Whitehawk Therapeutics Inc (WHWK) 2023 Q4 法說會逐字稿

Good day and thank you for standing by, and welcome to Aadi Bioscience fourth quarter 2023 earnings conference call. (Operator Instructions) Please note that today's conference is being recorded.

美好的一天，感謝您的支持，歡迎參加 Aadi Bioscience 2023 年第四季財報電話會議。（操作員指示）請注意，今天的會議正在錄製中。

I will now turn the call over to [Audrey Gruls], Head of Corporate Communications for Aadi Bioscience. Ms. Gruls. Please go ahead

我現在將把電話轉給 Aadi Bioscience 企業傳播主管 [Audrey Gruls]。格魯爾斯女士。請繼續

Thank you. Good morning and welcome to the Aadi bioscience conference call to provide an operational update and review results of the fourth quarter and full year 2023. On the call is Dr. Dave Lennon , our President and CEO; Scott Giacobello, our CFO and Chief Medical Officer, Dr. Loretta Itri.

謝謝。早上好，歡迎參加 Aadi 生物科學電話會議，我們將提供 2023 年第四季和全年的營運更新和審查結果。接聽電話的是我們的總裁兼執行長 Dave Lennon 博士； Scott Giacobello，我們的財務長兼首席醫療官 Loretta Itri 博士。

Today, we will provide an overview of operational activity and select financial results for the fourth quarter and full year of 2023. We will open the line for questions at the end of the call following closing comment.

今天，我們將概述 2023 年第四季和全年的營運活動和部分財務表現。我們將在電話會議結束時在結束評論後開通提問熱線。

A quick reminder that statements made on the call today will include forward looking statements, actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our annual and quarterly filings with the Securities and Exchange Commission, which can be found at www.SEC.gov or on our website at www.Aadibio.com.

快速提醒一下，今天的電話會議上的陳述將包括前瞻性陳述，由於各種風險、不確定性和其他因素（包括所闡述的因素），實際事件或結果可能與任何前瞻性陳述中明示或暗示的內容有重大差異請參閱我們向美國證券交易委員會提交的年度和季度文件的「風險因素」部分，該部分可在 www.SEC.gov 或我們的網站 www.Aadibio.com 上找到。

In addition, any forward-looking statements made on this call represent our views only as of today, March 13, 2024, and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements.

此外，本次電話會議中所做的任何前瞻性陳述僅代表我們截至今天（2024 年 3 月 13 日）的觀點，不應被視為代表我們在任何後續日期的觀點。我們特別聲明不承擔更新或修改任何前瞻性陳述的義務。

With that, I'll turn the call over to Dave for his opening statements. Dave?

接下來，我會把電話轉給戴夫，讓他作開場陳詞。戴夫？

Morning, everyone, and thank you for joining us today to review our financial and operational results for the fourth quarter and full year of 2023. At Aadi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining nab technology and the potent mTOR inhibitors Sirolimus. We believe Napster alignment has potential to deliver deeper inhibition and ultimately better outcomes for patients living with cancers that are dependent on the mTOR pathway. In 2023 was a year marked by progress and increasing momentum for the company as we delivered strong execution against both commercial and development goals.

大家早安，感謝您今天加入我們，回顧我們 2023 年第四季和全年的財務和營運表現。在 Aadi，我們致力於透過獨特地將 nab 技術與強效 mTOR 抑制劑西羅莫司結合，釋放 mTOR 抑制的全部潛力。我們相信 Napster 聯盟有可能為依賴 mTOR 路徑的癌症患者提供更深入的抑制並最終帶來更好的結果。2023 年是公司進步和成長動能的一年，我們針對商業和發展目標提供了強而有力的執行力。

First, FYARRO sales remained solid, achieving a cumulative $24.4 million for the full year of 2023, representing a 60% growth over prior year. FYARRO type penetration in the academic and community settings and is considered the preferred treatment for malignant PEComa. Clinically, a key focus for our organization has been realizing the potential of nab-sirolimus for patients with solid tumors, harbouring either TSC1 or TSC2 in activating alterations.

