Kymera Therapeutics Inc (KYMR) 2025 Q3 法說會逐字稿

Good day, everyone. My name is Sophie, and I will be your conference operator today. At this time, I would like to welcome you to the Kymera Therapeutics third quarter 2025 results call. (Operator Instructions)

大家好。我叫索菲，今天我將擔任你們的會議接線生。在此，我謹代表 Kymera Therapeutics 宣布 2025 年第三季業績，歡迎各位參加電話會議。（操作說明）

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

此時，我想把電話交給投資人關係副總裁賈斯汀‧科尼格斯伯格。

Good morning, and welcome to Kymera's quarterly update. Joining me this morning are Nello Mainolfi, Founder, President and CEO; Jared Gollob, our Chief Medical Officer; and Bruce Jacobs, our Chief Financial Officer. Following our prepared remarks, we will open the call to questions from our publishing analysts. (Operator Instructions)

早安，歡迎閱讀 Kymera 的季度更新報告。今天早上和我一起出席的有：創辦人、總裁兼執行長 Nello Mainolfi；首席醫療官 Jared Gollob；以及財務長 Bruce Jacobs。在宣讀完準備好的演講稿後，我們將開放提問環節，接受出版分析師的提問。（操作說明）

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. 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.

在開始之前，我想提醒各位，今天的討論將包含有關我們未來預期、計劃和前景的前瞻性陳述。這些聲明存在風險和不確定性，可能導致實際結果與預期結果有重大差異。有關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-Q 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 would like to turn the call over to Nello.

接下來，我想把電話交給內洛。

Thank you, Justine, and thanks, everybody, for joining us this morning. Now in the final quarter of the year, as we reflect on 2025, I'm happy to say that our team has executed exceptionally well across all parts of our business, and we're very proud of all that we have accomplished this year. We're committed to building a global biopharmaceutical company and have established a strong foundation that will serve us well as we scale an organization, and continue to advance our industry-leading oral immunology pipeline.

謝謝賈斯汀，也謝謝大家今天早上收看我們的節目。現在已是今年最後一個季度，當我們展望 2025 年時，我很高興地說，我們的團隊在業務的各個方面都表現出色，我們為今年取得的所有成就感到非常自豪。我們致力於打造一家全球生物製藥公司，並已奠定了堅實的基礎，這將有利於我們擴大組織規模，並繼續推進我們行業領先的口服免疫學產品線。

As shown on this slide, I'd like to highlight a few of the key achievements this year that positions us well for important future milestones. In less than two years since unveiling our STAT6 program, we have demonstrated exceptional progress in advancing our first-in-class STAT6 degrader, KT-621. To recap, we completed our healthy volunteer study ahead of schedule with impressive results.

如本投影片所示，我想重點介紹今年取得的一些主要成就，這些成就使我們為未來重要的里程碑奠定了良好的基礎。自我們推出 STAT6 計畫以來不到兩年，我們在推進我們首款 STAT6 降解劑 KT-621 方面取得了卓越的進展。總而言之，我們提前完成了健康志願者研究，並且取得了令人印象深刻的結果。

We enrolled and completed dosing in the Phase Ib trial in AD patients with data coming in December. We initiated our first of two Phase IIb trial, BROADEN2 in AD, and we're on track to start the BREADTH Phase IIb asthma trial in the first quarter of 2026. We were also featuring two recent late-breaking presentations, which have helped us maintain high level of visibility with the medical and scientific communities where there continues to be strong interest in oral medicines with potential for biologics-like activity.

我們已經完成了 AD 患者的 Ib 期試驗的給藥，相關數據將於 12 月公佈。我們啟動了兩項 IIb 期試驗中的第一項，即治療 AD 的 BROADEN2 試驗，並且我們正按計劃於 2026 年第一季啟動治療氣喘的 BREADTH IIb 期試驗。我們也重點介紹了兩個最新的研究成果，這有助於我們在醫學界和科學界保持較高的知名度，因為醫學界和科學界對具有生物製劑樣活性的口服藥物仍然抱有濃厚的興趣。

Beyond STAT6, we unveiled our IRF5 program this spring and presented the robust preclinical data at the American College of Rheumatology Annual Meeting just recently. We've also completed the KT-579 IND-enabling studies and remain on track to initiate the first clinical trial in healthy volunteers early in 2026. In addition to IRF5, we continue to advance our earlier-stage undisclosed immunology pipeline, and our goal remains to address many of the major immunology indications with oral medicines.

除了 STAT6 之外，我們今年春天推出了 IRF5 項目，並在最近的美國風濕病學會年會上展示了可靠的臨床前數據。我們也完成了 KT-579 IND 申報研究，並預計在 2026 年初啟動對健康志願者的首次臨床試驗。除了 IRF5 之外，我們還在繼續推進我們早期未公開的免疫學研發管線，我們的目標仍然是用口服藥物解決許多主要的免疫學適應症。

Importantly, we believe the synergies across our pipeline provide multiple development opportunities for broad patient populations. We also entered into a new partnership with Gilead outside of immunology. Gilead is an ideal partner to drive forward our CDK2 oncology molecular glue program, which we believe has broad potential in breast cancer and other solid tumors.

重要的是，我們相信我們產品線中的協同效應將為廣大患者群體提供多種開發機會。我們也與吉利德公司在免疫學以外的領域建立了新的合作關係。吉利德是推進我們 CDK2 腫瘤分子膠計畫的理想合作夥伴，我們相信該計畫在乳癌和其他實體瘤方面具有廣泛的潛力。

In summary, it's been a very busy year and a successful one, and we look forward to finishing this year strong as we advance our pipeline towards more and more important milestones. More broadly, we built what I believe is one of the strongest oral immunology pipeline in the industry, where we're well positioned to deliver novel oral treatment options for patients with highly prevalent immune-inflammatory diseases.

總而言之，今年是非常忙碌且成功的一年，我們期待在今年年底前取得佳績，並推進我們的專案朝著越來越重要的里程碑邁進。更廣泛地說，我們建構了我認為是業內最強大的口服免疫學產品線之一，我們有能力為患有高發免疫發炎性疾病的患者提供新型口服治療方案。

Several years ago, we made a deliberate strategic shift to focus our R&D efforts toward the significant opportunities in immunology. And the reason is quite simple. Within immunology, many pathways have been validated with upstream biologics. Traditional small molecule inhibitors are not able to block the signaling pathways as effective as biologics, given the direct correlation between PK and PD and the need of high drug exposures.

幾年前，我們做出了一項有意識的策略調整，將研發工作重點放在免疫學領域的巨大機會上。原因很簡單。在免疫學領域，許多路徑已經透過上游生物製劑得到驗證。由於 PK 和 PD 之間存在直接關聯，且需要高藥物暴露量，因此傳統的小分子抑制劑無法像生物製劑那樣有效阻斷訊號路徑。

As a result, the power -- of the power of protein degradation, we can now selectively remove disease-causing proteins through a catalytic mechanism and can block pathways completely, which we've consistently demonstrated across all of our programs. This allows us for potential of oral drugs with biologics-like activity for the first time in our industry, and our first-in-class pipeline is a testament to this strategy.

因此，憑藉蛋白質降解的力量，我們現在可以透過催化機制選擇性地去除致病蛋白質，並完全阻斷相關通路，這一點我們在所有項目中都得到了充分的證明。這使我們在業界首次擁有了具有生物製劑活性的口服藥物的潛力，而我們首創的產品線也證明了這項策略的正確性。

If we look specifically at our STAT6 program, KT-621 exemplifies this approach. There is a tremendous opportunity for a convenient, safe and effective oral pill in highly prevalent TYPE 2 diseases like atopic dermatitis, asthma, COPD, EoE and others. Despite the large size of the patient population, the penetration of other systemic advanced therapies like injectable biologics is actually quite low.

如果我們具體看一下我們的 STAT6 程序，KT-621 就是這種方法的典型例子。對於像異位性皮膚炎、氣喘、慢性阻塞性肺病、嗜酸性粒細胞性食道炎等高發生率的 2 型疾病而言，便捷、安全、有效的口服藥片具有巨大的市場潛力。儘管患者群體規模龐大，但其他系統性先進療法（如注射生物製劑）的普及率實際上相當低。

This creates a significant opportunity for safe and effective oral medicines, which we believe would have potential to change the quality of life for many patients and family around the world. We have moved our STAT6 program at a rapid pace from preclinical to IND to initial clinical proof of concept and we're now embarked on our first global Phase IIb trials.

這為安全有效的口服藥物創造了重大機遇，我們相信這些藥物有可能改變世界各地許多患者及其家庭的生活品質。我們的 STAT6 計畫已迅速從臨床前階段推進到 IND 階段，再到初步臨床概念驗證階段，現在我們已啟動了第一個全球 IIb 期試驗。

In fact, we filed our IND in September 2024 and by the fourth quarter of 2025, we've already launched our first Phase IIb study. This progress is a strong testament to the speed, focus and executional excellence of our team in driving this program forward. Looking back at KT-621 Phase I healthy volunteer study, we demonstrated at very low doses, we can degrade STAT6 fully and block TH2 disease-relevant cytokines in healthy volunteers as effectively as upstream biologics and in a well-tolerated manner.

事實上，我們在 2024 年 9 月提交了 IND 申請，到 2025 年第四季度，我們已經啟動了第一個 IIb 期研究。這項進展有力地證明了我們團隊在推進該專案方面展現出的速度、專注度和執行力。回顧 KT-621 I 期健康志願者研究，我們證明，在非常低的劑量下，我們可以完全降解 STAT6 並阻斷健康志願者體內與 TH2 疾病相關的細胞因子，其效果與上游生物製劑一樣有效，且耐受性良好。

We're moving quickly towards completion of the BROADEN Phase Ib trial, which we initiated in the spring. To remind you, the trial was designed to achieve three important goals: To confirm robust degradation in blood and skin and understand the translation from healthy volunteers to AD patients. To allow us to refine the Phase IIb doses based on that translation, and to demonstrate that robust STAT6 degradation in AD patients can impact biomarkers and clinical endpoints similar to upstream biologics, specifically dupilumab.

我們正在快速推進 BROADEN Ib 期試驗的完成，該試驗於今年春季啟動。提醒一下，該試驗旨在實現三個重要目標：確認血液和皮膚中存在嚴重的降解，並了解從健康志願者到 AD 患者的轉化情況。為了使我們能夠根據該轉化結果改進 IIb 期劑量，並證明 AD 患者中 STAT6 的強效降解可以影響生物標記和臨床終點，類似於上游生物製劑，特別是 dupilumab。

Given that the trial is fully enrolled and we plan to share the data next month, I wanted to use this call one last time to reiterate expectations we're setting into the study across the four dimensions we're evaluating KT-621 on, degradation, safety, biomarker and clinical activity. With respect to STAT6 degradation, the goal is to translate in AD patients, the robust degradation of STAT6 in blood and skin that we have seen in the Phase I healthy volunteer study.

