BioCryst Pharmaceuticals Inc (BCRX) 2023 Q4 法說會逐字稿

Good day and welcome to the BioCryst fourth-quarter 2023 earnings conference call.

美好的一天，歡迎參加 BioCryst 2023 年第四季財報電話會議。

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

（操作員說明）請注意，正在記錄此事件。

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

我現在想把會議交給 BioCryst 的 John Bluth。

Please go ahead.

請繼續。

Thank you very much.

非常感謝。

Good morning, and welcome to BioCryst fourth-quarter and yearend 2023 corporate update and financial results conference call.

早安，歡迎參加 BioCryst 第四季和 2023 年底公司更新和財務業績電話會議。

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

今天的新聞稿和隨附的幻燈片可在我們的網站上取得。

Participating with me today are CEO, Jon Stonehouse; CFO, Anthony Doyle; Chief Commercial Officer, Charlie Gayer; Chief Medical Officer, Dr. Ryan Arnold.

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；首席商務官查理·蓋爾；首席醫療官瑞安·阿諾德博士。

Following our remarks, we'll answer your questions.

在我們的發言之後，我們將回答您的問題。

Before we begin, please note that today's conference call will contain forward-looking statements, including the statements regarding future results unaudited and forward-looking financial information as well as the company's future performance and or achievements.

在開始之前，請注意，今天的電話會議將包含前瞻性聲明，包括有關未經審計的未來業績和前瞻性財務資訊以及公司未來業績和/或成就的聲明。

These statements are subject to known and unknown risks and uncertainties which may cause our actual results, performance, or achievements to be materially different from any future results or performance expressed or implied in this presentation.

這些陳述受到已知和未知的風險和不確定性的影響，這些風險和不確定性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。

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

您不應過度依賴這些前瞻性陳述。

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

如需了解更多信息，包括風險因素的詳細討論，請參閱公司向美國證券交易委員會提交的文件，這些文件可以在我們的網站上訪問。

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

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。

For 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 biocryst.com. Now I'd like to turn the call over to Jon Stonehouse.

如需將這些非 GAAP 指標與最直接可比較的 GAAP 財務指標進行核對，請參閱我們投資者關係網站 biocryst.com 新聞稿部分中發布的收益新聞稿。現在我想把電話轉給喬恩‧斯通豪斯。

Thanks, John. 2023 was another impressive year for ORLADEYO, starting with generating $326 million in revenue in just the third year of launch.

謝謝，約翰。 2023 年對 ORLADEYO 來說又是令人印象深刻的一年，在推出的第三年就創造了 3.26 億美元的收入。

We continue to make great progress toward our goal of global peak revenue of $1 billion.

我們持續朝著全球營收高峰 10 億美元的目標取得重大進展。

Let me explain why.

讓我解釋一下原因。

Late last year, we laid out a set of assumptions that would lead us to $800 million in peak sales in the US.

去年年底，我們提出了一系列假設，這些假設將使我們在美國的銷售額達到 8 億美元的高峰。

The first assumption was to exit last year with a base of approximately 1,050 patients on therapy.

第一個假設是去年退出，接受治療的患者基數約為 1,050 名。

We actually exited the year with a base of over 1,100 patients on therapy.

實際上，今年結束時，我們有超過 1,100 名患者接受了治療。

Second, we added over 300 net new patients, well above the average of 200 per year we need.

其次，我們淨增加了 300 多名新患者，遠高於我們每年所需的平均 200 名患者。

Third, we improve the percentage of paid therapy in the commercially insured part of the business from 7% to 79%.

第三，我們將商業保險部分的付費治療比例從7%提升到79%。

And fourth, we made a modest net annual price increase in the US.

第四，我們在美國的年度淨價格略有上漲。

In all four of these assumptions Charlie (technical difficulty) executed such that we met or exceeded each of these goals.

在查理（技術難度）的所有四個假設中，我們都執行了這些假設，從而使我們達到或超過了每個目標。

That's great execution and real progress towards our goal.

這是出色的執行力，也是實現我們目標的真正進展。

Today, we'll focus our prepared remarks on ORLADEYO in the financials.

今天，我們將重點放在奧拉德約的財務狀況。

We'll start with Ryan, who will cover the data presented at Quad AI this past weekend and how many patients ORLADEYO are seeing excellent control of their HAE, along with the convenience of once daily dosing.

我們將從 Ryan 開始，他將介紹上週末在 Quad AI 上提供的數據，以及有多少 ORLADEYO 患者的 HAE 得到了良好的控制，並且每天一次給藥的便利性。

With that, I'll pass it over to Ryan.

有了這個，我會把它交給瑞安。

Thanks, Jon.

謝謝，喬恩。

I've had the privilege during my career to work on several therapies that helped change the lives of patients who live with chronic life-altering diseases.

在我的職業生涯中，我有幸參與了多種療法的研究，這些療法幫助改變了患有慢性改變生活疾病的患者的生活。

An important lesson I've learned is that long-term data and particularly evidenced from real-world experience, especially in rare disease, are critical to understanding how a treatment can address unmet needs and change the lives of different patient populations.

我學到的一個重要教訓是，長期數據，特別是來自現實世界經驗的證據，尤其是在罕見疾病方面，對於理解治療如何解決未滿足的需求並改變不同患者群體的生活至關重要。

This is an exciting time for ORLADEYO because after three, four years on the market, we are seeing a very consistent picture emerged from the building evidence.

對於 ORLADEYO 來說，這是一個令人興奮的時刻，因為經過三、四年的市場推廣，我們看到建築證據中出現了非常一致的情況。

The real-world experience and the long-term clinical data are telling a very consistent story on how ORLADEYO can provide meaningful benefits to a variety of HAE patients.

現實世界的經驗和長期臨床數據講述了一個非常一致的故事，說明 ORLADEYO 如何為各種 HAE 患者提供有意義的益處。

We recently published the final analysis of data from the open label long-term extension portion of the APeX-2 study of berotralstat.

我們最近發布了 berotralstat 的 APeX-2 研究的開放標籤長期擴展部分數據的最終分析。

The patients who started on blinded berotralstat 150 milligrams and completed a full two years of the study, had an average reduction of 90.8% in HAE attacks compared to their baseline rates.

開始使用盲法 berotralstat 150 毫克並完成整整兩年研究的患者，與基線發生率相比，HAE 發作平均減少了 90.8%。

But most don't measure their tax and percentages.

但大多數人並沒有衡量他們的稅收和百分比。

What's most meaningful to people living with HAE, is that they get the chance to live a normal life by minimizing their attack burden and experience meaningful improvements in their everyday quality of life, all while avoiding the unnecessary potential burdens of treatment.

對於 HAE 患者來說，最有意義的是，他們有機會透過最大限度地減少發作負擔過正常的生活，並在日常生活品質方面獲得有意義的改善，同時避免不必要的潛在治療負擔。

ORLADEYO treated patients in this long-term study reported rapid and sustained improvements from baseline of 3.3 attacks per month to 0.3 attacks per month after two years with a median attack rate of zero at month 24.

在這項長期研究中，接受 ORLADEYO 治療的患者報告，兩年後從每月 3.3 次發作的基線快速持續改善至每月 0.3 次發作，第 24 個月的中位發作率為零。

These patients also reported meaningful long-term improvements in quality of life, treatment satisfaction, and an overall safety profile that is very reassuring for people living with this lifelong disease.

這些患者還報告說，生活品質、治療滿意度和整體安全狀況都得到了有意義的長期改善，這對於患有這種終生疾病的人來說非常令人放心。

That kind of change in a sustained low rate of attacks with just one pill once a day is transformative for many patients.

每天只需服用一粒藥就能實現持續低發作率的這種變化對許多患者來說是變革性的。

These long-term data from our clinical program tone important part of the story, which is being consistently reinforced by our expanding base of real-world evidence.

