Deciphera Pharmaceuticals Inc (DCPH) 2023 Q4 法說會逐字稿

Good morning, everyone, and welcome to Deciphera Pharmaceuticals fourth quarter and full-year 2023 financial results conference call. Today's call is being recorded. At this time, I would like to turn the call over to Jen Larson, Senior Vice President of Finance and Investor Relations. Jen?

大家早安，歡迎參加 Deciphera Pharmaceuticals 2023 年第四季和全年財務業績電話會議。今天的通話正在錄音。現在，我想將電話轉給財務和投資者關係高級副總裁 Jen Larson。珍？

Thank you, operator. Welcome, and thank you for joining us today to discuss Deciphera's fourth quarter and full-year 2023 financial results. I'm Jen Larson, Senior Vice President of Finance and Investor Relations.

謝謝您，接線生。歡迎，感謝您今天加入我們討論 Deciphera 2023 年第四季和全年財務表現。我是財務和投資者關係資深副總裁 Jen Larson。

With me this morning to discuss the financial results and provide a general corporate update are Steven Hoerter, President and Chief Executive Officer; Matt Sherman, Chief Medical Officer; Dan Martin, Chief Commercial Officer; Margarida Duarte, Head of International; and Tucker Kelly, Chief Financial Officer.

今天上午，與我一起討論財務業績並提供公司整體更新情況的有總裁兼首席執行官 Steven Hoerter、首席醫療官 Matt Sherman、首席商務官 Dan Martin、國際業務主管 Margarida Duarte 和首席財務官 Tucker Kelly。

Before we begin, I would like to remind you that any statements we make on this call that are not historical facts are forward-looking statements made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples include our expectations for our pre-clinical and clinical programs, our commercialization of QINLOCK and guidance. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we cannot assure you that our expectations will be achieved. Such risks and uncertainties include those set forth in our most recent annual report on Form 10-K as well as our other SEC filings. We assume no obligation to update or revise any forward-looking statements.

在我們開始之前，我想提醒您，我們在本次電話會議上做出的任何非歷史事實的陳述均為根據 1995 年《私人證券訴訟改革法》的安全港條款做出的前瞻性陳述。例子包括我們對臨床前和臨床計畫的期望、我們對 QINLOCK 的商業化和指導。前瞻性陳述涉及重大風險和不確定性，可能導致實際結果與前瞻性陳述所表達或暗示的結果有重大差異，我們無法向您保證我們的預期將會實現。這些風險和不確定性包括我們最近的 10-K 表年度報告以及我們向美國證券交易委員會提交的其他文件中所述。我們不承擔更新或修改任何前瞻性陳述的義務。

Following this call, a replay will be available on the company's website, www.deciphera.com.

本次電話會議結束後，重播將在公司網站 www.deciphera.com 上提供。

With that, I will now turn the call over to Steven Hoerter, President and Chief Executive Officer of Deciphera. Steve?

現在，我將把電話轉給 Deciphera 總裁兼執行長 Steven Hoerter。史蒂夫？

Thank you, Jen. Good morning, everyone, and thank you for joining us today as we provide an update from the fourth quarter and full year 2023, review our financial results, and discuss our strategic outlook and planned corporate milestones for 2024.

謝謝你，Jen。大家早安，感謝您今天的參加，我們將提供 2023 年第四季度和全年的最新情況，回顧我們的財務業績，並討論我們的戰略展望和 2024 年計劃的公司里程碑。

2023 was a year of significant progress toward our goal of becoming a self-sustaining company with multiple approved medicines. Continued strong QINLOCK growth in the US and internationally drove record annual revenue, demonstrating the global capabilities of our commercial organization.

2023 年是我們朝著成為一家擁有多種核准藥物的自給自足公司的目標邁出的重要一年。QINLOCK 在美國和國際上持續強勁成長，推動了創紀錄的年收入，展現了我們商業組織的全球能力。

With a highly successful Phase 3 study in TGCT, we expect vimseltinib to be our second approved medicine. We believe that at peak, QINLOCK and vimseltinib will be able to generate over $1 billion in global revenue. With a long IP runway for both products, we are actively pursuing label extension opportunities to create further value for patients and for our shareholders.

隨著 TGCT 第 3 階段研究取得巨大成功，我們預計 vimseltinib 將成為我們第二個核准的藥物。我們相信，QINLOCK 和 vimseltinib 在巔峰時期將能夠創造超過 10 億美元的全球收入。憑藉這兩種產品的長期智慧財產權跑道，我們正在積極尋求標籤擴展機會，為患者和股東創造更多價值。

Beyond these late-stage programs, we continue to strategically invest in key earlier-stage programs to help build a sustainable pipeline of potential new medicines to improve the lives of people with cancer.

除了這些後期項目外，我們還繼續對關鍵的早期項目進行策略性投資，以幫助建立可持續的潛在新藥管道，改善癌症患者的生活。

Last month, we outlined our key strategic priorities for 2024. We expect 2024 to be a year of continued growth in QINLOCK sales, driven by strong demand, both in the US and internationally.

上個月，我們概述了 2024 年的主要策略重點。我們預計，受美國和國際強勁需求的推動，2024 年 QINLOCK 銷售將持續成長。

Meanwhile, our clinical team is working towards our goal of expanding QINLOCK's label based on the ongoing Phase 3 INSIGHT study in second-line GIST patients with mutations in KIT exon 11 and 17/18, which has the potential to double peak sales.

同時，我們的臨床團隊正在努力實現擴大 QINLOCK 標籤的目標，該目標基於正在進行的針對 KIT 外顯子 11 和 17/18 突變的二線 GIST 患者的 3 期 INSIGHT 研究，這有可能使峰值銷售額翻一番。

A few weeks ago, we were thrilled to announce the publication in Nature Medicine of the exceptional results from the ctDNA analysis from the INTRIGUE study in second-line patients with mutations in KIT exon 11 and 17/18, showing that QINLOCK provided significant progression-free and overall survival benefit compared to the current standard of care, sunitinib. Publication in one of the world's leading medical journals highlights the clinical importance of this compelling data and serves as strong validation for the ongoing INSIGHT study.

幾週前，我們很高興地宣布，在《自然醫學》雜誌上發表了 INTRIGUE 研究對 KIT 外顯子 11 和 17/18 突變的二線患者的 ctDNA 分析的出色結果，表明與目前的標準治療舒尼替尼相比，QINLOCK 提供了顯著的無進展生存期和總體生存期益處。在世界領先的醫學期刊之一上發表的文章凸顯了這一令人信服的數據的臨床重要性，並為正在進行的 INSIGHT 研究提供了有力的驗證。

In addition to the Nature Medicine publication, we also recently presented the final overall survival results from the INTRIGUE study at the ASCO GI symposium, which showed that the overall survival rate was similar for both QINLOCK and sunitinib, and the treatment with QINLOCK continued to show a favorable safety profile compared to treatment with sunitinib. We believe that these results demonstrate the strong clinical activity of QINLOCK in the second-line GIST patient population studied in INTRIGUE.

除了《自然醫學》雜誌的論文外，我們最近還在 ASCO GI 研討會上展示了 INTRIGUE 研究的最終總體生存結果，該結果顯示 QINLOCK 和舒尼替尼的總體生存率相似，並且與舒尼替尼治療相比，QINLOCK 治療繼續顯示出良好的安全性。我們相信這些結果證明了 QINLOCK 在 INTRIGUE 研究的二線 GIST 患者群體中具有強大的臨床活性。

For vimseltinib, building upon the exciting positive results of the MOTION Phase 3 study in patients with tenosynovial giant cell tumor, we remain on track to submit the NDA to the FDA in the second quarter of this year, and an MAA to the EMA in the third quarter of this year.

對於 vimseltinib，基於 MOTION 第 3 階段研究在腱鞘鉅細胞瘤患者中取得的令人興奮的積極成果，我們仍有望在今年第二季度向 FDA 提交 NDA，並在今年第三季度向 EMA 提交 MAA。

With the potential approval of vimseltinib INSIGHT, we are also exploring potential indication expansion opportunities, including our plan to initiate a Phase 2 proof-of-concept study of vimseltinib for the treatment of chronic graft versus host disease, or cGVHD, in the fourth quarter of 2024.

隨著 vimseltinib INSIGHT 的潛在批准，我們也正在探索潛在的適應症擴展機會，包括計劃在 2024 年第四季度啟動 vimseltinib 用於治療慢性移植物抗宿主疾病 (cGVHD) 的 2 期概念驗證研究。

In addition, we're making focused investments in our earlier-stage pipeline, which we expect will fuel our future growth. For our ULK inhibitor, DCC-3116, our goal is to select a recommended Phase 2 dose later this year and move to our first expansion cohort. For DCC-3084, our pan-RAF inhibitor, we expect to initiate a Phase 1 study in the first half of this year.

此外，我們正在對早期階段的產品線進行重點投資，預計這將推動我們未來的成長。對於我們的 ULK 抑制劑 DCC-3116，我們的目標是在今年稍後選擇建議的 2 期劑量並進入我們的第一個擴展隊列。對於我們的泛 RAF 抑制劑 DCC-3084，我們預計將在今年上半年啟動第一階段研究。

Finally, for DCC-3009, our new pan-KIT inhibitor, we expect to submit an IND to FDA in the first half of this year and initiate a Phase 1 study in the second half of 2024.

最後，對於我們的新型泛 KIT 抑制劑 DCC-3009，我們預計將在今年上半年向 FDA 提交 IND，並在 2024 年下半年啟動第 1 階段研究。

We remain well capitalized with $352 million in cash at the end of the year and a cash runway into the second half of 2026.

