Lite Strategy Inc (LITS) 2022 Q4 法說會逐字稿

Good afternoon, and welcome to the MEI Pharma 2022 Fiscal Year-End Conference Call. Please be advised that the call is being recorded at the company's request. At this time, I would like to turn the call over to David Walsey, MEI's Senior Vice President on Corporate Affairs. Please go ahead.

下午好，歡迎來到 MEI Pharma 2022 財年年終電話會議。請注意，通話是應公司要求進行錄音的。現在，我想把電話轉給 MEI 公司事務高級副總裁 David Walsey。請繼續。

Thank you, and good afternoon, everyone, and thank you for joining us today. After the market closed today, we filed our Form 10-K for the fiscal year ended June 30, 2022, with the Securities and Exchange Commission and issued our financial results and corporate highlights press release, both of which are available on our website at www.meipharma.com.

謝謝，大家下午好，感謝您今天加入我們。今天收市後，我們向美國證券交易委員會提交了截至 2022 年 6 月 30 日的財政年度的 10-K 表格，並發布了我們的財務業績和公司亮點新聞稿，兩者均可在我們的網站 www. .meipharma.com.

On our call today, we will provide a summary of financials from the fiscal year ended June 30, 2022, and then review progress in our programs and business over the last year. We will then open the call to your questions.

在今天的電話會議上，我們將提供截至 2022 年 6 月 30 日的財政年度的財務摘要，然後回顧我們過去一年的計劃和業務進展。然後我們將打開您的問題的電話。

Before we get started, I want to call your attention to the fact that this conference call may contain certain forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You should be aware that our actual results could differ materially from those contained in these forward-looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties as discussed in our SEC filings, including our most recent annual report on Form 10-K filed earlier today. A replay of this call will be available on our website soon after its conclusion.

在我們開始之前，我想提請您注意，本次電話會議可能包含 1995 年《私人證券訴訟改革法案》安全港條款含義內的某些前瞻性陳述。您應該知道我們的實際情況結果可能與這些前瞻性陳述中包含的結果存在重大差異，這些陳述基於管理層當前的預期，並受到我們在 SEC 文件中討論的許多風險和不確定性的影響，包括我們最近提交的 10-K 表格年度報告今天早些時候。此電話會議的重播將在其結束後立即在我們的網站上提供。

I'd now like to introduce you to our speakers for today. With me are Dan Gold, our President and Chief Executive Officer; and Brian Drazba, our Chief Financial Officer. Additionally, David Urso, our Chief Operating Officer and General Counsel; as well as Richard Ghalie, our Chief Medical Officer, are also with us today. Brian will start with a summary of our financial results before Dan shares remarks reviewing the year and commenting on coming quarters. After that we will open the line for your questions.

現在我想向您介紹我們今天的演講者。和我一起的是我們的總裁兼首席執行官 Dan Gold；和我們的首席財務官 Brian Drazba。此外，我們的首席運營官兼總法律顧問 David Urso；以及我們的首席醫療官 Richard Ghalie 今天也和我們在一起。 Brian 將首先總結我們的財務業績，然後 Dan 分享對今年的回顧和對未來幾個季度的評論。之後，我們將開通您的問題熱線。

I'll now turn the call over to Brian.

我現在將電話轉給布賴恩。

Thank you, David. I'll provide a brief overview of our financial results. For more detailed information regarding our financial results, I invite you to review our Form 10-K filed earlier today.

謝謝你，大衛。我將簡要概述我們的財務業績。有關我們財務業績的更多詳細信息，我邀請您查看我們今天早些時候提交的 10-K 表格。

I'm pleased to report that we finished our fiscal year 2022 with about $153 million in cash, cash equivalents and short-term investments with no outstanding debt. For the year ended June 30, 2022, our net cash used in operations was $48.7 million compared to $52.4 million for 2021. The decrease primarily related to changes in working capital.

我很高興地報告，我們在 2022 財年結束時擁有約 1.53 億美元的現金、現金等價物和短期投資，沒有未償債務。截至 2022 年 6 月 30 日止年度，我們用於運營的淨現金為 4870 萬美元，而 2021 年為 5240 萬美元。減少主要與營運資金的變化有關。

Research and development expenses were $85.6 million for the year ended June 30, 2022, compared to $69.4 million in the prior year. The increase was primarily related to increased development costs associated with zandelisib, increased drug manufacturing costs and increased consulting fees to support our clinical trial activities. General and administrative expenses were $30.5 million for the year ended June 30, 2022, compared to $24.4 million for 2021. The increase primarily related to increased personnel costs, professional services costs and general corporate overhead expenses incurred during the year.

截至 2022 年 6 月 30 日止年度，研發費用為 8560 萬美元，上年同期為 6940 萬美元。增加的主要原因是與 zandelisib 相關的開發成本增加、藥物製造成本增加以及支持我們的臨床試驗活動的諮詢費用增加。截至 2022 年 6 月 30 日止年度，一般和行政費用為 3050 萬美元，而 2021 年為 2440 萬美元。增加的主要原因是年內發生的人員成本、專業服務成本和一般公司管理費用增加。

MEI recognized revenues of $40.7 million for the year ended compared to $34.8 million in 2021. The increase in revenue related to increased reimbursement of expenses from Kyowa Kirin due to research and development activity related to zandelisib. Net loss was $54.5 million or $0.44 per share for the year ended June 30, 2022, compared to a net loss of $41.3 million or $0.37 per share for 2021. We had 133,152,045 shares of common stock outstanding at the end of June 30, 2022, compared with 112,614,643 shares as of June 30, 2021.

MEI 確認截至本年度的收入為 4070 萬美元，而 2021 年為 3480 萬美元。收入的增加與 Kyowa Kirin 因與 zandelisib 相關的研發活動而增加的費用報銷有關。截至 2022 年 6 月 30 日止年度淨虧損為 5450 萬美元或每股 0.44 美元，而 2021 年淨虧損為 4130 萬美元或每股 0.37 美元。截至 2022 年 6 月 30 日止，我們有 133,152,045 股已發行普通股，與截至 2021 年 6 月 30 日的 112,614,643 股相比。

Our adjusted net loss for the year ended June 30, 2022, excluding noncash expenses related to changes in the fair value of our warrants, a non-GAAP measure, was $75.2 million compared to an adjusted net loss of $59.4 million for 2021. With that, I'll turn the call over to Dan.

截至 2022 年 6 月 30 日止年度，我們調整後的淨虧損為 7520 萬美元，不包括與我們的認股權證公允價值變動相關的非現金費用，這是一項非 GAAP 衡量標準，而 2021 年調整後的淨虧損為 5940 萬美元。 ，我會把電話轉給丹。

Thanks, Brian, and thanks, everyone, for joining us this afternoon. I hope you all had an enjoyable summer. This past fiscal year was marked by several key events in our lead zandelisib program, starting with the announcement of the first patient dosed in our global Phase III COASTAL study. Shortly thereafter, we were very excited to report top line data from the Phase II TIDAL study, demonstrating a 70.3% overall response rate in follicular lymphoma patients with at least 2 prior lines of therapy, about half of which obtained a complete remission.

