Travere Therapeutics Inc (TVTX) 2024 Q3 法說會逐字稿

Good morning, and welcome to the Travere Therapeutics Third Quarter 2024 Financial Results Conference Call.

早安，歡迎參加 Travere Therapeutics 2024 年第三季財務業績電話會議。

Today's call is being recorded.

今天的通話正在錄音。

At this time, I would like to turn the conference over to Nivi Nehra, Vice President of Corporate Communications and Investor Relations.

現在，我想將會議交給企業傳播和投資者關係副總裁 Nivi Nehra。

Please go ahead, ma'am.

請繼續，女士。

Thank you, Shelley.

謝謝你，雪萊。

Good morning, and welcome to Travere Therapeutics third quarter 2024 financial results and corporate update call.

早安，歡迎參加 Travere Therapeutics 2024 年第三季財務業績和公司更新電話會議。

Thank you all for joining.

感謝大家的加入。

Today's call will be led by our President and Chief Executive Officer, Dr. Eric Dube.

今天的電話會議將由我們的總裁兼執行長 Eric Dube 博士主持。

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.

我們的首席醫療官 Jula Inrig 博士將與 Eric 一起發表準備好的演講； Peter Heerma，我們的首席商務官；以及我們的財務長 Chris Cline。

Dr. Bill Rote, Senior Vice President of Research and Development will join us to the Q&A session.

研發資深副總裁 Bill Rote 博士將參加我們的問答環節。

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.

在我們開始之前，我想提醒大家，本次電話會議中關於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範圍內的前瞻性陳述。

Forward-looking statements are not guarantees of performance.

前瞻性陳述並不保證業績。

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 statements.

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、表現和成就與聲明中表達或暗示的結果、表現和成就有重大差異。

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.

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 表和 10-K 表中的風險因素部分。

In addition, any forward-looking statements represent our views only as of the date such statements are made, October 31, 2024, and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances.

此外，任何前瞻性陳述僅代表我們截至做出此類陳述之日（2024 年 10 月 31 日）的觀點，Travere 明確表示不承擔更新此類陳述以反映未來資訊、事件或情況的義務。

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

說完這些，我現在把電話轉給 Eric。

Thank you, Nivi, and good morning, everyone.

謝謝你，Nivi，大家早安。

Our team has delivered another exceptional quarter, advancing our leadership position in rare nephrology with the full approval of FILSPARI for IgA nephropathy and the ongoing commercial launch.

我們的團隊又度過了一個出色的季度，隨著 FILSPARI 獲得用於治療 IgA 腎病的全面批准和正在進行的商業發布，我們在罕見腎病學領域的領導地位得到了提升。

As you will hear shortly from Peter, our commercial team's execution resulted in continued strength in demand, more than 30% growth in net sales over last quarter and a recent acceleration in new patient start forms following full approval and the draft KDIGO guidelines.

正如您很快就會從 Peter 那裡聽到的那樣，我們商業團隊的執行導致需求持續強勁，上個季度淨銷售額增長了 30% 以上，並且在獲得全面批准和 KDIGO 指南草案後，新患者開始表格的數量近期也有所加速。

Our vision for FILSPARI to become foundational care in IgAN is clear and we are making great progress towards achieving this.

我們對 FILSPARI 成為 IgAN 基礎治療的願景非常明確，我們正在朝著實現這一目標的方向取得巨大進展。

As we look ahead, there are tangible growth drivers that we believe will enable us to reach significantly more patients with IgAN.

展望未來，我們相信實際的成長動力將使我們能夠惠及更多的 IgAN 患者。

These include the full approval label which now provides the ability to educate the nephrology community on the incredibly strong two-year data.

其中包括完整的批准標籤，該標籤現在可以根據令人難以置信的兩年數據對腎臟病學界進行教育。

The updated draft KDIGO guidelines which should drive nephrologists to treat more ambitiously and use FILSPARI as foundational care and the growing body of data providing further support for earlier treatment with FILSPARI and paving the way for use in combination with other medicines.

更新後的 KDIGO 指引草案應能促使腎臟科專家更積極地治療並使用 FILSPARI 作為基礎治療，越來越多的數據為早期使用 FILSPARI 治療提供進一步支持，並為與其他藥物聯合使用鋪平道路。

I'm pleased to share with you, we also recently submitted an sNDA to modify the frequency of liver monitoring in the FILSPARI REMS.

我很高興與大家分享，我們最近也提交了一份 sNDA，以修改 FILSPARI REMS 中的肝臟監測頻率。

If this modification is approved, it represents another step forward in improving access for patients as it would align their liver monitoring with regular schedule of lab work while maintaining patient safety as a key priority.

如果這項修改獲得批准，這將代表在改善患者就醫機會方面又向前邁出了一步，因為它將使患者的肝臟監測與常規實驗室工作計劃保持一致，同時將患者安全作為首要任務。

Moving beyond IgAN, the recent recommendations of the PARASOL group offer new hope to the FSGS community.

除了 IgAN 之外，PARASOL 小組最近提出的建議為 FSGS 社群帶來了新的希望。

As a reminder, there are currently no medicines approved and few in development for this progressive rare kidney disease.

提醒一下，目前尚無任何藥物獲批，而且針對這種罕見的漸進性腎病的藥物正在研發中。

Specifically, we were very pleased that this group of experts, including representatives from FDA, aligned around a potential proteinuria based clinical trial endpoint for FSGS.

具體來說，我們非常高興這個專家小組，包括來自 FDA 的代表，就 FSGS 的潛在蛋白尿臨床試驗終點達成了一致。

Jula will touch on this shortly, but when we look at the data from our DUET and DUPLEX studies, two of the largest prospective controlled studies ever completed in FSGS.

Jula 很快就會談到這一點，但當我們查看 DUET 和 DUPLEX 研究的數據時，這兩項研究是有史以來在 FSGS 中完成的最大前瞻性對照研究。

We see a statistically superior reduction in proteinuria with sparsentan compared to maximum dose standard of care across multiple proteinuria thresholds and time points.

我們發現，與最大劑量標準治療相比，Sparsentan 在多個蛋白尿閾值和時間點的蛋白尿減少方面具有統計上的優勢。

We now have a meeting with FDA scheduled where we look forward to reviewing these data in the context of the PARASOL findings.

我們目前已安排與 FDA 舉行一次會議，我們期待根據 PARASOL 調查結果審查這些數據。

With the goal of establishing a path to an sNDA submission for an FSGS indication.

目標是建立一條針對 FSGS 適應症的 sNDA 提交路徑。

We anticipate being able to provide an update on our discussions by our Q4 earnings call.

我們期望能夠在第四季度收益電話會議中提供有關討論的最新情況。

In parallel, we are working diligently in preparation of an sNDA filing.

同時，我們正在努力準備 sNDA 申請。

If we are able to submit, we would anticipate a potential full approval for sparsentan in FSGS next year.

如果我們能夠提交申請，我們預計明年 Sparsentan 將有可能獲得針對 FSGS 的全面批准。

Lastly, we're continuing to expand access to FILSPARI outside of the US with our partners CSL Vifor and Renalys Pharma.

最後，我們將與合作夥伴 CSL Vifor 和 Renalys Pharma 繼續擴大美國以外地區對 FILSPARI 的訪問。

Under CSL Vifor's leadership, FILSPARI has now launched in two key European markets, Germany and Austria.

在 CSL Vifor 的領導下，FILSPARI 現已進軍歐洲兩個主要市場—德國和奧地利。

And recently received temporary marketing approval in Switzerland.

並於近期在瑞士獲得了臨時上市許可。

We look forward to continued progress as they launch in other countries.

我們期待他們在其他國家推出產品時能夠繼續取得進展。

Now let me turn the call over to Jula.

現在讓我把電話轉給 Jula。

Jula?

朱拉？

Thank you, Eric.

謝謝你，埃里克。

I'm pleased to provide a medical perspective following the full approval of FILSPARI and the increasing confidence we hear from nephrologists about FILSPARI's role as a foundational treatment for patients with IgA nephropathy.

在 FILSPARI 獲得全面批准以及腎病專家對 FILSPARI 作為 IgA 腎病患者基礎治療的作用越來越有信心之後，我很高興能夠提供醫學觀點。

This confidence is rooted in FILSPARI 's compelling clinical profile as the only kidney targeted medicine which blocks two pathologic processes, endothelin-1 and angiotensin-2.

這種信心源自於 FILSPARI 令人信服的臨床特性，它是唯一能夠阻斷內皮素-1 和血管張力素-2 兩種病理過程的腎臟標靶藥物。

These two pathways work together to amplify inflammation and kidney injury in IgA nephropathy.

這兩種途徑共同作用，加劇了IgA腎病變的發炎和腎損傷。

Our growing scientific evidence demonstrates that FILSPARI, as the only dual endothelin and angiotensin receptor antagonist, significantly reduces proteinuria and preserves kidney function for patients with IgA nephropathy.

我們越來越多的科學證據表明，FILSPARI作為唯一的雙重內皮素和血管緊張素受體拮抗劑，可顯著降低蛋白尿並保護 IgA 腎病患者的腎功能。

We just attended ASN Kidney Week in San Diego, the largest worldwide gathering of nephrologists.

