Kymera Therapeutics, Inc. (KYMR) 2026 Q3 法說會逐字稿

Good day, everyone. My name is [Shell], and I will be your conference operator today. At this time, I would like to welcome you to the Kymera Therapeutics third quarter 2026 results call. (Operator Instructions)

各位好。我是[Shell]，今天將擔任本次電話會議的接線員。此刻，我謹代表主辦方歡迎各位參加 Kymera Therapeutics 2026 年第三季業績電話會議。(接線員指示)

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

現在，我想把電話會議交給投資人關係副總裁 Justine Koenigsberg。Justine，請開始。

Good morning and welcome to Kymera's quarterly update call, which will also include a discussion of the KT-579 Phase I healthy volunteer results. Joining me this morning with prepared remarks are Nello Mainolfi, our Founder, President, and CEO; Terence Rooney, our Chief Medical Officer; and Bruce Jacobs, our Chief Financial Officer.

各位早安，歡迎參加 Kymera 的季度更新電話會議，本次也將包含對 KT-579 第一階段健康受試者結果的討論。今天早上與我一同進行事先準備發言的有：我們的創辦人、總裁暨執行長 Nello Mainolfi；首席醫療長 Terence Rooney；以及首席財務長 Bruce Jacobs。

Following our prepared remarks, we will open the call for questions from our covering analysts. In order to have as much time for as many questions as possible, please limit your questions to one. If you would like to ask a question, please use the raise hand icon, which can be found at the bottom of your meeting window. A replay of today's call, including a copy of the corresponding presentation, will be available in the investor section of our website soon after the call concludes.

在我們的準備發言之後，我們將開放由追蹤我們的分析師提問。為了盡可能保留時間回答更多問題，請將您的提問限制為一題。若您想提問，請使用舉手圖示，可在會議視窗底部找到。今日電話會議的重播（包含相應簡報的副本）將在會議結束後不久於我們網站的投資人專區提供。

As a reminder, today's presentation 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. A description of these risks can be found in our most recent 10-Q 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.

提醒各位，今天的簡報將包含關於我們未來預期、計畫與前景的前瞻性陳述。這些陳述受風險與不確定性影響，可能導致實際結果與預測存在重大差異。相關風險說明可見於我們最近向美國證券交易委員會（SEC）提交的 10-Q。任何前瞻性陳述僅截至今日有效，我們不承擔更新今日電話會議中任何前瞻性陳述的義務。

Before we begin, we have one housekeeping item. Starting next week, we will enter our previously planned quiet period ahead of our upcoming STAT 6 data. As a result, we don't expect to provide additional commentary on our STAT 6 program until we report those results.

在開始之前，有一項例行事項。自下週起，我們將進入先前規劃、在即將公布 STAT 6 數據前的靜默期。因此，在我們發布這些結果之前，預期不會就 STAT 6 計畫提供額外評論。

With that, I will turn the discussion over to Nello.

接下來，我將把討論交給 Nello。

Thank you, Justine, and good morning, everyone. Thank you for joining us today. This is a very exciting time for Kymera. We're seeing our scientific vision take shape across our pipeline of oral medicines to address serious inflammatory diseases with KT-621, our STAT 6 degrader for atopic dermatitis, asthma, and more, and KT-579, our IRF5 degrader for lupus and potentially other autoimmune diseases. Together, they reflect our goal of developing medicines grounded in strong biology with the potential to reach many more patients than served by available treatments today.

謝謝你，Justine，各位早安。感謝各位今天加入我們。對 Kymera 而言，這是一個非常令人振奮的時刻。我們正看到科學願景在我們的口服藥物產品線中逐步成形：以 KT-621（我們的 STAT 6 降解劑）治療異位性皮膚炎、氣喘等嚴重發炎性疾病；以及以 KT-579（我們的 IRF5 降解劑）治療紅斑性狼瘡，並可能延伸至其他自體免疫疾病。兩者共同體現了我們的目標：以堅實的生物學基礎開發藥物，並有潛力觸及遠多於現有治療所能服務的患者。

I'll start today with an update on KT-621 as we approach its Phase IIb AD readout before year-end. I'll then briefly cover the rest of our pipeline before we turn to KT-579 Phase I results.

今天我將先就 KT-621 提供最新進展，因為我們正接近其在今年年底前公布的第二期 b（Phase IIb）異位性皮膚炎（AD）讀出。接著我會簡要說明我們其餘的產品線，然後我們將轉到 KT-579 第一階段結果。

Our STAT 6 program continues to advance according to plans across both AD and asthma. As shown here, we've advanced KT-621 through a series of studies, building on what we learned at each stage to guide the next steps.

我們的 STAT 6 計畫在 AD 與氣喘兩個適應症上皆依計畫持續推進。如圖所示，我們已推動 KT-621 完成一系列研究，並在每個階段所獲得的學習基礎上，指引下一步的決策。

In Phase I, we've evaluated KT-621 in more than 200 healthy volunteers in observing deep STAT 6 degradation, effects on downstream biomarkers, and a favorable safety and tolerability profile. We then treated 22 patients with AD in Phase Ib, where we saw the first evidence of strong clinical activity in patients. With each study, we built a stronger body of evidence and further de-risked KT-621, supporting its advancement into the ongoing Phase IIb studies.

在第一期（Phase I）中，我們已在超過 200 名健康受試者中評估 KT-621，觀察到深度的 STAT 6 降解、對下游生物標記的影響，以及良好的安全性與耐受性特徵。之後在第一期 b（Phase Ib）中，我們治療了 22 名 AD 患者，並在患者身上看到強勁臨床活性的初步證據。透過每一項研究，我們建立了更強的證據體系，並進一步降低 KT-621 的開發風險，支持其推進至目前進行中的第二期 b 研究。

In the BROADEN2 AD study, we're excited to report that we have completed the 16-week placebo-controlled portion of the study with the last patient just recently completing their final visit. We expect that the remaining activities to close out this portion of the study will enable us, as planned, to share the KT-621 Phase IIb data by year-end.

在 BROADEN2 AD 研究中，我們很高興報告：我們已完成該研究為期 16 週、安慰劑對照部分；最後一位患者也在近期完成其最後一次回診。我們預期，完成此部分研究結案所需的其餘工作將使我們能如計畫在年底前分享 KT-621 第二期 b 數據。

At the same time, we're well into our preparation for the first Phase III study in AD, which we plan to initiate, assuming both supportive data and alignment with FDA by middle of 2027. Before we move to an update on asthma, as we have shared previously, patients that complete the full 16 weeks of treatment in BROADEN2 are eligible to enter a 52-week open label extension. Today, we're happy to report that 98% of eligible patients have enrolled into the OLE.

同時，我們也正積極準備 AD 的第一項第三期（Phase III）研究；在數據支持且與 FDA 達成一致的前提下，我們計畫於 2027 年年中啟動。在我們更新氣喘進展之前，如同先前分享，完成 BROADEN2 全部 16 週治療的患者，符合資格可進入為期 52 週的開放標籤延伸試驗（OLE）。今天我們很高興報告，符合資格的患者中有 98% 已加入 OLE。

Now turning to asthma, enrollment in the BREADTH study continues to progress as planned, with top-line results expected in late 2027. In total, these studies have already enrolled hundreds of participants, providing a robust data set to assess safety and efficacy of this exciting novel mechanism. And as a reminder, the BREADTH study also includes an open-label extension, which, together with the AD OLE, are designed to further support a long-term safety database for regulatory requirements and the potential registration of KT-621.

接著談到氣喘，BREADTH 研究的收案持續依計畫推進，預計於 2027 年下半年公布主要結果。整體而言，這些研究已收納數百名受試者，提供強健的資料集，以評估這一令人振奮之新機轉的安全性與療效。並提醒各位，BREADTH 研究也包含開放標籤延伸試驗；其與 AD 的 OLE 一起，旨在進一步支持符合監管要求的長期安全性資料庫，以及 KT-621 潛在的註冊申請。

As we approach the BROADEN2 readout, I wanted to take a moment to put the opportunity for KT-621 in AD into perspective. As illustrated on slide 7, published epidemiological reports show that there are approximately 6 million to 9 million people in the U.S. 12 years and up with moderate to severe atopic dermatitis. Despite this high prevalence, only an estimated 400,000 receive advanced systemic therapies, a penetration of only about 5% of the total moderate to severe patient population.

在我們接近 BROADEN2 讀出之際，我想花點時間從更宏觀的角度說明 KT-621 在 AD 的機會。如投影片 7 所示，已發表的流行病學報告顯示，美國 12 歲以上中重度異位性皮膚炎患者約有 600 萬至 900 萬人。儘管盛行率很高，估計僅約 40 萬人接受進階全身性治療，滲透率僅約占中重度患者總數的 5%。

As we've been advancing KT-621, we've also been conducting market research to better understand the market dynamics of advanced systemic therapies. What we hear from both patients and prescribers is that the main reason for the limited adoption is that many patients don't perceive that their disease state justifies an injectable biologic or a medicine carrying a box warning. That perception creates a significant barrier to the use of currently available advanced therapies.

在推進 KT-621 的同時，我們也進行市場研究，以更深入了解進階全身性治療的市場動態。我們從患者與處方醫師那裡聽到，採用率受限的主要原因是：許多患者不認為自己的病況需要注射型生物製劑，或需要使用帶有黑框警語的藥物。這種認知對目前可用的進階治療形成了顯著的使用障礙。

Our market research tells us that patients and physicians want a safe, effective oral treatment. In fact, when we ask what level of efficacy that treatment needs to deliver, we consistently hear that it does not necessarily have to match biologics.

我們的市場研究顯示，患者與醫師都希望有一種安全、有效的口服治療。事實上，當我們詢問該治療需要達到何種療效水準時，我們一再聽到：它不一定必須與生物製劑相匹敵。

We have seen that opportunity play out in other markets. OTEZLA launched more than a decade ago with roughly half the efficacy of biologics and went on to become a multibillion-dollar franchise. More recently, icotekinra, despite efficacy that, by cross-trial comparisons, does not quite match IL-23 biologics, is experiencing one of the strongest launches in psoriasis, bringing new patients to treatment in an already more saturated market.

我們已在其他市場看到這樣的機會如何實現。OTEZLA 在十多年前上市時，其療效約為生物製劑的一半，之後仍發展成為數十億美元規模的產品系列。更近期，icotekinra 儘管以跨試驗比較來看，其療效尚未完全匹敵 IL-23 生物製劑，仍在乾癬領域出現最強勁的上市表現之一，在一個已更為飽和的市場中帶來新的治療患者。

Going back to KT-621, a safe and effective oral is what patients are looking for, and that is the profile we aim to deliver. Our focus is to serve the largest segment of moderate to severe AD population, those patients who are either untreated or, in many cases, poorly treated with non-systemic therapies. If we are successful, we believe that KT-621 would have the potential to dramatically expand the number of patients accessing advanced therapies.

回到 KT-621，患者所尋求的是一款安全且有效的口服藥物，而這正是我們力求交付的產品特徵。我們的重點是服務於中度至重度 AD 人群中最大的族群，也就是那些尚未接受治療，或在許多情況下僅以非全身性療法而治療不佳的患者。若我們成功，我們相信 KT-621 有潛力大幅擴增可獲得先進療法的患者人數。

All of that said and based on the preclinical and Phase I data we have generated so far, our scientific expectation remains that BROADEN2 efficacy should land in the ballpark of what dupilumab achieved at week 16 as compared to what was reported in the SOLO 1, SOLO 2 trials, while recognizing the limitation of comparing results across studies.

話雖如此，且基於我們迄今產生的臨床前與第一期數據，我們的科學預期仍是：BROADEN2 的療效應落在 dupilumab 於第 16 週所達成的水準區間（相較於 SOLO 1、SOLO 2 試驗所報告者），同時也認知到跨研究比較結果的侷限性。

Beyond KT-621, we are also tracking with expectations and timelines across our broader pipeline. Our partner programs are both progressing as planned. Sanofi continues to advance KT-485, our second-generation IRAK4 degrader, in a Phase I healthy volunteer study that is also expected to enroll HS patients. And Gilead is advancing KT-200, our CDK2 molecular glue, into IND-enabling activities with an IND planned for 2027.

除 KT-621 之外，我們也在更廣泛的產品線上，依照預期與時程推進。我們的合作夥伴專案皆按計畫進展。賽諾菲（Sanofi）持續推進 KT-485（我們第二代 IRAK4 降解劑）於第一期健康受試者研究中，該研究亦預計納入 HS 患者。而吉利德（Gilead）正推進 KT-200（我們的 CDK2 分子膠）進入 IND 申報前的使能性活動，並規劃於 2027 年提交 IND。

With respect to our research pipeline, our undisclosed programs are tracking with our expectations and to support our goal to advancing one program towards development candidate annually. Regarding the disclosure of our next program, given all that we have to share in the fourth quarter with today's KT-579 data and the upcoming KT-621 Phase IIb readout, we have decided to hold off on that introduction until next year.