謝謝布賴恩，也謝謝大家今天下午加入我們。我希望你們都度過了一個愉快的夏天。在過去的財政年度中，我們的主要 zandelisib 計劃發生了幾項關鍵事件，首先是我們全球 III 期 COASTAL 研究中第一位患者給藥的宣布。此後不久，我們非常興奮地報告了 II 期 TIDAL 研究的一線數據，表明濾泡性淋巴瘤患者的總體反應率為 70.3%，之前至少接受過 2 線治療，其中約一半獲得完全緩解。

On the safety and tolerability side, at the data cutoff date, the discontinuation rate due to any adverse event in TIDAL was 9.9%. Notably grade 3 adverse events of special interest tended to occur in the first 3 cycles, which coincides with the period of daily continuous dosing in our intermittent dosing regimen. Recall, patients that are administered zandelisib once daily for 2 28-day cycles as a response induction regimen, followed thereafter by once-daily dosing for the first 7 days of each subsequent 28-day cycle. We now look forward to reporting complete TIDAL data at an upcoming medical meeting.

在安全性和耐受性方面，在數據截止日期，TIDAL 中因任何不良事件導致的停藥率為 9.9%。值得注意的是，特別關注的 3 級不良事件往往發生在前 3 個週期，這與我們的間歇給藥方案中的每日連續給藥期相吻合。回想一下，作為反應誘導方案，每天一次給予 zandelisib 的患者持續 2 個 28 天週期，然後在每個後續 28 天週期的前 7 天每天一次給藥。我們現在期待在即將召開的醫學會議上報告完整的 TIDAL 數據。

It was very encouraging to see that the TIDAL data are consistent with the data from our previous Phase I experience, which was just published this July in the Lancet Oncology. Should that consistency carry forward to patients administered zandelisib plus Rituxan from the Phase Ib experience to patients being evaluated in COASTAL, we have the potential to provide a highly differentiated chemotherapy-free regimen to patients that should provide significant benefit to patients.

非常令人鼓舞的是，TIDAL 數據與我們之前第一階段經驗的數據一致，該數據剛剛於今年 7 月發表在《柳葉刀腫瘤學》上。如果這種一致性將 Ib 期經驗中給予 zandelisib 加 Rituxan 的患者延續到在 COASTAL 中接受評估的患者，我們有可能為患者提供高度差異化的無化療方案，這將為患者帶來顯著益處。

Following our announcement of the TIDAL data in December, we successfully completed a follow-on offering, raising gross proceeds in excess of $50 million to support our current programs during a rather turbulent time in the financial markets. With the addition of this raise, we now estimate we have sufficient cash to fund operations for about 2 years.

在我們於 12 月公佈 TIDAL 數據後，我們成功完成了後續發行，籌集了超過 5000 萬美元的總收益，以在金融市場相當動蕩的時期支持我們當前的計劃。加上這次加薪，我們現在估計我們有足夠的現金來為大約 2 年的運營提供資金。

Despite a good start to the year, our success was tempered by the changes at the FDA relating to its approach to the type of study designs required for potential accelerated approval under 21 CFR Part 314.500 Subpart H. The change in approach to accelerated approvals was first communicated to MEI in March of 2022, meeting with -- in a March of 2022 meeting with the FDA and then expanded upon publicly communicated during an ODAC meeting this past April. At the ODAC meeting, the FDA communicated a change in position regarding the benefit and risk assessment of PI3-kinase inhibitors due to a class associated toxicity concern, stating they would no longer consider granting accelerated approval based solely on single-arm studies.

儘管今年開局良好，但我們的成功因 FDA 的變化而受到影響，該變化涉及其根據 21 CFR 第 314.500 部分 H 部分加速批准所需的研究設計類型的方法。加速批准方法的變化首先是在 2022 年 3 月與 MEI 進行了溝通，並在 2022 年 3 月與 FDA 舉行了會議，然後在今年 4 月的 ODAC 會議上公開溝通。在 ODAC 會議上，由於類別相關的毒性問題，FDA 傳達了關於 PI3 激酶抑製劑的益處和風險評估的立場變化，表示他們將不再考慮僅根據單臂研究授予加速批准。

Subsequently the FDA communicated a new initiative they call Project FrontRunner, replacing its longstanding approach to accelerated approvals generally. This new initiative follows decades where the FDA granted accelerated approvals based on single-arm studies to open early access to new cancer drugs generally for patients who've already tried several other regimens, including a number of PI3-kinase inhibitors. In brief, under Project FrontRunner, the FDA has communicated its intent to consider support for accelerated approval of cancer drugs based on data from randomized studies, rendering data generated from single-arm studies such as TIDAL generally insufficient in the eyes of the FDA to adequately assess risk and benefit and thus support an accelerated approval marketing authorization.

隨後，FDA 傳達了一項他們稱為 Project FrontRunner 的新計劃，取代了其長期以來普遍採用的加速審批方法。幾十年來，FDA 根據單臂研究加速批准了這項新舉措，為已經嘗試過其他幾種治療方案（包括多種 PI3 激酶抑製劑）的患者開放早期使用新抗癌藥物的途徑。簡而言之，在 Project FrontRunner 下，FDA 已經表達了考慮支持加速批准基於隨機研究數據的抗癌藥物的意圖，使 TIDAL 等單臂研究產生的數據在 FDA 眼中通常不足以充分發揮作用評估風險和收益，從而支持加速批准上市許可。

Accordingly in our meeting with the FDA earlier this year, the agency discouraged a submission based on the Phase II single-arm TIDAL study and emphasized that MEI and our partner, Kyowa Kirin, continue our efforts with the ongoing randomized Phase III COASTAL study as planned. As announced in March and in line with the FDA's recommendation, the company do not plan to submit an FDA marketing application based solely on the single-arm Phase II TIDAL data. The meeting earlier this year with the FDA was the first instance that the agency indicated that data from TIDAL would not be sufficient to support an accelerated approval.

