Calliditas Therapeutics AB (CALT) 2022 Q4 法說會逐字稿

Welcome to the Calliditas Therapeutics Q4 report. (Operator Instructions)  Now I will hand the conference over to the speakers CEO, Renee Aguiar-Lucander CFO, Fredrik Johansson, Andrew Udell, President of North America; and Richard Philipson, CMO.

歡迎閱讀 Calliditas Therapeutics 第 4 季度報告。 （操作員說明）現在我將把會議交給演講者 CEO，Renee Aguiar-Lucander 首席財務官，Fredrik Johansson，北美總裁 Andrew Udell；和首席營銷官 Richard Philipson。

Welcome to the Calliditas Therapeutics Q4 report of 2022. I would ask you to turn the page and initially just bring your attention to our disclaimer page, -- this is just related to forward-looking statements, and I refer you to the company's reports and other filings, including those which contain risk factors and other relevant information. We can go to the next page. So thank you for joining us for this fourth quarter report of 2022, which concludes a very successful year for Calliditas in which we commercially launched the first ever approved medication IgA nephropathy in the U.S. There has been great interest from nephrologists for medication, which targets the pursued origin of the disease and which does all the potential of being disease modifying based on early and significant impact on eGFR in patients at risk of rapid disease progression. To further support our top line data, which we presented in late 2020, we published a full overview of the Part A data in October of 2022 in Kidney International, which was met with enthusiasm from physicians who took a special interest in the continued reduction of proteinuria in all patients who have been off drug for 3 months after the 9-month initial treatment and the stabilization of eGFR patients at risk of rapid disease progression. Based on the many interactions with nephrologists at ASN, it became clear that EGFR data as it becomes more and generally more available, this will clearly die their treatment decision as their treatment goal is obviously to preserve kidney function over their patients. We're therefore excited as we approach the completion of the confirmatory portion of our Phase III trial.

歡迎閱讀 Calliditas Therapeutics 2022 年第 4 季度報告。請您翻頁，最初請您注意我們的免責聲明頁面——這僅與前瞻性陳述有關，我建議您參考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。我們可以轉到下一頁。因此，感謝您加入我們的 2022 年第四季度報告，這是 Calliditas 非常成功的一年，我們在美國商業化推出了有史以來第一個批准的 IgA 腎病藥物。腎病學家對藥物產生了極大的興趣，該藥物針對追尋疾病的起源，並根據對處於疾病快速進展風險中的患者的 eGFR 的早期和顯著影響，它具有改變疾病的所有潛力。為了進一步支持我們在 2020 年末發布的頂線數據，我們於 2022 年 10 月在腎臟國際雜誌上發布了 A 部分數據的完整概述，這引起了對持續減少特別感興趣的醫生的熱情初始治療 9 個月後停藥 3 個月的所有患者的蛋白尿和處於疾病快速進展風險中的 eGFR 穩定的患者。基於與 ASN 腎病學家的多次互動，很明顯，隨著 EGFR 數據變得越來越普遍，這顯然會影響他們的治療決策，因為他們的治療目標顯然是保護患者的腎功能。因此，當我們即將完成 III 期試驗的確認部分時，我們感到很興奮。

We can go to the next page. From an overall corporate perspective, we reported total revenues in Q4 of SEK 429 million, it's equivalent to approximately $42.4 million. outage truck payer sales represented NOK 167 million or about $16.1 million. For the year, that took us to total revenues of around SEK 803 million, equivalent to about $79 million, again, out of which Tapio represented SEK 372 million or $36.8 million. We're very proud of this result, especially in a market that actually was defined by strong macro headwinds, including volatile capital markets, high inflation, increasing interest rates and unfortunately an ongoing war in Europe. Against this backdrop, we have been able to over the last 18 months or so, raised over NOK 1.2 billion of non-dilutive capital, ensuring a successful launch of a first-in-class product into the U.S. market. I do truly believe that we have a lot to be proud about for 2022. We did decide during the year to also expand our U.S.-based sales team, and we have recently also brought them in-house into Calliditas. And we've clearly seen that this expansion has already had an impact towards the end of the quarter. We obviously continue to educate nephrologists as to obviously in the U.S. market today. We have an oral product, which can be added to physicians' choice of optimized applicate and which is based on a well-characterized active ingredient with a differentiated approach of targeted treatment of the origin of the disease with a goal of specific down-regulating IgA . We believe that this has the potential to be disease-modifying based on our early data, and we do look forward to being able to share longer-term eGFR data from our Part B readout.

我們可以轉到下一頁。從整體公司的角度來看，我們報告的第四季度總收入為 4.29 億瑞典克朗，相當於約 4240 萬美元。停電卡車付款人的銷售額為 1.67 億挪威克朗或約 1610 萬美元。這一年，我們的總收入約為 8.03 億瑞典克朗，相當於約 7900 萬美元，其中 Tapio 代表 3.72 億瑞典克朗或 3680 萬美元。我們對這一結果感到非常自豪，尤其是在一個實際上由強大的宏觀逆風定義的市場，包括動蕩的資本市場、高通脹、利率上升以及不幸的是歐洲正在進行的戰爭。在此背景下，我們在過去 18 個月左右的時間裡籌集了超過 12 億挪威克朗的非稀釋性資本，確保成功向美國市場推出一流的產品。我確實相信，我們在 2022 年有很多值得驕傲的事情。我們確實在這一年決定擴大我們在美國的銷售團隊，最近我們還把他們帶到了 Calliditas 內部。我們清楚地看到，這種擴張已經對本季度末產生了影響。我們顯然繼續教育腎病學家，以了解今天在美國市場的情況。我們有一種口服產品，可以添加到醫生的優化應用選擇中，它基於一種充分錶徵的活性成分，採用差異化的方法針對疾病的起源進行靶向治療，目標是特異性下調 IgA .我們相信，根據我們的早期數據，這有可能改變疾病，我們確實期待能夠從我們的 B 部分讀數中共享長期 eGFR 數據。

We go to the next page, please. So in December, we also reported that we had out-licensed Nefecon to Biatris for the Japanese market. This resulted in a $20 million upfront payment with additional $80 million of development, regulatory and commercial milestones. We're very excited about being able to further expand the global franchise of Nefecon and look forward to work with our new partners. In November, our other partners, Ivers Medicines had their China NPA filing accepted. And in December, also the regulatory body recommended a priority review from Fin China, and we look forward to having some results from that regulatory review towards the second half of this year. And as you may know, there are a lot of patients -- biosuperime patients in China, the Chinese market. This is a very, very significant unmet medical need, and we look forward to working with our partners, Everest Medicines to hopefully be able to address that need once the regulatory view has been completed. In terms of our pipeline, we reported in the previous quarter that there has been a slowdown in terms of site activation. I'm happy to report that those have kind of picked up and ecruitment rates in our head and neck cancer trial is significantly improved, and we are presently targeting the delivery of the biomarker data as we previously have guided on in this year. And we're hoping to be able to do that sometime around the middle of the year, obviously, depending on final arrangements for that readout. The PBC trial does remain challenging, and we've implemented a range of activities in Q4 and Q1, and we will continue to work hard at trying to address somewhat of the issues around kind of the somewhat slower rerecruitment rate than what we would like to see. In terms of further kind of financial highlights, obviously, we did in this quarter reported positive operating profit in Q4 of about SEK 32.5 million and obviously also a positive cash flow from operations. We -- that leaves us with a very strong financial position for the end of the year, with cash amounting to over 1 billion [00:06:53] -- almost 1.250 billion in SEK and around $119 million. We believe on that basis, we're funded to profitability based on continued delivery of sales from Trapelo and the Nefecon franchise globally.

請轉到下一頁。所以在 12 月，我們還報告說我們已經將 Nefecon 的日本市場授權給了 Biatris。這導致了 2000 萬美元的預付款以及額外的 8000 萬美元的開發、監管和商業里程碑。我們很高興能夠進一步擴大 Nefecon 的全球特許經營權，並期待與我們的新合作夥伴合作。 11 月，我們的其他合作夥伴 Ivers Medicines 的中國 NPA 申請被接受。去年 12 月，監管機構還建議金融中國進行優先審查，我們期待在今年下半年從該監管審查中獲得一些結果。你可能知道，在中國，中國市場，有很多患者——biosuperime 患者。這是一個非常、非常重要的未滿足醫療需求，我們期待與我們的合作夥伴 Everest Medicines 合作，希望在監管意見完成後能夠解決這一需求。就我們的管道而言，我們在上一季度報告說，網站激活速度有所放緩。我很高興地報告說，我們的頭頸癌試驗的招募率有所提高，我們目前的目標是提供生物標誌物數據，正如我們今年之前所指導的那樣。我們希望能夠在今年年中左右的某個時候做到這一點，顯然，這取決於該讀數的最終安排。 PBC 試驗確實仍然具有挑戰性，我們在第四季度和第一季度實施了一系列活動，我們將繼續努力解決一些問題，這些問題與我們希望的招聘速度稍慢有關看。就進一步的財務亮點而言，顯然，我們在本季度確實報告了第四季度的正營業利潤，約為 3250 萬瑞典克朗，顯然也有正的運營現金流。我們 - 這使我們在年底的財務狀況非常強勁，現金總額超過 10 億 [00:06:53] - 接近 12.5 億瑞典克朗和約 1.19 億美元。我們相信，在此基礎上，我們將根據 Trapelo 和 Nefecon 全球特許經營權的持續交付來獲得盈利。

In terms of some post-period events, if we go to the next slide, please. Thank you. So in February, the MHRA announced that they had granted a conditional market authorization of Campego for the United Kingdom. And that CMA is in process of being transferred to our European partner, STADA, who obviously holds the commercial rights for that area. And also, obviously, based on the data, the completion of the last visit by the last subject in our Phase III trial NefIgArd. We now have a clearer view of when we will be able to share with you the top line data of our Part B. And so we are presently targeting somewhere around the middle of March in order to be able to provide that information. This readout will obviously provide long-term eGFR data, complementing really the eGFR data that we saw at 9 months, which was both statistically significant and clinically meaningful. For the year of 2023, we believe that on the basis of the -- what we're seeing in the market and some of the other points that Andy will be covering with you. We believe that we will have a U.S.-based revenues from tarpeyo, somewhere between $120 million to $150 million. And we believe that strong top line data from Part B could provide momentum to this uptake as the long-term eGFR data certainly will provide further insight into the potential disease-modifying activity of Tarpeyo. So with that, if we go to the next page, I will hand over to Richard Philipson, our Chief Medical Officer, who will take you through a little bit more detail around the Kidney International publication, which I mentioned in the beginning and which obviously has generated a lot of interest broadly in the nephrology area.

