Pharming Group NV (PHAR) 2024 Q2 法說會逐字稿

Good morning or good afternoon, ladies and gentlemen; I'm here. Next slide, please. Welcome to our results conference for the first half and second quarter of this year. And I'm here with my colleagues, Stephen Toor, our Chief Commercial Officer; Anurag Relan, our Chief Medical Officer; and Jeroen Wakkerman, our Chief Financial Officer who will -- we will collectively guide you through the story.

早安或下午好，女士們、先生們；我在這兒。請下一張投影片。歡迎參加我們今年上半年和第二季的業績發表會。我和我的同事史蒂芬·圖爾（Stephen Toor）一起來到這裡，他是我們的首席商務官。 Anurag Relan，我們的首席醫療官；我們的財務長 Jeroen Wakkerman 將共同引導您完成整個故事。

But before I do that, I would like to have this next slide and point you to these forward-looking statement slide. So we will be making forward-looking statements in this presentation. And as you well know, these are based upon our -- upon future expectations that are based on our current expectations and assumptions, and may involve known and unknown risks and uncertainties. As you well know, the results eventually could differ materially from what we have expressed or implied in our statements. Next slide, please.

但在此之前，我想先看下一張投影片，並向您介紹這些前瞻性聲明投影片。因此，我們將在本次演示中做出前瞻性陳述。如您所知，這些基於我們基於當前預期和假設的未來預期，並且可能涉及已知和未知的風險和不確定性。如您所知，結果最終可能與我們在聲明中表達或暗示的內容有重大差異。請下一張投影片。

And then, you can immediately move on to slide number 5, please. So what we're doing is -- this is the strategy that we've been embarked on for quite some time now. We're building this leading global rare disease biopharma company. And we do that on the basis of two strong pillars.

然後，您可以立即轉到第 5 張投影片。所以我們正在做的是——這是我們已經實施了一段時間的策略。我們正在打造這家全球領先的罕見疾病生物製藥公司。我們是在兩個強而有力的支柱的基礎上做到這一點的。

The first one on the left, of course, is RUCONEST, which has now been on the market for close to 10 years in the US, and of course, deliver sales mainly from the market. And we were very pleased to see that RUCONEST continues to grow very significantly, both in context of the comparison to the previous quarters -- in the second quarter, 23% versus last year; and both when you compare the first half to last year's first half, 16% which is, I would say, a very strong performance, which we're very pleased with.

左邊第一個當然是RUCONEST，它現在在美國上市已經接近10年了，當然銷售主要還是來自市場。我們非常高興地看到 RUCONEST 繼續顯著成長，無論是與前幾季相比，第二季與去年相比成長了 23%；當你將上半年與去年上半年進行比較時，兩者都是 16%，我想說，這是一個非常強勁的表現，我們對此感到非常滿意。

And Stephen will, a little bit later, give you more details on the underlying positive indicators also going forward into the second half of the year. And then, of course, we have to Joenja, which we launched last year in end of -- which was approved end of March last year, which we brought into the market beginning of the second quarter of last year. And we're very pleased to see that this continues to grow as well.

稍後，史蒂芬將向您提供有關今年下半年潛在積極指標的更多詳細資訊。當然，我們還有 Joenja，它是我們在去年年底推出的，去年 3 月底獲得批准，我們在去年第二季初將其推向市場。我們很高興看到這一數字也在持續成長。

Second quarter compared to the first quarter was 16%, and 44% if you compare the first half of this year to the last half of last year. So we are continuing to grow Joenja into the market. And of course, this, as we all know, is a very new disease and a ultra rare indication. And our colleagues, Stephen and Anurag will respectively address you and tell you why we are continuing to be very optimistic of the enormous commercial potential for Joenja not only in APDS, but also in subsequent therapies and subsequent indications.

第二季與第一季相比為16%，若與去年下半年相比，今年上半年為44%。因此，我們將繼續將 Joenja 推向市場。當然，眾所周知，這是一種非常新的疾病，也是一種極為罕見的適應症。我們的同事 Stephen 和 Anurag 將分別向您致辭，並告訴您為什麼我們繼續對 Joenja 的巨大商業潛力非常樂觀，不僅在 APDS 方面，而且在後續治療和後續適應症方面。

And that brings me to the pipeline on the right-hand side. We are very soon embarking on a Phase 2 study for the next indication for leniolisib. And we are, of course, we are also exploring a third indication, and Anurag Relan will talk to you about that in more detail.

這將我帶到了右側的管道。我們很快就會開始針對 leniolisib 的下一個適應症進行第 2 期研究。當然，我們也在探索第三種適應症，Anurag Relan 將與您更詳細地討論這一點。

And of course, last but not least, we continue to focus on in-licensing or acquiring clinical stage opportunities in rare diseases to broaden our portfolio and which we can, of course, given our strong financial performance. And then I would like to have the next slide on the cascade of the disease overview.

當然，最後但並非最不重要的一點是，我們繼續專注於罕見疾病的許可或獲得臨床階段的機會，以擴大我們的產品組合，當然，考慮到我們強勁的財務業績，我們可以做到這一點。然後我想用下一張投影片來介紹疾病的級聯概述。

And this slide is an important one because RUCONEST is in a very competitive market. RUCONEST, however, is unique product, as you can see here, because these are the three pathways that represent an attack of hereditary angioedema. And C1 inhibitor is the missing protein; and RUCONEST, as protein replacement therapy, is the only actively promoted C1 inhibitor on the US market and addresses all the pathways, as you can see.

這張投影片很重要，因為 RUCONEST 處於競爭非常激烈的市場。然而，正如您在這裡所看到的，RUCONEST 是一種獨特的產品，因為這些是代表遺傳性血管性水腫發作的三種途徑。而C1抑制劑就是缺失的蛋白質；如您所見，作為蛋白質替代療法的 RUCONEST 是美國市場上唯一積極推廣的 C1 抑制劑，可解決所有途徑。

RUCONEST has proven throughout the years to be a reliable product to actually treat those attacks of hereditary angioedema. And there is of course, a lot of competition, but all of these competing products and competing products that are in development do not address all the three pathways.

多年來，RUCONEST 已被證明是一種可靠的產品，可以真正治療遺傳性血管性水腫的發作。當然，存在著許多競爭，但所有這些競爭產品和正在開發的競爭產品並沒有解決所有這三個途徑。

And RUCONEST -- a typical patient profile for RUCONEST, therefore, over the years, has evolved and has become that type of patient that does not respond to products that are actually only serving that, for instance, kallikrein-independent pathway in the middle or the HMWK, releasing the BK, pathway on the bottom.

因此，RUCONEST——RUCONEST 的典型患者概況，多年來已經發展並成為對實際上僅服務於例如中間或中的激肽釋放酶獨立途徑的產品沒有反應的患者類型。

So RUCONEST has basically built his own unique position there. And all those patients that are using the other products suffer from breakthrough attacks, and also, in this case, RUCONEST comes into view.

所以RUCONEST基本上已經在那裡建立了自己獨特的地位。所有使用其他產品的患者都會遭受突破性的攻擊，在這種情況下，RUCONEST 也出現了。

So in other words, we strongly believe that despite current competition, and previous competition which we have seen, and oncoming competition which all are serving that single pathway. RUCONEST will be the go-to product for those severely affected patients, also known, for instance, as Type 3 hereditary angioedema of which more and more get diagnosed.

換句話說，我們堅信，儘管當前的競爭、我們之前看到的競爭以及即將到來的競爭都在為這條單一途徑服務。RUCONEST 將成為那些受到嚴重影響的患者的首選產品，例如，越來越多的患者被診斷為 3 型遺傳性血管性水腫。

That explains to you why more and more patients come to RUCONEST, and RUCONEST becomes the mainstay for their therapy for hereditary angioedema because. They cannot get by on any of these other products. Hence, we are very optimistic and very confident about the future delivery of RUCONEST for -- to basically underpin the growth of our company. And let's move then to the next slide.

這就解釋了為什麼越來越多的患者來到 RUCONEST，並且 RUCONEST 成為他們治療遺傳性血管性水腫的中流砥柱，因為。他們無法依靠任何其他產品生存。因此，我們對 RUCONEST 的未來交付非常樂觀和充滿信心——從根本上支撐我們公司的發展。然後讓我們轉到下一張投影片。

That's -- and again, Joenja, we believe, has a significant potential as well. This depicts here, and Stephen and Anurag will go into more detail, the fact where we are at the moment with the Joenja. We have a significant portion of the US patients already on paid therapy, of the ones that have been identified so far.

我們相信，Joenja 也具有巨大的潛力。這描述了這裡，史蒂芬和阿努拉格將更詳細地描述我們目前與喬恩賈在一起的事實。到目前為止，我們已經確定了很大一部分美國患者已經在接受付費治療。

We, however, have a great potential going forward with regards to finding, validating the variance of uncertain significance. And Anurag will talk about that, when that and how that will happen, and what kind of potential big impact that will have on the number of patients that become available in the US market.

然而，在尋找、驗證不確定顯著性的變異數方面，我們有很大的潛力。阿努拉格將討論這一點、何時以及如何發生，以及這將對美國市場上可用的患者數量產生什麼樣的潛在重大影響。

Outside of the US, we started to see sales, and continue to -- will continue to see sales, growing sales from patients on early access to Named Patient Programs. We're working with more regulatory agencies and looking forward to bringing leniolisib for APDS in more territories in the world.

在美國以外，我們開始看到銷售，並將繼續看到銷售，早期訪問指定患者計劃的患者的銷售不斷增長。我們正在與更多監管機構合作，並期待將用於 APDS 的 leniolisib 引入世界更多地區。

And last but not least, 25% -- an estimated 25% of patients are below 12 and can be served as and when the pediatric studies will report and as and when we get the pediatric label expansion as well. So in other words, leniolisib, Joenja, in APDS has a significant, a very significant, potential, we believe even way beyond RUCONEST at this point in time. And that's only for APDS.

