BioCryst Pharmaceuticals Inc (BCRX) 2024 Q2 法說會逐字稿

Good day, and welcome to the BioCryst second quarter 2024 earnings call. (Operator Instructions) Please note this event is being recorded. I would now like to turn the conference over to John Bluth at BioCryst. Please go ahead.

美好的一天，歡迎參加 BioCryst 2024 年第二季財報電話會議。 （操作員說明）請注意此事件正在被記錄。我現在想把會議交給 BioCryst 的 John Bluth。請繼續。

Thanks, Dave. Good morning, and welcome to BioCryst's second quarter 2024 corporate and financial results conference call. Today's press release and accompanying slides which we'll be referring to, 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，戴夫。早安，歡迎參加 BioCryst 2024 年第二季企業與財務績效電話會議。今天的新聞稿和我們將要提到的隨附幻燈片可在我們的網站上找到。今天和我一起參加的是執行長喬恩‧斯通豪斯 (Jon Stonehouse)；財務長安東尼·道爾；首席商務官 Charlie Gayer 和首席研發官 Helen Thackray 博士。在我們的發言之後，我們將回答您的問題。

Today's conference call will contain forward-looking statements, including those statements regarding future results, unaudited and forward-looking financial information as well as the company's future performance and/or achievements. These statements are subject to known and unknown risks and uncertainties, which may cause our actual results, performance or achievements to be materially different from any future results or performance expressed or implied in this presentation. You should not place undue reliance on these forward-looking statements.

今天的電話會議將包含前瞻性聲明，包括有關未來業績、未經審計和前瞻性財務資訊以及公司未來業績和/或成就的聲明。這些陳述受到已知和未知的風險和不確定性的影響，這可能導致我們的實際結果、業績或成就與本簡報中明示或暗示的任何未來結果或業績存在重大差異。您不應過度依賴這些前瞻性陳述。

For additional information, including a detailed discussion of our risk factors, please refer to the company's documents filed with the Securities and Exchange Commission, which can be accessed on our website. In addition, today's conference call includes non-GAAP pro forma financial measures. For a reconciliation of these non-GAAP measures against the most directly comparable GAAP financial measure, please refer to the earnings press release posted in the Press Releases section of our Investor Relations website at www.biocryst.com. I'd now like to turn the call over to Jon Stonehouse.

如需了解更多信息，包括對我們風險因素的詳細討論，請參閱公司向美國證券交易委員會提交的文件，這些文件可在我們的網站上訪問。此外，今天的電話會議還包括非公認會計準則預計財務指標。有關這些非 GAAP 指標與最直接可比較的 GAAP 財務指標的調節，請參閱我們投資者關係網站 www.biocryst.com 的新聞稿部分中發布的收益新聞稿。我現在想把電話轉給喬恩·斯通豪斯。

Thanks, John. Our second-quarter performance with ORLADEYO is nothing short of amazing, especially when you recall great start we had in the first quarter. This performance is due to the confidence we are seeing from our customers since late last year and that continues to build. Physicians who treat HAE in many of their patients are experiencing firsthand how well ORLADEYO works and that they can achieve this control with an oral once-daily therapy, efficacy and convenience.

謝謝，約翰。我們第二季與奧拉德約的表現簡直令人驚嘆，尤其是當你回想起我們在第一季的良好開局時。這項業績歸功於我們自去年底以來客戶對我們的信心，而這種信心仍在持續增強中。治療許多患者 HAE 的醫生正在親身體驗 ORLADEYO 的效果如何，他們可以透過每天一次的口服治療、功效和便利性來實現這種控制。

Many patients are experiencing efficacy similar to what they had on injectable therapy. As a result, halfway through the fourth year since approval, we are experiencing demand as strong as the start of the launch. Amazing. This confidence has also led us to increase our guidance for the year to between $420 million and $435 million. Charlie will provide more details on the quarter and share why the evidence is increasingly clear, we are on a path to $1 billion at peak.

許多患者的療效與注射療法相似。因此，自批准以來已進入第四年，我們的需求與發布之初一樣強勁。驚人的。這種信心也促使我們將今年的指導值提高到 4.2 億美元至 4.35 億美元之間。 Charlie 將提供有關本季度的更多詳細信息，並分享為什麼證據越來越清晰，我們正走在 10 億美元峰值的道路上。

I'd also like to give you an update on our pipeline. Remember, our goal with investment is to bring to market our next meaningful therapy to patients living with rare diseases like we did with ORLADEYO. We continue to make great progress overall advancing our programs.

我還想向您介紹我們管道的最新情況。請記住，我們的投資目標是將我們的下一個有意義的療法推向市場，為患有罕見疾病的患者提供治療，就像我們對 ORLADEYO 所做的那樣。我們繼續在全面推進我們的計劃方面取得巨大進展。

First, we remain on track to file for approval in younger children down to two years of age with the oral granule formulation of ORLADEYO next year. This is a very important patient population whose parents have been waiting for this therapy. Think about it. If your child is having HAE attacks, the only current treatment is injecting them. Any parent knows how dramatic that is. So to bring a therapy they can sprinkle in a glass of water on soft food is a game changer for these families. We are wrapping up the trial and preparation is in full gear for this filing and launch.

首先，我們仍有望在明年申請批准 ORLADEYO 口服顆粒製劑用於兩歲以下的兒童。這是一個非常重要的患者群體，他們的父母一直在等待這種療法。想一想。如果您的孩子患有 HAE 發作，目前唯一的治療方法是注射。任何父母都知道這是多麼戲劇化。因此，他們可以在軟性食物上撒上一杯水來進行治療，這對這些家庭來說是一個遊戲規則的改變者。我們正在結束試驗，並為此次備案和發布做好充分準備。

Next, I'd like to update you on BCX10013, our oral Factor D inhibitor. We have shared data from the PNH dose-ranging clinical trial with potential partners. There were no [sales]. The drug has been safe and well tolerated at all doses studied. However, while we are seeing some activity in PNH patients, the effect seen was less than other therapies on the market.

接下來，我想向您介紹我們的口服 D 因子抑制劑 BCX10013 的最新情況。我們已與潛在合作夥伴分享 PNH 劑量範圍臨床試驗的數據。沒有[銷售]。該藥物在所有研究劑量下都是安全且耐受性良好的。然而，雖然我們在 PNH 患者中看到了一些活性，但效果低於市面上的其他療法。

As a reminder, early this year, we announced that we had planned to stop spending on the program and reduce staff accordingly, while seeking a potential partner. Potential partners have declined to make the additional investment required to evaluate higher doses. Therefore, we will now discontinue development consistent with the plan we described in January.

提醒一下，今年年初，我們宣布計劃停止該專案的支出並相應減少員工，同時尋找潛在的合作夥伴。潛在的合作夥伴拒絕進行評估更高劑量所需的額外投資。因此，我們現在將按照我們一月份描述的計劃停止開發。

Regarding the rest of the pipeline, we have two exciting new molecules moving towards the clinic. We remain on track to start dosing healthy volunteers this year with our KLK5 inhibitor BCX17725 for patients living with Netherton syndrome.

至於其餘的產品線，我們有兩種令人興奮的新分子正在走向臨床。我們仍有望在今年開始為健康志願者服用 KLK5 抑制劑 BCX17725，治療 Netherton 症候群患者。

We are also on track to begin dose-ranging patients in our DME clinical trial next year with the avoralstat. This will likely give us data in patients in both programs by next year to inform us on activity and dose. So exciting progress in both programs. Finally, our complement programs with our bifunctional fusion protein and oral C5 inhibitor are also progressing towards selecting lead candidates.

我們也計劃明年在 DME 臨床試驗中開始使用 avoralstat 對患者進行劑量範圍調整。這可能會在明年為我們提供兩個項目中患者的數據，以便我們了解活動和劑量。這兩個項目都取得了令人興奮的進展。最後，我們的雙功能融合蛋白和口服 C5 抑制劑的補體項目也在選擇主要候選藥物方面取得進展。

Let me wrap up with two more important points. First, we are committed to accelerating our path to profitability to become independent of the capital markets for funding. Anthony will share more details, but we are well on our way to delivering on that commitment.