我們剛參加了在聖地牙哥舉辦的 ASN 腎臟週，這是全球最大的腎臟病專家聚會。

During Kidney Week, we presented important new data supporting the use of FILSPARI in a broad population of IgA nephropathy patients at risk of disease progression, data supporting the use of FILSPARI early in treatment, as well as early data paving the way for potential combination use with other medications.

在腎臟週期間，我們提供了重要的新數據，支持在廣大有病情進展風險的 IgA 腎病患者中使用 FILSPARI，支持在治療早期使用 FILSPARI 的數據，以及為與其他藥物的潛在聯合使用鋪平道路的早期數據。

I'll briefly highlight some of these datasets.

我將簡要介紹其中一些資料集。

First is the SPARTAN study of newly diagnosed RAS inhibitor naive patients with IgA nephropathy, which showed that FILSPARI reduced proteinuria up to nearly 70%, with approximately 60% of patients in the study achieving complete remission through 24 weeks.

首先是針對新診斷的 RAS 抑制劑初治 IgA 腎病患者的 SPARTAN 研究，該研究顯示 FILSPARI 可使蛋白尿減少近 70%，研究中約 60% 的患者在 24 週內達到完全緩解。

And eGFR was stable throughout the measurement period.

並且整個測量期間 eGFR 保持穩定。

Also, as part of SPARTAN, we examined initial human mechanistic data which demonstrates that FILSPARI reduces an important inflammatory biomarker called Urinary CD163.

此外，作為 SPARTAN 的一部分，我們檢查了初始人體機械數據，顯示 FILSPARI 降低了一種名為尿液 CD163 的重要發炎生物標記。

This biomarker is recognized as highly predictive of IgAN disease progression.

此生物標記被認為可以高度預測 IgAN 疾病進展。

The magnitude of CD163 reduction that was seen with FILSPARI has only previously been seen with a systemic immunosuppressive.

使用 FILSPARI 時觀察到的 CD163 減少程度先前僅在使用全身免疫抑制劑時出現。

These clinical data are consistent with our preclinical models and support the kidney targeted anti-inflammatory mechanism of FILSPARI.

這些臨床數據與我們的臨床前模型一致，並支持 FILSPARI 針對腎臟的抗發炎機制。

They're also promising given FILSPARI is the only non-immunosuppressive treatment available for patients with IgA nephropathy.

鑑於 FILSPARI 是唯一可用於治療 IgA 腎病患者的非免疫抑制治療方法，它們也具有良好的前景。

We look forward to presenting more data from SPARTAN on how FILSPARI impacts important pathologic processes that cause kidney inflammation and injury in patients with IgAN at upcoming meetings.

我們期待在即將舉行的會議上展示更多來自 SPARTAN 的數據，說明 FILSPARI 如何影響導致 IgAN 患者腎臟發炎和損傷的重要病理過程。

We also presented promising data in patients from PROTECT with lower ranges of proteinuria less than 1 gram per gram and showed treatment with FILSPARI reduced proteinuria and preserved kidney function similarly to patients with higher ranges of proteinuria.

我們也提供了 PROTECT 研究中蛋白尿水平較低（低於 1 克/克）的患者中令人鼓舞的數據，並表明使用 FILSPARI 治療可以降低蛋白尿水平並保留腎功能，效果與蛋白尿水平較高的患者相似。

This is especially important given the recent draft KDIGO guidelines calling for physicians to diagnose and treat all patients above 0.5 grams per day or even 0.3 grams per day.

鑑於最近的 KDIGO 指南草案呼籲醫生對所有每日攝取量超過 0.5 克甚至 0.3 克的患者進行診斷和治療，這一點尤其重要。

Uniquely, we also showed encouraging data on patient reported outcomes that suggests that treatment with FILSPARI versus irbesartan can improve a patient's burden of kidney disease.

獨特的是，我們也展示了令人鼓舞的患者報告結果數據，顯示與厄貝沙坦相比，使用 FILSPARI 治療可以改善患者的腎臟疾病負擔。

Lastly, in IgAN, consistent with the growing approach of using multiple treatment options for patients with IgA nephropathy, we presented compelling efficacy and safety data in combination with SGLT2 inhibitors and immunosuppressants, both from real world use as well as from our open label extension study.

最後，在 IgAN 中，與對 IgA 腎病患者使用多種治療方案日益增多的方法一致，我們展示了與 SGLT2 抑制劑和免疫抑制劑聯合使用的令人信服的療效和安全性數據，這些數據既來自現實世界的使用，也來自我們的開放標籤擴展研究。

We expect this will provide nephrologists with even greater confidence in using FILSPARI as foundational care.

我們希望這將使腎病專家更有信心使用 FILSPARI 作為基礎治療。

In a late breaking session at ASN, we also presented exciting new data in high-risk subgroups of genetic FSGS patients who were historically the most difficult to treat.

在 ASN 的最新會議上，我們還展示了有關歷史上最難治療的遺傳性 FSGS 患者高風險亞群的令人興奮的新數據。

The data demonstrated that sparsentan was able to deliver a rapid and sustained proteinuria reduction in high-risk patients with genetic FSGS, including only a sparsentan treated patient achieving complete remission and low rates of the kidney failure composite endpoint compared to irbesartan.

數據表明，sparsentan 能夠快速、持續地降低高風險遺傳性 FSGS 患者的蛋白尿，其中，與厄貝沙坦相比，只有一名接受 sparsentan 治療的患者實現了完全緩解，並且腎衰竭綜合終點發生率較低。

The efficacy of sparsentan in patients with genetic FSGS was consistent with the overall DUPLEX population, which is promising given the subgroup of FSGS patients is typically resistant to treatment.

sparsentan 對遺傳性 FSGS 患者的療效與整體 DUPLEX 族群一致，鑑於 FSGS 患者亞群通常對治療有抵抗力，這是很有希望的。

From a regulatory perspective, we have submitted an sNDA for a modification to our REMS for FILSPARI and IgA nephropathy to request a change in our liver monitoring frequency from monthly in the first year to quarterly.

從監管角度來看，我們已經提交了一份 sNDA，要求修改 FILSPARI 和 IgA 腎病的 REMS，要求將我們的肝臟監測頻率從第一年的每月一次更改為每季一次。

We remain confident in the safety profile of FILSPARI, especially given increased patient exposure from our clinical trials and commercial use, which continue to demonstrate no change in the low rates of asymptomatic LFT elevations and no cases of drug induced liver injury.

我們仍然對 FILSPARI 的安全性充滿信心，特別是考慮到我們的臨床試驗和商業使用增加了患者接觸，這繼續證明無症狀肝功能升高的低發生率沒有變化，也沒有藥物引起的肝損傷病例。

Thus, we believe we now have the data to support the proposed change to the liver monitoring frequency within our REMS and have aligned with the FDA on the presentation of the data package for them to consider the request.

因此，我們相信我們現在有數據來支持我們 REMS 中肝臟監測頻率的建議變更，並已與 FDA 就資料包的呈現方式達成一致，以便他們考慮該請求。

Quarterly monitoring of liver function is what was used in our clinical trials and it aligns well to the regular testing IgAN patients undergo with their nephrologist.

我們在臨床試驗中每季度對肝功能進行監測，這與 IgAN 患者在腎臟科醫生那裡進行的定期檢測一致。

We have requested priority review of this REMS submission with the potential for this modification to occur in the first half of next year.

我們已經要求優先審查該 REMS 提交，並有可能在明年上半年進行修改。

Let me now turn to FSGS to discuss the recent data from the PARASOL Initiative as well as our plans for a potential sNDA submission for sparsentan and FSGS.

現在，我來談談 FSGS，討論 PARASOL 計劃的最新數據以及我們針對 sparsentan 和 FSGS 的潛在 sNDA 提交計劃。

The PARASOL Group held their public workshop in early October and we were encouraged by the input of the patient community, thought leaders, regulators and industry who came together with a common goal to identify a path forward for medicines to be approved for the FSGS community.

PARASOL 集團於 10 月初舉辦了公開研討會，我們受到了患者群體、思想領袖、監管機構和行業的投入的鼓舞，他們齊聚一堂，共同致力於確定 FSGS 群體獲得藥物批准的前進道路。

During the workshop, participants heard firsthand from patients and family members stories of perseverance and of hope for a better future, such as an eight-year-old's wish to leave the hospital to attend his sister's third birthday.

研討會期間，參與者直接聽取了病人和家屬講述的堅持不懈和對美好未來的希望的故事，例如，一個八歲的孩子希望離開醫院去參加他妹妹的三歲生日。

These compelling stories are a consummate reminder that the data reviewed at PARASOL are from people living with a rare kidney disease with no approved treatment options.

這些引人入勝的故事充分提醒我們，PARASOL 審查的數據來自患有罕見腎病且尚無核准治療方案的患者。

In our view, the PARASOL meeting was a success as the consensus from the workshop, which reviewed comprehensive analyses for more than 20 databases encompassing over 1,600 children and adults with FSGS, represent a potential new path forward for regulatory approval in FSGS.

