Travere Therapeutics Inc (TVTX) 2022 Q4 法說會逐字稿

Good day, and welcome to the Travere Therapeutics Fourth Quarter and Full Year 2022 Financial Results and Corporate Update. Today's conference call is being recorded.

美好的一天，歡迎來到 Travere Therapeutics 第四季度和 2022 年全年財務業績和公司更新。今天的電話會議正在錄製中。

At this time, I would like to turn the conference call over to the Vice President of Investor Relations, Naomi Eichenbaum. Please go ahead, Naomi. Thank you.

此時，我想將電話會議轉交給投資者關係副總裁 Naomi Eichenbaum。請繼續，內奧米。謝謝。

Thank you, Rachel. Good afternoon, and welcome to Travere Therapeutics' Fourth Quarter and Full Year 2022 Financial Results and Corporate Update Call. Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. 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, Senior Vice President of Research and Development, will join us for the Q&A session.

謝謝你，雷切爾。下午好，歡迎來到 Travere Therapeutics 的第四季度和 2022 年全年財務業績和公司更新電話會議。謝謝大家加入我們。今天的電話會議將由我們的首席執行官 Eric Dube 博士主持。我們的首席醫療官 Jula Inrig 博士將與 Eric 一起發表準備好的講話；我們的首席商務官 Peter Heerma；和我們的首席財務官 Chris Cline。研發高級副總裁 Bill Rote 博士將加入我們的問答環節。

Before we begin, I would 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.

在我們開始之前，我想提醒大家，在本次電話會議中就非歷史事實的事項所做的陳述是 1995 年《私人證券訴訟改革法案》安全港條款內的前瞻性陳述。前瞻性陳述不是保證性能。它們涉及已知和未知的風險、不確定性和假設，這些風險、不確定性和假設可能導致實際結果、業績和成就與聲明中明示或暗示的結果、業績和成就存在重大差異。

Please see the forward-looking statement disclaimers on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K with the SEC.

請參閱公司今天早些時候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 和 10-K 表格中的風險因素部分。

In addition, any forward-looking statements represent our views as of only the date such statements are made, February 23, 2023, 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此類陳述作出之日（即 2023 年 2 月 23 日）的觀點，並且 Travere 特別聲明不承擔任何更新此類陳述以反映未來信息、事件或情況的義務。

During today's call, we will be covering certain financial results for the quarter and for the year ended December 31, 2022, including certain non-GAAP financial results. Please refer to the company's press release issued earlier today again, among other things, a reconciliation of the differences between the non-GAAP financial results and the most direct comparable GAAP financial results. You can access the press release on our website at travere.com.

在今天的電話會議中，我們將介紹截至 2022 年 12 月 31 日的季度和年度的某些財務業績，包括某些非 GAAP 財務業績。請再次參閱公司今天早些時候發布的新聞稿，其中包括對非 GAAP 財務業績與最直接可比的 GAAP 財務業績之間差異的調節。您可以在我們的網站 travere.com 上訪問新聞稿。

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

有了這個，讓我把電話轉給埃里克。埃里克？

Thank you, Naomi, and good afternoon, everyone. 2022 was a year of many achievements that have further strengthened our position as a leader in the rare disease community. This is founded in our mission to identify, develop and deliver life-changing therapies to people living with rare disease. Throughout last year, we advanced our pipeline, prepared our organization for launch and continue to reach the patients that currently rely on our approved medicines.

謝謝你，Naomi，大家下午好。 2022 年取得了許多成就，進一步鞏固了我們作為罕見病領域領導者的地位。這是建立在我們為患有罕見疾病的人確定、開發和提供改變生活的療法的使命之上的。去年全年，我們推進了我們的管道，為我們的組織做好啟動準備，並繼續接觸目前依賴我們批准的藥物的患者。

Perhaps most importantly, our work culminated in the recent accelerated approval of FILSPARI for the reduction of proteinuria in adults with primary IgA nephropathy or IgAN, at risk of rapid disease progression.

也許最重要的是，我們的工作最終導致最近加速批准 FILSPARI 用於減少原發性 IgA 腎病或 IgAN 成人患者的蛋白尿，這些患者有疾病快速進展的風險。

FILSPARI is the first and only non-immunosuppressive medicine approved for IgA, which has demonstrated a threefold superior proteinuria reduction compared to a standard of care, irbesartan.

FILSPARI 是第一個也是唯一一個被批准用於 IgA 的非免疫抑製藥物，與標準治療厄貝沙坦相比，它已證明其蛋白尿減少三倍。

As you heard us talk about on our recent approval call, we have high aspirations for FILSPARI as we believe it will become the foundational treatment option for IgAN patients who are at risk of rapid progression.

正如您在最近的批准電話會議上聽到我們談論的那樣，我們對 FILSPARI 寄予厚望，因為我們相信它將成為面臨快速進展風險的 IgAN 患者的基礎治療選擇。

Importantly, we have the deep market insights, the product profile, the team and the strategy to achieve that goal. If we are successful, we will be able to positively impact many patients in the U.S. with this important new medicine. We are only a few days into the launch in the U.S., but we're encouraged by the initial engagement with physicians, patients and payers. And Peter will go into in a bit more detail shortly.

重要的是，我們擁有深刻的市場洞察力、產品概況、團隊和實現該目標的戰略。如果我們成功了，我們將能夠用這種重要的新藥對美國的許多患者產生積極影響。我們在美國推出僅幾天，但我們對與醫生、患者和付款人的初步接觸感到鼓舞。 Peter 稍後會詳細介紹。

We still have more fighting milestones to come with FILSPARI in 2023. Beyond setting the launch trajectory in the U.S., we are anticipating a review decision from the EMA in the second half of 2023 for the conditional marketing authorization application for sparsentan in the treatment of IgAN in Europe. We will continue to work closely with our partner, CSL Vifor throughout the review process. And we also look forward to the 2-year data from the ongoing PROTECT study. As a reminder, the interim results from the study supported the accelerated approval of FILSPARI last week. As such, we are awaiting with anticipation of the 2-year data set, which is planned for the fourth quarter of this year.

2023 年，我們還有更多與 FILSPARI 一起取得的里程碑。除了設定在美國的發射軌跡外，我們預計 EMA 將在 2023 年下半年對 sparsentan 治療 IgAN 的有條件營銷授權申請做出審查決定在歐洲。在整個審查過程中，我們將繼續與我們的合作夥伴 CSL Vifor 密切合作。我們也期待來自正在進行的 PROTECT 研究的 2 年數據。提醒一下，該研究的中期結果支持 FILSPARI 上週的加速批准。因此，我們正在等待計劃於今年第四季度發布的 2 年數據集。

Based upon the interim results, we believe the preliminary eGFR data available at the time of the interim analysis were indicative of a potentially clinically meaningful treatment effect after 2 years of treatment and that we'll be able to utilize those data for a traditional approval submission in 2024.

根據中期結果，我們認為中期分析時可用的初步 eGFR 數據表明治療 2 年後可能具有臨床意義的治療效果，我們將能夠利用這些數據進行傳統的批准提交2024年。

Additionally, from sparsentan, we expect to have top line data from the 2-year endpoint in the ongoing DUPLEX study in FSGS during the second quarter of this year. If the results from DUPLEX are supportive of an FSGS regulatory submission, we would anticipate being in a position to submit an sNDA in the second half of this year and would also target submitting together with CSL Vifor as a subsequent variation to our European CMA application by end of the year.

此外，從 sparsentan 中，我們預計在今年第二季度正在進行的 FSGS 雙重研究中獲得來自 2 年終點的頂線數據。如果 DUPLEX 的結果支持 FSGS 監管提交，我們預計能夠在今年下半年提交 sNDA，並且還將與 CSL Vifor 一起提交，作為我們歐洲 CMA 申請的後續變更年底。

This would represent an incredible opportunity for us to help patients with FSGS, one of the leading causes of kidney failure due to glomerular disease. Beyond sparsentan, we continue to advance our novel pegtibatinase program for classical homocystinuria, or HCU. Later this year, we anticipate being in position to provide additional data from the ongoing COMPOSE study as well as plans for a potential Phase III program after we complete our regulatory engagements.

這對我們來說是一個難得的機會，可以幫助 FSGS 患者，FSGS 是腎小球疾病導致腎衰竭的主要原因之一。除了 sparsentan，我們還繼續推進我們針對經典同型半胱氨酸尿症 (HCU) 的新型 pegtibatinase 計劃。今年晚些時候，我們預計能夠在完成監管工作後提供正在進行的 COMPOSE 研究的更多數據以及潛在的 III 期計劃計劃。

2022 was a remarkable year for Travere, and I'm proud of our organization's accomplishments and perseverance that ultimately get us to our first approval from our pipeline of therapies targeting rare diseases. We have started off 2023 with a key milestone that has been years in the making, and we have much more to come and continue working towards our mission of delivering life-changing therapies to people living with rare disease.

2022 年對 Travere 來說是不平凡的一年，我為我們組織的成就和毅力感到自豪，這些成就和毅力最終使我們的針對罕見疾病的療法管道獲得了首次批准。我們從 2023 年開始了一個多年來一直在醞釀的關鍵里程碑，我們還有更多的事情要做，並繼續努力實現我們的使命，即為患有罕見疾病的人提供改變生活的療法。

Let me now turn the call over to Jula for a clinical update. Jula?

現在讓我將電話轉給 Jula 進行臨床更新。朱拉？

Thank you, Eric, and good afternoon, everyone. As Eric stated, 2023 promises to be an exciting year for Travere, the rare kidney community and the patients and families impacted by IgAN. We could not be more pleased with the recent accelerated approval of FILSPARI. This milestone has created momentum in the IgAN community and set the stage for many exciting developments to come.

謝謝埃里克，大家下午好。正如 Eric 所說，2023 年對於 Travere、罕見的腎臟社區以及受 IgAN 影響的患者和家庭來說將是激動人心的一年。我們對 FILSPARI 最近的加速批准感到非常高興。這一里程碑在 IgAN 社區中創造了動力，並為許多激動人心的發展奠定了基礎。

It is important to remember that IgAN is the most prevalent primary glomerulonephritis worldwide. It is often uncontrolled. And as a result, it is a major cause of kidney failure. In fact, high-risk people living with IgAN face a median time to kidney failure of approximately 11 years. Along the way, many faced pain and debilitating fatigue, depression and anxiety and challenges with keeping up with everyday work life.

重要的是要記住，IgAN 是全世界最普遍的原發性腎小球腎炎。它通常是不受控制的。因此，它是腎衰竭的主要原因。事實上，患有 IgAN 的高危人群出現腎衰竭的中位時間約為 11 年。在此過程中，許多人面臨著痛苦和虛弱的疲勞、抑鬱和焦慮，以及跟上日常工作生活的挑戰。

Patients and their nephrologists are desperately seeking new treatments that can effectively reduce proteinuria and be utilized long term with less concern for limiting side effects. Right now, that's limited to ACE inhibitors or angiotensin receptor blockers, which more than 50% of patients don't respond adequately to and SGLT2 inhibitors, which are less effective at reducing proteinuria. Steroids are also available, but are generally reserved for more severe IgAN patients because of their challenging safety and tolerability profile.

