Whitehawk Therapeutics Inc (WHWK) 2024 Q2 法說會逐字稿

Good day, and thank you for standing by. Welcome to the Aadi Bioscience, Inc. Second quarter 2024 earnings call. (Operator Instructions) Please be advised that today's conference is being recorded.

美好的一天，感謝您的支持。歡迎參加 Aadi Bioscience, Inc. 2024 年第二季財報電話會議。（操作員指示）請注意，今天的會議正在錄製中。

Now I will turn the call over to Audrey Gruls, Head of Corporate Communications for Aadi Bioscience. Ms. Gruls, please go ahead.

現在我將把電話轉給 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 for the second quarter 2024. We will be presenting slides as part of the live webcast of this call. Such slides will be posted on the Investors & News page of the Aadi Bioscience website at aadibio.com following the conference call.

謝謝。早上好，歡迎參加 Aadi Bioscience 電話會議，提供 2024 年第二季的營運更新和審查結果。我們將在本次電話會議的網路直播中展示投影片。電話會議結束後，此類投影片將發佈在 Aadi Bioscience 網站 aadibio.com 的投資者與新聞頁面上。

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 filing with the Securities and Exchange Commission, which can be found at www.sec.gov or on our website at aadibio.com.

快速提醒您，今天的電話會議中發表的聲明將包括前瞻性聲明。由於各種風險、不確定性和其他因素，包括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中列出的因素，實際事件或結果可能與任何前瞻性陳述中明示或暗示的事件或結果有重大差異。

In addition, any forward-looking statements made on this call represent our views only as of today, August 7, 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 8 月 7 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。

On the call is Dr. Dave Lennon, our President and CEO; Scott Giacobello, our CFO; and our Chief Medical Officer, Dr. Loretta Itri. Today, we will provide an overview of operational activity and financial results for the second quarter of 2024. We will then open the line for questions at the end of the call following closing comments. I'll now turn the call over to Dave for his opening statement. Dave?

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；以及我們的首席醫療官 Loretta Itri 博士。今天，我們將概述 2024 年第二季的營運活動和財務表現。然後，我們將在電話會議結束時在結束評論後開放提問熱線。現在我會把電話轉給戴夫，讓他作開場陳詞。戴夫？

Good morning, everyone, and thank you for joining us today to review our financial and operational results for the second quarter of 2024. I'd also like to take this opportunity to refresh everyone on Aadi's story, where we are today, and where we're going in the weeks and months ahead.

大家早安，感謝您今天加入我們回顧我們 2024 年第二季的財務和營運表現。我也想藉此機會向大家介紹 Aadi 的故事、我們今天的處境以及未來幾週和幾個月的發展方向。

On slide five, you'll see at Aadi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining nab technology and the potent mTOR inhibitor, sirolimus.

在第五張投影片上，您將在 Aadi 看到，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。

With more complete mTOR target inhibition, greater tumor suppression, and a wider therapeutic index, we believe nab-sirolimus has the potential to build on previous mTOR inhibitors to deliver better outcomes for people living with cancers that are dependent on that pathway.

憑藉更完整的mTOR 標靶抑制、更強的腫瘤抑制和更廣泛的治療指數，我們相信nab-西羅莫司有潛力在先前的mTOR 抑制劑的基礎上為依賴該途徑的癌症患者提供更好的結果。

We've established the value of this approach with FYARRO for the treatment of advanced malignant pacoma, an ultra-rare soft tissue sarcoma with poor outcomes and high biological evidence of the mTOR pathway activation. FYARRO has cemented its position as a preferred treatment for malignant PEComa after just two years on the market. Since launch in February 2022, we have achieved $51.1 million in sales. We're proud of the impact FYARRO has had and will continue to have for patients with this rare and aggressive cancer.

我們已經與 FYARRO 合作確定了這種方法在治療晚期惡性 pacoma 方面的價值，這是一種極其罕見的軟組織肉瘤，預後不佳，但 mTOR 路徑活化的生物學證據很高。上市僅兩年後，FYARRO 就鞏固了其作為惡性 PEComa 首選治療藥物的地位。自 2022 年 2 月推出以來，我們的銷售額已達 5,110 萬美元。我們為 FYARRO 已經並將繼續為患有這種罕見且侵襲性癌症的患者帶來的影響感到自豪。

Building on this commercial backbone, we're also exploring nab-sirolimus for larger indications across multiple types of mTOR-driven tumors. Most advanced of these studies is PRECISION1, a registration-intended tumor-agnostic trial in patients with solid tumors harboring TSC1 or TSC2 inactivating alterations.

在此商業支柱的基礎上，我們也正在探索 nab-西羅莫司用於多種 mTOR 驅動腫瘤的更大適應症。這些研究中最先進的是 PRECISION1，這是一項針對具有 TSC1 或 TSC2 失活改變的實體瘤患者的註冊意圖腫瘤不可知試驗。

This trial is fully enrolled and expected to complete by the end of the year. In a moment, I'll talk more about PRECISION1 and the opportunity it represents for patients and providers. We're also evaluating nab-sirolimus in two mTOR-driven cancers with promising potential.

該試驗已全部入組，預計今年底完成。稍後，我將更多地討論 PRECISION1 及其為患者和提供者帶來的機會。我們也正在評估 nab-西羅莫司在兩種 mTOR 驅動的癌症中的應用，具有良好的潛力。

The first is advanced or recurrent endometrioid-type endometrial cancer, or EEC, 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. There's an estimated 10,000 cases of EEC diagnosed annually in the US alone.

第一種是與芳香酶抑制劑來曲唑合併治療晚期或復發性子宮內膜樣子宮內膜癌（EEC）。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。據估計，僅在美國每年就會診斷出 10,000 例 EEC 病例。

Prior clinical studies of mTOR inhibitors combined with letrozole have yielded promising results, and recent changes in the recommended standard of care for early-stage disease creates a potential opportunity for this combination to be used in the first- and second-line settings.

mTOR 抑制劑與來曲唑聯合的先前臨床研究已經取得了有希望的結果，並且最近對早期疾病推薦治療標準的改變為該組合在一線和二線環境中使用創造了潛在的機會。

The second trial is in neuroendocrine tumors of lung, gastrointestinal tract, and pancreas. Neuroendocrine tumors, or NETs, are rare and have a historically low response rate to treatment with oral rapalogs and other agents, which, nonetheless, are used clinically and recommended in treatment guidelines.

第二個試驗是針對肺部、胃腸道和胰臟的神經內分泌腫瘤。神經內分泌腫瘤（NET）很少見，歷史上對口服雷帕黴素類似物和其他藥物治療的反應率較低，儘管如此，這些藥物仍在臨床使用並在治療指南中推薦。

In preclinical animal models, nab-Sirolimus demonstrated improved target suppression relative to other mTORs, warranting further exploration of nab-Sirolimus in this indication. These Phase 2 open-label studies are both enrolling well, and we look forward to presenting initial data from these trials later this year.

