Molecular Partners AG (MOLN) 2024 Q2 法說會逐字稿

Good day and welcome to the Molecular Partners first half 2024 results conference call. (Operator Instructions) Please note today's event is being recorded. I'd now like to turn the conference over to Seth Lewis, Senior Vice President, Investor Relations. Please go ahead.

美好的一天，歡迎參加 Molecular Partners 2024 年上半年業績電話會議。（操作員說明）請注意今天的活動正在錄製中。現在我想將會議交給投資者關係資深副總裁 Seth Lewis。請繼續。

Thanks, Rocco. Good morning and good afternoon, everyone. Welcome to the Molecular Partners first half 2024 results call. My name is Seth Lewis, Senior Vice President of Investor Relations, and I'm joined this morning by Patrick Amstutz, CEO; Philippe Legenne, Chief Medical Officer; Daniel Steiner, Senior Vice President, Research and Technology; and Robert Hendriks, Senior Vice President of Finance.

謝謝，羅科。大家早安，下午好。歡迎參加 Molecular Partners 2024 年上半年業績電話會議。我是投資者關係高級副總裁塞斯·劉易斯 (Seth Lewis)，今天早上與我一起參加的還有首席執行官帕特里克·阿姆斯圖茨 (Patrick Amstutz)。 Philippe Legenne，首席醫療官； Daniel Steiner，研究與技術資深副總裁；和財務高級副總裁 Robert Hendriks。

Management will take a few minutes to make brief remarks, and then we will open up for question and answer period. If you have not had a chance to review the H1 press release, please feel free to do so on our website, www.molecularpartners.com. Also on the website is today's updated presentation which management may refer to and speaking or answering your questions.

管理層將花幾分鐘時間進行簡短發言，然後我們將進入問答時間。如果您還沒有機會閱讀 H1 新聞稿，請隨時造訪我們的網站 www.molecularpartners.com。網站上還有今天更新的演示文稿，管理層可以參考並發言或回答您的問題。

As a reminder, today's call is being recorded. Today's discussion and presentation will contain certain forward-looking statements based on the information available to Molecular Partners as of the date of this release, and actual results may differ materially from what discussed today.

提醒一下，今天的通話正在錄音。今天的討論和演示將包含基於截至本新聞稿發布之日 Molecular Partners 所掌握資訊的某些前瞻性陳述，實際結果可能與今天討論的內容有重大差異。

With that, I'm happy to turn the call over to Patrick Amstutz, CEO to review the highlights and outlook for the company. Please go ahead.

至此，我很高興將電話轉給執行長 Patrick Amstutz，以回顧公司的亮點和前景。請繼續。

Thanks, Seth, for the nice introduction and a very warm welcome from my side to everyone on the call, investor, analysts and people interested in our update. As Seth alluded to, we have the slides on our home page and what we will do is not go through every slide, but really jump to the highlights. We will see which slide number we are on and go rather fast that we have more time in the end to answer your question.

感謝賽斯的精彩介紹，以及我這邊對電話會議中的每個人、投資者、分析師和對我們最新動態感興趣的人的熱烈歡迎。正如塞斯所提到的，我們的主頁上有幻燈片，我們要做的不是瀏覽每張幻燈片，而是真正跳到亮點。我們將查看我們正在播放的幻燈片編號，並且速度會相當快，以便最終我們有更多時間來回答您的問題。

With that, I will jump to slide number 5, the corporate highlights of the first half of 2024. The first half was really active, we progressed a lot of programs and I will start with 533, where we have great progress. We have reached a top dose and despite not reaching the optimal exposure or concentration due to half-life and target mediated drug disposition, we see activity and Philippe will allude to that. And we also see a way forward to dose higher and more frequent.

接下來，我將跳到第 5 張投影片，這是 2024 年上半年的企業亮點。上半場非常活躍，我們取得了很多進展，我將從 533 開始，我們取得了巨大的進展。我們已經達到了最高劑量，儘管由於半衰期和靶標介導的藥物處置而沒有達到最佳暴露或濃度，但我們看到了活性，菲利普將提到這一點。我們也看到了一種提高劑量和頻率的方法。

On the same with the immune cell engager from I go to 621 where we have update to the molecule presented at EHA, and this is a cKit targeting switch molecule, a very innovative way of killing HACTs and LSE and best applied in for stem cell conditioning.

與我轉到621 的免疫細胞接合器一樣，我們對EHA 上展示的分子進行了更新，這是一種cKit 靶向開關分子，是一種殺死HACT 和LSE 的非常創新的方法，最適用於幹細胞調理。

On 317, that's where we have finalized the clinical trial for our tumor, localized CD40 agonist we have a nice safety profile and we can conclude biological proof of concept and are looking into combination settings going forward.

在 317 上，我們已經完成了腫瘤局部 CD40 激動劑的臨床試驗，我們擁有良好的安全性，我們可以得出概念的生物學證明，並正在研究未來的組合設定。

And I do end with closet and most exciting part which is the Radio-DARPins whereas MPO712, we have a first candidate that's the DLL3 targeting DARPin optimized for low kidney uptake and high tumor accumulation. And that is in a collaboration with Orano Med, where we struck a strategic alliance earlier in the year to work together on targeting net based radio isotopes by a DARPins. And we call that a strategic collaboration as we believe led access circumvents key limitations of other isotopes, including supply, and Dony can speak a bit more about that.

最後，我要以最令人興奮的部分結束，即 Radio-DARPin，而 MPO712，我們的第一個候選藥物是針對 DARPin 的 DLL3，針對低腎攝取和高腫瘤積累進行了優化。這是與 Orano Med 的合作，我們在今年稍早建立了策略聯盟，共同致力於透過 DARPins 瞄準基於網路的放射性同位素。我們稱之為策略合作，因為我們相信主導獲取可以規避其他同位素的關鍵限制，包括供應，多尼可以對此多談一點。

On the operating side, we are in a strong financial position with $CHF59 million in cash and that puts our runway into 2027, which is a bit further than we had so far on our chart.

在營運方面，我們的財務狀況良好，擁有 5,900 萬瑞士法郎的現金，這使我們的計劃進入 2027 年，這比我們迄今為止的計劃要遠一些。

Before handing over to Philippe, I go to slide, I think it's now number 6, where I have a really personal nice announcement to make. I'm very happy about it, which is that Philippe Legenne, have been promoted to full Chief Medic after serving a year in that role as acting Chief medic.

在交給 Philippe 之前，我先去投影片，我想現在是第六張投影片，我有一個非常個人化的好消息要宣布。我對此感到非常高興，菲利普·萊根 (Philippe Legenne) 在擔任代理首席軍醫一年後，已晉升為正式首席軍醫。

And he really deserves this role on the one hand by impressing recruitment I mean, our trials, the cohorts were full when they were open and the execution was flawless. And for us in my new two CEO of biotechs, we know how important that is. That's where you build all the credibility. That's where you build all the value. So big thanks to Philippe and his team for that just excellent execution.

一方面，他真的值得這個角色，因為他給招募留下了深刻的印象，我的意思是，我們的試驗，當他們開放時，隊列已經滿了，而且執行力是完美的。對於我們新任的兩位生物技術執行長來說，我們知道這有多重要。這就是你建立所有信譽的地方。這就是你創造所有價值的地方。非常感謝菲利普和他的團隊的出色執行。

And that is only possible because Philips has a gift to engage investigators into our trials. So they think of our trials first, they understand the importance and he's really a strong networker there, and it doesn't really end on the investigator side. It includes the KOLs that he brings into review our data, help us on the next steps. And that's also how we came about, how to move forward on 533, with the top global experts in the room.

這之所以可能，是因為飛利浦有能力讓研究人員參與我們的試驗。因此，他們首先考慮我們的試驗，他們了解其重要性，而且他確實是那裡的強大網路人員，而且它並沒有真正結束於調查員方面。其中包括他邀請的 KOL 來審查我們的數據，幫助我們採取後續行動。這也是我們的初衷，如何與全球頂尖專家一起推進 533。

Given that he is not an only an AML specialist, but he has a really broad understanding of tumors. He can apply that also to our earlier pipeline of DLL3 radiotherapy. So in that sense, he is in a perfect position to apply his knowledge, skills and with his team bring forward the molecules in our pipeline and very profits also from the industry background with Novartis, GSK and Amgen.