我們的資本充足，年底擁有 3.52 億美元現金，到 2026 年下半年還有充足的現金儲備。

I'll now pass the call to Matt Sherman, our Chief Medical Officer, who will provide more detail on our development pipeline. Dan Martin, our Chief Commercial Officer, will then share insights on the US commercial performance and outlook for the year ahead. Margarida Duarte, our Head of International, will provide an update on the progress of the ongoing QINLOCK launch in Europe for fourth-line GIST and its continued strong momentum. We'll end with Tucker Kelly, our Chief Financial Officer, who will review highlights from the fourth quarter and full year 2023 financial results.

我現在將電話轉給我們的首席醫療官馬特·謝爾曼 (Matt Sherman)，他將提供有關我們開發管道的更多細節。我們的首席商務長 Dan Martin 將分享對美國商業表現和未來一年前景的見解。我們的國際主管 Margarida Duarte 將介紹 QINLOCK 在歐洲針對第四線 GIST 的推出的進展及其持續強勁的發展勢頭。最後，我們的財務長 Tucker Kelly 將回顧第四季和 2023 年全年財務表現的亮點。

Matt?

馬特？

Thanks, Steve. Together with our commercial success, we continue to make great strides with our development pipeline that we believe will provide continued growth for Deciphera over the coming years.

謝謝，史蒂夫。除了商業上的成功之外，我們還將繼續在開發管道方面取得長足進步，我們相信這將為 Deciphera 在未來幾年帶來持續的成長。

First, I'd like to start with our recent QINLOCK updates. As Steve mentioned, in January, we presented the final overall survival results from INTRIGUE Phase 3 study at the ASCO GI conference. As you may recall, in the INTRIGUE trial, 453 patients with second-line GIST were randomized 1:1 to receive QINLOCK or sunitinib.

首先，我想從我們最近的 QINLOCK 更新開始。正如史蒂夫所提到的，今年 1 月，我們在 ASCO GI 會議上展示了 INTRIGUE 第 3 階段研究的最終整體生存結果。您可能還記得，在 INTRIGUE 試驗中，453 名二線 GIST 患者以 1:1 的比例隨機分配接受 QINLOCK 或舒尼替尼治療。

The final analysis included 18 months of additional follow-up based on the data cut in March 2023. Median overall survival in the intent-to-treat population was very similar with QINLOCK at 35.5 months versus sunitinib at 31.5 months, resulting in a hazard ratio of 0.86. The long-term safety profile was consistent with the primary analysis, showing fewer patients with Grade 3/4 TEAEs and a lower rate of the treatment discontinuations due to TEAEs with QINLOCK versus sunitinib.

最終分析包括基於 2023 年 3 月數據進行的 18 個月的額外追蹤。在意向治療族群中，QINLOCK 組的中位總存活期為 35.5 個月，而舒尼替尼組為 31.5 個月，兩者非常相似，風險比為 0.86。長期安全性與主要分析結果一致，與舒尼替尼組相比，QINLOCK 組的 3/4 級 TEAE 患者較少，且因 TEAE 而停止治療的比例較低。

We also looked at whether treatment in the second line with QINLOCK versus sunitinib, any differential impact on clinical outcomes after third-line treatment. Irrespective of treatment with QINLOCK in the second line, the results show that the patient outcomes in the third line was similar. Median PFS on the next line of therapy was 7.7 months for QINLOCK versus 7.4 months for sunitinib.

我們也研究了 QINLOCK 與舒尼替尼的二線治療是否對三線治療後的臨床結果產生不同的影響。無論二線是否採用 QINLOCK 治療，結果顯示三線患者的結果相似。下一條線治療的中位 PFS：QINLOCK 為 7.7 個月，而舒尼替尼為 7.4 個月。

These final results for INTRIGUE demonstrate that QINLOCK offers similar efficacy versus sunitinib in the second-line GIST population studied in INTRIGUE.

INTRIGUE 的最終結果表明，QINLOCK 在 INTRIGUE 研究的二線 GIST 族群中具有與舒尼替尼相似的療效。

The Nature Medicine publication last month was another major achievement for Deciphera, showcasing the potentially practice-changing results from an exploratory ctDNA analysis from INTRIGUE in one of the world's leading medical journals.

上個月在《自然醫學》雜誌上發表的文章是 Deciphera 的另一項重大成就，在世界領先的醫學期刊之一上展示了 INTRIGUE 的探索性 ctDNA 分析可能改變實踐的結果。

In second-line GIST patients with KIT exon 11 and 17/18 mutations, treatment with QINLOCK resulted in a 78% reduction in the risk of disease progression, and a 66% reduction in the risk of death compared to sunitinib. Median PFS was 14.2 months for the QINLOCK patients compared to only 1.5 months for the sunitinib patients. Median overall survival for QINLOCK was not reached, versus 17.5 months for sunitinib. QINLOCK showed an objective response rate of 44% compared to 0% for sunitinib.

對於患有 KIT 外顯子 11 和 17/18 突變的二線 GIST 患者，與舒尼替尼相比，使用 QINLOCK 治療可使疾病惡化風險降低 78%，死亡風險降低 66%。QINLOCK 患者的中位 PFS 為 14.2 個月，而舒尼替尼患者的中位 PFS 僅為 1.5 個月。QINLOCK 的中位總存活期未達到，而舒尼替尼的中位總存活期為 17.5 個月。QINLOCK 的客觀反應率為 44%，而舒尼替尼的客觀反應率為 0%。

Together, the data represents a striking clinical benefit to these second-line GIST patients when treated with QINLOCK.

總的來說，這些數據表明，使用 QINLOCK 治療這些二線 GIST 患者俱有顯著的臨床益處。

We're excited that our INSIGHT pivotal Phase 3 study in the same patient population is now actively enrolling patients. If positive, we believe the results of the INSIGHT study will support and extend the label for QINLOCK and significantly improve clinical outcomes for patients based on the precise understanding of the GIST tumors.

我們很高興，我們針對同一患者群體的 INSIGHT 關鍵性 3 期研究目前正在積極招募患者。如果結果呈陽性，我們相信 INSIGHT 研究的結果將支持並擴展 QINLOCK 的標籤，並在對 GIST 腫瘤的精確了解的基礎上顯著改善患者的臨床結果。

We are also working hard to get our second potential approved medicine to patients as quickly as possible. We remain on track to submit an NDA for vimseltinib for patients with TGCT in the second quarter of 2024, and an MAA in the third quarter of 2024. These filings are supported by the outstanding success of the Phase 3 MOTION study, which achieved its primary endpoint of ORR at week 25 as well as all six key secondary endpoints.

我們也正在努力盡快將第二種可能核准的藥物提供給患者。我們仍計劃於 2024 年第二季為 TGCT 患者提交 vimseltinib 的 NDA，並於 2024 年第三季提交 MAA。這些申請得到了第 3 階段 MOTION 研究的出色成功的支持，該研究在第 25 週實現了 ORR 的主要終點以及所有六個關鍵次要終點。

In a disease such as TGCT, the secondary endpoints are critical measures of clinical benefit. These outcomes of how patients deal and function plays an incredibly important role in treatment decisions as well as for patients' interest in starting and staying on drug therapy. TGCT can be a difficult chronic condition associated with severe pain, swelling, stiffness, and loss of mobility. All of these can severely limit patients' daily activities and quality of life, including their ability to continue to work or function independently.

對於諸如 TGCT 之類的疾病，次要終點是臨床益處的關鍵指標。患者的處理和功能結果對於治療決策以及患者開始和繼續藥物治療的興趣起著極其重要的作用。TGCT 是一種難以治癒的慢性疾病，會引發劇烈疼痛、腫脹、僵硬和行動不便等症狀。所有這些都會嚴重限制患者的日常活動和生活質量，包括他們繼續工作或獨立活動的能力。

Without an effective treatment, a TGCT diagnosis can have a profound impact on their ability to lead a normal, active, and healthy life. And we look forward to making this important new medicine available to these patients as quickly as possible.

如果沒有有效的治療，TGCT 診斷會對她們過正常、積極和健康的生活的能力產生深遠的影響。我們期待盡快為這些患者提供這種重要的新藥。

We plan to present results from the MOTION study at a major medical meeting in the second quarter of 2024 as well as the updated results from the ongoing Phase 1/2 study in the second half of this year. Deciphera remains committed to ensuring that the full therapeutic potential of medicine and product candidates are explored. To that end, we plan to initiate a Phase 2 proof-of-concept study of vimseltinib and Chronic GVHD based on its potential as a best-in-class CSF1 receptor inhibitor.

我們計劃在 2024 年第二季的大型醫學會議上展示 MOTION 研究的結果，並在今年下半年展示正在進行的 1/2 期研究的最新結果。Deciphera 始終致力於確保探索藥物和候選產品的全部治療潛力。為此，我們計劃啟動 vimseltinib 和慢性 GVHD 的 2 期概念驗證研究，基於其作為同類最佳 CSF1 受體抑制劑的潛力。

Chronic GVHD affects 30% to 50% of allogeneic hematopoietic stem cell transplant recipients, with an estimated 14,000 prevalent patients in the US. There is a significant unmet medical need in this setting, with 50% of patients being refractory to treatment with steroids, and overall desire to move towards combination therapy.

慢性 GVHD 影響 30% 至 50% 的異體造血幹細胞移植接受者，美國估計有 14,000 名患病患者。在這種情況下，存在著巨大的未滿足的醫療需求，50％的患者對類固醇治療有抵抗力，並且總體上希望轉向聯合治療。

Inhibiting CSF1 receptor expressing pro-inflammatory and pro-fibrotic macrophages has been clinically validated for patients with GVHD based on the recent pivotal study, with an antibody targeting the CSF1 receptor.

根據最近的關鍵研究，使用針對 CSF1 受體的抗體抑製表達促炎和促纖維化的巨噬細胞的 CSF1 受體已針對 GVHD 患者進行了臨床驗證。

As an oral agent, vimseltinib may offer a best-in-class CSF1 receptor option as a single agent or in combination with other oral therapies. We expect to initiate a proof-of-concept study by the end of this year, putting us on a path to potentially expand the utility of vimseltinib for patients in the future.

