Calliditas Therapeutics AB (CALT) 2023 Q2 法說會逐字稿

Welcome to the Calliditas Therapeutics Q2 2023 report. (Operator Instructions) Now I'll hand over the conference to speakers; CEO, Renee Aguiar-Lucander; CFO, Fredrik Johansson; Andrew Udell, President of North America; and Richard Philipson, Chief Medical Officer. Please go ahead.

歡迎閱讀 Calliditas Therapeutics 2023 年第二季報告。 （操作員指示）現在我將會議交給發言人；首席執行官，Renee Aguiar-Lucander；財務長 Fredrik Johansson；安德魯‧尤德爾 (Andrew Udell)，北美區總裁；和首席醫療官理查德·菲利普森。請繼續。

Thank you very much, and welcome, everybody, to this Q2 report of 2023. I would just like to draw your attention to the disclaimer page related to forward-looking statements in the meaning of the Private Securities Litigation Reform Act of 1995 as amended. And I refer you to the company's reports and other regulatory filings including those which contain risk factors and other relevant information.

非常感謝並歡迎大家閱讀 2023 年第二季報告。我只想提請您注意與 1995 年《私人證券訴訟改革法案》修訂版含義中的前瞻性陳述相關的免責聲明頁面。我建議您參閱該公司的報告和其他監管文件，包括包含風險因素和其他相關資訊的文件。

So I want to take you through some of the Q2 highlights. So in June of this year, we filed our supplemental NDA with the FDA, which is based on the full data from the NefIgArd Phase III trial. The trial successfully made its endpoint of kidney function as measured by eGFR which was supported by durability of proteinuria reduction, reduction in microhematuria in the treatment arm and a highly significant benefit for Nefecon over placebo in terms of total slope.

所以我想帶您了解第二季的一些亮點。因此，今年 6 月，我們向 FDA 提交了補充 NDA，該 NDA 基於 NefIgArd III 期試驗的完整數據。該試驗成功地達到了透過 eGFR 測量的腎功能終點，治療組中蛋白尿減少的持久性、微量血尿的減少以及 Nefecon 在總斜率方面相對於安慰劑的顯著益處都支持了這一點。

The first data from the trial was presented to the nephrology community during the ERA EDTA Congress in Milan in June, and the reception was very positive. And we've also received very positive feedback from advisory board meetings held with U.S. nephrologists regarding the Phase III data. And we're obviously very excited about the recent publication in The Lancet, of the data.

該試驗的第一份數據在 6 月於米蘭舉行的 ERA EDTA 大會上向腎臟病學界提交，反應非常積極。我們也從與美國腎臟病專家舉行的顧問委員會會議上收到了關於 III 期數據的非常正面的回饋。我們顯然對《刺胳針》最近發表的數據感到非常興奮。

So in the second quarter, we saw a record level of 422 new enrollments for TARPEYO. So we're seeing a continued growth of the franchise. The number of prescribers also continue to grow with [Q2] seeing over a total of over 1,100 prescribers of TARPEYO compared to only around 300 or so in Q2 of 2022.

因此，在第二季度，TARPEYO 的新註冊人數達到創紀錄的 422 人。所以我們看到特許經營權的持續成長。處方者數量也持續成長，[第二季]TARPEYO 處方者總數超過 1,100 名，而 2022 年第二季僅為 300 名左右。

Total revenues of SEK 269 million or about $25 million, out of which TARPEYO net sales represented SEK 259 million, which reflects a 39% growth over Q1 and over 270% growth over Q2 2022. Based on our experience to date, as you know, we are pioneers in this whole area sector. So based on the limited label, continued market access friction and potential seasonality impact from the summer period, we've decided to revise our '23 outlook to $100 million to $120 million of net sales for TARPEYO for 2023.

總營收為2.69 億瑞典克朗，約2,500 萬美元，其中TARPEYO 淨銷售額為2.59 億瑞典克朗，比2022 年第一季成長39%，比2022 年第二季成長超過270%。根據我們迄今為止的經驗，如您所知，我們是整個領域的先驅。因此，基於有限的標籤、持續的市場准入摩擦以及夏季潛在的季節性影響，我們決定將 23 年 TARPEYO 2023 年淨銷售額展望修改為 1 億至 1.2 億美元。

In terms of post-period events and pipeline updates, we recently shared some exciting data from the interim readout of our head and neck cancer trial, which Richard will cover a bit later in some detail. And in light of recent clinical and biomarker data advances in the liver area and regulatory interactions. We decided to implement a revision of the trial design of TRANSFORM, which is our clinical trial in PBC, which will enable us to report out -- read out the Phase IIb data, which is targeted for the first half of 2024.

在後期事件和管道更新方面，我們最近分享了頭頸癌試驗中期讀數中的一些令人興奮的數據，理查德將在稍後詳細介紹這些數據。並根據肝臟領域和監管相互作用的最新臨床和生物標記數據進展。我們決定對 TRANSFORM 的試驗設計進行修訂，這是我們在 PBC 中的臨床試驗，這將使我們能夠報告 - 讀出 IIb 期數據，目標是 2024 年上半年。

Most importantly, enable us to make the most appropriate decision regarding the program going forward, including exploring potential different indications as well as partnerships which we have been having conversations regarding.

最重要的是，使我們能夠就未來的計劃做出最合適的決定，包括探索潛在的不同適應症以及我們一直在討論的合作夥伴關係。

As previously mentioned, our Phase III data was published in The Lancet very recently. And obviously, as you may know, obviously, The Lancet is one of the top medical journals in the world, all referred to as one of the big 5. And so we're certainly very excited about the recent publication and we believe that this really will kick off the dialogue with the nephrology community in the U.S. with regards to the data that we saw in our Phase III trial.

如前所述，我們的 III 期數據最近發表在《刺胳針》上。顯然，正如您所知，《柳葉刀》是世界頂級醫學期刊之一，被稱為五大醫學期刊之一。因此，我們對最近的出版物感到非常興奮，我們相信這確實將啟動與美國腎臟病學界就我們在第三階段試驗中看到的數據進行對話。

So with that, I'm going to hand over to Richard Philipson, our Chief Medical Officer, to take you through some of the clinical data.

因此，我將把工作交給我們的首席醫療官理查德·菲利普森（Richard Philipson），他將帶您了解一些臨床數據。

Thanks very much, Renee. I'll begin by reviewing some of the outcomes of the NefIgArd final analysis. So just as a brief reminder of the Phase III study design, the NefIgArd study enrolled patients with biopsy-proven [IgA] nephropathy, proteinuria of 1 gram per day or greater and an eGFR of 35 to 90 ml per minute and with well controlled blood pressure whilst on optimized RAS inhibition.

非常感謝，蕾妮。我將首先回顧 NefIgArd 最終分析的一些結果。因此，作為 III 期研究設計的簡要提醒，NefIgArd 研究納入了經活檢證實的 [IgA] 腎病、蛋白尿每天 1 克或以上、eGFR 為每分鐘 35 至 90 毫升且血液控制良好的患者壓力，同時優化RAS 抑制。

Immunosuppressive therapy was not permitted during the study and changes to anti-hypertensive medications were discouraged. Patients were randomized to receive TARPEYO at a dose of 16 milligrams per day or placebo for a 9-month treatment period. An interim analysis of change from baseline in proteinuria in the first 199 patients enrolled and treated for 9 months, formed the basis for accelerated and conditional approval in the U.S. and Europe, respectively.

研究期間不允許免疫抑制治療，也不鼓勵更換抗高血壓藥物。患者被隨機分配接受每天 16 毫克劑量的 TARPEYO 或安慰劑治療，為期 9 個月。對前 199 名入組並接受治療 9 個月的患者的蛋白尿較基線變化進行的中期分析，為分別在美國和歐洲加速批准和有條件批准奠定了基礎。

The final analysis of the NefIgArd study is based on 364 patients in the full analysis set for efficacy treated for 9 months and followed up for a further 15 months without investigational treatment with the primary endpoint of average change from baseline in eGFR over the entire 24-month period of treatment and observation and with eGFR slope based secondary end points.

NefIgArd 研究的最終分析是基於完整分析集中的364 名患者，他們接受了9 個月的治療，並在沒有進行研究性治療的情況下進一步隨訪了15 個月，主要終點是整個24 天內eGFR 相對於基線的平均變化。一個月的治療和觀察期以及基於 eGFR 斜率的次要終點。

As previously reported, the primary endpoint of average change in eGFR over the 2-year period of treatment and observation was met with a highly statistically significant difference between Nefecon and placebo. And all additional supportive analyses of eGFR 2-year total slope were also statistically significant.

如同先前所報導的，在 2 年的治療和觀察期間，eGFR 平均變化的主要終點在 Nefecon 和安慰劑之間存在高度統計顯著性差異。 eGFR 2 年總斜率的所有其他支持性分析也具有統計顯著性。

When we look at the effect of Nefecon treatment on eGFR 2-year total slope, we see a difference of approximately 1.8 to 3 ml per minute per year in favor of Nefecon compared to placebo, depending on the analysis method used. All estimates are well in excess of the difference per year and 2-year eGFR total slope required to predict clinically meaningful long-term effects.