鑑於他不僅是 AML 專家，而且對腫瘤有著非常廣泛的了解。他也可以將其應用於我們早期的 DLL3 放射治療流程。因此，從這個意義上說，他處於一個完美的位置，可以運用他的知識、技能，並與他的團隊一起推進我們管道中的分子，並從諾華、葛蘭素史克和安進的行業背景中獲益匪淺。

And as I just pointed out, is also his personal dedication, passion and his team leadership and the way he works not only with the KOLs but also with us and his team is inspiring every day. And it's a great pleasure to have you as full Chief Medic now. And it's also great pleasure to give you the work to give us an update on the 533 molecule.

正如我剛才指出的，他的個人奉獻精神、熱情和團隊領導力以及他不僅與 KOL 合作，而且與我們和他的團隊合作的方式每天都鼓舞人心。很高興您現在擔任正式的首席軍醫。我們也很高興為您提供有關 533 分子的最新資訊。

Many thanks, Patrick. You know, I'm glad it's audio, not video or otherwise, you would see blushing, I want to thank for this and against its honor to with this MP team and to help you and lead and contribute to push our progress so clinic and having good fortune to be able to reach and work with the worldwide experts.

非常感謝，派崔克。你知道，我很高興這是音頻，而不是視頻或其他方式，你會看到臉紅，我要為此表示感謝，並感謝它與這個MP 團隊一起幫助你、領導並為推動我們的進步做出貢獻，所以診所和很幸運能夠接觸到世界各地的專家並與他們一起工作。

So I will want to give you in a fairly quickly -- quick mode an update on the 533 and basically in my few minutes here, I will refer mainly to the slide number 14. We can spend more time later on to go through Q&A. Come back 20 slides where there will be a question, but basically, I want to give you a summary and outlook of where we are.

因此，我想以相當快的速度向您提供 533 的更新，基本上在我的幾分鐘內，我將主要參考第 14 號投影片。稍後我們可以花更多時間進行問答。回來 20 張投影片，其中會有一個問題，但基本上，我想給您一個總結和我們目前狀況的展望。

So on that slide 14. Basically, I will dive -- I have mainly four points of update on the program. First of all is that we are recording here of [record 6]. And as we speak, we are, account towards 7 now. But basically, we have seen an ongoing and a very, very steady engagement from the (inaudible) twos and basically there is a very good dynamics on this trial recruitments from the very beginnings up to now.

所以在幻燈片 14 上。基本上，我會潛水——我對程式的更新主要有四點。首先是我們在這裡記錄的[記錄6]。就在我們說話的時候，我們現在已經接近 7 點了。但基本上，我們看到了（聽不清楚）兩歲的持續且非常、非常穩定的參與，基本上從一開始到現在，這次試驗招募都有一個非常好的動態。

What have we observed, we have observed first is that an acceptable safety profile, a manageable safety profile with mainly for IRR and CRS as would be expected on the T-cell engager and you see them, basically in the first cycle and a rapid decrease in second cycle onwards.

我們觀察到的，我們首先觀察到的是，可接受的安全狀況，可管理的安全狀況，主要針對IRR 和CRS，正如T 細胞接合器所預期的那樣，您會看到它們，基本上在第在一個週期中，並且快速下降從第二個週期開始。

We've seen indisputable activity, reduction in milo blast on half of the patient population, which fit in on 25%, more than 50% reduction in dose. And that translates into yield and responses from with one responder per cohort from via 3, 4, 5, and 6.

我們已經看到了無可爭議的活動，一半患者群體的米洛母細胞減少，相當於劑量減少了 25%，超過 50%。這轉化為來自第 3、4、5 和 6 組每個隊列一名響應者的產量和響應。

So individual activity, yes, but in a way, we need to have more than that to be completely satisfied and to qualify that we would unlock the potential of that compound. And when observed in greater detail, in fact, we realized still have to improve the exposure of the product.

所以個人活動，是的，但在某種程度上，我們需要有更多的東西才能完全滿足，並有資格釋放該化合物的潛力。而當更詳細地觀察時，實際上我們意識到仍然需要提高產品的曝光度。

We -- in fact, we need to increase the exposure and have it more durable in order to increase the response rate with depth of response and the durability. And therefore we are further amending the protocol for, again, a higher and more frequent dosing, especially in the first week and to identify this exposure.

事實上，我們需要增加曝光並使其更持久，以便提高反應速度、反應深度和持久性。因此，我們正在進一步修改方案，再次進行更高、更頻繁的給藥，特別是在第一周，並確定這種暴露。

And we will share later this year at end and also in especially in the next year of 2025 results from these (inaudible) obviously, we will read those results very carefully to see whether we can truly gauge the future development and moving to the expansions in Phase 2 steps. So that's my update. And again, I'm very glad to go into more detail in the Q&A part of the discussion of the session.

我們將在今年晚些時候，特別是在明年 2025 年分享這些（聽不清楚）的結果，顯然，我們將非常仔細地閱讀這些結果，看看我們是否能夠真正衡量未來的發展並轉向擴展第2階段步驟。這就是我的更新。再次，我很高興在會議討論的問答部分中詳細介紹。

Thanks, Philip. And with that, I will then handover to an update more on the radio side of Donny Steiner, who is with his colleagues leading that effort.

謝謝，菲利普。接下來，我將向唐尼·斯坦納 (Donny Steiner) 匯報無線電方面的更多最新情況，他和他的同事正在領導這項工作。

And thanks, Patrick. So happy to guide you through these updates -- top-line update on the Radio DARPin therapy with the first candidate, as Patrick already introduced MP0712, the first program moving towards the clinic.

謝謝，派崔克。很高興引導您完成這些更新——關於第一個候選藥物的 Radio DARPin 療法的頂級更新，因為帕特里克已經推出了 MP0712，這是第一個走向臨床的項目。

So for those of you who are on this slide. I'm jumping now to slide number 25. And as I said, top line update here, and I'm super proud about the great progress the team has made to successfully move the RDT platform to profile with an attractive biodistribution profile in terms of tumor, to kidney, to blood ratios.

對於那些在這張幻燈片上的人來說。我現在跳到第 25 號幻燈片。正如我所說，這裡是最重要的更新，我對團隊的巨大進展感到非常自豪，他們成功地將 RDT 平台轉移到在腫瘤、腎臟和血液比率方面具有有吸引力的生物分佈特徵。

And we can dive into Q&A way more into the details if you're interested, it is a question. So year to date on MP0712, which has been selected as the lead candidate for targeted lead 212 DLL3 had been presented at [Essilor] and really showcase the strength of the platform that we have been establishing.

如果你有興趣，我們可以更深入地進行問答，這是一個問題。今年迄今為止，MP0712（已被選為目標先導 212 DLL3 的主要候選藥物）已在 [Essilor] 上展示，真正展示了我們一直在建立的平台的實力。

And of course, the IND-enabling activities are now ongoing before Orano Med and the initial clinical data is expected in 2025. So as I keep mentioning, super excited for the team has achieved here and even more excited about the opportunities that this opens up to, of course, we are advancing 0712 and the current pipeline together with Orano Med, which we see as a very strong and committed collaboration partner, but also with Novartis, where we have this -- an ongoing collaboration since the start of our activities in the radioligand space.

當然，在 Orano Med 之前正在進行 IND 授權活動，預計將於 2025 年獲得初步臨床數據。因此，正如我不斷提到的，我們對團隊在這裡的成就感到非常興奮，對這帶來的機會更加興奮，當然，我們正在與歐安諾Med 一起推進0712 和當前的管道，我們認為歐安諾Med 是一個非常強大的公司。

And we are evolving, expanding the platform for next differentiated RDT programs. And this what I'm looking for most and I'm going to tell you a bit more about this on the next slide, too, if you move to slide 26. So this is just an initial I say glimpse, a preview of how we are thinking about leveraging the DARPin properties to really build differentiated RDT and RDT portfolio, and RDT candidate with a high level of differentiation.

我們正在不斷發展和擴展下一個差異化 RDT 專案的平台。這就是我最尋找的內容，如果您轉到投影片 26，我也會在下一張投影片上告訴您更多相關資訊。所以這只是我所說的初步一瞥，預覽我們如何考慮利用 DARPin 屬性來真正建立差異化的 RDT 和 RDT 投資組合，以及具有高水平差異化的 RDT 候選產品。

So if you look at the top panel of this slide for me, this is just two examples, then there is more and we're going to tell you more about this in the months and the future to come.