作為口服藥物，vimseltinib 可以作為單一藥物或與其他口服療法聯合使用，提供一流的 CSF1 受體選擇。我們預計將在今年年底前啟動一項概念驗證研究，這將使我們在未來有可能擴大 vimseltinib 對患者的實用性。

Beyond QINLOCK and vimseltinib, we remain very excited about the potential for our clinical and research pipeline to fuel Deciphera's growth.

除了 QINLOCK 和 vimseltinib 之外，我們仍然對我們的臨床和研究管道推動 Deciphera 發展的潛力感到非常興奮。

As Steve mentioned earlier, we expect to select a recommended Phase 2 dose for DCC-3116 in 2024 to move into our first expansion cohort. We also expect to initiate a Phase 1 study for DCC-3084 in the first half of 2024. Finally, we expect to submit an IND for DCC-3009 with the FDA in the first half of 2024 and initiate a Phase 1 study in the second half of 2024.

正如史蒂夫之前提到的，我們預計將在 2024 年為 DCC-3116 選擇建議的 2 期劑量，以進入我們的第一個擴展隊列。我們也預計將在 2024 年上半年啟動 DCC-3084 的第 1 階段研究。最後，我們預計將於 2024 年上半年向 FDA 提交 DCC-3009 的 IND，並於 2024 年下半年啟動第 1 階段研究。

I will now turn the call over to Dan Martin to discuss our US commercial updates. Dan?

現在我將把電話轉給丹馬丁 (Dan Martin)，討論我們的美國商業更新。擔？

Thanks, Matt. 2023 was a very successful year for QINLOCK in the US, with net product revenue growing to $121.5 million, a 25% increase over 2022. In the fourth quarter, US net product revenue was $35.3 million, a 38% increase over Q4 2022. These record results were driven by strong demand in our core fourth-line business, increasing average duration of therapy, and contribution from unpromoted earlier line use.

謝謝，馬特。 2023 年對 QINLOCK 在美國來說是非常成功的一年，淨產品收入成長至 1.215 億美元，比 2022 年成長 25%。第四季度，美國淨產品收入為 3,530 萬美元，比 2022 年第四季成長 38%。這些創紀錄的業績得益於我們核心四線業務的強勁需求、治療平均持續時間的增加以及未推廣的早期線使用的貢獻。

In Q4, the percentage of total demand that was fulfilled through our patient assistance program, or PAP, was at the high end of our 20% to 30% expected range and gross to net was between 15% and 20%.

在第四季度，透過我們的病患援助計畫（PAP）滿足的總需求百分比處於我們預期的 20% 至 30% 範圍的高端，毛利率與淨利率之比在 15% 至 20% 之間。

Looking at 2023 as a whole, consistent with prior years, PAP was between 20% and 30%, and we expect the PAP percentage to be similar in 2024. Gross to net in 2023 was between 15% and 20%, and we expect it to be in a similar range in 2024 as a result of the Medicare inflation rebates required by the Inflation Reduction Act.

縱觀 2023 年全年，與前幾年一致，PAP 在 20% 到 30% 之間，我們預計 2024 年的 PAP 百分比將與之相似。2023 年的總額與淨額比率在 15% 至 20% 之間，我們預計，由於《通貨膨脹削減法案》要求的醫療保險通貨膨脹回扣，2024 年的總額與淨額比率將處於類似的範圍內。

We expect continued QINLOCK revenue growth in 2024, driven by a physician as the standard of care in fourth-line GIST, potential unpromoted off-label use in earlier lines of therapy based on physician decision, as well as increasing average duration of therapy.

我們預計 2024 年 QINLOCK 收入將繼續增長，這得益於醫生將其作為四線 GIST 的護理標準、根據醫生的決定在早期治療中潛在的未推廣的標籤外使用，以及治療平均持續時間的增加。

Further, we expect quarterly revenues this year to follow a similar pattern to what we have seen in prior years, including Q1 seasonality consistent with industry dynamics. We remain confident in the strength of our business and the potential for another record year for QINLOCK in 2024.

此外，我們預計今年的季度營收將遵循與前幾年類似的模式，包括與產業動態一致的第一季季節性。我們對我們的業務實力以及 QINLOCK 在 2024 年再創紀錄的潛力充滿信心。

Now, I will turn to the exciting opportunity we see in TGCT with vimseltinib, our potential second approved medicine. Based on our analysis of US claims data, we believe the total addressable market for TGCT in the US is approximately $700 million based on the estimated 1,400 treatment incident patients who are diagnosed, received systemic therapy, and have recently engaged with an oncologist.

現在，我將談談我們在 TGCT 中看到的令人興奮的機會，即我們潛在的第二種獲批藥物 vimseltinib。根據我們對美國索賠數據的分析，我們認為，基於估計有 1,400 名接受診斷、接受全身治療並最近與腫瘤科醫生接洽的治療事件患者，美國 TGCT 的總目標市場約為 7 億美元。

This US opportunity does not include the estimated 9,000 prevalent patients seen by oncologists or the estimated 1,300 treatment incident patients seen by surgeons.

美國的這一機會不包括腫瘤科醫生接診的約 9,000 名患病患者或外科醫生接診的約 1,300 名治療事件患者。

We believe there is a comparable number of patients in the five largest European markets where there are no approved treatments. We recently provided additional insight into the treatment landscape for these 1,400 treatment incident patients in the US that has increased our confidence in the market opportunity and in our commercial team's ability to reach these patients given our deep experience in GIST.

我們相信，在歐洲五大尚未獲得批准的治療方法中，也有相當數量的患者。我們最近對美國這 1,400 名治療事件患者的治療前景提供了額外的見解，鑑於我們在 GIST 領域的豐富經驗，這增強了我們對市場機會以及我們的商業團隊接觸這些患者的能力的信心。

Based on our claims analysis, we believe there is a 70% to 80% overlap in the prescriber base for GIST and TGCT, and that we are uniquely positioned to drive awareness and use in both the academic and community segments. We have tested a blinded product profile of vimseltinib versus pexidartinib, which is approved in the US but not in Europe, and versus imatinib, which is commonly used off-label to manage patients with TGCT.

根據我們的索賠分析，我們認為 GIST 和 TGCT 的處方基礎有 70% 到 80% 的重疊，並且我們在推動學術界和社區領域的認識和使用方面具有獨特的優勢。我們已經測試了 vimseltinib 與 pexidartinib（已在美國獲批但未在歐洲獲批）以及與伊馬替尼（常用於治療 TGCT 患者的非說明書用途）的盲法產品對比情況。

The results from the qualitative market research showed that vimseltinib is rated the highest across the key measures of efficacy and tolerability that physicians tell us they view as most important when selecting the TKI to treat their TGCT patients.

質性市場研究的結果顯示，在醫師選擇 TKI 治療 TGCT 患者時，他們認為維姆司替尼在療效和耐受性等關鍵指標中評價最高，而這些指標是他們認為最重要的。

In the same market research study, 100% of physicians surveyed selected the vimseltinib profile as their preferred agent for managing patients with TGCT. We are working diligently on prelaunch activities as we prepare to leverage our strong commercial capabilities to launch vimseltinib rapidly upon approval.

在同一項市場調查中，100% 受調查的醫生選擇 vimseltinib 作為治療 TGCT 患者的首選藥物。我們正在努力進行上市前活動，準備利用我們強大的商業能力在獲得批准後迅速推出 vimseltinib。

I will now turn the call over to Margarida Duarte, our Head of International, to discuss the progress of the QINLOCK launch in Europe. Margarida?

現在，我將把電話轉給我們的國際主管 Margarida Duarte，討論 QINLOCK 在歐洲推出的進展。瑪格麗達？

Thanks, Dan. We are very enthusiastic about the notable achievements we made in 2023 in our international business, delivering strong results that accounted for more than 25% of Deciphera's total revenue while laying the foundation for future growth.

謝謝，丹。我們對 2023 年國際業務的顯著成就感到非常興奮，取得了強勁的業績，佔 Deciphera 總收入的 25% 以上，同時也為未來的成長奠定了基礎。

In 2023, QINLOCK generated $37.5 million in international net product revenue, up 33% from 2022, as well as $4.3 million in collaboration revenue from our partner, Zai Lab, in Greater China.

2023年，QINLOCK 的國際淨產品收入為 3,750 萬美元，較 2022 年成長 33%，同時來自大中華區的合作夥伴 Zai Lab 的合作收入為 430 萬美元。

For the fourth quarter of 2023, international net product revenue increased 56% from fourth quarter of last year to $11.4 million, and collaboration revenue was an additional $1.6 million.

2023 年第四季，國際淨產品收入較去年第四季成長 56%，達到 1,140 萬美元，合作收入又增加了 160 萬美元。

Last year was a milestone year for Europe, with growth across the entirety of the business, strong price outcomes, significant progress in market access in multiple countries and the launch in Italy, which is off to an excellent start.

去年對歐洲來說是具有里程碑意義的一年，整個業務實現了成長，價格表現強勁，在多個國家的市場准入取得了重大進展，並且在義大利的推出也取得了良好的開端。

The initial strong results we are seeing in Italy are a testament to the high unmet medical needs, the exceptional KOL advocacies, and a remarkable full innovation rating granted to QINLOCK by the Italian authority, the highest for a non-curative disease, which has significantly accelerated the launch in the many Italian regions. Our recent entry in Italy is a good example of the type of opportunity that remains to be unlocked in Europe, and underscores the importance of geographic expansion to overall growth in the business.

我們在義大利看到的初步強勁業績證明了巨大的未滿足醫療需求、卓越的 KOL 倡導以及義大利當局授予 QINLOCK 的卓越全面創新評級，這是非治癒性疾病的最高評級，這大大加速了該藥物在義大利許多地區的上市。我們最近進入義大利市場是一個很好的例子，顯示歐洲仍有待開發的機會，並強調了地域擴張對業務整體成長的重要性。

Last month, we announced a new distribution agreement with Genesis Pharma for Central and Eastern Europe to expand the geographic reach of QINLOCK to 14 European Union countries, with a combined population of 118 million people. QINLOCK has already received regulatory approval in all of these countries under the EMI umbrella, which will significantly accelerate the time to commercialization for Central and Eastern Europe.