我們認為，PARASOL 會議取得了成功，因為研討會達成的共識回顧了對 20 多個資料庫（涵蓋 1,600 多名患有 FSGS 的兒童和成人）的綜合分析，為 FSGS 的監管批准提供了一條潛在的新途徑。

I'll walk through some of the key findings from the PARASOL work and how we believe data from our sparsentan program align.

我將介紹 PARASOL 研究的一些主要發現，以及我們如何看待 sparsentan 計畫的數據。

First, due to the relapsing and remitting nature of FSGS, there is clearly too much variability in eGFR measurements to remain a feasible endpoint for regulatory approval.

首先，由於 FSGS 的復發和緩釋特性，eGFR 測量結果顯然存在太大差異，無法作為監管部門批准的可行終點。

This was evident in our DUPLEX data set, the largest randomized study run in FSGS to date.

這在我們的 DUPLEX 資料集中得到了證實，這是迄今為止在 FSGS 中進行的最大規模的隨機研究。

Second, reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure in FSGS patients, including responder definitions based on thresholds of proteinuria that are both biologically plausible and strongly supported by epidemiologic data.

其次，24 個月內蛋白尿的減少與 FSGS 患者腎衰竭風險的降低密切相關，包括基於蛋白尿閾值的反應者定義，這些定義在生物學上合理​​且得到流行病學數據的有力支持。

We have seen this response consistently across both our Phase 2 DUET and Phase 3 DUPLEX studies.

我們在第 2 階段 DUET 和第 3 階段 DUPLEX 研究中都一致地看到了這種反應。

In DUET, we saw significantly more patients achieve the modified partial remission endpoint with sparsentan versus irbesartan and in the open label extension portion of the study, with approximately four years of follow-up on sparsentan, 43% of patients achieved complete remission.

在 DUET 中，我們發現使用 sparsentan 達到改良部分緩解終點的患者明顯多於使用厄貝沙坦的患者，並且在研究的開放標籤擴展部分中，經過大約四年的 sparsentan 隨訪，43% 的患者達到了完全緩解。

Among those patients who achieved complete remission with sparsentan, which was roughly an 80% reduction in proteinuria over time, they had a significantly slower rate of loss of kidney function, approximately 1 mil per minute per year and negligible rates of kidney failure.

對於使用 Sparsentan 達到完全緩解的患者來說，隨著時間的推移，蛋白尿減少了約 80%，他們的腎功能喪失速度明顯變慢，大約為每年每分鐘 1 毫升，腎衰竭發生率可以忽略不計。

In DUPLEX, sparsentan demonstrated statistically significant and clinically meaningful treatment effects on the modified partial remission endpoint at 36 weeks, and this treatment effect was durable to two years.

在DUPLEX研究中，sparsentan在36週時對改良部分緩解終點表現出了統計上顯著和臨床上有意義的治療效果，並且這種治療效果可持續至兩年。

And as published in the New England Journal of Medicine and its supplement, we see that at multiple pre-specified thresholds of proteinuria from 1.5 grams per gram down to 0.3 grams per gram of complete remission, sparsentan demonstrated a statistically significant treatment effect versus irbesartan.

正如《新英格蘭醫學雜誌》及其增刊所發表的，我們發現，在多個預先指定的蛋白尿閾值（從每克 1.5 克到完全緩解每克 0.3 克）下，Sparsentan 與厄貝沙坦相比表現出了統計學上顯著的治療效果。

Notably, the magnitude of the treatment effect became even stronger as the proteinuria thresholds got more stringent.

值得注意的是，隨著蛋白尿閾值變得更加嚴格，治療效果的強度變得更加加強。

And while DUPLEX was not powered to show statistically significant treatment effects on heart outcomes, the rates of kidney failure were nearly double with irbesartan versus sparsentan, with a meaningful 42% reduced risk of kidney failure.

儘管 DUPLEX 無法顯示對心臟結果具有統計意義的治療效果，但使用厄貝沙坦的腎衰竭發生率幾乎是使用 sparsentan 的兩倍，而腎衰竭風險降低了 42%。

Third, there needs to be clear biologic possibility for how a potential therapy works to reduce proteinuria and/or preserve kidney function.

第三，需要有明確的生物學可能性來顯示潛在的治療方法如何減少蛋白尿和/或保護腎功能。

With proteinuria as an indicator of podocyte injury, it is in the mechanistic pathway leading to kidney failure in FSGS.

蛋白尿是足細胞損傷的指標，也是導致 FSGS 腎衰竭的機制途徑之一。

And in our preclinical data, some of which was recently featured in the Journal of Clinical Investigation Insight, sparsentan led to improvements in podocyte number, glomerular, hemodynamics, cell functions, and tissue repair, resulting in reduced proteinuria and preserved kidney function.

在我們的臨床前數據中，其中一些數據最近發表在《臨床研究洞察雜誌》上，sparsentan 導致足細胞數量、腎小球、血液動力學、細胞功能和組織修復改善，從而減少蛋白尿並保留腎功能。

Most importantly, FDA was a key stakeholder in the PARASOL initiative and through these findings, proteinuria is now expected to be used as a validated surrogate endpoint for full approval in FSGS going forward.

最重要的是，FDA 是 PARASOL 計畫的關鍵利益相關者，透過這些發現，蛋白尿現在有望被用作 FSGS 全面批准的經過驗證的替代終點。

These data were again presented at ASN Kidney Week and were received with enthusiasm and support from the community.

這些數據在 ASN 腎臟週上再次被展示，並受到了社會的熱情和支持。

Overall, we believe that our data from DUET and DUPLEX align very well with the conclusions from the PARASOL group.

總體而言，我們認為 DUET 和 DUPLEX 獲得的數據與 PARASOL 小組的結論非常吻合。

Our next step will be to discuss our data with the FDA to understand their perspective now in the context of the PARASOL work and a potential path forward for an FSGS indication.

我們的下一步將與 FDA 討論我們的數據，以了解他們現在對 PARASOL 工作的看法以及 FSGS 指徵的潛在發展路徑。

As Eric mentioned, we now have a meeting scheduled with the FDA and we're preparing a robust briefing book that will align with the recent PARASOL work to discuss the potential for filing an sNDA for sparsentan and FSGS.

正如 Eric 所提到的，我們現在安排了與 FDA 的會議，我們正在準備一份詳盡的簡報，該簡報將與最近的 PARASOL 工作保持一致，討論為 sparsentan 和 FSGS 提交 sNDA 的可能性。

In parallel, we are preparing the sNDA, so that we will be in a position to move quickly following our FDA interaction.

同時，我們正在準備 sNDA，以便能夠在與 FDA 互動後迅速採取行動。

I'll now briefly touch on pegtibatinase as it remains the only development program that has the potential to be disease modifying for the HCU community who deserves better treatment.

現在我將簡單談談聚乙二醇丁醚酶，因為它仍然是唯一有潛力為值得獲得更好治療的 HCU 社區改變病情的開發項目。

While we recently announced a Voluntary Pause of Enrollment in the Phase 3 HARMONY Study due to necessary commercial scale up process improvements, we continue to have the utmost confidence in the program and in our team's ability to restart enrollment as quickly as possible.

儘管我們最近宣布由於必要的商業擴大流程改進而自願暫停第 3 階段 HARMONY 研究的招募，但我們仍然對該計劃以及我們團隊盡快恢復招募的能力充滿信心。

We are grateful for the continued support of the HCU community and our supply partners.

我們感謝 HCU 社區和我們的供應合作夥伴的持續支持。

Overall, we've made incredible progress with FILSPARI and its path to foundational positioning in IgA nephropathy.

總體而言，我們在 FILSPARI 及其在 IgA 腎病領域的基礎定位方面取得了令人難以置信的進展。

And we look forward to our upcoming regulatory engagement on the potential to deliver sparsentan to patients with FSGS.

我們期待即將開展的監管合作，探討將 Sparsentan 提供給 FSGS 患者的潛力。

Let me now hand the call over to Peter for the commercial update.

現在，讓我將電話交給彼得，請他播報商業更新。

Peter?

彼得？

Thank you, Jula, and good morning, everyone.

謝謝你，朱拉，大家早安。

During the third quarter we continued our strong and focused launch execution of FILSPARI for IgA nephropathy while also preparing to build upon our success with full approval and to draft KDIGO guidelines.

在第三季度，我們繼續強有力且專注地推出用於治療 IgA 腎病的 FILSPARI，同時也準備在獲得全面批准的基礎上再接再厲，並起草 KDIGO 指南。

And I couldn't be more pleased with the strong results driven by our talented and dedicated teams.

我對我們的才華橫溢、敬業奉獻的團隊所取得的出色成績感到非常滿意。

From a demand perspective, we continued our strong growth trajectory and again added more than 500 new patients start forms during the third quarter.

從需求角度來看，我們繼續保持強勁的成長軌跡，並在第三季再次增加了 500 多名新患者。

This is particularly noteworthy given that we encountered some seasonality as is typical during the summer holidays, as well as the fact that we took our field force out of the field for an entire week to train them on the new label after full approval on September 5.

