Calliditas Therapeutics AB (CALT) 2022 Q3 法說會逐字稿

Welcome to Calliditas Therapeutics Quarter 3 Presentation 2022.

歡迎來到 Calliditas Therapeutics 2022 年第 3 季度演講。

(Operator Instructions)

（操作員說明）

I will now hand over the word to CEO, Renee Aguiar-Lucander, please begin the meeting.

我現在將把話交給首席執行官 Renee Aguiar-Lucander，請開始會議。

Thank you very much, and welcome, everybody, to the Q3 report. With me on today's call, I have Fredrik Johansson, our Chief Financial Officer; Richard Philipson, Chief Medical Officer; and Mr. Andrew Udell, President of North America. So if you go to Page 2, please. I'd like to draw your attention to the disclaimer page related to forward-looking statements and refer you to the company's reports and other filings including those filings which contain risk factors and other relevant information.

非常感謝，歡迎大家來到第三季度報告。和我一起參加今天電話會議的還有我們的首席財務官 Fredrik Johansson；理查德·菲利普森，首席醫療官；以及北美總裁 Andrew Udell 先生。所以，如果你轉到第 2 頁，請。我想提請您注意與前瞻性陳述相關的免責聲明頁面，並請您參閱公司的報告和其他文件，包括那些包含風險因素和其他相關信息的文件。

So if we turn to Page 3, please. So some of the Q3 highlights. So in this quarter, Calliditas has achieved another major milestone as we received formal conditional approval of Kinpeygo in Europe. Subsequent to achieving this, we immediately started the transfer process of our market authorization to our commercial partner in Europe, STADA in order to enable a Swiss commercial launch in Europe.

請翻到第 3 頁。所以第三季度的一些亮點。因此，在本季度，Calliditas 取得了另一個重要里程碑，因為我們在歐洲獲得了 Kinpeygo 的正式有條件批准。實現這一目標後，我們立即開始將我們的市場授權轉移給我們在歐洲的商業合作夥伴 STADA，以便在歐洲進行瑞士商業發布。

During this quarter, we also received milestone payments amounting to EUR 12.5 million from STADA as we have previously announced. The results from the Q3 commercial activity of TARPEYO resulted in $12.1 million of net sales for the quarter which reflects the consistent build of our commercial launch plan, and we're very encouraged by the strong level of interest engagement that we're seeing, especially since the publication of our Part A data, which both Richard will cover later in the presentation, and Andy will take you through some more color with regards to our commercial activities also later in the presentation.

正如我們之前宣布的那樣，在本季度，我們還從 STADA 收到了 1250 萬歐元的里程碑付款。 TARPEYO 第三季度商業活動的結果導致本季度的淨銷售額為 1210 萬美元，這反映了我們的商業啟動計劃的一貫構建，我們對我們看到的強烈興趣參與水平感到非常鼓舞，尤其是自從我們的 A 部分數據發布以來，Richard 將在稍後的演示中介紹這些數據，Andy 將在演示的稍後部分為您介紹更多關於我們商業活動的顏色。

Based on the visibility we have today in our pipeline of our exits and revenues, we expect to have revenues in the range of $35 million to $40 million for this year. This is in line with our internal plans, and we expect strong continued growth based on recently published data, the importance of which really should not be underestimated as well as additional data expected in the first half of next year. With regard to core activities, we've experienced a lag in site recruitment rates, which seem mainly to be due to continued backlog pertaining to COVID-19 and the reduction of staff levels of clinics and hospitals, we still really do not seem to kind of be back at the level that they were prior to the pandemic.

根據我們今天在退出和收入渠道中的可見性，我們預計今年的收入將在 3500 萬至 4000 萬美元之間。這符合我們的內部計劃，我們預計基於最近公佈的數據將實現強勁的持續增長，這些數據的重要性確實不容低估，而且預計明年上半年還會有更多數據。關於核心活動，我們在現場招聘率方面出現了滯後，這似乎主要是由於與 COVID-19 相關的持續積壓以及診所和醫院員工人數的減少，我們似乎仍然不太友善恢復到大流行之前的水平。

This has created an impact on our recruitment levels. And so we do expect the head and neck cancer data we pushed into first half of next year and the interim analysis also to be pushed in to be conducted in the first half of 2024.

這對我們的招聘水平產生了影響。因此，我們確實預計我們將推入明年上半年的頭頸癌數據和中期分析也將推入到 2024 年上半年進行。

If we turn the page, please. So looking at post-period events. So regarding events which took place post the period of Q3. I've already mentioned that there was a publication clinical data in October. Something which we've been very aware of, obviously, that physicians have been waiting eagerly for, and some of you might have had a chance to listen to Dr. Barratt or Dr. Lafayette discussing this recently.

如果我們翻頁，請。所以看看後期事件。因此，關於第三季度之後發生的事件。我已經提到 10 月份有一份臨床數據發表。顯然，我們已經非常清楚，醫生們一直在熱切等待，你們中的一些人最近可能有機會聽 Barratt 博士或 Lafayette 博士討論這個問題。

In early November of this year, it was the Kidney Week ASN, which is the largest kidney congress held annually, held in the U.S., it was well attended, and we had a commercial TARPEYO-focused booth as well as the medical affairs booth there with a live presentation dedicated to pathophysiology, the gut-kidney connection was presented by Dr. Rappel and Dr. Wadhwani presented novel approach of TARPEYO in light of the recently published data. There was also a biomarker presentation related --- biomarker-related poster from the NeflgArd study. It was a very positive experience, apart from obviously the very nice thing of seeing everybody in person again.

今年11月初，在美國舉辦了每年最大的腎臟大會Kidney Week ASN，參加人數眾多，我們有一個TARPEYO商業展位和醫學事務展位在專門針對病理生理學的現場演示中，Rappel 博士介紹了腸-腎連接，Wadhwani 博士根據最近公佈的數據介紹了 TARPEYO 的新方法。 NeflgArd 研究中還有一個與生物標誌物相關的演示文稿——與生物標誌物相關的海報。這是一次非常積極的經歷，除了很明顯再次見到每個人都是非常好的事情。

I had the opportunity to interact with a large number of nephrologists who provided insights into their practice and treatment paradigm. Feedback from the part A data was all extremely valuable input. And so with that, I suggest that I hand over to our CMO, Richard Philipson, who will take you through a brief overview of the data in question. Richard?

我有機會與大量腎病學家互動，他們提供了對他們的實踐和治療模式的見解。來自 A 部分數據的反饋都是非常有價值的輸入。因此，我建議我將工作交給我們的首席營銷官 Richard Philipson，他將向您簡要介紹相關數據。理查德？

Thank you, Renee. I'm now on Page 6. So I'd like to start by saying how delighted we are that the results of Part A of the NeflgArd trial were published online by Kidney International on the 19th of October. I'd also like to extend my thanks and congratulations to all of the authors involved in producing this important publication that we believe will be a valuable resource for researchers and practicing positions in IgA nephropathy. I will provide a summary of the key outcomes presented in the publication. But first, we'll start with a description of the trial design. Next page.

謝謝你，芮妮。我現在在第 6 頁。首先，我想說我們非常高興 NeflgArd 試驗 A 部分的結果於 10 月 19 日由腎臟國際在線發布。我還要向參與製作這份重要出版物的所有作者表示感謝和祝賀，我們相信這將成為 IgA 腎病研究人員和實踐職位的寶貴資源。我將對出版物中提出的主要成果進行總結。但首先，我們將從試驗設計的描述開始。下一頁。

The NeflgArd study, which formed the basis for FDA's accelerated approval of TARPEYO comprises 2 parts, Part A and Part B. Patients with biopsy-proven IgA nephropathy, proteinuria of greater than 1 gram per day and eGFR of 35 to 90 ml per minute and with well controlled blood pressure whilst on optimized RAS inhibition were enrolled into Part A of the study and randomized to receive TARPEYO at a dose of 16 milligrams per day or placebo for a 9-month treatment period.

NeflgArd 研究構成了 FDA 加速批准 TARPEYO 的基礎，包括 A 部分和 B 部分兩部分。經活組織檢查證實為 IgA 腎病、每天蛋白尿量大於 1 克且 eGFR 為每分鐘 35 至 90 毫升且在優化 RAS 抑制的同時血壓控制良好的患者被納入研究的 A 部分，並隨機接受每天 16 毫克劑量的 TARPEYO 或安慰劑治療 9 個月。

The primary endpoint was assessed at the end of the 9-month treatment period. Treatment was discontinued and patients were then observed for 3 months. Patients then entered Part B of the study, which is a 12-month period of observation without study treatment. A total of 200 patients were enrolled in Part A for the primary analysis of that part of the study with the primary endpoint being change from baseline in proteinuria. A key secondary endpoint was changed from baseline in eGFR. This part of the study read out with positive results in November 2020.