上個月，我們宣布與 Genesis Pharma 達成針對中歐和東歐的新分銷協議，將 QINLOCK 的地理覆蓋範圍擴大到 14 個歐盟國家，總人口達 1.18 億。QINLOCK 已在 EMI 旗下所有這些國家獲得監管部門的批准，這將大大加快中歐和東歐的商業化時間。

We are also excited to announce that we have submitted for pricing and reimbursement in the Netherlands, and continue to address price negotiations in Spain, France and Switzerland. Our key growth drivers for 2024 include a continued focus on geographic expansion and open new markets to drive successful launches.

我們也很高興地宣布，我們已經在荷蘭提交了定價和報銷申請，並繼續在西班牙、法國和瑞士進行價格談判。我們 2024 年的主要成長動力包括繼續關注地域擴張和開拓新市場以推動成功發布。

We are very pleased by the strength of our execution, and we expect our international revenue to continue to grow as reimbursement agreements and approvals are achieved alongside the growth from our initial launch markets, positioning QINLOCK to reach more patients around the world.

我們對執行力感到非常滿意，我們預計，隨著報銷協議和批准的達成以及我們最初推出的市場的增長，我們的國際收入將繼續增長，這將使 QINLOCK 能夠覆蓋全球更多的患者。

Touching on vimseltinib, there is a possible excitement in Europe surrounding the outstanding Phase 3 MOTION data, where we believe the number of patients is comparable to the US in the five largest European markets and general feed is higher as there are no approved treatments.

談到 vimseltinib，歐洲可能對出色的 3 期 MOTION 數據感到興奮，我們認為歐洲五大市場的患者數量與美國相當，而且由於沒有批准的治療方法，總體費用更高。

We are working hard towards our first initial engagement with HTA agencies earlier this year, and I look forward to the MIA submission in the third quarter and preparing for the commercial launch.

我們正在努力爭取今年早些時候與 HTA 機構的首次合作，我期待在第三季提交 MIA 並為商業發布做好準備。

I will now turn the call over to Tucker Kelly, our Chief Financial Officer, to review the fourth quarter and full year financial results. Tucker?

現在，我將把電話轉給我們的財務長塔克凱利 (Tucker Kelly)，以回顧第四季和全年的財務表現。塔克？

Thanks, Margarida. Total revenue for the fourth quarter was $48.3 million, which included $46.7 million in net product revenue of QINLOCK, and $1.6 million in collaboration revenue.

謝謝，瑪格麗達。第四季總收入為4,830萬美元，其中包括QINLOCK淨產品收入4,670萬美元，合作收入160萬美元。

For the full year, total revenue grew 22% to $163.4 million, including net product sales of $159.1 million and collaboration revenue of $4.3 million.

全年總收入成長 22% 至 1.634 億美元，其中淨產品銷售額 1.591 億美元，合作收入 430 萬美元。

Cost of sales in the fourth quarter was $1.8 million, which includes $900,000 in cost of product sales compared to cost of product sales of $700,000 for the fourth quarter of 2022. For the full year, cost of sales were $3.7 million, including $2 million in cost of product sales, compared to cost of sales of $8.7 million in '22, including cost of product sales of $2.7 million.

第四季的銷售成本為 180 萬美元，其中包括 90 萬美元的產品銷售成本，而 2022 年第四季的產品銷售成本為 70 萬美元。全年銷售成本為 370 萬美元，其中包括 200 萬美元的產品銷售成本，而 22 年的銷售成本為 870 萬美元，其中包括 270 萬美元的產品銷售成本。

As a reminder, in the third quarter of 2022, we completed the sales of zero cost inventories of QINLOCK that had been expensed as R&D prior to FDA approval in 2020.

提醒一下，在 2022 年第三季度，我們完成了 QINLOCK 零成本庫存的銷售，這些庫存在 2020 年獲得 FDA 批准之前已作為研發費用。

Research and development expenses for the fourth quarter of 2023 were $58.6 million, compared to $48.1 million for the fourth quarter of 2022, and $234.1 million for the full year compared to $187.8 million in 2022.

2023 年第四季研發費用為 5,860 萬美元，而 2022 年第四季為 4,810 萬美元；全年研發費用為 2.341 億美元，而 2022 年為 1.878 億美元。

Selling, general, and administrative expenses in the fourth quarter were $39.1 million compared to $32.2 million in the fourth quarter of 2022. For the full year, SG&A was $136.5 million compared to $120.2 million in 2022. We ended the year with cash, cash equivalents and marketable securities of approximately $352.9 million.

第四季的銷售、一般及行政費用為 3,910 萬美元，而 2022 年第四季為 3,220 萬美元。全年銷售、一般及行政費用為 1.365 億美元，而 2022 年為 1.202 億美元。截至本財政年度末，我們的現金、現金等價物及有價證券總額約為 3.529 億美元。

In January, we announced that we had extended our cash runway guidance into the second half of 2026, which remains unchanged.

今年 1 月，我們宣布將現金流指引延長至 2026 年下半年，維持不變。

With that, I'll now turn the call back over to Steve.

說完這些，我現在將電話轉回給史蒂夫。

Thanks, Tucker. We're very excited for 2024 as we continue to drive commercial growth at QINLOCK, seek regulatory approval for vimseltinib and TGCT, and advance our clinical pipeline, including our plans to develop vimseltinib in GVHD.

謝謝，塔克。我們對 2024 年感到非常興奮，因為我們將繼續推動 QINLOCK 的商業成長，尋求 vimseltinib 和 TGCT 的監管批准，並推進我們的臨床管線，包括我們在 GVHD 中開發 vimseltinib 的計劃。

Building off our momentum in 2023, we're pleased by our late-stage clinical execution and global commercial excellence as we continue our evolution into a self-sustaining company with multiple approved medicines.

憑藉 2023 年的發展勢頭，我們對後期臨床執行和全球商業卓越感到滿意，我們將繼續發展成為一家擁有多種獲批藥物的自給自足的公司。

With that, operator, I'd now like to open the call for Q&A.

接線生，現在我想開始問答環節。

(Operator Instructions) Jessica Fye, JP Morgan.

（操作員指示） Jessica Fye，摩根大通。

Hey, guys, good morning. Thanks for taking my questions. Two from me. First, what's the latest you're hearing about when doctors are turning to QINLOCK for second line just in the unpromoted real-world use? Is this happening mainly with QINLOCK experienced treaters who are otherwise using it for fourth line? Or are you seeing any pickup of new prescribers as a result of that type of use?

嘿，大家早安。感謝您回答我的問題。我有兩個。首先，當醫生在未經推廣的實際應用中將 QINLOCK 用作第二線治療時，您聽到的最新消息是什麼？這種情況是否主要發生在 QINLOCK 經驗豐富的治療師身上，而他們將其用作第四線？或者您看到由於這種使用方式而出現新的開藥者增加的情況？

And second, I appreciate the details on vimseltinib. Can you just frame a little bit more how you think about the shape of that launch ramp? Thank you.

其次，我很欣賞有關 vimseltinib 的詳細資訊。您能否更詳細地闡述您對發射坡道形狀的看法？謝謝。

Good morning, it's Steve. Thanks for the two questions. I'll ask Dan to take both of those questions, the one with respect to unpromoted off-label use of QINLOCK in the second line based on physician decision, and then the expected ramp for a potential vimseltinib launch here in the US. Dan?

早安，我是史蒂夫。謝謝你的兩個問題。我會請丹回答這兩個問題，一個是關於根據醫生的決定在第二線使用未推廣的 QINLOCK 的標籤外用途，另一個是關於在美國潛在推出 vimseltinib 的預期增長。擔？

Thank you, Jess, for the questions. Good morning. So as it relates to your question about QINLOCK, as we've noted, it is challenging to measure exactly what and where we're seeing in terms of the contribution of earlier line use, the data sources for us to be able to do that just aren't great.

謝謝傑西的提問。早安.因此，關於您關於 QINLOCK 的問題，正如我們所指出的，要準確衡量我們在早期線路使用貢獻方面所看到的內容和位置是一項挑戰，我們能夠做到這一點的數據來源並不好。

We do believe that it's been a mix of existing and new prescribers. So we really think that it's something that reflects a broad appreciation for the role of ripretinib for patients across lines of therapy in GIST. Of course, I always want to underscore that, that's an unpromoted use. So of course, we're not out there promoting that, and it needs to happen spontaneously based on physician decision.

我們確實相信，這是現有處方人員和新處方人員的混合體。因此，我們確實認為，這反映了人們對利普替尼在 GIST 各療法患者中的作用的廣泛認可。當然，我一直想強調這一點，這是一種不被提倡的用途。所以當然，我們不會在那裡推廣這一點，而這需要根據醫生的決定自發進行。

With respect to your second question on the launch ramp, the shape of the ramp, we'll have the opportunity to get into more details about launch strategy and expectations as we draw closer to a potential approval. But what we're focused on right now is a significant unmet need that we know exists in the space with patients who are suffering from the significant morbidity of TGCT, and what physicians keep telling us, so if there's a real opportunity to improve upon the existing therapies.

關於您關於發射坡道形狀的第二個問題，隨著我們越來越接近潛在的批准，我們將有機會更詳細地了解發射策略和預期。但我們現在關注的是，我們知道，在患有 TGCT 嚴重發病率的患者中，存在著一個尚未滿足的重大需求，醫生也一直告訴我們，是否存在改進現有療法的真正機會。

So we look forward to continuing to work really hard to be ready to launch vimseltinib as rapidly as possible pending approval. Thank you.

