時間之早感到驚訝。這稍微改變了我們對市場的看法，即確實有更年幼的孩子需要這種藥物，因此這可能會增加機會。

Thanks, for the call guys.

謝謝你們的來電。

Seema Sheoran, Evercore ISI.

Seema Sheoran，Evercore ISI。

Hi, this is Seema, on to Lisa. I have a question on what that in DME. What's the target product profile for this drug and what should we be looking for in patient data to start to data asset towards this, target product profile. Thank you.

嗨，我是 Seema，接下來是 Lisa。我對 DME 中的內容有疑問。這種藥物的目標產品概況是什麼，我們應該在患者數據中尋找什麼來開始針對該藥物的目標產品概況進行數據資產。謝謝。

Charlie, you want to take that?

查理，你想拿走那個嗎？

Oh sure, then maybe you know Helen, can comment on some of this too. The TPP we're looking at for a oral stat for patients with DME, physicians are looking for other options. They're looking for other therapies because over 50% or -- close to 50% of patients don't respond fully to be inhibitors. So what we're looking for is, an infrequent injection that helps prevent leakage. So this could be every three months, it could be every six months, which could greatly reduce the burden of injections and improve efficacy for many patients. Was there a follow up?

哦，當然，那麼也許你認識海倫，也可以對此發表評論。我們正在研究 TPP 作為 DME 患者的口腔統計指標，醫生正在尋找其他選擇。他們正在尋找其他療法，因為超過 50% 或接近 50% 的患者對抑制劑沒有完全反應。因此，我們正在尋找一種有助於防止洩漏的不頻繁注射方法。因此，可以每三個月進行一次，也可以每六個月進行一次，這可以大大減輕注射負擔並提高許多患者的療效。有後續行動嗎？

Just need to, can you speak about the Phase 1, what's the design, what should we look for? And then moving into patients.

只是需要，您能談談第一階段嗎，設計是什麼，我們該尋找什麼？然後轉向患者。

We're going directly into patients, and I'll let Helen described that.

我們將直接面對病人，我會讓海倫描述這一點。

Yes. So this is a program that will actually go straight to patients first. So Phase 1 will be in patients, and it'll be using the injection [supercardal] injection for stat in the suspension. In order to observe safety in patients, tolerability locally in the eye, but also with that injection to observe in individual patients right from the first patient we dosed to see if there is a change in the Edema in the eye.

是的。因此這是一個實際上首先直接面向患者的項目。因此，第一階段將在患者身上進行，並將使用注射劑 [supercardal] 注射液來治療懸浮液中的 stat。為了觀察患者的安全性、眼睛局部的耐受性，同時也要從第一個患者開始就對個別患者進行注射觀察，看看眼睛水腫是否有變化。

And then longer term a change in visual acuity. So the first study will be, exploratory looking at using that injection and then and then assessing just one injection, assessing over time again sort of over four weeks, eight weeks, twelve weeks, sixteen weeks with this to observe for the Edema. In the eye and observe for any changes in the Edema.

然後長期來看視力會改變。因此，第一項研究將是探索性地觀察使用該注射劑，然後僅評估一次注射，並在四周、八週、十二週、十六週的時間內再次進行評估，以觀察水腫。觀察眼睛是否有水腫變化。

Once we have confidence that we've got a dose, we're seeing that the changes that we want to see, then we would move to a randomized program, probably randomized Phase 2, to assess this in a controlled manner for the pivotal program planning.

一旦我們確信我們已經獲得了劑量，我們就會看到我們想要看到的變化，然後我們將轉向一個隨機程序，可能是隨機的第 2 階段，以受控的方式評估關鍵程序規劃。

Helen, is it fair to say that this is an unusual setting where a sad and mad study could tell you a lot? Because you're in.

海倫，是否可以說這是一個不尋常的環境，一個悲傷而瘋狂的研究可以告訴你很多？因為你在。

Yes, right. So with the oral stat, we know, we already know a lot about the systemic safety of the drug because we've tested it in a Phase 3 with our oral program some time ago. Now we're at a point where we're just looking at the from a safety perspective, the local tolerability. And because this drug is potent and the suspension has a depot-like effect we think one dose could be sufficient to see that effect in each patient.

是的，對。因此，根據口服統計數據，我們已經對該藥物的系統性安全性有了充分的了解，因為我們不久前已經使用口服藥物計劃進行了第 3 階段的測試。現在我們只是從安全角度考慮當地的耐受性。由於這種藥物效力強，而且其混懸液具有類似儲庫的效果，我們認為一次劑量就足以在每位患者身上看到這種效果。

That puts us in a position to have, first, second, third patients and the very first patients we put on the trial to the ones who we observe with that one dose, observe over a number of months to see how they do.

這樣，我們就可以擁有第一位、第二位、第三位患者，以及參加試驗的第一批患者，我們會對這些患者用同一劑量進行觀察，觀察數月，看看他們的表現如何。

That's very helpful thank you.