主要終點在 9 個月的治療期結束時進行評估。停止治療，然後觀察患者 3 個月。然後患者進入研究的 B 部分，這是一個為期 12 個月的觀察期，沒有研究治療。共有 200 名患者參加了 A 部分，以對研究的該部分進行初步分析，主要終點是蛋白尿相對於基線的變化。一個關鍵的次要終點在 eGFR 中從基線發生了變化。這部分研究於 2020 年 11 月宣讀並取得積極成果。

The patient population for the Part A analysis had a median age of 44 years approximately 67% were male and approximately 86% were white. Our pressure control on enrollment was excellent and baseline UPCR and eGFR reflected the high-risk population enrolled into the study. I'll say a little bit more about Part B later in this presentation.

A 部分分析的患者群體的中位年齡為 44 歲，其中約 67% 為男性，約 86% 為白人。我們對入組的壓力控制非常好，基線 UPCR 和 eGFR 反映了參與研究的高危人群。我將在本演示文稿的稍後部分詳細介紹 B 部分。

Next slide. With respect to the key outcomes of Part A of NeflgArd, TARPEYO demonstrated a statistically significant and a clinically meaningful reduction in proteinuria at 9 months with stabilization of eGFR. Specifically, there was a 34% reduction in UPCR for TARPEYO treated patients versus a 5% reduction in placebo-treated patients. The difference was highly statistically significant. Patients receiving treatment with TARPEYO showed a minimal loss of eGFR of 0.17 ml per minute over the 9 months compared to a loss of just over 4 ml per minute in placebo-treated patients. The majority of adverse reactions were mild and moderate in severity. The most frequently reported adverse reactions are hypertension, peripheral edema, muscle spasms, acne, dermatitis, weight increased, dyspnea, face edema, dyspepsia, fatigue and hirsutism. It's worth noting that there were no reports of severe infections requiring hospitalization.

下一張幻燈片。關於 NeflgArd A 部分的主要結果，TARPEYO 證明在 9 個月時蛋白尿減少具有統計學意義和臨床意義，同時 eGFR 穩定。具體而言，TARPEYO 治療患者的 UPCR 降低了 34%，而安慰劑治療患者降低了 5%。差異具有高度統計顯著性。接受 TARPEYO 治療的患者在 9 個月內的 eGFR 最小損失為每分鐘 0.17 毫升，而接受安慰劑治療的患者每分鐘損失略高於 4 毫升。大多數不良反應的嚴重程度為輕度和中度。最常報告的不良反應是高血壓、外周水腫、肌肉痙攣、痤瘡、皮炎、體重增加、呼吸困難、面部水腫、消化不良、疲勞和多毛症。值得注意的是，目前尚無嚴重感染需要住院治療的報告。

Next slide. When we look at the profile of proteinuria change over time, it's apparent that the effect of TARPEYO was gradual and cumulative with the benefit of treatment on proteinuria emerging over the first few months of treatment. Proteinuria continues to improve through to 9 months when treatment was discontinued. And importantly, a further improvement in proteinuria was seen at the 12-month visit when patients have been off treatment for 3 months. At 12 months, there was a 52% reduction in proteinuria versus baseline or 48% when corrected for placebo. We also noted that proteinuria reduction was consistent across all baseline subgroups, including baseline proteinuria and baseline eGFR.

下一張幻燈片。當我們觀察蛋白尿隨時間變化的情況時，很明顯 TARPEYO 的作用是漸進的和累積的，在治療的最初幾個月中出現了對蛋白尿的治療益處。停止治療後，蛋白尿持續改善至 9 個月。重要的是，在患者停止治療 3 個月後的 12 個月訪視中，蛋白尿進一步改善。在 12 個月時，蛋白尿與基線相比減少了 52%，或在使用安慰劑校正後減少了 48%。我們還注意到蛋白尿減少在所有基線亞組中是一致的，包括基線蛋白尿和基線 eGFR。

Next slide. Turning to the profile of eGFR change over time. We saw early separation of the eGFR curves with an initial modest increase in eGFR in patients treated with TARPEYO. The separation of the eGFR curves was maintained throughout the treatment period. And again, importantly, it was also maintained at the 12-month visit when patients have been off treatment for 3 months.

下一張幻燈片。轉向 eGFR 隨時間變化的概況。在接受 TARPEYO 治療的患者中，我們看到 eGFR 曲線早期分離，eGFR 最初適度增加。在整個治療期間保持 eGFR 曲線的分離。再次重要的是，當患者停止治療 3 個月時，它也保持在 12 個月的訪問中。

Next slide. When we look at subgroups of patients with higher levels of baseline proteinuria, we are at particularly high risk of disease progression, we found that there was a more pronounced treatment benefit on eGFR. Here, we see presented the eGFR trajectory for a subgroup of patients with baseline UPCR greater than or equal to 1.5 gram per gram. It's worth noting the particularly rapid decline of eGFR in patients receiving placebo, with a loss from baseline of over 8 ml per minute at 9 months. In comparison TARPEYO treated patients had essentially stable eGFR with a loss of less than 1 ml per minute over the 9-month period. The eGFR trajectory for the 2 treatment groups clearly diverged and the separation between the 2 groups was maintained at 12 months.

下一張幻燈片。當我們觀察基線蛋白尿水平較高的患者亞組時，我們處於特別高的疾病進展風險中，我們發現對 eGFR 有更明顯的治療益處。在這裡，我們看到了基線 UPCR 大於或等於 1.5 克/克的患者亞組的 eGFR 軌跡。值得注意的是，接受安慰劑的患者的 eGFR 下降特別快，在 9 個月時每分鐘從基線下降超過 8 毫升。相比之下，TARPEYO 治療的患者俱有基本穩定的 eGFR，在 9 個月期間每分鐘損失小於 1 毫升。 2 個治療組的 eGFR 軌跡明顯不同，兩組之間的間隔保持在 12 個月。

Next slide. As already described, Part B of NeflgArd is a post-approval observational off-treatment follow-up to confirm the long-term renal benefit of the observed proteinuria reduction. The final analysis will be performed on approximately 360 patients, which includes the 200 patients that comprise the Part A analysis population. The primary endpoint will evaluate kidney function through eGFR change measured over the 2-year period. Completion of enrollment of these 360 patients was achieved in January 2021, and we expect the final readout in the first half of 2023.

下一張幻燈片。如前所述，NeflgArd 的 B 部分是批准後的停藥觀察性隨訪，以確認觀察到的蛋白尿減少對腎臟的長期益處。最終分析將對大約 360 名患者進行，其中包括構成 A 部分分析人群的 200 名患者。主要終點將通過 2 年期間測量的 eGFR 變化來評估腎功能。這 360 名患者的入組已於 2021 年 1 月完成，我們預計最終結果將在 2023 年上半年公佈。

Next slide. Finally, I will briefly mention the open label extension to the NeflgArd trial. This open-label extension or OLE is open to all patients who complete the 2-year NeflgArd trial, but it is optional. Eligibility requirements for entry into the open-label extension are broadly similar to the pivotal trial. In particular, the proteinuria requirement is the same but there's a slightly lower eGFR limited 30 ml per minute. By the end of quarter 3, approximately 180 patients adopted to enter screening for the OLE and the screen failure rate had been approximately 41%. The most common reason for screen failure is proteinuria level below the required minimum of 1 gram per 24 hours, which represents 61% of all screen failures.

下一張幻燈片。最後，我將簡要提及 NeflgArd 試驗的開放標籤擴展。這種開放標籤擴展或 OLE 對所有完成 2 年 NeflgArd 試驗的患者開放，但它是可選的。進入開放標籤擴展的資格要求與關鍵試驗大致相似。特別是，蛋白尿要求相同，但 eGFR 略低，限制為每分鐘 30 毫升。截至第 3 季度末，約有 180 名患者接受了 OLE 篩查，篩查失敗率約為 41%。篩查失敗的最常見原因是蛋白尿水平低於每 24 小時 1 克的最低要求，佔所有篩查失敗的 61%。

As the pivotal NeflgArd trial remains blinded, we can't draw any conclusion from this observation apart from the fact that low levels of both proteinuria and eGFR are the main reasons for screen failure. We look forward to unblinding the NeflgArd study once it is completed, which will provide us with further insights into these observations. I'll now hand over to Andy for the commercial update.

由於關鍵的 NeflgArd 試驗仍然採用盲法，因此除了蛋白尿和 eGFR 水平低是篩查失敗的主要原因這一事實外，我們無法從該觀察結果中得出任何結論。我們期待在 NeflgArd 研究完成後揭盲，這將使我們對這些觀察結果有更深入的了解。我現在將交給安迪進行商業更新。

Thanks, Richard. Please go to Slide 15. The third quarter was another quarter of solid growth as we continue to build on our success from the first half of the year. Quarterly net sales of more than $12 million brings us to more than $20 million net sales dollars of net sales in the first 8 months of promotion. As announced after last quarter, we began expansion efforts in July. This growth included the addition of 20 sales territories, which gives us a total of 60 sales executives, expanding our reach and call frequency to our target audience. We are impressed with the caliber of talent we continue to attract, most of which coming to us with rare disease and nephrology experience.