讓我以兩點更重要的觀點作為總結。首先，我們致力於加速獲利之路，獨立於資本市場融資。安東尼將分享更多細節，但我們正在努力兌現這項承諾。

And second, our impressive performance this quarter and for the first half of this year is a direct reflection of the commitment our employees have to our patients. This was an amazing quarter of performance on many fronts, and I want to thank every BioCryst employee for getting us here and for the momentum they have created to continue this throughout the remainder of the year.

其次，我們本季和今年上半年令人印象深刻的業績直接反映了我們的員工對病患的承諾。這是一個在許多方面都表現出色的季度，我要感謝每一位 BioCryst 員工讓我們來到這裡，並感謝他們所創造的動力，讓我們在今年剩餘的時間裡繼續保持這一勢頭。

Now I'd like to turn it over to Charlie to review the ORLADEYO quarterly performance.

現在我想把它交給查理來審查奧拉德約的季度業績。

Thanks, Jon. It was an absolutely great quarter with over $108 million in global revenue against our expectation of $97 million. Demand rate remains strong and was the key driver of our 34% year-over-year revenue growth. New patient prescriptions for the past three quarters continue to equal the high demand we experienced in the very first three quarters of the launch three years ago. But operational improvements made the immediate difference that drove our performance in the quarter.

謝謝，喬恩。這是一個絕對出色的季度，全球收入超過 1.08 億美元，而我們的預期為 9700 萬美元。需求率依然強勁，是我們營收年增 34% 的主要驅動力。過去三個季度的新患者處方數量繼續與三年前推出前三個季度的高需求持平。但營運方面的改進帶來了立竿見影的效果，推動了我們本季的業績。

The investments in our team that we have described previously are paying off significantly. The percentage of (technical difficulty) [unpaid] therapy, for example, is up nearly 3% since the end of 2023 from 71.5% to 74.4%. This is ahead of our expectations. Of note, we are up to a paid patient rate of 82% among commercially insured patients. Recall that about 60% of our patients are commercial and the paid rate in this segment is up from 79% at the end of 2023 and 72% at the end of 2022.

我們之前描述的對我們團隊的投資正在獲得顯著回報。例如，自 2023 年底以來，（技術難度）[無償]治療的比例從 71.5% 上升到 74.4%，增加了近 3%。這超出了我們的預期。值得注意的是，我們在商業保險患者中的付費患者比例高達 82%。回想一下，我們約 60% 的患者是商業患者，該領域的付費率高於 2023 年底的 79% 和 2022 年底的 72%。

This progress makes our long-term expectation to reach 85% paid even more clear. Other aspects, such as increased patient compliance and retention against our Q2 expectations added to the great result and we see these improvements being sustainable.

這項進展使我們達到 85% 的支付率的長期預期更加明確。其他方面，例如患者依從性的提高以及與我們第二季度預期相比的保留率的提高，都增加了出色的成果，並且我們認為這些改進是可持續的。

With that base of improving operations, let's move to the long-term demand and overall market opportunity. Patients have long told us that they want a convenient oral route of administration to prevent attacks but they won't compromise on efficacy and nor will their physicians.

有了改善營運的基礎，讓我們轉向長期需求和整體市場機會。患者長期以來一直告訴我們，他們想要一種方便的口服給藥途徑來預防發作，但他們不會在療效上妥協，他們的醫生也不會。

Our long-term data and real-world evidence are convincing patients and their physicians that both are possible with ORLADEYO, efficacy and convenience. The cornerstones to this motivating message, 91% reduction in attacks versus baseline in our pivotal trial and the growing and consistent body of real-world evidence that reflects the favorable experiences of individual patients and physicians all with one capsule once a day.

我們的長期數據和現實世界證據使患者及其醫生相信，ORLADEYO 的功效和便利性都可以實現。這項激勵訊息的基石是，在我們的關鍵試驗中，與基線相比，發作次數減少了91%，並且越來越多且一致的現實證據反映了個別患者和醫生每天服用一粒膠囊的良好體驗。

Physicians are increasingly confident that ORLADEYO will be effective as well as convenient for their patients. And physician confidence translates to patient confidence, particularly for the many patients who would prefer oral prophylaxis therapy regardless of their treatment history.

醫生們越來越相信 ORLADEYO 對病人來說既有效又方便。醫師的信心會轉化為患者的信心，特別是對於許多無論其治療史如何都願意接受口服預防治療的患者而言。

Slide 8 of today's presentation shows that 52% of all patients starting ORLADEYO to date, switched after having experienced with other HAE prophylaxis therapies, 32% with a history of on-demand treatment only and 17% were treatment naive. Again, regardless of their prior treatment experience, most patients do well.

今天簡報的第8 張幻燈片顯示，迄今為止開始使用ORLADEYO 的所有患者中，有52% 在經歷過其他HAE 預防治療後轉為接受治療，32% 的患者僅接受過按需治療，17%的患者從未接受過治療。同樣，無論他們之前的治療經驗如何，大多數患者都表現良好。

As you can see on slide 10, 61% of prior prophy and 67% of prophy naive patients who start on ORLADEYO and reach paid status stay on therapy for at least a year. What's notable is that that patient retention is similar, whether patients are starting ORLADEYO or injectable prophylaxis, as you can see from a preliminary analysis of claims data on Slide 11.

正如您在投影片 10 中看到的那樣，61% 的既往預防患者和 67% 的初次接受預防治療的患者開始接受 ORLADEYO 治療並達到付費狀態後，會繼續治療至少一年。值得注意的是，無論患者開始使用 ORLADEYO 還是注射預防藥物，患者保留率都是相似的，正如您從幻燈片 11 中索賠數據的初步分析中看到的那樣。

This is not surprising, at least to us, based on our internal data and what we hear from patients. But this point is worth repeating. There is no statistical difference in one-year retention for patients starting ORLADEYO, lanadelumab, or C1 inhibitor prophylaxis. I will point out, however, that the one year retention on ORLADEYO of 61% is numerically higher than the other two.

根據我們的內部數據和我們從患者那裡聽到的信息，這並不奇怪，至少對我們來說是這樣。但這一點值得重複。對於開始 ORLADEYO、lanadelumab 或 C1 抑制劑預防的患者，一年保留率沒有統計學差異。不過，我要指出的是，ORLADEYO 的一年保留率為 61%，在數字上高於其他兩個。

So why are patients staying on ORLADEYO at such high rates, rates that are comparable to other prophy therapies. Patients have told us individually and in large market research studies that they would prefer to control their attacks with a daily pill. This includes half the patients currently on injectable prophy as you can see from a recent survey of 120 patients shown on slide 12. They shared their (technical difficulty) to switch in that same market research study. No needles, no preparation, freedom to travel, feeling normal and forgetting they have HAE are all part of their dream. ORLADEYO is delivering on that dream.

那麼，為什麼患者繼續接受 ORLADEYO 治療的比例如此之高，與其他預防療法的比例相當。患者在個人和大型市場研究中告訴我們，他們更願意透過每日服用藥物來控制發作。這包括目前使用注射預防劑的一半患者，正如您從幻燈片 12 中顯示的最近對 120 名患者進行的調查中看到的那樣。 他們在同一市場研究中分享了轉換的（技術困難）。無需打針、無需準備、自由旅行、感覺正常並忘記自己患有 HAE，這些都是他們夢想的一部分。奧拉德約正在實現這個夢想。

In large -- in results from large surveys of patients taking ORLADEYO, you can see -- that you can see on slide 14, approximately 80% said they are having fewer attacks than they did before starting or on ORLADEYO. And about 75% told us they are having less severe attacks.