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。這些 2 期開放標籤研究的招募情況都很好，我們期待在今年稍後提供這些試驗的初步數據。

Aadi is led by an accomplished team with deep expertise and a track record of responsible capital management. With sustained commercial success of FYARRO, Cash runaway is anticipated to extend into Q4 2025, with a catalyst-heavy 2024 and 2025 ahead of us. We believe Aadi is well-positioned to achieve our goals.

Aadi 由一支經驗豐富的團隊領導，他們擁有深厚的專業知識和負責任的資本管理記錄。隨著 FYARRO 持續取得商業成功，現金失控預計將持續到 2025 年第四季度，我們將迎來催化劑密集的 2024 年和 2025 年。我們相信 Aadi 完全有能力實現我們的目標。

Now, turning to slide six, as mentioned, PRECISION1 is a registration-intended tumor agnostic trial evaluating patients with solid tumors harboring either TSC1 or TSC2 and activating alterations. As of May, the trial has fully enrolled 120 patients across a broad array of tumor types. TSC1 or TSC2-driven cancers are found across a wide range of tumor types clustering in the lung, gastrointestinal, general urinary, breast, and gynecological locations and are often difficult to treat. Although PRECISION1 is a single trial, TSC1 and TSC2 arms are independently evaluated and can effectively be viewed as two separate studies, each with its own outcome.

現在，轉向第六張投影片，如前所述，PRECISION1 是一項以註冊為目的的腫瘤不可知試驗，評估患有攜帶 TSC1 或 TSC2 並激活改變的實體瘤的患者。截至 5 月，該試驗已全面入組 120 名患者，涉及多種腫瘤類型。TSC1 或 TSC2 驅動的癌症存在於多種腫瘤類型中，集中在肺部、胃腸道、一般泌尿系統、乳癌和婦科部位，通常難以治療。儘管 PRECISION1 是一項單一試驗，但 TSC1 和 TSC2 組是獨立評估的，並且可以有效地視為兩項單獨的研究，每項都有自己的結果。

Importantly, by design, patients in PRECISION1 have received all standard therapies appropriate for their tumor type and stage of disease. Or, in the opinion of the investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from the appropriate standard of care.

重要的是，根據設計，PRECISION1 中的患者接受了適合其腫瘤類型和疾病階段的所有標準治療。或者，在研究者看來，患者不太可能耐受適當的護理標準或從適當的護理標準中獲得臨床上有意義的益處。

In essence, for most patients enrolled in this study, this means they have limited, if any, further treatment options and an extremely poor prognosis. By the design of this trial, nab-sirolimus is the last available line of systemic therapy for these patients and truly tests the ability of nab-sirolimus to address TSC1 and TSC2 mutated cancers in these sickest patients.

從本質上講，對於參與這項研究的大多數患者來說，這意味著他們的進一步治療選擇（如果有的話）是有限的，並且預後極差。透過本試驗的設計，白蛋白結合西羅莫司是這些患者最後可用的全身治療線，並真正測試了白蛋白結合西羅莫司治療這些病情最嚴重的患者中 TSC1 和 TSC2 突變癌症的能力。

We remain on track for our next planned interim readout, which is expected in Q3 2024. This analysis will include a total of 80 patients who have been followed for a minimum of six months and will evaluate the primary endpoint of the study, independently assessed overall response rate.

我們仍在按計劃進行下一次中期讀數，預計將於 2024 年第三季進行。該分析將包括總共 80 名接受至少六個月追蹤的患者，並將評估研究的主要終點，獨立評估整體緩解率。

Now looking at slide seven, as a reminder, in Q4 we provided top line results for the planned interim evaluation of the first 40 patients enrolled in PRECISION1. These data demonstrated sustained tumor reductions in a heavily pre-treated population based upon investigator assessed responses across both arms.

現在看投影片 7，提醒一下，我們在第四季度提供了對 PRECISION1 中登記的前 40 名病患計畫的中期評估的主要結果。這些數據表明，根據研究人員評估的雙臂反應，經過大量預處理的人群中腫瘤持續減少。

For TSC1, we reported investigator assessed overall response rate of 26%, which was in -- within the range of our expectations. These responses appear to be early, deep, and durable, which is especially noteworthy given this heavily pre-treated population with a medium of three prior lines of therapy.

對於 TSC1，我們報告研究者評估的整體緩解率為 26%，在我們的預期範圍內。這些反應似乎是早期、深入和持久的，考慮到這個接受過大量預先治療且之前接受過三種治療的人群，這一點尤其值得注意。

These responses were seen across four different tumor types, potentially supporting a tumor agnostic indication. For the TSC2 arm, we reported 11% overall response rate. This arm had a medium of 3.5 prior treatments, including 50% who had at least five prior lines of therapy.

這些反應出現在四種不同的腫瘤類型中，可能支持腫瘤不可知的適應症。對於 TSC2 組，我們報告的整體緩解率為 11%。該組之前接受過 3.5 次治療，其中 50% 接受過至少 5 次治療。

To put these early interim data in context, the overall response rate for the Phase 2 trial of Everolimus in a pan-cancer cohort of patients with mTOR pathway alterations was 8% for TSC1 and 6% for TSC2, both in slightly earlier lines of treatment. While this isn't a one-to-one comparison and studies have important differences, these historical data are helpful as we think about the clinical significance of the responses we reported in the first interim analysis, especially in light of the late line of treatment.

將這些早期中期數據放在背景中，在mTOR 路徑改變的泛癌患者群組中進行的依維莫司2 期試驗的總體緩解率，TSC1 為8%，TSC2 為6%，兩者均處於稍早的治療線中。雖然這不是一對一的比較，而且研究存在重要差異，但當我們思考我們在第一次中期分析中報告的反應的臨床意義時，這些歷史數據是有幫助的，特別是考慮到後期治療。

I also want to highlight that ongoing conversation with experts reinforced this view. We have heard from key opinion leaders that these data are compelling, especially for tumor types in late line for whom disease control is a meaningful outcome.

我還想強調的是，與專家的持續對話強化了這個觀點。我們從關鍵意見領袖那裡得知，這些數據令人信服，特別是對於晚期腫瘤類型來說，疾病控制對它們來說是有意義的結果。

Now turning to slide eight, it's important to note that PRECISION1 closely follows the most up-to-date guidance from regulators on how they would like to see tumor agnostic studies for targeted therapies run. As we've reiterated today, PRECISION1 is a truly tumor agnostic trial enrolling any solid tumor type harboring a TSC1 or TSC2 inactivating alteration.

現在轉向第八張幻燈片，值得注意的是 PRECISION1 嚴格遵循監管機構關於如何進行標靶治療腫瘤不可知研究的最新指導。正如我們今天重申的那樣，PRECISION1 是一項真正的腫瘤不可知論試驗，招募了任何含有 TSC1 或 TSC2 失活改變的實體瘤類型。

By design, PRECISION1 will not have more than 25% contribution of enrollment from any two tumor types combined. Additionally, patients in PRECISION1 are heavily pre-treated with a median of three prior lines of therapy as reported in our December interim data.

