Corvus Pharmaceuticals Inc (CRVS) 2024 Q4 法說會逐字稿

Good afternoon, everyone. Thank you for standing by, and welcome to the Corvus Pharmaceuticals fourth-quarter and full-year 2024 business update and financial results conference call. (Operator Instructions)

大家下午好。感謝您的支持，歡迎參加 Corvus Pharmaceuticals 2024 年第四季和全年業務更新和財務業績電話會議。（操作員指示）

It is now my pleasure to turn the call over to Mr. Zack Kubow of Real Chemistry. Thank you. Please go ahead, sir.

現在我很高興將電話轉給 Real Chemistry 的 Zack Kubow 先生。謝謝。先生，請繼續。

Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals' fourth-quarter and full-year 2024 business update and financial results conference call.

謝謝接線員，大家下午好。感謝您參加 Corvus Pharmaceuticals 2024 年第四季和全年業務更新和財務業績電話會議。

On the call to discuss the results and business updates are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Jeff Arcara, Chief Business Officer; and Ben Jones, Senior Vice President of Regulatory and Pharmaceutical Sciences. The executive team will open the call with some prepared remarks followed by a question-and-answer period.

執行長理查德·米勒 (Richard Miller) 參加電話會議討論業績和業務更新； Leiv Lea，首席財務官；傑夫·阿卡拉（Jeff Arcara），首席商務官；以及監管和製藥科學高級副總裁本·瓊斯 (Ben Jones)。執行團隊將在電話會議開始時發表一些準備好的講話，然後進行問答環節。

I would like to remind everyone that comments made by management today and answers to questions will include forward-looking statements. Forward-looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' annual report on Form 10-K for the year ending December 31, 2024, that was filed today and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward-looking statements except as required by law.

我想提醒大家，管理階層今天發表的評論和對問題的回答將包括前瞻性陳述。前瞻性陳述是基於截至今天的估計和假設，並受風險和不確定性的影響，這些風險和不確定性可能導致實際結果與這些陳述表達或暗示的結果存在重大差異，包括 Corvus 今天提交的截至 2024 年 12 月 31 日的 10-K 表格年度報告中描述的風險和不確定性，以及公司不時向美國證券交易委員會提交的其他文件。除法律要求外，本公司不承擔公開更新或修改任何前瞻性聲明的義務。

With that, I'd like to turn the call over to Leiv Lea. Leiv?

說完這些，我想把電話轉給 Leiv Lea。雷夫？

Thank you, Zack. I will begin with a quick overview of our fourth-quarter and full-year 2024 financials and then turn the call over to Richard for a business update.

謝謝你，扎克。我將首先簡要概述我們第四季和 2024 年全年的財務狀況，然後將電話轉給理查德，介紹業務最新情況。

Research and development expenses in the fourth-quarter 2024 totaled $6 million, compared to $4 million for the same period in 2023. The $2 million increase was primarily due to an increase in soquelitinib clinical trial expenses.

2024 年第四季研發費用總計 600 萬美元，而 2023 年同期為 400 萬美元。200萬美元的增加主要是由於索奎替尼臨床試驗費用的增加。

R&D expenses for the full-year 2024 totaled $19.4 million, compared to $16.5 million for the full-year 2023. For the full-year 2024, the increase of approximately $2.9 million was primarily due to higher clinical trial costs associated with the development of soquelitinib.

2024 年全年研發費用總計 1,940 萬美元，而 2023 年全年研發費用總計 1,650 萬美元。2024 年全年增加約 290 萬美元，主要是由於與索奎替尼開發相關的臨床試驗成本增加。

The net loss for the fourth-quarter 2024 was $12.1 million including a non-cash loss of $2.2 million related to Angel Pharmaceuticals, our partner in China. In addition, we recorded a non-cash loss of $2.3 million from the change in fair value of Corvus' warrant liability during the fourth-quarter 2024.

2024 年第四季的淨虧損為 1,210 萬美元，其中包括與我們在中國的合作夥伴 Angel Pharmaceuticals 相關的 220 萬美元的非現金損失。此外，2024 年第四季度，我們因 Corvus 認股權證負債公允價值變動而產生了 230 萬美元的非現金損失。

This compares to a net loss of $6.7 million for the same period in 2023, which included a $1.4 million non-cash loss related to Angel Pharmaceuticals. The net loss for the full-year 2024 was $63.3 million (sic – see Form 10-K, "$62.3 million") including a $3.2 million non-cash loss related to Angel and a non-cash loss of $33.4 million from the change in fair value of Corvus' warrant liability during the year.

相較之下，2023 年同期的淨虧損為 670 萬美元，其中包括與 Angel Pharmaceuticals 相關的 140 萬美元非現金損失。2024 年全年淨虧損為 6,330 萬美元（原文如此 - 請參閱 10-K 表格「6,230 萬美元」），其中包括與 Angel 相關的 320 萬美元非現金損失，以及因 Corvus 認股權證負債公允價值變動而產生的 3,340 萬美元非現金損失。

This compares to an -- this compares to a net loss of $27.0 million including a $5.3 million non-cash loss related to Angel for the full-year 2023. Total stock compensation expense for the fourth-quarter and full-year 2024 was $0.8 million and $3 million respectively, compared to $0.6 million and $2.1 million for the same periods in 2023.

相比之下，2023 年全年淨虧損為 2,700 萬美元，其中包括與 Angel 相關的 530 萬美元非現金損失。2024 年第四季和全年股票薪酬總費用分別為 80 萬美元和 300 萬美元，而 2023 年同期分別為 60 萬美元和 210 萬美元。

As of December 31, 2024, Corvus had cash, cash equivalents, and marketable securities totaling $52 million as compared to $27.1 million at December 31, 2023. Of note, associated with our financing in May 2024, we also sold common stock warrants that have an exercise price of $3.50 and expire on June 30, 2025.

截至 2024 年 12 月 31 日，Corvus 的現金、現金等價物及有價證券總額為 5,200 萬美元，而 2023 年 12 月 31 日為 2,710 萬美元。值得注意的是，與我們 2024 年 5 月的融資相關，我們也出售了行使價為 3.50 美元、到期日為 2025 年 6 月 30 日的普通股認股權證。

Two investors early exercised their warrants during the fourth quarter of 2024, resulting in $18.6 million in cash to the company. If all the remaining warrants are exercised, we will receive approximately $41 million in additional cash. Based on our current plans, we anticipate our cash provides runway into the first quarter of 2026.