在對服用 ORLADEYO 的患者進行的大型調查結果中，您可以在幻燈片 14 上看到，大約 80% 的患者表示，與開始服用 ORLADEYO 之前或服用 ORLADEYO 之前相比，他們的發作次數減少了。大約 75% 的人告訴我們，他們遭受的攻擊不太嚴重。

Overall, about 9 patients and 10 patients told us their attack control was at least as good as it was previously. And yes, those patients who switched from injectable prophylaxis told us the same thing. This is what efficacy and convenience looks like.

總體而言，大約 9 名患者和 10 名患者告訴我們，他們的發作控制至少與以前一樣好。是的，那些不再接受注射預防治療的患者也告訴了我們同樣的事情。這就是功效和便利性的樣子。

So what does this lead to? Well, recent market research with large samples of allergists immunologists shown on slide 15 indicates that over 9 and 10 HAE treaters now consider prescribing ORLADEYO for their patients, and over 50% of current prescribers are extremely likely to prescribe again compared to under 30% a year ago. That is a big shift over a year.

那麼這會導致什麼呢？幻燈片15 中顯示的最近對過敏專科免疫學家的大樣本進行的市場研究表明，超過9 到10 名HAE 治療師現在考慮為患者開ORLADEYO 處方，超過50% 的當前處方者極有可能再次開處方，而這一比例低於30%。這是一年多來的巨大轉變。

Why have they shifted? Because they have seen the evidence. Not only have we shown it to them, but they've also heard the evidence directly from their patients. This increasing enthusiasm from the physicians matches well with the considerable opportunity that remains for ORLADEYO.

他們為什麼轉移了？因為他們已經看到證據了。我們不僅向他們展示了它，而且他們還直接從患者那裡聽到了證據。醫生們日益高漲的熱情與奧拉德約仍然存在的巨大機會相匹配。

For example, the market research on slide 12 shows that three patients out of four patients currently on injectable prophy are willing to switch. We also have updated administrative claims based studies to size the market that you can see on slide 9. Since we first did these studies prior to the ORLADEYO launch, the number of treated HAE patients in the US has grown to 8,500, and the total number of patient of HAE patients has increased to over 11,000.

例如，投影片 12 的市場研究顯示，目前正在接受注射預防劑治療的四分之三的患者願意更換。我們也更新了基於行政索賠的研究，以調整市場規模，您可以在幻燈片9 中看到。總人數HAE患者的患者數已增加至11,000多人。

As I described earlier, patients from all segments are benefiting from ORLADEYO with comparable success in treatment outcomes, patient retention and rate of paid therapy. Even with a strong first three years of the launch and the 2,500 prescriptions through the end of 2023, fewer than one in four US HAE patients has tried ORLADEYO. With a high patient desire for oral therapy and the growing physician intent to prescribe, there is way more opportunity in front of us than behind us.

正如我之前所描述的，各個領域的患者都從 ORLADEYO 中受益，在治療結果、患者保留率和付費治療率方面取得了相當的成功。儘管上市前三年表現強勁，截至 2023 年底已收到 2,500 個處方，但只有不到四分之一的美國 HAE 患者嘗試過 ORLADEYO。隨著患者對口腔治療的強烈渴望以及醫生開處方的意願不斷增強，我們面前的機會比我們身後的機會多得多。

Finally, it is also increasingly clear that our global expansion is working. Ex-US sales in the second quarter were $12.4 million, up 51% year-over-year. We recently exceeded 500 patients in Europe and we are already selling ORLADEYO in over 20 countries globally, with many more actively preparing for market authorization, access and launch.

最後，我們的全球擴張正在發揮作用，這一點也越來越明顯。第二季美國以外地區的銷售額為 1,240 萬美元，年增 51%。最近，我們在歐洲的患者數量超過了 500 名，並且已經在全球 20 多個國家/地區銷售 ORLADEYO，還有更多國家正在積極準備市場授權、准入和上市。

To summarize, the operational improvements we saw in Q2 on top of what we saw in Q1 mean that the increasing paid rates and high patient compliance are sustainable, and we are on track toward our long-term goal of 85% paid treatment in the US.

總而言之，我們在第一季看到的營運改善意味著付費率的提高和患者的高依從性是可持續的，我們正在朝著美國 85% 付費治療的長期目標邁進。

In addition, patient and prescriber confidence are growing stronger because both groups are experiencing not just the convenience, but also the efficacy of ORLADEYO. We've been describing a $1 billion in peak global revenue for ORLADEYO for a few years now. The path to that sustainable peak is increasingly clear.

此外，患者和處方醫生的信心越來越強，因為兩個群體不僅體驗到了 ORLADEYO 的便利性，而且體驗到了 ORLADEYO 的功效。幾年來，我們一直在描述 ORLADEYO 的全球收入高峰為 10 億美元。通往永續高峰的道路越來越清晰。

Now I'll hand the call over to Anthony to describe our financial performance.

現在我將把電話交給安東尼來描述我們的財務表現。

Thanks, Charlie. It's very encouraging to see yet another really strong quarter for ORLADEYO. It's is great work for the whole team. You can find a detailed second 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 was $109.3 million and as Charlie said, $108.3 million of that came from ORLADEYO. That's a 34% increase in ORLADEYO revenue over the same quarter last year and ORLADEYO revenues in the past 12 months are over $373 million.

謝謝，查理。看到奧拉德約又一個真正強勁的季度，真是令人鼓舞。這對整個團隊來說都是一項偉大的工作。您可以在今天的收益新聞稿中找到詳細的第二季財務數據，我想提請您注意一些項目。該季度的總收入為 1.093 億美元，正如 Charlie 所說，其中 1.083 億美元來自 ORLADEYO。 ORLADEYO 的營收比去年同期成長了 34%，過去 12 個月的 ORLADEYO 營收超過 3.73 億美元。

Of the $108.3 million of global ORLADEYO revenue, $95.9 million came from US sales with the remaining $12.4 million or 11.4% coming from ex-US sales. Operating expenses, not including non-cash stock compensation for the quarter were $87.4 million, a decrease of $6.2 million from Q1 of this year and a decrease of $3 million from Q2 of 2023.

在 ORLADEYO 1.083 億美元的全球收入中，9,590 萬美元來自美國銷售，其餘 1,240 萬美元（即 11.4%）來自美國以外的銷售。該季度的營運費用（不包括非現金股票補償）為 8,740 萬美元，比今年第一季減少 620 萬美元，比 2023 年第二季減少 300 萬美元。

Full year 2024 guidance for OpEx remains unchanged at between $365 million and $375 million. We achieved an operating profit for the quarter of $21.9 million, excluding non-cash stock comp and an operating profit of $8.8 million, even when including non-cash stock comp, which was $13.2 million for the quarter.

2024 年全年營運支出指引維持在 3.65 億美元至 3.75 億美元之間不變。我們本季實現的營業利潤為 2,190 萬美元（不包括非現金股票補償），即使包括非現金股票補償（本季為 1,320 萬美元），營業利潤也為 880 萬美元。

Cash at the end of the quarter was at $338.1 million, and net cash utilization for the quarter was just $213,000. We had guided to net cash utilization of between $10 million to $12 million per quarter for the remainder of the year. The main driver for the improvement in cash flow for Q2 was the increase in revenue versus forecast of over $11 million. For the remaining two quarters of 2024, I expect net cash utilization to average out at single-digit millions of dollars per quarter. We're even more confident in our guidance of having quarterly positive cash flow late next year and more strong quarters like we saw in Q2 may help us to accelerate that.

該季度末的現金為 3.381 億美元，該季度的淨現金利用率僅為 213,000 美元。我們預計今年剩餘時間內每季的淨現金利用率將在 1,000 萬至 1,200 萬美元之間。第二季現金流改善的主要驅動力是營收的成長（與預期相比超過 1,100 萬美元）。在 2024 年剩餘的兩個季度，我預計每季淨現金利用率平均為數百萬美元。我們對明年底實現季度正現金流的指導更有信心，而像第二季度那樣強勁的季度可能會幫助我們加速實現這一目標。

To be clear, from both an operational and a financial perspective, Q2 was a stellar quarter. Let's also be clear that this is not a one-off or an anomaly. The performance of the commercial team, both in the US and ex-US since the launch of ORLADEYO has been nothing short of terrific. And yes, Q2 overachieved, even our initial expectations.