鑑於試驗已全部招募完畢，我們計劃下個月分享數據，我想利用這次電話會議最後一次重申我們對該研究的預期，該研究涵蓋了我們正在評估 KT-621 的四個方面：降解、安全性、生物標誌物和臨床活性。關於 STAT6 降解，我們的目標是將我們在 I 期健康志願者研究中觀察到的血液和皮膚中 STAT6 的顯著降解轉化到 AD 患者身上。

The safety profile is paramount, and we hope to continue to see a safety profile in line with what we've seen in both healthy volunteers as well as our preclinical studies. With respect to biomarkers, we plan to look in both blood and skin. In blood, we have highlighted TARC as the most relevant biomarker at the four-week time point.

安全性至關重要，我們希望繼續看到與我們在健康志願者和臨床前研究中看到的結果一致的安全性。關於生物標誌物，我們計劃同時檢測血液和皮膚。在血液中，我們發現 TARC 是四周時間點最相關的生物標記。

After achieving up to a median reduction of 37% of TARC in healthy volunteers and given that in atopic dermatitis patients generally have higher baseline TARC levels, our expectation is to show a meaningfully more robust TARC reduction. As a point of reference, in published dupilumab studies where baseline TARC levels were much higher than healthy volunteers, the reduction was in the range of 70% to 80% at four weeks, which is the bar we set for KT-621, assuming generally comparable baseline levels.

在健康志願者中實現了 TARC 平均降低 37% 之後，考慮到異位性皮膚炎患者的基線 TARC 水平通常較高，我們期望能夠顯示出更顯著的 TARC 降低。作為參考，在已發表的 dupilumab 研究中，基線 TARC 水平遠高於健康志願者，四周後 TARC 水平降低了 70% 至 80%，這是我們為 KT-621 設定的標準，假設基線水平大致相當。

In skin, we also plan to assess KT-621's impact on skin transcriptomics, which we have not assessed in the healthy volunteer studies. There, we anticipate changes in downstream genes that aligns with the expected biological effect of this pathway modulation. And finally, in terms of clinical endpoints, we went into the study with a robust body of evidence in all of our experiments demonstrating KT-621 blocks IL-4 and 13 as well as dupilumab, and this has resulted in comparable downstream pathway effects in both in vitro and in vivo studies.

在皮膚方面，我們也計劃評估 KT-621 對皮膚轉錄組學的影響，而我們在健康志願者研究中尚未評估過這一點。我們預期下游基因的變化與該路徑調控的預期生物效應一致。最後，就臨床終點而言，我們在所有實驗中都獲得了強有力的證據，證明 KT-621 可以像 dupilumab 一樣阻斷 IL-4 和 IL-13，這在體外和體內研究中都產生了類似的下游路徑效應。

As a result, we entered the BroADen study expecting clinical activity of KT-621 to be in the range of what dupi delivered at four-weeks in its published studies, including on both EASI score and itch with all the caveats of small ends and the lack of a placebo arm. I hope that this is helpful as we approach the data readout next month.

因此，當我們進入BroADen研究時，期望KT-621的臨床活性能達到dupi在其已發表的研究中四周時所達到的水平，包括EASI評分和瘙癢，但同時也要考慮到樣本量小和缺乏安慰劑組等所有註意事項。我希望這對我們下個月的數據公佈有所幫助。

Given that we have quite a bit of investor activities planned this month, please understand we will refer back to these key objectives and reserve any additional commentary for the final data presentation in December. So before I hand the call back to Jared, I wanted to take a moment to welcome Brian Adams, our new Chief Legal Officer, to Kymera.

鑑於我們本月計劃進行相當多的投資者活動，請理解我們將回顧這些關鍵目標，並將任何其他評論保留到 12 月的最終數據發布會上。所以在我把電話轉回給 Jared 之前，我想花一點時間歡迎 Brian Adams 加入 Kymera，他是我們新的首席法律官。

He's a seasoned life science executive with deep industry experience, bringing more than two decades of experience across legal and compliance, corporate development, strategic planning and governance. We're thrilled to have him join our team as we enter this next phase of growth and look forward to his contributions as we continue our efforts to building a fully integrated commercial stage company.

他是一位經驗豐富的生命科學產業主管，擁有深厚的產業經驗，在法律和合規、企業發展、策略規劃和治理方面擁有超過二十年的經驗。我們很高興他能加入我們的團隊，共同邁入下一個發展階段，並期待他能為我們繼續努力打造一家完全一體化的商業階段公司做出貢獻。

So to wrap up, as I said on the onset of the call, this has been a year of exceptionally strong execution, and we're well positioned to continue advancing all aspects of our pipeline as we head into 2026. I'm confident that through our expertise, scientific rigor, focused execution, we're building one of the most exciting immunology portfolios in this industry.

綜上所述，正如我在電話會議開始時所說，今年是執行力異常強勁的一年，我們已經做好充分準備，在邁向 2026 年之際，繼續推進我們所有業務流程的各個方面。我相信，憑藉我們的專業知識、科學嚴謹性和專注的執行力，我們正在打造業內最令人興奮的免疫學產品組合之一。

Let me pause here and turn the discussion over to Jared, who will provide us an update on the pipeline, including additional color on our newly initiated atopic dermatitis study. Jared?

我先暫停一下，把討論交給 Jared，他將為我們介紹研發管線的最新進展，包括我們新啟動的異位性皮膚炎研究的更多細節。賈里德？

Thanks, Nello. We have made significant progress with KT-621, our STAT6 degrader, and I'm happy to share the advancements we are making in the clinic with you this morning. As Nello described, we see this as a transformative opportunity to develop an oral therapy that delivers biologics-like efficacy without the limitations of injectables. KT-621 is the first and, we believe, only STAT6-directed oral medicine in the clinic.

謝謝你，內洛。我們在 STAT6 降解劑 KT-621 方面取得了重大進展，今天早上我很高興與大家分享我們在臨床上的進展。正如 Nello 所描述的那樣，我們認為這是一個變革性的機會，可以開發出一種口服療法，在不具備注射劑限制的前提下，提供類似生物製劑的療效。KT-621 是首個，我們相信也是目前唯一一個在臨床上使用的 STAT6 標靶口服藥物。

It has the potential to positively impact the more than 130 million people around the world living with Type 2 diseases, considering all the indications where dupilumab is approved today. Our first development indication is atopic dermatitis, or AD, a common but complex dermatologic condition with a significant unmet medical need.

考慮到度普利尤單抗目前獲準的所有適應症，它有可能對全球超過 1.3 億 2 型糖尿病患者產生積極影響。我們的第一個研發適應症是異位性皮膚炎（AD），這是一種常見但複雜的皮膚病，存在著巨大的未滿足醫療需求。

This is a chronic inflammatory skin disorder, more commonly referred to as eczema that manifests as inflamed, itchy and often painful patches on the skin. These lesions can appear anywhere on the body and range widely in severity from mild irritation to debilitating full body inflammation. One of the most burdensome aspects of this disease is the persistent itch.

這是一種慢性發炎性皮膚病，俗稱濕疹，表現為皮膚上出現發炎、搔癢且常疼痛的斑塊。這些病變可出現在身體的任何部位，嚴重程度也各不相同，從輕微刺激到嚴重的全身性發炎都有可能。這種疾病最令人痛苦的方面之一就是持續的搔癢。

It's not just a nuisance, it's a hallmark symptom that can severely impact quality of life by disrupting sleep, daily activities and overall well-being. While there are several treatments available today, they have limitations, forcing patients to make trade-offs. Antibody-based injected therapies like dupilumab have made a real difference for many patients, providing a well-tolerated and safe therapeutic option, but it's not a solution for everyone.

這不僅僅是令人煩惱的小事，而是一種標誌性症狀，它會擾亂睡眠、日常活動和整體健康，從而嚴重影響生活品質。雖然目前有多種治療方法，但它們都有局限性，迫使患者做出權衡。像度普利尤單抗這樣的抗體注射療法確實為許多患者帶來了改變，提供了一種耐受性良好且安全的治療選擇，但它並不是適合所有人的解決方案。

For starters, access can be very limited and is a challenge for many patients. For those who are prescribed these drugs, it can be inconvenient or a painful route of administration with compliance impacted by lack of tolerance of injection site reactions or phobia of needles. And there are also issues with cold storage requirements and immunogenicity risk.

首先，獲取途徑可能非常有限，這對許多患者來說是一個挑戰。對於服用這些藥物的人來說，給藥途徑可能很不方便或很痛苦，而且由於無法耐受注射部位反應或害怕針頭，依從性也會受到影響。此外，還存在冷藏要求和免疫原性風險的問題。

In fact, in an industry survey, 75% of patients taking biologics said that they would switch to orals with an equivalent profile. There are some oral options such as JAK inhibitors that offer an effective oral alternative. However, they come with significant safety concerns, including box warnings that limit their use, especially in long-term disease management.

事實上，在一項行業調查中，75% 的生物製劑使用者表示，他們會轉而使用具有相同療效的口服藥物。也有一些口服藥物可供選擇，例如 JAK 抑制劑，它們提供了一種有效的口服替代方案。然而，它們也存在一些重大的安全隱患，包括限制其使用的黑框警告，尤其是在長期疾病管理方面。

Given this important unmet need, coupled with the strong preclinical and clinical profile of KT-621 in healthy volunteers, we have developed an accelerated clinical development strategy, including conducting a small Phase Ib biomarker-focused trial in moderate to severe atopic dermatitis patients that we initiated earlier this year.

鑑於這一重要的未滿足需求，以及 KT-621 在健康志願者中表現出的強大的臨床前和臨床特徵，我們制定了一項加速臨床開發策略，包括開展一項針對中度至重度異位性皮膚炎患者的小型 Ib 期生物標誌物重點試驗，該試驗已於今年早些時候啟動。

The key aim of the 28-day BROADEN study is to show that robust STAT6 degradation in blood and skin lesions by KT-621 has a dupilumab-like effect on multiple Th2 biomarkers in the blood and skin. We will also assess KT-621's effect on clinical endpoints such as EASI and Pruritus NRS. The team has worked very hard to advance this program.

為期 28 天的 BROADEN 研究的主要目的是證明 KT-621 能有效降解血液和皮膚病變中的 STAT6，從而對血液和皮膚中的多種 Th2 生物標記產生類似 dupilumab 的作用。我們也將評估 KT-621 對 EASI 和搔癢 NRS 等臨床終點的影響。團隊為推進這個專案付出了巨大的努力。

And in line with expectations, we completed enrollment in the study last month and dosing is now complete. The final patients are completing follow-up, and we will collect and evaluate the rest of the data and report results in December. As we have said, this Phase Ib study was not gating to the start of the parallel Phase IIb dose range finding trials in AD and asthma, which in turn are designed to enable subsequent Phase III registrational studies across multiple indications.

正如預期的那樣，我們上個月完成了研究的招募工作，現在給藥也已完成。最後一批患者正在完成隨訪，我們將收集和評估剩餘數據，並在 12 月公佈結果。正如我們所說，這項 Ib 期研究並非啟動平行 IIb 期劑量範圍探索試驗（針對 AD 和氣喘）的先決條件，而這些試驗旨在為後續針對多種適應症的 III 期註冊研究奠定基礎。

This quarter, we initiated BROADEN2, our Phase IIb AD study, a global randomized, double-blind, placebo-controlled trial to evaluate KT-621 in approximately 200 patients with moderate to severe atopic dermatitis. This study is designed to evaluate three different doses of KT-621 over a 16-week treatment period compared to placebo.