關於一些後期事件，請轉到下一張幻燈片。謝謝。因此，在 2 月，MHRA 宣布他們已授予 Campego 在英國的有條件市場授權。該 CMA 正在轉讓給我們的歐洲合作夥伴 STADA，後者顯然擁有該地區的商業權利。而且，很明顯，根據數據，在我們的 III 期試驗 NefIgArd 中，最後一位受試者完成了最後一次訪問。現在，我們對何時能夠與您分享 B 部分的頂線數據有了更清晰的認識。因此，我們目前的目標是在 3 月中旬左右的某個時間，以便能夠提供該信息。該讀數顯然將提供長期 eGFR 數據，真正補充了我們在 9 個月時看到的 eGFR 數據，該數據具有統計學意義和臨床意義。對於 2023 年，我們相信，基於我們在市場上看到的情況以及 Andy 將與您討論的其他一些要點。我們相信我們將從 tarpeyo 獲得美國的收入，大約在 1.2 億美元到 1.5 億美元之間。我們相信，來自 B 部分的強勁頂線數據可以為這種吸收提供動力，因為長期 eGFR 數據肯定會進一步深入了解 Tarpeyo 的潛在疾病緩解活性。因此，如果我們轉到下一頁，我將交給我們的首席醫療官理查德·菲利普森，他將帶您詳細了解腎臟國際出版物，我在開頭提到過，顯然在腎髒病學領域引起了廣泛的興趣。

Thank you very much, Renee. So if we move to the next slide. So I share Renee's delight that the results of Part A of the NefIgArd Phase III clinical trial were published online in Kidney International on the 9th of October of last year and subsequently in this year's issued 2 of the print version of the journal. I'd like to summarize the results presented in the publication. So moving to the next slide. As a very brief recap, Part of the NefIgArd trial enrolled 201 patients with IgA nephropathy and randomized them in a 1:1 ratio to receive Nefecon 16 milligrams once daily or placebo for 9 months with 3 months of post-treatment observation of treatment for patients continued into part B of the study, which comprised a further 12 months of treatment. All patients were on optimized RAS blockade with median baseline proteinuria and eGFR, reflecting a population of patients at high risk of kidney disease progression. After 9 months of treatment, those a highly statistically significant 27% reduction in proteinuria measured by UPCR in patients receiving Metacom compared to placebo with stabilization of eGFR and a 3.87 ml per minute treatment benefit compared to placebo. When we look at the 1-year eGFR slope improvement, which compares the eGFR slope in patients treated with Nethacon versus those treated with placebo, we see an improvement of 3.37 ml per minute, representing a preservation of eGFR of approximately 70% of the maximum possible effect. This effect is consistent as it is in line with what we saw in the Phase II study. And importantly, it compares favorably with other treatments studied in IgA nephropathy. For example, treatment with the SGLT2 inhibit dapagliflozin in patients with IgA nephropathy results in a calculated preservation of eGFR after 12 months of only 26% of the maximum possible effect. The safety of the treatment was in line with what was expected for a targeted release formulation of budesonide. And importantly, there were no severe infections requiring hospitalization. So in summary, overall treatment with Nefecon resulted in clinically important improvements compared with optimized supportive care alone.

非常感謝你，芮妮。那麼，如果我們轉到下一張幻燈片。 NefIgArd III 期臨床試驗 A 部分的結果於去年 10 月 9 日在線發表在 Kidney International 上，隨後發表在今年出版的第 2 期印刷版雜誌上，我和 Renee 一樣感到高興。我想總結一下出版物中提出的結果。轉到下一張幻燈片。作為一個非常簡短的回顧，NefIgArd 試驗的一部分招募了 201 名 IgA 腎病患者，並以 1:1 的比例將他們隨機分配接受 Nefecon 16 毫克，每天一次或安慰劑，持續 9 個月，並對患者的治療進行 3 個月的治療後觀察繼續進入研究的 B 部分，其中包括另外 12 個月的治療。所有患者都接受了優化的 RAS 阻斷，中位基線蛋白尿和 eGFR，反映了腎病進展高風險的患者群體。經過 9 個月的治療後，與安慰劑相比，接受 Metacom 的患者通過 UPCR 測量的蛋白尿減少了 27%，具有高度統計學意義，eGFR 穩定，與安慰劑相比每分鐘治療獲益 3.87 毫升。當我們查看 1 年 eGFR 斜率改善時，將接受奈沙康治療的患者的 eGFR 斜率與接受安慰劑治療的患者進行比較，我們看到每分鐘改善 3.37 毫升，代表 eGFR 保持約最大值的 70%可能的效果。這種效果是一致的，因為它與我們在 II 期研究中看到的一致。重要的是，它與 IgA 腎病研究中的其他治療方法相比具有優勢。例如，在 IgA 腎病患者中使用 SGLT2 抑製劑達格列淨進行治療後，計算得出的 eGFR 保留值在 12 個月後僅為最大可能效果的 26%。治療的安全性與布地奈德靶向釋放製劑的預期一致。重要的是，沒有需要住院治療的嚴重感染。因此，總而言之，與單獨優化支持治療相比，Nefecon 的整體治療在臨床上取得了重要的改善。

So moving to the next slide. An important observation relating to the effect of methaqualone proteinuria in the Part A study population is that the effects were not immediate with no discernible effect following 3 months of treatment, rather the effects become apparent at 6 months with a continued and cumulative improvement at 9 months. A particular note, Proteinuria continued to improve even after treatment had been discontinued in 9 months. So at 12 months after 3 months of treatment, there was a 52% reduction in Proteinuria versus baseline. Moving to the next slide. When we look at improvements in proteinuria associated with treatment with Nefecon, we see an interesting observation in patients with higher levels of baseline proteinuria. Specifically, we see an earlier separation of the proteinuria curves, so that after only 3 months, there was a 14% reduction in proteinuria in methaqualone treated versus placebo-treated patients. It's nevertheless important to emphasize that all patients in the methaqualone treated group showed improvements in proteinuria, irrespective baseline proteinuria levels. Moving to the next slide. This earlier improvement in proteinuria translated to early and divergent eGFR curves in these patients. EGFR declined by over 10 ml per minute over the 12-month period in the placebo group compared to a reduction of only 1.1 ml per minute in the Nefecon group, a difference of nearly 9 ml per minute at 12 months. Again, it's worth noting that EGFR remains stable during the 3-month follow-up period when patients have discontinued treatment with no evidence of deterioration in eGFR during this 3-month follow-up period. And moving to the next slide. So in summary, for the Part A data, Nefecon met primary and key secondary endpoints in the NefIgArd Part. The effect of methaqualone on proteinuria, gradual and cumulative with continued improvement after discontinuation of treatment. And in patients with higher baseline proteinuria, an earlier beneficial effect on proteinuria is observed, which translates to clearly divergent eGFR trajectories with stabilization of eGFR in Nefecon-treated patients. So that concludes my part of the presentation.

轉到下一張幻燈片。與 A 部分研究人群中甲喹酮蛋白尿的影響相關的一項重要觀察結果是，效果不是立竿見影的，在治療 3 個月後沒有明顯效果，而是效果在 6 個月時變得明顯，並在 9 個月時持續和累積改善.特別要注意的是，即使在 9 個月內停止治療後，蛋白尿仍在繼續改善。因此，在治療 3 個月後的 12 個月，與基線相比，蛋白尿減少了 52%。移動到下一張幻燈片。當我們觀察與 Nefecon 治療相關的蛋白尿改善時，我們在基線蛋白尿水平較高的患者中看到了一個有趣的觀察結果。具體來說，我們看到蛋白尿曲線的分離較早，因此僅 3 個月後，與安慰劑治療的患者相比，接受甲喹酮治療的患者的蛋白尿減少了 14%。儘管如此，必須強調的是，無論基線蛋白尿水平如何，甲喹酮治療組中的所有患者均顯示蛋白尿有所改善。移動到下一張幻燈片。這種蛋白尿的早期改善轉化為這些患者早期和不同的 eGFR 曲線。在 12 個月期間，安慰劑組的 EGFR 每分鐘下降超過 10 毫升，而 Nefecon 組每分鐘僅下降 1.1 毫升，12 個月時每分鐘下降近 9 毫升。同樣，值得注意的是，當患者停止治療且在這 3 個月的隨訪期間沒有 eGFR 惡化的證據時，EGFR 在 3 個月的隨訪期間保持穩定。並移動到下一張幻燈片。因此，總而言之，對於 A 部分的數據，Nefecon 滿足了 NefIgArd 部分的主要和關鍵次要終點。甲喹酮對蛋白尿的影響在停止治療後逐漸改善並持續改善。在基線蛋白尿較高的患者中，觀察到對蛋白尿的早期有益作用，這轉化為明顯不同的 eGFR 軌跡，在 Nefecon 治療的患者中 eGFR 穩定。我的演示部分到此結束。

 Thanks, Richard. Slide 15, please. The fourth quarter was another strong quarter to finish the first calendar year of the commercialization of (inaudible) Quarterly net sales of more than $16 million brings us to $36.8 million in net sales after the first 11 months of promotion. We had 310 new patient enrollments in the quarter, which has the 2022 total more than 1,000 enrollments, which were written by over 640 unique nephrologists. In addition, we continue to see the average enrollments per prescriber growing, and we anticipate this rate will continue to grow as many of the nephrologists now have patients on therapy for several months and experiencing positive results as was demonstrated in our clinical trials that Richard just reviewed with you. As it relates to market access, as mentioned last quarter, we really reached our target of over 90% of U.S. lives having coverage for a payout in the middle of the year, which we are very proud of. The payer mix has reached a steady state without much change from the last quarter. Approximately 3/4 of our patients had either private commercial insurance or cash-paying customers, with the remainder of our business coming from government insured patients. Tarpeyo touchpoints and the high quality of our patient service programs are extremely important to us and continue to exceed industry standards. Nevertheless, we continue to assess our program to identify areas of improvement and to determine if additional resources are needed to maintain this high level of service during a period when our patient population continues to grow. Our targeted reach and promotional programs remain effective, as demonstrated by the awareness of Tarpeyo growing to over 90% of nephrologists and market research surveys conducted prior to the end of 2022. Most important and rewarding to us during the fourth quarter and early this year are the increasing number of success stories that are being reported as more and more patients have taken Tarpeyo for extended periods of time.