這一點尤其值得注意，因為我們遇到了暑假期間常見的一些季節性因素，而且在 9 月 5 日獲得全面批准後，我們將現場工作人員帶出現場整整一周時間，對他們進行新標籤的培訓。

And I'm very encouraged with the upward inflection in new patient start forms in the weeks following full approval.

我對在獲得全面批准後的幾週內新患者開始數量急劇上升感到非常高興。

As we highlighted prior to approval, we anticipated that demand would increase as physician prescribed FILSPARI to more of their patients and new physicians will write prescriptions for the first time.

正如我們在批准之前所強調的那樣，我們預計需求會增加，因為醫生為更多的患者開出 FILSPARI 並且新醫生會首次開出處方。

And we are seeing clear evidence of this coming through which provides added confidence to our outlook.

我們看到了明顯的證據，這為我們的前景增添了信心。

We also demonstrated continuing efficiencies in our fulfillment process while maintaining high patient compliance and persistency rates.

我們也展示了我們履行流程的持續效率，同時保持了較高的患者依從性和堅持率。

This has resulted in $35.6 million in net product sales of FILSPARI in the third quarter representing more than a 30% gross quarter-over-quarter growth.

這使得 FILSPARI 第三季的淨產品銷售額達到 3,560 萬美元，季增超過 30%。

With our execution, we continue to outperform the most recent rare nephrology launches prior to FILSPARI on all core launch metrics and we are on track to outperform these benchmarks on net revenue in the first full year of launch.

透過我們的執行，我們在所有核心發布指標上繼續超越 FILSPARI 之前最新的罕見腎病學發布，並且我們預計在發布的第一年以淨收入超越這些基準。

We are even more excited about the opportunity ahead of us.

我們對眼前的機會感到更加興奮。

As I outlined during our IgAN full approval call last month, FILSPARI's new label is allowing us to further accelerate FILSPARI's growth trajectory for two reasons.

正如我在上個月的 IgAN 全面批准電話會議上所概述的那樣，FILSPARI 的新標籤使我們能夠進一步加速 FILSPARI 的成長軌跡，原因有二。

One, we can now leverage the full potential of FILSPARI in our physician communication and educational initiatives.

首先，我們現在可以充分利用 FILSPARI 在我們的醫生溝通和教育計劃中的潛力。

This is important because under accelerated approval we were limited in our commercial communication efforts to discussing only proteinuria.

這很重要，因為在加速批准下，我們的商業溝通工作僅限於討論蛋白尿。

But now with full approval in our compelling label, we can discuss how FILSPARI's rapid and sustained proteinuria reduction translates into superior long term kidney function preservation relative to active comparator and maximally dosed irbesartan.

但現在，我們的引人注目的標籤已獲得全面批准，我們可以討論 FILSPARI 的快速和持續蛋白尿減少如何轉化為相對於活性對照藥和最大劑量的厄貝沙坦的優越的長期腎功能保存。

And this kidney preservation benefit accrues year-over-year over the course of the two year measurement period supporting long-term use of FILSPARI and two, the new indication statement supports broader use of FILSPARI in any adult patients with IgA nephropathy who is at risk of progression.

而這種腎臟保護效益在兩年的測量期內逐年累積，支持長期使用 FILSPARI；其次，新的適應症聲明支持在任何有病情進展風險的 IgA 腎病成年患者中更廣泛地使用 FILSPARI。

As a reminder, the full approval significantly expands the eligible patient population beyond the accelerated approval indication statement that guided physicians to generally use FILSPARI only in patients at or above 1.5 gram per gram.

提醒一下，全面批准大大擴大了符合條件的患者群體，超出了加速批准適應症聲明，該聲明指導醫生通常僅對每克 1.5 克或以上的患者使用 FILSPARI。

With our broader indication and the exciting data that was presented at ASN last week showing that patients below 1 gram per gram also benefit from FILSPARI.

我們的適應症更加廣泛，上週在 ASN 上公佈的令人興奮的數據顯示，每克低於 1 克的患者也能從 FILSPARI 中受益。

We are eager to reach these patients who can upgrade their foundational treatments.

我們渴望接觸到這些能夠升級其基礎治療的患者。

These messages resonate well with nephrologists and are representative of what we heard from the broad community of key opinion leaders and community physicians at ASN last week.

這些訊息引起了腎臟病專家的強烈共鳴，代表了我們上週在 ASN 上從廣大關鍵意見領袖和社區醫生那裡聽到的內容。

And as I mentioned earlier, we are very encouraged by the demand uptake we are seeing in the first month post full approval.

正如我之前提到的，我們對全面批准後第一個月內需求的成長感到非常鼓舞。

The recently published draft KDIGO guidelines are already being referenced by nephrologists and expected to build further momentum.

最近發布的 KDIGO 指南草案已被腎臟病專家參考，並有望獲得進一步的發展。

These draft guidelines emphasize the urgency to diagnose and treat patients earlier and more aggressively.

這些指南草案強調了對患者進行更早期、更積極的診斷和治療的迫切性。

More specifically, they call for every IgAN patient who isn't in remission to be treated with a kidney targeted medicine and highlight that FILSPARI is the only medicine to have shown superiority over in trial up titrated RAS inhibition.

更具體地說，他們呼籲對每位未處於緩解期的 IgAN 患者進行針對腎臟的藥物治療，並強調 FILSPARI 是唯一一種在試驗中顯示出優於滴定 RAS 抑制劑的藥物。

Before handing the call over to Chris, let me share an IgAN story that exemplifies why we are so excited about the impact that FILSPARI is having on patients.

在將電話交給克里斯之前，讓我分享一個 IgAN 故事，以說明為什麼我們對 FILSPARI 對患者的影響如此興奮。

His patient recently shared in one of our national broadcasts that he looks forward to taking FILSPARI every morning because he is in complete remission and feeling great.

他的病人最近在我們的一次全國廣播中分享說，他期待每天早上服用 FILSPARI，因為他的病情已經完全緩解並且感覺很好。

He describes receiving his lab results as IgAN to getting an A+ on a school report card.

他描述說，他的實驗室檢查結果為 IgAN，而學校成績單上卻獲得了 A+。

While this is the result of only one patient and may not reflect typical results, we hear similar stories regularly and these are the types of stories that motivate our teams every day.

雖然這只是一名患者的結果，可能不會反映典型的結果，但我們經常聽到類似的故事，這些故事每天都激勵著我們的團隊。

And we know there are so many more people living with IgA nephropathy who can benefit from a treatment that has shown superiority over maximally dosed RAS inhibition and how FILSPARI is convenient once daily oral, kidney targeted and non-immunosuppressive profile provides new hope.

我們知道，有更多患有 IgA 腎病的人可以從這種比最大劑量 RAS 抑制劑更優越的治療中受益，而 FILSPARI 每天口服一次，方便，腎臟靶向和非免疫抑制的特性為人們帶來了新的希望。

With our strong new label, the draft KDIGO guidelines and focused execution, we are confident in our ability to reach these patients, accelerating our growth trajectory and establishing FILSPARI as the foundational treatment option for IgA nephropathy patients.

憑藉我們強大的新標籤、KDIGO 指南草案和專注的執行，我們有信心接觸到這些患者，加速我們的成長軌跡，並將 FILSPARI 確立為 IgA 腎病患者的基礎治療選擇。

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

現在，讓我將電話轉給克里斯，聽聽他的財務更新。

Chris?

克里斯？

Thank you, Peter, and good morning.

謝謝你，彼得，早安。

During the third quarter our execution led to a significant increase in net product sales and disciplined investments in the areas we believe will drive growth.

第三季度，我們的執行力導致淨產品銷售額大幅增加，並在我們認為將推動成長的領域進行了嚴格的投資。

Net product sales for the third quarter of 2024 grew to $61 million, compared to $33.9 million for the same period in 2023.

2024 年第三季的淨產品銷售額成長至 6,100 萬美元，而 2023 年同期為 3,390 萬美元。

This increase of approximately 80% is attributable to strong performance in the ongoing US launch of FILSPARI in IgA nephropathy.

這一約 80% 的成長歸功於美國正在上市的用於治療 IgA 腎病變的 FILSPARI 的強勁表​​現。

During the quarter, we also recognized $1.9 million of license and collaboration revenue which results in $62.9 million in total revenue reported for the period compared to $37.1 million in the same period in 2023.

本季度，我們也確認了 190 萬美元的授權和合作收入，導致本期報告的總收入為 6,290 萬美元，而 2023 年同期為 3,710 萬美元。

Research and development expenses for the third quarter of 2024 were $51.7 million compared to $60.6 million for the same period in 2023.

2024 年第三季的研發費用為 5,170 萬美元，而 2023 年同期為 6,060 萬美元。

On a non-GAAP adjusted basis, R&D expenses were $48.4 million for the third quarter 2024 compared to $53.8 million for the same period in 2023.

以非 GAAP 調整後計算，2024 年第三季的研發費用為 4,840 萬美元，而 2023 年同期為 5,380 萬美元。

Selling general and administrative expenses for the third quarter of 2024 were $65.6 million compared to $67.8 million for the same period in 2023.