本季度，我們啟動了 BROADEN2，即我們的 IIb 期 AD 研究，這是一項全球隨機、雙盲、安慰劑對照試驗，旨在評估 KT-621 對約 200 名中度至重度異位性皮膚炎患者的療效。本研究旨在評估三種不同劑量的 KT-621 在 16 週治療期內的療效，並與安慰劑進行比較。

Patients from the study have the opportunity to participate in a 52-week open label extension period after completion of the trial, which will contribute to building the long-term safety database we'll need to support eventual regulatory filings and is also an additional incentive for patient recruitment to the trial. Eligibility criteria to ensure we're recruiting patients with moderate to severe AD include an EASI score of at least 16, at least 10% of body surface area affected and an average weekly Pruritus NRS score of at least four.

研究中的患者有機會在試驗結束後參加為期 52 週的開放標籤擴展期，這將有助於建立我們最終向監管機構提交申請所需的長期安全性資料庫，同時也為招募患者參與試驗提供了額外的動力。為確保我們招募的是中度至重度 AD 患者，入選標準包括 EASI 評分至少為 16 分，至少 10% 的體表面積受到影響，以及平均每週搔癢 NRS 評分至少為 4 分。

While prior use of biologics is permitted if treatment was not discontinued for lack of response and following a study-defined washout period, we expect to enroll a substantial number of systemic treatment-naive patients given the attractiveness of the ease and convenience of a once-daily oral treatment option. The primary endpoint is the percent change from baseline in EASI score at week 16.

如果治療未因缺乏療效而停止，並且經過研究規定的洗脫期，則允許先前使用生物製劑。鑑於每日一次口服治療方案的便利性，我們預期會招募大量未接受全身性治療的患者。主要終點是第 16 週 EASI 評分相對於基線的百分比變化。

Secondary endpoints will evaluate a range of additional safety and efficacy measures, including but not limited to, the proportion of patients achieving EASI-50, EASI-75, a validated Investigator Global Assessment score of zero to one and at least a four-point improvement in Peak Pruritus NRS. We expect top line results from the Phase IIb study will be available by mid-2027.

次要終點將評估一系列額外的安全性和有效性指標，包括但不限於達到 EASI-50、EASI-75 的患者比例，經驗證的研究者總體評估評分為 0 到 1 分，以及峰值搔癢 NRS 至少改善 4 分。我們預計 IIb 期研究的主要結果將於 2027 年年中公佈。

In addition to atopic dermatitis, we plan to initiate the BREADTH Phase IIb study in asthma in the first quarter of 2026. We'll share more information on the trial design next year when we get closer to initiation. Beyond the STAT6 program, we have completed IND-enabling studies with KT-579, our IRF5 degrader, which we plan to advance into a Phase I healthy volunteer study early next year with data expected in 2026 as well.

除了異位性皮膚炎，我們還計劃在 2026 年第一季啟動 BREADTH IIb 期氣喘研究。明年接近啟動時，我們將分享更多關於試驗設計的資訊。除了 STAT6 計畫之外，我們還完成了 KT-579（我們的 IRF5 降解劑）的 IND 申報研究，我們計劃在明年初將其推進到 I 期健康志願者研究，預計在 2026 年獲得數據。

Last month, we shared incremental updates in two posters at the ACR meeting in Chicago. In several preclinical efficacy models of lupus and RA, KT-579 was generally more efficacious than clinically active or marketed small molecule inhibitors and injectable biologics, phenocopying IRF5 knockout studies.

上個月，我們在芝加哥舉行的 ACR 會議上以兩張海報的形式分享了最新的進展。在狼瘡和類風濕性關節炎的幾個臨床前療效模型中，KT-579 通常比臨床活性或上市的小分子抑制劑和注射生物製劑更有效，表型與 IRF5 敲除研究相似。

The compelling preclinical data we have generated showcase that targeting IRF5 can lead to correction of immune dysregulation across multiple disease pathologies while generally sparing normal cells. We continue to be excited about this opportunity and look forward to moving it into the clinic soon.

我們獲得的令人信服的臨床前數據表明，靶向 IRF5 可以糾正多種疾病病理中的免疫失調，同時通常不會損傷正常細胞。我們對此機會依然感到非常興奮，並期待著盡快將其引入臨床應用。

I'll pause here and turn the discussion to Bruce to review our third quarter financial results. Bruce?

我先暫停一下，把討論交給布魯斯，讓他回顧我們第三季的財務表現。布魯斯？

Thanks, Jared. As I walk through the third quarter results, please reference the tables found in today's press release and 10-Q, which was filed this morning. Revenue in the third quarter of 2025 was $2.8 million, all of which was attributable to our collaboration with Gilead. With respect to operating expenses, R&D for the quarter was $74.1 million.

謝謝你，賈里德。在介紹第三季業績時，請參考今天發布的新聞稿和今天早上提交的 10-Q 表格中的表格。2025 年第三季的營收為 280 萬美元，全部歸功於我們與吉利德的合作。就營運費用而言，本季的研發費用為 7,410 萬美元。

Of that, approximately $8.4 million represented noncash stock-based compensation. The adjusted cash R&D spend of $65.7 million, which excludes that stock-based comp, reflects a 7% decrease from the comparable amount in the second quarter of 2025. On the G&A side, our spending for the quarter was $17.3 million, of which $7.4 million was noncash stock-based comp.

其中約 840 萬美元為非現金股票補償。經調整的現金研發支出為 6,570 萬美元，不包括股票選擇權補償，比 2025 年第二季的相應金額減少了 7%。在一般及行政費用方面，本季我們的支出為 1,730 萬美元，其中 740 萬美元為非現金股票補償。

The adjusted cash G&A spend of $9.9 million, again, excluding that stock-based comp, reflects a 3% decrease from the comparable amount in the second quarter. And overall, adjusted operating expenses were down slightly from the prior sequential quarter. We ended September with a cash balance of $978.7 million, providing a cash runway into the second half of 2028.

調整後的現金一般及行政支出為 990 萬美元，同樣不包括股票選擇權補償，比第二季的相應金額減少了 3%。整體而言，經調整後的營運費用較上一季略有下降。截至 9 月底，我們的現金餘額為 9.787 億美元，足以支撐到 2028 年下半年。

This runway allows us to complete both KT-621 Phase IIb trials in AD and asthma, cover start-up costs in the initial Phase III activities for the STAT6 program, advance KT-579 through initial POC testing and advance our research pipeline as we scale and grow Kymera. Just a quick reminder, our runway collaborations, calculations, I should say, exclude any unearned milestones from our collaborations with Sanofi and Gilead.

這項資金使我們能夠完成 KT-621 在 AD 和氣喘的 IIb 期試驗，支付 STAT6 計畫初始 III 期活動的啟動成本，推進 KT-579 完成初步 POC 測試，並在 Kymera 規模化發展的同時推進我們的研究計畫。簡單提醒一下，我們的時裝秀合作項目（或應該說是計算項目）不包括我們與賽諾菲和吉利德合作中獲得的任何未實現的里程碑。

Regarding Sanofi, we expect that they will advance KT-485 into Phase I testing in 2026, which would trigger a development milestone payable to Kymera. As for the Gilead collaboration, upon exercising its option for a CDK2 glue, we are entitled to a milestone payment. As previously announced at the time of signing the Gilead collaboration agreement, we are eligible to receive a total of $85 million in upfront and option payments, with approximately half of this already received as the upfront payment in the last quarter. We look forward to the continued progress of both the IRAK4 and CDK2 partnered programs.

關於賽諾菲，我們預計他們將在 2026 年將 KT-485 推進到 I 期試驗階段，這將觸發向 Kymera 支付的開發里程碑款項。至於與吉利德的合作，在吉利德行使 CDK2 膠水的選擇權後，我們將有權獲得里程碑付款。正如先前在簽署吉利德合作協議時宣布的那樣，我們有資格獲得總計 8500 萬美元的預付款和選擇權付款，其中大約一半已在上個季度作為預付款收到。我們期待IRAK4和CDK2合作計畫能夠繼續取得進展。

With that, we'll pause here so we can convene in our main conference room and open the call for your questions. Thank you.

接下來，我們將暫停一下，前往主會議室集合，並開始接受大家的提問。謝謝。

(Operator Instructions) Geoffrey Meacham, Citi.

（操作員說明）Geoffrey Meacham，花旗銀行。

I just had a couple of questions. So the first one is, when you look at the upcoming data for KT-621, maybe just highlight, Nello, what are the key characteristics that could enable it to potentially show differential efficacy versus dupilumab at relatively early time points, I think that's probably one of the bigger points of uncertainty with investors.

我還有幾個問題。所以第一個問題是，當你查看 KT-621 即將公佈的數據時，Nello，或許可以重點指出，有哪些關鍵特徵可能使其在相對較早的時間點上顯示出與 dupilumab 不同的療效？我認為這可能是投資者最大的不確定因素之一。

And then the second question is, when you look at the two doses of the BroADen study, is the -- the three doses, is the expectation that the lower one maybe has a lower impact on degradation and therefore, is subtherapeutic? Or is it to test the upper end of where you'd like to be from a safety tolerability? I'm just trying to get a sense for the selection of the doses and kind of how you would frame that out for what would be the ideal kind of result.

第二個問題是，當你觀察BroADen研究的兩種劑量時，三種劑量是否意味著較低的劑量對降解的影響較小，因此可能不具有治療效果？或者，是為了測試安全容忍度的上限嗎？我只是想了解一下劑量選擇的問題，以及您會如何安排劑量才能達到理想的效果。

Great. Thanks, Geoff, for the question. So on the first one, let me just take a step back. So in all the work that we've done with our STAT6 program for multiple years now, we've been working on this program for a very long time, we were able to demonstrate, I think, convincingly in all the preclinical studies that when you degrade STAT6, you're able to block IL-4 and 13 signaling as well as an upstream biologics, whether it's an IL-4 receptor blocking drug like DUPIXENT or even an IL-13 drug.

偉大的。謝謝傑夫的提問。那麼，關於第一個問題，讓我先退一步說。因此，在我們多年來對 STAT6 計畫所做的所有工作中，我們已經在這個計畫上投入了很長時間，我認為，在所有臨床前研究中，我們已經令人信服地證明，當 STAT6 降解時，能夠阻斷 IL-4 和 IL-13 信號傳導，以及上游生物製劑，無論是像 DUPIXENT 這樣的 IL-4 受體阻斷藥物甚至是藥物。

So generally, we're actually the only oral drug that is able to block IL-4 and 13 as well as upstream biologics. In all the studies that we've run, again, preclinically, as I said a few minutes ago, both in vitro and in vivo, we've seen comparable activity. And I think this speaks to the biology of the pathway. Whether you block the receptor or you block the specific transcription factor for the receptor, you see the same biology.

