Kymera Therapeutics Inc (KYMR) 2024 Q4 法說會逐字稿

Good day, everyone. My name is Megan, and I will be your conference operator today. At this time, I would like to welcome you to the Kymera Therapeutics fourth quarter 2024 results call. (Operator Instructions)

大家好。我叫梅根，今天我將擔任您的會議主持人。現在，我歡迎您參加 Kymera Therapeutics 2024 年第四季業績電話會議。（操作員指示）

At this time, I would like to turn the call over to Justine Koenigsberg, Vice President of Investor Relations.

現在，我想將電話轉給投資者關係副總裁 Justine Koenigsberg。

Good morning, and welcome to Kymera's quarterly update. As you will notice, we have moved to video format, which we hope you will enjoy. Joining me this morning are Nello Mainolfi, our Founder, President and CEO; Jared Gollob, our Chief Medical Officer; and Bruce Jacobs, our Chief Financial Officer.

早上好，歡迎閱讀 Kymera 的季度更新。正如您所注意到的，我們已轉向視訊格式，希望您會喜歡。今天早上與我一起出席的有我們的創辦人、總裁兼執行長 Nello Mainolfi、我們的首席醫療官 Jared Gollob 和我們的財務長 Bruce Jacobs。

Following our prepared remarks, we will open the call to questions where we will take questions from our publishing analysts on video. To be sure we have enough time to address everyone's questions, we ask that you please limit your questions to one and a relevant follow-up.

在我們準備好發言之後，我們將開始提問環節，透過影片回答出版分析師的提問。為了確保我們有足夠的時間回答每個人的問題，我們要求您將問題限制為一個，並進行相關的後續問題。

Before we begin, I would like to remind you that today's discussion will include forward-looking statements about our future expectations, plans and prospects. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those projected.

在我們開始之前，我想提醒大家，今天的討論將包括關於我們未來期望、計劃和前景的前瞻性陳述。這些聲明受風險和不確定性的影響，可能導致實際結果與預測結果有重大差異。

A description of these risks can be found in our most recent 10-K filed with the SEC. Any forward-looking statements speak only as of today's date, and we assume no obligation to update any forward-looking statements made on today's call.

這些風險的描述可以在我們最近向美國證券交易委員會提交的 10-K 文件中找到。任何前瞻性陳述僅代表截至今日的觀點，我們不承擔更新今日電話會議所作任何前瞻性陳述的義務。

With that, I will now turn the call over to Nello.

說完這些，我現在將電話交給 Nello。

Thank you, Justine. Welcome, everybody. We're excited to have you with us today as we transition our quarterly financial updates to a video format. I believe this reflects our continued commitment to transparency, open communication and deeper connections with our stakeholders. We will have lots of data update this year, so it will be productive to have videos and slides.

謝謝你，賈斯汀。歡迎大家。我們很高興今天能與您一起將季度財務更新轉換為視訊格式。我相信這反映了我們對透明度、開放溝通和與利害關係人更深層聯繫的持續承諾。我們今年將會有大量的數據更新，因此擁有影片和幻燈片將會很有成效。

We'll use today's call to briefly reflect on our achievements of 2024, which positions us for what I anticipate will be a very exciting 2025. Stepping back, we started 2024 with our R&D Day, where we shared our expanded focus on immunology with the goal of developing therapies that have the potential to deliver biologic-like efficacy with the convenience of an oral daily pill.

我們將利用今天的電話會議簡要回顧我們在 2024 年的成就，我預計這將為我們迎來非常令人興奮的 2025 年奠定基礎。回顧過去，我們在 2024 年伊始就開展了研發日活動，在會上，我們分享了對免疫學的進一步關注，目標是開發出有可能提供類似生物製劑功效的療法，並且只需每日口服藥丸即可。

There, we introduced STAT6 and TYK2, which exemplify programs we believe have the potential to disrupt conventional treatment paradigms and expand access to millions of patients around the world. As we mentioned at the time, the strategic effort was years in the making, but it has materialized rapidly with our recent clinical progress. Our team executed exceptionally over the past year and successfully delivered on all of our key priorities.

在那裡，我們推出了 STAT6 和 TYK2，我們認為這兩個計畫有潛力顛覆傳統的治療模式，並擴大全球數百萬名患者的治療範圍。正如我們當時所提到的，這項策略努力已經醞釀多年，但隨著我們最近的臨床進展，它已迅速實現。我們的團隊在過去一年中表現出色，並成功完成了所有關鍵優先事項。

Here's a quick recap of what we did last year. For STAT6, we completed IND-enabling studies for KT-621, filed an IND and initiated the Phase I healthy volunteer study. Now we're completing the final MAD cohorts. This is the first STAT6 targeted agent to enter clinical development.

以下是我們去年所做工作的簡要回顧。對於 STAT6，我們完成了 KT-621 的 IND 支持研究，提交了 IND 並啟動了 I 期健康志願者研究。現在我們正在完成最後的 MAD 佇列。這是第一個進入臨床開發的STAT6標靶藥物。

While the attractiveness of STAT6 as a target and the strong validation of our preclinical work has attracted many others to the space, we believe we are the unquestioned leader, a position on which we intend to build.

雖然 STAT6 作為目標的吸引力以及我們臨床前工作的強有力驗證吸引了許多其他人進入該領域，但我們相信我們是無可爭議的領導者，我們打算在此基礎上繼續發展。

With TYK2, progress continued as well. Since the first introduction in January again of last year, we named an advanced and novel development candidate, KT-295 and are now completing IND-enabling studies. Regarding IRAK4, we continue to support our partner, Sanofi, in their efforts to progress the 2 ongoing Phase IIb studies in HS and AD.

隨著 TYK2 的出現，進展也持續。自去年 1 月首次推出以來，我們已命名一種先進且新穎的開發候選藥物 KT-295，目前正在完成 IND 支援研究。關於 IRAK4，我們將繼續支持我們的合作夥伴賽諾菲努力推進 HS 和 AD 兩項正在進行的 IIb 期研究。

Importantly, following an interim analysis in the middle of last year, Sanofi expanded the studies to accelerate the overall development timelines on path to pivotal trials. Finally, while less visible to investors, we progressed our early pipeline of novel immunology programs to the point where we're poised to soon share our new exciting immunology target.

重要的是，在去年年中進行中期分析之後，賽諾菲擴大了研究範圍，以加快關鍵試驗的整體開發時間表。最後，雖然投資者不太了解，但我們已經取得了早期新型免疫學計畫的進展，準備很快分享我們令人興奮的新免疫學目標。

So, with all the progress that I just discussed, which reflect really a year of truly outstanding accomplishments, we're positioned to an even more productive 2025, where we'll have several clinical advancement across our immunology pipeline.

因此，我剛才討論的所有進展都反映了我們在這一年取得的真正傑出的成就，我們有望在 2025 年取得更加豐碩的成果，屆時我們的免疫學管道將取得多項臨床進展。

To summarize, here is what you can expect this year. Starting with STAT6, we're on track to report KT-621 Phase I data this year for both the healthy volunteer trial, which will happen in June and the Phase Ib trial in AD, which will happen in the fourth quarter of '25. And we also initiate 2 Phase IIb studies. AD will start in the later part of '25 and asthma will start in early '26.

總而言之，以下是您今年可以期待的事情。從 STAT6 開始，我們預計在今年報告 KT-621 第一階段數據，包括將於 6 月進行的健康志願者試驗和將於 25 年第四季度進行的 AD 第一階段試驗。我們也啟動了兩項 IIb 期研究。AD 將於 25 年後期開始，氣喘將於 26 年初開始。

For TYK2, we're on track to advance KT-295 into the clinic next quarter with Phase I healthy volunteer data before year-end. Stay tuned in May as we plan to unveil our next program, a previously undrugged transcription factor that has the potential to be first-in-class agent for multiple rheumatic as well as other autoimmune diseases. Importantly, we will not stop here.

對於 TYK2，我們預計在下個季度將 KT-295 推進到臨床階段，並在年底前獲得第一階段健康志願者的數據。請關注我們五月計畫推出的下一個項目，這是一種以前未曾用過的轉錄因子，有可能成為治療多種風濕病和其他自體免疫疾病的一流藥物。重要的是，我們不會就此止步。

Our goal remains to deliver at least one new IND per year, so you should expect more exciting new developments to be disclosed at a consistent pace. I want to finish my comments here where we started this call, which is with our drug development principles and strategy.

我們的目標仍然是每年至少推出一項新的 IND，因此您應該期待以穩定的速度披露更多令人興奮的新進展。我想在這裡結束我的評論，我們開始這次電話會議，這是我們的藥物開發原則和策略。

Kymera is deeply committed to developing an industry-leading immunology pipeline, featuring innovative oral small molecule therapies. We're determined to ensure that patients won't have to choose or make trade-off between efficacy, safety, convenience and cost. We believe that if we achieve this, we will expand the choices available to patients and transform how patients are treated in immunology and potentially beyond.

Kymera 致力於開發業界領先的免疫學管道，以創新的口服小分子療法為特色。我們決心確保患者不必在療效、安全性、便利性和成本之間做出選擇或權衡。我們相信，如果我們實現了這一目標，我們將擴大患者的選擇範圍，並改變患者在免疫學及其他領域的治療方式。

Traditional small molecules have always offered convenience benefits, but delivering powerful pharmacology compared with biologics has been elusive. We believe our oral medicines can provide a differentiated and potentially better solution, oral drugs with biologics like efficacy, and we're dedicated to making this a reality.

傳統的小分子總是具有便利性，但與生物製劑相比，其強大的藥理作用卻難以實現。我們相信，我們的口服藥物可以提供差異化且可能更好的解決方案，即具有生物製劑般功效的口服藥物，我們致力於將這一目標變為現實。

Our work to deliver on the promise continue. We look forward to delivering on and sharing multiple data readouts in the next 12 to 18 months that we believe will validate our strategy and put us that much closer to addressing many important markets with next-generation oral drugs. Before handing the call over to Jared, I'd like to take a moment to thank Leigh Morgan, who has been a Director at Kymera for the last three years.