因此，在我們今年早些時候與 FDA 的會議上，該機構不鼓勵基於 II 期單臂 TIDAL 研究的提交，並強調 MEI 和我們的合作夥伴 Kyowa Kirin 將繼續努力按計劃進行正在進行的隨機 III 期 COASTAL 研究.正如 3 月份宣布的那樣，根據 FDA 的建議，該公司不打算提交僅基於單臂 II 期 TIDAL 數據的 FDA 營銷申請。今年早些時候與 FDA 的會議是該機構首次表示來自 TIDAL 的數據不足以支持加速批准。

While the agency essentially closed the opportunity for submission based on the Phase II TIDAL study, it did emphasize that the companies continue their efforts to evaluate zandelisib in the ongoing randomized Phase III COASTAL study. In addition, while the agency has stated that the safety of our 60-milligram intermittent dosing schedule appears reasonable, as recommended, we will continue our efforts to further support the current dose and regimen as we continue to evaluate our existing data and consider any other additional efforts as appropriate to ensure we address any questions concerning the selection of our current zandelisib dose and schedule.

雖然該機構基本上關閉了基於 II 期 TIDAL 研究的提交機會，但它確實強調了公司在正在進行的隨機 III 期 COASTAL 研究中繼續努力評估 zandelisib 。此外，雖然該機構已表示我們的 60 毫克間歇給藥方案的安全性按照建議似乎是合理的，但我們將繼續努力進一步支持當前的劑量和方案，因為我們將繼續評估我們現有的數據並考慮任何其他適當的額外努力，以確保我們解決有關選擇我們當前的 zandelisib 劑量和時間表的任何問題。

As to COASTAL, you may recall, this is a randomized Phase III study comparing zandelisib plus rituximab or anti-CD20 to standard of care chemoimmunotherapy in patients with relapsed/refractory follicular or marginal zone lymphomas who have received more than one or more prior lines of therapy. COASTAL is intended to support marketing applications in the U.S. and globally with our partner, Kyowa Kirin. The first patient, as I mentioned, was dosed last August. The study now has over 135 sites activated worldwide. And while COVID has impacted the study and sites have closed in response to the war in Ukraine, we are continuing to add new sites to meet our objective of completing enrollment by the end of the year 2024. These efforts are at the forefront of our corporate focus, although various factors may impact our timelines and could push expected completion beyond the 2024 timeline.

至於 COASTAL，您可能還記得，這是一項隨機 III 期研究，比較 zandelisib 加利妥昔單抗或抗 CD20 與標準化學免疫療法對複發/難治性濾泡性或邊緣區淋巴瘤患者的治療效果治療。 COASTAL 旨在與我們的合作夥伴 Kyowa Kirin 一起支持美國和全球的營銷應用。正如我提到的，第一位患者於去年 8 月服藥。該研究目前在全球範圍內激活了超過 135 個站點。儘管 COVID 影響了研究並且站點因烏克蘭戰爭而關閉，但我們將繼續添加新站點以實現我們在 2024 年底前完成註冊的目標。這些努力是我們公司的最前沿重點，儘管各種因素可能會影響我們的時間表，並可能將預期完成時間推到 2024 年時間表之後。

With its pharmacological properties differentiating it from other PI3-kinase inhibitors that have been evaluated previously, we believe zandelisib may be ideally suited to be used eventually both as monotherapy or in combination with other important treatment modalities in various B-cell malignancies. Thus in addition to our ongoing efforts to treat patients with follicular and marginal zone lymphoma, we are also evaluating zandelisib in patients with CLL, MCL and DLBCL in combination with venetoclax, a BCL-2 inhibitor plus anti-CD20, zanubrutinib, a BTK inhibitor and R-CHOP, respectively.

由於其藥理學特性使其有別於之前評估過的其他 PI3 激酶抑製劑，我們認為 zandelisib 可能非常適合最終用作單一療法或與其他重要治療方式聯合用於各種 B 細胞惡性腫瘤。因此，除了我們正在努力治療濾泡性和邊緣區淋巴瘤患者外，我們還在評估 zandelisib 聯合維奈托克（一種 BCL-2 抑製劑加抗 CD20 藥物）、zanubrutinib（一種 BTK 抑製劑）對 CLL、MCL 和 DLBCL 患者的療效和 R-CHOP，分別。

Finally, in an effort to leverage the immunomodulatory properties of zandelisib, we are also evaluating potential opportunities in combination with other hematologic treatment modalities, as well as in combinations in solid tumor settings. Beyond the zandelisib program, we also share data updates from our 2 clinical stage programs as well as at various medical conferences over the past 12 months. With respect to voruciclib, our orally available CDK9 and MYC modulating drug candidate, we reported data from the Phase I data -- Phase I study demonstrating the identification of a well-tolerated dose and regimen as well as data demonstrating initial efficacy signals.

最後，為了努力利用 zandelisib 的免疫調節特性，我們還在評估與其他血液學治療方式相結合的潛在機會，以及在實體瘤環境中的組合。除了 zandelisib 計劃之外，我們還分享了過去 12 個月來自我們 2 個臨床階段計劃以及各種醫學會議的數據更新。關於 voruciclib，我們的口服 CDK9 和 MYC 調節候選藥物，我們報告了來自 I 期數據的數據——I 期研究證明了耐受性良好的劑量和治療方案的確定，以及證明初始療效信號的數據。

We look forward to updating you on the progress from the combination phase of this study, which is now open to enrollment where we will add voruciclib to venetoclax in patients with relapsed/refractory AML and then subsequently in patients with B-cell malignancies. With respect to the ME-344 program, we reported preclinical data at our medical meeting, demonstrating that our candidates enhanced the anti-leukemic activity also of venetoclax against AML cells, including venetoclax-resistant AML. While we may consider further exploring applications for ME-344 in hematologic cancer, our current efforts are focused on solid tumors. Specifically, the ME-344 program will be advancing into the next phase in development in the next few quarters to evaluate our candidate plus the VEGF inhibitor Avastin, in patients with relapsed and refractory colorectal cancer.

我們期待著向您介紹本研究聯合階段的最新進展，該研究現已開放註冊，我們將在復發/難治性 AML 患者中添加 voruciclib 至維奈托克，隨後在 B 細胞惡性腫瘤患者中。關於 ME-344 項目，我們在醫學會議上報告了臨床前數據，證明我們的候選藥物也增強了維奈托克對 AML 細胞（包括維奈托克抗性 AML）的抗白血病活性。雖然我們可能會考慮進一步探索 ME-344 在血液系統癌症中的應用，但我們目前的工作重點是實體瘤。具體而言，ME-344 計劃將在接下來的幾個季度進入下一階段的開發，以評估我們的候選人加上 VEGF 抑製劑阿瓦斯汀，用於復發和難治性結直腸癌患者。

From the corporate perspective, over the course of this last year, we strengthened our team with some key hires, including Anne Frese as Chief People Officer, Yomara Gomez as Senior Vice President, Quality; and Alejandro Ricart as Senior Vice President, Clinical Development. Additionally we added Sujay Kango to the Board, who provides significant commercial and industry experience.