最後但並非最不重要的一點是，25%——估計 25% 的患者年齡在 12 歲以下，可以在兒科研究報告時以及當我們獲得兒科標籤擴展時提供服務。換句話說，leniolisib、Joenja 在 APDS 中具有重要的、非常重要的潛力，我們相信目前甚至遠遠超越 RUCONEST。這僅適用於 APDS。

So the other thing on the right-hand side there is that we are now, of course, identifying -- we have identified the second indication, and we'll start a Phase 2 trial in that second indication, which is, as you can see on this slide, about more than three times the incidence of -- the estimated incidence of APDS, the PID, primary immune deficiency.

所以右邊的另一件事是，我們現在當然正在確定——我們已經確定了第二個適應症，我們將在第二個適應症中開始第二階段試驗，也就是說，你可以在這張幻燈片上看到，大約是APDS、PID、原發性免疫缺陷的估計發生率的三倍多。

In addition to that, we are now seeking regulatory feedback on a third primary immune deficiency indication. So in other words, we believe that not only does Joenja have an enormous potential over the coming years to develop itself into a very significant commercial asset for our company in APDS, but on top of that, it has even bigger potential to actually become a pipeline in a product, given that we have now identified at least two indications from which we could start development programs very soon.

除此之外，我們現在正在尋求有關第三種主要免疫缺陷適應症的監管回饋。換句話說，我們相信 Joenja 不僅有巨大的潛力在未來幾年發展成為我們公司在 APDS 的一項非常重要的商業資產，而且最重要的是，它還有更大的潛力成為真正的鑑於我們現在已經確定了至少兩個跡象，我們可以很快開始開發計劃。

So with this said, I happily hand over to our Chief Commercial Officer, Stephen Toor, to take you through a little bit more details on the revenues of RUCONEST and Joenja.

話雖如此，我很高興地請我們的首席商務官 Stephen Toor 為您介紹有關 RUCONEST 和 Joenja 收入的更多詳細資訊。

Thank you, Sijmen. Good morning and good afternoon, everybody. We go to the next slide. So I will, as Sijmen said, take you through the RUCONEST and the Joenja performance so far, and then on the last slide for me, before handing over to Anurag, just give you a little update on our medium-term expectations of why we're so confident in the business.

謝謝你，西吉門。大家早安，下午好。我們轉到下一張投影片。因此，正如Sijmen 所說，我將帶您了解迄今為止RUCONEST 和Joenja 的表現，然後在我的最後一張幻燈片上，在移交給Anurag 之前，只向您介紹我們的中期預期的一些最新情況，以及為什麼我們對生意很有信心。

So looking at this slide and specifically RUCONEST, you can see, I think in those first four boxes at the top, that the consistent strength in performance really relates to the unique attributes of RUCONEST in the patient population we serve that Sijmen alluded to that more severely affected group.

因此，看看這張幻燈片，特別是RUCONEST，您可以看到，我認為在頂部的前四個框中，性能的一致強度確實與RUCONEST 在我們服務的患者群體中的獨特屬性有關，Sijmen 提到了更多受影響嚴重的族群。

RUCONEST is, as you know, the only recombinant C1 esterase inhibitor in those key core benefits of 97% of patients whose attack is resolved in a single dose. And that sustained effect over a period of days is really why those patients really can abandon other products that don't work as well, find a home with RUCONEST. And it's what drives our continued strong performance.

如您所知，RUCONEST 是唯一的重組 C1 酯酶抑制劑，其關鍵核心益處是單劑量即可解決 97% 的患者的發作問題。這種持續幾天的效果正是這些患者真正可以放棄其他效果不佳的產品，並在 RUCONEST 中安家的原因。這也是我們持續保持強勁業績的動力。

And that performance over a decade now has made RUCONEST the most prescribed -- sorry, the second most prescribed acute therapy in the US, and of course, still posting solid results. In the first half of 2024 -- sorry, yes, first half '24, new patient enrollments have continued to strengthen over and above last year.

十多年來的表現使 RUCONEST 成為處方最多的藥物——抱歉，它是美國處方第二多的急性治療藥物，當然，仍然取得了可靠的結果。2024 年上半年—抱歉，是的，24 年上半年，新病患入組人數比去年持續增加。

And in that first half, we actually enrolled 170 new patients, and that represents an increase of 18% over the first half of '23. That, as you would expect, is driven by an increase in new prescribers as well as maintaining our existing ones. And our sales teams added another 36 new prescribers in the first half of '24, taking the totals at over 760, which is an all-time high.

在上半年，我們實際上招募了 170 名新患者，比 23 年上半年增加了 18%。正如您所期望的那樣，這是由新處方醫生的增加以及現有處方醫生的維持所推動的。我們的銷售團隊在 2024 年上半年又增加了 36 名新處方醫生，總數超過 760 名，創歷史新高。

So as you would expect, this translates into that quarterly growth of 23% and that plus 16% versus the first half of last year that Sijmen alluded to. And I think for the attributes I mentioned, the patient population we serve, and also the clinical overview Sijmen gave of where RUCONEST operates in all three pathways, is what -- is why we're very confident that we're well positioned even as the market evolves in the second half of next year. Next slide, please.

因此，正如您所期望的那樣，這意味著季度增長率為 23%，並且與 Sijmen 提到的去年上半年相比增加了 16%。我認為，對於我提到的屬性，我們服務的患者群體，以及 Sijmen 給出的 RUCONEST 在所有三種途徑中運作的臨床概述，就是為什麼我們非常有信心我們處於有利地位，即使明年下半年市場將發生變化。請下一張投影片。

So switching gears now to Joenja. That is, as Sijmen said, a product that we launched on March 31 of last year to treat the ultra-rare disease APDS. And just as a reminder, that's a serious and progressive disease with high mortality. And until Joenja was launched, there was no indicated disease modifying treatment.

所以現在換成Joenja。就是像Sijmen所說的，我們去年3月31日推出的一款產品，用於治療超罕見疾病APDS。提醒一下，這是一種嚴重的進行性疾病，死亡率很高。在 Joenja 上市之前，還沒有明確的疾病緩解治療方法。

As you also know, we were strong out of the gate with the US launch, and patients who were on Joenja were fully reimbursed within days -- within less than a week, in fact. So we continue to make good progress in 2024. At the end of Q2, 91 patients were on Joenja. Another two were in process at the end of the quarter and maybe should come on to therapy early in Q3.

如您所知，我們在美國推出後表現強勁，服用 Joenja 的患者在幾天內就得到了全額報銷——事實上，不到一周。因此，我們在 2024 年繼續取得良好進展。第二季末，有 91 名患者服用 Joenja。另外兩個在本季末正在進行中，也許應該在第三季初開始接受治療。

We added 10 newly diagnosed patients in the quarter, taking us past 230 which is -- close to half the total number that the literature suggests are out there already just 15 months post launch. And we believe it's highly likely, as with any ultra-rare disease, now that we're out there more actively patient finding, that actually there'll be more patients than literature suggests.

我們在本季新增了 10 名新診斷患者，使我們的患者人數超過了 230 名，接近發布後 15 個月內文獻顯示的總人數的一半。我們相信，與任何超罕見疾病一樣，既然我們更積極地尋找患者，那麼實際上患者的數量很有可能比文獻顯示的還要多。

We also have in our pipeline 40 more diagnosed patients whose doctors we're working with to enroll in our program, plus 60 and counting pediatric patients who've been diagnosed in within our pipeline who'll be ready to go on Joenja when we get the label expansion in the fullness of time. So just to summarize Joenja performance, we exited Q2 with $11.1 million in sales, which as Sijmen said is an increase of 16% over quarter one.

我們的管道中還有另外40 名確診患者，我們正在與他們的醫生合作參加我們的計劃，另外還有60 名在我們的管道中被診斷出的兒科患者，當我們得到信息時，他們將準備好繼續使用Joenja標籤在時間充裕時擴張。因此，總結 Joenja 的業績，我們第二季的銷售額為 1,110 萬美元，正如 Sijmen 所說，比第一季成長了 16%。

Next slide, please. Our teams remain, as you would expect, firmly focused on finding new patients and then, when found, mapping and testing, given this is another -- mapping and testing the whole family, given this is not the same dominant disease. In this approach, we have netted an additional 28 patient leads in Q2 that we're now working through to confirm whether they're actually APDS patients.

請下一張投影片。正如您所期望的那樣，我們的團隊仍然堅定地專注於尋找新患者，然後，一旦發現，就進行繪圖和測試，因為這是另一種情況——繪製和測試整個家庭，因為這不是同一種顯性疾病。透過這種方法，我們在第二季度額外獲得了 28 名患者線索，我們現在正在努力確認他們是否確實是 APDS 患者。

And it's through these efforts we remain excited and confident in the value we can bring to the APDS community, both in the US and ultimately globally. And as a result, our financial results keep us on track and are in line with the guidance that we've given for the year.

正是透過這些努力，我們對能夠為美國乃至全球的 APDS 社群帶來的價值仍然感到興奮和充滿信心。因此，我們的財務表現使我們保持在正軌上，並符合我們今年給予的指導。

Now if we look a little bit further forward, I think we've expressed confidence in both RUCONEST and, of course, the future of Joenja; and that's based on a few key factors. So the first is the continued strength of RUCONEST and the reasons that we've already mentioned for why that holds the position it does in the market, which is, of course, underpinned by growth of prescribers, new enrolments, and sales year on year.