我們將繼續努力兌現承諾。我們期待在未來 12 到 18 個月內提供和分享多個數據讀數，我們相信這將驗證我們的策略，並使我們更接近用下一代口服藥物滿足許多重要市場。在將電話交給 Jared 之前，我想花點時間感謝 Leigh Morgan，他在過去三年中一直擔任 Kymera 的董事。

As you may have seen in the filing today, she's decided not to stand for reelection at our upcoming Annual Shareholder Meeting in June. I would love to personally thank her for all the contributions she's made at Kymera over the last several years, which have been much appreciated.

正如您可能在今天的文件中看到的那樣，她決定不再參加我們即將於 6 月舉行的年度股東大會的連任競選。我要親自感謝她過去幾年來為 Kymera 做出的所有貢獻，我對此深表感謝。

With that, let me pause here so Jared can give you more details on our clinical strategy, plans and data.

說到這裡，請允許我在這裡暫停一下，以便 Jared 可以向您提供有關我們的臨床策略、計劃和數據的更多詳細資訊。

Thanks, Nello. This is an exciting time for Kymera from a development perspective. We are well positioned to achieve multiple clinical data readouts that will further validate our approach and strategy. So let's go ahead and jump in.

謝謝，尼洛。從發展角度來看，這對 Kymera 來說是一個令人興奮的時刻。我們已做好準備，實現多項臨床數據讀數，這將進一步驗證我們的方法和策略。那麼就讓我們開始吧。

Last month, we laid out our accelerated development strategy for the STAT6 program, which starts with Phase I, Phase Ib and parallel Phase IIb trials that enable subsequent registrational Phase III studies across multiple indications.

上個月，我們制定了 STAT6 計畫的加速開發策略，該計畫從 I 期、Ib 期和平行的 IIb 期試驗開始，隨後將針對多種適應症進行註冊 III 期研究。

Each of these trials serves a distinct and unique purpose in our clinical development strategy for KT-621. I'll walk you through some details on each of these trials today, but I want to first start at a high level. So starting with the Phase I healthy volunteer study, our primary goal there is to demonstrate STAT6 degradation and safety. In addition, we will also take an early look at several Th2 biomarkers.

在我們的 KT-621 臨床開發策略中，每項試驗都有獨特的目的。今天我將向你們詳細介紹每項試驗，但我想先從高層次開始。因此，從第一階段健康志願者研究開始，我們的主要目標就是證明 STAT6 的降解和安全性。此外，我們還將提前研究幾種 Th2 生物標記。

Now while we will look at biomarkers in the Phase Ia, the Phase Ib study will be a much more relevant and meaningful opportunity to assess the impact of STAT6 degradation on multiple Th2 biomarkers in blood and skin.

現在，雖然我們將研究 Ia 階段的生物標記物，但 Ib 階段的研究將是一個更相關、更有意義的機會，以評估 STAT6 降解對血液和皮膚中多種 Th2 生物標記的影響。

And that study will also take an early look at any clinical efficacy signals. After these 2 Phase I studies, the parallel Phase IIb trials in AD and asthma are intended to measure the clinical activity in 2 key indications and enable dose selection for registrational studies in multiple indications.

該研究還將儘早觀察任何臨床療效訊號。在這兩項 I 期研究之後，在 AD 和氣喘中平行進行的 IIb 期試驗旨在衡量 2 個關鍵適應症的臨床活性，並為多種適應症的註冊研究提供劑量選擇。

In terms of the specifics on some of these activities, our Phase I healthy volunteer study is ongoing and is evaluating single and multiple ascending doses of KT-621 versus placebo. The primary objective is to show that we can robustly degrade STAT6 in blood and skin, which we define as a reduction of 90% or more at doses that are safe and well tolerated.

就其中一些活動的具體情況而言，我們的第一階段健康志願者研究正在進行中，並正在評估 KT-621 與安慰劑的單次和多次遞增劑量。主要目標是證明我們可以強力降解血液和皮膚中的 STAT6，我們將其定義為在安全且耐受性良好的劑量下減少 90% 或更多。

Given all the human genetics data, the preclinical data we have generated and the pathway validation, we believe that if we can demonstrate this, it will largely derisk the program and increase the probability of success once we move into patients.

考慮到所有人類遺傳學數據、我們產生的臨床前數據和途徑驗證，我們相信，如果我們能夠證明這一點，它將在很大程度上降低該計劃的風險，並增加我們進入患者體內後成功的可能性。

As we've shared in the past, in healthy volunteers, we expect to see some impact on several Th2 biomarkers such as TARC and IgE. Our expectation entering the trial is that the effect would likely be comparable to what has been reported for dupilumab. Though as we have said, we believe the best opportunity to show effect on a variety of Th2 biomarkers will come in patient studies where these are greatly elevated at baseline.

正如我們過去所分享的，在健康志願者中，我們預計會看到對幾種 Th2 生物標記（如 TARC 和 IgE）的一些影響。我們期望，透過試驗，其效果可能與 dupilumab 的報告效果相當。然而，正如我們所說，我們相信，展示對各種 Th2 生物標記的影響的最佳機會將出現在基線時這些生物標記大幅升高的患者研究中。

In terms of the trial status, we are recruiting the last remaining cohorts, and we're on track to report results in June. As we approach the start of the Phase Ib trial next quarter, we want to take a moment and provide a few more details about the study.

就試驗狀態而言，我們正在招募最後一批試驗對象，並將於 6 月公佈結果。隨著下個季度 Ib 期試驗即將開始，我們想花點時間提供更多關於研究的細節。

The Phase Ib trial in moderate to severe atopic dermatitis will be a relatively small single-arm open label trial with dose selection optimized based on Phase I healthy volunteer results. Patients will be administered KT-621 once daily for four weeks.

針對中度至重度異位性皮膚炎的 Ib 期試驗將是一項相對較小的單臂開放標籤試驗，劑量選擇將根據 I 期健康志願者的結果進行優化。患者將每天接受一次 KT-621 治療，持續四週。

The trial is expected to include approximately 20 patients. The key study aim is to show that robust STAT6 degradation in blood and skin by KT-621 has a dupilumab-like effect on reducing multiple Th2 biomarkers in the blood, such as eotaxin TARC, periostin IgE and others and on the transcriptome of active AD skin lesions. The study will also assess KT-621 effect on AD clinical endpoints such as EASI and pruritus NRS.

預計該試驗將涉及約 20 名患者。這項研究的主要目的是證明 KT-621 對血液和皮膚中 STAT6 的強烈降解具有類似 dupilumab 的效果，可降低血液中的多種 Th2 生物標誌物，例如嗜酸細胞活化趨化因子 TARC、骨膜素 IgE 等，並可對活動性 AD 皮膚病變的轉錄組產生影響。該研究還將評估 KT-621 對 EASI 和搔癢 NRS 等 AD 臨床終點的影響。

We decided to make this a streamlined biomarker-focused study to transition quickly into Phase IIb, which is on a critical path to Phase III initiation and eventually registration. In the fourth quarter, we'll read out the Phase Ib data and also initiate the first Phase IIb placebo-controlled dose range finding trial in moderate to severe atopic dermatitis.

我們決定將其打造成一項以生物標記為重點的簡化研究，以便快速過渡到 IIb 期，這是進入 III 期並最終註冊的關鍵路徑。在第四季度，我們將讀出 Ib 期數據，並啟動針對中度至重度異位性皮膚炎的首個 IIb 期安慰劑對照劑量範圍探索試驗。

In the first quarter of 2026, we will start a second Phase IIb trial in moderate to severe asthma. This initial parallel development strategy is intended to accelerate late-stage development across multiple Th2 dermatological, gastrointestinal and respiratory indications. So turning now to TYK2.

2026 年第一季度，我們將啟動針對中度至重度氣喘的第二階段 IIb 試驗。此初步平行開發策略旨在加速多種 Th2 皮膚病、胃腸道和呼吸系統適應症的後期開發。現在轉向 TYK2。

This is another program where we believe we can mimic the human genetics TYK2 loss of function profile and achieve biologics-like activity with an oral drug. We're on track to start the KT-295 Phase I healthy volunteer study in the second quarter.

這是另一個項目，我們相信我們可以模仿人類遺傳學 TYK2 功能喪失概況，並透過口服藥物實現類似生物製劑的活性。我們將在第二季啟動 KT-295 第一階段健康志願者研究。

The primary goal is to demonstrate safety and full TYK2 degradation in blood and skin, which, if achieved, we believe would be the first time an oral small molecule was able to show complete blockade of TYK2 signaling. And we expect data will be shared in the fourth quarter of 2025. Now to round out our immunology franchise, I'll wrap up with IRAK4.

主要目標是證明其安全性以及 TYK2 在血液和皮膚中的完全降解，如果實現，我們相信這將是口服小分子首次能夠完全阻斷 TYK2 訊號傳導。我們預計數據將在 2025 年第四季實現共享。現在，為了完善我們的免疫學特許經營權，我將以 IRAK4 結束。

As Nello mentioned, last year, Sanofi took steps to accelerate the overall KT-474 development timeline. The decision to expand the Phase II program was to structure the hidradenitis suppurativa and atopic dermatitis trials with the necessary regulatory perspective to enable dose selection and advancement directly to pivotal Phase III studies, ultimately with a meaningfully shorter development timeline.

正如 Nello 所提到的，去年賽諾菲採取措施加快 KT-474 的整體開發時間表。擴大 II 期計畫的決定是為了以必要的監管視角建構化膿性汗腺炎和異位性皮膚炎試驗，以便能夠進行劑量選擇並直接推進到關鍵的 III 期研究，最終顯著縮短開發時間。

To support this strategy, the size of the studies increased with additional doses planned for evaluation in both trials. There are no changes to the Phase II study endpoints. With the planned expansion of the trials, the primary completion dates were adjusted to the first half of 2026 and mid-2026 for HS and AD, respectively.

為了支持這項策略，研究規模擴大，並計劃在兩項試驗中增加劑量進行評估。第二階段研究終點沒有改變。隨著試驗計畫的擴大，HS 和 AD 的主要完成日期分別調整為 2026 年上半年和 2026 年中期。

The progress made by our team in 2024 sets us up to execute in 2025. Importantly, within our immunology franchise, we believe KT-621, our first and we believe best-in-class oral STAT6 degrader has the ability to transform the treatment of Th2 inflammatory diseases, and we look forward to sharing Phase I data in healthy volunteers next quarter and advancing the program into patient studies while also initiating the TYK2, KT-295 Phase I trial next quarter and sharing data by year-end.

