Travere Therapeutics Inc (TVTX) 2025 Q4 法說會逐字稿

Good afternoon, and welcome to the Travere Therapeutics fourth quarter and full year 2025 financial results conference call. Today's call is being recorded. At this time, I would like to turn the conference call over to Nivi Nehra, Vice President, Corporate Communications and Investor Relations. Please go ahead, Nivi.

下午好，歡迎參加 Travere Therapeutics 2025 年第四季及全年財務業績電話會議。今天的通話將會被錄音。此時，我謹將電話會議交給企業傳播與投資者關係副總裁 Nivi Nehra。請繼續，妮維。

Thank you, operator. Good afternoon, and welcome to Travere Therapeutics fourth quarter and full year 2025 financial Results and corporate update call. Thank you all for joining. Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer; Dr. Bill Rote, our Chief Research Officer, will join us for the Q&A.

謝謝接線生。下午好，歡迎參加 Travere Therapeutics 2025 年第四季及全年財務業績和公司最新進展電話會議。感謝各位的參與。今天的電話會議將由我們的總裁兼執行長埃里克·杜貝博士主持。在準備好的發言環節，Eric 將與我們的首席醫療官 Jula Inrig 博士、首席商務官 Peter Heerma 和首席財務官 Chris Cline 一同發言；我們的首席研究官 Bill Rote 博士將與我們一起參與問答環節。

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement.

在開始之前，我想提醒大家，本次電話會議中提及的非歷史事實的陳述屬於1995年《私人證券訴訟改革法案》安全港條款所界定的前瞻性陳述。前瞻性陳述並非業績保證。它們涉及已知和未知的風險、不確定性和假設，可能導致實際結果、績效和成就與聲明中明示或暗示的內容有重大差異。

Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, February 19, 2026. and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

請參閱本公司今天稍早發布的新聞稿中的前瞻性聲明免責聲明，以及我們向美國證券交易委員會提交的 10-Q 表格和 10-K 表格中的「風險因素」部分。此外，任何前瞻性聲明僅代表我們截至該等聲明發布之日（2026 年 2 月 19 日）的觀點，Travere 特此聲明不承擔任何更新該等聲明以反映未來資訊、事件或情況的義務。

With that, let me now turn the call over to Eric.

那麼，現在讓我把電話交給艾瑞克。

Thank you, Nivi. Good afternoon, and thank you all for joining us today. 2025 was an incredible year for Travere, one that was defined by achieving a new high in the number of patients we were able to reach with our approved medicines and clear advancement of our pipeline. This success was driven by focused execution against our strategy, strong commercial performance and an unwavering commitment to bring new medicines to communities that have been waiting far too long. In IgA nephropathy, we saw record demand and strong revenue growth in the fourth quarter, even as additional therapies entered the market.

謝謝你，妮維。下午好，感謝各位今天蒞臨。 2025年對Travere來說是意義非凡的一年，我們獲批藥物惠及的患者人數創下新高，研發管線也取得了顯著進展。這一成功得益於我們策略的專注執行、強勁的商業表現以及為等待已久的社區帶來新藥的堅定承諾。在 IgA 腎臟病領域，即使有更多療法進入市場，我們在第四季度也看到了創紀錄的需求和強勁的收入成長。

Physician confidence in FILSPARI continues to build as real-world experience reinforces our long-term clinical data and its role as a foundational non-immunosuppressive therapy that can be used chronically and in combination. These results reflect growing use of FILSPARI in clinical practice, supported by strong execution across access, fulfillment and patient support.

隨著真實世界經驗不斷強化我們的長期臨床數據，醫生對 FILSPARI 的信心持續增強，FILSPARI 作為一種基礎的非免疫抑制療法，可以長期使用並與其他療法聯合使用。這些結果反映了 FILSPARI 在臨床實踐中日益廣泛的應用，這得益於在獲取、交付和患者支持方面的強有力執行。

We remain confident in our ability to deliver continued growth in IgA nephropathy and reach more patients in 2026 and in the years ahead. We also continue to advance the next phase of growth for Travere. In FSGS, patients face a rapidly progressive disease with no FDA-approved medication today. The acceptance of our sNDA and for an FSGS indication for FILSPARI last year marked an important step towards our goal of delivering the first approved medicine for this community.

我們仍有信心在 2026 年及以後的幾年裡，在 IgA 腎臟病領域持續成長，惠及更多患者。我們將繼續推進 Travere 的下一階段發展。FSGS 是一種快速進展性疾病，目前尚無 FDA 核准的藥物可用於治療。去年，我們的補充新藥申請 (sNDA) 和 FILSPARI 用於治療 FSGS 的適應症獲得批准，這標誌著我們朝著為該群體提供首個獲批藥物的目標邁出了重要一步。

In January, we received notification of a major amendment to our sNDA following additional information requests received before the holidays. As a result, our new FDA PDUFA target action date is April 13, 2026. While the date for an action by the FDA has shifted, our conviction in the clinical profile of FILSPARI as a potential FSGS therapy and the benefit it could provide to the FSGS community remains unchanged. We will continue to work with the agency as they advance their review. And with our expanded commercial team fully established are ready to execute with excellence, if approved.

1 月份，我們收到通知，由於假期前收到了額外的信息請求，我們的 sNDA 進行了重大修改。因此，我們新的 FDA PDUFA 目標行動日期為 2026 年 4 月 13 日。儘管 FDA 採取行動的日期有所改變，但我們對 FILSPARI 作為潛在的 FSGS 療法的臨床特性及其可能為 FSGS 患者群體帶來的益處的信念仍然不變。我們將繼續與該機構合作，推進他們的審查工作。我們擴大的商業團隊已經全面組建完畢，如果獲得批准，我們將以卓越的執行力完成任務。

Beyond FILSPARI, we are also advancing pegtibatinase for classical homocystinuria, or HCU, which we believe has the potential to become an important contributor to growth beyond FILSPARI. Pegtibatinase has the potential to be the first disease-modifying medicine to address the underlying cause of the disease. Notably, we have recently resumed site activation for our pivotal Phase 3 HARMONY study to enable enrollment globally.

除了 FILSPARI 之外，我們也正在推進用於治療經典同型半胱氨酸尿症 (HCU) 的 pegtibatinase 的研發，我們相信它有潛力成為 FILSPARI 之外的重要成長貢獻者。培替巴汀酶有可能成為首個針對疾病根本原因的疾病修飾藥物。值得一提的是，我們最近已恢復關鍵性 3 期 HARMONY 研究的現場激活，以便在全球範圍內招募受試者。

As we look ahead, our priorities are clear: solidified FILSPARI's foundational role in IGAM, successfully delivered the first approved medicine for FSGS, if approved; advanced enrollment in our Phase 3 HARMONY study; and continue to build a durable, growing rare disease company grounded in execution and scientific rigor. We entered 2026 with focus, discipline and confidence in our path forward. and most importantly, with a continued commitment to delivering meaningful progress for patients.

展望未來，我們的優先事項很明確：鞏固 FILSPARI 在 IGAM 中的基礎地位；成功交付首個獲批的 FSGS 藥物（如果獲得批准）；推進我們的 3 期 HARMONY 研究的患者招募；並繼續打造​​一家以執行力和科學嚴謹性為基礎的、可持續發展的罕見病公司。我們帶著專注、自律和對未來道路的信心邁入了2026年。最重要的是，我們將繼續致力於為患者帶來有意義的進步。

With that, I'll now turn the call over to Jula to talk more about the advancement of our programs. Jula?

接下來，我將把電話交給朱拉，讓她進一步談談我們專案的進度。朱拉？

Thank you, Eric. We are pleased with the consistent nephrologist feedback about the critical role of dual antagonism of endothelin and angiotensin as part of the foundational treatment paradigm to preserve kidney function in patients with IgA nephropathy. As we continue to generate FILSPARI barring data across a broad spectrum of patients with IgA nephropathy from early after diagnosis to recurrent post transplant as well as in combination with other therapies, we are hearing consistent feedback from nephrologists that they are aligned with KDIGO and that FILSPARI has the potential to replace the historic role of RAS inhibitors and provide long-term nephro protection for patients with IgA nephropathy.

謝謝你，埃里克。我們很高興看到腎臟科醫生一致回饋，內皮素和血管緊張素雙重拮抗劑在 IgA 腎病患者維持腎功能的基礎治療方案中起著至關重要的作用。隨著我們不斷收集 FILSPARI 在 IgA 腎病患者中的應用數據，涵蓋從早期診斷到移植後復發以及與其他療法聯合應用等各個階段，我們不斷收到腎臟科醫生的反饋，他們與 KDIGO 的研究結果一致，認為 FILSPARI 有潛力取代 RAS 抑製劑的歷史作用，為 IgA 腎病患者提供長期的腎臟保護。

This support is rooted in data such as our recently published secondary analysis of PROTECT, which demonstrated that achievement of complete remission of proteinuria to less than 0.3 grams per day, of which 80% were treated with FILSPARI was associated with an annual eGFR decline as recommended by KDIGO of less than 1 ml per minute per year, reflecting meaningful preservation of kidney function. Importantly, we believe the convergence of physician conviction and robust clinical evidence positions FILSPARI as foundational care in IgA nephropathy as we look ahead.

這項支持源於我們最近發表的 PROTECT 二次分析等數據，該分析表明，蛋白尿完全緩解至每天少於 0.3 克（其中 80% 的患者接受了 FILSPARI 治療）與 KDIGO 建議的每年 eGFR 下降小於 1 毫升/分鐘/年相關，這反映了腎功能的顯著保護。重要的是，我們相信，醫生的信念和強有力的臨床證據的結合，使 FILSPARI 成為 IgA 腎病治療的基礎療法。

Turning to FSGS. We continue working towards our new PDUFA date of April 13 and look forward to working with the agency as the review advances. We remain confident in FILSPARI's clinical profile and its potential, if approved, to meaningfully advance treatment for patients with FSGS by protecting (inaudible) site health. This confidence is based on the strength and consistency of the data generated across our Phase 2 DUET and Phase 3 DUPLEX studies, which together represent two of the largest interventional clinical trials ever conducted in FSGS.