需要明確的是，從營運和財務角度來看，第二季都是一個出色的季度。我們還要明確一點，這不是一次性或異常現象。自 ORLADEYO 推出以來，無論是在美國還是美國以外的商業團隊的表現都非常出色。是的，第二季度超出了我們最初的預期。

If asked was this a surprise, I would answer no. I've stopping surprise given what this team has achieved since launch and given the immense success that we have seen patients have while on ORLADEYO to achieve both efficacy and convenience with this best in class drug. Discontinued strength is what gives us the confidence to increase our 2024 revenue guidance for ORLADEYO so significantly to between $420 million and $435 million, a $30 million to $35 million increase in the range and an approximate $100 million increase over last year's total.

如果問這是不是一個驚喜，我會回答「不」。考慮到團隊自推出以來所取得的成就，以及我們看到患者在 ORLADEYO 上使用這種同類最佳藥物實現療效和便利性的巨大成功，我不再感到驚訝。持續的強勁使我們有信心將 ORLADEYO 的 2024 年收入指引大幅提高至 4.2 億至 4.35 億美元，該範圍增加了 3,000 萬至 3,500 萬美元，比去年的總額增加了約 1 億美元。

As another positive, the entirety of that additional $30 million to $35 million is at the lower royalty rate of 7.5%, which would bring the blended royalty rate down by 30 basis points to 50 basis points versus our prior guidance. With OpEx guidance unchanged at flat to last year, we're even more confident about our past profitability with an operating profit for full year this year, EPS and cash flow positivity on a quarterly basis next year and full year EPS positive and cash flow positive in 2026.

另一個積極因素是，額外的3000 萬至3500 萬美元全部以7.5% 的較低特許權使用費率計算，這將使混合特許權使用費率比我們之前的指導降低30 個基點至50 個基點。由於營運支出指引與去年持平，我們對過去的獲利能力更有信心，今年全年營業利潤、明年季度每股收益和現金流為正，全年每股收益和現金流為正2026年。

Operator, we'll now open it up for Q&A.

接線員，我們現在將打開它進行問答。

We will now begin the question and answer session. (Operator Instructions)

我們現在開始問答環節。 （操作員說明）

Tazeen Ahmad. Please go ahead. Tazeen Ahmad with Bank of America. Please go ahead. Is your line on mute?

塔辛·艾哈邁德.請繼續。塔津‧艾哈邁德 (Tazeen Ahmad)，美國銀行。請繼續。您的線路處於靜音狀態嗎？

We're going to transition to Jessica Fye with JPMorgan. Please go ahead.

我們將由傑西卡·法耶 (Jessica Fye) 擔任摩根大通的職務。請繼續。

This is Nick on for Jessica. Congrats on the quarter and thanks for taking our questions. So based on these results, including the updated guidance for ORLADEYO and maintain expectations around operating expenses, can you discuss your level of feeling around if you could reach GAAP operating profits in 2024 and not just full year operating profits, excluding non-cash stock compensation?

這是傑西卡的尼克。恭喜本季度，感謝您提出我們的問題。因此，根據這些結果，包括ORLADEYO 的最新指導並維持對營運費用的預期，您能否討論一下您對是否能夠在2024 年實現GAAP 營運利潤而不僅僅是全年營運利潤（不包括非現金股票補償）的感受層次？

Yeah, Q2 as it relates to both revenue and our control on operating expenses, like we said, were terrific. And so when we have guided to previously was getting there not including non-cash stock compensation, we're still guiding to that. Is there a chance that we would get there even including the non-cash stock compensation? Absolutely. Just depends on for the remainder of the year revenue and then the offset between that and OpEx. But what I would guide to is our increased confidence of getting there excluding non-cash stock comp.

是的，第二季度因為它與收入和我們對營運費用的控制有關，就像我們所說的那樣，非常棒。因此，當我們先前指導要實現不包括非現金股票補償時，我們仍然會指導這一點。即使包括非現金股票補償，我們是否有可能實現這一目標？絕對地。僅取決於今年剩餘時間的收入以及收入與營運支出之間的抵銷。但我想說的是，我們對實現這一目標的信心增強，排除非現金股票補償。

Okay. And then within that raised guidance for ORLADEYO, can you just discuss in a bit more detail your underlying assumptions around new patient starts, the percent of patients on paid drug and maybe compliance retention for the remainder of the year and how that changes -- could change versus 1Q, 2Q?

好的。然後，在針對ORLADEYO 提出的指導意見中，您能否更詳細地討論一下您對新患者開始治療的基本假設、付費藥物患者的百分比以及今年剩餘時間內的依從性保留情況以及這種情況如何變化- 可能與1Q、2Q相比有何變化？

Sure. Yeah, Nick, we've -- as you know, we've reported very consistent new patient starts, and then the last three quarters have been even stronger, as strong as the first three quarters of the launch. So we would expect the consistent demand, based on all the metrics that I described today.

當然。是的，尼克，我們——如你所知，我們報告了非常一致的新患者啟動情況，然後過去三個季度的情況甚至更加強勁，與啟動的前三個季度一樣強勁。因此，根據我今天描述的所有指標，我們預計需求將保持一致。

As far as paid rate, like I said, we're ahead of our expectations. We are not expecting major increases for the rest of the year. The goal is to at least hold that consistent with the 74.4% that we were at the end of Q2. And compliance is just really strong. So compliance at this point, if you measure it by the number of treatment days available to the -- your overall patient population, and then the number of drug days basically delivered, we're in the mid-90s at this point, and we would expect that to continue.

就付費率而言，正如我所說，我們超出了我們的預期。我們預計今年剩餘時間不會大幅成長。我們的目標是至少與第二季末的 74.4% 保持一致。而且合規性非常強。因此，此時的依從性，如果您透過整個患者群體可用的治療天數來衡量，然後是基本交付的藥物天數，那麼我們此時正處於 90 年代中期，我們預計這種情況會繼續下去。

Thanks so much.

非常感謝。

Tazeen Ahmad, Bank of America.

塔津·艾哈邁德，美國銀行。

Hi, guys. Can you hear me?

嗨，大家好。你聽得到我嗎？

Yeah.

是的。

Okay, great. Thank you. Can I ask a question about the pipeline, your focus now another 10 disease? Maybe can you talk about the data that you've collected internally that that gives you confidence in pursuing this particular molecule for this indication and maybe the cadence of data to expect over the next year or so? Thanks.

好的，太好了。謝謝。我可以問一個關於管道的問題嗎？也許您可以談談您內部收集的數據，這些數據讓您有信心針對該適應症追求這種特定分子，以及未來一年左右預期的數據節奏？謝謝。

Sure. So let me take that last piece first, the cadences is that we, for [17, 75], we are proceeding into first-in-human this year. And so that's an important milestone to keep in mind for this program. In terms of the data that we have to support that, we have all of the required data to be able to proceed to first human.

當然。因此，讓我先談談最後一部分，節奏是我們，對於 [17, 75]，我們今年將進入首次人體試驗。因此，這是該計劃需要牢記的一個重要里程碑。就我們必須支持的數據而言，我們擁有能夠進行第一個人類研究所需的所有數據。

Generally, that includes safety from a non-clinical toxicology perspective as well as data to support the importance of the mechanism for treating the disease and the potential to improve clinical symptoms in patients. So we have non-clinical data for both safety and efficacy that's supportive of proceeding to humans. We also have data around the likely exposure range, and we will be going to first in-human this year.

一般來說，這包括非臨床毒理學角度的安全性，以及支持治療疾病機制重要性的數據以及改善患者臨床症狀的潛力。因此，我們擁有安全性和有效性的非臨床數據，並支持人類治療。我們也掌握了可能的暴露範圍的數據，今年我們將首先進行人體試驗。

Yeah, and Helen and I were in Birmingham this week and we got to see the animal model work that the team is working on. It's an inflammation model, and it was really impressive what we saw the control animals have an inflammation and then the inflammation going down with each higher dose. So the key is that you not only have good drug levels, but the drug levels get to the target, which is the skin and so far so good. So we're hoping we'll see that in humans as well.