就我們的研究產品線而言，未揭露的專案正依照我們的預期推進，並支持我們每年推進一個專案朝向開發候選藥物的目標。至於下一個專案的揭露，鑑於我們在第四季已有許多內容要分享，包括今日的 KT-579 數據以及即將公布的 KT-621 第二期 b 期讀出結果，我們已決定將該介紹延後至明年。

With all of that said, before I turn the call over to Terence to share the IRF5 healthy volunteer data, I wanted to talk a little bit about the importance of today's IRF5 data release. We have now successfully advanced multiple degrader programs from target selection and drug discovery through preclinical and into the clinic. This is, in fact, our seventh first-in-class degrader to enter the clinic, and today we are sharing that we continue to demonstrate impeccable human translation.

在我把電話交給 Terence 分享 IRF5 健康受試者數據之前，我想先談談今日 IRF5 數據發布的重要性。我們如今已成功將多個降解劑專案，從靶點選擇與藥物發現推進至臨床前並進入臨床。事實上，這是我們第七個同類首創（first-in-class）的降解劑進入臨床，而今天我們分享的是：我們持續展現無可挑剔的人體轉譯能力。

While each target and molecule is unique and must ultimately prove itself independently, this repeated execution is indicative of the positive and compounding effect of all our learnings and experience across our programs. IRF5 itself is a highly compelling and genetically validated target that has historically been difficult to drug with conventional drug discovery approaches. And this study is an important first step in establishing our IRF5 thesis in humans.

雖然每個靶點與分子皆具獨特性，且最終都必須各自獨立證明其價值，但這種反覆的執行成果，顯示了我們在各專案中累積的學習與經驗所帶來的正向且疊加的效應。IRF5 本身是一個極具吸引力且經遺傳學驗證的靶點，過去以傳統藥物發現方法一直難以成藥。而本研究是在人類中建立我們 IRF5 論點的重要第一步。

As you will hear shortly, KT-579, which was well-tolerated in this study, robustly degraded IRF5. Importantly, the potent IRF5 degradation led to meaningful reductions in multiple disease-relevant biomarkers. With this data in hand, we now plan to move the program with confidence into a Phase Ib lupus trial. The study is designed to establish whether KT-579 can demonstrate the biological and clinical activity we would expect based on this mechanism.

如各位稍後將聽到的，KT-579 在本研究中耐受性良好，並能強力降解 IRF5。重要的是，強效的 IRF5 降解帶來多項與疾病相關生物標記的顯著下降。在掌握這些數據後，我們現在計畫有信心地將該專案推進至第一期 b 期紅斑性狼瘡試驗。該研究旨在確認 KT-579 是否能展現我們基於此作用機制所預期的生物學與臨床活性。

Overall, the KT-579 data represent another important example of our ability to target a highly compelling but historically undrugged target, in this case, a transcription factor. It also demonstrates our ability to translate our preclinical work into humans in a predictable and compelling way. We have now done this across multiple programs, and with each success, we are building on a strong and increasingly repeatable foundation for selecting the right targets, developing differentiated degraders against them, and efficiently translating those programs from discovery into the clinic.

整體而言，KT-579 的數據再次提供一個重要例證，顯示我們有能力鎖定高度具吸引力但歷來難以成藥的靶點——在此案例中為轉錄因子。它也展現我們能以可預測且具說服力的方式，將臨床前工作轉譯至人體。我們已在多個專案中做到這點；每一次成功，都讓我們在選擇正確靶點、開發具差異化的降解劑，並有效率地將專案從發現推進至臨床方面，建立起更強且愈發可重複的基礎。

I know everyone is eager to get into the data, so with that, I will turn it over to Terence to walk you through the results. Terence?

我知道大家都迫不及待想深入了解數據，因此接下來我把時間交給 Terence，請他帶各位走過研究結果。Terence？

Thanks, Nello. It is a pleasure to join you all today to review the positive Phase I results for KT-579. As a rheumatologist by training, I am particularly excited by what we have demonstrated with this program. The translation from the strong preclinical profile into humans is an important milestone and validates our confidence both in the biology and the potential of IRF5 degradation as we prepare to move KT-579 into patients.

謝謝你，Nello。很高興今天與各位一同回顧 KT-579 正向的第一期結果。以受訓背景而言我是一名風濕科醫師，因此對於我們在此專案所展現的成果特別振奮。從強勁的臨床前特徵轉譯至人體是一項重要里程碑，也驗證了我們對生物學本身以及 IRF5 降解潛力的信心，並為我們準備將 KT-579 推進至患者奠定基礎。

I will start with an overview of the Phase I study design and the demographics of the healthy volunteers enrolled in the study. I will then walk through the PD data, beginning with the depth and durability of IRF5 degradation in blood. Next, I will cover the functional consequences of that degradation across three distinct IRF5-dependent immune pathways, assessed using disease-relevant ex vivo stimulation assays. Finally, I will review the safety profile observed and then discuss how the totality of these data inform our plans to advance KT-579 into lupus patients. As we have been saying for some time, primarily for competitive reasons, in some areas of the presentation, we are sharing only limited data.

我將先概述第一期研究設計，以及納入研究之健康受試者的人口統計特徵。接著我會帶各位檢視 PD 數據，從血液中 IRF5 降解的深度與持久性開始。然後，我將說明該降解在三條不同的 IRF5 依賴性免疫途徑上的功能性後果，這些是透過與疾病相關的離體（ex vivo）刺激試驗來評估。最後，我會回顧觀察到的安全性特徵，並討論這些數據的整體意涵如何支持我們推進 KT-579 至紅斑性狼瘡患者的計畫。如同我們一段時間以來所說，主要出於競爭考量，在簡報的某些部分我們僅分享有限數據。

As shown on slide 12, the Phase I study was designed to characterize the safety, PK, and PD of KT-579 following both single and multiple ascending doses in healthy volunteers. We evaluated a range of doses up to 600 milligrams in the MAD cohorts.

如投影片 12 所示，第一期研究旨在於健康受試者中，在單次與多次遞增劑量給藥後，描述 KT-579 的安全性、PK 與 PD。在 MAD 隊列中，我們評估了最高至 600 毫克的一系列劑量。

In the SAD portion of the study, eight subjects per cohort were randomized, six to two, to receive a single oral dose of KT-579 or placebo. In the MAD portion, 12 subjects per cohort were randomized nine to three to receive once daily oral KT-579 or placebo for 14 days.

在研究的 SAD 部分，每個隊列 8 名受試者以 6 比 2 隨機分派，接受 KT-579 單次口服劑量或安慰劑。在 MAD 部分，每個隊列 12 名受試者以 9 比 3 隨機分派，連續 14 天每日一次口服 KT-579 或安慰劑。

While the primary objective of the study was to evaluate the safety and tolerability of KT-579, the study was also designed to establish proof of mechanism in humans. In both SAD and MAD, we evaluated IRF5 degradation across dose levels, and in the MAD portion, we also assessed the downstream functional consequences of IRF5 degradation using disease relevant ex vivo stimulation assays measuring inflammatory biomarkers.

雖然本研究的主要目標是評估 KT-579 的安全性與耐受性，但研究亦設計用以在人體中建立作用機制的概念驗證（proof of mechanism）。在 SAD 與 MAD 中，我們評估不同劑量水準下的 IRF5 降解；而在 MAD 部分，我們也使用與疾病相關的離體刺激試驗（測量發炎生物標記）來評估 IRF5 降解的下游功能性影響。

Together, these endpoints allow us to address the key questions we set out to answer in the study. First, can we safely achieve deep and sustained degradation of IRF5 with KT-579? Second, does that degradation translate into the expected functional impact on our IRF5-dependent biology? And as you will hear today, the answer to both questions is yes.

綜合而言，這些終點使我們得以回答本研究設定的關鍵問題。第一，我們是否能以 KT-579 安全地達成深度且持續的 IRF5 降解？第二，該降解是否能轉化為我們對 IRF5 依賴性生物學所預期的功能性影響？而如各位今天將聽到的，這兩個問題的答案都是肯定的。

Turning to slide 13, the demographics of the volunteers enrolled in the SAD and MAD portions of the study. Overall, there were no meaningful imbalances in baseline characteristics that would impact our interpretation of the study results.

接著看投影片 13，這是研究 SAD 與 MAD 部分所納入受試者的人口統計特徵。整體而言，基線特徵並無任何具實質意義的不平衡，足以影響我們對研究結果的解讀。

Now before turning to the MAD degradation data, although it is not shown in this presentation, we did want to mention that KT-579 exhibited the predicted PK profile with dose responsive exposures in SAD and MAD cohorts. Additionally, while we generated degradation data across both the SAD and MAD portions of the study, we are only sharing the MAD degradation data here, as repeated daily dosing most closely reflects the intended clinical use of KT-579.

在進入 MAD 的降解數據之前，雖然本簡報未呈現，我們仍想提及：KT-579 展現了預測的 PK 特徵，在 SAD 與 MAD 隊列中呈現隨劑量反應的暴露量。此外，雖然我們在研究的 SAD 與 MAD 兩部分皆產生了降解數據，但此處僅分享 MAD 的降解數據，因為每日重複給藥最能反映 KT-579 預期的臨床使用方式。

Now looking at slide 14, which illustrates degradation across the MAD dose cohorts with data shown at day 7 and 14. The top five dose cohorts all reached median IRF5 degradation greater than 90%, with saturation of degradation by dose level 3, with blood degradation achieving 94%.

現在來看第14張投影片，該投影片呈現MAD多次給藥劑量隊列在第7天與第14天的降解情況。最高的五個劑量隊列其IRF5降解的中位數皆超過90%，且在第3個劑量水準即達到降解飽和，血液中的降解達到94%。

Importantly, while not shown, we also observed comparable reductions in IRF5 levels in skin, demonstrating target degradation in tissue as well as blood. Overall, KT-579 demonstrated robust degradation of IRF5 at or above levels predicted by our preclinical work in both the SAD and MAD. And this profile shows that the target remains continuously suppressed with once daily dosing, providing sustained pharmacologic coverage of IRF5 expression.

重要的是，雖然此處未展示，我們也觀察到皮膚中的IRF5水準出現相當程度的下降，顯示在組織以及血液中皆可達成標的降解。整體而言，KT-579在SAD單次遞增劑量與MAD多次遞增劑量中，均展現出強勁的IRF5降解效果，達到或高於我們臨床前研究所預測的水準。而此一特徵顯示，在每日一次給藥下，標的可持續受到抑制，提供對IRF5表達的持續藥理覆蓋。

Now in addition to degradation, we also assess the impact of IRF5 degradation on downstream biomarkers, which we believe is an important indicator of the potential biological effects. As a reminder, IRF5 has a role in the regulation of three major immune pathways relevant to several autoimmune diseases. These include, first, inflammatory cytokines. IRF5 promotes the production of key inflammatory cytokines by myeloid cells, including monocytes and macrophages. When dysregulated, these responses can sustain chronic inflammation.

除了降解之外，我們也評估IRF5降解對下游生物標誌物的影響，我們認為這是衡量潛在生物學效應的重要指標。提醒一下，IRF5在與多種自體免疫疾病相關的三大免疫途徑調控中扮演角色。其中第一個是發炎性細胞激素。IRF5會促進髓系細胞（包括單核球與巨噬細胞）產生關鍵的發炎性細胞激素。當此反應失衡時，可能維持慢性發炎。

Second, interferon response. IRF5 helps connect nucleic acid sensing with interferon production and associated gene expression responses. Dysregulation of this pathway can amplify immune activation and inflammation.

第二個是干擾素反應。IRF5有助於將核酸感知與干擾素產生及其相關基因表達反應連結起來。此途徑的失調可能放大免疫活化與發炎。

And the third pathway is B-cell biology. IRF5 contributes to B-cell activation and pathways associated with plasmablast differentiation and autoantibody production. So this breadth of biology is an important feature of the IRF5 mechanism. By degrading IRF5, KT-579 has the potential to modulate multiple interconnected drivers of inflammation through a single oral approach.

第三個途徑是B細胞生物學。IRF5有助於B細胞活化，以及與漿母細胞分化與自體抗體生成相關的途徑。因此，IRF5機制所涵蓋的廣泛生物學面向是一項重要特徵。透過降解IRF5，KT-579有潛力以單一口服方式調節多個彼此相互連結的發炎驅動因子。

Now to assess this biology in healthy volunteers, we use three orthogonal ex vivo stimulation assays that our team developed internally. These assays activate distinct RNA and DNA-sensing toll-like receptor pathways and measure downstream changes in inflammatory mediators and gene expression. This allowed us to assess whether IRF5 degradation translated into functional effects across all three key areas.