首先，FYARRO 銷售額保持穩健，2023 年全年累計實現 2,440 萬美元，較上年增長 60%。FYARRO 型在學術和社區環境中滲透並被認為是惡性 PEComa 的首選治療方法。在臨床上，我們組織的一個重點是認識到白蛋白結合西羅莫司對於攜帶 TSC1 或 TSC2 活化改變的實體瘤患者的潛力。

These types of genetic alterations are thought to activate the mTOR pathway leading to uncontrolled cell growth. And our PRECISION1 trial is an interventional study, designed to elucidate the potential of nab-Sirolimus to treat all types of solid tumors with either of these alterations. As a reminder, the unmet need in TSC1 and TSC2 mutated cancers is sizable, whether considering together or independently and represents about 2% of all solid tumor cancer patients.

這些類型的基因改變被認為會活化 mTOR 通路，導致細胞生長失控。我們的 PRECISION1 試驗是一項介入研究，旨在闡明白蛋白結合西羅莫司治療具有這些變化的所有類型實體瘤的潛力。提醒一下，無論是一起考慮還是單獨考慮，TSC1 和 TSC2 突變癌症的未滿足需求都相當大，約佔所有實體腫瘤癌症患者的 2%。

Our latest internal analysis indicates there are approximately 16,000 new patients with these mutations across a variety of tumor types each year in the US alone. With mutations roughly evenly split between genes, each mutation represents a potential multibillion dollar addressable market for nab-Sirolimus. TSC1 or TSC2 driven cancers are found across a wide range of tumor types, clustering and lung, gastrointestinal general urinary, breast and gynecological locations and are often very difficult to treat.

我們最新的內部分析表明，僅在美國，每年就有大約 16,000 名新患者攜帶多種腫瘤類型的這些突變。由於突變在基因之間大致均勻分佈，每個突變都代表了白蛋白結合西羅莫司潛在的數十億美元的潛在市場。TSC1 或 TSC2 驅動的癌症存在於多種腫瘤類型、聚集性腫瘤、肺癌、胃腸道、一般泌尿系統、乳癌和婦科部位，通常非常難以治療。

We believe PRECISION1 is a cutting-edge trial testing our innovative therapy, nab-Sirolimus in these cancer types. Although PRECISION1 is designed as a single trial, each arm is independently evaluated, providing us with the ability to assess one arm separately from the other. Given this design, PRECISION1 can effectively be viewed as two separate studies each with its own outcome. In Q4, we provided top-line results from a planned interim evaluation of the first 40 patients involved in PRECISION1. These data demonstrated sustained tumor reductions in a heavily pretreated population based on investigator-assessed responses in the first 40 patients across both arms.

我們相信 PRECISION1 是一項前沿試驗，測試我們的創新療法 nab-西羅莫司對這些癌症類型的療效。儘管 PRECISION1 被設計為單一試驗，但每個臂都經過獨立評估，使我們能夠單獨評估一個臂與另一個臂。鑑於這種設計，PRECISION1 可以有效地被視為兩項獨立的研究，每項研究都有自己的結果。在第四季度，我們提供了參與 PRECISION1 的前 40 名患者計劃的中期評估的主要結果。這些數據表明，根據研究者對雙臂前 40 名患者的反應評估，經過大量預處理的人群中腫瘤持續減少。

As a reminder, for the TSC1 arm, 19 efficacy evaluable patients were included in the cutoff date for the interim analysis who had at least one post-baseline scan. We reported an overall response rate of 26%, which was within the range of our expectations. Importantly, responses appear to be early, deep and durable. Median time to response was 1.4 months and all responses were ongoing at the time of data cutoff. This is especially noteworthy, given this is a heavily pretreated population with a median of three prior lines of therapy.

提醒一下，對於 TSC1 組，19 名可評估療效的患者被納入中期分析的截止日期，他們至少進行了一次基線後掃描。我們報告的總體回應率為 26%，這在我們的預期範圍內。重要的是，反應似乎是早期、深入和持久的。中位數回應時間為 1.4 個月，所有回應在數據截止時仍在進行中。這是特別值得注意的，因為這是一個經過大量預先治療的人群，之前接受過三種治療的中位數。

Lastly, these response were seen across four different tumor types supporting a tumor-agnostic indication. In the TSC2 arm, we reported a lower response rate, but given these patients were heavily pretreated, including 50% who has had at least five prior lines of therapy, each early TSC2 results are challenging to interpret. PRECISION1 continues to enroll steadily, and we now expect the trial to be fully enrolled by May. We are still on track for our next planned interim readout, which is expected in Q3 of 2024, this readout will include a total of 80 patients who have been followed for a minimum of six months will evaluate the primary endpoint in the study, independently assessed overall response rate.