我們團隊在 2024 年的進展為我們在 2025 年實現目標奠定了基礎。重要的是，在我們的免疫學特許經營中，我們相信 KT-621，我們的第一個也是我們認為最好的口服 STAT6 降解劑，有能力改變 Th2 炎症疾病的治療，我們期待下個季度在健康志願者中分享 I 期數據，並將該計劃推進到患者研究中，同時在下個季度啟動 TYK2、KT-295 I 期，並在年底前分享數據。

And as Nello mentioned, we're excited to introduce our next immunology program, which aligns perfectly with our pipeline portfolio strategy. We're planning to host a company webcast in early May to unveil the new target, and we'll share more information as we get closer. I should point out that the KT-621 Phase I healthy volunteer data, which we expect will be reported in June, will be its own separate event.

正如 Nello 所提到的，我們很高興推出我們的下一個免疫學項目，它與我們的管道組合策略完美契合。我們計劃在 5 月初舉辦一次公司網路廣播來公佈新的目標，隨著目標的臨近，我們將分享更多資訊。我應該指出的是，我們預計將於 6 月報告的 KT-621 第一階段健康志願者數據將是一個獨立的事件。

I'll now turn the presentation over to Bruce for a review of the fourth quarter and full year financials. Bruce?

現在我將把簡報交給布魯斯，讓他回顧第四季和全年的財務狀況。布魯斯？

Thanks, Jared. As I review our fourth quarter 2024 financial highlights, please reference the tables found in today's press release. Revenue in the fourth quarter of 2024 was $7.4 million, all of that was attributable to our Sanofi collaboration.

謝謝，賈里德。當我回顧我們 2024 年第四季的財務亮點時，請參考今天新聞稿中的表格。2024 年第四季的營收為 740 萬美元，全部歸功於我們與賽諾菲的合作。

With respect to operating expenses, R&D for the quarter was $71.8 million, of that, approximately $6.8 million represented noncash stock-based compensation. Adjusted cash R&D spend of $65 million, excluding that stock-based comp, reflects a 23% sequential increase from the third quarter.

就營運費用而言，本季研發費用為 7,180 萬美元，其中約 680 萬美元為非現金股票薪資。調整後的現金研發支出為 6,500 萬美元（不含股票補償），較第三季季增 23%。

G&A for the quarter was $16.3 million, of that, approximately $7 million was noncash stock-based comp and adjusted cash G&A spend of $9.3 million, again, excluding stock-based comp was up 13% sequentially. Our cash balance at the end of 2024 was $851 million, our cash balance is expected to provide a runway into mid-2027, and that will enable us to execute on multiple data readouts you've heard today, including several important Phase II trials across our programs.

本季的 G&A 費用為 1,630 萬美元，其中約 700 萬美元為非現金股票補償，調整後的現金 G&A 支出為 930 萬美元，同樣，不包括股票補償，季增 13%。我們 2024 年底的現金餘額為 8.51 億美元，預計我們的現金餘額將為 2027 年中期提供支撐，這將使我們能夠執行您今天聽到的多個數據讀數，包括我們項目中的幾個重要的 II 期試驗。

So, this concludes our prepared remarks. If you just give us a moment to assemble in our conference room, we'll be happy to address any questions you have there. Thanks very much.

我們的準備好的演講到此結束。如果您給我們一點時間在我們的會議室集合，我們將很樂意解答您的任何問題。非常感謝。

(Operator Instructions)

（操作員指示）

Faisal Khurshid with Leerink Partners.

Faisal Khurshid 與 Leerink Partners 合作。

Hi, guys. Good to literally see you and congrats on the updates. Just a quick one for us. What supports your view that the 28 dosing in the atopic derm Phase Ib is enough time to show robust biomarker activity? And then could you also comment a little bit on how you've kind of thought about the inclusion/exclusion criteria for that Phase Ib?

嗨，大家好。很高興見到你並祝賀你的更新。對我們來說這只是一個快速步驟。您認為，在異位性皮膚病 Ib 期中進行 28 次給藥足以顯示出強大的生物標記活性，這背後有什麼依據？然後，您能否稍微評論一下您對 Ib 階段的納入/排除標準的看法？

Good to see you as well. Jared, why don't you take this one?

我也很高興見到你。賈里德，你為什麼不接受這個？

Sure. It's an important question. And we know from prior dupilumab trials where there have been 16-week endpoints in AD -- in moderate to severe AD that when you look at the time course of what's happening, they don't just look at six weeks, they also look at earlier time points.

當然。這是一個重要的問題。我們從先前的 dupilumab 試驗中得知，AD 的終點時間為 16 週——對於中度至重度 AD，當你觀察事情發生的時間過程時，他們不僅關註六週，還關注更早的時間點。

And looking at four weeks, it was shown that there was a clear -- very clear impact on Th2 biomarkers as well as on clinical endpoints like EASI and pruritus NRS. I think we're very confident that 28 days of treatment using an optimal dose selected from Phase Ia should allow us to see a clear impact on Th2 biomarkers, which is the primary objective of the study and to also give us an opportunity to see an impact on clinical endpoints.

四週的觀察表明，它對 Th2 生物標記以及 EASI 和搔癢 NRS 等臨床終點有非常明顯的影響。我認為我們非常有信心，使用從 Ia 期選擇的最佳劑量進行 28 天的治療應該讓我們看到對 Th2 生物標誌物的明顯影響，這是研究的主要目標，也讓我們有機會看到對臨床終點的影響。

In terms of eligibility criteria, I think here, it's going to be very important that we have stringent criteria that make sure that we're getting, number one, patients that definitely have AD; and secondly, patients that have moderate to severe disease.

就資格標準而言，我認為，制定嚴格的標準非常重要，以確保我們接收的患者首先是肯定患有 AD 的患者；其次是患有中度至重度疾病的患者。

I think that's very important in trying to minimize any sort of placebo effect is to pay close attention to those particular eligibility criteria. That's going to be a very important part of the study. Maybe just mention a few other things that are important to reduce or minimize placebo effect.

我認為，在盡量減少任何安慰劑效應時，密切注意那些特定的資格標準非常重要。這將是研究中非常重要的一部分。也許只需提及一些對於減少或最小化安慰劑效應很重要的其他事項。

One is having a rigorous approach to site selection, making sure we bring on sites that are able to select the right AD patients for the study and have personnel that can perform the clinical assessments in a rigorous manner and to also make sure that we're closely monitoring for drug compliance on the study and also making sure that patients are not taking any other con meds.

一是要嚴格選擇研究地點，確保我們選擇的地點能夠為研究選擇合適的 AD 患者，並配備能夠以嚴格方式進行臨床評估的人員，同時還要確保我們密切監測研究中的藥物依從性，並確保患者沒有服用任何其他藥物。

Maybe look if I can just add one thing. Obviously, hopefully, it's appreciated that I think we have not only an amazing opportunity with this drug, but I also think we have a unique responsibility to do the right type of drug development.

也許看看我是否可以添加一件事。顯然，我希望大家能夠意識到，我認為我們不僅在這種藥物方面擁有絕佳的機會，而且我還認為我們肩負著進行正確類型藥物開發的獨特責任。

And so also another reason for the 28-day study besides being long enough to measure -- and actually, the study is powered enough for 28 day to measure strong biomarker changes is that what's a critical path is going into a dose-ranging Phase IIb study, which is on path to go to Phase III in registration.

因此，除了足夠長的時間進行測量之外，進行 28 天研究的另一個原因是 — — 事實上，該研究有足夠的動力在 28 天內測量強烈的生物標誌物變化，因為關鍵路徑是進入劑量範圍 IIb 期研究，該研究正在註冊進入 III 期。

So, what we don't want to do is spend time unnecessarily in early clinical development in studies that are informative but not critical.

因此，我們不想在早期臨床開發中花費不必要的時間進行那些雖然提供資訊但並不重要的研究。

Yes. And then just to kind of clarify on the choice to not have a placebo arm in the Phase Ib, especially given kind of like what's been seen in other atopic derm studies?

是的。然後，只是想澄清為什麼選擇在 Ib 階段不設置安慰劑組，特別是考慮到在其他特異性皮膚病研究中看到的情況？

Yes. Maybe -- Jared, maybe I'll start and then you -- it kind of goes back to what I just said. So the goal of the study, as Jared said, is to demonstrate a biomarker profile in blood and skin that we believe will be robust and can be compared to, for example, the dupilumab 4-week data. And that's -- for that type of study, actually, we don't believe we need a placebo. We know that biomarkers do not move substantially in the placebo arm of these studies.

是的。也許——賈里德，也許我會開始，然後你——這有點回到我剛才說的話。因此，正如 Jared 所說，這項研究的目標是展示血液和皮膚中的生物標記概況，我們相信該概況將是穩健的，並且可以與例如 dupilumab 4 週數據進行比較。事實上，對於這種類型的研究，我們認為我們不需要安慰劑。我們知道，在這些研究的安慰劑組中，生物標記並沒有實質的變化。

And again, if we had to run a placebo-controlled study for four weeks powered to demonstrate a difference on clinical endpoints, this would be a much larger and longer study. And again, this does not fulfill our drive, which is to go into Phase IIb ASAP.

再說一次，如果我們必須進行為期四週的安慰劑對照研究來證明臨床終點的差異，那麼這將是一項更大、更長的研究。但這並不能滿足我們盡快進入 IIb 階段的願望。

Got it. Super helpful. Thank you, guys, so much.

知道了。超有幫助。非常感謝你們。

Andy Chen with Wolfe Research.

沃爾夫研究公司的安迪陳 (Andy Chen)。

Hi. Nice to see you in person. So the Phase Ib is designed to be single arm. So we won't be able to see dose response on biomarkers. Do you think the Th2 biomarker data is going to be so clean that we won't need to see dose response across different doses to be comfortable with the data? Just curious if we're going to have enough data to answer additional questions about efficacy by Q4.

你好。很高興見到你。因此，Ib 階段被設計為單臂。所以我們無法看到生物標記的劑量反應。您是否認為 Th2 生物標記數據會非常清晰，以至於我們不需要觀察不同劑量的劑量反應就可以對數據感到滿意？只是好奇到第四季我們是否有足夠的數據來回答更多有關功效的問題。

Yes. So maybe I'll start, Jared can add more specific point. So thanks, Andy. I think this is a great question. So our goal is to take into this Phase Ib study, a dose that has demonstrated in healthy volunteer the type of profile that we're looking for.