當我們觀察 Nefecon 治療對 eGFR 2 年總斜率的影響時，我們發現與安慰劑相比，Nefecon 每年每分鐘約有 1.8 至 3 毫升的差異，具體取決於所使用的分析方法。所有估計值均遠遠超過預測具有臨床意義的長期影響所需的每年差異和 2 年 eGFR 總斜率。

Specifically, comparison with the met analysis by increased hours has shown that all estimates of the Nefecon treatment benefit on 2-year eGFR total slope are well in excess of the threshold of 1.23 ml per minute per year required to predict with a high degree of confidence, clinically meaningful treatment effects on the composite clinical endpoint of kidney failure, eGFR decline to less than 15 ml per minute or sustain doubling in serum creatinine.

具體來說，與增加小時數的met分析進行比較表明，Nefecon治療效益對2年eGFR總斜率的所有估計都遠遠超過了高置信度預測所需的每年每分鐘1.23毫升的閾值，對腎衰竭、eGFR 下降至每分鐘15 毫升以下或血清肌酸酐持續加倍的複合臨床終點具有臨床意義的治療效果。

An evaluation of microhematuria was also included as a secondary endpoint in the final analysis of the NefIgArd trial. This was measured using dipstick testing at each visit during observational follow-up. A baseline in patients included in this analysis, the proportion of patients with microhematuria was 66.5% and 67.8% in the Nefecon and placebo groups, respectively. In other words, the proportion of patients with microhematuria was very similar in the 2 treatment groups at baseline.

NefIgArd 試驗的最終分析中還包括了微量血尿的評估作為次要終點。這是在觀察追蹤期間每次訪問時使用試紙測試來測量的。在本分析納入的患者基線中，Nefecon 組和安慰劑組出現微量血尿的患者比例分別為 66.5% 和 67.8%。換句話說，基線時兩個治療組中出現微量血尿的患者比例非常相似。

During observational follow-up, the proportion of patients with microhematuria decreased to 40.5% in patients previously treated with Nefecon. Whereas in patients previously treated with placebo, the proportion of microhematuria doing observational follow-up was only slightly lower than at baseline at 61.2%. These observations with respect to microhematuria further support the potential disease-modifying effect of Nefecon.

在觀察性追蹤期間，先前接受 Nefecon 治療的患者中出現微量血尿的患者比例下降至 40.5%。而在先前接受安慰劑治療的患者中，進行觀察性追蹤的微量血尿比例僅略低於基線時的 61.2%。這些關於微量血尿的觀察結果進一步支持了 Nefecon 潛在的疾病緩解作用。

I'd like to take a moment now to discuss our evolving understanding of the long-term outcomes in IgA nephropathy. A recent published registry analysis of a representative cohort of patients with IgA nephropathy underscores the poor outcomes observed in patients with the disease and provides evidence that proteinuria levels traditionally considered benign or low-risk are, in fact, associated with increased risk of kidney failure.

我現在想花點時間討論一下我們對 IgA 腎病長期結果的不斷發展的理解。最近發表的一項針對具有代表性的IgA 腎病患者隊列的登記分析強調了在該病患者中觀察到的不良結果，並提供了證據表明傳統上被認為是良性或低風險的蛋白尿水平實際上與腎衰竭風險增加有關。

This analysis showed that most patients progress to kidney failure within 10 to 15 years, irrespective of age of diagnosis with a median kidney survival of approximately 10 years. The analysis also showed that all patients diagnosed with IgA nephropathy before the age of 40 years and with an annual eGFR decline of 3 ml per minute would progress to kidney failure in their lifetime. But even an annual rate of eGFR decline as small as 1 ml per minute would lead to a significant proportion of patients reaching kidney failure within their lifetime.

該分析表明，無論診斷年齡如何，大多數患者在 10 至 15 年內進展為腎衰竭，中位腎臟存活期約為 10 年。分析還顯示，所有在 40 歲之前診斷出 IgA 腎病且每年 eGFR 下降每分鐘 3 毫升的患者將在其一生中進展為腎衰竭。但即使 eGFR 年下降率小至每分鐘 1 毫升，也會導致很大一部分患者在其一生中出現腎衰竭。

The analysis confirmed our understanding that proteinuria is a clear risk factor for kidney disease progression in IgA nephropathy with higher time average proteinuria being associated with greater likelihood of progressing to kidney failure more quickly. However, what was particularly striking in the analysis was the increased risk of kidney failure in patients with levels of proteinuria traditionally considered to confer a low risk of progression to kidney failure.

該分析證實了我們的理解，即蛋白尿是 IgA 腎病腎臟疾病進展的一個明顯危險因素，較高的時間平均蛋白尿與更快進展為腎衰竭的可能性更大相關。然而，分析中特別引人注目的是，蛋白尿水平傳統上被認為進展為腎衰竭的風險較低的患者腎衰竭的風險增加。

Specifically, and when considering time average proteinuria levels, 30% of patients with proteinuria of 0.44 to 0.88 grams per gram, and approximately 20% of patients with proteinuria less than 0.44 grams per gram, developed kidney failure within 10 years. This further emphasizes the importance of intervention to reduce proteinuria levels early in the disease course. Indeed, the manuscript commented that disease-modifying therapies that specifically target the immune system are more likely to be effective early in the natural history of IgA nephropathy before the kidneys accumulate significant irreversible fibrosis.

具體而言，考慮到時間平均蛋白尿水平，蛋白尿為 0.44 至 0.88 克/克的患者中有 30% 以及蛋白尿低於 0.44 克/克的患者中約 20% 在 10 年內出現腎衰竭。這進一步強調了在病程早期進行幹預以降低蛋白尿水平的重要性。事實上，該手稿評論說，專門針對免疫系統的疾病緩解療法更有可能在 IgA 腎病自然史的早期、腎臟積累顯著的不可逆纖維化之前有效。

I'd like to move on now to discuss our interim review of data from the ongoing head and neck cancer study. As a brief reminder, the ongoing Phase II study of setanaxib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck will evaluate the effect of setanaxib or placebo in conjunction with pembrolizumab on clinical and biomarker outcomes.

我現在想繼續討論我們對正在進行的頭頸癌研究數據的中期審查。簡單提醒一下，正在進行的 setanaxib 在頭頸部復發或轉移性鱗狀細胞癌患者中的 II 期研究將評估 setanaxib 或安慰劑聯合派姆單抗 (pembrolizumab) 對臨床和生物標記結果的影響。

Patients with recurrent or metastatic disease and tumors characterized by moderate or high levels of cancer-associated fibroblasts, or CAFs, are randomized to receive setanaxib or placebo on top of pembrolizumab, with tumor biopsies taken prior to enrollment and again after 9 weeks of treatment corresponding to 3 cycles of pembrolizumab. Treatment continues until disease progression, unacceptable toxicity or patient and/or investigator decision and patients have followed up for progression-free survival.

患有復發性或轉移性疾病以及以中度或高水平癌症相關成纖維細胞(CAF) 為特徵的腫瘤的患者被隨機分配接受塞那昔布或安慰劑聯合派姆單抗治療，並在入組前進行腫瘤活檢，並在治療9 週後再次進行相應的腫瘤活檢。至 3 個週期的派姆單抗。治療持續直至疾病惡化、不可接受的毒性或患者和/或研究者的決定以及患者追蹤無惡化存活期。

The planned interim review of clinical and biomarker data are scheduled to occur after 12 patients with paired biopsies. Tumor had completed at least 9 weeks of study treatment. The data cutoff of this data review was the 26th of May of this year. 20 patients contributed data on clinical outcomes, and 12 of these 20 patients had paired tumor biopsies for a review. We evaluated clinical outcomes such as change in tumor size and disease progression and biomarker changes, including histological and transcriptomic assessments. We did not perform a review of safety data since this is done separately by an IDMC, which reviewed safety data and identified no concerns earlier this year in March. Second IDMC meeting is planned for next month.

計劃對 12 名患者進行配對活檢後進行臨床和生物標記數據的中期審查。腫瘤已完成至少 9 週的研究治療。本次資料審核的資料截止日期為今年5月26日。 20 名患者提供了臨床結果數據，這 20 名患者中有 12 名進行了配對腫瘤活檢以供審查。我們評估了臨床結果，例如腫瘤大小和疾病進展的變化以及生物標記的變化，包括組織學和轉錄組學評估。我們沒有對安全資料進行審查，因為這是由 IDMC 單獨進行的，該委員會在今年 3 月初審查了安全資料並沒有發現任何問題。第二次 IDMC 會議計劃於下個月舉行。

At the cutoff for this data review, 7 of the 16 evaluable patients were progression-free with either stable disease or partial response. Of these 7 patients, 6 were in the setanaxib treatment arm and 1 was in the placebo arm. 6 of the 7 patients were still on the study drug at the time of the data readout. Of these 6 patients, 5 were in the setanaxib treatment arm and the longest period on drug was reported as 21 weeks in a patient in the setanaxib arm.

在本次數據審查截止時，16 名可評估患者中有 7 名無進展，疾病穩定或部分緩解。在這 7 名患者中，6 名屬於 setanaxib 治療組，1 名屬於安慰劑組。在讀取數據時，7 名患者中有 6 名仍在服用研究藥物。在這 6 名患者中，有 5 名屬於 setanaxib 治療組，據報道，setanaxib 組患者的最長用藥時間為 21 週。

Turning to the biomarker analysis. And again, at the cutoff for this data review, transcriptomic analysis indicated that downregulation of gene expression in the idiopathic lung fibrosis and hepatic fibrosis pathways was more significant in the patients receiving setanaxib compared to patients receiving placebo. There was also a potentially favorable effect of setanaxib treatment on the immunological activity of the tumor observed through Foxp3 staining and the combined positive score.