謝謝，理查德。請轉到幻燈片 15。第三季度是又一個穩健增長的季度，因為我們繼續在今年上半年的成功基礎上再接再厲。超過 1200 萬美元的季度淨銷售額使我們在促銷的前 8 個月的淨銷售額超過 2000 萬美元。正如上個季度後宣布的那樣，我們在 7 月開始了擴張工作。這一增長包括增加了 20 個銷售區域，這使我們共有 60 名銷售主管，擴大了我們對目標受眾的覆蓋面和呼叫頻率。我們對不斷吸引的優秀人才印象深刻，他們中的大多數人都具有罕見疾病和腎髒病學經驗。

While the onboarding and training took place during the quarter, we anticipate to begin to feel the impact of the additional educators in the fourth quarter. September enrollments were strong after the anticipated slower July and August summer holiday period with a quarter total of enrollments of 281 and prescriber receptivity remains positive as we grew our prescriber base to 480 unique prescribers since launch, and this total includes addition of 166 new prescribers during the third quarter. In addition, we continue to see the average enrollments per prescriber growth.

雖然入職和培訓是在本季度進行的，但我們預計將在第四季度開始感受到更多教育工作者的影響。在預期較慢的 7 月和 8 月暑假期間之後，9 月的入學人數強勁，四分之一的入學人數為 281 人，並且開處方者的接受度保持積極，因為自推出以來我們的開處方者人數增加到 480 名，這一總數包括在期間增加的 166 名新開處方者第三季度。此外，我們繼續看到每個處方者的平均註冊人數增長。

We anticipate this rate will continue to grow as many physicians now have patients on therapy for several months and are experiencing positive results as was demonstrated in our clinical trials. As it relates to market access, we've reached our target of over 90% of U.S. lives having coverage for TARPEYO, which is impressive for a specialty company. The payer mix has reached a steady state without much change from last quarter. We have less than 25% of our business coming from government-insured patients and the remaining being either private commercial insurance or cash-paying customers.

我們預計這一比率將繼續增長，因為許多醫生現在已經對患者進行了數月的治療，並且正在經歷積極的結果，正如我們的臨床試驗所證明的那樣。由於它涉及市場准入，我們已經達到了超過 90% 的美國人生活覆蓋 TARPEYO 的目標，這對於一家專業公司來說是令人印象深刻的。付款人組合已達到穩定狀態，與上一季度相比沒有太大變化。我們只有不到 25% 的業務來自政府投保的患者，其餘業務要么是私人商業保險，要么是現金支付客戶。

During the quarter, we added resources to our TARPEYO Touchpoints dedicated team in order to maintain the high service levels for increasing patient population. Our reach and promotional programs remain effective with awareness of TARPEYO growing to over 80% of nephrologists and market research surveys. The final highlight of the third quarter was IgA Nephropathy Foundation Spark Patient summit meeting. The interactions with the advocacy group leaders and patients continues to motivate and provide encouragement to our team and the potential this market represents.

在本季度，我們為 TARPEYO Touchpoints 專門團隊增加了資源，以便為不斷增加的患者人數保持高服務水平。我們的影響力和促銷計劃仍然有效，超過 80% 的腎病學家和市場研究調查對 TARPEYO 的認識不斷增加。第三季度的最後一個亮點是 IgA 腎病基金會 Spark 患者峰會。與宣傳小組領導和患者的互動繼續激勵和鼓勵我們的團隊以及這個市場所代表的潛力。

Next slide, please. These last several weeks post Q3 have been encouraging. The receptivity and reaction to the NeflgArd publication and information Richard reviewed with you has been nothing short of extremely positive from the nephrology community. This was demonstrated with inbound notifications upon publication as well as in person during the Annual Meeting of the American Society of Nephrology that Renee had mentioned earlier. The in-person ASM meeting was a great opportunity for us to reach, educate and interact with our target audience.

請換下一張幻燈片。第三季度後的最後幾周令人鼓舞。腎髒病學界對 NeflgArd 出版物和 Richard 與您一起回顧的信息的接受度和反應非常積極。這一點在發表時的入站通知以及 Renee 之前提到的美國腎髒病學會年會期間親自出席都證明了這一點。面對面的 ASM 會議是我們接觸、教育和與目標受眾互動的絕佳機會。

The traffic at our booth and attending our sponsored educational events was impressive. The nephrology market is clearly eager to learn more and more about IgA nephropathy and how TARPEYO best fits with their patients. As our first patients are nearing the 9-month mark, we are hearing of more and more TARPEYO patient success stories. We anticipate these successes, coupled with further nephrologists and patient experience will result in continued growth of TARPEYO over the next several months as we eagerly anticipate the results of Part B of the NeflgArd trial in the first half of 2023. I'll now turn it over to Fredrik to provide you the financial overview.

我們展位和參加我們贊助的教育活動的人流令人印象深刻。腎髒病學市場顯然渴望越來越多地了解 IgA 腎病以及 TARPEYO 如何最適合他們的患者。隨著我們的第一批患者接近 9 個月大關，我們聽到了越來越多的 TARPEYO 患者成功故事。我們預計這些成功，再加上更多的腎病學家和患者經驗，將導致 TARPEYO 在未來幾個月內持續增長，因為我們熱切期待 2023 年上半年 NeflgArd 試驗 B 部分的結果。我現在將它轉過來請 Fredrik 為您提供財務概覽。

Thank you, Andy. Let's continue to Slide 17. So good afternoon and good morning, everyone. I will now present to you the financial overview for the first 9 months of 2022, and all numbers presented to you are in MSEK, as always, unless otherwise stated. To start with, we achieved SEK 373.8 million in net revenues for the 9-month period. For the same period last year, we reported revenues of SEK 198.2 million. This is the third quarter, we report net product sales following the TARPEYO FDA accelerated approval in December last year with the start of sales in January earlier this year. Out of the SEK 373.8 million in net revenue, TARPEYO net product sales, 9-month period amounted to SEK 205 million or $20.7 million, where of SEK 123.4 million or $12.1 million came in the third quarter, an increase of 94% compared to the second quarter and was in line with our internal expectations.

謝謝你，安迪。讓我們繼續幻燈片 17。大家下午好，早上好。我現在將向您介紹 2022 年前 9 個月的財務概覽，除非另有說明，否則向您提供的所有數字一如既往地以 MSEK 為單位。首先，我們在 9 個月期間實現了 3.738 億瑞典克朗的淨收入。去年同期，我們報告的收入為 1.982 億瑞典克朗。這是第三季度，我們報告了去年 12 月 TARPEYO FDA 加速批准並於今年 1 月開始銷售後的淨產品銷售額。在 3.738 億瑞典克朗的淨收入中，TARPEYO 前 9 個月的產品淨銷售額為 2.05 億瑞典克朗或 2070 萬美元，其中第三季度為 1.234 億瑞典克朗或 1210 萬美元，與去年同期相比增長 94%第二季度，符合我們的內部預期。

In addition, we recorded SEK 163.8 million for the 9-month period in revenues related to out licensing transactions, where we in the third quarter recorded SEK 135 million in revenue from STADA for the conditional approval and launch in EU. As you remember, we also received upfront fee in the first quarter from Everest of SEK 28.8 million, which was equivalent to USD 3 million for the extension of the Everest license contract to South Korea.

此外，我們在 9 個月期間記錄了與許可交易相關的收入 1.638 億瑞典克朗，我們在第三季度記錄了 STADA 的 1.35 億瑞典克朗收入，用於有條件地批准並在歐盟推出。您還記得，我們還在第一季度從 Everest 收到了 2880 萬瑞典克朗的預付費用，這相當於將 Everest 許可合同擴展到韓國的 300 萬美元。

Our total operating expenses for the 9-month period amounted to SEK 821 million compared to SEK 500.5 million for the same period last year. In the third quarter, our total operating expenses was SEK 292.2 million compared to the second quarter this year, our OpEx had increased by around SEK 20 million quarter-to-quarter, which is mainly attributable to the current FX headwind, we still see due to weaker SEK against U.S. dollar and Euro. After the total operating expenses for the 9 months, marketing and selling expenses increased by SEK 214.3 million to SEK 323.3 million compared to SEK 109 million for the same period last year. The increase in marketing and selling expenses originates from us having a full commercial team in place from the start of Q1 this year.

我們前 9 個月的總運營費用為 8.21 億瑞典克朗，而去年同期為 5.005 億瑞典克朗。第三季度，與今年第二季度相比，我們的總運營費用為 2.922 億瑞典克朗，我們的 OpEx 環比增加了約 2000 萬瑞典克朗，這主要歸因於當前的外匯逆風，我們仍然看到由於瑞典克朗兌美元和歐元走弱。扣除 9 個月的總運營費用後，營銷和銷售費用增加了 2.143 億瑞典克朗，達到 3.233 億瑞典克朗，而去年同期為 1.09 億瑞典克朗。營銷和銷售費用的增加源於我們從今年第一季度開始就擁有一支完整的商業團隊。

Cost for research and development increased by SEK 55.3 million to SEK 312.5 million compared to SEK 257.2 million for the same period previous year. Increase in R&D expenses originates primarily from the ongoing operations for the setanaxib trial. Our operating loss amounted to SEK 454.4 million for the 9-month period compared to an operating loss of SEK 302.3 million for the same period last year. For the third quarter alone, we had an operating loss of SEK 36.2 million compared to an operating loss of SEK 209.8 million for the second quarter. The cash flow used in operating activities for the 9 months amounted to SEK 541.4 million compared to SEK 300.3 million for the same period previous year. For the third quarter, the cash flow used in operating activities amounted to SEK 124.7 million compared to SEK 225.2 million for the second quarter. This is an improvement of almost SEK 100 million between the quarters, and it was mainly driven by the increased net sales of TARPEYO.