兩位投資者在 2024 年第四季提前行使了認股權證，為公司帶來了 1,860 萬美元的現金。如果所有剩餘認股權證都被行使，我們將獲得約 4,100 萬美元的額外現金。根據我們目前的計劃，我們預計我們的現金供應將持續到 2026 年第一季。

I will now turn the call over to Richard, who will discuss our clinical progress and elaborate on our strategy and plans.

現在我將電話轉給理查德，他將討論我們的臨床進展並詳細闡述我們的策略和計劃。

Thanks, Leiv, and good afternoon, everyone. Thank you for joining us today for our business update call.

謝謝，Leiv，大家下午好。感謝您今天參加我們的業務更新電話會議。

As we look into 2025, we remain optimistic on the potential for soquelitinib to provide a powerful new approach for the treatment of a broad range of immune diseases and cancer. Soquelitinib is well-positioned as a first-in-class oral therapy that selectively inhibits ITK to modulate and control parallel signaling pathways in the immune system. Our confidence is backed by a strong and growing body of evidence both from our clinical efforts and preclinical research conducted by us and others.

展望 2025 年，我們仍然對索奎替尼為治療多種免疫疾病和癌症提供強有力的新方法的潛力持樂觀態度。索奎替尼作為一流的口服療法，具有良好的優勢，可以選擇性抑制 ITK，從而調節和控制免疫系統中的平行訊號路徑。我們的信心得到了我們和其他人進行的臨床努力以及臨床前研究的大量且不斷增長的證據的支持。

First, we have reported a 39% objective response rate from our Phase 1 trial of soquelitinib in patients with relapsed T cell lymphoma. This included a 26% complete response rate, which is more than double the rate seen with standard chemotherapies. Based on this data, we are enrolling a registrational Phase 3 trial of soquelitinib in patients with relapsed peripheral T cell lymphoma, and we have gained a significant amount of experience that we are applying to our other soquelitinib programs.

首先，我們報告了索奎替尼在復發性 T 細胞淋巴瘤患者中的 1 期試驗的客觀緩解率為 39%。其中包括 26% 的完全緩解率，是標準化療的兩倍以上。基於這些數據，我們正在對複發性週邊 T 細胞淋巴瘤患者進行索奎替尼的註冊性 3 期試驗，並且我們已經獲得了大量經驗，並將這些經驗應用於我們的其他索奎替尼計畫。

Second, we observed a favorable safety and efficacy profile from interim data from our Phase 1 trial of soquelitinib in patients with moderate to severe atopic dermatitis. This includes significant responses in the soquelitinib treatment groups compared to placebo or the clinically significant endpoints of Investigator Global Assessment or IGA 0 or 1, and Eczema Area and Severity Index, or EASI 75.

其次，我們從索奎替尼對中度至重度異位性皮膚炎患者進行的 1 期試驗的中期數據中觀察到了良好的安全性和有效性。這包括與安慰劑相比，索奎替尼治療組的顯著反應，或研究者總體評估或 IGA 0 或 1，以及濕疹面積和嚴重程度指數或 EASI 75 的臨床顯著終點。

Third, preclinical data supports the potential of ITK inhibition in a broad range of indications, including solid tumors, immune conditions such as autoimmune lymphoproliferative syndrome or ALPS, systemic sclerosis, pulmonary fibrosis, and graft-versus-host disease, and inflammatory conditions such as asthma, psoriasis, and inflammatory bowel disease.

第三，臨床前數據支持 ITK 抑制在廣泛適應症中的潛力，包括實體瘤、自體免疫性淋巴增生症候群或 ALPS、系統性硬化症、肺纖維化和移植物抗宿主疾病等免疫疾病，以及氣喘、牛皮癬和發炎性腸道疾病等發炎疾病。

The data also highlights its mechanism of action, skewing differentiation to Th1 cells, reducing Th2 and Th17 cells and their downstream cytokines, and promoting a switch to two T regulatory cells that suppress inflammation.

數據還強調了其作用機制，即向 Th1 細胞分化，減少 Th2 和 Th17 細胞及其下游細胞因子，並促進向抑制發炎的兩種 T 調節細胞的轉換。

Given the broad applicability of its mechanism of action, we view the potential of ITK inhibition as analogous to BTK inhibition, a category that members of the Corvus' team, including myself, helped to develop. BTK inhibitors were first approved for B cell malignancies and then expanded into autoimmune conditions.

鑑於其作用機制的廣泛適用性，我們認為 ITK 抑制的潛力類似於 BTK 抑制，包括我在內的 Corvus 團隊成員幫助開發了這個類別。BTK 抑制劑最初被批准用於治療 B 細胞惡性腫瘤，後來擴展到治療自體免疫疾病。

Today I will recap our previously reported data in atopic dermatitis and next steps for the trial. Share some detail on the recently initiated NIH trial in ALPS and highlight the upcoming milestones for soquelitinib.

今天，我將回顧我們先前報告的異位性皮膚炎數據以及試驗的後續步驟。分享一些關於最近在 ALPS 啟動的 NIH 試驗的細節，並強調索奎替尼即將取得的里程碑。

In January, we reported interim data from the Phase 1 trial of soquelitinib in patients with moderate to severe atopic dermatitis. The trial includes four cohorts that are enrolling 16 subjects each at a 3:1 ratio of active to placebo, 12 active, 4 placebo. The trial is double blind, meaning the patient and the doctor do not know what they're taking. The active medicine and placebo are indistinguishable tablets.

今年 1 月，我們報告了索奎替尼治療中度至重度異位性皮膚炎患者的 1 期試驗中期數據。該試驗包括四個隊列，每個隊列招募 16 名受試者，活性藥物與安慰劑的比例為 3:1，即 12 名活性藥物患者和 4 名安慰劑患者。該試驗是雙盲的，這意味著患者和醫生都不知道他們服用的是什麼藥物。活性藥物和安慰劑是無法區分的藥片。

The company and the data review committee are not blinded. The treatment period is 28 days, and then we follow patients off therapy for another 30 days. The 28-day treatment period is relatively short compared to later-stage atopic dermatitis studies with other agents which typically treat up to 16 weeks or longer.

公司和數據審查委員會並不知情。治療期為 28 天，之後我們會對停止治療的患者進行另外 30 天的追蹤。與其他藥物治療異位性皮膚炎的後期研究（通常治療時間長達 16 週或更長時間）相比，28 天的治療期相對較短。

The primary endpoint is safety and tolerability. Secondary endpoints measure based on IGA and EASI scores along with patient reported measures of itch and biomarkers. The first two cohorts received soquelitinib doses of 100 milligram twice a day and 200 milligram once per day. The same total dose of drug was used in the first two cohorts. Based on our lymphoma studies, we know that 100 milligrams will provide 50% to 80% occupancy of the target, and 200 milligrams will provide about 80% to 100% occupancy.