轉向生物標誌物分析。同樣，在本次數據審查截止時，轉錄組分析表明，與接受安慰劑的患者相比，接受 setanaxib 的患者特發性肺纖維化和肝纖維化途徑中基因表達的下調更為顯著。透過 Foxp3 染色和綜合陽性評分觀察到，setanaxib 治療對腫瘤的免疫活性也有潛在的有利影響。

So in summary, at the time of the cutoff of the interim review of data, we saw a numerical difference in progression events and patients remaining on randomized treatment in favor of setanaxib and detected a preliminary signal suggesting greater down regulation of important genes in the idiopathic lung fibrosis and hepatic fibrosis pathways in patients treated with setanaxib versus placebo, which is consistent with the mechanism of action of setanaxib. Detecting changes in tumor staining was more challenging because of the small size of tissue biopsies. But nevertheless, we saw some evidence of an increase in the immunological activity of tumors in association with setanaxib treatment.

總之，在數據中期審查截止時，我們看到進展事件和仍接受隨機治療的患者在數字上存在差異，有利於塞那昔布，並檢測到一個初步信號，表明特發性重要基因的下調更大。setanaxib 與安慰劑治療患者的肺纖維化和肝纖維化途徑比較，這與 setanaxib 的作用機制一致。由於組織切片的尺寸較小，檢測腫瘤染色的變化更具挑戰性。但儘管如此，我們還是看到了一些證據顯示腫瘤免疫活性的增加與塞那昔布治療有關。

So that completes my part of the presentation. I'll hand over to Andy Udell.

我的演示部分就這樣完成了。我將把工作交給安迪·烏德爾。

Thank you, Richard. Next slide. So during the second quarter of 2023, Calliditas commercial team continued to build on the achievements from the previous quarter, further reinforcing the position of TARPEYO as a transformative and foundational treatment option for IgA nephropathy. Net sales of $25 million in Q2 represented a 39% growth over Q1. In addition, our specialty sales force generated 422 enrollments during the quarter, which represents further growth coming off of Q1 record of enrollments and brings the 2023 total to 831 at midyear.

謝謝你，理查。下一張投影片。因此，在2023年第二季度，Calliditas商業團隊繼續在上一季取得的成就的基礎上再接再厲，進一步鞏固了TARPEYO作為IgA腎病變革性和基礎性治療選擇的地位。第二季淨銷售額為 2,500 萬美元，比第一季成長 39%。此外，我們的專業銷售團隊在本季度招收了 422 名註冊人數，這意味著在第一季度的註冊人數記錄基礎上進一步增長，使 2023 年年中註冊人數達到 831 名。

This strong 85% growth compared to the first half of '22 and the addition of 232 new prescribers during the quarter underscore the growing recognition of TARPEYO's clinical value among health care providers. In the second quarter, over 90% of the patients enrolled in TARPEYO touch points, excluding those still waiting for the final insurance decision received TARPEYO. In addition, compared to the first quarter, we saw a 14% improvement in the average time to fill, reflecting our continuous investment in supporting providers and patients in accessing TARPEYO.

與 22 年上半年相比，這一強勁增長為 85%，並且本季度新增了 232 名處方醫生，這突顯了 TARPEYO 的臨床價值在醫療保健提供者中的日益認可。第二季度，超過 90% 的患者加入了 TARPEYO 接觸點（不包括仍在等待最終保險決定的患者）。此外，與第一季相比，我們發現平均就診時間縮短了 14%，這反映出我們在支援提供者和病患存取 TARPEYO 方面的持續投資。

Next slide, please. During the second quarter, our medical and commercial teams had a robust presence at major nephrology conferences, including the National Kidney Foundation Spring Clinical Meeting and the European Renal Association Congress held in Milan in June. ERA EDTA proved instrumental in Calliditas' scientific exchange efforts with NefIgArd pivotal data receiving recognition as a late-breaker presentation. This marked the scientific community's first encounter with these critical findings capturing the interest level of nephrologists around the globe. Additionally, abstracts with valuable data on proteinuria and hematuria were presented from the full NefIgArd study population, which further demonstrated the uniqueness and benefits of TARPEYO in the treatment of IgAN.

請下一張投影片。第二季度，我們的醫療和商業團隊在主要腎臟病學會議上表現強勁，包括美國國家腎臟基金會春季臨床會議和 6 月在米蘭舉行的歐洲腎臟協會大會。事實證明，ERA EDTA 在 Calliditas 的科學交流工作中發揮了重要作用，NefIgArd 的關鍵數據被認為是後來者的演示。這標誌著科學界首次接觸這些引起全球腎臟科醫師興趣的關鍵發現。此外，還提供了來自完整 NefIgArd 研究人群的蛋白尿和血尿有價值數據的摘要，這進一步證明了 TARPEYO 在治療 IgAN 方面的獨特性和益處。

Discussions at ERA EDTA centered around the evolving IgAN treatment landscape and the importance of immunomodulatory therapies to suppress pathogenic IgA production and control glomerular inflammation, highlighting TARPEYO's pivotal role in the treatment paradigm. Calliditas has and will always remain dedicated to IgA nephropathy patients and caregivers. Our patient and advocacy support is unwavering.

ERA EDTA 的討論圍繞著不斷發展的 IgAN 治療格局以及免疫調節療法抑制致病性 IgA 產生和控制腎小球發炎的重要性，強調了 TARPEYO 在治療範例中的關鍵作用。 Calliditas 一直並將永遠致力於 IgA 腎臟病患者和照護者。我們的耐心和倡導支持是堅定不移的。

Early in Q3, we led the sponsorship and support of the IgA Nephropathy Foundation second annual in-person patient summit called SPARK. This event is extraordinary and special. It's filled with approximately 200 patients that are eager to learn, connect, support, smile, cry, and even dance together. Attendance at the event is motivation and confirmation to our team members that focus on access, availability and education of IgA nephropathy on a daily basis.

第三季初，我們主導贊助並支持了名為 SPARK 的 IgA 腎臟病基金會第二屆年度面對面患者高峰會。此次活動非比尋常、特殊。這裡擠滿了大約 200 名患者，他們渴望學習、交流、支持、微笑、哭泣，甚至一起跳舞。參加這項活動對我們每天關注 IgA 腎病的獲取、可用性和教育的團隊成員來說是一種激勵和肯定。

Next slide, please. We've seen very rapid and significant growth from the launch of our product delivered by a dedicated team with great execution capabilities, however, due to primarily 2 factors our indication and label during accelerated approval and the market access friction that while it's typical for specialty products is new to many in the nephrology specialty, we are revising our guidance.

請下一張投影片。然而，我們的產品由具有強大執行能力的專業團隊推出後，我們看到了非常快速和顯著的增長，然而，主要由於兩個因素，即我們在加速審批過程中的指示和標籤以及市場准入摩擦，儘管這是專業產品的典型現象產品對於腎臟病學專業的許多人來說是新的，我們正在修訂我們的指南。

As you are aware, our indication during this accelerated approval period is based on proteinuria reduction and describes rapid disease progression as generally a UPCR of greater than or equal to 1.5 grams per gram. While this is not a cutoff, some payers do manage more strictly to the 1.5 grams per gram, which has skewed the initial usage of TARPEYO towards patients with a higher UPCR level, which has reduced the addressable market size compared to the population represented in our pivotal trial, which aligns with how rapid progression is defined in the KDIGO guidelines.

如您所知，我們在此加速批准期內的適應症是基於蛋白尿減少，並將疾病快速進展描述為通常 UPCR 大於或等於每克 1.5 克。雖然這不是一個界限，但一些付款人確實更嚴格地控制每克1.5 克，這使得TARPEYO 的初始使用偏向UPCR 水平較高的患者，與我們的人口相比，這減少了可尋址市場規模。關鍵試驗，與 KDIGO 指南中定義的快速進展一致。

As it relates to market access, as we've mentioned previously, at a given time, approximately 15% to 20% of enrollments are still in process. This typically means that the enrollment requires more information or they are going through the approval or appeal process with payers, which can require some back and forth between payer, nephrology office, and our hub. While TARPEYO coverage is broad, with over 90% of U.S. lives having coverage, we are seeing that between 5% and 15% of enrollments do not ultimately convert due to a variety of reasons.

由於它與市場准入有關，正如我們之前提到的，在特定時間，大約 15% 到 20% 的註冊仍在進行中。這通常意味著註冊需要更多信息，或者他們正在與付款人一起進行批准或上訴流程，這可能需要付款人、腎臟病辦公室和我們的中心之間進行一些來回。雖然 TARPEYO 的覆蓋範圍很廣，超過 90% 的美國人都有保險，但我們發現，由於各種原因，有 5% 到 15% 的註冊者最終沒有轉換。

This is most often due to payer management, which, while is typical once again for a specialty drug, has several inexperienced and under-resourced office staff unwillingness to go through the process, which can include appealing initial payer decisions. This is different from other disease categories such as oncology or rheumatoid arthritis, where a payer management is expected and integrated into the office workflow and providers generally understand how to navigate payer management using clinical rationale.