患者和他們的腎病學家正在拼命尋找新的治療方法，以有效減少蛋白尿並長期使用，而不必擔心限制副作用。目前，這僅限於 ACE 抑製劑或血管緊張素受體阻滯劑，超過 50% 的患者對它們的反應不充分，而 SGLT2 抑製劑在減少蛋白尿方面效果較差。類固醇也可用，但由於其具有挑戰性的安全性和耐受性特徵，通常保留給更嚴重的 IgAN 患者。

FILSPARI is the only once-daily oral non-immunosuppressive medication approved for the reduction of proteinuria in IgAN. As the first of its kind, dual endothelin, angiotensin receptor antagonist. FILSPARI targets 2 causal pathways critical to IgAN disease progression.

FILSPARI 是唯一批准用於減少 IgAN 蛋白尿的每日一次口服非免疫抑製藥物。為同類首創，雙重內皮素、血管緊張素受體拮抗劑。 FILSPARI 針對 2 條對 IgAN 疾病進展至關重要的因果途徑。

In the PROTECT study, we observed a rapid sustained and 3x greater reduction in proteinuria compared to irbesartan while showing a consistent and tolerable safety profile similar to irbesartan. We are thankful for the FDA's accelerated approval of FILSPARI, and are proud of the label we have received, which highlights the strongest clinical data demonstrated in a head-to-head Phase III study in IgAN to date.

在 PROTECT 研究中，我們觀察到與厄貝沙坦相比，蛋白尿快速持續減少 3 倍，同時顯示出與厄貝沙坦相似的一致且可耐受的安全性。我們感謝 FDA 加速批准 FILSPARI，並為我們收到的標籤感到自豪，該標籤突出了迄今為止在 IgAN 的頭對頭 III 期研究中展示的最強大的臨床數據。

I encourage you to review the entire label at filspari.com to further understand the clinical performance, safety profile and the REMS process. A point worth noting is that both the liver and pregnancy REMS monitoring can be obtained with a single blood draw. Since high-risk patients typically undergo monthly medical visits and labs, we expect that integrating REMS monitoring into their current course of care will be seamless and serve as an effective tool for physicians monitoring their patients.

我鼓勵您在 filspari.com 上查看整個標籤，以進一步了解臨床表現、安全概況和 REMS 過程。值得注意的一點是，肝臟和妊娠 REMS 監測都可以通過單次抽血獲得。由於高風險患者通常每月進行一次醫療訪問和實驗室檢查，我們希望將 REMS 監測無縫集成到他們當前的護理過程中，並作為醫生監測患者的有效工具。

Overall, we believe this label will provide nephrologists with the confidence needed to prescribe FILSPARI for their IgAN patients at risk of rapid disease progression and that this is just the beginning for realizing FILSPARI's potential.

總的來說，我們相信這一標籤將為腎病學家提供信心，為他們有快速疾病進展風險的 IgAN 患者開出 FILSPARI 處方，而這僅僅是實現 FILSPARI 潛力的開始。

Later this year, we're expecting top line data from the confirmatory portion of the PROTECT study. If these data demonstrate a clinically meaningful benefit on eGFR after 2 years of treatment, this will further solidify FILSPARI's potential as a new treatment standard.

今年晚些時候，我們期待來自 PROTECT 研究確認部分的頂線數據。如果這些數據表明在治療 2 年後對 eGFR 具有臨床意義的益處，這將進一步鞏固 FILSPARI 作為新治療標準的潛力。

Achieving this would enable us to submit for a traditional approval with the expectation of a label that would be more representative of the total population studied in PROTECT and reflect the long-term benefits of FILSPARI. Beyond IgAN, we're nearing the topline results from the DUPLEX study of sparsentan in FSGS.

實現這一點將使我們能夠提交傳統批准，並期望標籤更能代表 PROTECT 研究的總人口，並反映 FILSPARI 的長期利益。除了 IgAN，我們接近 FSGS 中 sparsentan 的雙重研究的頂線結果。

The DUPLEX study is progressing according to plan, and we're pleased with the continued conduct and efforts to get to database lock. If the 2-year data progresses in a favorable manner, we expect to submit an sNDA for sparsentan to gain an indication for FSGS and be added to the FILSPARI label. We would also look to submit a variation to our CMA application, if approved for IgAN in Europe. This could be paramount for people living with FSGS as many are facing an even faster progression to kidney failure and fewer effective and safe treatment options.

DUPLEX 研究正在按計劃進行，我們很高興為獲得數據庫鎖定而持續進行和努力。如果 2 年的數據進展順利，我們希望提交一份 sNDA 用於 sparsentan 以獲得 FSGS 的適應症並添加到 FILSPARI 標籤中。如果 IgAN 在歐洲獲得批准，我們還希望提交對我們的 CMA 申請的變更。這對於 FSGS 患者來說可能是最重要的，因為許多人正面臨更快的腎衰竭進展和更少的有效和安全的治療選擇。

Beyond sparsentan, we continue to advance our pegtibatinase program in classical homocystinuria. During the fourth quarter, we completed enrollment activities in the sixth and final cohort of the ongoing Phase I/II COMPOSE study.

除了 sparsentan，我們繼續推進我們在經典同型半胱氨酸尿症中的 pegtibatinase 計劃。在第四季度，我們完成了正在進行的 I/II 期 COMPOSE 研究的第六個也是最後一個隊列的註冊活動。

As a reminder, pegtibatinase demonstrated dose-dependent reductions in total homocystine during 12 weeks of treatment in COMPOSE. In the 1.5 milligrams per kilogram twice weekly dose cohort, treatment with pegtibatinase resulted in rapid and sustained reductions in total homocystine of approximately 55%, resulting in maintenance of total homocystine below a clinically meaningful threshold of 100 micromoles from week 2 through week 12 of treatment.

提醒一下，聚乙二醇酶在 COMPOSE 的 12 周治療期間表現出劑量依賴性總同型半胱氨酸減少。在每週兩次 1.5 毫克/千克的劑量隊列中，用 pegtibatinase 治療導致總同型半胱氨酸快速和持續減少約 55%，導致從治療的第 2 周到第 12 週，總同型半胱氨酸維持在 100 微摩爾的臨床有意義閾值以下.

Our sixth cohort is evaluating one additional higher dose and also a lyophilized formulation that if effective could be utilized in a potential pivotal program and the commercial setting if approved. We remain on track for additional data from COMPOSE later this year. These data will be helpful for completing our engagement with regulators and potentially initiating a Phase III study in the second half of this year.

我們的第六個隊列正在評估一種額外的更高劑量和一種凍乾製劑，如果有效，可以在潛在的關鍵項目和商業環境中使用，如果獲得批准。今年晚些時候，我們仍有望從 COMPOSE 獲取更多數據。這些數據將有助於完成我們與監管機構的接觸，並有可能在今年下半年啟動 III 期研究。

Finally, on the development programs. We received Fast Track designation for our Chenodal development program in 2022. As many of you may recall, Chenodal is currently approved for the treatment of radiolucent gallstones, but it has been recognized as the standard of care for cerebrotendinous xanthomatosis or CTX for many years.

最後，關於發展計劃。我們在 2022 年獲得了 Chenodal 開發計劃的快速通道指定。你們中的許多人可能還記得，Chenodal 目前被批准用於治療射線可透性膽結石，但多年來它一直被認為是腦腱黃瘤病或 CTX 的護理標準。

Our ongoing Phase III RESTORE study is designed to provide a data set that will allow us to submit an sNDA to have the label amended to reflect what we believe is the true use of the product. We believe this could significantly aid patient identification and help people living with CTX gain earlier access to a greatly needed treatment option.

我們正在進行的 III 期 RESTORE 研究旨在提供一個數據集，使我們能夠提交 sNDA 以修改標籤以反映我們認為是產品的真實用途。我們相信這可以極大地幫助識別患者，並幫助患有 CTX 的人更早地獲得急需的治療選擇。

We know that if CTX is identified and treated early, oftentimes, patients can go on to live a relatively normal life. We expect to have data from the Phase III study in-house this year and to subsequently submit an sNDA if the data are supportive.

我們知道，如果及早發現並治療 CTX，患者通常可以繼續過上相對正常的生活。我們預計今年將獲得內部 III 期研究的數據，如果數據支持，我們將隨後提交 sNDA。

With that, I'll turn the call over to Peter for the commercial update, including additional color on the FILSPARI launch. Peter?

有了這個，我會把電話轉給彼得進行商業更新，包括 FILSPARI 推出的其他顏色。彼得？

Thank you, Jula. This has already been an exciting week for us. As I mentioned on the call last Friday, we built our FILSPARI launch team upon our proven commercial infrastructure, which has delivered consistent results over the past 8 years. We further strengthened our executing capabilities and now have a dedicated launch team with specific experience and expertise to be successful with FILSPARI.

謝謝你，朱拉。這對我們來說已經是激動人心的一周了。正如我在上週五的電話會議上提到的那樣，我們在經過驗證的商業基礎設施的基礎上建立了 FILSPARI 發射團隊，該基礎設施在過去 8 年中取得了一致的成果。我們進一步加強了我們的執行能力，現在擁有一支具有特定經驗和專業知識的專門發射團隊，可以通過 FILSPARI 取得成功。

I mentioned that this team was ready to execute with a sense of urgency. And I'm pleased to report that our team has been executing very well since approval Friday afternoon. Within one1 day, our materials were finalized consistent to the label in the FILSPARI, FILSPARI REMS and Travere TotalCare for websites were live and operational. Even though Monday was a public holiday, our commercial field teams were excited to finish that framing and get out into the field, engaging with their customers, both nephrologists as well as payers.

我提到這個團隊已經準備好以緊迫感執行。我很高興地報告說，自周五下午獲得批准以來，我們的團隊一直表現出色。在一天之內，我們的材料最終確定為與 FILSPARI、FILSPARI REMS 和 Travere TotalCare 中的標籤一致，因為網站是實時和可操作的。儘管星期一是公眾假期，但我們的商業現場團隊很高興能夠完成該框架並進入該領域，與他們的客戶（包括腎髒病學家和付款人）進行交流。

All these extensive planning and execution efforts led to the first FILSPARI prescription being written within 8 business hours of approval. We anticipate this positive momentum to continue to build.

所有這些廣泛的計劃和執行工作導致第一個 FILSPARI 處方在批准後的 8 個工作小時內寫出。我們預計這種積極勢頭將繼續增強。

To provide you a bit more context on our initial date of FILSPARI commercialization, our experienced commercial field team of more than 80 seasoned professionals is engaging in productive conversations with nephrologists and payers. Focusing on the burden of disease in IgAN. The challenges with current standard of care and how FILSPARI's profile could potentially address the shortcomings in the addressable IgAN population of adult patients had risk of rapid progression.

為了向您提供更多有關我們 FILSPARI 商業化初始日期的背景信息，我們經驗豐富的商業現場團隊由 80 多名經驗豐富的專業人士組成，正在與腎病學家和付款人進行富有成效的對話。關注 IgAN 的疾病負擔。當前護理標準面臨的挑戰以及 FILSPARI 的概況如何潛在地解決成年患者可尋址 IgAN 人群中存在快速進展風險的缺點。

The receptivity and initial interest from the nephrology community is in line with our expectations, simplifying that patients have been waiting for a product like FILSPARI. Prior to approval, nephrologists have consistently expressed that they need more efficacious treatment options that allow for long-term use in treating their IgAN patients, who are at risk of rapid progression without the tolerability issues of immunosuppressive agents.

