BridgeBio Pharma Inc (BBIO) 2025 Q3 法說會逐字稿

Good afternoon. I will be your conference operator today. (Operator Instructions)

午安.我今天將擔任你們的會議接線生。（操作說明）

Before we begin, I would like to remind everyone that today's call may contain forward-looking statements within the meaning of the federal securities laws, including, but not limited to, statements about BridgeBio's future operating and financial performance, business plans and prospects, and strategy. These statements are based on current expectations and assumptions that are subject to risks and uncertainties, which could cause actual results to differ materially from those expressed or implied in these forward-looking statements.

在開始之前，我想提醒大家，今天的電話會議可能包含聯邦證券法意義上的前瞻性陳述，包括但不限於有關 BridgeBio 未來營運和財務業績、業務計劃和前景以及戰略的陳述。這些聲明是基於目前的預期和假設，但存在風險和不確定性，可能導致實際結果與這些前瞻性聲明中明示或暗示的結果有重大差異。

For a discussion of these risks and uncertainties, please refer to the disclosure in today's earnings release and BridgeBio's periodic reports and SEC filings. All statements made here are based on information available to BridgeBio as of today, and the company undertakes no obligation to update any forward-looking statements made during this call, except as required by law.

有關這些風險和不確定性的討論，請參閱今天發布的收益報告中的披露資訊以及 BridgeBio 的定期報告和提交給美國證券交易委員會的文件。本文中的所有陳述均基於 BridgeBio 截至今日可獲得的信息，除法律要求外，本公司不承擔更新本次電話會議中任何前瞻性陳述的義務。

With that completed, BridgeBio, you may begin your conference.

BridgeBio，完成這些步驟後，你們就可以開始會議了。

Good afternoon, everyone, and thank you for joining BridgeBio Pharma's third-quarter 2025 earnings call. I'm Chinmay Shukla, Senior Vice President of Strategic Finance at BridgeBio. With me today are Neil Kumar, our CEO, who will provide opening remarks and discuss overall corporate performance; Matt Outten, our Chief Commercial Officer, who will provide more details about our commercial performance, particularly the continued success of Attruby; and Tom Trimarchi, our President and CFO, who will review our financial results.

各位下午好，感謝各位參加 BridgeBio Pharma 2025 年第三季財報電話會議。我是 Chinmay Shukla，BridgeBio 的策略財務高級副總裁。今天與我一同出席的有：首席執行官尼爾·庫馬爾，他將致開幕詞並討論公司整體業績；首席商務官馬特·奧滕，他將詳細介紹我們的商業業績，特別是 Attruby 的持續成功；以及總裁兼首席財務官湯姆·特里馬爾基，他將回顧我們的財務業績。

During today's call, we'll cover our strong commercial execution in Attruby's third quarter on the market. We'll provide updates on our late-stage pipeline, including the Phase 3 readouts of encaleret and BBP-418, which were announced this week, as well as discuss infigratinib in achondroplasia, which we expect to read out in early '26.

在今天的電話會議上，我們將介紹 Attruby 在第三季上市後的強勁商業業績。我們將提供有關我們後期研發管線的最新信息，包括本周公布的 encaleret 和 BBP-418 的 3 期臨床試驗結果，以及討論 infigratinib 在軟骨發育不全中的應用，我們預計將在 2026 年初公佈結果。

We will end with a discussion of our robust financial position. Following our prepared remarks, we will open the call for Q&A. For the question-and-answer session, we will also be joined by Ananth Sridhar, Anna Wade and Justin To, who lead encaleret, BBP-418 and infigratinib, respectively.

最後，我們將討論我們穩健的財務狀況。在宣讀完準備好的演講稿後，我們將開放問答環節。在問答環節，我們也將邀請 encaleret、BBP-418 和 infigratinib 的負責人 Ananth Sridhar、Anna Wade 和 Justin To 出席。

With that, I'll turn it over to Neil for his remarks.

接下來，我將把發言權交給尼爾。

Thank you, everyone, for joining us today. As always, this is a forum in which we communicate salient aspects of our business that are of interest to investors, and we welcome your questions and feedback along the way. On the first two of these calls we have done, I've focused my early comments on Attruby, which continues to be the core of our business. As both Matt and I will elaborate on, we see continued momentum, both scientifically and commercially in this franchise and are ever more confident today that we will achieve our goal of 30-plus percent market share by volume in the years to come.

謝謝各位今天蒞臨。一如既往，這是一個我們向投資者傳達公司重要業務訊息的論壇，我們歡迎您在過程中提出問題和回饋。在我們進行的頭兩次電話會議中，我首先重點談到了 Attruby，它仍然是我們業務的核心。正如我和 Matt 將要詳細闡述的那樣，我們看到該系列產品在科學和商業方面都保持著持續的發展勢頭，並且我們越來越有信心在未來幾年內實現 30% 以上的市場份額（按銷量計）的目標。

But I wanted to start today by talking about our recent R&D progress. As you all know, we had the distinct privilege of announcing two stellar Phase 3 top-line results over the last three days. It is quite the coincidence that these readouts happen to stack on top of one another after six plus years of working on these programs. But these few days serve as a testament to the longer-term productivity of the R&D engine we have created.

但我今天想先談談我們最近的研發進展。如大家所知，在過去三天裡，我們非常榮幸地宣布了兩項出色的第三階段主要研究結果。非常巧合的是，經過六年多的程序開發，這些讀數竟然重疊在一起。但這幾天證明了我們所創造的研發引擎具有長期的生產力。

Slide 10 of our updated corporate presentation shows the industry-leading time lines that we have been able to achieve, and slide 11 shows the remarkably high probability of technical success across our programs across the nearly 10 years that we've been operating. Probabilities of technical success north of 70% start to move us from a lottery ticket-like entity to an engineering company-like entity, one that will undoubtedly face failure, but that can reliably produce medicines that matter with reasonable cadence.

我們更新後的公司簡報第 10 頁展示了我們所取得的行業領先的時間表，第 11 頁展示了在我們近 10 年的營運中，我們所有專案取得技術成功的機率都非常高。當技術成功機率超過 70% 時，我們就開始從一個類似彩票的實體轉變為一個類似工程公司的實體，這個實體無疑會面臨失敗，但可以以合理的節奏可靠地生產出重要的藥物。

The speed and efficiency of the BridgeBio engine is only possible because we target well-described genetic diseases at their source. It's also the product of our decentralized hub-and-spoke model that is fueled by our tireless employees that are dedicated to making an impact to the patient communities that we serve. I'd now like to highlight some of the most remarkable aspects of the data we have shared over the last few days and encourage those seeking to learn more to access our webcast on each readout.

BridgeBio引擎的速度和效率之所以能夠實現，是因為我們針對的是已明確描述的遺傳疾病的根源。這也是我們去中心化中心輻射模式的產物，而這種模式又得益於我們不知疲倦的員工，他們致力於為我們服務的患者群體帶來影響。現在我想重點介紹我們在過去幾天分享的數據中最引人注目的一些方面，並鼓勵那些想要了解更多資訊的人訪問我們每次發布數據的網路直播。

On Monday, we read out our Phase 3 FORTIFY trial of BBP-418 in limb-girdle muscular dystrophy type 2i. The study exceeded all of our expectations, meeting all primary and secondary interim analysis endpoints. The primary endpoint, glycosylated alpha-dystroglycan was successful to a high degree of statistical significance. Though even small changes in ADG have been shown to be clinically meaningful, it is remarkable to see some patients attaining normalized levels of ADG.

週一，我們公佈了 BBP-418 治療肢帶型肌肉營養不良症 2i 型的 3 期 FORTIFY 試驗結果。該研究超出了我們所有的預期，達到了所有主要和次要中期分析終點。主要終點，糖基化α-肌肉營養不良蛋白聚醣，取得了高度統計意義的成功。儘管 ADG 的微小變化已被證明具有臨床意義，但看到一些患者達到正常 ADG 水平仍然令人矚目。

And the 80% increase in glycosylation meaningfully moved patients to healthier levels of muscle function. Across the key clinical endpoint studied, ambulatory function and pulmonary function, BBP-418 not only stopped the decline that was seen in the placebo, but showed a statistically significant incline in function. Patients are walking better and breathing better than when they started.

糖基化水平提高 80%，顯著改善了患者的肌肉功能，使其達到更健康的水平。在研究的關鍵臨床終點（步行功能和肺功能）方面，BBP-418 不僅阻止了安慰劑組出現的下降趨勢，而且在功能方面顯示出統計意義上的顯著上升。患者的行走能力和呼吸狀況都比剛開始時好多了。

In addition, this small molecule is distributed systemically, and we look forward to sharing additional data associated with its impact on other tissues, including importantly, the heart muscle. Earlier today, we shared the top-line data from our Phase 3 CALIBRATE trial of encaleret in autosomal dominant hypocalcemia type 1.

此外，這種小分子在體內分佈廣泛，我們期待分享更多與其對其他組織（包括重要的心肌）的影響相關的數據。今天早些時候，我們分享了 encaleret 治療 1 型常染色體顯性低鈣血症的 3 期 CALIBRATE 試驗的主要數據。

We saw profound and highly statistically significant normalization across blood and urine calcium as well as highly statistically significant normalization of PTH. Just to reiterate, a vast majority of patients fully normalized urine, serum and PTH levels. As I mentioned on the webcast, when we speak of cures in therapeutic medicine, this is the type of impact we seek. And as I mentioned on our last earnings call, we are moving expeditiously not only to launch this drug, but also to initiate its Phase 3 in chronic hypoparathyroidism.

我們看到血液和尿液中的鈣含量出現了顯著且具有高度統計意義的正常化，PTH 含量也出現了具有高度統計意義的正常化。再次強調，絕大多數患者的尿液、血清和 PTH 水平完全恢復正常。正如我在網路直播中提到的，當我們在治療醫學中談到治癒時，這就是我們所追求的影響。正如我在上次財報電話會議上提到的，我們不僅正在迅速推進該藥物的上市，而且還將啟動其在慢性甲狀旁腺功能減退症中的 3 期臨床試驗。

Here, encaleret in a cohort of 10 patients normalized urine and serum calcium in 80% of subjects within 5 days of dosing. Importantly, this drug brings differentiated promise to the hypoparathyroidism community across at least 3 potential dimensions. First, it's oral. Second, it potentially normalizes urine calcium, the cause of downstream kidney conditions. And third, it might avoid potential downstream bone-associated resorption issues that could require bisphosphonates.

在一項針對 10 名患者的研究中，恩卡雷特在給藥 5 天內使 80% 的受試者的尿液鈣和血清鈣恢復正常。重要的是，這種藥物至少在三個潛在方面為副甲狀腺功能減退症患者帶來了不同的希望。首先，它是口服的。其次，它有可能使尿鈣正常化，而尿鈣是導致下游腎臟疾病的原因。第三，它或許可以避免可能需要使用雙磷酸鹽的潛在下游骨吸收問題。

Finally and importantly, for both small molecules in LGMD2I and ADH1, we saw a safe profile, supporting their ability to provide lifelong improvement for patients who have no disease-modifying therapies available today. Of course, these data are only interesting to the extent that we can get the therapies into the hands of patients. This is where the ongoing success of Attruby gives me confidence that we can distribute at scale.