為了在健康受試者中評估這些生物學效應，我們使用團隊內部開發的三種相互獨立的離體（ex vivo）刺激試驗。這些試驗會活化不同的RNA與DNA感知型Toll樣受體途徑，並量測下游發炎介質與基因表達的變化。這使我們得以評估IRF5降解是否能在三個關鍵領域皆轉化為功能性效應。

In the following slides, we will focus on the impact of IRF5 degradation demonstrated in each pathway. In each graph, we will show the median of all KT-579 MAD dose cohorts combined compared to placebo.

在接下來的投影片中，我們將聚焦於IRF5降解在各途徑中所展現的影響。在每張圖中，我們會呈現所有KT-579 MAD劑量隊列合併後的中位數，並與安慰劑組比較。

So shown here on slide 16, IRF5 degradation translated into deep and sustained inhibition of core inflammatory cytokines, including TNF alpha, IL-12/23p40, and IL-1 beta. As shown here, median cytokine reduction across all MAD cohorts combined range from 87% to as high as 94%.

如第16張投影片所示，IRF5降解可轉化為對核心發炎性細胞激素的深度且持續抑制，包括TNFα、IL-12/23p40與IL-1β。如圖所示，合併所有MAD隊列後的細胞激素中位數降幅介於87%至最高94%。

The kinetics of cytokine inhibition track with the kinetics of IRF5 degradation, and the magnitude of the effect is consistent or superior to what was observed preclinically. These reductions are particularly encouraging as this is a core pathway involved in lupus through TLR7/8, and in IBD through TNF alpha and interleukin-12/23, 2 of our highest priority indications.

細胞激素抑制的動力學與IRF5降解的動力學一致，且效應幅度與臨床前觀察結果一致或更佳。這些下降尤其令人振奮，因為此為紅斑性狼瘡中經由TLR7/8的核心途徑，亦是發炎性腸道疾病（IBD）中經由TNFα與介白素12/23的核心途徑，這兩者皆為我們最優先的適應症之一。

We interrogated the same inflammatory cytokine pathway more broadly with transcriptomics. The transcriptomics provide a complementary confirmation of the cytokine data, showing modulation of IRF5-dependent inflammatory biology.

我們也以轉錄體學更廣泛地檢視同一發炎性細胞激素途徑。轉錄體學結果對細胞激素數據提供互補性的驗證，顯示IRF5依賴性的發炎生物學受到調節。

Though anonymized, the heat map shows the changes in selected pathway genes with placebo and across all KT-579 dose cohorts at day 14 in relation to their respective pre-dose sample, while the graph quantifies the overall modulation of a gene set. We observed strong gene-to-protein concordance with genes like TNF alpha and interleukin-12 moving in the same direction as the corresponding functional cytokine readouts as described in the previous slide.

雖然已去識別化，熱圖顯示安慰劑組以及所有KT-579劑量隊列在第14天相對於各自給藥前樣本的特定途徑基因變化，而圖表則量化一組基因集合的整體調節程度。我們觀察到強烈的基因與蛋白一致性，例如TNFα與介白素12等基因的變化方向，與前一張投影片所描述的對應功能性細胞激素讀出一致。

The second major axis we tested was interferon response, another important component of IRF5-dependent inflammation and a particularly relevant pathway in heterogeneous diseases. The effect on this pathway cytokine is particularly pronounced. We demonstrated near complete reductions in TLR7 and 8 stimulated interferon beta levels, with the MAD dose cohorts showing a median inhibition of 98%.

我們測試的第二個主要面向是干擾素反應，這是IRF5依賴性發炎的另一個重要組成，且在異質性疾病中特別相關。對此途徑細胞激素的影響尤為顯著。我們顯示在TLR7與TLR8刺激下的干擾素β水準幾乎完全下降，MAD劑量隊列的中位數抑制達98%。

Importantly, the transcriptional data independently support and extend this result, showing modulation results in broad coverage across key interferon pathway genes. And these data validate the pharmacology beyond the inflammatory cytokine pathway we showed in the prior slides, demonstrating that IRF5 degradation can translate into profound functional modulation of the interferon axis, which is well-recognized as overactive in the biology of several autoimmune disorders, including lupus and Sjogren's disease.

重要的是，轉錄層面的數據亦獨立支持並延伸此結果，顯示調節效應可廣泛覆蓋關鍵干擾素途徑基因。這些數據也在我們先前投影片所示的發炎性細胞激素途徑之外，進一步驗證其藥理作用，證明IRF5降解可轉化為對干擾素軸的深度功能性調節；而干擾素軸被廣泛認為在多種自體免疫疾病（包括紅斑性狼瘡與修格蘭氏症）之生物學中呈現過度活化。

Finally, as shown on slide 19, the effects of KT-579 reach into the third major axis of IRF5, B-cell biology. Selected TLR9-driven transcripts are significantly modulated with KT-579, including key genes associated with DNA sensing and B-cell activation. Again, important steps in the pathogenesis of autoimmune diseases, including lupus.

最後，如第19張投影片所示，KT-579的效應亦延伸至IRF5的第三個主要面向：B細胞生物學。在KT-579作用下，部分由TLR9驅動的轉錄本出現顯著調節，包括與DNA感知與B細胞活化相關的關鍵基因。這些同樣是自體免疫疾病（包括紅斑性狼瘡）發病機制中的重要步驟。

In summary then, KT-579-driven IRF5 degradation translates into coherent functional modulation across three major pathways we set out to interrogate, inflammatory cytokines, interferon response, and B-cell biology. That breadth of pharmacology is one of the key takeaways from this first human data set.

總結而言，由KT-579驅動的IRF5降解，可在我們所要檢視的三大途徑——發炎性細胞激素、干擾素反應與B細胞生物學——上，轉化為一致且連貫的功能性調節。這種廣泛的藥理覆蓋，是這份首次人體數據集的關鍵重點之一。

Okay, moving to safety. KT-579 was well-tolerated and had a safety profile comparable to placebo. As shown here in slide 20, there were no serious adverse events, very few mild treatment-related adverse events, no adverse events leading to discontinuation of study drug or from the study, and no clinically relevant changes in vital signs, lab tests, or ECGs. There were also no imbalances in the rates of infections. It is very encouraging that KT-579 was able to robustly degrade IRF5 in blood and also functionally modulate disease-relevant biomarkers across three key immune pathways while demonstrating a placebo-like safety profile.

接著談安全性。KT-579耐受性良好，其安全性概況與安慰劑相當。如第20張投影片所示，未出現嚴重不良事件，與治療相關的輕度不良事件極少，亦無因不良事件而停止研究用藥或退出研究的情況，生命徵象、實驗室檢查或心電圖亦無具臨床意義的變化；感染發生率亦未見不平衡。令人非常鼓舞的是，KT-579在展現類似安慰劑的安全性概況之同時，能在血液中強力降解IRF5，並在三個關鍵免疫途徑上對與疾病相關的生物標誌物產生功能性調節。

The Phase I data represent an important milestone for KT-579, for our IRF5 program, and for Kymera. These results establish important human proof of mechanism for KT-579. We have demonstrated that we can achieve deep and sustained degradation of IRF5 with an oral medicine with a favorable safety and tolerability profile.

第一期數據對KT-579、我們的IRF5計畫以及Kymera而言，代表一個重要里程碑。這些結果為KT-579建立了重要的人體作用機制（proof of mechanism）證據。我們已證明可透過一款口服藥物，在具良好安全性與耐受性概況的前提下，達成深度且持續的IRF5降解。

Importantly, we have also seen that IRF5 degradation translates into strong and encouraging downstream effects on the disease-relevant inflammatory biology. So taken together, this gives us increased confidence that we are achieving the profile we designed KT-579 to deliver and provide a strong foundation to move into patients.

同樣重要的是，我們也看到IRF5降解可轉化為對與疾病相關之發炎生物學的強勁且令人振奮的下游效應。因此，綜合來看，這使我們更有信心：我們正在達成KT-579在設計上所要提供的特徵，並為推進至病人研究奠定堅實基礎。

As the program following our STAT6 efforts, IRF5 is yet another example of Kymera's ability to develop potentially transformational medicines for patients. So on that note, we now plan to advance KT-579 into its first patient study in lupus. Lupus remains an area of significant unmet need, where many patients continue to cycle through therapies without achieving adequate or durable disease control, and treatment often requires combinations of immunosuppressive agents with meaningful safety and tolerability limitations.

作為接續我們STAT6工作的計畫，IRF5再次展現Kymera開發可能具變革性之病患用藥的能力。因此，在此基礎上，我們計畫推進KT-579進入其首個紅斑性狼瘡病人研究。紅斑性狼瘡仍是高度未被滿足的醫療需求領域，許多病患仍在不同療法間反覆更換卻無法達到足夠或持久的疾病控制，而治療往往需要合併使用免疫抑制藥物，並伴隨具實質影響的安全性與耐受性限制。

We see significant opportunity for a new, safe, and effective oral therapy. Lupus is a compelling indication for this program, given there is strong genetic evidence linking IRF5 to lupus, and IRF5 plays a central role in lupus disease biology.

我們看到一個重大的機會，可開發一種全新、安全且有效的口服療法。鑑於有強而有力的遺傳學證據將 IRF5 與狼瘡連結，且 IRF5 在狼瘡疾病生物學中扮演核心角色，狼瘡是本計畫極具吸引力的適應症。

We have previously shown disease-modifying activity in multiple preclinical lupus models. As you have seen today, we have now demonstrated exciting biomarker data suggesting a strong connection between IRF5 degradation and three important disease-relevant pathways. So this gives us a high degree of confidence in the underlying biology and a clear rationale for evaluating the impact of IRF5 degradation directly in patients.

我們先前已在多個狼瘡臨床前模型中顯示具疾病修飾（disease-modifying）活性。如同各位今天所見，我們現在已展示令人振奮的生物標誌物數據，顯示 IRF5 降解與三條重要且與疾病相關的途徑之間具有強烈關聯。因此，這讓我們對其基礎生物學具有高度信心，並為直接在患者中評估 IRF5 降解的影響提供了明確的理據。

The planned Phase Ib study will allow us to begin answering the next important questions, whether IRF5 degradation and downstream biology we observed in healthy volunteers carry through to patients with lupus, and whether KT-579 can affect the disease pathways that are active in those patients.

規劃中的 Ib 期研究將使我們得以開始回答下一些重要問題：我們在健康受試者中觀察到的 IRF5 降解及其下游生物學是否也會在狼瘡患者中同樣呈現，以及 KT-579 是否能影響這些患者體內活躍的疾病途徑。

In healthy volunteers, we measured pathway effects after stimulating blood samples ex vivo, while in patients, we will be able to assess those effects in the setting of active disease, as well as look for early signs of clinical benefit. We view this as an important next step for the program and towards establishing IRF5 degradation as a potentially new therapeutic approach for patients with autoimmune disease.

在健康受試者中，我們是在體外（ex vivo）刺激血液樣本後測量途徑效應；而在患者中，我們將能在疾病活動狀態下評估這些效應，並同時觀察是否出現早期臨床獲益的跡象。我們將此視為本計畫的重要下一步，並朝向建立「IRF5 降解」作為自體免疫疾病患者一種潛在新治療途徑邁進。

Here is a snapshot of the Phase Ib study design for the trial, which we have named LUMORA. We plan to enroll approximately 30 patients with SLE randomized 2 to 1 to KT-579 or placebo and treat it for 16 weeks. Oral corticosteroid background therapy is permitted. In fact, our upcoming oral presentation at the American College of Rheumatology conference demonstrates that KT-579 shows significant activity alone or in the presence of background therapies in preclinical lupus models.

以下是我們命名為 LUMORA 的 Ib 期試驗之研究設計概覽。我們計畫納入約 30 名 SLE 患者，以 2 比 1 隨機分派至 KT-579 或安慰劑組，並治療 16 週。允許使用口服皮質類固醇作為背景治療。事實上，我們即將在美國風濕病學會（American College of Rheumatology）年會的口頭報告將展示：在臨床前狼瘡模型中，KT-579 無論單獨使用或在背景治療存在下皆顯示顯著活性。

The Phase Ib will evaluate the impact on inflammatory cytokines, interferon signatures, B-cell subsets, and other key immune pathways implicated in lupus. And we will also explore measures of lupus disease activity, including changes in the mucocutaneous and musculoskeletal symptoms that patients experience. In this small Phase Ib study, those measures will help us look for early signs of clinical activity alongside the safety and biomarker results.

Ib 期將評估其對發炎性細胞激素、干擾素特徵（interferon signatures）、B 細胞亞群，以及其他與狼瘡相關的關鍵免疫途徑之影響。我們也將探索狼瘡疾病活動度的衡量指標，包括患者所經歷的皮膚黏膜與肌肉骨骼症狀之變化。在這項小型 Ib 期研究中，這些衡量指標將協助我們在安全性與生物標誌物結果之外，同步尋找早期臨床活性訊號。

And so with that, I will turn the call over to Bruce.