主要終點是安全性和耐受性。次要終點測量是基於 IGA 和 EASI 評分以及患者報告的搔癢和生物標記測量結果。前兩組患者接受索奎替尼治療，每日兩次，每次 100 毫克，以及每日一次，每次 200 毫克。前兩組使用了相同的藥物總劑量。根據我們的淋巴瘤研究，我們知道 100 毫克將提供 50% 到 80% 的目標佔有率，而 200 毫克將提供約 80% 到 100% 的佔有率。

In January, we reported data from 16 patients in Cohort 1 and 10 patients in Cohort 2, for which 28 days of treatment had been completed. In total, from the combined Cohort 1 and 2, this included 19 patients treated with soquelitinib and 7 patients treated with placebo.

1 月份，我們報告了第 1 組 16 名患者和第 2 組 10 名患者的數據，這些患者已完成 28 天的治療。整體而言，第 1 組和第 2 組的合併研究包括 19 名接受索奎替尼治療的患者和 7 名接受安慰劑治療的患者。

In the soquelitinib group, 26% achieved IGA 0 or 1 and 37% achieved EASI 75. Recall, these have been accepted as measures of clinical benefit and have been used as the basis for regulatory approval for several approved treatments for atopic dermatitis.

在索奎替尼組中，26% 的患者達到 IGA 0 或 1，37% 的患者達到 EASI 75。回想一下，這些已被接受為臨床益處的衡量標準，並已被用作幾種經批准的異位性皮膚炎治療方法的監管批准的基礎。

In the placebo group, no patients achieved IGA 0 or 1 or EASI 75. No significant safety issues were observed and no clinically significant laboratory abnormalities were seen. Cohort 3 of the trial, which administers a dose of 200 milligrams twice a day, that is twice the total daily dose we used in the earlier cohorts, is nearing completion of enrollment, and some patients have already reached the 28-day follow-up period.

在安慰劑組中，沒有患者達到 IGA 0 或 1 或 EASI 75。沒有觀察到重大的安全問題，也沒有發現臨床上顯著的實驗室異常。該試驗的第 3 組患者每天服用兩次 200 毫克的劑量，這是我們在早期組中每日總劑量的兩倍，該組患者招募工作即將完成，部分患者已經進入 28 天的隨訪期。

The efficacy results so far in the trial, including full milligrams 1 and 2 and the initial experience in cohort 3, have been positive and consistent with what we have reported to date. No patients in the active treatment groups received concomitant topical steroids or required rescue medications. One patient in the placebo group did receive concomitant topical corticosteroids.

到目前為止，試驗的療效結果（包括第 1 毫克和第 2 毫克以及第 3 組的初步經驗）都是正面的，並且與我們迄今為止報告的結果一致。積極治療組中沒有患者同時接受局部類固醇治療或需要救援藥物。安慰劑組的一名患者確實接受了同時局部皮質類固醇治療。

In Cohorts 1 and 2, two placebos experience flares in their disease during the 28-day treatment period, whereas no disease flares were seen in the patients receiving active drug during the 28-day treatment period, as well as the follow up period off treatment.

在第 1 組和第 2 組中，兩名接受安慰劑治療的患者在 28 天的治療期間出現病情復發，而接受活性藥物治療的患者在 28 天的治療期間以及治療後的後續期間均未出現病情復發。

Soquelitinib has been very safe to date as well, with no patients requiring interruption of therapy. We now have experience in over 100 patients with lymphoma and atopic dermatitis, representing more than 9,000-patient days of treatment, including patients with lymphoma on therapy for up to two years.

索奎替尼迄今也非常安全，沒有病人需要中斷治療。目前，我們已經為超過 100 名淋巴瘤和異位性皮膚炎患者提供了治療，治療天數超過 9,000 天，其中包括接受長達兩年治療的淋巴瘤患者。

We continue to believe that soquelitinib is an active medicine for atopic dermatitis with several advantages: oral route of administration, attractive safety profile, a novel mechanism of action with an opportunity for unique positioning, including the potential to bridge between topical therapies and systemic injectables. We plan to report data covering the first three cohorts at the Society of Investigative Dermatology meeting taking place May 7 to 10 in San Diego. Our abstract has already been accepted for an oral and poster presentation at this meeting.

我們仍然相信索奎替尼是一種治療異位性皮膚炎的有效藥物，具有多種優勢：口服給藥途徑、良好的安全性、具有獨特定位機會的新穎作用機制，包括在局部治療和全身注射之間架起橋樑的潛力。我們計劃在 5 月 7 日至 10 日於聖地牙哥舉行的研究皮膚病學會會議上報告涵蓋前三個隊列的數據。我們的摘要已被接受在本次會議上進行口頭和海報展示。

Outside of atopic dermatitis, we continue to enroll patients in our registrational Phase 3 trial of soquelitinib in patients with relapsed PTCL. Recently we presented updated data from our Phase 1 trial at the T cell lymphoma forum with longer follow-ups showing that the median progression free survival is 6.2 months and the 18-month progression free survival is 30%. The median duration of response was 17.2 months.

除異位性皮膚炎外，我們還將繼續招募患者參與索奎替尼治療復發性 PTCL 患者的註冊性 3 期試驗。最近，我們在 T 細胞淋巴瘤論壇上展示了我們第 1 階段試驗的最新數據，更長的追蹤顯示，中位無惡化存活期為 6.2 個月，18 個月無惡化存活率為 30%。平均緩解持續時間為 17.2 個月。

PFS, or progression free survival, is the primary endpoint of our Phase 3 trial, which is comparing soquelitinib to either Belinostat or Pralatrexate, the standard of care agents with reported median PFSs of about 3 months and 18-month PFSs of under 20%.

PFS，即無惡化存活期，是我們 3 期試驗的主要終點，該試驗將索奎替尼與貝利諾他或普拉曲沙進行比較，後者是標準治療藥物，報告的中位 PFS 約為 3 個月，18 個月 PFS 低於 20%。

We also have recently announced the initiation of enrollment in a Phase 2 trial of soquelitinib in patients with ALPS, autoimmune lymphoproliferation syndrome. This study not only addresses a disease with unmet need but will also provide additional information on the activity of selective ITK inhibition in a serious autoimmune disease.