最後也是非常重要的一點，對於 LGMD2I 和 ADH1 中的兩種小分子，我們都觀察到了安全性，這支持了它們能夠為目前尚無疾病修飾療法的患者提供終身改善的能力。當然，這些數據只有在我們能夠將這些療法送到患者手中時才有意義。Attruby 的持續成功讓我有信心，我們可以大規模分銷。

We have been in the marketplace for nearly a year, and I feel our message is just beginning to resonate. The numbers to support that include the fact that we have delivered 5,259 unique patient prescriptions to 1,355 unique HCPs, generating this quarter $108.1 million in net product sales. In the long term, although our goal is 30% to 35% share by volume, I believe we have the potential to be a market leader. The best point estimates to date on key endpoints at the lowest price point backed by an aggressive research plan support that future.

我們進入市場已經近一年了，我覺得我們的理念才剛開始引起共鳴。支持這項結論的數據包括：我們已向 1,355 位不同的醫療保健專業人員提供了 5,259 份獨特的患者處方，本季淨產品銷售額達 1.081 億美元。從長遠來看，雖然我們的目標是按銷量計算達到 30% 到 35% 的市場份額，但我相信我們有潛力成為市場領導者。到目前為止，關鍵終點指標的最佳預測值，以及最低價格點和積極的研發計劃，都為這一未來提供了支持。

Early performance of Beyonttra in Europe where physicians have been quick to recognize the strength of our data also supports that future. Our partners at Bayer have done a wonderful job prosecuting the acoramidis hypothesis in Europe, closing in on market leadership in Germany with an NBRx of nearly 50% just 6 months into launch.

Beyonttra 在歐洲的早期表現也印證了這一點，醫生們很快就意識到我們數據的優勢，這也支持了這個未來。我們在拜耳的合作夥伴在歐洲推廣阿科拉米迪斯假說方面做得非常出色，在德國上市僅 6 個月後，其 NBRx 就接近 50%，從而取得了市場領先地位。

In that geography, among other tailwinds, regulators have also been quick to shut down Pfizer's inaccurate claims of near complete stabilization. On that topic, as I was putting together my comments, I stumbled upon an old e-mail that Dr. Jeff Kelly, the inventor of tafamidis, had sent to Dr. Isabella Graef, one of the inventors of acoramidis.

在該地區，除了其他有利因素外，監管機構也迅速駁斥了輝瑞公司關於病情幾乎完全穩定的不準確說法。關於這個主題，當我整理我的評論時，我偶然發現了一封舊電子郵件，是 tafamidis 的發明者 Jeff Kelly 博士發給 acoramidis 的發明者之一 Isabella Graef 博士的。

In it, and I directly quote him, he says, given the variability in stoichiometry in the experiments between tafamidis and AG10 and TTR, the data always tell the same story that AG10 is better than tafamidis as would be expected from the determined binding constant. I have to say I agree with him.

在文中，我直接引用他的話，他說，考慮到 tafamidis 與 AG10 和 TTR 之間的實驗化學計量存在差異，數據總是表明 AG10 比 tafamidis 更好，正如從確定的結合常數所預期的那樣。我必須說，我同意他的觀點。

Moving on from competing, we are also asking ourselves what is unique about our product. As many of you know, in patients with cardiac arrhythmic involvement, we observed a 43% reduction in risk of CVH associated with cardiac arrhythmia and a 17% reduction in TEAEs related to new onset AFib. That is unique. In patients with the most common variant, V122I, we published a 59% hazard reduction, which to our knowledge is the largest point estimate in terms of reduction demonstrated in the field.

除了競爭之外，我們也在思考我們的產品有何獨特之處。正如你們許多人所知，在患有心律不整的患者中，我們觀察到與心律不整相關的 CVH 風險降低了 43%，與新發房顫相關的 TEAE 降低了 17%。這是獨一無二的。在患有最常見變異體 V122I 的患者中，我們公佈了 59% 的風險降低，據我們所知，這是該領域所證明的降低幅度最大的點估計值。

We expect to further elaborate on these data at the upcoming AHA conference, so please stay tuned for that later this weekend. Additionally, we've continued to interrogate what in my mind is an incredibly unique factor, our early time to separation.

我們計劃在即將召開的 AHA 大會上進一步闡述這些數據，敬請關注本週末稍後的會議內容。此外，我們一直在探討一個在我看來非常獨特的因素，那就是我們很早就分居了。

In a recent JACC paper, we published that the effect of acoramidis on recurrent and cumulative cardiovascular outcomes was observed as early as one month. One question is, why is this prompt effect occurring? One hypothesis is that the answers may reside in the cardiorenal axis similar to what has been described for SGLT2 inhibitors, and we intend to explore this further in the clinic.

在最近發表於 JACC 的一篇論文中，我們指出，早在一個月內，就觀察到了 acoramidis 對復發性和累積性心血管事件的影響。一個問題是，為什麼會出現這種快速效應？一種假設是，答案可能存在於心腎軸中，類似於 SGLT2 抑制劑所描述的情況，我們打算在臨床上進一步探索這一點。

In addition, we intend to bring a new clinical CMR study to the field to further interrogate Attruby's impact on disease regression as measured by cardiac function and structure. Some of you may have seen another single-site CMR study recently published by Zlibut et al. in which they suggest the potentially superior effect of acoramidis versus tafamidis on important parameters like LVEF and LV mass.

此外，我們計劃進行一項新的臨床 CMR 研究，以進一步探討 Attruby 對疾病消退的影響，並以心臟功能和結構作為衡量標準。你們中的一些人可能已經看過 Zlibut 等人最近發表的另一項單中心 CMR 研究，其中他們指出，與 tafamidis 相比，acoramidis 在 LVEF 和 LV 質量等重要參數方面可能具有更優的效果。

These new research areas marry nicely with the continued execution of our ACT-EARLY, a potentially profound study that explores the effect of acoramidis in presymptomatic variant patients and in the context of this mass action disease. Finally, we'll continue to study the efficaciousness of the drug in the context of real-world evidence studies. We've been proponents of leveraging RWE as early as the survival studies done by Dr. Masri, Moore, and others.

這些新的研究領域與我們持續進行的 ACT-EARLY 研究完美契合，這是一項可能意義深遠的研究，旨在探索 acoramidis 對無症狀變異患者以及這種大塊病變疾病的影響。最後，我們將繼續在真實世界證據研究的背景下研究該藥物的療效。早在 Masri 博士、Moore 等人進行的生存研究時期，我們就一直倡導利用真實世界證據 (RWE)。

Given that in the modern marketplace, it is an exceptionally difficult thing to conduct double-blind head-to-head studies, RWE will serve as an important tool in identifying the right patients for the right drug. and we'll have more to publish on this front in the months to come. These research efforts tie together with the continued strengthening of our access profile and increasing diagnosis rates of patients with ATTR cardiomyopathy. Matt will have more to say about our access program, but we continue to offer best-in-class programs and are improving with every month the ability to make it easy for those patients and physicians that desire access to Attruby.

鑑於在當今市場環境下，進行雙盲頭對頭研究極為困難，真實世界證據（RWE）將成為識別適合特定藥物的患者的重要工具。未來幾個月，我們將就此發表更多研究成果。這些研究工作與我們持續加強醫療服務體系和提高 ATTR 心肌病變患者的診斷率密切相關。Matt 將對我們的准入計劃發表更多評論，但我們將繼續提供一流的計劃，並且每個月都在改進，以便讓那些希望獲得 Attruby 服務的患者和醫生能夠更輕鬆地獲得服務。

I'll end with a brief comment on future growth. The obvious growth in our portfolio today sits with the expansion programs of hypochondroplasia and in chronic hypoparathyroidism, branching from our achondroplasia and ADH1 programs, respectively. But shareholders should not overlook the deep ownership and close oversight we have with our sister companies.

最後，我想就未來的發展做個簡要評論。目前我們產品組合中顯而易見的成長體現在軟骨發育不全和慢性副甲狀腺功能低下症的擴展計畫中，這兩個計畫分別源自於我們的軟骨發育不全和 ADH1 計畫。但股東們不應忽視我們對姊妹公司的深厚所有權和密切監督。

At GondolaBio , in particular, we now have 17 programs across the Mendelian landscape, including what we believe to be a potentially best-in-class asset in EPP in Phase 2 and buttressed by exciting programs in alpha-1 antitrypsin deficiency, hereditary pancreatitis, ADPKD and many other areas. As these programs move forward and we continue to solidify BridgeBio, we can access new growth opportunities at the right time to increase the scope of work we are doing for patients.

特別是 GondolaBio，我們現在在孟德爾遺傳領域擁有 17 個項目，其中包括我們認為在 EPP 領域處於 2 期臨床試驗階段的潛在一流資產，以及在 α-1 抗胰蛋白酶缺乏症、遺傳性胰腺炎、ADPKD 和許多其他領域令人興奮的項目。隨著這些計畫的推進和 BridgeBio 的不斷鞏固，我們可以在適當的時機獲得新的成長機會，從而擴大我們為患者所做的工作範圍。

With that, I'll turn it over to Matt, our Chief Commercial Officer.

接下來，我將把發言權交給我們的首席商務官馬特。

Thanks, Neil. I'm excited to share our Q3 progress and discuss some of the positive trends behind Attruby's continuing success, along with the excitement that the new Phase 3 data from both encaleret and BBP-418 have created. Starting with Attruby, as we have seen throughout the year, the ATTR-CM market continues to expand with growth coming from all segments of the market.

謝謝你，尼爾。我很高興與大家分享我們第三季度的進展，並探討 Attruby 持續成功背後的一些積極趨勢，以及 encaleret 和 BBP-418 的第三階段新數據所帶來的興奮之情。從 Attruby 開始，正如我們今年所看到的，ATTR-CM 市場持續擴張，成長來自市場的各個細分領域。

We've been particularly encouraged by the increase in prescribing from both returning and new physicians with a steady rise in first-time prescribers adopting Attruby in their practice. Importantly, once physicians begin prescribing Attruby, they continue doing so, a clear reflection of the consistent clinical performance we've seen in real-world use. This persistence stems from Attruby's differentiated profile of being the only near-complete stabilizer on the market versus a partial stabilizer and a partial knockdown.