根據設計，PRECISION1 的任何兩種腫瘤類型的入組貢獻不會超過 25%。此外，正如我們 12 月中期數據中所報告的那樣，PRECISION1 中的患者接受了中位數為三線治療的大量預先治療。

By contrast, when we look at other targeted therapies that have gained approval in the past, they relied on a cohort approach with significant enrollment from just one or two tumor types, as much as 79% in one case. Patients also appeared to be less advanced with these interventions often coming in earlier line settings, which impacts the overall response rate seen in these trials.

相較之下，當我們觀察過去獲得批准的其他標靶療法時，它們依賴於隊列方法，僅針對一種或兩種腫瘤類型進行大量入組，在一個病例中，入組率高達 79%。由於這些幹預措施通常在較早的線路中進行，患者似乎也不太先進，這影響了這些試驗中的整體反應率。

Based on these precedents, we feel confident in the design of PRECISION1 to meet the standard established for this type of study. We continue to believe that should these results reported in the one-third interim hold or improve in a larger group of patients, we have a path to submission and potential approval for TSC mutations.

基於這些先例，我們對 PRECISION1 的設計充滿信心，能夠滿足為此類研究制定的標準。我們仍然相信，如果三分之一中期報告的這些結果在更大的患者群體中保持或改善，我們就有了一條提交 TSC 突變並可能獲得批准的途徑。

Now looking at the market opportunity on slide nine, TSC1 and TSC2 mutations define a large mutation- driven oncology population with broad distribution amongst tumor indications and specialties. Our latest internal analysis indicates there's approximately 16,000 patients with TSC1 and TSC2 mutations across a variety of tumor types, and these mutations are roughly evenly split between genes.

現在看看第九張投影片上的市場機會，TSC1 和 TSC2 突變定義了一個大型突變驅動的腫瘤群體，廣泛分佈在腫瘤適應症和專業中。我們最新的內部分析表明，大約 16,000 名患者在多種腫瘤類型中存在 TSC1 和 TSC2 突變，並且這些突變在基因之間大致均勻分佈。

Notably, we are seeing an increasing utilization of NGS testing by oncologists to help inform treatment decisions. There are some populations in particular for whom NGS testing is more common, so-called high NGS testing specialties. Nearly half of TSC1 and TSC2 tumors present in these high NGS testing specialties, which include tumors of gynecological and thoracic origin, as well as Melanoma and sarcomas. These physicians see roughly half of all TSC1 and TSC2 positive cancers.

值得注意的是，我們看到腫瘤學家越來越多地利用 NGS 測試來幫助制定治療決策。對於某些人群來說，NGS 測試更為常見，即所謂的高 NGS 測試專業。近一半的 TSC1 和 TSC2 腫瘤存在於這些高 NGS 檢測專業中，其中包括婦科和胸部來源的腫瘤，以及黑色素瘤和肉瘤。這些醫生看到了大約一半的 TSC1 和 TSC2 陽性癌症。

According to our research for the product profile, similar to our interim results to date, high NGS testing specialties indicate they would be likely to use nab-Sirolimus after second and third-line preferred treatments, which aligns with what we've observed in PRECISION1.

根據我們對產品概況的研究，與我們迄今為止的中期結果類似，高NGS 測試專業表明他們可能會在二線和三線首選治療後使用白蛋白結合西羅莫司，這與我們在PRECISION1 中觀察到的結果一致。

We anticipate that market adoption would be led by these specialties, with initial uptakes occurring in later-line settings where patients are -- often thoroughly tested for mutations and physicians are looking for unique treatment options.

我們預計市場採用將由這些專業主導，最初的採用發生在患者所在的後期環境中——通常對突變進行徹底測試，醫生正在尋找獨特的治療方案。

Even if we limit the majority of nab-Sirolimus utilization to be in the third line with these high NGS testing segments, TSC1 and TSC2 mutated cancers would represent a significant $300 million to $600 million projected market opportunity in the US alone.

即使我們將大多數白蛋白結合西羅莫司的使用限制在這些高 NGS 檢測領域的第三線，僅在美國，TSC1 和 TSC2 突變癌症就將代表著 3 億至 6 億美元的重大市場機會。

So, if PRECISION1 delivers similar results to our prior interim analysis, we know there's a significant unmet need that we're addressing. We remain confident that we've designed and conducted the appropriate tumor agnostic trial for the FDA, and we remain bullish on the significant commercial potential for nab-Sirolimus beyond the PEComa.

因此，如果 PRECISION1 提供與我們先前的中期分析類似的結果，我們就知道我們正在解決一個重大的未滿足的需求。我們仍然相信，我們已經為 FDA 設計並進行了適當的腫瘤不可知試驗，並且我們仍然看好白蛋白結合西羅莫司在 PEComa 之外的巨大商業潛力。

With that, I'll now turn it over to Scott for updates on our Q2 financial progress. Scott?

現在，我將把它交給史考特，以獲取有關我們第二季財務進展的最新資訊。史考特？

Thanks, Dave. Looking at slide 11 and starting with FYARRO. FYARRO net product sales were $6.2 million in the second quarter, in line with the prior year period and up 15% over Q1. In the quarter, we saw a 14% increase in the number of ordering accounts compared to the first quarter, and growth was observed across all segments, including large accounts.

謝謝，戴夫。檢視投影片 11，從 FYARRO 開始。FYARRO 第二季產品淨銷售額為 620 萬美元，與去年同期持平，比第一季成長 15%。在本季度，我們的訂購帳戶數量比第一季度增長了 14%，並且所有細分市場（包括大帳戶）都出現了增長。

Since launch in February 2022, we've achieved $51.1 million in cumulative sales. FYARRO has a high demand and penetration across both academic and community settings, and we have seen the consistent addition of new accounts ordering FYARRO, with more than 200 accounts ordering since launch.

自 2022 年 2 月推出以來，我們的累計銷售額已達 5,110 萬美元。FYARRO 在學術和社區環境中都有很高的需求和滲透率，我們看到訂購 FYARRO 的新帳戶不斷增加，自推出以來已有 200 多個帳戶訂購。

Turning to slide 12, the end of the second quarter 2024, we saw $78.6 million in cash, cash equivalents, and short-term investment. Responsible capital management continues to support a healthy balance sheet that will fund operations into Q4 2025, based on current plans.

轉向投影片 12，即 2024 年第二季末，我們看到現金、現金等價物和短期投資為 7,860 萬美元。負責任的資本管理將繼續支持健康的資產負債表，根據當前計劃，為 2025 年第四季的營運提供資金。

Research and development expenses for the quarter amounted to $13.1 million, compared to $13.3 million in the prior year quarter. R&D expenses were primarily related to the continued progress of the ongoing Phase 1 trial and the programs in endometrial cancer and NETs. Selling general and administrative expenses for the second quarter was $7.9 million, compared to $11.8 million in the same period in 2023.

本季的研發費用為 1,310 萬美元，而去年同期的研發費用為 1,330 萬美元。研發費用主要與正在進行的 1 期試驗以及子宮內膜癌和 NET 計畫的持續進展有關。第二季的銷售一般和管理費用為 790 萬美元，而 2023 年同期為 1,180 萬美元。

This decrease was driven mainly by reduced commercial, marketing, and personnel expenses related to the right sizing of our operations earlier in the year, and reduced legal expenses versus the prior year quarter. Net loss for the second quarter was $14.6 million, compared to $18 million in the second quarter of 2023.