所以總的來說，我們實際上是唯一能夠阻斷 IL-4 和 IL-13 以及上游生物製劑的口服藥物。在我們進行的所有研究中，正如我幾分鐘前所說，無論是在臨床前、體外或體內，我們都觀察到了類似的活性。我認為這體現了該通路生物學的原理。無論你阻斷受體或阻斷受體的特定轉錄因子，你都會觀察到相同的生物學現象。

So the reason why we say the opportunity here is to have dupilumab in a pill-like profile is not because it's actually what we hope to see. Obviously, we hope to see that. But it's because it's the activity, the biology that we've seen so far. So as a data-driven company as we are, we're reporting the observation of so far, we've seen dupi-like activity.

所以，我們說這裡的機會是讓度普利尤單抗以藥丸的形式出現，並不是因為我們真的希望看到這種情況。當然，我們希望看到這種情況。但這是因為我們目前為止所看到的活動和生物學現象。作為一家數據驅動型公司，我們在此報告目前為止的觀察結果，我們已經看到了類似 dupi 的活動。

In our Phase I healthy volunteer study, where we measured, as you remember, biomarkers in blood in healthy volunteers, we were able to show also in those biomarkers that we were generally comparable, some would say even numerically superior to dupilumab. So for me, it's really hard to say KT-621 is going to be better than dupilumab or worse than dupilumab.

在我們的 I 期健康志願者研究中，我們測量了健康志願者血液中的生物標誌物（如您所知），我們也能夠在這些生物標誌物方面證明，我們總體上與 dupilumab 相當，有些人甚至認為我們在數值上優於 dupilumab。所以對我來說，很難說 KT-621 會比 dupilumab 更好還是更差。

All we've seen so far that we're generally blocking the pathway the same way. Hence, that's where the expectations are set. Now as a data-driven drug development company with, I think, astute people in the company, we're very keen to see how the two profiles will evolve and where they would differentiate. We're talking about obviously an injectable biologic versus a small molecule degrader.

到目前為止，我們看到的都是，我們基本上是用同樣的方法阻斷這條路徑。因此，這就是期望的來源。作為一家以數據驅動的藥物研發公司，我認為公司裡有很多精明的人，我們非常渴望看到這兩種模式將如何發展，以及它們將在哪些方面有所不同。顯然，我們討論的是注射型生物製劑與小分子降解劑之間的差異。

So you will see probably small differences or larger difference here and there. But our priority is very difficult for us to like set the expectation one way or the other. I would be probably the happiest CEO in the world if we're able to deliver a dupi-like profile. Going to your second question, I think I understand what you're saying, what you were asking, but maybe not.

所以你可能會看到一些細微的差別，也可能會看到一些較大的差別。但是，我們的優先事項很難讓我們明確預期。如果能夠打造出類似 Dupi 的形象，我可能會成為世界上最幸福的 CEO。關於你的第二個問題，我想我明白你的意思，你問的是什麼，但也許我並沒有完全理解。

So you can correct me if I got it wrong. So maybe the way that I'm going to answer your question is, so we selected two doses for the Phase Ib study because we wanted to really understand well what was the translation of healthy volunteer degradation profile into patients to then have a high level of confidence in selecting the three doses for the Phase IIb.

如果我說錯了，請糾正我。所以，我回答你問題的方式可能是，我們為 Ib 期研究選擇了兩種劑量，因為我們想真正了解健康志願者的降解情況如何轉化為患者的療效，從而更有信心為 IIb 期研究選擇三種劑量。

The only thing I'm going to say right now is that the two doses of the Phase Ib as well as the three doses for the Phase IIb are all within the doses that we studied in the healthy volunteer study. And generally, our approach for the Phase IIb is to evaluate a range in which we see maximal pharmacology and at the top dose or some would call it super pharmacology and then in the bottom dose, a dose that reaches less than the optimal pharmacology and then obviously, a dose in between. So that's the general philosophy without going into details.

我現在唯一要說的是，Ib 期的兩個劑量以及 IIb 期的三個劑量都在我們在健康志願者研究中研究的劑量範圍內。一般來說，我們在 IIb 期試驗中採用的方法是評估一個劑量範圍，在這個範圍內，我們可以看到最大的藥理作用，最高劑量（有些人稱之為超級藥理作用），然後是最低劑量（低於最佳藥理作用的劑量），然後顯然是介於兩者之間的劑量。以上就是大致的理念，這裡就不贅述細節了。

Marc Frahm, TD Cowen.

馬克·弗拉姆，TD Cowen。

Maybe just on the Phase Ib. Nello, in your comments, you mentioned the kind of target of 70% to 80% TARC reduction, but with that caveat of assuming similar baseline characteristics. Now that you've enrolled the patients with a group of 10 per dose level, there's always some chance that you end up with a little bit of a skewed population relative to the comparators.

或許只是在 Ib 期。Nello，你在評論中提到了 TARC 減少 70% 到 80% 的目標，但前提是假設基線特徵相似。既然你已經招募了每劑量組 10 名患者，那麼你最終得到的群體與對照組相比總會有一些偏差。

Just anything you'd highlight there based on the patients that have actually enrolled that might be a little bit different than the historical DUPIXENT comparators? And then I'll probably have a follow-up.

根據實際入組的患者情況，您認為有哪些方面可能與以往的DUPIXENT對照組略有不同？然後我可能還會有後續報道。

Yes. No, Marc, thanks for that. That's a great question. So let me clarify. So there is two aspects of this trial. One is the baseline, let's say, the baseline EASI of patients. And then I think what I was referring to back a few minutes ago was the baseline TARC levels. So I think if you study dupilumab TARC reduction over both the AD study, but actually if you study over all the other studies that were run in other indications, whether it's chronic rhinositis, asthma, EoE, et cetera, you see that there is a clear relationship between baseline level of TARC in patients and reduction of TARC.

是的。不，馬克，謝謝你。這是一個很好的問題。讓我解釋一下。所以這次審判有兩面。一個是基線，比如說，患者的基線 EASI 評分。然後，我想我幾分鐘前提到的應該是基線 TARC 水平。所以我認為，如果你研究度普利尤單抗在 AD 研究中的 TARC 減少情況，實際上，如果你研究在其他適應症中進行的所有其他研究，無論是慢性鼻炎、氣喘、嗜酸性粒細胞性食道炎等等，你就會發現患者 TARC 的基線水平與 TARC 的減少之間存在明顯的關係。

And so that's what I was referring to when I'm talking about baseline level of TARC, baseline levels, I was referring to the TARC baseline levels. And obviously, I'm not going to comment about what the baselines of the study -- of our study are, but obviously, we'll share the data when the time is right. Then there is another element, which I want to clarify, then there is the EASI baseline levels.

所以，當我談到 TARC 的基線水平時，我指的就是 TARC 的基線水平。顯然，我不會評論這項研究的基線是什麼——或者說，我們這項研究的基線是什麼，但顯然，時機成熟時，我們會分享這些數據。還有另一個因素，我想澄清一下，那就是 EASI 基線水平。

And I think what we've said in the past, as we've seen generally when dupilumab was developed, it was the first systemic drug for atopic dermatitis. And so if you look at those studies, the baseline EASI were in the high-20s, low-30s. If you look at studies from all companies in the past five-years or so, you see that the baseline EASI has shifted down in the, let's call it, mid-20s.

我認為我們過去說過的話，正如我們通常所看到的，當度普利尤單抗被研發出來時，它是第一種用於治療異位性皮膚炎的全身性藥物。因此，如果你查看這些研究，你會發現基線 EASI 值在 20 多到 30 左右。如果你查看過去五年左右所有公司的研究，你會發現 EASI 基準值已經下降到，我們姑且稱之為 20 多。

And that's mostly because the patient population that we're accessing to these trials in the sites that most companies go to, obviously has changed given that these sites in these countries and these regions have access to dupilumab. So generally, the most severe patients are on systemic biologics. Some are not. But generally, the mean number has come down a bit, and that's what we're observing.

這主要是因為我們在大多數公司進行的試驗中接觸到的患者群體顯然發生了變化，因為這些國家和地區的試驗點可以獲得度普利尤單抗。因此，一般來說，病情最嚴重的患者會接受全身性生物製劑治療。有些則不是。但總體而言，平均值有所下降，這也是我們所觀察到的。

And so that's kind of another element to the whole study and the outcome of the study. But I just want to separate the point that I was making before where on TARC baseline levels, not necessarily on the EASI baseline level.

所以，這算是整個研究及其結果的另一個組成部分。但我只想澄清一下我之前提出的觀點，即 TARC 基線水平，不一定是 EASI 基線水平。

Okay. And should we expect that same trend kind of to lower EASI scores, it should apply here. But does that have an impact on TARC level -- likely TARC levels as well, do you think?

好的。如果我們預期同樣的趨勢會導致 EASI 分數下降，那麼這種情況也應該適用於此。但這會對 TARC 水準產生影響嗎？你認為可能會對 TARC 水平產生影響嗎？

I think that's something that we'll discuss when we release the data. I think we understand really well, obviously, the level of TARC at baseline in healthy volunteers, right, where we've seen reduction in the mid to high 30s in many patients on our studies in the healthy volunteers. And we show that also dupilumab when baseline levels were in the range of healthy volunteer at similar reduction.

我認為這是我們在發布數據時會討論的問題。我認為我們顯然對健康志願者的基線 TARC 水平非常了解，對吧？在我們的研究中，許多健康志願者的 TARC 水平在 30 多度到 35 度之間有所下降。我們也證明，當基線水準在健康志願者的範圍內時，度普利尤單抗也能達到類似的降低效果。

I think, again, as I've said, if you look at other studies, dupilumab level, you see a correlation between baseline level and percent reduction of TARC. And so I think that's the observation that we're sharing looking at those studies. I don't want to preview our study because -- as I mentioned a few minutes ago, I don't think it would be productive to preview some data here versus December.

我認為，正如我之前所說，如果你看看其他研究，dupilumab 水平，你會發現基線水平與 TARC 減少百分比之間存在相關性。所以我認為，這就是我們透過這些研究得出的共同結論。我不想提前透露我們的研究結果，因為——正如我幾分鐘前提到的，我認為在這裡提前透露一些數據與 12 月的數據相比並沒有什麼意義。

Brian Abrahams, RBC.

Brian Abrahams，RBC。

Congratulations on all the progress. I'm wondering how are you guys thinking now that it's been initiated about the powering overall for the Phase IIb AD study, just considering the population you expect to enroll, the mix of biologics and experienced and naive patients and your expectations for effect size? And then just as a follow-up, it sounds like you're thinking about maybe different doses for asthma and respiratory diseases versus dermatologic diseases. I was wondering if you could elaborate a little bit more about what you think are the important considerations around that.

祝賀你們取得的所有進展。我想知道，既然 IIb 期 AD 研究已經啟動，你們是如何考慮整體的樣本量問題的？考慮到你們預期招募的族群、生物製劑的使用情況以及先前接受過治療和未接受過治療的患者的組合，以及你們對療效的預期？另外，我想補充一點，聽起來您似乎在考慮氣喘和呼吸系統疾病與皮膚病的劑量是否不同。我想請您再詳細闡述一下，您認為這方面有哪些重要的考量。

Jared, do you want to take that?

