Calliditas Therapeutics AB (CALT) 2023 Q1 法說會逐字稿

Thank you very much, and welcome, everybody, to this Q1 2023 report. With me today, I have Fredrik Johansson, Chief Financial Officer; Richard Philipson, our Chief Medical Officer; and Andrew Udell, President of North America.

非常感謝並歡迎大家閱讀這份 2023 年第一季度報告。今天和我在一起的還有首席財務官 Fredrik Johansson；理查德·菲利普森，我們的首席醫療官；以及北美區總裁 Andrew Udell。

Next slide, please. I'd like to just draw your attention to the disclaimer page. It relates to any forward-looking statements, and I would like to refer you to the company's reports and other filings, including those which contain risk factors and other relevant information.

請下一張幻燈片。我想提請您注意免責聲明頁面。它涉及任何前瞻性陳述，我想請您參閱公司的報告和其他文件，包括包含風險因素和其他相關信息的文件。

Next page, please. So some highlights for Q1. In February, we received conditional marketing authorization from the MHRA for Kinpeygo, which thus became the first-ever approved treatment for IgA nephropathy in the U.K. In March, we obviously had our main event for the quarter. We read out top line data from the global placebo-controlled randomized Phase III study known as NefIgArd, which met its primary endpoint of kidney function expressed as eGFR. The trial was very successful and met the primary endpoint with a highly significant statistical p-value of 0.0001.

請下一頁。第一季度的一些亮點。 2 月份，我們獲得了 MHRA 的 Kinpeygo 有條件營銷授權，從而成為英國首個獲批的 IgA 腎病治療藥物。 3 月份，我們顯然迎來了本季度的重頭戲。我們讀出了名為 NefIgArd 的全球安慰劑對照隨機 III 期研究的主要數據，該研究達到了以 eGFR 表示的腎功能的主要終點。該試驗非常成功，達到了主要終點，統計 p 值為 0.0001，非常顯著。

With regards to TARPEYO, Q1 saw a record number of new enrollments, reflecting growth of over 30% over Q4. And in addition, the quarter also saw the largest ever increase in unique subscribers, resulting in a total 918 unique nephrologists prescribing TARPEYO since launch.

就 TARPEYO 而言，第一季度新入學人數創歷史新高，較第四季度增長超過 30%。此外，該季度的獨立訂戶數量也出現了有史以來最大的增長，自推出以來共有 918 名獨立腎病專家開出 TARPEYO 處方。

Revenues for the quarter amounted to SEK 191.4 million, with net sales from TARPEYO representing SEK 185.7 million of that or just under $18 million for the quarter.

該季度收入為 1.914 億瑞典克朗，其中 TARPEYO 的淨銷售額為 1.857 億瑞典克朗，即該季度略低於 1800 萬美元。

Our outlook for the year remains unchanged, and we're very excited about the initial reaction we've had from KOLs and with select nephrologists with whom we had the opportunity to share the Phase III data with. And yes, we really look forward to being able to share that data a bit broadly with the nephrology community going forward.

我們對今年的展望保持不變，我們對 KOL 和精選腎髒病專家的初步反應感到非常興奮，我們有機會與他們分享 III 期數據。是的，我們真的期待著能夠與腎髒病學界更廣泛地分享這些數據。

Next page, please. So about the NefIgArd trial. So actually, Richard will shortly provide you with the details from our top line readout from the Phase III trial. As I mentioned, though, we're extremely excited about the results as really this focus on the top of the disease cascade. Targeting this presumed origin of the disease seems to generate not only an immediate kidney protective benefit, but really actually also have long-term durability. And these strong results, we believe, will further support our thesis that TARPEYO is indeed disease-modifying in IgA nephropathy. And it's even more exciting, obviously, this effect has been seen irrespective of baseline UPCR levels.

請下一頁。關於 NefIgArd 試驗。事實上，理查德很快就會向您提供我們從第三階段試驗中讀出的詳細信息。不過，正如我所提到的，我們對結果感到非常興奮，因為我們真正關注的是疾病級聯的頂端。針對這種假定的疾病起源似乎不僅能產生立竿見影的腎臟保護作用，而且實際上還具有長期的持久性。我們相信，這些強有力的結果將進一步支持我們的論點，即 TARPEYO 確實可以緩解 IgA 腎病的疾病。顯然，更令人興奮的是，無論 UPCR 基線水平如何，都可以看到這種效應。

We do believe that this data, once it does become more familiar in the nephrology community, is going to be -- have a very significant impact on treatment paradigm of IgA nephropathy.

我們確實相信，一旦腎病學界更加熟悉這些數據，將會對 IgA 腎病的治療模式產生非常重大的影響。

In addition to the eGFR data, we also saw a dual-UPCR response where UPCR levels remain below 30% reduction for the -- also for the entire observational period of 15 months for initial treatment period of 9 months.

除了 eGFR 數據之外，我們還看到了雙重 UPCR 反應，其中 UPCR 水平在 9 個月的初始治療期的 15 個月的整個觀察期內仍然低於 30% 的降低。

On the basis of these data, we plan to file for full approval with the FDA for the entire study population of NefIgArd in July, with a regulatory decision to be expected in the first half of 2024. And the exact timing of that decision is dependent on whether that regulatory process will be conducted under a priority or standard review.

根據這些數據，我們計劃於 7 月份向 FDA 申請對 NefIgArd 整個研究人群的全面批准，預計監管決定將在 2024 年上半年做出。該決定的確切時間取決於關於該監管程序是否將在優先審查或標準審查下進行。

Next slide, please. A quick pipeline update. We are on track to report out our biomarker data for the setanaxib head and neck cancer trial around midyear this year, as we previously disclosed. We are still experiencing some challenges in terms of recruitment of the TRANSFORM study in PBC. The IPF -- the (inaudible) IPF trial is still recruiting on plan.

請下一張幻燈片。快速管道更新。正如我們之前所披露的，我們有望在今年年中左右報告 setanaxib 頭頸癌試驗的生物標誌物數據。我們在 PBC 招募 TRANSFORM 研究方面仍然遇到一些挑戰。 IPF——（聽不清）IPF 試驗仍在按計劃招募。

In terms of the biomarker data, we're super excited about reading that out. And we hope, obviously, that this proof-of-concept study will provide us with information that will be very helpful across all of the kind of different rare disease trials, which are presently running.

就生物標誌物數據而言，我們對讀出這些數據感到非常興奮。顯然，我們希望這項概念驗證研究將為我們提供對目前正在進行的所有不同罕見疾病試驗非常有幫助的信息。

In addition, we've decided to expand our clinical pipeline with the study in Alport syndrome. That's an orphan renal disease, whereas of today, there are no FDA or EMA approved drugs. And we will, on the basis of extensive preclinical work, launch a clinical trial in Alport involving approximately 20 patients, and we hope to start then second half of this year. And we also continue to explore the whole NOX inhibitor platform for other renal diseases, which we may be in a position to pursue later on.

此外，我們還決定通過阿爾波特綜合徵的研究來擴大我們的臨床產品線。這是一種孤兒腎病，而目前還沒有 FDA 或 EMA 批准的藥物。我們將在廣泛的臨床前工作的基礎上，在Alport啟動一項涉及大約20名患者的臨床試驗，我們希望在今年下半年開始。我們還繼續探索針對其他腎臟疾病的整個 NOX 抑製劑平台，我們以後可能會繼續研究。

Next slide, please. So with that, I'm going to hand over to Richard Philipson, who will take you through the top line data.