是的。所以也許我會開始，賈里德可以補充更具體的觀點。所以謝謝你，安迪。我認為這是一個很好的問題。因此，我們的目標是在 Ib 期研究中採用一種劑量，這種劑量已在健康志願者身上顯示出我們所尋求的特徵類型。

And as we said, at least 90% degradation in blood and skin. We have shown preclinically that, that type of profile leads to extremely robust biomarkers effect in a plethora of readouts. So our development is based on our understanding of the biology and both in terms of all the preclinical data we've amassed as well as on human genetics.

正如我們所說，血液和皮膚至少有 90% 的降解。我們在臨床前已證明，這種類型的概況會在大量讀數中產生極其強大的生物標記效應。因此，我們的發展是基於我們對生物學的理解以及我們累積的所有臨床前數據以及人類遺傳學的理解。

So we expect that a dose with that profile will have a dupilumab-like effect, and that's really what we want to show. If we were not certain and if this was really an exploratory Phase Ib study to show an early proof-of-concept, we'll probably design it differently.

因此，我們預期具有該特徵的劑量將產生類似度普利尤單抗的效果，而這正是我們想要展示的。如果我們不確定，並且如果這真的是一項探索性的 Ib 期研究，以展示早期的概念驗證，我們可能會採用不同的設計。

We're designing this study with expecting a successful outcome based on all the experience that we've built internally and all the data we've generated so far.

我們正在設計這項研究，並期望根據我們內部累積的所有經驗和迄今為止產生的所有數據取得成功的結果。

And maybe just to add, the opportunity for being able to see an impact on both Th2 biomarkers and clinical endpoints to see a dose response there will come from Phase IIb, where that will be a true dose range finding study, and that will give us a strong opportunity to do that.

也許只是補充一下，能夠看到對 Th2 生物標記和臨床終點的影響以觀察劑量反應的機會將來自 IIb 期，這將是一項真正的劑量範圍探索研究，這將為我們提供一個很好的機會來做到這一點。

And as Nello said earlier, the key really is for us to use Phase Ia information to select the doses for the dose range finding Phase IIb study and to get to Phase IIb as quickly as possible. And then Phase IIb becomes a great platform for us to show perhaps differences in impact on Th2 biomarkers and clinical endpoints depending on the doses that we select for Phase IIb.

正如 Nello 先前所說，關鍵在於我們要利用 Ia 期資訊來選擇劑量範圍來探索 IIb 期研究的劑量，並儘快進入 IIb 期。然後，IIb 期成為一個很好的平台，讓我們能夠展示根據我們為 IIb 期選擇的劑量對 Th2 生物標記和臨床終點的影響的差異。

And that will ultimately allow us to pick the optimal dose for the Phase III registrational studies.

這最終將使我們能夠為第三階段註冊研究選擇最佳劑量。

Thank you, Nello. Thank you, Jared.

謝謝你，尼洛。謝謝你，賈里德。

Next question.

下一個問題。

Michael Schmidt with Guggenheim.

麥可·施密特與古根漢美術館。

Hey, guys. Thanks for taking our question. This is Paul on for Michael Schmidt. Just on the STAT6 program, what do we know currently about the potential bioavailability of KT-621 in tissues of interest, for example, skin versus lung tissue or others that might be disease relevant down the line. How predictive are the preclinical models there? Is there any opportunity to look into that in the early Phase I or Ib?

嘿，大家好。感謝您回答我們的問題。這是保羅，代替麥可·施密特。僅在 STAT6 程序中，我們目前對 KT-621 在目標組織中的潛在生物利用度了解多少，例如皮膚與肺組織或其他可能與疾病相關的組織。那裡的臨床前模型的預測能力如何？是否有機會在 I 期或 Ib 期的早期研究這個問題？

Yes. So obviously, I can't speak to the Phase I healthy volunteer data, but I can speak to the preclinical data that we've generated. And we generated extensive data across all species that you can imagine mouse, rat, dog, nonhuman primates and others where we have been able to demonstrate that KT-621 not only is orally bioavailable, but is actually highly active at low oral doses and distributes evenly across all tissues of interest. We've shown in nonhuman primates equal both distribution and degradation in blood, skin, spleen, lungs. And so our expectation is that the preclinical profile will translate equally in human.

是的。顯然，我無法談論第一階段健康志願者的數據，但我可以談論我們產生的臨床前數據。我們對包括小鼠、大鼠、狗、非人靈長類動物和其他動物在內的所有物種都產生了大量數據，證明 KT-621 不僅具有口服生物利用度，而且在低口服劑量下也具有高活性，並均勻分佈在所有目標組織中。我們已經證明，非人靈長類動物的血液、皮膚、脾臟和肺部的分佈和降解都是均勻的。因此，我們預期臨床前概況能夠在人類身上得到同樣的體現。

And a way to measure that, obviously, we can take lung and spleen, but obviously, we can take blood and skin as we've done for other programs. And so we believe that those are great surrogate tissues to show not only hopefully the desired degradation that we expect to have, but also a consistent degradation across multiple tissues.

測量方法很明顯，我們可以取肺和脾，但顯然，我們也可以取血液和皮膚，就像我們在其他項目中所做的那樣。因此，我們相信，這些都是很好的替代組織，不僅有望顯示出我們期望的降解效果，而且還能顯示出跨多種組織的一致降解效果。

I would just go back to what we've been saying for the past years, I would say, that we've been fortunate that all of our programs have translated impeccably, I would say, between preclinical and clinical. So we hope and expect that 621 will follow suit on that particular front.

我想回顧一下過去幾年我們一直在說的話，我想說，我們很幸運，我們所有的計畫在臨床前和臨床之間都進行了完美的轉化。因此，我們希望並期待 621 能夠在這方面效仿。

Great. And if I could just have a quick follow-up on the planned design for the Phase II AD study. Is the sort of ongoing IRAK4 study a reasonable comp, three different doses plus placebo. Any meaningful differences in the type or severity of AD patients you might recruit there?

偉大的。我是否可以快速跟進第二階段 AD 研究的計劃設計。正在進行的 IRAK4 研究是否是合理的對照，三種不同劑量加安慰劑。您招募的 AD 患者的類型或嚴重程度有何顯著差異？

I'm going to save Jared on this one. I think at this point, we're not going to comment. Hopefully, you guys appreciate that we're sharing the relevant information when it's the right time as we're doing today for the Phase Ib. We promise you that when it's the right time, we will share that kind of information as well.

這次我要拯救賈里德。我認為目前我們不會發表評論。希望你們能夠理解，我們在適當的時候分享相關訊息，就像我們今天為 Ib 階段所做的那樣。我們向您保證，在適當的時候，我們也會分享此類資訊。

Great. Thanks very much.

偉大的。非常感謝。

Thanks, Paul.

謝謝，保羅。

Ron Feiner with JPMorgan.

摩根大通的 Ron Feiner。

You guys don't have to show the video in case you don't want to, right? I think it's okay just to ask your question. But anyway, go ahead.

如果你們不想的話，就不必播放視頻，對嗎？我認為只問你的問題是可以的。但無論如何，請繼續。

It's Ron on for Eric. I just wanted to ask again on the dose selection, maybe you will be evaluating only one dose in this Phase Ib for AD? And how does the SAD/MAD data so far from the healthy volunteers trial kind of give you information on the effective range, at least from a PD perspective?

羅恩代替埃里克上場。我只是想再次詢問劑量選擇，也許您會在 Ib 階段僅評估 AD 的一個劑量？到目前為止，健康志願者試驗中的 SAD/MAD 數據如何為您提供有關有效範圍的信息，至少從 PD 角度來看？

Yes. I mean, unfortunately, we can't go into the answer. But what I think I can say, Jared has already said it, but I'll say it again. The beauty of protein degradation, unlike any other technology out there that you can measure target engagement both in a dose-responsive manner as well as in a time-responsive manner. So you know what is the level of degradation of your target at different doses at different time points.

是的。我的意思是，不幸的是，我們無法深入探究答案。但我認為我可以說，賈里德已經說過了，但我會再說一次。蛋白質降解的美妙之處在於，它不同於任何其他技術，您可以以劑量響應的方式以及時間響應的方式測量目標參與度。因此，您知道在不同時間點、不同劑量下目標的降解程度。

And so we have designed a really comprehensive Phase I healthy volunteer study that is looking at a range of doses that will allow us to understand as well as we can, the relationship between dose, PK and degradation in blood and skin.

因此，我們設計了一項非常全面的第一階段健康志願者研究，該研究考察了一系列劑量，以便我們盡可能地了解劑量、藥物動力學 (PK) 以及血液和皮膚降解之間的關係。

With that set of data, as we said in clinicaltrials.gov, we expect up to 120 subjects on the study. So we'll have a really large data set. We would be able to have enough to confidently select the, let's say, three doses for the Phase IIb studies. And we don't believe -- and we've already shown with IRAK4 that there is a really strong translation of degradation between healthy and diseased patients in terms of degradation profile.

正如我們在 clinicaltrials.gov 中所說，有了這組數據，我們預計研究對象將達到 120 名。所以我們將擁有一個非常大的資料集。我們將能夠有足夠的信心為 IIb 期研究選擇三種劑量。我們不相信—我們已經透過 IRAK4 證明，就降解概況而言，健康患者和患病患者之間存在著非常強烈的降解轉變。

And so we believe that everything that we've designed going from a very comprehensive Phase I healthy going into Ib to really demonstrate that one of the doses that likely will be taken into Phase II is given the type of profile that we expect in patients. It's, let's say, a confirmatory study and then Ron, go into a Phase IIb ASAP.

因此，我們相信，我們設計的一切，從非常全面的 I 期健康試驗到 Ib 期，都真正證明了可能進入 II 期的劑量之一具有我們預期的患者特徵類型。可以說，這是一項確認性研究，然後 Ron 會盡快進入 IIb 階段。

I think we feel very confident about our plan right now. And so again, we look forward to sharing the data along the way and then get to the end of the year with these big studies.

我認為我們現在對我們的計劃非常有信心。因此，我們再次期待在此過程中分享數據，然後在年底完成這些大型研究。

Thanks. And then just maybe if I can try on the new program, are you guys geared more towards staying in the Th2 space or anything additive or orthogonal to current programs or is it going to be completely new?