“謝謝，理查德。請放幻燈片 15。第四季度是另一個強勁的季度，完成了（聽不清）商業化的第一個日曆年，季度淨銷售額超過 1600 萬美元，在前 11 個月的促銷活動後，我們的淨銷售額達到了 3680 萬美元。本季度我們有 310 名新患者登記，到 2022 年總登記人數超過 1,000 人，由 640 多位獨特的腎病學家撰寫。此外，我們繼續看到每位開處方者的平均註冊人數在增長，我們預計這一比率將繼續增長，因為許多腎病學家現在有患者接受了幾個月的治療並取得了積極的結果，正如理查德剛剛在我們的臨床試驗中所證明的那樣和你一起回顧。正如上個季度所提到的，與市場准入有關，我們確實實現了超過 90% 的美國人在年中獲得支付保險的目標，我們為此感到非常自豪。付款人組合已達到穩定狀態，與上一季度相比沒有太大變化。我們大約 3/4 的患者擁有私人商業保險或現金支付客戶，其餘業務來自政府保險患者。 Tarpeyo 接觸點和我們患者服務計劃的高質量對我們來說極其重要，並且會繼續超越行業標準。儘管如此，我們將繼續評估我們的計劃，以確定需要改進的領域，並確定在我們的患者人數持續增長期間是否需要額外的資源來維持這種高水平的服務。我們的目標覆蓋面和促銷計劃仍然有效，Tarpeyo 的意識增長到 90% 以上的腎病學家和在 2022 年底之前進行的市場研究調查就證明了這一點。在第四季度和今年年初對我們來說最重要和有益的是隨著越來越多的患者長期服用 Tarpeyo，越來越多的成功案例被報導。

Next slide, please.. 2023 promises to be another exciting year of growth for Tarpeyo and our commercial organization. While we felt the initial positive impact of the expansion of our field during the fourth quarter, we look forward to the full impact from the impressive commercial team that we've assembled. -- Tarpeyo demonstrated a clear reduction in proteinuria and the early impacts on EGFR demonstrated in(inaudible)are unprecedented and extremely important. In addition to the increasing positive patient experiences we, along with the nephrology community anxiously await the results of Part B to gain increasing information on the lasting impact of Tarpeyo on this chronic kidney disease. We anticipate this information in the first half of 2023 and look forward to sharing the results with nephrologists and the iGame community. Lastly, we are enthusiastic about the progress and availability of Torpeyo in the U.S., Compego in Europe and Nefecon as it grows around the globe. IgA nephropathy is a rare orphan disease and the global patient KOL experience and education will be important in the continued growth and success of the brand and our company. And with that, I'm going to turn it over to our CFO, Fredrik Johansson.

請下一張幻燈片.. 2023 年有望成為 Tarpeyo 和我們的商業組織又一個激動人心的增長年。雖然我們在第四季度感受到了我們領域擴張的初步積極影響，但我們期待著我們組建的令人印象深刻的商業團隊的全面影響。 -- Tarpeyo 證明蛋白尿明顯減少，並且在（聽不清）中證明的對 EGFR 的早期影響是前所未有的和極其重要的。除了越來越積極的患者體驗，我們與腎髒病學界一起焦急地等待 B 部分的結果，以獲取有關 Tarpeyo 對這種慢性腎臟疾病的持久影響的更多信息。我們預計將在 2023 年上半年獲得這些信息，並期待與腎病學家和 iGame 社區分享結果。最後，我們對 Torpeyo 在美國、歐洲的 Compego 和 Nefecon 在全球範圍內的發展和可用性充滿熱情。 IgA 腎病是一種罕見的孤兒病，全球患者 KOL 的經驗和教育對於品牌和我們公司的持續發展和成功至關重要。有了這個，我將把它交給我們的首席財務官 Fredrik Johansson。

Thank you very much, Andy, and good afternoon and good morning, everyone. I will first present to you the financial overview for the fourth quarter of 2022 and thereof to present the full year numbers for 2022. As always, all numbers presented to you are in million SEK, unless otherwise stated. To start with, we are proud to report SEK429 million in net revenues for the quarter. For the same period last year, we reported net revenues of $31.2 million. In the fourth quarter of the pay of commercialization Tarpeyo product sales for the quarter amounted to $167.3 million or $16.1 million, a growth of SEK 36 million, 36% compared to the third quarter. In addition, we also recorded SEK 26.2 million for the period in revenues related to transaction with our partners, especially from the USD 20 million signing fee from the Viatris out license deal, but also from a $5 million regulatory milestone from Everest relating to China. Our total operating expense for the fourth quarter amounted to SEK 388.7 million compared to SEK 253.3 million for the same period last year. Compared to the third quarter this year, our OpEx did increase by around SEK 96 million from Q3. And this increase is mainly due to certain costs related to the marketing activities were concentrated into Q4 instead of spread out of both Q3 and Q4. Certain onetime costs and also a cost increase in the quarter from our expansion of our sales force in Q4. I'm very pleased to report that our increased revenues for the quarter led to an operating profit of SEK 22.5 million for the fourth quarter compared to an operating loss of SEK 280.5 million for the fourth quarter 2021. In the fourth quarter, we also had a positive cash flow from operating activities of SEK 230 million compared to a negative cash flow used in operating activities of SEK 161.3 million for the same previous year. And the positive cash flow was mainly achieved through -- we received payments in the quarter from our licensing activities and from the increase of the Tarpeyo sales.

非常感謝，安迪，大家下午好，早上好。我將首先向您介紹 2022 年第四季度的財務概覽及其 2022 年的全年數字。與往常一樣，除非另有說明，否則向您提供的所有數字均以百萬瑞典克朗為單位。首先，我們很自豪地報告本季度的淨收入為 4.29 億瑞典克朗。去年同期，我們報告的淨收入為 3120 萬美元。第四季度商業化 Tarpeyo 產品銷售額為 1.673 億美元或 1610 萬美元，比第三季度增長 3600 萬瑞典克朗。此外，我們在此期間還記錄了與合作夥伴交易相關的收入 2620 萬瑞典克朗，特別是來自 Viatris 許可交易的 2000 萬美元簽約費，以及來自 Everest 與中國相關的 500 萬美元監管里程碑。我們第四季度的總運營費用為 3.887 億瑞典克朗，而去年同期為 2.533 億瑞典克朗。與今年第三季度相比，我們的運營支出確實比第三季度增加了約 9600 萬瑞典克朗。而這一增長主要是由於與營銷活動相關的某些成本集中在第四季度，而不是分散到第三季度和第四季度。某些一次性成本以及我們在第四季度擴大銷售人員後本季度的成本增加。我很高興地報告，我們本季度收入的增加導致第四季度的營業利潤為 2250 萬瑞典克朗，而 2021 年第四季度的營業虧損為 2.805 億瑞典克朗。第四季度，我們還經營活動產生的正現金流為 2.3 億瑞典克朗，而去年同期經營活動產生的現金流為負，為 1.613 億瑞典克朗。正現金流主要是通過——我們在本季度從我們的許可活動和 Tarpeyo 銷售額的增加中收到付款來實現的。

In the fourth quarter, we also made a last drawdown of $25 million from the Krios loan facility, which is now fully utilized, bringing our cash flow from financing activities in the fourth quarter to SEK 282.6 million. This leaves us with a net increase in cash in the quarter of SEK 511.2 million and a very healthy cash position at the end of the quarter of SEK 1.249 billion. And we take the next slide -- just a quick summary of the financial key takeaways from the full financial year of 2022. For the full year of 2022, we are very happy to report SEK 82.9 million in net revenues for the period. This is a growth of 250% for the year compared to 2021, where we reported revenues of SEK 229.3 million. Tarpeyo product sales for the year amounted to SEK 372.2 million or $36.8 million revenues related to outlying transactions and royalties were SEK 427.4 million compared to reported revenues from our placing transaction for the full year of 2021 of SEK 229.3 million. Our total operating expenses for 2022 amounted to SEK 1.296 billion compared to SEK 753.8 million for the full year of 2021. Out of the total operating expenses for the full year of 2022, marketing and sale expenses increased by SEK 335.6 million to SEK 515.2 million compared to SEK 19.6 million for the full year of 2021. The increase in marketing and selling expenses originated from the commercialization of Tarpeyo the U.S., including our sales force compared to 2021 when we were in preparation mode only prior to the start of the commercialization. The cost for research and development for 2022 increased by SEK 57.2 million to SEK 44.7 million compared with SEK 37.5 million for the previous year. The increase in R&D expenses originates primarily from the ongoing operations for the CETX trials. The cost for administration for the full year of 2022 increased by SEK 48.9 million to SEK 259.5 million compared to SEK 210.6 million for 2021. The increase in cost between the years was primarily related to general cost increase for administration due to organizational growth, increased cost for compliance and increased complexity being a company in the commercial stage. Our operating loss improved by SEK 102.5 million and amounted to SEK 421.9 million for the full year of 2022 compared to an operating loss of SEK 524.5 million for 2021.