令我們倍感鼓舞的是，無論是回歸醫生還是新醫生，處方量的增加，以及首次開處方的醫生在實踐中採用 Attruby 的人數穩步上升。重要的是，一旦醫生開始開 Attruby 處方，他們就會繼續這樣做，這清楚地反映了我們在實際使用中看到的持續的臨床表現。這種持久性源自於 Attruby 的獨特定位，它是市場上唯一接近完整的穩定器，而不是部分穩定器和部分拆卸器。

Attruby has also shown the fastest time to separation from placebo to date. While patients are getting diagnosed faster and at a younger age, many continue to go undiagnosed or progress on their current medications. When that happens, they need something that can stabilize the tetramer and do so quickly. The bottom line is that patients and physicians want a medication that works well and works fast and Attruby continues to deliver on both efficacy and speed.

Attruby 也展現了迄今為止與安慰劑分離速度最快的能力。雖然患者的診斷速度較快，確診年齡也較小，但許多患者仍無法確診，或服用現有藥物後病情反而加重。當這種情況發生時，他們需要某種能夠穩定四聚體並快速發揮作用的物質。歸根究底，患者和醫生都希望藥物療效好、起效快，而 Attruby 在療效和起效速度方面一直都能滿足這一需求。

As we look towards Q4 and the one-year anniversary of the launch of Attruby, there are several factors I would like to highlight. First, Attruby's strong launch trajectory continues to demonstrate consistent growth across all market segments. We expect this momentum to carry into the coming quarters, positioning Attruby for meaningful share expansion over time as awareness and adoption continue to increase.

展望第四季以及 Attruby 發布一周年之際，我想重點介紹以下幾個因素。首先，Attruby 強勁的上市勢頭持續在所有細分市場中展現出穩定的成長。我們預計這一勢頭將延續到接下來的幾個季度，隨著認知度和採用率的不斷提高，Attruby 將逐步實現顯著的市場份額成長。

Second, the ATTR-CM market itself continues to grow quarter-over-quarter with no signs of slowing. This ongoing expansion effectively enlarges the total opportunity that Attruby is competing for and supports a sustained growth runway for the brand.

其次，ATTR-CM 市場本身繼續逐季成長，沒有放緩的跡象。這種持續擴張有效地擴大了 Attruby 所競爭的整體機會，並為該品牌提供了持續成長的空間。

Third, as the US healthcare environment becomes increasingly cost conscious, Attruby remains the least expensive option in the ATTR-CM market. Combined with being commercialized by a US-based company, this positions Attruby well for long-term competitiveness as pricing and access pressure continue to evolve.

第三，隨著美國醫療保健環境越來越注重成本，Attruby 仍然是 ATTR-CM 市場中最便宜的選擇。由於是由一家美國公司進行商業化，這使得 Attruby 在價格和准入壓力不斷變化的情況下，能夠保持長期的競爭力。

Finally, we continue to see encouraging underlying trends for Attruby with continued growth in the total number of patients on therapy and a steady increase in ongoing treatment utilization. Together, these trends underscore growing prescriber confidence and sustained demand for Attruby.

最後，我們看到 Attruby 的潛在趨勢持續令人鼓舞，接受治療的患者總數持續成長，持續治療的使用率也穩定提高。這些趨勢共同表明，處方醫生對 Attruby 的信心不斷增強，需求持續旺盛。

Building on the momentum from Attruby, we are now turning to the next wave of potential launches in our pipeline. Let me begin by reinforcing how excited we are by the recent readouts for BBP-418 and encaleret, which represent one of the most remarkable dual clinical successes in rare disease drug development. Both encaleret and BBP-418 exceeded expectations across their primary and secondary endpoints, positioning each as a potential first and best-in-class therapy with a compelling value proposition.

憑藉著 Attruby 的成功勢頭，我們現在正著手開發下一波潛在的新產品。首先，我要強調我們對 BBP-418 和 encaleret 的最新研究結果感到非常興奮，這代表了罕見疾病藥物開發中最引人注目的雙重臨床成功之一。encaleret 和 BBP-418 在主要和次要終點方面都超出預期，使二者都成為潛在的首創和同類最佳療法，具有令人信服的價值主張。

Together, these programs will redefine care for patients with anticipated strong support from the clinician and payer communities based on the strength of each respective data set if approved by the FDA. We expect an additional readout for infigratinib in the first half of 2026 and look forward to discussing the commercial opportunity at that time.

這些計畫將共同重新定義患者的護理，如果獲得 FDA 批准，預計將得到臨床醫生和支付方的大力支持，這主要取決於各個數據集的可靠性。我們預計在 2026 年上半年獲得 infigratinib 的更多數據，並期待屆時將討論其商業機會。

The launch of Attruby has provided invaluable experience in scaling rare disease commercialization from building disease awareness and engaging HCP networks to executing patient identification and access strategies. These learnings are directly informing our next wave of launches, including encaleret, BBP-418 and infigratinib.

Attruby 的推出為擴大罕見疾病商業化規模提供了寶貴的經驗，從提高疾病意識和與 HCP 網路合作，到執行患者識別和獲取策略。這些經驗將直接引導我們下一波產品上市，包括 encaleret、BBP-418 和 infigratinib。

Many of the same leadership, operations and market access teams who drove the success of Attruby are already in place to support these programs. In preparation for these upcoming launches, we have continued to expand disease state education initiatives and have begun hiring key commercial leadership positions. The response to our initial positions has been remarkable, underscoring both the strength of the BridgeBio platform and the excitement around our pipeline of transformative therapies that will meaningfully improve outcomes for the communities we serve.

推動 Attruby 取得成功的許多領導層、營運團隊和市場准入團隊已經到位，為這些專案提供支援。為迎接即將到來的產品發布，我們不斷擴大疾病狀態教育計劃，並已開始招募關鍵的商業領導職位。我們最初的定位得到了顯著的反響，這既凸顯了 BridgeBio 平台的實力，也展現了人們對我們一系列變革性療法的興奮之情，這些療法將切實改善我們所服務社區的治療效果。

The hiring momentum will continue to ramp over the next several quarters, leading into the respective potential approvals for each indication. Importantly, encaleret and BBP-418 will represent first-in-class options in their indications, while infigratinib would be the first daily oral medication in achondroplasia, allowing children a needle-free option for their daily care regimen.

未來幾個季度，招募動能將持續增強，為各項適應症的相應潛在批准做好準備。重要的是，encaleret 和 BBP-418 將成為各自適應症中的首創藥物，而 infigratinib 將成為首個用於治療軟骨發育不全的每日口服藥物，使兒童能夠以無針方式進行日常護理。

Beyond the US, we're actively building the infrastructure to support global commercialization, enabling coordinated launches and sustained access. Through our expanding global footprint, we are well positioned to deliver meaningful innovation to rare disease communities worldwide, ensuring global access, continuity and impact.

除了美國以外，我們正在積極建立基礎設施以支援全球商業化，從而實現協調一致的發布和持續的市場准入。憑藉我們不斷擴大的全球影響力，我們有能力為世界各地的罕見疾病群體帶來有意義的創新，確保全球範圍內的可及性、連續性和影響力。

With that, I will turn it over to Tom, who will discuss BridgeBio's financials.

接下來，我將把發言權交給湯姆，他將討論 BridgeBio 的財務狀況。

Thank you, Matt, and good morning, everyone. I'll now discuss our financial results for the third quarter of 2025. Please note that our commentary on today's call will focus on GAAP financials unless otherwise indicated. Total revenues were $120.7 million in 3Q 2025, consisting of $108.1 million of Attruby net product revenue, $4.3 million of royalty revenue and $8.3 million of license and services revenue compared to $2.7 million of the same period last year.

謝謝你，馬特，大家早安。接下來我將討論我們2025年第三季的財務表現。請注意，除非另有說明，我們今天電話會議的評論將主要圍繞GAAP財務數據。2025 年第三季總營收為 1.207 億美元，其中包括 Attruby 淨產品收入 1.081 億美元、特許權使用費收入 430 萬美元和授權及服務收入 830 萬美元，而去年同期為 270 萬美元。

The $118 million increase in total revenues was primarily due to a $108.1 million increase in net product revenue from Attruby driven by strong growth across all market segments. We also recorded $4.3 million in royalty revenue from ex-US net sales of Beyonttra in Europe and Japan.

總收入增加 1.18 億美元，主要歸功於 Attruby 的淨產品收入增加 1.081 億美元，這得益於所有市場領域的強勁增長。我們也記錄了來自歐洲和日本的 Beyonttra 在美國以外的淨銷售額的 430 萬美元版稅收入。

Total operating expenses for the third quarter of 2025 were $259.3 million compared to $193.9 million in the same period in the prior year. The $65.4 million increase in operating expenses was primarily driven by a $68.8 million increase in SG&A expenses, partially offset by a slight decline in R&D expenses. This reflects our continued investment in the Attruby brand awareness and ongoing investments in our late-stage clinical programs.

2025 年第三季總營運支出為 2.593 億美元，而去年同期為 1.939 億美元。營運費用增加 6,540 萬美元，主要是因為銷售、一般及行政費用增加 6,880 萬美元，部分被研發費用的略微下降所抵銷。這體現了我們對 Attruby 品牌知名度的持續投入，以及對後期臨床項目的持續投入。

Turning to our balance sheet, we ended the third quarter with a strong cash position of $645.9 million in cash, cash equivalents and marketable securities, which provides significant cash runway to continue supporting our transition into a diversified late-stage multiproduct business. In closing, our commercial launch of Attruby continues to accelerate, and our pipeline has never been stronger. Following the positive results from LGMD2I/R9 and ADH1, we now look forward to top line results from achondroplasia in early 2026. With that, I'll turn the call back over to Chinmay.

從資產負債表來看，截至第三季末，我們擁有強勁的現金儲備，包括現金、現金等價物和有價證券共計 6.459 億美元，這為我們繼續向多元化的後期多產品業務轉型提供了充足的現金支持。總之，Attruby 的商業化推廣正在加速進行，我們的產品線從未如此強大。繼 LGMD2I/R9 和 ADH1 取得積極成果後，我們現在期待在 2026 年初獲得軟骨發育不全的初步結果。這樣，我就把電話轉回欽邁了。

Thank you, Neil, Matt and Tom. We will now turn the call over to the operator, who will open the line for questions. We kindly request that you limit yourself to 1 question. Thank you.

謝謝尼爾、馬特和湯姆。現在我們將把電話轉接給接線員，由他/她接聽提問。請您只提一個問題。謝謝。

(Operator Instructions) Salim Syed, Mizuho.

（操作說明）Salim Syed，瑞穗。

Congrats on all the week's successes. Neil, Matt, maybe this one for you. Possible to comment on the percentage of new patient share. I know last time you provided the number, I think it was 18% to 20% on the 2Q call. Just wondering if that's increased since then.

恭喜你本週的所有成就。尼爾，馬特，或許這個適合你們。可以對新患者佔比百分比進行評論。我知道你上次提供這個數字的時候，我想是在第二季財報電話會議上說的18%到20%。想知道從那時起這個數字是否有增加。

And if that remains the primary focus for growth? Or are you also seeing an increase in the switch category?