這通常是由於付款人管理造成的，雖然這對於特殊藥物來說再次是典型的，但一些缺乏經驗和資源不足的辦公室工作人員不願意完成這個過程，其中可能包括對最初的付款人決定提出上訴。這與腫瘤或類風濕性關節炎等其他疾病類別不同，在這些疾病類別中，付款人管理被期望並整合到辦公室工作流程中，並且提供者通常了解如何使用臨床原理來引導付款人管理。

While we have many patients that have received longer than 9 months of therapy, the average duration of therapy over the last 12 months is approximately 8 months long, as we've heard from some of the top KOLs that are familiar with our product and the full study results that were published in The Lancet this week, TARPEYO works differently than any other product. And this requires education and time to disseminate to prescribers and change long-lasting habits and how they've treated IgAN in these patients for many years.

雖然我們有許多患者接受了超過 9 個月的治療，但正如我們從一些熟悉我們產品和產品的頂級 KOL 那裡聽到的那樣，過去 12 個月的平均治療持續時間約為 8 個月。完整的研究結果本週發表在《刺胳針》上，TARPEYO 的角色與其他產品都不同。這需要教育和時間來向處方者傳播並改變長期習慣以及他們多年來治療這些患者的 IgAN 的方式。

Next slide, please. We continue to center efforts and resources on education and market access support and remain confident that we will demonstrate continued growth and enhanced sales trajectory following full approval in the broader population due to the following: first, full approval reduced payer limitations and would, on the basis of approval in the full trial population substantially increase the size of the addressable market.

請下一張投影片。我們繼續將努力和資源集中在教育和市場准入支持上，並仍然有信心在更廣泛的人群中獲得全面批准後，我們將展示持續增長和增強的銷售軌跡，原因如下：首先，全面批准減少了付款人限制，並將在全面試驗人群中獲得批准的基礎上，大大增加了目標市場的規模。

Market access friction will continue to decline with the additional resources we put forth and also be supported by our full trial results from NefIgArd being published and the expanded scientific exchange of information that is anticipated with payers and nephrologists while we move towards full approval and a new label. Physicians will gain further confidence with continued use, patient success stories as well as familiarity to the data of both NefIgArd trial as well as our open-label study -- extension study, which will conclude in the middle of 2024.

隨著我們提供額外資源，市場准入摩擦將繼續減少，同時我們還得到了NefIgArd 的全面試驗結果的支持，以及在我們邁向全面批准和新的過程中預計與付款人和腎臟病學家進行的擴大的科學資訊交流的支持。標籤。透過繼續使用、患者成功案例以及對 NefIgArd 試驗數據以及我們將於 2024 年中期結束的開放標籤研究（擴展研究）數據的熟悉，醫生將獲得進一步的信心。

Once again, I want to reiterate our strong anticipation of substantial growth from our full approval in a broader population and the general confidence in the differentiated and ground baking benefits of our product and the caliber of our team as we move to the second half of '23 and beyond.

我想再次重申，隨著我們進入下半年，我們對更廣泛人群的充分認可以及對我們產品的差異化和地面烘焙效益以及我們團隊的能力的普遍信心所帶來的大幅增長的強烈預期。23及以後。

So please move to the next slide as I turn it over to our Chief Financial Officer, Fredrik Johansson.

請轉到下一張投影片，我將其交給我們的財務長 Fredrik Johansson。

Thank you, Andy, and good afternoon and good morning, everyone. I will now present to you the financial overview for the second quarter of 2023. And as always, all numbers presented to you are million SEK, unless other was stated. To start with, we report SEK 269.4 million in net revenues for the quarter. For the same quarter last year, we reported net revenues of SEK 64 million.

謝謝你，安迪，大家下午好，早安。我現在將向您介紹 2023 年第二季的財務概況。與往常一樣，除非另有說明，否則向您提供的所有數字均為百萬瑞典克朗。首先，我們報告本季淨收入為 2.694 億瑞典克朗。去年同一季度，我們報告的淨收入為 6,400 萬瑞典克朗。

TARPEYO net product sales for the quarter amounted to SEK 259.2 million or $24.7 million which is an impressive 39% growth from Q1 and a 275% increase over the same quarter previous year. In addition, we also recorded SEK 10.1 million for the quarter in revenues related to partners primarily from Kinpeygo royalties from STADA.

TARPEYO 本季產品淨銷售額達 2.592 億瑞典克朗（2,470 萬美元），較第一季成長 39%，較去年同期成長 275%，令人印象深刻。此外，本季我們還記錄了 1,010 萬瑞典克朗的與合作夥伴相關的收入，主要來自 STADA 的 Kinpeygo 特許權使用費。

Our total operating expenses for the quarter amounted to SEK 330.3 million compared to SEK 271.5 million for the same quarter last year. The cost for R&D decreased by SEK 7.3 million in the quarter to SEK 89 million compared with SEK 96.3 million for the same quarter previous year. The decrease in R&D expenses origins primarily from the, in all essence, completion of the NefIgArd study in the first quarter 2023, reducing the trial cost in Q2 compared to the same quarter prior year.

本季我們的總營運費用為 3.303 億瑞典克朗，去年同期為 2.715 億瑞典克朗。本季研發成本減少 730 萬瑞典克朗，降至 8,900 萬瑞典克朗，去年同期為 9,630 萬瑞典克朗。研發費用的減少主要源自於 NefIgArd 研究在 2023 年第一季完成，與去年同期相比減少了第二季的試驗成本。

The trial design in a study in PBC, TRANSFORM, is currently under review, and the shorter study has the potential to significantly reduce the planned R&D cost for the trial for both 2024 and 2025. The cost for sales and marketing increased by SEK 78.2 million to SEK 191.5 million compared to SEK 113.3 million for the same quarter previous year. The increase is primarily related to the cost for sales and marketing of TARPEYO in the U.S., where the marketing activities has been intensified and the sales force has been increased compared to the corresponding period of the prior year.

PBC 的一項研究 TRANSFORM 的試驗設計目前正在審查中，較短的研究有可能顯著降低 2024 年和 2025 年試驗計劃的研發成本。銷售和營銷成本增加了 7820 萬瑞典克朗增至1.915 億瑞典克朗，而去年同期為1.133 億瑞典克朗。這一成長主要與TARPEYO在美國的銷售和行銷成本有關，與去年同期相比，美國的行銷活動有所加強，銷售人員也有所增加。

The above led to an operating loss of SEK 75.2 million for the quarter compared to SEK 209.8 million for the same quarter last year. And we did continue to reduce the operating loss quarter-over-quarter as our TARPEYO sales are growing. In the second quarter, cash used in operating activities was SEK 163 million compared to SEK 225.2 million for the same quarter previous year. This leaves us with a net decrease in cash in the quarter of SEK 167.1 million. And we have a very healthy cash position at the end of the quarter of SEK 866.2 million, which we believe is sufficient to take us to profitability.

上述因素導致本季營運虧損 7,520 萬瑞典克朗，去年同期為 2.098 億瑞典克朗。隨著 TARPEYO 銷售額的成長，我們確實繼續逐季度減少營運虧損。第二季度，經營活動使用的現金為 1.63 億瑞典克朗，去年同期為 2.252 億瑞典克朗。這使得我們本季的現金淨減少 1.671 億瑞典克朗。截至本季末，我們的現金狀況非常健康，為 8.662 億瑞典克朗，我們相信這足以使我們獲利。

That was all for me. Thank you. And now back to you, Renee.

這就是我的全部。謝謝。現在回到你身上，蕾妮。

Thank you very much. We're ready to take questions, if there are any.

非常感謝。如果有任何問題，我們隨時準備回答。

(Operator Instructions) First question comes from Vamil Divan, Guggenheim Securities.

（操作員說明）第一個問題來自古根漢證券公司的 Vamil Divan。

Just a little bit around the guidance and some of the assumptions you have around when the market access friction and some of the points you mentioned will resolve. I know you filed now for the full approval assuming you get that early part of next year. When do you expect some of these friction time points to kind of ease? Would that be first half of next year? Is it more like second half of next year? Or is it more 2025? Just trying to get a sense of the timing there. And then I have one quick follow-up.

只是稍微介紹一下當市場准入摩擦以及您提到的一些問題將會解決時的指導和一些假設。我知道您現在已申請完全批准，假設您能在明年初獲得批准。您預計這些摩擦時間點什麼時候會有所緩解？那是明年上半年嗎？是不是明年下半年比較好？還是更2025年？只是想了解那裡的時間安排。然後我會進行快速跟進。

Sure. So I guess the interactions with payers, obviously, can be initiated I would say, kind of as of this period of time when there is kind of a peer reviewed journal kind of manuscript out there that's been published. But obviously, these processes do take a while and ultimately, payers are going to be guided not just by kind of published data, but obviously also what the ultimate label will say. And that, obviously, they will have to take into consideration. So my assumption is that we will start -- definitely start seeing this in 2024. But obviously, it will be kind of over time, this will build in 2024 as more and more payers have the opportunity to kind of take this through their process.

當然。因此，我想顯然可以啟動與付款人的互動，就像在這段時間內，當有某種同行評審期刊的手稿已經出版時。但顯然，這些過程確實需要一段時間，最終，付款人不僅會受到已發布數據的指導，而且顯然還會受到最終標籤的內容的指導。顯然，他們必須考慮到這一點。所以我的假設是，我們將開始——肯定會在2024 年開始看到這一點。但顯然，這將隨著時間的推移，這將在2024 年建立，因為越來越多的付款人有機會透過他們的流程來完成這一點。

I don't know if you have anything to add, Andy?

我不知道安迪你還有什麼要補充的嗎？

No, I agree. I think it's over time and experience from those that don't have the staff to support, and that's what we've improved on. That's somewhat of that's something that we can assist with. But as it relates to payers and their decisions and formulary for that, which will also ease it, It's as Renee said, once a label has changed or guidelines come out, these are kind of important pieces of information in how a payer decides to manage a product.