這些來自我們臨床計畫的長期數據為故事的重要部分奠定了基礎，而我們不斷擴大的現實世界證據基礎不斷強化了這一點。

This past weekend at the Quad AI meeting in Washington, DC, we presented five posters showing strong real with evidence with ORLADEYO in a variety of patients with HAE.

上週末在華盛頓特區舉行的 Quad AI 會議上，我們展示了五張海報，展示了 ORLADEYO 在各種 HAE 患者中的真實證據。

What patients are experiencing in the real world is consistent with the two-year clinical data.

患者在現實世界中的經驗與兩年的臨床數據一致。

Patients with type 1 or 2 HAE are reporting long-term median attack rates of around half an attack per month after switching from other prophylactic therapies.

1 型或 2 型 HAE 患者報告，在改用其他預防性治療後，長期中位數發生率約為每月一半。

By their own account, these patients are having fewer attacks on ORLADEYO than on their prior therapies.

根據他們自己的說法，這些患者接受 ORLADEYO 治療後的發作次數比之前接受治療的患者要少。

Patients report rapid and sustained reduction in attacks or maintaining attack-free status regardless of whether their baseline monthly attack rate was very high or very low prior to starting on ORLADEYO.

患者報告發作迅速持續減少或保持無發作狀態，無論在開始使用 ORLADEYO 之前他們的基線每月發作率是非常高還是非常低。

These data on attacks regardless of baseline attack rate, are consistent with evidence we have presented from our clinical trials.

無論基線攻擊率如何，這些攻擊數據都與我們從臨床試驗中提供的證據一致。

Patients diagnosed by their physicians as having HAE with normal C1-inhibitor levels, also are reporting rapid and sustained reductions in attacks on ORLADEYO.

被醫生診斷為患有 HAE 且 C1 抑制劑水平正常的患者也報告 ORLADEYO 的發作迅速且持續減少。

And we are seeing similar outside of the United States, particularly in countries like France where patients can be followed in comprehensive programs with the active involvement of healthcare providers.

我們在美國以外也看到了類似的情況，特別是在法國這樣的國家，在醫療保健提供者的積極參與下，患者可以透過綜合計劃進行追蹤。

This real-world evidence demonstrating the long-term safety and effectiveness of ORLADEYO is exciting.

這一現實世界的證據證明了 ORLADEYO 的長期安全性和有效性，令人興奮。

Our team has been hearing the stories of ORLADEYO oil a day over the past three years.

在過去的三年裡，我們的團隊每天都會聽到奧拉德約石油的故事。

And these data further illustrate why there's such a favorable treatment option for people living with HAE.

這些數據進一步說明了為什麼 HAE 患者有如此有利的治療選擇。

What is even more exciting is that the data we presented at Quad AI are just the start.

更令人興奮的是，我們在 Quad AI 上提供的數據只是一個開始。

We will continue to generate more real evidence with ORLADEYO over the coming years.

未來幾年，我們將繼續與 ORLADEYO 一起提供更多真實證據。

And we look forward to showing again and again how this treatment can help change the lives of patients and families impacted by HAE.

我們期待一次又一次地展示這種治療方法如何幫助改變受 HAE 影響的患者和家庭的生活。

I'll now turn it over to Charlie to describe how this emerging evidence is translating to our commercial efforts.

現在我將把它交給查理來描述這些新出現的證據如何轉化為我們的商業努力。

Thanks, Ryan.

謝謝，瑞安。

As John noted earlier, we recently described how consistent net patient growth of 200 per year for the next several years puts us on track for $800 million in sales in the United States.

正如約翰之前指出的，我們最近描述了未來幾年每年 200 名患者的淨增長將如何使我們在美國的銷售額預計將達到 8 億美元。

Entering our fourth year on the market, we are very much on track because we added 321 ORLADEYO patients in the US in 2023.

進入市場第四年，我們的進展非常順利，因為我們在 2023 年在美國新增了 321 名 ORLADEYO 患者。

The real-world evidence that Ryan described helps explain this growth.

瑞安所描述的現實世界證據有助於解釋這種增長。

Patients would like convenience, there's no doubt about that.

毫無疑問，患者希望獲得便利。

But what they demand is efficacy control of their attacks.

但他們要求的是對其攻擊的有效控制。

The real-world data with ORLADEYO clearly demonstrate that patients can have both, efficacy and convenience.

ORLADEYO 的真實世界數據清楚地表明，患者可以同時獲得療效和便利性。

No trade-offs.

無需權衡。

Our teams have done a very good job of launching ORLADEYO, but in the end, patient experience will dictate how far we go.

我們的團隊在推出 ORLADEYO 方面做得非常出色，但最終，患者的體驗將決定我們能走多遠。

Ryan shared that after switching to ORLADEYO from other prophylaxis therapies, patients experienced a median rate of about half an attack per months.

Ryan 表示，從其他預防療法轉向 ORLADEYO 後，患者的中位發病率約為每月一半。

What that means for patients is that many or most months are attack-free, and attacks that need to be treated are often less severe.

對於患者來說，這意味著許多或大多數月份都不會發作，需要治療的發作通常不太嚴重。

Half an attack per month is also an important benchmark.

每月半次攻擊也是一個重要的基準。

We do market research with large samples of HAE patients, and we've reported previously at a medical congress that half an attack per month matches the level of attack control reported by patients taking injectable prophylaxis therapies in the real world.

我們對大量 HAE 患者樣本進行市場研究，我們之前在一次醫學大會上報告稱，每月有一半的發作與現實世界中接受注射預防療法的患者報告的發作控制水平相符。

This low and consistent rate of attacks on ORLADEYO meets patients' expectations because they know from experience that perfect control is unlikely with any product.

ORLADEYO 的這種低且一致的發作率符合患者的期望，因為他們從經驗中知道任何產品都不可能實現完美的控制。

For many patients to be able to get that level of control with an oral once daily therapy is transforming how they live with HAE.

對於許多患者來說，每天一次口服治療能夠獲得一定程度的控制，這正在改變他們患有 HAE 的方式。

We recently conducted an anonymous market research project with a sizable cohort of patients who have experience with ORLADEYO and asked them as part of an exercise to write a letter to ORLADEYO describing that experience.

我們最近對大量有 ORLADEYO 經歷的患者進行了一項匿名市場研究項目，並要求他們寫一封信給 ORLADEYO 描述這一經歷，作為練習的一部分。

Themes such as, you gave me confidence, you changed my life, and I feel like a normal person again, were common.

諸如「你給了我信心，你改變了我的生活，我感覺又像個正常人了」這樣的主題很常見。

The strong evidence from patients also continues to shape prescriber expectations and give them confidence.

來自患者的有力證據也繼續塑造處方者的期望並給他們信心。

Our large quarterly surveys of allergists in 2023, showed they consistently expected to grow the proportion of their HAE patients treated with ORLADEYO by about 30% over the next 12 months.

我們在 2023 年對過敏症專家進行的大型季度調查顯示，他們一致預計在未來 12 個月內接受 ORLADEYO 治療的 HAE 患者比例將增加約 30%。

As we noted in our press release today, the number of patients on paid therapy or our long-term free product program also grew by 30% in 2023, tracking with physician predictions.

正如我們在今天的新聞稿中指出的那樣，根據醫生的預測，接受付費治療或長期免費產品計劃的患者數量在 2023 年也增加了 30%。

Currently about 50% of patients on ORLADEYO has switched from other prophylaxes.

目前，約 50% 的 ORLADEYO 患者已放棄其他預防措施。

But the allergists in our 2023 surveys expect about two thirds of ORLADEYO growth over the next year to come from switches from injectable prophylaxis.

但我們 2023 年調查中的過敏專家預計，奧拉德約明年約三分之二的成長來自於注射預防藥物的轉變。

By the end of 2023 ORLADEYO have been prescribed over 2,500 times in the United States.