是的，海倫和我這週在伯明翰，我們看到了團隊正在研究的動物模型工作。這是一個炎症模型，令人印象深刻的是，我們看到對照動物有炎症，然後炎症隨著劑量的增加而下降。所以關鍵是你不僅要有良好的藥物水平，而且藥物水平要達到目標，即皮膚，到目前為止一切都很好。所以我們希望我們也能在人類身上看到這一點。

Brian Abrahams, RBC Capital Markets.

布萊恩‧亞伯拉罕斯 (Brian Abrahams)，加拿大皇家銀行資本市場部。

Hey, good morning. Thanks for taking my questions and congrats on the quarter. I'm wondering if you could maybe elaborate a little bit more on why we saw such a big uptick in the paid drug just on a quarter-over-quarter basis and maybe some of the seasonal trends underlying that versus kind of operational trends?

嘿，早安。感謝您回答我的問題並祝賀本季。我想知道您是否可以詳細說明為什麼我們看到付費藥品的季度環比增長如此之大，也許還有一些季節性趨勢與營運趨勢之間的關係？

And then, can you talk a little bit more about the inputs that went into your resizing of the HAE market and I guess just in terms with the additional 1,000 patients, just kind of wondering if you can talk about the characteristics or anything you've learned about those additional patients who are out there, how accessible they are, what you might need to do to engage them? Thanks.

然後，您能否多談談調整 HAE 市場規模的投入，我想只是針對額外的 1,000 名患者，只是想知道您是否可以談談特點或您所了解的任何內容了解了那裡的其他患者、他們有多容易親近、您可能需要做什麼才能吸引他們？謝謝。

Hey, Brian. First off, on the uptick in the paid. As I mentioned in my comments and we've talked about this before, we've invested a lot in the team to really make sure that we are helping patients and healthcare providers do everything possible to not only put in kind of a complete start form upfront, all the information that payers want, but then to go through the appeals process when that's necessary. And since we made that investment last year, I think the team is really hitting stride, and that's what's making the difference.

嘿，布萊恩。首先，付費的增加。正如我在評論中提到的以及我們之前討論過的那樣，我們在團隊上投入了大量資金，以真正確保我們正在盡一切可能幫助患者和醫療保健提供者，而不僅僅是提供完整的開始表格預先提供付款人想要的所有信息，然後在必要時進行上訴流程。自從我們去年進行了這項投資以來，我認為團隊確實取得了長足進步，這就是造成差異的原因。

It's not a seasonal factor in Q2 and Q1 is really the seasonal time with the re-authorizations. But now it's just really about every single patient and the -- just the operational improvements that we've made. So I'm really pleased with their progress.

這不是第二季的季節性因素，第一季實際上是重新授權的季節性時間。但現在，這實際上關係到每位患者以及我們所做的營運改善。所以我對他們的進步感到非常滿意。

As far as the resizing of the market, we've done this kind of work with claims data regularly and you'll recall that prior to launch we talked about 7,500 diagnosed and treated patients. We knew that there was a larger population of untreated patients, but we were conservative in those initial numbers that we put out.

就市場規模調整而言，我們定期對索賠數據進行此類工作，您會記得在推出之前我們討論了 7,500 名診斷和治療的患者。我們知道還有大量未經治療的患者，但我們對最初公佈的數字持保守態度。

What we're seeing now with ORLADEYO attracting patients from all segments, from prophy switches, from on-demand only, and then also treatment-naive patients, we're attracting all three. And so we redid the numbers. We've seen that the market has grown. We think a good portion of that growth is due to our promotion with ORLADEYO. And so we thought it was time to update the overall.

我們現在看到 ORLADEYO 吸引了來自各個領域的患者，從預防轉換患者、僅按需患者，以及未接受過治療的患者，我們正在吸引所有這三個患者。所以我們重新計算了數字。我們看到市場已經成長。我們認為這一增長的很大一部分歸功於我們對 ORLADEYO 的促銷。所以我們認為是時候更新整體了。

Got it. Thanks so much for the color, Charlie.

知道了。非常感謝你的顏色，查理。

Chris Raymond, Piper Sandler.

克里斯·雷蒙德，派珀·桑德勒。

Thanks for taking the question and congrats on the progress. Great to see. Just maybe one question on ORLADEYO, one on the pipeline. So I was kind of struck by your patient activation slide with the market research showing that, essentially three in four patients are willing to switch. Can you maybe give a little bit more color on -- as you sort of distill those patients down, how do you activate those patients? That would seem to be a dynamic that would indicate, certainly understand why your guidance has been raised here, but that there's maybe a little bit more opportunity if you can really convert all those patients. So maybe how many of those do you think are really candidates for activation?

感謝您提出問題並祝賀取得的進展。很高興看到。也許只是關於奧拉德約的一個問題，一個正在醞釀中的問題。因此，我對您的患者啟動幻燈片感到震驚，市場研究表明，基本上四分之三的患者願意轉換。您能否提供更多資訊—當您對這些患者進行提煉時，您如何啟動這些患者？這似乎是一種動態，表明，當然理解為什麼你的指導在這裡提出，但如果你真的能夠改變所有這些患者，可能會有更多的機會。那麼，您認為其中有多少真正是啟動的候選人？

And then maybe just a pipeline question. With respect to the Netherton syndrome program, just maybe talk about why you think a KLK5 inhibitor would be effective in this population? And just looking at some of the other programs that are in this disease, talk about maybe how you look at the differentiation. Thanks.

然後也許只是一個管道問題。關於 Netherton 症候群項目，也許可以談談為什麼您認為 KLK5 抑制劑對這一人群有效？看看這種疾病中的一些其他程序，談談您如何看待差異化。謝謝。

I'll start with the question about the patient activation. Yeah, we're thrilled to see that so many patients are willing to switch and so many patients who are on injectable prophylaxis and that that's continued and actually grown throughout the launch.

我將從有關患者激活的問題開始。是的，我們很高興看到如此多的患者願意更換藥物，並且有如此多的患者接受注射預防治療，並且在整個發布過程中這種情況一直持續並且實際上在增長。

We have a number of ways that we try to activate them. We have extensive digital marketing, other kind of direct marketing programs to patients. But I'll say the number one way to activate them is to make them aware that ORLADEYO is out there, and then to make sure that their healthcare providers are confident in the product. And what you can see from the data I've shown you today is physicians are increasingly confident, and I think when physicians have that conversation with their patient about all of their treatment options, you combine that with the strong patient desire for oral therapy and the willingness to switch, that is what is going to activate more patients to switch. That's going to be the strongest driver.

我們有多種方法可以嘗試激活它們。我們有廣泛的數位行銷和其他類型的針對患者的直接行銷計劃。但我想說，啟動他們的第一個方法是讓他們意識到 ORLADEYO 就在那裡，然後確保他們的醫療保健提供者對該產品充滿信心。從我今天向您展示的數據中您可以看到，醫生越來越有信心，我認為當醫生與患者就所有治療方案進行對話時，您會將其與患者對口服治療的強烈願望結合起來，願意改變，這將促使更多患者改變。這將是最強的車手。

Yeah, maybe I'll start and then pass it to you. So it's a great question because we're really excited to bring something forward that actually treats the underlying disease rather than the inflammation and the system, the inflammation due to the disease. But I'll let Helen talk a bit more about it.

是的，也許我會開始然後將其傳遞給你。所以這是一個很好的問題，因為我們真的很高興能提出一些真正治療潛在疾病的東西，而不是發炎和系統，即疾病引起的發炎。但我會讓海倫多談談它。

Yeah, thanks, Jon. So KLK5 is dysregulated in Netherton syndrome. That's the cause of the disease. So the KLK5 inhibitor is a way to place the function that's missing and improve the cause of the disease. It’s -- so we believe we have a differentiated product for this for two different reasons. One, we've achieved very, very high potency with our drug and that means that we could potentially deliver a subcutaneous dose and also deliver it on a less frequent basis than is typical for this type of therapy.