謝謝。那麼，如果我可以嘗試新的程序，你們是否更傾向於停留在 Th2 空間或任何與當前程序相附加或正交的東西，或者它將是全新的？

Well, I think what we've tried to do, if you look at our pipeline, so in immunology, I think we're shaping up to have the best oral immunology pipeline in the industry. I know my team doesn't like me to say it, but I keep saying it. The -- if you look at IRAK4, this is a classical Th1, Th17 program with IL-1 TLR activity. If you look at TYK2 is IL-23 type 1 interferon. If you look at STAT6, it's a classical, maybe the best Th2 target, I would say.

嗯，我認為我們已經嘗試去做了，如果你看看我們的管道，那麼在免疫學方面，我認為我們正在形成業內最好的口服免疫學管道。我知道我的團隊不喜歡我這麼說，但我一直這麼說。如果你看一下 IRAK4，這是一個具有 IL-1 TLR 活性的經典 Th1、Th17 程式。如果你看一下，TYK2 就是 IL-23 1 型乾擾素。如果你看 STAT6，我會說它是一個經典的、也許是最好的 Th2 目標。

And so these are all complementary pathway that actually one can imagine could be synergistic in a combination one day. And so you should expect this other target to be a complementary pathway to the ones that we've shared so far.

因此，這些都是互補的途徑，實際上我們可以想像有一天它們可以結合起來產生協同作用。因此，您應該期望這個其他目標是我們迄今為止所分享的目標的補充途徑。

Thanks.

謝謝。

Jeff Jones with Oppenheimer.

傑夫瓊斯和奧本海默。

Good morning, guys. Thanks for taking question. I think we've asked a lot on STAT6. Curious to get your view on the TYK2 program from a similar perspective as we think about biomarkers and tissue penetration, how we should think about looking at that data, which -- at the healthy volunteer data, which is obviously some way out. So can you share how you're going to be looking at not only safety, but efficacy signals there from a perspective of TYK2 and biomarkers?

大家早安。感謝您的提問。我認為我們在 STAT6 上問了很多問題。我很好奇，想從類似的角度了解您對 TYK2 計劃的看法，就像我們考慮生物標誌物和組織滲透一樣，我們應該如何看待這些數據——健康志願者的數據，這顯然是一種出路。那麼，您能否從 TYK2 和生物標誌物的角度分享您如何看待安全性和功效訊號？

Jared, do you want to take this?

賈里德，你想接受這個嗎？

Sure. Yes. I think for the TYK2 program, I think we have a unique opportunity to show pharmacology that is differentiated from what's out there for typical TYK2 small molecules. And that's why we believe this program can eventually attain biologics like activity, hopefully, which has not really been attained by the small molecules.

當然。是的。我認為對於 TYK2 項目，我們有一個獨特的機會來展示與典型的 TYK2 小分子不同的藥理學。這就是為什麼我們相信這個計畫最終能夠達到類似生物製劑的活性，而小分子實際上還無法達到這種活性。

And to do that is important, we believe that for the pharmacology to show that we can fully degrade TYK2 95%-plus percent and keep that degradation level 24/7 sort of around the clock, in order to give us that full pathway blockade that would be the equivalent of what you can get with an injectable upstream biologics.

要做到這一點很重要，我們相信藥理學表明我們可以完全降解 TYK2 95％ 以上，並全天候保持這種降解水平，以便為我們提供完全的通路阻斷，這相當於使用可注射的上游生物製劑所能獲得的效果。

So I think when we look at the Phase I study, just as we've done in STAT6, we're going to have very detailed looks at the impact on TYK2 levels in blood and in skin in healthy volunteers, looking over time, looking at different dose levels in SAD as well as in MAD.

因此，我認為，當我們研究第一階段研究時，就像我們在 STAT6 中所做的那樣，我們將非常詳細地觀察對健康志願者血液和皮膚中 TYK2 水平的影響，隨著時間的推移，觀察 SAD 和 MAD 中的不同劑量水平。

And that's going to really give us a very good idea as to whether our pharmacology can really achieve what we've seen preclinically in animals, where we can achieve that sort of profile, a very deep chronic degradation of TYK2 at doses that are safe and well tolerated.

這將讓我們真正了解我們的藥理學是否真的能夠達到我們在動物身上臨床前所看到的效果，即在安全且耐受性良好的劑量下實現 TYK2 的深度慢性降解。

So that's going to be, I think, critical for us in terms of the biomarkers that will be looked at in that TYK2 study. There will be other opportunities potentially to look at additional biomarkers that reflect impact on IL-12, IL-23 type 1 interferon pathways and sparing IL-10. But I think the primary focus will be on achieving that sort of pharmacology that I just mentioned in terms of the impact on TYK2.

因此，我認為，就 TYK2 研究中要研究的生物標記而言，這對我們來說至關重要。可能還有其他機會來研究反映對 IL-12、IL-23 1 型乾擾素路徑和保留 IL-10 的影響的其他生物標記。但我認為主要的重點將放在實現我剛才提到的對 TYK2 的影響的藥理學上。

And if we're able to see that sort of impact, I think that will be very encouraging for us. And our plan then is the next step after Phase I is to then do a Phase II proof-of-concept study, probably a placebo-controlled study that might be in a disease like psoriasis where there, we want to be able to bring optimal dose or doses from that Phase Ia study into Phase II and really demonstrate there that we have biologics like activity, for example, that we have SKYRIZI-like effect on PASI 90 in psoriasis.

如果我們能夠看到這種影響，我想這對我們來說將是非常令人鼓舞的。我們的計劃是，在第一階段之後的下一步是進行第二階段的概念驗證研究，可能是針對牛皮癬等疾病的安慰劑對照研究，我們希望能夠將第一階段研究中的最佳劑量帶入第二階段，並真正證明我們具有類似生物製劑的活性，例如，我們對牛皮癬的 PASI 90 具有類似 SKYRIZI 的效果。

And that would be the key inflection point for us to then say, okay, here we have a compound that is clearly differentiated from small molecule inhibitors. It has biologics like activity. And then we would want to move it forward potentially across multiple potential different indications that are both interferonopathies, such as lupus, IBD in addition to psoriasis.

這對我們來說將是一個關鍵的轉折點，然後我們會說，好吧，我們這裡有一個與小分子抑制劑明顯不同的化合物。它具有類似生物製劑的活性。然後，我們希望將其推廣到多種潛在的不同適應症，這些適應症都是乾擾素病，例如狼瘡、IBD 以及牛皮癬。

Great. Appreciate that. And just one quick follow-up. As you mentioned, the possibilities in Phase II, how do you think about in terms of patient selection, patients who prior exposure to, say, deucrav or one of the biologics impacting the IL-23 pathway.

偉大的。非常感謝。還有一個快速的後續問題。正如您所提到的，第二階段的可能性，您如何考慮患者選擇，那些先前接觸過 deucrav 或影響 IL-23 路徑的生物製劑的患者。

Maybe it's a bit too early, Jeff, to discuss it. Obviously, let's say, we end up going in psoriasis, there is lots of patients that are available to us to ask the question in a way that is not influenced by failures on, let's say, pathway agents. So we'll obviously be very thoughtful about the patient selection, but we'll share more of that as we're getting closer to the study.

傑夫，現在討論這個問題可能還為時過早。顯然，假設我們最終研究牛皮癬，那麼有很多患者可以向我們提出問題，而這些問題不會受到途徑藥物失敗的影響。因此，我們顯然會非常認真地選擇患者，但隨著研究的臨近，我們會分享更多資訊。

Thank you guys.

謝謝你們。

Kelly Shi with Jefferies.

傑富瑞 (Jefferies) 的 Kelly Shi。

Hi. Thank you for taking my question. This is Evan on behalf of Kelly from Jefferies. Another question on STAT6. So for the biomarker analysis in the MAD portion, how long is the follow-up going to be? Can we expect like data from IgE and TARC at multiple time points across the dosing period and after 14 days of dosing or we may only expect 1 or 2 time point? And also wondering how would this biomarker data in healthy volunteer guide your decision on dose levels in Phase Ib and the Phase II trials in patients?

你好。感謝您回答我的問題。我是傑富瑞集團凱利的代表艾文。關於 STAT6 的另一個問題。那麼對於 MAD 部分的生物標記分析，後續追蹤需要多長時間？我們是否可以預期在給藥期間和給藥 14 天後的多個時間點獲得 IgE 和 TARC 的類似數據，或者我們可能只預期 1 或 2 個時間點？並且還想知道健康志願者的生物標記數據如何指導您決定患者在 Ib 期和 II 期試驗中的劑量水平？

Maybe I'll start. This is a great question, actually. So the first part, it's obviously -- it's easy. Yes, we will have several time points, both during doses and post-dosing period. The second question is -- actually, it's a great question because it allows us to touch on a very important point, which is if you look at the dupilumab healthy volunteer studies where we now have in our deck sometimes to show to investors what does the data look like.

也許我會開始。事實上，這是一個很好的問題。因此，第一部分顯然很簡單。是的，我們會有幾個時間點，包括服藥期間和服藥後期。第二個問題是——實際上，這是一個很好的問題，因為它讓我們觸及一個非常重要的點，那就是如果你看一下 dupilumab 健康志願者研究，我們現在有時會向投資者展示數據是什麼樣的。

Instead of just talking about numbers, actually looking at the totality of the dupilumab data, you will actually see that in most cases, if not in all cases, there is actually a lack of dose response between the different doses. So if you actually chose the healthy volunteer biomarker data for dose selection for dupilumab, let's talk about dupilumab. You will probably pick the wrong dose to go into Phase II or Phase III. But obviously, how we're going to select this dose is by looking at the totality of the data, right? For us, the key information is can we degrade STAT6 robustly.

不僅僅是談論數字，實際上查看 dupilumab 數據的整體，您實際上會發現在大多數情況下（如果不是所有情況），不同劑量之間實際上缺乏劑量反應。因此，如果您實際上選擇了健康志願者生物標記數據來選擇度普利尤單抗的劑量，那麼讓我們來討論度普利尤單抗。您可能會選擇錯誤的劑量進入第二階段或第三階段。但顯然，我們要透過查看全部數據來選擇劑量，對嗎？對我們來說，關鍵訊息是我們能否穩健地降解 STAT6。

And by that, we mean 90% or more in blood and skin. Is that safe and well tolerated? And that's really what we're going to use to make a dose selection. But we'll also look at the totality of the data and obviously share it with you at the right time.