研發成本增加了 5530 萬瑞典克朗，達到 3.125 億瑞典克朗，而去年同期為 2.572 億瑞典克朗。研發費用的增加主要源於 setanaxib 試驗的持續運營。我們前 9 個月的經營虧損為 4.544 億瑞典克朗，而去年同期的經營虧損為 3.023 億瑞典克朗。僅第三季度，我們的運營虧損就達到了 3620 萬瑞典克朗，而第二季度的運營虧損為 2.098 億瑞典克朗。前 9 個月用於經營活動的現金流量為 5.414 億瑞典克朗，而去年同期為 3.003 億瑞典克朗。第三季度，用於經營活動的現金流為 1.247 億瑞典克朗，而第二季度為 2.252 億瑞典克朗。這在兩個季度之間增加了近 1 億瑞典克朗，主要是由於 TARPEYO 淨銷售額的增加。

As of September 13, we reported a strong cash position of SEK 736.2 million, down from SEK 846.8 million from the second quarter. In addition to our cash at the end of September, there is SEK 25 million unused in the Kreos credit facility, and we expect approximately SEK 160 million in cash payments from milestones from STADA and Everest in the fourth quarter, where the STADA milestones were recognized as revenue in the third quarter. The progress of the commercial loans after pay in the third quarter continued to support our view that based on our current operational plan and our current cash position, we believe that we have sufficient funds for our planned operations and capital expenditures until we become cash flow positive on a monthly basis, which is currently projected for the first half of 2023 subject to continued successful commercialization of TARPEYO.

截至 9 月 13 日，我們報告現金頭寸強勁，為 7.362 億瑞典克朗，低於第二季度的 8.468 億瑞典克朗。除了我們 9 月底的現金外，Kreos 信貸額度中還有 2500 萬瑞典克朗未使用，我們預計第四季度 STADA 和 Everest 的里程碑將支付大約 1.6 億瑞典克朗的現金，其中 STADA 里程碑被確認作為第三季度的收入。第三季度支付後商業貸款的進展繼續支持我們的觀點，即根據我們目前的運營計劃和我們目前的現金狀況，我們相信我們有足夠的資金用於計劃的運營和資本支出，直到我們的現金流為正每月一次，目前預計在 2023 年上半年進行，具體取決於 TARPEYO 的持續成功商業化。

Next slide, please. Just let me give a quick summary of the financial key takeaways. On the revenue side, it was very encouraging that we saw TARPEYO net sales of SEK 123.4 million, the $12.1 million to growth of 94% from Q2 was very encouraging. It's also encouraging that we managed to see the milestones of SEK 135 million from STADA recognized in Q3. The SEK 20 million increase in the operating expense between the Q2 to Q3 was mainly FX driven due to a weak SEK. Cash used in operating expenses significantly improved from Q2 to Q3, mainly driven by an increased net sales of TARPEYO. And we think that we are well funded with a cash position of SEK 736.2 million. And please be aware of that approximately SEK 110 million of the STADA milestones that was recognized in revenue in Q3 are due for payment in Q4 and hence was not included in September cash position.

請換下一張幻燈片。讓我快速總結一下財務要點。在收入方面，我們看到 TARPEYO 的淨銷售額為 1.234 億瑞典克朗，與第二季度相比增長 94% 的 1210 萬美元，這非常令人鼓舞。同樣令人鼓舞的是，我們在第三季度成功地看到了來自 STADA 的 1.35 億瑞典克朗的里程碑。第二季度至第三季度營業費用增加 2000 萬瑞典克朗，主要是由於瑞典克朗疲軟導致的外匯驅動。用於運營支出的現金從第二季度到第三季度顯著改善，這主要是由於 TARPEYO 淨銷售額的增加。我們認為我們的資金充足，現金頭寸為 7.362 億瑞典克朗。請注意，在第三季度收入中確認的大約 1.1 億瑞典克朗的 STADA 里程碑將在第四季度支付，因此不包括在 9 月份的現金狀況中。

I think this was all for me. Thank you, and now back to you, Renee.

我想這一切都是為了我。謝謝，現在回到你身邊，蕾妮。

Thank you, Fredrik. So if you turn the page to Page 19. These are just some key takeaways which we've already now have gone through. So basically, we are very pleased with our results and progress during Q3 in this very first year after achieving approval of TARPEYO. The fact that we've achieved over $35 million of revenues to date with product sales representing over SEK 20 million makes us very encouraged about the future. We continue to penetrate the nephrology prescriber base. And as Andy mentioned, we are starting to now hear very positive patient experiences from the field. I'm confident that we have the right team in place, ensuring that we will continue to execute on our plan. And as Fredrik mentioned, in Q3, we do see lower net cash burn compared to Q2 when taking -- also when just taking product sales into account, which we expect to continue in Q4 and onwards, making us set for a very stable financial position. So with that, we're happy to take any questions that there might be operator.

謝謝你，弗雷德里克。因此，如果您將頁面翻到第 19 頁。這些只是我們現在已經經歷過的一些關鍵要點。所以基本上，在獲得 TARPEYO 批准後的第一年，我們對我們在第三季度的結果和進展感到非常滿意。迄今為止，我們已經實現了超過 3500 萬美元的收入，產品銷售額超過 2000 萬瑞典克朗，這讓我們對未來充滿信心。我們繼續滲透腎髒病學處方基地。正如安迪提到的，我們現在開始從該領域聽到非常積極的患者體驗。我相信我們擁有合適的團隊，確保我們將繼續執行我們的計劃。正如 Fredrik 提到的那樣，在第三季度，我們確實看到與第二季度相比，淨現金消耗有所減少——同時僅考慮產品銷售，我們預計這種情況將在第四季度及以後繼續存在，這使我們的財務狀況非常穩定.因此，我們很樂意回答運營商可能提出的任何問題。

(Operator Instructions)

（操作員說明）

And our first question comes from Jon Berggren from Kepler Cheuvreux.

我們的第一個問題來自 Kepler Cheuvreux 的 Jon Berggren。

So I was wondering, I mean, in the report, you mentioned 730 patients enrolled from January to the end of Q3. So I'm wondering how many of these 730 patients were actually on treatment at the end of Q3.

所以我想知道，我的意思是，在報告中，你提到從 1 月到第三季度末有 730 名患者入組。所以我想知道這 730 名患者中有多少人在第三季度末實際接受了治療。

So I think that at this point in time, we're not really separating this out. And the reason for doing that is that it's a multifactorial process from actually kind of going from enrollment down to kind of receiving revenues, and this is mainly due to the fairly complex health care system in the U.S., which really requires a fairly extensive process for all specialty products to really kind of go through verification, et cetera, in order for shipping to take place.

所以我認為在這個時間點，我們並沒有真正把它分開。這樣做的原因是它實際上是一個多因素的過程，從入學到獲得收入，這主要是由於美國相當複雜的醫療保健系統，這確實需要一個相當廣泛的過程所有特殊產品都需要經過驗證等，才能發貨。

But obviously, we provided some of those metrics as Andy has gone through, but it does become kind of not very helpful at this early stage to provide this, once we're actually in a more kind of stable state I think this is a number that we'll be happy to report on.

但很明顯，我們提供了一些安迪已經經歷過的指標，但在這個早期階段提供這些指標確實變得不太有用，一旦我們實際上處於更穩定的狀態，我認為這是一個數字我們很樂意報告。

And just another question then on R&D costs. I was wondering if you could provide a split on how much you're spending on Nefecon relative to your Setanaxib programs?

還有一個關於研發成本的問題。我想知道您是否可以分開說明您在 Nefecon 上的花費與您的 Setanaxib 計劃相關的費用？

Yes. Sure. We are not separating this in our report. But since we are sort of on the last mile of the Nefecon studies, we are, of course, spending less R&D costs on the Nefecon program and with 2 Setanaxib programs ongoing and fully running. The majority of the R&D costs are going towards the Setanaxib.

是的。當然。我們沒有在報告中將其分開。但由於我們處於 Nefecon 研究的最後一英里，我們當然會在 Nefecon 項目上花費更少的研發成本，並且有 2 個 Setanaxib 項目正在進行並全面運行。大部分研發成本用於 Setanaxib。

The next question comes from Yigal Nochomovitz from Citigroup.

下一個問題來自花旗集團的 Yigal Nochomovitz。

This is [Ashik Mubarak] on for Yigal. I just wanted to ask about the timing of your NRDL listing in China by Everest, and if that's even part of the commercial strategy? And if so, maybe what would you expect in terms of pricing discounts in China? And maybe what has Everest publicly said about the launch in China, if anything?