現在，如果我們再向前看一點，我認為我們已經表達了對 RUCONEST 以及 Joenja 未來的信心；這是基於幾個關鍵因素。因此，第一個是 RUCONEST 的持續實力，以及我們已經提到的其在市場中保持地位的原因，當然，這得益於處方醫生、新註冊人數和銷售額的逐年增長。

The second is the execution around the Joenja launch and the progress being made in patient finding, family testing, and building a pipeline for future months and years. But also, for Joenja, I just want to expand briefly on some of the products on this slide.

第二個是圍繞 Joenja 上市的執行情況，以及在患者尋找、家庭測試以及為未來幾個月和數年建立管道方面所取得的進展。而且，對於 Joenja，我只想簡單介紹一下這張投影片上的一些產品。

There are another few factors -- another four factors that give us good confidence in the future. So one is the VUS resolution efforts that Sijmen alluded to and that Anurag will discuss. That'll be a significant inflection point for us and should deliver a bonus of patients in 2025. Another important factor is geographic expansion.

還有另外幾個因素──另外四個因素讓我們對未來充滿信心。其中之一就是 Sijmen 提到的 VUS 解決方案，Anurag 將討論該方案。這對我們來說將是一個重要的轉捩點，並且應該會在 2025 年為患者帶來紅利。另一個重要因素是地域擴張。

Right now, we're launching in the US, but we will launch in other key markets which include Japan, the world's second biggest market in the broader APAC region; the United Kingdom; the European Union; Canada; the Middle East. And across these countries and regions, we so far found 900 -- almost 900 patients which represents almost half of the 2,000 of prevalence data would suggest that in these markets and, additionally, where we're currently assessing while we work through those other key markets, the key countries in LatAm and our options there.

目前，我們正在美國推出，但我們將在其他主要市場推出，其中包括日本，它是整個亞太地區的全球第二大市場；英國；歐盟；加拿大;中東。在這些國家和地區，我們迄今為止發現了900 名——近900 名患者，幾乎佔2,000 名患病率數據的一半，這表明在這些市場以及我們目前正在評估的地方，同時我們正在研究其他關鍵因素市場、拉丁美洲的主要國家以及我們在那裡的選擇。

We have -- as I alluded to the pediatric patients and we're building that pipeline up globally and over time, when we get that indication, that will be another bonus of patients that comes through in the future. And then finally, and Sijmen talked about this, the life cycle management of leniolisib to create a pipeline of new indications for the molecule. And as these launches and events occur, we see multiple years of growth ahead from Joenja for APDS and potentially those other indications.

正如我所提到的兒科患者，我們正在全球範圍內建立這一管道，隨著時間的推移，當我們得到這一跡象時，這將是未來患者的另一個好處。最後，Sijmen 談到了 leniolisib 的生命週期管理，以創建該分子的新適應症管道。隨著這些發布和活動的發生，我們看到 Joenja 的 APDS 以及其他潛在適應症將出現多年的增長。

So to expand on these and other related themes, I'd like now to hand over to our Chief Medical Officer, Anurag Relan.

因此，為了擴展這些和其他相關主題，我現在想將時間移交給我們的首席醫療官阿努拉格·雷蘭 (Anurag Relan)。

Thanks, Steve. Now, we can jump to the next slide and we can review some first -- some detail about Joenja.

謝謝，史蒂夫。現在，我們可以跳到下一張投影片，我們可以先回顧一下 Joenja 的一些細節。

So Joenja is FDA approved to treat activated PI3K delta syndrome, or APDS, in adult and pediatric patients who are 12 years of age and older. APDS, as Steve mentioned, is a rare, serious genetic disease caused by hyperactivity in this PI3K pathway; and it's associated with early mortality, often due to lymphoma.

因此，Joenja 已獲 FDA 批准用於治療 12 歲及以上成人和兒童患者的活化 PI3K δ 症候群 (APDS)。正如 Steve 所提到的，APDS 是一種罕見的嚴重遺傳性疾病，由 PI3K 路徑過度活躍引起。它與早期死亡有關，通常是由於淋巴瘤所致。

And it's also important to note that APDS is progressive. So experts state that early treatment is important. Joenja is a PI3K delta inhibitor which regulates this hyperactive signaling pathway that's found in APDS patients.

同樣重要的是要注意 APDS 是漸進的。因此專家表示，早期治療很重要。Joenja 是一種 PI3K δ 抑制劑，可調節 APDS 患者中這種過度活躍的訊號路徑。

The FDA approval last year was based on a randomized pivotal study as well as an open-label, long-term extension study. And Joenja treats the root cause of APDS by correcting the underlying immune defect, thereby addressing both the immune deficiency and immune dysregulation that's found in APDS patients.

FDA 去年的批准是基於一項隨機關鍵研究以及一項開放標籤的長期擴展研究。Joenja 透過糾正潛在的免疫缺陷來治療 APDS 的根本原因，從而解決 APDS 患者中發現的免疫缺陷和免疫失調問題。

The safety of Joenja was evaluated in this placebo-controlled study as well as the long-term study that is just wrapping up, in fact. And no drug related serious adverse events or study withdrawals were seen in these trials.

事實上，Joenja 的安全性在這項安慰劑對照研究以及剛結束的長期研究中得到了評估。在這些試驗中沒有發現與藥物相關的嚴重不良事件或研究退出。

And on the next slide, we can see some of our patient finding efforts. Specifically, we are supporting numerous activities to raise the awareness of APDS and share data about leniolisib and Joenja. So on the left, you can see the medical education types of things that we engage with and the organizations that we're working with to raise this type of awareness.

在下一張投影片上，我們可以看到一些患者尋找工作的努力。具體來說，我們正在支持眾多活動，以提高 APDS 的認識並分享有關 leniolisib 和 Joenja 的數據。因此，在左側，您可以看到我們參與的醫學教育類型的事情以及我們正在合作以提高此類意識的組織。

But also importantly, we have several efforts to help patients get an accurate diagnosis. The first of which is genetic testing. We have a sponsored, no-cost genetic testing program. We have support from genetic counselors and, as Steve mentioned, we're also working to help perform family testing among patients who've already been diagnosed with APDS.

但同樣重要的是，我們做了多項努力來幫助患者獲得準確的診斷。第一個是基因檢測。我們有一個贊助的免費基因檢測計劃。我們得到了遺傳諮詢師的支持，正如 Steve 所提到的，我們也致力於幫助已被診斷出患有 APDS 的患者進行居家檢測。

Because APDS is an inherited disease, we expect to find patients within families. But most APDS patients that have been diagnosed and that are in our databases actually don't have family members diagnosed. So we're supporting clinicians to be able to educate and encourage family testing and also offering patient initiated testing so that patients with family members can get those family members tested easily.

由於 APDS 是一種遺傳性疾病，我們希望在家庭中找到患者。但我們資料庫中大多數已確診的 APDS 患者實際上沒有家庭成員被診斷出來。因此，我們支持臨床醫生能夠教育和鼓勵家庭檢測，並提供患者發起的檢測，以便有家庭成員的患者可以輕鬆地對這些家庭成員進行檢測。

And then on the right side, one large area where we're focused on is when a patient actually goes through all of this process and receives their genetic test results. But unfortunately, it's what's called a variant of uncertain significance, or a VUS. And in essence, this is an inconclusive result that indicates that a patient has a novel gene abnormality, but it is not known whether this abnormality causes APDS or not.

然後在右側，我們關注的一個大領域是患者何時實際經歷所有這些過程並收到他們的基因測試結果。但不幸的是，這就是所謂的意義不確定的變體，或 VUS。從本質上講，這是一個不確定的結果，表明患者存在一種新的基因異常，但尚不清楚這種異常是否會導致APDS。

To help doctors and patients, we have several projects which will enable these VUS results to be definitively classified. So some ways that we do this is, first, what's called Variant Curation, which is collecting known data about the variant. In addition, we also make available and support programs to allow functional testing to occur in patients.

為了幫助醫生和患者，我們有幾個項目可以對這些 VUS 結果進行明確分類。因此，我們做到這一點的一些方法是，首先，所謂的變體管理，即收集有關變體的已知數據。此外，我們還提供並支援允許對患者進行功能測試的計劃。

So actually measuring the activity of the pathway in a patient who has a VUS diagnosis or a VUS result. And then lastly, we're supporting a large-scale experiment, what's called a multiplex assay of a variant effect, which is a high-throughput method whereby we can do in vitro testing of every -- or almost every possible variant that could exist. And this is a study that's going to read out later this year, which we think will be very important in helping these VUS resolution efforts.

因此，實際測量具有 VUS 診斷或 VUS 結果的患者的路徑活性。最後，我們支持一項大規模實驗，即所謂的變異效應多重測定，這是一種高通量方法，我們可以對每一種或幾乎每一種可能存在的變異進行體外測試。這項研究將於今年稍後公佈，我們認為該研究對於幫助解決 VUS 問題非常重要。

And on the next slide, we can talk a little bit more about the scale of the problem, because this -- this VUS problem is something that frustrates patients and doctors and limits the diagnosis of genetic diseases such as APDS. And we are aware of more than 1,200 or approximately 1,200 patients in the US that have received a VUS result in either of the PIK3CD gene or PIK3R1 gene.

在下一張投影片中，我們可以更多地討論問題的嚴重程度，因為這個 VUS 問題讓患者和醫生感到沮喪，並限制了 APDS 等遺傳疾病的診斷。我們知道美國有超過 1,200 名或大約 1,200 名患者已收到 PIK3CD 基因或 PIK3R1 基因的 VUS 結果。

This figure will continue to grow over time because this -- any time that a patient gets a genetic test done, this remains a possibility. And in fact, VUS results or VUS patients are identified at approximately four times the rate of an APDS or what's called a likely pathogenic or pathogenic variant.