賈里德，你想拿嗎？

Sure. Yes. I mean we can't give specifics around powering for the Phase IIb. What we can say is -- and we have stated that the end for that study is going to be approximately 200 with there being four arms, three drug, one placebo. So we look very carefully at what the expectations are, what the patterns have been in the past with regard to EASI responses, NRS Pruritus responses, et cetera.

當然。是的。我的意思是，我們無法提供關於二期工程b階段供電的具體資訊。我們可以說的是——而且我們已經說過，這項研究最終的樣本量將達到約 200 人，分為四個組，三個藥物組，一個安慰劑組。因此，我們會非常仔細地研究預期結果，以及過去在 EASI 反應、NRS 搔癢反應等方面的模式。

And that's all gone into calculating what sort of ends we need to make sure that the study is adequately powered. So we've been very careful in the design of the study to make sure that we are powered to show the desired effect relative to placebo. Another important aim of the study, obviously, is to be able to look across the three different doses and to see if we can discern any sort of a dose response. So the study is powered to enable us to do all of those things.

所有這些都被納入了計算，以確定我們需要什麼樣的結果，以確保研究具有足夠的統計效力。因此，我們在研究設計上非常謹慎，以確保我們有足夠的統計效力來顯示相對於安慰劑的預期效果。顯然，這項研究的另一個重要目的是能夠檢視三種不同劑量，看看我們是否能辨別出任何劑量反應。因此，這項研究旨在使我們能夠完成所有這些事情。

And the doses between AD.

以及 AD 之間的劑量。

The doses between AD. So right now, so I think what we've guided is that our plan is to -- in the Phase IIb to use the same doses for both AD and asthma across both Phase IIb studies.

AD 與氣喘之間的劑量。所以目前，我認為我們指導的計劃是——在 IIb 期研究中，對 AD 和氣喘使用相同的劑量。

And then maybe just to add, then the Phase III doses or dose that will be used for AD Phase III and asthma Phase II might be different based on the dose ranging. To be honest, our expectation is that it will not be different, and we will use one dose for all studies. But that's why we're running different dose ranging in different diseases with different target tissues so that we actually understand what the right dose will be.

另外，可能需要補充一點，根據劑量範圍的不同，用於 AD III 期和氣喘 II 期的 III 期劑量或劑量可能會有所不同。坦白說，我們預計結果不會有任何不同，所有研究都將使用相同劑量。但正因如此，我們才要針對不同的疾病和不同的目標組織進行不同的劑量範圍試驗，以便真正了解正確的劑量是多少。

Brian Cheng, JPMorgan.

Brian Cheng，摩根大通。

Some of the color you're providing here for the December readout is pretty much in line with what you already messaged. But I'm just curious, just given the gap between the time you selected your three doses for the Phase IIb and when Phase Ib finished enrollment around early October, what could be additive to what you already know in the December readout? Or do you think the data is most likely going to be in line with the data that you had already seen when you picked the three doses? And I have a follow-up.

您在這裡提供的關於 12 月報告的一些資訊與您之前傳達的訊息基本一致。但我很好奇，考慮到您為 IIb 期選擇三種劑量的時間與 Ib 期在 10 月初完成招募的時間之間存在時間間隔，在 12 月份的公佈結果中，除了您已知的信息之外，還有哪些信息可以補充呢？或者您認為這些數據最有可能與您在選擇三種劑量時已經看到的數據一致嗎？我還有一個後續問題。

Well, so I'd like to maybe clarify. I think what we said before is the same thing that we've been saying for 9- or 10-months. But that's maybe just my small additional color. So I just want to clarify, when we selected the doses for the Phase IIb was actually a few months before October, right? We started the study recently in the Phase IIb study.

嗯，我想澄清一下。我認為我們之前說的話，和過去九到十個月以來我們一直在說的話是一樣的。但這可能只是我身上那一點額外的色彩而已。所以我想澄清一下，我們選擇 IIb 期試驗劑量實際上是在 10 月之前的幾個月，對嗎？我們最近啟動了 IIb 期研究。

But in order to submit the protocol and do start-up activities, you had to actually have chosen the doses much earlier. And I think I've said this many times, I believe, publicly that when we selected the doses, we had visibility into partial data for both doses for both the first dose in the Ib and less but still some data from the second dose in the Phase Ib.

但要提交方案並進行啟動活動，實際上必須更早選擇劑量。我想我曾多次公開說過，當我們選擇劑量時，我們對 Ib 期試驗中的第一個劑量和第二個劑量都有部分數據了解，雖然第二個劑量的數據較少，但仍然有一些數據。

And again, we did not have access to the totality of the data, but we -- because we're focused mostly on the translation of degradation and obviously, safety, which is understood, we had enough information to make the right selection for the Phase IIb doses.

再次強調，我們無法獲得全部數據，但是——因為我們主要關注降解的轉化以及安全性（這是眾所周知的），我們有足夠的資訊來為 IIb 期劑量做出正確的選擇。

In the prepared remarks, in the BROADEN2 trial design, I think you mentioned that you expect a substantial number of patients to be naive to advanced therapy. So I'm just curious what's the driver behind that? And how should we take that into account as investors think about comparing the BROADEN2 future data against other benchmarks?

在準備好的演講稿中，關於 BROADEN2 試驗設計，我認為您提到您預計會有相當數量的患者對先進療法不熟悉。所以我很好奇這背後的驅動因素是什麼？那麼，當投資人考慮將 BROADEN2 未來數據與其他基準進行比較時，我們應該如何考慮這一點？

Yes. So I'll start, Jared, please jump in. So the reason why we believe that will be the case is multifold. But I will start with -- we believe KT-621 and our STAT6 program is -- the whole value proposition is to expand patient access to advanced systemic therapy. The penetration of these advanced biologics in moderate to severe patients is less than 10%.

是的。那我先來，賈里德，你也快點加入。我們認為這種情況會發生的原因有很多。但我想先說——我們相信 KT-621 和我們的 STAT6 計畫——其全部價值主張是擴大患者獲得先進系統療法的機會。這些先進生物製劑在中重度患者的滲透率不到 10%。

Some companies claim it to be more than 10%. Maybe we align on, let's say, 10%. So we don't have to argue with other companies. So the majority of the patients do not have access to advanced systemic therapy. That's where we are coming from. Then another part, which we've discussed as well is patients that have gone on to systemic therapies that have failed systemic -- pathway systemic therapy, IL-4, IL-13, JAKs will not come on to our study.

有些公司聲稱這個數字超過 10%。或許我們可以達成共識，比如說，10%。這樣我們就不用跟其他公司爭論了。因此，大多數患者無法獲得先進的全身性治療。這就是我們的出發點。還有一部分，我們也討論過，那就是接受全身治療但全身治療失敗的患者——通路全身治療、IL-4、IL-13、JAKs 將不會參加我們的研究。

So they will have to have responded to those therapy, then decided not to continue and then jump on our 621 study. So for those two main reasons, and also, I would say, for the experience that we had in the Phase Ib, we believe the majority of patients will be naive. And I would also add, hopefully, I will not be proven wrong, that we don't believe there will be issue out there finding naive patients because those patients are in dire need of an active systemic oral safe therapy.

所以他們必須先對這些療法產生反應，然後決定不再繼續治療，然後加入我們的 621 研究。因此，基於這兩個主要原因，而且，我認為，根據我們在 Ib 期試驗中獲得的經驗，我們相信大多數患者都是初治患者。我還要補充一點，希望我的判斷不會出錯，我們認為在尋找初次接受治療的患者方面不會存在問題，因為這些患者迫切需要一種積極的全身性口服安全療法。

The only thing I would add would be just as a reminder that this is a global study. And so we're running the study in North America, Europe, Australia and Japan, with the majority of sites actually being ex US. So ex US, in particular, there are going to be a number of patients who don't have access to IIb. And so that's another reason why we expect a substantial proportion of patients on IIb to be dupi-naive.

我唯一要補充的是，提醒大家這是一項全球性研究。因此，我們正在北美、歐洲、澳洲和日本進行這項研究，其中大部分地點實際上都位於美國以外。因此，尤其是在美國以外，將會有許多患者無法獲得 IIb 類藥物。所以這也是我們預期 IIb 期患者中相當一部分人之前未接受過杜匹洛韋治療的另一個原因。

Mayank Mamtani, B. Riley.

Mayank Mamtani，B. Riley。

Congrats on the progress. Could you give us a little bit more detail on the asthma BREADTH? I think you're calling it trial considerations. And in terms of if you're looking at a 12- or 24-week FEV1 endpoint or a longer duration exacerbation, you could be looking at both, but just wonder in terms of which is your primary endpoint?

恭喜你取得進展。能詳細介紹一下氣喘的BREATH嗎？我想你指的是試驗方面的考慮因素。至於你是關注 12 週或 24 週的 FEV1 終點，還是專注於更長的病情加重，你可能兩者都在關注，但我想知道哪個才是你的主要終點？

And then also curious about the kind of patients you're thinking to enroll there and the allowance of background therapies. And obviously, the question is around timelines for data readout for the asthma and atopic derm. Will they be stacked together in 2027? And then I have a quick follow-up.

此外，我還想了解您打算招募哪些類型的患者，以及是否允許進行背景治療。顯然，問題在於氣喘和異位性皮膚炎數據讀取的時間表。到 2027 年它們會堆疊在一起嗎？然後我還有一個簡短的後續問題。

Yes. No, thank you for the question. Unfortunately, as we've said, we're going to talk more about the Phase IIb BREADTH study when we're in the start-up mode, when we're close to dosing our first patient. So give us a few more weeks, and then we'll provide all the color that you're asking for. So why don't you ask the follow-up so that at least we have a question.

是的。不，謝謝你的提問。不幸的是，正如我們所說，我們將在啟動階段，也就是接近給第一位患者用藥時，再來詳細討論 IIb 期 BREADTH 研究。所以再給我們幾週時間，我們就會提供您想要的所有顏色。那你為什麼不問個後續問題呢？這樣至少我們還有問題可以問。

And maybe just to talk a little bit beyond 621 and about your pipeline beyond that. Just on the 579, could you maybe give us some color on what the initial targeted indications would be just given the broader inflammation cascade that you're targeting there?

或許還可以稍微聊聊 621 以外的內容，以及你們後續的研發計畫。關於 579，鑑於你們的目標是更廣泛的發炎級聯反應，能否簡單介紹一下最初的目標適應症是什麼？

Yes. Maybe just high level. So thanks for asking about IRF5. This is a program that I think has mostly been unparalleled in the industry where you have highly validated genetically validated transcription factor that has been, I think, the object of many drug development efforts in the biopharma industry for a decade or so, but has maintained -- has remained elusive where Kymera has that solution using targeted protein degradation.

是的。或許只是水平比較高。感謝您詢問有關IRF5的問題。我認為，這個計畫在業界幾乎是獨一無二的，它擁有經過高度驗證的基因驗證的轉錄因子，我認為，在過去十年左右的時間裡，生物製藥行業一直在努力開發這種轉錄因子，但它一直難以捉摸，而 Kymera 利用靶向蛋白質降解技術解決了這個問題。

So if you look at human genetics, the top four places where one would go directly are generally lupus, SLE and other subcategories of this disease, some other interferon-related pathologies, RA, IBD. So those are where human genetics point to our preclinical data point to. I think when we're closer to the Phase I study, we'll be able to share more about our development plans. Jared, anything you want to add?