接下來討論FSGS。我們將繼續朝著4月13日新的PDUFA日期努力，並期待在審查過程中與監管機構合作。我們仍然對 FILSPARI 的臨床表現和潛力充滿信心，如果獲得批准，它將透過保護（聽不清楚）部位健康，顯著推進 FSGS 患者的治療。這種信心源自於我們 2 期 DUET 研究和 3 期 DUPLEX 研究所產生的數據的強度和一致性，這兩項研究加起來是 FSGS 領域有史以來規模最大的兩項幹預性臨床試驗。

Across these studies, FILSPARI consistently reduced proteinuria, a well-established driver of long-term kidney outcomes in this disease. Importantly, the trial data demonstrate consistent proteinuria reduction across a heterogenous patient population, including both primary and genetic forms of FSGS as well as in pediatric patients. And the magnitude of treatment effect on proteinuria observed with FILSPARI versus active comparator irbesartan translated into a clinically meaningful reduction in kidney failure events, both within the DUPLEX trial and when extrapolated based on external data such as radar.

在這些研究中，FILSPARI 持續降低了蛋白尿，而蛋白尿是該疾病長期腎臟預後的一個公認的驅動因素。重要的是，試驗數據表明，在異質性患者群體中，包括原發性和遺傳性 FSGS 以及兒科患者，蛋白尿均持續減少。與活性對照藥物厄貝沙坦相比，FILSPARI 對蛋白尿的治療效果顯著，這轉化為腎衰竭事件的臨床意義的減少，無論是在 DUPLEX 試驗中還是根據雷達等外部數據進行推斷時都是如此。

In our ongoing engagements with the nephrology community, we continue to hear strong alignment around the clinical relevance of the DUPLEX data, which is even more compelling given the absence of any FDA-approved medication indicated for FSGS today and the urgent need for earlier, more effective interventions relative to historical standard of care. Many clinicians emphasize the importance of proteinuria reduction as the primary treatment goal and recognize the consistency of FILSPARI's antiproteineric effect across patient subgroups. Taken together, the totality of the data and the feedback we continue to hear from the FSGS community reinforce our belief in FILSPARI's potential to meaningfully change the treatment paradigm for patients living with FSGS and we look forward to the FDA's upcoming review decision.

在我們與腎臟病學界的持續交流中，我們不斷聽到大家對 DUPLEX 數據的臨床相關性表示強烈認同，考慮到目前尚無任何 FDA 批准的藥物用於治療 FSGS，以及相對於以往的標準治療而言，迫切需要更早、更有效的干預措施，這一點就更加令人信服了。許多臨床醫生強調減少蛋白尿是主要治療目標的重要性，並認識到 FILSPARI 的抗蛋白尿作用在患者亞群中具有一致性。綜合所有數據以及我們不斷從 FSGS 患者群體中聽到的反饋，我們更加堅信 FILSPARI 有潛力從根本上改變 FSGS 患者的治療模式，我們期待 FDA 即將作出的審查決定。

Let me now turn to Pegtibatinase and classical homocystinuria. Classical HCU is a serious genetic metabolic disorder with limited treatment options. These patients are born with a deficiency in their CBS enzyme that would normally help to metabolize certain proteins in their diet. This deficiency results in a toxic buildup of homocystine, which can lead to serious and life-threatening thrombotic events such as stroke and pulmonary embolism or deep vein thrombosis in addition to vision and skeletal abnormalities and developmental delays.

現在讓我來談談培替巴汀酶和經典型同型半胱胺酸尿症。經典型HCU是一種嚴重的遺傳代謝失調疾病，治療選擇有限。這些患者天生缺乏CBS酶，這種酶通常有助於代謝他們飲食中的某些蛋白質。這種缺乏會導致同型半胱氨酸毒性積聚，除了視力、骨骼異常和發育遲緩外，還會導致嚴重的、危及生命的血栓事件，如中風、肺栓塞或深部靜脈栓塞。

To put this into context, if untreated, approximately 25% of these patients have an ischemic event before they become a teenager and 50% experience an ischemic events before they turn 30. Pegtibatinase is an investigational inbound replacement therapy designed to address the underlying CBS enzyme deficiency that drives toxic homocystine accumulation rather than managing downstream consequences alone. The Phase 1/2 composed data demonstrated clinically meaningful reductions in total homocystine, including normalization for one patient, a clear dose response and a favorable tolerability profile, supporting advancement into Phase 3 development.

換個角度來看，如果不進行治療，大約 25% 的這類患者在青少年時期會發生缺血性事件，50% 的這類患者在 30 歲之前會發生缺血性事件。Pegtibatinase 是一種研究性內源性替代療法，旨在解決導致有毒同型半胱氨酸累積的潛在 CBS 酶缺乏症，而不是僅僅控制下游後果。1/2 期綜合數據顯示，總同型半胱氨酸水平在臨床上顯著降低，其中一名患者的同型半胱氨酸水平恢復正常，劑量反應清晰，耐受性良好，支持推進至 3 期開發。

In 2025, we achieved key manufacturing process optimizations, an important milestone that positions the program for late-stage development and future potential commercialization. We have now resumed activating clinical trial sites for the Phase 3 HARMONY study and the long-term extension study on Sabal, which are designed to evaluate sustained total homocystine control and explore outcomes that matter to patients, including the potential for greater dietary flexibility.

2025 年，我們實現了關鍵的製造流程最佳化，這是一個重要的里程碑，使該專案能夠進入後期開發階段，並實現未來的潛在商業化。我們現在已經恢復啟動 HARMONY 3 期研究和 Sabal 長期擴展研究的臨床試驗點，這些研究旨在評估持續的總同型半胱氨酸控制，並探索對患者重要的結果，包括更大的飲食靈活性的可能性。

Harmony is a randomized double-blind study of Pegtibatinase versus placebo. The double-blind period will follow patients for 24 weeks, which includes the primary end point measuring change from baseline in plasma total homocystine averaged over weeks 6 through 12, with durability of treatment measured as a secondary endpoint to week 24. There's also a four-week screening period, and following initial screening, there is a pretreatment diet stabilization period of up to 6 weeks to help minimize protein intake variability. The total study duration can range up to 38 weeks prior to entering into the Ensemble extension study.

Harmony 是一項隨機雙盲研究，比較了培替巴汀酶與安慰劑的療效。雙盲期將對患者進行 24 週的隨訪，主要終點是測量第 6 週至第 12 週血漿總同型半胱氨酸平均值相對於基線的變化，治療的持久性作為次要終點測量至第 24 週。此外，還有四周的篩選期，初步篩選後，還有長達 6 週的預處理飲食穩定期，以幫助最大限度地減少蛋白質攝取量的變化。在進入 Ensemble 擴展研究之前，整個研究持續時間最長可達 38 週。

We believe Pegtibatinase has the potential to become the first disease-modifying therapy for classical HCU, and importantly, to meaningfully improve the day-to-day lived experience for patients and families. Our focus is now on building momentum as the trial resumes, and we expect to reinitiate dosing of new patients in the near future. Across our programs, we're looking forward to presenting new data at medical congresses this year. In IGAM, these efforts are intended to further support FILSPARI's role as foundational therapy, while in FSGS, they're focused on deepening the understanding of FILSPARI's clinical profile and its potential role in addressing the high unmet need in these patients.

我們相信，培替巴汀酶有潛力成為首個治療經典型 HCU 的疾病修飾療法，更重要的是，它能夠實際改善患者及其家人的日常生活體驗。我們現在的重點是隨著試驗的恢復而積蓄力量，我們預計在不久的將來重新開始對新患者進行給藥。我們各個計畫組都期待今年在醫學大會上展示新的數據。在 IGAM 中，這些努力旨在進一步支持 FILSPARI 作為基礎療法的作用；而在 FSGS 中，這些努力則著重於加深對 FILSPARI 臨床特徵及其在滿足這些患者高度未滿足的需求方面的潛在作用的理解。

With that, I'll now turn it over to Peter for a commercial update. Peter?

接下來，我將把麥克風交給彼得，讓他帶來商業上的最新進展。彼得？

Thank you, Jula. I am pleased to share that the fourth quarter of 2025 marked a strong finish to the year for FILSPARI with continued momentum driven by growing physician adoption, robust demand and increasing confidence in FILSPARI's role as a foundational therapy in IgA nephropathy.

謝謝你，朱拉。我很高興地宣布，2025 年第四季度，FILSPARI 取得了強勁的業績，為這一年畫上了圓滿的句號。醫生對 FILSPARI 的接受度不斷提高，市場需求強勁，人們對 FILSPARI 作為 IgA 腎病基礎療法的信心也日益增強，這些因素共同推動了 FILSPARI 的持續增長。

During the fourth quarter, we saw a record demand of 908 new patient platform for FILSPARI. Notably, we are seeing a strong level of demand continue into the first quarter. The demand in the fourth quarter was driven by both new prescribers and increasing use among established prescribers. Importantly, we continue to see an increasing number of practices treating multiple patients with FILSPARI, which we view as a meaningful indicator of physicians' confidence and experience in the therapy's effectiveness, tolerability and long-term utility.