最後，在四種不同的腫瘤類型中觀察到這些反應，支持腫瘤不可知的適應症。在 TSC2 組中，我們報告的緩解率較低，但考慮到這些患者接受了大量的預處理，其中 50% 的患者之前至少接受過五線治療，因此每個早期 TSC2 結果都難以解釋。PRECISION1 繼續穩定入組，我們現在預計該試驗將在 5 月全部入組。我們仍在按計劃進行下一次中期讀數，預計在 2024 年第三季度進行，該讀數將包括總共 80 名接受至少六個月隨訪的患者，這些患者將評估研究中的主要終點，並進行獨立評估總體響應率。

As opposed to our December analysis, which reported investigate [responses]. We expect the study to be completed by the end of 2024 with full data in early 2025. In addition to PRECISION1, enrolment is underway for both of the previously announced Phase two single indication trials for two promising mTOR driven cancer targets.

與我們 12 月的分析相反，該分析報告了調查[回應]。我們預計研究將於 2024 年底完成，並於 2025 年初獲得完整數據。除了 PRECISION1 之外，先前宣布的兩項針對兩個有希望的 mTOR 驅動癌症靶標的二期單一適應症試驗的入組工作也正在進行中。

Overactivation and dysregulation of the mTOR pathway is commonly found in various tumors and unique delivery and excellent safety profile of nab-Sirolimus provides the opportunity to combat these difficult to treat cancers.

mTOR 路徑的過度活化和失調常見於各種腫瘤中，nab-西羅莫司獨特的給藥方式和出色的安全性為對抗這些難以治療的癌症提供了機會。

The first trial is evaluating nab-Sirolimus in neuroendocrine tumors or NETs. NETs are rare with approximately 3,500 patients per year. NETs have historically had a low response rate to treatment with oral [rapid logs] and other agents, which nonetheless are used clinically and recommended in treatment guidelines today. In preclinical animal models, nab-Sirolimus demonstrated improved target suppression relative to other mTORs, warranting further exploration of nab-Sirolimus in this indication. We're excited about this trial because it provides the opportunity to demonstrate what we believe is nab-Sirolimus is best-in-class efficacy in a known mTOR sensitive tumor type.

第一項試驗是評估白蛋白結合西羅莫司在神經內分泌腫瘤或 NET 中的作用。NET 很少見，每年約有 3,500 名患者。歷史上，NETs 對口服[快速日誌]和其他藥物的治療反應率較低，儘管如此，這些藥物仍在臨床上使用，並在當今的治療指南中得到推薦。在臨床前動物模型中，nab-西羅莫司表現出相對於其他 mTOR 改善的靶點抑製作用，值得進一步探索 nab-西羅莫司在該適應症中的作用。我們對這項試驗感到興奮，因為它提供了機會來證明我們認為白蛋白結合西羅莫司在已知的 mTOR 敏感腫瘤類型中具有一流的療效。

The second trial we started last year is evaluating the therapeutic potential of nab-Sirolimus in advanced and recurrent endometrial type endometrial cancer in combination with the aromatase inhibitor, letrozole. Endometrial cancer is the most common cancer of the female reproductive tract and one of the few cancers with increasing mortality.

我們去年開始的第二項試驗是評估白蛋白結合西羅莫司與芳香酶抑制劑來曲唑合併治療晚期和復發性子宮內膜型子宮內膜癌的治療潛力。子宮內膜癌是女性生殖道最常見的癌症，也是死亡率不斷增加的少數癌症之一。

There is an estimated 10,000 cases of EEC diagnosed annually in the US alone. Prior clinical studies that the mTOR inhibitors combined with letrozole have yielded promising results and recent changes in the recommended standard of care for early-stage disease creates potential opportunity for our combination to be used in these first and second line settings. Both of these open label studies are actively ongoing, and we plan to present initial data later this year.

據估計，僅在美國每年就診斷出 10,000 例 EEC 病例。先前的臨床研究表明，mTOR 抑制劑與來曲唑聯合使用已取得了有希望的結果，並且近期疾病推薦治療標準的變化為我們的組合在一線和二線環境中使用創造了潛在的機會。這兩項開放標籤研究正在積極進行中，我們計劃在今年稍後提供初步數據。

Rounding out our clinical development program, we also have ongoing trial with combination of [ARISE KRAS] inhibitor and lung cancer and other solid tumors. With a solid commercial foundation provided by FYARRO robust in both clinical development programs spanning genetically driven tumors and other mTOR sensitive tumors and a cash runway into Q4 2025. We are well positioned to realize our ambition of becoming a multi-indication precision oncology company.