因此，我們期待繼續努力工作，以便在獲得批准後儘快推出 vimseltinib。謝謝。

Tyler Van Buren, Steve Cohen.

泰勒範布倫、史蒂夫科恩。

Hey, guys, good morning. Congrats on the progress during the quarter. Can you, guys, discuss what else needs to be done to have the vimseltinib filing ready for submission next quarter? And related to that, what is your confidence that you will not see a REMS program or a black box warning upon approval?

嘿，大家早安。恭喜本季取得的進展。你們能討論一下還需要做些什麼才能讓 vimseltinib 文件準備好在下個季度提交嗎？與此相關，您有信心在批准後不會看到 REMS 計劃或黑框警告嗎？

And Tyler, it's Steve. Good morning. Thanks for the question. Tyler, it's Steve. So first, we remain very much on track for the filing of the NDA for vimseltinib here in quarter two coming up and then the MAA to the EMA in Q3. So it's really just the usual and customary activities as we prepare for that filing that we are engaged in.

泰勒，我是史蒂夫。早安.謝謝你的提問。泰勒，我是史蒂夫。因此，首先，我們將繼續按計劃在即將到來的第二季度提交 vimseltinib 的 NDA，然後在第三季度向 EMA 提交 MAA。因此，這實際上只是我們在準備提交文件時進行的通常和慣常的活動。

We remain very confident in the profile of vimseltinib based on the MOTION data. As you know, the study achieved the primary endpoint in all six key secondary end points, and also demonstrated that the drug is well tolerated in the patient population.

根據 MOTION 數據，我們對 vimseltinib 的概況仍然非常有信心。如您所知，該研究在所有六個關鍵次要終點中都達到了主要終點，並且還證明該藥物在患者群體中耐受性良好。

So we believe we have a very clean and well-characterized safety profile with the drug and continue to have the expectation that we would -- there's no reason to expect a REMS program or a black box warning for the potentially fatal hepatotoxicity that is seen with pexidartinib, and is believed to be an off-target effect.

因此，我們相信該藥物的安全性非常清晰且特徵明確，並且我們繼續抱持這樣的期望——沒有理由期待 REMS 計劃或黑框警告，以防出現與 pexidartinib 一樣的潛在致命肝毒性，並且被認為是脫靶效應。

So we remain on track for the filings, and we're excited to bring our potential next approved medicine forward to patients.

因此，我們仍在按計劃進行申請，並且我們很高興將我們可能獲得的下一個核准藥物帶給患者。

Eun Yang, Jefferies.

傑富瑞 (Jefferies) 的 Eun Yang。

Thank you. So QINLOCK's second line off-label use, is that -- is it largely driven by patients who were intolerant to Sutent or patients with exon 11 and 17/18 mutations?

謝謝。那麼 QINLOCK 的二線非說明書用途是否主要是由對 Sutent 不耐受的患者或外顯子 11 和 17/18 突變的患者驅動的？

Eun, this is Steve. I'll ask Dan to take the question on the off-label use that we're seeing in earlier lines based on physician decision. Dan?

恩，這是史蒂夫。我將請丹根據醫生的決定來回答我們之前看到的有關標籤外使用的問題。擔？

Yes. Hi, Hugh, and good morning and thanks for the question. So we believe that the two significant events that occurred last year on our what's behind the contribution that we've seen from earlier line use on promoted earlier-line use. So there was the, as you noted, the NCCN listing for patients who are intolerant of suite and second line as well as the really exceptional data that was presented and now recently published in Nature Medicine showing the dramatic treatment benefit that ripretinib can offer patients with C. Exon 11, 17, 18 mutation. We think that both of those certainly have increased the noise level on again, I always score this is something we don't promote, but just through that national dissemination of this information, the presentation, the publication, you'll certainly have raise the noise level. So it's hard to discern on which which patient which bottle is being driven by which of those factors. But we think that both are reflective of real interest in opportunities to use ripretinib in patients with GIST and of course, on.

是的。你好，休，早安，謝謝你的提問。因此，我們相信，去年發生的兩件大事是我們對早期線路使用做出貢獻的背後原因，而這些貢獻正是我們之前所看到的，並促進了早期線路的使用。因此，正如您所說，NCCN 列出了不耐受一線和二線治療的患者，並且最近在《自然醫學》雜誌上發表了非常出色的數據，顯示了利普替尼可以為 C 外顯子 11、17、18 突變患者帶來顯著的治療益處。我們認為這兩者肯定再次增加了噪音水平，我一直認為這是我們不提倡的事情，但僅僅通過在全國範圍內傳播這些信息、展示和出版，你肯定會提高噪音水平。因此，很難辨別哪個病人的哪個藥瓶是由哪個因素驅動的。但我們認為，兩者都反映了人們對在 GIST 患者中使用利普替尼的真正興趣。

Yes, we think that it's important to note the level of energy that we see around the Incyte study and the excitement that we have for a potential approved indication pending a positive study.

是的，我們認為，重要的是要注意我們在 Incyte 研究中所看到的活力水平，以及我們對等待積極研究的潛在批准適應症的興奮程度。

You and I have one question for Tucker and so OpEx in 4Q, sequentially, R&D is down slightly but SG&A is up. So could you could you give us some guidance of how OpEx level would be in 2024 as well as the collaboration revenue line? Thank you. Sure.

您和我對塔克有一個問題，即第四季度的營運支出，環比而言，研發費用略有下降，但銷售、一般及行政費用有所上升。那麼，您能否給我們一些關於 2024 年營運支出水準以及協作收入線的指導？謝謝。當然。

Yeah, Eun. So we believe that the two significant events that occurred last year are what's behind the contribution that we've seen from earlier line use, on promoted earlier line use. So there was, as you noted, the NCCN listing for patients who are intolerant to Sutent in the second line, as well as the really exceptional data that was presented and now recently published in Nature Medicine, showing the dramatic treatment and fit that ripretinib can offer patients with the exon 11 17/18 mutation.

是的，恩。因此，我們認為，去年發生的兩件重大事件是我們看到早期線路使用對促進早期線路使用做出貢獻的原因。因此，正如您所說，NCCN 列出了對二線 Sutent 不耐受的患者，並且最近在《自然醫學》雜誌上發表了非常出色的數據，顯示了利普替尼可以為外顯子 11 17/18 突變患者提供顯著的治療效果和適應性。

We think that both of those certainly have increased the noise level. Again, I always score, this is something we don't promote, but just through that natural dissemination of this information, the presentation, the publication certainly have raised the noise level.

我們認為這兩者都肯定增加了噪音水平。再說一次，我總是認為，這是我們不提倡的事情，但僅僅透過這種訊息的自然傳播，演示和出版肯定會提高噪音水平。

So it's hard to discern which patient, which bottle is being driven by those factors, but we think that both are reflective of real interest in opportunities to use ripretinib in patients with GIST. And of course, we think that -- it's important to note the level of energy that we see around the INSIGHT study and the excitement that we have for a potential approved indication pending a positive study.

因此，很難辨別哪個患者、哪個藥瓶受到這些因素的驅動，但我們認為兩者都反映了對 GIST 患者使用利普替尼機會的真正興趣。當然，我們認為——重要的是要注意我們在 INSIGHT 研究中所看到的活力水平，以及我們對等待積極研究的潛在批准適應症的興奮之情。

And I have one question for Tucker. So OpEx in 4Q sequentially R&D is down slightly but SG&A is up. So could you give us some guidance on how OpEx level would be in 2024 as well as the collaboration revenue line?

我還有一個問題想問塔克。第四季的營運支出較上季研發費用略有下降，但銷售、一般及行政費用（SG&A）有所上升。您能否為我們預測一下2024年的營運支出水準以及協作收入狀況？

Sure. So on the OpEx side, it was a little higher sequentially mentioned in the SG&A. There's some one-off items and end of year items that we think are more exceptional. So we wouldn't expect necessarily to have that to run rate going forward for SG&A. We will have some -- in the second half of the year, expenses as we prepare for the launch of vimseltinib as well.

當然。因此，在營運支出方面，其在銷售、一般及行政費用 (SG&A) 中連續提及略高。我們認為有些一次性物品和年終物品更為特殊。因此，我們並不期望銷售、一般及行政開支 (SG&A) 的未來運作率一定達到這個水準。在準備推出 vimseltinib 的下半年，我們會產生一些費用。

And in terms of collaboration revenue, as we've always said, that's composed really a couple of components. One is the royalty revenue that we get from our collaborations side. And then secondly, there's often supply revenue. The supply revenue is much more episodic. So some quarters, we have it, in some quarters, we don't. There was some supply revenues, you'll see in the cost of goods line for the collaboration revenue this quarter, and that's difficult to predict.

就合作收入而言，正如我們一直所說，它實際上由幾個部分組成。一是我們從合作中獲得的版稅收入。其次，通常還有供應收入。供應收入的波動性較大。在某些方面我們有，在某些方面我們沒有。有一些供應收入，您會在本季的合作收入的商品成本中看到，這很難預測。

So I think we always try and guide people to focus on the expectation for the royalty revenue. And then there'll be upside in quarters where we do have supply revenue come in.

所以我認為我們總是試圖引導人們專注於對特許權使用費收入的期望。而當我們確實有供應收入的季度裡，就會出現上行趨勢。

Michael Schmidt, Guggenheim Securities.

古根漢證券公司的麥可‧施密特。

I had one on vimseltinib as of your plans in GVHD, and how do you think about potential differentiation of vimseltinib and GVHD from somebody who's like axatilimab? And can you comment about the possible design of your planned Phase 2 study? Will that be in axatilimab naive patients? Will you include pretreated patients. How do you think about that space?

根據您在 GVHD 治療計劃中對 vimseltinib 的介紹，我有一個 vimseltinib 治療 GVHD 的計劃，您如何看待 vimseltinib 和 GVHD 與 axatilimab 等藥物的潛在區別？您能否評論一下您計劃的第二階段研究的可能設計？這會發生於未接受阿沙替利單抗治療的患者嗎？您是否會包括已接受過治療的患者？您如何看待那個空間？

Yeah, Michael, Good morning. It's Steve. I'm happy to take the question.