截至 2023 年底，美國已開出 ORLADEYO 超過 2,500 次。

That means that at least 5,000 diagnosed and treated patients have not yet tried ORLADEYO.

這意味著至少有 5,000 名診斷和治療的患者尚未嘗試過 ORLADEYO。

Over 1,000 US healthcare providers have now prescribed ORLADEYO, including over 200 new prescribers in 2023.

目前已有超過 1,000 家美國醫療保健提供者開出了 ORLADEYO 處方，其中包括 2023 年新增的 200 多名處方者。

But clearly, there's an opportunity for HAE treaters to (technical difficulty) -- for many more of their patients, just as our market research predicts.

但顯然，正如我們的市場研究預測的那樣，HAE 治療者有機會（技術難度）為更多的患者解決這個問題。

We have way more opportunity in front of us than behind us.

我們面前的機會比我們身後的機會多得多。

And the growing body of evidence about how ORLADEYO is changing patients' lives is going to help us get there.

越來越多的證據表明 ORLADEYO 如何改變患者的生活，這將幫助我們實現這一目標。

I'll pass it to Anthony to describe our financial performance.

我將把它交給安東尼來描述我們的財務表現。

Thanks, Charlie.

謝謝，查理。

So it was great to see such a strong Q4 and full year 2023 for ORLADEYO.

因此，很高興看到奧拉德約第四季和 2023 年全年表現如此強勁。

Not just the revenue performance, but the continued underlying strength in net new patient adds, giving us confidence of achieving between $380 million (technical difficulty) $400 million in global ORLADEYO revenue this year on our path to peak sales of $1 billion.

不僅是收入表現，還有淨新患者的持續潛在實力增加，使我們有信心今年奧拉德約全球收入達到3.8 億美元（技術難度）4 億美元，並朝著10 億美元的峰值銷售額邁進。

You can find our detailed fourth quarter financials in today's earnings press release and I call your attention to a few items.

您可以在今天的收益新聞稿中找到我們詳細的第四季度財務數據，我請您注意一些項目。

Total revenue for the quarter came in at $93.4 million, $90.9 of which came from ORLADEYO and ORLADEYO net sales for full year 2023 at $326 million, an increase of $74 million or 30% year over year.

該季度總收入為 9,340 萬美元，其中 90.9 美元來自 ORLADEYO，ORLADEYO 2023 年全年淨銷售額為 3.26 億美元，年增 7,400 萬美元，即 30%。

Of the $90.9 million of global ORLADEYO revenue, $79.4 million came from US sales, with the remaining $11.5 million or 12.7% coming from ex-US.

ORLADEYO 全球 9,090 萬美元收入中，7,940 萬美元來自美國銷售，其餘 1,150 萬美元（即 12.7%）來自美國以外地區。

On a full-year basis, US ORLADEYO sales contributed $288.4 million of the $326 million global total, with the remaining $37.6 million or 11.5% coming from ex-US.

在全年 3.26 億美元的全球總銷售額中，美國奧拉德約的銷售額貢獻了 2.884 億美元，其餘 3,760 萬美元（即 11.5%）來自美國以外地區。

Operating expenses, not including non-cash stock comp for the quarter were approximately $119.6 million, included in this are significant one-time expenses.

本季的營運費用（不包括非現金股票補償）約為 1.196 億美元，其中包括大量一次性費用。

These include about $5.4 million attributable to the R&D reorganization, including costs related to the reduction in force and the postponement of the expansion of the Discovery Center in Birmingham, Alabama.

其中包括約 540 萬美元的研發重組費用，其中包括與減少兵力和推遲阿拉巴馬州伯明翰探索中心擴建相關的費用。

The $5 million upfront payment we made to Clearside related to our partnership as well as around $7 million in CMC, another trial costs related to our partnership decision for BCX-10013, all of which explain the increase in OpEx from Q3 of 2023.

我們向Clearside 支付的與我們的合作夥伴關係相關的500 萬美元預付款，以及約700 萬美元的CMC 費用，以及與我們BCX-10013 合作夥伴決定相關的另一項試驗成本，所有這些都解釋了2023 年第三季營運支出的成長。

Operating expenses, not including non-cash stock comp for the full year came in at $379.5 million, which when excluding the $5.4 million of restructuring one-time adjustments I mentioned, landed within our guidance range.

全年營運費用（不包括非現金股票補償）為 3.795 億美元，在排除我提到的 540 萬美元重組一次性調整後，該費用落在我們的指導範圍內。

We expect that quarterly expenses in 2024 will normalize in the low to mid $90 million range, taking us in line with our full year 2024 guidance of between $365 million and $375 million, and essentially flat to 2023.

我們預計 2024 年的季度支出將在 9,000 萬美元的低至中水平範圍內正常化，這使我們與 2024 年全年 3.65 億至 3.75 億美元的指導保持一致，並與 2023 年基本持平。

Cash at the end of the year was up $390.8 million and net cash utilization for the quarter was $8.4 million.

年末現金增加 3.908 億美元，本季淨現金利用率為 840 萬美元。

In January, we provided guidance on our near-term timeline to achieve profitability.

一月份，我們就實現盈利的近期時間表提供了指導。

For 2024, we expect that revenue will exceed OpEx, not including non-cash stock comp, and this will result in us generating an operating profit this year.

到 2024 年，我們預計收入將超過營運支出（不包括非現金股票補償），這將使我們今年產生營業利潤。

Additionally, with revenue exceeding $350 million, it puts us into tier whereby the incremental revenue will be more profitable as the blended royalty rate is reduced.

此外，隨著收入超過 3.5 億美元，它使我們進入了隨著混合特許權使用費率降低而增加的收入將變得更有利可圖的階段。

In the second half of 2025, we expect to be approaching net income and cash flow positivity on a quarterly basis.

2025 年下半年，我們預期季度淨利和現金流將接近正值。

And then in 2026, we expected to achieve net income and cash flow positivity on a full-year basis, achieving independence from the capital markets.

然後到2026年，我們預計全年實現淨利和現金流為正，並獨立於資本市場。

While we also continue to invest in further expanding our global reach for ORLADEYO and expanding our label with the pediatric indication, while also further advancing our exciting early-stage pipeline, puts the company in a very strong position moving forward.

我們也繼續投資，進一步擴大 ORLADEYO 的全球影響力，擴大我們的兒科適應症品牌，同時進一步推進我們令人興奮的早期產品線，使該公司在前進中處於非常有利的地位。

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

我們現在將開放接線員進行問答。

(Operator Instructions) Tazeen Ahmad, Bank of America.

（操作員指示）Tazeen Ahmad，美國銀行。

Hi, guys.

嗨，大家好。

Good morning, thanks for taking my questions.

早上好，感謝您回答我的問題。

Can you give us a little bit of color regarding the patients that you're able to add last year that came as you said higher than what you anticipated.

您能否給我們一些關於您去年能夠添加的患者的信息，這些患者的數量高於您的預期。

Was there a particular profile of patients that was added that you weren't expecting?

是否新增了您未預料到的特定患者資料？

And in general, do you have a sense of what level of baseline attacks patients have when they are switching in particular to your drug from another drug?

一般來說，當患者從另一種藥物轉向您的藥物時，您是否了解患者的基線發作程度是多少？

And then I have a follow-up.

然後我有一個後續行動。

Thanks.

謝謝。

Sure.

當然。

Tazeen, there wasn't really a profile that we weren't expecting.

Tazeen，確實沒有我們沒有預料到的個人資料。

Since the beginning of launch, we've been getting patients from all different profiles as Ryan laid out with some of the data. (technical difficulty) -- sorry, some of the data's that we've presented this weekend at Quad AI, regardless of baseline attack rate, regardless of background therapy, patients do really well on ORLADEYO and -- sorry, I can't.