因此，如果您查看我這張投影片的頂部面板，這只是兩個範例，然後還有更多範例，我們將在未來幾個月和未來告訴您更多有關此內容的資訊。

This is two examples of how we are thinking about targeting proteins, tumor targets, which are difficult to address this classical I say radioligand in the sense of low molecular weight or peptide. And one cloud, as depicted on the left hand side is like where you have a high amount of soluble antigen, which is interfering shed soluble antigen, which is in the interferon in the tumor uptake. And there we found an approach to target specifically the membrane-bound forms only there we're building on the selectivity and the binding properties of the DARPin.

這是我們如何考慮靶向蛋白質、腫瘤標靶的兩個例子，這些標靶很難解決這個經典的低分子量或勝肽意義上的放射性配體。一朵雲，如左邊所示，就像有大量可溶性抗原，這是乾擾脫落的可溶性抗原，它存在於腫瘤攝取的干擾素中。在那裡，我們發現了一種專門針對膜結合形式的方法，我們只是在 DARPin 的選擇性和結合特性的基礎上進行建構。

And on the right hand side, you see another class of targets, we are heavily investing to like I guess we've had have homologues high identity on healthy cells where you by just using the selectivity of DARPin can be tumors specifically tied to the DARPin by only recognizing the specific spots.

在右側，您可以看到另一類目標，我們正在大力投資，就像我猜我們在健康細胞上有高度同一性的同源物，您只需使用DARPin 的選擇性就可以成為與DARPin 特異性相關的腫瘤僅辨識特定點。

And of course, on the other side, and that's at the lower part of the of the slide, we are building on the deep expertise we have built in making multi-specific molecules here in the context of having a broader and more homogeneous former and distribution to address heterogeneity, which we believe is especially in the context of short-range alpha emitting particles a key aspect to consider.

當然，在另一邊，即幻燈片的下部，我們正在建立在製造多特異性分子方面所積累的深厚專業知識的基礎上，擁有更廣泛和更均質的前體和前體。質性，我們認為這是特別是在短程阿爾法發射粒子的背景下需要考慮的關鍵方面。

And there and that's what we see, on the left hand side, we are not thinking mainly about classical multi-specific SDR, and is used in our IO project, it's really more building on the concept of having two parentals in one single DARPin domain, which we call the two in one, which keeps the size of the molecules small by maintaining all the binding properties of the DARPin.

這就是我們所看到的，在左側，我們主要考慮的不是經典的多特定SDR，而是在我們的IO 項目中使用的，它實際上更多地建立在一個DARPin 域中擁有兩個父母在的概念之上，我們稱之為二合一，它透過保持 DARPin 的所有結合特性來保持分子的大小較小。

So this is something just a teaser in what to come in the next 12 months looking very much forward to give you more details on that starting to present on those approaches on conferences of this, just like giving you a bit of an outlook of what we are up for. And with this, I would like to hand over to Robert to give you an insight into our financial forecast.

因此，這只是未來 12 個月內即將發生的事情的預告片，非常期待為您提供更多有關開始在會議上介紹這些方法的詳細信息，就像給您一些我們的展望一樣準備好了。在此，我想請羅伯特向您介紹我們的財務預測。

Thank you, Danny and prior speakers. Before we move to the summary and the Q&A, I will briefly guide you through the financial highlights and the key figures and the updated guidance for this year.

謝謝丹尼和之前的發言者。在我們進行總結和問答之前，我將簡要地引導您了解今年的財務亮點、關鍵數據和更新的指導。

My name is Robert Hendriks and I'm the SVP of Finance here at MP. The numbers I'll show are stated in million Swiss francs and full detail of the financials is available on the website and on other means.

我叫 Robert Hendriks，是 MP 的財務資深副總裁。我將展示的數字以百萬瑞士法郎為單位，財務數據的完整詳細資訊可以在網站和其他方式上找到。

If I move to slide 28 with the highlights, I'd like to focus firstly on our cash position. We ended last year with around CHF187 million and by the end of June, we are at CHF159 million. So that's a cash burn of CHF28 million in line with our expectations. If we take this to a full year, 12 months running the burn is CHF59 million. We have no additional cash coming in -- from collaborations in '24.

如果我轉到投影片 28 的重點內容，我想先關注我們的現金狀況。去年年底，我們的收入約為 1.87 億瑞士法郎，到 6 月底，我們的收入為 1.59 億瑞士法郎。因此，現金消耗為 2,800 萬瑞士法郎，符合我們的預期。如果我們將其計算為一整年，則 12 個月的燃燒金額為 5,900 萬瑞士法郎。我們沒有從 24 年的合作中獲得額外的現金。

With that, moving on to the updated guidance for the full year, we are now guiding our operating expenses to end up in the CHF65 million to CHF75 million range. This is a reduction from the previous guidance, largely based on what we see in our actuals at the moment and the current expectations we have on the development of the cost and the workforce. We will not guide on revenue and for clarity this guidance is always subject to the progress and changes of our pipeline.

至此，進入更新的全年指導，我們現在指導我們的營運支出最終在 6500 萬瑞士法郎至 7500 萬瑞士法郎範圍內。這比先前的指導有所減少，主要基於我們目前的實際情況以及我們對成本和勞動力發展的當前預期。我們不會對收入進行指導，為了明確起見，該指導始終取決於我們管道的進展和變化。

Thirdly, following also from the updated guidance is our runway. We are now comfortable to say that we are funded into '27, which is a small change from late '26, which we had guided on before. We do feel that there's runway and the cash that we have at the moment to put us in a privileged position in the industry. It will allow us to reach the milestones as presented by my colleagues, in particularly, the funds of the ring fence for 533, as indicated by Philippe as well as the further progression of the radio pipeline.

第三，遵循更新後的指導方針的是我們的跑道。現在，我們可以放心地說，我們已在 27 年獲得了資金，這與我們之前指導的 26 年底相比，有一個小小的變化。我們確實認為我們目前擁有的跑道和現金可以使我們在行業中處於特權地位。這將使我們能夠實現我的同事所提出的里程碑，特別是 Philippe 指出的 533 圍欄資金以及無線電管道的進一步進展。

We then turn over to the next slide. I'll briefly show comparison with last year for six months running. Overall results, you can see are in a pretty similar range. Revenue were slightly up as well as operating expenses resulting in an almost equal operating results.

然後我們翻到下一張投影片。我將簡要地展示連續六個月與去年的比較。您可以看到，整體結果處於非常相似的範圍內。收入和營運費用略有上升，導致營運績效幾乎持平。

Financial results was driven in the first six months by the positive exchange impact on our cash positions, as well as an increase in the interest income on the same balances. The revenue that we show continues to be driven by the Novartis radio ligand, contract, collaboration.

前六個月的財務表現受到匯率對我們現金頭寸的積極影響以及相同餘額的利息收入增加的推動。我們顯示的收入持續受到諾華無線電配體、合約、合作的推動。

And the focus on operating expenses, R&D expenses are up a bit. G&A expenses came down a bit. On SG&A, we were able to see a reduction in our D&O insurance expense. We're looking at R&D in the first six months of '24 as in comparison to last year, we did invest more in drug product in the dose escalation trials for 533, as indicated by Philippe.

重點在於營運費用、研發費用略有上升。一般行政費用略有下降。在 SG&A 方面，我們發現 D&O 保險費用有所減少。我們正在研究 24 年前六個月的研發情況，與去年相比，我們確實在 533 的劑量遞增試驗中對藥品進行了更多投資，正如 Philippe 所說。

We also were able to increase our investments in the overall platform and radio space and a few reductions we saw on, for instance, both 317 and some legacy programs.

我們還能夠增加對整體平台和廣播空間的投資，並減少一些投資，例如 317 和一些遺留節目。

We are in do remain diligent and careful in looking at our expenses, we feel that we are cost effective, run a tight ship., that remains, on course, for us to deliver on the promises. In combination, I think that these numbers continue to show the strong financial base entering into the second half that will allow us to keep investing in the pipeline. Thank you for your attention, any questions happy to take them in the Q&A.