我們最近也宣布開始招募索奎替尼治療 ALPS（自體免疫性淋巴球增生症候群）患者的 2 期臨床試驗。這項研究不僅解決了一種尚未滿足需求的疾病，還將提供有關選擇性 ITK 抑制在嚴重自體免疫疾病中的活性的更多資訊。

ALPS patients are born with a genetic mutation in fast signaling that results in lymphoproliferation and a myriad of autoimmune problems such as anemia, neutropenia, thrombocytopenia, and others. Some of these patients go on to also develop malignant lymphomas.

ALPS 患者出生時就存在快速訊號基因突變，導致淋巴球增生和一系列自體免疫問題，如貧血、嗜中性白血球減少症、血小板減少症等。其中一些患者還會患上惡性淋巴瘤。

The ALPS trial is being conducted under a clinical research and development agreement with the National Institutes of Allergy and Infectious Diseases at NIH. It will enroll up to 30 patients aged 16 years or older with confirmed ALPS based on genetic testing. There will be two dosing cohorts, 200 milligrams or 400 milligrams of soquelitinib twice per day for a period of up to 360 days.

ALPS 試驗是根據與美國國立衛生研究院國家過敏和傳染病研究所簽訂的臨床研究和開發協議進行的。它將招募多達 30 名年齡 16 歲或以上、經基因檢測確診為 ALPS 的患者。將有兩種劑量組，每天服用兩次 200 毫克或 400 毫克索奎替尼，最長服用 360 天。

The primary endpoint of the trial is efficacy determined by reductions in spleen and lymph node volumes as measured by CT scans. In addition, improvements in cytopenias, or lower blood cell levels, will be assessed by complete blood counts. Improvements in cytopenias can improve quality of life and overall health and serve as a biomarker associated with ALPS disease activity, including autoantibody levels that are reactive with red cells, white cells, and or platelets. Secondary endpoints include safety and tolerability.

試驗的主要終點是透過 CT 掃描測量的脾臟和淋巴結體積的減少來確定療效。此外，血球減少症或血球水平降低的改善情況將透過全血球計數來評估。血球減少症的改善可以提高生活品質和整體健康狀況，並可作為與 ALPS 疾病活動相關的生物標記物，包括與紅血球、白血球和/或血小板反應的自身抗體水平。次要終點包括安全性和耐受性。

We are also planning a single-agent soquelitinib solid tumor trial in relapsed renal cell cancer or RCC, representing a new approach to immunotherapy of this disease. We plan to initiate this trial during the third quarter of 2025.

我們也計劃對復發性腎細胞癌或 RCC 進行單藥索奎替尼實體瘤試驗，這代表了該疾病免疫療法的新方法。我們計劃於 2025 年第三季啟動此項試驗。

Outside of soquelitinib, we also continue to advance our other clinical stage development programs. We have been one of the leaders in the development of adenosine A2A receptor antagonists for the treatment of cancer with ciforadenant. This includes our Phase 1b/2 clinical trial that is being conducted in collaboration with the Kidney Cancer Research Consortium.

除了索奎替尼之外，我們也繼續推進其他臨床階段的開發案。我們一直是開發腺苷A2A受體拮抗劑（ciforadenant）治療癌症的領導者之一。這包括我們與腎癌研究聯盟合作進行的 1b/2 期臨床試驗。

The trial was evaluating ciforadenant or ciforadenant as a potential first line therapy for metastatic renal cell cancer in combination with ipilimumab and nivolumab. The study has reached full enrollment of 60 patients at sites including MD Anderson, Vanderbilt, Duke, and the University of Pennsylvania. The patients are being followed, and we anticipate our partners at the Kidney Cancer Research Consortium will present data from the trial sometime later in 2025.

該試驗評估了 ciforadenant 或 ciforadenant 與 ipilimumab 和 nivolumab 聯合作為轉移性腎細胞癌的潛在一線療法。該研究已在 MD 安德森癌症中心、范德堡大學、杜克大學和賓州大學等機構招募了 60 名患者。我們正在對患者進行跟踪，預計腎癌研究聯盟的合作夥伴將在 2025 年稍後展示試驗數據。

Finally, I should mention that we are advancing several second- and third-generation ITK selective inhibitors designed to preferentially affect particular ITK signaling pathways.

最後，我應該提到，我們正在推進幾種第二代和第三代 ITK 選擇性抑制劑，旨在優先影響特定的 ITK 訊號通路。

Summarizing the outlook for the remainder of 2025, we remain focused on advancing the broad opportunity for soquelitinib, which has several potential upcoming catalysts. This includes, number one, additional data from the Phase 1 trial in atopic dermatitis in May at the Society for Investigative Dermatology meeting. Number two, full data from the Phase 1 trial on atopic dermatitis in the third quarter. Number three, initiating a Phase 2 clinical trial with soquelitinib in solid tumors in the third quarter of 2025, with initial data anticipated in the first half of 2026.

總結 2025 年剩餘時間的前景，我們仍然專注於推進索奎替尼的廣泛機遇，該藥物具有幾個潛在的即將到來的催化劑。首先，其中包括 5 月在研究皮膚病學會會議上進行的異位性皮膚炎 1 期試驗的補充資料。第二，第三季異位性皮膚炎第一階段試驗的完整數據。第三，2025年第三季啟動索奎替尼治療實體瘤的2期臨床試驗，預計2026年上半年獲得初步數據。

Number four, initiating a Phase 2 atopic dermatitis trial in late 2025. Number five, continuing to activate sites and drive enrollment in the registrational Phase 3 trial of soquelitinib and PTCL driving towards interim data in late 2026. And depending on enrollment trends, it's possible we could see initial data from the Phase 2 ALPS study in late 2025 or early 2026.

第四，將於2025年底啟動第二階段異位性皮膚炎試驗。第五，繼續啟動站點並推動索奎替尼和 PTCL 註冊 3 期試驗的註冊，以期在 2026 年底獲得中期數據。根據入學趨勢，我們可能會在 2025 年末或 2026 年初看到第二階段 ALPS 研究的初步數據。

Our current cache gives us runway into the first quarter of 2026, allowing us to execute on these important milestones and further demonstrate the value of our programs and in particular the significant opportunity for ITK inhibition in immunology and cancer. We look forward to providing updates on our programs in the coming quarters.

我們目前的儲備為我們進入 2026 年第一季提供了基礎，使我們能夠實現這些重要的里程碑，並進一步證明我們計畫的價值，特別是 ITK 抑制在免疫學和癌症領域的重要機會。我們期待在未來幾個季度內提供有關我們計劃的最新資訊。

I will now turn the call over to the operator for a questions-and-answer period. Operator?