自推出以來，我們一直在收集來自各種不同情況的患者，正如 Ryan 列出的一些數據一樣。 （技術難度）——抱歉，我們本週末在 Quad AI 上提供的一些數據，無論基線發病率如何，無論背景治療如何，患者在 ORLADEYO 上的表現都非常好——抱歉，我不能。

Do you want to take the rest of that Ryan?

你想帶走瑞安剩下的部分嗎？

Yeah.

是的。

Is there any phenotype?

有沒有表型？

I think what she's asking is, is there a baseline attack rate?

我想她問的是，是否有基線攻擊率？

Is there any phenotype that we're seeing, any particular group that's going into switching to ORLADEYO.

我們是否看到任何表型，是否有任何特定群體將轉向奧拉德約。

And I'll call your attention to slide 6 and slide 8 in our deck, both of these speak to the background our baseline attack rates.

我會提醒您注意我們幻燈片中的幻燈片 6 和幻燈片 8，這兩張幻燈片都說​​明了我們的基線攻擊率的背景。

And what you'll see here is despite varying attack rate speed, high or low, patients do very well in ORLADEYO.

您將在這裡看到的是，儘管發病率速度不同，無論高低，患者在奧拉德約的表現都非常好。

Slide 8 specifically calls out a baseline attack rate of 1.33 at baseline for those with HAE type 1 or type 2.

第 8 張投影片特別指出，對於第 1 型或第 2 型 HAE 患者，基線發生率為 1.33。

And again, those patients did very well, achieving an attack rate of 0.50 at day 540.

同樣，這些患者的表現也非常好，在第 540 天時的發生率達到了 0.50。

So they had a rapid and sustained reduction in their attack rates.

所以他們的攻擊率迅速且持續地降低。

So basically, a variety of patients can benefit from ORLADEYO regardless of what their baseline attack rate is.

因此，基本上，各種患者都可以從 ORLADEYO 中受益，無論他們的基線發病率是多少。

Yeah, so Tazeen, you really can't predict it.

是的，所以塔津，你真的無法預測它。

So the goal is to get everybody to try it and see if it works for them.

因此，我們的目標是讓每個人都嘗試一下，看看它是否適合他們。

Yeah, I just want to ask about whether in real life, you are seeing something different relative to what you would see in clinical trials.

是的，我只是想問一下，在現實生活中，您是否看到了與臨床試驗中看到的不同的東西。

(inaudible) And then maybe, just as a follow up, how are you thinking about discontinuation rates on a go-forward basis?

（聽不清楚）然後，也許，作為後續行動，您如何考慮未來的停藥率？

How have they been trending?

他們的趨勢如何？

Any changes from the time that you launched?

自推出以來有什麼變化嗎？

Thanks.

謝謝。

So Charlie's

所以查理的

(multiple speakers) --

（多位發言者）——

I think I can talk again.

我想我可以再說話了。

It's my asthma attack.

這是我的氣喘發作。

The discontinuation has been really steady in 2023 and the last few years.

2023 年和過去幾年的停產情況非常穩定。

So still when a patient starts ORLADEYO, we get 60% of those patients to 12 months and then very few discontinuations after that.

因此，當患者開始使用 ORLADEYO 時，我們將其中 60% 的患者治療至 12 個月，之後很少有人停藥。

And I think relating to your earlier questions too, we see the same retention rate regardless of patients' background.

我認為也與您先前的問題相關，無論患者的背景如何，我們都看到相同的保留率。

So regardless of their attack rate, regardless on whether they're switching from prophylaxis or coming in from acute only, they're all staying on it at about that same rate, 60% a year.

因此，無論他們的發病率如何，無論他們是從預防治療轉為急性治療，還是僅從急性治療開始，他們都以大約相同的速度堅持使用治療，即每年 60%。

Okay, thank you.

好的謝謝。

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, guys.

嘿，早上好，夥計們。

Thanks for taking my question.

感謝您提出我的問題。

Congrats on the continued progress.

祝賀您不斷取得進步。

I'm curious if you could talk a little bit about your sales and marketing strategy this year relative to last year.

我很好奇您能否談談今年與去年相比的銷售和行銷策略。

Do you expect continued pull through from some of the team territory changes that were implemented in 2023?

您預計 2023 年實施的一些團隊區域變更會繼續發揮作用嗎？

In 2024, what do you expect to be the focus of the additional SG&A investment for this year?

2024 年，您預計今年額外 SG&A 投資的重點是什麼？

And are there any changes to your commercial approach or strategy with an expected even greater proportion of the opportunity now coming from the switchers versus those patients who are on on-demand only?

您的商業方法或策略是否有任何變化，與那些僅按需服務的患者相比，現在預計更大比例的機會來自轉換者？

Charlie, you want to take that?

查理，你想要那個嗎？

Yeah.

是的。

Hey, Brian.

嘿，布萊恩。

So one of the reasons I do think we did so well last year is we did make those adjustments to the teams in the beginning of 2023.

因此，我確實認為我們去年表現如此出色的原因之一是我們確實在 2023 年初對團隊進行了這些調整。

By the end of last year, the additional sales folks, the additional patient services market access that we added, everyone was active and really comfortable in their roles and working well together.

到去年年底，我們增加了額外的銷售人員、額外的患者服務市場准入，每個人都非常活躍，在自己的角色中感到非常自在，並且合作良好。

And I think that is a big part of our performance.

我認為這是我們表現的重要組成部分。

And then going forward to your question about any changes in the kind of data that again, that Ryan presented, I think, is really critical.

然後繼續回答你關於瑞安再次提出的數據類型是否發生變化的問題，我認為這非常關鍵。

And we're very focused on getting patients and physicians comfortable with the switching from an injectable prophylaxis to ORLADEYO is opportunity for patients to really benefit.

我們非常注重讓患者和醫生接受從注射預防藥物轉向 ORLADEYO 的轉變，這是患者真正受益的機會。

And I think we're seeing that our customers are starting to understand that.

我認為我們看到我們的客戶開始理解這一點。

So we'll focus on that messaging.

因此，我們將重點關注該訊息傳遞。

And Brian

還有布萊恩

--

--

Got it.

知道了。

I'd add.

我想補充一下。

One thing I'd add, Brian, is that Charlie mentioned, was this increasing competition.

布萊恩，我要補充的一件事是查理提到的，競爭日益激烈。

And one of the things is that we're seeing at Quad AI and other place, we had a standing room only session at Quad AI and the confidence in the docs is really high.

其中一件事是，我們在 Quad AI 和其他地方看到，我們在 Quad AI 上舉行了一場只有站著的會議，對文件的信心非常高。

You compare that to a year ago where people were still kind of on the fence.

與一年前相比，人們仍然持觀望態度。

And it's only because they've had experienced and they're seeing it work extremely well in patients.

這只是因為他們有過經驗並且看到它在患者身上效果非常好。

So that will have an effect on that will be really positive for ORLADEYO and for patients.

因此，這將對奧拉德約和患者產生真正積極的影響。

Got it, thanks, Jon.

明白了，謝謝，喬恩。

And maybe just a quick follow-up.

也許只是快速跟進。

It sounds like you've got some visibility to getting to the goal of a paid rate of 85% by the end of the decade.

聽起來您對在本十年末實現 85% 付費率的目標有了一定的了解。

Where do you think you can get the paid rate this year relative to 2023?

相對於 2023 年，您認為今年的繳費率在哪裡？

What's embedded in your guidance and how much potential upside could there be versus your guidance if things go better than expected on that front?

您的指導包含哪些內容？如果這方面的情況比預期好，那麼與您的指導相比，潛在的上行空間有多大？

And I'll hop back in the queue, thanks.

我會重新加入隊列，謝謝。

Brian, what we've said before is that 85% number, we are very confident we'll get there, but it's going to take us a few years.