請下一張幻燈片。因此，我將把工作交給理查德·菲利普森（Richard Philipson），他將帶您了解最重要的數據。

Thanks very much, Renee. Next slide, please. So I'll start by briefly reviewing the Phase III study trial design, the NefIgArd study enrolled patients with biopsy-proven IgA nephropathy, proteinuria of 1 gram per day or higher and an eGFR of 35 to 90 mls per minute and with well controlled blood pressure whilst on optimized RAS inhibition. 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. The final analysis of the NefIgArd study is based on 364 patients full analysis sector efficacy treated for 9 months and followed up for a further 15 months without investigational treatment with a primary endpoint of average change from baseline in eGFR over the entire 24-month period of treatments and observation.

非常感謝，蕾妮。請下一張幻燈片。因此，我首先簡要回顧一下 III 期研究的試驗設計，NefIgArd 研究納入了經活檢證實的 IgA 腎病、蛋白尿每天 1 克或更高、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。研究期間不允許進行免疫抑制治療，也不鼓勵改變抗高血壓藥物。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。 NefIgArd 研究的最終分析基於 364 名患者的全面分析，這些患者接受了 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 個月期間 eGFR 相對於基線的平均變化。治療和觀察。

Next slide, please. In total, 395 patients were randomized into the study. This includes an additional 29 Chinese patients require a local Chinese regulatory purposes only. The safety analysis set of 389 patients includes all randomized patients who received at least one dose of study medication. The full analysis set comprising 364 patients is the way to set useful efficacy analyses performed for the (inaudible) study. Please note while these are only just over 10% of patients with approven study at any time, indicating a group rate of retention of patients in the study and the early discontinuations are broadly similar in the Nefecon and placebo treatment groups.

請下一張幻燈片。總共 395 名患者被隨機分配進入該研究。其中包括另外29名中國患者，僅需要中國當地監管目的。 389 名患者的安全性分析組包括所有接受至少一劑研究藥物的隨機患者。包含 364 名患者的完整分析集是為（聽不清）研究進行有用療效分析的方法。請注意，雖然這些患者在任何時候都只佔批准研究的患者的 10% 多一點，這表明 Nefecon 和安慰劑治療組中患者的組保留率和早期終止情況大致相似。

Next slide, please. Moving on to demographics. Overall, the enrolled patient population clearly represent state of the intended primary IgA nephropathy population. Disease characteristics describe a clinically relevant high-risk population. Treatment groups of balanced with (inaudible) baseline characteristics and that note blood pressure was well controlled for study entry.

請下一張幻燈片。繼續人口統計。總體而言，納入的患者群體清楚地代表了預期原發性 IgA 腎病群體的狀態。疾病特徵描述了臨床相關的高危人群。治療組與（聽不清）基線特徵相平衡，並且注意到血壓在研究進入時得到了很好的控制。

There's been an increase in the proportion of Asian patients in the study population since the use of data from the interim analysis reflective of the active recruitment of patients in China.

自從使用反映中國積極招募患者的中期分析數據以來，研究人群中亞洲患者的比例有所增加。

Next slide. Primary endpoint of time-weighted average change from baseline in eGFR during 9 months of treatment and 15 months of observation was, on average, during 2 years of treatment and observation, the loss of eGFR was 2.47 mls per [Audio Gap] the Nefecon 16 milligrams versus a loss of 7.52 mls net for placebo. So therefore, an average treatment difference 5.05 mls per minute favoring Nefecon a result that was highly statistically significant.

下一張幻燈片。在 9 個月的治療和 15 個月的觀察期間，eGFR 相對於基線的時間加權平均變化的主要終點是，在 2 年的治療和觀察期間，平均 eGFR 損失為 2.47 mls/[音頻間隙] Nefecon 16毫克，而安慰劑則淨損失 7.52 毫升。因此，平均每分鐘 5.05 毫升的治療差異有利於 Nefecon，這一結果具有高度統計顯著性。

Next slide, please. Several different supportive analyses of eGFR total 2-year slope were performed. These are all statistically significant with improvements in slope estimated to fall in the range of approximately 1.8 (inaudible) per minute per year. The differences in 2-year total slope observed between Nefecon and placebo are considered clinically relevant since all of the estimates are well in excess of the difference (inaudible) required to predict (inaudible) treatment effect for composite endpoint of end-stage kidney disease, eGFR less than 15 mls per minute or a sustained doubling of serum creatinine as published by Audio Gap in 2019.

請下一張幻燈片。對 eGFR 總 2 年斜率進行了幾種不同的支持性分析。這些在統計上都是顯著的，坡度的改善估計在每年每分鐘約 1.8（聽不清）的範圍內。 Nefecon 和安慰劑之間觀察到的 2 年總斜率差異被認為具有臨床相關性，因為所有估計值都遠遠超過了預測（聽不清）終末期腎病複合終點治療效果所需的差異（聽不清）， Audio Gap 於 2019 年發布的 eGFR 低於每分鐘 15 毫升或血清肌酐持續翻倍。

Next slide, please. When we look at the eGFR outcomes in placebo-treated patients at 9 months, there was a decline in eGFR of approximately 8%, corresponding to a loss of approximately 4.6 mls per minute, which increased a decline of 21.5% or 12 mls per minute by 24 months. In contrast, in patients treated with Nefecon and eGFR was essentially stable compared to baseline at 9 months. And by 24 months, there have been a decline in eGFR of 11%, corresponding to a loss of approximately 6 mls per minute. So in summary, 9 months of dosing with 16 milligrams of Nefecon in 364 patients resulted in 50% or less loss of kidney function compared to placebo at 24 months.

請下一張幻燈片。當我們觀察安慰劑治療患者 9 個月時的 eGFR 結果時，eGFR 下降了約 8%，相當於每分鐘減少約 4.6 毫升，這增加了 21.5% 或每分鐘 12 毫升的下降到 24 個月。相比之下，在接受 Nefecon 治療的患者中，9 個月時 eGFR 與基線相比基本穩定。到 24 個月時，eGFR 下降了 11%，相當於每分鐘流失約 6 毫升。總之，364 名患者服用 16 毫克 Nefecon 9 個月後，與安慰劑相比，24 個月時腎功能喪失了 50% 或更少。

Next slide, please. So turning to proteinuria. We've seen a cumulative improvement in proteinuria in patients treated with Nefecon versus placebo during the 9-month treatment period, which continued to improve at 12 months. At month 24, proteinuria levels in patients who had received Nefecon was still at a reduced level, similar to that observed with the 9-month time point.

請下一張幻燈片。所以轉向蛋白尿。我們發現，在 9 個月的治療期間，接受 Nefecon 治療的患者與安慰劑相比，蛋白尿有了累積改善，並在 12 個月時繼續改善。在第 24 個月時，接受 Nefecon 治療的患者的蛋白尿水平仍處於降低水平，與 9 個月時間點觀察到的水平相似。

Next slide. So in summary, the primary endpoint of average change from baseline in eGFR over the 2-year treatment and observation period was met and was highly statistically significant. Supportive analyses of 2-year eGFR slope were also statistically significant and are clinically relevant. All estimates are well in excess of the threshold required to predict clinically meaningful treatment effects.