這一下降主要是由於與今年早些時候適當調整業務規模相關的商業、行銷和人員費用的減少，以及與去年同期相比法律費用的減少。第二季淨虧損為 1,460 萬美元，而 2023 年第二季淨虧損為 1,800 萬美元。

For more information on our financial performance in the second quarter, a detailed discussion of the results reported on this call will be provided in our form 10-Q.

有關我們第二季度財務業績的更多信息，我們將在 10-Q 表格中提供對本次電話會議報告結果的詳細討論。

I'll now hand the call back over to Dave.

我現在將把電話轉回給戴夫。

As discussed today, we're making tremendous progress against our clinical development plans with two sizable markets in TSC1 and TSC2 in activating alterations, as well as other mTOR-driven cancers.

正如今天所討論的，我們在 TSC1 和 TSC2 活化改變以及其他 mTOR 驅動的癌症方面擁有兩個相當大的市場，在臨床開發計劃方面取得了巨大進展。

On slide 14, what you'll see is the back half of the year will be an important time for Aadi, and we look forward to providing the anticipated two-thirds interim analysis from PRECISION1 later this quarter, and if appropriate, sharing those data with the FDA thereafter. We expect to complete PRECISION1 by the end of the year.

在幻燈片14 上，您將看到今年下半年對Aadi 來說將是一個重要時期，我們期待在本季度稍後提供PRECISION1 預期的三分之二中期分析，並在適當的情況下共享這些數據此後與 FDA 合作。我們預計在今年年底前完成 PRECISION1。

Additionally, we plan to provide an initial look at data coming out of the EEC and NET trials by the end of the year as well. Looking ahead to 2025, we expect to have full results of PRECISION1, and if the data continue to hold, we believe this would form the basis of a filing with the FDA in 2025 as well.

此外，我們也計劃在今年底前對 EEC 和 NET 試驗的數據進行初步分析。展望 2025 年，我們預計將獲得 PRECISION1 的完整結果，如果資料繼續保持不變，我們相信這也將成為 2025 年向 FDA 提交文件的基礎。

With that, we can now open the line for questions.

這樣，我們現在就可以打開提問專線了。

(Operator Instructions) Roger Song, Jefferies.

（操作員說明） Roger Song，Jefferies。

Great, thanks for the update and taking our questions. Maybe we first talk about the PRECISION -- Dave, if we may -- understanding you will have the second interim data in 3Q, first of all, given the first interim data, what kind of the expectation you have for TSC1 and TSC2?

太好了，感謝您的更新並回答我們的問題。也許我們首先談談精度 - 戴夫，如果可以的話 - 了解您將在第三季度獲得第二個中期數據，首先，考慮到第一個中期數據，您對 TSC1 和 TSC2 有什麼樣的期望？

And the second part of the question is that you say you will discuss with the FDA with the second interim data, and then just curious to what will be the key topics there, and then what could be the potential outcome out of the FDA discussion of the second interim as a follow-up. Thank you.

問題的第二部分是，你說你將與 FDA 討論第二個中期數據，然後只是好奇那裡的關鍵主題是什麼，然後 FDA 討論的潛在結果是什麼第二次臨時行動作為後續行動。謝謝。

Sure. Thanks, Roger. I'll make a couple comments and ask Loretta if she has anything she'd like to add. Our PRECISION1 outcome in Q3 will be -- present, obviously, just a reminder, this is a primary endpoint analysis on two-thirds patients, so 80 patients or 40 patients in each arm.

當然。謝謝，羅傑。我會發表一些評論，並詢問 Loretta 是否有什麼要補充的。我們在第三季的 PRECISION1 結果將是——顯然，只是提醒一下，這是對三分之二患者的主要終點分析，因此每組有 80 名患者或 40 名患者。

The primary endpoint of independently assessed overall response rate after six months -- minimum six months of follow-up, will be reported out along with key demographic and select secondary data. We -- I wouldn't, draw any anticipation in terms of the direction of what we see that data going at this point in time. We'll have to wait for that report to see that. But those are the, that's the information. If you want more specifics, just let me know the follow-up there.

六個月後獨立評估的整體緩解率的主要終點（至少六個月的追蹤）將與關鍵人口統計和選定的輔助數據一起報告。我們——我不會對我們此時看到的數據的發展方向做出任何預期。我們必須等待該報告才能看到這一點。但這些就是資訊。如果您想了解更多具體信息，請讓我知道後續情況。

And then presumably, since this is representative of the primary endpoint and a preplanned interim analysis, we do think this would be a good foundation for data discussion, data-driven discussion with the FDA on a potential path to submission. And that would be the goal of that next discussion with the FDA.

然後據推測，由於這代表了主要終點和預先計劃的中期分析，我們確實認為這將成為數據討論、與 FDA 就潛在提交路徑進行數據驅動討論的良好基礎。這將是與 FDA 下次討論的目標。

Loretta, anything you would add to that?

洛雷塔，你還有什麼要補充的嗎？

No, Dave, I think you covered it nicely. Thank you.

不，戴夫，我認為你講得很好。謝謝。

Got it. Yeah, thank you. And then, since the enrollment for the EEC and the NET phase studies are going pretty well, and then just curious, what should we expect from the later this year's initial data update? Will that be focusing on the, maybe some of the safety, turbidity, or you expect to see some clinical activity from this -- those initial data results, and how many patients we should expect to see for the data? Thank you.

知道了。是的，謝謝。然後，由於 EEC 和 NET 階段研究的註冊進展順利，我們很好奇，我們應該對今年稍後的初始數據更新有何期待？是否會專注於一些安全性、濁度，或者您期望從中看到一些臨床活動——那些初始數據結果，以及我們應該看到多少患者的數據？謝謝。

Yeah, I'll let Loretta start by commenting on where we are with those trials, and I can follow up if there's anything to add. So, Loretta, why don't you comment on this?

是的，我會讓 Loretta 先評論我們在這些試驗中的進展情況，如果有什麼需要補充的，我可以跟進。那麼，洛雷塔，你為什麼不對此發表評論呢？

Sure. Thanks, Dave, and thank you for the question. For the EEC trial, we have been recruiting very rapidly which I think reflects the support in the community for this combination. Currently, although we're not giving exact numbers, we have completed enrollment of the entire first cohort, and we're well into the second cohort at this point in time.

當然。謝謝戴夫，也謝謝你提出這個問題。對於 EEC 試驗，我們一直在非常迅速地招募人員，我認為這反映了社區對這項組合的支持。目前，雖然我們沒有給出確切的數字，但我們已經完成了整個第一批的註冊，並且此時我們已經進入了第二批。

My expectation is that by the end of the year, we will be able to give a fairly fulsome report on the first cohort of patients, and probably some partial information on the second cohort. So, that's EEC, and for the NET program, again, we are accruing quite rapidly, and I have full expectation that by end of year, we will be able to report on the first cohort of patients quite completely.