腎髒病學界的接受度和最初的興趣符合我們的預期，簡化了患者一直在等待像 FILSPARI 這樣的產品。在獲得批准之前，腎病學家一直表示，他們需要更有效的治療方案，以便長期用於治療 IgAN 患者，這些患者有快速進展的風險，而沒有免疫抑製劑的耐受性問題。

We believe FILSPARI is well positioned to fill that need. It blocks angiotensin, consistent with how nephrologists have been doing over the past 30 years. So it was built upon a common belief and routine, but it adds the missing component of antagonizing the endothelin A receptor. And we know that endothelin and angiotensin stimulate each other and act in tandem to amplify damage to the filtration barrier in the kidney, resulting in increased proteinuria levels. Integrally blocking, endothelin and angiotensin with FILSPARI has allowed for the superior efficacy relative to irbesartan as observed in the interim readout on the landmark PROTECT trial.

我們相信 FILSPARI 能夠很好地滿足這一需求。它可以阻斷血管緊張素，這與過去 30 年來腎病學家的做法一致。所以它建立在共同的信念和常規之上，但它增加了拮抗內皮素 A 受體的缺失成分。我們知道內皮素和血管緊張素相互刺激並協同作用，以放大對腎臟過濾屏障的損害，從而導致蛋白尿水平升高。正如在具有里程碑意義的 PROTECT 試驗的中期讀數中所觀察到的，FILSPARI 整體阻斷內皮素和血管緊張素具有優於厄貝沙坦的療效。

Based on FILSPARI for novel motivation in robust efficacy and safety data, we are convinced that FILSPARI has the potential to become the foundational treatment option for the roughly 30,000 to 50,000 IgAN patients addressable under the current indication.

基於 FILSPARI 在穩健療效和安全數據方面的新動機，我們相信 FILSPARI 有可能成為目前適應症下可尋址的大約 30,000 至 50,000 名 IgAN 患者的基礎治療選擇。

It is our goal to make FILSPARI, the cornerstone therapy for these patients within the evolving IgAN treatment paradigm. Lastly, I mentioned on the approval call that we have learned from recent product launch in rare nephrology and that we know that nephrologists have -- are largely mechanism and data driven. Therefore, our initial focus is to educate nephrologists on the FILSPARI profile, both the efficacy and safety filings as outlined in the label, to give them a solid understanding how FILSPARI may help their rapidly progressing IgAN patients.

我們的目標是讓 FILSPARI 成為不斷發展的 IgAN 治療範式中這些患者的基石療法。最後，我在批准電話會議上提到，我們從最近在罕見腎髒病學中推出的產品中了解到，我們知道腎髒病學家在很大程度上是機制和數據驅動的。因此，我們最初的重點是讓腎病學家了解 FILSPARI 概況，包括標籤中概述的療效和安全性文件，讓他們深入了解 FILSPARI 如何幫助他們快速進展的 IgAN 患者。

Another launch dynamic that we will be navigating is, the process of getting to pay a coverage. Here, I believe we are also off to a solid starts. Prior to approval, we have already conducted scientific pre-approval engagement with payers covering over 150 million lives. And we are building upon those initial conversations now.

我們將導航的另一個啟動動態是支付保險費的過程。在這裡，我相信我們也有了一個堅實的開端。在批准之前，我們已經與覆蓋超過 1.5 億人的付款人進行了科學的預批准接觸。我們現在正在建立這些最初的對話。

This week, we have already interacted with several national payers and these interactions have reinforced that payers are generally well aware of burden of IgAN and appreciate the importance of proteinuria reduction in relation to disease progression.

本週，我們已經與幾個國家的付款人進行了互動，這些互動加強了付款人普遍了解 IgAN 的負擔，並認識到減少蛋白尿對疾病進展的重要性。

Last week, I also referenced that we plan for an exclusive first FILSPARI experience for patients and physicians. We have established Travere TotalCare to help patients by offering personalized education, support in the reimbursement process and co-pay-assistance for eligible patients. Travere TotalCare also assists patient and physicians with their REMS enrollments, which is typically a simple procedure.

上週，我還提到我們計劃為患者和醫生提供獨家的首次 FILSPARI 體驗。我們已經建立了 Travere TotalCare，通過為符合條件的患者提供個性化教育、報銷流程支持和共同支付援助來幫助患者。 Travere TotalCare 還協助患者和醫生進行 REMS 登記，這通常是一個簡單的程序。

During this process, physicians will review the prescriber guide and acknowledge their understanding of the label. Then they will be prepared to prescribe FILSPARI. It is also worth emphasizing that our REMS monitoring integrate seamlessly with the established REMS processes nephrologist currently used for other therapies.

在此過程中，醫生將查看處方指南並確認他們對標籤的理解。然後他們將準備開 FILSPARI 處方。還值得強調的是，我們的 REMS 監測與腎病學家目前用於其他治療的既定 REMS 過程無縫集成。

From a logistical standpoint, we remain on track for FILSPARI to be shipped to our specialty pharmacies next week. In summary, our launch execution has started according to plan, and we are well positioned to deliver on our powerful purpose, bring FILSPARI to patients who need it most.

從物流的角度來看，我們仍有望在下週將 FILSPARI 運送到我們的專業藥房。總而言之，我們的上市執行已按計劃開始，我們已準備好實現我們強大的目標，將 FILSPARI 帶給最需要它的患者。

Turning to the performance of our in-line product portfolio in the fourth quarter of 2022. I continue to be very pleased with the execution of our commercial organization. For Thiola, we continue to see solid demand as we have further supported the identification and treatment of cystinuria patients.

談到我們在線產品組合在 2022 年第四季度的表現。我仍然對我們商業組織的執行感到非常滿意。對於 Thiola，我們繼續看到強勁的需求，因為我們進一步支持了胱氨酸尿症患者的識別和治療。

This is a testament to our organizations patient inspired way of operating and our established capabilities in the rare kidney space. We are pleased with the meaningful Thiola performance within the evolving competitive landscape. As we have talked about historically, we are seeing the impact of generic dynamics that affect net sales of Thiola and we expected this could materialize further this year.

這證明了我們組織以患者為靈感的操作方式以及我們在罕見腎臟領域的既定能力。我們對 Thiola 在不斷變化的競爭格局中有意義的表現感到滿意。正如我們在歷史上談到的那樣，我們看到了影響 Thiola 淨銷售額的通用動力的影響，我們預計今年這可能會進一步實現。

Our bile acid portfolio continued to deliver solid growth in the fourth quarter. The CHOLBAM team has a long-standing reputation of performance and dedication to educating pediatric geneticists and hepatologists. These efforts have been key to CHOLBAM's continued growth. Our team's capability to help physicians in patient identification of these ultra-rare conditions is fundamental. This expertise provides a solid foundation to build upon, as we prepare for a potential future CTX indication for Chenodal. And as we progress it is the fact that pegtibatinase development program.

我們的膽汁酸產品組合在第四季度繼續實現穩健增長。 CHOLBAM 團隊在培養兒科遺傳學家和肝病學家方面的表現和奉獻精神享有長期聲譽。這些努力是 CHOLBAM 持續增長的關鍵。我們團隊幫助醫生識別患者這些極罕見病症的能力至關重要。在我們為 Chenodal 未來潛在的 CTX 適應症做準備時，這種專業知識為我們奠定了堅實的基礎。隨著我們的進步，事實是 pegtibatinase 開發計劃。

In 2023, we expect to return to year-over-year growth in net product sales, while we expect further pressure on Thiola. We anticipate that this will be offset by expected growth of our bile acid portfolio in the FILSPARI launch performance. As a reminder, we anticipate that FILSPARI's performance will be in line with recent rare nephrology benchmarks in the first 6 to 9 months. And once we gain meaningful FILSPARI payer coverage and prescribers gain their initial experiences and observed the same consistent proteinuria reduction as observed in the PROTECT trial, we anticipate accelerated adoption towards the end of the year.

到 2023 年，我們預計產品淨銷售額將恢復同比增長，同時我們預計 Thiola 將面臨進一步壓力。我們預計這將被我們的膽汁酸產品組合在 FILSPARI 發布性能中的預期增長所抵消。提醒一下，我們預計 FILSPARI 的表現將在前 6 至 9 個月內符合近期罕見的腎髒病學基準。一旦我們獲得有意義的 FILSPARI 付款人覆蓋範圍並且處方者獲得他們的初步經驗並觀察到與 PROTECT 試驗中觀察到的一致的蛋白尿減少，我們預計將在今年年底加速採用。

Beyond this first year, we are well positioned for ongoing growth of FILSPARI, which is exemplified by our ability to execute, as demonstrated with our commercial performance in 2022. This, together with the high (inaudible) IgAN, the robust profile of FILSPARI and our meaningful timing advantage before additional therapies may potentially be approved gives us confidence that we will succeed in our strategic objective to make FILSPARI the foundational treatment for rapidly progressing IgAN patients.

在第一年之後，我們為 FILSPARI 的持續增長做好了準備，這體現在我們的執行能力上，正如我們在 2022 年的商業業績所證明的那樣。這與高（聽不清） IgAN 一起， FILSPARI 的強大形象和在可能批准其他療法之前，我們有意義的時間優勢使我們有信心，我們將成功實現我們的戰略目標，使 FILSPARI 成為快速進展的 IgAN 患者的基礎治療。

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

現在讓我把財務更新的電話轉給克里斯。克里斯？

Thank you, Peter, and good afternoon, everyone. With the continued execution of our commercial organization and the focus on our key priorities throughout the business, we ended 2022 in a strong financial position.

謝謝你，彼得，大家下午好。隨著我們商業組織的持續執行以及對我們整個業務的關鍵優先事項的關注，我們在 2022 年結束時財務狀況良好。

For the fourth quarter of 2022, net product sales were $52.3 million, compared to $54.6 million for the same period in 2021.

2022 年第四季度，產品淨銷售額為 5230 萬美元，而 2021 年同期為 5460 萬美元。

For the full year 2022, net product sales were $200.5 million, compared to $210.8 million for the same period in 2021. The difference is largely attributable to a decrease in Thiola sales, partially offset by an increase in sales for the company's bile acid products.

2022 年全年，產品淨銷售額為 2.005 億美元，而 2021 年同期為 2.108 億美元。差異主要歸因於 Thiola 銷售額的減少，部分被公司膽汁酸產品銷售額的增加所抵消。

Research and development expenses for the fourth quarter of 2022 were $60.2 million, compared to $62.2 million for the same period in 2021. For the full year 2022, R&D expenses were $235.8 million, compared to $210.3 million for the same period in 2021. The difference is largely attributable to the continued advancement of the Company's sparsentan and pegtibatinase clinical programs, including clinical trial expenses, manufacturing and increased headcount.

2022 年第四季度研發費用為 6020 萬美元，2021 年同期為 6220 萬美元。2022 年全年研發費用為 2.358 億美元，2021 年同期為 2.103 億美元。主要歸因於公司 sparsentan 和 pegtibatinase 臨床項目的持續推進，包括臨床試驗費用、製造和增加員工人數。

On a non-GAAP adjusted basis, R&D expenses were $54.2 million for the fourth quarter of 2022, compared to $57.7 million for the same period in 2021. Selling, general and administrative expenses for the fourth quarter of 2022 were $62.9 million, compared to $42.1 million for the same period in 2021. For the full year 2022, SG&A expenses were $220.2 million, compared to $149.9 million for the same period in 2021. The difference is largely attributable to the commercial launch preparations for FILSPARI, including having the full sales team on board and ready to launch this week.