第四季度，我們看到 FILSPARI 新患者平台的需求量創下紀錄，達到 908 個。值得注意的是，我們看到強勁的需求動能延續到了第一季。第四季的需求成長是由新處方醫生的增加和現有處方醫生使用量的增加共同推動的。重要的是，我們看到越來越多的診所使用 FILSPARI 治療多名患者，我們認為這是醫生對該療法的有效性、耐受性和長期效用的信心和經驗的重要指標。

The strong demand translated into robust growth to the end of the year. In the fourth quarter, FILSPARI generated approximately $103 million in net product sales and approximately $322 million for the full year of 2025, representing a 144% year-over-year growth. We believe these results underscore the momentum and a significant growth opportunity for FILSPARI and its ability to continue to perform strongly as the IgA nephropathy treatment landscape evolves with new entrants. We believe FILSPARI's continued success in the fourth quarter was driven by a differentiated profile, simplification of the ramps monitoring requirements and the publication of the KDIGO guidelines.

強勁的需求轉化為年底前的穩健成長。第四季度，FILSPARI 的淨產品銷售額約為 1.03 億美元，預計 2025 年全年淨產品銷售額約為 3.22 億美元，年增 144%。我們相信，這些結果凸顯了 FILSPARI 的發展勢頭和巨大的成長機會，以及隨著 IgA 腎病治療領域不斷湧現的新競爭者，FILSPARI 繼續保持強勁增長的能力。我們認為，FILSPARI 在第四季度的持續成功得益於其差異化的市場定位、簡化的坡道監控要求以及 KDIGO 指南的發布。

As a once-daily nonimmunosuppressive oral therapy, FILSPARI provides a proven and convenient option for chronic use in a disease that requires long-term nephroprotective treatment. In addition, FILSPARI's ability to be used in combination with other therapies provides flexibility for nephrologist as they tailor treatment strategies to individual patients.

作為一種每日一次的非免疫抑制性口服療法，FILSPARI 為需要長期腎臟保護治療的疾病提供了一種經過驗證且方便的慢性藥物選擇。此外，FILSPARI 可以與其他療法合併使用，這為腎臟科醫生提供了靈活性，使他們能夠根據個別患者的情況制定治療策略。

We are also seeing broad utilization of FILSPARI across the full spectrum of adult patients with IgA nephropathy, with increasing adoption in patients with elevated popery levels, but below 1.5 gram per gram. This trend is consistent with the direction of the KDIGO guidelines, as they emphasize a lower treatment target and earlier intervention. It is important as well FILSPARI continues to be used in patients with higher levels of proteinuria, we are seeing accelerating adoption in those below 1.5 grams per gram, which represent approximately two-thirds of the addressable IgA nephropathy population.

我們也看到 FILSPARI 被廣泛應用於患有 IgA 腎病的成年患者，尤其是在血漿蛋白水平升高但低於 1.5 克/克的患者中，其應用越來越廣泛。這一趨勢與 KDIGO 指南的方向一致，因為這些指南強調降低治療目標和儘早介入。重要的是，FILSPARI 繼續用於蛋白尿水平較高的患者，我們看到，在每克尿蛋白低於 1.5 克的患者中，FILSPARI 的採用率正在加速提高，這約佔 IgA 腎病可治療人群的三分之二。

From the patient perspective, feedback indicates that satisfaction with FILSPARI and our patient support services remain high with strong patient compliance and sustained persistence observed over time. Patients frequently cite the convenience of a once-daily oral medicine in the non-munisuppressive and nephroprotective profile with long-term kit depreservation as important factors in their treatment experience.

從患者的角度來看，回饋表明，患者對 FILSPARI 和我們的患者支持服務的滿意度仍然很高，並且隨著時間的推移，患者的依從性和持續堅持性都得到了體現。患者常提到，每日一次口服藥物的便利性、非抑菌和腎臟保護作用以及長期保存藥物成分，是他們治療經驗中的重要因素。

In parallel, we have continued to build commercial readiness in anticipation of a potential approval in FSGS. Given the rapidly progressive nature of FSGS and the lack of approved therapies today, we believe our existing relationships, experience in IgA nephropathy and commercial infrastructure position us well to support patients and physicians in this setting. Based on the feedback from the FSGS community, we believe this indication is approved could be an even larger opportunity with a more rapid uptake compared to IgA nephropathy, and we stand ready to deliver for this patient community.

同時，我們繼續進行商業準備，以期在 FSGS 領域獲得潛在批准。鑑於 FSGS 的快速進展性和目前缺乏核准療法，我們相信我們現有的關係、在 IgA 腎病方面的經驗和商業基礎設施使我們能夠很好地支持這方面的患者和醫生。根據 FSGS 患者群體的回饋，我們認為，如果該適應症獲得批准，與 IgA 腎病相比，可能會帶來更大的機遇，並更快地被接受，我們已準備好為該患者群體提供服務。

In summary, the fourth quarter of 2025 demonstrated exceptional commercial execution and performance, evidenced by record demand and revenue. Building on our established commercial foundation and the strong performance amidst additional treatment options becoming available, I am confident in FILSPARI's ability to deliver sustainable growth and long-term leadership in rare kidney disease care. I couldn't be proud of our commercial team and the impact they make on patients' lives on a daily basis. And I'm excited about how they will continue to support patients and physicians in 2026.

總而言之，2025 年第四季展現了卓越的商業執行力和業績，創紀錄的需求和收入證明了這一點。憑藉我們已建立的商業基礎以及在更多治療方案出現的情況下取得的強勁業績，我對 FILSPARI 在罕見腎病治療領域實現可持續增長和長期領先地位充滿信心。我為我們的商業團隊感到無比自豪，他們每天對患者的生活產生著正面的影響。我很期待他們在 2026 年繼續為患者和醫生提供支援。

Let me now turn the call over to Chris for the financial update. Chris?

現在我把電話交給克里斯，讓他報告財務狀況。克里斯？

Thank you, Peter, and good afternoon all. We ended the year in a strong financial position. This was bolstered by continued net product sales growth, focused investment in key priorities to support our current performance and sustainable growth potential and strategic partner milestones that added to our balance sheet strength.

謝謝你，彼得，大家下午好。我們以穩健的財務狀況結束了這一年。持續的淨產品銷售成長、對關鍵優先事項的集中投資以支持我們當前的業績和可持續成長潛力以及戰略合作夥伴的里程碑，都增強了我們的資產負債表實力。

Beginning with revenue. For the fourth quarter, we reported US net product sales of $126.6 million and for the full year 2025, total net product sales were $410.5 million. This marks significant year-over-year growth in our revenue base. FILSPARI generated $103.3 million in US net product sales for the fourth quarter, resulting in $322 million in net product sales for the full year 2025. Thiola and Thiola EC contributed $23.3 million in US net product sales during the fourth quarter and $88.5 million for the full year 2025. For the fourth quarter and full year 2025, we also recognized $3.1 million and $80.3 million, respectively, in license and collaboration revenue.

首先從收入說起。第四季度，我們報告美國淨產品銷售額為 1.266 億美元；2025 年全年，淨產品總銷售額為 4.105 億美元。這標誌著我們的收入基礎實現了顯著的同比增長。FILSPARI 第四季在美國的淨產品銷售額為 1.033 億美元，預計 2025 年全年淨產品銷售額將達到 3.22 億美元。Thiola 和 Thiola EC 在第四季度為美國貢獻了 2,330 萬美元的淨產品銷售額，2025 年全年貢獻了 8,850 萬美元的淨產品銷售額。2025 年第四季和全年，我們還分別確認了 310 萬美元和 8,030 萬美元的授權和合作收入。

Moving to operating expenses. Our research and development expenses for the fourth quarter of 2025 were $57.9 million compared to $62.1 million for the same period in 2024. On a non-GAAP adjusted basis, R&D expenses were $54 million compared to $58.6 million for the same period in 2024.

接下來是營運費用。2025 年第四季度，我們的研發費用為 5,790 萬美元，而 2024 年同期為 6,210 萬美元。按非GAAP調整後，研發費用為5,400萬美元，而2024年同期為5,860萬美元。

Selling, general and administrative expenses for the fourth quarter were $101.7 million compared to $69.5 million for the same period in 2024. And on a non-GAAP and adjusted basis, SG&A expenses were $76 million for the fourth quarter compared to $51.6 million in the same period in 2024. The increase in SG&A is primarily attributable to investments in preparations for a potential launch in FSGS, including the first full quarter with an expanded sales force, increased amortization expense related to FILSPARI royalties as FILSPARI continues to grow significantly as well as increased investments to support commercial efforts for FILSPARI and IgA nephropathy.

第四季的銷售、一般及行政費用為 1.017 億美元，而 2024 年同期為 6,950 萬美元。以非GAAP調整後的資料計算，第四季銷售、一般及行政費用為7,600萬美元，而2024年同期為5,160萬美元。銷售、一般及行政費用的增加主要歸因於為 FSGS 的潛在上市做準備的投資，包括擴大銷售團隊後的第一個完整季度，隨著 FILSPARI 的持續顯著增長，與 FILSPARI 特許權使用費相關的攤銷費用增加，以及為支持 FILSPARI 和 IgA 腎病商業化工作而增加的投資。

Total other income net for the fourth quarter of 2025 was $11.4 million compared to less than $1 million for the same period 2024. The difference is largely attributable to approximately $10 million in proceeds received as a result of the Reais acquisition by Chugai that was completed in the fourth quarter.

2025 年第四季其他淨收入總額為 1,140 萬美元，而 2024 年同期則少於 100 萬美元。這一差異主要歸因於第四季度中外製藥完成對 Reais 的收購後獲得的約 1000 萬美元收益。

During the fourth quarter, we also recognized approximately $25 million of income from discontinued operations. This resulted from Veran Pharmaceuticals achieving a sales-based milestone of $25 million that is expected to be paid to Travere in the first half of this year. Net income for the fourth quarter of 2025 was $2.7 million or $0.03 per basic share compared to a net loss of $6.3 million or $0.73 per basic share for the same period in 2024. On a non-GAAP adjusted basis, net income for the fourth quarter of 2025 was $33.3 million or $0.37 per basic share compared to a net loss of $39 million or $0.47 per basic share for the same period in 2024. As of December 31, 2025, we had cash, cash equivalents and marketable securities totaling approximately $322.8 million.