隨著時間的推移，這個數字將繼續增長，因為每當患者完成基因測試時，這種情況仍然存在。事實上，VUS 結果或 VUS 患者的識別率大約是 APDS 或所謂的可能致病或致病變異的四倍。

Of course, this is a worldwide problem since these patients who get genetic testing can get this type of results anywhere. And when we look in the literature, what we see is -- across all genes, what we see is that when there are reclassification efforts put in place, that approximately 20% of all of the VUSs that are out there get upgraded to a likely pathogenic or pathogenic or what's called disease causing. And this again is cross-made genes.

當然，這是一個世界性問題，因為接受基因檢測的患者可以在任何地方得到這種類型的結果。當我們查看文獻時，我們看到的是——在所有基因中，我們看到的是，當重新分類工作到位時，大約 20% 的 VUS 會升級為可能的基因致病性或致病性或所謂的致病性。這又是交叉基因。

In the case of APDS, we've done a pilot study with 25 patients who have a VUS result, and we found consistent findings of APDS in five of these 25 patients or 20%. And one of these patients is already preparing for enrollment now.

就 APDS 而言，我們對 25 名具有 VUS 結果的患者進行了一項試驗研究，我們在這 25 名患者中的 5 名（即 20%）中發現了一致的 APDS 結果。其中一名患者現在已經準備入組。

So the key takeaway for us is that there is a significant opportunity to identify incremental patients with APDS through the US resolution efforts. And we'll look for more news for this as the year goes on, especially towards the end of the year.

因此，我們得出的關鍵結論是，透過美國的解決工作，有一個重要的機會來識別更多的 APDS 患者。隨著時間的推移，尤其是接近年底，我們將尋找更多這方面的消息。

On the next slide, we'd like to talk to you a little bit about some of the other efforts beyond the current FDA approval. As we've previously discussed, the CHMP review has been extended to January 2026. There is a single outstanding CMC request, and the CHMP have determined positive clinical benefit as well as safety, which has now concluded.

在下一張幻燈片中，我們想與您談談目前 FDA 批准以外的一些其他努力。正如我們之前討論的，CHMP 審核已延長至 2026 年 1 月。有一個未完成的 CMC 請求，CHMP 已確定積極的臨床效益和安全性，現在已得出結論。

In addition, we are expecting a decision from the UK MHRA later this year. And importantly, no major objections were noted in our Day 70 questions from the MHRA. We've also completed our Japanese clinical study, and we're engaged with PMDA to discuss the filing strategy there following the completion of the necessary studies.

此外，我們預計英國 MHRA 將在今年稍後做出決定。重要的是，MHRA 在第 70 天提出的問題中沒有發現重大異議。我們也完成了日本臨床研究，在完成必要的研究後，我們正在與 PMDA 討論提交策略。

And you've seen in our press release, too, there are significant clinician interest in our Expanded Access and Named Patient Programs, again reflecting the number of patients that are diagnosed out there, but also the unmet need in this patient population. And as previously mentioned, we received marketing authorization in Israel earlier this year.

您在我們的新聞稿中也看到，臨床醫生對我們的擴展訪問和指定患者計劃表現出濃厚的興趣，這再次反映了那裡被診斷的患者數量，但也反映了該患者群體中未得到滿足的需求。如前所述，我們今年稍早在以色列獲得了行銷授權。

We have submissions under review in Canada as well as Australia. And we have two pediatric studies which are also very important because, as we mentioned, this is a progressive disease. We've already identified a significant number of patients who are below the age of 12, and we have now completed enrollment in our first study that goes down to age four. And then there is a second study where enrollment is continuing.

我們正在加拿大和澳大利亞審查提交的資料。我們有兩項兒科研究也非常重要，因為正如我們所提到的，這是一種進行性疾病。我們已經確定了大量 12 歲以下的患者，現在我們已經完成了第一項年齡為 4 歲的研究的入組。然後還有第二項研究，招募仍在繼續。

And then I'll spend the next couple of slides talking to you a little bit about our plans beyond APDS with leniolisib. So when we think about that, we see several development opportunities for leniolisib.

然後我將在接下來的幾張投影片中與您討論我們除了 APDS 和 leniolisib 之外的計劃。因此，當我們思考這一點時，我們看到了 leniolisib 的幾個發展機會。

Just as a review, primary immune deficiencies are a broad group of disorders with several key features. Often, they have a genetic basis. Of course, as an immune deficiency, they have an increased risk of infection, but there's also a subset of these immune deficiencies that also have a feature of immune dysregulation.

如回顧一樣，原發性免疫缺陷是一大類具有幾個關鍵特徵的疾病。通常，它們有遺傳基礎。當然，作為一種免疫缺陷，它們的感染風險會增加，但這些免疫缺陷中還有一部分也具有免疫失調的特徵。

Specifically, that immune dysregulation causes lymphoproliferation, autoimmunity, and other auto inflammatory conditions. And because of that, these PIDs are associated with high morbidity and mortality. APDS, of course, is an example of one of these immune deficiencies with this regulation.

具體來說，免疫失調會導致淋巴細胞增生、自體免疫和其他自身發炎。正因為如此，這些 PID 與高發病率和死亡率有關。當然，APDS 就是這種調節的免疫缺陷之一。

And now we are looking at leniolisib for other PIDs with these same features. The first of which will be -- we're looking at PIDs with immune dysregulation linked to this specific signaling pathway. And we'll talk a little bit about this in the next slide.

現在我們正在尋找具有相同功能的其他 PID 的 leniolisib。第一個是──我們正在研究與這種特定訊號路徑相關的免疫失調的 PID。我們將在下一張投影片中對此進行一些討論。

But these are, again, the patients who have clinical manifestations, disease onset, and severity very similar to APDS. There are no specifically approved therapies for this, and we're beginning with a Phase 2 study imminently.

但這些患者的臨床表現、發病和嚴重程度與 APDS 非常相似。目前還沒有專門批准的治療方法，我們即將開始第二階段研究。

In addition, as Sijmen mentioned, we are working on another disease in the same area. And we're in the midst of obtaining regulatory feedback on the proposed clinical development plan. But in essence, this is another primary immune deficiency with the same clinical phenotype of immune dysregulation, so something obviously very common across these three indications that we're pursuing.

此外，正如 Sijmen 所提到的，我們正在同一領域研究另一種疾病。我們正在收集有關擬議臨床開發計劃的監管回饋。但本質上，這是另一種原發性免疫缺陷，具有相同的免疫失調臨床表型，因此在我們正在尋求的三個適應症中顯然非常常見。

And then on the next slide, you can see some details about the Phase 2 study that is about to start. And this is a Phase 2 proof-of-concept study that's going to be starting soon at the NIH with 12 patients.

然後在下一張投影片上，您可以看到即將開始的第二階段研究的一些詳細資訊。這是一項 2 期概念驗證研究，即將在 NIH 開始，有 12 名患者參加。

These are going to be patients that are known to have hyperactive signaling based on a genetic diagnosis of one of this. And you see there are several of the genes that are involved, including what's called the ALPS-FAS gene, CTLA4, PTEN, as well as a couple of others.

根據其中一項基因診斷，這些患者將被認為具有過度活躍的信號傳導。你會看到有幾個基因參與其中，包括所謂的 ALPS-FAS 基因、CTLA4、PTEN 以及其他幾個基因。

Overall, this represents a treatable population estimated at approximately five per million or which is about three times as large as APDS. This Phase 2 study will look at dosing, but also safety and tolerability; and we'll also have some exploratory efficacy measures here. And the goal is to pick the best dose regimen for the Phase 3 study. And as I mentioned, we're expecting the final IRB approvals evidently which will enable us to start the study this month.

總體而言，這代表了可治療的人群估計約為百萬分之五，約為 APDS 的三倍。這項二期研究將著眼於劑量、安全性和耐受性；我們也將在這裡採取一些探索性的有效性措施。目標是為 3 期研究選擇最佳劑量方案。正如我所提到的，我們顯然期待 IRB 的最終批准，這將使我們能夠在本月開始研究。

So with that, I will turn over to my colleague, Jeroen to review our finance.

因此，我將交給我的同事 Jeroen 來審查我們的財務狀況。

Thank you very much, Anurag. And good morning, good afternoon, everybody. I am starting off with the financial highlights of the second quarter 2024 versus last year.

非常感謝你，阿努拉格。大家早安，下午好。我首先介紹 2024 年第二季與去年相比的財務亮點。

You see that we grew our revenues by 35%, and that was driven by volume of both RUCONEST and Joenja. RUCONEST went up by 23%. Gross profit was fairly stable at 89%. So the margin was at 89%. So the gross profit basically grew in line with our revenues.

您會看到，我們的收入成長了 35%，這是由 RUCONEST 和 Joenja 的銷售所推動的。RUCONEST 上漲了 23%。毛利相當穩定，為89%。所以利潤率為 89%。所以毛利基本上與我們的收入成長一致。

OpEx development. The OpEx went from $65.8 million last year in the period to $70.1 million, and that is reflecting a continued investment in Joenja, both in the US and EU, rest of the world; and also investment in compliance, IT, HR-related areas. And that is to support the growth of the company.

營運支出開發。營運支出從去年的 6,580 萬美元增加到 7,010 萬美元，反映出 Joenja 在美國、歐盟和世界其他地區的持續投資；以及對合規、IT、人力資源相關領域的投資。那就是支持公司的發展。

We see an operating profit that we adjusted. So this is not the reported operating profit, but adjusted for a few one-offs that we had last year, and we had a milestone payment of $10.5 million. So that was a cost, but we also had a gain on the Priority Review Voucher that you may remember.