是的，謝謝，喬恩。因此，在內瑟頓症候群中 KLK5 失調。這就是疾病的原因。因此，KLK5抑制劑是一種定位缺失功能並改善病因的方法。所以我們相信，出於兩個不同的原因，我們為此擁有了一個差異化產品。第一，我們的藥物已經實現了非常非常高的效力，這意味著我們有可能提供皮下劑量，並且與此類療法相比，以較低的頻率提供劑量。

And so two, in terms of the (technical difficulty) important to go back to that KLK5 dysregulation of the cause of the disease. This -- approaching this target means that you don't just affect the cause of the disease in the skin, you're also affecting the downstream inflammation, whereas some other programs that are in the pipeline for this disease are affecting just the downstream inflammation.

因此，就（技術難度）而言，重要的是回到疾病原因的 KLK5 失調。接近這個目標意味著你不僅會影響皮膚疾病的原因，還會影響下游炎症，而正在針對這種疾病的其他一些計劃只會影響下游炎症。

So we expect to see healing of the skin and improvement of the disease from that perspective, as well as preventing then the downstream inflammation that causes other effects in the disease.

因此，我們期望從這個角度看到皮膚的癒合和疾病的改善，以及預防導致疾病其他影響的下游發炎。

And one of the things you see in rare diseases like this where there's nothing to treat it is there are way more patients than you originally estimated and that's really exciting as well.

在這種無法治療的罕見疾病中，你會看到的一件事是患者數量比你最初估計的要多得多，這也非常令人興奮。

Thank you.

謝謝。

Gena Wang, Barclays.

王吉娜，巴克萊銀行。

Thank you for taking my questions. And also I wanted to add my congrats on the strong quarter. So I was revised the guidance. Just wondering where do you see the main increase? Would that be mainly from on-demand patients, untreated patient or continue to be from the switch over patient? And then for the pipeline assets, just wondering, will you at some point sharing the preclinical data?

感謝您回答我的問題。我還想對強勁的季度表示祝賀。所以我修改了指導。只是想知道您看到主要增長在哪裡？這主要來自按需患者、未經治療的患者還是繼續來自轉換患者？然後對於管道資產，只是想知道，您會在某個時候共享臨床前數據嗎？

on which program, Gena?

在哪個節目上，吉娜？

The lead assets, the pipeline assets, the 17725.

主導資產，管道資產，17725。

Okay, got it. Gena, I think we've -- what I showed today, we're thrilled that we are getting over 50% of patients from prophylaxis switches and then we're also getting the on-demand patients and even treatment naive.

好的，明白了。 Gena，我認為我們今天所展示的，我們很高興我們有超過 50% 的患者接受了預防性治療，而且我們還獲得了按需患者，甚至是未經治療的患者。

We expect that to continue, and the market research that I showed on slide 12 is specific to patients on injectable prophylaxis. And you can see from that the 50% of the patients have a -- of those patients have a preference, specifically for oral prophylaxis therapy and three out of four -- three out of four of those patients are willing to switch. And so what I would expect is the same dynamics to continue about half the patients coming from prophy and then the other half coming from on-demand and treatment naive.

我們預計這種情況會持續下去，我在幻燈片 12 上展示的市場研究專門針對接受注射預防的患者。你可以從中看到，50% 的患者有一種偏好，特別是對於口服預防治療，四分之三的患者願意轉換，四分之三的患者願意轉換。因此，我預計同樣的動態將持續下去，大約一半的患者來自預防治療，然後另一半來自按需和未經治療的患者。

While it's great to see that growth this year and growth next year is going to come from that growth in patient demand, the increase in the guidance for this year, a lot of that's driven by the operational activity that Charlie explained. So it's great to see both things happening simultaneously.

雖然很高興看到今年和明年的成長將來自患者需求的增長，但今年指導的增加，其中很大一部分是由查理解釋的營運活動推動的。所以很高興看到這兩件事同時發生。

Helen, you want to take the --

海倫，你想要—

Yeah, so in terms of sharing preclinical data, we would, of course, publish data in the future as we have excellent results for our pipeline programs. In terms of the Netherton syndrome program, Jon mentioned earlier the data that we have in an animal model showing changes in the skin.

是的，所以在共享臨床前數據方面，我們當然會在未來發布數據，因為我們的管道專案取得了出色的成果。就內瑟頓症候群計畫而言，喬恩之前提到了我們在動物模型中獲得的顯示皮膚變化的數據。

We also have disease animal model information showing the extreme potency with this molecule. So we would expect to share data supporting both potency and effect. But for the purposes of today, I think it's important to know that we have sufficient information to be ready to proceed to first in human, and we're very excited about this program's potential.

我們還有疾病動物模型訊息，顯示該分子的極強效力。因此，我們希望分享支持效力和效果的數據。但就今天而言，我認為重要的是要知道我們有足夠的資訊來準備繼續進行人類第一，並且我們對這個計畫的潛力感到非常興奮。

Yeah, and we're going to have human data by the end of next year. So you're going to start to get a sense of activity and dose by the end of next year, both in this program and the DME avoralstat program, which is super exciting.

是的，我們將在明年年底前獲得人類數據。因此，到明年年底，您將開始了解該計劃和 DME avoralstat 計劃的活動和劑量，這非常令人興奮。

Thank you.

謝謝。

(Operator Instructions)

（操作員說明）

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Hi, good morning. I'll add my congrats on the quarter and thanks for taking my question. Just to follow up on the paid patients improvement this quarter, you said you could potentially get to 85% paid patients over the next few years, but it sounds like you're doing better than expected on this front. At this point, are you able to provide more clarity into when you could achieve the 85% of patients on pay track?

嗨，早安。我將對本季表示祝賀，並感謝您提出我的問題。為了跟進本季度付費患者的改善情況，您表示在未來幾年內您可能會為 85% 的付費患者提供服務，但聽起來您在這方面的表現比預期要好。目前，您能否更清楚地說明何時可以讓 85% 的患者實現付費？

Hey, Maury. I think the real key with the 85% is that's part of our growth, too, the $800 million in the US as we achieve $1 billion peak sales. We previously mapped out a path to that by 2029, we will tried to get there as quickly as we can. But if we get there by 2029, we will achieve that $1 billion. And based on what we've talked about today, it's increasingly clear that we're going to get there.

嘿，莫里。我認為 85% 的真正關鍵在於，這也是我們成長的一部分，也就是我們在美國實現 10 億美元高峰銷售額時的 8 億美元。我們之前已經規劃了在 2029 年實現這一目標的路徑，我們將盡力盡快實現這一目標。但如果我們在 2029 年實現這一目標，我們將實現 10 億美元。根據我們今天所討論的內容，越來越清楚我們將實現這一目標。

What I'm particularly excited about it, I noted this in my comments is the fact that we're at 82% paid already for the commercial segment, which is our biggest segment. And it just shows that we're going to get there. It's just it's just a matter of time.

令我特別興奮的是，我在評論中指出，我們已經為商業部門支付了 82% 的費用，這是我們最大的部門。它只是表明我們即將實現這一目標。這只是時間問題。

And Charlie, is it fair to say that next year could be a really interesting year with Medicare patients in particular, and we don't want to project what we think will happen, but there's a possibility that we could make real progress there as well as.

查理，可以公平地說，明年對醫療保險患者來說可能是非常有趣的一年，我們不想預測我們認為會發生的事情，但我們也有可能在這方面取得真正的進展。

Right. There's an opportunity to hopefully get a lot of the Medicare patients have not -- or their copayments, and that's led them to be on free product with the full introduction of the IRA next year and the max out of pocket for patients going to $2,000. That could be an opportunity that creates more affordability and thus more paid patients.