第四季度，我們也確認了約 2,500 萬美元的終止經營收入。這是因為 Veran Pharmaceuticals 實現了 2500 萬美元的銷售里程碑，預計將在今年上半年支付給 Travere。2025 年第四季淨收入為 270 萬美元，即每股基本收益 0.03 美元，而 2024 年同期淨虧損為 630 萬美元，即每股基本虧損 0.73 美元。依非GAAP調整後，2025年第四季淨收入為3,330萬美元，即每股基本虧損0.37美元，而2024年同期淨虧損為3,900萬美元，即每股基本虧損0.47美元。截至 2025 年 12 月 31 日，我們擁有現金、現金等價物及有價證券總計約 3.228 億美元。

This balance reflects the proceeds of the $40 million milestone payment received from CSL during the quarter as well as approximately $10 million from the renals acquisition by Chugai. Looking ahead in 2026, we expect meaningful net product sales growth from FILSPARI and Iga nephropathy to continue strengthening our financial position. While we anticipate modestly higher gross to net discounts compared to last year, as Peter mentioned, underlying demand remains strong, and we expect FILSPARI to deliver robust growth of foundational therapy.

該餘額反映了本季從 CSL 收到的 4000 萬美元里程碑付款，以及從 Chugai 收購腎臟業務中獲得的約 1000 萬美元。展望 2026 年，我們預期 FILSPARI 和 Iga 腎病變將帶來顯著的淨產品銷售成長，從而繼續增強我們的財務實力。雖然我們預計毛利與淨利之間的折扣將比去年略有增加，但正如 Peter 所提到的，潛在需求依然強勁，我們預計 FILSPARI 將帶來基礎療法的強勁增長。

If approved by FSGS, we believe this represents a meaningful opportunity to build on our momentum from IgA nephropathy and further support potential top line growth. And from an operating expense perspective, we will continue to invest thoughtfully to advance both our current performance and long-term growth potential.

如果獲得 FSGS 的批准，我們相信這將為我們提供一個有意義的機會，鞏固我們在 IgA 腎臟病領域的進展，並進一步支持潛在的營收成長。從營運費用角度來看，我們將繼續謹慎投資，以提升我們目前的績效和長期成長潛力。

We expect moderate operating expense growth versus 2025, primarily driven by the restart and execution of the global Phase 3 HARMONY study as well as supply for Pegtibatinase, continued evidence generation for FILSPARI and commercial investment to support a potential FSGS launch. Importantly, we do not anticipate a near-term need for additional capital to support our current priorities. Our strong balance sheet, coupled with expected revenue growth and a focused investment approach position us to drive near and long-term value.

我們預計與 2025 年相比，營運費用將溫和增長，主要原因是全球 3 期 HARMONY 研究的重啟和執行，以及 Pegtibatinase 的供應、FILSPARI 的持續證據生成以及支持潛在的 FSGS 上市的商業投資。重要的是，我們預計近期內不需要額外的資金來支持我們目前的優先事項。我們強勁的資產負債表，加上預期的收入成長和專注的投資方式，使我們能夠創造近期和長期的價值。

I'll now turn it over to Eric for his closing comments. Eric?

現在我將把發言權交給艾瑞克，請他作總結陳詞。艾瑞克？

Thank you, Chris. In closing, Travere is well positioned as we enter the next phase of growth with strong commercial momentum in IgA nephropathy, a meaningful potential opportunity in FSGS as FILSPARI advances through the regulatory review process and a pipeline advancing with purpose. Our strategy is focused. Our teams are executing with discipline, and our balance sheet provides the flexibility to deliver on our priorities. Most importantly, we remain driven by the urgency felt by the patients and families we serve and by our responsibility to deliver meaningful progress on their behalf.

謝謝你，克里斯。總之，隨著我們進入下一個成長階段，Travere 已做好充分準備，在 IgA 腎病領域擁有強勁的商業勢頭，隨著 FILSPARI 透過監管審查程序，FSGS 領域也蘊藏著重要的潛在機會，並且我們的產品線也在有條不紊地推進。我們的戰略重點明確。我們的團隊執行力強，紀律嚴明，我們的財務狀況也為我們實現優先事項提供了靈活性。最重要的是，我們始終受到我們所服務的患者及其家屬的緊迫感以及我們為他們取得實質進展的責任感所驅動。

Now let me turn the call over to Nivi for Q&A. Nivi?

現在我把電話交給Nivi，讓他回答問題。妮維？

Thank you, Eric. Operator, we can now open up the line for Q&A.

謝謝你，埃里克。操作員，我們現在可以開通問答環節了。

(Operator Instructions) Vamil Divan, Guggenheim Securities.

（操作員指令）Vamil Divan，古根漢證券。

Great. So just want to dig a little deeper into the IAN performance, obviously, strong inpatient start forms. I'm wondering now that you've been in the market for a little bit, we also have some new competition, obviously, in the market over the last year or so. If you can give a little more detail in terms of how and where are the products being prescribed in IDM more of a breakdown between community-based nephrologists and those that maybe more academic centers and then also in terms of the treatment paradigm. So where is it being added on?

偉大的。所以我想更深入地了解 IAN 的表現，顯然，住院病人的開局非常強勁。我想知道，既然你們已經進入市場一段時間了，而且很明顯，在過去一年左右的時間裡，市場上也出現了一些新的競爭對手。如果您能更詳細地說明一下IDM中產品處方的方式和地點，特別是社區腎臟科醫生和學術中心醫生之間的細分情況，以及治療模式，那就太好了。那麼，它被加到哪裡了？

And sir, in combination, are you seeing any issues with providers trying to use two branded products at the same time, as the payers push back and mean providers to prioritize one over the other?

先生，您認為同時使用兩種品牌產品時，如果醫療服務提供者試圖同時使用兩種品牌產品，是否會遇到支付方反對並要求醫療服務提供者優先使用其中一種產品的問題？

Vamil, thanks for the question. Peter, I will turn that over to you, and I'll make sure that we capture all the kind of questions that Vamil asked there. Go ahead, Peter.

Vamil，謝謝你的提問。彼得，我會把這件事交給你，我會確保我們記錄下瓦米爾提出的所有問題。請繼續，彼得。

Yes. Thank you, Eric, and thank you, Vamil, for that question. And I did get your several components, so let me try to unpack that. And Vamil, let me know if I answered your question to your satisfaction. But first of all, to your point on like what was driving the demand in Q4?

是的。謝謝艾瑞克，也謝謝瓦米爾提出這個問題。我確實收到了你的幾個組件，讓我試著把它們拆開看看。Vamil，請告訴我我的回答是否令你滿意。但首先，我想回答你提出的問題，第四季需求成長的驅動因素是什麼？

And to your point, like a very strong demand quarter with 908 new patient platforms, which was mainly driven by the modification of our REMS requirements as well as the publication of the KDIGO. And the education of the broader community really allows for a growth opportunity on the market, FILSPARI in particular. We can like built into your second part of your question, like where do you see most of the utilization community relative to academic prescribers.

正如您所說，這是一個需求非常強勁的季度，新增了 908 個患者平台，這主要是由於我們修改了 REMS 要求以及發布了 KDIGO 指南所推動的。對更廣泛的社區進行教育，確實為市場，特別是 FILSPARI 市場，帶來了成長機會。我們可以把這個問題融入你問題的第二部分，例如，你認為相對於學術處方者，大多數醫療資源利用群體在哪裡？

And as we mentioned in the past, I mean, the vast majority of those patients reside in the community and our utilization is reflective of that. So we have more use in the community, consistent to where the patient community resides.

正如我們之前提到的，絕大多數患者都居住在社區內，我們的醫療資源利用也反映了這一點。因此，我們在社區中擁有更多用途，這與患者社區的居住地一致。

I think the last component of your question was regarding a changing treatment landscape, what is the payer situation. Well, as we have discussed in the past, we have a very strong position in payer formularies. We -- our objective was always to have broad utilization, and we have accomplished that with like over 96% of the patient population have a pathway to reimbursement for FILSPARI. And that remains unchanged in this evolving landscape with new competition going in. I think I did answer all three of your questions, but Vamil, please add if you -- if I didn't.

我認為你問題的最後一部分是關於不斷變化的治療環境，以及支付方的情況。正如我們過去討論過的，我們在支付方處方集方面擁有非常強大的地位。我們的目標始終是廣泛應用，而我們已經實現了這一目標，超過 96% 的患者群體都可以透過途徑獲得 FILSPARI 的報銷。即使面對不斷湧現的新競爭對手，這種情況仍沒有改變。我想我已經回答了你的三個問題，但Vamil，如果你還有什麼沒回答到，請補充。

No, that's helpful color. I'll jump back in the queue --

不，那是很有幫助的顏色。我重新排隊。--

Vamil, one thing that maybe I can just add is that we see a robust level of growth that's coming not just from the dynamics that Peter talked about, but also from new and repeat prescribers. When I think about sustainable growth in terms of the longer-term potential, this is exactly what we would hope to see that we're seeing new physicians start to prescribe as driven by the modification of REMS, KDIGO and the comfort that they're hearing from their peers, but we're also seeing physicians find new patients as repeat prescribers.