因此，如果你研究人類遺傳學，最先想到的四個領域通常是狼瘡、系統性紅斑狼瘡 (SLE) 和這種疾病的其他亞型、其他一些幹擾素相關病理、類風濕性關節炎 (RA)、發炎性腸道疾病 (IBD)。所以，人類遺傳學和我們的臨床前數據都指向了這些方向。我認為，當我們接近第一階段研究時，我們將能夠分享更多關於我們研發計劃的資訊。賈里德，你還有什麼要補充的嗎？

No.

不。

Sudan Loganathan, Stephens.

蘇丹·洛加納坦，史蒂芬斯。

Looking back at the healthy volunteer data for KT-621, I noticed that the median percent change in the serum TARC and the IgE were similar to that of dupilumab healthy volunteer outcomes for those same levels when on treatment. There was a noticeable rebound higher, obviously, whenever these -- on these levels when the patients were off of KT-621, as you showed.

回顧 KT-621 的健康志願者數據，我注意到血清 TARC 和 IgE 的中位數百分比變化與接受 dupilumab 治療的健康志願者在相同水平下的結果相似。正如你所展示的，當患者停止服用 KT-621 時，這些水平明顯出現了更高的反彈。

My question is how important is the durability for the AD and asthma patients' quality of life outcomes? And will KT-621's daily oral dose -- dosing regimen make up for any deficiencies and maybe durability outcomes that it could have compared to dupi? And does dupilumab mode of administration and systemic effects just inherently lend to a more durable outcome?

我的問題是，對於 AD 和氣喘患者的生活品質結果而言，耐久性有多重要？KT-621 的每日口服劑量方案能否彌補其與 dupi 相比可能存在的任何不足，以及其在持久性方面可能存在的缺陷？度普利尤單抗的給藥方式和全身性作用本身就更容易帶來更持久的療效？

It's a great question. So I mean, I will answer part of it, and then I'll let Jared also speak to part of all of it. So the beauty about our drug is that it's a once-a-day oral that allows you to block IL-4 and 13 continuously at steady state. The beauty of our drug is that you can stop and start when you want, if needed without long washout period.

這是一個很好的問題。所以我的意思是，我會回答一部分，然後我會讓 Jared 也談談其中的一部分。因此，我們這種藥物的優點在於，它是一種每日一次的口服藥物，可以讓你持續穩定地阻斷 IL-4 和 IL-13。我們這種藥物的優點在於，您可以根據需要隨時停止和開始使用，而無需長時間的停藥期。

The beauty about a once-a-day oral drug is that as long as you continue to take the drug once a day orally, you will see profound effects or at least the effect that the biology -- the underlying biology will have. I don't believe that if these drugs are taken as prescribed, obviously, we're still very early to compare to dupilumab, that you have more or less duration of the effect.

每日一次口服藥物的好處在於，只要你堅持每天口服一次，你就會看到顯著的效果，或至少會看到生物學——潛在的生物學——所產生的效果。我不認為如果按照處方服用這些藥物，（顯然，現在就將其與度普利尤單抗進行比較還為時過早）會比預期的效果持續時間更長或更短。

The only main difference that I will say between an injectable biologic and a once-a-day oral degrader, not small molecule inhibitor, is that the once-a-day oral degraders allow you to have steady-state complete pathway blockade. I believe with dupilumab, a couple of days before your next dose, you're not maximizing the pharmacology as much.

注射型生物製劑和每日一次口服降解劑（而非小分子抑制劑）之間唯一的主要區別在於，每日一次口服降解劑可以實現穩態完全阻斷路徑。我認為，對於度普利尤單抗，在下次給藥前幾天服用，並不能最大限度地發揮其藥理作用。

So you might actually have less pathway blockade, continuous pathway blockade than a once-a-day oral degrader. Now what would that mean from a therapeutic perspective, obviously, well, time will tell and studies will tell.

所以，你實際上可能會減少通路阻塞，持續的通路阻塞，而不是像每天服用一次口服降解劑那樣。那麼從治療角度來看，這又意味著什麼呢？顯然，時間會證明一切，研究也會給出答案。

Yes. And maybe coming back to your comment around the Phase Ia, just to clarify, patients who were on the MAD portion were getting 14 daily doses. And so when we look at the effect on TARC and Eotaxin-3 in particular, that suppression or inhibition was seen throughout the entire 14-day dosing period.

是的。回到您關於 Ia 期的評論，為了澄清一下，接受 MAD 治療的患者每天接受 14 次劑量。因此，當我們觀察 TARC 和 Eotaxin-3 的影響時，會發現在整個 14 天的給藥期間都觀察到了這種抑製作用。

In fact, if you looked at day-7 versus day-14, levels were actually continuing to go down TARC and Eotaxin-3 between day-7 and 14, which suggested that if we had continued dosing beyond day-14, we might have seen more suppression. So there was no recovery of TARC and Eotaxin-3 until dosing was stopped after day 14 and then you see a gradual recovery.

事實上，如果你比較第 7 天和第 14 天，你會發現 TARC 和 Eotaxin-3 的水平在第 7 天到第 14 天之間持續下降，這表明如果我們在第 14 天之後繼續給藥，我們可能會看到更多的抑製作用。因此，直到第 14 天停止給藥後，TARC 和 Eotaxin-3 才開始恢復，然後才逐漸恢復。

So that just speaks to what Nello was referring to in terms of the durability of the effect as evidenced by even in healthy volunteers, a durable effect on those biomarkers.

這正好印證了 Nello 所指的效果的持久性，即使在健康的志願者身上，這些生物標誌物也表現出了持久的效果。

Brandon Frith, Wolfe Research.

Brandon Frith，Wolfe Research。

This is Brandon on for Andy. Within BROADEN2, are you doing anything to control the rising trend of placebo that we're seeing in atopic dermatitis where recent trials have seen a higher placebo response?

這是布蘭登替安迪發言。在 BROADEN2 中，您是否採取任何措施來控制我們在異位性皮膚炎中看到的安慰劑效應上升趨勢？最近的試驗表明，安慰劑效應更為顯著。

Thanks for the question. So I just want to answer the first part, and then Jared will address it. So I think that's an important point. I think as I was speaking earlier, I think with a drifting of patients with EASI, shifting from, let's say, early 30s to mid-20s, I think it's almost physiological to have seen an increase of the placebo rates. I think though, there are ways in which one can minimize the effect. And maybe, Jared, you can speak to it.

謝謝你的提問。所以我只想回答第一個問題，然後 Jared 會來解答。所以我認為這一點很重要。我認為，正如我之前所說，隨著 EASI 患者的年齡從 30 歲出頭轉移到 20 歲中期，安慰劑率的上升幾乎是生理性的。但我認為，有一些方法可以最大限度地減少這種影響。或許，賈里德，你可以談談這件事。

Sure. Yes. I think as far as we see it, I think this is based on the general learnings from prior studies. There are really three main things that one can do to try to limit that placebo rate. One is making sure that you have the right protocol design and site selection so that you're making sure you actually have patients with atopic dermatitis, not other skin diagnoses and that you make sure you have moderate to severe patients that you're not somehow also getting mild patients.

當然。是的。我認為就我們目前所見，這應該是基於先前研究的一般性結論。要降低安慰劑效應發生率，主要有三件事可以做。首先，要確保方案設計和選址正確，這樣才能確保你實際招募的是異位性皮膚炎患者，而不是其他皮膚病患者；其次，要確保你招募的是中度至重度患者，而不是輕度患者。

The milder patients, the more mild patients you have who should not really be enrolled in these studies, but they are enrolled, are going to have a contribution to placebo rate. The second important thing is to select very experienced sites because you want the raters, the people who are assessing the endpoints to have the right expertise, the right derm expertise here for AD.

病情較輕的患者越多，那些不應該參加這些研究但卻被納入研究的病情較輕的患者就越多，這必然會對安慰劑率產生影響。第二件重要的事情是選擇經驗豐富的站點，因為你希望評分者，也就是評估終點的人員，擁有正確的專業知識，尤其是針對 AD 的皮膚病專業知識。

And you also want to have the proper training of those raters to make sure they're able to assess EASI, for example, consistently and accurately. And then finally, it's really important that there'll be close sponsor oversight of the sites involved and also the CRO that's helping to execute on the study. That oversight is really our study conduct and the sponsor has to really be all over study conduct.

此外，你還需要對這些評分員進行適當的培訓，以確保他們能夠一致且準確地評估 EASI 等指標。最後，贊助商對參與研究的機構以及協助執行研究的合約研究組織 (CRO) 進行嚴格監督，這一點非常重要。這種監督其實就是我們的研究實施，申辦方必須全面監督研究實施。

So I think all of those elements combined, I think, are important in helping to mitigate placebo rate, and those are all things that we're addressing in our study.

所以我認為所有這些因素結合起來，對於降低安慰劑效應都很重要，而這些都是我們在研究中要解決的問題。

Kripa Devarakonda, Truist.

Kripa Devarakonda，Truist。

Can you hear me?

你聽得到我嗎？

Yes.

是的。

I was actually wondering how you think about the evolution of the competitive landscape for 621. I know you guys are significantly advanced in terms of the clinical development. There are competitors, whether you talk about degraders or some inhibitors. But based on what you've seen, how important is the fact that you're ahead in development versus any potential areas of differentiation? And where does the next-gen STAT6 degrader fit into this context?

我其實想知道您如何看待 621 的競爭格局演變。我知道你們在臨床開發方面已經取得了顯著進展。無論是降解劑或某些抑制劑，都存在著競爭對手。但根據你所看到的，你在研發方面處於領先地位這一事實，與任何潛在的差異化領域相比，究竟有多重要？那麼，下一代 STAT6 降解器在這個背景下又扮演著怎樣的角色呢？

Thanks, Kripa. So obviously, yes, we're aware of other companies that -- I think we've enabled with our amazing data, right, over the past couple of years, which is obviously always great to see, at least from an industry perspective. So first, let me start with -- this is not just about being first. I think this is about being first and best because that's what is going to almost guarantee commercial success, right?

謝謝你，克里帕。所以很明顯，是的，我們知道其他公司——我認為在過去的幾年裡，我們憑藉我們驚人的數據賦能了他們，這當然總是令人高興的，至少從行業的角度來看是這樣。首先，我要說的是──這不只是關於爭第一的問題。我認為關鍵在於成為第一名和最好，因為這幾乎可以保證商業上的成功，對吧？

You're ahead of the competition, which is important. But more importantly, you have a drug that is going to be extremely difficult, if not impossible, to do better than. And that's what KT-621 is. It's a drug that is exceptionally potent as we've seen, exceptionally well-tolerated with a profile that we believe would allow us to go in any potential indications of patients with Th2 diseases.