為了完善我們的臨床開發計劃，我們也正在進行 [ARISE KRAS] 抑制劑與肺癌和其他實體腫瘤聯合治療的試驗。憑藉 FYARRO 提供的堅實商業基礎，該計畫在涵蓋基因驅動腫瘤和其他 mTOR 敏感腫瘤的臨床開發項目中均表現強勁，並為 2025 年第四季度提供了現金跑道。我們有能力實現成為多適應症精準腫瘤公司的野心。

I will now turn the call over to Scott for updates on our financial progress. Scott?

我現在將把電話轉給斯科特，以了解我們財務進展的最新情況。史考特？

Thanks, Dave. We had a solid fourth quarter and ended 2023 with $108.8 million in cash, cash equivalents and short term investments. And early 2024, we implemented measures to streamline our operations and reduce costs, which included headcount reductions in our customer facing operations and corporate functions. Following these measures, we anticipate that our balance sheet will fund operations into Q4 2025 based on current plans.

謝謝，戴夫。我們第四季表現強勁，截至 2023 年，現金、現金等價物和短期投資為 1.088 億美元。2024 年初，我們實施了精簡營運和降低成本的措施，其中包括減少面向客戶的營運和公司職能部門的員工人數。根據這些措施，我們預計我們的資產負債表將為根據目前計劃到 2025 年第四季的營運提供資金。

FYARRO net product sales were $6.3 million for the fourth quarter, representing 6% growth over Q3 2023 and 21% over the prior year quarter. Full year, FYARRO sales were $24.4 million, an increase of 60% over prior year sales of $15.2 million. Research and development expenses for the quarter increased to $12.8 million compared to $9.4 million in the prior year quarter.

FYARRO 第四季產品淨銷售額為 630 萬美元，比 2023 年第三季成長 6%，比去年同期成長 21%。FYARRO 全年銷售額為 2,440 萬美元，比上年銷售額 1,520 萬美元成長 60%。本季的研發費用增加至 1,280 萬美元，去年同期為 940 萬美元。

For the year, R&D expense amounted to $48.9 million compared to $32.7 million last year. This increase was primarily related to the continued progress of the ongoing PRECISION1 trial and initiation of the programs and endometrial cancer and NETs. Selling, general and administrative expenses for the fourth quarter were $10.3 million compared to $11.1 million in the same period in 2022.

今年研發費用為 4,890 萬美元，去年為 3,270 萬美元。這一增長主要與正在進行的 PRECISION1 試驗的持續進展以及子宮內膜癌和 NET 計畫的啟動有關。第四季的銷售、一般和管理費用為 1,030 萬美元，而 2022 年同期為 1,110 萬美元。

For the year SG&A expenses totaled $44.5 million compared to $40.2 million in the prior year. This increase is due primarily to higher legal and company infrastructure costs and increased marketing expenses related to FYARRO.

本年度 SG&A 費用總計 4,450 萬美元，而前一年為 4,020 萬美元。這一增長主要是由於法律和公司基礎設施成本增加以及與 FYARRO 相關的營銷費用增加。

Net loss for the fourth quarter was $16.3 million compared to $13.9 million in the fourth quarter of 2022. Net loss for the year was $65.8 million compared to $60.5 million in the prior year. For more information on our financial performance for 2023. A detailed discussion of the results reported on this call will be provided in our 10-K to be filed later today.

第四季淨虧損為 1,630 萬美元，而 2022 年第四季淨虧損為 1,390 萬美元。本年度淨虧損為 6,580 萬美元，而上年度淨虧損為 6,050 萬美元。了解有關我們 2023 年財務業績的更多資訊。關於本次電話會議報告結果的詳細討論將在今天稍後提交的 10-K 中提供。

I'll now hand the call back to Dave for his closing comments. Dave?

現在，我將把電話轉回給戴夫，讓他發表結束語。戴夫？

Thank you, Scott. I'm so proud of the progress we made in Q4 and what the team accomplished in 2023. FYARRO remains a valuable asset with sustained demand to help meet the needs of patients with the PEComa. We're making tremendous progress against our clinical development plans with two sizable markets in TSC1 and TSC2 and activating alterations as well, other mTOR-driven cancers.