按非美國通用會計準則調整後，2022 年第四季度的研發費用為 5420 萬美元，而 2021 年同期為 5770 萬美元。2022 年第四季度的銷售、一般和管理費用為 6290 萬美元，而 2021 年同期為 42.1 美元百萬美元。2022 年全年，SG&A 費用為 2.202 億美元，而 2021 年同期為 1.499 億美元。差異主要歸因於 FILSPARI 的商業發布準備工作，包括擁有完整的銷售團隊在船上並準備在本週發射。

On a non-GAAP adjusted basis, SG&A expenses were $50.2 million for the fourth quarter of 2022, compared to $30.9 million for the same period in 2021. Total other income, net for the fourth quarter of 2022 was $1.1 million, compared to total other expense net of $4.4 million in the same period in 2021. The difference is largely attributable to increased interest income and lower interest expense during the period.

在非 GAAP 調整的基礎上，2022 年第四季度的 SG&A 費用為 5020 萬美元，而 2021 年同期為 3090 萬美元。2022 年第四季度的其他總收入淨額為 110 萬美元，而其他總收入2021 年同期的支出淨額為 440 萬美元。差異主要歸因於該期間利息收入增加和利息支出減少。

Net loss for the fourth quarter of 2022 was $65.8 million or $1.03 per basic share, compared to a net loss of $51.6 million or $0.84 per basic share for the same period in 2021. For the full year 2020, net loss was $278.5 million, compared to $180.1 million for the same period in 2021. On a non-GAAP adjusted basis, net loss for the fourth quarter of 2022 was $49.1 million or $0.76 per basic share, compared to a net loss of $37.6 million or $0.61 per basic share for the same period in 2021.

2022 年第四季度淨虧損為 6580 萬美元或每股基本股 1.03 美元，而 2021 年同期淨虧損為 5160 萬美元或每股基本股 0.84 美元。2020 年全年淨虧損為 2.785 億美元，相比之下到 2021 年同期為 1.801 億美元。在非 GAAP 調整的基礎上，2022 年第四季度的淨虧損為 4910 萬美元或每股基本股 0.76 美元，而 2022 年第四季度的淨虧損為 3760 萬美元或每股基本股 0.61 美元2021 年同期。

As of December 31, 2022, the company had cash, cash equivalents and marketable securities of $450.2 million. As we look to the year ahead, we anticipate that our operating expenses will continue to increase and may be variable quarter-to-quarter as we advance our programs. For SG&A, this is primarily driven by having a full year of the expanded sales team in place and our associated launch investments positioned FILSPARI for success. For R&D, it is primarily driven by the continuation of both the PROTECT and DUPLEX studies of sparsentan as well as our work to evaluate sparsentan in combination with SGLT2 inhibitors and preparing pegtibatinase for a potential pivotal program, including building supply.

截至 2022 年 12 月 31 日，公司擁有現金、現金等價物和有價證券 4.502 億美元。展望未來一年，我們預計我們的運營費用將繼續增加，並且隨著我們推進我們的計劃，每個季度可能會有所不同。對於 SG&A 而言，這主要是由於擁有一整年的擴大銷售團隊以及我們相關的啟動投資使 FILSPARI 取得成功。對於研發，它的主要驅動力是繼續開展 sparsentan 的 PROTECT 和 DUPLEX 研究，以及我們評估 sparsentan 與 SGLT2 抑製劑聯合使用的工作，以及為潛在的關鍵項目（包括建立供應）準備 pegtibatinase 的工作。

Accordingly, we anticipate that we can manage our balance sheet to support our operations well into 2024. This takes into account potential further competitive dynamics for Thiola, investing in launches for both IgAN and potentially FSGS, advancing pegtibatinase as well as milestone payments related to achievements for the programs.

因此，我們預計我們可以管理我們的資產負債表，以支持我們到 2024 年的運營。這考慮到了 Thiola 潛在的進一步競爭動態，投資於 IgAN 和潛在 FSGS 的發布，推進 pegtibatinase 以及與成就相關的里程碑付款對於程序。

Importantly, we entered the new year with a strong financial position to support this exciting period of launch execution and the continued advancement of our pipeline to a number of key milestones in 2023.

重要的是，我們以強勁的財務狀況進入了新的一年，以支持這一激動人心的發射執行期，以及我們的管道在 2023 年繼續推進到多個關鍵里程碑。

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

我現在將其轉回給埃里克，聽取他的結束評論。埃里克？

Thank you, Chris. I want to express my gratitude to the rare disease community, the patients, their families and the Travere team for their hard work and dedication that has led us to the successful moment, the launch of FILSPARI. The strong reception by physicians, patients and payers, even in these early days, demonstrates the value of FILSPARI in addressing the unmet need of those in the rare kidney community.

謝謝你，克里斯。我想對罕見病社區、患者、他們的家人和 Travere 團隊表示感謝，感謝他們的辛勤工作和奉獻精神，使我們走向了成功的時刻，即 FILSPARI 的推出。即使在早期，醫生、患者和付款人的強烈接受也證明了 FILSPARI 在解決罕見腎臟社區未滿足的需求方面的價值。

We are committed to improving the lives of patients and to do so, are focused on the advancement of our pipeline. In this regard, we still have a number of exciting milestones to come, including the potential approval of sparsentan for IgAN in Europe in the second half of this year and the 2-year data from the PROTECT trial in IgAN in the fourth quarter. We also anticipate top line data from the 2-year endpoints in the DUPLEX study of sparsentan in FSGS in the second quarter of this year, which could lead to an important new indication for sparsentan. And finally, we expect to be able to share more this year on our novel pegtibatinase program as we prepare for a potential Phase III program. Our years of hard work has set us up for an incredibly bright 2023.

我們致力於改善患者的生活，為此，我們專注於改進我們的產品線。在這方面，我們還有許多激動人心的里程碑即將到來，包括今年下半年歐洲可能批准用於 IgAN 的 sparsentan 以及第四季度 IgAN PROTECT 試驗的 2 年數據。我們還預計今年第二季度 FSGS 中 sparsentan 的 DUPLEX 研究的 2 年終點的頂級數據，這可能導致 sparsentan 的重要新適應症。最後，在我們為潛在的 III 期項目做準備時，我們希望今年能夠分享更多關於我們新的 pegtibatinase 項目的信息。經過多年的努力，我們已經為 2023 年的輝煌做好了準備。

I am confident our talented team will deliver strong results for our patients and for the rare disease community.

我相信我們才華橫溢的團隊將為我們的患者和罕見病社區帶來出色的成果。

Let me now turn the call over to Naomi for Q&A. Naomi?

現在讓我將電話轉給 Naomi 進行問答。內奧米？

Thanks, Eric. Rachel, can you please go ahead and open the lines for Q&A?

謝謝，埃里克。雷切爾，你能打開問答熱線嗎？

(Operator Instructions)

（操作員說明）

We will take our first question from the line of Greg Harrison with Bank of America.

我們將從美國銀行的 Greg Harrison 那裡回答我們的第一個問題。

Maybe just to start off, could you walk me through the process from a patient's perspective of getting the script, enrolling in the REMS program and then the monthly maintenance testing for the REMS?

也許只是開始，您能否從患者的角度引導我完成獲取腳本、註冊 REMS 程序以及 REMS 每月維護測試的過程？

Yes, Greg, thank you very much for the question. Jula, maybe we'll turn to you first and you can walk through how this fits within, how these patients are treated. And Peter, you can walk through what the process is for prescription and receiving FILSPARI.

是的，格雷格，非常感謝你提出這個問題。朱拉，也許我們會先求助於你，你可以了解一下這在其中是如何適應的，這些患者是如何接受治療的。 Peter，你可以了解處方和接收 FILSPARI 的過程。

Certainly. Thanks, Greg, for the question. So realize that patients who are at risk for progression are going to see their nephrologists and more frequently, particularly if you have a change in their treatment algorithm. So they may see them every month with labs. And so as the patient is going to go see their nephrologist, they're going to discuss their overall risk of progression, having significant proteinuria as well as their eGFR decline and the nephrologist is going to sign up for the REMS.

當然。謝謝，格雷格，提出這個問題。因此，要意識到有進展風險的患者會更頻繁地去看腎病專家，尤其是當您改變他們的治療算法時。所以他們可能每個月都會在實驗室看到他們。因此，當患者去看他們的腎臟科醫生時，他們將討論他們進展的總體風險、顯著的蛋白尿以及他們的 eGFR 下降，並且腎臟科醫生將註冊 REMS。

And the process for signing up for the REMS is relatively simple from both the physician perspective as well as the patient. They need to be educated. That's a significant proportion of the REMS that means reading the label, reading the prescriber and pharmacy guide and then signing up means filling out your contact details and then signing a statement that says, you're going to monitor your patient appropriately.

從醫生和患者的角度來看，註冊 REMS 的過程都相對簡單。他們需要接受教育。這是 REMS 的很大一部分，這意味著閱讀標籤、閱讀處方者和藥房指南，然後註冊意味著填寫您的聯繫方式，然後簽署一份聲明，說明您將適當地監測您的患者。

That's the same process for a patient. They give their contact details, state that they've been informed about the overall risk, benefit and that they're going to follow the process. And for a patient, what that means is, that they're going to get their labs every month and then they're going to get the therapy through the specialty pharmacy. And then just I'll add one additional detail is we have just a couple of specialty pharmacies, and they're going to go through the similar process, read the label, be informed, read the prescriber pharmacy guide and then give their contact details and then attest that they're going to follow this process.

這與患者的過程相同。他們提供了他們的聯繫方式，聲明他們已被告知整體風險、收益，並且他們將遵循該流程。對於患者來說，這意味著他們每個月都要進行化驗，然後他們將通過專業藥房接受治療。然後我要添加一個額外的細節，我們只有幾家專業藥房，他們將經歷類似的過程，閱讀標籤，被告知，閱讀處方藥房指南，然後提供他們的聯繫方式然後證明他們將遵循這個過程。

Yes, let me build on what Jula said and thanks, Greg, for that question. Before giving you a little more details on the mechanistics of the Travere TotalCare patient services, I think it's good to realize the high need for these patients. And that's the reason why we have accelerated approval in the first place. We have to realize this is a younger patient population and it's often diagnosed in the late teens or early 20s. Half of those patients progress to kidney failure within 11 years, as Jula mentioned in the prepared remarks. So that means that a lot of those patients will end up in dialysis in their midst of their productive lives.

是的，讓我以 Jula 所說的為基礎，感謝格雷格提出這個問題。在向您詳細介紹 Travere TotalCare 患者服務的機制之前，我認為了解這些患者的高需求是件好事。這就是我們首先加速批准的原因。我們必須意識到這是一個年輕的患者群體，而且通常在十幾歲或二十出頭時被診斷出來。正如 Jula 在準備好的評論中提到的那樣，這些患者中有一半在 11 年內發展為腎衰竭。因此，這意味著許多患者將在他們富有成效的生活中最終接受透析。

When we talk about the REMS and the early responses we have seen so far, and this is still early days, it's day 4 of promoting FILSPARI, but early response from nephrologists confirm that they don't have alternative treatment options today for these patients as they have still ACEs and ARBs and still it is not an option. So once nephrologists understand the efficacy and safety profile of FILSPARI, they appreciate the simple procedure of the REMS enrollment and they focus back to the clinical value that FILSPARI may have for their patients.