這非常有幫助，謝謝。

Serge Belanger, Needham & Co

貝朗格（Serge Belanger），Needham & Co

Hi, good morning. A couple of questions for Charlie on [Erlich Dale]. First one, can you tell us how many patients were on drugs at your end and how that number compares to year end 2023? And then secondly, regarding the positive impacts you've seen from the, from IRA so far, you've highlighted the expected improvements in paid rates, but do you also expect it could help improve volumes in the form of new patient ads.

嗨，早安。向 Charlie 提幾個問題[埃利希·戴爾]首先，您能告訴我們有多少患者在服用藥物嗎？與 2023 年底相比，這個數字如何？其次，關於您迄今為止從 IRA 中看到的積極影響，您強調了預期的付費率提高，但您是否也預計它可以幫助提高新患者廣告的數量。

Thanks, Serge. I haven't commented specifically on the number of patients. What we have said, as before, is that in that path to a billion dollars, the path to $800 million in the US, we need to average 200 patients through 2029. We were well above that in 2023. We said in the early years we would expect to be above that. We were well above that number again in 2024.

謝謝，塞爾吉。我沒有具體評論患者的數量。正如我們之前所說的，為了達到 10 億美元，即在美國達到 8 億美元的目標，到 2029 年我們需要平均接待 200 名患者。2023 年我們的目標已經遠高於這個數字。我們早年就說過，我們期望達到更高的水準。到 2024 年，我們的數字將再次遠高於這個數字。

So we are well on our path to what we laid out in that $800 million to the US. And then the demand that I described today, there's no sign that the opportunity is slowing down or running out in any way. As far as I think the other part of your question was on the Medicare paid rate and whether that could have a positive impact in prescribing, I think it's a possibility. It's a good question.

因此，我們正順利實現向美國提供的 8 億美元貸款目標。然後，就我今天所描述的需求而言，沒有任何跡象表明機會正在放緩或消失。至於我認為您的問題的另一部分是關於醫療保險支付率以及這是否會對處方產生積極影響，我認為這是可能的。這是個好問題。

I don't think we've seen that yet, but for patients and for physicians, getting to paid therapy gives them confidence. Knowing that their payer will pay for this drug gives them more confidence about prescribing and we've known that since before the launch. We've always done everything that we can to remove that that paid rate paid of therapy, insurance approval, remove that as a fear for patients and doctors, but it's always there. And so seeing more patients get to paid therapy, I think generally gives confidence and can't help but have a positive impact over time.

我認為我們還沒有看到這種情況，但對於患者和醫生來說，獲得付費治療可以給他們信心。知道他們的付款人將支付這種藥物的費用使他們對開處方更有信心，我們在藥物上市之前就知道這一點。我們一直竭盡所能消除治療費用、保險批准等對患者和醫生的恐懼，但它始終存在。因此，看到越來越多的患者接受付費治療，我認為這通常會增強信心，並且隨著時間的推移會產生積極的影響。

And I think something that's really important that maybe isn't obvious is the machinery that Charlie has built and the team that Charlie has built to make that go smoothly is a real competitive advantage. I think in terms of just it's taken stress away from doctors. I mean, Charlie and I heard from a doctor recently about how our empowered patient services is like a model for other, drugs even outside of HAE. And that that took time to build, that took investment, and I think his team is really good at it.

我認為真正重要但可能不明顯的一點是查理所建立的機器以及查理為使機器順利運轉而組建的團隊是真正的競爭優勢。我認為它確實減輕了醫生的壓力。我的意思是，查理和我最近從一位醫生那裡聽說，我們的授權病患服務就像是其他藥物甚至 HAE 之外的典範。這需要時間來構建，需要投資，我認為他的團隊在這方面非常擅長。

I agree and a shout out to the team because again they are right in the middle of what we call the blizzard season a because it's cold, and because there's a lot of work to do. So they're working super hard to help as many patients as possible.

我同意，並向團隊致敬，因為他們正處於我們所說的暴風雪季節，天氣很冷，而且有很多工作要做。因此他們非常努力地幫助盡可能多的患者。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特（Maury Raycroft），傑富瑞集團（Jefferies）。

Hi, good morning, congrats on the progress and thanks for taking my questions. You talked about Netherton being underdiagnosed. What is BioCryst doing or planning to do to help find these patients and get them on the radar for your clinical study program and to help set up the commercial opportunity.

你好，早安，恭喜你取得進展，謝謝你回答我的問題。您談到了 Netherton 的診斷不足。BioCryst 正在做什麼或計劃做什麼來幫助找到這些患者並讓他們進入您的臨床研究計劃的視野並幫助建立商業機會。

Sure, you want to start how we're thinking about how we identify patients and what we plan to put in place.