這是 [Ashik Mubarak] 替 Yigal 上場。我只是想問一下你們珠穆朗瑪峰在中國國家醫保目錄上市的時間，這是否是商業策略的一部分？如果是這樣，也許您對中國的定價折扣有何期待？如果有的話，也許珠穆朗瑪峰對在中國的發射公開說過什麼？

Sure. So obviously, as they're kind of -- as Everest has become closer and closer to filing in China, they've obviously spent some more time also doing more market research, et cetera. So this is also why we have -- they've shared with us in terms of their estimate now kind of biopsy-proven patients in China that, that number is somewhere kind of estimated to be around 5 million, which is obviously significantly higher than what we had been aware of previously.

當然。很明顯，隨著 Everest 越來越接近在中國提交申請，他們顯然花了更多的時間也做了更多的市場研究，等等。所以這也是為什麼我們 - 他們與我們分享了他們對中國目前經活檢證實的患者的估計，這個數字估計在 500 萬左右，這明顯高於我們之前已經知道的。

In terms of the actual pricing, et cetera, we have not -- we don't have any access to that at this point in time. So actually, I can't share anything with regards to that with you at this time. My assumption is that Everest is still working on those -- on that. In terms of the filing, obviously, the target has always been for them to file and get an acceptance first half. And so obviously, now it's in this Q4 period is what we would expect. And obviously, if the filing is accepted, then the indications that we've received from Everest is because they have breakthrough designation that they would expect a review period of no more than 12 months. So that would put a potential approval towards the second half of next year.

就實際定價等而言，我們還沒有——我們目前沒有任何訪問權限。所以實際上，我目前無法與您分享任何相關信息。我的假設是，Everest 仍在致力於這些——就此而言。在備案方面，顯然，目標一直是讓他們在上半年提交並獲得接受。很明顯，現在正是我們所期望的第四季度。顯然，如果申請被接受，那麼我們從 Everest 收到的指示是因為他們有突破性指定，他們預計審查期不超過 12 個月。因此，這可能會在明年下半年獲得批准。

So I think this is -- it is very exciting. I think as we mentioned before, obviously, this is a -- it's a strong contributing factor, quite common for younger people in China to actually have IgA nephropathy as a reason for their dialysis. And I think that it would be super exciting to actually have a drug available there as well to address this fairly large patient population. But I think we're going to have to -- we'll share with you once we hear something from our partner in terms of what their plans are with regards to other metrics of their commercialization.

所以我認為這是 - 這非常令人興奮。我認為正如我們之前提到的，顯然，這是一個 - 這是一個強大的促成因素，對於中國的年輕人來說，實際上患有 IgA 腎病作為他們透析的原因是很常見的。而且我認為，如果真的有一種藥物可以用來解決這個相當大的患者群體，那將是非常令人興奮的。但我認為我們將不得不——一旦我們從我們的合作夥伴那裡聽到他們關於商業化其他指標的計劃，我們將與您分享。

Okay. Totally understandable. Maybe one more on the launch in Europe. I know you're not being this specific necessarily on timing. But I guess, generally, can you give us any color on how far away the actual launch is, maybe year-end a reasonable assumption or is that more of a 2023 thing?

好的。完全可以理解。也許還有一個在歐洲推出。我知道你不一定在時間上如此具體。但我想，總的來說，你能告訴我們距離實際發布還有多遠的顏色嗎，也許年底是一個合理的假設，或者更像是 2023 年的事情？

No, they have actually -- so STADA has launched. They've launched the product. They've launched it in Germany. So it is now available in Germany. It is one of the few countries in Europe where you're actually able to launch kind of immediately, more or less immediately after approval. The other kind of countries in Europe require kind of a negotiation with regards to pricing and market access, et cetera. So we would expect STADA to roll out the product in other European geographies or in other European countries as those kind of negotiations progress. But the product has been launched. It was launched in late September, early October if I am not mistaken in Germany.

不，他們實際上已經——所以 STADA 已經啟動了。他們已經推出了產品。他們已經在德國推出了它。所以它現在在德國有售。它是歐洲為數不多的幾個國家之一，在這些國家中，您實際上能夠在獲得批准後立即或多或少地立即推出某種產品。歐洲的其他國家需要就定價和市場准入等進行談判。因此，我們預計 STADA 會隨著此類談判的進展在其他歐洲地區或其他歐洲國家推出該產品。但產品已經推出。如果我沒記錯的話，它是在 9 月底、10 月初在德國推出的。

Okay. Okay. Got it. So I assume we'll see some revenues flowing in this quarter from that. And then last question for me, just in terms of the U.S. launch. I guess, in order to hit the midpoint of your sort of guided range. It seems like you might see a little bit of deceleration in the fourth quarter in terms of U.S. sales. So I'm wondering what's behind your fourth quarter assumptions. Is there -- was there a component of inventory stocking that may drive a little bit of a slowdown in the fourth quarter?

好的。好的。知道了。因此，我假設我們會在本季度看到一些收入從中流入。然後是我的最後一個問題，就美國發射而言。我想，為了達到您的指導範圍的中點。就美國銷售額而言，您似乎會在第四季度看到一些減速。所以我想知道你第四季度假設的背後是什麼。是否有 - 是否存在可能導致第四季度放緩的庫存庫存組成部分？

No. There's no kind of inventory stocking component. And I'm not sure that we are expecting any deceleration in Q4. I think it's more a metric in terms of the time it takes just to kind of from enrollment to revenue generation. But Andy, maybe you want to take this?

不，沒有任何庫存庫存組件。而且我不確定我們是否預計第四季度會出現任何減速。我認為它更像是一個衡量從註冊到創收所需時間的指標。但是安迪，也許你想接受這個？

Yes. No, I would agree with your assessment that it's not at all a deceleration. I think we're looking to continue the growth and that target would mean a very healthy fourth quarter.

是的。不，我同意你的評估，即這根本不是減速。我認為我們正在尋求繼續增長，而這個目標將意味著第四季度非常健康。

The next question comes from Dan Akschuti from Pareto Securities.

下一個問題來自 Pareto Securities 的 Dan Akschuti。

Congrats on the great numbers. One question on the unique prescribers. So how many in percentage are there left in the U.S.? Is it that you're around that 20% of the available prescribers currently or no?

祝賀偉大的數字。一個關於獨特處方者的問題。那麼美國還剩下多少百分比？是您目前大約有 20% 的可用處方者嗎？

I'm sorry, can you repeat that, sorry?

對不起，你能再重複一遍嗎？

So the unique prescribers that you have reached thus far, how much in relative, like how much in percentage does that represent of the prescribers available in the U.S.?

那麼到目前為止，您接觸到的獨特處方者，相對多少，比如代表美國可用處方者的百分比是多少？

I see. Sorry. So Andy, do you want to take that? I mean, in terms of our target of 3,500 or 3,700.

我懂了。對不起。所以安迪，你想接受嗎？我的意思是，就我們的目標 3,500 或 3,700 而言。

Yes. Yes. I mean it's not even 10%. It's a little bit more than -- I'm sorry, than 10% of probably what we would anticipate a peak of prescribers, but this is -- not every prescriber is equal. In other words, as far as they're prescribing their patient load, et cetera. So we're very pleased with the amount of prescribers that we've already -- that have already initiated patients on TARPEYO.

是的。是的。我的意思是它甚至不到 10%。這比 - 抱歉，比我們預期的處方者高峰可能多出 10%，但這是 - 並非每個處方者都是平等的。換句話說，就他們規定的患者負荷而言，等等。因此，我們對我們已經開處方的數量感到非常滿意——他們已經開始使用 TARPEYO 治療患者。

Okay. And a follow-up on that. Could you give us some color on the incentive model for the sales force? And when we can expect that 20 additional FTEs are fully trained, is that already now in end of Q3? And what are the lessons learned maybe from the -- lessons learned from the first quarter? And do you have any plans that you could share in that could increase the efficiency of your sales force?

好的。並對此進行後續跟進。您能否給我們介紹一下銷售人員的激勵模型？當我們可以預期另外 20 名 FTE 得到全面培訓時，現在是否已經在第三季度末？從第一季度吸取的教訓可能吸取了哪些教訓？您是否有任何可以分享的計劃可以提高您的銷售團隊的效率？

So good questions. The answer is they were all trained, they're in the field. So they're fully compliant and trained and that took place during Q3. And so the timing, I think we think we're going to -- while some we feel impacts quicker than others. A lot of that is due to relationships and when they're -- they've been in the space prior. And the fortunate part for us is that the vast majority of the 20 new sales executives come with experience in this market. So we're very pleased with that.

那麼好的問題。答案是他們都受過訓練，他們在現場。因此，他們完全合規並接受了培訓，這發生在第三季度。所以時機，我認為我們認為我們會 - 而有些我們感受到的影響比其他人更快。這在很大程度上是由於人際關係以及他們何時 - 他們之前已經進入過這個領域。對我們來說幸運的是，這 20 名新銷售主管中的絕大多數都具有該市場的經驗。所以我們對此非常滿意。

As far as lessons learned, this is a process that takes continued education and repeat calls. Some are quicker uptake than others, and they like to see the data, and we're pleased with the fact that now we have a publication that provides this data so that they want to see the peer-reviewed journal indicating exactly the results or further than what we can "promote" for the reps, that's also beneficial.