我的期望是，到今年年底，我們將能夠提供有關第一組患者的相當豐富的報告，並可能提供有關第二組患者的一些部分資訊。這就是 EEC，對於 NET 項目，我們的累積速度相當快，我完全期望到年底，我們將能夠相當完整地報告第一批患者。

Dave, I don't know if you want to add something else.

戴夫，我不知道你是否還想補充一些東西。

That's great, Loretta. Thank you. The only thing I might add is that these are two indications where there is precedent data with mTOR inhibitors, and so one of the opportunities we have here is to compare what we know from prior studies with mTOR inhibitors in these indications to the data we're seeing with nab-sirolimus, which will be something we'll bring forward as we look at that data, dependent on the patients that we enroll in these early trials.

太好了，洛麗塔。謝謝。我唯一要補充的是，這兩個適應症有mTOR 抑制劑的先例數據，因此我們在這裡擁有的機會之一就是將我們從這些適應症中mTOR 抑制劑的先前研究中了解到的資訊與我們的數據進行比較。

Dave, if I might add, I just want to remind everyone that these studies are open-label, unlike precision, so there will be no problem statistically with reporting the information. Thank you.

戴夫，如果我可以補充的話，我只是想提醒大家，這些研究是開放標籤的，與精確性不同，因此報告資訊在統計上不會有問題。謝謝。

Thanks.

謝謝。

Thanks, Roger. Can we move on to the next set of questions?

謝謝，羅傑。我們可以繼續討論下一組問題嗎？

Joe Catanzaro, Piper Sandler.

喬·卡坦扎羅，派珀·桑德勒。

Hey, guys. Thanks for taking my questions here. Maybe following up a bit on sort of what happens post the second two-thirds interim analysis here and the range of outcomes, I'm guessing if -- I'm wondering if there's any scenario in which the design and execution of the remainder of PRECISION1 is altered or changed in any way.

嘿，夥計們。感謝您在這裡提出我的問題。也許對第二個三分之二中期分析後發生的事情以及結果的範圍進行一些跟進，我猜測 - 我想知道是否存在任何場景，其中其餘部分的設計和執行PRECISION1 以任何方式更改或更改。

I do recall maybe some speculation that there's a possibility of maybe increasing the target enrollment of the trial, again, depending on sort of the outcome, so maybe you could just speak a little bit more to that on sort of the various scenarios that may play out.

我確實記得也許有人猜測，根據結果的不同，有可能再次增加試驗的目標註冊人數，所以也許你可以就可能發生的各種情況多談談這一點出去。

Sure, Joe. Thanks for the question. It's a good one. We have talked in the past about that ability to adjust the trial at this point in time, but we will say that the trial has been fully enrolled at this point in time, and so we anticipate being able to report out on the full 120-patient data set in early 2025 once those patients have completed their follow-up period.

當然，喬。謝謝你的提問。這是一件好事。我們過去曾討論過在此時調整試驗的能力，但我們會說試驗在此時已完全註冊，因此我們預計能夠報告完整的 120-患者數據將於 2025 年初完成隨訪期後設置。

And so we do feel we're in good position on the full trial enrollment in terms of -- so at this point, we don't anticipate any adjustments to the trial given the trajectory that we've seen so far, and we wouldn't anticipate that that would be an outcome in the short term. That's -- of course, we still would be waiting for our Data Monitoring Committee's recommendation on that, as well as kind of internal deliberations, and any changes we do would be part of our disclosure when we report out that data later this quarter.

因此，我們確實認為我們在全面試驗註冊方面處於有利位置 - 因此，鑑於我們迄今為止所看到的軌跡，我們預計不會對試驗進行任何調整，而且我們不會預期短期內會出現這種情況。當然，我們仍然會等待數據監測委員會對此的建議以及內部審議，我們所做的任何更改都將成為我們在本季度稍後報告數據時披露的一部分。

Okay. Got it. That's helpful. And then maybe one quick one on FYARRO. I know you maybe previously have spoken to expectations to continue to see some incremental growth there. Just wondering if that's still your expectations and what would be sort of the driver of that. Thanks.

好的。知道了。這很有幫助。然後也許是關於 FYARRO 的快速報導。我知道您可能之前曾說過期望繼續看到那裡的一些增量增長。只是想知道這是否仍然是您的期望以及其驅動因素是什麼。謝謝。

Yeah, I want to -- I mean, I do want to highlight that we did have a low Q1, which we discussed had -- likely was being impacted by potentially some cannibalization we were seeing at some of our large centers. Importantly, in Q2, we saw a really strong rebound in demand across all of our key segments of business.

是的，我想 - 我的意思是，我確實想強調我們的第一季確實較低，我們討論過 - 可能受到我們在一些大型中心看到的潛在蠶食的影響。重要的是，在第二季度，我們看到所有關鍵業務領域的需求都出現了真正強勁的反彈。

And we do believe that that's being sustained as we go into the next quarter, and that we're seeing from a demand perspective -- our demand numbers in Q2 actually outperformed what we saw in net sales as we had some deductions on a gross-to-net basis related to inventory movement still in Q2. And so we remain very positive on the outlook for continued incremental growth in the business in Q3 and Q4 of this year.

我們確實相信，隨著我們進入下一個季度，這種情況將會持續下去，而且我們從需求的角度來看——我們第二季度的需求數字實際上超過了我們在淨銷售額中看到的情況，因為我們對總銷售額進行了一些扣除額——與庫存變動相關的淨值基礎仍在第二季。因此，我們對今年第三季和第四季業務持續增量成長的前景仍然非常樂觀。

Okay, great. That's helpful. Thanks for taking my question.

好的，太好了。這很有幫助。感謝您提出我的問題。

Thanks, Joe. Next question, operator?

謝謝，喬。下一個問題，接線生？

Tara Bancroft, TD Cowen.

塔拉·班克羅夫特，TD·考恩。

Hi, this is Greg Eigner on behalf of Tara Bancroft. So the -- sorry. Is there any particular tumor type that you're favoring at this point for future trials, or will this continue to be a pan-tumor approach? And if it's the latter, what guidance does the FDA give for registrational trial requirements? Thank you.

大家好，我是塔拉·班克羅夫特 (Tara Bancroft) 的格雷格·艾格納 (Greg Eigner)。所以——抱歉。目前您在未來的試驗中是否青睞任何特定的腫瘤類型，或者這將繼續是泛腫瘤方法？如果是後者，FDA 對註冊試驗要求有何指導？謝謝。

Sure, Greg. Thanks for the question. We -- this is -- as I pointed out, I think, and we tried to discuss deeper in the slides, this is truly a tumor-agnostic trial, and therefore, the FDA has no guidance on biasing the trial for any particular indications.

當然，格雷格。謝謝你的提問。我們——這——正如我所指出的，我想，我們試圖在幻燈片中進行更深入的討論，這確實是一項與腫瘤無關的試驗，因此，FDA 沒有關於使試驗偏向任何特定適應症的指導。

And we certainly enroll any and all patients who qualify regardless of tumor type into the trial based on their TSC1, TSC2 status, and a few other of the inclusion criteria. So we do believe that this will be conducted and reviewed as a tumor-agnostic trial. Our indication will not be tumor specific. It will be for that tumor-agnostic label, assuming we submit and gain approval around that.