不，我同意。我認為這是隨著時間的推移和那些沒有員工支持的人的經驗的積累，這就是我們改進的地方。這在某種程度上是我們可以提供幫助的。但由於它與付款人及其決定和處方有關，這也將緩解這一問題，正如蕾妮所說，一旦標籤發生變化或指南出台，這些都是付款人決定如何管理的重要信息一個產品。

Okay. Great. And then one quick follow-up. Just in terms of -- sorry if I missed this on the call, but just in terms of the duration you're seeing of treatment, is there any comments you can give there in terms of sort of the 9 months that was studied what are you seeing in the real world now in terms of how long patients are generally staying on therapy?

好的。偉大的。然後是快速跟進。就——抱歉，如果我在電話中錯過了這一點，但就您所接受的治療持續時間而言，您是否可以就所研究的 9 個月的時間發表任何評論？您現在在現實世界中看到患者通常接受治療的時間有多長？

Yes. I think as we've said before, I mean, obviously, it's a variable time that people stay on treatment. But obviously, as we've also mentioned, for those patients to reach 9 months, the majority of them actually stay on beyond 9 months. But I think that's why we really needed to have a slightly longer time series where we could look at this because it does vary. And I think that's why we kind of today would say that the best kind of estimate to use for right now is probably 8 months. But obviously, we would expect that to kind of to be extended to longer periods of time as kind of physicians have more experience of the product, more data comes out, et cetera.

是的。我認為正如我們之前所說，我的意思是，顯然，人們接受治療的時間是可變的。但顯然，正如我們也提到的，對於那些達到 9 個月的患者，他們中的大多數實際上都停留在 9 個月以上。但我認為這就是為什麼我們確實需要一個稍長的時間序列來觀察這個問題，因為它確實有所不同。我認為這就是為什麼我們今天會說目前使用的最佳估計可能是 8 個月。但顯然，我們預計這種情況會延長到更長的時間，因為醫生對產品有更多的經驗，更多的數據出現，等等。

Andy, anything you want to add to that?

安迪，你還有什麼要補充的嗎？

No. I think that that's right. We have many patients on greater than 9 months now, but that's just to assist with the overall average seems to be around 8% if we look back the last 12 months or so.

不，我認為這是對的。現在我們有許多患者的治療時間超過 9 個月，但這只是為了幫助我們回顧過去 12 個月左右的情況，總體平均值似乎約為 8%。

The next question comes from Christopher Uhde, SEB.

下一個問題來自 SEB 的 Christopher Uhde。

So a couple first on TARPEYO. So are you seeing any signs now that we're, I guess, a little more than halfway through this quarter, of any pickup enrollments -- in enrollments since the data was presented? Or is it too soon?

首先是 TARPEYO 上的一對。那麼，我想，自從數據公佈以來，本季度已過半，您是否看到任何跡象表明有任何臨時註冊人數？還是太快了？

And then in terms of the clinical program, would it be wise to consider a trial in patients with low levels of proteinuria given the data that you presented at the conference and today. And if so, what can you tell us about the impact of dose level on proteinuria decline in patients at the lower end of baseline proteinuria in the [Nefecon] , so the Phase IIb trial? And then I have a couple on -- one on setanaxib as well, but I'll wait for that.

然後就臨床計劃而言，考慮到您在會議上和今天提供的數據，考慮對低蛋白尿患者進行試驗是否明智。如果是這樣，您能告訴我們關於 [Nefecon] 以及 IIb 期試驗中劑量水平對處於基線蛋白尿下限的患者蛋白尿下降的影響嗎？然後我服用了兩種藥物——一種也服用了 setanaxib，但我會等待。

So I think it is too soon. To your first question, I think it's too soon to kind of draw any conclusions from that. I think we're going to have to wait for that. In terms of your second question, I think that this is -- we haven't seen in terms of the trial, any kind of difference in terms of the effect of people having lower or higher levels of proteinuria. It is quite consistent across kind of baseline UPCR levels.

所以我認為現在還為時過早。對於你的第一個問題，我認為現在得出任何結論還為時過早。我認為我們將不得不等待這一點。關於你的第二個問題，我認為，在試驗方面，我們沒有看到蛋白尿水平較低或較高的人的影響有任何差異。它在各種基線 UPCR 水平上非常一致。

But what we are seeing, and I think this is something that you bring up, which is an excellent comment, which is obviously part of what is being done in this whole sector is that there is I think, building slowly perhaps, but they're certainly building more of a sense of urgency. And that is coming from the fact that there is now reported data. There's actual eGFR data, there is placebo data. And I think that all of these things will contribute to the fact that what we're hearing is more and more that actually it's becoming more of an impetus to treat early and specifically with something that has the ability to really significantly impact eGFR and eGFR trajectory.

但我們所看到的，我認為這是你提出的，這是一個很好的評論，這顯然是整個部門正在做的事情的一部分，我認為，也許建設緩慢，但他們'我們肯定會增強一種緊迫感。這是因為現在有數據報告。有實際的 eGFR 數據，有安慰劑數據。我認為所有這些事情都將促成這樣一個事實：我們聽到的越來越多的信息實際上越來越成為早期治療的動力，特別是那些能夠真正顯著影響 eGFR 和 eGFR 軌蹟的藥物。

So it is moving away to some extent from kind of symptoms to actually more hard data because that data is now becoming available. And yes, I think it is moving towards physicians actually realizing that this is something that you can't just kind of wait for and potentially just have a benefit in proteinuria. You really need to treat this in order to keep kind of patients out of dialysis, hopefully. So I do think that, that is something that we're going to see more and more of. And I think, yes, it will -- it wouldn't surprise me if the kind of levels will move down in terms of which patient population should be considered for treatment compared to kind of where it's been previously.

因此，它在某種程度上正在從某種症狀轉向實際上更硬的數據，因為這些數據現在已經變得可用。是的，我認為醫生們正在真正意識到，這不能只是等待，而且可能對蛋白尿有好處。你確實需要治療這個問題，希望這樣的病人能夠免於透析。所以我確實認為，我們將會看到越來越多的情況。我認為，是的，它會——如果與以前相比，應考慮接受治療的患者群體的水平下降，我不會感到驚訝。

Okay. And then if I could quickly just throw in a couple more. So setanaxib in head and neck, how many evaluable patients were there in each arm? And then for NefIgArd, so some experts have written that in part A the placebo group outcomes underperformed versus outcomes in other trials like testing. What's your view about that? And any potential causes?

好的。然後如果我能很快再投入幾個。那麼頭頸部的setanaxib，每隻手臂有多少個可評估的病人？然後，對於 NefIgArd，一些專家寫道，在 A 部分中，安慰劑組的結果與其他試驗（如測試）的結果相比表現不佳。您對此有何看法？有什麼潛在的原因嗎？

Richard, do you want to take that?

理查德，你想接受這個嗎？

In terms of the balance between the treatment groups at the time of that interim review of data, they were essentially balanced. I mean I think for the biomarker analysis of 12 patients, I think 7 were on placebo, 5 on setanaxib. And overall, the 20 is pretty balanced, so.

就中期數據審查時治療組之間的平衡而言，它們基本上是平衡的。我的意思是，我認為對於 12 名患者的生物標記分析，我認為 7 名患者服用安慰劑，5 名患者服用 setanaxib。總的來說，20 是相當平衡的，所以。

In terms of the actual kind of on the Nefecon placebo arm, I think this is something I don't -- It's actually -- in my view, I think this is something that, again, I think we'll see more and more of this as actually kind of more trials come out, but I've actually heard both of these that supposedly, we had much too -- too much kind of decline in placebo arm compared to what people would expect and suddenly people are saying we have too little.

就 Nefecon 安慰劑組的實際情況而言，我認為這是我不知道的事情——實際上——在我看來，我認為這是我們會看到越來越多的事情事實上，更多的試驗已經出現，但我實際上聽說過，與人們的預期相比，安慰劑組的下降太多了，突然人們說我們有太多的下降太少了。

I think that at the end of the day, I think it's very similar to what we saw in our Phase IIb. I think it's actually very similar to what's been seen in other trials where there's been placebo arm. And so I don't really think that it's kind of relevant or helpful to really start kind of comparing one trial to another trial. I think you can pick and choose a variety of trials then to do that. So I think overall, that it is it is -- this kind of patient population group that is at risk of progression, do you seem to have a fairly similar kind of development of the placebo arms. And I don't know if you have anything to add.

我認為最終，我認為這與我們在 IIb 階段看到的非常相似。我認為這實際上與其他安慰劑組試驗中所見的情況非常相似。因此，我真的不認為真正開始將一項試驗與另一項試驗進行比較是相關或有幫助的。我認為你可以選擇多種嘗試來做到這一點。所以我認為總的來說，這種有進展風險的患者群體，安慰劑組的發展似乎相當相似。我不知道你是否還有什麼要補充的。

Yes, I completely agree. I mean, I think we've looked at this in detail. I mean our view is our placebo decline in terms of eGFR is absolutely in line with what would be expected in this category of patient population. And as Renee has said, and hopefully, through what I talked about during the presentation, it underlines the importance of early intervention patients on placebo who are receiving supportive care only, there is a significant risk of progressing to end stage kidney disease in a relatively short period of time, 10 to 15 years.