我們確實會保持勤奮和謹慎地考慮我們的開支，我們認為我們具有成本效益，管理嚴格，當然，這仍然需要我們兌現承諾。總的來說，我認為這些數字繼續表明進入下半年的強勁財務基礎將使我們能夠繼續投資管道。感謝您的關注，如有任何問題，歡迎在問答中提出。

And now I hand back to Patrick.

現在我把話交還給派崔克。

Thanks, Robert. Thanks, Donny. Thanks, Philip. Thanks, Seth. And before turning to questions, let me quickly summarize, I'm on slide 34, which is the outlook on the upcoming milestones. 533, we have heard we're testing both higher and more frequent dosing to come to a conclusion on the potential of this molecule where we will update in 2025.

謝謝，羅伯特。謝謝，唐尼。謝謝，菲利普。謝謝，塞思。在開始提問之前，讓我快速總結一下，我在投影片 34 上，這是對即將到來的里程碑的展望。 533，我們聽說我們正在測試更高和更頻繁的劑量，以得出該分子潛力的結論，我們將在 2025 年更新。

Switch DARPin, we are in animal trials, we'll summarize the data present and then define the next development step for that molecule. 317, the Phase 1 is completed, we are in discussions with investigators -- to investigator-initiated trials for that. We don't plan to invest heavily ourselves, but we would like to understand more on 317, what combination trials could help. And there is a good news to test that.

切換 DARPin，我們正在進行動物試驗，我們將總結現有數據，然後定義該分子的下一步開發步驟。 317，第一階段已經完成，我們正在與研究人員討論 - 調查人員為此啟動試驗。我們不打算自己投入大量資金，但我們想進一步了解 317，以及組合試驗可以提供哪些幫助。有一個好消息可以測試這一點。

And last but not least, obviously, the radio franchise where 712 going into clinics next year. I'm also very excited, as Donny pointed out, the differentiated DARPin programs where we will update our portfolio and give you a deep insight, how we are thinking about those programs and how clinical value can then build in the future.

最後但並非最不重要的一點是，廣播特許經營權 712 將於明年進入診所。正如 Donny 指出的，我也非常興奮，我們將更新我們的產品組合併為您提供深入的見解、我們如何考慮這些項目以及未來如何建立臨床價值的差異化 DARPin 項目。

And obviously, we're not doing that alone. We're working with Novartis and especially also with Orano Med, where we are excited to be working with the leader in the lead based isotope field.

顯然，我們並不是孤軍奮戰。我們正在與諾華合作，特別是與 Orano Med 合作，我們很高興能與鉛基同位素領域的領導者合作。

As Robert said, we're running a tight ship. So the cash runway is now into 2027. And I think with really the effectiveness of our research and development engine, it puts us, on course, to find many important programs, many updates to come and really exciting year ahead of us.

正如羅伯特所說，我們正在嚴格管理。因此，現金跑道現在已進入 2027 年。我認為，憑藉我們研發引擎的真正有效性，它使我們能夠找到許多重要的項目、許多即將到來的更新以及真正令人興奮的一年。

Before moving on to Q&A, I would like to take the opportunity to first of all, thank the people here with me in the room, my speakers, but also all other coworkers at Molecular Partners.

在進行問答之前，我想藉此機會首先感謝與我一起在房間裡的人、我的演講者，以及 Molecular Partners 的所有其他同事。

We are curious, were coworkers, were a team and what we presented today is really the hard work of a whole company coming together and executing and debating and thinking and positioning our DARPin work.

我們很好奇，我們是同事，是一個團隊，我們今天展示的實際上是整個公司齊心協力、執行、辯論、思考和定位我們的 DARPin 工作的辛勤工作。

I would also like to extend the thanks to our partners, Novartis and Orano Med, but also our academic partners that we have and obviously also our investigators and KOLs who are using our molecules for applying the molecules in the clinic.

我還要感謝我們的合作夥伴諾華和歐安諾醫療，還有我們的學術合作夥伴，當然還有我們的研究人員和 KOL，他們正在使用我們的分子在臨床中應用分子。

And there, my last thanks goes to all the patients in our trials and their families because without them, this would not be possible and that links me back to the key purpose of our company. We're all here today to make drugs that matter.

最後，我要感謝參與我們試驗的所有患者及其家人，因為沒有他們，這一切都是不可能的，這讓我回到了我們公司的主要目標。今天我們齊聚一堂，是為了製造重要的藥物。

With that, I would close the presentation and open for your questions. Thanks.

至此，我將結束演示並開始回答大家的問題。謝謝。

(Operator Instructions) Daina Graybosch, Leerink Partners.

（操作員說明）Daina Graybosch，Leerink Partners。

Hi guys. Thanks for the update and the question. I have one back on MP0533, I loved your thoughts on how you're thinking about escalating now the higher doses and the trade-off between efficacy and toxin. I wonder as you get to these higher doses, do you expect to bind and single antigen expressing tumor cells or normal cells?

嗨，大家好。感謝您的更新與提問。我有一篇關於 MP0533 的文章，我喜歡你關於如何考慮現在升級更高劑量以及功效和毒素之間權衡的想法。我想知道當您達到這些更高的劑量時，您是否期望結合併表達單一抗原的腫瘤細胞或正常細胞？

And what specific talks are you looking for that might indicate that you're actually at such a high dose that you no longer have the advantageous therapeutic window, I mean, to bind multiple antigen. So basically what you have, what are you looking for in the clinical signal to balance that tox and efficacy as you go higher? Thank you.

您正在尋找哪些具體的談話，這些談話可能表明您實際上處於如此高的劑量，以至於您不再具有有利的治療窗口，我的意思是，結合多種抗原。所以基本上你所擁有的，你在臨床訊號中尋找什麼來平衡毒性和功效，因為你更高了？謝謝。

I can lead in, as maybe more of the generalist here, and then I'll hand over to Philippe for more expert view. I think first of all, why are we going to higher doses? And it was an observation also by our KOLs when we looked at the data is that we have the dose up shame where we have a induction at very low dose, and then we dose up, and that was to manage to safety.

我可以作為這裡的多面手來引導，然後我將移交給菲利普以獲取更多專家的觀點。我想首先，為什麼我們要提高劑量？當我們查看數據時，我們的 KOL 也觀察到，我們有劑量增加的恥辱，我們以非常低的劑量進行誘導，然後我們增加劑量，這是為了達到安全。

And so we started low dose. And then over the first 20 days, we had injections with always higher doses, and they realize that with maybe a bit touch faster PK that expected and maybe also more target mediated drug deposition than expected. We were not getting the exposure that we were hoping for and we were rather under dosing.

所以我們開始低劑量。然後在最初的 20 天裡，我們總是以更高的劑量進行注射，他們意識到，PK 可能比預期更快，而且標靶介導的藥物沉積也可能比預期更多。我們沒有得到我們所希望的暴露，而且我們的劑量相當不足。

So the dose intensification now is that we will give more higher doses, but maybe not even higher top doses, but just go faster to the full dose and then dose more frequent that in the side effect that we have seen so far, our IRR and CRS, which is really the T-cell activation so far I don't think we have seen target dependent toxicities, and Philippe can talk about that.

因此，現在的劑量強化是，我們將給予更多更高的劑量，但可能不會更高的最高劑量，而是更快地達到全劑量，然後更頻繁地給藥，比我們迄今為止看到的副作用、我們的IRR 和CRS，實際上是 T 細胞激活，到目前為止，我認為我們還沒有看到靶點依賴性毒性，Philippe 可以談論這一點。

Now if the patients will tolerate this intensification, that's what we have to explore. There is -- a maybe there will even be a lower dose but more frequent dose that will actually end up being the most efficacious dose in the beginning. We also know that once the disease is under control, we cannot dose every two, three days that's not possible and also not practical. So then we'll go back to the weekly dosing scheme at that point in time.

現在，如果患者能夠忍受這種強化，那就是我們必須探索的。甚至可能會有較低劑量但更頻繁的劑量，實際上最終會成為一開始最有效的劑量。我們也知道，一旦疾病得到控制，我們不能每兩三天就給藥一次，這是不可能的，也不切實際。那我們將回到那個時間點的每週給藥方案。

So that's why we're talking about the dose in intensification in the early weeks and then back to weekly. Hopefully that then enough once the disease is under control, we also don't expect the target mediated drug deposition anymore.