2024 年第三季的銷售一般及行政費用為 6,560 萬美元，而 2023 年同期為 6,780 萬美元。

On a non-GAAP adjusted basis, SG&A expenses were $49.7 million for the third quarter of 2024 compared to $51.8 million for the same period in 2023.

以非 GAAP 調整後計算，2024 年第三季的銷售、一般及行政費用為 4,970 萬美元，而 2023 年同期為 5,180 萬美元。

The decline in year-over-year operating expenses is attributable to the restructuring enacted at the end of 2023 and reduced clinical expenses as the sparsentan Phase 3 studies advance towards completion.

同比營業費用的下降歸因於2023年底實施的重組以及隨著Sparsentan第3階段研究接近完成而導致的臨床費用減少。

Importantly, we continue to invest in evidence generation to support FILSPARI in IgA nephropathy and potentially FSGS as well as continue to invest in commercial efforts in IgA nephropathy.

重要的是，我們將繼續投資於證據生成，以支持 FILSPARI 在 IgA 腎病和潛在的 FSGS 中的應用，並繼續投資於 IgA 腎病的商業化努力。

Now with full approval and draft KDIGO guidelines in hand.

目前已獲得全面批准並收到 KDIGO 指南草案。

Total other income net for the third quarter of 2024 was $1.3 million compared to $3.4 million in the same period in 2023.

2024 年第三季的其他淨收入總額為 130 萬美元，而 2023 年同期為 340 萬美元。

The difference is largely attributable to a decrease in interest income.

差異主要歸因於利息收入的減少。

Net loss including from discontinued operations from the third quarter of 2024 was $54.8 million or $0.70 per basic share compared to a net income of $150.7 million or $1.97 per basic share for the same period in 2023.

2024 年第三季（包括停止營運）的淨虧損為 5,480 萬美元或每股基本虧損 0.70 美元，而 2023 年同期的淨收入為 1.507 億美元或每股基本虧損 1.97 美元。

On non-GAAP adjusted basis, net loss including from discontinued operations for the third quarter of 2024 was $35.6 million or $0.46 per basic share compared to net income of $173.5 million or $2.27 per basic share for the same period in 2023.

在非 GAAP 調整後基礎上，2024 年第三季（包括停止經營在內的）淨虧損為 3,560 萬美元或每股基本虧損 0.46 美元，而 2023 年同期的淨收入為 1.735 億美元或每股基本虧損 2.27 美元。

The difference is largely attributable to a gain related to the sale of the bile acid product which was recorded in the third quarter of 2023.

差異主要歸因於 2023 年第三季記錄的膽汁酸產品銷售相關收益。

As of September 30, 2024, the company, cash equivalents and marketable securities of $277.4 million, with continued growth in FILSPARI sales, measured investments including shifting some of our investments and pegtibatinase beyond 2025, we continue to expect our cash used to decline over time.

截至 2024 年 9 月 30 日，公司現金等價物和有價證券為 2.774 億美元，隨著 FILSPARI 銷售額的持續增長、衡量投資（包括將我們的部分投資和 pegtibatinase 轉移到 2025 年以後），我們繼續預計我們的現金使用量將時間的推移而減少。

We also anticipate multiple incoming milestone payments from CSL Vifor upon conversion of FILSPARI to full approval in Europe and market access achievements.

我們也預計，在 FILSPARI 獲得歐洲全面批准並實現市場准入後，CSL Vifor 將支付多筆里程碑款項。

All of which continues to position our balance sheet to support current operations into 2028.

所有這些都將繼續使我們的資產負債表能夠支援到2028年的當前營運。

I'll end with one administrative note.

最後我想說一句行政方面的說明。

Alongside the filing of our 10-Q today, we're also filing a new ATM agreement with the SEC.

除了今天提交的 10-Q 表之外，我們還將向美國證券交易委員會提交新的 ATM 協議。

This is a housekeeping measure as our previous ATM which had been in place since 2020, did not transfer over to the new shelf registration that was filed in August.

這是一項管理措施，因為我們先前的 ATM 自 2020 年起就已投入使用，但並未轉移到 8 月提交的新擱置登記。

With that, I'll now turn it over to Eric for his closing comments.

現在，我將把時間交給 Eric 來做結束語。

Eric?

埃里克？

Thank you, Chris.

謝謝你，克里斯。

I could not be prouder of the execution and performance of our organization.

我對我們組織的執行力和表現感到無比自豪。

The underlying dynamics of our FILSPARI launch are strong and have created positive momentum for growth moving forward as a foundational therapy in IgAN.

我們推出的 FILSPARI 的潛在動力非常強勁，並為其作為 IgAN 的基礎療法向前發展創造了積極的勢頭。

As our near-term opportunities for growth in 2025 and beyond hold great promise for the rare kidney community.

因為我們在 2025 年及以後的近期成長機會為罕見腎臟病領域帶來了巨大的希望。

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

現在，讓我將電話轉給 Nivi 進行問答。

Nivi?

尼維？

Thank you, Eric.

謝謝你，埃里克。

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

接線員，我們現在可以開通問答熱線。

(Operator Instructions) Joseph Schwartz, Leerink Partners.

(操作員指示) Joseph Schwartz，Leerink Partners。

This is Will on for Joe today.

今天由威爾代替喬主持。

Congrats on the great quarter here.

恭喜您本季的優異成績。

So just one for us on PSF metrics.

關於 PSF 指標，我們只提一個。

We saw that very minor dip in numbers between the second and third quarter.

我們發現第二季和第三季之間的數字出現了輕微的下降。

And as Peter mentioned, it seems like this could be chalked up to summer seasonality and taking the sales force out for a week in September.

正如彼得所提到的，這似乎可以歸咎於夏季季節性因素以及九月份銷售人員外出一周的時間。

But are there other dynamics here that we should appreciate?

但這裡還有其他值得我們關注的動態嗎？

And how have things been trending now early in the fourth quarter?

目前第四季初的情況如何？

Any additional color here would be helpful.

這裡的任何附加顏色都會有幫助。

Thanks, Will.

謝謝，威爾。

Well, let me first say that I am incredibly impressed with what we've seen and I'll ask Peter to talk about the dynamics, particularly what we've seen since full approval.

好吧，首先讓我說，我對我們所看到的情況印象深刻，我會請彼得談談動態，特別是自完全批准以來我們所看到的情況。

Peter?

彼得？

Yes.

是的。

Thanks, Eric, and thanks, Will for the question.

謝謝 Eric，也謝謝 Will 提出這個問題。

Let me start to say that I'm really pleased how we have continued our growth trajectory during the accelerated approval period and how we have outperformed recent rare nephrology benchmarks.

首先我要說的是，我很高興我們在加速審批期間繼續保持增長軌跡，並超越了近期罕見腎臟病學基準。

To the point in what I mentioned in the prepared remarks, in Q3 we saw some typical summer seasonality and we also took the teams out of the field for a week for training for full approval.

正如我在準備好的發言中提到的那樣，在第三季度，我們看到了一些典型的夏季季節性，我們也讓球隊離開賽場進行為期一周的訓練以獲得全面批准。

So I'm actually really pleased with a continuation of strong growth over 500 patient start forums.

因此，我真的很高興看到 500 多個患者啟動論壇繼續保持強勁成長。

But I'm mostly excited about the opportunity ahead of us and how we will accelerate momentum based on the full approval.

但最讓我興奮的是我們面臨的機遇，以及我們將如何在獲得全面批准的基礎上加速發展勢頭。

And to what I said in the prepared remark, the demand uptake we are seeing in the first month after full approval is really encouraging and allows us to end the year strongly.

正如我在準備好的演講中所說的那樣，我們在全面批准後的第一個月看到的需求增長確實令人鼓舞，並使我們能夠強勁地結束這一年。

Vamil Divan, Guggenheim Securities.

古根漢證券的 Vamil Divan。

It's Arseniy for Vamil.

瓦米爾 (Vamil) 的名字是阿爾謝尼 (Arseniy)。

Congrats on all your progress and thank you for taking our questions.

恭喜您所取得的所有進步，並感謝您回答我們的問題。

In regard to PARASOL recommendations and FSGS, how much do you feel the discussions with the FDA will focus on hitting specific proteinuria's thresholds at certain time points?

關於 PARASOL 建議和 FSGS，您認為與 FDA 的討論在多大程度上會集中在達到特定時間點的特定蛋白尿閾值？

And perhaps reanalyzing the data that way versus considering the totality of data more holistically and focusing more on the mechanistic rationale and the biological visibility argument?

或許以這種方式重新分析數據，而不是更全面地考慮全部數據並更多地關注機械原理和生物可見性論點？

Great.

偉大的。

Thank you so much for the question.

非常感謝您的提問。

Bill, I'll turn that over to you.

比爾，我將把這個交給你。

Yes.

是的。

Thank you for the question, and I think it's a good one.

感謝您的提問，我認為這是一個很好的問題。

I think you hit on the elements of what's important.