如果這仍然是成長的主要重點呢？或者，您是否也觀察到交換器類別的成長？

Yes. Salim, good question. I'll take a crack and Matt, you can elaborate if I miss something. I mean I'd say our naive share, it's hard to tell, honestly, because we don't have all the numbers yet from Alnylam and Pfizer for the quarter. But our best guess is that the naive share is well in the 20s now.

是的。薩利姆，問得好。我來試著解釋一下，馬特，如果我漏掉了什麼，你可以補充說明。我的意思是，說實話，很難說我們目前的份額是多少，因為我們還沒有收到 Alnylam 和輝瑞公司本季的全部數據。但我們估計，目前天真投資者的份額已經超過 20%。

We've seen double-digit growth, obviously, in overall script quarter-on-quarter number, and that script growth has been even more profound in the NBRx setting. That means that we've seen a little bit of a downturn in the switch setting, and that's mostly because we're seeing a lot of combo use. There's some work that we could do in terms of reminding people that why not use the best stabilizer on top of a knockdown if you're going to go that route, but our NBRx share continues to grow nicely.

顯然，我們已經看到整體處方數量實現了兩位數的季度環比增長，而且在 NBRx 環境中，處方增長更為顯著。這意味著我們看到切換設定略有下降，這主要是因為我們看到很多連招的使用。我們也可以做一些工作，例如提醒人們，如果要使用避震器，為什麼不使用最好的穩定器呢？但我們的 NBRx 份額持續穩定成長。

Why do we focus on that? I mean, you know this as well as I do. But ultimately, your peak steady-state share is pretty simple, right? It's a fraction of new patients that you're capturing multiplied by the fraction of the total market that is new each year divided by the annual dropout rate. And if you look at this marketplace, the annual dropout rate is pretty high, something like 40% is what we modeled when you certainly look at Pfizer.

我們為什麼要關注這一點？我的意思是，你和我一樣清楚這一點。但歸根究底，你的峰值穩態份額其實很簡單，對吧？這是指您吸引的新患者比​​率乘以每年新增患者佔總市場的比例，然後除以年度流失率。如果你觀察這個市場，你會發現年度流失率相當高，我們模擬的結果顯示，以輝瑞為例，流失率約 40%。

And the fraction of the new markets that are adding patients to the market, it's not just replacement over time is going to be greater than that. So any time those two things are -- effectively, that fraction is greater than one . What you ultimately want to do is maximize a fraction of new patients that you capture.

而且，新增患者所佔的比例，不僅是隨著時間的推移而發生的替代，將會更大。所以，當這兩個條件都成立的時候──實際上，這個比例大於一。。你最終想要做的，是最大限度地提高你所吸引的新患者的比例。

So whatever if it's at 30%, then we're going to be a multiplier of that on peak year share. So -- as we look forward over the course of the next three to four years, obviously, our goal is 30-plus percent market share. We're well in range to do that even with the numbers that we have today, and I expect them to continue to grow.

所以，即便佔比達到 30%，我們也會將其乘以高峰年份的份額。所以——展望未來三到四年，很顯然，我們的目標是獲得 30% 以上的市場份額。即使以我們目前的數字，我們也完全有能力實現這一目標，而且我預計數字還會繼續增長。

Tyler Van Buren, TD Cowen.

泰勒·範·布倫，TD·考恩。

Congrats on another solid quarter of Attruby commercialization. So could you elaborate on the ATTR cardiomyopathy diagnosis rates and if you're continuing to see momentum build since the launch? And forgive me, but I have to ask a second one. So there are some centers that might prefer AMVUTTRA as they collect money on a much higher ASP despite the cost that it adds to the system.

恭喜 Attruby 商業化又一個季度取得穩健成果。那麼，您能否詳細說明 ATTR 心肌病變的診斷率，以及自產品上市以來，診斷率是否持續成長？請原諒，但我還得問第二個問題。因此，儘管 AMVUTTRA 會增加系統成本，但其平均售價更高，因此有些中心可能更喜歡 AMVUTTRA。

So curious to get your thoughts on that market dynamic. Do you expect this to impact a minority of the centers and patients -- and is it something that you have to adjust your strategy to in those centers?

非常想聽聽您對這種市場動態的看法。您預計這種情況只會影響少數中心和患者嗎？您是否需要針對這些中心調整策略？

Yes, 2 great questions, Tyler. Thanks for them. And I would say just in terms of market growth, again, until we get the full revenue numbers from Alnylam and Pfizer, I won't know precisely or be able to back into precisely the number of scripts on the quarter. But I can say pretty reliably, if you go back 1 year, so quarter and what that looked like this quarter last year, there's been a pretty robust and continued growth in diagnosis.

是的，泰勒，問得好，兩個問題。謝謝。至於市場成長，我想說，在 Alnylam 和輝瑞公佈完整的營收數據之前，我無法準確地知道或反推該季度的處方數量。但我可以相當肯定地說，如果你回顧一年前，也就是上個季度，看看去年這個季度的情況，你會發現診斷數量一直保持著相當強勁且持續的成長。

Certainly, what we're seeing in the field is a lot of growth in diagnosis. new practices, as you can see from our ACP data as well as doctors finding more of these patients. I think the PYP reimbursement concerns were overstated. We don't see that being a drag in terms of people finding new patients. And there's a lot of excitement and education going on in and around this category.

當然，我們在實際工作中看到的是診斷方面的大幅增長，新的診療方法也層出不窮，正如您從我們的ACP數據中看到的那樣，醫生們也發現了更多這類患者。我認為對 PYP 報銷問題的擔憂被誇大了。我們認為這不會對人們尋找新病人造成阻礙。在這個領域內外，湧現出了很多令人興奮的事情，也帶來了許多教育意義。

If you go to any of the conferences, and I'm sure the same is going to be at AHA, these sessions are packed. People are keen to learn more about ATTR cardiomyopathy. And with all the publications ongoing, there's a lot of people who want to throw their hat in to be part of the next wave of learning in this space. So I expect that diagnosis rates will continue to increase and get us closer to that 250,000 that ultimately we should get to in the US

如果你去參加任何一次會議（我相信 AHA 會議也會如此），你會發現這些會議都非常火爆。人們渴望了解更多關於ATTR心肌病變的資訊。隨著各種出版物的不斷湧現，許多人都想加入這個領域的下一波學習浪潮。所以我預期診斷率會繼續上升，使我們更接近美國最終應該達到的25萬例的目標。

Second question on the buy-and-bill dynamic. I mean it's not -- I don't think we have to adjust our strategy because we always knew that, that was going to be the case. Certainly, there are certain centers of excellence that if you have a reasonable CFO at a hospital system, you're going to be 340B pricing. And so there's a lot of profit that one can take. from that.

關於買進結算動態的第二個問題。我的意思是，我認為我們不需要調整策略，因為我們一直都知道情況會是這樣。當然，對於某些卓越中心而言，如果你在醫院系統中擁有一位合理的財務官，你將會採用 340B 定價。因此，從中可以獲得許多利潤。

But I would say, writ large, unlike rheumatology, when you get out into the high-volume heart failure practices, this is not a meaningful part of the profit center associated with those practices. And so you're not see a lot of cardiologists just looking at buy-and-bill as the way to make more money. So we haven't seen that. And overall, I would say, amidst the specialty community, you see just a lot of focus on doing the right thing in terms of data efficacy, in terms of safety and ultimately in terms of cost.

但我想說，總的來說，與風濕病不同，當你深入了解大量心臟衰竭患者的診療過程時，你會發現這並不是這些診療過程利潤中心的重要組成部分。因此，你不會看到很多心臟科醫生僅僅把「買斷收費」當作賺錢的途徑。所以我們還沒有看到這種情況。總的來說，我認為，在專業領域，人們非常注重在資料有效性、安全性和最終成本方面做正確的事情。

Right now, you're seeing a lot of combo use. You're seeing some centers do a lot of super high-priced drug use, but I even hear physicians within those centers saying, I'm not sure I should be putting someone on $1 million worth of therapy if indeed there's no data to back up the fact that, that's more efficacious than a low-cost small molecule like ours.

現在，你會看到很多連招的使用。你會看到一些醫療中心大量使用價格極高的藥物，但我甚至聽到這些中心的醫生說，如果確實沒有數據支持這種藥物比像我們這樣的低成本小分子藥物更有效，我不確定我是否應該讓某人接受價值 100 萬美元的治療。

So I think, again, in the long term, as you saw in the TNFs and other buy-and-bill type things, the combination of good data and what payers will ultimately do as they control this category more, I think, will drive certainly that NBRx share up for the small molecule stabilizers as compared to the high cost with worst point estimates, knockdowns that are buy and bill.

所以我認為，從長遠來看，正如你在 TNF 和其他「買藥計費」類型的藥物中所看到的，良好的數據以及支付方最終會採取的措施（隨著他們更好地控制這一類別），我認為肯定會推動小分子穩定劑的 NBRx 份額上升，而「買藥計費」的高成本和最差的預估結果，以及由此上升的預估結果，以及由此上升。

Biren Amin, Piper Sandler.

比倫·阿明，派珀·桑德勒。

I got to say it's the first to have three positive investor calls by a single company in one week. So congrats on that. My question, you talked about market access as a top priority for the company. Thoughts on Pfizer matching the 28-day free trial with VYNDAMAX, any impact from this program that you foresee?

不得不說，這是第一家在一周內獲得三家來自投資者的正面評價的公司。恭喜你！我的問題是，您曾提到市場准入是公司的首要任務。輝瑞公司推出與 VYNDAMAX 相同的 28 天免費試用計劃，您對此有何看法？您預見該計劃會產生什麼影響？

Yes. Great question, Biren, and thanks for the compliment there. We see it as a positive. Anytime you actually roll out a program that's generous to patients, I assume our competition is going to match it. And ultimately, it gets us thinking about what else we can do.

是的。比倫，問得好，也謝謝你的讚美。我們認為這是件好事。任何時候，只要你推出一項對病人慷慨的計劃，我都會認為我們的競爭對手會跟進。最終，它讓我們思考我們還能做些什麼。

I mean, I think if you look across the totality of our programs, they continue to be the most generous in the space.

我的意思是，如果你縱觀我們所有的項目，它們仍然是該領域最慷慨的。

But overall, we welcome that type of competition. It shouldn't really be access ultimately that's driving the differential share that we gain. Ultimately, all we want is an even playing field, and that's what we've been talking about writ large across the payer and provider landscape and then ultimately to let our efficacy data speak. If you add anything?

但總的來說，我們歡迎這種類型的競爭。最終，真正決定我們市場佔有率差異的不應該是市場進入。歸根究底，我們想要的只是一個公平的競爭環境，這也是我們一直在支付方和提供方領域廣泛討論的問題，最終還是要讓我們的療效數據來說明一切。還要補充什麼嗎？

No, I think that's exactly right. It's it's not a bad thing when someone copies a good program. And so in terms of it impacting, I don't think we've seen an impact from it. It's -- when you're the first one to do it, I think people remember that one maybe a little bit more, but we were happy to see them offer that. Any competitor ought to be thinking about doing the same thing, whether it's the free drug for life that we did for our patients in the clinical trial or with the 28-day free trial.