Brian，我們之前說過的是 85% 的數字，我們非常有信心能夠實現這一目標，但這需要我們幾年的時間。

And so we announced this morning in the press release that we ended last year at a rate of 71.5%.

因此，我們今天早上在新聞稿中宣布，去年的成長率為 71.5%。

So we'll make some incremental improvements to that.

因此，我們將對此進行一些漸進式改進。

But don't expect any major changes.

但不要指望會發生任何重大變化。

We're not going to jump straight to 85%.

我們不會直接跳到 85%。

We'll get there probably more in the 2026, 2027 timeframe.

我們可能會在 2026 年、2027 年的時間範圍內實現更多目標。

Got it.

知道了。

Thanks, Charlie, thanks again.

謝謝，查理，再次感謝。

Jessica Fye, JPMorgan.

潔西卡法耶，摩根大通。

Hey, guys, good morning.

嘿，夥計們，早安。

Thanks for taking my questions.

感謝您回答我的問題。

Can you just talk about the extent to which your near and long-term top-line expectations for ORLADEYO reflects the introduction of less frequently dosed injectables and other orals.

您能否談談您對 ORLADEYO 的近期和長期營收預期在多大程度上反映了較少劑量注射劑和其他口服藥物的引入。

Thank you.

謝謝。

Hi, Jess.

嗨，傑西。

We take into account all the introductions of new products, including new injectables and possibly in the future, new orals.

我們考慮了所有新產品的推出，包括新的注射劑以及未來可能的新口服劑。

And what Jinky Rosselli and I described at the last earnings call is that the patients once they're on therapy and doing well are tend to be really sticky on that therapy.

金基·羅塞利和我在上次財報電話會議上描述的是，患者一旦接受治療並且表現良好，往往會非常堅持這種治療。

And when patients are doing as well as they are on ORLADEYO, we don't see them moving to other therapies.

當患者在 ORLADEYO 上表現良好時，我們不會看到他們轉向其他療法。

The other key part of it is that we have a very differentiated product in a once daily oral, and that's something that patients and healthcare providers really want.

另一個關鍵部分是，我們擁有一個非常差異化的每日口服產品，這是患者和醫療保健提供者真正想要的。

And so a new injectable therapy offers some incremental benefits, but it is not highly differentiated the way ORLADEYO is.

因此，一種新的注射療法提供了一些增量益處，但它並不像 ORLADEYO 那樣高度差異化。

Yeah, I think Jess, flip the question around and ask, why would they go on to another product?

是的，我想傑西，把問題反過來問，為什麼他們會繼續使用另一種產品？

What's the incremental benefit?

增量收益是什麼？

And I think what Charlie presented today and what Ryan presented, is patients aren't sacrificing efficacy for convenience.

我認為查理今天和瑞安提出的觀點是，病人不會為了方便而犧牲療效。

This drug works spectacularly well in certain patient, and it's a once-a-day drug.

這種藥物對某些患者效果非常好，而且是每日一次的藥物。

So what incremental benefit is going to cause them to switch?

那麼什麼增量利益會導致他們轉變呢？

And we've seen where getting switches, you'd have to have some incremental benefit.

我們已經看到，在哪裡進行切換，您必須獲得一些增量收益。

So the question is, it can't be efficacy, right?

那麼問題來了，這不可能有功效吧？

Because if you're controlled on our drugs, then you can't do any better.

因為如果您對我們的藥物進行了控制，那麼您就無法做得更好。

Thank you.

謝謝。

You're welcome.

不客氣。

Liisa Bayko, Evercore ISI.

莉莎·貝科，Evercore ISI。

Hi, just a follow up on that.

嗨，只是後續行動。

I mean you do have a half an attack rate per month, right?

我的意思是你每個月的攻擊率確實有一半，對嗎？

Which is one in every two months which is six per year after switching from other prophylax.

每兩個月就有一次，從其他預防措施轉換後每年有六次。

So would that not be, like those types of patients would they not be interested in maybe trying something else?

那麼，就像那些類型的患者一樣，他們不會對嘗試其他東西不感興趣嗎？

That would just be my like one question, but I actually have other questions beyond that.

這只是我的一個問題，但除此之外我實際上還有其他問題。

Ryan, do you want to tackle that one?

瑞安，你想解決這個問題嗎？

I mean, the bottom line is nobody does better than that.

我的意思是，底線是沒有人比這做得更好。

That's kind of the standard.

這就是某種標準。

Every drug has breakthrough attacks.

每種藥物都有突破性的攻擊。

And in that number is a mixture of people that aren't having attacks and some that are.

這個數字中既有未遭受攻擊的人，也有遭受攻擊的人。

But Ryan, I don't know if there's anything else to add.

但 Ryan，我不知道還有什麼要補充的嗎？

Yeah.

是的。

As Jon alluded to, you've seen similar attack control with other injectable therapies.

正如喬恩所提到的，您已經看到其他注射療法具有類似的攻擊控製作用。

And we view this not as a trade off, but a trade up.

我們認為這不是一種權衡，而是一種升級。

Because again, patients don't want just attack control, they want the added convenience as the quality-of-life improvements.

因為，患者不僅想要控制發作，他們也希望隨著生活品質的改善而增加便利性。

And again, we've reported all of that both in our clinical studies as well as in the real-world evidence.

再說一次，我們在臨床研究和現實世界的證據中報告了所有這些。

So, half an attack per month is doing very well.

因此，每月進行一半的攻擊效果非常好。

And again, that doesn't include attack severity, which for some they've shared these are very manageable.

再說一次，這不包括攻擊的嚴重程度，對某些人來說，這些嚴重程度是非常容易管理的。

So again, this is a very notable improvement and looks very similar to injectables in terms of attack rate control.

再說一次，這是一個非常顯著的改進，在攻擊率控制方面看起來與注射劑非常相似。

Yeah, so Liisa, don't get confused by the numbers of attack rate reduction in a pivotal study because the confidence intervals from those studies it overlap.

是的，所以莉莎，不要對關鍵研究中攻擊率降低的數字感到困惑，因為這些研究的置信區間是重疊的。

They all work is the bottom line.

它們都是工作的底線。

And they're not perfect, they all have some breakthrough attacks.

而且他們都不是完美的，他們都有一些突破性的攻擊。

Okay, and have you done any convenience analysis, like market research on this sort of like very long acting agents?

好的，您是否做過任何便利分析，例如對此類長效代理的市場研究？

Because it seems like at some point you might flip a balance between taking an oral pill and frequent injections.

因為似乎在某些時候，您可能會在服用口服藥和頻繁注射之間取得平衡。

I realize there's some people don't like injection too but is there any elasticity there in a way?

我知道有些人也不喜歡注射，但某種程度上有彈性嗎？

Yeah, no, that's a really good question because we're super paranoid.

是的，不，這是一個非常好的問題，因為我們非常偏執。

And one of the things I asked Jinky is, what's the tipping point on frequency of injectable dosing that would make it as attractive as a once daily oral?

我問 Jinky 的一件事是，注射劑量的頻率臨界點是多少，才能使其像每日口服藥物一樣有吸引力？

Found it yet.

還沒找到呢

I mean, we run that research, we haven't found it yet and so.

我的意思是，我們進行了這項研究，但我們還沒有找到它等等。

--

--

Okay.

好的。

But we'll keep looking.

但我們會繼續尋找。

Sorry to interrupt.

抱歉打擾。

I would just add, I think people underestimate the fear of injections that patients experience.

我想補充一點，我認為人們低估了患者對注射的恐懼。

And while it can be convenient for some, I think that fear and fatigue of injections can be underestimated.

雖然這對某些人來說很方便，但我認為注射的恐懼和疲勞可能被低估。

So when we hear that continuously from our physicians and from patients as well.

因此，當我們不斷從醫生和病人那裡聽到這樣的說法時。

So they are seeking convenience as well as that aspect of having a normal life and carrying around a once-a-day oral feels very normal for a lot of patients.