那麼接下來，我把電話交給 Bruce。

Thanks, Terence. Turning to our third-quarter results, I will quickly walk you through the income statement shown here. As expected, we did not recognize any collaboration revenue in the third quarter. And as a reminder, we do not expect additional collaboration revenue for the remainder of 2026, as the milestones and our previous deferred revenue under our collaborations with Sanofi and Gilead were fully recognized as of the second quarter.

謝謝你，Terence。接著看我們第三季的結果，我會快速帶各位看一下這裡的損益表。如預期，我們在第三季未認列任何合作收入。提醒各位，我們預期 2026 年剩餘期間不會再有額外合作收入，因為我們與 Sanofi 與 Gilead 合作案的里程碑款及先前遞延收入已於第二季全數認列完畢。

In terms of operating expenses, reported R&D expenses for the quarter were $128.5 million, excluding approximately $10.9 million in non-cash stock-based compensation. R&D expense was $117.6 million, an increase of 8% compared to the second quarter of 2026.

在營運費用方面，本季報告的研發費用為 1.285 億美元，不包含約 1,090 萬美元的非現金股票基礎給付（stock-based compensation）。研發費用為 1.176 億美元，較 2026 年第二季增加 8%。

Reported G&A expenses for the quarter were $18.7 million, excluding approximately $7.9 million in stock-based compensation. Adjusted cash G&A expense was $10.8 million, a decrease of 14% compared to the second quarter of 2026.

本季報告的一般及行政（G&A）費用為 1,870 萬美元，不包含約 790 萬美元的股票基礎給付。調整後現金 G&A 費用為 1,080 萬美元，較 2026 年第二季下降 14%。

We ended September with cash, cash equivalents, and investments of approximately $1.6 billion, providing a runway into 2029 and positioning us to continue to execute on a number of important value-driving milestones over the coming years. Our financial position gives us the resources to advance both our wholly-owned programs into and through their next phases of development.

截至 9 月底，我們的現金、約當現金與投資約為 16 億美元，可支應至 2029 年，並使我們得以在未來幾年持續推進多項重要的價值驅動里程碑。我們的財務狀況提供資源，推進我們兩項自有（wholly-owned）計畫進入並完成其下一階段的開發。

Specifically, it allows us to complete the KT-621 Phase IIb study in asthma and to take KT-579 through our planned Phase Ib study in lupus. We also expect to fund the KT-621 Phase III studies in AD in the initial stages of the Phase III development in asthma within our current runway.

具體而言，這使我們能完成 KT-621 在氣喘的 IIb 期研究，並推進 KT-579 進入我們規劃的狼瘡 Ib 期研究。我們也預期在目前的資金跑道內，能支應 KT-621 在異位性皮膚炎（AD）的 III 期研究，以及在氣喘 III 期開發初期階段的資金需求。

Alongside these clinical priorities, we will continue to invest in our research pipeline and build the capabilities needed as we move toward later-stage development and commercialization. We believe this puts us in a strong position to execute our plans while remaining disciplined in how we deploy capital.

除這些臨床優先事項外，我們將持續投資研發管線，並在邁向後期開發與商業化之際，建立所需能力。我們相信，這使我們在執行計畫的同時，仍能在資本配置上保持紀律，並處於有利位置。

I will pause here so Nello can provide a few closing comments before we open the call to questions.

我先在此暫停，讓 Nello 在我們開放提問前做幾點結語。

Thank you, Bruce. To wrap up, we have an important milestone ahead for KT-621, building on the compelling profile observed in Phase I healthy volunteers and patients with AD. In dermatology, we expect Phase IIb AD data by year-end, as I have said earlier. Subject to those results of regulatory discussions, we plan to begin Phase III development by mid-2027, and that planning is already well underway. In respiratory, our Phase IIb asthma study is ongoing, with data expected in late 2027.

謝謝你，Bruce。總結來說，KT-621 即將迎來一個重要里程碑，這是建立在 I 期健康受試者與 AD 患者中所觀察到的具吸引力特徵之上。在皮膚科方面，如我先前所說，我們預期在年底前取得 IIb 期 AD 數據。在這些結果以及與主管機關討論的情況下，我們計畫於 2027 年年中前啟動 III 期開發，而相關規劃已在積極進行中。在呼吸領域，我們的 IIb 期氣喘研究正在進行，預期於 2027 年底取得數據。

As for KT-579, today's results are an important step for that program. In healthy volunteers, we saw evidence that degrading IRF5 can modulate multiple disease-driving pathways. Along with the safety and tolerability profile observed in this study, these findings support our plans to advance KT-579 into patients with lupus by early next year.

至於 KT-579，今天的結果是該計畫的重要一步。在健康受試者中，我們看到 IRF5 降解可調節多條驅動疾病的途徑之證據。結合本研究所觀察到的安全性與耐受性特徵，這些發現支持我們的計畫：於明年年初將 KT-579 推進至狼瘡患者研究。

We also plan to expand beyond lupus, and we will be sharing more on our broader development strategy next year. These programs are emblematic of our strategy to build a world-class pipeline of wholly-owned immunology programs that are directed at fundamental disease pathways with the potential to help large patient populations. In closing, I want to thank the study participants, investigators, and our team for making all of this progress possible.

我們也計畫擴展至狼瘡以外的適應症，並將在明年分享更完整的整體開發策略。這些計畫體現了我們的策略：建立世界級、自有的免疫學研發管線，聚焦於根本性的疾病途徑，並具備幫助龐大患者族群的潛力。最後，我要感謝研究參與者、研究者以及我們的團隊，讓這一切進展成為可能。

With that, we will open the call for questions.

接下來，我們開放提問。

(Operator Instructions) Brian Cheng, J.P. Morgan.

(接線員指示) Brian Cheng，摩根大通（J.P. Morgan）。

Thanks for taking our questions today. On the Phase Ib LUMORA trial design, I am curious how you are thinking about the bar for success there. And any color in terms of which doses you would pick to move forward into this study, just given that it is interesting to note that you are already saturating at dose level 3? Just one tiny question at the end is, any opportunity for patients to also taper off steroids as well? Thank you.

謝謝今天讓我們提問。關於 Ib 期 LUMORA 試驗設計，我很好奇你們如何看待其成功門檻。另外，關於要推進到這項研究的劑量選擇，能否提供一些補充說明？因為值得注意的是，你們在第 3 劑量層級似乎已經達到飽和。最後一個小問題是：患者是否也有機會逐步減量類固醇？謝謝。

Thanks, Brian. So I will take a little bit of the question, then I will pass it to Terence, who is our expert. So I think it is important to remember that the goal of this study is to demonstrate for the first time that in patients where there is obviously disease, and we believe this pathway of activation, we can modulate the biology of patients with the drug, obviously without the need of ex vivo stimulation. So it is really demonstrating for the first time that IRF5 is relevant in the disease biology of lupus.

謝謝你，Brian。我先回答部分問題，接著我會交給我們的專家 Terence。我認為重要的是要記得，這項研究的目標是首次在患者身上證明：在明顯存在疾病、且我們相信此活化途徑存在的情況下，我們可以用藥物調節患者的生物學反應，而且顯然不需要體外（ex vivo）刺激。因此，這真正是在首次證明 IRF5 與狼瘡的疾病生物學具有相關性。

I would like to, Terence, maybe talk about some of the other specific goals that we have. I just want to touch a little bit on the dose. So as you pointed out well, Brian, again, we are so proud that in other first-in-class targets, there has never been drug before. We have been able to do it robustly, safely, and showing probably better than expected biomarker outcomes.

Terence，我想也許可以談談我們其他一些具體目標。我也想稍微提一下劑量。所以如你所說得很好，Brian，再次強調，我們非常自豪，因為在其他同類首創（first-in-class）的標的上，以前從未有過藥物。我們能夠以強健、且安全的方式做到，並且顯示出可能優於預期的生物標誌物結果。

We have many options in terms of doses, right? Because we have shown pre-clinically that 85% is actually enough to drive the biology, and you saw all of our doses at more than 85% degradation. So we will continue the mystery around the dose for now, but obviously, we have several options, and we will pick the one that we believe will allow us to answer that question well.

就劑量而言，我們有很多選項，對吧？因為我們在臨床前已經證明，85%其實就足以驅動生物學效應，而你也看到我們所有劑量都達到超過85%的降解。所以目前我們會繼續對劑量保持一些神秘感，但顯然我們有幾個選項，我們會選擇我們相信能讓我們很好回答那個問題的方案。

Terence, on the Phase Ib, maybe you can add more color.

Terence，關於Ib期，也許你可以補充更多細節。

Thanks, Brian. Good to see you. Success criteria. We will look to recapitulate degradation in the setting where the target is active and much more highly expressed than in healthy volunteers. And then downstream of that, we will look for movement of relevant biomarkers in those three key pathways that we discussed in the healthy volunteer study.

謝謝，Brian。很高興見到你。成功標準。我們會希望在標的活化、且表達量遠高於健康受試者的情境下，重現（recapitulate）降解效果。接著在此之下游，我們會觀察在健康受試者研究中討論的三個關鍵路徑中相關生物標誌物的變化。

Inflammatory biomarkers, interferon response, and B-cell biology. We will be able to do that without having to artificially stimulate the pathway ex vivo. We will also have the opportunity, obviously, to also look at clinical outcome measures, and so we will take heed of that too.

發炎生物標誌物、干擾素反應，以及B細胞生物學。我們將能在不需要於離體（ex vivo）人工刺激該路徑的情況下做到這點。當然，我們也會有機會觀察臨床結局指標，因此我們也會一併納入考量。

Steroid taper, I think, was your final question. We will get into a little more detail around trial design at a later date when we launch the trial and post clinical trials, et cetera. But I think it is fair to say that across lupus studies these days, the expectation is that taper is incorporation design.

類固醇減量（taper），我想那是你最後一個問題。我們會在之後、當我們啟動試驗並公布臨床試驗等資訊時，再更詳細說明試驗設計。但我想可以公平地說，如今在紅斑性狼瘡研究中，普遍的期待是把減量納入設計之中。

Great. Thank you. Congrats on this data.

很好。謝謝。恭喜這些數據。

Thomas Smith, Leerink Partners.

Thomas Smith，Leerink Partners。

Good morning. Thanks for taking our questions. Congrats on all the progress and these very nice IRF5 data. Just with respect to the IRF5 degradation, I was wondering if you could comment on how much inter-patient variability you observed. Were there any patients who didn't achieve at least that 80% threshold you were aiming for? Was there any difference in serum versus skin?

早安。謝謝回答我們的問題。恭喜你們的進展，以及這些非常漂亮的IRF5數據。關於IRF5降解，我想請問你們觀察到多少病人間變異（inter-patient variability）。是否有任何病人沒有達到你們目標的至少80%門檻？血清與皮膚之間是否有差異？

I was also wondering if you could just comment on some recent data we've seen from the TLR7/8 class and how that maybe influences your thinking around probability of success in an indication like lupus. Thanks so much.

我也想請你們評論一下我們最近看到的TLR7/8類別的一些數據，以及這可能如何影響你們對於像狼瘡這類適應症成功機率的看法。非常感謝。

Okay, I will take the first two. I do want to encourage people to try and focus on one, because if you have three in one, we are not really doing one. This is for future questions.

好的，我先回答前兩個。我也想鼓勵大家盡量聚焦在一個問題上，因為如果一次問三個，其實我們就沒有真正回答任何一個。這是給未來提問的建議。

So on the degradation, if you look at our graph, the slides should be up on our website, by the way, to everybody listening, so you should be able to see it. Our degradation profile as now for, this is the sixth program we show data for, is always extremely robust and consistent. Our error bars are extremely small, so there are no outliers in the degradation profile in the subject in our study.

關於降解，如果你看我們的圖表——順帶一提，投影片應該已經放在我們網站上，所有正在收聽的人都可以看到——我們目前展示數據的這是第六個專案，我們的降解曲線一向非常強健且一致。我們的誤差棒非常小，所以在本研究受試者的降解曲線中沒有離群值。

The difference between blood and skin is minimal, if any. The IRF5 expression in skin is extremely low. In fact, we actually did not set the expectation around skin because actually we thought we were not going to be able to measure it. But we have an amazing team here that has developed unique assays, some of which we are not sharing because they are assays that we have invented and we want to protect as well. But we were able to actually measure even very low expression level, we were able to robustly reduce with this drug. That was another important milestone.

血液與皮膚之間的差異很小，若有的話也是如此。皮膚中的IRF5表達量非常低。事實上，我們並沒有對皮膚設定預期，因為我們原本以為無法測量。但我們這裡有一支很棒的團隊，開發了獨特的檢測方法，其中有些我們不會分享，因為那是我們自行發明、也希望加以保護的檢測。不過，我們確實能夠測量到即使非常低的表達量，並且能用這個藥物強健地降低。那是另一個重要的里程碑。

There was a question around the competitive landscape. Terence, do you want to make a comment there?