下一張幻燈片。總而言之，在 2 年的治療和觀察期內，eGFR 相對於基線的平均變化這一主要終點已得到滿足，並且具有高度統計顯著性。 2 年 eGFR 斜率的支持性分析也具有統計學意義且具有臨床相關性。所有估計值都遠遠超過了預測有臨床意義的治療效果所需的閾值。

The treatment benefit on eGFR was apparent and cross baseline UPCR subgroups. And sustained proteinuria effect and long-lasting EGFR treatment benefit was observed even after 15 months of treatment supporting disease (inaudible).

eGFR 的治療益處是明顯的並且跨基線 UPCR 亞組。即使在支持疾病治療 15 個月後，仍觀察到持續的蛋白尿效應和持久的 EGFR 治療益處（聽不清）。

So now next slide refers to safety. When we look specifically here at the 9-month treatment period, overall, we saw a pattern of adverse events and the safety analysis set that was similar to the interim analysis, which has previously been described in our publication in Kidney International and which is also described in product information. The most frequently occurring adverse events occurring in 5% or more Nefecon treated patients and 2% or higher than placebo or peripheral edema, hypertension, muscle spasm, acne, upper expiratory tract infection, face edema, increased weight, dyspepsia arthralgia and increase in white cell death.

現在下一張幻燈片涉及安全。當我們具體觀察 9 個月的治療期時，總體而言，我們看到了不良事件的模式和與中期分析類似的安全性分析集，這在我們之前在《腎臟國際》雜誌上的出版物中進行了描述，並且產品信息中描述。最常發生的不良事件發生在 5% 或更多 Nefecon 治療患者和 2% 或更高的安慰劑或周圍水腫、高血壓、肌肉痙攣、痤瘡、上呼氣道感染、面部水腫、體重增加、消化不良關節痛和白蛋白增加細胞死亡。

It's important to note that any ongoing adverse events typically resolve at the end of treatment and common adverse events occurring during the 15-month follow-up period are generally unremarkable with a similar frequency of reporting in Nefecon versus placebo treatment groups.

值得注意的是，任何持續的不良事件通常會在治療結束時得到解決，並且在 15 個月的隨訪期間發生的常見不良事件通常並不顯著，Nefecon 與安慰劑治療組的報告頻率相似。

So next slide. So in summary, overall, the adverse event profile was similar to that reported in the interim analysis. The most commonly reported adverse events observed with an increased frequency compared to placebo were peripheral edema and potential muscle spasms and acne. The majority of these events were mild or moderate in severity, and adverse events led to discontinuation of study drug in fewer than 10% Nefecon treated patients. And when we looked at objective measures of mean weight and blood pressure these show unclinically relevant fully reversible changes.

那麼下一張幻燈片。總而言之，總體而言，不良事件概況與中期分析中報告的情況相似。與安慰劑相比，最常見報告的不良事件是外周水腫和潛在的肌肉痙攣和痤瘡，且頻率增加。大多數這些事件的嚴重程度為輕度或中度，只有不到 10% 的 Nefecon 治療患者因不良事件而停止研究藥物。當我們觀察平均體重和血壓的客觀測量結果時，這些結果顯示出與臨床無關的完全可逆的變化。

I'll now pass over to Andy Udell.

我現在請安迪·烏德爾發言。

Thank you, Richard. Next slide. While our $17.8 million in net sales were impacted by the typical end of year early patient refills and patient insurance changes at the beginning of the year, the first quarter of the year saw substantial enrollment and new prescriber growth, which are both key leading indicators for future net sales growth.

謝謝你，理查德。下一張幻燈片。雖然我們 1,780 萬美元的淨銷售額受到典型的年底早期患者續藥和年初患者保險變化的影響，但今年第一季度的入院人數和新處方醫生數量大幅增長，這都是關鍵的領先指標未來淨銷售額增長。

March was a record month in sales and enrollments, pushing the quarter total to 408 patient enrollments, representing a 30% growth over Q4. In addition, we had 276 new nephrology prescribers prescribed TARPEYO during the quarter, which is also a record, and as of this report, now totals over 1,000 unique prescribers during our first 14 months of promotion.

3 月份的銷售額和註冊人數創下歷史新高，使該季度的註冊患者總數達到 408 名，比第四季度增長 30%。此外，本季度我們有 276 名新的腎臟科處方者開了 TARPEYO，這也是一個記錄，截至本報告，在我們推廣的前 14 個月內，目前共有超過 1,000 名獨特的處方者。

We also continue to grow the number of patients and are improving the speed at which they are receiving TARPEYO. During the quarter, 85% of patients enrolled in TARPEYO Touchpoints, excluding those still waiting for an insurance decision, received TARPEYO. This conversion rate is consistent with the rate reported for full year 2022.

我們還繼續增加患者數量，並提高他們接受 TARPEYO 治療的速度。本季度，85% 加入 TARPEYO Touchpoints 的患者（不包括仍在等待保險決定的患者）接受了 TARPEYO。該轉化率與 2022 年全年報告的轉化率一致。

As time goes on, we have more and more patient success stories and patients that have reached 9 months of treatment with TARPEYO. While treatment length can be variable, as we see more patients completing 9 months on treatment, we observed that the majority of those that completed 9 months remained on therapy beyond this. We believe this reflects the risk/reward profile of the product as more and more of these patients will benefit from the consistent clinical results demonstrated in our trials.

隨著時間的推移，我們有越來越多的患者成功案例以及接受TARPEYO治療達到9個月的患者。雖然治療時間可能會有所不同，但隨著我們看到更多患者完成 9 個月的治療，我們觀察到大多數完成 9 個月的患者仍在接受治療。我們相信這反映了該產品的風險/回報概況，因為越來越多的患者將受益於我們試驗中所證明的一致的臨床結果。

Next slide, please. Commercial and promotional efforts regarding the full data from the NefIgArd phase 3 clinical trial won't take place until after regulatory filing and approval. However, as announced earlier this month, we have several late-breaking oral presentations and posters accepted for the European Renal Association Congress coming up in June next month. These presentations and posters will provide further information and build upon the impressive results that Richard just reviewed with us. As you would suspect, the peer-to-peer conversations and reactions to the data by advisers and investigators is extremely positive. The next 3 quarters have additional key nephrology meetings and conferences providing opportunities for further data exchange and presentations as we continue to assess the results of the NefIgArd Phase III study.

請下一張幻燈片。有關 NefIgArd 3 期臨床試驗完整數據的商業和推廣工作要等到監管部門備案和批准後才會進行。然而，正如本月早些時候宣布的那樣，我們有幾項最新的口頭報告和海報已被接受，供下個月 6 月舉行的歐洲腎臟協會大會使用。這些演示文稿和海報將提供更多信息，並以理查德剛剛與我們回顧的令人印象深刻的結果為基礎。正如您所懷疑的那樣，顧問和調查人員之間的對話以及對數據的反應是非常積極的。隨著我們繼續評估 NefIgArd III 期研究的結果，接下來的 3 個季度將舉行更多重要的腎髒病學會議，為進一步的數據交換和演示提供機會。

And with that, I will turn it over to Fredrik to provide our financial results.

至此，我將把它交給 Fredrik 來提供我們的財務業績。

Thank you, Andy, and good afternoon and good morning, everyone. I will now present to you the financial overview for the first quarter of 2023. And as always, all numbers presented to you are in SEK million, unless otherwise stated.

謝謝你，安迪，大家下午好，早上好。現在，我將向您介紹 2023 年第一季度的財務概況。與往常一樣，除非另有說明，向您提供的所有數字均以百萬瑞典克朗為單位。

To start with, we reported SEK 191.4 million in net revenues for the quarter. For the same period last year, we reported net revenues of SEK 49.7 million. TARPEYO net product sales for the first quarter amounted to SEK 185.7 million or $17.8 million. In addition, we also recorded SEK 5.7 million for the period revenues related to partners primarily from Kinpeygo royalities from STADA.