當然，您想開始思考如何識別患者以及我們計劃採取什麼措施。

Yes. And Maury, Helen alluded to some of this in her comments. This bamboo hair is a distinctive feature of that that patients with Netherton have. There is no diagnosis code for Netherton Syndrome but most of these patients do have this bamboo hair. We did a claim study that helped us identify about 600 patients with this bamboo hair feature.

是的。莫里，海倫在她的評論中提到了其中的一些內容。這種竹狀頭髮是 Netherton 患者的顯著特徵。內瑟頓症候群沒有診斷代碼，但大多數患者都有這種竹狀頭髮。我們進行了一項索賠研究，幫助我們識別出大約 600 名具有這種竹發特徵的患者。

And so part of our plan is to expand on that. And as we're getting into the clinical trials here, make sure we're working to find more sites where these patients are treated. There's some a small handful of real expert centers at this point. But most of these patients, as Helen was saying, are probably lost a little bit in the broader dermatology practice, potentially misdiagnosed with general [icosis]. And so as we move into this next Phase of trials, we expect to start doing more to educate the market about the need for this and the different the -- differential diagnosis for these patients.

因此，我們的計劃的一部分是擴大這一點。當我們進入臨床試驗時，請確保我們正在努力尋找更多可以為這些患者提供治療的地點。目前，有少數真正的專家中心。但正如海倫所說，這些病人中的大多數可能在更廣泛的皮膚病學實踐中迷失了方向，可能被誤診為一般[異物感]。因此，當我們進入下一階段的試驗時，我們希望開始做更多的工作來教育市場了解這種療法的必要性以及針對這些患者的不同鑑別診斷。

And there's some great playbooks on. These rare diseases where there was no drug and no diagnostic code and how did you find the patients and I think one of the beauties here is the genetic test. And what we do with that genetic test and how do we implement that playbook to start and when you have a therapy that has, we're hoping for a real significant treatment effect, those two things in combination, you start to really be able to find patients.

還有一些很棒的劇本。這些罕見疾病沒有藥物，也沒有診斷代碼，你是如何找到病人的？我認為這裡最美妙的事情之一就是基因測試。我們如何進行基因測試以及如何實施劇本，當您擁有一種我們希望獲得真正顯著治療效果的治療方法時，將這兩件事結合起來，您就能真正開始找到患者。

So we'll I don't think we have to recreate anything here. There are playbooks for this stuff that we can follow that will help us build that over time.

所以我認為我們不必在這裡重新創建任何東西。我們可以遵循針對這些事情的劇本，這將幫助我們隨著時間的推移建立這些劇本。

And I'll add just one piece, one part of that playbook is to engage very closely with the patient community, and we've started doing that with the Netherton's community and the patient voice in all of this is in rare diseases becomes really important. And so we'll do what we can to work with them and our early interactions with them has been very positive.

我只想補充一點，該劇本的一部分是與患者社區密切接觸，我們已經開始與 Netherton 社區進行這樣的接觸，在所有這些罕見疾病中，患者的聲音變得非常重要。因此，我們將盡我們所能與他們合作，我們與他們的早期互動非常積極。

Got it. That's helpful. And maybe one quick second question just for the ORLADEYO pediatric formulation, do you plan to price that differently than the adult version?

知道了。這很有幫助。也許我只想問一下 ORLADEYO 兒科配方，你們計劃將其定價為與成人版不同的價格嗎？

We haven't made any final decisions on that, but in most markets, probably not. It would probably be comparable, but that'll be a decision that we make as we get closer to launch.

我們尚未就此做出任何最終決定，但在大多數市場，可能不會。這可能是可以比較的，但這將是我們在接近發佈時做出的決定。

Got it. Okay, thanks for taking my questions.

知道了。好的，感謝您回答我的問題。

Thanks, Maury.

謝謝，莫里。

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

我們的問答環節到此結束。我想將會議交還給喬恩·斯通豪斯 (Jon Stonehouse) 做最後演講。

Thank you. So as I said at the beginning, 2024 was one of the best years in the company's history in terms of performance and execution, and the evidence for that is the strong continued growth in ORLADEYO on its path to a billion dollars programs now advancing and getting to the point where they're going into the clinic and then our path to profitability.

謝謝。因此，正如我在一開始所說的那樣，2024 年是公司歷史上業績和執行力最好的年份之一，而 ORLADEYO 在邁向 10 億美元項目的道路上持續強勁增長就是證據，這些項目目前正在推進並進入臨床階段，然後走向盈利。

So there's no letting up going into this year. We've got a lot of momentum, we're off to a strong start as you can see by the raising of our guidance, and we're really excited to continue to update you over the course of this year. Thank you.

所以今年我們不會放鬆。我們擁有強大的發展勢頭，正如您從我們提高的指導意見中看到的那樣，我們開局良好，我們非常高興能夠在今年繼續向您通報最新情況。謝謝。

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

會議現已結束。感謝您參加今天的演講。您現在可以斷開連線。