我們指的是血液和皮膚中含有 90% 或更多的物質。這是否安全且耐受性良好？這確實是我們要用來選擇劑量的依據。但我們也會查看全部數據，並在適當的時候與您分享。

Thank you.

謝謝。

Brad Canino with Stifel.

布拉德·卡尼諾 (Brad Canino) 與 Stifel 合作。

Great. Good morning. So look, I think you've done a really good job previewing the STAT6 healthy volunteer data. And I can see how the target profile will allow you to move into patients with conviction. You can marry that to the preclinical outcomes.

偉大的。早安.所以，我認為您在預覽 STAT6 健康志願者數據方面做得非常好。我可以看到目標概況將如何幫助您堅定地治療患者。您可以將其與臨床前結果結合。

It's the outstanding question, and you started to touch on this in some of the prior responses, is how you see the Phase Ib building on that conviction, 20 patient study, short four week treatment. How do you really see that being a useful tool to shape the view of the profile potential, even though it's not designed to be a definitive assessment of the drug in patients?

這是一個懸而未決的問題，您在先前的一些回答中已經開始觸及這個問題，您如何看待基於此信念的 Ib 期研究，即 20 名患者的研究，為期四週的短期治療。儘管它並非旨在對患者用藥情況進行最終評估，但您如何看待它成為塑造概況潛力觀點的有用工具？

Yeah. So look, Brad, our view is that this is going to be -- I don't know where we want to call it, the drug of the decade or the drug of the century. So we have to be really thoughtful about the study designs along the way. And we have to really ask the right question in each study. Otherwise, we end up creating confusion instead of clarity.

是的。所以，布拉德，我們的觀點是，這將是──我不知道我們該怎麼稱呼它，十年之毒還是世紀之毒。因此，我們必須認真考慮研究設計。我們必須在每項研究中提出正確的問題。否則，我們最終只會造成混亂而不是清晰。

So the questions for our studies are very well thought out. And I think we're going to get the right question in the right study. So for healthy volunteer, the question is, I'm going to keep saying it, can we degrade the target? Well, robustly, I should use the same word. And is that safe and well tolerated?

所以我們研究的問題是經過深思熟慮的。我認為我們會在正確的研究中得到正確的問題。因此，對於健康志工來說，問題是，我會繼續說，我們可以降低目標嗎？好吧，我應該用同樣的字。這是否安全且耐受性良好？

To me, to us, this is a huge derisking step. This is the first time that STAT6 have been drugged. So this is paramount type of information. We will collect the biomarkers. I expect they will look like dupilumab in healthy, I was talking about.

對我來說，對我們來說，這是一個巨大的降低風險的舉措。這是 STAT6 首次被用藥。所以這是最重要的資訊類型。我們將收集生物標記。我希望它們看起來就像我所說的健康狀態下的度匹魯單抗。

And then the study is really designed for us to move into Phase IIb ASAP. Now why are we running the Phase Ib study? First of all, the main goal is really to generate data, especially around biomarkers that will allow us to, I think, close the circle on is a STAT6 degrader a dupi-like agent. We really cannot do it in healthy volunteers for all the reasons we discussed. These biomarkers don't move enough.

這項研究的目的實際上是讓我們盡快進入 IIb 階段。現在我們為什麼要進行 Ib 期研究？首先，主要目標實際上是產生數據，特別是圍繞生物標記的數據，我認為，這將使我們能夠完成 STAT6 降解劑和類似 dupi 的藥劑的循環。由於我們討論過的所有原因，我們確實無法在健康志願者身上做到這一點。這些生物標誌物移動得不夠。

There is a lot of noise. In many cases, you don't even see a dose response. It's more of a yes or no, that will they move? Can we change them? I expect, right?

噪音很大。在許多情況下，您甚至看不到劑量反應。這更像是一個“是”或“否”的問題，他們會搬家嗎？我們能改變它們嗎？我期待，對吧？

But in patients, we have a plethora of chemokine, cytokines in blood and skin. And in four weeks, we can actually see a big window that we should be able to reduce robustly with our drug. And to me, that's really what we're trying to show in that study.

但在患者體內，血液和皮膚中存在大量的趨化因子和細胞激素。四周後，我們實際上可以看到一個很大的窗口，我們應該能夠透過藥物強有力地減少這一窗口。對我來說，這正是我們試圖在該研究中展示的內容。

That study is telling potential investigators and patients on our Phase IIb studies, look, this is a drug that is safe and well tolerated, degrades the target well and actually also shows that has a dupi-like effect in biomarkers. And I'm confident that, that will translate into a beneficial clinical effect in these patients, so that we can power up the studies and recruit faster Phase IIb studies.

這項研究告訴我們 IIb 期研究中的潛在研究人員和患者，這是一種安全且耐受性良好的藥物，可以很好地降解靶標，實際上還顯示出在生物標記中具有類似 dupi 的效果。我相信，這將轉化為對這些患者有益的臨床效果，以便我們能夠加強研究並更快地招募 IIb 期研究。

That's really what we're trying to do. I think the Phase Ib, it's in a luxury. It's not a critical path study, but we believe it's a powerful study to really demonstrate everything that we've been saying for the past 1.5 years on the STAT6 to be a dupi in a pill. I think that data will clearly demonstrate that without the need of other doses or placebo because biomarkers don't lie

這確實是我們正在努力做的事情。我認為 Ib 階段是豪華的。這不是一個關鍵路徑研究，但我們相信這是一項有力的研究，可以真正證明我們在過去 1.5 年裡所說的關於 STAT6 的一切都是藥丸中的騙局。我認為數據將清楚證明這一點，無需其他劑量或安慰劑，因為生物標記不會說謊

Thank you.

謝謝。

Marc Frahm with TD Cowen.

馬克·弗拉姆 (Marc Frahm) 與 TD Cowen 合作。

Yes. Thanks for taking my question. Maybe just start off with one clarifying question on some of the enrolment criteria you mentioned earlier for the Phase Ib. Just take that obviously, no concomitant meds, but will you be requiring people to be biologic and JAK therapy naive? Or could there be a patient or 2 that end up in this trial that at some point seen some of these more modern agents? And then I'll have a follow-up after that.

是的。感謝您回答我的問題。也許首先要澄清一個問題，關於您之前提到的第一階段的一些入學標準。顯然，只需服用該藥物，無需同時服用藥物，但您是否要求人們接受生物製劑和 JAK 療法？或者，參加本次試驗的一兩名患者在某個時間點是否見過一些較現代化的藥物？然後我會跟進。

Yes, that's a good question, Marc. No, I mean, we will allow patients who have had prior systemic therapy or biologics that could include dupi or could include JAK inhibitor as long as they responded to it. So there will be those patients enrolled onto the study as well as patients who are biologics naive.

是的，這是個好問題，馬克。不，我的意思是，只要患者對藥物有反應，我們就會允許他們接受先前的全身性治療或生物製劑治療，其中可能包括 dupi 或 JAK 抑制劑。因此，將會有那些參與研究的患者以及未使用過生物製劑的患者。

Okay. And then just on the Phase IIbs that you're planning in AD and asthma, I mean DUPIXENT has kind of a range of -- a handful of different kind of dosing paradigms depending upon the indication. Do you think those trials give you enough -- will ultimately give you enough information about dosing to go to Phase III for kind of across the board of the IL-4 STAT6 pathway? Or are you expecting that you'll ultimately need more Phase IIbs in some of these other indications as well to help select dose for the different indications.

好的。然後，就您計劃在 AD 和氣喘中進行的 IIb 期研究而言，DUPIXENT 有一系列不同的給藥範例，具體取決於適應症。您是否認為這些試驗會為您提供足夠的信息——最終會為您提供有關劑量的足夠信息，以便進入 IL-4 STAT6 通路的第三階段？或者您是否預計最終還需要針對其他一些適應症進行更多 IIb 期臨床試驗，以幫助選擇針對不同適應症的劑量。

And if so, should we see -- expect to see those trials done in parallel to AD and asthma, or you're going to really wait for AD asthma data until you would open up anymore?

如果是這樣，我們是否應該看到——期望看到這些試驗與 AD 和哮喘同時進行，或者您真的要等待 AD 哮喘數據，直到您開放更多？

So as we said in the last discussion around our healthcare conference early in the year, our development plan is based on previous experience of other pathway agents in this space in Th2, where eventually, they were able to select a dose from, let's say, AD to go a Phase III dose in AD to go into other skin indications and a Phase III dose from asthma to go into the other respiratory indications.

因此，正如我們在今年年初醫療保健會議的最後一次討論中所說的那樣，我們的開發計劃是基於 Th2 領域中其他途徑藥物的先前經驗，最終，他們能夠從 AD 中選擇一個劑量，以進入 AD 的 III 期劑量，以進入其他皮膚適應症，並從哮喘中選擇一個 III 期劑量，以進入其他呼吸系統適應症。

And so we have a high degree of confidence that these would be the only Phase IIb studies that we will run that will allow us to go into seven, eight or more Phase III programs. But obviously, just to be absolutely clear, that will have to be demonstrated also along the way. We obviously -- we think that can happen, but we'll have to go through the studies to make sure that will happen.

因此，我們非常有信心，這些將是我們將要進行的唯一 IIb 期研究，這將使我們能夠進行七個、八個或更多個 III 期計畫。但顯然，為了絕對清楚，這一點也必須在整個過程中得到證明。我們顯然——我們認為這可能會發生，但我們必須進行研究以確保這會發生。

Okay. And then lastly, as we get that more robust efficacy readout from these Phase IIbs, obviously, the goal is to every bit match DUPIXENT, maybe even potentially exceed it a little bit. But if that isn't the case and you end up being a bit lower on efficacy, is that acceptable? And how close do you think you need to be to justify kind of the expense of late-stage trials?

好的。最後，當我們從這些 IIb 期中獲得更強大的功效讀數時，顯然，我們的目標是完全匹配 DUPIXENT，甚至可能稍微超過它。但如果不是這樣，最終功效會稍微降低，這可以接受嗎？您認為需要達到何種程度才能證明後期試驗的費用是合理的？

Yes. So first, I'd like to say -- I'd like to clarify our expectations. I hear yours, Marc. So our expectation is that based on the biology and what we've seen preclinically that we should have an effect in Th2 diseases that is similar to dupilumab. Again, we've shown some numerical superiority preclinically, but I think for us, our expectation is that it will look to be like.