首先，我們報告本季度淨收入為 1.914 億瑞典克朗。去年同期，我們的淨收入為 4970 萬瑞典克朗。 TARPEYO 第一季度產品淨銷售額達 1.857 億瑞典克朗（1,780 萬美元）。此外，我們還記錄了 570 萬瑞典克朗的期內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 first quarter amounted to SEK 362.4 million compared to SEK 257.5 million for the same period last year. Compared to fourth quarter last year, our OpEx decreased by $26.3 million in Q1. And in comparison, if we remove the effect in the quarter from a weakened SEK and increased social secured accruals from auction programs due to increase in our share price in March, we would have decreased the OpEx by additional SEK 21 million for a total increase of SEK 47 million between Q4 and Q1.

我們第一季度的總運營費用為 3.624 億瑞典克朗，而去年同期為 2.575 億瑞典克朗。與去年第四季度相比，我們第一季度的運營支出減少了 2630 萬美元。相比之下，如果我們消除本季度瑞典克朗疲軟以及由於 3 月份股價上漲而導致拍賣計劃中社會保障應計項目增加的影響，我們將額外減少 2100 萬瑞典克朗的運營支出，總計增加第四季度至第一季度為 4700 萬瑞典克朗。

The cost for research and development increased by SEK 13.4 million in the first quarter to SEK 126.7 million compared with SEK 113.3 million for the year -- previous year. Increase in R&D expenses originates primarily from the ongoing operations for the Setanaxib trials and the preparations for the start of the Alport trial.

第一季度的研發成本增加了 1,340 萬瑞典克朗，達到 1.267 億瑞典克朗，而去年同期為 1.133 億瑞典克朗。研發費用的增加主要來自 Setanaxib 試驗的持續運營以及 Alport 試驗啟動的準備工作。

The cost for sales and marketing increased by SEK 73.3 million to SEK [167.3] million compared to SEK 93.9 million for the same period previous year. In Q1, we now have the cost for the full extended commercial team, which would be compared to the same period last year, which we were in the first quarter of commercialization. The above led to an operating loss of [Audio Gap] for the first quarter compared to SEK 208.4 million for the same period last year.

銷售和營銷成本增加了 7,330 萬瑞典克朗，達到 [1.673] 億瑞典克朗，而去年同期為 9,390 萬瑞典克朗。在第一季度，我們現在有了完整擴展商業團隊的成本，這將與去年同期（我們處於商業化的第一季度）進行比較。上述因素導致第一季度 [Audio Gap] 運營虧損，而去年同期為 2.084 億瑞典克朗。

In the first quarter, cash used in operating activities was SEK 231.9 million compared to SEK 194 million for the same year previous year. This leaves us with a net decrease in cash in the quarter of SEK 237.8 million, and we have a very healthy cash position at the end of the quarter of SEK 1.013 billion, which we believe is sufficient to take us to profitability.

第一季度經營活動使用的現金為2.319億瑞典克朗，去年同期為1.94億瑞典克朗。這使得我們本季度的現金淨減少 2.378 億瑞典克朗，而我們在季度末擁有非常健康的現金狀況，達到 10.13 億瑞典克朗，我們相信這足以使我們實現盈利。

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, Fredrik. So just some key kind of summary takeaways to finish up the presentation. After which, we will take questions.

謝謝你，弗雷德里克。因此，我們僅提供一些關鍵的總結來完成演示。之後，我們將接受提問。

So as you heard from Richard, we had very strong eGFR data, really showing a kidney protective effect and a positive readout from Phase III NefIgArd trial, which we believe support disease modification from the treatment of Nefecon in which are branded is TARPEYO in the U.S. and Kinpeygo in Europe. We will be filing for full approval for the entire study population, which is planned for July this year. And STADA is expected to file with EMA for full approval also in the second half of this year.

正如您從理查德那裡聽到的，我們有非常強大的 eGFR 數據，確實顯示了腎臟保護作用，並且 III 期 NefIgArd 試驗的積極讀數，我們相信該試驗支持 Nefecon 治療的疾病改變，該藥物在美國的品牌為 TARPEYO。和歐洲的金佩戈。我們將在今年 7 月提交針對整個研究人群的全面批准申請。 STADA 預計也會在今年下半年向 EMA 提交全面批准的文件。

As you heard from Andy, we had record numbers of enrollments for the quarter and the highest ever growth to date of new prescribers in Q1. We also -- which resulted in revenues of SEK 191 million in total and TARPEYO sales of SEK 185.7 million. We also got MHRA conditional approval of Nefecon, which provided the first and only approved medication for IgA nephropathy in the U.K.

正如您從安迪那裡聽到的那樣，我們本季度的註冊人數創歷史新高，並且第一季度新處方醫生的增長率達到了有史以來最高。我們的總收入為 1.91 億瑞典克朗，TARPEYO 銷售額為 1.857 億瑞典克朗。我們還獲得了 MHRA 有條件批准 Nefecon，該藥物是英國第一個也是唯一一個獲得批准的治療 IgA 腎病的藥物。

So with that, I'm going to hand over for any questions.

因此，我將回答任何問題。

(Operator Instructions) Our first question comes from the line of Yigal Nochomovitz from Citi.

（操作員說明）我們的第一個問題來自花旗銀行的 Yigal Nochomovitz。

This is Ashiq Mubarik on for Yigal. Just the first one on the TARPEYO guidance. It seems like you're assuming some significant acceleration of growth in the remainder of 2023. Can you talk about some of the dynamics behind that and what you think the key drivers will be? Seems to hit the midpoint, you're going to need to achieve some pretty significant growth rate. So just wondering what your thoughts on how that might appear quarter-over-quarter for the next 2 or 3 quarters.

我是阿希克·穆巴里克 (Ashiq Mubarik)，代表伊加爾 (Yigal) 發言。這只是 TARPEYO 指南中的第一個。您似乎假設 2023 年剩餘時間內增長將出現顯著加速。您能否談談其背後的一些動力以及您認為的關鍵驅動因素是什麼？似乎達到了中點，您將需要實現一些相當顯著的增長率。因此，我想知道您對未來 2 或 3 個季度的季度環比情況有何看法。

Sure. And I'll have -- I'll start, and then Andy can fill in with any other additional details. So in terms of what we've seen, obviously, this quarter already is really a high level of enrollment together with significant growth in kind of new prescribers. And as we've kind of mentioned before already in the kind of Q4 report, we are talking about the fact that we're hearing more and more kind of success stories from patients, and there's more and more kind of peer-to-peer recommendations amongst nephrologists. This obviously provides leverage into the entire system. And we also believe that in addition to that, we will, by actually kind of getting this kind of Phase III data out into the nephrology community, not in a kind of commercial fashion, but just merely from kind of abstracts and oral presentations at conferences or manuscripts, et cetera, we believe that this data truly is groundbreaking. And we've certainly had the feedback that we've had from KOLs who have -- we've been able to share some of this data with really support the fact that this is truly disease-modifying, and we believe we'll have a significant impact on the treatment kind of paradigm. So that's really, I think, would be the driving force from my perspective. Andy, do you have anything to add?

當然。我將開始，然後安迪可以填寫任何其他附加詳細信息。因此，就我們所看到的情況而言，顯然，本季度的註冊人數已經很高，而且新處方醫生的數量也顯著增長。正如我們之前在第四季度報告中提到的那樣，我們正在談論這樣一個事實：我們從患者那裡聽到了越來越多的成功故事，並且有越來越多的點對點腎病專家的建議。這顯然為整個系統提供了槓桿作用。我們還相信，除此之外，我們將通過實際上將此類 III 期數據引入腎病學界，而不是以商業方式，而只是通過會議上的摘要和口頭演示或者手稿等等，我們相信這些數據確實是開創性的。當然，我們也從 KOL 那裡得到了反饋，我們已經能夠分享其中一些數據，真正支持這樣一個事實：這確實可以改變疾病，我們相信我們會對治療範式產生重大影響。所以，我認為，從我的角度來看，這確實是驅動力。安迪，你還有什麼要補充的嗎？

Yes. So I mean I would just echo everything Renee said. I think that you're going to start to see, beginning with ERA-EDTA, the full trial results hit the podium. And I think then people will enjoy and see the reaction to the data as we have with advisers and people that have been brought in to assess the data with us. So I think that that's one -- certainly one catalyst as well as more and more successes.