從公司的角度來看，在去年的過程中，我們通過一些重要的招聘加強了我們的團隊，包括 Anne Frese 擔任首席人事官，Yomara Gomez 擔任質量高級副總裁；和 Alejandro Ricart 擔任臨床開發高級副總裁。此外，我們將 Sujay Kango 添加到董事會，他提供了重要的商業和行業經驗。

Together with Kyowa Kirin, we remain committed to the ultimate potential of zandelisib to address important medical needs as a single agent or in combination with other therapies to provide physicians and their patients important new treatment options. While the FDA's sudden change in approach is undoubtedly a disappointing factor to our plans, it's important to realize that our clinical program continues to deliver a consistent and positive data set that suggests the opportunity to ultimately have a very strong clinical profile and supports our investment in this program. I am confident given the knowledge and experience of the team here at MEI and our partner, Kyowa Kirin, along with our healthy cash position that we have set a good course for getting zandelisib to patients and building value for our shareholders.

我們與 Kyowa Kirin 一起，繼續致力於發揮 zandelisib 的最終潛力，以作為單一藥物或與其他療法聯合使用來滿足重要的醫療需求，從而為醫生及其患者提供重要的新治療選擇。雖然 FDA 突然改變方法無疑是我們計劃中令人失望的因素，但重要的是要認識到我們的臨床計劃繼續提供一致和積極的數據集，表明有機會最終擁有非常強大的臨床資料並支持我們在這個程序。鑑於 MEI 團隊和我們的合作夥伴 Kyowa Kirin 的知識和經驗，以及我們健康的現金狀況，我相信我們已經為患者提供 zandelisib 並為我們的股東創造價值制定了良好的路線。

As we advance the zandelisib program in general and in particular, COASTAL, over the coming quarters, we look forward to providing updates as follows. We plan to provide an update on the complete TIDAL data likely at the upcoming medical meeting by the end of the calendar year. Additionally we look forward to dosing the first patients in the CORAL study evaluating zandelisib plus rituximab and venetoclax in patients with relapsed CLL. And we look forward to the potential for certain additional investigator-initiated studies to accompany the already ongoing investigator study evaluating zandelisib plus R-CHOP in first-line DLBCL.

隨著我們在未來幾個季度全面推進 zandelisib 計劃，特別是 COASTAL，我們期待提供如下更新。我們計劃在日曆年年底即將召開的醫學會議上提供完整的 TIDAL 數據更新。此外，我們期待在評估 zandelisib 聯合利妥昔單抗和維奈托克治療復發性 CLL 患者的 CORAL 研究中對第一批患者進行給藥。我們期待著某些額外的研究者發起的研究有可能與已經在進行的研究者研究一起評估一線 DLBCL 中的 zandelisib 加 R-CHOP。

On the voruciclib front, we plan to share an update on the Phase I program, in particular, on the combination with venetoclax in patients with AML, probably toward the end of the next calendar year. For the ME-344 program, we look forward to initiating the Phase Ib study, evaluating the combination with Avastin in relapsed colorectal cancer patients in the quarter -- in the first quarter of the calendar 2023, and sharing initial data in around -- in or around year-end.

在 voruciclib 方面，我們計劃分享 I 期項目的最新進展，特別是與 Venetoclax 聯合治療 AML 患者，時間可能會在下個日曆年年底。對於 ME-344 計劃，我們期待啟動 Ib 期研究，在 2023 年第一季度評估與阿瓦斯汀聯合治療復發性結直腸癌患者的情況，並在大約 2023 年共享初始數據或年底左右。

In summary, we've achieved multiple successes over the last year, and I am proud of the progress across our pipeline. While the FDA's adoption of Project FrontRunner outline the new requirements for accelerated approval necessitates a reconfiguration of our zandelisib program, I think our ultimate success and the value we can deliver to our stakeholders can best be measured by how we approach and overcome obstacles to achieving our mission to improve outcomes for patients with cancer through our efforts to develop and commercialize novel best-in-class therapies.

總而言之，我們在過去一年取得了多項成功，我為我們在整個管道中取得的進展感到自豪。雖然 FDA 對 Project FrontRunner 的採用概述了加速批准的新要求需要重新配置我們的 zandelisib 計劃，但我認為我們最終的成功和我們可以為利益相關者提供的價值最好通過我們如何處理和克服障礙來實現我們的目標來衡量我們的使命是通過我們努力開發和商業化一流的新型療法來改善癌症患者的預後。

I'll now ask the operator to provide the instructions for asking questions and then open the call for Q&A.

我現在將要求接線員提供提問說明，然後打開電話進行問答。

(Operator Instructions) And our first question will come from Stephen Willey of Stifel.

（操作員說明）我們的第一個問題將來自 Stifel 的 Stephen Willey。

So I think last time we had a conference call, there was some suggestion that you and Kyowa were going to try to engage FDA surrounding potentially expeditious path to approval that may not necessarily be accelerated, but might allow for some data submission, I guess, ahead of a primary endpoint. So is it safe to say now kind of post this Project FrontRunner mandate that FDA has pushed out since those comments were made that it's more likely than not that we see a final primary endpoint read on COASTAL.

所以我認為上次我們召開電話會議時，有人建議您和 Kyowa 將嘗試讓 FDA 圍繞可能不一定加速的快速批准途徑進行接觸，但我猜可能會允許提交一些數據，在主要終點之前。因此，現在可以肯定地說，自從發表這些評論以來，FDA 已經推出了這個 Project FrontRunner 授權，我們更有可能在 COASTAL 上看到最終的主要終點。

Yes. Hello, Steve. I guess I was following you right up to the end of the question. I think that our plan, I mean, if you recall the Project FrontRunner, the FDA has said that they are still willing to entertain accelerated approval as an example, based on randomized data and then the final primary endpoint as full approval. We are continuing efforts to pursue this dialogue with the FDA to really understand what Project FrontRunner is intended and whether the randomized data from the COASTAL study could be used in a -- in some sort of an accelerated filing with a follow-up of PFS for the final endpoint, which is the final -- the primary endpoint of the study. So I think that we will definitely keep you posted as we make progress on those discussions. But we do continue to dialogue with the agency on this very issue.

是的。你好，史蒂夫。我想我一直跟著你直到問題結束。我認為我們的計劃，我的意思是，如果你還記得 FrontRunner 項目，FDA 曾表示他們仍然願意接受加速批准作為一個例子，基於隨機數據，然後是最終的主要終點作為完全批准。我們正在繼續努力與 FDA 進行對話，以真正了解 Project FrontRunner 的意圖，以及來自 COASTAL 研究的隨機數據是否可以用於某種加速申報以及 PFS 的後續行動最終終點，即研究的最終——主要終點。所以我認為，隨著我們在這些討論中取得進展，我們一定會及時通知您。但我們確實繼續就這個問題與該機構進行對話。

And then maybe just as a follow-up, I know one of the other FDA mandates here is Project Optimus. And I believe you had received some feedback regarding the agency's desire to maybe see some additional dose exploration work. So is that something that you guys plan on initiating here at some point? Can you maybe just speak to how you plan on addressing some of those FDA concerns/feedback?