當我們談論 REMS 和我們迄今看到的早期反應時，現在仍處於早期階段，現在是推廣 FILSPARI 的第 4 天，但腎病學家的早期反應證實他們今天對這些患者沒有其他治療選擇，因為他們仍然有 ACE 和 ARB，但這仍然不是一個選擇。因此，一旦腎病學家了解了 FILSPARI 的療效和安全性，他們就會欣賞 REMS 登記的簡單程序，並重新關注 FILSPARI 可能對患者產生的臨床價值。

I think you have talked already about like what the physician as well as the specialty pharmacist will be doing, but I will also say that within Travere TotalCare, we provide the services to make this process as convenient as possible for both physicians with specialty pharmacists and especially the patients.

我想你已經談到了醫生和專業藥劑師將做什麼，但我還要說的是，在 Travere TotalCare 中，我們提供的服務使這個過程盡可能方便醫生和專業藥劑師和特別是病人。

Great. That's really helpful. And then could you remind us how many IgAN patients are treated by community nephrologists and how this has influenced your launch strategy?

偉大的。這真的很有幫助。然後您能否提醒我們社區腎病學家治療了多少 IgAN 患者，這對您的啟動策略有何影響？

So the far majority of those patients are being treated by the community nephrologists. And we have plans for that as well. That's why I mentioned in the call last week that we will be consistently calling on about 6,000 nephrologists to cover about 85% of the patient potential.

因此，這些患者中的絕大多數正在接受社區腎髒病學家的治療。我們也有這方面的計劃。這就是為什麼我在上週的電話會議中提到，我們將持續呼籲約 6,000 名腎病學家來覆蓋約 85% 的潛在患者。

We will take our next question from the line of Maury Raycroft from Jefferies.

我們將從 Jefferies 的 Maury Raycroft 那裡回答我們的下一個問題。

When you did your most recent market research at the end of last year and asked about intent to prescribe in 6 months or 1 year of launch, I'm wondering if you tested key aspects of the label in your market research.

當您在去年年底進行最近的市場調查並詢問在上市後 6 個月或 1 年內開處方的意圖時，我想知道您是否在市場調查中測試了標籤的關鍵方面。

Thanks, Maury for that great question. Peter, would you like to take that?

謝謝，Maury 提出了這個很好的問題。彼得，你願意接受嗎？

Yes, absolutely. And thanks, Maury, for that question. So we have done consistent market research and that also consolidated by external research, for example, by syndicated market research. It was quite surprising to me like that, their intent to prescribe did not change after we announced the liver monitoring REMS, that intent to prescribe remained 90%. And we just did -- I just saw a result actually this week of the latest profile, The Label. And again, the intent to prescribe came in at 88%. So very consistent at around 90% prescription in the first year and about 70% intent to prescribe in the first 6 months. So they didn't really meaningfully change.

是的，一點沒錯。感謝 Maury 提出這個問題。因此，我們進行了一致的市場研究，並且還通過外部研究（例如聯合市場研究）進行了整合。令我感到非常驚訝的是，在我們宣布肝臟監測 REMS 後，他們的開藥意願沒有改變，開藥意願保持在 90%。我們剛剛做了——我剛剛在本週看到了最新簡介 The Label 的結果。同樣，開處方的意圖達到了 88%。因此非常一致，第一年約 90% 的處方和前 6 個月約 70% 的處方意向。所以他們並沒有真正有意義的改變。

Got it. And Peter, you highlighted some of the plans around doctor education efforts. Can you talk about where the most challenging learning curves will be? And how will you message around eGFR to doctors?

知道了。彼得，你強調了一些圍繞醫生教育工作的計劃。你能談談最具挑戰性的學習曲線在哪裡嗎？您將如何向醫生傳達有關 eGFR 的信息？

Yes, absolutely. I mean it's early days, as I mentioned it's day 4 -- but what we see so far, what I'm hearing from our field reps, there is great excitement for the promise of FILSPARI. In fact, I got a text yesterday from one of our camps saying who has been in the field for 30 years. Saying that he has never seen this level of excitement among nephrologists. So I think there is a certain level of excitement to learn about the profile of FILSPARI. And proteinuria is often the market that physicians are measuring on a monthly basis and also how they monitor progression of disease and how they change their treatment plan. So the [conversational] eGFR has not come up yet in many of those conversations. They understand it's an ongoing trial and they are excited to learn more about the FILSPARI profile over time.

是的，一點沒錯。我的意思是，現在還處於早期階段，正如我提到的，現在是第 4 天——但到目前為止，我們所看到的，以及我從我們的現場代表那裡聽到的，都對 FILSPARI 的承諾感到非常興奮。事實上，我昨天從我們的一個營地收到一條短信，說誰已經在這個領域工作了 30 年。說他從未在腎病專家中看到過這種程度的興奮。所以我認為了解 FILSPARI 的概況會有一定程度的興奮。蛋白尿通常是醫生每月測量的市場，也是他們監測疾病進展和改變治療計劃的方式。因此，[對話] eGFR 在許多對話中尚未出現。他們知道這是一項持續的試驗，他們很高興隨著時間的推移了解更多關於 FILSPARI 資料的信息。

Our next question comes from the line of Joseph Schwartz with SVB Securities.

我們的下一個問題來自 SVB 證券公司的 Joseph Schwartz。

I have a question on IgA nephropathy and then FSGS. So how do you expect the rate of FILSPARI uptake to differ, if at all, amongst patients treated at academic versus community nephrology centers? And beyond those segments, are there any other particular physician demographics that you expect to be earlier or later adopters?

我有一個關於 IgA 腎病和 FSGS 的問題。那麼，在學術和社區腎病中心接受治療的患者中，您認為 FILSPARI 攝取率有何不同（如果有的話）有何不同？除了這些細分市場之外，您是否希望有任何其他特定的醫生人口統計數據成為較早或較晚的採用者？

Joe, thank you very much for the great question. Peter, I'll pass that over to you.

喬，非常感謝你提出這個很好的問題。彼得，我會把它轉交給你。

Yes, very timely question, Joe, because this was also part of the market research that I was just referencing. So I saw that yesterday. Very interesting, the utilization, the intended utilization for FILSPARI is basically similar across community nephrologists as it is in academic nephrology. So we will see how that materializes over time, but the intent to prescribe is quite similar among those 2 specialty categories.

是的，非常及時的問題，喬，因為這也是我剛才提到的市場研究的一部分。所以我昨天看到了。非常有趣的是，FILSPARI 的使用和預期使用在社區腎髒病學家中與在學術腎髒病學中基本相似。所以我們將看到隨著時間的推移它是如何實現的，但在這兩個專業類別中開處方的意圖非常相似。

Thanks, Peter. Maybe if I could just add, Joe, one of the things that we are reflecting in our launch plans, and Peter's team has done a fantastic job is really helping to understand not just those 6,000 for targeting but also the segments to make sure that we recognize who are those physicians that have through their behavior adopted recent innovation more quickly. There are sort of early adopters versus late adopters.

謝謝，彼得。也許我可以補充一點，Joe，我們在發布計劃中反映的一件事，Peter 的團隊做得非常出色，這真的有助於了解不僅是那 6,000 個目標，而且還包括細分市場，以確保我們認識到那些通過他們的行為更快地採用最新創新的醫生是誰。有早期採用者和晚期採用者之分。

And so our team is making sure that we're very much focusing our efforts in the first part of launch. -- on those clinicians that we would see as early adopters, very similar to many other launches. So I think it's not just about academic versus community, but it's also a number of patients and, as I say, behavior such as adoption of recent rare renal launches.

因此，我們的團隊確保我們在發布的第一部分非常集中精力。 ——關於那些我們將視為早期採用者的臨床醫生，與許多其他發布非常相似。所以我認為這不僅僅是關於學術與社區的問題，它也是一些患者的問題，而且正如我所說，還有諸如採用最近罕見的腎臟發射等行為。

If I may build on that, Eric, I just mentioned that we will be consistently calling about 6,000 nephrologists. So maybe to give you a little more context how we go to those 6,000. It's really based on 3 different segmentation and targeting assessment that we did. One was based on patient volume. One was based on behavior, in particular on new product utilization to really get to those in early adopters. And the third one is to influence on the nephrology community. So we have a very clear way to target and segment those physicians that we see as most valuable in the prescription process to get to that broad patient population.

埃里克，如果我可以以此為基礎，我剛才提到我們將持續拜訪大約 6,000 名腎病學家。因此，也許可以為您提供更多背景信息，了解我們如何處理這 6,000 人。它實際上基於我們所做的 3 種不同的細分和目標評估。一個是基於患者數量。一個是基於行為，特別是新產品的使用，以真正吸引那些早期採用者。第三個是對腎髒病學界的影響。因此，我們有一種非常明確的方法來定位和細分那些我們認為在處方過程中最有價值的醫生，以接觸到廣泛的患者群體。

Very interesting. And then for the FSGS data next quarter, how should we be thinking about the bar for success in terms of eGFR difference? What is the overlap between what's clinically meaningful and the bar for approval. How does that look? And do you have any specific guidance from the FDA that says what you need to achieve there in order to be able to file for approval?

很有意思。然後對於下個季度的 FSGS 數據，我們應該如何考慮 eGFR 差異方面的成功標準？具有臨床意義的內容與批准門檻之間的重疊是什麼？那看起來怎麼樣？您是否有來自 FDA 的任何具體指導說明您需要在那裡實現什麼才能申請批准？

Sure. Thank you, Joe, for the question. I'll turn Jula first to you on the clinical relevance of an eGFR treatment effect and where we would see success. And then Bill, you can share insights and expectations from a regulatory perspective.

當然。喬，謝謝你提出這個問題。我將首先向 Jula 介紹 eGFR 治療效果的臨床相關性以及我們將在哪些方面取得成功。然後 Bill，你可以從監管的角度分享見解和期望。

Certainly. Thanks for the question. I think it's important to note that we saw a clinically meaningful and significant reduction in proteinuria in FSGS that should translate into a significant treatment effect on eGFR. And if you look historically at other trials looking at a difference in eGFR slope, most of them, I mean, if you look at the SGLT2 inhibitor data the difference in slope that's clinically meaningful for showing a long-term kidney protection is anywhere in the range from 0.75 to 1 ml per minute difference.

當然。謝謝你的問題。我認為重要的是要注意，我們看到 FSGS 中蛋白尿的臨床意義和顯著減少應該轉化為對 eGFR 的顯著治療效果。而且，如果您從歷史上看其他研究 eGFR 斜率差異的試驗，我的意思是，如果您查看 SGLT2 抑製劑數據，對於顯示長期腎臟保護具有臨床意義的斜率差異在任何地方都存在每分鐘差異從 0.75 到 1 毫升不等。

And so we powered the trial appropriately to show both a clinically meaningful and a statistically significant difference based on the proteinuria reduction that we've seen to date.

因此，我們適當地推動了試驗，以顯示基於我們迄今為止所見蛋白尿減少的臨床意義和統計學上的顯著差異。

Yes. I think when I think about it from a regulatory perspective -- yes, this is Bill. From a regulatory perspective, it lines up pretty closely with what is clinically meaningful. We've seen tolvaptan was approved with a 0.75 difference. So the agency is clearly recognizing what Jula is talking about. And with the therapy that's treated for years, a consistent therapy, a small difference in mls per minute has a very large impact on time to progression or if you're looking at time to renal replacement or need for dialysis, impact is really quite significant even with small differences in eGFR slopes.

是的。我認為，當我從監管角度考慮時——是的，我是比爾。從監管的角度來看，它與臨床意義非常接近。我們已經看到托伐普坦以 0.75 的差異獲得批准。因此，該機構清楚地認識到 Jula 在說什麼。並且經過多年的治療，一致的治療，每分鐘毫升數的微小差異都會對進展時間產生非常大的影響，或者如果您正在尋找進行腎臟置換或需要透析的時間，影響確實非常顯著即使 eGFR 斜率的差異很小。

We will take the next question from the line of Tim Lugo from William Blair.