是的。所以我的意思是我會附和蕾妮所說的一切。我認為您將開始看到，從 ERA-EDTA 開始，完整的試驗結果登上了領獎台。我認為那時人們會喜歡並看到對數據的反應，就像我們與顧問和與我們一起評估數據的人員一樣。所以我認為這就是一個——當然是一個催化劑，也是越來越多的成功的催化劑。

Patients that were started late in 2022 -- we'll start to see a lot more of those success stories with new prescribers. You heard about the large number of new prescribers at the beginning of this year in the first quarter. So I think that these things will build on itself during the launch growth year.

對於 2022 年末開始使用的患者，我們將開始看到更多新處方醫生的成功案例。您聽說今年年初第一季度有大量新處方醫生。因此，我認為這些事情將在發布增長年中自行建立。

Got it. That's super helpful. And if I can ask one more. You alluded to patients at this point, the majority of the patients on TARPEYO staying on treatment longer than 9 months. Are you able to give us any more detail on that, maybe how much longer than 9 months they are staying and if there are any challenges with the reimbursement associated with that?

知道了。這非常有幫助。如果我可以再問一個。您此時提到了患者，大多數 TARPEYO 患者的治療時間超過 9 個月。您能否向我們提供更多詳細信息，例如他們停留的時間超過 9 個月多長時間以及與此相關的報銷是否存在任何挑戰？

Sure. So just to be clear, length of treatment can be variable, okay? But what we are seeing is -- and it is still early for -- to talk about long and length of treatment here, but what we are seeing is those that have completed 9 months seem to stay on a little longer in the majority of those patients, okay? But we are -- there are success stories of patients that have -- that are more mild, let's just say, that may stop after 7, 8 months, and those are deemed as successes. So that's -- we just want to provide that feedback in the sense that it's panning out almost exactly how market research since for the last 5 years has told us, which is the nephrologists are going to treat this disease based on the patients, okay? And they're going to treat if it's patient starts and is a much more severe patient and they're doing well and they're avoiding dialysis, they're going to stay on treatment if they're tolerating the medication, okay? And if not, if they are a more mild patient or earlier in the disease and they're doing well and their proteinuria is well below the threshold for them considering them at risk, they would stop, but they continue to see these patients. And should the patients start to progress again, they would treat again.

當然。所以需要明確的是，治療時間可以是可變的，好嗎？但我們看到的是——現在談論治療的時間長短還為時過早，但我們看到的是，大多數已經完成 9 個月的患者似乎停留的時間更長一些病人，好嗎？但我們——有一些患者的成功故事——病情較輕，可以說，可能會在 7、8 個月後停止，而這些被視為成功。所以，我們只是想提供這種反饋，因為它幾乎準確地說明了過去 5 年以來的市場研究告訴我們的情況，腎科醫生將根據患者的情況來治療這種疾病，好嗎？如果患者開始治療並且病情嚴重得多，並且他們狀況良好並且正在避免透析，他們將進行治療，如果他們能夠耐受藥物，他們將繼續接受治療，好嗎？如果不是，如果他們是病情較輕或處於疾病早期的患者，並且他們狀況良好，並且他們的蛋白尿遠低於他們認為處於危險之中的閾值，他們會停止治療，但他們會繼續看望這些患者。如果患者再次開始進展，他們將再次治療。

And the last part of your question, just as far as payers, no, we have not seen any issues or concerns as far as coverage with that. And if there are requirements, we would certainly make sure a patient didn't discontinue or have any interruptions of treatment. So I think that, that provides it.

你問題的最後一部分，就付款人而言，不，我們沒有看到任何問題或擔憂。如果有要求，我們當然會確保患者不會停止或中斷治療。所以我認為，這提供了它。

I can't -- your last question -- actually, you had a point about how long, it's way too early for us to tell how long they go on for these patients.

我不能——你的最後一個問題——實際上，你有一個關於持續時間的觀點，對於我們來說，判斷這些患者的持續時間還為時過早。

The next question comes from the line of Maury Raycroft from Jefferies.

下一個問題來自 Jefferies 的莫里·雷克羅夫特 (Maury Raycroft)。

As a follow-up to the earlier guidance question, I'm wondering how does your latest commercial data shape your assumptions for upper or lower ends of revenue guidance for this year. Are you relying more on keeping patients on drug or getting new patients on drug?

作為先前指導問題的後續問題，我想知道您的最新商業數據如何影響您對今年收入指導上限或下限的假設。您更依賴於讓患者繼續用藥還是讓新患者繼續用藥？

I mean I think that in terms of what we're kind of confident, I mean, obviously, it's both. I mean, obviously, I think that there's going to be a -- as Andy mentioned, there's going to be a combination of shorter duration treatment -- actually, the physicians have achieved their treatment goal. And there also seems to be, I think, a higher number than what we were initially expecting to actually are staying on drug longer than the 9-month kind of initial treatment cycle would indicate. So I think that there will be -- clearly, there's kind of a combination there.

我的意思是，我認為就我們的信心而言，我的意思是，顯然，兩者都是。我的意思是，顯然，我認為將會有一個——正如安迪提到的，將會有一個較短持續時間的治療組合——實際上，醫生已經實現了他們的治療目標。我認為，似乎還有比我們最初預期的人數更多的人，實際用藥時間比 9 個月的初始治療週期所表明的要長。所以我認為，顯然，會有某種組合。

I think in terms of -- from our perspective, I think our role really is to educate the market and to actually kind of just get this information as well as the data that we published fairly recently in October, November, really from the interim analysis, even getting that kind of truly kind of penetrating the community so that there is sufficient information about the drug out there. So I think that's really what we are kind of focused on.

我認為，從我們的角度來看，我認為我們的作用實際上是教育市場，實際上只是從中期分析中獲取這些信息以及我們最近在 10 月、11 月發布的數據。 ，甚至真正滲透到社區中，以便獲得有關該藥物的足夠信息。所以我認為這才是我們真正關注的重點。

So in terms of the guidance, I mean, I think it's certainly kind of easier from this particular quarter to say that it's clear that hitting the upper end of that guidance might be kind of somewhat challenging. But I do think at the end of the day, the reactions that we are getting again from nephrologists relating to this data, I think, is very, very important and quite unique. So I still think that we'll have to wait a little bit longer then from Q1 to be able to kind of give you a proper answer to that question.

因此，就指導而言，我的意思是，我認為從這個特定季度來看，顯然達到該指導的上限可能有點具有挑戰性，這肯定更容易說。但我確實認為，歸根結底，我們再次從腎髒病學家那裡得到的與這些數據相關的反應，我認為是非常非常重要且非常獨特的。因此，我仍然認為我們需要等待比第一季度更長的時間才能為您提供該問題的正確答案。

Got it. That's really helpful. And one other question. Just wondering if you can elaborate on next steps for pursuing full approval. Do you need to have another round of a pre-NDA regulatory feedback in order to file? And what are your expectations for the review time line?

知道了。這真的很有幫助。還有一個問題。只是想知道您是否可以詳細說明爭取完全批准的後續步驟。您是否需要獲得另一輪新藥申請前監管反饋才能提交？您對審核時間有何期望？

So obviously, I think that with this data, which is extremely clear, I mean, both in terms of statistical significance and, clearly, also in terms of clinical relevance if you look at kind of what's being published and what's out there. We are not planning to have any kind of clarifying meeting with the FDA. It's a very consistent response across the entire study population and, as I said, a very kind of clear and crisp data. So we would file, and the timing for filing really that we're targeting in July.