不，我覺得完全正確。有人抄襲優秀的程式並不是壞事。所以就其影響而言，我認為我們還沒有看到它產生影響。當你是第一個這麼做的人時，我想人們可能會對這件事記住得更多一些，但我們很高興看到他們提供了這項服務。任何競爭對手都應該考慮採取相同的做法，無論是像我們在臨床試驗中為患者提供的終身免費藥物，還是 28 天的免費試用。

So I think --

所以我覺得--

Maybe one final thing, Biren. Obviously, our LDN is completely differently designed than theirs and the entirety of the patient and physician experience is pretty different, not just because of some of the programs that we rolled out.

比倫，或許還有最後一件事。顯然，我們的 LDN 與他們的設計完全不同，患者和醫生的整個體驗也截然不同，這不僅僅是因為我們推出了一些專案。

So I'd encourage you to go and hear from patients and physicians, just how quickly are they receiving therapy in the context of our drug and how easy is it for them to continue on the drug product. regardless of the programs that are put in place, just the way we've designed this with a high-touch, white glove rare disease approach has meaningful advantages.

因此，我鼓勵大家去聽聽患者和醫生的回饋，了解他們在接受我們藥物治療後多久才能起效，以及他們能否順利地繼續服用該藥物。無論後續實施何種方案，我們以高度個人化、細緻入微的罕見病診療模式所設計的方案本身就具有顯著優勢。

Our next question comes from the line of Mani Foroohar with Leerink.

我們的下一個問題來自 Mani Foroohar 與 Leerink 的對話。

You have Ryan on for Mani. Congrats on the quarter. Maybe just could you talk about how you see the size of the OUS opportunity relative to that of the US and ATTR, particularly as those launches start to ramp up?

瑞恩代替馬尼上場。恭喜你本季取得佳績。您能否談談您如何看待美國境外市場相對於美國和ATTR市場的機會規模，尤其是在這些發射開始加速的情況下？

Yes, I can take that, and Matt, you can elaborate on it. I think the OUS opportunity has been quite interesting, obviously, as I mentioned in my outset comments, Bayer has done a very, very nice job in the countries that they've commercialized in to date.

是的，我可以接受，馬特，你可以詳細解釋。我認為 OUS 的機會非常有趣，顯然，正如我在開篇評論中提到的，拜耳在迄今為止已實現商業化的國家中做得非常出色。

What makes it interesting, obviously, is ultimately, in some ways, they're able to fast forward to what I think the ultimate answer is in the United States, which is accurate advertising, obviously, issuing some of the incomplete statements around near complete stabilization that our competitors have. And I think secondly, a lot of the experts are able to look at the totality of the data and understand from a health economic real-world evidence standpoint, which therapy should be used frontline and which therapies should not.

顯然，有趣的是，最終，在某種程度上，他們能夠快速推進到我認為的美國最終答案，那就是準確的廣告，顯然，發布一些關於近乎完全穩定的不完整聲明，而我們的競爭對手卻有這樣的聲明。其次，我認為許多專家能夠全面審視數據，並從衛生經濟學和現實世界證據的角度理解哪些療法應該作為第一線療法，哪些療法不應該作為第一線療法。

So I think we're relatively advantaged in that marketplace in terms of share. Where we're not advantaged, obviously, from an overall market standing standpoint is the price point. The price point is going to come down as we move from some of the countries we're already commercializing in countries like the U.K. And so ultimately, I expect to see the ratio of sales between Europe and the US to be pretty similar to what we see in TAF.

所以我認為，就市場佔有率而言，我們在這個市場中具有相對優勢。顯然，從整體市場地位來看，我們不佔優勢的地方在於價格點。隨著我們從一些已經在英國等國家進行商業化的國家擴展到其他國家，價格將會下降。因此，最終，我預計歐洲和美國的銷售比例將與我們在TAF看到的比例非常相似。

But again, I think Bayer has done a really nice job of accelerating some of those market dynamics in Europe in ways that we simply can't do given the current status of the playing field in the United States.

但我認為，拜耳在歐洲加速某些市場動態方面做得非常出色，而鑑於美國目前的競爭環境，我們根本無法做到這一點。

Josh Schimmer, Cantor.

喬許希默，坎托爾。

Quite the weak for you guys. Have you had any discussions with payers regarding what might happen to formulary positioning of Attruby when TAF generics do enter? And separately, have you discussed with payers the use of combination therapy as it stands now? I'm a little surprised they're on board with it given the cost and the lack of data.

對你們來說，這實力也太弱了吧。您是否與支付方討​​論過，當TAF仿製藥進入市場時，Attruby的處方集地位可能會發生怎樣的變化？另外，您是否與支付方討​​論過目前聯合療法的使用情況？考慮到成本和數據不足，我對他們能接受這個方案感到有些驚訝。

So no, to the first question, we've been focused on Attruby solely and really getting it as on equal playing field with TAF and to date. I think on the second, we also haven't had conversations around combo therapy.

所以，對於第一個問題，答案是否定的，我們一直專注於 Attruby，並真正努力使其與 TAF 處於同等地位，而且到目前為止也是如此。我認為第二個問題是，我們還沒有討論過聯合療法。

I think we've had conversations with physicians around it, and I expect that payers will do more to control this category as we move forward. But right now, the mechanisms of B versus D and things of that nature make it, I think, a slow-moving train in that respect. It will ultimately happen, but I don't think it happens in the next 6 to 12 months.

我認為我們已經就此與醫生們進行了討論，我預計隨著事態發展，支付方將採取更多措施來控制這一類別。但就目前而言，B 與 D 之間的機制以及類似的事情，我認為，就這方面而言，它就像一列行駛緩慢的火車。這件事最終會發生，但我認為不會在未來 6 到 12 個月內發生。

Yes. And I think we just really remain -- as Neil said earlier, we just remain focused on making sure Attruby is available to any patient who wants it. And as long as that is out there, we feel really good about our data, and we can fight it out in the doctor's office versus trying to fight it out in the payer space.

是的。正如尼爾之前所說，我認為我們仍然專注於確保任何需要 Attruby 的患者都能獲得治療。只要這些數據存在，我們就對自己的數據充滿信心，我們可以在醫生的診間與之抗爭，而不是在支付方領域與之抗爭。

Cory Kasimov, Evercore.

Cory Kasimov，Evercore。

So your prepared comments noted the impressive growth, both in unique prescribers as well as prescriptions per prescriber. Can you talk about what's primarily driving that momentum, whether it's the greater penetration within existing accounts, expansion into new centers or improved conversion rate?

所以，您事先準備好的評論指出，無論是處方醫生的數量還是每位處方醫生的處方數量，都取得了令人矚目的增長。您能否談談推動這一成長動能的主要因素是什麼，是現有客戶滲透率的提高、向新中心的擴張還是轉換率的提高？

Yes, I won't break it down quantitatively, but it's actually kind of equivalently both. And I would say one interesting piece is a lot of these new prescribing HCPs are effectively capitated parts of a center of excellence or the referrers into centers of excellence. One thing we were finding early on were some centers of excellence where our share might not have been as high.

是的，我不會進行量化分析，但實際上兩者在某種程度上是等價的。我想說，一個有趣的現像是，許多新的處方權醫療保健專業人員實際上是卓越中心的按人頭付費成員，或是卓越中心的轉診人員。我們早期發現的一點是，在一些卓越中心，我們的份額可能並不高。

When we went and spoke to the physicians, they would say, yes, we believe that Attruby is a stellar drug, and we would like 30%, 40% of our patients to be on it. But if a patient comes in already on TAF, we're not going to change them. And so it behooved us to get out to those practices that we weren't covering. We have a smaller sales force than does Pfizer or Alnylam.

當我們去和醫生們交談時，他們會說，是的，我們認為 Attruby 是一種非常優秀的藥物，我們希望 30% 到 40% 的患者都能服用它。但如果病人入院時已經在使用TAF，我們就不會改變他們的用藥。因此，我們有責任去了解那些我們沒有報導過的實作活動。我們的銷售團隊規模比輝瑞或Alnylam小。

But we've started to do that, and we've employed some IT techniques as well so that we get sort of alerts anytime someone is prescribing. And we're just getting to know some of those what people call ancillary or satellite practices better. So both things have been driving the scripts.

但我們已經開始這樣做了，我們也採用了一些IT技術，以便在有人開處方時收到警報。我們正在逐漸更了解一些人們所說的輔助性或附屬性醫療機構。所以，這兩件事都對劇本產生了影響。

Anupam Rama, JPMorgan.

Anupam Rama，摩根大通。

Just two quick ones for me, just I'm wondering what the marketing message is around -- to docs around patients with mixed phenotype for Attruby. And then actually a higher-level strategic question. After the first couple of days of this week, like the path to top-line diversification here is pretty clear, and I know we're waiting on infigratinib. But Neil, maybe following on some of your prepared comments, how should we be thinking about investments into kind of the early-stage and mid-stage pipeline? And when do we learn more about those programs and catalyst time lines and things like that?

我只有兩個問題想問一下，我想知道針對 Attruby 的混合表型患者的營銷訊息是什麼——針對醫生而言。然後，實際上還有一個更高層次的策略問題。經過本週的前幾天，實現頂級多元化的道路已經相當清晰，我知道我們正在等待 infigratinib。但是尼爾，也許在你事先準備好的一些發言之後，我們該如何看待對早期和中期研發管線的投資呢？我們何時才能了解更多關於這些項目、催化劑時間表以及類似的事情的資訊？

Yes. Thanks for those questions. On mixed pheno, honestly, we don't see -- I mean, this is more of a question that we get from investors than we do from physicians or in the field. For the most part, the patients that we serve have to do with cardiomyopathy, and that's the salient set of characteristics that drive their mortality and morbidity.

是的。謝謝您提出這些問題。說實話，關於混合表型，我們很少見到——我的意思是，這個問題更多是來自投資者，而不是醫生或業內人士。我們服務的患者大多患有心肌病變，而心肌病變正是導致他們死亡率和發病率的主要特徵。

In and around mixed phenotype, the best thing we can do is continue to hammer our variant message. Obviously, variants are where you get mixed phenotype, you don't get mixed phenotype within the context of the wild-type population. And as we suggested in our prepared comments, we continue to, I think, publish the most impressive data within the context of the variant population, that 59% hazard reduction, I think it's the largest point estimate and the only statistically significant point estimate in that space. Again, stay tuned for some of the things that we're going to be publishing at AHA, but I think it builds on that within the variant population.