Vamil，我或許可以補充一點，我們看到強勁的成長勢頭不僅來自 Peter 所談到的動態，也來自新處方醫生和重複處方醫生。當我從長期潛力的角度思考可持續增長時，這正是我們希望看到的：我們看到，由於 REMS 和 KDIGO 的修改以及同行們的認可，越來越多的醫生開始開具處方，同時我們也看到醫生們通過重複處方找到了新的患者。

That is very encouraging and particularly as new treatment options come to these patients, we're very encouraged and I want to emphasize one thing that Peter mentioned in his prepared remarks, which is these trends for strong demand continued in the first part of this year to start out this year very strongly. So we're very excited about the future potential growth for FILSPARI and IgA nephropathy.

這非常令人鼓舞，尤其是隨著新的治療方案的出現，我們深受鼓舞。我想強調彼得在事先準備好的發言稿中提到的一點，那就是今年上半年強勁的需求趨勢仍在繼續，使得今年開局非常強勁。因此，我們對 FILSPARI 和 IgA 腎病變的未來成長潛力感到非常興奮。

Tyler Van Buren, TD Cowen.

泰勒·範·布倫，TD·考恩。

Great to see the progress during the quarter. Can you tell us if you've had more significant data requests from the FDA following the last disclosure in the new year?

很高興看到本季的進展。您能否告知我們，在新年的上次資訊披露之後，您是否收到了來自 FDA 的更多重要數據請求？

And if so, what the nature of them were? And maybe just as a kicker here, given the ALIGN IGAM study data with 2.5 years of follow-up that Novartis reported for Benrafia last week, can you help us put that into context and compare it to what you've all reported for FILSPARI?

如果存在，它們的性質是什麼？或許可以作為一點補充，鑑於諾華上周公布了 Benrafia 的 ALIGN IGAM 研究數據（隨訪時間為 2.5 年），您能否幫助我們將其置於背景中，並將其與您之前公佈的 FILSPARI 的數據進行比較？

Tyler, thanks for the questions. I'll take the first one on FDA, and then I'll ask Jula to comment on the IgA nephropathy data. So we are continuing to have FDA engage and review our file. Our practice is not to comment on ongoing reviews.

泰勒，謝謝你的提問。我先回答關於FDA的第一個問題，然後我會請Jula對IgA腎病變的數據發表評論。因此，我們將繼續與FDA接洽並審查我們的文件。我們的慣例是不對正在進行的審查發表評論。

We did provide comments on the information request that we got at the end of last year just based on the unusual timing of those. But at this point, I'd say we provided FDA what they've asked for and we're on track for the April 13 PDUFA date. Jula?

鑑於去年底收到的資訊請求時間異常，我們確實提供了評論。但就目前而言，我認為我們已經向 FDA 提供了他們要求的東西，我們正按計劃推進，預計在 4 月 13 日的 PDUFA 日期前完成審批。朱拉？

Yes. And with regards to the ALIGN trial data, we can't really make cross-trial comparisons given there's different trial designs and different time points for the end points. But I want to reiterate FILSPARI was studied for two years against a max dose active comparator, which we know also preserve kidney function versus atrasentan was setting against a placebo with an endpoint in about 2.5 years. But let me reiterate what we demonstrated in PROTECT with FILSPARI. First, there was a 3.7 milliliter greater absolute preservation in eGFR at two years versus an active control.

是的。至於 ALIGN 試驗數據，由於試驗設計和終點時間點各不相同，我們無法進行跨試驗比較。但我想重申，FILSPARI 的研究歷時兩年，與最大劑量活性對照藥物進行比較，我們知道該藥物也能保護腎功能，而阿曲生坦的研究則與安慰劑進行比較，終點約為 2.5 年。但讓我重申一下我們在 PROTECT 中使用 FILSPARI 所展示的內容。首先，與積極對照組相比，兩年後 eGFR 的絕對保留量高出 3.7 毫升。

And this effect was nominally statistically significant. Importantly, we saw an accrual of benefit on kidney function over time, such that at one year, there was a 1.8 milliliter greater preservation in eGFR. And as I mentioned, at two years, this grew to 3.7 milliliter difference.

而且這種影響在統計上具有顯著性。重要的是，我們看到腎功能隨著時間的推移而逐漸改善，一年後，eGFR 的保留率提高了 1.8 毫升。正如我之前提到的，兩年後，這個差距擴大到了 3.7 毫升。

Lastly, our primary endpoint of total eGFR slope in the preferred FDA analysis, which we have in our label, that was statistically significant with a treatment effect of 1.2 milliliters per minute per year versus active comparator. So in totality, we're confident in the data to support FILSPARI provide superior long-term nephroprotection versus a max dose irbesartan in PROTECT and that's what provides support for its first-line placement in the KDIGO guidelines.

最後，我們在標籤中列出的首選 FDA 分析的主要終點是總 eGFR 斜率，該斜率具有統計意義，與活性對照相比，治療效果為每年每分鐘 1.2 毫升。綜上所述，我們有信心，在 PROTECT 研究中，FILSPARI 能夠提供優於最大劑量厄貝沙坦的長期腎臟保護作用，這也支持了它在 KDIGO 指南中被列為一線藥物。

Laura Chico, Wedbush Securities.

Laura Chico，Wedbush Securities。

For the FILSPARI sNDA, I'm sorry if I missed this in the earlier response, wondering if you could further elaborate on some of the specific aspects of clinical benefit characterization the agency is focused on. I guess I'm just trying to understand whether this signals any change in the agency's receptivity to proteinuria as an endpoint for FSGS?

關於 FILSPARI sNDA，如果我之前的回覆中遺漏了這一點，我深感抱歉。我想請您進一步詳細說明該機構關注的臨床獲益特徵的具體方面。我只是想了解這是否意味著該機構對將蛋白尿作為 FSGS 終點的接受度發生了任何變化？

And then just a separate follow-up for Peter. What proportion of the new 4K PSF came from patients with proteinuria less than 1.5 gram per gram? It sounds like it's an increasing proportion. I'm just wondering if you could kind of contextualize that versus the earlier days of launch.

然後，還有一份針對彼得的單獨後續報導。新 4K PSF 中有多少比例來自尿蛋白低於 1.5 克/克的患者？聽起來這個比例還在增加。我只是想問您能否將這種情況與公司早期發布的情況進行一些對比分析。

Laura, thanks for the questions. I will take the first one on the sNDA and then I'll hand over to Peter on the PS. We've not provided the level of detail on the types of information request that FDA provides us. Our practice is not to comment on that level of detail. What we have said is that all of the information requests we received late last year were focused on clinical benefit.

勞拉，謝謝你的提問。我會先簽保密協議，然後再把PS交給Peter。我們尚未提供 FDA 向我們提供的各種資訊請求的詳細資訊。我們的慣例是不對這種細節發表評論。我們之前說過，去年底我們收到的所有資訊請求都集中在臨床獲益方面。

And what I would say is that from what we've seen throughout our engagements with the FDA as well as what other sponsors have commented on in their discussions around Premier is an endpoint, we believe that this is the endpoint that could be used as a validated surrogate endpoint for full approval. So we're on track for the PDUFA date. And there's nothing that we've seen that would suggest that they're questioning or walking away from proteinuria as an end point.

我想說的是，根據我們與 FDA 的互動以及其他贊助商在討論 Premier 作為終點時所發表的評論，我們認為 Premier 可以作為已驗證的替代終點，用於獲得全面批准。所以，我們正按計劃推進 PDUFA 日期。到目前為止，我們還沒有看到任何跡象表明他們正在質疑或放棄將蛋白尿作為終點指標。

And with that, I'll turn it over to Peter.

接下來，我將把麥克風交給彼得。

Perfect. Thank you, Eric, and thanks, Laura, for that question. To clarify your question, we still see demand also with patients with proteinuria levels of 1.5 and higher. But if you look at the totality of patient start forms that we are receiving, you see more and more patient platform with proteinuria level below 1.5.

完美的。謝謝艾瑞克，也謝謝勞拉提出這個問題。為了澄清您的問題，我們仍然看到蛋白尿水平為 1.5 及以上的患者也有需求。但如果你查看我們收到的所有患者入院表格，你會發現越來越多的患者尿蛋白水平低於 1.5。

And if I look at the median, it continues to go down. It's well below 1.5, but we haven't split it out like in percentage-wise. So I can't comment on that.

如果我看一下中位數，它還在持續下降。遠低於 1.5，但我們還沒有像百分比那樣將其拆分出來。所以我對此不予置評。

Our next question comes from the line of Anupam Rama from JPMorgan.

我們的下一個問題來自摩根大通的 Anupam Rama。

This is Priyanka on for Anupam. Can you remind us of the sales infrastructure for IgAN and how this will need to be expanded for an FSGS approval?

這是普里揚卡為阿努帕姆主持節目。您能否提醒我們 IgAN 的銷售基礎設施，以及為了獲得 FSGS 批准，需要如何擴展該基礎設施？

Priyanka, thanks for the question, and I will hand that one over to Peter.

Priyanka，謝謝你的提問，我會把這個問題交給Peter來回答。

Yes. Thanks, Priyanka. So first of all, I think it's good to realize that the prescriber base for FSDS is very similar compared to IgA nephropathy. I mean in the past, I've called out there is like an over 80% overlap between IgA nephropathy and FSGS.

是的。謝謝你，普里揚卡。首先，我認為應該認識到，FSDS 的處方醫生群體與 IgA 腎病的處方醫生群體非常相似。我的意思是，過去我曾指出，IgA 腎病和 FSGS 之間有超過 80% 的重疊。

The only real different prescriber base would be pediatric nephrologist, but to the point that you're making, we want to make sure that we continue to deliver for IgA nephropathy patients while also really optimizing the opportunity for FSGS. And so we have expanded our field team for that, and that is fully operational already.