是的，邁克爾，早安。我是史蒂夫。我很高興回答這個問題。

First, we're excited about the potential to expand vimseltinib and its utility beyond TGCT, and a new potential indication in chronic GVHD. And certainly, one of the factors that enables us to do that in addition to the strong data we have now in TGCT is the very long IP runway that we have in vimseltinib, the composition of matter patent that takes us to 2034, plus PTE, which we believe takes us to the end of the decade, and that doesn't include secondary patents for vimseltinib.

首先，我們對擴大 vimseltinib 及其在 TGCT 之外的實用性的潛力以及在慢性 GVHD 中的新潛在適應症感到興奮。當然，除了我們現在在 TGCT 方面擁有的強大數據之外，使我們能夠做到這一點的因素之一是我們在 vimseltinib 方面擁有非常長的 IP 跑道，物質組成專利可以帶我們到 2034 年，再加上 PTE，我們相信這將帶我們到這個十年的末期，這還不包括 vimseltinib 的二級專利。

So ample opportunity for us to make additional investments in vim to take it into additional indications where we'll have the opportunity to benefit patients.

因此，我們有充足的機會對 vim 進行額外投資，使其應用於更多適應症，從而有機會使患者受益。

So in terms of the landscape of GVHD and how we see differentiation at this early stage, first, I would just comment that certainly, the target CSF1 receptor is now clinically validated in this disease, which is very important. So it's a derisked mechanism in GVHD. We believe the data that we've generated in tenosynovial giant cell tumor demonstrates that we have a very potent and selective inhibitor against the target.

因此，就 GVHD 的概況以及我們如何看待早期階段的分化而言，首先，我只想評論一下，目標 CSF1 受體現在已在該疾病中得到臨床驗證，這非常重要。因此，這是 GVHD 中的一種低風險機制。我們相信，我們在腱鞘鉅細胞瘤中產生的數據表明，我們擁有一種針對該標靶的非常有效且有選擇性的抑制劑。

And in a disease where the current backbone of treatment is all oral regimens, we believe that an oral agent like vimseltinib and oral CSF1 receptor inhibitor could play an important role as an add-on therapy, in addition to a monotherapy in later lines, but as an add-on therapy to current standard of care, whether that be a JAK inhibitor or whether it be a drug like REZUROCK as an example.

對於目前主要以口服療法為主的疾病，我們認為，除了後期的單一療法外，像維姆司替尼和口服 CSF1 受體抑製劑這樣的口服藥物可以作為附加療法發揮重要作用，但作為當前標準治療的附加療法，無論是 JAK 抑製劑還是像 REZUROCK 這樣的藥物。

So we haven't yet disclosed full details of our clinical development strategy in GVHD. I'm sure we'll have incremental additional disclosures over time, particularly once we get the Phase 2 study stood up at the end of this year. But we're excited about the potential now to expand the places where vim can benefit patients.

因此，我們尚未揭露 GVHD 臨床開發策略的全部細節。我相信隨著時間的推移，我們將會有逐步的額外披露，特別是在今年年底我們完成第二階段研究之後。但現在，我們很高興看到 vim 可以擴大其惠及患者的範圍。

Chris Raymond, Piper Sandler.

克里斯雷蒙德、派珀桑德勒。

Just another question, I guess, on vimseltinib. And this is on the adjuvant opportunity. I know this has come up in the past. But what do you guys see as sort of the go to no-go points to running a study in the adjuvant setting? As you guys even noted in your market landscape slide, that's a pretty sizable opportunity. Just any sort of plan there that you guys can articulate. And then maybe a second part of that question is, is there an opportunity or a chance that you get a broad label that could be potentially inclusive of the adjuvant setting?

我想，這只是關於 vimseltinib 的另一個問題。這是輔助機會。我知道過去曾發生過這樣的事。但是，你們認為在輔助治療環境中進行研究的禁忌點是什麼？正如你們在市場前景幻燈片中指出的那樣，這是一個相當大的機會。只要你們能清楚地表達出任何計劃就行。那麼，也許這個問題的第二部分是，是否有機會獲得一個可能包含輔助治療的廣泛標籤？

Yeah, Chris, it's Steve. Really good questions. So of course, excited about the data from MOTION, which will give us this initial label in tenosynovial giant cell tumor.

是的，克里斯，我是史蒂夫。確實是好問題。因此，我們當然對 MOTION 的數據感到興奮，它將為我們提供腱鞘鉅細胞瘤的初步標籤。

As you'll remember, the patient population that we treated in the MOTION study is patients who are not amenable to surgery. So it's too early for me to comment on what ultimately FDA will decide as the indication statement or the label for vimseltinib in TGCT. But we, too, have heard also from investigators interest in exploring a role of an inhibitor like vimseltinib in other lines or earlier lines of treatment for tenosynovial giant cell tumor.

您可能還記得，我們​​在 MOTION 研究中治療的患者群體是不適合接受手術的患者。因此，現在評論 FDA 最終將如何決定 vimseltinib 在 TGCT 中的適應症聲明或標籤還為時過早。但我們也聽說研究人員有興趣探索像維姆替尼這樣的抑制劑在腱鞘鉅細胞瘤的其他治療線或早期治療線中的作用。

So recall, this is a disease that, particularly, in the localized form of the disease is often curable through surgery alone. So we'd probably be speaking about a patient population that would not be amenable to surgery, but potentially could be made amenable to surgery with adjuvant or neoadjuvant treatment.

所以回想一下，這是一種疾病，特別是局部形式的疾病，通常僅透過手術就可以治癒。因此，我們談論的可能是不適合接受手術但可能透過輔助或新輔助治療而適合接受手術的患者群體。

So again, too early for us to comment on any specific plans. But certainly, with the evidence that we have now in the patient population that we've studied, it's very clear we have strong activity in this disease with vimseltinib, and there may be opportunity for us to pursue whether label-enabling studies or non-label enabling studies to further characterize the potential of vimseltinib to benefit patients here.

所以，現在我們對任何具體計劃發表評論還為時過早。但可以肯定的是，根據我們目前在研究的患者群體中掌握的證據，很明顯，vimseltinib 對這種疾病具有很強的療效，而且我們可能有機會進行標籤支持研究或非標籤支持研究，以進一步表徵 vimseltinib 對患者有益的潛力。

Andrew Berens, Leerink Partners.

安德魯貝倫斯，Leerink Partners。

Hi. This is [Ken] on for Andrew. So you guys, I think, have been saying that the average duration for QINLOCK in the fourth-line setting has started to come, I believe, about seven months now, increasing potentially up to 8.5. I'm wondering, do you have any color on the penetration in the fourth line? Where that could be right about now?

你好。我是 [Ken]，代表 Andrew 發言。所以，我想你們一直在說，QINLOCK 在第四線治療中的平均持續時間已經開始，我相信現在大約是 7 個月，可能會增加到 8.5 個月。我想知道，您對第四線治療的滲透率有什麼了解嗎？現在那裡可能在哪裡？

Thanks for the question. Yes. Dan, would you like to take that?

謝謝你的提問。是的。丹，你想接受這個嗎？

Sure. Absolutely. So yes, you had mentioned about the average duration of therapy. In fact, we think that's a really important dynamic to our continued growth as we think about 2024. We look to the continued strength in our fourth line opportunity, we look to a continuing increasing average duration of therapy, and as we've noted in earlier questions, contribution from unpromoted earlier line use. So as we think about the opportunity for 2024, we're looking forward to another potential record year in the US for QINLOCK.

當然。絕對地。是的，您提到了治療的平均持續時間。事實上，我們認為，當我們展望 2024 年時，這對我們的持續成長是一個非常重要的動力。我們期待第四線治療機會的持續強勁，我們期待平均治療持續時間的持續增加，並且正如我們在先前的問題中所指出的，未推廣的早期治療線的使用也做出了貢獻。因此，當我們考慮 2024 年的機會時，我們期待 QINLOCK 在美國再創紀錄。

As it relates to penetration in the fourth-line setting, as we've said in the past, we feel as though we've done a really good job penetrating that opportunity and that it's a pretty highly penetrated opportunity as a result of not only a really strong drug at high unmet need and our ability to execute over the last number of years.

正如我們過去所說的那樣，就第四線治療的滲透率而言，我們覺得我們已經很好地滲透了這一機會，而且這是一個滲透率相當高的機會，這不僅因為該藥物確實具有很高的未滿足需求，而且因為我們在過去幾年中一直具有執行能力。

Brad Berning, Stifel.

布拉德·伯寧（Brad Berning），Stifel。

Morning and thank you. Another question for me on vimseltinib. I wonder how many doses do you think you plan to use in the proof-of-concept study in chronic GVHD? And I'm asking in light of the inverse dose response noted for the antibody and the working hypothesis there around allowing for some degree of macrophage function recovery.

早安，謝謝。關於 vimseltinib，我還有另一個問題。我想知道您計劃在慢性 GVHD 的概念驗證研究中使用多少劑量？我問這個問題是基於抗體所觀察到的逆劑量反應以及允許一定程度的巨噬細胞功能恢復的工作假設。

Yes, thanks for the question, Brad. Matt, would you like to take that on GVHD?

是的，謝謝你的提問，布拉德。馬特，你願意接受 GVHD 治療嗎？

Sure. Good morning, Brad. Yes, this is Matt. So yeah, so what you're referring to is the pivotal segments done with axatilimab in GVHD, where we tested 3 dose levels and different schedules as well, too. And what they did demonstrate in inverse dose response, where some of the lower doses and more efficacy for much tolerated in the higher doses. And that may be more unique to antibodies because as we know the antibody inhibition of T cell interceptor has led to a much more prolonged on-target effect and it's been difficult in other indications to develop those antibodies clinically.