正確的。希望有機會獲得許多 Medicare 患者尚未獲得的醫療保險或他們的自付費用，隨著 IRA 明年全面推出，患者的自付費用上限將達到 2,000 美元，這使得他們可以使用免費產品。這可能是一個機會，可以創造更多的負擔能力，從而為患者帶來更多的報酬。

Got it. That's helpful. And just to clarify for the 74.4% for this quarter, you expect that to be consistent for the rest of this year, or could that potentially improve some as well?

知道了。這很有幫助。澄清一下，本季的 74.4%，您預計今年剩餘時間保持一致，或者也可能有所改善？

We will always trying to improve it. The time where we can make the biggest progress is during the big re-authorization season in Q1, and we did a great job in Q1 and then some of that rate job bled into the early part of Q2. The rest of the year will be driven more by new patient prescriptions coming in the opportunity to convert long-term free product over to paid will be less than it was in the first part of the year, kind of the seasonal cycle that we should expect going forward.

我們將始終努力改進它。我們能夠取得最大進展的時間是在第一季的大型重新授權季節，我們在第一季做得很好，然後一些費率工作滲透到了第二季的早期。今年剩餘時間將更多地受到新患者處方的推動，將長期免費產品轉換為付費產品的機會將少於今年上半年，這是我們應該預期的季節性週期繼續前進。

Got it. Okay. Thanks for taking my questions.

知道了。好的。感謝您回答我的問題。

Stacy Ku, TD Cowen.

史黛西·庫，TD·考恩。

Wonderful. Thanks so much for taking our questions, and congratulations on the progress. So we have a few follow-ups. First, I appreciate your detailed market research. Our KOLs and survey also tell us that additional injectable entrance are very unlikely to impact oral prophylactic options in HAE. So curious if Charlie or [Jon] can discuss long term where they expect the oral share to stabilize versus the injectable share. That's the first question.

精彩的。非常感謝您提出我們的問題，並祝賀我們的進展。所以我們有一些後續行動。首先，我感謝您詳細的市場研究。我們的 KOL 和調查也告訴我們，額外的注射入口不太可能影響 HAE 的口服預防選擇。很好奇查理或[喬恩]是否可以長期討論他們期望口服份額與注射份額相比穩定的情況。這是第一個問題。

And then the second question is a question on clinician outreach. So Charlie, can you talk about the progress this year? How many new prescribers are adopting ORLADEYO? And what percentage are still in the early days of a prescribing? Just remind us our goals for this year and what target you might have for next year. And then last, a quick follow-up. Just, can you elaborate a little bit more on the ex-US versus US [split] in Q2? Thanks so much.

第二個問題是關於臨床醫師外展的問題。查理，你能談談今年的進展嗎？有多少新處方醫生正在採用 ORLADEYO？仍處於處方初期的比例是多少？請提醒我們今年的目標以及明年的目標。最後，快速跟進。只是，您能否詳細說明一下第二季度的前美國與美國[分裂]？非常感謝。

Sure. So on the long-term oral share, I mean, ORLADEYO obviously is the only oral drug on the market and -- once a day. You really, you can't get better than that. So and we talked about our path to $1 billion and 2,000 paid patients in the US. And so, 2,000 out of over 11,000 total patients, you can imagine ORLADEYO is going to get to at least about 20% share. We'll see what happens with other products in the future, but we're very confident in our overall growth.

當然。因此，就長期口服藥物而言，我的意思是，ORLADEYO 顯然是市場上唯一的口服藥物，並且每天一次。你真的，沒有比這更好的了。因此，我們討論了我們在美國實現 10 億美元和 2,000 名付費患者的之路。因此，您可以想像，在 11,000 多名患者中，有 2,000 名患者將獲得 ORLADEYO 至少約 20% 的份額。我們將看看未來其他產品會發生什麼，但我們對我們的整體成長非常有信心。

The -- as far as prescribers, we continue to see new prescribers coming on board, and we've talked before about our Tier 1 doctors that cover about 50% of the market, sort of 500 doctors to 600 doctors there. And then the bigger Tier 2 group in Q2, we got equal number of prescriptions from both of those groups. So very -- continues to be very balanced.

就處方者而言，我們不斷看到新的處方者加入，我們之前談到我們的一級醫生涵蓋了大約 50% 的市場，大約有 500 名醫生到 600 名醫生。然後是第二季更大的二級組，我們從這兩個組中獲得了相同數量的處方。所以非常——仍然非常平衡。

And we had a very similar number of new prescribers to what we've seen in recent quarters. And as far as kind of adopters in the Tier 1 group, we're now to the point where over 70% of them have prescribed and we keep chipping away at that number. We may never get to 100% with them, but we're going to get close. And all the metrics we see is doctors across the board intend to do more.

我們的新處方醫生數量與最近幾季的情況非常相似。就第一級群體中的採用者而言，我們現在已經達到了超過 70% 的人已經開處方的程度，我們正在不斷減少這個數字。我們可能永遠無法與他們達成 100% 的合作，但我們會接近的。我們看到的所有指標都顯示，醫生們都打算做得更多。

Hey, Charlie, on that 30%, can you talk about how things like more prophy medicines come into the market and the noise of prophy going up? Can be an opportunity and the [peak] opportunity as well?

嘿，查理，關於那 30%，你能談談更多的預防藥物進入市場以及預防的噪音是如何上升的嗎？可以是機會，也可以是[巔峰]機會嗎？

That's a great point, Jon brings up. So we have two big opportunities. One, we do expect, of course, other competitors injectable products to launch. One may come as soon as the end of this year. And with that, there's just going to be more conversation around switching patients, more treatment options, maybe lower burden treatment injectable products. And so we're going to take advantage of that because we have the product that patients want with an oral once daily therapy.

喬恩提出，這是一個很好的觀點。所以我們有兩個很大的機會。第一，我們當然期望其他競爭對手推出注射產品。最快可能在今年底到來。隨之而來的是，將會有更多關於更換患者、更多治療選擇、也許更低負擔的治療注射產品的討論。因此，我們將利用這一點，因為我們擁有患者想要的每日一次口服療法的產品。

And then peak, that we intend to file next year. That is an opportunity in itself, but also there's the halo effect from that there. It's a genetic disease, their families and their doctors where this may become their first real experience with ORLADEYO and starting with the kids and then they maybe move on to the rest of the family. So both of these are opportunities over the next couple of years for us.

然後達到峰值，我們打算明年提交。這本身就是一個機會，但也有光環效應。這是一種遺傳性疾病，他們的家人和醫生可能會成為他們在奧拉德約的第一次真正經歷，從孩子開始，然後他們可能會轉移到家庭的其他成員。因此，這對我們來說都是未來幾年的機會。

Yeah. So these KOLs that tell us, if it’s not broke, don't fix it, if they've got a pediatric patient on injectable it's going to be pretty hard for them to not want to switch to an oral. So we think that's a real opportunity to have that conversation with them. And then, ex-US, Charlie?

是的。因此，這些 KOL 告訴我們，如果它沒有壞，就不要修理它，如果他們的兒科患者接受注射劑，他們將很難不想改用口服劑。所以我們認為這是與他們進行對話的真正機會。然後，美國以外的地方，查理？

Yeah, ex-US, what we see is the same consistent pattern of demands. We see many of the ex-US countries moving increasingly towards prophylaxis. For market access reasons, they may never get to quite the same levels of the US. But we're seeing prophy become the standard of care for patients and ORLADEYO to be growing very strongly and patient retention, too, has been very consistent with what we're seeing in the US. So Europe, Japan, Canada, Eastern Europe, we're starting to launch now with our partners in Latin America, a lot of opportunity and a lot of excitement about ORLADEYO coming to the market.

是的，除了美國之外，我們看到的是同樣一致的需求模式。我們看到許多美國以外的國家越來越多地採取預防措施。出於市場准入的原因，他們可能永遠無法達到與美國相同的水平。但我們看到預防成為患者的護理標準，ORLADEYO 的成長非常強勁，患者保留率也與我們在美國看到的情況非常一致。因此，歐洲、日本、加拿大、東歐，我們現在開始與拉丁美洲的合作夥伴一起推出，ORLADEYO 進入市場帶來了許多機會和很多興奮。

Wonderful. Thank you.