唯一真正不同的處方者群體是兒科腎臟科醫生，但正如您所說，我們希望確保繼續為 IgA 腎病患者提供服務，同時真正優化 FSGS 的治療機會。因此，我們擴大了現場團隊，目前團隊已全面運作。

That's right. And we previously commented that we had about 80 field-based personnel and we have expanded that to more than 100 in the field. We've not broken down that, but I think that certainly provides us with a very strong infrastructure to be able to realize strong growth in reaching patients with IgA nephropathy and FSGS, if approved.

這是正確的。我們之前曾說過我們有大約 80 名現場工作人員，現在我們已經將現場工作人員增加到 100 多人。我們還沒有對此進行細分，但我認為這無疑為我們提供了一個非常強大的基礎設施，如果獲得批准，我們將能夠在接觸 IgA 腎病和 FSGS 患者方面實現強勁增長。

Joe Schwartz, Leerink Partners.

Joe Schwartz，Leerink Partners。

I was wondering if you could elaborate on your commentary earlier regarding gross to net and give us some insight into how we should expect that to evolve over the balance of the year.

我想請您詳細解釋一下您之前關於毛利潤與淨利潤的評論，並讓我們了解一下在今年剩餘時間裡，這一數字將如何變化。

Joe, thanks for the question. I will hand that one over to Chris.

喬，謝謝你的提問。我會把那個交給克里斯。

Sure. Thanks for the question, Joe. So just in terms of the mechanics for gross to nets, we anticipate the flow of them to be similar to what we've seen in previous years. That being that we would expect that in the first quarter, you're going to see the highest differential in growth in that -- or the largest discount, and then you'll see that lessen in the second and third quarters. So a very similar dynamic.

當然。謝謝你的提問，喬。就毛利潤到淨利潤的轉換機製而言，我們預期其流程將與往年類似。也就是說，我們預期第一季成長差異最大——或者說折扣最大，然後第二季和第三季這種差異會縮小。所以情況非常相似。

I think the thing that is a little bit different this year is that our gross and net are expected to increase modestly. So this year, we're expecting to be in the mid-20s -- mid-20 percentage for the full year for FILSPARI and that's up a little bit from last year where we ended the year right around 20%.

我認為今年略有不同的是，我們的毛利潤和淨利潤預計都會小幅增長。所以今年，我們預計 FILSPARI 全年的成長率將達到 20% 左右，比去年略有上升，去年我們年底的成長率約為 20%。

Prakhar Agrawal, Cantor.

Prakhar Agrawal，坎托爾。

Congrats on the strong quarter. So I had two. Maybe firstly, on FSGS. Given that externally, we have limited information on the nature of these information requests from the FDA. What is your confidence level in getting FILSPARI approval for FSGS based on FDA's level of questioning and what is driving that conviction?

恭喜你們本季業績出色。所以我有兩個。或許首先，關於FSGS。有鑑於此，我們對美國食品藥物管理局（FDA）提出的這些資訊請求的性質了解有限。根據 FDA 的提問程度，您對 FILSPARI 獲得 FSGS 批准的信心有多大？是什麼讓您如此確信？

And secondly, on IgAN with the Otsuka's launch of their April blocker seems like they have got 500 patient start forms since launch. Where are beginning new patient starts versus FILSPARI? And how much impact from orcas drug and future bacipril drugs? Are you incorporating in 2026?

其次，關於 IgAN，大塚製藥自 4 月推出 IgA 阻斷劑以來，似乎已經收到了 500 份患者開始治療申請表。與 FILSPARI 相比，新病患治療的起始點在哪裡？奧卡斯藥物和未來的巴西普利藥物會產生多大影響？您計劃在 2026 年成立公司嗎？

Prakhar, thanks so much for the questions. I will take the first question on FSGS, and I'll hand it over to Peter for the discussion on the evolving treatment landscape. So with regard to FSGS, again, we've provided information on the nature of the questions, but not specifically.

Prakhar，非常感謝你的提問。我將回答關於 FSGS 的第一個問題，然後把問題交給 Peter，讓他來討論不斷變化的治療現況。所以關於 FSGS，我們已經提供了有關問題性質的信息，但沒有具體說明。

What I can say is that our confidence has only increased in the profile of FILSPARI as a potential treatment in FSGS because not only do we see the data that we've presented and published as part of the New England Journal of Medicine, but all the work that we've done to be able to contextualize in the context of the parasol analysis showing how proteinuria has an independent predictive value of longer-term kidney -- risk of kidney failure further strengthen through our review and through our further analyses, some of which was presented at ASN in the fall. So again, our confidence remains very high in the profile.

我可以肯定地說，我們對 FILSPARI 作為 FSGS 潛在治療方法的信心與日俱增，因為我們不僅看到了我們在《新英格蘭醫學雜誌》上發表的數據，而且我們還做了大量工作，將這些數據與陽傘分析相結合，表明蛋白尿對長期腎衰竭風險具有獨立的預測價值——我們的審查和進一步分析已進一步分析所以，我們對這款產品依然充滿信心。

And as Jula mentioned, two of the largest studies ever done in PROTECT -- in FSGS, now reflective of some of the conclusions that we saw coming out of Parasol. Jula, is there anything else that you'd want to add on the data?

正如 Jula 所提到的，PROTECT 中進行的兩項最大的研究——FSGS——現在反映了我們在 Parasol 研究中看到的一些結論。Jula，還有什麼要補充的數據嗎？

No. Just we continue to feel quite confident in the data that we presented, as you mentioned as well as what we submitted in our file and presented at ASN. FILSPARI clearly reduces proteinuria, as I mentioned in my prepared remarks across a broad spectrum of patients with FSGS and we have strong conviction that it should be available for treatment for the high-risk patient population that really has very little other treatment options.

不。正如您所提到的，我們對我們提交的資料以及我們在文件中提交並在 ASN 上展示的資料仍然非常有信心。正如我在準備好的演講稿中提到的，FILSPARI 可以明顯減少 FSGS 患者的蛋白尿，我們堅信它應該用於治療那些幾乎沒有其他治療選擇的高風險患者群體。

And Peter, why don't you take the question about the Azuca launch?

彼得，你來回答關於 Azuca 發射的問題吧？

Yes, happy to do so. I think the 500 basis platforms that you were referring to from Otsuka is really indicative of the overall IGAN market growing and the urgency to intervene earlier is reflecting that. And I think KDIGO is really outlining that this is a two-prong approach. You need to have kidney targeted therapies that historically was done with Agin ARPS and now with FILSPARI as novel superior alternative. It had historically generic steroids, and now you have B-cell therapy that could replace that.

是的，我很樂意這樣做。我認為你提到的來自大塚的 500 個基礎平台確實表明了 IGAN 市場的整體成長，而更早介入的緊迫性也反映了這一點。我認為 KDIGO 確實在強調這是一個雙管齊下的方法。您需要接受腎臟標靶治療，過去通常使用 Agin ARPS 進行治療，而現在可以使用 FILSPARI 作為新型的更優替代方案。歷史上曾使用過普通類固醇，現在有了 B 細胞療法，可以取代它。

And what we are hearing so far is that physicians act accordingly. They really see this as replacing steroids in the higher proteinuria patient population. And maybe good to articulate to my earlier comment in the prepared remarks, we see a very nice continuation of demand -- strong demand in the first part of the year, which indicates that we are not seeing any signs of switching, and we're not seeing any signs of sequencing B-cells before FILSPARI. So I'm very encouraged by what we are seeing right now, and it's very consistent to how we were anticipating the marketplace and very consistent also to the KDIGO guidelines.

目前我們聽到的消息是，醫生們都採取了相應的行動。他們認為這可以取代類固醇，用於治療高蛋白尿患者族群。或許可以補充一下我之前在準備好的演講稿中提到的，我們看到需求持續強勁，這表明我們沒有看到任何轉變的跡象，也沒有看到在 FILSPARI 之前對 B 細胞進行測序的任何跡象。因此，我對我們目前所看到的情況感到非常鼓舞，這與我們對市場的預期非常一致，也與 KDIGO 的指導方針非常一致。

Yes. Thank you, Peter. The way that I like to think this -- about this as we take a step back is, this is going to be a marketplace that is going to have a real acceleration of growth as there are new treatment options for these patients. And certainly, the KDIGO guidelines outline why that's going to take place.

是的。謝謝你，彼得。我喜歡這樣看待這個問題——當我們退後一步來看——隨著這些患者有新的治療選擇，這個市場將會真正加速成長。當然，KDIGO 指南也概述了這樣做的原因。

We expect to see therapies that are immune targeted like the Asuka compound grow in parallel to the growth that we expect to see as we look to replace the traditional role of RAS inhibitors just as they will be replacing the traditional role that steroids play. So there's going to be evolution of innovation that really is going to fuel growth for both sides of the treatment algorithm.

我們預計，像 Asuka 化合物這樣的免疫標靶療法將與我們預期的增長同步增長，因為我們將尋求取代 RAS 抑制劑的傳統作用，就像它們將取代類固醇的傳統作用一樣。因此，創新將會不斷發展，真正推動治療方案雙方的成長。

Our next question comes from the line of Mohit Bansal from Wells Fargo.

我們的下一個問題來自富國銀行的莫希特·班薩爾。

This is Sadia Rahman on for Mohit. So you've been seeing really good traction in the market recently and it sounds like you expect robust growth this year. So just wondering if you can comment on how penetrated the US market is today and how you view FILSPARI's potential, how much further you think this can grow? I think The Street's expectations currently imply that penetration could double over time from current levels, which still seem low.

這裡是薩迪亞·拉赫曼，她正在為莫希特做報道。看來你們最近在市場上取得了非常好的進展，而且聽起來你們預計今年將實現強勁成長。所以我想請您談談目前美國市場的滲透率，以及您如何看待 FILSPARI 的潛力，您認為它還能成長多少？我認為華爾街目前的預期表明，滲透率可能會在目前的水平基礎上翻一番，而目前的水平仍然很低。

So just wondering if you think that's appropriate given the new competition that's coming? Or do you think FILSPARI's expansion potential might be underappreciated?