我們將從 William Blair 的 Tim Lugo 那裡接聽下一個問題。

This is Lachlan for Tim. First, I guess, maybe for Chris, I was just wondering if we should expect any stocking dynamics for the next month I guess? Or yes, they're not much stocking at the specialty pharmacies. And then second one quickly, just we noticed that there's a late breaker at WCN. Can you give any color on what will be presented there or will new data that's not in the label be presented in that presentation?

這是蒂姆的拉克蘭。首先，我想，也許對於克里斯來說，我只是想知道我們是否應該期待下個月的任何庫存動態？或者是的，專業藥店的存貨不多。然後是第二個，我們注意到 WCN 有一個遲到的 breaker。您能否為將在那裡呈現的內容提供任何顏色，或者標籤中沒有的新數據是否會在該演示文稿中呈現？

All right. Chris, why don't you take that? Do look and cover WCN?

好的。克里斯，你為什麼不接受呢？看看並報導 WCN 嗎？

Sure. Thanks for the question, Lachlan. So with our distribution model, you really shouldn't expect to have any kind of meaningful stocking. And really when we get to stable state here, which we expect it to be somewhere in the range of a week or 2 weeks at most. So not much of a dynamic there to work through. At the beginning, there will be a little bit, but not really much at stable state.

當然。謝謝你的問題，拉克蘭。因此，使用我們的分銷模式，您真的不應該期望有任何有意義的庫存。實際上，當我們在這里達到穩定狀態時，我們預計它最多會在一周或兩週的範圍內。所以沒有太多的動態可以解決。一開始會有一點點，但在穩定狀態下真的不多。

Yes. And thanks. We're really excited to be able to present our data at WCN. Next month, you can expect to see additional efficacy data as well as our safety data. We will not be releasing our eGFR data as we have agreement with the FDA that we won't release that until we complete the clinical trial. But we're really excited to be able to present that to the nephrology community.

是的。謝謝。我們真的很高興能夠在 WCN 上展示我們的數據。下個月，您可以期待看到更多的療效數據以及我們的安全數據。我們不會發布我們的 eGFR 數據，因為我們與 FDA 達成協議，我們不會在完成臨床試驗之前發布該數據。但我們真的很高興能夠將其呈現給腎髒病學界。

We will take the next question from the line of Do Kim with Piper Sandler.

我們將接聽 Do Kim 和 Piper Sandler 的下一個問題。

A question on the Phase III DUPLEX study in FSGS. When we look at or think about the eGFR slope, it is in the 108-week data readout, could we use the DUET extension study and the slope that was calculated for there as a good estimate. And when you calculate the slope of the eGFR curve, what time points do you look at? I know for DUET, you were looking starting at day 42 to week 108, -- just wanted to know where the starting point is?

關於 FSGS 中 III 期 DUPLEX 研究的問題。當我們查看或考慮 eGFR 斜率時，它是在 108 週的數據讀數中，我們是否可以使用 DUET 擴展研究和為此計算的斜率作為一個很好的估計。而當你計算eGFR曲線的斜率時，你會看哪些時間點？我知道對於 DUET，您正在尋找從第 42 天到第 108 週的時間——只是想知道起點在哪裡？

Do, thanks for the question. I'd say we certainly do feel that there is a parallel between what we have seen in DUET and what we expect to see and how we designed DUPLEX. I'll turn the question to you on. Sorry, I'm getting a little feedback. But I'll turn the question to you on how we might expect to see the slopes for sparsentan, but also perhaps natural history given that we didn't have a long-term follow-up of our active comparator in that trial.

做，謝謝你的問題。我想說我們確實覺得我們在 DUET 中看到的與我們期望看到的以及我們設計 DUPLEX 的方式之間存在相似之處。我會把問題轉給你。抱歉，我收到一點反饋。但我會把問題轉給你，關於我們如何期望看到 sparsentan 的斜率，但也可能是自然歷史，因為我們在該試驗中沒有對我們的活性比較器進行長期隨訪。

Yes. I think the long-term data that we've received from DUET shows kidney preservation compared to what we would expect to see in long term for patients who are at high risk of progression with primary FSGS. I would say historically, those patients can progress more at a rate of greater than 5 ml per minute, more like 7, 8, 9, 10 mls per minute per year, and we saw less than that in our long-term eGFR data that we presented last year at ASN. And then in particular, in patients who achieve complete remission, we saw significant preservation in those patients with regards to long-term eGFR slope. I don't know if there's any additional granularity you'd like me to provide around that.

是的。我認為我們從 DUET 收到的長期數據顯示，與我們預期長期看到的原發性 FSGS 進展風險高的患者相比，腎臟得到了保護。我想說，從歷史上看，這些患者的進展速度可以超過每分鐘 5 毫升，更像是每年每分鐘 7、8、9、10 毫升，而我們在長期 eGFR 數據中看到的比這少我們去年在 ASN 上展示過。然後特別是，在實現完全緩解的患者中，我們看到這些患者在長期 eGFR 斜率方面有顯著的保留。我不知道您是否希望我提供任何額外的細節。

Just wanted to see how the slope is calculated. Do you look at the slope of the curve from the beginning of the study out to 108 weeks? I know it's not a difference of a moment in time at week 108, but just the overall slope of the curve.

只是想看看斜率是如何計算的。您是否查看從研究開始到 108 週的曲線斜率？我知道這不是第 108 週的時間差異，而是曲線的整體斜率。

You do look at the total data from the very beginning, all the way to the steady end. And that's what's so great about looking at the slope. You use every single data point for all patients to look at the trajectory of the curve and we will look at the total slope which is from the very beginning all the way to the end and wait all the data equally as well as chronic slope, which looks more after 6 weeks to the study end to minimize the effect of the acute hemodynamic effect.

你確實從一開始就查看了總數據，一直到穩定的結束。這就是看斜坡的好處。您使用所有患者的每個數據點來查看曲線的軌跡，我們將查看從一開始一直到結束的總斜率，並等同地等待所有數據以及慢性斜率，這6 週後到研究結束時看起來更多，以盡量減少急性血液動力學效應的影響。

Great. That's helpful. And a quick question for Chris. How will you account for the FILSPARI royalty to ligand in the income statement?

偉大的。這很有幫助。還有一個簡短的問題要問 Chris。您將如何在損益表中核算配體的 FILSPARI 特許權使用費？

Thanks for the question. We'll be updating that when we report 1Q, so we're finalizing that now. But we'll make sure that it's clear out to you guys and being able to view the financial statements as to how exactly we're paying that.

謝謝你的問題。我們將在報告 1Q 時更新它，所以我們現在正在完成它。但我們會確保你們清楚，並且能夠查看財務報表，了解我們到底是如何支付的。

We'll take the next question from the line of Liisa Bayko with Evercore ISI.

我們將接受來自 Evercore ISI 的 Liisa Bayko 的下一個問題。

I think most of my questions have been answered. But I guess I would just ask what's your level confidence for a good outcome in the upcoming FSGS final data? Maybe you can just explain that level of confidence? Are you highly confident, kind of hopeful, but moderate, not so confident. Just curious on how you're thinking about it getting a ton of questions on FSGS these days.

我想我的大部分問題都得到了回答。但我想我只想問一下，您對即將發布的 FSGS 最終數據取得良好結果的信心水平是多少？也許你可以解釋一下這種信心水平？你是否非常自信，有點充滿希望，但適度，不那麼自信。只是好奇你是如何考慮這些天在 FSGS 上收到大量問題的。

Sure. Yes, Liisa, thank you very much for the question. We certainly are excited about this upcoming data readout next quarter. I would say that we remain confident in the outcome, and that's largely because the way that we designed the trial was based on showing a robust and statistically significant superiority on proteinuria that then would predict out to eGFR.

當然。是的，Liisa，非常感謝你提出這個問題。我們當然對下個季度即將公佈的數據感到興奮。我要說的是，我們對結果仍然充滿信心，這主要是因為我們設計試驗的方式是基於在蛋白尿方面顯示出強大且具有統計學意義的優勢，然後可以預測出 eGFR。

And certainly, as we've looked at the way that the trial is conducted, the number of patients that we've retained in the trial, all of those things that we look at to ensure that the study is being conducted as we had hoped is there. I'll turn it over to Jula, maybe, Bill, if you have any further thoughts on why we remain confident and really what does that look like coming out of the 2-year results.

當然，當我們研究了試驗的進行方式、我們在試驗中保留的患者數量時，我們研究的所有這些都是為了確保研究按我們希望的方式進行有沒有。我會把它交給朱拉，也許，比爾，如果你有任何進一步的想法，為什麼我們仍然充滿信心，以及從 2 年的結果來看，這到底是什麼樣子。

Yes. I'll just continue on with what Eric was saying. We see clinically capable and statistically significant separation and reduction in proteinuria with sparsentan versus irbesartan. And I would say importantly, when we met with the FDA, they said the study is designed can support traditional approval. And so that also what gives us the confidence that we will be able to achieve what we have set out. We powered the study appropriately. We -- as Eric said, we continue to have a significant number of patients to be able to achieve our endpoint and we had separation (inaudible) or to show the treatment effect on eGFR. And we'll also be going under -- or maybe I handover to Bill to talk about looking at an sNDA versus accelerated approval. It's a very different situation. Bill, do you want to add color around that?

是的。我將繼續 Eric 所說的內容。我們看到 sparsentan 與厄貝沙坦相比具有臨床能力和統計學意義的蛋白尿分離和減少。我要說的是重要的是，當我們與 FDA 會面時，他們說這項研究的設計可以支持傳統的批准。因此，這也使我們有信心能夠實現我們所設定的目標。我們適當地推動了這項研究。我們——正如埃里克所說，我們繼續有大量患者能夠實現我們的終點，我們有分離（聽不清）或顯示對 eGFR 的治療效果。我們也將陷入困境——或者我可能會交給 Bill 來討論查看 sNDA 與加速批准的問題。這是一個非常不同的情況。比爾，你想在它周圍添加顏色嗎？

Sure. I think that when you're in the position as the agency on accelerated approval, they've demonstrated that they approach it very deliberately and somewhat conservatively because you have a partial data set both for safety and for efficacy.

當然。我認為，當你作為加速批准的機構時，他們已經證明他們非常謹慎地並且有點保守地處理它，因為你有部分數據集用於安全性和有效性。

At the end of the study, it's a much more traditional approval. So that's helpful and that we aren't asking them at that point to take regulatory risk and their ability to be more flexible is there in looking at the totality of the data. I think the other additional element is last Friday's approval of FILSPARI means that we're now looking at an additional indication for a drug that's already approved, both safe and efficacious.

在研究結束時，這是一種更為傳統的認可。所以這很有幫助，而且我們當時並沒有要求他們承擔監管風險，而且他們在查看數據的整體性時更加靈活。我認為另一個額外的因素是上週五 FILSPARI 的批准意味著我們現在正在尋找一種已經獲得批准的藥物的額外適應症，既安全又有效。

So I think that puts it in a different frame from a regulatory standpoint when compared with an interim analysis under Subpart H accelerated approval.

因此，我認為，與 H 子部分加速批准下的中期分析相比，從監管的角度來看，它處於不同的框架中。

That's a really good point. Thanks for mentioning that.