這就是為什麼我們要討論前幾週加強劑量，然後回到每週一次的原因。希望一旦疾病得到控制，我們也不再期望目標介導的藥物沉積。

So Philippe, maybe you can explain a bit more. And there's also some slides in our deck that where we showed that, especially the low the patients with low disease burden profited more because obviously, they also had maybe a bit less of those problems. And there was just enough drug to keep the disease under control. Philippe?

菲利普，也許你可以解釋一下。我們的幻燈片中還有一些幻燈片，我們在這些幻燈片中表明，特別是疾病負擔低的患者獲益更多，因為顯然，他們的這些問題可能也更少。而且藥物剛好夠控制病情。菲利普？

So thanks to add a couple of complements to what Patrick just said. First of all, again, we have seen good tolerability, manageable toxicity up to now and mainly CRS with very little pattern beyond that dose CRS I outlined. So and we've been carefully looking, for example, cytopenia or neutropenia, which could be expected. We have seen it on some other programs.

因此，感謝對帕特里克剛才所說的內容進行一些補充。首先，到目前為止，我們已經看到了良好的耐受性、可控的毒性，主要是 CRS，除了 CRS I 概述的劑量之外，幾乎沒有任何模式。因此，我們一直在仔細觀察，例如，血球減少症或嗜中性球減少症，這是可以預料的。我們在其他一些節目中也看到過。

So we want to densify that. We've said why, because we see the higher sink for target to dose drug disposition than we had anticipated. And on -- and so we want to 00 and also because it's safe so far, we think we can go quicker high. So we put that in place.

所以我們想要強化這一點。我們已經說過原因，因為我們發現目標劑量藥物處置的吸收量比我們預期的要高。繼續——所以我們想要00，而且因為到目前為止是安全的，我們認為我們可以更快地達到高點。所以我們把它落實到位。

We see totally yet what will be the exact impact on the half-life, but we may still have, significant sync, and that's why we do not anticipate so far too much drug accumulation. Therefore, we do not think that we wish we would get into much more on-target toxicity and but we will be a special monitoring the cytopenia. So that's the one we'll be looking at and mostly for the moment.

我們也完全了解對半衰期的確切影響，但我們可能仍然具有顯著的同步性，這就是為什麼我們預計到目前為止不會有太多的藥物累積。因此，我們認為我們不希望出現更多的目標毒性，但我們將特別監測血球減少症。這就是我們目前要關注的問題。

Can I ask a follow-up then? So as you have modeled out the PK and the drug mediated clearance, you model it to a specific dose? What sort of dose level do you expect (inaudible) and the exposure based on your preclinical models?

那我可以問後續嗎？那麼，當您對 PK 和藥物介導的清除進行建模後，您將其建模為特定劑量嗎？根據您的臨床前模型，您預期的劑量水平（聽不清楚）和暴露量是多少？

Basically, we are ready and protocol and the amendment which were kind of putting allows for a few higher dose escalation to not know doesn't but a few higher dose escalation and again, counting a lot on the densification, even more than the higher than the dose increase.

基本上，我們已經準備好，協議和修正案允許進行一些更高的劑量升級，但不知道是否會增加一些更高的劑量，並且再次依賴緻密化，甚至比更高的劑量增加更多。劑量增加。

And so that's basically -- we want to modify the exposure. We are not very far from where we would be hoping to be in terms of C-max, but need to work on the stitch off and longer exporter or at least identifying all those peaks, which we've already seen. But I want to really, harmonize, if I may say.

基本上，我們想要修改曝光。就 C-max 而言，我們離我們希望達到的目標並不遠，但需要致力於縫合和更長的出口，或至少識別我們已經看到的所有這些高峰。但如果我可以說的話，我真的想要和諧。

This is Philippe, is it fair to say from the modeling, we saw that with the MAX increase, we will not reach what we need. That's why we need to intensify with mortals.

這是Philippe，公平地說，從建模中我們看到，隨著MAX的增加，我們將達不到我們所需要的。這就是為什麼我們需要加強與凡人的關係。

Yes, we see again, on one hand, we are reassured and the experts with us are reassured that we see there is an impact, on the tumors. There is an impact on the blasts. We will hit them, but we think it's not long as long as, if it's disappearing too quickly and we need to modify that trend. So to gain that increase in effect and especially the duration of effect.

是的，我們再次看到，一方面，我們感到放心，我們身邊的專家也感到放心，我們看到對腫瘤有影響。對爆炸有影響。我們會打擊它們，但我們認為它不會太長，如果它消失得太快，我們需要改變這個趨勢。因此，要獲得效果的增加，尤其是效果的持續時間。

Thanks.

謝謝。

Richard Vosser, JPMorgan.

理查沃瑟，摩根大通。

Hi. Thanks for taking my question. And maybe another one on 0533. Just back on that, I suppose the dose intensifying after a period of time. If you then go to back to weekly dosing, are you going to have enough drug onboard to maintain the response? How should we think about that would be the first question.

你好。感謝您提出我的問題。也許還有 0533 上的另一個。話又說回來，我想一段時間後劑量會加大。如果您隨後恢復每週給藥，您是否會有足夠的藥物來維持反應？我們應該如何思考這是第一個問題。

Very good question. You should join us for our protocol discussions, I assume, but what we hope is that we are going to the bulk, if I may say or reduce the tumor magnitude -- to tumor burden, because we see again that we see that we have more responses in the lower tumor burden than in the higher.

非常好的問題。我想你應該加入我們的協議討論，但我們希望的是，如果我可以說或減少腫瘤的大小的話，我們將減少腫瘤的負擔，因為我們再次看到我們看到我們有腫瘤負荷較低的患者的反應多於腫瘤負荷較高的患者。

So we want to and we hold that when we are there, then we may need less because there could be some less of a sync. So that's one aspect. We are still discussing, in fact and in terms of -- we also want to avoid by design having chronic exposure because we are also conscious, that concept of a T-cell exhaustion.

因此，我們希望並認為，當我們到達那裡時，我們可能需要更少，因為同步可能會減少。這是一方面。事實上，我們仍在討論——我們也希望透過設計避免長期暴露，因為我們也有意識，T 細胞衰竭的概念。

So we would want to be continuous all the time then the question is how little is enough. And so we are -- in fact discussing [usually do] one day of exposure of in that maintenance phase or more than one day. But we know that it will not be continuous and it will be a short time, too. So we are just finalizing that discussion as we speak, but very, very, very close to finalize and submit.

所以我們希望始終保持連續，那麼問題是多少才足夠。因此，我們實際上正在討論[通常]在維護階段的暴露一天或一天​​以上。但我們知道這不會是連續的，而且也將是很短的時間。因此，我們剛結束討論，但非常、非常、非常接近最終確定和提交。

Excellent. I've got a separate question, not related, so I'll get back in the queue and ask it in a second, if it's still there. Thanks.

出色的。我有一個單獨的問題，不相關，所以我會回到隊列中並稍後詢問它是否仍然存在。謝謝。

Thanks, Richard.

謝謝，理查。

Sebastian van der Schoot, Kempen.

塞巴斯蒂安范德斯庫特，肯彭。

Hi, team. Thank you for taking my questions. Regarding the Radio DARPin, can you remind us when the clinical trial, suppose, to start?

大家好。感謝您回答我的問題。關於 Radio DARPin，您能否提醒我們臨床試驗何時開始？

And can you also give some insight into what the clinical trial design will be, how you are thinking about the different steps and when we can see first data for the DARPin, can you gave to the less payload? Thank you.

您能否提供一些關於臨床試驗設計的見解，您如何考慮不同的步驟，以及當我們可以看到 DARPin 的第一個數據時，您能否給予較少的有效載荷？謝謝。

Yeah, so I can give you a rough outline. So we have defined the candidate, we are now starting up production is going to be GMP production, then we will be working with Orano Med for that less payload. So we are expecting clinical entry next year, second half. So first half is not possible.

是的，所以我可以給你一個粗略的輪廓。所以我們已經確定了候選者，我們現在開始生產將是 GMP 生產，然後我們將與 Orano Med 合作以減少有效負載。所以我們預計明年下半年就會進入臨床。所以前半部是不可能的。

And then we have guided that we are expecting to have first data and the data will not be efficacy or safety it will be immature, where we can follow the molecule, that is the beauty of this setup where we can create an image after dosing and see where the drug is.