然後也許只是作為後續行動，我知道這裡的其他 FDA 授權之一是 Project Optimus。我相信你已經收到了一些關於該機構希望看到一些額外劑量探索工作的反饋。那麼你們是否計劃在某個時候在這裡發起？您能否談談您計劃如何解決 FDA 的一些問題/反饋？

Yes. That's really important. It's a very proper question, Steve. Thanks for asking. So just to -- if you recall, we have done dose exploration in the program. We did start at a dose of 60 milligrams, which was much lower than what we were counseled to do based on our animal safety data. We went up by 60 to 120 and then 180 and without seeing any change in safety signals and no -- importantly, no change in the efficacy signal. So we dropped back down to 60. Further then as we continue to study on the continuous and noted the toxicity profile following continuous doses, we, in fact, cut the dose again by 75% by moving to the intermittent dosing schedule.

是的。這真的很重要。這是一個非常恰當的問題，史蒂夫。謝謝你的提問。所以只是 - 如果你還記得，我們已經在該計劃中進行了劑量探索。我們確實以 60 毫克的劑量開始，這遠低於我們根據動物安全數據建議的劑量。我們上升了 60 到 120，然後上升了 180，沒有看到安全信號有任何變化，而且沒有——重要的是，功效信號沒有變化。所以我們下降到 60。然後，當我們繼續研究連續給藥並註意到連續給藥後的毒性特徵時，我們實際上通過轉向間歇給藥方案再次將劑量減少了 75%。

So we do think that we have addressed a number of the FDA's concern. However, as we've learned from the ODAC and from subsequent FDA postings that the FDA is very concerned about the balance between efficacy and safety. It isn't just about maximizing efficacy. We think that we have done that. We have a large data set now of looking from TIDAL as well as from our Phase I studies, as well as our partners, Kyowa Kirin, and the MIRAGE study. So we have a very robust data set that we're now analyzing for exposure response as well as exposure safety to see if there really is an association.

所以我們確實認為我們已經解決了 FDA 的一些擔憂。然而，正如我們從 ODAC 和隨後的 FDA 公告中了解到的那樣，FDA 非常關注有效性和安全性之間的平衡。這不僅僅是為了最大限度地提高療效。我們認為我們已經做到了。我們現在擁有大量數據集，來自 TIDAL 以及我們的第一階段研究，以及我們的合作夥伴 Kyowa Kirin 和 MIRAGE 研究。所以我們有一個非常強大的數據集，我們現在正在分析暴露反應和暴露安全性，看看是否真的存在關聯。

We believe, unlike some of the other PI3 kinases, which are given on a daily dosing, that you cannot achieve this balance unless you get to a non-efficacious dose. But with the intermittent dosing, we think we may be able to achieve it. So that's our first goal is to evaluate that data. And if need be, we can then consider other potential ways of doing some quicker studies and just making that final point in patients. But our first goal is to evaluate the data we have in hand. And recall, the FDA did say that they felt that the 60-milligram dose, especially on the intermittent dosing schedule, appeared reasonable and just asked us to do further work to justify that dosing schedule.

我們相信，與每日給藥的其他一些 PI3 激酶不同，除非達到無效劑量，否則您無法達到這種平衡。但是通過間歇給藥，我們認為我們可以實現它。所以我們的首要目標是評估這些數據。如果需要，我們可以考慮其他可能的方法來進行一些更快的研究，並在患者身上做出最後一點。但我們的首要目標是評估我們手頭的數據。回想一下，FDA 確實說過，他們認為 60 毫克的劑量，尤其是在間歇給藥方案中，似乎是合理的，只是要求我們做進一步的工作來證明該給藥方案的合理性。

The next question comes from Robyn Karnauskas of Truist.

下一個問題來自 Truist 的 Robyn Karnauskas。

I know the focus is going to be on zandelisib later for the call. Can you help me understand the cadence of news flow outside of that regarding our pipeline, including your 344 as well as other products, like help us understand like what we can look at over the next 12 months to see as catalyst for the company?

我知道稍後電話會議的重點將放在 zandelisib 上。你能幫我了解關於我們管道的新聞流的節奏嗎，包括你的 344 以及其他產品，比如幫助我們了解我們在未來 12 個月內可以看到什麼，以將其視為公司的催化劑？

Yes, that's great question, Robyn. Thanks for asking it. So as we mentioned, the -- I will just say the voruciclib program because it is in recent relapsed and refractory AML specialty and the B-cell malignancies. It was deeply impacted by COVID and -- but it's definitely on track as we reported the -- we've completed the dose escalation as monotherapy as requested by the FDA. We reported that data at ASCO or ASH, yes.

是的，這是個很好的問題，羅賓。謝謝你問。所以正如我們提到的，我只想說 voruciclib 程序，因為它是最近復發和難治性 AML 專業和 B 細胞惡性腫瘤。它深受 COVID 的影響，而且——但正如我們所報告的那樣，它肯定在軌道上——我們已經按照 FDA 的要求完成了作為單一療法的劑量升級。我們在 ASCO 或 ASH 報告了這些數據，是的。

And we now have -- we have an agreement with the FDA on the protocol. The protocol is now at IRBs and we expect it to be enrolling patients very shortly in AML patients first. So our hope is that there is a lot of -- there appears to be a lot of interest in the AML community on this particular combination. So we're hoping that the enrollment of the dose escalation enrollment with venetoclax will go rapidly, and we definitely look forward to being able to at least report some initial data from that in the coming year.

我們現在已經 - 我們與 FDA 就協議達成了協議。該協議現在在 IRB，我們預計它會很快在 AML 患者中招募患者。因此，我們希望 AML 社區對這種特定組合有很多興趣。因此，我們希望維奈托克的劑量遞增登記能夠迅速進行，我們絕對期待能夠在來年至少報告一些初步數據。

I think the important issue to point out about the CDK9 inhibitors is there has been historically a significant amount of marrow toxicity, which combined with venetoclax is probably not a good recipe. We have never seen that to any significant degree with voruciclib. So the question, I think it's going to be a little hard to tease out at AML because it is a marrow disease and treating with venetoclax, but certainly, we will start to get some information if these 2 drugs play well together and hopefully we'll start to see some signals of activity as well.