所以我想知道，考慮到即將到來的新競爭，你認為這樣做是否合適？或者您認為 FILSPARI 的發展潛力可能被低估了？

Thanks, Sadia. Very insightful and great questions. Let me first start before I hand it over to Peter in saying we're not -- I don't want to provide any type of guidance. But I think what we can talk about is some of the potential and some of the dynamics. And I think, Peter, if you can start with what are we seeing with the estimated penetration, I think then we can reflect on what is the real potential for further growth in our segment of this market.

謝謝你，薩迪婭。很有見地，問得很好。在把麥克風交給彼得之前，我先聲明一下，我們──我不想提供任何形式的指導。但我認為我們可以討論的是一些潛力和一些動態因素。彼得，我認為，如果你能先從我們目前看到的預期滲透率入手，那麼我們就可以思考一下，在這個市場細分領域，我們真正的成長潛力是什麼。

Yes. I think that's a good way to start. I think overall, you have to realize this was a market that historically was treated with generic medicine. And if you look at proxies in other disease areas, you see there is a substantial opportunity for branded superior treatment options. And with our data, I think we have a very strong opportunity.

是的。我認為這是一個不錯的開始。我認為總的來說，你必須意識到，這個市場歷來都是用仿製藥來治療的。如果你看看其他疾病領域的替代療法，你會發現品牌化的優質治療方案有很大的機會。我認為，憑藉我們的數據，我們擁有非常大的機會。

I mean if you look at our cumulative amount of patient start forms, we don't even hit that 10% of the addressable patient population. So I think that allows a very strong growth opportunity ahead of us. I mean if I think about the amount of bases are still treated with ACE inhibitors or ARBs for IgA nephropathy, while there is a superior treatment available that's the opportunity we have. And to provide a finer point on that, I think there are three categories, how I would classify continued growth. I think the first one to my earlier point, innovation matters.

我的意思是，如果你看看我們累積的病患登記表數量，我們甚至連目標病患群體的 10% 都沒達到。所以我認為這為我們帶來了非常強勁的成長機會。我的意思是，想想看，現在還有很多 IgA 腎病患者仍然在使用 ACE 抑制劑或 ARB 治療，而實際上已經有了更好的治療方法，這就是我們所擁有的機會。為了更清楚地說明這一點，我認為持續成長可以分為三類。我認為第一點與我先前的觀點一致，創新至關重要。

We have the opportunity with the superior product to replace generic RAS inhibition with FILSPARI. The second point is as we mentioned earlier in the prepared remarks, and Eric was mentioning in answering the earlier question as well, with KDIGO and with a recognition to treat those patients earlier and more aggressively. We have an opportunity to further build that market and expand the patient population that are yet untreated. And I think the guidelines really allow us to move into that segment as well.

我們有機會憑藉這款卓越的產品，以 FILSPARI 取代普通的 RAS 抑制劑。第二點正如我們在事先準備好的演講稿中提到的，埃里克在回答前面的問題時也提到過，那就是與 KDIGO 合作，並認識到應該更早、更積極地治療這些患者。我們有機會進一步拓展這個市場，並擴大尚未接受治療的患者群。我認為這些指導方針確實允許我們進入那個領域。

And then the third category, building on what Eric said earlier on the Otsuka question, we are expecting that you will see increased combination therapies, in particular with like in a more ambitious treatment target. One treatment category may not bring you there, and that's why we are anticipating that you will see a continuation of use of novel foundational therapies like FILSPARI as well as immunosuppressive -- novel immunosuppressive treatment agents like, for example, the B cells or the complement inhibitors.

第三類，基於 Eric 先前在 Otsuka 問題上所說的，我們預期你會看到聯合療法的增加，尤其是在更雄心勃勃的治療目標方面。單一的治療類別可能無法達到預期效果，因此我們預計，像 FILSPARI 這樣的新型基礎療法以及免疫抑制劑（例如 B 細胞或補體抑制劑）等新型免疫抑制治療藥物將繼續被應用。

All in all, I feel that this market is going to grow. I think with FILSPARI, we are very well positioned in that foundational treatment category. And I think this -- you will see that this market will continue to grow.

總而言之，我認為這個市場將會成長。我認為憑藉 FILSPARI，我們在基礎治療領域佔據了非常有利的地位。我認為，你會看到這個市場會繼續成長。

Yes. Thank you, Peter. And just to round out, Sadia, the other aspect is that we have shared that at peak. We believe that IGA nephropathy alone, FILSPARI will be well above $1 billion potential. So real opportunity for further growth in the years to come.

是的。謝謝你，彼得。最後補充一點，Sadia，另一方面，我們在巔峰時期也分享過這一點。我們相信，僅就 IGA 腎病變而言，FILSPARI 的市場潛力就將遠遠超過 10 億美元。因此，未來幾年仍有很大的成長機會。

Gavin Clark-Gartner, Evercore.

Gavin Clark-Gartner，Evercore。

I was just wondering what your plans are for communicating with the investor community more broadly as we approach the FSGS PDUFA over the next two months or so.

我想知道，在接下來的兩個月左右的時間裡，隨著 FSGS PDUFA 的臨近，你們有什麼計劃與更廣泛的投資者群體進行溝通。

Gavin, thanks for the question. I will hand that one over to Chris.

加文，謝謝你的提問。我會把那個交給克里斯。

Thanks, Gavin. We're going to approach this very similar to how we did the last time around, and we're going to enter into a quiet period here at the end of the month. And then once we have a material communication from the FDA on their decision for the PDUFA action, we'll provide an update and make sure everybody is on the same page. But it will be done very similar to before we'll go into quieter and you shouldn't expect to hear much from us on an incremental basis between now and then.

謝謝你，加文。我們將採取與上次非常相似的方法來處理此事，並且我們將在本月底進入一段平靜期。一旦我們收到 FDA 關於 PDUFA 行動決定的實質通知，我們將提供最新信息，並確保每個人都了解情況。但我們會採取與之前非常相似的方式，之後我們會進入一個較為平靜的時期，從現在到那時，你們不應該指望我們會陸續發布太多消息。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑富瑞。

You've commented a few times on the demand going into your first quarter can you set expectations for first quarter as it relates to new patient starts and how insurance resets or other variables could influence your sales number relative to fourth quarter 2025? And then for FSGS, have you had any discussions with FDA on the label yet? And what are your latest expectations on what the label could look like?

您曾多次談到第一季的需求，能否就第一季的新病患數量以及保險重置或其他變數將如何影響您相對於 2025 年第四季的銷售額給出一些預期？那麼對於 FSGS，您是否已經與 FDA 就標籤問題進行過任何討論？那麼，你對這個品牌未來的發展方向有什麼新的期待呢？

Maury, thanks for the question. Peter, I will have you talk about demand in Q1. And then Bill, if you can take the question on the FSGS label.

莫里，謝謝你的提問。Peter，第一季我會請你談談需求狀況。然後比爾，如果你能回答一下關於 FSGS 標籤的問題的話。

Very good. Well, thanks, Maury, for the question. And yes, indeed, we are very happy with the very strong demand exceeding $900 million. I think it's too early to say if that would be our new baseline, but I'm in course is what we are seeing so far in the beginning of the year.

非常好。謝謝你的提問，莫里。沒錯，我們對超過 9 億美元的強勁需求感到非常高興。現在說這是否會成為我們的新基準線還為時過早，但就今年年初的情況來看，這確實是我們目前所看到的。

Having said that, I also want to make sure that we realize this is a rare disease and that you may see variability quarter-over-quarter. But most importantly, I'm confident to deliver sustainable growth and long-term leadership in IgA nephropathy with FILSPARI.

話雖如此，我也想確保我們意識到這是一種罕見疾病，而且每季的病情可能會有所波動。但最重要的是，我有信心透過 FILSPARI 在 IgA 腎病領域實現永續成長和長期領先地位。

And I'll tackle the label question. We're about 7 weeks out from our action date, which is a little bit early for us to be getting the initiation of label negotiation. We expect that to begin as we get a little bit closer. As to what the label should look like, we believe that FILSPARI has broad applicability in FSGS and should be used across all forms. We've submitted a label that matches that intent.

接下來我會解答標籤的問題。距離我們的行動日期還有大約 7 週，現在就開始與唱片公司談判有點早了。我們預計隨著比賽日期臨近，這種情況會開始出現。至於標籤應該是什麼樣子，我們認為 FILSPARI 在 FSGS 中具有廣泛的適用性，應該用於所有形式的 FSGS。我們提交的標籤符合此意圖。

And we have seen across all patients used very broad efficacy with a consistent safety profile. So that's the expectation that we have around the indication of the --

我們看到，在所有使用的患者中，該藥物具有非常廣泛的療效和一致的安全性。所以這就是我們對該指標的預期。--

And Maury, maybe just to add one thing on the revenue side on 1Q to answer your question fully. I mentioned earlier on the call that we expect higher growth than us for the year. But in the first quarter, you see the biggest effect of that. So 4Q going to 1Q, you will see an increase in that discount.

莫里，或許我還需要補充一點關於第一季營收的信息，才能完整回答你的問題。我之前在電話會議上提到過，我們預計今年的成長速度會高於我們。但在第一季度，這種影響最為明顯。所以從第四季到第一季度，你會看到折扣強度增加。

So I want to make sure that everybody is thinking that into account for the model. Again, same as what we've seen in previous years, but we will see a higher discount in 1Q relative to the other quarters.