另外有一個關於競爭格局的問題。Terence，你要不要在這裡評論一下？

Thanks, Thomas. I would say the TLR7/8 direct inhibition gives us confidence in probability of success. But, of course, this mechanism goes beyond just TLR7 and 8. That, I think, is a good guide for us, too, and really looking forward to interrogating that profile in lupus patients very, very soon.

謝謝，Thomas。我會說，TLR7/8的直接抑制讓我們對成功機率更有信心。但當然，這個機制不僅僅超越TLR7與TLR8。我想那也為我們提供了很好的參考，我們也非常期待在非常、非常近期於狼瘡病人中深入檢視該特徵。

Thanks, guys.

謝謝各位。

Derek Archila, Wells Fargo.

Derek Archila，Wells Fargo。

Good morning, and thanks for taking the questions, and congrats on the data today. More of a market question in terms of atopic dermatitis, but the beyond opportunities for KT-621. I was wondering if you could help quantify how the atopic dermatitis market may expand with the introduction of a safe and effective oral. I guess the bigger question is could you expect similar expansions in other indications like asthma, COPD, and so on? Thanks.

早安，謝謝讓我提問，也恭喜今天的數據。這比較偏市場面的問題，關於異位性皮膚炎（atopic dermatitis, AD），以及KT-621的延伸機會。我想請你們協助量化：若引入一款安全且有效的口服藥，異位性皮膚炎市場可能會如何擴大。更大的問題是：你們是否預期在其他適應症如氣喘、COPD等，也會出現類似的市場擴張？謝謝。

Thanks, Derek. So this gives me an opportunity to also make another point, which sometimes we forget to do, which is KT-621, potentially the first safe, effective oral for type 2 diseases, is something that has never actually been accomplished before. So not only we can focus on AD in a minute, not only this is a drug for AD, but it is the drug that will or should, I should say, be treating all comorbidities.

謝謝，Derek。這也讓我有機會再補充一點：我們有時會忘了強調，KT-621作為可能第一個針對第二型疾病（type 2 diseases）的安全、有效口服藥，是過去從未真正達成的事。所以我們不只可以稍後聚焦在AD；這不僅是一個治療AD的藥物，它也是一個將會——或我應該說，應該——用來治療所有共病的藥物。

One of the main reason for dupilumab success is not only the robust efficacy and pretty amazing safety profile, but it is the fact that it is the preferred options for most doctors because it treats comorbidities that most patients have when they have any one type 2 disease. So that is something that we often forget to remind, but I just wanted to take the opportunity to remind. This is a unique drug also because of it.

Dupilumab成功的主要原因之一，不僅是其強健的療效與相當驚人的安全性概況，也在於它是多數醫師的首選，因為它能治療大多數病人在罹患任何一種第二型疾病時常見的共病。所以這點我們常常忘了提醒，但我想藉此機會再提醒一次。這也是一個獨特的藥物，原因就在於此。

Now, when we go back to your point about, we had a slide today earlier in our presentation, that there is millions of patients with moderate to severe AD in the U.S., six to nine we said. This is actually a publication. This is not our numbers. And another data that is not ours, but it is a fact, it is about 400,000 are on advanced systemic therapy.

回到你提到的重點：我們今天稍早的簡報中有一張投影片提到，美國有數百萬名中度至重度AD患者，我們說大約600萬到900萬。這其實是文獻發表的數據。不是我們自己的估算。另外一個也不是我們的數據、但屬於事實的是：大約有40萬人正在使用進階的全身性治療（advanced systemic therapy）。

So the opportunity here that we have with potentially the first safe, effective oral drug is to expand the market of patients that are sitting on the sidelines because they are not comfortable with the idea of taking an injectable biologic. So we think this would be transformative almost regardless of where exactly the efficacy profile will land. Although, as we said, we expect it obviously to be in the dupilumab ballpark.

因此，我們在這裡的機會是：若能推出可能第一個安全、有效的口服藥，就能擴大那些仍在觀望的患者市場，因為他們對於使用可注射的生物製劑並不自在。所以我們認為，這將具有變革性，幾乎不論最終療效曲線落在何處。當然，如我們所說，我們預期它顯然會落在dupilumab的同等級範圍內。

And that could be applied, as you were implying, to other diseases where actually either there is mostly, if not only, biologics, for example, asthma, or diseases where there is only one drug or two drugs. If you think about EoE, only injectable drug. For so far, only DUPIXENT. We probably have TEZSPIRE being, we assume, approved relatively soon. CRS, again, these are dominated by injectable drugs that are not what people are looking for.

而且正如你所暗示的，這也可以應用到其他疾病上；在那些疾病中，實際上主要（甚至可能只有）是生物製劑，例如氣喘，或是只有一種藥或兩種藥的疾病。如果你想想 EoE，目前只有注射劑。到目前為止只有 DUPIXENT。我們推測 TEZSPIRE 可能會在相對不久後獲得核准。CRS 也是一樣，這些領域同樣由注射藥物主導，而這並不是人們所期待的。

We believe that the opportunity here, we continue to make the case, is not so much that we will have to compete with biologics, which I am sure we will do as a highly competitive team here, but it is actually about expanding the market to new patients. Even in psoriasis, as you have seen with icotrokinra recently, a much more mature market, 60% of new prescription for icotrokinra are new patients, which is pretty impressive for a market that has been built for now almost 15 years.

我們相信這裡的機會——我們也持續在闡述這個觀點——與其說是我們必須和生物製劑競爭（我確信我們會以一支高度具競爭力的團隊來面對），不如說其實是把市場擴大到新的病患族群。即便在乾癬這樣你最近從 icotrokinra 看到的、更成熟的市場中，icotrokinra 的新處方有 60% 來自新病患；對一個已經建立將近 15 年的市場而言，這相當令人印象深刻。

Very helpful. Thanks, guys.

非常有幫助。謝謝各位。

Geoff Meacham, Citi.

Geoff Meacham，花旗。

This is Nishant on for Geoff. Thanks for taking our questions. Looking at today's data from KT-579, are there any elements that most strongly support development beyond lupus, maybe like in IBD, Sjogren's, or RA? Thank you.

我是 Nishant，代 Geoff 提問。謝謝你們回答我們的問題。看今天 KT-579 的數據，有哪些要素最能支持在紅斑性狼瘡之外的開發，例如 IBD、乾燥症或 RA？謝謝。

Yeah, maybe I'll let Terence take this question, and then I might add one thing at the end. Go ahead.

好的，也許我先請 Terence 回答這個問題，最後我再補充一點。請。

Thanks. So genetically, there are strong genetic links to each of those diseases for IRF5 overactivity, so that gave us confidence as a starting point. From the data today, obviously, we looked at those three pathways, pro-inflammatory cytokines, type 1 interferon, and B-cell biology, and you can draw threads between each of those and rheumatoid arthritis and/or Sjogren's disease or IBD.

謝謝。從遺傳學角度來看，IRF5 過度活化與你提到的每一種疾病都有很強的遺傳關聯，這讓我們在起點上就有信心。就今天的數據而言，很明顯我們看了三條路徑：促發炎細胞激素、第一型干擾素，以及 B 細胞生物學；而你可以在這些路徑與類風濕性關節炎和／或乾燥症或 IBD 之間找到連結。

Just as an example, in IBD, obviously, in the pro-inflammatory cytokine panel, things that we looked at included TNF alpha and IL-23. Each of those have been successfully targeted as monotherapies and recently in combination. In Sjogren's disease, it's well-recognized as an interferonopathy with strong interferon signature, and we saw good damping of type 1 interferon in today's readout. And finally, it's also well-recognized as a B-cell-driven autoantibody associated disease, and we saw signals there, too. I think we've got good evidence of a broad waterfront of opportunity.

舉例來說，在 IBD 中，顯然在促發炎細胞激素面板裡，我們觀察的項目包含 TNF alpha 和 IL-23。這兩個靶點都已成功作為單藥治療，且近期也有合併治療的成功案例。在乾燥症方面，它被廣泛認為是一種干擾素病（interferonopathy），具有強烈的干擾素特徵訊號，而我們在今天的讀出中看到第一型干擾素有良好的抑制效果。最後，它也被公認為是一種由 B 細胞驅動、與自體抗體相關的疾病，而我們在那裡也看到了訊號。我認為我們已經有很好的證據顯示，存在一個相當廣泛的機會版圖。

Yeah, the only thing I would add, thanks, Terence, is that the lupus LUMORA study, which is bound to start soon, you should expect it to be one of multiple patient study that we plan to initiate around this program with the KT-579.

是的，我唯一要補充的——謝謝你，Terence——是狼瘡的 LUMORA 研究很快就會啟動；你們應該預期，這會是我們計畫在 KT-579 這個專案上啟動的多項病患研究之一。

Mike Coles, Morgan Stanley.

Mike Coles，摩根士丹利。

Great. Good morning. Thanks for taking the question. Maybe I could just ask a follow-up just on the upcoming BROADEN2 data. Just given you (technical difficulty) just wondering if you can share any thoughts on baseline characteristics and how that might impact our thinking when we try and do cross-trial comparisons to the DUPIXENT Phase III studies. Thanks.

很好。早安。謝謝讓我提問。我想就即將公布的 BROADEN2 數據追問一下。鑑於你們（技術問題）我想知道你們是否能分享一些對基線特徵的看法，以及這可能如何影響我們在嘗試與 DUPIXENT 第三期研究做跨試驗比較時的判讀。謝謝。

Thanks, Mike. As we've said in the past, we're trying to just preserve all the patient baseline characteristics as well as obviously the data when we report the data later this year before year-end, as we've said. The only new update we gave today in our remarks was around the percentage of patients that went from the 16-week study to the OLE, just because we have completed that study, and now the study is officially in an open-label extension.

謝謝你，Mike。正如我們過去所說，我們希望在今年稍晚、也就是我們所說的年底前公布數據時，能完整保留並呈現所有病患的基線特徵，當然也包括數據本身。我們今天在談話中提供的唯一新更新，是關於從 16 週研究進入 OLE 的病患比例，因為我們已完成該研究，而目前研究已正式進入開放標籤延伸期。

We said that of the eligible patients, 98% enrolled into the OLE. That's the only comment we were going to make around that study, and then the next update would be when we share the data. Thank you. Next one.

我們表示，在符合資格的病患中，有 98% 進入 OLE。這是我們對該研究唯一要做的評論；下一次更新將會是在我們分享數據時。謝謝。下一位。

Biren Amin, Piper Sandler.

Biren Amin，Piper Sandler。

Thanks for taking my questions, and congrats on the IRF5 update. Maybe a question on KT-621 and BROADEN2. What measures did you take in the trial to mitigate against high placebo response, which typically we've seen that historically in other AD studies? Thank you.

謝謝讓我提問，也恭喜 IRF5 的更新。我想問 KT-621 和 BROADEN2。你們在試驗中採取了哪些措施來降低安慰劑反應偏高的風險？我們過去在其他 AD 研究中通常都看到這種情況。謝謝。

Yeah, thanks for the question. I'll let maybe Terence take this one.

好的，謝謝這個問題。我想請 Terence 來回答。

Thanks, Biren. So the priority of the company in enrolling that study was to focus on quality rather than speed, hence it was actually a particularly pleasant surprise that the study enrolled a couple of quarters early. Measures included careful site selection, careful investigator selection, control of factors that can sometimes drive placebo response rate, like previous medications or concomitant therapies coming into the trial.

謝謝你，Biren。因此，公司在招募該研究時的優先事項是重質不重量，所以研究能提前幾個季度完成入組其實是個相當令人愉快的驚喜。我們採取的措施包括：謹慎選擇試驗中心、謹慎選擇研究者，以及控制一些有時會推高安慰劑反應率的因素，例如入組前既往用藥或試驗期間的合併治療。

Careful patient selection coming in, including some fairly novel measures to assure that patients had atopic dermatitis, that it was moderate to severe. So despite that tight filter, as I say, there was a lot of enthusiasm. The trial enrolled approximately two quarters early. Some of that enthusiasm, I think, came from appetite for a safe, effective oral in the space, comfort with the pathway, a high-touch approach by the team, and a transparent scientific disclosure. We're really looking forward to disclosing the results very soon.

也包括謹慎的病患篩選，並採用一些相當新穎的措施，以確保病患確實患有異位性皮膚炎，且屬於中重度。因此，儘管篩選條件很嚴格，如我所說，仍然有很高的熱情。該試驗大約提前兩個季度完成入組。我認為這部分熱情來自於市場對安全、有效口服藥的需求，對該作用路徑的熟悉度，團隊的高接觸式執行方式，以及透明的科學資訊揭露。我們非常期待能在不久後公布結果。

Thanks, Biren. Next question.

謝謝你，Biren。下一個問題。

Alex Thompson, Stifel.