我認為需要指出的關於 CDK9 抑製劑的重要問題是歷史上存在大量的骨髓毒性，與維奈托克聯合使用可能不是一個好的配方。我們從未在 voruciclib 中看到任何顯著的程度。所以這個問題，我認為在 AML 上會有點難以梳理，因為它是一種骨髓疾病並用維奈托克治療，但當然，如果這兩種藥物一起發揮良好作用，我們將開始獲得一些信息，希望我們'您也會開始看到一些活動信號。

So for that program, I think that's really the -- going to be the one that we're focusing on is looking at the profile of the combination and then getting the final cohort completed in the B-cell arm. We do have a non-clinical collaboration with Matt David at the Dana-Farber where he's actually looking at inhibition of various important markers like MYC and MCL1 from blood samples from these patients. And we hope that, that will help us interpret the dose and schedule that we're using in these studies. So I think in the coming year, we'll have a lot of information on voruciclib especially in combination with venetoclax.

因此，對於該計劃，我認為這真的是——我們關注的重點是研究組合的概況，然後在 B 細胞組中完成最後的隊列。我們確實與 Dana-Farber 的 Matt David 進行了非臨床合作，他實際上正在研究對這些患者血液樣本中各種重要標記物（如 MYC 和 MCL1）的抑製作用。我們希望，這將幫助我們解釋我們在這些研究中使用的劑量和時間表。所以我認為在接下來的一年裡，我們將有很多關於 voruciclib 的信息，尤其是與 venetoclax 的結合。

And then with 344, we're finally at the point now. We have a great group that we're working with. It's a -- essentially a cooperative group that does a lot of early studies in this case, in particular in third line colorectal. Everything is set to go. And so we're really hopeful that we'll get those patients started in the first quarter next month -- next year. And presumably that should go pretty quickly because these patients are up there. And there's not a lot of good available treatment with them. So I think it's going to be a very data rich year for us with our pipeline as well as zandelisib and some of the other studies that we hope to be rolling out in the near future.

然後有了 344，我們終於到了這一點。我們有一個很棒的團隊正在與之合作。這是一個 - 本質上是一個合作小組，在這種情況下做了很多早期研究，特別是在三線結直腸癌中。一切準備就緒。因此，我們真的很有希望在下個月的第一季度開始讓這些患者開始——明年。並且大概這應該會很快進行，因為這些患者就在那裡。而且他們沒有很多可用的治療方法。因此，我認為對於我們的管道以及 zandelisib 和我們希望在不久的將來推出的其他一些研究來說，這將是數據非常豐富的一年。

One other big broad question, I don't want to take up too much time in the call. People have questions, but you bring up 2 points, #1, the FDA. Do you think there are more changes in how they view development on for drugs in this space? Because you're probably one of the few companies that have given that much color and you actually are in the midst of it.

另一個寬泛的大問題，我不想在通話中佔用太多時間。人們有疑問，但你提出了 2 點，#1，FDA。您認為他們對這個領域藥物開發的看法是否有更多變化？因為您可能是為數不多的提供如此多色彩的公司之一，而您實際上身處其中。

And second, when you think about small molecule development in the face of the new requirements for the government with only 9 years, like what are you hearing from people who might want to collaborate about the struggles or thought processes and how you actually do that? How you act instead of going short first line versus, or early line versus later line, are you seeing that as well with your partners?

其次，當你考慮面對政府提出的新要求時的小分子開發只有 9 年的時間，比如你從那些可能想要就鬥爭或思維過程進行合作的人那裡聽到了什麼，以及你實際上是如何做到的？您如何採取行動，而不是做空第一線與較短線，或者較早線與較晚線，您是否也與您的合作夥伴看到了這一點？

It's a very packed question. I mean, I think, the first is about the space specifically. I mean, clearly, many of us have dialed into the ODAC presentation -- FDA's presentation. I mean, it is interesting that they -- even though there is concerns and they are absolutely valid concerns, we think that zandelisib solves a lot of the problems that the previous entrants had. But nonetheless, there isn't certainly that concern at the FDA. The FDA still has not formally pulled any of the formal approvals. There are -- 2 companies did voluntarily pull their accelerated approvals.

這是一個非常緊湊的問題。我的意思是，我認為，首先是關於空間的。我的意思是，很明顯，我們中的許多人已經撥通了 ODAC 的介紹——FDA 的介紹。我的意思是，有趣的是，儘管存在顧慮，而且這些顧慮是絕對合理的，但我們認為 zandelisib 解決了之前參賽者遇到的許多問題。但是，儘管如此，FDA 肯定不存在這種擔憂。 FDA 仍未正式撤銷任何正式批准。有 - 2 家公司確實自願取消了他們的加速批准。

But certainly the other entrants that have been on the market are still on the market. So I'm not -- I mean, I think there is a heightened concern because the FDA was seeing signals that it didn't like with different drugs of the same class. We've always emphasized that we are actually not part of the chemical class of all the other entrants nor do we use our drug in a way that the others do based on our dose and schedule. So we're hopeful that the FDA will evaluate us as any other drug rather than as a member of a class. And that's what we're alluding to Steve's question. That's what we hope to gain some clarity with the agency at the appropriate time.

但可以肯定的是，已經上市的其他進入者仍在市場上。所以我不是——我的意思是，我認為人們更加擔心，因為 FDA 看到的信號表明它不喜歡同一類別的不同藥物。我們一直強調，我們實際上不屬於所有其他參賽者的化學類別，我們也不會按照其他人根據我們的劑量和時間表使用我們的藥物。因此，我們希望 FDA 將我們作為任何其他藥物而不是作為某個類別的成員進行評估。這就是我們對史蒂夫問題的暗示。這就是我們希望在適當的時候與該機構弄清楚的事情。

In general, I mean, I think that the FDA is laying down some new ground that they're encouraging sponsors to think about moving up in line of therapy, but in a randomized fashion, especially with combinations. I think it's going to take a lot of time for all of us. And we have 3 -- all 3 of our pipeline are small molecules. So it is going to take some rethinking about clinical design, and how to satisfy the new mandates without making these studies take so long, especially the field that we're playing in with at least follicular, it's basically an orphan disease to some extent. And so getting patients and doing big studies that are being required, it does provide some challenges, but it's what we signed up for. So we just have to learn how to accommodate the agency's needs.

總的來說，我的意思是，我認為 FDA 正在奠定一些新的基礎，他們鼓勵贊助商考慮提升治療線，但以隨機方式，尤其是聯合治療。我認為這對我們所有人來說都會花費很多時間。我們有 3 個——我們的所有 3 個管道都是小分子。因此，需要重新考慮臨床設計，以及如何在不讓這些研究花費這麼長時間的情況下滿足新的要求，尤其是我們正在研究的領域，至少在濾泡性方面，它在某種程度上基本上是一種孤兒病。因此，獲得患者並進行所需的大型研究確實帶來了一些挑戰，但這正是我們簽約的目的。所以我們只需要學習如何適應該機構的需求。

The next question comes from I-Eh Jen of Laidlaw & Co.