在第四季度，我們還從 Krios 貸款設施中提取了 2500 萬美元，該貸款現已完全使用，使我們在第四季度融資活動產生的現金流量達到 2.826 億瑞典克朗。這使我們本季度現金淨增加 5.112 億瑞典克朗，本季度末現金狀況非常健康，為 12.49 億瑞典克朗。我們看下一張幻燈片——快速總結 2022 年整個財政年度的財務要點。對於 2022 年全年，我們很高興報告該期間的淨收入為 8290 萬瑞典克朗。與 2021 年相比，這一年增長了 250%，我們報告的收入為 2.293 億瑞典克朗。今年 Tarpeyo 產品銷售額為 3.722 億瑞典克朗或 3680 萬美元，與外圍交易和特許權使用費相關的收入為 4.274 億瑞典克朗，而我們 2021 年全年配售交易的報告收入為 2.293 億瑞典克朗。我們 2022 年的總運營費用為 12.96 億瑞典克朗，而 2021 年全年為 7.538 億瑞典克朗。在 2022 年全年的總運營費用中，營銷和銷售費用比 2022 年增加了 3.356 億瑞典克朗，達到 5.152 億瑞典克朗到 2021 年全年將增加到 1960 萬瑞典克朗。營銷和銷售費用的增加源於美國 Tarpeyo 的商業化，包括我們的銷售人員與 2021 年相比，當時我們僅在商業化開始之前處於準備模式。與上一年的 3750 萬瑞典克朗相比，2022 年的研發成本增加了 5720 萬瑞典克朗，達到 4470 萬瑞典克朗。研發費用的增加主要來自 CETX 試驗的持續運營。與 2021 年的 2.106 億瑞典克朗相比，2022 年全年的行政費用增加了 4890 萬瑞典克朗，達到 2.595 億瑞典克朗。年度之間的費用增加主要與由於組織增長導致的一般行政費用增加有關，成本增加作為一家處於商業階段的公司，合規性和復雜性增加。我們的營業虧損減少了 1.025 億瑞典克朗，2022 年全年達到 4.219 億瑞典克朗，而 2021 年的營業虧損為 5.245 億瑞典克朗。

The cash flow used in operating activities for the full year of 2022 amounted to SEK 311.4 million compared to SEK 461.6 million used for 2021. Our cash from financing activities were SEK 576 million for the full year of 2022 compared to SEK 435.2 million for 2021. This leaves us with a net increase in cash for 2022 of SEK 259.5 million compared to a net decrease in cash for 2021 of SEK 50.8 million. And finally, and again, we are very happy with the cash position of SEK 1.249 billion at the end of the year. That was all for me. And now back to you, Renee.

2022 年全年用於經營活動的現金流為 3.114 億瑞典克朗，而 2021 年為 4.616 億瑞典克朗。2022 年全年來自融資活動的現金為 5.76 億瑞典克朗，而 2021 年為 4.352 億瑞典克朗。這使我們 2022 年的現金淨增加 2.595 億瑞典克朗，而 2021 年的現金淨減少 5080 萬瑞典克朗。最後，我們再次對年底的 12.49 億瑞典克朗現金頭寸感到非常滿意。這就是我的全部。現在回到你身邊，蕾妮。

Thank you. So as I mentioned upfront, 2022 was a very successful year for Calliditas . We saw overall revenue growth in 2022 of 250%, reaching over SEK 800 million, which shows obviously strong revenue from the year both from product sales and partner income. In terms of the Tarpeyo revenues, it came in line with our guidance, which we had provided of around $37 million for the year and $16.1 million for the quarter. There is clear excitement in the nephrology area around our ability to being able to share our Part A data was very clear from interactions at the ASN -- and I think it is considered very interesting in terms of the specifics of the data, which Richard covered previously, which seems to stand out from other product -- potential product candidates. In terms of the sales force, as we mentioned, we did expand this towards the end of the year. And so we are seeing continued penetration into the prescriber base and look forward to having continued growth in uptake in 2023. In terms of commercial partnerships, obviously, we mentioned in Japan, we would be outlicensed epacontoviatrist in IgA nephropathy, obviously, an additional kind of nondilutive cash rate of $20 million, but also, obviously, very importantly, we look forward to work with our new partner and expand the Nefecon global franchise.

謝謝。因此，正如我前面提到的，2022 年對 Calliditas 來說是非常成功的一年。我們看到 2022 年的整體收入增長了 250%，達到超過 8 億瑞典克朗，這表明今年的產品銷售收入和合作夥伴收入都明顯強勁。就 Tarpeyo 的收入而言，它符合我們的指導意見，我們提供的年度收入約為 3700 萬美元，本季度收入約為 1610 萬美元。在 ASN 的互動中，我們能夠分享我們的 A 部分數據的能力在腎髒病學領域引起了明顯的興奮——我認為就數據的細節而言，這被認為是非常有趣的，理查德涵蓋了這一點以前，這似乎從其他產品中脫穎而出——潛在的候選產品。正如我們所提到的，就銷售人員而言，我們確實在年底前進行了擴展。因此，我們看到繼續滲透到處方者基礎中，並期待在 2023 年繼續增長。在商業合作夥伴關係方面，顯然，我們在日本提到，我們將在 IgA 腎病方面獲得許可的 epacontoviatrist，顯然，另一種類型2000 萬美元的非稀釋現金利率，而且顯然非常重要的是，我們期待與我們的新合作夥伴合作並擴大 Nefecon 的全球特許經營權。

In China, as I mentioned, the NDA was accepted and towards the end of last year, and we're looking forward to the regulatory review process and the ultimate decision, which we expect to happen towards the second half of this year. In terms of guidance, obviously, we mentioned that based on these patients, we are seeing really kind of the beginning of patient success stories, peer-to-peer recommendations in the market, that kind of momentum in combination with streamlined market access, the published data that came in towards the end of last year. So we're expecting net sales of our Tarpeyo in the U.S. of between $120 million to $150 million. And with that, that concludes the presentation, and we're happy to take any kind of questions.

正如我所提到的，在中國，NDA 已於去年年底被接受，我們期待著監管審查程序和最終決定，我們預計這將在今年下半年發生。在指導方面，顯然，我們提到，基於這些患者，我們確實看到了患者成功故事的開始，市場上的點對點推薦，這種勢頭與簡化的市場准入相結合，公佈了去年年底的數據。因此，我們預計 Tarpeyo 在美國的淨銷售額在 1.2 億美元至 1.5 億美元之間。至此，演示結束，我們很樂意回答任何問題。

(Operator Instructions) The next question comes from Maurice Raycroft from Jefferies.

（操作員說明）下一個問題來自 Jefferies 的 Maurice Raycroft。

This is Farzin on for Maury. You are projecting a strong $120 million to $150 million. So can you walk us through the assumptions that went into it like potential treatment duration beyond 9 months PSS use sales and potential competition to from Travere getting approved?

這是莫里的 Farzin。你預計會有 1.2 億到 1.5 億美元的強勁增長。那麼，您能否向我們介紹其中的假設，例如超過 9 個月的潛在治療持續時間？PSS 使用銷售和潛在競爭，以便 Travere 獲得批准？

So I think that, obviously, there are multitude of variety variety of kind of inputs into that estimate. But I think that, obviously, it is based on, as I kind of briefly mentioned, we are now having patients on drug for a longer period of time. We're hearing a lot more about kind of patient successes, physician successes, there's a more -- there's a buzz in terms of peer to peer recommendations and obviously, also the data that fairly recently got get into the market from our kind of publication. So I think that there is -- and obviously, we are expecting additional kind of data this year, which we also believe can impact the momentum of the uptake. Very specifically in terms of exactly when these kind of -- when the momentum really picks up and how it goes, it is difficult to to judge. But I think in terms of any other kind of potential approval, we don't really think that's going to have any real impact on our kind of projections for 2023.

所以我認為，顯然，該估計中有多種多樣的輸入。但我認為，很明顯，正如我簡要提到的那樣，它是基於我們現在讓患者服用藥物的時間更長。我們聽到了更多關於患者成功、醫生成功的信息，還有更多——在同行推薦方面有一個嗡嗡聲，顯然，最近從我們的出版物中進入市場的數據也很明顯.所以我認為 - 顯然，我們預計今年會有更多類型的數據，我們也相信這些數據會影響吸收的勢頭。非常具體地講，這種勢頭何時真正回升以及如何發展，很難判斷。但我認為就任何其他類型的潛在批准而言，我們真的認為這不會對我們對 2023 年的預測產生任何實際影響。

And then the other question is on the expectations for the eGFR data from the Part B like and how much and how you think it will impact the label from a disease modifying caim perspective?

然後另一個問題是對 B 部分的 eGFR 數據的期望，以及從疾病改變 caim 的角度來看，您認為它將對標籤產生多大影響以及如何影響？

Yes. Well, obviously, that's going to really be judged in conversations with the FDA and EMA. And so I think that will truly just depend on kind of the strength of the data that we see coming out of that trial.

是的。好吧，很明顯，這將在與 FDA 和 EMA 的對話中得到真正的判斷。因此，我認為這將真正取決於我們從該試驗中看到的數據的強度。

The next question comes from Annabel Samimy from Stifel.

下一個問題來自 Stifel 的 Annabel Samimy。

Congratulations on the progress. So just in terms of the success stories that you're hearing and some of the anecdotals, have you started seeing patients staying on drug for longer than 9 months, I mean the drug has been out for, I guess, about a year now. So I think you can have some metrics around that. So are you seeing them stay on drug beyond 9 months? Are there restrictions around patients getting treated if they're responding well and just a little bit of color around that. And then when you think about the EGFR data, if it's positive, -- do you have any additional initiatives for new educational efforts around that to change the label and for work with payers and potentially improving terms or ease of onboarding or facility if that data actually comes out positive? Any kind of work that you're doing there to streamline the process?

祝賀你的進步。因此，就您聽到的成功故事和一些軼事而言，您是否開始看到患者服用藥物超過 9 個月，我的意思是這種藥物已經停用大約一年了。所以我認為你可以有一些衡量標準。那麼你看到他們吸毒超過 9 個月了嗎？如果患者反應良好並且周圍有一點顏色，那麼他們接受治療是否有限制。然後當你考慮 EGFR 數據時，如果它是積極的，你是否有任何額外的舉措來圍繞它進行新的教育工作以改變標籤並與付款人合作並可能改善條款或簡化入職或設施，如果該數據實際結果呈陽性？你在那裡做了什麼工作來簡化流程？

Great. Andrew, do you want to take the first part?