是的。首先，我想說──我想澄清一下我們的期望。我聽到了你的聲音，馬克。因此，我們的預期是，基於生物學和我們在臨床前所觀察到的情況，我們應該對 Th2 疾病產生與 dupilumab 類似的效果。再說一次，我們在臨床前已經展示了一些數字優勢，但我認為對我們來說，我們的期望是它看起來會是這樣的。

We, to be honest, are not expecting that we will have lesser an effect. We have talked to and others have done calls with KOLs in the space that have made the case that a less active drug that is oral and safe and well tolerated could be also extremely successful. So we believe that the bar for success is not dupi-like, but our bar is that we're going to be dupi-like.

說實話，我們並不期望我們的影響力會這麼小。我們和其他人都與該領域的 KOL 進行過交談，他們認為，一種活性較低、口服、安全且耐受性良好的藥物也可能非常成功。因此，我們相信，成功的標準不是像 dupi 那樣，而是我們的標準是我們要像 dupi 一樣。

Okay, super helpful. Thank you.

好的，非常有幫助。謝謝。

Ellie Merle with UBS Securities.

瑞銀證券的 Ellie Merle。

Hey guys. Congrats on all the progress. Maybe just in terms of dose selection, how are you thinking about how the doses you plan to study in Phase IIb will compare between atopic derm and asthma? I guess do you expect to study the same doses in each indication? And then kind of a broader question about STAT6 as it relates to dose selection. How does STAT6 expression potentially differ across indications or maybe between patients? Thanks.

嘿，大家好。祝賀你取得的所有進展。也許僅就劑量選擇而言，您如何考慮您計劃在 IIb 期研究的劑量在特異性皮膚病和氣喘之間如何比較？我猜您是否希望研究每種適應症的相同劑量？然後是關於 STAT6 與劑量選擇關係的一個更廣泛的問題。STAT6 表現在不同適應症或不同患者之間有何潛在差異？謝謝。

So I'll let Jared answer the question. I just want to add one thing that -- to address the later part of your question. So we have seen, and I can only speak about preclinical data that expression level of STAT6 have no effect on our degradation kinetics. So -- which means that our expectation is no matter the expression levels, we'll be able to degrade it to the level that we need to or we want to, which preclinically has been 90% plus. But Jared, do you want to speak to the Phase II dose?

所以我請賈里德來回答這個問題。我只想補充一點——回答你問題的後半部。所以我們已經看到，我只能說臨床前數據顯示 STAT6 的表達量對我們的降解動力學沒有影響。所以——這意味著我們的期望是，無論表達水平如何，我們都能夠將其降低到我們需要或想要的水平，臨床前水平已經達到 90% 以上。但是賈里德，你想談談第二階段的劑量嗎？

Yes, Ellie, in our preclinical models, and we have, I think, good preclinical models for both asthma and atopic dermatitis, we've shown in both those models that doses of 621 that give us at least 90% degradation lead to sort of optimal activity or dupi-like effect. So, I think our expectation, therefore, is that the doses that we choose for Phase IIb coming out of Phase Ia will be similar doses for both the Phase IIb asthma study and the Phase IIb AD study.

是的，艾莉，在我們的臨床前模型中，我認為，我們有針對氣喘和異位性皮膚炎的良好臨床前模型，我們在這兩種模型中都表明，621 的劑量使我們至少 90% 的降解會導致最佳活性或類似 dupi 的效果。因此，我認為我們的預期是，我們為 Ia 期之後的 IIb 期選擇的劑量將與 IIb 期氣喘研究和 IIb 期 AD 研究的劑量相似。

And the question could be, is the Phase III dose going to be different? I think it's unlikely, but that's the point of the Phase IIb studies. I asked a follow-up already, Ellie.

問題可能是，第三階段的劑量會有所不同嗎？我認為這不太可能，但這就是 IIb 期研究的重點。我已經問了後續問題，艾莉。

Great. Thanks guys.

偉大的。謝謝大家。

Parth Patel with Morgan Stanley.

摩根士丹利的 Parth Patel。

Hi guys. Can you hear me?

嗨，大家好。你聽得到我嗎？

Yes.

是的。

My video is not working. This is Parth on for Vikram. So just a question on 621. So following the Phase II studies in AD and asthma, how expansive of a Phase III development program would you expect to initiate for KT-621? And how would you prioritize indications given the broad potential you've laid out for the molecule?

我的影片無法播放。這是 Vikram 的 Parth。這只是關於 621 的一個問題。那麼，在完成 AD 和氣喘的 II 期研究之後，您預計 KT-621 的 III 期開發計畫將有多大範圍？鑑於您為該分子列出的廣泛潛力，您會如何確定其適應症的優先順序？

Okay. I'm going to take this, and we're going to try more quickly because I hear we have many questions and limited time. So what we've said is that we want to develop this drug with two key goals in mind that are actually not mutually exclusive. One is a pace and path to registration and breadth of opportunities. And so we're going to run these important Phase IIb studies to inform Phase III selection for potentially eight different indications.

好的。我將接受這個採訪，而且我們會加快速度，因為我聽說我們有很多問題，但時間又有限。因此，我們所說的是，我們在開發這種藥物時要考慮兩個實際上並不互相排斥的關鍵目標。一是註冊的速度和途徑以及機會的廣度。因此，我們將進行這些重要的 IIb 期研究，為潛在的八種不同適應症的 III 期選擇提供資訊。

And we're going to run parallel Phase III campaigns for several of those indications. I think it's too early for us to say which and how many. But you can expect that if you look at dupi MAD market where now asthma and AD account for more than 80% of the revenues, I would add that once COPD picks up, it probably be another important pillar of the revenues for the drug. I would expect that we will definitely prioritize those 3.

我們將針對其中幾種適應症同時進行第三階段研究。我認為現在談論哪些以及有多少還為時過早。但你可以預料，如果你看看 dupi MAD 市場，現在氣喘和 AD 佔收入的 80% 以上，我想補充一點，一旦 COPD 流行起來，它可能會成為該藥物收入的另一個重要支柱。我希望我們一定會優先考慮這三個。

And then we have to -- between now and Phase III campaign start, decide whether we want to add additional campaigns in parallel versus slightly staggered.

然後，我們必須－從現在到第三階段活動開始，決定是否要同時或稍微交錯地加入其他活動。

Okay. Thank you.

好的。謝謝。

Yeah. Thanks.

是的。謝謝。

(Operator Instructions)

（操作員指示）

Kripa Devarakonda with Truist Securities.

Kripa Devarakonda 與 Truist 證券公司。

Hey guys. Thank you so much for taking my question. This is a really interesting format. So you've mentioned this before, but in terms of degradation levels, do you expect to see similar to what you've seen in the preclinical studies, degradation levels similar in different tissues, skin and plasma, I know you're measuring it in healthy volunteers. And do you expect that to be -- to follow through into patients as well? Like what you see in healthy volunteers, would you expect similar degradation levels in patients as well?

嘿，大家好。非常感謝您回答我的問題。這是一個非常有趣的格式。所以你之前提到過這一點，但是就降解水平而言，你是否希望看到與臨床前研究中看到的類似的情況，不同組織、皮膚和血漿中的降解水平相似，我知道你正在健康志願者身上進行測量。您是否希望這一點也能惠及病患？就像您在健康志願者身上看到的那樣，您是否認為患者體內也會出現類似的退化程度？

Yeah. So again, preclinically, we've seen robust degradation. If you look at our studies, we were able to show more than 90% degradation in all species. We've also seen, as I mentioned, we have nonhuman primate. We also have other species that we haven't shared data for, but where we've seen consistent degradation across tissues.

是的。因此，在臨床前階段，我們再次看到了嚴重的退化。如果你看我們的研究，我們就能發現所有物種的退化率都超過了 90%。正如我所提到的，我們也看到了非人靈長類動物。我們還沒有分享其他物種的數據，但我們已經看到其組織中持續的退化。

So we do expect to see robust degradation, again, 90% or above in healthy volunteers. And yes, based on both STAT6 preclinical data where we've done, let's say, healthy animals versus disease models where we haven't seen changes of degradation profile. But I would probably speak more about, for example, IRAK4, where we haven't seen any difference of degradation between healthy and AD, which is relevant, obviously, for STAT6 in a way. So yes, we expect all of that. Obviously, we'll have to show it.

因此，我們確實預期健康志願者的病情會大幅下降，達到 90% 或更高。是的，根據我們所做的 STAT6 臨床前數據，例如健康動物與疾病模型，我們沒有看到降解情況的變化。但我可能會更多地談論 IRAK4，例如，我們沒有看到健康和 AD 之間有任何退化的差異，這顯然與 STAT6 在某種程度上有關。是的，我們期待這一切。顯然，我們必須展示這一點。

And that's the point of some of these studies that are ongoing or will be ongoing.

這就是一些正在進行或將要進行的研究的重點。

Derek Archila with Wells Fargo.

富國銀行的 Derek Archila。

Hey guys. This is Eva on for Derek. A quick one from us. So you mentioned on biomarkers for the STAT6 that they should be comparable to dupi. So could you provide a little bit more color on what this means in terms of like the Th2 biomarkers? And just remind us like what did we see for dupi here? Thanks.

嘿，大家好。這是 Eva 為 Derek 表演的。我們快速說一下。所以您提到 STAT6 的生物標記應該與 dupi 相當。那麼，您能否更詳細地解釋 Th2 生物標記的含義？只是提醒我們一下，我們在這裡看到了 dupi 什麼？謝謝。

Well, yes, thank you. Well, yes, thank you. So if you're talking about healthy volunteer studies, so if you look at data from a publication from Regeneron, they showed, for example, that dupilumab dose in a dose response manner, both IV and subcu with multiple doses, we're able to show within the first two weeks, right, we need to compare the first two weeks of effect, a maximal effect in TARC around, I believe, 35%, actually peaked early and then started to be less already by week two.

嗯，是的，謝謝你。嗯，是的，謝謝你。因此，如果您談論的是健康志願者研究，如果您查看 Regeneron 出版物中的數據，他們顯示，例如，dupilumab 劑量以劑量反應的方式給藥，無論是靜脈注射還是皮下注射多次劑量，我們都能夠在前兩週內顯示出來，對，我們需要比較前兩週的效果，TARC 的最大效果大約為 35%，我認為，然後在第二週開始減弱。

Again, it was not really dose responsive. So it seemed a bit stochastic in nature, but there was a clear reduction for one of the doses. And then for IgE, for the first two weeks, we really don't see much.