因此，他們尋求的是便利，以及過著正常的生活和攜帶每天一次的口服藥物對許多患者來說是非常正常的。

Okay, great.

好的，太好了。

And then just a quick question for me.

然後問我一個簡單的問題。

Can you kind of go through the math of like how many patients you've treated so far?

您能算一下到目前為止您治療了多少患者嗎？

How many patients, like HAE patients are out there?

像 HAE 患者這樣的患者有多少？

And how many more need to try ORLADEYO?

還有多少人需要嘗試奧拉德約？

Given the kind of like stickiness of the product, like maybe whatever half the patients or so end up like sticking to it long term.

考慮到產品的黏性，可能有一半的患者最終會長期堅持使用它。

Think of kind of go through from here to get to that $800 million US number.

想像一下從這裡開始就可以得到 8 億美元的數字。

So start with the 7,500 onward and afterwards.

因此，請從 7,500 及之後開始。

Yeah, Liisa, near the end of my remarks today, I pointed out that there are at least 5,000 patients who have not yet tried ORLADEYO.

是的，Liisa，在我今天演講快結束時，我指出至少有 5,000 名患者尚未嘗試過 ORLADEYO。

That's based on our previous estimates that they're about 7,500 diagnosed and treated patients.

這是基於我們先前的估計，大約有 7,500 名確診和治療的患者。

We've had 2,500 prescriptions to date.

到目前為止，我們已經開出 2,500 個處方。

So there's at least another 1,000 patients.

所以至少還有1000名患者。

And with what we're hearing from physicians and patients, we expect a lot more trials in that 5,000.

根據我們從醫生和患者那裡聽到的情況，我們預計這 5,000 項試驗中會有更多的試驗。

So plenty of room to grow.

有足夠的成長空間。

Okay.

好的。

And like as you think about what you need to get to that $800 million number, is it half of those that need to try it or what is the amount?

就像當你思考需要什麼才能達到 8 億美元的數字時，是需要嘗試的人的一半還是金額是多少？

That's probably a pretty good estimate.

這可能是一個相當不錯的估計。

What we need to get is to about 2000 patients who are sticky at peak, and we are more than halfway there at this point.

我們需要的是大約 2000 名高峰期黏性患者，目前我們已經完成了一半以上。

Great.

偉大的。

Thank you so much, guys.

十分感謝大家。

Stacy Ku, TD Cowen.

史黛西·庫，TD·考恩。

Thanks for taking our questions.

感謝您回答我們的問題。

So first question is around kind of potential implications with the change in the Medicare Part D redesign with IRA.

因此，第一個問題是關於 Medicare D 部分與 IRA 重新設計的變化的潛在影響。

So could there be any potential impact to patient volumes with the decrease in the next out of pocket spend?

那麼，下次自付費用的減少是否會對病患數量產生任何潛在影響呢？

And what would be the timing of something like this?

這樣的事情發生的時機是什麼？

So that's one.

這就是其中之一。

And then just a follow-up to some of the questions that have been asked.

然後是對所提出的一些問題的後續行動。

Can you just further characterize your commentary around the clinicians that are prescribing in more academic, more community?

您能否進一步描述您對在更學術、更社區中開處方的臨床醫生的評論？

Is it really still just that 50% split now?

現在真的還是那50%的分割嗎？

Thanks so much.

非常感謝。

Thanks, Stacy.

謝謝，史黛西。

So on the IRA, particularly next year, when the max out of pocket shifts to $2,000, we think that will be an advantage for patients in terms of affordability.

因此，對於 IRA，特別是明年，當最高自付費用變為 2,000 美元時，我們認為這對患者的負擔能力而言將是一個優勢。

And then very important is that next year, that $2000 can be paid over the course of the year in the 12-month increments.

然後非常重要的是，明年，這 2000 美元可以在一年內以 12 個月的增量支付。

And so we think that'll increase affordability and likely increase the rate for ORLADEYO.

因此，我們認為這將提高負擔能力，並可能提高奧拉德約的利率。

I don't think it will really change the volume of patients treated.

我認為這不會真正改變治療的患者數量。

It's just going to affect the rate.

只會影響速率。

And then as far as clinicians, we see a great mix.

對於臨床醫生來說，我們看到了一個很好的組合。

Again, we see the academic physicians as well as a lot of community physicians.

我們再次看到學術醫生以及許多社區醫生。

As I said, over 1,000 healthcare providers have prescribed so far.

正如我所說，迄今為止已有 1,000 多家醫療保健提供者開出處方。

And that is really distributed very evenly across the deciles of our healthcare provider potential index, and it's been very consistent that way every quarter.

這確實非常均勻地分佈在我們的醫療保健提供者潛力指數的十分之一中，並且每個季度都非常一致。

So we're getting both academic and community.

所以我們得到了學術和社區的雙重支持。

Understood.

明白了。

And just a follow-up, does that mean that you think as the rate is improved for the IRA changes, do you think that you'll be able to switch more patients over to paid?

作為後續行動，這是否意味著您認為隨著 IRA 變化的費率提高，您是否認為您能夠將更多患者轉為付費？

Is that a fair kind of thinking about it?

這樣的想法公平嗎？

Yes we do, next year in 2025 and beyond.

是的，我們會的，明年、2025 年及以後。

Okay, wonderful.

好吧，太棒了。

Thank you.

謝謝。

Serge Belanger, Needham & Co.

塞爾吉貝朗格，李約瑟公司

Hi, good morning.

早安.

Thanks for taking my questions.

感謝您回答我的問題。

The first one for Charlie, just give a little color on the 1Q seasonality this year.

查理的第一個，只是對今年第一季的季節性進行一些說明。

Is it similar to prior years?

與往年是否相似？

And then second question, I guess for Jon and maybe the rest of the team.

然後是第二個問題，我想是針對喬恩，也許還有團隊的其他成員。

I think you've all been consistent, but do you expect competition from an oral prophylactic by the end of the decade?

我認為你們的觀點都是一致的，但你們是否預期到本世紀末會出現口服預防藥物的競爭？

Just curious your thoughts on an oral on-demand treatments and what impact that could have for the market.

只是好奇您對口服按需治療的想法以及這可能對市場產生什麼影響。

Thanks.

謝謝。

Hey, Serge, I'll start with that.

嘿，Serge，我就從這個開始吧。

For 1Q, yes, we expect similar seasonality with the first quarter revenue being down versus Q4.

對於第一季度，是的，我們預計會有類似的季節性，第一季營收將比第四季有所下降。

This, we had a really strong Q4, so we actually think that percentage reduction could be a little bit more this year.

我們第四季的表現非常強勁，所以我們實際上認為今年的百分比下降可能會更多一些。

So I think 7% or 8% drop from Q4 and probably mid 80s in revenue for Q1.

因此，我認為第一季的營收較第四季下降 7% 或 8%，甚至可能下降 80 年代中期。

And with regard to oral competition, specifically on-demand therapy.

關於口頭競爭，特別是按需治療。

We certainly can't argue that orals are important, and if you have an oral alternative for a breakthrough attack, we think that's great.

我們當然不能說口頭是重要的，如果你有突破性攻擊的口頭替代方案，我們認為那很好。

And so having that as a choice for patients, we think is just another benefit.

因此，我們認為將其作為患者的選擇是另一個好處。

And an all-oral option would be fantastic, right, prophy, and when you have a breakthrough attack, take an oral on demand.

全口頭選擇將是非常棒的，對吧，預防，當你有突破性的攻擊時，按需進行口頭。

Thanks.

謝謝。

You're welcome.

不客氣。

(Operator Instructions) Gena Wang, Barclays.

（操作員指示）Gena Wang，巴克萊銀行。

Thank you for taking my questions.

感謝您回答我的問題。

I just have one regarding the data report.