偉大的。安德魯，你想參加第一部分嗎？

Yes, sure. So I'll comment on the duration of therapy. You're absolutely right. We are now seeing patients that have been on therapy greater than 9 months, while it's obviously the first patients that are on product. But the good news is what we're seeing is it really seems to be determined by the physician. -- right? This is a heterogeneous progressive disease. And as we've always said, we want these decisions to be made by the nephrologists, the treating physician. And so we are seeing that. We have definitely a good portion of patients that are on for more than 9 months and some that stop at 9 months on treatment. I think this is going to be based on patient to patient. And like you said, the market access, it hasn't been a barrier to this. And so these patients are able to continue as long as they qualify, and they're still taking their medication there.

是的，當然。所以我會評論治療的持續時間。你是絕對正確的。我們現在看到接受治療超過 9 個月的患者，而這顯然是第一批使用產品的患者。但好消息是我們所看到的是它似乎真的是由醫生決定的。 - 正確的？這是一種異質性進行性疾病。正如我們一直所說的，我們希望這些決定由腎病學家、主治醫師做出。所以我們看到了。我們肯定有很大一部分患者接受了 9 個月以上的治療，有些患者在治療 9 個月時停止。我認為這將基於患者與患者。就像你說的，市場准入並不是障礙。因此，只要符合條件，這些患者就可以繼續治療，並且他們仍在那裡服藥。

In terms of kind of the EGFR data point that you mentioned, obviously, yes, we do have quite a lot of activities in preparation for that data. And yes, I mean, obviously, that will be a kind of a separate FDA review with a full kind of 360 patients and obviously, with the endpoint as communicated in terms of EGFR. So yes, our expectation is that, that may very well lead to expansion of label or a different label because, obviously, we would be able to kind of have slightly -- we will have different data to support some of that development. And I don't know, Andy, if you have any additional comments on the market...

就您提到的 EGFR 數據點的種類而言，顯然，是的，我們確實有很多活動來準備該數據。是的，我的意思是，很明顯，這將是一種單獨的 FDA 審查，涉及全部 360 名患者，顯然，終點是根據 EGFR 傳達的。所以是的，我們的期望是，這很可能會導致標籤的擴展或不同的標籤，因為很明顯，我們能夠稍微有點——我們將有不同的數據來支持其中的一些發展。我不知道，安迪，如果你對市場有任何額外的評論......

Yes, sure. So Part A, once it's published or Part B, I should say, once it's announced and then published, there is -- we are permitted to share some of this information certainly with payers in confidential. I think we've been very pleased with our management to date, but certainly, obviously, we could only improve from there with positive data. So we do anticipate sharing it as soon as possible. And hopefully, that will have some even further favorable treatment.

是的，當然。所以 A 部分，一旦它發布或 B 部分，我應該說，一旦它被宣布然後發布，我們就可以與付款人秘密分享其中的一些信息。我認為我們對迄今為止的管理感到非常滿意，但當然，顯然，我們只能通過積極的數據從那裡改進。所以我們確實希望盡快分享它。希望這會得到更進一步的優惠待遇。

The next question comes from Yigal Nochomovitz from Citigroup.

下一個問題來自花旗集團的 Yigal Nochomovitz。

 Renee, can you comment -- I know it's early in the launch, but can you comment at this point on what your market share looks like in the United States and you referenced some of the statistics for the prescribers, 642 and the enrollment 2039. -- can you connect that to your guidance in terms of how many prescribers you would expect by the end of 2023 and the number of enrollments by the end of 2023?

�Renee，你能評論一下嗎——我知道它還處於發布初期，但你現在能評論一下你在美國的市場份額嗎？你參考了一些開處方者的統計數據，642 和入學人數 2039。--您能否將其與您預計到 2023 年底開處方的人數和到 2023 年底入學人數的指導聯繫起來？

So obviously, what we've said before is really, I mean, when we're looking at when we've done our mapping, our market research on other work before we kind of launched, we really identified that probably the prescribing integration is kind of the most relevant for us would be around 3,700 to 4,000 nephrologists -- so obviously, from that perspective, we're really only kind of -- we have a very small amount, we're really kind of scratching the surface in terms of where what we can do with regards to that based on where we are on our first kind of 11 months of commercial activity. But obviously, there is -- in the actual kind of enrollment in prescribers, there's obviously this combination of refills and actually kind of patients staying on drug is then well new enrollments, et cetera. And obviously, then when those enrollments actually happen. And so I think it's very, very difficult at this point in time to kind of share that because it's a multitude of factors that go into that.

很明顯，我們之前所說的實際上是，我的意思是，當我們查看我們完成地圖繪製時，我們在推出之前對其他工作的市場研究，我們確實確定處方整合可能是與我們最相關的是大約 3,700 到 4,000 名腎病學家 - 所以很明顯，從這個角度來看，我們真的只是 - 我們有非常小的數量，我們真的有點觸及表面根據我們在第一種 11 個月的商業活動中所處的位置，我們可以在哪些方面做些什麼。但顯然，在處方醫生的實際註冊類型中，顯然存在這種補充劑的組合，實際上繼續服藥的患者類型是新註冊，等等。顯然，然後是這些註冊實際發生的時間。因此，我認為在這個時間點很難分享這一點，因為其中涉及多種因素。

Okay. And then just on the duration question. Is it fair to assume that pretty much everyone that's starting is going through the 9 months? Or is there a discontinuation rate that you're observing this for some patients is less than 9 months?

好的。然後是持續時間問題。假設幾乎每個剛開始的人都經歷了這 9 個月是否公平？還是您觀察到某些患者的停藥率低於 9 個月？

I think it's hard to answer that, obviously, because patients are continually moving through the process. But I think as far as discontinuation rates, it's probably similar to assume similar to our trial in Phase III. That's probably the best I can give as far as estimates on discontinuation rates.

顯然，我認為很難回答這個問題，因為患者不斷經歷這個過程。但我認為就停藥率而言，它可能與我們在 III 期試驗中的假設相似。就停藥率而言，這可能是我能給出的最好的估計。

 Okay. And then just going back to the Part B data, I mean, sort of as before but maybe ask in a different way. Could you kind of characterize how you would frame the base case for what that EGFR data would look like? What would the bull case look like for that data readout? And also what might be the less optimal bear case for that readout...

好的。然後回到 B 部分數據，我的意思是，有點像以前，但可能會以不同的方式提問。您能否描述一下您將如何構建 EGFR 數據的基本情況？對於該數據讀數，牛市情況會是什麼樣子？還有什麼可能是該讀數的不太理想的熊案例......

So I guess, obviously, I mean -- so we're looking for 2 things, obviously. One would obviously be to kind of see the duration or durability of the proteinuria reduction. We do have the 3-month kind of already kind of across all patients that we're seeing between the 9 and the 12 months. And then so the question is really, will that be persistent across the entire population, some of the population? Because obviously it is a heterogeneous group of patients or we know that they kind of develop in heterogeneous way. But I think, obviously, the longer we can see that kind of protein reduction or continued reduction, I think, obviously, that would make us -- that would be kind of go towards a stronger and stronger case, the longer that we can show that. In terms of the other aspect is obviously then eGFR. And I think, obviously, again, the longer that we can show that there is kind of a difference in eGFR kind of trajectory between kind of the treatment group and the placebo group, then obviously, again, that goes towards kind of disease modification. So I think that those are kind of the old views kind of directionally what we would find would be will we be looking for kind of in the trial. And then I think it really comes down to is this really kind of a very homogeneous population. Is it heterogeneous, -- we're going to see slightly different kind of things depending on kind of what type of profile these patients had when they came into the trial, et cetera. So I think that would really kind of be my view. I don't know, Richard, do you have anything to add?

所以我想，很明顯，我的意思是 - 所以我們顯然正在尋找兩件事。很明顯，一種方法是觀察蛋白尿減少的持續時間或持久性。我們確實有 3 個月的時間，我們在 9 個月到 12 個月之間看到的所有患者都有這種情況。那麼問題真的是，這會在整個人口中持續存在嗎？部分人口？因為很明顯這是一個異質的患者群體，或者我們知道他們以異質的方式發展。但我認為，顯然，我們看到這種蛋白質減少或持續減少的時間越長，我認為，顯然，這將使我們——這將是一種越來越強大的情況，我們可以展示的時間越長那。就另一方面而言，顯然是 eGFR。而且我認為，很明顯，我們可以證明治療組和安慰劑組之間的 eGFR 軌跡存在某種差異的時間越長，那麼顯然，這又會導致某種疾病的改變。因此，我認為這些是我們在試驗中尋找的方向性的舊觀點。然後我認為這真的歸結為這種非常同質的人口。它是異質的嗎，——我們會看到略有不同的東西，這取決於這些患者在進入試驗時的概況類型，等等。所以我認為這確實是我的觀點。我不知道，理查德，你有什麼要補充的嗎？

No, I don't think so. I think that really summarizes the position pretty nicely, actually.

不，我不這麼認為。實際上，我認為這真的很好地總結了這個立場。

The next question comes from Dan Akschuti from Pareto Securities.

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

Congratulations from the great programs with Tarpeyo and also on the upfront and milestones received from global partnerships. So my first  question is that do you see a need to increase the sales force further, considering the competitor sustained FDA approval that will start with a bigger sales force.ÂÂ

祝賀 Tarpeyo 的偉大計劃，以及從全球合作夥伴關係中獲得的前期和里程碑。所以我的第一個問題是，考慮到競爭對手獲得了 FDA 的批准，你認為有必要進一步增加銷售隊伍，這將從更大的銷售隊伍開始。

So we assess this kind of information at different points. And currently, there's no plan to increase our sales force. But I would say that if it made sense in optimizing the product and the brand, we would certainly would consider doing so at some point, but there's no set plans on doing so at this point.

因此，我們在不同的時間點評估此類信息。目前，我們沒有增加銷售人員的計劃。但我要說的是，如果優化產品和品牌有意義，我們肯定會考慮在某個時候這樣做，但目前還沒有這樣做的既定計劃。

Regarding the European market, could you provide some thoughts on the sales uptick? Is the sale fully reflected on the royalty income in '22? And do you have any discussion with that you are able to provide?

關於歐洲市場，您能否提供一些關於銷售增長的想法？銷售是否完全反映在 22 年的特許權使用費收入中？你有什麼可以提供的討論嗎？

Andy, do you want to add to...