當然。早安，布拉德。是的，這是馬特。是的，您指的是 GVHD 中使用阿沙替利單抗進行的關鍵部分，我們也測試了 3 種劑量水平和不同的時間表。他們確實證明了劑量反比，即在較低劑量下療效更好，而在較高劑量下耐受性更好。這可能對抗體來說更為獨特，因為我們知道抗體對 T 細胞攔截器的抑制導致了更持久的靶向效應，並且在其他適應症中很難在臨床上開發這些抗體。

So as Steve said earlier, excited about moving forward with our proof-of-concept study in the second half of this year in GVHD. We haven't yet given the details of the study. But as we are closer to the initiation of that study, we certainly will be speaking to the design of that study and what we expect to achieve.

正如史蒂夫之前所說，我們很高興能夠在今年下半年推進 GVHD 概念驗證研究。我們尚未提供該研究的細節。但隨著我們越來越接近研究的啟動，我們肯定會談論研究的設計以及我們期望實現的目標。

Reni Benjamin, Citizen's GMP.

雷尼·本傑明 (Reni Benjamin)，公民 GMP。

Thanks for taking the questions and congratulations on the progress. Maybe just to start off, Steve, can you give us any sort of color on the INSIGHT study and how that's progressing? Have you kind of hit all the trial sites, are they all kind of already -- are you still ramping that up? Any sort of color as to how that's progressing because that seems to be key in terms of unlocking the second line just opportunity.

感謝您回答問題，並祝賀您取得進展。首先，史蒂夫，您能否向我們介紹 INSIGHT 研究以及其進展？您是否已經造訪過所有試驗網站？它們是否都已經訪問過？您是否還在繼續推進這些工作？關於進展的任何細節都很重要，因為這似乎是解鎖第二線機會的關鍵。

And then just as a follow-up with vimseltinib, you're filing the NDA and MAA. Any chance that we could get some sort of a priority review? Or is the best case scenario a standard review both in the US as well as Europe? And how long does it take in Europe just to get the decision?

然後，作為 vimseltinib 的後續行動，您正在提交 NDA 和 MAA。我們有機會獲得某種優先審查嗎？或者最好的情況是美國和歐洲都進行標準審查？歐洲需要多長時間才能做出決定？

Yeah. Reni, it's Steve. Good morning and thanks for the great questions.

是的。雷尼，我是史蒂夫。早安，感謝您提出這些精彩的問題。

So first, for INSIGHT, as you're aware, I should first note that we published the results from the analysis of INTRIGUE in Nature Medicine last month. So really exciting to see the data in such a top-tier journal. And the noise that, that analysis has generated, both with presentations at ASCO and now with the publication in Nature Medicine, has been a real tailwind in terms of building enthusiasm for the ongoing INSIGHT study.

首先，對於 INSIGHT，如您所知，我應該首先指出，我們上個月在《自然醫學》雜誌上發表了 INTRIGUE 分析的結果。在如此頂尖的期刊上看到這樣的數據真是令人興奮。該分析在 ASCO 大會上發表以及現在在《自然醫學》雜誌上發表後引起的反響，為正在進行的 INSIGHT 研究注入了新的熱情。

So we continue to make really good progress in getting sites open, actively screening and enrolling patients in that study. And the enthusiasm from investigators, really helpable, I think they're really excited, not only about the data that's been published and presented so far from the analysis of INTRIGUE, but just also the potential to be part of advancing how second-line GIST is treated based on insights into a patient's tumor using circulating tumor DNA.

因此，我們在開放研究站點、積極篩選和招募患者方面繼續取得良好進展。研究人員的熱情確實很有幫助，我認為他們真的很興奮，不僅是因為迄今為止已經發表和呈現的 INTRIGUE 分析數據，還因為他們有可能基於使用循環腫瘤 DNA 對患者腫瘤的了解，推動二線 GIST 的治療。

So drawing a simple tube of blood in order to understand a secondary mutation status. That is an aim or a goal, I think, that the field and thought leaders in the field are really excited about, and their participation in the INSIGHT study, we believe will help us to achieve that goal of demonstrating prospectively this outsized benefit of QINLOCK versus sunitinib in the selected patient population.

因此，抽取一根簡單的管子來了解二次突變的狀態。我認為，這是一個目標，該領域和該領域的思想領袖對此感到非常興奮，並且我們相信他們參與 INSIGHT 研究將幫助我們實現這一目標，即在選定的患者群體中前瞻性地展示 QINLOCK 相對於舒尼替尼的巨大優勢。

So we continue to be moving forward very much on schedule and on track with the INSIGHT study and we'll have further updates. I'm sure, over the coming queries on our progress with that specific study in second line GIST patients.

因此，我們將繼續按照計劃和進度推進 INSIGHT 研究，並且我們將提供進一步的更新資訊。我確信，在接下來的詢問中我們會詢問我們在二線 GIST 患者中進行的具體研究的進展。

Your second question was related to vimseltinib and what our expectations are in terms of regulatory review and timing, and your specific question was with respect to whether we may enjoy priority review with the application.

您的第二個問題與 vimseltinib 有關，以及我們對監管審查和時間表的期望，您的具體問題是關於我們是否可以享受申請的優先審查。

So it's too soon for us to comment on that. And certainly, the FDA will make that determination as whether we're not the application qualifies for priority review. As you may remember, the ENLIVEN study and the application for pexidartinib was reviewed by FDA with priority review status. So that certainly is the precedent if you will, in this disease. So we're looking forward to our ongoing and continued productive dialogue with the FDA as we prepare to file here in the second quarter, and we'll, of course, make appropriate disclosures at the right time in terms of whether that is a priority review or a regular review at the FDA's discretion.

因此我們現在對此發表評論還為時過早。當然，FDA 將決定該申請是否符合優先審查的資格。您可能還記得，ENLIVEN 研究和 pexidartinib 申請均已獲得 FDA 優先審查資格。所以如果你願意的話，這肯定是這種疾病的先例。因此，我們期待在第二季度準備提交申請時與 FDA 進行持續富有成效的對話，當然，我們會在適當的時候根據 FDA 的判斷，做出適當的披露，說明這是優先審查還是定期審查。

And then in terms of the European review process, that, as you may remember, is a lengthier process. So we would expect that, that will take potentially longer than the FDA review. But as we get into our further dialogue with the EMA, we may able to better cast a timeline as to when we might expect action on the application once it gets filed.

就歐洲審查程序而言，您可能還記得，這是一個較長的過程。因此我們預計這可能比 FDA 審查花費的時間更長。但隨著我們與 EMA 進一步對話，我們或許能夠更好地制定時間表，確定申請提交後何時可以採取行動。

But we remain super excited about the profile of the drug. The MOTION data are very clear and compelling, and we're looking forward to delivering our second potential approved medicine to patients.

但我們仍然對該藥物的特性感到非常興奮。MOTION 數據非常清晰且令人信服，我們期待向患者提供第二種可能核准的藥物。

Great. And then if I can just have a follow-up regarding vimseltinib and what could ultimately be involved in prelaunch activities. Is this something that we should just be -- just given the overlap, I think that Dan mentioned in the call, is this something that could just be as easy as kind of dropping it into the bag of sales and they're sort of off and running? Or are there significant prelaunch activities that need to be conducted given this market?

偉大的。然後，我是否可以跟進一下 vimseltinib 的情況以及最終可能涉及的上市前活動。這是我們該做的事嗎？考慮到重疊部分，我認為丹在電話中提到過，這是否可以像將其放入銷售袋中然後開始運行一樣簡單？或是針對這個市場是否需要進行重要的預發布活動？

Yeah. I'll ask Dan to comment on the prelaunch activities. But you're right, Ren, we believe there is 70% to 80% overlap in terms of the prescriber base. So a really meaningful opportunity both in the U.S. as well as in Europe for meaningful synergy with our existing commercial organization.

是的。我會請丹對發布前活動發表評論。但您說得對，任，我們認為在處方基礎方面有 70% 到 80% 的重疊。因此，無論在美國還是在歐洲，這都是一個與我們現有的商業組織實現有意義的協同效應的真正有意義的機會。

Dan, do you want to comment further on the prelaunch activities?

丹，你想進一步評論一下發布前的活動嗎？

Yeah, absolutely. Thanks, Ren, for the question. So we think that investment in market development or prelaunch activities is important. Our focus will be on disease education, largely to make sure that all potential treaters of TGCT are thoroughly educated on the -- how common TGCT is and the burden that these patients deal with.

是的，絕對是如此。謝謝 Ren 提出這個問題。因此我們認為對市場開發或預發布活動的投資很重要。我們的重點將放在疾病教育上，主要是為了確保所有潛在的 TGCT 治療者都得到徹底的教育——TGCT 的普遍性以及這些患者所承受的負擔。

This is a really debilitating disease. It's something that isn't a lethal disease, of course, but it is one that can be very locally aggressive and really have a significant impact on how patients feel and function. And we want to really paint that patient picture, bring that to light, raise that awareness.

這是一種真正使人衰弱的疾病。當然，這不是一種致命的疾病，但它是一種局部侵襲性極強的疾病，對患者的感覺和功能有重大影響。我們希望真正描繪出病人的形象，讓其為人所知，提高人們的認識。

So certainly, that, coupled with our med affairs, organization and data from our studies, all of this will be part of making sure that prior to launch, physicians, appropriately so, know the information that they need.

因此，可以肯定的是，結合我們的醫療事務、組織和研究數據，所有這些都將有助於確保醫生在推出之前能夠適當地了解他們所需的資訊。

And then as Steve mentioned, at launch, yes, we think there's tremendous synergy. We think we're really uniquely positioned to take advantage of both the opportunity in GIST with QINLOCK and the opportunity in TGCT with vimseltinib.