對於混合表型，我們能做的最好的事情就是繼續大力宣傳我們的變異訊息。顯然，變異體中會出現混合表型，而野生型群體中不會出現混合表型。正如我們在準備好的評論中所建議的那樣，我認為，我們繼續發布變異人群中最令人印象深刻的數據，即 59% 的風險降低，我認為這是最大的點估計值，也是該領域中唯一具有統計意義的點估計值。再次提醒大家，我們將在 AHA 上發表一些內容，但我認為它是在變異族群中建立起來的。

And all of that connects back to the fact that biochemically, we have a differentiated binding profile for those variants. And I think if you look at the JACC paper associated with the AMVUTTRA trial, you can see that they didn't quite do in variants what people suspected they might in terms of a differentiated efficacy. So we continue to believe we have the most efficacious profile within that space and the V122Is are going to be the most common of the variant population that we see.

所有這些都與以下事實相關：從生物化學角度來看，我們對這些變體具有不同的結合特性。我認為，如果你看看與 AMVUTTRA 試驗相關的 JACC 論文，你會發現，在差異化療效方面，他們在變體方面並沒有完全達到人們預期的效果。因此，我們仍然相信我們在該領域擁有最有效的方案，而 V122Is 將是我們所見到的變異群體中最常見的。

I would say, finally, just on that variant population, it's just another good example of how we're trying to really view Attruby as a unique property and look to see whether or not we can in presymptomatic patients, intervene early so that they can stave off future heart failure altogether, and that's that ACT-EARLY trial. So I think we're doing quite a bit to address that marketplace.

最後，我想說，就這個變異族群而言，這又是一個很好的例子，說明我們如何真正地將 Attruby 視為一種獨特的特性，並研究我們是否可以對無症狀患者進行早期幹預，以便他們能夠完全避免未來的心臟衰竭，這就是 ACT-EARLY 試驗。所以我認為我們正在為滿足這個市場需求做很多工作。

Secondly, just in and around top line diversification, I'd say, first and foremost, we're laser-focused on nailing the launch of the two, hopefully, the third product to come here in early next year. Three launches for any company, I think, is a big thing to do, and it's going to be big for BridgeBio here for us to stick it. Obviously, it's going to be a couple of first-in-class launches and then another competitive launch. So a couple of different characteristics as we build out our commercial muscle.

其次，就營收多元化而言，我認為，首先也是最重要的，我們正全力以赴地確保明年年初推出的兩款產品（希望還有第三款產品）能夠順利上市。我認為，對任何公司來說，推出三款產品都是一件大事，對 BridgeBio 來說，能否成功更是意義重大。顯然，將會有幾款同類首創產品上市，然後再有一款具有競爭力的產品上市。因此，在我們增強商業實力的過程中，會呈現出一些不同的特質。

That being said, this is maybe -- save eight, nine years ago, the most interesting time to do research and early development in rare and orphan disease, almost no competition, to be honest. And the scientific tailwinds are, I mean, nothing short of mesmerizing. You're reading the journals, Anup, I know, just as I am, but the pan-genome, long-read sequencing, what we're learning about non-coding regulatory regimes, all of that is really suggesting a wide variety of new targets we can go after to help patients in profound ways.

也就是說，除了八、九年前，現在可能是進行罕見疾病和孤兒病研究和早期開發的最佳時期，說實話，幾乎沒有競爭。而科學領域的發展勢頭，我的意思是，簡直令人著迷。阿努普，我知道你和我一樣都在閱讀期刊，但是泛基因組、長讀測序，以及我們對非編碼調控機制的了解，所有這些都表明我們可以著手研究各種各樣的新靶點，從而以深刻的方式幫助患者。

And that's why the buildup of some 17 assets in the context of Gondola. And I would say, again, as Bridge shareholders, there's 0 information asymmetry between those 2 entities and a high degree of ownership that Bridge has into Gondola. So at the right time, again, when shareholders and the Board and management are aligned that we have capacity, I think we have growth that we can access from there.

這就是為什麼在纜車背景下累積了大約 17 項資產的原因。我再次強調，作為 Bridge 的股東，這兩個實體之間不存在任何資訊不對稱，而且 Bridge 對 Gondola 擁有高度的所有權。所以，在適當的時機，當股東、董事會和管理階層意見一致，我們有能力時，我認為我們就能成長。

And by the way, we're looking across the industry right now. There are several other entities out there that may be deprioritizing rare and orphan disease because investors don't view it as high a priority as I&I or certain areas of oncology. And where we do view it as attractive, we can be a reasonable partner all the way through the life cycle of early research all the way to commercial.

順便說一句，我們目前正在關注整個行業。還有一些機構可能降低了對罕見疾病和孤兒病的重視程度，因為投資者認為罕見疾病和孤兒疾病不如免疫和感染性疾病或某些腫瘤領域那麼重要。如果我們認為某個專案有吸引力，我們就可以在整個生命週期中，從早期研究到商業化，成為一個合理的合作夥伴。

So the aperture is pretty broad right now. I'd say the competitive intensity is pretty low. So at the right time, I think we'll be able to return to growth in terms of programmatic growth in the right way. But we got to stick the landing on these launches first.

所以目前光圈相當大。我認為競爭強度相當低。所以，我認為在合適的時機，我們將能夠以正確的方式恢復程序化成長。但我們首先得確保這些發射順利降落。

Andrew Tsai, Jefferies.

Andrew Tsai，傑富瑞集團。

Congrats on the strong execution. My question is around -- back to Attruby. You're accumulating a lot of real-world evidence suggesting better efficacy over tafamidis. That's great. But I'm curious what your guys' thoughts are in doing a head-to-head study to fully prove that out.

恭喜你們出色地完成了任務。我的問題是關於——回到阿特魯比。你們正在累積大量真實世界的證據，顯示其療效優於他法米地。那太棒了。但我很好奇你們覺得做一項直接對比研究來徹底證明這一點有什麼想法。

I'd also imagine that could help mitigate against any risk of a future tafamidis generic, so kill 2 birds with one stone.

我也認為這有助於降低未來 tafamidis 仿製藥的風險，可謂一舉兩得。

Yes. I mean, I think great question. Thanks for the question. A couple of comments there. Number one is, I think we've been doing a lot of this sort of head-to-head competitive.

是的。我覺得這個問題問得很好。謝謝你的提問。有幾點要說明。第一點是，我認為我們一直在進行很多這種正面交鋒的競爭。

We are a better stabilizer across the 4 in vitro assays across every single serum TTR measurement that we've seen across NT-proBNP, across whatever point estimates we can look at where you can line things up, it appears that we are a better stabilizer and that better stabilization leads to better outcomes.

在 4 項體外試驗中，我們在每項血清 TTR 測量中都表現出更好的穩定性，在 NT-proBNP 中也表現出更好的穩定性，在我們能夠看到的任何點估計中，只要能夠進行對比，我們的穩定性似乎都更好，而更好的穩定性會帶來更好的結果。

I'm not so sure that, that is going to continue to resonate with the clinical community versus kind of the area that we're set off now in, which is describing what's unique about our property given the fact that it is an ever more potent stabilizer.

我不太確定這是否能繼續引起臨床界的共鳴，而我們現在所處的領域，即描述我們產品的獨特之處，因為它是一種越來越有效的穩定劑，是否更能引起臨床界的共鳴。

So some of the things you're seeing in terms of publications in the variant population in terms of AFib and the cardiac arrhythmic population, some of the things that we'll be looking at in terms of the cardiorenal axis, those are all completely unique. And I think aspects of the compound that are -- they won't easily be matched by the other therapies in this space. So I would say that's one thing.

因此，在心房顫動和心律不整人群的變異人群的出版物中，你看到的一些事情，以及我們將在心腎軸方面研究的一些事情，都是完全獨特的。而且我認為這種化合物的某些方面——是該領域其他療法難以匹敵的。所以我覺得這是其中一點。

The second thing is the double-blind head-to-head is something that I still think about a lot, but the double-blind head-to-head that's doable for us at this size is a double-blind head-to-head against serum TTR, which we obviously win, and I'm not so sure it drives any market share or a double-blind head-to-head against NT-proBNP, which I also think we will pretty obviously win. But also, I'm not sure it would drive a ton of market share.

第二件事是雙盲頭對頭試驗，我仍然經常考慮這個問題，但以我們目前的規模，能夠進行的雙盲頭對頭試驗是與血清 TTR 進行的雙盲頭對頭試驗，我們顯然會贏，但我不太確定它能否帶來任何市場份額，或者與 NT-proBNP 進行的雙盲頭對頭試驗，我也認為我們顯然會贏。但是，我也不確定它能否獲得很大的市場份額。

And the reason I say that is I think people are really -- they think about different patient populations, what patients want. When we talk to our customers, they're not looking for a double-blind head-to-head to say this drug product is definitively the one I'm going to use in every case. And a good sort of eye-opener on that was the JACC paper that AMVUTTRA published. But if you really cared about double-blind head-to-head, you look at the vu arm and you look at the TAF arm, both monotherapy, and you see that they deliver the exact same results.

我這麼說的原因是，我認為人們真的會——他們會考慮不同的患者群體，考慮患者想要什麼。當我們與客戶交談時，他們並不需要進行雙盲直接對比試驗來斷定這種藥物產品一定是他們在任何情況下都會使用的。AMVUTTRA 發表在 JACC 上的論文對此進行了很好的闡述，讓我大開眼界。但如果你真的關心雙盲頭對頭試驗，你看看 vu 組和 TAF 組，都是單藥治療，你會發現它們的結果完全相同。

And by the way, acoramidis beat TAF everywhere we looked in our trial. And that was actually baselines were very, very close in the HELIOS-B trial. So if people really, really cared about these like head-to-head type studies, they would look at that data and scratch their heads and be like, what's going on?

順便說一句，在我們的試驗中，acoramidis 在所有方面都勝過了 TAF。事實上，HELIOS-B 試驗的基線非常非常接近。所以，如果人們真的非常關心這些直接對比的研究，他們就會查看這些數據，然後搔頭納悶，到底發生了什麼事？

Obviously, what's going on is that the PK of knockdown starts in the 60s and ultimately gets to the 80s only after 22 months for AMVUTTRA, and that's probably why it doesn't outperform TAF in that HELIOS-B characterization. So I'm not so sure that spending $300 million or whatever, $400 million and et cetera, et cetera, to run a double-blind head-to-head would do much here.

顯然，AMVUTTRA 的擊倒 PK 值從 60 多開始，最終在 22 個月後達到 80 多，這可能是為什麼它在 HELIOS-B 特性方面沒有超過 TAF 的原因。所以我不太確定花費 3 億美元、4 億美元等等，進行一場雙盲一對一比賽在這裡會有多大作用。

And then finally, you and Josh both referred to TAF generic, and I'm not going to make any comments on timing there, although I have a view that I think most of you know. But even if it does go generic and Pfizer determines that they don't want to defend this property in any way, shape or form, I mean, look, we're basically a generic in terms of pricing as compared to AMVUTTRA. I don't see payers stepping in and saying, you can't use this drug or you have to step through this drug, certainly in the United States anytime soon and especially given the differentiated data that we have already presented.