我只有一份關於數據報告的資料。

I think if we look at the slide 6, 7, 8, when we look at number of patients more than two thirds of patients.

我想如果我們看投影片 6、7、8，當我們看患者數量超過三分之二的患者。

I mean the beginning of a patient number and the end of the patient numbers; it was about one-third of patient continue and to the end of data report.

我的意思是患者編號的開頭和患者編號的結尾；大約有三分之一的患者繼續到數據報告結束。

So any color you could give regarding the other two third of the patient?

那麼對於另外三分之二的病人，你能給出什麼顏色嗎？

Maybe I'll let you start Ryan.

也許我會讓你開始瑞安。

Yeah.

是的。

Thanks for the question.

謝謝你的提問。

These are patients that are reporting, self-reporting their attack rates.

這些患者正在報告、自我報告他們的發生率。

And because this is real-world data, there's always limitations in terms of how that is recorded.

由於這是真實世界的數據，因此記錄方式始終存在限制。

In some months patients may not share what their attack rates are.

在某些月份裡，患者可能不會透露他們的發病率。

But that doesn't mean they've necessarily come off therapy.

但這並不代表他們一定會停止治療。

And all of these patients have, that you've seen in these slides, have completed 540 days of therapy.

您在這些幻燈片中看到的所有這些患者都已完成 540 天的治療。

We're still waiting for some few to complete that same timeframe to include them in the analysis.

我們仍在等待一些人完成相同的時間範圍，以便將它們納入分析中。

Yeah, keeping somebody in a study for two years is challenging, certainly.

是的，讓一個人繼續研究兩年確實是一個挑戰。

And remember, some patients don't do well in our drug.

請記住，有些患者使用我們的藥物效果不佳。

We've got about a 60% retention.

我們的保留率約為 60%。

And so it's not uncommon to see people not succeed, and you see that in some of these results.

因此，人們失敗的情況並不少見，你可以在其中一些結果中看到這一點。

Just to underline what Ryan said, just to make sure it's really clear.

只是為了強調瑞安所說的話，只是為了確保它真的很清楚。

In this real-world evidence, we measure patients based on the length of time that they're in therapy and some of them just haven't had the opportunity to reach 540 days because they started at a later time point.

在這個現實世界的證據中，我們根據患者接受治療的時間長度來衡量他們，其中一些只是沒有機會達到 540 天，因為他們開始的時間點較晚。

So it's a dynamic sample.

所以這是一個動態樣本。

Off course some patients do drop out, but this represents how well patients when they're doing well in ORLADEYO, they're doing really well and sticking on therapy.

當然，有些患者確實會退出，但這代表了患者在奧拉德約表現良好時的情況，他們做得非常好並堅持治療。

That's the point, Gena, is that the patients that do well, do really well in this drug.

吉納，這就是重點，那些表現良好的患者，在這種藥物中表現得非常好。

Okay, great.

好的，太好了。

Thank you.

謝謝。

François Brisebois.

弗朗索瓦·布里斯布瓦。

Oppenheimer.

奧本海默。

Hi, thanks for taking the question.

您好，感謝您提出問題。

I was just wondering in terms of the discontinuation rate, so what leads to this discontinuation rate?

我只是想知道停藥率，那麼是什麼導致了這種停藥率呢？

Is it that for those patients that just aren't doing well, is there other any other reason out there?

難道那些身體狀況不佳的患者還有其他原因嗎？

And if they do discontinue, what do they usually end up doing?

如果他們真的停止了，他們通常會做什麼？

Thanks, François.

謝謝，弗朗索瓦。

The discontinuation rate, there are two main reasons for discontinuation, and these won't be surprising.

就停藥率而言，停藥有兩個主要原因，這並不奇怪。

The number one reason is perceived lack of efficacy.

第一個原因是人們認為缺乏效率。

So as we've said no drug is perfect and no one HAE therapy is for everybody.

正如我們所說，沒有一種藥物是完美的，也沒有一種 HAE 療法適合所有人。

And so that's the number one reason reported.

這就是報告的首要原因。

The number two reason is adverse events, specifically gastrointestinal, which is not surprising given the product label in our clinical trial experience.

第二個原因是不良事件，特別是胃腸道不良事件，考慮到我們臨床試驗經驗中的產品標籤，這並不奇怪。

What we do know is that some patients give up too early.

我們所知道的是，有些患者過早放棄。

And so part of our messaging is for physicians and others to set expectations that you can have a breakthrough attack, you might have GI events.

因此，我們的部分訊息是讓醫生和其他人設定預期，您可能會出現突破性的發作，您可能會發生胃腸道事件。

The GI events tend to go away after a few weeks of therapy for most patients.

對大多數患者來說，經過幾週的治療後，胃腸道事件往往會消失。

And so it's important that patients don't give up too early.

因此，患者不要過早放棄，這一點很重要。

We actually see in 2023 about 10% of the patients starting ORLADEYO were actually restarts.

事實上，我們發現到 2023 年，大約 10% 開始 ORLADEYO 的患者實際上重新開始接受治療。

They're people who gave up in the past and came back because they knew that they have given up to early.

他們是過去放棄的人，但又回來了，因為他們知道自己放棄得太早了。

And François, John can send you the slide.

弗朗索瓦，約翰可以將幻燈片發送給您。

But one of the slides we've had in previous decks, shows the pattern of discontinuations over two years, and it's flat.

但我們在之前的幻燈片中看到的一張幻燈片顯示了兩年多的停產模式，而且很平淡。

And so I think now we have a pretty good idea of what that pattern is.

所以我認為現在我們已經很清楚這種模式是什麼了。

And if we've got you for out to a year, we've got you.

如果我們能陪你一年，我們就能陪你。

Understood.

明白了。

And then can you just help me understand a little bit the US versus ex-US dynamics in terms of the growth and your assumptions and expectations?

那麼您能否幫助我了解美國與美國以外地區在成長方面的動態以及您的假設與期望？

Are there challenges maybe ex-US, that aren't happening in the US?

是否存在美國以外地區未發生的挑戰？

Just any color there would be helpful.

任何顏色都會有幫助。

Thank you.

謝謝。

Sure.

當然。

Ex-US first of all, one's with the biggest challenge or the biggest time factor is getting market access in an ex-US market.

首先，在美國以外的市場，最大的挑戰或最大的時間因素是獲得美國以外市場的市場進入。

And so that always takes longer.

所以這總是需要更長的時間。

And we have countries that rolling on all the time.

我們有一些國家一直在前進。

So a number of countries in Europe for example, like Germany, UK, and France.

例如，歐洲的許多國家，如德國、英國和法國。

We got market access a few years ago.

幾年前我們獲得了市場准入。

But we're just now getting market access in others like Spain and Italy.

但我們現在剛剛獲得西班牙和義大利等其他國家的市場准入。

And so that's one factor.

這是一個因素。

Pricing is a lot lower.

定價低很多。

Ex-US, so it takes four to five ex-US patients to add up to one US patient.

來自美國，因此需要四到五名來自美國的患者才能加起來成為美國患者。

So our strategy is very much a volume strategy outside the US.

因此，我們的策略很大程度上是美國以外地區的銷售策略。

And then finally, what we're seeing in the real world in these countries where we have market access and we've launched, is the same consistent pattern of patient adds.

最後，我們在這些擁有市場准入並已推出的國家的現實世界中看到的是患者添加的相同一致模式。

Depending on the market, the HAE market dynamics, sometimes that's patients switching from other prophys, sometimes is growing the prophylaxis market with a with a drug like ORLADEYO.

根據市場的不同，HAE 市場動態有時是患者從其他預防藥物轉向，有時是使用 ORLADEYO 等藥物來擴大預防市場。

At peak, we expect ex-US to equal about $200 million of the $1 billion in sales.