就經驗教訓而言，這是一個需要繼續教育和重複調用的過程。有些人比其他人接受得更快，他們喜歡看數據，我們很高興現在我們有一份提供這些數據的出版物，這樣他們就希望看到同行評審的期刊準確地指出結果或進一步比我們可以為代表“提升”的東西，這也是有益的。

So I think there's a lot of positive momentum coming out of Q3 that we've seen at the very beginning of Q4. And I think the impact of the increased reach and frequency, coupled with the data will be exciting. Plus I think the last piece of it, it really is the successes we started to hear. I think there are prescribers that you could understand, they put a patient or 2 on the product. They want to wait a few months to see the success and once you build on that and if you see a success with some patients, you're going to want to expand your usage. So we're starting to get to that point now.

因此，我認為我們在第四季度初看到的第三季度出現了很多積極勢頭。而且我認為增加的覆蓋面和頻率的影響，加上數據將是令人興奮的。另外我認為它的最後一部分，它確實是我們開始聽到的成功。我認為您可以理解有些處方者，他們將一兩個患者放在產品上。他們想等幾個月才能看到成功，一旦你以此為基礎，如果你看到一些患者取得成功，你就會想要擴大你的使用範圍。所以我們現在開始達到這一點。

Okay. And the last follow-up, considering the -- that there's still a lot of prescribers out there left. Do you see a possibility that you would increase the sales force next year additionally?

好的。最後的後續行動，考慮到——仍然有很多開處方者。您認為明年是否有可能額外增加銷售人員？

Do I see that possibility. We don't close off the possibility to anything. It's not the plan. It really isn't the plan right now, but there's a way that you assess that and you look and you see are we reaching enough people with the right frequency. So we're constantly looking at this information and it is not in the plans today to expand further.

我看到這種可能性了嗎？我們不會關閉任何事情的可能性。這不是計劃。這確實不是現在的計劃，但有一種方法可以評估它，你會看到我們是否以正確的頻率接觸了足夠多的人。因此，我們一直在查看這些信息，目前還沒有進一步擴展的計劃。

The next question comes from Jacob Mekhael from Kempen.

下一個問題來自 Kempen 的 Jacob Mekhael。

I'm just curious if there are any factors that can predict why the approval process may take longer for some patients compared to others? And maybe if you can provide any color on the challenges that patients experience in the process to get approval?

我只是好奇是否有任何因素可以預測為什麼某些患者的批准過程可能比其他患者花費更長的時間？也許您能否提供有關患者在獲得批准的過程中遇到的挑戰的任何顏色？

Sure. Andy, do you want to start?

當然。安迪，你想開始嗎？

Sure. Sure. So as you know, in the states, there's thousands of different plans, and they have different policies that they go through. So that can make -- that's one factor right there that can make the approval process take different amounts of time for different patients. But every time there's an approval for every specialty product, you have to remember, there's several players involved. So you have the physician, you have the patient and you have the payer, okay? And so some payers require different levels of evidence or information. So that can take time. Sometimes it requires the physician to provide this information. That could take time, and some of the offices are more equipped than others to handle providing this level of evidence.

當然。當然。如您所知，在各州，有數以千計的不同計劃，他們有不同的政策。所以這可以——這是一個因素，可以使不同患者的批准過程花費不同的時間。但每次每種特殊產品獲得批准時，你都必須記住，涉及多個參與者。所以你有醫生，你有病人，你有付款人，好嗎？因此，一些付款人需要不同級別的證據或信息。所以這需要時間。有時需要醫生提供這些信息。這可能需要時間，而且一些辦公室比其他辦公室更有能力提供這種級別的證據。

And then there's also parts of that, which is contacting the patient, you want to coordinate the shipment date and exactly when they're going to receive it to make sure that they're there to receive their medication. So there's a lot of different factors that can add up and cause differences. We've been very pleased to date with those that are receiving their medication that it's under 30 days. I think if you look at industry standards, I feel pretty good at where it currently sits.

然後還有一部分，就是聯繫病人，你想要協調發貨日期以及他們將要收到它的確切時間，以確保他們在那裡收到他們的藥物。所以有很多不同的因素可以加起來並導致差異。我們很高興與那些正在接受不到 30 天藥物治療的人約會。我想如果你看看行業標準，我覺得它目前所處的位置相當不錯。

But as I've indicated in prior quarters, we're not going to be satisfied with that, and we're always looking for ways to make it more efficient, quicker so that when the prescription is and the patient is enrolled, that we can get them the medication as quickly as possible.

但正如我在前幾個季度所指出的那樣，我們不會對此感到滿意，我們一直在尋找方法使其更高效、更快捷，以便在處方和患者登記時，我們可以盡快讓他們拿到藥物。

And I would say that one of the things that we have kind of heard as well as experienced from nephrologists is obviously that they are not necessarily -- they don't have huge amounts of specialty products that are being approved over the last kind of 10 years. And so for some of these kind of offices and with some nephrologists having to deal with administration related to any specialty product is something different and relatively new. And so this is something where, again, we have made sure that we are -- made sure that we have enough resources in kind of the TARPEYO Touchpoints and the hub to really try and make this as easy as possible for them.

我想說的是，我們從腎病學家那裡聽到和體驗到的一件事顯然是他們不一定——他們沒有大量的特殊產品在過去 10 年中獲得批准年。因此，對於其中一些辦公室和一些腎病學家來說，他們必須處理與任何專業產品相關的管理，這是不同的，而且相對較新。因此，在這方面，我們再次確保我們 - 確保我們在 TARPEYO 接觸點和中心方面擁有足夠的資源，真正嘗試讓他們盡可能輕鬆地做到這一點。

But I do think that this is a little bit of a novelty. And obviously, this is something that they're going to have to deal with, with any product that kind of comes to market here. So -- but that is something where we have specifically in terms of lessons learned and some of the things is that we -- that is something that we've listened to, taken on board, and actually, again, we're trying to be as helpful as possible in this process because it's unfortunately just a structural issue with regards to kind of U.S. health care.

但我確實認為這有點新奇。很明顯，這是他們將不得不處理的事情，任何在這裡上市的產品。所以 - 但這是我們在吸取經驗教訓方面的具體內容，其中一些是我們 - 這是我們已經聽取、採納的內容，實際上，我們再次嘗試在此過程中盡可能提供幫助，因為不幸的是，這只是美國醫療保健方面的結構性問題。

The next question comes from Rami Katkhuda from LifeSci Capital.

下一個問題來自 LifeSci Capital 的 Rami Katkhuda。

This is Oliver from LifeSci on for Rami. Congrats on the update. I just have 2 questions today. So first, while the launch is still early, have you identified any trends in the patients receiving TARPEYO? And second is the expanded sales force fully deployed and what proportion of nephrologists treating IgAN?

我是來自 LifeSci 的 Oliver for Rami。恭喜更新。我今天只有兩個問題。所以首先，雖然發布還早，但您是否發現接受 TARPEYO 的患者有任何趨勢？其次，擴大後的銷售隊伍是否得到充分部署，治療 IgAN 的腎病專家比例是多少？

So Andy, do you want to take those?

那麼安迪，你想接受這些嗎？

Sure. As far as the specific patients, it's too early to give you a trend. You have to remember that there's one product that's actually indicated now. And so this is where their usage has been pretty broad, meaning patients are coming to us, both first diagnosed as well as those that have been diagnosed several years earlier. We have some that are more severe than others and some that have less. So I can't really give you too much color, unfortunately, on the trends in the patients. I know we are seeing more patients per prescriber and that kind of stuff will typically increase over time as comfort levels.

當然。至於具體的患者，現在給你一個趨勢還為時過早。您必須記住，現在實際指示的是一種產品。因此，這就是它們的用途非常廣泛的地方，這意味著患者會來找我們，既有首次診斷的患者，也有幾年前被診斷出來的患者。我們有一些比其他人更嚴重，有些則更少。因此，不幸的是，關於患者的趨勢，我真的不能給你太多顏色。我知道我們每個開處方者都會看到更多的病人，而且隨著時間的推移，這種事情通常會隨著舒適度的增加而增加。

Some people want to start with their most severe patients and then they'll move to more -- to less severe probably as they get more and more comfortable. As far as the expansion of sales force and reach, I think was the question, that is typically there's a lot of factors that go into that, obviously, geography, et cetera. But we typically have formulas that we use when you're looking at a specialty sales force as far as the number of calls they can make in a day and the number of different unique prescribers and how much you want their frequency. You want a higher frequency from -- for some prescribers versus others. So there's no exact number that I'm really going to discuss now, but we feel that the expanded 20 provides us really, really strong reach and the appropriate frequency that we're going to need.

有些人想從他們最嚴重的患者開始，然後他們會轉向更嚴重的患者——可能隨著他們變得越來越舒適而轉向不太嚴重的患者。至於銷售隊伍和範圍的擴大，我認為這是一個問題，通常有很多因素會影響到這一點，顯然，地理等等。但是，當您查看專業銷售人員時，我們通常會使用公式來計算他們一天可以撥打的電話數量、不同的獨特處方醫生的數量以及您想要他們的頻率。你想要更高的頻率 - 對於一些處方者與其他人。因此，我現在沒有真正要討論的確切數字，但我們認為擴大後的 20 個為我們提供了非常非常強大的覆蓋面和我們需要的適當頻率。

The next question comes from Annabel Samimy from Stifel.