謝謝你，斯科特。我對我們在第四季度取得的進展以及團隊在 2023 年的成就感到非常自豪。FYARRO 仍然是一項寶貴的資產，具有持續的需求，有助於滿足 PEComa 患者的需求。我們在 TSC1 和 TSC2 兩個相當大的市場以及激活其他 mTOR 驅動的癌症的臨床開發計劃方面取得了巨大進展。

So looking forward to sharing the two thirds interim analysis from PRECISION1 in the third quarter with full enrollment inspected in May, and study completion by the end of 2024.

因此，期待分享 PRECISION1 第三季度的三分之二中期分析，並在 5 月檢查全部入學情況，並在 2024 年底完成研究。

We can now open the line for questions. Operator?

我們現在可以開通提問專線。操作員？

(Operator Instructions)

（操作員說明）

Joe Catanzaro, Piper Sandler.

喬·卡坦扎羅，派珀·桑德勒。

Yeah, thanks. Appreciate you taking the questions here. Maybe first one, I know the first 40 patients were characterized as being very heavily pretreated. So wondering if you have any visibility or updates around what the remainder of the trials look like? And maybe along these lines, whether you've seen any change in enrollment dynamics in any way since the interim data disclosure? Thanks. And I have one follow-up.

是的，謝謝。感謝您在這裡提出問題。也許是第一個，我知道前 40 名患者的特徵是接受了非常嚴格的預處理。那麼想知道您是否對其餘試驗的情況有任何了解或更新？也許沿著這些思路，自從臨時資料揭露以來，您是否看到招生動態發生任何變化？謝謝。我還有一個後續行動。

Great. Joe, thank you for the question. Always appreciate talking more about PRECISION1. Yeah, so the first 40 patients were heavily pretreated, we saw three or more lines of prior therapy as those patients enrolled in that first 40 group. We anticipate right by the trial design that this is -- we're going to get a number of late-line patients. Patients have to have satisfied the criteria for the indication that they enroll in, in terms of being having received all appropriate standard of care prior to their entry and treatment with nab-Sirolimus in our trial.

偉大的。喬，謝謝你的提問。總是喜歡多談論 PRECISION1。是的，所以前 40 名患者接受了大量的預處理，當這些患者加入前 40 組時，我們看到了三種或更多線的先前治療。根據試驗設計，我們預計我們將獲得許多晚期患者。患者必須符合他們參加的適應症標準，即在我們的試驗中接受白蛋白結合西羅莫司治療之前接受所有適當的護理標準。

And so we anticipate it to continuing to enroll later line patients within the trial. I wouldn't comment on the overall nature of what we're going to end up with. We're still enrolling patients in the trial, we'll obviously report out the next or the total 80 patients as the two-thirds interim later this year.

因此，我們預計它將繼續在試驗中招募後期患者。我不會評論我們最終會得到什麼的整體性質。我們仍在招募患者參加試驗，顯然我們將在今年稍後報告下一批患者或總共 80 名患者，作為臨時患者的三分之二。

Okay. Thanks. And then just a follow up maybe unrelated to PRECISION1. Wondering if there are any early expectations around when you could report initial data from the endometrial or NET studies, appreciate those are still in the early days. And then any updates on the aggressive combo trial? Wondering maybe if there's been any changes there with the [ABRAXANE] acquisition by Bristol? Thanks.

好的。謝謝。然後只是跟進可能與 PRECISION1 無關。想知道您何時可以報告子宮內膜或 NET 研究的初始數據是否有任何早期預期，感謝這些仍處於早期階段。那麼激進的組合試驗有什麼更新嗎？想知道布里斯託收購 [ABRAXANE] 是否有任何變化？謝謝。

Yeah, so great questions. I think I mentioned earlier that we do anticipate potentially sharing data on endometrial or neuroendocrine trial later this year. Those are open-label, single-arm Phase two studies, and we have the opportunity to enroll those. We'll share the data when we think it's appropriate and we have something meaningful to say about how that data is -- those patients are enrolling, and that data is maturing.

是的，非常好的問題。我想我之前提到過，我們確實預計今年稍後可能會共享子宮內膜或神經內分泌試驗的數據。這些是開放標籤、單臂二期研究，我們有機會招募這些研究。當我們認為合適時，我們將分享這些數據，我們對這些數據有一些有意義的看法——這些患者正在入組，而這些數據正在成熟。

I'm happy to say the pace of both studies are actively enrolling patients, and they're good engagement with the community on generatin patients for each of those trials, which we just think is some initially a great sign in terms of folks' interest on indies therapeutic regiments in each of those indications.