顯然，我認為這些數據非常清楚，我的意思是，無論是在統計顯著性方面，還是在臨床相關性方面，如果你看看正在發表的內容和現有的內容。我們不打算與 FDA 舉行任何形式的澄清會議。這是整個研究人群的非常一致的反應，正如我所說，這是一種非常清晰明了的數據。所以我們會提交申請，而且我們的目標是在 7 月份提交申請。

And in terms of the -- we will request priority review as this is kind of a supplemental filing. But obviously, it's always up to the regulators to, based on the workload that they have and other considerations, to decide whether they will do the priority review of the standard view. And the difference there is obviously 6 months review time for priority and 10-month review time for standard procedure.

就這一點而言，我們將要求優先審查，因為這是一種補充備案。但顯然，監管機構始終要根據自己的工作量和其他考慮因素來決定是否對標準視圖進行優先審查。明顯的區別是優先程序的審查時間為6個月，標準程序的審查時間為10個月。

The next question comes from Sushila Hanandus from CLK.

下一個問題來自 CLK 的 Sushila Hanandus。

This is Shushila for Suzanne. Do you already see an uptake in prescriptions after the top line Phase III results? And also, could you elaborate on how you expect your operating expenses to develop over the quarters? And what will be the driver?

這是蘇珊娜的舒希拉。在第三階段的頂線結果之後，您是否已經看到處方的使用量有所增加？另外，您能否詳細說明您預計這些季度的運營費用將如何發展？司機會是誰？

Sure. I mean I think that obviously, this is really between -- so the first quarter would be way too early to see any impact from that. Really, I mean, the real impact really is going to be in 2024 because we are not really able to commercially promote on the basis of the new data until there's been a regulatory approval and an updated label.

當然。我的意思是，我認為顯然，這確實是介於兩者之間的，所以第一季度要看到任何影響還為時過早。事實上，我的意思是，真正的影響將在 2024 年出現，因為在獲得監管部門批准和更新標籤之前，我們無法真正根據新數據進行商業推廣。

I think the only kind of benefit that I think we will have is just, as I mentioned before, that through kind of oral presentations, at conferences, at abstracts, at other kind of manuscripts, et cetera. I think that will start making its way into the kind of nephrology community really from the -- in the second half of this year, so that will really start with the ERA-EDTA, which takes place in the middle of June.

我認為我們將獲得的唯一好處就是，正如我之前提到的，通過口頭報告、會議、摘要、其他類型的手稿等。我認為這將從今年下半年開始真正進入腎髒病學界，因此這將真正從 6 月中旬舉行的 ERA-EDTA 開始。

Fredrik, I will hand over the second question to you.

Fredrik，我將第二個問題交給你。

Yes. We don't give any guidance on the operating expenses. But looking at the start of the last year's OpEx of SEK 1.25 billion, we of course, also see an inflation effect in our operations. And this year also, we do have the extended sales force on board for the full year. We'll also start getting program in Alport. So I think that is the drivers of what we will see in addition to last year.

是的。我們不對運營費用提供任何指導。但從去年 12.5 億瑞典克朗的運營支出開始來看，我們當然也看到了運營中的通脹效應。今年，我們也確實擴大了全年的銷售隊伍。我們還將開始在奧爾波特舉辦節目。所以我認為除了去年之外，這也是我們將看到的推動因素。

The next question comes from the line of Rami Katkhuda from LifeSci Capital.

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

Two quick ones for me. First, has the expanded sales force been fully deployed? And when do you expect to see the impact of that on TARPEYO sales? And then do you plan on running any post-marketing studies with Nefecon and IgAN to evaluate longer-term dosing, retreatment combination with SGLT2s, et cetera?

對我來說兩個快點。第一，擴大的銷售隊伍是否已全部部署完畢？您預計什麼時候會看到這對 TARPEYO 銷售的影響？那麼您是否計劃使用 Nefecon 和 IgAN 進行任何上市後研究，以評估長期給藥、與 SGLT2 的再治療組合等？

So I guess I can handle the first part about the sales force. While they certainly have been deployed, meaning they're in the field working, this takes time to build relationships and establish your routes and who you're seeing and priority calls and learning your territory, while they come with -- most of them come with nephrology experience, you're going to see more and more uptake as the year wears on. So they were in the field deployed in November, all of them. And I think you're going to start to see them hit their stride soon.

所以我想我可以處理有關銷售人員的第一部分。雖然他們肯定已經被部署，這意味著他們在現場工作，但這需要時間來建立關係、建立你的路線、你要見的人、優先呼叫和了解你的領地，而他們中的大多數人都來了憑藉腎髒病學經驗，隨著時間的推移，您會看到越來越多的人使用它。所以他們在 11 月份就部署到了現場。我想你很快就會開始看到他們邁出步伐。

As far as the other stuff, I'll let Renee comment or Richard.

至於其他的事情，我會讓蕾妮或理查德來評論。

Sure. So with regards to additional studies, that is something that we are looking into. And so we are having kind of internal discussions with regards to what type of studies may be most useful from the kind of nephrologist and patient perspective and also whether those potential studies are best run -- kind of managed by the company or whether there is some investigator-led studies, which would be -- would better serve that purpose. So we are discussing that. But at this point in time, we haven't made any decision with regards to any additional studies, but it's certainly something that we're looking into on the basis of having read out the full Phase III data.

當然。因此，關於其他研究，這是我們正在研究的事情。因此，我們正在進行內部討論，討論從腎髒病學家和患者的角度來看哪種類型的研究可能最有用，以及這些潛在的研究是否最好進行——由公司管理，或者是否有一些研究由研究者主導的研究將更好地服務於這一目的。所以我們正在討論這個問題。但目前，我們還沒有就任何額外的研究做出任何決定，但這肯定是我們在讀出完整的 III 期數據的基礎上正在研究的事情。

The next question comes from Dan Akschuti from Pareto Securities.

下一個問題來自 Pareto 證券公司的 Dan Akschuti。

One question would be regarding the mentioning that you saw a record enrollment in December. How did that translate into sales? Or some of that's maybe not booked them in January? And could you comment if you see the same growth as you have seen now in March also in April and May?

一個問題是關於您在 12 月份看到創紀錄的入學人數。這如何轉化為銷售額？或者其中一些可能在一月份沒有預訂？如果您在 3 月以及 4 月和 5 月看到了與現在相同的增長，您能發表評論嗎？

Why don't you clarify the first (inaudible), Andy, and I'll take the second.

安迪，你為什麼不澄清第一個（聽不清），我來談談第二個。

Yes. No. Just -- we did not see a record enrollments in December. And December, in -- the record enrollments was for the quarter, for first quarter. Typically for us, if you get an enrollment in 1 month, you start to see later -- if it's at the beginning of the month, it's -- usually, our fill is right around or less than 30 days. So it takes a little bit to realize the income from an enrollment. But the record enrollments, just to clarify, was during Q1 and March was in particularly strong.

是的。不。只是 - 我們沒有看到 12 月份的入學人數創紀錄。 12 月，第一季度的入學人數創紀錄。通常情況下，對於我們來說，如果您在 1 個月內註冊，您就會開始看到較晚的時間 - 如果是在月初，那麼 - 通常，我們的填滿時間大約為 30 天左右或不到 30 天。因此，需要一點點才能實現註冊收入。但需要澄清的是，創紀錄的入學人數是在第一季度和三月份特別強勁。

And in terms of kind of continuing, I think we're very encouraged by the level of enrollments that we are seeing post Q1.