然後我們指導我們期望獲得第一個數據，這些數據不會是有效性或安全性的，它是不成熟的，我們可以追蹤分子，這就是這個設定的美妙之處，我們可以在給藥後創建影像，看看藥物在哪裡。

And I think from the image, we can do some predictions. I mean, is it less in the kidney, more indicate anymore in the tumor, but the safety and efficacy will obviously follow later.

我認為從圖像中，我們可以做一些預測。我的意思是，是不是腎臟中的含量減少了，腫瘤中的含量增加了，但安全性和有效性顯然會在以後出現。

Now I will be happy to hand over to the experts and Philippe from the clinical side. And I think the good thing is the image is actually available rather short after dosing. So you don't have to wait for three months for the pictures, you actually can get them rather fast. That's why clinical entry and initial data are rather close together. Philippe?

現在我很高興將工作交給臨床方面的專家和Philippe。我認為好處是圖像實際上在給藥後很短的時間內就可用。所以你不必等三個月才能拿到照片，實際上你可以很快得到它們。這就是為什麼臨床輸入和初始數據相當接近。菲利普？

Thanks for that. So again, we want to very quickly or quickly after patients are included, so they will be imaged or biodistribution and dosimetry. And then on the heels of that, obviously, dose escalation starts to. I just also want to make sure this we are envisioned even with a single drug with which has to do have those two steps.

謝謝你。因此，我們希望在患者被納入後非常快速或很快地進行，以便對他們進行成像或生物分佈和劑量測定。顯然，緊隨其後，劑量開始增加。我還想確保我們所設想的即使是單一藥物也必須完成這兩個步驟。

But again, the images come first and then therapeutic comes in. So that then obviously we would want to go what we are planning to do for the moment is to include patients with small cell lung cancer, mainly and we depending on the signal that we get to the we'll expand in potentially because to state new endocrine. But I think it's a bit difficult to integrate both subpopulation at very start.

但同樣，影像是第一位的，然後才是治療。因此，顯然我們目前計劃要做的就是將小細胞肺癌患者納入其中，主要取決於我們收到的訊號，我們可能會擴大範圍，因為要說明新的情況內分泌。但我認為從一開始就將這兩個亞群整合起來有點困難。

Got it. Very clear. Thank you.

知道了。非常清楚。謝謝。

(Operator Instructions) Michael Nedelcovych, TD Cowen. Please go ahead.

（操作員說明）Michael Nedelcovych，TD Cowen。請繼續。

Thanks for the question. I have another follow-up on 0533, and this is maybe a slightly different version of a question was already asked, but do you all have a C-max or an exposure level in mind at which you would expect activity or at least more activity than you've seen and are aiming for that level? Or are you approaching this more empirically in trying to raise the dose and the dose frequency and the dose regimen and just waiting to see what you see?

謝謝你的提問。我對 0533 有另一個後續行動，這可能是已經提出的問題的一個稍微不同的版本，但是你們心中是否都有一個 C-max 或一個您期望活動或至少更多活動的暴露水平比你所見過的和你的目標是達到那個水準？或者您是否更憑經驗來嘗試提高劑量、劑量頻率和劑量方案，然後只是等待看到您所看到的結果？

And so that's the first question. And then I have to admit that the language around this program is a little bit ominous in the slides. If we were in about a year that, you have discontinued this program. What do you think would be the most likely reason would it be because your hypothesis has not panned out?

這是第一個問題。然後我不得不承認幻燈片中圍繞該程式的語言有點不祥。如果我們在大約一年內，您已經停止了該計劃。您認為您的假設沒有得到證實最可能的原因是什麼？

Or would it be that you have so many other compelling opportunities that resource allocation has to come first and you'll pursue those other opportunities. And I realize that's not the fairest hypothetical, but I'm just curious where your minds are at the moment. Thank you.

或者，您是否擁有許多其他令人信服的機會，必須先進行資源分配，然後您將尋求這些其他機會。我意識到這不是最公平的假設，但我只是好奇你現在在想什麼。謝謝。

Maybe Philip can take the first and I'll take it (multiple speaker)

也許菲利普可以拿第一個，我也會拿（多個發言者）

Okay, congratulations on your promotion Philippe, please go ahead.

好的，恭喜你升職，菲利普，請繼續。

Thank you for this, so very good question on the C-max, and our model. Obviously we models and we think that we are not very far in terms of (inaudible) where we were -- where we wanted to be and we see activity. So it's more about we see too much, too quickly disappearance of the drug. That's why we need to change every our dosing pattern, our scheme of administration, to really it's the -- have a more dense approach during that first phase.

謝謝您提出這個關於 C-max 和我們的模型的非常好的問題。顯然，我們進行了建模，我們認為就我們所處的位置（聽不清楚）而言，我們離我們想要達到的位置並不遙遠，而且我們看到了活動。所以更多的是我們看到藥物消失得太多、太快。這就是為什麼我們需要改變我們的每一個劑量模式、我們的管理方案，以便在第一階段真正採用更密集的方法。

So we are not very far, and we still think we can go a bit higher and we'd like to keep it out. Again, we can do this because it has been safe up to now or safe enough. But it will be much, it will be more about looking at the shape of that exposure curve more than the C-max. And again, will have a heavy focus on the trough because we need to have more time with, higher than mean expected exposure during that time.

所以我們還不是很遠，我們仍然認為我們可以走得更高一點，我們不想把它排除在外。同樣，我們可以這樣做，因為到目前為止它是安全的或足夠安全的。但它會很多，更多的是專注於曝光曲線的形狀，而不是 C-max。再次強調，我們將重點放在低谷，因為我們需要有更多的時間，比這段時間的平均預期暴露要高。

Maybe just kind of always been another metric, but a bit more delayed than view, and please apologize if it is too crude. But this disease progresses very fast. If you cannot control the patient in the first days, even you are behind the disease. And if you look at the data that we also did show, I think on slide 12, you see we have some impact and then just the disease takes off.

也許只是另一個指標，但比視圖延遲一點，如果它太粗糙，請道歉。但這種疾病進展非常快。如果你不能在第一天控制病人，即使你也是疾病的幕後黑手。如果你看看我們也確實展示的數據，我想在投影片 12 上，你會看到我們產生了一些影響，然後疾病就開始流行了。

And so it's very important that we not only, I think it's more the trough that we actually give the dose and we give it also faster, just to get the drug more chance to actually act before it's too late.

因此，非常重要的是，我們不僅，我認為我們實際上給予劑量的谷值，而且我們給予的速度也更快，只是為了讓藥物有更多的機會在為時已晚之前真正發揮作用。

And I would -- and you were asking about imperatives at [Moffitt]. I personally was surprised that we saw, let's say no dose response in the sense of we had patients in almost a full cohort that responded, but we don't see dose response in that sense, we see activity in patients that have low disease burden.

我會——而你問的是當務之急[莫菲特]。我個人感到驚訝的是，我們看到，假設沒有劑量反應，因為我們幾乎整個隊列中的患者都有反應，但我們沒有看到這種意義上的劑量反應，我們看到疾病負擔低的患者的活動。

Maybe that's also why we just need to tease that out and see if we can expand that activity to more patients by what we call intensifying the dose. And we will have a poster at ASH where you then can see what dose we have now. And it is definitely less than we would like and I think that was the modeling call it a bit surprised that we saw less, drug in circulation, and that's what we are correcting for. Based on also some responses we see in despite to the low exposure.

也許這也是為什麼我們只需要弄清楚這一點，看看我們是否可以透過所謂的加強劑量將這種活動擴展到更多患者。我們將在 ASH 上張貼海報，您可以在其中看到我們現在的劑量。這肯定比我們想要的要少，我認為模型稱它有點令人驚訝，我們看到循環中的藥物較少，這就是我們正在糾正的。儘管曝光率較低，但我們也看到了一些回應。

I'll now take the other part of the question as to sort of what to expect. It was a good discussion with our investigators and there is just a high medical need and everyone in the room, the KOLs on the trial, but also the dose not on the trials that we should really test this.

我現在將討論問題的另一部分，即預期會發生什麼。這是與我們的研究人員進行的一次很好的討論，醫療需求很高，房間裡的每個人、試驗中的 KOL，還有我們應該真正測試的試驗劑量。

As we have activity, there is a need there, and the higher dosing is just what just jumped into the eye when you saw the data that we have. So I think there is almost an ethical imperative for us to test this, at the same time outcome, we will see what it is.