現在我將把電話轉給接線員進行問答。操作員？

(Operator Instructions)

（操作員指示）

Jeff Jones, Oppenheimer.

傑夫瓊斯，奧本海默。

Good afternoon, guys, and thanks for taking the question. Lots of data updates to come, so really exciting time for you guys. I guess, starting out on the AD front and the update in May, will the -- should we expect full data on Cohort 3 as well as additional patients on Cohort 2? And then as you think about the efficacy hurdle there, what do you guys have in your head to move this ahead into the Phase 2A that you just mentioned or and just competitiveness in the field?

大家下午好，感謝你們回答這個問題。大量數據即將更新，這對你們來說真的是令人興奮的時刻。我想，從 AD 方面開始以及 5 月的更新，我們是否應該期待第 3 組以及第 2 組其他患者的完整數據？然後，當您考慮那裡的功效障礙時，您有什麼想法可以將其推進到您剛才提到的第 2A 階段或該領域的競爭力？

Okay. So Jeff, the meeting in May, the Society of Investigative Dermatology, we intend to report the full data set on Cohort 1, the full data set on Cohort 2. We've already completed enrollment and follow up in those two cohorts. Cohort 3 is almost completed enrollment, a 28-day follow up is coming in on patients now. We're also going to have additional one-month follow up beyond that. So we'll have the full data for Cohort 1, 2, and 3. I also expect to have biomarker data for those first 3 cohorts as well.

好的。傑夫，在 5 月的會議上，研究皮膚病學會，我們打算報告第 1 組的完整資料集，以及第 2 組的完整資料集。我們已經完成了這兩個群體的招生和後續工作。第 3 組患者招募工作已接近尾聲，目前正在對患者進行 28 天的追蹤。除此之外，我們還將進行額外一個月的後續追蹤。因此我們將獲得第 1、2 和 3 組的完整數據。我還希望獲得前 3 個隊列的生物標記數據。

Okay, great. And then just in terms of the success hurdles and efficacy bar that you guys are looking at.

好的，太好了。然後就你們所關注的成功障礙和功效標準而言。

Well, first of all, we're pretty pleased with the efficacy we saw in Cohort 1 and 2. Let me remind you, that's 28 days of treatment. We see what a 30% difference in some of these 25% to 35% difference between placebo, which was zero in Cohort 1 and 2, and our actives, that's a pretty good number. And that number sustained or improved would be very good in our opinion.

首先，我們對第 1 組和第 2 組所見的療效非常滿意。讓我提醒你，那是28天的治療。我們看到，在安慰劑（在第 1 組和第 2 組中為零）和我們的活性物質之間的 25% 到 35% 的差異中，有 30% 的差異，這是一個相當不錯的數字。我們認為，維持或提高這一數字就非常好了。

Now, of course, many people are asking about what would happen if we increased the duration of therapy, and that's something that we're thinking about and will come in time. So we're pretty pleased with the efficacy results we have to date.

現在，當然，很多人都在問如果我們增加治療時間會發生什麼，這是我們正在考慮的事情，並且會及時實現。因此，我們對迄今為止的療效結果非常滿意。

In terms of a competitive landscape, of course we're oral, we have a different mechanism of action. Safety looks really good so far, convenience, the study -- the design of our study was really intended to determine whether or not selective inhibition of ITK had some role in immune disease. Is there some signal, some indication of efficacy in an autoimmune disease? And I think we've got that.

就競爭格局而言，我們當然是口服的，我們有不同的作用機轉。到目前為止，安全性看起來確實很好，方便，研究——我們的研究設計實際上是為了確定 ITK 的選擇性抑制是否在免疫疾病中發揮了一定作用。是否存在一些訊號或跡象顯示自體免疫疾病具有療效？我想我們已經做到了。

Now, of course, as we think about Phase 2 trials and beyond, we'll begin to think about what's required for registration. But I think from a competitive standpoint, to my knowledge, we're the only selective ITK inhibitor. I know there's some other companies that have ITK inhibitors and are talking about it now, but they're not selective and we view that as critical in the biology. And so I think we're in pretty good shape on this.

現在，當然，當我們考慮第二階段試驗及以後的試驗時，我們會開始考慮註冊需要什麼。但我認為從競爭的角度來看，據我所知，我們是唯一的選擇性 ITK 抑制劑。我知道其他一些公司也有 ITK 抑制劑，並且正在討論它，但它們不具有選擇性，我們認為這在生物學中至關重要。所以我認為我們在這方面的進展相當順利。

Great. Thanks, Richard. I'll hop back in queue.

偉大的。謝謝，理查。我會重新回到隊列中。

Aydin Huseynov, Ladenburg Thalmann.

艾丁‧侯賽諾夫，拉登堡‧塔爾曼。

Hi, good afternoon, everyone. Richard, congratulations with the progress this quarter. I've got a couple of questions here.

大家好，下午好。理查德，恭喜你本季的進展。我這裡有幾個問題。

So regarding the potential Cohort 4, so could you clarify your plans for Cohort 4, whether you still would like to enroll in 400 milligrams? And just if you could give us like a general idea what is the difference in terms of the doses? I mean, why would you like 400 milligram doses as compared to the oncology trial where you maximum -- what were your optimal dose is just 200 milligram?

那麼關於潛在的第 4 組，您能否澄清一下您對第 4 組的計劃，您是否仍想參加 400 毫克的課程？您能否大致告訴我們，劑量方面有什麼不同？我的意思是，與腫瘤學試驗中的最大劑量相比，為什麼你想要 400 毫克的劑量——你的最佳劑量只有 200 毫克？

Thank you, Aydin. Good question. So just for the benefit of everyone else, Cohort 1 was 100 milligrams BID, Cohort 2 was same, total dose 200 milligrams once a day, Cohort 3, 200 milligrams twice a day, and Cohort 4, as you indicate, would be 200 -- 400 milligrams at the same total dose one time. So before deciding whether we're going to do Cohort 4, that is the plan. But we want to look at the full data set from Cohort 3.

謝謝你，艾登。好問題。因此，為了其他人的利益，第 1 組為每天兩次 100 毫克，第 2 組相同，總劑量每天一次 200 毫克，第 3 組為每天兩次 200 毫克，而第 4 組，正如您所指出的，每次服用 200-400 毫克，總劑量相同。因此，在決定是否進行第 4 組之前，這就是計劃。但我們想查看第 3 組的完整資料集。

We already have Cohort 1 and 2. We'll look at the data from Cohort 3, and then we'll decide whether we would do that or not. Right now the plan is to do that, although we are thinking about other possibilities, like, extending duration of therapy. Each of the doses 100, 200, 400 is very good occupancy of the receptor.