我們看到我們調整了營業利潤。所以這不是報告的營業利潤，而是根據去年我們的一些一次性利潤進行了調整，我們的里程碑付款為 1050 萬美元。因此，這是一項成本，但您可能還記得，我們​​還獲得了優先審評券的收益。

But basically, on a like-for-like basis, we see that the operating profit gap narrowed from $5.3 million last year to $3.1 million this year. And the net profit was around $1.3 million last year, minus $1.2 million, so a loss this year.

但基本上，在同類基礎上，我們看到營業利潤差距從去年的 530 萬美元縮小到今年的 310 萬美元。去年淨利約130萬美元，減去120萬美元，因此今年出現虧損。

And please be aware for the analysts that in the finance result, we had a gain of $3.4 million this year versus a loss of $1.8 million, and that gain is related to the convertible bonds and a reclassification of the derivative to equity issuance, technical adjustment that you are to be aware of.

請分析師注意，在財務業績中，我們今年的收益為 340 萬美元，而虧損為 180 萬美元，該收益與可轉換債券以及衍生品重新分類為股票發行、技術調整有關。 。

And the overall cash and marketable securities, they went down by almost $42 million. The biggest driver of that was the issue and the repurchase of the bonds. The old bonds had a nominal value of EUR 125 million. The new one that we issued this year had a value of EUR 100 million.

現金和有價證券總額下降了近 4,200 萬美元。最大的推動因素是債券的發行和回購。舊債券的面額為 1.25 億歐元。我們今年發行的新債券價值1億歐元。

And overall, the cash out because of the payback was EUR 30 million. And the remainder is mainly driven by an increase in receivables from higher sales quarter before.

總體而言，由於投資回收而獲得的現金為 3000 萬歐元。其餘部分主要是由於先前銷售季度較高的應收帳款增加所致。

So moving on to the same KPIs, but for the first half of the year, revenues increased by 33%, again, mainly volume from products. RUCONEST went up 16% as was mentioned before. Gross profit for the first half was 87%. Gross margin was 87% and yes, the profit -- gross profit increased to $113.3 million.

因此，繼續採用相同的 KPI，但上半年收入成長了 33%，同樣主要是產品銷售。如同先前所提到的，RUCONEST 上漲了 16%。上半年毛利為87%。毛利率為 87%，是的，利潤——毛利增加到 1.133 億美元。

And OpEx reflects the same basically development as I've just mentioned, so it went up by $15.5 million to $134 million. The adjusted operating loss was roughly the same as it was last year. And the net profit was minus $13.7 million, sorry a loss of $13.7 million, a slight increase versus last year.

營運支出反映了我剛才提到的基本相同的發展，因此增加了 1550 萬美元，達到 1.34 億美元。調整後的營業虧損與去年大致相同。淨利為負1,370萬美元，虧損1,370萬美元，較去年略有成長。

And in the first half year for the reasons that I've just mentioned, went down by $53 million to $161.8 million. A bit of a focus on the Joenja revenues on the next slide. So that's the breakdown of the geographies in the different periods.

由於我剛才提到的原因，上半年下降了 5,300 萬美元，降至 1.618 億美元。下一張投影片重點在於 Joenja 的收入。這就是不同時期的地理分佈。

So quarterly, the revenue almost tripled to $11.1 million and the Q2 2024 revenue mainly came obviously from the US, but also already from the early access and Named Patient Programs outside of the US. And for the half year, we increased the Joenja sales by 44% against last year, and you see the different numbers for region.

因此，按季度計算，收入幾乎增加了兩倍，達到 1,110 萬美元，2024 年第二季的收入顯然主要來自美國，但也已經來自美國以外的搶先體驗和指定患者計劃。在半年裡，我們的 Joenja 銷售額比去年增加了 44%，您會看到不同地區的數字不同。

And by the end of Q2, we have 91 patients on therapy in the US, which meant an increase of eight patients in Q2, and we had a -- in Q1, we had an increase of two patients. And also important to note is that we've had a very stable gross to net discount percentage of 15% versus previous year, i.e. the discounts doesn't play a role in increased sales.

到第二季度末，我們在美國有 91 名患者正在接受治療，這意味著第二季度增加了 8 名患者，而在第一季度，我們增加了兩名患者。另外需要注意的是，與去年相比，我們的毛淨折扣百分比非常穩定，為 15%，即折扣並未對銷售額成長產生影響。

Now looking at the financial guidance on the next slide for 2024. So we reconfirm our revenue guidance of 14% to 20% sales growth being between $280 million and $295 million for the full year.

現在來看看下一張投影片上的 2024 年財務指引。因此，我們再次確認全年營收成長 14% 至 20% 的目標為 2.8 億美元至 2.95 億美元之間。

And obviously, Joenja will be a significant driver, but we also continue -- expect to continue -- recognize growth. And for Joenja, the revenue assumptions are continued growth in patients on paid therapy as we have shown so far this year.

顯然，喬恩賈將成為一個重要的推動者，但我們也將繼續——預計將繼續——認識到增長。對 Joenja 來說，收入假設是接受付費治療的患者數量持續增長，正如我們今年迄今所展示的那樣。

Continued high adherence or compliance rate of 85% and the US pricing with an annual cost of $566,000 and continuing discount of around GTN discount of around 15%. For the second half of 2024, in terms of OpEx, we are making some adjustments and savings, therefore, because of the EMA delay.

85% 的持續高遵守率或合規率，美國定價，年成本為 566,000 美元，GTN 折扣持續約 15%。對於 2024 年下半年，就營運支出而言，由於 EMA 延遲，我們正在進行一些調整和節省。

And with that, I would like to hand over back to Sijmen de Vries for the 2024 outlook.

至此，我想將 2024 年的展望交還給 Sijmen de Vries。

Thank you, Jeroen, and thank you very much. So yes, you have just heard from Jeroen that we are sticking to our total revenue guidance for this year between $280 million and $295 million. Obviously, there were these quarterly fluctuations which are typical.

謝謝你，傑倫，非常感謝你。所以，是的，您剛從 Jeroen 那裡聽說，我們今年的總收入指引將維持在 2.8 億美元至 2.95 億美元之間。顯然，這些季度波動是典型的。

Then you heard about our patient finding efforts on all fronts for Joenja and a number of increasing patients that we have identified and especially the expectations that we currently have on the current base on the basis of current initial results from that small trial with regards to the VUS validation efforts, which amount to about 20% of those 1,200 patients that we expect to become available over the coming year, and of course, will drive significantly the growth of Joenja in the US in '25 and onwards.

然後您聽說了我們為 Joenja 的患者在各個方面所做的努力，以及我們已經確定的越來越多的患者，特別是我們目前根據該小型試驗的初步結果對當前基礎的期望VUS 驗證工作約占我們預計明年可用的1,200 名患者的20%，當然，這將顯著推動Joenja 在25 年及以後在美國的成長。

The [actual US] leniolisib sales, you have heard that there is a great interest and that's obviously, these Named Patient Programs have a lot of administrative procedures and are, of course, not always very fast, but we know that there's quite a few patients in the pipeline waiting for clearance to enter into the program all over the world.

[實際的美國] leniolisib 銷售，你聽說有很大的興趣，很明顯，這些指定患者計劃有很多行政程序，當然，並不總是很快，但我們知道有很多世界各地正在等待批准加入該計劃的患者。

The clinical trials you heard Anurag talk about for the regulatory filings for Japan, the second biggest market in the world. And of course, the pediatric label expansion which will make, again, a bonus of at least 25% of additional patients available for therapy for Joenja.

您聽到 Anurag 談論的針對世界第二大市場日本監管備案的臨床試驗。當然，兒科標籤的擴展將再次帶來至少 25% 的額外患者可以接受 Joenja 治療的額外好處。

You heard about regulatory approval progress, especially in the United Kingdom, where we expect at the end of fourth quarter of this year to hear back from the regulators. And of course, that we are confident that we will be able to speak to EMA again following the submission in January '26 of the remaining -- last remaining question by EMA and the confirmation, of course, that EMA confirmed the clinical benefits and safety of leniolisib makes us very confident as we're looking forward to also getting into the European markets in 2026.

您聽說了監管審批的進展情況，特別是在英國，我們預計在今年第四季末會收到監管機構的回覆。當然，我們有信心在 26 年 1 月 EMA 提交剩餘的最後一個問題並確認 EMA 確認了臨床益處和安全性後，我們將能夠再次與 EMA 交談leniolisib 的上市讓我們非常有信心，因為我們期待在2026年進入歐洲市場。

Then you heard about the initiation of that Phase 2 clinical trial for that second indication which Anurag described for PIDs with immune dysregulation and our plans for the third that have been submitted to the regulators and where we're expecting feedback and hopefully, starting a trial in the not too distant future as well. So in other words, we will then start developing two subsequent indications for Joenja.

然後您聽說了針對第二個適應症的2 期臨床試驗的啟動，Anurag 描述了針對免疫失調的PID 的情況，以及我們已提交給監管機構的第三個適應症的計劃，我們期待反饋並希望開始試驗在不久的將來也是如此。換句話說，我們將開始為 Joenja 開發兩個後續適應症。

And last but not least, the continued focus on potential acquisitions and in-licensing of clinical stage opportunities in rare diseases to further build our portfolio and diversify the company further. And let me tell you, we have a lot of activity going on there, but we are, of course, very precise in terms of what kind of opportunities we actually will bolt on to our company.

最後但並非最不重要的一點是，繼續關注罕見疾病臨床階段機會的潛在收購和許可，以進一步建立我們的產品組合並使公司進一步多元化。讓我告訴你，我們在那裡正在進行很多活動，但我們當然非常精確地了解我們實際上將為我們公司提供什麼樣的機會。

So that concludes the call, and I would like to now go back to the operator and ask and open the floor for questions. Thank you.