下一個問題來自 Stifel 的 Annabel Samimy。

I just wanted to ask about the data that you presented at ASN as well as the publications. You mentioned that there was very enthusiastic feedback from the physicians. I guess can you -- if you can get a little bit more granular in terms of how they responded to that. Does that -- do they express any motivation to keep patients on treatment longer, keep it intermittent based on what their -- these observations are? And have any of the drugs that they've used to date shown this kind of continued benefit post removal of treatment that they would start to think about how to use this drug differently?

我只是想問一下您在 ASN 上提供的數據以及出版物。你提到醫生的反饋非常熱情。我想你能——如果你能更詳細地了解他們對此的回應。那是否 - 他們是否表達了讓患者接受更長時間治療的任何動機，根據他們的這些觀察結果保持間歇性治療？他們迄今為止使用過的任何藥物是否顯示出這種在取消治療後的持續益處，以至於他們會開始考慮如何以不同的方式使用這種藥物？

And then I guess, as a carry-on to that, does this give you any further what does this potentially mean for Part B just to give you further comfort that the Part B is going to read out positively? Or I guess, what kind of extrapolations can you make?

然後我想，作為對它的延續，這是否讓您進一步了解這對 B 部分可能意味著什麼，只是讓您進一步安慰 B 部分將積極讀出？或者我猜，你能做出什麼樣的推斷？

Okay. Why don't I start, and I'll hand over to Richard. So I think that, obviously, what we heard at ASN and I think in other interactions, the key here is obviously that in all CKD, not just in IgA nephropathy, but the experience from the treating physician as well as this comes through in a lot of the larger analytical papers that have been published, et cetera, is that a kind of a durable kind of significant and durable kind of proteinuria reduction is something that physicians really assume will lead to a benefit for their patients. And that's really how they've been treating this patient population for a long time.

好的。為什麼我不開始，我會交給理查德。所以我認為，很明顯，我們在 ASN 上聽到的以及我在其他互動中所聽到的，這裡的關鍵顯然是在所有 CKD 中，不僅僅是 IgA 腎病，而且治療醫師的經驗以及這都來自於許多已經發表的較大的分析論文，等等，是一種持久的、顯著的和持久的蛋白尿減少是醫生真正認為會給他們的病人帶來好處的東西。這就是他們長期以來一直在治療這個患者群體的方式。

So I think that the -- this differentiated profile and to answer your question, I mean, at least we have not met anyone so far. I have not met anyone anyway so far that can show to any other drug that shows this particular profile in terms of that, you get the significant continued benefit when you actually withdraw the drug. So I think the benefits are, obviously, they look at a benefit in term -- early benefit, in terms of eGFR it is obviously very good. Most drugs actually have a negative impact on eGFR to start with. So that was kind of a positive effect that the continued kind of proteinuria reduction, I think, is seen as very intriguing and very interesting by physicians. And the fact that it's kind of that significant and durable. And obviously, this is what we ultimately have to wait for Part B to see how long of this kind of durability we have.

所以我認為 - 這種差異化的形象並回答你的問題，我的意思是，至少我們到目前為止還沒有見過任何人。無論如何，到目前為止，我還沒有遇到任何人可以證明任何其他顯示這種特殊情況的藥物，當你真正停藥時，你會獲得顯著的持續利益。所以我認為這些好處顯然是他們從術語上看的好處——早期的好處，就 eGFR 而言，這顯然非常好。大多數藥物實際上對 eGFR 有負面影響。所以這是一種積極的影響，我認為持續的蛋白尿減少被醫生認為是非常有趣和有趣的。事實上，它具有重要意義和持久性。顯然，這就是我們最終必須等待 B 部分才能看到我們擁有多長時間的這種耐用性。

But I think those are really the things that they find is extremely interesting. And I think the last part is obviously the eGFR stabilization really from an immediate perspective in these patients at risk of rapid progression is obviously also something that they find very important because these patients, obviously, at the end of the day, it is all about trying to preserve kidney function in all of these patients. And proteinuria is obviously a big look at that, is a forerunner to that kind of effect, obviously. But before we go into Part B, maybe I'll hand over to Richard to reflect on what interactions you may have had with physicians.

但我認為這些確實是他們發現的非常有趣的東西。我認為最後一部分顯然是 eGFR 的穩定，對於這些有快速進展風險的患者來說，從直接的角度來看，這顯然也是他們認為非常重要的事情，因為這些患者，顯然，在一天結束時，這一切都是關於試圖保護所有這些患者的腎功能。蛋白尿顯然是一個大問題，顯然是那種效果的先驅。但在我們進入 B 部分之前，也許我會交給理查德來反思您可能與醫生進行過哪些互動。

Well, I think it's very similar. I mean, I echo your comment. I think the profile of effects that we see are intriguing and differentiated and in particular, the cumulative improvement in proteinuria that we see during the treatment period. And as Renee has already said, I mean, I think a particularly important observation is the continued improvement in proteinuria after patients have discontinued treatment.

好吧，我認為這非常相似。我的意思是，我附和你的評論。我認為我們看到的效果概況是有趣和差異化的，特別是我們在治療期間看到的蛋白尿的累積改善。正如 Renee 已經說過的，我的意思是，我認為一個特別重要的觀察結果是患者停止治療後蛋白尿的持續改善。

And that's also reflected in data that I showed, which also confirms the maintenance of separation of the eGFR curves after discontinuation of treatment. So I think there's a great deal of positive reflections on that from the physician community. And I think that certainly, obviously, we're not going to provide a prediction of exactly what will happen in Part B, but I mean it certainly makes us comfortable that the study is well designed that we're seeing the appropriate relevant treatment effects in terms of improvements in proteinuria. We've already seen that translate through to stabilization of eGFR, and we're very encouraged about what that means in terms of the final analysis for Part B.

這也反映在我展示的數據中，這也證實了停止治療後 eGFR 曲線分離的維持。所以我認為醫生社區對此有很多積極的反映。我認為，當然，很明顯，我們不會準確預測 B 部分會發生什麼，但我的意思是，這項研究設計良好，我們看到了適當的相關治療效果，這肯定讓我們感到舒服在改善蛋白尿方面。我們已經看到這轉化為 eGFR 的穩定，我們對這對 B 部分的最終分析意味著什麼感到非常鼓舞。

I would just add the final piece there is obviously just the -- in terms of -- the only thing that we can do is really kind of then look at what the screening criteria, what we're seeing in the open-label extension. What we've kind of shown is obviously that, of course, there is a significant portion of patients, obviously, who have proteinuria below 1 gram where obviously, the entire population did have proteinuria above 1 gram at the inclusion of the start of the study. It is speculation, obviously, because it's still blinded, but I still think that it's a very interesting observation, but that is obviously what we're seeing after 2 years in a fairly significant number of the patients.

我只想添加最後一塊，顯然只是 - 就 - 而言 - 我們唯一能做的就是真正地看看篩選標準是什麼，我們在開放標籤擴展中看到了什麼。我們所展示的顯然是，當然，有很大一部分患者的蛋白尿明顯低於 1 克，顯然，整個人群的蛋白尿確實高於 1 克。學習。顯然，這是猜測，因為它仍然是盲目的，但我仍然認為這是一個非常有趣的觀察結果，但這顯然是我們在 2 年後在相當多的患者中看到的結果。

And the next question comes from Maury Raycroft from Jefferies.

下一個問題來自 Jefferies 的 Maury Raycroft。

Congrats on the quarter and progress. You mentioned 180 patients went into screening for the open-label extension, and there was a 41% failure rate there. Can you clarify if all of those patients do not qualify because of the low UPCR less than 1 gram? Or what are the other reasons for screen failure? And can you remind what are some of the measures you're collecting and objectives for the open label extension study?

祝賀本季度和進步。你提到有 180 名患者接受了開放標籤擴展的篩查，失敗率為 41%。您能否澄清是否所有這些患者都因為 UPCR 低於 1 克而不符合條件？或者屏幕故障的其他原因是什麼？你能提醒一下你正在收集的一些措施和開放標籤擴展研究的目標是什麼嗎？

Sure. I'll let Richard take the second part of that study, I mean that question. In terms of the -- in terms of the screen failure, so basically, what we've said is that out of the 180 patients who are screened, 106 are enrolled. And so the remainder screen failed. And so for those patients, the largest -- the biggest reason for screen failure really over 60% was the fact that they did not qualify in proteinuria, so they had proteinuria of have less than 1 gram. The second most significant reason was that they had too low of an eGFR. So the eGFR was below the 30 milliliters per minute. And then there is a range of other kind of reasons. But those were the 2 kind of most significant reasons for screen failure. So Richard, do you want to take the second part?