我們已經有第 1 組和第 2 組了。我們將查看第 3 組的數據，然後決定是否要這樣做。目前的計劃是這樣做，儘管我們正在考慮其他可能性，例如延長治療時間。劑量 100、200、400 均能很好地佔據受體。

And, of course, as I've indicated in previous calls, we don't really know what it takes to get a clinical effect or biologic effect in atopic dermatitis, whether you really need a 100% occupancy. But even at our starting dose of 100, there's pretty good occupancy. So right now the plan is to do Cohort 4, but before we decide definitively on that, we want to look at our data.

當然，正如我在先前的電話會議中所指出的，我們並不真正知道如何在異位性皮膚炎中獲得臨床效果或生物學效果，是否真的需要 100% 的佔用率。但即使我們的起始劑量為 100，佔用率也相當高。所以現在的計劃是進行第 4 組，但在我們最終決定之前，我們想查看我們的數據。

That makes sense. And regarding the prior therapies, I know that many of those patients previously failed to fix in first two cohorts. How about the Cohort 3? Did you see the patients --sorry they're DUPIXENT naive, sorry, the first two cohorts. So is the Cohort 3 also sort of mostly DUPIXENT naive patients?

這很有道理。關於先前的治療方法，我知道許多患者在前兩組治療中都未能治癒。第三組怎麼樣？你看到病人了嗎——對不起，他們很天真，對不起，是前兩組。那麼第 3 組是否也大多是未接受過 DUPIXENT 治療的患者？

We have deliberately searched for sicker patients in Cohort 3. So we do have more DUPIXENT and systemic treatment failures in Cohort 3. We also have, so far, I mean, we're not done with the cohort. We do appear to have higher baseline EASI scores. So we'll have to look at that and we'll see how that turns out, whether there's a particularly good or effect in dupi failures, we don't know yet. We don't really know how that variable fits in yet.

我們特意在第 3 組尋找病情更嚴重的患者。因此，在第 3 組中，我們確實有更多的 DUPIXENT 和全身治療失敗。到目前為止，我們還沒有完成這個團體的工作。我們的 EASI 基線分數確實看起來更高。所以我們必須研究這一點，看看結果如何，對於 dupi 失敗是否有特別好的影響，我們還不知道。我們實際上還不知道該變數是如何發揮作用的。

Okay, understood. And the last one is the biomarker question. I think you mentioned that you will be talking about biomarkers in May. So could you elaborate a little bit on that? What kind of biomarkers are out there for atopic dermatitis?

好的，明白了。最後一個是生物標記問題。我想您提到您將在五月討論生物標誌物。那你能詳細說明一下嗎？異位性皮膚炎有哪些類型的生物標記？

Well, I would say that some of the work that we presented back in January on biomarkers or in December, is being confirmed in our ongoing studies. In addition, we've picked up a couple of other things that I think are quite interesting. I've been talking about, we've been talking and studying these deregulatory suppressor cells and other cells, and I think those are turning out to be extremely interesting.

嗯，我想說的是，我們在一月份或十二月提出的一些有關生物標誌物的研究正在我們正在進行的研究中得到證實。此外，我們還發現了一些我認為非常有趣的事情。我一直在談論，我們一直在討論和研究這些失調的抑制細胞和其他細胞，我認為它們變得非常有趣。

We continue to see a very durable effect of our treatment in patients who receive the drug. And, I mean, it's a small data set, it's very early, but it's also very provocative at this point.

我們持續看到接受該藥物治療的患者獲得非常持久的治療效果。而且，我的意思是，這是一個很小的資料集，還處於非常早期的階段，但目前它也非常具有啟發性。

Okay. Understood. Thanks so much.

好的。明白了。非常感謝。

Graig Suvannavejh, Mizuho Securities.

Graig Suvannavejh，瑞穗證券。

Hi, this is Sam on for Graig. Thanks for taking our questions. Maybe one on ALPS, just given that it's a new indication. Can you just tell us in terms of like the addressable patient population that you guys are kind of due diligence? And also, what if there's a subset of patients that would be ideal candidates for soquelitinib among people with ALPS? Thank you.

大家好，我是 Sam，代表 Graig。感謝您回答我們的問題。也許是 ALPS 上的一個，只是因為它是一個新的跡象。您能否就可尋址患者群體告訴我們，你們進行了怎樣的盡職調查？此外，如果 ALPS 患者中有一部分患者是索奎替尼的理想候選人，那該怎麼辦？謝謝。

Okay, so in the United -- so ALPS or ALPS, autoimmune lymphoproliferative syndrome is a genetic disease. You're born with it. I'll give you a little background on the disease. Babies are born with it. They at around age two, they start to develop anemia and big spleen and lymphadenopathy, infections, and they get a diagnosis made, of course. And then they're on lifelong immunosuppressive therapies, cyclophosphamide, steroids, mTOR inhibitors, things like that.

好的，所以在美國——ALPS 或 ALPS，自體免疫淋巴增生綜合症是一種遺傳性疾病。這是你生來就有的。我將向您介紹一下這種疾病的背景。嬰兒一出生就有這種症狀。他們在兩歲左右開始出現貧血、脾臟腫大、淋巴結腫大和感染，當然，他們會得到診斷。然後他們就要接受終生免疫抑制治療，使用環磷酰胺、類固醇、mTOR 抑制劑等藥物。

And they can be on that a long time. The disease is not curable, and they'll have waxing and waning adenopathy and cytopenia, anemia, neutropenia, thrombocytopenia. They can live 30, 40, 50 years old now. But they suffer a lot of the complications. They have massive splenomegaly, that's another problem they have with sometimes can rupture.

而且他們可以堅持很久。這種疾病無法治愈，患者會出現淋巴結腫大和血球減少、貧血、嗜中性白血球減少、血小板減少等症狀。現在它們可以活30、40、50歲。但他們卻遭遇了許多併發症。他們有嚴重的脾腫大，這是他們的另一個問題，有時會破裂。

A subset of these patients, maybe 10%, 20%, go on to develop malignant lymphomas. Usually they're B cell lymphomas. But the abnormal cell in the ALPS is a T cell. It's an abnormal T cell called the double negative T cell that does not have CD8 or CD4. I won't go into the biology of it, but it has a lot of ITK expression.