當然，我們會根據 TSC1、TSC2 狀態和其他一些納入標準，將所有符合資格的患者納入試驗，無論腫瘤類型為何。因此，我們確實相信這將作為一項與腫瘤無關的試驗進行和審查。我們的適應症不是腫瘤特異性的。假設我們提交並獲得批准，它將用於與腫瘤無關的標籤。

And we don't -- just to reiterate, we don't anticipate or guide this trial, PRECISION1, towards any specific tumor types. Obviously, we are very interested in thinking about our endometrial and neuroendocrine specific tumor indications, where we know mTOR plays a role regardless of TSC1 and TSC2 status.

我們不會—只是重申一下，我們不會預測或指導這項試驗 PRECISION1 針對任何特定的腫瘤類型。顯然，我們對思考子宮內膜和神經內分泌特異性腫瘤適應症非常感興趣，我們知道無論 TSC1 和 TSC2 狀態如何，mTOR 都發揮作用。

And actually, those trials exclude patients with those mutations, and therefore, we are -- or we haven't had any -- I should say we haven't had any patients with those mutations in that trial. And so that's looking at the impact of the mTOR pathway in those specific indications, where we know they are potentially more mTOR-sensitive.

實際上，這些試驗排除了帶有這些突變的患者，因此，我們——或者我們沒有——我應該說，我們在那次試驗中沒有任何帶有這些突變的患者。因此，我們正在研究 mTOR 路徑對這些特定適應症的影響，我們知道它們可能對 mTOR 更敏感。

Okay, wonderful. Thank you. That's very helpful. And if I can just ask one quick follow-on question. Is there a particular conference that you're targeting for the second interim, or would this be something that we can expect from a PR?

好吧，太棒了。謝謝。這非常有幫助。如果我可以快速問一個後續問題。您是否有為第二次中期會議準備的特定會議，或者這是我們可以從 PR 中期望的內容嗎？

Yeah, we would imagine this will be a company presentation at this point.

是的，我們認為這將是一次公司演示。

Great, thank you.

太好了，謝謝。

Ahu Demir, Ladenburg Thalmann.

阿胡·德米爾，拉登堡·塔爾曼。

Thank you very much for taking my question, and I appreciate the additional information with the results today. Two questions from us, perhaps one more after the second question would be. My initial question is, you mentioned the earlier lines of treatment having a better impact, as we have seen in many targeted therapies.

非常感謝您提出我的問題，我很感謝您今天提供的附加資訊和結果。我們提出了兩個問題，也許在第二個問題之後還會有一個問題。我的第一個問題是，您提到早期的治療方案具有更好的效果，正如我們在許多標靶治療中看到的那樣。

Curious if you are planning to maybe disclose that data with the next data release? Are we going to see distinct populations where patients are treated more than three lines of treatment versus earlier lines of treatment? Are you planning to disclose that information?

好奇您是否計劃在下一次數據發佈時披露該數據？我們是否會看到不同的人群接受超過三線的治療與早期的治療？您打算透露該資訊嗎？

We'll certainly disclose the response rate overall. I think the question, once we get the data, will be, did we see a difference between lines of treatment? Is that meaningful, given the data set that we have?

我們肯定會披露整體回應率。我認為，一旦我們獲得數據，問題將是，我們是否看到治療方案之間存在差異？考慮到我們擁有的數據集，這有意義嗎？

So I think, Ahu, that would be a decision that's highly data-dependent in terms of what we actually see from the patient population. I can say in the early line -- in the early interim we did in December, we didn't see any. It was a very small data set, so it's hard to extrapolate, but we didn't see any particular pattern. And we had responses spread across different lines of treatment.

所以我認為，Ahu，這將是一個高度依賴我們從患者群體中實際看到的數據的決定。我可以說，在我們 12 月的早期中期工作中，我們沒有看到任何情況。這是一個非常小的數據集，因此很難推斷，但我們沒有看到任何特定的模式。我們的反應分佈在不同的治療領域。

Makes sense. And my second question is on the endometrial cancer program. You did mention the biggest idea of the trial is to compare it to the other mTOR inhibitors.

有道理。我的第二個問題是關於子宮內膜癌計畫。您確實提到該試驗的最大想法是將其與其他 mTOR 抑制劑進行比較。

And the patient baseline demographics can impact the trial readouts significantly. So what was the other trials' patient demographics look like? Are you planning to focus on those, any particular populations that you would be targeting, anything we should pay attention to? Because sometimes it's very challenging when we are comparing apples to oranges and baseline demographics can impact a lot.

患者基線人口統計資料可顯著影響試驗讀數。那麼其他試驗的患者人口統計是什麼樣的呢？您是否計劃重點關注那些您要針對的特定人群以及我們應該注意的事項？因為有時候，當我們將蘋果與橘子進行比較時，這是非常具有挑戰性的，而且基線人口統計可能會產生很大的影響。

Yeah, understood. I probably oversimplified the comparison or statement in that. So I'm going to allow Loretta to comment on kind of our strategy with the endometrial trial and where we think the real benefit is here for patients. Loretta?

是的，明白了。我可能過於簡化了其中的比較或陳述。因此，我將允許 Loretta 評論我們的子宮內膜試驗策略以及我們認為真正為患者帶來的好處。洛蕾塔？

Sure, Dave. Good morning, Ahu, and thank you for that question. As usual, it's a good one. So the design of the EEC study was largely based on an earlier study that was performed by GOG, the Gynecologic Oncology Group. This was study GOG-209. And this is actually an older study that established platinum and palataxel as a standard of care for patients who had advanced endometrial cancer.

當然，戴夫。早安，阿胡，謝謝你提出這個問題。像往常一樣，這是一件好事。因此，EEC 研究的設計很大程度上是基於 GOG（婦科腫瘤學組）進行的早期研究。這是研究 GOG-209。這實際上是一項較早的研究，將鉑和紫杉醇確立為晚期子宮內膜癌患者的護理標準。

And in that study, there was a cohort of patients who were chemo-naïve. And in that group, they saw a response rate of about 51%. Now, this was compared to a later study of the combination of Everolimus and Letrozole, in which the response rate in the chemo-naïve patients was 47%. So not very different than what was seen with platinum and palataxel.

在那項研究中，有一組未接受過化療的患者。在該組中，他們的回覆率約為 51%。現在，將此與後來的依維莫司和來曲唑聯合研究進行了比較，其中初治患者的緩解率為 47%。因此與白金和帕拉他賽所觀察到的情況沒有太大不同。

But what was really riveting was the fact that the PFS reported for the platinum and palataxel combination was 14 months, which is healthy. But for the Everolimus-Letrozole combination, it was 28 months, a doubling. And PFS in this population, where quality of life is extremely important, really was what was the driver behind the design of our study.

但真正引人入勝的是，據報道，鉑和紫杉醇組合的 PFS 為 14 個月，這是健康的。但對於依維莫司-來曲唑組合來說，這個時間是 28 個月，翻了一倍。在這群人中，生活品質極為重要，無惡化存活期 (PFS) 確實是我們研究設計背後的驅動力。

Now, because the standard of care has recently changed in recurrent or advanced stage endometrial cancer, we had an opening, a chance, to put this combination in front line or in second line, in some cases, to take a look at how well it would work and to see if we could repeat or improve on the original Everolimus-Letrozole combination data in a chemo-naïve patient population.