這是一個非常好的觀點。謝謝你提到這一點。

We'll take the next question from the line of Carter Gould with Barclays.

我們將從 Carter Gould 與 Barclays 的對話中回答下一個問題。

I guess the first -- I guess the first half is on the top line FSGS data in 2Q. I guess, how much data is going to be in that top line release? Are we going to have -- see enough data that we can assess the clinical significance for that? Or are you going to prioritize saving that data for a medical meeting? And then I guess maybe alongside that, Peter and Jula, when you think about that data coming out, to what extent do you think nephrologists may read through from potentially positive eGFR data in FSGS to IgAN and potentially pulling forward some of the demand in that launch?

我猜是第一個——我猜上半年是第二季度 FSGS 數據的頂線。我想，該頂線發布中將包含多少數據？我們是否會看到足夠的數據來評估其臨床意義？還是您要優先保存該數據以用於醫療會議？然後我想也許與此同時，Peter 和 Jula，當您考慮這些數據時，您認為腎病學家可能在多大程度上從 FSGS 中潛在的陽性 eGFR 數據通讀到 IgAN 並可能推動其中的一些需求發射？

Carter, thanks for the question. Jula, why don't you take the top line, what the team is thinking and any potential read-through? And then Peter, you can add your thoughts.

卡特，謝謝你的提問。 Jula，你為什麼不說說最重要的，團隊在想什麼以及任何可能的通讀？然後彼得，你可以添加你的想法。

Well, it's a great question. I mean, we'll have a trial that's completed. So we're not limited with regards to keeping data. However, it's a balance because we do want to have a very high tiered publication and presentation at an important meeting, but we will be able to release the eGFR data, our total -- whether we give you all the curves and all the additional data, we're going to have to make that decision probably pretty soon, but at least enough to give you confidence about the results of the trial.

嗯，這是一個很好的問題。我的意思是，我們將完成一項試驗。所以我們在保存數據方面不受限制。然而，這是一個平衡，因為我們確實希望在一次重要會議上有一個非常高層次的出版物和演示，但我們將能夠發布 eGFR 數據，我們的總數——我們是否給你所有的曲線和所有額外的數據，我們可能很快就會做出決定，但至少足以讓您對試驗結果充滿信心。

With regards to the nephrologists and the read-through, I would point through to the SGLT2 inhibitor data, where we don't necessarily see the same magnitude and treatment effect in one disease versus the other with regards to the endpoint of 40% decline in eGFR kidney failure, dialysis and transplant. Each disease is quite different.

關於腎病學家和通讀，我會指出 SGLT2 抑製劑數據，我們不一定會看到一種疾病與另一種疾病在 40% 下降終點方面具有相同的幅度和治療效果eGFR 腎功能衰竭、透析和移植。每種疾病都大不相同。

And even though the drug you might think should work across the board with regards to one or the other, it may not for a number of different reasons, whether it's the underlying disease, the heterogeneity, the patient population studied and other things. So I wouldn't say that there's necessarily going to be carried through from one or the other depending on the magnitude of the treatment effect or what we see there.

即使您可能認為這種藥物應該在其中一個方面全面發揮作用，但由於多種不同的原因，無論是潛在的疾病、異質性、所研究的患者群體還是其他因素，它可能並非如此。因此，我不會說根據治療效果的大小或我們在那裡看到的情況，必然會從一個或另一個中進行。

Peter, do you want to make other comments around that?

彼得，你想就此發表其他評論嗎？

No. Let me echo what you said. I think it's right those patient profiles are quite different. The way I think about it, Carter, is really excited that we have that continuous data stream and has something continuously to talk about with the physician. And I think they only built the excitement for FILSPARI. So it is -- in that aspect, it's almost like a continuing launch with new data and new approvals coming in the next year.

不，讓我重複你說的話。我認為這些患者的情況完全不同是正確的。卡特，我的想法是，我們擁有持續不斷的數據流，並且有持續不斷的事情可以與醫生討論，這讓我感到非常興奮。而且我認為他們只是為 FILSPARI 製造了興奮。所以它是——在這方面，它幾乎就像是在明年繼續推出新數據和新批准。

We will take the question from the line of Mohit Bansal with Wells Fargo.

我們將從 Mohit Bansal 與 Wells Fargo 的對話中回答這個問題。

This is Adam on for Mohit. Is it fair to say that you prescribe information for FILSPARI, the specificity on UPCR and class effects compared to the FDA label during nephrology approvals? And then separately, could the EU preserves be better equipped to do any monitoring that they would conduct due to a greater share of doctors practicing in academic centers?

這是 Mohit 的 Adam。可以公平地說，你們在腎髒病學批准期間為 FILSPARI 開具了信息、UPCR 的特異性和與 FDA 標籤相比的類別效應嗎？然後，由於在學術中心執業的醫生比例更大，歐盟保護區能否更好地進行監測？

Adam, thanks so much for the question. Let me clarify the first question around the label. Are you asking just the level of detail and data that we have on UPC in our label compared to others? I want to make sure that I answer the right question.

亞當，非常感謝你提出這個問題。讓我澄清有關標籤的第一個問題。與其他標籤相比，您是否只是在詢問我們標籤中 UPC 的詳細程度和數據？我想確保我回答了正確的問題。

No, I'm asking for the approval in Europe that when you would ultimately get put in that geography ultimately, whether it have the same specificity on what you UPCR ranges of patients you treat as well as some of the safety detail potentially could be heavier in the U.S. label relative to what the past your labels have looked like?

不，我要求歐洲批准，當你最終被安置在那個地區時，它是否對你治療的患者的 UPCR 範圍具有相同的特異性，以及一些可能更重的安全細節在美國的標籤相對於過去你們的標籤是什麼樣子的？

Okay. Got it. Bill, maybe we can turn that to you. I mean, certainly, we won't be able to speak to specifics on the European label, given that we're still in that process. But Bill, maybe you can give some thoughts on how the labeling may vary across regions.

好的。知道了。比爾，也許我們可以把它交給你。我的意思是，當然，鑑於我們仍在該過程中，我們將無法談論歐洲標籤的具體細節。但是比爾，也許你可以就標籤在不同地區的差異提出一些想法。

Yes. No, thanks for the question. And you're right, Eric. It's a speculative answer because we're in process with the review with EMA. It's important to realize they're looking at the same data set. The filing for one doesn't contain different data from the filing for the U.S. FDA, NDA, but they do have differences in how they present data, how they treat data. For example, there isn't such a thing as a REMS in Europe. They treat risks in a different fashion.

是的。不，謝謝你的提問。你是對的，埃里克。這是一個推測性的答案，因為我們正在與 EMA 進行審查。重要的是要意識到他們正在查看相同的數據集。一個文件與美國 FDA、NDA 的文件不包含不同的數據，但它們在如何呈現數據、如何處理數據方面確實存在差異。例如，歐洲沒有 REMS 這樣的東西。他們以不同的方式對待風險。

I think it's -- we don't have indication at this point in the review of any great differences between the agencies, but it's too early to really be definitive on anything. So we look forward to that, updating you on that in the future.

我認為這是 - 我們目前在審查機構之間的任何重大差異時沒有跡象表明，但現在就任何事情做出決定還為時過早。因此，我們期待著這一點，並在未來為您更新。

Peter, do you want to take any thoughts on the -- any difference in practice based on patients being seen more predominantly in academic centers in Europe and how that might play out?

彼得，你是否想考慮一下——基於患者主要在歐洲學術中心就診的實踐中的任何差異以及這可能如何發揮作用？

Having had the experience to be in Europe as European. I think it is generally right. I mean it depends country by country. I think, the standard of care, I think, generally is more established in Europe. I think overall, you see higher eGFR levels for patients that are being referred to nephrologists. I think that is generally right, it depends very much market to market.

有過作為歐洲人在歐洲的經歷。我覺得大體上是對的。我的意思是這取決於國家/地區。我認為，我認為，護理標准通常在歐洲更為成熟。我認為總體而言，您會看到轉介給腎病學家的患者的 eGFR 水平更高。我認為這通常是正確的，這在很大程度上取決於市場。

We will take the next question from the line of Laura Chico with Wedbush Securities.

我們將從 Wedbush Securities 的 Laura Chico 那裡接聽下一個問題。

I've got 2. One first on the clinical and I guess our own market research has shown about 20%, 25% of IgAN patients are now receiving SGLT2 inhibitors. And I'm not sure if Jula or Peter could comment of the patients that are on an SGLT2 inhibitor, what proportion of those remain over a gram on proteinuria?

我有 2 個。第一個在臨床上，我想我們自己的市場研究表明大約 20%，25% 的 IgAN 患者現在正在接受 SGLT2 抑製劑。而且我不確定 Jula 或 Peter 是否可以評論使用 SGLT2 抑製劑的患者，其中有多少比例的蛋白尿仍然超過 1 克？

All right. Who would like to take that question.

好的。谁愿意回答這個問題。

Yes, I'm happy to kick that off. And Laura, I think your mode of research findings are quite consistent to what we have found as well. I think one of the important things to mention is, what Jula mentioned on the call earlier as well. SGLT2 has the outcome data but does not have the profound proteinuria-reducing effect as FILSPARI. And the nephrologist, I have been speaking to as well as what we saw in market research, they're very excited about the complementary mechanism of FILSPARI versus SGLT2.

是的，我很高興開始。勞拉，我認為你的研究結果模式也與我們的發現非常一致。我認為值得一提的重要事情是，Jula 在早些時候的電話會議上也提到過。 SGLT2 有結果數據，但沒有 FILSPARI 那樣顯著的蛋白尿減少作用。腎病學家，我一直在和我們在市場研究中看到的一樣，他們對 FILSPARI 與 SGLT2 的互補機制感到非常興奮。

And they're excited about the novel and non-immunosuppressive combination approach that they may have now. And additionally, I think also, Jula can talk more about it, is the complementary profile of SGLT2 with regards to sodium excretion and the diuretic effect. Jula, I think probably you can speak in more detail on that.

他們對他們現在可能擁有的新穎的非免疫抑制組合方法感到興奮。此外，我認為 Jula 還可以多談談它，它是 SGLT2 在鈉排泄和利尿作用方面的互補特徵。 Jula，我想你可以更詳細地談談這個問題。

Yes, I would agree with that. Probably excited to use them in complementary mechanism -- the most interesting combination that they're interested in using together is SGLT2 inhibitors plus sparsentan due to the complementary mechanism of action of SGLT2 if we don't know how they're kidney protective exactly, but you do have the tubular glomerular feedback that helps to enhance sodium excretion. And we know that sparsentan has a direct benefit on the glomerulus, the podocyte, the tubular interstitium to have that kidney protection reducing proteinuria. And the magnitude of proteinuria is significantly greater with sparsentan.

是的，我同意這一點。可能很高興在互補機制中使用它們——他們有興趣一起使用的最有趣的組合是 SGLT2 抑製劑加 sparsentan，因為 SGLT2 的互補作用機制如果我們不知道它們是如何保護腎臟的，但是你確實有有助於增強鈉排泄的管狀腎小球反饋。我們知道 sparsentan 對腎小球、足細胞、腎小管間質有直接的好處，可以保護腎臟，減少蛋白尿。 sparsentan 蛋白尿的嚴重程度明顯更高。

All the proteinuria data that we have with SGLT2 other than anecdotally, when you talk to nephrologists of where they get their patients. All the trials were done in patients with low levels of proteinuria, less than a gram.