這些患者中的一部分，大概有 10%、20%，會發展為惡性淋巴瘤。通常是B細胞淋巴瘤。但ALPS中的異常細胞是T細胞。這是一種異常 T 細胞，稱為雙陰性 T 細胞，不具有 CD8 或 CD4。我不會深入研究它的生物學特性，但它有很多 ITK 表達。

And in our work looking at the effect of soquelitinib in various murine autoimmune models, we found that the same -- there's a strain of mouse called the MRL/lpr negative mouse that has the very same mutation that you see in these patients, same disease basically, genetically. And when we treated animals with our drug, it was dramatically effective, really dramatically effective.

當我們研究索奎替尼對各種小鼠自體免疫模型的影響時，我們發現了相同的情況——有一種稱為 MRL/lpr 陰性小鼠的小鼠品系，它具有與這些患者身上看到的完全相同的突變，從基因上來說，基本上是相同的疾病。當我們用我們的藥物治療動物時，效果顯著，真的非常顯著。

Cytopenias' go reverse and become normal, splenomegaly, lymphadenopathy, all that thing, basically these animals become normal. And so that prompted us to say, hey, let's go treat the human genetic -- identical genetic disease in humans. And that led us to the NIAID that has a very big collection of these patients.

血球減少症會逆轉並恢復正常，脾腫大、淋巴結腫大等所有症狀，基本上這些動物都會恢復正常。這促使我們說，嘿，讓我們去治療人類遺傳疾病──人類相同的遺傳疾病。這讓我們了解到 NIAID 收集了大量此類患者。

Now, most pediatric hospitals have patients like this and you asked about the market. There are about 2,500 patients with this disease in the United States currently. They live a long time. They live to be age 40, 50, as I said, some die sooner, but that in general is their lifespan. .

現在大部分兒科醫院都有這樣的病人，你問的是市場狀況。目前美國約有2500名患者患有此病。他們壽命很長。它們的壽命為 40、50 歲，正如我所說，有些人死得更早，但一般來說這就是他們的壽命。。

I don't think there's any particular subset that would be, not to our knowledge now, that would be more or less amenable to this therapy. So we just don't know. Sometimes there are slightly different mutations in patients, but the main problem in the mouse and in the human beings is that their cells, their lymphocytes do not undergo apoptosis.

我認為，就我們目前所知，沒有任何特定的亞群會或多或少適合這種療法。所以我們只是不知道。有時患者體內的突變會略有不同，但小鼠和人類的主要問題是他們的細胞、淋巴球不會凋亡。

Now, there's a very strong connection between T cell receptor signaling an apoptosis. Think about it. When there's antigen or you have an infection, you want your T cells to proliferate, kill off the infection, but then you want those T cells to go away when the infection is eliminated. That requires apoptosis. That is regulated by ITK. ITK has many roles in various signaling pathways, and when you block ITK, you restore apoptosis to these cells. And so that's the rationale for this.

現在，T 細胞受體訊號與細胞凋亡之間存在著非常緊密的關聯。想一想。當存在抗原或感染時，您希望 T 細胞增殖，殺死感染，但當感染消除時，您希望這些 T 細胞消失。這需要細胞凋亡。這是受 ITK 監管的。ITK 在各種訊號路徑中發揮多種作用，當你阻斷 ITK 時，你就會恢復這些細胞的凋亡。這就是這個現象的理由。

So basically, this is a treatment that I think you would take for a long time. And given the safety we've seen so far, we think this could be very important. Now, also from a regulatory standpoint, this is not a disease I don't think where you're going to be asked to do big randomized clinical trials. So that's something else to think about.

所以基本上，我認為這是一種需要長期接受的治療。鑑於我們迄今為止所看到的安全性，我們認為這可能非常重要。現在，從監管的角度來看，我認為這不是一種需要進行大型隨機臨床試驗的疾病。所以這是另外需要考慮的事情。

We're very excited and interested in this disease, you can tell by my long-winded answer. And then finally, what this does is, I mean, this is really an opportunity to look at the effect of our drug on all sorts of autoimmune manifestations, anti-red cell antibodies, antiplatelet antibodies, all that sort of stuff which we think will have important relevance to other autoimmune diseases.

我們對這種疾病非常興奮和感興趣，您可以從我冗長的回答中看出來。最後，我的意思是，這確實是一個機會來觀察我們的藥物對各種自體免疫表現、抗紅血球抗體、抗血小板抗體​​等所有我們認為與其他自體免疫疾病具有重要相關性的物質的影響。

Does that answer your question? Probably.

這回答了你的問題嗎？大概。

Definitely, very insightful. Thanks so much, Richard, for taking our question.

絕對非常有見地。非常感謝理查德回答我們的問題。

Roger Song, Jefferies.

傑富瑞 (Jefferies) 的羅傑宋 (Roger Song)。

Hi, this is Cha Cha Yang on for Roger. I'm looking towards your Phase 2 for AD, and I'm wondering if you can give some color on what subpopulations within the disease you're hoping to target. More specifically, if you could talk about aspects like prior medication use based on EASI scores, and then any geography and demographics insights, that would be great.

大家好，我是 Cha Cha Yang，為 Roger 播報。我正在期待您針對 AD 的第二階段研究，並想知道您是否可以詳細說明您希望針對的疾病亞群。更具體地說，如果您可以談論基於 EASI 分數的先前藥物使用情況等方面，以及任何地理和人口統計見解，那就太好了。

Well, that's a pretty tough question considering we haven't finished Phase 1 yet, but moderate to severe atopic dermatitis, failed topical corticosteroids, or a systemic therapy, very similar to the criteria we're using now. I don't know if I would require, I mean, baseline EASI scores to be moderate or 16 or greater. So I don't think we would have any requirements beyond that.

嗯，這是一個相當棘手的問題，因為我們還沒有完成第一階段，但是中度至重度異位性皮膚炎、局部皮質類固醇治療失敗或全身性治療，與我們現在使用的標準非常相似。我不知道我是否要求，我的意思是，基線 EASI 分數為中等或 16 或更高。所以我認為我們不會有任何超出此範圍的要求。

I think a typical study would be look at two different dose levels, plus a placebo, so probably a three-arm study, maybe around 200 patients total. But that's an, kind of, an approximate answer at this point. But that's all pretty standard.

我認為一項典型的研究會檢視兩種不同的劑量水平，加上安慰劑，所以可能是一項三組研究，總共約有 200 名患者。但這只是目前的一個近似答案。但這一切都非常標準。

Sounds good.

聽起來不錯。

And but in the endpoint would be either EASI 75, those who achieve EASI 75 or IGA 0 or 1. That's pretty standard in point now.

但終點要么是 EASI 75，即達到 EASI 75 的人，要么是 IGA 0 或 1。現在這一點已經相當標準了。

Great. Thank you for that.