現在，由於復發性或晚期子宮內膜癌的治療標準最近發生了變化，我們有一個機會，在某些情況下將這種組合置於一線或二線，看看它的效果如何會起作用，並看看我們是否可以在未接受過化療的患者群體中重複或改進原始的依維莫司-來曲唑組合數據。

So that was the basis of the study design, and the community has been extremely supportive of this idea and has enrolled very rapidly because of their wish to replace or try and replace chemotherapy as front line treatment for this population. I hope that helped.

這就是研究設計的基礎，社區非常支持這個想法，並且非常迅速地入組，因為他們希望取代或嘗試取代化療作為該人群的一線治療。我希望這有幫助。

Yes, definitely. Thank you, Loretta.

是的，絕對是。謝謝你，洛麗塔。

Thanks, Ahu. As I mentioned, I do it too simply. Loretta does it wonderfully. So thank you for the question. Do you have a follow-up?

謝謝，阿胡。正如我所提到的，我做得太簡單了。洛雷塔做得非常出色。謝謝你的提問。你有後續行動嗎？

Well, one last question I have, David, if I may. You have two distinct approaches to assess nab-Sirolimus. So I'm curious, when you talk to the KOLs community, so where do you see the most excitement? Is it for more of the TSC1/2 approach, patient-agnostic approach, or do you see more of an excitement for the endometrial NETs, where there's an indication-specific approach?

好吧，我還有最後一個問題，大衛，如果可以的話。您有兩種不同的方法來評估白蛋白結合西羅莫司。所以我很好奇，當您與 KOL 社區交談時，您在哪裡看到最令人興奮的地方？是更多的 TSC1/2 方法、與患者無關的方法，還是您看到更多對子宮內膜 NET 的興奮，其中有特定適應症的方法？

I'll let Loretta comment first, and then I'll go.

我先讓洛蕾塔評論一下，然後我就走了。

So first of all, Ahu, they're totally different populations. Remember that for precision, we are dealing with sort of a pan representation of specialties. So they don't necessarily talk to each other, but the ones who do talk to each other remain really very bullish on the fact that we are seeing responses in some of these very sick late-stage patients, as Dave mentioned in his commentary.

首先，Ahu，他們是完全不同的人群。請記住，為了精確起見，我們正在處理某種專業的泛表示。因此，他們不一定會互相交談，但那些確實互相交談的人仍然非常樂觀地認為，正如戴夫在他的評論中提到的那樣，我們在一些病情嚴重的晚期患者中看到了反應。

It's perhaps easier to see the enthusiasm in the community for EEC, where these tend to be a group of specialists who are together all of the time, and they talk about this disease all of the time, and they treat the same kind of patients all of the time.

也許更容易看到社區對 EEC 的熱情，這些專家往往是一群一直在一起的專家，他們一直在談論這種疾病，並且他們都治療相同類型的患者。

So their excitement is palpable, and they are looking for the next big thing. So immunotherapy was, of course, big and changed the standard of care, and now they are looking for a way to replace chemotherapy. And they are hopeful and actually quite vocal that we will fill that gap. So that's as best as I can represent it, I think. Dave, you wanted to say something else?

所以他們的興奮是顯而易見的，他們正在尋找下一件大事。因此，免疫療法當然規模很大，改變了護理標準，現在他們正在尋找一種替代化療的方法。他們充滿希望，而且實際上非常直言不諱地希望我們能夠填補這一空白。我想這就是我能描述的最好的了。戴夫，你還想說點別的嗎？

I think that's a great summary of it, Loretta, from firsthand experience. I would say we also went out with the TSC1 and 2 interim analysis I mentioned and talked to a large number of physicians to get reactions to that profile and understand across different specialties what that reaction would be.

洛雷塔，我認為這是一個很好的總結，來自第一手經驗。我想說的是，我們還進行了我提到的 TSC1 和 2 中期分析，並與大量醫生進行了交談，以獲得對該資料的反應，並了解不同專業的反應是什麼。

And consistently, physicians are quite interested in finding solutions for late-line patients, particularly through targeted mutations where there's an identifiable mutation, and where often not just overall response rate but even stable disease is a meaningful outcome for those patients who have progressed through multiple lines of therapy.

一直以來，醫生對為晚期患者尋找解決方案非常感興趣，特別是透過有針對性的突變，其中存在可識別的突變，對於那些經歷了多次進展的患者來說，通常不僅是總體緩解率，甚至穩定的疾病也是有意義的結果。

And we had excellent reactions to the profile of nab-Sirolimus, especially amongst folks who are familiar with the mTOR pathway and or doctors who have seen this product in the PEComa setting.

我們對 nab-西羅莫司的概況反應很好，特別是在熟悉 mTOR 通路的人們和/或在 PEComa 環境中見過該產品的醫生中。

So thank you all for the questions. Operator, next question?

謝謝大家提出的問題。接線員，下一個問題？

Robert Burns, H.C. Wainwright.

羅伯特·伯恩斯，H.C.溫賴特。

Good morning. This is Dan on for Rob. Thanks for taking our question. We wanted to ask, given the data demonstrating preferential tumor uptake for nab-Sirolimus versus [nab-Sirolimus] and Everolimus, are you thinking of any drug combinations and subsequent target indications for the future or to rephrase any ideas on future directions or expansions? And would you be able to give a little more color around when in this upcoming quarter you expect to report the interim analysis? And I'd like to have some follow-ups if I could.

早安.這是丹為羅布代言的。感謝您提出我們的問題。我們想問的是，考慮到數據顯示白蛋白結合西羅莫司相對於[白蛋白結合西羅莫司]和依維莫司有優先腫瘤攝取，您是否正在考慮未來的任何藥物組合和後續目標適應症，或重新表達任何有關未來方向或擴展的想法？當您預計在即將到來的季度報告中期分析時，您能否提供更多資訊？如果可以的話，我希望能有一些後續行動。

Sure. Thanks, Dan, for the questions. Yeah, so I think, as you point out, we do see that preferential accumulation of Sirolimus in the nab-Sirolimus combination driven by that nanoparticle bound albumin technology. And we do think that's one of the key advantages that we have with this product.

當然。謝謝丹提出的問題。是的，所以我認為，正如您所指出的，我們確實看到西羅莫司在奈米顆粒結合白蛋白技術驅動的白蛋白結合西羅莫司組合中優先積累。我們確實認為這是我們該產品的主要優勢之一。

Obviously, (technical difficulty) the TSC1 and 2 trial is a monotherapy trial, so there's no combination there. But the EEC trial is in combination with letrozole, and the NET trial is a monotherapy or in combination for functional tumors with a standard of care.