當我們有活動時，就有需求，當您看到我們擁有的數據時，更高的劑量正是您所看到的。因此，我認為我們幾乎有道德上的必要性來測試這一點，同時我們將看看結果是什麼。

The good thing and our turn almost your question around is we have options. We don't have to progress this one if the radio franchise works well. I means not that we would stop it for no reason. But it puts a clear bar that we can put out there and say, if we don't reach to 20 or even 30 plus response rate, if we don't pass the duration of three, six, maybe nine months just not going to be good enough and it will be a clinic to respond.

好的事情是，我們幾乎可以扭轉你的問題，因為我們有選擇。如果廣播特許經營權運作良好，我們就不必推進這項計畫。我的意思並不是說我們會無緣無故地阻止它。但它提出了一個明確的標準，我們可以在那裡說，如果我們沒有達到 20 甚至 30 以上的回應率，如果我們沒有超過三、六、也許九個月的持續時間，就不會只要夠好，診所就會做出回應。

I mean, that's what you're looking for. And I think the cost base more or less the same as we always have. I mean, that's what would allow you to move forward in to Phase 2/registrational trials, and we can just be very Ilene about that.

我的意思是，這就是你要找的。我認為成本基礎或多或少與我們一貫的相同。我的意思是，這將使您能夠進入第二階段/註冊試驗，我們對此可以非常重視。

I don't think it will just go away. So we will definitely update on the data. We want to update on the data and our reasoning why we would stop it or not. So but I do think that the idea that we have options, obviously the good ones and the more competition there is for the cash we have it a good sign for the company.

我不認為它會消失。所以我們肯定會更新數據。我們想要更新數據以及我們是否會停止它的理由。所以，但我確實認為，我們有選擇的想法，顯然是好的選擇，而且對現金的競爭更加激烈，這對公司來說是一個好兆頭。

Very helpful. Thank you.

非常有幫助。謝謝。

Thanks, Mike.

謝謝，麥克。

Richard Vosser, JPMorgan.

理查沃瑟，摩根大通。

Hi. Thanks for taking my question. It was just back on the Radio DARPin side of things. Just maybe an update on the Novartis partnership as much as you can give just where we are with that one, how that's progressing relative to 0712? And when we might see something from that side of that collaboration?

你好。感謝您提出我的問題。它剛剛回到 DARPin 無線電方面。您可以盡可能多地介紹一下我們與諾華合作夥伴關係的最新情況，相對於 0712 來說進展如何？我們什麼時候才能看到合作的另一面？

Maybe Donny can give a short update and I maybe just frame that obviously in our pipeline, our compounds are like we have five and they're all five high priority. And in Novartis pipeline there close to 30 compounds and that explains maybe a bit less feed, but maybe over to Donny to explain how we are progressing our pipeline and why we think we are faster and how Novartis is going forward.

也許唐尼可以提供一個簡短的更新，我也許只是在我們的管道中顯然地框架，我們的化合物就像我們有五個，它們都是五個高優先級。在諾華的研發管線中，有近30 種化合物，這解釋了原料可能會少一些，但也許需要Donny 來解釋我們如何推進我們的研發管線，以及為什麼我們認為我們的速度更快，以及諾華將如何前進。

I'm happy to give you as much insight as we as we can in that context of that collaboration. So as outlined on the slide, it to specific targets we are collaborating on with Novartis that Patrick said, we are part of a bigger, bigger endeavor to Novartis takes in the whole retail space, which makes a lot of sense for them to keep the leadership in this space, which has been entering as one of -- as the first one in the field.

我很高興在合作的背景下為您提供盡可能多的見解。因此，正如幻燈片中概述的那樣，對於我們與諾華合作的具體目標，帕特里克表示，我們是諾華在整個零售領域更大、更大努力的一部分，這對他們保持該領域的領導者，它一直作為該領域的第一個進入。

So we're progressing with the candidates. We're analyzing the candidate. And as many of you know, or might know that our wells, knowledgeable in the field is like it's a lot about testing by bringing forward molecules, testing them in vivo models, they're going through the iterations. And there it's just like what observations we are making with Orano Med.

所以我們正在與候選人取得進展。我們正在分析候選人。正如你們許多人所知，或者可能知道，我們在該領域知識淵博的井就像通過提出分子進行大量測試，在體內模型中測試它們，它們正在經歷迭代。這就像我們在歐安諾醫療公司所做的觀察一樣。

And that's turned the other side of the whole equation Orano Med on forward found a partner that is extremely agile and following our approach to test as quick as possible as many as possible candidates in the relevant models, often in vivo models, unfortunately, there is not a lot of preclinical and in vitro models that help you to predict the outcome in the in vivo models.

這改變了整個等式的另一面，歐安諾醫療向前找到了一個非常敏捷的合作夥伴，並遵循我們的方法，在相關模型（通常是體內模型）中盡可能快地測試盡可能多的候選者，不幸的是，有沒有很多臨床前和體外模型可以幫助您預測體內模型的結果。

So that's how we are progressing. And that's why I think also we are that allowed us that agility and way to maneuver that whole preclinical pipeline allowed us to nominate the first candidate before Orano Med and I'm very much look forward to also nominate further candidates in that collaboration.

這就是我們正在取得進展的方式。這就是為什麼我認為我們也能夠以敏捷性和方式來操縱整個臨床前管道，使我們能夠在歐安諾醫療之前提名第一個候選人，我非常期待在該合作中提名更多候選人。

And maybe just I will add because there is a bit of a conceptual difference between how Novartis looks at radio and we and it goes back to the isotopes that we have and we work with LED, which has a very short half-life. And the decay in the blood is likely going to be much more safe than if the absolute peak tumor even actinium and the jury there is out.

也許我會補充一點，因為諾華對無線電的看法和我們對無線電的看法存在一些概念上的差異，這可以追溯到我們擁有的同位素以及我們使用 LED 的情況，它的半衰期非常短。與絕對峰值腫瘤甚至錒和陪審團退出相比，血液中的腐爛可能會安全得多。

But Novartis also is looking for a slightly different profile than what we are looking for because we have different isotopes. So not all learnings and other all technology that we are developing for our pipeline is one to one addressing the Novartis needs. So it's also there a slight difference so not every learning from our own amid collaboration from what we do applies directly to Novartis, and that is their history on that (inaudible) and now maybe more actinium versus LED.

但諾華也在尋找與我們正在尋找的略有不同的特徵，因為我們有不同的同位素。因此，並非我們為管道開發的所有知識和其他所有技術都是一對一地滿足諾華的需求。因此，也存在細微的差異，因此並非我們在合作中從我們所做的事情中學到的所有知識都直接適用於諾華，這就是他們的歷史（聽不清），現在可能更多的是錒而不是LED。

Excellent. Thank you.

出色的。謝謝。

Thanks.

謝謝。

Daina Graybosch, Leerink Partners.

戴娜‧格雷博斯 (Daina Graybosch)，Leerink 合夥人。

Thank you guys. The discussion on MP0533 has been very helpful. I have one more follow up there. And when I look at page 11 in your presentation in the top, I do see some of the tox you said you'd be looking at before. So it looks to me like two Grade 3 febrile neutropenia as well as some Grade 3 lymphopenia. And I wonder if you could talk through those toxicities in those patients, then why that shouldn't be concerning in terms of the therapeutic window and the tox that is on target?

謝謝你們。關於 MP0533 的討論非常有幫助。我還有一個後續行動。當我查看您頂部簡報中的第 11 頁時，我確實看到了您之前所說的一些有毒物質。所以在我看來，這就像兩個 3 級發燒性嗜中性球減少症以及一些 3 級淋巴球減少症。我想知道您是否可以談談這些患者的毒性，那麼為什麼在治療窗口和目標毒性方面不應該擔心呢？

Yeah, I just like in general, that's why I think just to add to what Philippe was saying, we're not only trying to do to C-max but to see trough by more frequent dosing. But Philippe, maybe you gave the insight.

是的，我只是喜歡一般情況，這就是為什麼我想補充一下 Philippe 所說的，我們不僅試圖達到 C-max，而且透過更頻繁的給藥來看到谷值。但是菲利普，也許你給了見解。

Yeah. And also good review. And obviously we are following those. What we do, we also have, as you see, a dose escalation committee -- I just -- what I want to say is that we are following those very carefully and not just costs. Okay. So I'm comfortable talking a with our dose escalation committee and our safety review committee.