下一個問題來自 Laidlaw & Co. 的 I-Eh Jen。

Just going to start with a housekeeping one that since the last quarter, the top line number is quite different from the previous 3. So starting the new fiscal year, is there any sort of suggestion or guidance to what we are looking for, for remaining of -- for the fiscal 2023?

從上個季度以來的內務管理開始，頂線數字與之前的 3 個大不相同。所以從新的財政年度開始，對於我們正在尋找的東西，是否有任何建議或指導，以保持的——2023 財年？

I'm sorry, I-Eh. I'm not quite sure what you mean the top line, the cash number or?

對不起，我-呃。我不太清楚你的意思是頂線，現金號碼還是？

No, I mean the -- that the revenue number and this quarter as compared to the previous 3 quarter is significantly lower, actually in the negative. So I'm just curious what kind of quarterly top line in general we should think about for fiscal '23.

不，我的意思是 - 本季度的收入數字與前 3 個季度相比明顯較低，實際上是負數。所以我很好奇我們應該為 23 財年考慮什麼樣的季度總收入。

Yes. I mean, I-Eh, in large part the revenue reporting is really a function of our reimbursements, our cost sharing with KKC. So as the clinical activity ramps up or slows, it's just reflected. It's more of an accounting treatment than anything else. I mean, we did have a few milestone payments that came in, which I don't think are counted on as revenue. So the revenue is really more of a reflection of the reimbursements in the way that the agreement is set up with KKC. So I think it's pretty much straight. It may fluctuate quarter-to-quarter, but it's pretty much consistent over time as our clinical activities either increase or decrease. TIDAL is winding down whereas COASTAL is ramping up.

是的。我的意思是，I-Eh，在很大程度上，收入報告實際上是我們報銷的功能，我們與 KKC 的成本分攤。因此，隨著臨床活動的增加或減慢，它就會得到反映。它更像是一種會計處理方式。我的意思是，我們確實收到了一些里程碑式的付款，我認為這些付款不算作收入。因此，收入實際上更多地反映了與 KKC 達成協議的報銷方式。所以我認為這很直接。它可能會按季度波動，但隨著時間的推移，隨著我們的臨床活動增加或減少，它幾乎是一致的。 TIDAL 正在減少，而 COASTAL 正在增加。

And then maybe 2 quick ones. The first one, excuse me, is the TIDAL study the sort of full top line data? Do we consider that at ASH of this year or maybe there is other venues we could think about?

然後可能是 2 個快速的。第一個，請問，TIDAL 研究是那種完整的頂級數據嗎？我們會在今年的 ASH 上考慮這一點，還是我們可以考慮其他地點？

Well, I think that ASH is always a very appropriate meeting for us, especially for the patient population that we treat. So I think that it's quite reasonable to expect that if the committee deems it warranted and a value that we would like to be able to report the final top line data at a meeting like ASH, yes.

好吧，我認為 ASH 對我們來說總是一個非常合適的會議，尤其是對我們治療的患者群體而言。所以我認為，如果委員會認為有必要並且我們希望能夠在像 ASH 這樣的會議上報告最終的頂線數據，那麼期望是非常合理的。

And then maybe the last one, a tuck-in here is for the COASTAL study. Any update or any thoughts, anything we can -- you can review regarding the enrollment, patient enrollment status or situations at this point?

然後也許是最後一個，這裡是為 COASTAL 研究準備的。任何更新或任何想法，我們可以做的任何事情——您現在可以查看有關註冊、患者註冊狀態或情況的信息嗎？

Yes. Well, I mean, in general we don't usually give numbers enrollment and I won't right now. That's why, as we have said in the past, the most critical thing you can do early in a clinical trial especially of this size and magnitude is get your sites open and initiate it and -- so they can start screening and treating patients. That's where all of our efforts or the majority of our efforts have been over this past year. As I mentioned, we are now open in over 135 sites all over the world essentially or almost, and we continue to open new sites. Hopefully that will come to an end at some point soon. But we do continue to open more sites, and so that our trajectory of enrollment will continue to grow and will meet our objective of completing in '24.

是的。好吧，我的意思是，一般來說，我們通常不會提供註冊人數，我現在也不會。這就是為什麼，正如我們過去所說的那樣，在臨床試驗的早期，您可以做的最關鍵的事情，尤其是這種規模和規模的臨床試驗，就是讓您的網站開放並啟動它，這樣他們就可以開始篩查和治療患者。這就是過去一年我們所有努力或大部分努力的方向。正如我所提到的，我們現在基本上或幾乎在全世界超過 135 個站點開放，並且我們將繼續開設新站點。希望這會很快結束。但我們確實會繼續開設更多站點，這樣我們的招生軌跡將繼續增長，並將實現我們在 24 年完成的目標。

(Operator Instructions) And our next question will come from Nick Abbott of Wells Fargo.

（操作員說明）我們的下一個問題將來自富國銀行的 Nick Abbott。

First one, Dan, when do you expect Kyowa to report data from the Japanese Phase II trial of zandelisib in advanced lymphoma? And is the intention for Kyowa still to submit these data for full approval?

第一個，Dan，你預計 Kyowa 什麼時候報告日本 zandelisib 治療晚期淋巴瘤的 II 期試驗數據？ Kyowa 是否仍打算提交這些數據以供完全批准？

Right, Nick. Hello. I don't believe that Kyowa has previously publicly stated what their plan was for announcing the data. I believe that the enrollment is completed and they're doing their assessments. They intend -- their intent in running that study was to seek a full approval. They don't -- I don't know that they even have an accelerated approval mechanism, but their intent was always to seek a full approval in Japan. I'm not sure exactly what their true -- their timelines are for doing that now, but I think that we should know in not too long what their intentions are, but they operate in a different way than we do here. And so all we know is that, to your question, is that -- is their intent is to file -- when they ran that study was to file for full approval and to do it when they're ready, I guess, is the best way of saying it.

對，尼克。你好。我不相信 Kyowa 之前公開表示他們公佈數據的計劃是什麼。我相信註冊已經完成，他們正在進行評估。他們打算 - 他們進行該研究的目的是尋求完全批准。他們沒有——我不知道他們甚至有加速批准機制，但他們的意圖始終是在日本尋求全面批准。我不確定他們的真實情況 - 他們現在的時間表是什麼，但我認為我們應該很快就會知道他們的意圖是什麼，但他們的運作方式與我們在這裡的方式不同。所以我們所知道的是，對於你的問題，他們的意圖是提交 - 當他們進行該研究時是為了提交完全批准並在他們準備好時進行，我猜，是最好的說法。

(inaudible) clinical trials have gone. They completed accrual last October of 61 patients. So it's a reasonably -- a reasonable size trial and they're sort of going to have 12 months of follow-up data here in the fourth quarter.