安迪，你想添加到...

 Sure. I think that the information is our partner is pleased with the uptake to date. They launched in September and data shows that they have just shy of about 70 patients on therapy before the end of the calendar year, which puts them on mark for where they estimated they would be, and they feel very encouraged at this launch so far in Germany. I didn't hear the second part of the question. Can you repeat that?

當然。我認為我們的合作夥伴對迄今為止的信息感到滿意。他們於 9 月推出，數據顯示他們在日曆年結束前只有大約 70 名患者接受治療，這使他們達到了他們估計的水平，並且他們在迄今為止的這次推出中感到非常鼓舞德國。我沒有聽到問題的第二部分。你可以再說一遍嗎？

So is that all fully reflected on the royalty income in '22? And do you have any detection that you are able to provide. So yes, that's pretty much it. And -- sorry, and the last question is the R&D cost is over SEK 100 million. Can we expect that to remain stable over the coming years? And what is the strategy with that a flip in the next stage to plan the partner or to plan to finance both indications by yourself?

那麼這一切是否都完全反映在 22 年的版稅收入中？您是否可以提供任何檢測？所以是的，差不多就是這樣。而且 - 抱歉，最後一個問題是研發成本超過 1 億瑞典克朗。我們可以期望它在未來幾年保持穩定嗎？在下一階段計劃合作夥伴或計劃自己資助這兩個適應症的策略是什麼？

So --sorry, can you repeat that...

所以——抱歉，你能重複一遍嗎……

 It was R&D costs? Are we expecting -- if I understand you correctly, you're asking if the R&D costs are going to stay the same. Is that -- was that your first part of the question?

“這是研發成本？我們是否期待——如果我理解正確的話，你是在問研發成本是否會保持不變。那是——那是你問題的第一部分嗎？

We would expect it to stay in the ballpark basically. We do have a new program with Alport, which will increase the cost a little bit, but there will be no material increases for this year, we think.

我們希望它基本上保持在球場上。我們確實有一個與 Alport 的新計劃，這會增加一點成本，但我們認為今年不會有實質性的增加。

And in terms of kind of our kind of ongoing plans for kind of doing development ourselves or with partners, which I believe was your second part of the question. And obviously, what we've communicated before is obviously, if there are rare disease programs, and obviously, Alport is something that fits very well into our existing franchise. It's a renal asset. There is really nothing approved in all course. They're really significant unmet medical need, and we're super excited about being able to start that clinical trial. And obviously, PBC is another rare disease where we believe that we could commercialize that ourselves. Again, not in all geographic territories, but in select geographic territories. Head and neck cancer is obviously different because that really is a parallel kind of if you want to call it parallel path that really is more to characterize the mode of action of this drug because there's so much kind of preclinical data that exists in head and neck. And to the extent that the biomarker data that we read out if we get very strong biomarker data from that trial, we would not plan to take that R&D effort onwards, which would then go into potentially several kind of solid tumor types and would be a very, very significant R&D program. So we would then look to really partner that asset to the extent that there would be strong data, and there will be interest from big pharmacy to do so.

就我們自己或與合作夥伴一起進行開發的持續計劃而言，我相信這是你問題的第二部分。顯然，我們之前傳達的信息顯然是，如果有罕見疾病項目，顯然，Alport 非常適合我們現有的特許經營權。這是一種腎資產。在所有課程中確實沒有任何批准。它們確實是未滿足的重大醫療需求，我們對能夠開始該臨床試驗感到非常興奮。顯然，PBC 是另一種罕見疾病，我們相信我們可以自己將其商業化。同樣，不是在所有地理區域，而是在選定的地理區域。頭頸癌明顯不同，因為這確實是一種平行的，如果你想稱之為平行路徑，那實際上更多地是為了描述這種藥物的作用方式，因為頭頸癌中存在如此多的臨床前數據.如果我們從該試驗中獲得非常強大的生物標誌物數據，就我們讀出的生物標誌物數據而言，我們不打算繼續進行研發工作，這將進入潛在的幾種實體瘤類型，並且將是非常非常重要的研發計劃。因此，我們將尋求真正與該資產合作，以獲得強大的數據，並且大型藥房會有興趣這樣做。

The next question comes from Ingird Gafanhão from Bryan Garnier.

下一個問題來自 Bryan Garnier 的 Ingird Gafanhão£o。

I have a couple actually. So first on the price, I know you disclosed the 14.20 sort of in the beginning of next year. Should we expect any price increase for this year? And what would be a reasonable number to you soon? And then I have a follow-up.ÂÂ

我實際上有一對。所以首先關於價格，我知道你在明年初披露了 14.20 的價格。我們應該期待今年的價格上漲嗎？很快對您來說合理的數字是多少？然後我有一個後續行動。

So we did take a price increase at the end of January of 6.8%, in line with increased costs and inflation in those type of factors that go into these kind of decisions.

因此，我們確實在 1 月底將價格上漲了 6.8%，這與影響此類決策的那些因素的成本增加和通貨膨脹一致。

 I think for a follow-up, you did mention that you're still quite far for reaching the number of unique prescribers that you have for your target physicians. At the moment, what is keeping you from actually increasing this number a little bit faster? Is it a matter of sales force size or just time did you need to get to those accounts?

�我認為對於後續行動，您確實提到您距離達到您為目標醫生擁有的獨特處方者的數量還有很長的路要走。目前，是什麼阻止您實際更快地增加這個數字？是銷售人員規模的問題還是您需要獲得這些客戶的時間？

This is a rare disease. So that's not -- they don't see the patients every day. We see the physicians and it's a process that they go through. It's an educational process. No one's talked to them before about IgA nephropathy, the source of the disease, and this data is unique to them, seeing something like this. So it just takes time. different physicians have different adoption rates. -- some are adopting slow as far as one patient at a time where others put multiples on. So I don't think it's -- I think it's going very well. I don't think it's slower than we thought as far as reaching our target. You have to cast this wider net to get these prescribers on board.

這是一種罕見的疾病。所以那不是——他們不是每天都看病人。我們看到醫生，這是他們經歷的一個過程。這是一個教育過程。以前沒有人和他們談過 IgA 腎病，疾病的根源，這個數據對他們來說是獨一無二的，看到這樣的事情。所以這只是需要時間。不同的醫生有不同的採用率。 - 有些人一次只接受一個病人，而其他人則接受多個病人。所以我不認為它 - 我認為它進展順利。就實現目標而言，我認為它並不比我們想像的慢。你必須撒下這張更大的網才能讓這些開處方者參與進來。

 And if I may ask one quick last question on the financials as well. So you mentioned that you have enough cash to reach profitability. And would you feel comfortable with saying when that could be possible or how you're looking into that?

“如果我也可以問一個關於財務的最後一個快速問題。所以你提到你有足夠的現金來實現盈利。您是否願意說出何時可能或您正在如何調查？

No, we will not specify specify a specific time point given that we -- I mean, as you see, we do have a certain range in our guidance and also we would -- we are also starting the Alport program. So adding on a little more cost to it. So we are not specifying that to a specific quarter.

不，我們不會指定具體的時間點，因為我們——我的意思是，正如你所看到的，我們的指導中確實有一定的範圍，而且我們也會——我們也正在啟動 Alport 計劃。所以增加一點成本。所以我們沒有將其指定給特定的季度。

But it is clearly kind of our direction and our focus, obviously, to get there. So I mean, that hasn't changed at all. It's just difficult to kind of, again, know when this momentum is really going to pick up. It's kind of peer to peer, and when we're going to start seeing that kind of -- which we have started to see, but it's difficult to kind of judge exactly the impact of that. So -- but our kind of focus and direction there is obviously still clear.

但這顯然是我們的方向和重點，顯然，要到達那裡。所以我的意思是，這根本沒有改變。再次，很難知道這種勢頭何時真正回升。這是一種點對點，當我們開始看到那種——我們已經開始看到了，但很難準確判斷它的影響。所以 - 但我們的重點和方向顯然仍然很明確。

 The next question comes from Rami Katkhuda from Life SCI Capital.

下一個問題來自 Life SCI Capital 的 Rami Katkhuda。

 Congrats on the progress. Two quick ones for me. But in your guidance, do you expect net sales of Tarpeyo to kind of continue linearly growing? Or is that an inflection point going to be around successful Part B data or full approval by the FDA, et cetera? And then with regards to market access, are you seeing big differences between commercial and Medicare lives or our coverage in prior as similar across the board?

恭喜你取得了進步。兩個快速的給我。但在您的指導下，您是否預計 Tarpeyo 的淨銷售額會繼續線性增長？或者，一個拐點將圍繞成功的 B 部分數據或 FDA 的完全批准，等等？然後關於市場准入，您是否看到商業和 Medicare 生活之間存在巨大差異，或者我們之前的覆蓋範圍是否全面相似？

 So I think that to some extent, uptake is partly organic. It's this is kind of based on just kind of education and people understanding and understanding the mode of action and seeing patient success, et cetera. So I think there's a kind of an underlying kind of uptake and growth. Obviously, we are expecting all physicians want to see more data. And so we're expecting, obviously, that, that would be kind of -- it could provide additional momentum to do that. I personally don't think that the ultimate approval per say would be kind of a major change apart from obviously the label impact. That could obviously be quite significant. But in terms of kind of the way the physicians will be using it in the meanwhile. But I don't know, Andy, do you have a different view?

“因此，我認為在某種程度上，吸收部分是有機的。這是基於某種教育和人們對行動方式的理解和看到患者的成功等等。所以我認為有一種潛在的吸收和增長。顯然，我們期望所有醫生都希望看到更多數據。因此，很明顯，我們期望那會是——它可以提供額外的動力來做到這一點。我個人認為，除了明顯的標籤影響之外，每個人的最終批准不會是一種重大變化。這顯然可能非常重要。但就醫生同時使用它的方式而言。但我不知道，安迪，你有不同的看法嗎？

Yes. No, I think pretty much all the factors that you say go into things over the year and uptake, meaning they're going to certainly get increased comfort, Part B would be certainly another catalyst, but I think it's just time that we'll take care of increased growth with increased successes. You asked about market access and the difference between the different channels. So just to be clear, there's 2 things. Number one, as far as coverage is concerned, over 90% of U.S. lives. So the coverage is great for even the government subsidizes as well as commercial patients. So that's all U.S. laws. And then when you look at our specific book of business, where the patients come from when you're looking at IgA nephropathy, that's when I discuss around 70% or almost 75%, if you want to look at, that's private insurance and cash-paying patients versus the government subsidized. Does that make sense?