最後，你和 Josh 都提到了 TAF 通用名，關於時機我就不多說了，雖然我個人認為你們大多數人都知道這一點。但即使它真的變成了仿製藥，而輝瑞決定不以任何方式捍衛這一特性，我的意思是，你看，與 AMVUTTRA 相比，我們在定價方面基本上就是仿製藥了。我不認為支付方會介入並說，你不能使用這種藥物，或者你必須逐步使用這種藥物，尤其是在美國，考慮到我們已經提出的差異化數據，這種情況近期內肯定不會發生。

And the final point on that is I really do think real-world evidence is -- I mean, you talk to the FDA, you talk to a lot of clinicians these days. They're very keen on understanding how these drugs perform in the real world. And so I think a lot of differential work that we do will be associated with real-world evidence. And I think a lot of that will actually be pretty impactful for the prescribing universe we look at, maybe even more impactful than a very specific clinical trial. So those would be my comments on that.

最後一點是，我真的認為現實世界的證據——我的意思是，你去問問FDA，你現在和很多臨床醫生談談就知道了。他們非常渴望了解這些藥物在現實世界中的表現。因此，我認為我們所做的許多差異化研究都將與現實世界的證據相關聯。我認為這其中很多內容實際上會對我們所關注的處方領域產生相當大的影響，甚至可能比某個非常具體的臨床試驗的影響更大。以上就是我對此事的看法。

Danielle Brill, Truist.

Danielle Brill，Truist。

And since we're going to expect a positive Phase 3, maybe I'll pivot and ask a question on infigratinib. Neil, what are the most important differentiating elements for infigratinib in achondroplasia in view? Is it more about efficacy or route of administration? And can you talk about safety and how important that is? What level of hyperphosphatemia is acceptable in your view?

既然我們預期 3 期臨床試驗會取得正面成果，也許我會轉換主題，問一個關於 infigratinib 的問題。Neil，對於軟骨發育不全患者而言，英菲格替尼最重要的鑑別要素是什麼？是療效比較重要還是給藥途徑比較重要？您能談談安全問題以及安全的重要性嗎？您認為可接受的高血磷症水平是多少？

Yes. Great question. One thing I've learned from Matt and others now having a commercial franchise is that the customer is always right, and you can never really tell why a customer may prefer one drug product versus the next. That's what makes market share relatively hard to project in the absence of head-to-head -- double-blind head head-to-head trials. The good news here is that we're more efficacious, we're safer and we're more convenient with an oral ROA.

是的。問得好。我從 Matt 和其他擁有商業特許經營權的人身上學到的一點是，顧客永遠是對的，而且你永遠無法真正知道為什麼顧客會更喜歡一種藥品而不是另一種藥物。正因如此，在沒有進行直接對比試驗（雙盲直接對比試驗）的情況下，市佔率才比較難以預測。好消息是，口服給藥途徑更有效、更安全、更方便。

So whatever your preference in terms of why you're determining which drug to use, infigratinib is going to win. As a scientist, obviously, down deep, I would prefer the most efficacious product win. And I think we've already demonstrated and we'll continue to demonstrate superior efficacy. Why? Because, as you know, this targets this well-described condition at its source, addressing both of the salient effector signaling pathways.

所以無論你是因為什麼原因決定使用哪一種藥物，英菲格拉替尼都會勝出。身為科學家，很顯然，從內心深處來說，我更希望療效最好的產品勝出。我認為我們已經證明並將繼續證明我們具有卓越的療效。為什麼？因為，如您所知，這種方法從根源解決了這種已充分描述的病症，同時解決了兩個顯著的效應訊號路徑。

It's superior in every preclinical model. It's superior in animal models. It's superior in Phase 2 data. It's the only product that's provided proportionality impact.

它在所有臨床前模型中都表現出優越性。在動物模型中表現較佳。二期臨床試驗數據顯示其表現較優。它是唯一一款能夠產生比例效應的產品。

And I think over the longer term, we'll provide a broader diaspora of impact for this community that we serve as compared to the CMP products. So I don't think there's any aspect. We obviously don't see the hypotensive results, and I don't think we're going to have as robust a Section 4 as the CNP products have in terms of safety. I think this will be a safer product. Grade 1 hyperphosph, I think it could be 15%, 20% could be -- like people do not care about that as much as the Street cares about that.

而且我認為從長遠來看，與 CMP 產品相比，我們將為我們所服務的社區帶來更廣泛的影響。所以我覺得這方面沒有任何問題。我們顯然沒有看到低血壓的結果，而且我認為我們在安全性方面不會像 CNP 產品那樣擁有強大的第 4 部分。我認為這將是一款更安全的產品。1級高磷化氫，我認為可能是15%，也可能是20%——就像人們不像華爾街那樣關心這個一樣。

Again, what they do care about are things that ultimately would be things associated with hypergrowth, spinal situations, things of that nature. And we see no evidence of any safety issues in and around that. So I think the drug will be more efficacious, safer and ultimately more convenient. And I think that will open up the market, which obviously is starting to stagnate a bit given the current profile of the drugs. I think we can continue to address unmet need.

再說一遍，他們真正關心的是那些最終與過度生長、脊椎問題以及類似性質的問題有關的事情。我們沒有發現該地區及其周邊有任何安全問題。所以我認為這種藥物會更有效、更安全，最終也會更方便。我認為這將打開市場，鑑於目前藥物的狀況，市場顯然開始有些停滯不前。我認為我們可以繼續滿足未被滿足的需求。

And I think however you want to slice and dice it, we'll have a great offering for the community here.

我認為無論你怎麼分析，我們都會為社群帶來許多好處。

Jason Zemansky, Bank of America.

傑森‧澤曼斯基，美國銀行。

On all the progress. Maybe to connect some of the dots from your previous comments here, I mean, in thinking about infigratinib as a growth driver, I mean, you've guided to opportunities of $2 billion each in achondroplasia and hypochondroplasia.

關於所有進展。也許為了將您先前的評論聯繫起來，我的意思是，在考慮將 infigratinib 作為成長驅動力時，您指出，軟骨發育不全和軟骨發育不良領域各有 20 億美元的機會。

Can you walk us through some of your key assumptions here given the competitive landscape? Is this more that you're capturing share from a competitor? Are you growing the market appreciably? I mean what gives you confidence in both of these numbers?

鑑於當前的競爭格局，您能否為我們詳細介紹您的一些關鍵假設？這是否意味著你正在從競爭對手手中奪取市場份額？你們的市佔率是否顯著成長？我的意思是，是什麼讓你對這兩個數字都這麼有信心？

Yes. I mean I think, first, we do tend to estimate these numbers starting with the treatable population and making assumptions in and around there. Certainly, in the context of an already launched product, we're going to be looking to both take share as well as to grow the market.

是的。我的意思是，我認為，首先，我們傾向於從可治療人群開始估算這些數字，並在此基礎上做出假設。當然，對於一款已經上市的產品，我們既要爭取市場份額，也要努力擴大市場。

I think it's important to realize that there are substantial parts of the unmet need here that aren't addressed by once-daily injectables. We've heard that when we go out into the community. We've heard that in talking to physicians. I think it's a bit unfair to look at the market sometimes with a suboptimal therapy and conclude that, that is the market size. I play in EPP as well, and I wouldn't look at CLINUVEL's product and determine that EPP is an extraordinarily small market.

我認為重要的是要認識到，這裡存在相當一部分未被滿足的需求，而這些需求是每日一次注射劑無法解決的。我們訪問社區時都聽過這樣的說法。我們在與醫生交談時也聽過這種說法。我認為，有時用一種不理想的療法來衡量市場，並得出這就是市場規模的結論，這有點不公平。我也玩EPP，我不會因為CLINUVEL的產品就斷定EPP是一個特別小的市場。

So I think the unmet need is relatively well described in terms of numbers of patients. And it's not in the context of this condition that we don't know how to find the patients and that they are not already well identified. So I think it just comes down to offering them something that they want, and I think this could be that from our research.

所以我認為，從患者人數來看，未滿足的需求已經得到了較充分的描述。並不是因為這種情況，我們才不知道如何找到患者，也不是因為這些患者還沒有被充分辨識出來。所以我覺得關鍵在於提供他們想要的東西，而根據我們的研究，我認為這可能是他們想要的東西。

Paul Choi, Goldman Sachs.

Paul Choi，高盛。

Congrats on the string of good news this week. I also want to stay on the topic of achondroplasia, Neil. And as you know, the current approved product is three quarters of the sales are coming from ex-US, with only one quarter of the sales from the US market. And so could you maybe comment on what could be market expanding for the US market in particular here?

恭喜你本周喜訊連連。尼爾，我還想繼續談軟骨發育不全這個話題。如您所知，目前獲批產品的銷售額中，四分之三來自美國以外的地區，只有四分之一來自美國市場。那麼，您能否就美國市場，特別是哪些因素可能有助於市場擴張發表一下看法？

How large -- you talked a little bit about the TAM, but just sort of what are the key factors from market expansion happening here? And then in terms of the product, just sort of how much you think incremental the hypochondroplasia opportunity could be to your infigratinib sales?

市場規模有多大？您剛剛談到了TAM（總市場規模），但目前市場擴張的關鍵因素是什麼？那麼就產品而言，您認為軟骨發育不全的市場機會能為英菲格替尼的銷售額帶來多大的增量？

Yes. Thanks, Paul. I'm a bit remiss to comment on the commercial tactics or performance of one of our competitors. There's nothing in and around the unmet need, the physician community or the community affected with achondroplasia that's starkly different between Europe and the United States. And so I think, again, a solid therapy could work well in both markets.

是的。謝謝你，保羅。我不太適合評論我們競爭對手的商業策略或績效。在未滿足的需求、醫生群體或受軟骨發育不全影響的群體方面，歐洲和美國之間並沒有明顯的差異。所以我認為，一種有效的療法在兩個市場都能取得良好的效果。

And I'd expect actually the normal ratio that you see with drug products to be true in the context of this category as well. So why the launch hasn't gone that well for our competitor in this case? I mean, number one, I go back to injectables. We do hear a lot of needle phobia, particularly in the US markets, which we know better since we're a US-based company.

而且我預計，藥品中常見的正常比例，在這個類別中也同樣適用。那麼，為什麼我們的競爭對手這次的產品發表不太順利呢？我的意思是，首先，我會重新選擇注射類藥物。我們確實經常聽到人們對針頭的恐懼，尤其是在美國市場，而我們作為一家總部位於美國的美國公司，對美國市場的情況更加了解。

So we talk a lot to folks here, and I think there is a reasonable amount of needle phobia.

所以我們經常和這裡的人們交談，我認為他們對針頭的恐懼程度相當高。

I can't comment on the way that they've targeted and their commercial sales force, but recall that in Europe, generally, you have centers of excellence that have taken on a higher percentage of the population in any given geography. So it's easier to identify precisely who to call on and when to call on them.