我很高興地說，這兩項研究的步伐都在積極招募患者，並且他們與社區就每一項試驗的生成患者進行了良好的互動，我們只是認為這最初是人們興趣方面的一個很好的跡象關於每種適應症的獨立治療方案。

And then on the Mirati's BMS collaboration that continues and is ongoing, and we are enrolling patients into that trial, and we don't have any further updates at this point.

然後，Mirati 的 BMS 合作仍在繼續，我們正在招募患者參加試驗，目前我們沒有任何進一步的更新。

Okay, thanks. That's helpful. And thanks for taking my questions.

好的謝謝。這很有幫助。感謝您回答我的問題。

Thanks, Joe.

謝謝，喬。

Liang Cheng, Jefferies.

梁誠，杰弗里斯.

Sure. Thank you. This down for Roger. So thank you for taking our questions. I guess from us, we have two questions. Why is there a lot of firewalls, so gets more FYARRO in the coming year? Can you provide us any detailed guidance on or commercial plans?

當然。謝謝。這對羅傑來說是不利的。感謝您回答我們的問題。我想我們有兩個問題。為什麼有很多防火牆，所以來年會有更多 FYARRO？您能給我們詳細的指導或商業計劃嗎？

Second question is about, you know, I know you guys been interacting with FDA about the blood tumor agnostic. So what's -- in your understanding, what's the most important thing for FDA to consider label as a tumor agnostic. Thank you.

第二個問題是，我知道你們一直在與 FDA 就血液腫瘤不可知論互動。那麼，根據您的理解，FDA 考慮將標籤標記為腫瘤不可知論最重要的事情是什麼。謝謝。

Great. Thank you, Liang, and thanks for stepping in for Roger. So maybe in terms of FYARRO our outlook, maybe I'll turn it over to Scott to talk a little bit about that and then we'll talk about your second question.. But Scott you want to just comment on the FYARRO outlook for the coming year?

偉大的。謝謝你，梁，也謝謝你為羅傑介入。因此，也許就 FYARRO 我們的前景而言，也許我會將其交給 Scott 來討論一下，然後我們將討論您的第二個問題。但斯科特，您只想評論一下 FYARRO 來年的前景嗎？

Sure, absolutely. thanks for the question, Liang. Yes, I think for FYARRO, I mean, as you've seen, I mean we're not going to provide guidance for this year. I think what we've seen over the last few quarters the sales stabilizing around the $6 million mark or slightly above. And I think so the expectation there is we continue to be excited about the about FYARRO and the potential to grow there. But I think that over the last few quarters, you've seen the sales stabilizing in that $6 million to $6.5 million range, and I think that's what we would expect for 2024.

當然，絕對。謝謝樑的提問。是的，我認為對於 FYARRO，我的意思是，正如您所看到的，我的意思是我們不會為今年提供指導。我認為過去幾季我們看到銷售額穩定在 600 萬美元左右或略高於。我認為我們對 FYARRO 及其發展潛力繼續感到興奮。但我認為，在過去的幾個季度中，您已經看到銷售額穩定在 600 萬美元至 650 萬美元的範圍內，我認為這就是我們對 2024 年的預期。

Thanks, Scott. And it is, you know, Liang it is a very our team's done a great job penetrating the market here where available and preferred for PEComa, in the first line setting and unpacked widely recognized as the preferred therapy for PEComa. It is just an ultra rare population. And ultimately, we may be reaching saturation of that market and expect more incremental growth from here on out.

謝謝，斯科特。梁，您知道，我們的團隊在滲透 PEComa 可用且首選的市場方面做得非常出色，在一線環境中，並被廣泛認為是 PEComa 的首選療法。這只是一個極為稀有的群體。最終，我們可能會達到該市場的飽和狀態，並預計從現在開始會有更多增量成長。

And then your second question was on what are the most important considerations when we think about the FDA's view on the tumor-agnostic indication, I'm going to turn it over to Loretta to give her thoughts on and how we think or how we interpret the FDA's guidance around tumor-agnostic indication and what's most important there. So Loretta, do you want to comment?.