就持續而言，我認為我們對第一季度後看到的入學水平感到非常鼓舞。

Okay. And then another question. How is Everest Medicines planning for launch? Assuming approval in the second half, are they ready to launch directly? Or do we need to assume a few months until they launch after approval?

好的。然後還有一個問題。 Everest Medicines 計劃如何推出？假設下半年獲得批准，他們準備好直接啟動了嗎？或者我們是否需要假設他們在獲得批准後啟動需要幾個月的時間？

I think that it will be a similar situation as the one we had in Europe because, obviously, we are the market authorization holder as we actually were -- was the sponsor in that trial. So there will be a requirement to do -- kind of a handover from a market authorization holdership perspective. So that may very well result in a couple of months of delay between kind of the actual approval and the first kind of shipment of product.

我認為這將與我們在歐洲遇到的情況類似，因為顯然，我們實際上是市場授權持有者——是該試驗的申辦者。因此，需要做一些事情——從市場授權持有權的角度進行移交。因此，這很可能會導致實際批准和第一種產品發貨之間出現幾個月的延遲。

Okay. And the last question -- you reached around 2,000 prescribers now. They are around 10x as many around there in the U.S. What are your plans to accelerate the pace of reaching them and educating them? And do you see a change now with the full data since March?

好的。最後一個問題 - 現在您的處方者數量約為 2,000 名。他們的數量大約是美國的 10 倍。您有什麼計劃來加快接觸和教育他們的步伐？從三月份以來的完整數據來看，您現在看到變化了嗎？

Do you want to take that, Andy?

安迪，你想接受嗎？

Yes. Sure. So just to be clear, while there may be over 10,000 nephrologists, there's really not -- many of them don't treat IgA nephropathy patients, and they're not in the clinics and -- that see these patients. So we believe that, that number is in the 4,000 range to cover the vast majority of nephrologists treating these patients. So over 1,000, you can do the math. And these typical markets are 80-20, and 80% of the load comes from about 20% of the targets. So that gives you a better sense of the size of the market as far as prescribers.

是的。當然。因此需要明確的是，雖然可能有超過 10,000 名腎臟科醫生，但實際上沒有——他們中的許多人不治療 IgA 腎病患者，而且他們也不在診所——看這些患者。因此，我們相信，這個數字在 4,000 人范圍內，可以涵蓋治療這些患者的絕大多數腎臟科醫生。所以超過1000，你可以算一下。而這些典型的市場是80-20個，80%的負載來自於20%左右的目標。因此，這可以讓您更好地了解處方者的市場規模。

And as far as the data and those kind of things, as we keep saying, I mean, you're not going to see the impact of the full data from NefIgArd trial. You guys are more in tune, those on this call listening to it than many of the nephrologists because it hasn't hit their inbox yet. And as Renee said, we're not permitted to promote on this. This will come out in peer-to-peer meetings, congresses. And the first one of those is next month, in the middle of the month in Milan at ERA-EDTA.

就數據和此類事情而言，正如我們一直說的，我的意思是，你不會看到 NefIgArd 試驗的完整數據的影響。你們比許多腎臟科醫生都更合拍，因為這個電話還沒有到達他們的收件箱。正如蕾妮所說，我們不被允許對此進行宣傳。這將在同行會議、代表大會上公佈。其中第一個是下個月中旬在米蘭舉行的 ERA-EDTA。

The next question comes from Ingrid Gafanhão from Brian Garnier & Co. Then we'll move to Vamil Divan from Guggenheim.

下一個問題來自 Brian Garnier & Co. 的 Ingrid Gafanhão。然後我們將轉向古根海姆的 Vamil Divan。

This is (inaudible) on for Vamil. Maybe expanding on some of the prior questions about these new prescribers translating in sales. Have there been a new shift this quarter in the gross to net or the Medicaid channel contribution or any other factor besides the way from enrollment to shipment that kind of impacted sales this quarter?

這是 Vamil 的（聽不清）。也許可以擴展一些關於這些新處方者轉化為銷售的先前問題。本季度毛額到淨額或醫療補助渠道貢獻是否有新的轉變，或者除了從註冊到發貨的方式影響本季度銷售的任何其他因素？

No. I would say no, there's no change on gross to net or anything like that this quarter.

不。我想說不，本季度毛額和淨額沒有任何變化或類似的變化。

And then maybe one more. So dramatic growth in the number of new prescribers. How should we think about the rate at which the old prescribers are enrolling new patients? Because based on the numbers this quarter, it looks like the majority of new enrollments obviously came from the new prescribers. So kind of...

然後也許還有一個。新開處方者的數量急劇增長。我們應該如何考慮老處方者招募新患者的速度？因為根據本季度的數據，看起來大部分新註冊患者顯然來自新開處方者。這麼...

Yes. I think it's variable depending on their patient mode, and some see more patients than others, and some are faster adopters than others. And some nephrologists may try a product on a patient or 2 and do their own kind of clinical trial, meaning to see the success. So sometimes it takes a few months before they start to write their next patient or the patient after that. So there's no real set answer. We may have a new prescriber now that becomes one of our big fans that writes a lot of it. It's just -- there's no set answer to that. Sorry.

是的。我認為這取決於他們的患者模式，有些人比其他人看到更多的患者，有些人比其他人更快地採用。一些腎臟科醫生可能會在一名或兩名患者身上嘗試一種產品，並進行自己的臨床試驗，以期看到成功。因此，有時他們需要幾個月的時間才能開始寫下一個或之後的患者。所以沒有真正的固定答案。我們現在可能有一位新的處方者，他成為我們的忠實粉絲之一，寫了很多處方。只是——這個問題沒有固定的答案。對不起。

I think it's just worthwhile pointing out, obviously, that there are -- this is a rare disease. And a lot of these physicians don't have a huge number of solutions necessarily. And so that's obviously why it is important to kind of continue to penetrate the actual prescriber universe as well as obviously continuing to support those prescribers who have already written prescriptions and you have patients on drug. And obviously, we do that by having our hub services and providing a lot of these additional support to the community as well as education.

我認為值得指出的是，顯然，這是一種罕見的疾病。而且很多醫生不一定有大量的解決方案。因此，這顯然就是為什麼繼續深入實際處方者領域以及繼續支持那些已經開出處方並且有正在服用藥物的患者的處方者很重要。顯然，我們通過提供中心服務並向社區和教育提供大量額外支持來做到這一點。

The next question comes from Arthur from H.C. Wainwright.

下一個問題來自 H.C. 的 Arthur。溫賴特。

This is Arthur from H.C. Wainwright. So I guess my first question is for Nefecon in the Japanese market. When could we hear more regarding the development strategy and time line for Nefecon in Japan?

這是來自 H.C. 的 Arthur。溫賴特。所以我想我的第一個問題是關於日本市場的 Nefecon。我們什麼時候可以聽到更多有關 Nefecon 在日本的發展戰略和時間表的信息？

So I don't have an exact time to provide to you. There are quite a lot of ongoing discussions and collaborations with regards to kind of establishing the most effective way to kind of design that kind of program. And so I have to get back to you once I actually -- that's been a little bit better established, but it's certainly being worked on very actively. But obviously, it'll have to kind of be after we hear back from the regulators in terms of their acceptance of the proposed development program, and we have not yet done that. So I'm going to have to come back to you about that when we have more information.