你領先競爭對手，這很重要。但更重要的是，你現在擁有的這種藥物，即使不是不可能，也極難找到比它更好的替代品。這就是 KT-621 的本質。我們已經看到，這是一種效力極強、耐受性極佳的藥物，我們相信它的特性將使我們能夠將其應用於任何潛在的 Th2 疾病患者。

I think others will have to talk about their differentiation versus KT-621. I'm not familiar with many of the other programs because there haven't been any publications or presentations with actual data. What I will say going on record here is I believe a small molecule inhibitor STAT6 is impossible to reach the level of pharmacological effect that our degrader will have, mostly because we'll not be able to block this pathway 24/7 almost completely or completely as we do.

我認為其他人需要談談它們與 KT-621 的區別。我對其他許多項目都不太了解，因為還沒有相關的出版品或簡報提供實際數據。我在此要公開聲明的是，我認為小分子抑制劑 STAT6 不可能達到我們降解劑的藥理作用水平，主要是因為我們無法像現在這樣 24/7 全天候幾乎完全或完全地阻斷這條通路。

And we believe that, that's required to have biologics-like activity. On the other, obviously, degrader programs, again, I don't know enough. But the important thing here is that we have confidence in our drug. We're years ahead of competitors. And so our team mandate here, including us around the table, is to execute flawlessly in the next few years, so that we can accomplish the commercial success that will make KT-621 a double-digit billion-dollar drug in the Th2 space.

我們認為，這是具有類似生物製劑活性的必要條件。另一方面，很顯然，降級程序，我對此了解不多。但重要的是，我們對我們的藥物有信心。我們領先競爭對手數年。因此，我們團隊的任務，包括我們這些坐在桌旁的人，是在未來幾年內完美地執行任務，以便我們能夠取得商業上的成功，使 KT-621 成為 Th2 領域價值數千億美元的藥物。

Jeff Jones, Oppenheimer.

傑夫瓊斯，奧本海默。

We've been talking about TARC, Eotaxin and some of the other critical biomarkers for the STAT6 program. Can you comment on key biomarkers we should be focusing on for the IRF5 program when we see that data? And should we be expecting healthy volunteer data in 2026?

我們一直在討論 TARC、嗜酸性粒細胞趨化因子 (Eotaxin) 以及 STAT6 程序的一些其他關鍵生物標記。看到IRF5計畫的數據後，您能否就我們應該重點關注的關鍵生物標記發表一些看法？我們是否可以期待在 2026 年獲得健康的志工數據？

Yes. Jeff, you always ask very orthogonal question. I love it. So yes, we expect to have Phase I data from 579 in 2026, next year. It's a bit early to speak to the biomarkers. But as you know us, as you do know us well, we tend to run Phase I healthy volunteer study that are quite rich in terms of information. So as we get closer to the start of the study, we'll share more about our biomarker strategy.

是的。傑夫，你總是問一些非常不相關的問題。我喜歡它。所以，是的，我們預計明年（2026 年）將獲得 579 的第一階段數據。現在談論生物標誌物還為時過早。但如您所知，您非常了解我們，我們傾向於進行資訊非常豐富的 I 期健康志工研究。隨著研究開始日期的臨近，我們將分享更多關於我們生物標記策略的資訊。

Jeet Mukherjee, BTIG.

Jeet Mukherjee，BTIG。

You folks have spoken at length about the niche and the opportunity for KT-621 in the atopic derm space. But could you just elaborate a bit further on how you see it fitting within the asthma landscape?

各位已經詳細討論了 KT-621 在異位性皮膚炎領域的利基市場和機會。您能否進一步闡述您認為它如何融入氣喘治療領域？

Yes. I mean I'll start with -- actually, there's a more fundamental issue, I think, in the asthma space, and I'll let Jared speak to the medical part of it. I just want to talk strategically. So Th2 asthma, eosinophilic asthma, which obviously we expect this drug to address, right, just to level set, is a disease that starts very early in life.

是的。我的意思是，我先從——實際上，我認為在氣喘領域存在一個更根本的問題，我會讓 Jared 來談談其中的醫學方面。我只想談戰略層面。所以 Th2 型氣喘，嗜酸性粒細胞性氣喘，顯然我們希望這種藥物能夠解決，對吧，為了平衡一下，這是一種在生命早期就開始發生的疾病。

And actually, it turns out that if you're not able to impact the disease until or before your lung fully develops, you're actually going to have reduced lung function for the rest of your life. And children, young adults are on non -- on therapies that do not address the underlying Th2 inflammation for many years before they are graduated to systemic biologics.

事實上，如果你在肺部完全發育之前或之後無法控制這種疾病，那麼你餘生的肺功能就會下降。兒童和青少年在接受全身性生物製劑治療之前，需要多年時間才能擺脫對潛在 Th2 發炎的治療。

I think there is a paradigm that needs to change because we're actually putting kids' lives at risk or we're not carrying as much as we should or do for the best quality of life possible of children and young adults with Th2 inflammation. So that's where an oral drug with, hopefully, the safety and the efficacy that we expect should fit in, in the treatment paradigm, that help patients earlier in their trajectory.

我認為我們需要改變一種範式，因為我們實際上是在拿孩子的生命冒險，或者我們沒有盡到應盡的責任，或者沒有為患有 Th2 發炎的兒童和年輕人提供盡可能最好的生活品質。因此，我們希望有一種口服藥物，它具有我們所期望的安全性和有效性，並能夠融入治療模式，幫助患者在治療早期階段獲得幫助。

I'm not saying that this is a patient for mild asthma, a drug for mild asthma, but this is an opportunity to change the treatment landscape in respiratory diseases, given that this is a disease of young people, and we need to change how this disease is treated. Maybe, Jared, you can bring us back to earth and maybe talk more medically.

我不是說這是治療輕度氣喘的病例，也不是說這是治療輕度氣喘的藥物，但這是一個改變呼吸系統疾病治療格局的機會，因為這是一種年輕人的疾病，我們需要改變這種疾病的治療方式。賈里德，或許你可以讓我們回歸現實，從醫學角度多談談。

Yes. No, I think in addition to the, I think, important opportunity in pediatric patients, I think also in the adolescent and adult patients with asthma, I think being able to access a much greater proportion of those patients with moderate to severe disease, right, who have a significant unmet need, but just are not going on injectable biologics for all the reasons around market access or concerns about being on an injectable or a biologic to be able to really penetrate the adult and adolescent space as well with our drug for those patients with moderate to severe because now we have an oral drug, which hopefully, if it says if it's comparable to dupi in its efficacy and safety, it could really transform how these adult and adolescent patients are also treated with asthma.

是的。不，我認為除了兒科患者之外，對於患有氣喘的青少年和成人患者來說，這也是一個重要的機會。我認為，能夠接觸到更多中重度氣喘患者，對他們來說意義重大，因為他們存在著巨大的未滿足需求，但由於市場准入或對注射生物製劑的擔憂等各種原因，他們無法使用注射生物製劑。現在我們有了口服藥物，如果其療效和安全性能夠與度匹克林（dupi）相媲美，那麼它有望真正改變這些成人和青少年氣喘患者的治療方式。

Clara Dong, Jefferies.

克拉拉‧董，傑富瑞。

I think you're on mute.

我想你已靜音。

Clara, we can't hear you.

克拉拉，我們聽不到你的聲音。

Now?

現在？

No.

不。

Yes. Maybe, operator, do you want to put her back in queue and we go to the next one and she can try to sort that out.

是的。操作員，或許您可以讓她重新排隊，我們再去處理下一個，讓她試著解決這個問題。

Alex Thompson, Stifel Europe AG.

Alex Thompson，Stifel Europe AG。

I guess on the Phase IIb AD study again, you mentioned obviously, patients that had experience with biologics. And I think, Nello, you also mentioned JAK inhibitors. Is there going to be a cap for how many of those advanced therapy experienced patients you might have in the study? And then on rescue therapy, how are you dealing with that as well?

我想再次回到 IIb 期 AD 研究，您顯然提到了有生物製劑使用經驗的患者。內洛，我想你也提到了JAK抑制劑。研究中接受過高級治療的患者人數是否會有上限？那麼關於搶救治療，您又是如何應對的呢？

Yes, there would be no cap. Again, as long as you have not failed advanced systemic therapies that block this path to IL-4, IL-13 and even JAKs, there will be no cut for those. And I don't think we're discussing rescue therapy. Obviously, there is a system on how we're going to deal with it, but I don't believe we're going to disclose it at this point.

是的，不會有上限。再次強調，只要你沒有嘗試過阻斷 IL-4、IL-13 甚至 JAK 路徑的高階系統療法，就不會有這些方面的限制。而且我認為我們討論的不是搶救療法。顯然，我們有一套處理此事的方案，但我認為目前我們不會公開這套方案。

Faisal Khurshid, Leerink.

Faisal Khurshid，Leerink。

So I know you've put kind of a benchmark out there of 70% to 80% on TARC reduction from baseline. Could you talk to us about what you would -- what efficacy endpoint you think people should focus on, given that people are focused on this, given that you already showed nice TARC in healthy volunteers? And then if you're not willing to put out a numerical benchmark, can you just clarify for investors why that's the case?

我知道你們已經設定了一個基準，即 TARC 減少 70% 到 80%（相對於基線）。鑑於大家都在關注療效終點，而且您已經在健康志願者身上證明了良好的TARC，您能否和我們談談您認為人們應該關注的療效終點是什麼？如果你不願意公佈具體的數值基準，能否向投資人解釋原因？

No. So thanks. That's a very good question, actually. So we're just basically stating the facts. And we've said that this is a biomarker-focused study mostly because we -- I think we can gather from the data that there is very little, if almost no, let's call it, placebo effect on biomarkers. So the absence of placebo should not impact the interpretation of biomarkers, right?

不。謝謝。這確實是個很好的問題。所以我們基本上只是在陳述事實。我們說過，這是一項以生物標記為重點的研究，主要是因為我們——我認為我們可以從數據中得出結論，生物標記幾乎沒有安慰劑效應。所以，沒有安慰劑效應不應該影響生物標記的解讀，對嗎？

So we're honestly a bit more comfortable saying for TARC, assuming the baseline levels are in the range of what we've seen with the dupilumab study, we expect to see the 70% plus, 70% to 80%. That's a fact, right? That's what dupilumab has seen. Now you would say it's also a fact that the EASI reduction on day 28, there is a number to it.

所以，我們比較有信心說，對於 TARC，假設基線水平在我們觀察到的 dupilumab 研究的範圍內，我們預計會看到 70% 以上的有效率，達到 70% 到 80%。這是事實，對吧？這就是度普利尤單抗所取得的成果。現在您可能會說，第 28 天 EASI 減少也是一個事實，這是一個具體的數字。

The reason, again, why we've been shy about putting a number on that is because, as you know, clinical endpoints are much more noisy and much more impacted by the potential placebo effect. And so I think we like to be data-driven and science-first company, as you know as well. And I think we'll put out things when we can confidently say that those numbers are something that we can scientifically then follow and adhere to.