我無法評論他們的目標客戶定位和銷售團隊，但請記住，在歐洲，通常情況下，卓越中心會涵蓋特定地區有更高比例的人口。這樣就更容易準確地確定該聯絡誰以及何時聯絡他們。

So I think the dynamic could -- that could lead to a slower ramp for them here in the United States. But again, I just go back to the treatable population, both for hypochon and achon. And I think that even under conservative assumptions, this is a large unmet need that then translates into a reasonably large TAM.

所以我認為這種動態可能會導致他們在美國的擴張速度放緩。但是，我還是會回到可治療人群，無論是低位性 ...我認為，即使在保守的假設下，這也是一個巨大的未滿足需求，進而轉化為相當大的潛在市場規模。

Martin Auster, Raymond James.

Martin Auster，Raymond James。

This is Thomas on for Marty. I want to add our congrats on all the news this week. I actually want to circle back on the CALIBRATE data this morning. Could you provide any more detail on the serious treatment-related adverse events observed with encaleret in periods two and three? And anything to say about those on standard of care in period 1 as well would be helpful.

這是托馬斯替馬蒂發言。我謹對本週的所有新聞表示祝賀。我今天早上其實想再討論一下 CALIBRATE 數據。您能否提供更多關於恩卡瑞特治療第二期和第三期觀察到的嚴重治療相關不良事件的詳細資訊？此外，關於第一階段接受標準治療的患者，任何建議都將不勝感激。

Yes. So this is really a -- I mean, it sounds serious, serious related TEAE is a serious thing. But in the context of these drugs, it's all hypercalcemia. So basically driving calcium levels in the serum higher than what you had intended. And in the case of the standard of care, it actually was quite high.

是的。所以這真的是一件——我的意思是，聽起來很嚴重，與TEAE相關的嚴肅的事情。但就這些藥物而言，全部都是高血鈣症。所以基本上就是把血清中的鈣含量提高到比你預期的更高的水平。就醫療護理標準而言，實際上相當高。

Again, like standard of care is taking calcium. So this does happen. You titrate it. In this case, the patient had to go in to the hospital and received IV fluid until that blood calcium was decreased. Actually, in the case of encaleret, it was much milder.

再次強調，補充鈣質是標準治療方案之一。這種事確實會發生。你用滴定法。在這種情況下，患者必須入院接受靜脈輸液，直到血鈣降低為止。事實上，就恩卡萊雷特而言，情況要溫和得多。

It was a very mild digression into hypercalcemia, but that patient had some altered mental status and UTI, obviously, nothing to do with the drug at all.

雖然只是輕微的高血鈣症，但該患者出現了一些精神狀態改變和泌尿道感染，顯然與藥物沒有任何關係。

So that's what took them into the hospital and they were dosed down, no discontinuation. So again, I think the most important part here is that the drug is probably -- we saw less discontinuations on drug than we did on standard of care. So the drug is safer than standard of care and obviously driving 76% normalization versus less than 5% that's profound.

所以他們才被送進醫院，醫生給他們減量用藥，但沒有停藥。所以，我認為最重要的一點是，這種藥物可能——我們看到服用該藥物的患者停藥率比服用標準療法的患者要低。因此，這種藥物比標準療法更安全，而且顯然能讓 76% 的患者恢復正常，而標準療法的恢復率不到 5%，這意義重大。

And I think in large part because you've got an allosteric mechanism that very precisely targets the calcium sensing receptor. So very much like Attruby or acoramidis, when you've got something like that, you've got a small molecule with a very specific target, not likely to have a significant side effect profile.

我認為這很大程度上是因為你有一種變構機制，可以非常精確地靶向鈣感應受體。所以，就像 Attruby 或 acoramidis 一樣，當你擁有這樣的藥物時，你就擁有了一個靶向非常具體的小分子，不太可能產生明顯的副作用。

Trevor Allred, Oppenheimer.

特雷弗·奧爾雷德，奧本海默。

Congrats on the quarter. I wanted to follow up again on encaleret as well. Can you give us -- can you talk a little bit more about what gives you confidence in encaleret as a $1 billion-plus product? And can you talk a little bit about your expectations for the potential upside opportunity in chronic hypopara?

恭喜你本季取得佳績。我還想再了解 encaleret 的情況。您能否再詳細談談是什麼讓您對 Encaleret 作為一款價值超過 10 億美元的產品充滿信心？您能否談談您對慢性甲減潛在上漲機會的預期？

Yes, sure. I guess I don't necessarily like to talk about things in terms of the dollar amount, but I'm curious what's your price assumption? We haven't determined the price, but what will be your pricing assumption on encaleret for ADH1?

當然可以。我不太喜歡用美元金額來談論事情，但我很好奇你對價格的預期是多少？我們尚未確定價格，但您對 ADH1 的 encaleret 定價有何假設？

I think I'm in the range of $200,000.

我覺得我的預算應該在 20 萬美元左右。

So less than Yorvipath?

所以比 Yorvipath 少？

Yes.

是的。

Why?

為什麼？

I mean it could be more than that --

我的意思是，可能不只如此。--

That's like 8x or 10x the population. Anyway, that's an extremely low number. I've not heard that. But let's just put it in a normal rare disease context of whatever, $300,000, $400,000, $500,000 in that range, you're talking about a couple of thousand to 3,000 patients on drug to achieve the touch of numbers that you put forth.

那相當於人口的 8 倍或 10 倍。總之，這是一個極低的數字。我沒聽過這件事。但讓我們把它放在普通罕見疾病的背景下，例如 30 萬美元、40 萬美元、50 萬美元，在這個範圍內，你需要讓幾千到三千名患者服用藥物才能達到你提出的目標數字。

And we always start with prevalence here. Obviously, the prevalence is much higher than the identified population. But the thing -- and I think in large part due to like what happened over the last 5 or 6 years, where everyone claimed every large -- every genetic disease was a super large disease. Recall, this is not SCITX1 OR GACI or one of these conditions that severely limits lifespan.

我們總是從普遍性入手。顯然，患病率遠高於已確定的人群。但問題是——我認為這很大程度上是由於過去 5 或 6 年發生的事情，每個人都聲稱每種大型遺傳疾病都是超級大型疾病。請注意，這不是 SCITX1 或 GACI 疾病，也不是嚴重限制壽命的疾病之一。

For those conditions, I think over -- you take the number and then people apply the genzyme factor and say, it's going to be 4x larger, not usually because those children aren't necessarily having children. Most of those mutations are germline. Those are very, very constrained populations. Same would be true, for instance, for Canavan disease, which is another disease we work on.

對於這些情況，我想——你把這個數字加上基因酶因子，然後說，它會增加 4 倍，這通常不是因為這些孩子不一定會生孩子。這些突變大多是生殖細胞突變。這些都是非常非常有限的人口。例如，卡納萬病也是如此，這是我們正在研究的另一種疾病。

It's not going to be a large population. It just -- it makes no epidemiologic sense that it would be. In this case, totally different, a large population, mostly germline that even when untreated, allows people to go on and have children. Obviously, 2, 3, 4 different studies that we and others have conducted suggesting a prevalence of up to 12,000 in the US That's not going to be off by an order of magnitude, 1,000 people on the ICD-10 code, 3,500 patients already identified.

人口不會很多。這完全——從流行病學角度來看，這根本說不通。在這種情況下，情況完全不同，人口眾多，主要是生殖細胞，即使不進行治療，也能讓人們繼續生育子女。顯然，我們和其他人進行的 2、3、4 項不同研究表明，美國患病人數高達 12,000 人。這不會有數量級的誤差，ICD-10 代碼中有 1,000 人，已經確定了 3,500 名患者。

And an easy way to identify them in terms of going and looking at the nonsurgical hypopara community and doing genetic testing is another tailwind that I believe allows us to believe that we could get a few thousand people on this drug.

而識別非手術性下視丘性閉經患者群體並進行基因檢測的簡單方法，是另一個有利因素，我相信這能讓我們相信，我們可以讓數千人服用這種藥物。

I think importantly, the guidelines are already in place to suggest that for nonsurgical hypopara patients, they get genetic testing. And so it's up to us to really drive that into the community. I'm not going to suggest that it's going to be a quick launch because we have to educate.

我認為重要的是，現有的指導方針建議，對於非手術治療的下視丘性閉經患者，應該進行基因檢測。因此，真正將這種理念融入社區，就取決於我們了。我不會說這會是一個快速啟動的過程，因為我們需要進行宣傳教育。

We have to ultimately get physicians to work into their work protocol, the fact that they're genetic testing and even in the cases, as you know, of BRCA or targeted cancer therapy, sometimes you can see as little as 40% testing in the community. So it's up to us to ensure that we work with the right providers and make sure that people are looking for ADH1 where they ought to be looking.

我們最終必須讓醫生將基因檢測納入他們的工作流程中，即使在 BRCA 或標靶癌症治療的情況下，正如你所知，有時社區中的檢測率也只有 40%。因此，我們有責任確保與合適的供應商合作，並確保人們在應該尋找的地方尋找 ADH1。

ut I would say the final thing that gives me hope that we can start to identify these patients and get them on product is just how good the drug is. When you're talking about less than 5% response on standard of care, you're talking about a lifelong set of symptoms like fatigue, brain fog, seizures.

但我認為，讓我抱持希望，能夠開始識別這些患者並讓他們使用該產品的最後一點，就是這種藥物的療效非常好。當標準治療的有效率低於 5% 時，意味著患者將面臨一系列終身症狀，例如疲勞、腦霧、癲癇發作等。

I mean, this is -- I know a lot of people in the rare disease world think if people aren't passing away from the disease, it's not severe. This is like way more severe than having acne every day or losing your hair, both of which I have. But I mean, this is really life-destroying.

我的意思是，我知道很多罕見疾病領域的人認為，如果人們沒有死於這種疾病，那就表示這種疾病並不嚴重。這比每天長痘痘或掉髮嚴重得多，而這兩種情況我都有。但我的意思是，這真的會毀掉人生。

And so 76% response rate, full normalization, getting close to a therapeutic cure for a majority of patients. That's the type of thing that I think will drive physician excitement and patient excitement and will allow us to find a reasonable fraction of these patients.

因此，有效率達到 76%，完全恢復正常，大多數患者接近治癒。我認為正是這類事情會激發醫生和患者的熱情，並使我們能夠找到相當一部分這樣的患者。

And that will conclude our question-and-answer session. I'll hand the call back to Chinmay for closing comments.

我們的問答環節到此結束。我將把電話轉回給 Chinmay，請他做總結發言。

Thank you, everyone, for joining us for our Q3 2025 earnings call. We appreciate the interest and look forward to updating you on the progress of our company in three months. Thank you.

感謝各位參加我們2025年第三季財報電話會議。感謝您的關注，我們期待在三個月後向您報告我們公司的最新進展。謝謝。

This will conclude today's call. Thank you all for joining. You may now disconnect.

今天的電話會議到此結束。感謝各位的參與。您現在可以斷開連線了。