然後你的第二個問題是，當我們考慮 FDA 對腫瘤不可知適應症的看法時，最重要的考慮因素是什麼，我會把它交給 Loretta，讓她談談我們的想法或我們如何解釋FDA 關於腫瘤不可知適應症的指導以及其中最重要的內容。Loretta，你想發表評論嗎？

Sure, I'll be happy to. I think, from what we have seen recently, perhaps the most important thing that the agency wants to see in tumor-agnostic studies, is a variety of different tumor types. What they do not want in a tumor-agnostic studies to see concentrations of inflammation in certain subtypes of patients, they are looking for a representation of the mutation across a variety of different tumor types. That is why you do a tumor-agnostic study.

當然，我很樂意。我認為，從我們最近看到的情況來看，該機構希望在腫瘤不可知研究中看到的最重要的事情也許是各種不同的腫瘤類型。他們不希望在與腫瘤無關的研究中看到某些亞型患者的發炎濃度，而是尋找各種不同腫瘤類型的突變代表。這就是您進行腫瘤不可知研究的原因。

So I think that that is perhaps the single most important element in terms of their determination regarding whether or not a drug classifies for tumor-agnostic approval. And then of course, I think they are looking for a reasonable response rate and of course, a good safety profile. And in our case, since we already have approval in a single indication, I think they would be looking to see that the safety profile in the agnostic population closely resembles what we have seen in sarcoma.

因此，我認為這可能是他們決定某種藥物是否屬於腫瘤不可知批准的最重要因素。當然，我認為他們正在尋找合理的回應率，當然還有良好的安全性。在我們的案例中，由於我們已經在單一適應症中獲得批准，我認為他們會希望看到不可知論群體的安全性與我們在肉瘤中看到的安全性非常相似。

Thanks, Loretta. And just to add onto to what Laura was saying, what we saw so far, we have enrolled a very diverse tumor population within our trial. And I think you saw that even in the early results where we had a kind of broad distribution of tumor types that we shared back in December.

謝謝，洛麗塔。為了補充勞拉所說的話以及我們迄今為止所看到的內容，我們在試驗中招募了非常多樣化的腫瘤群體。我想你也看到了，即使在早期結果中，我們在 12 月分享的腫瘤類型也有廣泛的分佈。

Thanks, Liang, for the questions. And I think if there's no follow-ups, we can move to the next that are coming through.

謝謝梁老師的提問。我認為如果沒有後續行動，我們可以繼續下一個後續行動。

Thank you. Appreciate it.

謝謝。欣賞它。

And thank you.

謝謝你。

Thank you. (Operator Instructions)

謝謝。（操作員說明）

Ahu Demir, Ladenburg.

阿胡‧德米爾，拉登堡。

Good morning. Thank you so much for taking my questions. I have two questions. A follow-up to Joe's question regarding endometrial cancer. One, could you give us a sense of the type opened, how many sites are open and inclusion exclusion criteria for the patients? And what are we expecting to see this year? How many patients are heavily pretreated. If you can provide a little bit color, that would be great.

早安.非常感謝您回答我的問題。我有兩個問題。喬有關子宮內膜癌的問題的後續行動。第一，您能否讓我們了解開放的類型、開放的站點數量以及患者的納入排除標準？今年我們期待看到什麼？有多少患者接受過嚴格的預處理。如果你能提供一點顏色，那就太好了。

Sure. I think so I'm happy to answer those questions. I'm going to turn it over to Loretta for some of the details. But at the same time, we probably wouldn't discuss number of sites or number of patients at this point, just given where we are in the trial and it is active and we're kind of continuing to build that story. But maybe just in the design of the trial and what we might expect to see later this year. I'll let Loretta give you an update there. So Loretta?

當然。我想是的，我很高興回答這些問題。我將把它交給 Loretta 了解一些細節。但同時，我們目前可能不會討論試驗地點的數量或患者的數量，只是考慮到我們在試驗中的進展情況，而且試驗正在進行中，我們正在繼續構建這個故事。但也許只是在試驗的設計以及我們今年晚些時候可能會看到的情況中。我會讓洛雷塔向您通報最新情況。那麼洛蕾塔？

Good morning, Ahu. Always great questions as usual coming from you. And so basically this is an open label Phase two study looking to evaluate the combination of nab-sirolimus with letrozole. In patients who have advanced that would be on advanced or unresectable stage three or four more recurrent endometrioid endometrial carcinoma, patients will have received either no or one prior line of chemotherapy.