是的，我完全同意。我的意思是，我認為我們已經詳細研究過這個問題。我的意思是，我們的觀點是，安慰劑在 eGFR 方面的下降絕對符合此類患者群體的預期。正如蕾妮所說，希望透過我在演講中談到的內容，它強調了僅接受支持性護理的安慰劑患者早期幹預的重要性，相對而言，進展為終末期腎病的風險很大。時間很短，10到15年。

So that, to me, is the key message that's coming from the placebo group. We found nothing that suggests that placebo group is behaving in any way unusually absolutely reflects that patient population that was enrolled.

所以，對我來說，這是來自安慰劑組的關鍵訊息。我們沒有發現任何跡象顯示安慰劑組的行為有任何異常，絕對反映了入組的患者群體。

Okay. Let's take the next question.

好的。我們來看下一個問題。

Next question comes from Yigal Nochomovitz from Citi.

下一個問題來自花旗銀行的 Yigal Nochomovitz。

Can you hear me?

你聽得到我嗎？

Yes. We can here you.

是的。我們可以在這裡為您服務。

Renee, can you just reexplain -- I know you probably explained this in the past, but in the paper, you're seeing, obviously, that there's no convergence in the slopes on the eGFR after the -- during the observational period, which is obviously showing disease modification regardless of the split by proteinuria. But then in the proteinuria graph, you see that after the 12 months, you do start to see a rebound. So can you just help explain why you're seeing the continued disease modification on the eGFR side of things, but on the UPCR side, it's -- things are starting to converge? So I'm just curious if you could maybe reexplain the thinking around that.

Renee，你能重新解釋一下嗎——我知道你過去可能解釋過這一點，但在論文中，你顯然看到，在觀察期間，eGFR 的斜率沒有收斂，這無論是否因蛋白尿而分裂，都明顯顯示出疾病緩解。但在蛋白尿圖中，您會看到 12 個月後，您確實開始看到反彈。那麼您能否幫助解釋為什麼您看到 eGFR 方面的疾病持續改變，但在 UPCR 方面，情況開始趨同？所以我很好奇你是否可以重新解釋一下對此的想法。

So I guess I'll give my view, and Richard, you can provide your commentary. So I guess my view is actually this is -- I mean, this is kind of when we're starting to look at the relationship between kind of proteinuria and eGFR and maybe it is slightly more complex than what people had actually thought or how you kind of simplistically can explain it. So you're absolutely right. We are not seeing a kind of first, a significant reduction in proteinuria followed by an impact on eGFR. There seems to be a more complex relationship between proteinuria and eGFR than what may have been kind of depicted in various papers.

所以我想我會發表我的觀點，理查德，你可以發表你的評論。所以我想我的觀點實際上是——我的意思是，這就是我們開始研究蛋白尿和 eGFR 之間關係的時候，也許它比人們實際想像的或你如何理解的要復雜一些。可以簡單地解釋一下。所以你是完全正確的。我們並沒有看到蛋白尿顯著減少，然後 eGFR 受到影響。蛋白尿和 eGFR 之間的關係似乎比各種論文中描述的更為複雜。

And I think this is really when we're going to start seeing this in terms of different modes of action, different drugs. They may very well have a different impact on proteinuria and/or eGFR. And so I think that we'll probably won't have kind of one size fits all here. I think that we will very well may see quite big differences in terms of proteinuria versus eGFR. And I think this is something that we're just going to have to rely on the data sets that are going to become available to see in terms of what this relationship kind of looks like and if it's actually constant or not based on the different modes of action. Richard?

我認為這確實是我們開始從不同的作用方式、不同的藥物角度看待這個問題的時候。它們很可能對蛋白尿和/或 eGFR 有不同的影響。所以我認為我們可能不會有一種適合所有情況的方法。我認為我們很可能會看到蛋白尿與 eGFR 之間有很大差異。我認為這是我們必須依靠的資料集，這些資料集將變得可用，以了解這種關係是什麼樣子，以及它是否實際上是恆定的或不是基於不同的模式的行動。理查德？

Yes. I mean I agree. I'm not sure I can add too much more, but as you've -- as you've observed, Yigal, I mean, clearly, there's evidence of the disease modifying effect with the maintenance of the separation of the eGFR curves over the second year where patients are not receiving treatment. But as Renee has said, I think this opens the door to recognizing that there's no -- there isn't necessarily a completely simple relationship between proteinuria change and change in eGFR trajectory over time. And I think you will see different patterns of relationship between proteinuria and eGFR change related to the mechanism of action of the treatment.

是的。我的意思是我同意。我不確定我可以添加太多，但正如你所觀察到的，Yigal，我的意思是，很明顯，有證據表明通過維持 eGFR 曲線的分離可以改善疾病。患者未接受治療的第二年。但正如 Renee 所說，我認為這為認識到蛋白尿變化和 eGFR 軌跡隨時間變化之間不一定存在完全簡單的關係打開了大門。我認為您會看到蛋白尿和 eGFR 變化之間關係的不同模式，這與治療的機制有關。

Okay. And then just one very specific question. Are you able to say anything more about just the split or the percent of patients that have received our payout so far that are above versus below this 1.5 gram order?

好的。然後是一個非常具體的問題。您能否進一步說明到目前為止已收到我們付款的高於和低於 1.5 克訂單的患者的比例或百分比？

I don't actually have -- I don't know, Andy, do you...

我實際上沒有——我不知道，安迪，你…

No. No, we don't have the exact numbers on that.

不，不，我們沒有確切的數字。

And we have the next question from Rami Katkhuda, LifeSci Capital.

LifeSci Capital 的 Rami Katkhuda 提出了下一個問題。

You touched upon the average duration of treatment with TARPEYO being around 8 months. Are you hearing any physician feedback as to why patients may not be completing the full treatment course? Is it primarily due to AEs or are there other factors involved here?

您提到 TARPEYO 的平均治療時間約為 8 個月。您是否聽到任何醫生回饋關於患者為何無法完成整個治療過程的回饋？主要是因為 AE 還是還涉及其他因素？

Andy, do you want to take that?

安迪，你想接受這個嗎？

Sure. There's several factors. Obviously, there's always -- there could be AEs. But what we're seeing is, interestingly, we've asked some physicians and sometimes they're saying it's been successful, the drug. And remember the typical treatment length of therapy for a product that's probably replacing in lab instances or systemic steroids, and they typically prescribe them for about 6 months.

當然。有幾個因素。顯然，總有可能存在不良事件。但有趣的是，我們問了一些醫生，有時他們說這種藥物很成功。請記住可能在實驗室實例中替代的產品或全身性類固醇的典型治療長度，他們通常會開出大約 6 個月的處方。

So interestingly, a lot of times, they would even say, Well, no, no this patient had success and they stop, less than 6 months. And this goes to how this product works different. We talked about even on the last question, people stop taking the drug and their proteinuria continue to decline. Let's remember, they stopped taking the drug while their eGFR stayed stable.

有趣的是，很多時候，他們甚至會說，好吧，不，不，這個病人取得了成功，然後他們就停止了，不到 6 個月。這就是該產品的不同工作原理。我們甚至在最後一個問題上也談到，人們停止服用藥物，他們的蛋白尿繼續下降。讓我們記住，當他們的 eGFR 保持穩定時，他們停止服用藥物。

So this drug works differently and I think it's going to take time for people to get used to an initial treatment course of 9 months. But as we said earlier, it's pretty variable right now. We have people that are on for well over 9 months, some that are on 6, 7 months and deeming a success and then stopping as well. And this doesn't speak to -- let me just make one other point. This doesn't speak to retreatment, which is obviously something that's going to start to happen more and more.

所以這種藥物的作用不同，我認為人們需要時間來適應 9 個月的初始療程。但正如我們之前所說，現在情況變化很大。我們有些人堅持了 9 個月以上，有些人堅持了 6、7 個月，認為成功了，然後也停止了。這並不能說明問題──讓我再提出另一點。這並不意味著重新治療，這顯然會開始越來越多地發生。

Got it. Makes sense. And then really quickly, with regards to the interim data with setanaxib. Of the 6 patients on treatment who are progression-free, can you touch upon how many were actual responses? And were these patients treatment-naive or refractory coming into the study?

知道了。說得通。然後很快，關於 setanaxib 的中期數據。在接受治療且無進展的 6 名患者中，您能透露有多少人獲得了實際緩解嗎？這些患者是否未接受治療或難治性進入研究？

Well, in terms of treatment, they may have -- because these are patients with recurrent or metastatic disease. So they will have received previous treatment, probably an initial treatment plan that could have comprised anything -- any combination of radiotherapy, chemotherapy and surgery before they come into the study with a recurrent or metastatic disease. And we haven't given that level of granularity around the various responses.

嗯，就治療而言，他們可能有——因為這些是患有復發或轉移性疾病的患者。因此，在他們因復發或轉移性疾病進入研究之前，他們將接受過先前的治療，可能是初始治療計劃，其中可能包括任何放射治療、化療和手術的組合。我們還沒有給出各種回應的詳細程度。

Our next question comes from Annabel Samimy.

我們的下一個問題來自安娜貝爾·薩米米。

This is Jack calling on for Annabel. So I know it's not a hard cutoff, but you've previously mentioned requesting a change of the full label language to patients with generally greater than 0.8 grams of proteinuria from the 1.5 grams like it is now. what influenced the selection of that particular number in the context of that long-term outcome study you discussed on the call? And about what additional percent of the overall IgAN population with that capture for the payers who treat that number like hard cutoff?