是的。不，我認為你所說的幾乎所有因素都會在一年內發生並被接受，這意味著他們肯定會獲得更多的舒適感，B 部分肯定會成為另一個催化劑，但我認為現在是時候了照顧隨著成功的增加而增加的增長。您詢問了市場准入以及不同渠道之間的區別。所以要明確一點，有兩件事。第一，就覆蓋率而言，超過 90% 的美國人生活。因此，即使是政府補貼的患者和商業患者，覆蓋範圍也很大。這就是美國的所有法律。然後，當你查看我們具體的業務手冊時，當你查看 IgA 腎病時，患者來自哪裡，那時我討論了大約 70% 或幾乎 75%，如果你想看的話，那是私人保險和現金-付費患者與政府補貼。那有意義嗎？

And I guess with prior ops, it's pretty much the same.

我想對於之前的操作，它幾乎是一樣的。

 Yes, there's similar types of coverage. It's -- as you would anticipate, a specialty product being covered and that's how it's been across both commercial as well as government subsidized.

是的，有類似類型的報導。正如您所預料的那樣，這是一種特殊產品，這就是它在商業和政府補貼方面的表現。

The next question comes from Erik Hultgård from Carnegie.

下一個問題來自卡內基的 Erik HultgÃ¥rd。

I have 2, if I may. First, some of your peers or competitors are considering doing studies -- combination studies with SGLT2s. I was just wondering from a mechanistical point of view and also return on investment point of view, is that something you're planning? And does it make sense? And then just a quick follow-up on previous question on price hike. The list price increase in late January, do you expect that to sort of fall down to the net price line as well?

如果可以的話，我有 2 個。首先，您的一些同行或競爭對手正在考慮進行研究——與 SGLT2 的聯合研究。我只是想從機械的角度和投資回報的角度來看，這是你計劃的嗎？這有意義嗎？然後快速跟進之前關於價格上漲的問題。 1 月下旬的標價上漲，您是否預計它也會下降到淨價線？

 So I guess I'll have Richard give his view on this as well. I guess in terms of the SGLT2s, this is very complement. I mean, we are a locally targeted medication. We're not kind of really focused on the systemic distribution of the drug. So -- and we know obviously today that there are quite a few patients who are on SGLT2 today and also on Tarpeyo talk to physicians, I think a lot of all the physicians that I personally have been in contact with anyone talked to would consider this to be highly complementary. I mean SDLT2 are -- obviously, they're approved in CKD, not specifically Ng. I don't think people look at them as being kind of disease-modifying or anything like that. I think -- but I think they're very safe, and I think they do obviously provide some cardiovascular protection, general cardio protection, et cetera. So do we do already see that being used in quite a lot of kind of patients already with Tarpeyo -- and as I said, it seems to be kind of a positive view from the nephrologist perspective. But I don't know, Richard, if you have anything to add?

“所以我想我也會讓理查德就此發表他的看法。我想就 SGLT2 而言，這是非常互補的。我的意思是，我們是針對當地的藥物。我們並沒有真正關注藥物的系統分佈。所以——我們今天顯然知道，今天有相當多的患者在接受 SGLT2 治療，也在接受 Tarpeyo 治療時與醫生交談，我想我個人接觸過的所有醫生中的很多人都會考慮這個高度互補。我的意思是 SDLT2 - 顯然，它們在 CKD 中獲得批准，而不是特別是 Ng。我認為人們不會將它們視為一種疾病緩解或類似的東西。我認為——但我認為它們非常安全，而且我認為它們顯然確實提供了一些心血管保護、一般心臟保護等。那麼我們是否已經看到它已經用於很多已經使用 Tarpeyo 的患者——正如我所說，從腎病學家的角度來看，這似乎是一種積極的觀點。但我不知道，理查德，你有什麼要補充的嗎？

Yes. I mean I think we have an active internal program looking at potential studies that we can undertake to develop franchise for Nefecon. And certainly, we're interested in other treatments that are available. I completely agree with Renee's comments. There's absolutely no reason why Nefecon can't be given on top of an SGLT2 inhibitor. The mechanisms of action are completely different, but they're complementary. So I think it's something that we're actively watching and considering...

是的。我的意思是我認為我們有一個積極的內部計劃，著眼於我們可以進行的潛在研究，以開發 Nefecon 的特許經營權。當然，我們對其他可用的治療方法很感興趣。我完全同意 Renee 的意見。絕對沒有理由不能在 SGLT2 抑製劑之上給予 Nefecon。作用機製完全不同，但它們是互補的。所以我認為這是我們正在積極觀察和考慮的事情......

And as far as the price increase and its impact, I'm not sure I completely understand the question. But I mean, in general, the patient out-of-pocket costs are typically a percentage if it's coinsurance or it's a set amount. And we have 0 out-of-pocket costs for commercially covered patients, and no patient will ever not receive our medication due to affordability. So it's not going to have an impact on patient out of pockets really from that aspect.

至於價格上漲及其影響，我不確定我是否完全理解這個問題。但我的意思是，一般來說，如果是共同保險或固定金額，患者的自付費用通常是一個百分比。對於商業承保的患者，我們的自付費用為 0，並且沒有患者會因為負擔能力而無法接受我們的藥物治療。因此，從這方面來看，它不會對患者自掏腰包產生影響。

Sorry, it was more related to the sort of gross versus net price. So the 6.8% price hike, do you expect a similar increase in net price? Or are there higher reset coming in...

抱歉，它與總價與淨價的關係更密切。那麼 6.8% 的價格上漲，您預計淨價也會有類似的上漲嗎？或者是否有更高的重置...

 Yes. No, no. We don't contract with payers, number one, -- so it won't have, but it should have a similar -- we're not going to see a change in any noticeable or anything change from gross to net that you should use in the calculations.ÂÂ

是的。不，不。我們不與付款人簽訂合同，第一， - 所以它不會有，但它應該有類似的 - 我們不會看到任何明顯的變化或任何你應該看到的從總值到淨值的變化在計算中使用。

The next question comes from Sebastian Van Scout from BLK.

下一個問題來自 BLK 的 Sebastian Van Scout。

This is Sebastian dropping in for Suzanne today. Congrats on the progress. A couple of questions from our side. For the Phase III Part B readout for the EGFR result, assuming that you will meet the primary endpoint with statistical significance. Some conversations you have with physicians and KOLs, what is the difference from EGFR that would be considered to be the minimum bar and clinically meaningful? And what would you consider to be a strong EFR results? And then I have a follow-up question.

我是塞巴斯蒂安今天順道拜訪蘇珊娜。祝賀進步。我們這邊的幾個問題。對於 EGFR 結果的 III 期 B 部分讀數，假設您將達到具有統計顯著性的主要終點。您與醫生和 KOL 的一些對話，與 EGFR 有什麼區別被認為是最低限度和臨床意義？您認為什麼是強大的 EFR 結果？然後我有一個後續問題。

Well, I'll take a crack at that and Richard, you can complement that. I mean, I think that my view is actually talking to a veriety of physicians that there isn't a specific number or a minimum bar that they would be looking at. I think it is more about kind of actually what can you see in terms of what's the difference in eGFR kind of development in the placebo versus the active arm. But I don't know, Richard, if you have a different experience in your interactions with KOLs.

好吧，我會嘗試一下，理查德，你可以補充一下。我的意思是，我認為我的觀點實際上是在與許多醫生交談，他們沒有看到具體的數字或最低標準。我認為這更多的是關於安慰劑組和活性組中 eGFR 發展類型的差異，你能看到什麼。但我不知道，理查德，你在與 KOL 的互動中是否有不同的經歷。

I mean no I broadly agree with that. It's not like the external KOLs, experts have some magic number in there, head that says this is the EGFR that you have to achieve below is not good above is good. And I think it's about -- clearly, we need to meet our primary endpoint for the study. And there's also a number of different important secondary endpoints and supportive data. I think we need to take a holistic look at the information that we get from the outcomes of Part B and look at all of that information. So I don't think you can simply say this is the number that we have to achieve.

我的意思是不，我大致同意這一點。它不像外部 KOL，專家在那裡有一些神奇的數字，頭上說這是你必須實現的 EGFR 下面不好，上面很好。我認為這是關於 - 顯然，我們需要達到研究的主要終點。還有許多不同的重要次要終點和支持數據。我認為我們需要全面審視我們從 B 部分的結果中獲得的信息，並審視所有這些信息。所以我認為你不能簡單地說這是我們必須達到的數字。

Okay. Got it. But then can you maybe elaborate on the statistics for what difference is the trial powered on eGFR.

好的。知道了。但是，您能否詳細說明基於 eGFR 的試驗有何不同的統計數據。

Well, I mean, we don't typically comment on the sort of the detailed statistics of the clinical trial, to be honest.

好吧，我的意思是，老實說，我們通常不會對臨床試驗的詳細統計數據發表評論。

Okay. Got it. And then the final question is on the Alport trial. I was just wondering what the biological rationale and the preclinical data is that supports testing (inaudible) in the renal space?

好的。知道了。最後一個問題是關於 Alport 的審判。我只是想知道支持在腎臟空間進行測試（聽不清）的生物學原理和臨床前數據是什麼？

Richard, do you want to take that?

理查德，你要拿那個嗎？

 Yes, sure. So I'll try and answer it reasonably briefly in summary. Alport's disease is a rare hereditary genetic disease. There's a clear genetic defect in Alport syndrome. It's a disease of collagen and patients with all ports disease developers. -- progressive renal failure relating to glomerulonephropathy where a significant component of that is a podocytopathy and fibrosis. And we know from -- and maybe you've heard from previous presentations, that setanaxib has a very important role in fibrogenesis relating to the -- its effects on Loxenzyes through NOx inhibition and the inhibition of the generation of reactive oxygen species, which are important in activating fibrogenic pathways. So from that point of view, there's a clear underlying rationale and we have supporting preclinical data from a relevant Alport mouse model that does indeed support that hypothesis. So if you like, we now have preclinical data that are sort of biological biochemical and histological outcomes that support that thesis that setanaxib could have beneficial effects in Alport syndrome.