Alex Thompson，Stifel。

Thanks for taking our question. Maybe another on BROADEN2. What should we expect in terms of data beyond the primary and key secondary endpoints as it relates to subpopulations like those with comorbid asthma and as well as biomarkers? Anything there would be helpful. Thank you.

謝謝讓我們提問。我也想再問一個關於 BROADEN2 的問題。除了主要與關鍵次要終點之外，針對像是合併氣喘等亞族群，以及生物標記（biomarkers）方面，我們應該期待看到哪些數據？任何相關資訊都會很有幫助。謝謝。

Thanks, Alex. Obviously, we don't have visibility into the data yet, so it's really hard for us to commit 100% to beyond what we've already said. I think the goal of the first disclosure is to ensure that we share all the data that we believe is material to, obviously, the company and to investors to assess the safety and efficacy profile of the drug.

謝謝你，Alex。很明顯我們目前還看不到數據，所以很難對超出我們已經說過的內容做出 100% 的承諾。我認為第一次揭露的目標，是確保我們分享所有我們認為對公司以及投資人評估該藥物安全性與有效性概況而言屬於重大（material）的數據。

Some things that we believe are additional interesting scientific information but are not critical. We love to keep them for eventual presentation and publication. So that's kind of the overarching philosophy. I think once we'll share the data, we'll be able to then explain what's in there and what will come at a later point.

有些我們認為屬於額外且有趣的科學資訊，但並非關鍵。我們希望把這些留待未來的發表與出版。這就是整體的指導原則。我想一旦我們分享了數據，我們就能進一步說明其中包含哪些內容，以及哪些會在之後的時間點再公布。

Faisal Khurshid, Jefferies.

Faisal Khurshid，Jefferies。

Thank you so much for taking the question. Just wanted to ask maybe a little bit different of a question. With regard to your degrader platform, can you talk to us, there's some interesting extracellular degrader programs and platforms that are out there? Can you talk to us about whether that's something that is kind of within the Kymera repertoire, or is that something that you could be interested in going into in the future?

非常感謝讓我提問。我想問一個可能稍微不同的問題。關於你們的降解劑（degrader）平台，市面上有一些很有意思的細胞外降解劑（extracellular degrader）計畫與平台。你們能否談談這是否屬於 Kymera 的能力範疇，或是未來你們可能有興趣切入的方向？

Thanks for the orthogonal question. So let me explain what we are very good at. I think we are the best at identifying the right targets for the technology, identifying small molecule, highly specific ligand for novel targets, making exceptionally well-behaved and specific degraders, and I think designing and executing, so far, early to mid-development studies, in immunology. That sounds like start of school, but actually, that is really hard to do, all in a completely novel company.

謝謝這個正交（orthogonal）的問題。我先說明我們非常擅長的部分。我認為我們最強的是：為這項技術找出正確的標的、為新穎標的辨識小分子且高度特異性的配體、打造表現非常良好且具特異性的降解劑，以及我認為在免疫學領域設計並執行（截至目前）從早期到中期開發研究。這聽起來像在上課的開場白，但其實在一家完全新創的公司裡，要把這些都做到位是非常困難的。

Another thing that we are really good at is any type of heterobifunctional molecule chemistry. So that obviously could incorporate, by just nature of the business, extracellular degraders, these Bridgers, obviously molecular glues. And so, we, as a curious and well-financed company, look at other contiguous technologies as well.

我們另一個非常擅長的，是各類異雙功能分子（heterobifunctional molecule）的化學設計。因此，就業務本質而言，這當然可能涵蓋細胞外降解劑、這些 Bridgers（橋接分子），以及顯然也包括分子膠（molecular glues）。所以，作為一家好奇心強且資金充裕的公司，我們也會關注其他相鄰（contiguous）的技術。

What I will say is that I find it extremely hard to develop a technology, let us say an extracellular degrader solution that is not oral. I mean, I think the power of heterobifunctional molecules is the ability to make these drugs oral drugs that can replace or expand beyond these injectable biologics. So I do not think you are going to see us making extracellular degraders that are injected, because I do not think there is a need for that. There are other technologies that can trap extracellular proteins much more efficiently, or even now, probably lower cost than novel technologies.

但我要說的是，我認為要開發一項技術——例如一個非口服的細胞外降解劑解決方案——是極其困難的。我的意思是，我認為異雙功能分子的威力在於能把這些藥物做成口服藥，從而取代或拓展超越這些需要注射的生物製劑。因此，我不認為你們會看到我們去做需要注射的細胞外降解劑，因為我不覺得有這個必要。還有其他技術能更有效率地捕捉細胞外蛋白，甚至現在可能成本也比新技術更低。

Jeff Jones, Oppenheimer.

Jeff Jones，Oppenheimer。

Good morning, guys. Again, congrats on the really striking data. As far as Phase III planning for KT-621 beyond AD and asthma, any updates on your thinking around additional indications and programs there? You have disclosed some thoughts previously, but just if there are any updates to your thinking.

各位早安。再次恭喜你們拿到非常亮眼的數據。關於 KT-621 在異位性皮膚炎（AD）與氣喘之外的第三期（Phase III）規劃，你們對其他適應症與相關計畫的思考有沒有更新？你們之前披露過一些想法，但想請問目前是否有任何新的進展。

Thanks, Jeff. Great question. I will try and address this quickly. So our goal is to launch KT-621 in all indications that we believe are relevant to type 2 inflammation.

謝謝你，Jeff。我會盡量簡短回答。我們的目標是在所有我們認為與第二型發炎（type 2 inflammation）相關的適應症中推出 KT-621。

In terms of priority indications, are the ones that we believe there is highest unmet need and opportunity for an oral drug to change the landscape. Those go beyond AD and asthma. I think we want to have that conversation post the BROADEN2 data so that at some point early next year, we can share a bit more comprehensively what our late development plan is, because that will be obviously highly dependent on this upcoming data readout.

就優先順序而言，我們會優先考量那些我們認為未被滿足需求最高、且口服藥有機會改變治療格局的適應症。這些會超出 AD 與氣喘。我想我們希望在 BROADEN2 數據出來之後再進一步討論；因此在明年年初的某個時間點，我們可以更全面地分享我們的後期開發計畫，因為這將明顯高度取決於即將公布的數據讀出。

Brian Abrahams, RBC Capital.

Brian Abrahams，RBC Capital。

Good morning, team. This is Kevin on for Brian. Thank you for taking our questions. On the Phase Ib lupus study, will you enroll both interferon high and low patients? And for later stage development, do you think there is value in focusing on interferon high patients, should the effect be more pronounced there? Thank you.

團隊早安。我是 Kevin，代 Brian 提問。謝謝你們回答我們的問題。關於第一期 Ib 期狼瘡研究，你們會同時納入干擾素高（interferon high）與干擾素低（interferon low）的患者嗎？而在後期開發上，如果在干擾素高患者中效果更明顯，你們是否認為聚焦干擾素高患者會更有價值？謝謝。

Thanks, Brian. Thanks for the question. We will enroll both interferon high and low patients. It's premature at this stage, I think, to focus on a biomarker-driven subset. Obviously, we're well aware of interferon high and its potential for controlling placebo response rates in lupus trials. But just hearkening back to the mechanism of action here, obviously, the MOA includes but goes well beyond just interferon inhibition. So at this stage, we're in learn mode. We'll enroll a well-controlled, well-defined lupus population, but not necessarily tightly focused on just interferon high.

謝謝你，Brian。謝謝這個問題。我們會同時納入干擾素高與干擾素低的患者。我認為在這個階段就聚焦於以生物標記（biomarker）驅動的特定子群還為時過早。當然，我們很清楚干擾素高狀態及其在狼瘡試驗中可能用於控制安慰劑反應率的潛在價值。但回到這裡的作用機轉（MOA），顯然其機轉包含但遠不僅僅是干擾素抑制。所以在這個階段，我們處於學習模式。我們會納入一個控制良好、定義清楚的狼瘡族群，但不會必然只緊扣在干擾素高。

Yeah, I agree, Terence. More importantly, because we want to learn whether there will be a different biomarker response based on heterogeneity of baseline. I think at this stage, it's very important to be more open-minded than not.

是的，我同意，Terence。更重要的是，因為我們想了解：基線異質性不同時，是否會出現不同的生物標記反應。我認為在這個階段，保持更開放的心態非常重要。

Andy Chen, Wolfe Research.

Andy Chen，Wolfe Research。

Thank you so much for taking my question. This is Jason on for Andy. We just had a quick question on the PD for IRF5. Did the data suggest any flexibility in dosing frequency or rapid reversibilities if any safety issues emerge? Thank you.

非常感謝讓我提問。我是 Jason，代 Andy 提問。我們想快速問一個關於 IRF5 藥效動力學（PD） 的問題。數據是否顯示在給藥頻率上有彈性，或如果出現任何安全性問題，是否具有快速可逆性？謝謝。

So our drugs, as you can see, even from the biomarker responses, when you stop dosing the degradation, obviously the target comes back to baseline in a few days. You can see it again in the biomarker response, but whose kinetics is very similar to the degradation as Terence said.

我們的藥物，如你們所見，即使從生物標記反應來看，當你停止給藥後，降解作用停止，標的蛋白顯然會在幾天內回到基線。你也能在生物標記反應中再次看到這一點，其動力學如 Terence 所說，與降解的動力學非常相似。

So I think we know how to obviously dose this drug, what doses we need to adopt. We, personally, I should say, maybe I personally don't expect it will have to react to some emerging adverse event based on mechanism. But even if that was the need of cessation of dosing, again, these are drugs whose half-life are in the hours, not in the days. You can see a re-uptake of pathway signaling, relatively quickly. We're not concerned.

所以我認為我們很清楚該如何給這個藥、需要採用哪些劑量。就我們而言——我應該說，可能就我個人而言——我不預期會需要因機轉而去應對某些新出現的不良事件。但即便真的需要停藥，這些藥物的半衰期是以小時計，而不是以天計。你會相對快速地看到訊號通路活性恢復。我們不擔心。

Gotcha. Thank you.

了解。謝謝。

Morgan Lamberti, Goldman Sachs.

Morgan Lamberti，Goldman Sachs。

Thank you. This is Morgan. On IRF5, how are you thinking about the translation of biomarker reduction in healthy volunteers to lupus patients, in terms of whether you would expect to see similar or greater reductions? And how should we think about the safety or the ramifications of achieving greater than 90% IRF5 degradation? Just if there's any specific AEs you're monitoring there. Thank you so much.

謝謝。我是 Morgan。關於 IRF5，你們如何看待健康受試者中生物標記下降，轉譯到狼瘡患者時的情況——也就是你們預期會看到相近或更大的下降幅度？以及我們應如何看待達到超過 90% 的 IRF5 降解在安全性或影響（ramifications）上的意義？是否有任何特定的不良事件（AEs）是你們在那裡特別監測的？非常感謝。

So maybe just quickly, I'll try to answer and then Terence can help me. Just remember the ex vivo cytokine activation is a, let's call it an artificial pathway activation. And this allows us to measure, in the absence of IRF5, how much pathway inhibition you see when you have a robust activation. So the fact that we're able to practically inhibit fully these pathways with IRF5 degradation, it's telling you that this target is central to these pathway activations when we use the stimuli.

我先簡短回答，然後 Terence 可以補充。請記得，離體（ex vivo）的細胞激素活化是一種——我們姑且稱之為——人工的通路活化。這讓我們能在缺乏 IRF5 的情況下，於強烈活化的條件中衡量你能看到多少通路抑制。因此，我們能夠透過 IRF5 降解幾乎完全抑制這些通路，這告訴你：當我們使用這些刺激條件時，這個標的是這些通路活化的核心。

I think in patients, you obviously have this pathway activated, but not with this type of stimuli. There is obviously disease-driven stimuli that might be, often they would be probably less robust than these. It's always difficult to being able to predict. I think the fact that we can block them fully gives us confidence that no matter what the stimuli is in patient, we should be able to see robust pathway inhibition.

我認為在患者身上，你顯然會看到這條路徑被活化，但不會是由這種刺激所引發。顯然存在由疾病驅動的刺激因素；通常它們可能不如這些刺激來得強。要能預測一直都很困難。我認為我們能夠將其完全阻斷這一點，讓我們有信心：無論患者體內的刺激是什麼，我們都應該能看到強而有力的路徑抑制。

What was the second part?

第二部分是什麼？

Safety.

安全性。

The safety. Terence, you want to take that?

安全性。Terence，你要回答這題嗎？

Yes. So thanks, Morgan. I think we expect to see movement in all three key pathways unstimulated in lupus patients. Some of which are obviously clinically validated in that disease, including type 1 interferon and B-cell biology.

好的。謝謝你，Morgan。我想我們預期在紅斑性狼瘡患者中，即使在未刺激的狀態下，也會看到三條關鍵路徑都有所變化。其中一些在該疾病中顯然已獲臨床驗證，包括第一型干擾素以及B細胞生物學。

On the safety side, we've been encouraged by the safety profile seen preclinically before this study. And I'm particularly encouraged by the preliminary safety data we've seen here in Phase I, including a lack of any signal with respect to infection. We'll continue to watch carefully, but so far so good.