早上好，阿胡。像往常一樣，你總是提出很好的問題。基本上，這是一項開放標籤的第二階段研究，旨在評估白蛋白結合西羅莫司與來曲唑的組合。對於晚期或不可切除的第三期或第四期復發性子宮內膜樣子宮內膜癌的患者，患者將沒有接受過化療或接受過一次化療。

So this is a population of patients who are relatively early in their treatment course, which is somewhat differentiated, of course, from what we're doing in PRECISION. And so that patients are treated with the same dose of nab-sirolimus as they as they were in to sarcoma, that is a well-established and safe dose. And I think pretty much this is a Simon two-stage study. So we plan to enroll the first cohort. And we anticipate, since this is an open-label study being able to report out early results come by the end of this year. Does that address your question Ahu? who would you like more detail?

因此，這是一個處於治療過程相對早期的患者群體，當然，這與我們在 PRECISION 中所做的事情有所不同。因此，患者接受與肉瘤治療相同劑量的白蛋白結合西羅莫司治療，這是一個公認的安全劑量。我認為這幾乎是西蒙的兩階段研究。所以我們計劃招收第一批學生。由於這是一項開放標籤研究，我們預計能夠在今年年底前報告出早期結果。這解決了你的問題嗎？您想向誰提供更多詳細資訊？

This is great. Thank you so much, Loretta, this is very helpful and thank you for your compliments as well. I have one more conceptual question for you, Loretta, if I may. So you mention M4 sensitive tumors, besides TSC1 and TSC2. Could you comment on what other mutational background versus different employing inhibitors?

這很棒。非常感謝你，洛雷塔，這非常有幫助，也感謝你的讚美。如果可以的話，洛雷塔，我還有一個概念性問題想問你。所以你提到了除了 TSC1 和 TSC2 之外的 M4 敏感腫瘤。您能否評論一下與不同使用的抑制劑相比還有哪些突變背景？

Well, I think that's quite a difficult question because I think there are many mutations along the mTOR pathway that may provide some targets. However, I don't think that any of those specifically has been identified as a specific mutational target for mTOR inhibition, there are suggestions, but I don't think is any of those are proven.

嗯，我認為這是一個相當困難的問題，因為我認為 mTOR 路徑上有許多突變可能提供一些標靶。然而，我認為其中任何一個都沒有被明確確定為 mTOR 抑制的特定突變靶點，有一些建議，但我認為這些都沒有得到證實。

Very helpful. Thank you so much.

很有幫助。太感謝了。

You're most welcome.

非常歡迎您。

Thanks, Ahu. Operator, are there any other questions?

謝謝，阿胡。接線員，還有其他問題嗎？

And I see no further questions in the queue at this time. I'll now turn the call back over to you, Dr. Dave Lennon, for any closing remarks.

目前我在隊列中沒有看到更多問題。現在，戴夫·列儂博士，我將把電話轉回給您，請您發表結束語。

Thank you, operator, and thank you, everyone, for joining the call today. I think as you see, we are delivering on the operational goals we have set for goal 2023 and looking ahead into 2024. We're very confident on our ability to do deliver against our number one priority, which is the PRECISION1 trial. And we look forward to providing an update on that two-thirds interim later this year. And finishing that trial within 2024.

謝謝接線員，也謝謝大家今天加入通話。我認為，正如您所看到的，我們正在實現為 2023 年設定的營運目標，並展望 2024 年。我們對實現我們的首要任務（即 PRECISION1 試驗）的能力非常有信心。我們期待在今年稍後提供有關三分之二臨時的最新資訊。並在 2024 年完成試驗。

We're also excited about the new programs we mentioned today, and it got to discuss a little bit in the Q&A and look forward to providing updates on both our NET and endometrial trials later this year. At the same time, we remain really confident in the continued progress we're making in PEComa market with FYARRO. This is an ultra-orphan indication, and we're highly penetrated within that market and that continues to deliver solid sales for us as we go forward.

我們也對今天提到的新計劃感到興奮，並且在問答中進行了一些討論，並期待在今年晚些時候提供有關我們的 NET 和子宮內膜試驗的最新信息。同時，我們對 FYARRO 在 PEComa 市場的持續進展仍然充滿信心。這是一個超級孤兒適應症，我們在該市場的滲透率很高，隨著我們的前進，它繼續為我們帶來穩定的銷售。

Overall otherwise, I thank you all for your time and attention today, and we look forward to the next update with you all. Thank you and have a great day.

總的來說，我感謝大家今天的時間和關注，我們期待與大家一起進行下次更新。謝謝您，祝您有美好的一天。

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連線。