這是傑克來找安娜貝爾。所以我知道這不是一個硬性的界限，但您之前提到過要求將蛋白尿普遍大於 0.8 克的患者的完整標籤語言從現在的 1.5 克更改為。在您在電話會議中討論的長期結果研究的背景下，是什麼影響了該特定數字的選擇？對於那些將這一數字視為硬性截止的付款人來說，獲得該捕獲的 IgAN 總體人口的額外百分比大約是多少？

So just to kind of make sure that I can understand your question. So obviously, the 1.5 is a UPCR level that's in our label right now, which really obviously, really wants to kind of drive usage towards patients who are at risk of rapid disease progression. The 0.8 of UPCR is the actual kind of level of inclusion into the Phase III trial, which is the NefIgArd trial. So that obviously is consistent with the kind of 1 gram of proteinuria which is in the KDIGO guidelines and represent the broader population at risk of progression.

只是為了確保我能理解你的問題。很明顯，1.5 是我們目前標籤中的 UPCR 水平，這非常明顯，確實希望推動有疾病快速進展風險的患者的使用。 UPCR 的 0.8 是納入 III 期試驗（即 NefIgArd 試驗）的實際水準。因此，這顯然與 KDIGO 指南中的 1 克蛋白尿一致，代表更廣泛的人群存在進展風險。

So this would obviously go from kind of having a fairly limited kind of part of the kind of population at risk to include the full population at risk. And so obviously, what we've said is that the estimate that what we have for this is that 50% or just over 50% of the population is kind of expected to be at risk of progression and therefore, may kind of fall into that type of category. So it's obviously a very -- it's quite a significant broadening of the kind of the patient population.

因此，這顯然會從只有相當有限的一部分處於危險之中的人群轉變為包括全部處於危險之中的人群。顯然，我們所說的是，我們對此的估計是 50% 或略高於 50% 的人口預計有進展風險，因此可能會陷入這種情況類別的類型。因此，這顯然是患者群體類型的顯著擴大。

In terms of the label. In terms of kind of how big exactly this kind of subgroup is I think it's really almost impossible to know. I mean, unfortunately, this is a rare disease, and we don't have a lot of data about the prevalence, the population or these kind of the sizes of subpopulations. So I think we're not really unfortunately able to comment on exactly how big that would be. But we know, obviously, that it's significantly smaller than the overall population at risk, which was studied in the Phase III.

從標籤來看。就這種子群體到底有多大而言，我認為幾乎不可能知道。我的意思是，不幸的是，這是一種罕見疾病，我們沒有大量關於患病率、人口或亞人口規模的數據。所以我認為不幸的是我們無法準確評論它有多大。但我們顯然知道，它明顯小於第三階段研究的處於危險中的總人口。

Next question comes from Dan Akschuti at Pareto Securities.

下一個問題來自 Pareto 證券公司的 Dan Akschuti。

First question would be on the enrollment. So Q1 was a bit slower than expected with 408 and now it's 422 so the pace is not really increasing. Do you expect a slowdown in Q3 now because of the summer holidays? Or what's your explanation that it's not increasing this [faster]?

第一個問題是關於招生。因此，第一季的速度比預期慢一些，為 408，現在為 422，因此速度並沒有真正增加。您預計第三季會因為暑假而放緩嗎？還是你對它沒有[更快]增加的解釋是什麼？

So again, I think that what we've -- really, what we're seeing is that there is a -- it is a function of the fact that actually there is some market friction in this area. We don't have -- physicians are not necessarily seeing the sense of urgency in terms of actually kind of wanting or needing to treat patients kind of immediately. What we are seeing is a very steady growth, and I think, obviously, also new subscribers who are adding to this.

所以，我再次認為，我們所看到的——實際上，我們所看到的是——這是一個事實的結果，即該領域實際上存在一些市場摩擦。我們沒有 - 醫生不一定會看到真正想要或需要立即治療患者的緊迫感。我們看到的是非常穩定的成長，而且我認為，顯然，新訂閱者也在不斷增加。

And so I think that even if we haven't necessarily kind of reached a very significant inflection point, I think that, obviously, the franchise with the kind of growth that we're seeing in revenues, et cetera, I think, is having a very healthy growth trajectory overall. I think that in terms of when would we kind of potentially have that change, I do think that it does come back to not having accelerated approval, not having kind of a smaller subgroup. And also, I think, obviously, having more data out there for people to really understand because as we've mentioned, I think this is differentiated from everything out there in terms of that.

因此，我認為，即使我們不一定達到非常重要的拐點，我認為，顯然，我們在收入等方面看到的那種增長的特許經營權，我認為，正在總體而言，這是一個非常健康的成長軌跡。我認為，就我們何時可能進行這種改變而言，我確實認為這確實會回到沒有加速批准、沒有更小的子群體的問題。而且，我認為，顯然，有更多的數據可供人們真正理解，因為正如我們所提到的，我認為這與現有的一切都不同。

It is not a generally systemic approach to trying to kind of impact proteinuria. It really is a kind of local approach really focused on being disease modifying and really kind of having an impact on the kidney function. So I think that there is an educational component of this. But in terms of the summer, again, it's -- I think what we have so that we can expect potentially to see that seasonality again during this kind of Q3. And I think it's hard to know whether we are going to experience that or not, but it's certainly something that we're taking into account that, that might be the case. And that's obviously also one of the reasons for our revised guidance.

這並不是一種試圖影響蛋白尿的系統性方法。這確實是一種真正專注於改變疾病並且確實對腎功能產生影響的局部方法。所以我認為這其中有教育的成分。但就夏季而言，我認為我們所擁有的，我們可以預期在第三季再次出現這種季節性。我認為很難知道我們是否會經歷這種情況，但這肯定是我們正在考慮的事情，也許就是這樣。這顯然也是我們修訂指南的原因之一。

Okay. And yes, you mentioned the clinical data is so far unique on the eGFR effect. So I'm a bit puzzled by the feedback from physicians you're getting that considering that there is no other drug in the market that has shown this effect and it's a progressive disease that there is no interest or not bigger interest to prescribe the drug. So Is that maybe in the end, still label-related as you also said? There's something else that you see?

好的。是的，您提到迄今為止關於 eGFR 效應的臨床數據是獨一無二的。因此，我對醫生的回饋感到有點困惑，考慮到市場上沒有其他藥物顯示出這種效果，而且這是一種進行性疾病，沒有興趣或沒有更大的興趣開這種藥。那麼這最終是否仍像您所說的那樣與標籤相關？您還看到其他東西嗎？

I mean I think, I think it is a combination of the fact that this is very -- I mean the renal area has not seen lots of specialty products to start with. It is not something that nephrologists deal with. It's not like they have 100 drugs to kind of choose from their own specialty that they know exactly how to manage. So I think there is clearly kind of a process here to go through. And so apart from the fact that this is a specialty product and it's not that well established.

我的意思是，我認為，我認為這是一個非常重要的事實的結合——我的意思是腎臟領域還沒有看到很多特殊產品。這不是腎臟病專家處理的事情。他們並不是有 100 種藥物可以從他們自己的專業中進行選擇，並且他們確切地知道如何管理。所以我認為這裡顯然需要經歷一個過程。因此，除了這是一種特殊產品而且還沒有那麼成熟這一事實之外。

I think that there is -- part of that is the sense of urgency. I think that a lot of these data sets that are coming out, ours -- we just talked about the data set from registry. That really, I think, is shedding light on this for physicians to kind of say, listen, you may not have a patient who's going to have an event in the next 6 months, but this patient is going to end up in dialysis unless you actually treat this disease and treat it fairly aggressively with a focus on actually stabilizing their kidney function.

我認為其中一部分是緊迫感。我認為我們的許多數據集即將發布——我們剛剛討論了註冊表中的數據集。我認為，這確實讓醫生明白了這一點，讓他們說，聽著，你可能不會有一個病人在未來 6 個月內發生任何事件，但這個病人最終將接受透析，除非你實際上治療這種疾病並且相當積極地治療它，重點是實際穩定他們的腎功能。

And I think that we will see more and more of this as actually this data is making its way into the nephrology community. And unfortunately, it's not immediate. There is a kind of educational process here. But I have no doubt that there will be more and more kind of information and I think that the nephrology community is very data-driven. And I think the more data that comes out there, they will review it and they will start making decisions around treatment paradigms and how to best preserve kidney function for their patients.

我認為我們會看到越來越多的此類數據，因為實際上這些數據正在進入腎臟病學界。不幸的是，這不是立竿見影的。這裡有一種教育過程。但我毫不懷疑將會有越來越多的信息，而且我認為腎臟病學界是非常數據驅動的。我認為，出現的數據越多，他們就會對其進行審查，並開始圍繞治療模式以及如何最好地保護患者的腎功能做出決策。

Okay. And last follow-up on Europe, how is the progress there has been also fairly close so far?

好的。上次關於歐洲的後續行動，到目前為止，進展如何？

Yes. So I think that what we've -- generally, what I think is seen in Europe from any kind of launch in the kind of medical product is that it does take a lot longer in Europe, obviously because, again, of the difference in the negotiation cycles and difference in terms of country-by-country kind of launch. But I think in terms of start, I think they're very happy with the progress that they're seeing. I think that they've started to kind of now launch also in some other countries.