在安全性方面，我們一直受到本研究前臨床所見安全性概況的鼓舞。而我特別受到我們在此第一期試驗中看到的初步安全性資料所鼓舞，其中包括在感染方面沒有任何訊號。我們會持續密切觀察，但到目前為止一切良好。

Yeah, we know that there are redundancies in the IRF5 family. So while -- we'll have a watch drive, we're not concerned about the long-term safety of this drug.

是的，我們知道IRF5家族之間存在功能冗餘。所以雖然——我們會持續監測，但我們不擔心這個藥物的長期安全性。

David Hoang, Deutsche Bank.

德意志銀行（Deutsche Bank）的David Hoang。

Good morning. Thanks so much for taking our questions, and congrats on today's IRF5 data. Before you head into the quiet period ahead of the BROADEN2 readout in AD, just wanted to ask you, could you remind us what is your view of in the ballpark of DUPIXENT for endpoints like EASI-75 and IGA 0/1? And then in terms of the scenarios that could occur, knowing what we know about STAT6 biology, is there a scenario where 621 could outperform DUPIXENT at 16 weeks? Thanks so much.

早安。非常感謝讓我們提問，也恭喜今天公布的IRF5數據。在你們進入BROADEN2於AD讀出前的靜默期之前，想請你們提醒一下：對於像EASI-75與IGA 0/1這類終點，你們認為大致上與DUPIXENT相比會落在什麼區間？另外，就可能出現的情境而言，基於我們對STAT6生物學的理解，是否存在一種情境，使得621在16週時可能優於DUPIXENT？非常感謝。

Yeah, thank you. So I mean, the reason why we've continued to talk about this ballpark is because for all the data that we have generated so far for more than half a decade, we've seen that blocking IL-4 and 13 with an upstream biologics or blocking IL-4 and 13 with a STAT6 degrader seems to block all downstream signaling in a similar way. So that's where our thesis hypothesis comes from.

好的，謝謝。我的意思是，我們之所以持續談「大致區間」，是因為在過去超過半個世紀（五年多）我們所產生的所有數據中，我們看到：用上游生物製劑阻斷IL-4與IL-13，或用STAT6降解劑阻斷IL-4與IL-13，似乎都能以相似方式阻斷所有下游訊號傳導。所以我們的論點／假設就是從這裡來的。

The other aspect is, if there are differences between the two drugs, obviously that could be driven by many things. It could be, obviously these are different technologies, small molecules versus antibodies. It's still an intracellular versus extracellular target. But it's difficult for us a priori to determine the impact of these nuances on the clinical effect that we will see.

另一方面，如果兩個藥物之間存在差異，顯然可能由很多因素所驅動。例如，這是不同的技術：小分子對比抗體。另外，目標也不同：一個是細胞內目標，另一個是細胞外目標。但我們很難在事前判斷這些細微差異會如何影響我們將看到的臨床效果。

With regards to defining the ballpark, it's actually I'm trying to define unscientifically something that is also unscientific. So cross-trial comparisons are technically not doable. And they have an inherent flaw in the approach. And so it is impossible for me to tell you exactly what the numbers should be that we should be looking at.

至於如何界定「大致區間」，其實我是在用不科學的方式去界定一個同樣不科學的東西。因此跨試驗比較在技術上是做不到的。而且這種方法本身就有內在缺陷。所以我不可能告訴你我們應該期待看到的確切數字是多少。

But I think for people that are students of the space, you should be able to have a reasonable interpretation when you see a data set across several endpoints between two studies that are around a decade apart. You have to look at the placebo rates. You have to look at the absolute treatment effect. You have to look at the consistency across endpoint. At the end of the day, it actually does not matter because we are not trying to replicate dupilumab study. We are trying to develop one of the most exciting oral drugs for type 2 patients that is right now in clinical development. And the important thing is that we demonstrate safety, efficacy, and tolerability.

但我認為，對於熟悉這個領域的人來說，當你看到兩項相隔大約十年的研究、在多個終點上的一組數據時，你應該能做出合理的解讀。你必須看安慰劑反應率。你必須看絕對治療效果。你必須看各終點之間的一致性。歸根結底，這其實並不重要，因為我們不是要複製dupilumab的研究。我們是要開發目前臨床開發中、針對第二型（type 2）患者最令人興奮的口服藥物之一。重要的是我們要證明安全性、有效性與耐受性。

I know that there is a lot of focus on comparisons, and we will do that comparison, too. I am not trying to be a purist here, but I am just trying to say that actually the important thing is that we deliver on the profile that we believe would be commercially successful and for the scientific curiosity, there are many tools that one can use to compare trials that will all be wrong but will give us a sense of what it looks like. This is the definition of ballpark, what I said in the past one and a half minutes maybe.

我知道大家非常關注比較，我們也會做這樣的比較。我不是想在這裡當純粹派，但我只是想說，真正重要的是我們能交付我們相信在商業上會成功的產品特性；至於科學上的好奇心，有很多工具可以用來比較試驗——它們都會有偏差，但能讓我們對結果大概長什麼樣有個感覺。這就是我剛才大概一分半鐘所說的「大致區間」的定義。

Tyler Van Buren, TD Cowen.

TD Cowen的Tyler Van Buren。

Great. Good morning, guys. Thanks so much for the KT-579 presentation. Regarding BROADEN2, should we expect to see itch data with the initial release, and can you discuss the potential to differentiate there given the IL-31 reductions observed? Our KOLs have recently brought this up in discussions.

很好。各位早安。非常感謝KT-579的簡報。關於BROADEN2，我們是否應該預期在首次發布時就會看到搔癢（itch）數據？另外，鑑於觀察到IL-31下降，你們能否談談在這方面做出差異化的潛力？我們的KOL最近在討論中也提到這點。

Yeah, we plan to have itch data, of course. Itch, sleep, itch, quality of life, these are actually important measures of how well the drug is actually serving patients. If you do market research, the number one complaints for patients that are actually on therapy continues to be itch.

是的，我們當然計畫提供搔癢數據。搔癢、睡眠、搔癢、生活品質——這些其實都是衡量藥物是否真正服務患者的重要指標。如果你做市場調查，正在接受治療的患者排名第一的抱怨仍然是搔癢。

With regards to differentiation, it's hard for me, and obviously I should be the most biased person in the world for the STAT6 program. It's hard for me to over-index on the IL-31 data. It's great that we saw IL-31 blood reduction in the BROADEN study. This is the Phase Ib.

至於差異化，我很難——而且顯然我應該是全世界對STAT6計畫最有偏見的人。我很難把重點過度放在IL-31數據上。我們在BROADEN研究中看到IL-31血中濃度下降，這很棒。這是第一期Ib。

It is also true that hasn't been measured by others. There was a study with dupilumab in Japanese patients where they didn't see a reduction of IL-31. But again, we're 10 years apart. We have an amazing translational medicine team under Terence's guidance. I think that it's probably more likely that we're just better at measuring than we are different biologically from DUPIXENT. But anyway, we'll know soon, so we'll definitely share the data.

同時也確實，其他人並沒有測量這個指標。曾有一項在日本患者中使用dupilumab的研究，他們沒有看到IL-31下降。但再說一次，我們相隔了10年。在Terence的帶領下，我們有一支非常出色的轉譯醫學團隊。我認為更有可能的是，我們只是更擅長測量，而不是在生物學上與DUPIXENT真的不同。不過無論如何，我們很快就會知道，所以一定會分享數據。

Jeet Mukherjee, BTIG.

BTIG的Jeet Mukherjee。

Great. Good morning. Thanks for taking the question, and congrats on the data. It almost seems you guys make degraders of this quality in your sleep now. My question was just focused around the KT-579 Phase Ib lupus study. Could you just elaborate on some of those exploratory endpoints, and what would tell you that you have a clinically differentiated profile here for KT-579? Thanks.

很好。早安。謝謝讓我提問，也恭喜數據表現。看起來你們現在連睡覺都能做出這種品質的降解劑了。我的問題主要聚焦在KT-579第一期Ib紅斑性狼瘡研究。你能否更詳細說明其中一些探索性終點？以及什麼結果會讓你們認為KT-579在這裡具有臨床上的差異化特徵？謝謝。

Terence, you want to take that?

Terence，你想回答這個嗎？

Sure. Jeet, I assume you are referring to the exploratory clinical outcome measures. We look at all of the usual lupus clinical outcome measures, including composites like SLEDAI and BILAG. We look at the individual components, and obviously that will sit alongside the biomarker data, which are the chief focus of the study. And we will take the whole set of data together in making our decisions downstream of that.

當然。Jeet，我想你指的是探索性的臨床結局衡量指標。我們會看所有常見的狼瘡臨床結局指標，包括像 SLEDAI 和 BILAG 這類的複合指標。我們也會看各個單項組成部分，而這些顯然會與生物標誌物資料並列；生物標誌物資料是本研究的主要重點。我們會把整套資料一起納入考量，用於後續的決策。

Yeah, I want to add two things. First, the reason why we make drugs in our sleep is because we do not sleep, so we actually can make drugs effectively. That is a joke, by the way. And then the other thing, I just want to remind everybody the study is not powered for clinical endpoints. That is why we have said that they are more exploratory than the usual exploratory.

對，我想補充兩點。第一，我們之所以能在睡夢中做藥，是因為我們不睡覺，所以其實能有效地做藥。順帶一提，這是個玩笑。第二，我只想提醒大家，這項研究並沒有針對臨床終點做統計效力設計。這也是為什麼我們說，這些指標比一般所謂的探索性還要更偏探索性。

So everything Terence said, obviously, I agree, but just remind everybody, this is a small study, a biomarker focus to understand the biology in the right clinical context of IRF5 degradation. Obviously, it is a 16-week study, so we will keep an eye on any move on clinical endpoints, understanding that, as you guys all know, placebo rates in lupus are high, so we got to be careful on how we interpret those data sets.

所以 Terence 說的我當然都同意，但也提醒大家，這是一項小型研究，重點在生物標誌物，用來在 IRF5 降解的正確臨床情境下理解其生物學。顯然，這是一項 16 週的研究，所以我們會留意臨床終點是否有任何變化；但也要理解，正如各位都知道的，狼瘡的安慰劑反應率很高，因此我們在解讀這些資料集時必須謹慎。

Jasmine Fels, Barclays.

Barclays 的 Jasmine Fels。

Jasmine on for Ellie Merle. So congratulations on the IRF5 data. I wanted to ask a little bit more about dose selection and dose response. Can you characterize the dose response you saw across the different MAD cohorts for the ex vivo stimulation biomarkers? Did you see a similar trend as degradation for these with saturation at dose level 3, or was there a wider range of dose response across the different biomarkers?

我是代替 Ellie Merle 的 Jasmine。首先恭喜你們的 IRF5 數據。我想再多問一點關於劑量選擇與劑量反應。你們能否描述在不同 MAD 隊列中，針對 ex vivo 刺激生物標誌物所觀察到的劑量反應？你們是否看到與降解相似的趨勢，在第 3 劑量層級達到飽和，還是不同生物標誌物之間的劑量反應範圍更廣？

Thank you. It is a great question. So to be honest, the reason why we're not sharing what we usually share, Terrence said it earlier, it's we want to retain some competitive advantage over fierce competition that we've seen increasing over the past few years. We feel with KT-621, we probably taught the market too much. And I should say the market, our competitors. So we're trying to be a bit more thoughtful.

謝謝。這是個很好的問題。坦白說，我們之所以沒有分享我們通常會分享的內容，Terence 先前也提到，是因為我們希望在過去幾年愈來愈激烈的競爭中保留一些競爭優勢。我們覺得在 KT-621 上，我們可能教了市場太多。我應該說，是教了市場——也就是我們的競爭對手——太多。所以我們正試著更審慎一些。

The reason why we're not sharing, let's call it the dose response on biomarkers, because I personally don't want to share what is the level of IRF5 degradation that leads to the optimal biomarker changes that we're seeing. So we have a really good understanding of what is the dose we need to use, and that dose selection has been based on what we think the level of degradations are, what we know the level of biomarker changes are. For now, we're going to leave it at that.

我們之所以不分享——姑且稱之為——生物標誌物的劑量反應，是因為我個人不想透露：達到我們所看到的最佳生物標誌物變化，需要多高程度的 IRF5 降解。我們對需要使用的劑量有非常清楚的理解，而這個劑量選擇是基於我們認為所需的降解程度，以及我們所了解的生物標誌物變化幅度。目前我們就先說到這裡。

Seamus Fernandez, Guggenheim.