偉大的。謝謝你。

Li Watsek, Cantor.

李·瓦特塞克，領唱。

Hi team. This is [Daniel Bronder] on for Li. I have a question about the prioritizing of opportunities for soquel in oncology versus inflammatory disease and how you look at it as you move into later stage trials?

大家好。我是 [Daniel Bronder]，代表李播報。我有一個問題，關於 Soquel 在腫瘤學和發炎性疾病領域的機會優先順序，以及您在進入後期試驗時如何看待它？

Okay. Well, right now we have soquelitinib in a Phase 3 registration trial that could produce data in less than two years. And so we're pushing on all fronts as aggressively as we can. So the strategy is try to get an approval in lymphoma, try to get an approval in immune disease. Now, we are aware of some of the issues with having a similar-same drug for autoimmune disease and cancer.

好的。嗯，現在我們正在進行索奎替尼的 3 期註冊試驗，可以在不到兩年的時間內產生數據。因此，我們正在盡最大努力在各個方面做出積極努力。因此，我們的策略是嘗試獲得淋巴瘤的批准，嘗試獲得免疫疾病的批准。現在，我們意識到使用類似藥物治療自體免疫疾病和癌症存在一些問題。

We have a very aggressive program in second- and third-generation compounds. We also think that the dosing and duration of therapy are going to be very different in oncology versus immunology. A very good example would be RITUXAN, for example, which, came out of my lab at IDEC.

我們在第二代和第三代化合物方面有非常積極的計劃。我們也認為，腫瘤學和免疫學的治療劑量和治療持續時間將會有很大不同。一個很好的例子就是 RITUXAN，它是由我在 IDEC 的實驗室所研發的。

RITUXAN is approved for lymphomas, as it's also approved for rheumatoid arthritis, pemphigus, ITP and probably a few more autoimmune diseases. And it is really no issue with pricing because the treatment regimens are such that on a per milligram basis, it turns out to be pretty similar.

RITUXAN 已被批准用於治療淋巴瘤，因為它也被批准用於治療類風濕性關節炎、天皰瘡、ITP 以及其他一些自體免疫疾病。這其實不是定價問題，因為治療方案以毫克計算結果非常相似。

So our strategy now is push forward on all these fronts and get deeper and deeper into the pipeline and at some point of course, we recognize that autoimmune diseases is a vast undertaking. There's many different diseases and competitive areas and of course, we would at the right time consider some sort of a collaboration or partnership.

因此，我們現在的策略是在所有這些方面向前推進，並不斷深入研究，當然，在某種程度上，我們認識到自體免疫疾病是一項艱鉅的任務。有許多不同的疾病和競爭領域，當然，我們會在適當的時候考慮某種形式的合作或夥伴關係。

Okay, cool. Thank you so much for that detailed answer. And the other question we were wondering about is you alluded to earlier a little bit. The delay in the presentation of Cohort 4, is that more driven by your waiting and seeing of Cohort 3 results or has there been a delay in enrollment more generally?

好的，很酷。非常感謝您如此詳細的回答。我們想知道的另一個問題是您之前稍微提到的。組別 4 學生的展示延遲，是否更多是由於您等待第 3 組學生的結果，還是因為招生普遍延遲？

No delay in enrollment. We're waiting to see the data from Cohort 3, and we'll make a decision about proceeding with Cohort 4, or maybe, extend one of the other cohorts.

入學無延誤。我們正在等待第 3 組的數據，然後決定是否繼續第 4 組，或擴展其他組之一。

Okay, cool. Thank you so much.

好的，很酷。太感謝了。

Sean Lee, H.C. Wainright.

李（H.C.）溫賴特。

Hi. Good afternoon and thanks for taking my question. I just have one on the upcoming solid tumor study that's been planned. I was wondering whether there are specific indications that you feel are most suitable for circulated or would it be just a general basket study? And also, would you need to do a dose escalation again or would you start with the PTCR dose? Thanks.

你好。下午好，感謝您回答我的問題。我剛剛了解了即將進行的實體腫瘤研究計畫。我想知道您是否認為有最適合流通的具體跡象，或者這只是一項一般性的籃子研究？此外，您是否需要再次增加劑量，或者您是否從 PTCR 劑量開始？謝謝。

So the first part of the question, which tumors? We will start with the immune responsive tumors. So what are those? Those are renal cell cancer, lung cancer would be good. Those would be probably the top choices to start because you want tumors where you think there's some evidence for immunotherapeutic effects. Melanoma might be another one, although that's a much less common disease and is adequately -- somewhat adequately, treated by other treatments.

那麼問題的第一部分是哪些腫瘤呢？我們將從免疫反應性腫瘤開始。那麼這些是什麼？那些是腎細胞癌，肺癌就好了。這些可能是開始的最佳選擇，因為您想要的是那些您認為有證據表明具有免疫治療效果的腫瘤。黑色素瘤可能是另一種疾病，儘管這是一種不太常見的疾病，並且可以透過其他治療方法得到充分治療。

So I would say, renal, lung, I don't think we need to do a dose escalation, but certainly you would want to do different doses. You'd want to look at different doses. It wouldn't be a dose escalation in the usual sense that you're thinking of like a Phase 1 oncology study. But you would probably want to look at different doses.

所以我想說，對於腎臟、肺，我認為我們不需要增加劑量，但你肯定會想要採用不同的劑量。您可能想看看不同的劑量。它不會像您通常所想的那樣像第一階段腫瘤學研究那樣增加劑量。但您可能想看看不同的劑量。

But we have a pretty good handle now on the dose and we have a very good pharmacodynamic marker, which is we know what it takes to saturate the ITK target. 100, 200, 300, or 400, we're all in the same ballpark. They're all going to be give you pretty much the same, similar findings.

但是我們現在對劑量有很好的掌握，我們有非常好的藥效動力學標記，也就是說我們知道達到 ITK 目標需要什麼。 100、200、300 或 400，我們都在同一個範圍內。它們都會給你幾乎相同、相似的發現。

Great. Thanks for that.

偉大的。謝謝。

Thank you. There are no further questions at this time. I would not have a call back to Mr. Richard Miller for any closing remarks.

謝謝。目前沒有其他問題。我不會再打電話給理查德·米勒先生並讓他做任何結束語。

Okay, I want to thank everyone for participating in the call, and we look forward to additional updates in the future. Thank you very much.

好的，我要感謝大家參加電話會議，我們期待未來有更多更新。非常感謝。

Thank you and this concludes today's call. Thank you for participating me all disconnect.

謝謝，今天的通話到此結束。謝謝大家的參與，我斷網了。