是的。而且還好評。顯然我們正在關注這些。正如你所看到的，我們所做的還有一個劑量遞增委員會——我只是——我想說的是，我們正在非常仔細地關注這些問題，而不僅僅是成本。好的。因此，我很樂意與我們的劑量遞增委員會和安全審查委員會進行交談。

So basically, those are imminently or those are mainly disease related and they are long lasting. So and it's always difficult to aggregate in the context of structural trial, but for the moment, we have not seen -- we have discovered through that lens and have they not -- they are in a way, it's hard to completely see that they are not related because they have been new temporary during the trial.

所以基本上，那些是迫在眉睫的，或者是主要與疾病相關的，而且是長期持續的。因此，在結構性試驗的背景下進行匯總總是很困難，但目前，我們還沒有看到——我們已經透過這個鏡頭發現了，但他們沒有——在某種程度上，很難完全看到它們不相關，因為他們在審判期間是新的臨時人員。

However, with adjudication, they are not worrying from the study a safety committee standpoint. So we will keep obviously, looking at this and we want to see whether is that transforming into a pattern or not. But so far, we do not think it is. (multiple speaker)

然而，透過裁決，從安全委員會的角度來看，他們並不擔心這項研究。所以我們顯然會繼續關注這一點，我們想看看它是否會轉變為一種模式。但到目前為止，我們認為並非如此。（多個發言者）

But again, just maybe one last thought on this, as Patrick has mentioned, we need to -- best proof of that will be to show that because the drug is active very quickly in those patients' vision, we can be seen no reduction or non-recurrence of those. It's very difficult to choose to keep that promise in the context of a relapse refractory patients. And but that's what we want to aim at. And that's why we say we should take more risk. And finally, see in terms of safety as we think we can, and identify that exposure during the first we can.

但同樣，正如帕特里克所提到的，我們需要對此進行最後一個思考，最好的證明是證明，由於藥物在這些患者的視力中非常快速地發揮作用，我們可以看到沒有減少或那些不再發生。在復發難治性患者的背景下，選擇信守這項承諾是非常困難的。但這就是我們想要的目標。這就是為什麼我們說我們應該承擔更多風險。最後，盡我們所能地從安全角度考慮，並在第一時間識別出這種暴露。

Thanks, Philip.

謝謝，菲利普。

Thanks, Daina.

謝謝，戴娜。

George Zimmerman, Octavian.

喬治·齊默爾曼，奧克塔維安。

Yeah, thank you. Thank you to the Molecular Partners team for the presentation and answering all the questions. So, we have talked quite a bit about MP0533 and the radio DARPin and we are in platform. I feel we have not talked too much about the switch program.

是的，謝謝。感謝 Molecular Partners 團隊的示範和回答所有問題。所以，我們已經討論了很多關於 MP0533 和無線電 DARPin 的問題，我們現在已經進入平台了。我覺得我們還沒有過多談論切換計劃。

So maybe just a little update on as well on the progress with your switch platform. And you specifically mentioned additional preclinical data announced in H2 this year still. So what can we expect there? Can you give us a little bit of flavor on also in particular to the translatability of those data?

因此，也許只是對您的交換器平台的進展進行一些更新。您也特別提到了今年下半年宣布的其他臨床前數據。那我們可以期待什麼呢？您能為我們介紹一下這些數據的可翻譯性嗎？

That's great question. And so maybe I'll quickly allude to this platform that is an either or DARPin. So we can create in an immune cell engager and off DARPin that is switched on while we on target. And in this case, it's the Ckit which don't fit where we then bind or open block CD40 and engage (inaudible) to kill.

這是一個很好的問題。因此，也許我會很快提到這個平台，它是一個 DARPin 或一個 DARPin。因此，我們可以創建一個免疫細胞接合器，並在我們瞄準目標時關閉 DARPin。在這種情況下，Ckit 不適合我們然後綁定或打開塊 CD40 並參與（聽不清楚）殺死。

So this molecule is at the moment, we are running non-primate trials and we expect the translatability to be rather high from the data we have in the Cynon versus the human. The data we'll collect, and that will also inform, obviously, a clinical trial. And there we are looking into different routes and one could be more into, call it, AML, cells more into -- more global stem cell conditioning.

因此，目前我們正在進行非靈長類動物試驗，根據我們在 Cynon 與人類中獲得的數據，我們預計該分子的可翻譯性相當高。我們將收集的數據顯然也將為臨床試驗提供資訊。我們正在研究不同的途徑，一種可能是更多研究，稱之為 AML，細胞更多研究——更多的全球幹細胞調節。

AML is a very high bar because you need very complete killings, stem cell conditioning is a high medical need in the field for all the gene therapy companies, but a bit less on our radar, as that is really more than again, in sum -- in the setting of a partnership as the key value is in stem cell transplants.

AML 是一個非常高的標準，因為你需要非常徹底的殺戮，幹細胞調理對於所有基因治療公司來說都是該領域的一個很高的醫療需求，但在我們的雷達上有點少，因為這真的不只一次，總而言之 - - 在建立夥伴關係時，關鍵價值在於幹細胞移植。

So we are taking the data and we will then also analyze and see what the best clinical route is based on that data. And so I think your question is spot on that again, will link to what is the best clinical position and how to investigate that versus maybe the other pipeline assets.

因此，我們正在獲取數據，然後我們還將根據這些數據進行分析並了解最佳的臨床途徑。所以我認為你的問題再次切中要害，將與什麼是最佳臨床位置以及如何相對於其他管道資產進行調查相關。

So I think that we didn't speak about it that, strongly is because we have to focus on radio. Radio is really where it's happening, where it's groundbreaking, while it stem cell transplant, given the high medical need, it may be a bit less to call it strategic for Molecular Partners. That's the way to think about it.

所以我認為我們沒有談論這個問題，很大程度上是因為我們必須專注於廣播。無線電確實是它正在發生的地方，它是開創性的，而它是乾細胞移植，考慮到很高的醫療需求，將其稱為分子合作夥伴的策略可能有點不那麼重要。這就是思考問題的方式。

At this point in time, we believe it's high value because of high translatability and the medical need. And we will definitely see how if and how we then would move forward seeing the rest of the pipeline developing. I hope that helps to more on the strategic side, how we think about it.

目前，我們認為由於高可翻譯性和醫療需求，它具有很高的價值。我們肯定會看到我們是否以及如何繼續推進管道的其餘部分的發展。我希望這對戰略方面以及我們的思考方式有更多幫助。

Yes, certainly, very helpful. Thanks.

是的，當然，非常有幫助。謝謝。

Thank you. And this concludes your question and answer session. I'd like to turn the conference back over to Patrick Anstutz for closing remarks.

謝謝。您的問答環節到此結束。我想將會議轉回給帕特里克·安斯塔茨（Patrick Anstutz）致閉幕詞。

So big thanks to everyone and especially all the great questions we had. And I think it has turned out a good way to do it. I think we'll keep on doing a rather extensive slide deck, shorter presentation and opening for the Q&A. As you guys are following our work, you have to questions, and we'd love to take the time to listen to you, see how we can answer those questions and remain in a very open and good dialogue.

非常感謝大家，特別是我們提出的所有重要問題。我認為這是一個很好的方法。我認為我們將繼續製作相當廣泛的幻燈片、較短的簡報和問答環節。當你們關注我們的工作時，你們一定會提出問題，我們很樂意花時間傾聽你們的意見，看看我們如何回答這些問題，並保持非常開放和良好的對話。

With that I thank you all, for that all the others who are listening. Thanks our investors for the trust and support you give us, to the team again, and we look forward to meet you at investor conferences as they come or reach out to us, if you want the meeting, we have a lot to tell. We will be sharpening the story a lot about the radio therapy, be out there and really look forward to interact with all of you.

在此，我感謝大家，感謝所有其他正在傾聽的人。感謝我們的投資者再次給予我們團隊的信任和支持，我們期待在投資者會議上與您見面或聯繫我們，如果您想參加會議，我們有很多話要說。我們將進一步豐富放射治療的故事，並真誠地期待與你們所有人互動。

Thanks for that. Take care and stay safe.

謝謝你。小心並保持安全。

Thank you. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.

謝謝。今天的電話會議到此結束。我們感謝大家參加今天的演講。您現在可以斷開線路並度過美好的一天。