當然。我會讓 Richard 參與該研究的第二部分，我是說那個問題。就篩查失敗而言，基本上，我們所說的是，在接受篩查的 180 名患者中，有 106 名入組。因此剩餘屏幕失敗。因此，對於那些患者來說，篩查失敗的最大 - 超過 60% 的最大原因是他們不符合蛋白尿的條件，因此他們的蛋白尿少於 1 克。第二個最重要的原因是他們的 eGFR 太低。所以 eGFR 低於每分鐘 30 毫升。然後還有一系列其他原因。但這是屏幕故障的兩種最重要的原因。理查德，你想參加第二部分嗎？

Yes. So in terms of your other points, so for this study, the data collected will be similar to the data that we collected in the pivotal study. So we'll be evaluating the effects of treatment on UPCR and eGFR over the 9-month treatment period as well as other outcomes, obviously, safety and tolerability will be collected, so safety data will be collected.

是的。所以就你的其他觀點而言，對於這項研究，收集的數據將與我們在關鍵研究中收集的數據相似。因此，我們將在 9 個月的治療期間評估治療對 UPCR 和 eGFR 的影響以及其他結果，顯然，將收集安全性和耐受性，因此將收集安全數據。

Got it. That's helpful and makes sense. And I had another question to you, just for the Phase III Part B off-treatment data. Is there a bar for what proportion of patients you get into a complete remission or for a certain amount of durability that you need in order to make claims around that and add that to your label? Or if you can just talk about what additional changes to a label you could make based off of the Part B data?

知道了。這很有幫助，也很有意義。我還有另一個問題要問你，只是關於 III 期 B 部分的停藥數據。有多少患者獲得完全緩解或需要一定的耐久性，以便圍繞它提出索賠並將其添加到您的標籤中，是否有一個標準？或者，如果您可以談談您可以根據 B 部分數據對標籤進行哪些額外更改？

So I guess that the most -- the most obvious, I guess, obviously, in terms of Part B really would be the impact on eGFR, right? So obviously, in terms of what we have to date really is kind of just the impact on proteinuria, which, as we all know, is a surrogate. So I think this is really kind of considered more of a hard endpoint than proteinuria reduction generally by the regulators. And so I think that, that data is obviously going to be critical in terms of disease modification, for example, right?

所以我想，就 B 部分而言，最 - 最明顯的，我想，顯然是對 eGFR 的影響，對吧？很明顯，就我們迄今為止所知道的而言，實際上只是對蛋白尿的影響，眾所周知，這是一種替代因素。所以我認為這實際上比監管機構普遍認為的減少蛋白尿更像是一個硬終點。因此，我認為，這些數據顯然在疾病改良方面至關重要，例如，對嗎？

So I mean, what is -- what are you going to be able to say exactly when the disease modification, it's difficult to kind of have a view on here. But I think that, that's obviously kind of a one avenue. I think that another avenue is, as you say, in terms of, if you can -- if we can show -- have some views at least on the durability of response and the kind of the consequences of that on eGFR is obviously also going to be something, I think, that everyone is going to be very interested in.

所以我的意思是，什麼是——你能準確地說出什麼時候疾病發生變化，很難對這裡有看法。但我認為，這顯然是一種單一途徑。我認為另一個途徑是，正如你所說，如果你能——如果我們能證明——至少對反應的持久性和對 eGFR 的影響類型顯然也有一些看法我認為，成為每個人都會非常感興趣的東西。

I think that how long will this affect lasts? Because obviously, this is this more unique focus on the kind of treating the origin of the disease. And so I think there's a lot of interest around that. I do think that physicians, in general, are very positively implying towards increasing that kind of proteinuria reduction over time, which is what we've seen and obviously also then kind of the durability of it. But I think in terms of what we can see in the label, as always, I think that's going to be ultimately a negotiation with the regulators, which is always very difficult to kind of have a view on at this point in time. But I think those are kind of the type of areas that we will obviously be discussing with them.

我認為這種影響會持續多久？因為很明顯，這是這種更獨特的專注於治療疾病根源的方式。所以我認為人們對此很感興趣。我確實認為，一般來說，醫生非常積極地暗示隨著時間的推移增加這種蛋白尿的減少，這是我們所看到的，顯然也是它的持久性。但我認為，就我們在標籤中看到的內容而言，一如既往，我認為這最終將是與監管機構的談判，在這個時間點總是很難對此發表看法。但我認為這些是我們顯然會與他們討論的領域類型。

The next question comes from Johan Unnerus from Redeye.

下一個問題來自 Redeye 的 Johan Unnerus。

Partly in follow-ups. In the patients that were in the extension there, OLE group, some 74 did not follow up. And earlier, you clarified that 61% or about 45-ish did not continue due to those proteinuria levels. The other 29-ish, can you say anything to what extent the group that had too low eGFR represents in this group?

部分在後續行動中。在 OLE 組的擴展患者中，約有 74 名患者未進行隨訪。早些時候，您澄清說，由於那些蛋白尿水平，61% 或大約 45-ish 沒有繼續。其他 29 歲左右，你能說說 eGFR 過低的群體在這個群體中代表的程度嗎？

Well, I mean, again, as I said, because it's blinded it is kind of -- this is speculation because we won't be able to unblind this trial until the completion of the Phase III program as a whole. But one could obviously speculate and assume that there are some patients who would have been in this trial for 2 years who would have entered into the trial with a fairly low eGFR and may, therefore, over the 2-year period be in a situation where their eGFR is below 30. And if it was below 30, they would not be included in the open-label extension.

好吧，我的意思是，正如我所說，因為它是盲的，所以這是一種猜測，因為在整個 III 期計劃完成之前，我們無法揭開這個試驗的盲點。但是很明顯可以推測並假設有些患者本應參加該試驗 2 年，他們本可以以相當低的 eGFR 進入試驗，因此，在 2 年期間可能處於以下情況：他們的 eGFR 低於 30。如果低於 30，他們將不會被納入開放標籤擴展。

And as we've seen, there obviously are patients at risk of kind of rapid progression, has had quite a significant decline in their eGFR. So that, I think -- but again, that would be speculation.

正如我們所見，顯然有一些患者處於快速進展的風險中，他們的 eGFR 顯著下降。所以，我認為 - 但同樣，這將是猜測。

Yes. So we don't -- at this stage, we can't say if it's 5 or 10 or whatever. It's the second largest group.

是的。所以我們不——在這個階段，我們不能說它是 5 還是 10 或其他什麼。這是第二大群體。

Yes.

是的。

Anyway, yes. And also, you have, of course, now a fair amount of patients that have been treated more than 25 months. Is there any indication of the second growth for any of these patients? Or is this also sort of blinded?

無論如何，是的。而且，當然，現在有相當數量的患者已經接受了超過 25 個月的治療。這些患者中有任何二次生長的跡象嗎？或者這也有點盲目？

So is it -- okay, I'm not sure what that means, so all patients obviously have been treated for 9 months and are then observed after that period of time. And so obviously, are you referring to -- so obviously, for those patients who go into...

是嗎——好吧，我不確定那是什麼意思，所以顯然所有患者都接受了 9 個月的治療，然後在這段時間後接受觀察。很明顯，你指的是 - 很明顯，對於那些進入......

Yes, I'm thinking about the group that has completed these 24 months and there must be a fair amount of patients that have done that.

是的，我正在考慮完成這 24 個月的小組，並且必須有相當數量的患者已經完成了。

Yes. exactly. Yes. Exactly. And those are -- that's what we refer to as the patients who have exited that study, out of those who have finished the trial of 2 years, that's what we're saying, 180 have screened for the open-label extension, and 106 as of the end of Q3 were enrolled into that study, and are therefore receiving an additional or their first kind of treatment of 9 months. So obviously, it's not enough -- we do not know whether this is patients who are retreated or whether these are patients who are in the placebo group and therefore, are getting their first treatment. That is something that we don't know since the trial is blinded. But 106 of them are as of now enrolled in that open-label extension.

是的。確切地。是的。確切地。這些是——這就是我們所說的退出該研究的患者，在那些完成了 2 年試驗的患者中，這就是我們所說的，180 人已經篩選了開放標籤擴展，106 人截至第三季度末被納入該研究，因此正在接受額外的或他們的第一種治療 9 個月。很明顯，這還不夠——我們不知道這是接受治療的患者，還是安慰劑組的患者，因此他們正在接受第一次治療。這是我們不知道的事情，因為試驗是盲目的。但其中 106 人已經加入了該開放標籤擴展。

Of course, the patients themselves will, of course, if they have the second one. Yes. No, I think that was all for me and congratulations on good results. And I think as earlier answers were alluded to, it's a bit early on the dynamics between unique prescribers and number of patients and it was also very useful to get a feel for the dynamics between prescribers and sales and the time that takes at this stage in a way.

當然，如果他們有第二個，患者自己當然會。是的。不，我想這就是我的全部，祝賀我取得了好成績。而且我認為，正如前面提到的那樣，獨特的處方者和患者數量之間的動態關係還為時過早，了解處方者和銷售人員之間的動態關係以及在這個階段所花費的時間也非常有用離開。

Well, thank you very much. So with that, thank you very much to everybody who's participated, and we look forward to sharing our Q4 report with you in February. Thank you very much.

好的，謝謝。因此，非常感謝所有參與的人，我們期待在 2 月份與您分享我們的第四季度報告。非常感謝。