正如史蒂夫所提到的，在發佈時，是的，我們認為存在巨大的協同效應。我們認為，我們確實擁有獨特的優勢，可以利用 QINLOCK 在 GIST 領域的機會以及 vimseltinib 在 TGCT 領域的機會。

(Operator Instructions) Peter Lawson, Barclays.

（操作員指示）巴克萊銀行的彼得·勞森。

Thank you so much for taking the questions I guess, two, first just on the seasonality and how we should think about that for the US versus ex US as you've invested model out 2024 revenues. And then just moving into GVHD, just your thoughts on differentiation as well around safety and potential efficacy versus an antibody and the ability to combine with other regimens in that GVHD space.

非常感謝您回答我的問題，我想有兩個問題，首先是關於季節性，以及我們應該如何看待美國與美國以外的地區，因為您已經投資了 2024 年的收入模型。然後談談 GVHD，您對差異化以及安全性和潛在功效的看法，與抗體相比，以及與 GVHD 領域中其他方案結合的能力。

Yeah, Peter, thanks for the two questions. So I'll ask Dan and Margarida to comment on expectations for the year broadly in 2024 and our expectation of the usual seasonality patterns. And then I'll ask Matt to take your second question with respect to vimseltinib and GVHD. Dan, do you want to go first?

是的，彼得，謝謝你的兩個問題。因此，我會請丹和瑪格麗達對 2024 年的整體預期以及我們對通常季節性模式的預期進行評論。然後我會請馬特回答您關於 vimseltinib 和 GVHD 的第二個問題。丹，你想先走嗎？

Sure, absolutely. Hi, Peter. Good morning, thanks for the question. So as we noted on the call, we feel really excited and pleased with the progress that we've made in the -- I'll speak to the US specifically, in the fourth quarter, delivering $35.3 million in net product revenue, which was a 38% year-over-year increase for the full year 2023, $121.5 million, which is a 25% year-over-year increase. So we feel really pleased with that.

當然，絕對是如此。你好，彼得。早安，感謝您的提問。因此，正如我們在電話會議上提到的那樣，我們對所取得的進展感到非常興奮和高興——具體來說，美國在第四季度實現了 3530 萬美元的淨產品收入，同比增長 38%，2023 年全年實現 1.215 億美元，同比增長 25%。因此我們對此感到非常高興。

And as we look to 2024, we think some of the core drivers of our recent success will continue to be the core drivers of what we expect to be another record year for QINLOCK, specifically strengthen our core business, increasing average duration of therapy. And then as noted earlier, contribution from unpromoted earlier line use.

展望 2024 年，我們認為我們近期成功的一些核心驅動因素將繼續成為 QINLOCK 再創紀錄一年的核心驅動因素，特別是加強我們的核心業務，增加平均治療時長。然後如前所述，來自未推廣的早期線路使用的貢獻。

So when we take a step back and look at the year as a whole, those are sort of the themes and the reason for our excitement. As we think about just the quarter-to-quarter pattern, we wanted to note that we would expect a patterns similar to past years, which reflects some seasonality dynamics, specifically as it relates to Q1, very common in the industry to see a strong quarterly buying pattern at the end of the year that can potentially impact Q1 as well as some early in the year, sort of post holiday demand seasonality or demand softness.

因此，當我們回顧整個一年時，這些就是主題和我們興奮的原因。當我們考慮季度模式時，我們想要指出的是，我們預計會出現與過去幾年類似的模式，這反映了一些季節性動態，特別是與第一季相關的模式，在行業中非常普遍的是，年底會出現強勁的季度購買模式，這可能會影響第一季以及年初的一些情況，例如假期後的需求季節性或需求疲軟。

Of course, the other factor that we've noted in the past and would expect this year to also play out true to form is the PAP dynamic, which we typically see a lower PAP percentage in the early part of the year with a gradual increase throughout the year.

當然，我們過去已經注意到的另一個因素，並且預計今年也將如期發揮作用，那就是 PAP 的動態，我們通常會在年初看到 PAP 百分比較低，然後在全年逐漸上升。

So those are some of the moving parts that we wanted to note. Margarida?

這些就是我們想要注意的一些活動部分。瑪格麗達？

Sure. So regarding ex US, I mean, let me start by saying that we are delighted with the launch, how it's going and the strong revenue growth from last quarter, which was driven by strong performance in existing markets, but also the contribution from the launch in Italy.

當然。因此，關於美國以外的市場，首先我想說的是，我們對產品的發布、進展以及上個季度的強勁收入增長感到非常高興，這得益於現有市場的強勁表現，也得益於意大利市場的貢獻。

So I would say that as we continue to successfully advance our price and reimbursement and launch in new markets, we expect QINLOCK to continue to grow in international. It is always difficult to predict when new markets will open, given the different reimbursement processes and different timelines in each market. But assuming we get there, I expect this to happen more towards the second part of 2024.

因此我想說，隨著我們繼續成功提高價格和報銷額度並開拓新市場，我們預計 QINLOCK 將在國際上繼續成長。由於每個市場的報銷流程和時間表不同，因此很難預測新市場何時開放。但假設我們能夠實現這一目標，我預計這將在 2024 年下半年實現。

So another thing to note is that while we expect future growth, we cannot exclude quarter-over-quarter variability. So we have seen this in the past, and we may see this again in the future.

因此，需要注意的另一件事是，雖然我們預計未來會成長，但我們不能排除季度季比的變化。我們過去曾見過這種情況，將來也可能會再次見到這種情況。

So I would say, all in all, geographic expansion is a key focus for us in 2024. QINLOCK is well positioned for growth and the recent deal with GENESIS for Central and Eastern Europe is a good example of the type of transactions that you can expect from the future.

所以我想說，總而言之，地理擴張是我們 2024 年的重點。QINLOCK 擁有良好的成長定位，最近與 GENESIS 達成的中歐和東歐交易就是未來可以期待的交易類型的一個很好的例子。

Thanks, Margarita. Matt, do you want to take those vimseltinib question?

謝謝，瑪格麗塔。馬特，你想回答那些 vimseltinib 問題嗎？

Yeah. So in regards to your question, vimseltinib in TGCT -- I'm sorry, in graft versus host disease and our ability to be able to differentiate this, we do remain very excited about plans to initiate our proof-of-concept study in the second half of this year.

是的。因此，關於您的問題，vimseltinib 在 TGCT 中的作用——抱歉，在移植物抗宿主疾病方面，以及我們能夠區分這一點的能力，我們仍然對在今年下半年啟動概念驗證研究的計劃感到非常興奮。

And also, we have a very large database of safety based on vimseltinib and TGCT, both from the MOTION Phase 3 study as well as from the Phase 1/2 study. And GVHD is a chronic disease, and particularly with the skin and joint involvement, there can be some rare limitations of patients with mobility, and the antibody therapy would have to be given intravenously, every two weeks for a chronic disease such as GVHD. That's a pretty significant burden on patients.

此外，我們擁有基於 vimseltinib 和 TGCT 的非常龐大的安全性資料庫，其中既有來自 MOTION 第 3 階段研究的數據，也有來自第 1/2 階段研究的數據。而且 GVHD 是一種慢性疾病，特別是皮膚和關節受累時，患者的活動能力可能會受到一些罕見的限制，對於像 GVHD 這樣的慢性疾病，必須每兩週進行一次靜脈注射抗體療法。這對患者來說是一個相當大的負擔。

So one of the major features of using vimseltinib as an oral agent will be to combine with other oral therapies. As you know, the standard of care now consists primarily of oral agents, whether it's a JAK2 kinase inhibitor or [Fura 2] inhibitor, and in fact, on steroids as well, too. And so our ability to differentiate from the antibody is pretty, pretty significant with vimseltinib in our Phase 2 study.

因此，使用維姆司替尼作為口服藥物的主要特徵之一是與其他口服療法結合。如您所知，目前的治療標準主要包括口服藥物，無論是 JAK2 激酶抑制劑還是 [Fura 2] 抑制劑，事實上，也包括類固醇。因此，在我們的第 2 階段研究中，我們區分 vimseltinib 與抗體的能力非常顯著。

Is there any way from, I guess, preclinical data to see any differentiation of an oral drug versus an antibody? If you think that could drive differences in efficacy or durability or safety?

我猜，從臨床前數據有什麼方法可以看出口服藥物和抗體的差異嗎？您是否認為這會導致功效、耐用性或安全性的差異？

I think most of the preclinical data just speaks to the role of the macrophage and the profibrotic medicine manifestations of the disease. And that's particularly important in several organs, as I mentioned, particularly the skin because these patients can have pretty severe sclerotic skin lesions and even joint contractions. And also, particularly in the ones as too, and fibrosis [macrophage] is currently -- is not a satisfactory treatment in current regiments for GVHD. So the role in macrophaging, in macrophages in those particular organs could really be a benefit for vimseltinib in this disease.

我認為大多數臨床前數據只是說明了巨噬細胞的作用和疾病的促纖維化藥物表現。正如我所提到的，這對於幾個器官來說尤其重要，特別是皮膚，因為這些患者可能會出現相當嚴重的硬化性皮膚病變，甚至關節收縮。而且，特別是在這些情況下，纖維化 [巨噬細胞] 目前——在目前的 GVHD 治療方案中並不是令人滿意的治療方法。因此，巨噬細胞在特定器官中的功能確實可能對 vimseltinib 治療這種疾病有益。

Thank you. I would now like to turn the call back over to Steve Hoerter for any closing remarks.

謝謝。現在我想將電話轉回給史蒂夫霍爾特 (Steve Hoerter) 來做結束語。

Yeah. Thank you for joining us on today's call, and thanks for your support. We look forward to keeping you updated on our continued progress here at Deciphera during the course of the year. Hope you have a great day.

是的。感謝您參加今天的電話會議，感謝您的支持。我們期待今年內向您通報 Deciphera 的持續進展。祝您有個愉快的一天。

Thank you for your participation. You may now disconnect.

感謝您的參與。您現在可以斷開連線。