通話到此結束，我現在想回到接線員處詢問並開始提問。謝謝。

(Operator Instructions) Sushila Hernandez, Van Lanschot Kempen.

（操作員說明）Sushila Hernandez、Van Lanschot Kempen。

I have a few, if I may. On leniolisib. So it's a first in APDS that you're about to start the Phase 2 studies in PIDs with immune dysregulation and now looking into a third indication. Could you share a bit more on what prompts you going after this third indication? And are you expecting that this would expand addressable patient population significantly?

如果可以的話，我有一些。關於leniolisib。因此，這是 APDS 中的第一次，您即將開始免疫失調 PID 的 2 期研究，現在正在研究第三個適應症。您能否分享更多關於是什麼促使您遵循第三個跡象？您是否期望這會顯著擴大可尋址的患者群體？

And also on Joenja -- or sorry, on the VUS validation studies, could you elaborate on the 12,000 patients identified in the US? How did you find these patients? And how many of these patients would you expect to be diagnosed with APDS and refer to enter treatment?

還有 Joenja，或抱歉，關於 VUS 驗證研究，您能否詳細介紹在美國發現的 12,000 名患者？你是怎麼找到這些病人的？您預計這些患者中有多少人會被診斷為 APDS 並轉診接受治療？

And then lastly, with the MHRA decision near, how many patients have you already identified in the UK and similar to the US, can we expect a large portion of these patients to get on paid therapy in the first half year of the launch?

最後，隨著 MHRA 決定的臨近，您已經在英國確定了多少患者（與美國類似），我們是否可以期望這些患者中的很大一部分在推出的上半年接受付費治療？

Sushila, I'm happily handing over to Anurag to answer your -- to start answering your question. Anurag?

蘇西拉，我很高興將任務交給阿努拉格來回答你的問題——開始回答你的問題。阿努拉格？

Sushila, so with respect to your first question about the Phase 2 study that we're starting. So that one is in patients who have one of the several genes. So the examples I gave were PTEN, CTLA4 or ALPS-FAS. These are genes that are known to be linked through hyperactive signaling and these patients have an immune deficiency as well as an immune dysregulation or the dysregulation of often times a predominant feature in these patients.

Sushila，關於你關於我們正在開始的第二階段研究的第一個問題。因此，其中之一是具有這幾種基因之一的患者。所以我給的範例是PTEN、CTLA4或ALPS-FAS。已知這些基因透過過度活躍的信號傳導聯繫在一起，並且這些患者俱有免疫缺陷以及免疫失調或通常是這些患者的主要特徵的失調。

So that's the first indication that we're pursuing outside of APDS. In addition to that, we are looking at another indication, which is, in fact, even larger. So yes, to your question that this will expand the potential population.

這是我們在 APDS 之外尋求的第一個跡象。除此之外，我們正在研究另一個跡象，事實上，這個跡象甚至更大。所以，是的，對於你的問題，這將擴大潛在人口。

But we're looking at this second indication, which also has immune dysregulation and is a subset of primary immune deficiency, and it has features again similar to APDS. So I think that's something you can see across these three potential indications is that they all have these features of immune dysregulation or autoimmunity and auto inflammation.

但我們正在研究第二種適應症，它也有免疫失調，是原發性免疫缺陷的子集，它具有與 APDS 類似的特徵。所以我認為你可以從這三個潛在跡像中看到，它們都具有免疫失調或自體免疫和自身發炎的這些特徵。

So on the second question was about the US resolution efforts and how we expect that to evolve? So what we've identified already is 1,200 patients. So what does that mean? That means that these are patients who are -- have had a genetic test usually as a part of a primary immune deficiency panel.

那麼第二個問題是關於美國的解決努力以及我們期望它如何發展？我們已經確定了 1,200 名患者。那麼這意味著什麼呢？這意味著這些患者已經進行了基因測試，通常是作為原發性免疫缺陷小組的一部分。

And again, these are patients that have genetic testing most of which that we were not involved with. So they had this genetic testing perform. The result came back with a result that showed either in one of those two genes, this VUS result. And we are aware of this through these databases that we have access to at large genetic testing companies in the US.

再說一遍，這些患者接受了基因檢測，其中大部分我們沒有參與。所以他們進行了基因測試。傳回的結果顯示這兩個基因之一，即 VUS 結果。我們透過美國大型基因檢測公司可以存取的資料庫意識到了這一點。

And we expect that over time, we'll be able to eventually resolve these in the US. Now we know again, historically, looking at other genes, that's about 20% of the VUSs get resolved and converted into disease causing or what's called likely pathogenic or pathogenic.

我們預計，隨著時間的推移，我們最終將能夠在美國解決這些問題。現在我們再次知道，從歷史上看，觀察其他基因，大約 20% 的 VUS 得到解決並轉化為致病基因或所謂的可能致病或致病基因。

The other data point that we have is that we recently tested 25 of these US patients, and we had what's called functional testing performed in these patients, and we found a similar number, so about 20%, five out of the 25 were then upgraded or reclassified into APDS. So when you start doing some simple math, you see that this could significantly increase the population of APDS patients in the US.

我們掌握的另一個數據點是，我們最近對其中25 名美國患者進行了測試，我們對這些患者進行了所謂的功能測試，我們發現了類似的數字，所以大約20%，這25 名患者中的5 名隨後進行了升級或重新分類至 APDS。因此，當您開始做一些簡單的數學計算時，您會發現這可能會顯著增加美國 APDS 患者的數量。

Thanks, Anurag. And with regards to your question about the UK, Sushila, we have currently 11 patients on early access therapy in the UK. There's 61 patients identified, of which 37 are over 12 years of age. So there's already a quite an interesting population in the UK available.

謝謝，阿努拉格。關於你關於英國的問題，Sushila，我們目前有 11 位患者在英國接受早期治療。已確診 61 名患者，其中 37 人年齡超過 12 歲。因此，英國已經有相當有趣的人口可供選擇。

And of course, we expect that once we had the reimbursement, which will take some time and will be somewhere, I suppose, normally in the first half next year, those first patients will go on paid therapy pretty quickly. And of course, by that time, we will have also clarified the VUSs.

當然，我們預計一旦獲得報銷（這將需要一些時間，並且通常在明年上半年），第一批患者很快就會接受付費治療。當然，到那時我們也會澄清 VUS。

And of course, there will be in the UK also patients with the VUSs. So they will be additionally coming potentially on to therapy as well. So that's the sort of numbers for the UK that we currently see. And of course, we continue to seek for patients in the UK, but there's already one per million identified, as you can see from 61 out of a population of roughly 60 million in the UK. I hope that answers your question, Sushila.

當然，英國也有 VUS 患者。因此，他們也有可能接受治療。這就是我們目前看到的英國數字。當然，我們會繼續在英國尋找患者，但已經發現了每百萬分之一的患者，正如您從英國約 6000 萬人口中的 61 人中看到的那樣。我希望這能回答你的問題，蘇西拉。

Yes. And if I may ask one other question. Could you provide an update on your BD efforts? Have you brought in your search?

是的。我可以問另一個問題嗎？您能否提供有關 BD 工作的最新資訊？你帶了你的搜尋嗎？

Yes, we will broaden. We have basically a lot more incoming and also we reached out a lot more because we have now a Chief Business Officer on board since the last quarter of last year. That has led to quite a few interactions, which quite actually even resulted in some non-binding offers that we issued. But of course, when you then look into the diligence following your non-binding offer, you sometimes find stuff that you were not expecting.

是的，我們會擴大範圍。我們基本上收到了更多的訊息，我們也接觸了更多的人，因為自去年最後一個季度以來，我們現在有了一位首席商務官。這導致了相當多的互動，實際上甚至導致了我們發出的一些不具約束力的報價。但當然，當您在不具約束力的要約之後進行盡職調查時，有時您會發現一些意想不到的東西。

And of course, it is also sometimes possible that the other party does not necessarily in the end, want to conclude the deal because it takes 2 to 10 as you know. But yes, there's been a lot of activity and we're virtually all the time assessing an asset under due diligence as we speak. So there's quite a lot of intensity here going on.

當然，有時也有可能對方最終不一定想達成協議，因為如你所知，這需要 2 到 10 個時間。但是，是的，已經有很多活動，就在我們說話的時候，我們幾乎一直在盡職調查下評估資產。所以這裡發生了相當大的強度。

Jeff Jones, Oppenheimer.

傑夫瓊斯，奧本海默。

Right. Congratulations on the quarter, gentlemen. Just two from us. You spoke to it to a degree early on. But with -- for RUCONEST with the anticipated launch of a competing product or competing products in '25 and beyond., what do you see the impact to be? And how are you planning your response?

正確的。先生們，恭喜這個季度。離我們只有兩個人。你很早就在某種程度上談到了它。但是，對於 RUCONEST 來說，預計在 25 年及以後推出一種或多種競爭產品，您認為這會產生什麼影響？您打算如何應對？

And then for leniolisib in Europe or in the EU specifically, can you provide any additional detail on the work that needs to be done in completing your definition of regulatory starting materials? And when would you anticipate being able to respond to the CHMP? Sijmen, I think you almost said January of '26. And in that case, how does that impact your potential approval time line?

然後，對於歐洲或特別是歐盟的 leniolisib，您能否提供有關完成監管起始材料定義所需完成的工作的任何其他詳細資訊？您預計什麼時候能夠對 CHMP 做出回應？Sijmen，我想你幾乎說的是 26 年 1 月。在這種情況下，這對您的潛在批准時間表有何影響？

Jeff, thanks. So let me just first answer your second question about Europe. Yes, we are -- we have already initiated that work, and we have a precise time line, that's why we agreed with the European authorities to actually grant us the extension until '26 -- January '26, that is when we plan to hand in the response. We precisely do what they want.