Guggenheim 的 Seamus Fernandez。

Thanks for the questions, and congrats on the IRF5 data. The question that I have on IRF5 and maybe at some upcoming meetings, would be the potential links of the robust biomarker effects that you are seeing targeting IRF5, and some of the data that we are going to learn coming out of ACR, particularly as it relates to Sjogren's disease. Terrence, what would you be looking for from other disease states, given this sort of B-cell versus T-cell dynamic, CD40 ligand versus APRIL/BAFF, and the opportunity that you see in other disease states from some of those learnings?

謝謝讓我提問，也恭喜 IRF5 的數據。我關於 IRF5 的問題，以及可能在接下來一些會議上會討論的，是你們在靶向 IRF5 時看到的強勁生物標誌物效應，與我們將從 ACR 讀到的一些數據之間可能的連結，特別是與乾燥症（Sjogren's disease）相關的部分。Terence，鑑於這種 B 細胞對 T 細胞的動態、CD40 配體對 APRIL/BAFF 的差異，你會希望從其他疾病領域看到什麼訊號？以及你從這些學習中在其他疾病領域看到的機會是什麼？

Thanks, Seamus. I think Sjogren's is a really good indication for the target. There is a lot of unmet medical need in Sjogren's, as yet no approved advanced therapies. The biology is a good fit. We have got good genetic links between IRF5 and Sjogren's risk, and some of the pathways are clearly activated.

謝謝，Seamus。我認為乾燥症對這個靶點而言是一個非常好的適應症。乾燥症仍有大量未被滿足的醫療需求，而且目前尚無已核准的進階療法。其生物學機制非常契合。我們已經看到 IRF5 與乾燥症風險之間有良好的遺傳學連結，而且其中一些路徑顯然是被活化的。

So for example, we know Sjogren's to be a highly high interferon flavored disease, and we know that B-cell targeted therapies have shown efficacy, including one that is hopefully on the cusp of approval out of Novartis. So I think we are very encouraged that Sjogren's could be a good indication, and one we are carefully considering.

例如，我們知道乾燥症是一種高度偏向干擾素特徵的疾病；我們也知道以 B 細胞為靶點的療法已顯示療效，其中包括 Novartis 有一項產品希望正接近核准門檻。因此，我認為我們非常受到鼓舞，乾燥症可能是一個很好的適應症，而且我們正在審慎評估。

Cool. Next one. We will try and accelerate. I am being told we are being too slow, so let us see if we can accelerate.

很好。下一位。我們會試著加快。有人告訴我我們太慢了，所以看看能不能加速。

Tazeen Ahmad, Bank of America.

美國銀行的 Tazeen Ahmad。

Guys, good morning. Thanks for squeezing me in on a busy morning. A couple of questions. So for this big data update that you have upcoming, as it relates to safety, in particular for conjunctivitis, what if you don't see any instance of it? Because I think mechanistically it should be something to expect. But if at this juncture you're still not showing it, how should we be thinking about what that means? Could that differentiate from other treatments, for example?

各位，早安。謝謝在忙碌的早晨把我排進來。我有幾個問題。關於你們即將發布的這次大型數據更新，就安全性而言，特別是結膜炎，如果你們沒有看到任何病例，會怎麼解讀？因為我認為從機制上來看，這應該是可以預期的。但如果到目前為止仍未顯示，對於這代表什麼，我們應該如何思考？例如，這是否可能與其他治療形成差異化？

And then secondly, can you just give us a sense of what the top catalyst for 2027 in your mind would be as we think about next year and beyond? Thanks.

第二，你能否讓我們了解一下，就你看來 2027 年最重要的催化劑會是什麼，當我們思考明年及更長遠的時候？謝謝。

Thanks, Tazeen. I love that we haven't gone through the biggest catalyst, but we'll talk about the next one. So the next one, let's start with your second question. Obviously, we have big data with asthma, which will be a huge catalyst to initiate multiple Phase III programs in asthma and other respiratory indications. That, from where we stand today, is probably the biggest data set of 2027.

謝謝，Tazeen。我很喜歡我們還沒談到最大的催化劑，但我們先談下一個。那麼先從你的第二個問題開始。很明顯，我們在氣喘方面會有大型數據，這將是啟動多個氣喘及其他呼吸道適應症第三期計畫的重大催化劑。以我們今天的立場來看，這大概是 2027 年最大的數據集。

We have other things that we will be sharing more in the near future. But I think for now, I would say this year, next year was supposed to be both AD and asthma. AD has moved to this year. So this year is AD, next year asthma, and other things.

我們還有其他事項，近期會分享更多。但我想目前可以說的是，今年、原本明年應該會同時有 AD 和氣喘。AD 已經提前到今年。所以今年是 AD，明年是氣喘，還有其他事項。

On your question about conjunctivitis, the mechanisms that, as we've always said, biologically is coherent with IL-4 and 13 biology, so I've said it for a couple of years, we expect to see conjunctivitis. If we don't see it, obviously, we could talk about potential reasons for it. Again, as we're saying, we're closing up, and we'll have that conversation then, what we see or don't see.

關於你提到的結膜炎，正如我們一直說的，從生物學上與 IL-4 和 IL-13 的生物學機制是一致的，所以我已經說了好幾年，我們預期會看到結膜炎。如果我們沒有看到，當然我們可以討論可能的原因。同樣地，如我們所說，我們快要收尾了，到時候我們再就看到或沒看到的情況進一步討論。

Mayank Mamtani, B. Riley.

Mayank Mamtani，B. Riley。

Good morning. Mayank Mamtani (inaudible). Congrats on the quarter and the data. When you report for BROADEN2, will you break out AEs using the same conjunctivitis and keratitis clusters from DUPIXENT's label? This is just so investors can kind of compare KT-621 with like for like? And also, considering that NEMLUVIO is kind of seen as the itch benchmark, how do you think KT-621 compares to NEMLUVIO when it comes to itch? Thank you.

早安。Mayank Mamtani（聽不清）。恭喜本季表現與數據。你們在公布 BROADEN2 的結果時，會不會依照 DUPIXENT 標籤上的相同結膜炎與角膜炎分群，把不良事件（AE）拆分揭露？這主要是讓投資人能以同類對照的方式比較 KT-621？另外，考量到 NEMLUVIO 某種程度上被視為止癢的基準，你們認為在止癢方面 KT-621 與 NEMLUVIO 相比如何？謝謝。

I think for both questions, we will know soon. I do not know the data to know what is going to be put with what. But for sure, we will present the data in a way that, as I said earlier, everybody should be able to assess the efficacy and the safety of the drug, as well as whether there has to be any comparator, way of looking at also safety. We will do it in the way that is interpretable.

我想這兩個問題，我們很快就會知道答案。我目前沒有看到數據，因此不知道最後會把哪些項目放在一起呈現。但可以確定的是，我們會以一種方式呈現數據——如我先前所說——讓每個人都能評估藥物的療效與安全性，以及如果需要比較對照時，也能用適當方式來看安全性。我們會用可解讀的方式來呈現。

With NEMLUVIO, it is not a very active drug, but it does have an impact on itch by IL-31. We do have also a downstream effect on IL-31. I am not sure NEMLUVIO would be our competitor, let us put it this way. But we will see. The data will come out soon.

至於 NEMLUVIO，它不是一個非常強效的藥物，但確實透過 IL-31 對搔癢有影響。我們也對 IL-31 有下游效應。我不確定 NEMLUVIO 會是我們的競爭對手——就先這麼說。但我們會再看看。數據很快就會出來。

David Dai, UBS.

David Dai，UBS。

Great. Thanks for taking my questions, and congrats on the IRF5 data as well. So you noted a similar IRF5 reduction skin and blood. So I am just curious, how does the skin tissue data give you the confidence that the peripheral blood IRF5 degradation will be a reliable surrogate for target engagement in disease-relevant tissues in lupus and potentially IBD?

很好。謝謝回答我的問題，也恭喜 IRF5 的數據。你們提到皮膚與血液中的 IRF5 降幅相近。我想請教的是：皮膚組織的數據如何讓你們更有信心，認為周邊血液中的 IRF5 降解可以作為在紅斑性狼瘡、以及可能的 IBD 等疾病相關組織中，靶點結合（target engagement）的可靠替代指標？

Well, the reason why we always look for a non-central tissue, and skin really is the only thing we can look at in healthy volunteers, is to, again, de-risk the distribution and degradation profile of the drug beyond the central compartment. So I am a big believer through, again, 10 years of work here, that skin is actually the hardest tissue to degrade targets in. And that is why we always measure it, because we know that if you degrade in skin, you will probably going to be fine for the rest of the body. We also have preclinical data that shows that we can consistently degrade this target in all the relevant tissues. So this was just an additional validation of our profile.

嗯，我們之所以總是尋找一個非中樞的組織來觀察，而在健康受試者中皮膚幾乎是唯一能看的組織，是為了再次降低風險：確認藥物在中樞區室之外的分布與降解特性。以我在這裡十年的工作經驗，我非常相信皮膚其實是最難在其中降解靶點的組織。因此我們總是測量皮膚，因為我們知道如果能在皮膚中達到降解，那在身體其他部位大概率也會沒問題。我們也有臨床前數據顯示，我們能在所有相關組織中一致地降解這個靶點。所以這只是對我們特性的一個額外驗證。

Kripa Devarakonda, Truist Securities.

Kripa Devarakonda，Truist Securities。

Thank you so much for taking my question, and congratulations on the data. So you accelerated your atopic derm program because of the high level of demand that you saw. Are you seeing similar demand with asthma program as well, and has that led to increase in enrollment rates? And if not, why do you think there is a difference? And how predictive do you think the FEV1 endpoint is of eventual exacerbation benefit? Thank you.

非常感謝回答我的問題，也恭喜你們的數據。你們因為看到很高的需求而加速了異位性皮膚炎（AD）計畫。在氣喘計畫方面，你們也看到類似的需求嗎？這是否也帶動了入組速度的提升？如果沒有，你們認為差異的原因是什麼？另外，你們認為 FEV1 這個終點對於最終急性惡化（exacerbation）獲益的預測性有多高？謝謝。

I will take the first question so we can move more quickly. So we are seeing the same level of enthusiasm in AD as we have in asthma. The main difference is that in asthma, our inclusion/exclusion criteria are much more strict, and so the screen failure rate is much higher, and that is what determines how quickly or not quickly we are enrolling the study. Next question.

我先回答第一個問題，這樣我們可以快一點往下進行。我們在 AD 看到的熱度，與在氣喘看到的熱度是同等的。主要差異在於氣喘的納入／排除標準嚴格得多，因此篩選失敗率高很多，而這才是決定我們入組速度快或不快的因素。下一題。

Joseph Holden, Canaccord Genuity.

Joseph Holden，Canaccord Genuity。

Hey, everybody. This is Joe Holden on for Edward Nash. Thanks for taking my question. I just wanted to see if you could provide any guidance on expected R&D expenditure into 2027, given KT-579 Phase I in lupus and the expected Phase III program in AD. Thanks so much, and congrats on the data.

各位好。我是 Joe Holden，代 Edward Nash 提問。謝謝回答我的問題。我想請問，考量到 KT-579 在狼瘡的第一期試驗，以及 AD 預期的第三期計畫，你們是否能提供到 2027 年的研發支出（R&D）預期指引？非常感謝，也恭喜你們的數據。

I'll just be brief because we don't give explicit guidance. I would guide you to the runway, which is into 2029, and you should see, I would say, increases in operating expenses that are gradual but consistent to get you to the point that you're into 2029.

我簡短回答，因為我們不提供明確的指引。我會請你參考我們的資金可支撐期（runway），也就是到 2029 年。你應該會看到營運費用逐步但持續地增加，以讓你們看到我們能一路支撐到 2029 年。

Obviously, the expenses will accelerate as we start the Phase III study in AD, which we've guided to you by mid-2027. So we are also adding significantly to the team in preparation for those studies as well. So those will be the biggest factors in driving the cash year-over-year, I'd say, use of cash in 2027 and beyond.

很明顯地，當我們開始 AD 的第三期研究時，費用會加速上升；我們先前給的時程指引是 2027 年年中。同時，我們也正在為這些研究做準備而大幅擴編團隊。因此，這些將是推動現金逐年變化——我會說是 2027 年及之後的現金使用（use of cash）——的最大因素。

I believe this was the last question. I want to thank everybody for attending the call and also staying to 9:40 PM. Please take the opportunity to check out our website. The slides are there. We're very excited about where we're going with now two very exciting first-in-class programs in patients, and we're happy to follow up with any of you in the next couple of days, apparently, but not beyond. Thank you.

我相信這是最後一個問題。我要感謝各位參加本次電話會議，也感謝大家一路待到晚上 9:40。請把握機會到我們的網站看看。投影片都在那裡。我們對於目前在病人端推進的兩個非常令人振奮、同類首創（first-in-class）的計畫未來走向感到非常興奮；我們也很樂意在接下來幾天內與各位再做後續交流——顯然是接下來幾天，但不會更久。謝謝。