是的，當然。因此，我將嘗試簡要地簡要回答它。阿爾波特病是一種罕見的遺傳性遺傳病。 Alport 綜合徵有明顯的遺傳缺陷。這是一種膠原蛋白病，患者患有各種疾病。 -- 與腎小球腎病相關的進行性腎衰竭，其中一個重要組成部分是足細胞病和纖維化。我們從——也許你從之前的演講中聽說過，setanaxib 在纖維發生中起著非常重要的作用——它通過抑制 NOx 和抑制活性氧的產生對 Loxenzyes 產生影響，這些是對激活纖維化途徑很重要。因此，從這個角度來看，有一個明確的基本原理，我們有來自相關 Alport 小鼠模型的支持臨床前數據，這些數據確實支持該假設。因此，如果您願意，我們現在擁有臨床前數據，這些數據是某種生物生化和組織學結果，支持 setanaxib 可能對 Alport 綜合徵產生有益影響的論點。

The next question comes from Johan Unnerus from Redeye.

下一個問題來自 Redeye 的 Johan Unnerus。

Congratulations on the good quarter. Very interesting releases continued dosing-- and and I guess, eventually, second dosing. Could you remind us regarding the part if we can get any more insight to the need or use of extended dose or second dose?

祝賀這個好季度。非常有趣的釋放持續給藥——我猜，最終，第二次給藥。如果我們能更深入地了解延長劑量或第二劑的需要或使用，您能否就這部分提醒我們？

 Yes, I'll start and then maybe Richard can complement the in the Part B, obviously, we are not kind of -- we are not redosing as part of the protocol and the Part B. It really is just an initial treatment and then there is a follow-up period which is observational. But as I think I mentioned in the Q3 report, obviously, there is an open-label extension that's available for patients who have concluded the Phase III. So once they've been in the study for 2 years, they have an ability to then enroll into an open-label extension, where all patients will be given active treatment for 9 months. And as I think we've mentioned there, obviously, there is a fairly significant number failures and those are the at over 60% of those are even related to the fact that the patients actually don't qualify due to the fact that they do not have 1 gram of proteinuria, so they are not considered strictly according to Cicada guidelines to be in that kind of higher risk population. But there will obviously be patients who will have enrolled into that open-label extension. So we will be getting additional information from that study, which obviously is also still blinded and ongoing. But once that study, obviously, once we are able to kind of look into that study, that is probably more likely to give us some more information around retreatment, et cetera. But obviously, I'm sure that in the Part B, we will be -- we will see some trends and see some information regarding how proteinuria reduction performs an EGFR, et cetera. So Richard, do you want to complement on that?

是的，我會開始，然後也許 Richard 可以補充 B 部分中的內容，顯然，我們不是——我們不會將重做作為協議和 B 部分的一部分。這真的只是一個初始治療，然後有一個觀察期的隨訪期。但正如我想我在第三季度報告中提到的那樣，顯然，有一個開放標籤擴展適用於已經完成 III 期的患者。因此，一旦他們參加了 2 年的研究，他們就有能力參加開放標籤擴展，所有患者都將接受為期 9 個月的積極治療。正如我認為我們在那裡提到的那樣，顯然，有相當多的失敗，其中超過 60% 甚至與患者實際上不符合資格的事實有關，因為他們符合資格沒有 1 克蛋白尿，因此嚴格按照 Cicada 指南，他們不屬於那種高風險人群。但顯然會有患者加入該開放標籤擴展。因此，我們將從該研究中獲得更多信息，該研究顯然仍處於盲態且仍在進行中。但是，顯然，一旦這項研究，一旦我們能夠對這項研究進行某種程度的調查，那可能更有可能為我們提供更多關於再治療等的信息。但顯然，我確信在 B 部分，我們將看到一些趨勢，並看到一些關於減少蛋白尿如何執行 EGFR 等的信息。那麼理查德，你想補充一下嗎？

Sure. So just to make sure it's clear how the open-label extension performs. So it's open label in the sense that everyone in the who gets into the open-label extension receive active treatment. -- but is blinded in the sense that investigators and patients don't know what their original randomized treatment was in the pivotal study. So as relays that gives us an opportunity to get some really interesting information at the end of the study, and we expect that study to complete in early 2024. So we expect to be able to see the performance of patients who did previously receive Metacom and then have received a second course in the Oakland label extension compared with patients who received placebo in the original study and then went on to receive their first course of Metacom in the open-label extension. So some very interesting information will come out of that follow-up study.

當然。因此，只是為了確保清楚開放標籤擴展的執行方式。所以它是開放標籤，因為參與開放標籤擴展的每個人都接受積極治療。 -- 但在研究人員和患者不知道他們在關鍵研究中最初的隨機治療是什麼的意義上是盲目的。因此，作為中繼，我們有機會在研究結束時獲得一些非常有趣的信息，我們預計該研究將在 2024 年初完成。因此，我們希望能夠看到之前接受過 Metacom 和然後在奧克蘭標籤擴展中接受了第二個療程，與在原始研究中接受安慰劑的患者相比，然後繼續在開放標籤擴展中接受他們的第一個療程的 Metacom。因此，一些非常有趣的信息將從該後續研究中得出。

Excellent. And so this is to be expected in the first half of '24 and thereabout?

出色的。因此，這在 24 年上半年及左右是可以預期的嗎？

Yes, most likely would...

是的，很有可能會……

And even if it's still relatively early days, is there any sort of take from real life in terms of continuing usage is still well the first patients have been on 11 months, so it's still obviously very early days. And the second part of that question can be also if there is a sense of changing characteristics in the patients quite often when a new product is launched, it then be the more sort of severe patients and as time goes and especially feel more comfortable, they may also opt to treat perhaps some less severe patients.

即使現在還處於早期階段，在持續使用方面是否有任何來自現實生活的東西仍然很好，第一批患者已經接受了 11 個月的治療，所以現在顯然還處於早期階段。這個問題的第二部分也可以是，如果推出新產品時患者的特徵經常發生變化，那麼它就是更嚴重的患者，隨著時間的推移，尤其是感覺更舒服，他們也可能選擇治療一些不太嚴重的患者。

Andy, do you want to take that?

安迪，你要拿那個嗎？

Yes. So I think if I heard you correctly, on the length of therapy, those folks that are on in a longer period of time, we're not seeing anything different with those patients. They're tolerating the medication and we're not hearing back anything, anything noteworthy of patients that have been on longer than the 9 months. And then your comment about patient population for the physicians and uptake. I think that naturally, I think when a new product launches, a physician will try something on maybe a more severe patient and then they'll move to more of a comfort zone or additional patients with success that they achieved with the patient population. That's what we were talking about earlier. I think we're starting to get these success story more and more from our fields, reported back to us on patients, and that can only encourage physician prescribing and wanting to treat additional patients.

是的。所以我認為，如果我沒聽錯的話，關於治療時間的長短，那些接受較長時間治療的人，我們沒有看到這些患者有任何不同。他們耐受藥物治療，我們沒有收到任何關於服藥時間超過 9 個月的患者的任何值得注意的信息。然後是您對醫生的患者人數和接受情況的評論。我認為自然而然地，我認為當一種新產品推出時，醫生會在可能更嚴重的患者身上嘗試一些東西，然後他們會轉移到更多的舒適區或其他患者，他們在患者群體中取得了成功。這就是我們之前所說的。我認為我們開始越來越多地從我們的領域獲得這些成功故事，向我們報告患者，這只會鼓勵醫生開處方並希望治療更多患者。

And then finally, you -- it's clear that market access is great. Wireless is great. Is there any sort of change in unique prescriber characteristics in terms of level of specialists are you seeing more activities on especially closer to the patient? Or is it more larger centers that is more dynamic or is there sort of great interest across the board?

最後，你 - 很明顯市場准入很好。無線很棒。就專家水平而言，獨特的處方者特徵是否有任何變化？您是否看到更多的活動特別接近患者？或者是更大的中心更有活力，還是對整個行業都有很大的興趣？

Yes. I would say there has been a change in that makeup. A lot of times, that's an individual physician adoption comfort level and when you see them and how often that determines their uptake. So over time, we've just seen an increase in new prescribers as you would anticipate. And that's a lot of time left on there based really on their adoption comfort level and their understanding of the product, the clinical information. Some want to see more information than others. So there's really no one answer as far as that's related. I don't think there's any difference in the new prescribers. I will say though, our targeting segmenting and targeting has been pretty accurate as far as who we anticipated would be the higher enrollers of patients. So that seems to be accurate and targeted which is who we call on the most with our sales force.

是的。我會說妝容髮生了變化。很多時候，這是一個個體醫生的接受舒適度，當你看到他們以及多久決定他們的吸收。因此，隨著時間的推移，正如您所預期的那樣，我們剛剛看到新開處方者有所增加。根據他們的採用舒適度和他們對產品、臨床信息的理解，還有很多時間留在那裡。有些人希望看到比其他人更多的信息。因此，就相關問題而言，確實沒有人回答。我認為新的處方者沒有任何區別。不過我要說的是，就我們預期的患者登記人數而言，我們的目標細分和目標定位非常準確。因此，這似乎是準確且有針對性的，這是我們與銷售人員聯繫最多的人。

And mainly, any surprises in the feedback from the sales and marketing team or commercial clinical team.

主要是來自銷售和營銷團隊或商業臨床團隊的反饋中的任何驚喜。

 Yes, no real surprises, no. NothingÂÂ

是的，沒有真正的驚喜，沒有。什麼都沒有

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

目前沒有其他問題。因此，我將會議交還給發言者以徵求任何結束評論。

Thank you very much for participating in this Q4 call for 2023. We look forward to talking to you again for Q1 of 2023.

非常感謝您參與 2023 年第 4 季度的電話會議。我們期待在 2023 年第 1 季度再次與您交談。