是的。因此，我認為，總的來說，我認為在歐洲，從任何類型的醫療產品的推出來看，在歐洲確實需要更長的時間，這顯然是因為，再次，談判週期以及各國啟動方式的差異。但我認為就開始而言，我認為他們對所看到的進展感到非常滿意。我認為他們現在也開始在其他一些國家推出。

And so we would expect to start seeing again, some of that kind of additional revenue coming from other regions outside of Germany. But my understanding really is and what we're hearing from our partner is that they're very happy with the development. And I think here, EMA really did put quite a strong kind of line in the sand in terms of they did not use the word generally. So I think here, it is very much limited to just that population about the kind of 1.5 UPCR level, which, again, I think we have to kind of take into account when looking at Europe.

因此，我們預計將再次開始看到其中一些額外收入來自德國以外的其他地區。但我的理解是，我們從合作夥伴那裡聽到的是，他們對開發感到非常滿意。我認為，EMA 確實在沙上劃了一條相當強硬的界線，因為他們通常不會使用這個詞。所以我認為，這在很大程度上僅限於 1.5 UPCR 水平的人口，我認為我們在考慮歐洲時必須考慮到這一點。

Next question comes from Maury Raycroft from Jefferies.

下一個問題來自 Jefferies 的 Maury Raycroft。

Wanted to clarify, does the market access friction resulting in the 5% to 15% not converting. Does that include the patients with UPCR less than 1.5 gram per gram? And I also wanted to know if any of the market access friction issues are due to competition with (inaudible) launch?

想澄清一下，市場准入摩擦是否導致 5% 至 15% 的轉換率不高。這是否包括 UPCR 低於 1.5 克/克的患者？我還想知道市場准入摩擦問題是否是由於（聽不清楚）發布的競爭造成的？

So I would say that -- I would say the answer to your first one is yes. Obviously, this relates to the entire population that prescribers are prescribing for. So obviously, some of the reasons why there is frustration from a kind of physician's perspective and why they kind of ultimately may choose not to go forward is because of the fact that the payers are potentially giving them a difficult time if they're trying to prescribe for a patient that has lower levels.

所以我想說——我想說你的第一個問題的答案是肯定的。顯然，這涉及到處方醫生所開處方的整個人群。顯然，從醫生的角度來看，他們感到沮喪以及他們最終可能選擇不繼續的部分原因是因為如果付款人試圖這樣做，他們可能會給他們帶來困難。為水平較低的患者開處方。

I think in terms of payers, I wouldn't expect any of that to have an impact as I think that this is a process that other companies are going to have to go through the P&T committees and get their kind of views on. But I don't think that -- I don't think we have any kind of impact on that from a payer perspective.

我認為就付款人而言，我不認為這會產生任何影響，因為我認為這是其他公司必須通過 P&T 委員會並獲得他們的意見的過程。但我不認為——從付款人的角度來看，我們對此沒有任何影響。

But Andy, I don't know if you have a different view on that, Andy?

但是安迪，我不知道你對此有什麼不同的看法嗎，安迪？

No. No, I don't think they have an impact. I think what is definitely clear, there are definitely patients that are above 0.8 grams and less than the 1.5 grams that have their -- the time is -- that's where they're seeing some friction, clearly. That's where you might get these patients that aren't filled or these that aren't converted to your first part of your question.

不，不，我不認為它們有影響。我認為很清楚的是，肯定有一些體重高於 0.8 克和低於 1.5 克的患者，他們明顯地看到了一些摩擦。這就是您可能會遇到未填寫的患者或未轉換為問題第一部分的患者的地方。

And obviously, we've also seen situations where actually it's very severely sick patients that actually you are prescribing for someone who may actually be -- have lost a lot of kidney function. And actually, they may actually get on to the transplant -- get into the transplant queue and therefore, will not kind of complete a cure or take kind of the drug. So it is really quite different. I mean, there's quite a variety of reasons. I would say why, not just the fact that it is below. It can be a variety of other reasons as well and also actually being quite far progressed can obviously be another reason why there is a frustration or a decision not to kind of go forward.

顯然，我們也看到過這樣的情況，實際上，您為病情非常嚴重的患者開出的處方可能實際上已經喪失了許多腎功能。事實上，他們可能會真正進行移植——進入移植隊列，因此不會完成治癒或服用某種藥物。所以這確實是非常不同的。我的意思是，原因有很多種。我會說為什麼，而不僅僅是因為它在下面。這也可能是各種其他原因，而且實際上取得了相當大的進展顯然可能是令人沮喪或決定不繼續前進的另一個原因。

Got it. That's helpful. And any impact with 2Q due to competition?

知道了。這很有幫助。競爭對第二季有何影響？

I guess, I mean it's impossible for me to know. I mean I'm assuming that every time that you have kind of another kind of company coming into the market, you would expect that there would be some impact from that. However, I think also that this is a very early stage in the launch. I think that it's been very limited revenue so far. But I haven't really -- I mean I don't have any insight into how that launch is being run or what they're seeing or how they're kind of progressing with this.

我想，我的意思是我不可能知道。我的意思是，我假設每次有另一種公司進入市場時，您都會預期會產生一些影響。然而，我也認為這還處於啟動的非常早期階段。我認為到目前為止，收入非常有限。但我真的沒有——我的意思是我對這次發布是如何進行的，或者他們看到了什麼，或者他們在這方面的進展如何沒有任何了解。

So I think from our perspective, we're kind of focusing on kind of our market and building our franchise. And again, I think that the -- ultimately, the data the strength of the data will ultimately decide how physicians will derive their treatment paradigm. And so I think it is, as I've said before, it's clearly an extremely data-driven group. Again, they don't like to go to specialty products. I'm sure if you give them free drug, they will definitely like that.

所以我認為從我們的角度來看，我們有點專注於我們的市場並建立我們的特許經營權。再說一次，我認為，最終，數據的強度將最終決定醫生如何得出他們的治療模式。所以我認為，正如我之前所說，這顯然是一個極其數據驅動的團隊。同樣，他們不喜歡購買特色產品。我確信如果你給他們免費的藥物，他們一定會喜歡的。

On the other hand, I think that the actual kind of decision medium-term will clearly be based on what is the patient profile I have in front of me, how will I actually kind of treat that patient best based on the needs of this patient. And then I think you will have a variety of different options, which I think is great for the patient. And then I think that the physician will make the appropriate decision based on the data that they have in front of them as to how the mode of action, the type of drug, et cetera. And I think that's ultimately where we're going to end up.

另一方面，我認為中期的實際決策顯然將基於我面前的患者概況，我實際上將如何根據該患者的需求最好地治療該患者。然後我認為你會有多種不同的選擇，我認為這對病人來說很好。然後我認為醫生會根據他們面前的數據做出適當的決定，包括作用方式、藥物類型等。我認為這就是我們最終要達到的目標。

Okay. That's helpful and makes sense. And maybe just one other question, and then I'll hop back in the queue. Just wondering if you can -- thinking about the longer-term opportunity, wondering if you can elaborate on the open-label extension study and how that's going. If you have any insights from the study as far as how many patients have enrolled and how they're responding to the second round of treatment?

好的。這很有幫助並且有意義。也許只是另一個問題，然後我會跳回隊列。只是想知道您是否可以 - 考慮長期機會，想知道您是否可以詳細說明開放標籤擴展研究及其進展。您是否對這項研究有任何了解，包括有多少患者入組以及他們對第二輪治療的反應如何？

Do you want to take that, Richard?

理查德，你想接受這個嗎？

Yes. I mean I think that study is going well. According to plan, we -- as Andy has said, we expect to have data from that study in the middle of next year. 119 patients were enrolled in that study. Most of these patients have completed the treatment. I think we have around about 16 continuing in the study at the moment. Dropout rates have been relatively low.

是的。我的意思是我認為學習進展順利。按照計劃，正如安迪所說，我們預計在明年年中獲得該研究的數據。 119 名患者參加了研究。這些患者大多數已經完成治療。我想目前我們大約有 16 個人在繼續這項研究。輟學率相對較低。

And as we've said before, I mean, I think we saw when patients were coming in, that one of the main reasons patients weren't getting in was because they weren't meeting the proteinuria requirements, and we can see why now. That's reflected in the sustained improvement in proteinuria that we saw in the second year of follow-up in the main study, so that then translated through to fewer patients being able to get into the open-label study.

正如我們之前所說，我的意思是，我認為當患者進來時，我們看到患者沒有進來的主要原因之一是因為他們沒有達到蛋白尿要求，我們現在可以看到為什麼。這反映在我們在主要研究的追蹤第二年中看到的蛋白尿持續改善，從而導致能夠參與開放標籤研究的患者數量減少。

But I think that study is, as I say, to reiterate, it's going well. We expect data to come out in the middle of next year, and I think that will be very important information to help us understand the potential benefits of the second course of treatment.

但我認為，正如我所說，這項研究進展順利。我們預計數據將在明年年中公佈，我認為這將是非常重要的訊息，可以幫助我們了解第二個療程的潛在益處。

But to be clear, obviously, that is still blinded and it's -- so we have no insights into any data or readouts or anything such.

但要明確的是，顯然，這仍然是盲目的，所以我們對任何數據或讀數或任何類似的東西都沒有洞察力。

There are no more questions at this time. So I hand the conference back to speakers for any closing comments.

目前沒有更多問題。因此，我將會議交還給發言人以徵求結束意見。

Thank you very much. Thank you for the questions. Thank you for listening to our Q2 report. We look forward to speaking to you again when we report our third quarter.

非常感謝。謝謝你的提問。感謝您收聽我們的第二季報告。我們期待在報告第三季時再次與您交談。