在高峰時期，我們預計美國以外地區的銷售額將相當於 10 億美元銷售額中的約 2 億美元。

And what we see so far gives us confidence that we'll get there.

到目前為止我們所看到的讓我們有信心實現這一目標。

And if Tech Syros and Analog here right time that the US starts to flatten out, the ex-US continues to grow.

如果 Tech Syros 和 Analog 恰逢美國市場開始趨於平緩，那麼美國以外的市場將繼續成長。

So you have overall growth of the brands still.

因此，品牌的整體成長仍然存在。

So that's what we're expecting right now.

這就是我們現在所期待的。

Understood.

明白了。

Thank you very much.

非常感謝。

You're welcome.

不客氣。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Hi, good morning and thanks for taking my questions.

你好，早安，感謝您回答我的問題。

I just wanted to ask a clarifying question on the seasonality of this quarter.

我只是想問一個有關本季季節性的澄清問題。

Is that for the same reason as in first quarter '23, where there were budget issues with external charities, which increased the number of patients on free drug program?

這是否與 23 年第一季的原因相同？當時外部慈善機構存在預算問題，導致接受免費藥物計劃的患者數量增加？

Or what are you seeing this year so far?

或是今年到目前為止你看到了什麼？

Sure, Maury.

當然，莫里。

That's one of the situations the Medicare issue.

這就是醫療保險問題的情況之一。

We've got a little bit of insight into that.

我們對此有一些了解。

What I'd say is, it's not solved yet.

我想說的是，事情還沒解決。

It doesn't seem to be worse than line, but it's not solved.

看起來不比line差，但沒有解決。

We think next year, as I said earlier, with the IRA rolling in fully, we have expectations that budget issue will be more solved in 2025.

我們認為明年，正如我之前所說，隨著 IRA 的全面啟動，我們預計預算問題將在 2025 年得到更好的解決。

The main reason for the dip in Q1 is the broader percentage of patients getting reauthorizations.

第一季下降的主要原因是獲得重新授權的患者比例更大。

And when that happens, we have to drop many patients back to temporarily to free product.

當這種情況發生時，我們不得不讓許多患者暫時返回免費產品。

And then also in the first quarters, it's the highest hit to gross to net because in the commercial market we're helping pickup patient co-pays.

同樣在第一季度，毛淨值受到的打擊最大，因為在商業市場，我們正在幫助提高患者的自付費用。

And the majority of that happens in the first quarter.

其中大部分發生在第一季。

And you'll see a corresponding nice pop in the second quarter when we get those people back to paid.

當我們讓這些人恢復工資時，你會在第二季度看到相應的良好成長。

Got it, make sense.

明白了，有道理。

And one other quick question.

還有另一個簡單的問題。

What proportion of the 321 new patients are on short term quick start?

321 名新患者中接受短期快速啟動治療的比例是多少？

And how long on average does it take to convert these patients to long term paid patients?

將這些患者轉變為長期付費患者平均​​需要多長時間？

The 321 was the net growth across the whole year.

321是全年淨增長。

So what we did say is that we ended the year with a 1,000 -- sorry, 1,104 patients on either paid therapy or long-term free product.

因此，我們確實說過，今年年底，我們有 1,000 名（抱歉，是 1,104 名）患者接受付費治療或長期免費產品。

There was also a sizable chunk of patients on short term quick start new patients coming in.

還有相當大一部分患者是短期快速開始的新患者進來的。

And it usually takes us, we get the product out very quickly.

這通常需要我們很快就能把產品推出來。

For most patients, we get them to either paid or from free product within about a month.

對於大多數患者，我們會在大約一個月內讓他們獲得付費或免費產品。

Got it.

知道了。

Okay.

好的。

Thanks for taking my questions.

感謝您回答我的問題。

You're welcome.

不客氣。

[John Wolleben, Citizen].

[約翰·沃萊本，公民]。

Hi, this is [Katherine] on for John.

大家好，我是約翰的[凱瑟琳]。

We just have a question about how you're thinking about profitability versus your earlier pipeline kind of prioritizing those not just a question about the data coming.

我們只是想問一下，與您早期的管道相比，您如何考慮盈利能力，而不僅僅是關於即將到來的數據的問題。

It's the coming in midyear for the PNH trial.

PNH 審判將於年中進行。

Thanks.

謝謝。

Yes.

是的。

I think we've been very clear about our path to profitability.

我認為我們對獲利之路非常清楚。

Very excited to get to the point where we are independent of capital markets.

非常高興能夠達到我們獨立於資本市場的地步。

We've been seeing over the past years, that convergence of the lines between revenue and OpEx.

在過去的幾年裡，我們已經看到收入和營運支出之間的界線正在趨同。

We continue to see it this year and beyond.

今年及以後我們將繼續看到這種情況。

So being able to generate an operating profit this year, getting towards both cash positivity in EPS at the end of next year is an achievement in 2026.

因此，今年能夠產生營業利潤，並在明年底實現每股收益現金正值，這就是 2026 年的一項成就。

I think it puts us in a great spot.

我認為這讓我們處於一個很好的位置。

We do that at the same time as continuing to invest in that early phase pipeline.

我們在這樣做的同時，繼續投資於早期階段的管道。

So the two things coexist, and actually the opportunity to be able to invest in whatever we can do to move as fast as we can in those periods.

因此，這兩件事是共存的，實際上我們有機會投資我們所能做的一切，以便在這些時期盡可能快地採取行動。

Because that early phase pipeline that we generated in or that we announced in November is in fact, early-phase, puts us in spot where the expenditure within the next kind of three years is not as meaningful as it would be when you get them to pivotal trials.

因為我們在 11 月生成的或我們在 11 月宣布的早期階段管道實際上是早期階段，使我們處於未來三年內的支出並不像讓它們實現時那樣有意義。關鍵的試驗。

So I think the companies in a great spot and if there's anything we can do to accelerate.

所以我認為這些公司處於一個很好的位置，如果我們可以做些什麼來加速。

We absolutely will.

我們絕對會的。

And there's nothing to update on 10013, nothing's change on the timeline.

10013 上沒有任何可更新的內容，時間軸上也沒有任何變化。

Thank you.

謝謝。

You're welcome.

不客氣。

This concludes our question-and-answer session.

我們的問答環節到此結束。

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

我想將會議轉回喬恩·斯通豪斯（Jon Stonehouse）發表閉幕詞。

Thank you.

謝謝。

So one of the things that we're hearing from investors is they have so many things coming at them and it's hard to keep up with the opportunities to invest in.

因此，我們從投資者那裡聽到的一件事是，他們面臨太多的事情，很難跟上投資機會。

And if you're in that camp, a question you may want to stop and ask yourself is, how many companies do I have in my portfolio that have a growing product.

如果你屬於這個陣營，你可能想停下來問自己一個問題：我的投資組合中有多少家公司的產品正在成長。

Have a discovery engine that created the growing product.

擁有一個創造不斷增長的產品的發現引擎。

Have a pipeline that came from the discovery engine that's going to create another growing product or more.

擁有來自發現引擎的管道，該管道將創建另一個或更多不斷增長的產品。

And has an accelerated path to profitability, where we're probably going to be cash-flow positive or near that in the second half of next year.

並且有加速獲利的途徑，我們可能會在明年下半年實現正現金流或接近正現金流。

And if the answer to that is none or too few and you want to diversify your portfolio, reach out to us.

如果答案是否定的或太少，並且您希望使您的投資組合多樣化，請與我們聯繫。

We're happy to get you up to speed on our company and answer any questions you may have.

我們很高興讓您了解我們公司的最新情況並回答您可能提出的任何問題。

So have a great day and thanks for your interest in BioCryst.

祝您有個愉快的一天，感謝您對 BioCryst 的興趣。

The conference has now concluded.

會議現已結束。

Thank you for attending today's presentation.

感謝您參加今天的演講。

You may now disconnect.

您現在可以斷開連線。