（聽不清）臨床試驗已經結束。他們在去年 10 月完成了 61 名患者的應計。所以這是一個合理的——一個合理規模的試驗，他們將在第四季度在這裡獲得 12 個月的後續數據。

Correct. Yes.

正確的。是的。

And then, I know you said you are in discussion with FDA. Have you made a proposal to FDA on revising COASTAL or revising the statistical analysis plan for COASTAL? Or is that something you're still working on?

然後，我知道你說過你正在與 FDA 進行討論。有沒有向FDA提出修改COASTAL或者修改COASTAL統計分析計劃的建議？還是您仍在努力？

Right. So again, I don't -- typically we don't like to discuss in-depth what our -- operationally how we approach our discussions with the FDA. It just to be -- give you a little color, it's not as straightforward as it might appear because as we know, one of the concerns that the FDA has raised in general, but in particular about this class, is mortality. And they acknowledge that these are rare events. So how one does the statistical analysis around that and the penalties one may pay for taking a look or not, it's very complicated.

正確的。所以再一次，我不——通常我們不喜歡深入討論我們——在操作上我們如何處理與 FDA 的討論。它只是 - 給你一點顏色，它並不像看起來那麼簡單，因為據我們所知，FDA 普遍提出的擔憂之一，但特別是關於這一類，是死亡率。他們承認這些都是罕見的事件。因此，如何圍繞這一點進行統計分析，以及人們可能因看或不看而付出的代價，這是非常複雜的。

We've spent a lot of time with statisticians and former FDA consultants, really trying to get our arms around all the issues so that we can have the most meaningful discussion with the FDA as possible. And that said, we do look forward to letting -- to articulating once we've had those discussions and what the outcomes are. We will look forward to articulating that to you in as timely fashion as possible, but I guess I think that's about as deep as I'm comfortable going with that question.

我們花了很多時間與統計學家和前 FDA 顧問一起，真正試圖解決所有問題，以便我們可以盡可能與 FDA 進行最有意義的討論。話雖如此，我們確實期待讓——在我們進行了這些討論後闡明結果是什麼。我們期待盡可能及時地向您闡明這一點，但我想我認為這與我對這個問題感到滿意的程度差不多。

No, that's good. And then also for me, there was this recent peer review publication to use of a PI3K delta inhibitor as neoadjuvant therapy in the clinic in head and neck cancer. They saw T-reg depletion, which is what they were obviously using the drug for, but was too toxic dose continuously and so part of the publication was also on preclinical data using intermittent dosing.

不，那很好。然後對我來說，還有這篇最近的同行評審出版物，使用 PI3K delta 抑製劑作為頭頸癌臨床的新輔助療法。他們看到了 T-reg 耗竭，這顯然是他們使用該藥物的目的，但持續劑量毒性太大，因此該出版物的一部分也是關於使用間歇給藥的臨床前數據。

So what do you think of these data? How interested is MEI in repeating the trial using intermittently dosed zandelisib? And obviously of note is that these authors were around the -- well, many of these authors were just around the corner from new scripts.

那麼你如何看待這些數據呢？ MEI 對使用間歇給藥的 zandelisib 重複試驗有多感興趣？顯然值得注意的是，這些作者都在——嗯，這些作者中的許多人都在新劇本的拐角處。

Yes. So it hasn't escaped our attention, Nick, as you might imagine. In fact the authors of that particular paper that you're mentioning are -- have faculty appointments here in La Jolla. So we know them. We were actually very heartened because I think it sort of supported our thesis that continuous dosing is going to be too toxic, especially as they pointed out in patients who are less heavily pretreated in their head and neck experience. And for them to see that intermittent dosing seems to be really important, I think that was very heartening to us.

是的。所以它並沒有逃過我們的注意，尼克，正如你想像的那樣。事實上，您提到的那篇特定論文的作者是——在拉霍亞這裡有教職。所以我們認識他們。我們實際上非常振奮，因為我認為這在某種程度上支持了我們的論點，即持續給藥會產生太大的毒性，尤其是正如他們指出的那樣，這些患者在頭頸部經歷中接受的預處理較少。讓他們看到間歇性給藥似乎真的很重要，我認為這讓我們非常振奮。

And I think as we have said previously, we have done some -- a fair bit of preclinical work on dosing and scheduling in combination with PD-1 antibodies, for example, in models where CTLA-4 or T-regs are -- appear to be important in solid tumor setting. And we do feel that with the known property of delta and its importance in regulatory T-cells could be taken advantage of or with an appropriate scheduling as a way of very surgically inhibiting T-regs in solid tumor setting as well as in B-cell malignancy setting. So I think that we're very interested in this.

我認為正如我們之前所說，我們已經完成了一些 - 與 PD-1 抗體相結合的劑量和安排的相當多的臨床前工作，例如，在 CTLA-4 或 T-regs 的模型中 - 出現在實體瘤環境中很重要。我們確實認為，由於 delta 的已知特性及其在調節性 T 細胞中的重要性，可以利用或通過適當的安排作為一種非常外科手術抑制實體瘤環境和 B 細胞中的 T-regs 的方法惡性設置。所以我認為我們對此非常感興趣。

As I said, we know this group very well. And I think, for now, I'll just say, stay-tuned. We -- this is on our radar obviously. We don't want to lose focus about COASTAL, but certainly we do think that there is significant opportunities to be had by exploring the immunoregulatory aspect of PI3 delta expression because it is important in multiple different facets, in T-regs and in homing and micro environment. So we think it's very analogous to the sort of lenalidomide situation where it's really an immunomodulator. We really do want to explore the possibility of taking advantage of zandelisib in that respect.

正如我所說，我們非常了解這個群體。我想，現在，我只想說，敬請期待。我們 - 這顯然在我們的雷達上。我們不想失去對 COASTAL 的關注，但我們確實認為探索 PI3 delta 表達的免疫調節方面存在重要機會，因為它在多個不同方面很重要，在 T-regs 和歸巢和微環境。所以我們認為它非常類似於來那度胺的情況，它實際上是一種免疫調節劑。我們真的很想探索在這方面利用 zandelisib 的可能性。

This concludes our question-and-answer session. I would like to turn the conference back over to Dan Gold for any closing remarks.

我們的問答環節到此結束。我想將會議轉回給 Dan Gold 以發表任何閉幕詞。

Thank you. And thank you all again for the time you spent with us today. We do look forward to continuing to share our progress as we advance all of our programs. And we wish you the best for the rest of the day and your coming weekend. All the best.

謝謝。再次感謝大家今天與我們共度時光。我們確實期待在推進所有計劃時繼續分享我們的進展。我們希望您在今天餘下的時間和即將到來的周末一切順利。一切順利。

The conference has now concluded. Thank you for attending today's presentation and you may now disconnect.

會議現已結束。感謝您參加今天的演講，您現在可以斷開連接。