我認為你已經抓住了重要的要素。

Certainly based on PARASOL, the agency has said publicly that proteinuria can be used as a validated surrogate for full approval in FSGS, but the agency will always look at the full data in the submission.

當然，基於 PARASOL，該機構已公開表示蛋白尿可作為 FSGS 完全批准的有效替代品，但該機構將始終查看提交的完整數據。

So totality is important in parallel with hitting proteinuria targets.

因此，整體水平與達到蛋白尿目標同樣重要。

And I think additionally, as you noted, the biologic plausibility is key to the entire story, that your reduction in proteinuria in the case of sparsentan is due to the biology and the pathology of FSGS.

此外，我認為，正如您所指出的，生物學上的合理性是整個故事的關鍵，在 Sparsentan 病例中蛋白尿的減少是由於 FSGS 的生物學和病理學。

It's a podocyte driven disease and the only way you can reduce proteinuria is to make that cell healthier and sparsentan achieves that.

這是一種由足細胞驅動的疾病，減少蛋白尿的唯一方法是使該細胞更健康，而 Sparsentan 可以實現這一點。

We have clinical data, we have preclinical data that support that.

我們有臨床數據，有臨床前數據支持這一點。

So all-in-all, you hit on three very key elements of this mission and I don't know how they will weight them, but we're confident that we have very strong data across that whole space.

總而言之，你觸及了這次任務的三個關鍵要素，我不知道他們會如何權衡它們，但我們相信我們擁有整個領域非常強大的數據。

Yes.

是的。

Thank you, Bill.

謝謝你，比爾。

The only thing that I would add is that's the opportunity that we have to speak with Evan and why we're eager to meet with them here soon to be able to understand what specifically information do they want.

我唯一想補充的是，這是我們與埃文交談的機會，也是我們渴望盡快與他們會面的原因，以便了解他們具體想要什麼資訊。

That said, as we take a step back, we're very confident in the data that we generated in our programs.

話雖如此，當我們退一步考慮時，我們對我們在程式中產生的數據非常有信心。

Anupam Rama, JPMorgan.

摩根大通的 Anupam Rama。

Congrats on all the progress at ASN and in the quarter.

恭喜 ASN 和本季取得的所有進展。

Can you give us a sense of the scope of the additional data you've provided on liver monitoring sort of beyond the clinical experience?

您能否向我們介紹除了臨床經驗之外，您在肝臟監測方面提供的額外數據的範圍？

I'm assuming that package includes all of the data from FSGS and IgAN again, clinical trial work, but correct me if I'm wrong there?

我假設該包中包含了來自 FSGS 和 IgAN 的所有數據以及臨床試驗工作，但如果我錯了，請糾正我？

Anupam.

阿努帕姆。

So Bill, why don't you take that question as well?

那麼比爾，你為什麼不也回答這個問題呢？

Yes.

是的。

Thanks for the question.

謝謝你的提問。

It does.

是的。

Your supposition is accurate.

你的假設是正確的。

We pulled the data from the ongoing clinical trials, the open label extensions for both DUET, DUPLEX and PROTECT.

我們從正在進行的臨床試驗、DUET、DUPLEX 和 PROTECT 的開放標籤擴展中提取了數據。

So that's an increasing body of data as well as the data that we're gaining from all of the commercial experience.

因此，這是我們從所有商業經驗中獲得的數據以及不斷增加的數據。

So we have a substantial body of data and all of that was pooled.

因此，我們擁有大量的數據，而這些數據都被匯總起來了。

Importantly, what we've seen is in both the trial extensions as well as in the real world, the commercial experience, we see the same thing that we saw in the trials that low levels of LFT elevation and no evidence of Hy's Law, or liver failure events or liver injury.

重要的是，我們在試驗擴展和現實世界的商業經驗中都看到了與試驗中相同的情況，即肝功能不全升高水平較低，沒有海氏定律、肝衰竭事件或肝損傷的證據。

So having that consistent story with a much larger body of evidence was the basis on which we built our submission to go back and change the REMS frequency to match that, that hits the cadence that patients see their nephrologists on a quarterly basis.

因此，擁有一致的故事和大量的證據是我們提出提案的基礎，我們回去修改 REMS 頻率以匹配該頻率，從而達到患者每季度看腎病科醫生的節奏。

Tyler Van Buren, TD Cowen.

泰勒·範布倫（Tyler Van Buren），TD Cowen。

This is Greg Wiesner on for Tyler from TD Cowen.

這是 TD Cowen 的 Tyler 的 Greg Wiesner。

I'm curious to get some insight on what you will propose during the Type C meeting and what are the key questions you would need to ask of the FDA?

我很好奇您會在 C 類會議期間提出什麼建議，以及您需要向 FDA 提出哪些關鍵問題？

Great.

偉大的。

Thanks so much for the question, Greg.

非常感謝你提問，格雷格。

Bill, back to you.

比爾，回到你身邊。

Yes.

是的。

Well, I think we leverage the discussions that have been had at PARASOL where the agency has suggested a threshold of proteinuria reduction so that you have a treatment effect for both the control and the treatment arm, sparsentan versus irbesartan in our case, they haven't suggested or they haven't nailed down a specific endpoint.

好吧，我認為我們可以利用 PARASOL 上的討論，該機構在該討論中提出了蛋白尿減少的閾值，這樣對照組和治療組都能獲得治療效果，在我們的案例中，Sparsentan 與厄貝沙坦的比較，他們沒有建議或沒有確定具體的終點。

What they've said is you need to make a proposal and come in and talk to us.

他們說你需要提出一個建議然後來和我們談談。

But with their presentation, they have spoken the most about the value of 0.7 gram per gram per day, patients that get below that.

但在演講中，他們最多談論的是每天每克 0.7 克的價值，低於這個水平的患者。

So they think that's a reasonable spot to think about when you picture what will go in and propose to the agency.

因此，他們認為，當你設想將要採取什麼措施並向機構提出建議時，這是一個值得考慮的合理點。

And the question really is, here's our proposal, here's how we're going to analyze the data.

真正的問題是，這是我們的建議，這是我們分析數據的方法。

What else do you need to see in the submission so that we're aligned with the agency and we make sure our filing has everything in it that they need for their review.

您還需要在提交的文件中看到什麼，以便我們與機構保持一致，並確保我們的文件包含他們審查所需的所有內容。

Maurie Raycroft, Jefferies.

莫里·雷克羅夫特（Maurie Raycroft），傑富瑞（Jefferies）。

This is Farzin on for Maurie.

這是 Farzin 代替 Maurie 上場。

Congrats on the progress as well.

也祝賀你所取得的進步。

Following up on the FSGS Type C meeting, are you going to include any data from the open label extension?

在 FSGS C 型會議之後，您會包含任何來自開放標籤擴充功能的資料嗎？

And then do you also on the post hoc analysis, like what would be considered like sufficient?

然後，您是否也進行事後分析，例如什麼才算是充分的？

Like is the pre-specified data already good enough or any post hoc work would be needed?

例如，預先指定的資料是否已經夠好或是否需要任何事後工作？

Okay, thanks so much, Farzin for the question.

好的，非常感謝 Farzin 提出這個問題。

Bill?

帳單？

Yes.

是的。

Well the short answer for the open label extension data is yes.

那麼對於開放標籤擴展數據來說，簡短的回答是肯定的。

That will be included from both the ongoing DUET, open label as well as DUPLEX from both studies.

這將包括正在進行的 DUET、開放標籤以及兩項研究的 DUPLEX。

As far as post-hoc analysis, we have threshold proteinuria cut points that were pre-specified and we looked at those as part of the statistical analysis plan and looked at in addition to FPRE or the modified partial remission, we looked at 1.5 gram per gram,

就事後分析而言，我們有預先指定的蛋白尿閾值截點，我們將其作為統計分析計劃的一部分進行研究，除了 FPRE 或改良部分緩解外，我們還研究了 1.5 克/克，

1.5 and [.3].

1.5 和 [.3].

The agents -- so that brackets around the target that the agency has seemed to align around.

代理商——這樣機構圍繞的目標就被括起來了。

We're not doing a lot of post-hoc analysis ahead of that meeting.

在那次會議之前我們不會做大量的事後分析。

So we will go in with the data that we have and work with them on what additional analyses they want to see in that submission and get that aligned so that we have in the file everything they need to complete their review.

因此，我們將根據我們擁有的數據，與他們一起研究他們希望在提交的內容中看到哪些額外分析，並進行協調，以便我們在文件中包含完成審查所需的一切。

Yes.

是的。

Thank you, Bill.

謝謝你，比爾。

And I'll point you all to our corporate presentation which is posted on our website.

我會向大家介紹我們網站上發布的公司介紹。

If you look at slide 29, you can see very nicely laid out the treatment effect across those different pre-specified thresholds, clearly showing a benefit and superiority for sparsentan over irbesartan and FSGS.

如果您看投影片 29，您可以非常清楚地看到在不同的預定閾值上治療效果的佈局，清楚地顯示了 Sparsentan 相對於厄貝沙坦和 FSGS 的益處和優越性。

Thanks, Bill.