再一次，它實際上並不是劑量反應性的。因此，從本質上看，它似乎有點隨機，但其中一個劑量明顯減少。至於 IgE，在最初的兩週內，我們確實看不到太多。

I think if you draw a line, it's probably 5%, 6%, 7%. I haven't actually done the calculation myself yet. So for the first 2 week IgE is pretty minor. And it does take -- I think people that understand Th2 biology, it's understood that it does take longer to impact IgE.

我認為如果畫一條線，它可能是 5%、6%、7%。我實際上還沒有親自做過計算。因此，前兩週的 IgE 非常少。而且它確實需要——我認為了解 Th2 生物學的人都知道，它確實需要更長的時間來影響 IgE。

So now that I've shared some numbers and a bit of context around, it's not surprising that we're trying to guide to -- we'll probably look like that without getting too hung up on the actual number because those are, again, noisy and for example, for IgE, pretty close to baseline.

所以現在我已經分享了一些數字和一些背景信息，我們試圖引導並不奇怪——我們可能會這樣看，而不太糾結於實際數字，因為這些數字再次變得嘈雜，例如，對於 IgE 來說，非常接近基線。

Okay. Thanks.

好的。謝謝。

Excellent.

出色的。

Eric Wong with Goldman Sachs.

高盛的 Eric Wong。

Hi. This is Eric Wong on for Chris Shibutani. Just a quick one for me. So just thinking beyond the Sanofi collaboration, how are you thinking about strategic partnerships to accelerate development or derisking programs? I guess, particularly in oncology, can you elaborate on the criteria you'll be using to select partners and how you intend to maximize the value of those assets and potential deals?

你好。我是 Eric Wong，代替 Chris Shibutani 報道。對我來說只是一個快速的步驟。那麼，除了與賽諾菲的合作之外，您如何考慮建立策略夥伴關係來加速發展或降低專案風險？我想，特別是在腫瘤學領域，您能否詳細說明您選擇合作夥伴的標準以及您打算如何最大化這些資產和潛在交易的價值？

Yes. So I would start maybe with mostly general answer. So I think that the biopharma industry can thrive by creating win-win partnerships and has done so for decades. So we are part of this ecosystem, and we will continue to think about where are the win-win opportunities.

是的。因此我可能會從一般性的答案開始。因此，我認為生物製藥產業可以透過建立雙贏的合作關係而蓬勃發展，而且幾十年來一直如此。所以我們是這個生態系統的一部分，我們會繼續思考雙贏的機會在哪裡。

As we said clearly, for our immunology pipeline, we don't believe that partnering at this point will add any value or accelerate our programs.

正如我們明確表示的那樣，對於我們的免疫學管道，我們認為此時的合作不會增加任何價值或加速我們的計畫。

So for those reasons, we are continuing to advance our immunology pipeline independently, and we're building the team, Jared is building a great team of immunology development that I believe is and will be even more so best-in-class in doing what we're doing.

因此，出於這些原因，我們將繼續獨立推進我們的免疫學管道，我們正在組建團隊，賈里德正在組建一支優秀的免疫學開發團隊，我相信這支團隊在我們所做的事情上是一流的，而且將會是一流的。

So with regards to the oncology -- again, in immunology, at some point, that might happen, right, as we get closer to Phase III registration. And if we're amazingly successful across the whole pipeline, it is possible, if not likely, that there could be some partnership for a program or another.

因此，就腫瘤學而言——同樣，在免疫學方面，在某種程度上，這可能會發生，對吧，隨著我們越來越接近第三階段的註冊。如果我們在整個過程中取得了驚人的成功，那麼即使不是很有可能，我們也有可能在某個專案上建立某種合作關係。

For oncology, as we said clearly last year now that we have decided to continue those programs through the end of Phase I and then advance it beyond only in partnerships. And so in order for us to partner program, it will have to be a win-win for both parties, the company that takes the program on and us.

對於腫瘤學，正如我們去年明確表示的那樣，我們已決定繼續這些項目直至第一階段結束，然後僅通過合作來推進。因此，為了使我們的合作夥伴計劃順利進行，它必須對雙方，即承擔該計劃的公司和我們雙方，實現雙贏。

And the criteria are simple. I don't know that I need to go through the details. But obviously, a company that is driven interested and has the capability to do justice to those programs. Next question.

標準很簡單。我不知道我是否需要了解詳細資訊。但顯然，一家有興趣並且有能力公正地執行這些計劃的公司。下一個問題。

Jeet Mukherjee.

吉特·穆克吉。

Great. Thanks for taking the question. So just given the novel nature of STAT6 as a target, thoughts on its potential in the post-DUPIXENT setting? And if this is an area you plan to evaluate in a more fulsome manner considering the Phase Ib will enroll some biologic experienced patients, as you just mentioned?

偉大的。感謝您回答這個問題。那麼，鑑於 STAT6 作為目標的新穎性，您認為它在後 DUPIXENT 環境中的潛力如何？正如您剛才提到的，考慮到 Ib 期將招募一些有生物學經驗的患者，您是否計劃以更全面的方式評估這個領域？

Yes, I just want to clarify. So the biologically experienced would have to -- would be enrolled only if they didn't fail for kind of lack of response, right? So it might be that they discontinued for other reasons, tolerability or they just got tired of injecting themselves, for example, which we know happens. So I would say, look, the potential for STAT6 is to be the Th2 drug and to be the first option for every patient that has Th2 inflammation, whether it's asthma, AD, COPD or EoE, et cetera.

是的，我只是想澄清一下。因此，具有生物學經驗的人必須——只有在沒有因缺乏反應而失敗的情況下才會被招募，對嗎？因此，他們可能因為其他原因而停止注射，例如耐受性問題，或者只是厭倦了注射，我們知道這種情況會發生。所以我想說，STAT6 有潛力成為 Th2 藥物，並成為每個患有 Th2 發炎的患者的首選，無論是氣喘、AD、COPD 或 EoE 等等。

So yes, is there an opportunity for post-dupi? Sure. But I don't think that's really the problem we're solving. I think the problem we're solving is getting these millions of patients that are not on dupi that either can get it, can get reimbursed, they don't like the needles to actually have an effective drug. And I'm sure we will recruit enough patients as we continue development to also look at what that will look like.

那麼，是的，還有機會獲得 post-dupi 嗎？當然。但我不認為這真正是我們要解決的問題。我認為我們正在解決的問題是讓數百萬沒有使用 Dupi 的患者能夠獲得這種藥物，可以獲得報銷，他們不喜歡針頭，但實際上可以使用有效的藥物。我相信，隨著我們繼續開發，我們將招募足夠的患者，並觀察其效果。

But I would say, honestly, it's not really where I think this drug will be positioned for. That's not the problem we're trying to solve. The problem is patient access to an amazing drug that solves a lot of problems.

但我想說，說實話，這並不是我所認為的這種藥物的真正定位。這不是我們要解決的問題。問題在於患者能否獲得一種可以解決許多問題的神奇藥物。

Thank you.

謝謝。

Sudan Loganathan with Stephens.

蘇丹·洛加納森和史蒂芬斯。

Yes. Thank you for taking the questions and being on video today. So mine is going to be just on the R&D spend. Just kind of curious on as you're ramping up 2025 in those 2 trials for 295 and 621, how do you expect that to be the R&D expenses to be allocated between the two programs? And then could we anticipate any expense profile changes as -- depending on the progress of those two trials over the next one to two years?

是的。感謝您今天回答問題並參加影片。所以我的支出將只用於研發。我只是有點好奇，當您在 2025 年針對 295 和 621 的這兩項試驗中加大力度時，您預計這兩個項目之間的研發費用將如何分配？那麼，我們是否可以預測任何費用狀況的變化——取決於未來一到兩年這兩項試驗的進展？

Thanks, Sudan. I thought I was going to escape talking on this call, but I guess not or at least on the Q&A part. So just obviously, we have $850 million that runway takes us into the middle part of 2027. If you just do the math over that 10 quarters, obviously, our cash burn will increase. I'd say that the trajectory gets a little steeper into 2026 when the bulk of the -- some of the clinical trial activity really kicks into higher gear and then maybe rises at a slower rate into 2027.

謝謝，蘇丹。我以為我會逃避這通通話，但我想不是，或至少在問答部分不是。因此，顯然，我們有 8.5 億美元的資金可以支撐我們到 2027 年中期。如果你計算這 10 個季度，顯然我們的現金消耗會增加。我想說的是，到 2026 年，這一軌跡會變得更加陡峭，因為屆時大部分臨床試驗活動將真正進入更高速的發展階段，然後到 2027 年，這一軌跡可能會以較慢的速度增長。

So hopefully, that gives you a little perspective. But obviously, the important point is that we are well capitalized to get us through many of these important readouts that we discussed on the call today.

希望這能給你一些見解。但顯然，重要的一點是，我們擁有充足的資金來幫助我們完成今天電話會議上討論的許多重要事項。

Maybe the only thing I'd add is you should expect the STAT6 portion of it to be dramatically superior to the TYK2 portion of expenses, especially as we continue at least in the next two to three years.

也許我唯一要補充的是，您應該預期其中的 STAT6 部分的費用將大大優於 TYK2 部分的費用，特別是因為我們至少在未來兩到三年內會繼續這樣做。

That’s it. Thank you.

就是這樣。謝謝。

There are no more questions at this time. I'd now like to turn the call over to Nello for closing remarks.

目前沒有其他問題。現在我想將電話交給 Nello 來做結束語。

Well, great. I want to thank everybody for joining us today. I also -- hopefully, the new video format is appreciated. I assure you the background is real. It's not fake. And we -- as you all know, we're available for any follow-up. We'll be at the Cowen conference in Boston, finally, a conference in Boston next week and happy to, again, take any questions offline. Thanks again, and see you again.

嗯，太好了。我要感謝大家今天的出席。我還希望新的視訊格式能夠受到歡迎。我向你保證背景是真的。這不是假的。而我們——正如你們所知，我們隨時準備跟進任何事宜。我們將參加下週在波士頓舉行的 Cowen 會議，很高興再次在線下解答您的任何問題。再次感謝，再見。