傑夫，謝謝。首先讓我回答你關於歐洲的第二個問題。是的，我們已經啟動了這項工作，並且我們有一個精確的時間表，這就是為什麼我們與歐洲當局達成一致，實際上允許我們延期到“26 年 1 月”，也就是我們計劃的時間提交答。我們正是按照他們的要求去做的。

So that is also very clear. And then in that case, we expect that probably towards the end of the first quarter, there could be an opinion, which we are quite confident because we have received clinical -- the confirmation of clinical benefit and safety of the product.

所以這也是非常清楚的。然後在這種情況下，我們預計可能在第一季末，可能會出現一個意見，我們對此非常有信心，因為我們已經收到了臨床 - 產品臨床效益和安全性的確認。

And when we have resolved that, we are quite confident about the opinion being positive. So all that said, then it takes two months for the European -- for the European Commission to confirm that.

當我們解決了這個問題後，我們對正面的意見充滿信心。綜上所述，歐盟委員會需要兩個月的時間來確認這一點。

So in other words, you could expect that we entered the European -- the first European market, that's probably Germany in, let's say, the end of the second quarter, beginning of the third quarter of '26. That's basically the time line at this point in time for entering the European markets.

換句話說，你可以預期我們進入了歐洲——第一個歐洲市場，可能是德國，比如說，2026 年第二季末、第三季初。這基本上就是目前進入歐洲市場的時間線。

And then your first question was about -- yes, had a competition for RUCONEST, thank you. Yes. Well, the slide I showed about the hereditary angioedema market is there showing that basically RUCONEST is protein replacement therapy.

然後你的第一個問題是——是的，舉辦了 RUCONEST 競賽，謝謝。是的。嗯，我展示的有關遺傳性血管水腫市場的幻燈片表明 RUCONEST 基本上是一種蛋白質替代療法。

And Stephen alluded to the response rates, consistent response rates on RUCONEST. And Sebetralstat is a product that works on that bradykinin/kallikrein pathway, and has, of course, good results. So it's good news for patients that there is new therapeutic options available. However, we're also aware that some Sebetralstat was tested in a patient population that is generally responsive to Icatibant or Firazyr.

史蒂芬提到了 RUCONEST 上的回應率，一致的回應率。Sebetralstat 是作用於緩激肽/激肽釋放酶途徑的產品，當然具有良好的效果。因此，對於患者來說，有新的治療選擇是個好消息。然而，我們也知道一些 Sebetralstat 在通常對 Icatibant 或 Firazyr 有反應的患者群體中進行了測試。

And it's exactly the difference between the patient population that they tested and the patient population that we are testing, i.e., or that we are serving, i.e., we serve patients that have failed on Icatibant and therefore, they must use RUCONEST because they can't get by on a product that only serves the bradykinin/kallikrein pathway. So in other words, we're pretty confident that this in the end, will not have a significant impact on RUCONEST going forward because we serve that unique patient population.

這正是他們測試的患者群體和我們正在測試的患者群體之間的差異，即我們正在服務的患者群體，即我們為艾替替班失敗的患者提供服務，因此，他們必須使用RUCONEST，因為他們可以'不能依靠僅作用於緩激肽/激肽釋放酶途徑的產品。換句話說，我們非常有信心這最終不會對 RUCONEST 的未來產生重大影響，因為我們為獨特的患者群體提供服務。

Having said that, we are, of course, very aware that in the very beginning of the product being launched, a number of our patients, as we have seen with previous competitive entries will try, of course, whether they can be successful in treating their hereditary angioedema attacks with the oral alternative.

話雖如此，我們當然非常清楚，在產品推出之初，正如我們在之前的競爭產品中看到的那樣，我們的許多患者當然會嘗試，他們是否能夠成功治療他們的遺傳性血管性水腫通過口服替代品發作。

Having said that, you also have to realize that if you take a pill, which is, of course, a much more convenient way, and you actually then see that you have to take a second dose, which is not rarely the case with products like Sebetralstat -- reach the clinical trials correctly, then that patient will continue to suffer enormously from that very, very painful hereditary angioedema attack.

話雖如此，您還必須意識到，如果您服用藥丸（這當然是一種更方便的方法），那麼您實際上會發現必須服用第二劑，這種情況在產品中並不罕見像Sebetralstat一樣——正確地進行臨床試驗，那麼該患者將繼續遭受非常非常痛苦的遺傳性血管性水腫發作的巨大痛苦。

You just have to realize that, right. And then if you take after six hours of suffering, another pill because the symptoms don't necessarily go away or come back, and that is a very different experience than when you are used to RUCONEST, where you actually place the shot, which is admittedly less convenient because you have to basically place the shot, but you are well trained and confident and almost all of our patients do that in the privacy of their own home.

你只需要意識到這一點，對吧。然後，如果您在經歷六個小時的痛苦後服用另一粒藥，因為症狀不一定會消失或復發，這與您習慣使用 RUCONEST 時的體驗非常不同，在 RUCONEST 中您實際注射的是不可否認，不太方便，因為你基本上必須進行注射，但你訓練有素且自信，幾乎我們所有的患者都是在自己家裡的隱私中進行注射。

Then you basically have a normal experience where immediately almost immediately the symptom starts fading away and the attack doesn't come through, and that is basically, if you look at the RUCONEST response rate, you see nothing about breakthrough attacks or hardly anything about or nothing about second shots being necessary.

然後你基本上會有一個正常的體驗，症狀幾乎立即開始消失，攻擊不會發生，基本上，如果你看RUCONEST 回應率，你看不到任何關於突破性攻擊的信息，或者幾乎看不到任何關於或沒有必要進行第二次射擊。

So I think you should really carefully consider those elements when you look at an oncoming new competitor. That is, of course, good news for patients who now have to give stinging and painful subcutaneous shots for instance, Icatibant and then the pill, of course, is a very nice alternative.

因此，我認為當您考慮即將到來的新競爭對手時，您應該認真考慮這些因素。當然，這對現在必須進行刺痛和痛苦的皮下注射（例如艾替班特）和避孕藥的患者來說是個好消息，當然，這是一個非常好的選擇。

But unfortunately, for our patients, they probably will have not the best of experiences in the very -- in most of the cases. And we are therefore confident that RUCONEST will continue to bring them the benefits and the good experience that they have with RUCONEST over a longer time.

但不幸的是，對於我們的患者來說，在大多數情況下，他們可能不會獲得最好的體驗。因此，我們相信 RUCONEST 將在更長的時間內繼續為他們帶來與 RUCONEST 相關的好處和良好體驗。

Again, having said that, we are aware, of course, that people will start trying this drug. But in the long-term, we believe that RUCONEST is there to stay. Hence why, we showed this slide where it is absolutely clear that the missing protein C1 esterase inhibitor is the protein that we replace in a very good dose in a very strong -- in a very high doses and in the bonus injection which RUCONEST have -- the protein is immediately there to actually make the attack go away. Sorry for the long-winded answer, Jeff, but I thought it was necessary to actually explain these ailments here.

話雖如此，我們當然知道人們會開始嘗試這種藥物。但從長遠來看，我們相信 RUCONEST 會繼續存在。因此，我們展示了這張幻燈片，其中非常清楚地表明，缺失的蛋白質 C1 酯酶抑製劑是我們以非常好的劑量、非常強的劑量和 RUCONEST 的額外注射中替換的蛋白質 - - 蛋白質立即出現，使攻擊消失。傑夫，很抱歉回答冗長，但我認為有必要在這裡實際解釋這些疾病。

Alistair Campbell, Royal Bank of Canada.

阿利斯泰爾·坎貝爾，加拿大皇家銀行。

I just really wanted to talk a little bit about Joenja. You've obviously got quite a significant pool of diagnosed patients in the US. Can you talk about the pathway from getting a diagnosed patients to be basically enrolled? What are the key hurdles you have to overcome and then how onerous is that process?

我真的很想談談喬恩賈。顯然，美國有相當多的確診患者。您能談談從確診患者到基本入組的路徑嗎？你必須克服的關鍵障礙是什麼？

Yes. So I hand over to Steve in the (inaudible).

是的。所以我把任務交給史蒂夫（聽不清楚）。

It is, as you would expect, can be quite convoluted, but we try to make that as smooth as possible through our own patient services. So essentially, the first part of the process is obviously the patient coming in. That can take some years sometimes, although we're calling all those key centers of excellence.

正如您所料，這可能相當複雜，但我們嘗試透過我們自己的患者服務使這一切盡可能順利。所以本質上，這個過程的第一部分顯然是病人進來。儘管我們將所有這些關鍵的卓越中心稱為關鍵的卓越中心，但有時這可能需要幾年的時間。

Then once the symptom is reviewed and the patient is worked up, it's the genetic test and if they get that positive test, then they immediately can go into our enrollment program where we'll start to work with their payer on getting them approved.

然後，一旦檢查了症狀並對患者進行了檢查，就進行基因測試，如果他們得到陽性測試，那麼他們可以立即進入我們的註冊計劃，我們將開始與他們的付款人合作以獲得批准。

And we've seen a mixed picture there with the payers. But what I will say is that our approval rate is at 98%. And that 2% is they're in NDC blocks. So they will eventually come on stream. They just take a little longer to actually pull through the entire market access or managed care system.

我們看到付款人的情況好壞參半。但我要說的是，我們的支持率是98%。那 2% 是在 NDC 區塊中。所以它們最後會投產。他們只是需要更長的時間來真正完成整個市場准入或管理式醫療系統。

So that's the kind of simplified version, which is patient comes in, patient gets diagnosed. They work with outpatient services and then land on therapy.