所以我想確保每個人在構建模型時都將這一點考慮在內。與往年一樣，但第一季的折扣幅度將高於其他季度。

Jason Zemansky, Bank of America.

傑森‧澤曼斯基，美國銀行。

Congrats on the progress in. Peter, one for you, if I may. Can you speak to the potential of a halo effect if FILSPARI receives approval in FSGS for IgAN? I know you said the prescriber base overlaps about 80%. But I guess, any opportunities for increased awareness or I don't know, potentially a lowering of some of the friction points that might cause an IgAN prescriber, some pause or, I don't know, underlying inertia.

恭喜你的進展。彼得，如果可以的話，給你一個。如果 FILSPARI 獲準用於治療 IgAN 引起的 FSGS，您能否談談其可能產生的光環效應？我知道你說過處方醫生群體重疊率約 80%。但我想，任何提高認識的機會，或者，我不知道，或許可以降低一些摩擦點，這些摩擦點可能會導致 IgAN 處方醫生猶豫不決，或者，我不知道，潛在的惰性。

Thanks, Jason. Peter?

謝謝你，傑森。彼得？

Yes, I think, Jason, for that question. And I think it's a very good point that you bring up. Is there a halo effect once you get an FSGS approval and wouldn't have a good reflection on our IGN property as well. Well, to your point, I mean, given that this is largely the same prescriber base, I think you're absolutely right. There will be a halo effect and there will be some cross talk between the two indications. And yes, I think even more reason to be very excited about the FSGS opportunity, not only for serving this patient community that has been without an approved treatment for far too long, but also how that could reflect them on further confidence in the profile of FILSPARI for IgA nephropathy patients.

是的，傑森，關於這個問題，我覺得可以回答。我認為你提出的觀點非常好。獲得 FSGS 認證後是否會產生光環效應，對我們的 IGN 資產產生不利影響？嗯，你說得對，我的意思是，考慮到處方醫生群體基本上相同，我認為你的說法完全正確。會出現光環效應，並且兩個指標之間會有一些串擾。是的，我認為更有理由對 FSGS 的機會感到非常興奮，不僅可以服務於長期以來沒有獲批治療的患者群體，而且還能進一步增強他們對 FILSPARI 在 IgA 腎病患者中的療效的信心。

Got it. Any idea of kind of magnitude or --

知道了。任何關於規模或類型的想法--

Tough to say. I think directionally, we absolutely expect there to be a synergistic effect between the 2. And certainly, as you point out, simplifying the process for these offices that are incredibly busy, particularly community nephrology offices. But I'd say it's too early for us to be able to quantify. But directionally, absolutely, we would expect there to be a synergistic effect.

很難說。我認為從方向來看，我們絕對預期這兩者之間會產生協同效應。當然，正如您所指出的，簡化這些非常繁忙的診所（特別是社區腎臟病診所）的流程非常重要。但我認為現在量化還為時過早。但從方向來看，我們絕對預期會產生綜效。

Alex Thompson, Stifel.

Alex Thompson，Stifel。

Maybe again on FDA interactions over the last few months related to filing. Could you comment on the consistency of interactions among members of the cardio real division? Has it been the same group throughout this process? And does it continue to be the same group?

或許再次與過去幾個月FDA在備案方面的互動有關。能否評估一下有氧運動部門成員之間互動的一致性？整個過程中一直是同一批人嗎？還是同一批人嗎？

Thanks, Alex. Bill, I'll turn that one over to you.

謝謝你，亞歷克斯。比爾，這事就交給你了。

Sure. Recently, we've been made aware of some changes within the review team, but I think it's important to note that we also see continuity through the team, especially in those folks that were involved in the PARASOL project, looking at proteinuria as an endpoint for FSGS. Importantly, our recent interactions have also included the division level of leadership, and that leadership has remained consistent and engaged throughout the process.

當然。最近，我們了解到審查團隊內部發生了一些變化，但我認為值得注意的是，我們也看到了團隊的連續性，特別是那些參與 PARASOL 計畫的人，他們將蛋白尿作為 FSGS 的終點進行研究。重要的是，我們最近的互動也包括與部門領導層的互動，而這個領導層在整個過程中始終保持一致性和積極性。

Yigal Nochomovitz, Citi Group.

Yigal Nochomovitz，花旗集團。

I had one on FILSPARI and then one on Pegtibatinase. So I was just curious, looking at the quarter-on-quarter trends from 3Q to 4Q, you were up 13% and on revenue, and you were up just almost twice that on start forms. So I wonder if you could expand a bit in terms of the lag between the strong growth in the start forms of 25 -- 24%, 25% and the quarter-on-quarter revenue growth?

我服用過一次 FILSPARI，然後又服用過一次 Pegtibatinase。所以我很好奇，從第三季到第四季的季度環比趨勢來看，你們的營收成長了 13%，而註冊表單數量的成長幾乎是營收的兩倍。所以我想知道您能否詳細解釋一下，25%（24%、25%）的強勁成長與季度環比營收成長之間的滯後情況？

And then secondarily, on Pegtibatinase, with regard to the study that you're conducting, can you just describe what the -- what you would need to see in terms of reduction in homocystine levels to be stats on the primary endpoint? And also, are you looking at some responder analyses, for example, percent of patients that get below, say, 12 micromolar or even lower, say, below 10 micromolar or those part of the analysis?

其次，關於 Pegtibatinase，就您正在進行的研究而言，您能否描述一下——您需要看到同型半胱氨酸水平降低到什麼程度才能達到主要終點統計數據？另外，您是否在研究一些應答者分析，例如，達到低於 12 微摩爾甚至更低（例如低於 10 微摩爾）的患者百分比，或者分析中包含的那些患者百分比？

Yigal, thanks for the questions. Peter, why don't you take the one on demand versus revenue? And then, Jula, if you can take the question on our endpoints.

Yigal，謝謝你的提問。彼得，為什麼不選擇按需付費與按營收付費的方案呢？然後，朱拉，如果你能回答一下關於我們端點的問題的話。

Absolutely. Thank you all. Yes. The last few quarters, we actually had the opposite. We had strong revenue growth relative to patient start forms. I think the most important point is to the point that you made. There's always a time lag between patients start from generation and revenue recognition.

絕對地。謝謝大家。是的。最近幾個季度，情況恰恰相反。相對於患者起始表格而言，我們的收入實現了強勁成長。我認為最重要的一點就是你剛才提出的觀點。從患者開始就診到確認收入之間總是存在時間差。

And we saw the same phenomenon after our full approval in September 2024. Too specific to call out here on December was our strongest month. So they will carry over into Q1 revenue recognition. And the second part is something that we highlighted in the Q3 earnings call is that our gross to net will be higher in Q4.

我們在 2024 年 9 月獲得全面批准後也看到了同樣的現象。12月是我們業績最好的一個月，具體情況不便在此贅述。因此，這些影響將計入第一季的收入確認。第二部分是我們第三季財報電話會議重點提到的，那就是第四季我們的毛利與淨利比將會更高。

And then I'll talk about the HARMONY study. We haven't stated externally what treatment effect we need to reach statistical significance, but I'll point back to our COMPOSE study where we had about between 5 and 6 patients per cohort. And we saw a 67% reduction in total homocystine, which was highly statistically significant with the small number of patients. We're obviously going to a larger sample size. We have about 70 patients that we're planning to enroll for this and are well powered to achieve statistical significance if we even reach something comparable to what we saw or less.

然後我會談談 HARMONY 研究。我們沒有對外說明我們需要達到統計意義的治療效果，但我可以回顧我們的 COMPOSE 研究，其中每個隊列大約有 5 到 6 名患者。我們發現總同型半胱氨酸減少了 67%，考慮到患者數量較少，這一結果具有高度統計意義。顯然，我們將採用更大的樣本量。我們計劃招募大約 70 名患者參與這項研究，即使結果與我們觀察到的結果相當甚至更低，我們也有足夠的統計效力來達到統計意義。

And I'll reiterate that we have already looked at long-term durability of treatment effect. Our primary endpoint is 6 to 12 weeks, which is where we saw that 67% reduction in total homocystine in our Phase 1/2 study, but we've also seen a durability when we follow these patients from Compose out to even one year where they still maintain a greater than 50% reduction in total homocystine one year. So we feel very confident in our study design to be able to achieve our primary end point. In addition, you've asked about some secondary endpoints or other things.

我再次重申，我們已經研究過治療效果的長期持久性。我們的主要終點是 6 到 12 週，我們在 1/2 期研究中觀察到總同型半胱氨酸減少了 67%，但我們也觀察到，當我們從 Compose 治療開始追蹤這些患者長達一年時，他們的總同型半胱氨酸仍然保持 50% 以上的減少。因此，我們對研究設計非常有信心，能夠達到我們的主要終點。此外，您也詢問了一些次要終點或其他事項。

We certainly will look at clinically meaningful thresholds I would say you asked about -- a little bit about a responder, importantly, but we've seen to date with Pegtibatinase as everyone has a reduction in total homocystine based on the mechanism of action and in our study. So we feel comfortable with our study design and that we'll be able to show both a clinically meaningful treatment effect and then different thresholds that we will look at.

我們當然會關注您提到的具有臨床意義的閾值——重要的是，我們會稍微關註一下應答者，但到目前為止，根據作用機制和我們的研究，我們看到使用培替巴汀酶後，每個人的總同型半胱氨酸水平都有所降低。因此，我們對研究設計感到滿意，相信能夠展示具有臨床意義的治療效果，以及我們將要研究的不同閾值。

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I'll hand the call over back to Nivi.

女士們、先生們，今天的電話會議問答環節到此結束。我會把電話轉回給妮維。

Thank you, everyone, for joining today's call. Have a great rest of your day.

感謝各位參加今天的電話會議。祝您今天餘下的時間過得愉快。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線了。