顯然，（技術難度）TSC1 和 2 試驗是單一療法試驗，因此沒有組合。但 EEC 試驗是與來曲唑合併治療，而 NET 試驗則是單一療法或與標準護理的功能性腫瘤合併療法。

In terms of more exploratory combinations that would build on that, we're absolutely looking at those opportunities. But I think it's premature for us to comment on that. I think we're looking for these results from these initial trials over the second half to really set the path for the future. And then in terms of timing, all I can say is later in Q3.

就以此為基礎的更具探索性的組合而言，我們絕對會關注這些機會。但我認為我們對此發表評論還為時過早。我認為我們正在從下半年的初步試驗中尋找這些結果，以便真正為未來設定道路。然後就時間而言，我只能說是在第三季晚些時候。

Thanks. That makes sense. So regarding follow-ups, what are you looking for from the Phase 2 program in neuroendocrine tumors regarding efficacy and safety? And are there specific tumor types that you expect to see the greatest impact in? (multiple speakers) Do you also have an updated view on what maximum sales [endopathyomas] could look like in the United States and around what that would be? I'm curious on the Paclitaxel versus Everolimus trial. How did those overall survivals compare back in the day?

謝謝。這是有道理的。那麼關於後續行動，您對神經內分泌腫瘤二期計畫的有效性和安全性有何期待？您預計哪些特定的腫瘤類型會受到最大的影響？（多名發言者）您是否也對美國的最大銷售量（內病瘤）以及大約的情況有最新的看法？我對紫杉醇與依維莫司的試驗很好奇。與當時相比，這些整體存活率如何？

Yeah, I'll let Loretta take the first question. Go ahead.

是的，我會讓洛雷塔回答第一個問題。前進。

Okay. So I'll take the last question first because there were so many questions, I kind of forgot what the earlier ones are. But I can tell you that the overall survival for the combination of Paclitaxel and Cisplatin, it was 32 months. And it was not reported for the Letrozole Everolimus combination. But if the PFS was 28 months, it ain't that far from 32-month overall survival. So you may assume that it was significantly better.

好的。所以我先回答最後一個問題，因為問題太多了，我有點忘記前面的問題是什麼了。但我可以告訴你，紫杉醇和順鉑合併用藥的總存活期是 32 個月。並且還沒有關於來曲唑依維莫司組合的報導。但如果 PFS 為 28 個月，那麼它距離 32 個月的總存活期就不遠了。所以你可能會認為它明顯更好。

Loretta, thanks. The first question was in regards to the net trial expectations and any particular tumor types that we might see better responses.

洛麗塔，謝謝。第一個問題是關於淨試驗預期以及我們可能會看到更好反應的任何特定腫瘤類型。

Okay. You want me to answer that?

好的。你想讓我回答這個問題嗎？

Yeah. Go ahead. Thanks. If you could add.

是的。前進。謝謝。如果可以補充的話。

So I wasn't clear with the question whether you were talking about subtypes of NETs because NETs occur in different organ sites. We don't actually have enough information if that is the question. We don't have enough information to know which of the subset NETs is going to have a better response rate. We just don't have enough information at this point in time.

所以我不清楚你是否在談論 NET 的亞型，因為 NET 發生在不同的器官部位。如果這是問題的話，我們實際上沒有足夠的資訊。我們沒有足夠的資訊來知道哪個 NET 子集將具有更好的回應率。目前我們還沒有足夠的資訊。

Yeah. And Dan if I can add on the net trial. Historically, mTOR inhibitors have been utilized in the setting for neuroendocrine tumors. The reality is that those approvals were driven off of progression-free survival benefit that was demonstrated. NETs can be quite indolent and long-lasting. But there is benefit that has been derived from mTOR inhibitors in terms of extending time on treatment for those patients relative to other approaches.

是的。丹，如果我可以新增網路試用版。歷史上，mTOR 抑制劑已被用於治療神經內分泌腫瘤。現實情況是，這些批准是基於已證實的無惡化存活獲益。NET 可能非常懶惰且持久。但與其他方法相比，mTOR 抑制劑在延長這些患者的治療時間方面有好處。

The reality is, though, that those prior mTOR inhibitor trials show very low overall response rates, though, often in the single-digit setting. And we think an early indication of the potential of our mTOR inhibitor would be to show superior or not superior because that's not a direct comparison, but to show numbers that would be better in terms of initial response rates that could guide to that longer-term, better outcome for those patients.

但現實是，先前的 mTOR 抑制劑試驗顯示整體緩解率非常低，而且通常只有個位數。我們認為，我們的 mTOR 抑制劑潛力的早期跡象將是顯示優越或不優越，因為這不是直接比較，而是顯示在初始反應率方面更好的數字，可以指導長期，為這些患者帶來更好的結果。

And then on the PEComa sales, we haven't provided guidance to the ultimate potential in PEComa. What I would say is that PEComa is a very rare indication. We're talking 200 to 300 patients in the US in total. That means we're finding one in 1 million kind of what we're looking for in terms of finding those patients and getting them to the right treatment setting.

然後，在 PEComa 銷售方面，我們尚未對 PEComa 的最終潛力提供指導。我想說的是，PEComa 是一種非常罕見的適應症。我們談論的是美國總共 200 到 300 名患者。這意味著我們正在尋找百萬分之一的患者，並讓他們接受正確的治療。

Many physicians will never see a PEComa patient. And so, therefore, our goal is to continue to hunt and find these patients and make sure they're getting to the right treating positions so they can get exposed to the potential for nab-sirolimus to support their disease journey.

許多醫生永遠不會見到 PEComa 患者。因此，我們的目標是繼續尋找和找到這些患者，並確保他們得到正確的治療位置，以便他們能夠接觸到白蛋白結合西羅莫司的潛力，以支持他們的疾病之旅。

That ultimately is a -- it's hard to predict exactly where that can land over time. What we have said consistently is that we do believe we've penetrated most of the marketplace at this point, and any further growth will be incremental.

最終，很難準確預測隨著時間的推移它會落在哪裡。我們一貫表示，我們確實相信目前我們已經滲透了大部分市場，任何進一步的成長都將是漸進的。

Thanks. That makes sense. And I apologize for the inundation of questions.

謝謝。這是有道理的。我對大量的問題表示歉意。

No worries. We take notes as we go. So, thank you, Dan. Thank you. Operator, are there any other questions on the line?

不用擔心。我們邊走邊記筆記。所以，謝謝你，丹。謝謝。接線員，還有其他問題嗎？

I'm showing no further questions at this time. I would now like to turn it back to Dave Lennon for closing remarks. Thank you.

我目前沒有提出任何進一步的問題。現在我想請戴夫·列儂致閉幕詞。謝謝。

Thank you, Audrey, Loretta, Scott, for your comments today. Thank you, everyone on the call, for joining us for today's call. We appreciate your time and look forward to the opportunity in the near future to provide additional updates on our progress. Otherwise, have a great, wonderful rest of your day and week, and look forward to speaking to you all soon. Thank you.

謝謝奧黛麗、洛雷塔、史考特今天的評論。感謝所有參加電話會議的人加入我們今天的電話會議。感謝您抽出寶貴的時間，並期待在不久的將來有機會提供有關我們進展的更多最新資訊。否則，祝您度過愉快的一天和一周，並期待很快與大家交談。謝謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。