這就是一個簡化的版本，病人進來，病人得到診斷。他們與門診服務合作，然後接受治療。

What can sometimes slow things down, and that's why you see a bolus in the first part of the launch and then slower. But nevertheless, still growth as we move forward before those bigger inflection points that Anurag referred to with the US population and the pediatrics, is we're now into those groups where there may be other complications. So perhaps they're on chemotherapy or for whatever reason there are other comorbidities that are being managed.

有時會減慢速度，這就是為什麼您會在發射的第一部分看到推注，然後速度變慢。但儘管如此，隨著我們在阿努拉格提到的美國人口和兒科更大的拐點之前前進，我們現在仍然進入那些可能存在其他併發症的群體。因此，也許他們正在接受化療，或者出於某種原因正在治療其他合併症。

So they remain within our diagnosed pool, and we monitor and we worked already with the doctor and when we can the patient tell them the right time they can move on to therapy. So I think that's the high-level overview of what happens with managed care. That's where we are today with the existing pool of patients before we get those next big boluses in '25, '26 and beyond. Is that okay Alister? Was there any other questions on that?

因此，他們仍然留在我們的診斷池中，我們會進行監測，並且我們已經與醫生合作，當我們可以讓患者告訴他們正確的時間時，他們可以繼續接受治療。所以我認為這就是管理式醫療發生的情況的高級概述。這就是我們今天在現有患者池中所處的情況，然後我們將在 25 年、26 年及以後進行下一次大劑量注射。阿利斯特可以嗎？對此還有其他問題嗎？

Yes, maybe just -- can I just follow-up on that? So in terms of those like the -- you've got -- let's say, pool of 50 diagnosed patients over 12. So you have some of these hurdles to maybe sort of get them on therapy. Do you have any kind of sense of the pace at which you see them sort of come on to therapy ahead of the boluses to come? I'm just trying to get a sense of the temper we should be thinking about in terms of patient adds before some of those big boluses you've pointed come through?

是的，也許只是──我可以跟進一下嗎？因此，就諸如 50 名 12 歲以上確診患者而言。所以你可能會遇到一些障礙來讓他們接受治療。您是否對他們在推注之前接受治療的速度有任何感覺？我只是想了解一下，在您指出的一些大推注之前，我們應該考慮一下患者的脾氣？

It's -- I would love to give you a specific answer on that, unlike the mass markets I've worked on in the past, these are very low absolute numbers. So for example, we added eight this quarter. I think it was two last quarter, and we have these ones that we're working through today. The good news is we would expect that to keep going. But it just -- it won't be linear.

我很樂意就此問題給你一個具體的答案，與我過去研究過的大眾市場不同，這些絕對數字非常低。例如，我們本季增加了 8 個。我認為上個季度有兩個，我們今天正在處理這些問題。好消息是我們預計這種情況會持續下去。但它只是——它不會是線性的。

Whereas if we say, cholesterol lowering, you can very easily predict that. With this, I'll give you some example. There was literally one patient who's going to come in, in July because they needed to finish their school year first.

而如果我們說，降低膽固醇，你可以很容易地預測這一點。說到這裡，我舉一些例子給你聽。確實有一個病人會在七月來，因為他們需要先完成學年。

But what I can say is that those over 40 patients are close to 50 right now that we're working through, we know every detail there is some pretty much know about where they're at and what the tipping point will be, even down to patients whose 12th birthday will be this year.

但我能說的是，我們正在解決的 40 多名患者現在接近 50 名，我們知道每一個細節，有些人幾乎知道他們所處的位置以及轉折點是什麼，甚至是下降的致今年12 歲生日的患者。

We're ready in front to go and speak to those physicians and say, okay, the 12th birthday is coming up, are they in the right place now? Are they the right weight, et cetera, et cetera. But the simpler answer is I couldn't give you a good prediction on the pace of which that all those patients will come in and over what time period. Only that we're working very hard on every single one of them on a very regular basis and in a very detailed way.

我們已經準備好去跟那些醫生談談，好吧，12 歲生日快到了，他們現在在正確的地方嗎？它們的重量是否合適，等等等等。但更簡單的答案是，我無法給您一個很好的預測，即所有這些患者的就診速度和時間段。只是我們非常定期、非常詳細地對每一項工作都非常努力。

(Operator Instructions) Simon Scholes, First Berlin.

（操作員說明）西蒙·斯科爾斯，第一柏林。

I've got two. The first is on the second indication for leniolisib. I mean I gather that you're expecting the Phase 2 data early next year. Once you get the Phase 2 data, I was just wondering what the further timetable might look like as regards to Phase 3? And then the second question is on approval in Canada and Australia. I mean you're now talking about 2025 for both markets. Can you give us a slightly more precise timing for those markets? I mean is it like to be H1 or H2?

我有兩個。第一個是關於 leniolisib 的第二個適應症。我的意思是，我了解到您正在等待明年初的第二階段數據。一旦獲得第二階段的數據，我只是想知道第三階段的進一步時間表可能是什麼樣的？第二個問題是加拿大和澳洲的批准情況。我的意思是，您現在談論的是兩個市場的 2025 年。您能為我們提供這些市場的更準確的時間安排嗎？我的意思是H1還是H2？

Yes. Maybe, first of all, Simon, I think you're that optimistic here with regards to when this Phase 2 study reports. Obviously, it's an open label study. But I think you should more think about and, Anurag, correct me if I'm wrong here. But by the end of next year is probably a more likely thing that we will have insights and can actually formulate the -- how we are talking about with regards to the following Phase 3 trial.

是的。也許，首先，西蒙，我認為你對第二階段研究報告的時間持樂觀態度。顯然，這是一項開放標籤研究。但我認為你應該多考慮一下，如果我錯了，阿努拉格請糾正我。但到明年年底，我們更有可能獲得見解，並能夠真正制定我們正在談論的有關接下來的第三階段試驗的方式。

And secondly, we don't necessarily always give detailed information on regulatory interactions because they can be a little bit unpredictable. But you're right, you have seen this -- we are anticipating that we have got regulatory action in 2025 from those and not necessarily in 2024. So basically, yes, that is correct. I hope I answered to those questions.

其次，我們不一定總是提供有關監管相互作用的詳細信息，因為它們可能有點不可預測。但你是對的，你已經看到了這一點 - 我們預計我們將在 2025 年採取監管行動，而不一定是在 2024 年。所以基本上，是的，這是正確的。我希望我回答了這些問題。

(Operator Instructions) As there are no further questions, I would now like to hand back to Sijmen de Vries for any closing remarks.

（操作員說明） 由於沒有其他問題，我現在想請 Sijmen de Vries 發表結束語。

Thank you very much. And thanks, ladies and ladies and gentlemen, for attending our conference. As you've seen, we've posted some stellar results for both the second quarter and the first half of this year. We illustrated to you that we are very confident that RUCONEST will be an important driver for our financials for the coming years to come.

非常感謝。感謝女士們、女士們、先生們參加我們的會議。正如您所看到的，我們在今年第二季和上半年都發布了一些出色的業績。我們向您表明，我們非常有信心 RUCONEST 將成為我們未來幾年財務狀況的重要驅動力。

Given the fact, that we serve this very unique patient population despite expected competitive entries. We also showed you that in -- and although, indeed, as you heard, the growth for Joenja is continuing this year, it is not going to be linear from Stephen, but that we have a big bolus of patients expecting to come online in the United States from next year -- beginning of next year onwards because of the expected outcomes of the VUS, which will, of course, being an important growth stimulus for Joenja in '25 and '26.

鑑於事實上，儘管預期競爭激烈，但我們仍為這個非常獨特的患者群體提供服務。我們也向您展示了——雖然，事實上，正如您所聽到的，Joenja 今年的增長仍在繼續，但它不會與斯蒂芬呈線性增長，但我們有大量患者預計將在 2019 年上線。由於VUS 的預期結果，從明年年初開始，這將成為Joenja 在25 年和26 年的重要成長刺激因素。

You also heard that we expect that we get a positive discussion with the Europeans in the first quarter of '26 and that we are working very hard on getting our pediatrics and our Japanese trials worked out and so that we can actually submit to the Japanese authorities and enter the second biggest market in the world and have another at least 25% bolus of additional patients under the age of 12 available for commercialization, both in that at that point in time, of course, in the US and the Rest of the World and the European Union where we expect to be on the market by then.

您還聽說我們希望在 26 年第一季與歐洲人進行積極的討論，並且我們正在非常努力地完成我們的兒科和日本試驗，以便我們能夠真正向日本當局提交申請並進入世界第二大市場，並有至少25% 的12 歲以下患者可用於商業化，當然，無論是在美國還是世界其他地區以及我們預計屆時將進入市場的歐盟。

And then you heard, of course, how we are going to build a pipeline and a product by starting with a Phase 2 study in -- for PIDs with immune dysregulation as a second indication for Joenja imminently. And we are, as of course, waiting for regulatory feedback for the start of a third indication, also a Phase 2 trial that we expect to start in the not too distant future.

當然，然後你聽說了我們將如何透過針對免疫失調的 PID 的 2 期研究開始建立管道和產品，作為 Joenja 即將推出的第二個適應症。當然，我們正在等待監管部門的回饋，以啟動第三個適應症，這也是我們預計在不久的將來開始的第二階段試驗。

And last but not least, about the intensifying efforts to in-license or acquire new opportunities so that we can broaden our portfolio in the rare disease and build this global rare disease company. So thank you very much for being here, and we look forward to updating you on our expectation at the end of October when we have our third quarter results. Thank you very much.

最後但並非最不重要的一點是，加大力度引進許可或獲得新機會，以便我們能夠擴大我們在罕見疾病領域的投資組合，並建立這家全球罕見疾病公司。非常感謝您來到這裡，我們期待在 10 月底公佈第三季業績時向您通報我們的最新預期。非常感謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。