我們擁有的所有關於 SGLT2 的蛋白尿數據，除了軼事，當你與腎病學家談論他們從哪裡得到他們的病人時。所有試驗都是在蛋白尿水平較低（低於 1 克）的患者中進行的。

I mean if you look at the DAPA-CKD, [EMPA] kidney, they were relatively low levels. So they tend to be used in kind of later stage in general. So we don't have the more high-risk patient profile to tell you what proportion get under a gram. But I think the vast majority are going to need combination therapy to really get them to where we want the less than the gram and even further, the complete remission patient, where you can get them under than 0.3 grams to get them to that really lower-risk patient profile.

我的意思是，如果你看一下 DAPA-CKD、[EMPA] 腎臟，它們的水平相對較低。因此，它們通常傾向於在後期階段使用。所以我們沒有更高風險的患者資料來告訴你低於一克的比例。但我認為絕大多數人將需要聯合治療才能真正讓他們達到我們想要的低於克的水平，甚至更進一步，完全緩解患者，在那裡你可以讓他們低於 0.3 克，使他們達到真正更低的水平- 風險患者概況。

You talking through the -- sorry, Laura, it might be worth, Jula, just speaking to some of the data that we would expect to have next year from the study that we have because I think, Laura, it would be useful to be able to see those data in a clinical setting in the trials that we are doing.

你在談論——抱歉，勞拉，這可能是值得的，朱拉，只是談談我們希望明年從我們的研究中獲得的一些數據，因為我認為，勞拉，這將是有用的能夠在我們正在進行的試驗中的臨床環境中查看這些數據。

Yes. I think, Laura, we already do have a drug-drug interaction that shows that we can safely combine. And then additionally, we're going to have 2 types of combination studies, one, where you've got patients on sparsentan and you add an SGLT2 inhibitor and the other of the opposite direction where patients are on an SGLT2 inhibitor, and we add sparsentan. And we'll have safety data and we'll have proteinuria and efficacy and then eGFR data, and we'll have that information on that next year.

是的。我想，勞拉，我們已經有了藥物相互作用，表明我們可以安全地結合。此外，我們將進行兩種類型的聯合研究，一種是讓患者服用 sparsentan 並添加 SGLT2 抑製劑，另一種是相反方向的患者服用 SGLT2 抑製劑，我們添加稀疏的。我們將獲得安全數據，我們將獲得蛋白尿和療效，然後是 eGFR 數據，我們將在明年獲得這些信息。

We are certainly looking forward to that. And then maybe one follow-up question on the financial. Chris, I heard you mention cash runway well into '24. I believe I heard correctly. Could you talk a little bit more about the flexibility on the balance sheet for extending runway? I know they're a milestone payment due to Ligand and Bristol, but any other inbound milestones that we should be considering in terms of our modeling?

我們當然對此充滿期待。然後可能是一個關於財務的後續問題。克里斯，我聽說你提到 24 年的現金跑道。我相信我沒有聽錯。您能否多談談資產負債表上用於延長跑道的靈活性？我知道這是 Ligand 和 Bristol 的里程碑付款，但是我們在建模方面應該考慮的任何其他入境里程碑？

Yes. Thanks for that question, Laura. So when I think about the balance sheet and specifically to the milestones, we have some that would be coming in potentially for things like regulatory approvals in Europe. And then also, we will have some coming out for things like pegtibatinase advancing, right? So there may be a net effect to those.

是的。謝謝你提出這個問題，勞拉。因此，當我考慮資產負債表，特別是里程碑時，我們有一些可能會用於歐洲監管批准等事情。然後，我們也會有一些像 pegtibatinase 推進這樣的事情出現，對吧？因此，這些可能會產生淨效應。

And when I think about the balance sheet overall and we look at cash burn, there certainly flexibility. There's a number of things that go into our estimate there, and we've commented in the past where we take a conservative approach, right? We're taking into account the potential for further generic erosion for Thiola. We're taking into account all the investments needed for positioning FILSPARI appropriately for IgAN and FSGS launch, et cetera. So there certainly is some flexibility in that, but we're trying to give you guys a good view as to what we expect to use for our operations going forward.

當我考慮整體資產負債表並查看現金消耗時，肯定會有靈活性。我們的估計中有很多事情，我們過去曾評論過我們採取保守的方法，對吧？我們正在考慮對 Thiola 進行進一步仿製藥侵蝕的可能性。我們正在考慮為 IgAN 和 FSGS 發布等適當定位 FILSPARI 所需的所有投資。所以這當然有一些靈活性，但我們正試圖讓你們很好地了解我們期望在未來的運營中使用什麼。

We will take the next question from the line of Alex Thompson from Stifel.

我們將從 Stifel 的 Alex Thompson 那裡接聽下一個問題。

Just maybe a quick follow-up on SGLT2 inhibitors. I guess, at this stage in the launch and based on some of your initial conversations with payers, what has been the receptivity with covering FILSPARI on top of SGLT2 prior to some of this clinical data you're going to generate next year?

也許只是對 SGLT2 抑製劑的快速跟進。我想，在發布的這個階段，根據您與付款人的一些初步對話，在明年您將生成的一些臨床數據之前，在 SGLT2 之上覆蓋 FILSPARI 的接受度如何？

Alex, thanks for the great question. Peter, would you like to take that?

亞歷克斯，謝謝你提出的好問題。彼得，你願意接受嗎？

Yes. I think, Alex, thanks for that. It's early days to comment on that. But I think we have had quite some pre-approval conversation with payers. They -- what I took away from that is that payers are not anticipating to have like a step through with SGLT2. SGLT2 has a broad label is both for diabetic and nondiabetic CKD. And it's kind of like of the rate of IgA nephropathy, particularly. So we don't anticipate that to be a road map for reimbursement for FILSPARI.

是的。我想，亞歷克斯，謝謝你。現在對此發表評論還為時過早。但我認為我們已經與付款人進行了相當多的批准前對話。他們 - 我從中得到的是，付款人並不期望通過 SGLT2 邁出一步。 SGLT2 具有廣泛的標籤，適用於糖尿病和非糖尿病 CKD。這有點像 IgA 腎病的發病率，尤其如此。因此，我們預計這不會成為 FILSPARI 報銷的路線圖。

Great. And then maybe a quick follow-up on sort of the base commercial business outside of FILSPARI. I guess with potential expansion of the Chenodal label how should we think about sort of the trajectory of that base commercial business over time? Is that a meaningful uptick in the potential opportunity? How are you thinking about that over the next few years?

偉大的。然後可能對 FILSPARI 之外的基礎商業業務進行快速跟進。我想隨著 Chenodal 標籤的潛在擴張，我們應該如何考慮隨著時間的推移該基礎商業業務的軌跡？這是潛在機會的有意義的增長嗎？您如何看待未來幾年的情況？

Sure. Peter?

當然。彼得？

Well, we're certainly excited about the extension in particular, as I think there may be more adult patients with CTX that we will have an opportunity to reach by educating the physicians. We haven't given any guidance what the upside potential is. And we may be in a better position once we see the data of the trial.

好吧，我們當然對擴展感到特別興奮，因為我認為可能會有更多成年 CTX 患者，我們將有機會通過對醫生進行教育來接觸這些患者。我們沒有給出任何上行潛力的指導。一旦我們看到試驗數據，我們可能會處於更好的位置。

We will take the next question from the line of Ed Arce with H.C. Wainwright.

我們將接受 Ed Arce 和 H.C. 的下一個問題。溫賴特。

Some have already been asked, but I did want to follow up on a point made earlier, and that is on the upcoming readout next quarter, the 2-year eGFS, the eGFR, excuse me. Just wanted to make sure I understood correctly, the primary endpoint here whether it was total slope or the other slope, I think you mentioned, started after the first 6 weeks, both of those include interval data points throughout the period, and I'm just wondering what those intervals are as well.

有些人已經被問到，但我確實想跟進之前提出的一點，那就是下個季度即將公佈的 2 年期 eGFS，eGFR，不好意思。只是想確保我理解正確，這裡的主要終點無論是總斜率還是其他斜率，我想你提到過，在前 6 週後開始，這兩個都包括整個期間的間隔數據點，我是只是想知道這些間隔是多少。

Sure. Jula, would you like to take that?

當然。朱拉，你願意接受嗎？

Yes. So we'll be looking at and -- we have agreements with the regulatory agencies on looking at the chronic slope as well as total slope, and that's an end point from the beginning of the study to week 108.

是的。因此，我們將關注並且——我們與監管機構就關注慢性斜率和總斜率達成了協議，這是從研究開始到第 108 週的終點。

And what are the measurement intervals throughout the period?

整個期間的測量間隔是多少？

Are you asking when patients get labs? Is that what you're asking? Or should we clarify?

你問病人甚麼時候得到實驗室？那是你要問的嗎？還是我們應該澄清一下？

Yes.

是的。

Okay. So patients get labs at the beginning and then there's a subsequent lab at, I believe it's 2, 4 and then 8 weeks and then it's every 3 months thereafter.

好的。因此，患者在開始時會進行實驗室檢查，然後會有後續的實驗室檢查，我相信是 2 週、4 周和 8 週，之後每 3 個月進行一次。

Maybe just one last one. I know this has been discussed before. But just wondering, as you start this launch and have some patients switch from their current therapy on to FILSPARI, do you have a sense for the proportion of patients today that visit their nephrologists on a monthly basis as a routine?

也許只是最後一個。我知道之前已經討論過這個問題。但只是想知道，當你開始這次發射並讓一些患者從他們目前的治療轉向 FILSPARI 時，你是否了解今天每月定期拜訪他們的腎臟科醫生的患者比例？

Ed, thank you for the question. We certainly have looked into the patient journey and how frequently these patients are visiting. Peter, would you like to share a bit of that work?

埃德，謝謝你的問題。我們當然已經調查了患者的旅程以及這些患者來訪的頻率。彼得，你願意分享一下這項工作嗎？

Yes, thanks for that question. I think there is -- especially when you talk about the rapidly progressing patients, those patients are being seen by nephrologists at least quarterly, but it's not uncommon to see those patients actually on a monthly basis. Is the heart of your question is like, what does that mean from a REMS perspective? Is it good to realize that for the REMS program, those patients don't need to be seen by the nephrology on a monthly base. They do the lab testing on a monthly base and the physician will see the results, but there is not an obligation for those patients to see their nephrologists every month. Even though it is quite common for quite some patients to see those -- their nephrologists that often.

是的，謝謝你提出這個問題。我認為有——特別是當你談論快速進展的患者時，腎病學家至少每季度看一次這些患者，但實際上每月看一次這些患者並不少見。您問題的核心是，從 REMS 的角度來看，這意味著什麼？意識到對於 REMS 計劃，這些患者不需要每月接受腎臟科檢查，這是件好事嗎？他們每月進行一次實驗室測試，醫生會看到結果，但這些患者沒有義務每月都去看腎病專家。儘管對於相當多的患者來說，看到這些是很常見的——他們的腎臟科醫生經常這樣。

This concludes today's question-and-answer session. I will turn the call back to Naomi Eichenbaum.

今天的問答環節到此結束。我會把電話轉回給 Naomi Eichenbaum。

Thank you, everyone, for joining us for our fourth quarter and full year 2022 financial results and corporate update call. We look forward to the exciting year ahead and providing updates on our progress along the way. Have a great rest of your day. Thank you for joining.

感謝大家參加我們的第四季度和 2022 年全年財務業績和公司更新電話會議。我們期待著激動人心的一年，並提供我們一路上取得的最新進展。祝您度過愉快的一天。感謝您的加入。