精彩的。謝謝。

Jon Wolleben, JMP Securities.

喬恩‧沃勒本 (Jon Wolleben)，JMP 證券。

Good morning. Congrats and thanks for taking the question. Just a couple more for me on the market sizing update. I'm assuming in that 8,500, you guys gave us that's including acute and prophylactic patients but wondering if you had any sense of reasons why that other 2,600 or so are not being treated? And then do you have any sense today of what percentage of treatment-naive patients are going to ORLADEYO first?

早安.恭喜並感謝您提出問題。我還需要了解更多關於市場規模更新的資訊。我假設你們給我們提供的這 8,500 名患者中包括急性患者和預防性患者，但想知道你們是否知道為什麼另外 2,600 名左右的患者沒有得到治療？那麼，您今天是否知道有多少比例的初治患者會先前往奧拉德約？

Sure, Jon. Of the 8,500, that includes patients that are in HAE specific medicines. So when we do this analysis, we look at all the prophy products. We also look at all the acute -- the modern prophy products, I should say. So ORLADEYO plus the injectables and then the acute therapies. So that's what's included there. You saw the data where we're attracting 17% of ORLADEYO patients launched to date have come from the treatment naive and what that tells us is that that treatment naive group is going to increasingly become a treated group.

當然，喬恩。在這 8,500 名患者中，其中包括服用 HAE 特定藥物的患者。因此，當我們進行分析時，我們會查看所有預防產品。我應該說，我們也關注所有急性的現代預防產品。所以 ORLADEYO 加上註射劑，然後是急性療法。這就是其中包含的內容。您看到的數據顯示，迄今為止，我們吸引了 17% 的 ORLADEYO 患者來自未接受治療的患者，這告訴我們，未接受治療的群體將越來越多地成為接受治療的群體。

Some of those patients are probably just becoming aware of their disease or their physicians are starting to become more aware about HAE and so again, it may never reach 100% of those patients treated, but we expect more and more of them will be treated and it's a great opportunity to help more patients.

其中一些患者可能剛開始意識到自己的疾病，或者他們的醫生開始更了解 HAE，因此，可能永遠不會達到 100% 接受治療的患者，但我們預計越來越多的患者將得到治療，而這是幫助更多患者的好機會。

Okay, but you don't have a sense from market research or what you're seeing in claims, like, a new patient coming into the system is preferring ORLADEYO or [RO]?

好的，但是您沒有從市場研究或您在索賠中看到的內容中獲得任何感覺，例如，進入系統的新患者更喜歡 ORLADEYO 還是 [RO]？

Yeah, I knew I was missing one part of your question. We do, ORLADEYO, we have at least 50% of those patients in our market research get ORLADEYO first before other prophylaxis products.

是的，我知道我遺漏了你問題的一部分。我們確實如此，ORLADEYO，在我們的市場研究中，至少有 50% 的患者首先使用 ORLADEYO，然後再使用其他預防產品。

That's helpful. Thanks, Charlie.

這很有幫助。謝謝，查理。

Serge Belanger, Needham & Company.

謝爾蓋貝蘭格 (Serge Belanger)，李約瑟公司。

Hi, good morning, and congrats on another solid ORLADEYO quarter. First one, given the nice growth we've seen over the first half of 2024, can you tell us a little bit about where you are in terms of market share in the market?

大家好，早安，恭喜奧拉德約又一個穩定的季度。首先，考慮到我們在 2024 年上半年看到的良好成長，您能否告訴我們一些您在市場佔有率方面的情況？

And then maybe for Charlie, regarding the prescribers survey, we've seen a pretty drastic increase in the likelihood of prescribing year-over-year. Just curious, what do you think drove that increase over such a short period of time? And if I'm not mistaken, you've conducted a survey, I think, every year. Just curious how it is, how predictive it is for future use and uptake of ORLADEYO? Thanks.

然後，對於查理來說，關於處方者調查，我們發現開處方的可能性逐年大幅增加。只是好奇，您認為是什麼推動瞭如此短的時間內的成長？如果我沒記錯的話，我想你們每年都會進行一項調查。只是好奇它是怎樣的，它對 ORLADEYO 未來的使用和吸收有多大的預測作用？謝謝。

Sure. As far as share goes, Serge, I'll point you back to the 2,500 prescriptions we had at the end of last year. Some of those, of course, are repeat patients who had dropped off and come back. But I think that's a pretty good mark -- marker roughly of where we are. So depending on how you want to do the math, either of treated patients or if the total market, we're probably nearing 20% market share, roughly a little bit below that, but growing very strongly.

當然。就份額而言，Serge，我將向您介紹去年年底我們擁有的 2,500 個處方。當然，其中一些是曾經離開過又回來的回頭客。但我認為這是一個非常好的標記——大致標記了我們所處的位置。因此，根據您想要如何計算，無論是治療患者還是整個市場，我們的市場份額可能接近 20%，大約略低於這個數字，但成長非常強勁。

And then as far as kind of the indicators of increased prescribing and the physician confidence, I think it's what I said in my remarks, they're just -- they're experiencing, they're learning more about the data and they're seeing it in their patients. So I think the best way for a physician to learn about this drug is to trial in their patients and see how well the patients respond. And that's why of current prescribers now 52% of them say they are extremely likely to prescribe more because they are seeing the response in their patients.

至於增加處方和醫生信心的指標，我認為這就是我在演講中所說的，他們只是——他們正在經歷，他們正在了解更多關於數據的信息，他們正在在他們的病人身上看到了這一點。因此，我認為醫生了解這種藥物的最佳方法是在患者身上進行試驗，看看患者的反應如何。這就是為什麼目前的處方醫生中有 52% 表示他們極有可能開更多處方，因為他們看到了患者的反應。

And we do these surveys every quarter and we always ask physicians, what are you going to treat your patients with over the next 12 months? And what we've seen over the last year is that the drug they seek to grow over the next 12 months is ORLADEYO. That is where they see the most growth in the marketplace. And I think it's because of what they're seeing with the results in their patients.

我們每季都會進行這些調查，我們總是會問醫生，在接下來的 12 個月裡你們將用什麼來治療你的病人？去年我們看到的是，他們尋求在未來 12 個月內開發的藥物是 ORLADEYO。這是他們看到市場成長最快的地方。我認為這是因為他們在患者身上看到的結果。

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

我們的問答環節到此結束。我想將會議轉回吉姆·斯通豪斯（Jim Stonehouse）發表閉幕詞。

Yeah, I'd just like to wrap it up by saying, again, what I said before. It was an absolutely amazing quarter. It's two in a row now. The momentum we have, we see no signs of it slowing down. We're now having revenue over $100 million per quarter. And you should ask yourself, why is this happening? It's because this drug really works, right? When a patient sees control, they have the same kind of control they had with any other prophy medicine they were on before, and they get it with a once daily oral medicine. And that is why we're seeing this great success.

是的，我想再說一遍我之前說過的話來結束它。這絕對是一個令人驚嘆的季度。現在已經連續兩場了我們所擁有的勢頭沒有放緩的跡象。我們現在每季的營收超過 1 億美元。你應該問自己，為什麼會發生這種事？因為這個藥確實有效吧？當患者看到控制時，他們會得到與之前使用的任何其他預防藥物相同的控制，並且每天一次口服藥物即可獲得控制。這就是我們取得如此巨大成功的原因。

And then the last thing I'd say is thanks to the commercial team for just have an outstanding performance and continuing to build the momentum in this company. Thank you.

最後我要說的是感謝商業團隊的出色表現並繼續為公司發展勢頭。謝謝。

This concludes our question and answer session. I would like to thank everybody for joining today's presentation. You may now disconnect.

我們的問答環節到此結束。我要感謝大家參加今天的演講。您現在可以斷開連線。