我們一直不願給出具體數字的原因在於，如您所知，臨床終點指標的波動性更大，更容易受到潛在安慰劑效應的影響。所以，我認為我們喜歡成為一家數據驅動、科學至上的公司，你也知道這一點。我認為，只有當我們能夠自信地說這些數字是我們可以從科學角度進行追蹤和遵循的，我們才會公佈這些資訊。

What we said, again, we're not going to hide behind it. The numbers are out there for dupi, right? I don't have to say what the numbers are. The numbers are out there. The treatment arm numbers are out there. We expect in this study at day 28 to be in that ballpark because we know that, say, KT-621 blocks the pathway as well as dupilumab. So here is how we've always characterized it, and we're not going to change it now a month from the data disclosure.

我們之前說過的話，我們不會躲在它背後。dupi 的數據是公開的，對吧？我沒必要說出具體數字。數據就在那裡。治療組的具體數據都已公佈。我們預期本研究第 28 天的結果將與此大致相符，因為我們知道，例如，KT-621 和 dupilumab 一樣可以阻斷該路徑。所以，我們一直以來都是這樣描述它的，現在距離資料揭露已經過去一個月了，我們不會改變這一點。

Appreciate it. We look forward to the data next month.

謝謝。我們期待下個月的數據。

Judah Frommer, Morgan Stanley.

猶大‧弗洛默，摩根士丹利。

Maybe just one, if there's anything you can share on early recruitment trends, even anecdotally for BROADEN2. Obviously, the Phase Ib was tougher to recruit just given the 28-days dosing here, you can get patients on drug for a year plus. And curious about just awareness of the healthy data and how all that might be helping in recruiting patients and what investigator feedback is.

如果您能分享一些關於早期招聘趨勢的信息，即使只是關於 BROADEN2 的軼事，那就太好了。顯然，Ib 期試驗的招募難度更大，因為這裡的給藥週期為 28 天，患者可能需要服用藥物一年以上。我很好奇大家對健康數據的了解程度，以及這些數據如何幫助招募患者，還有研究人員的回饋。

Yes. I mean high level, again, we just started the study. We just activated a few sites. So we're very, very early into that process. I think what we believe right now is even on the healthy people -- on the Phase Ib, there was a lot of excitement by sites and investigators and eventually patients, we believe, in accessing an oral option.

是的。我的意思是，從宏觀層面來說，我們才剛開始這項研究。我們剛剛啟用了一些網站。所以我們還處於這個過程的非常非常早期階段。我認為我們目前所相信的是，即使是對於健康人群——在 Ib 期臨床試驗中，研究中心、研究人員以及最終的患者都對獲得口服治療方案感到非常興奮，我們相信。

Obviously, the 28-day study was not set up to get patients excited because it's a short study without an OLE. So the Phase IIb, it's a whole different value proposition. And I believe between that and hopefully, the data that we'll disclose in December, I think it will be -- we are confident that this will be a study that we can recruit in a timely manner.

顯然，這項為期 28 天的研究並不是為了激發患者的熱情，因為它是一項沒有開放標籤擴展研究的短期研究。所以，IIb期產品完全是另一種價值主張。我相信，結合這些數據以及我們希望在 12 月公佈的數據，我們有信心能夠及時招募到受試者進行這項研究。

Now recruiting the study as fast as possible is not our goal. Our goal is to recruit the study as fast as possible with the right patient. Going back to what Jared was saying earlier, we have a paranoid oversight of this whole study because we want to try and control the placebo rates as much as possible, even if that has to be at the expense of a week or two or four. So that's where we're coming from. But hopefully, we'll be able to share more about your question as we get deeper into the study.

現在，我們追求的並不是盡快招募研究對象。我們的目標是盡快招募到合適的患者參與研究。回到 Jared 之前所說的，我們對整個研究都抱持著偏執的監督態度，因為我們想盡可能地控制安慰劑率，即使這意味著要花費一兩週甚至四周的時間。這就是我們的出發點。但隨著研究的深入，希望我們能夠就您的問題分享更多資訊。

Clara Dong, Jefferies.

克拉拉‧董，傑富瑞。

Can you hear me now?

現在能聽到我說話嗎？

We can hear you. We see somebody else, we can hear you. Go ahead.

我們能聽到你的聲音。我們能看到其他人，也能聽到你的聲音。前進。

Thank you for letting me try again. So my question is on the Phase Ib trial. So this trial has a relatively short follow-up for weeks of patients. So among all the key endpoints like biomarkers, clinical efficacy and safety, which ones are -- in your view, are relatively less affected by the treatment duration and which endpoint do you think is more complex to interpret because of the trial design?

謝謝您讓我再試一次。所以我的問題是關於 Ib 期試驗的。因此，這項試驗的追蹤時間相對較短，僅對患者進行了幾週的追蹤。那麼，在生物標記、臨床療效和安全性等所有關鍵終點中，您認為哪些終點受治療持續時間的影響相對較小？您認為哪個終點會因為試驗設計的原因而更難解釋？

Yes. So I think very quickly because we're almost running out of time. If you look at the dupilumab study, I don't believe -- and hopefully, I'm not wrong, Jared, correct me. I don't believe there was any endpoint that reached maximal effect at week four. So I think it's hard for me to say which one is going to be less or more impacted by this 28-day duration. I think we'll look at all the data together in December and answer the question better.

是的。所以我覺得得抓緊時間，因為時間不多了。如果你看看度普利尤單抗的研究，我不相信──希望我沒說錯，賈里德，請糾正我。我不認為有任何終點指標在第四週達到最大效果。所以我覺得很難說哪一方會受到這 28 天的影響較小或較大。我認為我們會在12月份一起分析所有數據，並更好地回答這個問題。

Brad Canino, Guggenheim.

布拉德卡尼諾，古根漢美術館。

Maybe just to close out on a capital allocation question for Nello because you're in the most comfortable cash position you've ever been in with the company, but also have the highest capital demands ever faced by the company. So how do you think about deployment of each incremental investor dollar across KT-621, the name pipeline and the platform to really maximize value for Kymera at this juncture?

也許可以就 Nello 的資本配置問題做個總結，因為你們公司目前的現金狀況是前所未有的最佳狀態，但同時也面臨著公司有史以來最高的資本需求。那麼，您認為在這個關鍵時刻，如何將每一筆新增投資者資金部署到 KT-621、名稱管道和平台，才能真正最大限度地為 Kymera 創造價值？

Yes, great question. So I probably need half an hour for this. But in 30 seconds is, I think there has never been a biotech company that has developed a program like KT-621 on their own fully. So we appreciate this is a unique both opportunity and responsibility to do capital allocation in the right way. I would also say that if we became a STAT6-only company, we will not be fulfilling the mission that we have of a global company that develops drugs that impact patients across the world with different diseases.

是的，問得好。所以，我大概要半小時。但僅用 30 秒，我認為從來沒有一家生技公司能夠完全獨立地開發出像 KT-621 這樣的計畫。因此，我們意識到這是一個獨特的機會，也是一個責任，需要以正確的方式進行資本配置。我還要說，如果我們變成一家只研發 STAT6 的公司，我們將無法實現我們作為全球性公司的使命，即開發能夠影響世界各地患有不同疾病的患者的藥物。

Obviously, there is a medium -- and happy medium between going all in on 621 and spending a lot of money on the other programs. And I always believe that we need to earn the right to invest more. So our ability to invest more in 621 will be driven by the success of 621. Our ability to invest more also in other programs will depend on also our ability to have success with our clinical pipeline.

顯然，在全力投入 621 項目和在其他項目上花費大量資金之間，存在著一個中間地帶——一個令人滿意的中間地帶。我始終認為，我們需要透過努力才能贏得更多投資的權利。因此，我們能否對 621 進行更多投資，將取決於 621 的成功與否。我們能否對其他項目進行更多投資，也取決於我們的臨床試驗計畫能否成功。

So we don't do resource allocation because we have money. We allocate capital because we earn the right to do more. And that's the strategy since day-1.

所以我們進行資源分配不是因為我們有錢。我們之所以分配資本，是因為我們贏得了做更多事情的權利。而這正是我們從一開始就採取的策略。

Joe Catanzaro, Mizuho.

Joe Catanzaro，瑞穗銀行。

Maybe a follow-up sort of along the lines of duration of effect. Wondering if you could say anything about the level of compliance that you observed in the Phase Ib, but maybe more importantly, looking towards the Phase IIb and 16-weeks of dosing, what you guys can do to ensure a high level of compliance there?

或許可以做一個後續調查，例如考察效果持續時間。我想請您談談在 Ib 期試驗中觀察到的依從性水平，但更重要的是，展望 IIb 期試驗和為期 16 週的給藥，你們可以採取哪些措施來確保較高的依從性水平？

Yes. No, it's a great question. So obviously, with an oral drug, industry data will tell you that getting 100% compliance is difficult just because we all forget to take one pill one day. And with biologics, you can ensure compliance asking patients to be injected in the site. So obviously, we're aware of it. We're actually using novel technologies to increase as much as we can adherence to the study protocol with regarding to taking the drug. And we're confident that will deliver what we need.

是的。不，這是一個很好的問題。顯然，對於口服藥物來說，行業數據會告訴你，要達到 100% 的依從性是很難的，因為我們每個人都可能有一天忘記吃一片藥。而使用生物製劑，您可以要求患者在註射部位進行注射，以確保患者依從性。所以很顯然，我們都知道這件事。我們實際上正在使用新技術來盡可能提高受試者在服用藥物方面對研究方案的依從性。我們相信這能夠滿足我們的需求。

I will add one last thing. I know we're way out of time. The beauty about a degrader drug is that you can actually skip a dose and maintain maximal pharmacology, assuming you have the right dose that reaches complete degradation that you will never see with a traditional occupancy-based small molecule inhibitor. So we have a bit of a cushion on the adherence question. But obviously, we're not sitting on it. We need to ensure as much as we can, 100% adherence because we want to maximize the benefit to patients.

我還要補充最後一點。我知道我們時間已經非常緊迫了。降解藥物的優點在於，即使漏服一次，也能保持最大的藥理作用，前提是劑量合適，能夠達到完全降解，而傳統的基於佔有率的小分子抑製劑永遠無法達到這種完全降解的效果。所以，在依從性問題上，我們還是有一定的緩衝空間的。但很顯然，我們並沒有坐視不管。我們需要盡可能確保 100% 的依從性，因為我們希望最大限度地造福患者。

Thank you. I'd now like to turn the call over to Nello Mainolfi for closing remarks.

謝謝。現在我把電話交給內洛·馬伊諾爾菲，請他作總結發言。

Okay. Thank you. I'm sorry, we ran beyond the 9:30 goal that we had. I want to thank everybody. Obviously, lots of questions. We are always available to continue to engage. This has been the most exciting year of Kymera, and we have 1.5 more months or so to go. So stay close. I think it's going to be an exciting time in the next few years developing this really once-in-a-generation drug and the broader pipeline. So thank you again today, and we'll talk more soon.

好的。謝謝。抱歉，我們超時了，超過了我們設定的9分30秒的目標時間。我要感謝大家。顯然，問題很多。我們隨時願意繼續與您交流。這是 Kymera 最令人興奮的一年，我們還有大約一個半月的時間。所以要保持距離。我認為未來幾年將會是個令人興奮的時期，我們將開發這種百年一遇的藥物以及更廣泛的研發管線。再次感謝您今天的來訪，我們下次再聊。