所以我沒有具體的時間可以提供給你。關於建立設計此類程序的最有效方法，正在進行大量討論和合作。因此，一旦我確實——這已經稍微好一點了，但它肯定正在非常積極地進行工作，我就必須回复你。但顯然，這必須是在我們收到監管機構關於接受擬議開發計劃的答復之後，而我們還沒有這樣做。因此，當我們獲得更多信息時，我將不得不回复您。

Sure. No issue. And my second question is, could you give us a little bit update on the enrollment for PBC study? And remind us what's the date that we could expect for the initial update or interim readout.

當然。沒有任何問題。我的第二個問題是，您能給我們介紹一下 PBC 學習招生的最新情況嗎？並提醒我們預計初始更新或臨時讀數的日期是哪一天。

Sure. So in terms of the interim readout, so that's -- that interim readout is a biomarker readout. It's a subset of the patients. This is in the head and neck cancer trial. So a subset of those patients we will have matched biopsies, and we will actually then be able to have a biomarker-related readout, which really looks at the microenvironment of the tumor. And we're doing this, obviously, to really do this as a translational study from what we've observed in the preclinical models that we have, obviously, with a view to seeing a similar effect in the clinic. So that's really something that is still expected to be around midyear, kind of July-ish probably. And so that's still on track, and I think this will be something that we really look forward to. We think it'll be very exciting to see if we can actually kind of show that translational effect, which we believe will have an impact and be very helpful across kind of the different rare disease programs that we're presently running.

當然。因此，就臨時讀數而言，臨時讀數是生物標誌物讀數。這是患者的一部分。這是頭頸癌試驗中的結果。因此，我們將對這些患者的一部分進行匹配的活檢，然後我們實際上將能夠獲得與生物標誌物相關的讀數，從而真正了解腫瘤的微環境。顯然，我們這樣做是為了根據我們在臨床前模型中觀察到的情況，真正將其作為一項轉化研究，顯然是為了在臨床中看到類似的效果。因此，這確實預計會在年中左右發生，可能是在七月左右。所以這仍然在正軌上，我認為這將是我們真正期待的事情。我們認為，如果我們真的能夠展示這種轉化效應，那將是非常令人興奮的，我們相信這將對我們目前正在運行的不同罕見疾病項目產生影響並且非常有幫助。

In terms of PBC, this is obviously a larger study. And at the moment, we're running the Phase IIb portion of that adaptive design. And so we're recruiting patients. And the view is that the target is for the first half of next year to actually then select the dose, which would be the kind of the dose level for the Phase III portion of that trial.

就 PBC 而言，這顯然是一項規模更大的研究。目前，我們正在運行該自適應設計的 IIb 階段部分。所以我們正在招募患者。人們的觀點是，目標是在明年上半年實際選擇劑量，這將是該試驗第三階段部分的劑量水平。

The final question comes from the line of Johan Unnerus from Redeye.

最後一個問題來自 Redeye 的 Johan Unnerus。

It's a follow-up. Of course, unique subscriber is a prerequisite and very important, but the ratio between enrolled patients and unique subscribers seems to be fairly steady, slightly north of 1.5. Should we expect that to pick up going forward?

這是一個後續。當然，獨立訂閱者是先決條件，而且非常重要，但入組患者與獨立訂閱者之間的比率似乎相當穩定，略高於 1.5。我們是否應該預期這種情況會繼續好轉？

Andy, do you want to take that?

安迪，你想接受這個嗎？

I think it's hard to answer that question in the sense that, as I said before, there's going to be -- like any market, there are people that see a lot more patients and treat a lot more patients than some others. So there's value obviously in someone that even writes a few prescriptions as a few patients. But obviously, there's more value in a prescriber that has a larger patient load. So it's -- yes, I would expect it to grow. But at some point -- when the denominator keeps growing with ones at the beginning, it's hard to change that ratio. But we have plenty of prescribers that write for several, several patients.

我認為很難回答這個問題，因為正如我之前所說，就像任何市場一樣，有些人會比其他市場看到更多的患者並治療更多的患者。因此，即使是為幾個病人開一些處方的人顯然也是有價值的。但顯然，患者負荷較大的處方醫生更有價值。所以，是的，我預計它會增長。但在某些時候——當分母一開始就不斷增長時，這個比率就很難改變。但我們有很多處方醫生為好幾個病人開處方。

Yes. You pointed out that's the sort of 80-20 rule applies in this area as well. And do you recognize an element that some of the specialists sort of go ahead with the first patient and then wait for experience -- and clinical real-life experience before moving ahead?

是的。您指出 80-20 規則也適用於該領域。您是否認識到一些專家會先對第一位患者進行治療，然後等待經驗以及臨床現實生活經驗後再繼續治療？

Absolutely. Absolutely. You see that everyone is different as far as their level of adoption, but we do see prescribers, certainly nephrologists that, will try it and wait for results. And this is not something that you see 24 hours later, that the patients substantially different. So that -- those kind of trials -- those individual trials by prescribers sometimes take a few months. So absolutely see that.

絕對地。絕對地。你會看到，每個人的採用程度都不同，但我們確實看到處方者，當然是腎病專家，會嘗試並等待結果。這並不是 24 小時後你會看到的情況，即患者有本質上的不同。因此，處方醫生進行的此類試驗有時需要幾個月的時間。所以絕對看到這一點。

And a few short ones, the COGS is slightly higher in the quarter. Should we expect it to come down a bit? Not that it's a major point, but it's an important point.

還有一些短期的，本季度的 COGS 略高。我們應該預期它會下降一點嗎？不是說這是重點，但這是重點。

Fredrik, do you want to take that?

弗雷德里克，你想要那個嗎？

Yes, I can take that. I think in the quarter -- first quarter of last year, we had extremely low cost of goods sold and also in the remainder of 2022. So I think we are at a normal level now.

是的，我可以接受。我認為在去年第一季度，我們的銷售成本極低，在 2022 年剩餘時間內也是如此。所以我認為我們現在處於正常水平。

Okay. (inaudible) clarification. And what about the breakeven? You alluded to that earlier. I think you mentioned perhaps midyear '23. Is that still feasible?

好的。 （聽不清）澄清。那麼盈虧平衡點又如何呢？你之前提到過這一點。我想你可能提到過23年年中。那還可行嗎？

I mean I think what we've kind of guided to kind of a couple of quarters ago is actually obviously our whole -- we are clearly targeting to become profitable this year. We have not -- actually, we don't want to speak in that -- to a particular quarter or a particular kind of time because it is very dependent on this kind of acceleration and the curve -- what the curve from the revenue perspective actually looks like. And so I think that we will probably -- I think it'd be highly unlikely that we will do that in Q2. And so I think it's -- but it's definitely something that's a core focus for us and that we continue to drive towards. And we certainly think that that's still possible as we sit here today.

我的意思是，我認為我們幾個季度前的指導實際上顯然是我們的整體——我們的目標顯然是今年實現盈利。我們沒有——實際上，我們不想談論特定的季度或特定的時間，因為它非常依賴於這種加速和曲線——從收入角度來看曲線是什麼實際上看起來像。因此，我認為我們可能會——我認為我們不太可能在第二季度做到這一點。所以我認為，但這絕對是我們的核心焦點，也是我們繼續努力的方向。當我們今天坐在這裡時，我們當然認為這仍然是可能的。

Do we expect to breakeven on run rate during '23?

我們預計 23 年運行率會實現盈虧平衡嗎？

Yes.

是的。

There are no more questions from the telco at this time. So I hand the word back to you, Renee.

目前電信公司沒有再提出任何問題。所以我把話交還給你，蕾妮。

Well, thank you very much for listening to our Q1 2023 report, and we look forward to catching up again when we report our Q2 numbers. Thank you.

非常感謝您收聽我們的 2023 年第一季度報告，我們期待在報告第二季度數據時再次跟進。謝謝。