謝謝，比爾。

Greg Harrison, Scotiabank.

加拿大豐業銀行的格雷格·哈里森。

Congrats on the quarter.

恭喜本季取得佳績。

This is Joe Thomas on for Greg, just one kind of on the patient and physician education front, can you maybe comment on any ongoing efforts or opportunities you might have to help patients be getting diagnosed earlier and treated earlier based on the recent KDIGO draft guideline update?

我是 Greg 的 Joe Thomas，我只想就患者和醫生教育方面的問題發表看法，您能否根據最近的 KDIGO 指南草案更新，談談您正在做出哪些努力或提供哪些機會來幫助患者儘早得到診斷和治療？

Thanks, Joe. Peter?

謝謝，喬。彼得？

Yes, I think the presentation that Jula mentioned earlier in the prepared remarks tells about the benefit that FILSPARI has also with patients with lower proteinuria levels.

是的，我認為 Jula 在先前準備好的發言中提到的介紹說明了 FILSPARI 對蛋白尿水平較低的患者也有益處。

And I think what I'm hearing from physicians, especially coming back from ASN, where we had many conversations with thought leaders as well as community physicians, is there is like a higher urgency and a call to action to treat patients earlier and more aggressively.

我認為我從醫生那裡聽到的，特別是從 ASN 回來後聽到的，我們與思想領袖以及社區醫生進行了多次對話，他們表示，情況更加緊迫，需要採取行動，儘早、更積極地治療患者。

And I think KDIGO really helps there.

我認為 KDIGO 確實提供了幫助。

And I think we have the data now also in hand to show that FILSPARI acts consistently across different patient populations.

我認為我們現在掌握的數據也顯示 FILSPARI 在不同患者群體中的作用一致。

Jason Zemansky, Bank of America.

美國銀行的傑森·澤曼斯基（Jason Zemansky）。

This is [Dina Ramedi] on for Jason Zemansky, Congrats on the progress this quarter, and thank you for taking our question.

我是 Jason Zemansky 的 [Dina Ramedi]，恭喜您本季的進展，感謝您回答我們的問題。

Though it might be a little bit too premature to speak to FILSPARI's upside in FSGS.

不過，現在談論 FILSPARI 在 FSGS 方面的優勢可能還為時過早。

Could you discuss what the broader opportunity might look like?

您能討論一下更廣泛的機會是什麼樣的嗎？

Is this something you anticipate needing to build the market, or do you think dynamics are likely to quickly shift?

您是否預期這是建立市場所需要的？ 或者您認為動態可能會迅速改變？

And maybe what sort of challenges is, is a new entrant likely to face given the lack of approved therapies, especially given the potential shift in trial endpoints?

那麼，在缺乏核准療法的情況下，尤其是考慮到試驗終點的潛在轉變，新進入者可能面臨什麼樣的挑戰呢？

Thanks, Dina, for the question.

謝謝 Dina 提出這個問題。

Peter, why don't I turn that over to you and then Jula, if there's anything further that you'd like to add on how physicians are thinking about FSGS.

彼得，我把這個交給你吧，然後朱拉，如果你想補充一點關於醫生如何看待 FSGS 的內容的話。

Peter?

彼得？

Yes.

是的。

Thanks, Dina.

謝謝，黛娜。

Well, we are really excited about the opportunity for FSGS.

嗯，我們對 FSGS 的機會感到非常興奮。

In the US in particular, the market may be slightly smaller than IgA nephropathy.

特別是在美國，市場規模可能比 IgA 腎病市場規模略小。

We anticipate about 15,000 to 30,000 patients as directly addressable for FILSPARI.

我們預計約有 15,000 至 30,000 名患者可直接接受 FILSPARI 治療。

But to the point you're making, this is a patient population that is served by basically the same prescriber group as we have for IgA nephropathy.

但正如您所說，這群患者基本上與我們為 IgA 腎病患者提供的處方相同。

So it's basically the same call point.

因此，這基本上是相同的呼叫點。

And if we would get like a full approval, I am expecting that we will have a rapid uptake since the brand name of FILSPARI is so well established as well as the clinical profile.

如果我們獲得全面批准，我預計我們將獲得迅速的推廣，因為 FILSPARI 的品牌名稱和臨床特徵已經非常完善。

And many of the physicians have already the experience with FILSPARI in IgA nephropathy and they have seen the rapid and sustained proteinuria benefit in their patients.

許多醫生已經有使用 FILSPARI 治療 IgA 腎病的經驗，並且看到患者在蛋白尿方面獲得快速且持續的改善。

So I think the opportunity is real and we are really excited about it.

因此我認為這個機會是真實存在的，我們對此感到非常興奮。

And as I said, we have a strong position that we can build upon.

正如我所說的，我們擁有強大的優勢，我們可以繼續發展。

And let me just add that remember, well, FSGS is a patient population with a really high unmet need.

我還要補充一點，請記住，FSGS 是一個有著大量未滿足需求的患者群體。

They have symptomatic disease, they might wake up one day, be very swollen and there's really almost nothing that is effective and safe for these patients.

他們有症狀性疾病，可能某一天醒來，發現自己腫脹得很厲害，而且對這些患者來說，幾乎沒有任何有效且安全的治療方法。

They get treated with immunosuppressants and if they have genetic disease that doesn't work for them.

他們會接受免疫抑制劑治療，但如果他們患有遺傳疾病，那麼這種治療對他們不起作用。

So there is a high unmet need particularly for non-immunosuppressive therapy that can reduce their proteinuria and help their symptomatology as well.

因此，對於非免疫抑制療法存在著很大的未滿足需求，這種療法可以減少蛋白尿並有助於緩解症狀。

So to Peter's point, it's the same physicians who are treating IgAN and FSGS.

所以正如彼得所說，治療 IgAN 和 FSGS 的是相同的醫生。

So we do believe that there is a significant unmet need here that we can address with FILSPARI.

因此，我們確實相信，這裡存在著一個尚未滿足的重大需求，我們可以透過 FILSPARI 來解決。

Dina, thanks so much for the question.

黛娜，非常感謝你提問。

And certainly we recognize that there's additional education and outreach but as, as you would have heard from Julie and Peter, there's a high recognition and certainly brand awareness.

當然，我們認識到還有額外的教育和推廣，但正如你從朱莉和彼得那裡聽到的，人們的認可度很高，而且品牌知名度也很高。

We expect to be first if approved and certainly the leader and the new standard of care within FSGS.

如果獲得批准，我們希望成為第一個，並且肯定能成為 FSGS 領域的領導者和新的治療標準。

So more to come there, but certainly a tremendous opportunity for us to serve this community.

因此還有更多的事要做，但這對我們為這個社區服務無疑是一個絕佳的機會。

Laura Chico, Wedbush Securities.

勞拉‧奇科（Laura Chico），韋德布希證券公司。

I had one on FSGS.

我有一個關於 FSGS 的問題。

There was some commentary at the PARASOL meeting earlier this month and just coming out of ASN now, I'm wondering if you have any thoughts on whether groups like KDIGO would consider making an update to FSGS treatment guidelines in response to the observational data that PARASOL presented.

本月早些時候的 PARASOL 會議上有一些評論，現在 ASN 剛剛發布了一些評論，我想知道您是否認為像 KDIGO 這樣的組織是否會考慮根據 PARASOL 提供的觀察數據對 FSGS 治療指南進行更新。

Thanks, Laura.

謝謝，勞拉。

Jula, I'll turn that one over to you.

朱拉，我會把這個交給你。

Well, it's certainly potential.

嗯，這確實是有潛力的。

They typically do update if there's new treatment or there's change in where we want to target the thresholds for.

如果有新的治療方法或我們想要設定的閾值發生變化，他們通常會進行更新。

There was just recently an update to those guidelines, but I would anticipate if we get full approval for sparsentan and FSGS, then that would be an appropriate time for them to make an update.

這些指南最近剛剛更新，但我預計，如果我們獲得對 sparsentan 和 FSGS 的全面批准，那麼這將是他們進行更新的適當時機。

Yigal Nochomovitz, Citi.

花旗的 Yigal Nochomovitz。

This is [Rina] on for Yigal.

這是 Yigal 的 [Rina]。

Thanks for taking my question.

感謝您回答我的問題。

I just wanted to ask if you could comment on any compliance or adherence metrics for FILSPARI with regard to the monthly REMS monitoring, and how you might expect this rate of compliance to change with the reduction in frequency for the liver monitoring?

我只是想問一下，您是否可以對 FILSPARI 就每月 REMS 監測方面的任何合規性或依從性指標進行評論，以及您預計隨著肝臟監測頻率的降低，這種合規率將如何變化？

Thank you, Reena.

謝謝你，Reena。

Peter, I'll turn that over to you.

彼得，我將把這個交給你。

Yes, thanks for the question.

是的，謝謝你的提問。

What we are seeing is that the compliance as well as the persistency rates of FILSPARI are really high.

我們看到的是，FILSPARI 的依從性和持久性率非常高。

And I think that speaks to that patients experience that this product works for them.

我認為這說明患者體驗到該產品對他們有效。

This is a patient population that historically has seen very little innovation.

從歷史上看，這個患者群體很少見到創新。

Many of the patients, every time they see their physicians, they hear you're not yet to the targets.

許多病人每次見到醫生，都會聽到你尚未達到目標。

And for the first time with FILSPARI, they are actually reaching targets.

並且，透過 FILSPARI，他們首次真正達到了目標。

And some of those patients are in full remission, which is really encouraging for patients.

其中一些患者的病情已完全緩解，這對患者來說確實是令人鼓舞的。

And I think that's also the explanation for the high compliance and the persistency rates.

我認為這也是高依從性和持續性率的原因。

Yes.

是的。

We would expect certainly that with not just the lab values but also the support and the education that these patients have, including as part of the REMS.

我們當然期望，這些患者不僅能獲得實驗室數值，還能獲得支持和教育，包括作為 REMS 的一部分。

We'd be very thoughtful around if there is a modification to less frequent monitoring that we would ensure that these patients still have the right level of support and engagement from us and from their clinicians.

如果對較低頻率的監測進行修改，我們會非常認真地考慮，以確保這些患者仍然能得到我們和他們的臨床醫生的適當程度的支持和參與。

Mohit Bansal, Wells Fargo.

富國銀行的莫希特·班薩爾 (Mohit Bansal)。

This is Sadia Rahman on for Mohit.

這是 Sadia Rahman，代替 Mohit 上場。

So a question on the IgAN launch, given the KDIGO update recommending lower targeted proteinuria levels.

因此，鑑於 KDIGO 更新建議降低目標蛋白尿水平，關於 IgAN 的推出存在一個問題。

Wondering if you're seeing that payers are willing to reimburse for patients that start below 1 gram.

想知道您是否看到付款人願意為​​起始劑量低於 1 克的患者報銷費用。

Given that your trial enrolled patients that were above that, has there been any resistance there from payers?

鑑於您的試驗招募的患者數量超過了這個數字，付款人是否遇到了任何阻力？

Thanks for the question, Peter.

謝謝你的提問，彼得。

I'll turn that over to you.

我會把這個交給你。

And might also be helpful to talk about how these patients are at risk based on the radar data to frame.

根據雷達數據來討論這些患者面臨的風險也可能會有所幫助。

Peter, go ahead.

彼得，說吧。

Yes, maybe Eric, to the last point, maybe it's good to start at, like patients -- according to the radar registry data set, patients reach even 0.5 gram per gram of proteinuria There is still like a 22% chance that they progress to dialysis or kidney failure by within 10 years.

是的，也許 Eric，對於最後一點，也許從患者開始是個好主意——根據雷達登記數據集，患者即使達到每克蛋白尿 0.5 克，在 10 年內發展為透析或腎衰竭的可能性仍然有 22%。

So this is a progressive disease.

這是一種進行性疾病。

Payers are also recognizing the progressive nature of the disease and we have invested quite a bit in education for payers as well on this aspect.

付款人也認識到這種疾病的漸進性，我們在這方面對付款人的教育也投入了相當多的資金。

On your specific question with regards to like how quickly are payers adopting new guidelines as well as our new label?

關於您提出的具體問題，例如付款人採用新指南以及我們的新標籤的速度有多快？

Well, we have an active account team that is focusing on this.

嗯，我們有一個活躍的客戶團隊專注於此事。

I'm really pleased with the progress we are making with payers.

我對我們與付款人所取得的進展感到非常高興。

Some of the authorization criteria are already being updated but the majority, that's the reality is early in the year, early in 2025.

一些授權標準已在更新，但大多數，也就是實際情況是在年初，即 2025 年初。

But we're seeing good uptake and we also start to see that patients with lower proteinuria levels are being treated with FILSPARI.

但我們看到了良好的接受度，我們也開始看到蛋白尿水平較低的患者正在接受 FILSPARI 治療。

Alex Thompson, Stifel.

亞歷克斯·湯普森（Alex Thompson），Stifel。

This is Charles Ndiaye on for Alex.

查爾斯·恩迪亞耶 (Charles Ndiaye) 代替亞歷克斯 (Alex) 上場。

Congrats on all the progress this quarter.

恭喜本季取得的所有進展。

I guess from our end just wanted to ask about your current expectations for LOE in IgAN and how you see those changing in the near future?

我想我們只是想問一下您目前對 IgAN 中 LOE 的預期以及您認為在不久的將來這些預期將如何變化？

Sure.

當然。

Thanks, Charles for the question.

謝謝查爾斯提出這個問題。

So our current planning assumption for LOE with sparsentan is into 2033.

因此，我們目前對使用 sparsentan 的 LOE 的規劃假設是到 2033 年。

We were very pleased to announce that we have an additional term for orphan drug exclusivity that was associated with the full approval in IgAN that would take us to September 31.

我們非常高興地宣布，我們獲得了與 IgAN 的全面批准相關的孤兒藥獨佔權的額外期限，該期限將持續到 9 月 31 日。

Sorry, September of 2031.

抱歉，2031年9月。

So we are very pleased to have both of those layers of protection.

因此，我們很高興擁有這兩層保護。

But our current base assumption is into 2033.

但我們目前的基本假設是到 2033 年。

Vamil Divan, Guggenheim Securities.

古根漢證券的 Vamil Divan。

It's Arseniy on for Vamil.

阿爾謝尼 (Arseniy) 替換瓦米爾 (Vamil)。

In regards to FILSPARI's IgAN launch, could you comment on your feel for the uptake with community based nephrologists versus academic thought leaders now versus when you first launched?

關於 FILSPARI 的 IgAN 推出，您能否評論一下現在與首次推出時相比，社區腎臟病專家和學術思想領袖的接受程度如何？

In other words, do you feel that your message is getting out to a broader group of nephrologists now?

換句話說，您是否覺得您的訊息現在已經傳達給了更廣泛的腎臟科專家？

Arseniy, thanks for the question, Peter.

Arseniy，謝謝你的提問，Peter。

I'll turn that over to you.

我會把這個交給你。

Let me rephrase the question.

讓我重新表達一下這個問題。

I think the question is like, what is the uptake that you're seeing with thought leaders, academia, relatives to the community, physicians.

我認為問題在於，思想領袖、學術界、社區親屬和醫生對此有何看法。

So what we have here is, and I think it's good to -- go ahead.

所以我們現在擁有的是，而且我認為很好 - 繼續吧。

And essentially how that changed now on the full approval versus when you first launched.

與您首次推出時相比，現在的全面批准基本上發生了怎樣的變化。

Yes, how that changed?

是啊，那是怎麼改變的？

It's early days.

現在還為時過早。

I mean we are now four or five weeks post full approval.

我的意思是我們現在距離完全批准已經過了四到五週的時間。

But I can give you like a broader sense on how uptake has been for FILSPARI so far.

但我可以更廣泛地向您介紹迄今為止 FILSPARI 的接受程度。

And I think it's good to realize also that you have to get a broad net to reach all the patients.

我也認為，認識到這一點是件好事，你必須要廣泛地普及醫護人員才能涵蓋所有病人。

And what we have said is we are planning to reach about 6,000 nephrologists out of an universe of about 10,000 nephrologists in the US to be able to get to about 85% of the patient population.

我們計劃在美國約 10,000 名腎病專家中接觸約 6,000 名腎病專家，以便能夠涵蓋約 85％ 的患者群體。

So the majority of those patients are residing in the community.

因此，大多數患者都居住在社區中。

And that's what we also see in the prescription patterns that the majority comes from the community.

我們在處方模式中也看到，大多數處方來自社區。

Having said that, I'm really encouraged with the strong feedback that we get from academia and thought leaders about the profile of FILSPARI and in particular where FILSPARI is being positioned.

話雖如此，學術界和思想領袖對 FILSPARI 的形像以及特別是 FILSPARI 的定位給予了強烈的回饋，這確實令我感到鼓舞。

I think the recent KDIGO guidelines really outlining that you have to target the kidney as well as the immune system really resonates with physician.

我認為最近的 KDIGO 指南確實概述了您必須針對腎臟和免疫系統，這確實引起了醫生的共鳴。

And what I'm hearing is that physicians really feel that FILSPARI is well positioned to be that foundational care targeting the kidney with a broad utility for a broad patient population.

我聽到的是，醫生確實認為 FILSPARI 非常適合成為針對腎臟的基礎治療，並且對廣大患者群體具有廣泛的用途。

So hopefully that answers your question.

希望這能回答你的問題。

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call.

女士們、先生們，今天電話會議的問答環節到此結束。

I'll now hand the call back over to Nivi.

我現在將電話轉回給 Nivi。

Great.

偉大的。

Thank you, everyone, for joining us for our third quarter 2024 financial results call.

感謝大家參加我們的 2024 年第三季財務業績電話會議。

We look forward to providing additional updates on our progress.

我們期待提供有關我們進展的更多更新。

Have a great rest of your day.

祝您今天剩餘的時間過得愉快。

This concludes today's call.

今天的電話會議到此結束。

Thank you for your participation.

感謝您的參與。

You may now disconnect.

您現在可以斷開連線。