Celcuity Inc (CELC) 2025 Q1 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Celcuity first-quarter 2025 financial results webcast conference call. (Operator Instructions)

女士們、先生們，下午好，歡迎參加 Celcuity 2025 年第一季財務業績網路直播電話會議。（操作員指示）

I would now like to turn the conference over to Apoorva Chiluri with ICR Healthcare. Please go ahead.

現在，我想將會議交給 ICR Healthcare 的 Apoorva Chiluri。請繼續。

Thank you, operator, and good afternoon to everyone. Thank you for joining us to review Celcuity's First Quarter 2025 Financial Results and Business Update. Earlier today, Celcuity Inc. released financial results for the first quarter ended March 31, 2025. The press release can be found on the Investors section of Celcuity's website.

謝謝接線員，大家下午好。感謝您與我們一起回顧 Celcuity 2025 年第一季的財務表現和業務更新。今天早些時候，Celcuity Inc. 發布了截至 2025 年 3 月 31 日的第一季財務表現。新聞稿可在 Celcuity 網站的投資者部分找到。

Joining me on the call today are Brian Sullivan, Celcuity's Chief Executive Officer and Co-Founder; Vicky Hahne, Chief Financial Officer; as well as Igor Gorbatchevsky, Chief Medical Officer, who will be available during Q&A. Before we begin, I would like to remind listeners that our comments today will include some forward-looking statements. These statements involve a number of risks and uncertainties, which are outlined in today's press release and in our reports and filings with the SEC. Actual events or results may differ materially from those projected in the forward-looking statements. Such forward-looking statements and their implications involve known and unknown risks, uncertainties and other factors that may cause actual results or performance to differ materially from those projected.

今天參加電話會議的還有 Celcuity 執行長兼聯合創始人 Brian Sullivan、財務長 Vicky Hahne 以及首席醫療官 Igor Gorbatchevsky，他將在問答環節出席。在我們開始之前，我想提醒聽眾，我們今天的評論將包括一些前瞻性的陳述。這些聲明涉及許多風險和不確定性，這些風險和不確定性在今天的新聞稿以及我們向美國證券交易委員會提交的報告和文件中均有概述。實際事件或結果可能與前瞻性陳述中的預測有重大差異。此類前瞻性陳述及其意義涉及已知和未知的風險、不確定性和其他因素，可能導致實際結果或績效與預測有重大差異。

On this call, we will also refer to non-GAAP financial measures. These non-GAAP measures are used by management to make strategic decisions, forecast future results and evaluate the company's current performance. Management believes that the presentation of these non-GAAP financial measures is useful for investors' understanding and assessment of the company's ongoing core operations and prospects for the future. You can find the table reconciling the non-GAAP financial measures to GAAP measures in today's press release.

在本次電話會議上，我們也將參考非公認會計準則財務指標。管理階層使用這些非公認會計準則指標來制定策略決策、預測未來結果並評估公司當前績效。管理層認為，這些非公認會計準則財務指標的呈現有助於投資者了解和評估公司正在進行的核心業務和未來前景。您可以在今天的新聞稿中找到非 GAAP 財務指標與 GAAP 指標的對照表。

And with that, I would now like to turn the call over to Brian Sullivan, CEO of Celcuity. Please go ahead.

現在，我想將電話轉給 Celcuity 執行長 Brian Sullivan。請繼續。

Thank you, Apoorva. Good afternoon, everyone, and thank you for joining our first quarter financial results conference call. We have an exciting year ahead of us with multiple upcoming clinical data readouts. We expect to report top line data from the PIK3CA wild-type patient cohort of our Phase III VIKTORIA-1 trial in Q3 2025 and from the PIK3CA mutated patient cohort in Q4 2025. We also anticipate reporting preliminary top line data for the Phase Ib portion of our Phase Ib/II trial in prostate cancer in late second quarter.

謝謝你，Apoorva。大家下午好，感謝大家參加我們的第一季財務業績電話會議。我們即將迎來令人興奮的一年，即將發布多項臨床數據。我們預計將於 2025 年第三季報告 III 期 VIKTORIA-1 試驗的 PIK3CA 野生型患者隊列的頂線數據，並於 2025 年第四季度報告 PIK3CA 突變患者隊列的頂線數據。我們也預計將在第二季末報告前列腺癌 Ib/II 期試驗 Ib 部分的初步頂線數據。

And finally, we made great progress activating trial sites for our Phase III first-line VIKTORIA-2 trial over the past few months. In our view, each of our 3 programs has the potential to generate significant levels of revenue. If these programs ultimately result in regulatory approvals, we estimate that nearly 200,000 late-stage cancer patients globally would be eligible to be treated with gedatolisib. Let's turn now to our VIKTORIA-1 trial. Our Phase III VIKTORIA-1 trial is designed to evaluate gedatolisib in combination with fulvestrant with and without palbociclib in patients with hormone receptor positive HER2-negative advanced breast cancer, whose disease has progressed on or after treatment with a CDK4/6 inhibitor.

最後，在過去的幾個月裡，我們在啟動 III 期一線 VIKTORIA-2 試驗的試驗地點方面取得了巨大進展。我們認為，我們的三個項目均有潛力產生可觀的收入。如果這些項目最終獲得監管部門的批准，我們估計全球將有近 20 萬名晚期癌症患者有資格接受 gedatolisib 治療。現在讓我們來談談 VIKTORIA-1 試驗。我們的 III 期 VIKTORIA-1 試驗旨在評估 gedatolisib 與氟維司群聯合使用或不聯合使用 palbociclib 對激素受體陽性 HER2 陰性晚期乳腺癌患者（其病情在使用 CDK4/6 抑製劑治療期間或治療後出現進展）的效果。

The VIKTORIA-1 trial includes 2 patient cohorts with independent statistical analysis plans and primary endpoints. The primary endpoints for VIKTORIA-1 are progression-free survival or PFS as assessed by blinded independent central review. Study is designed to independently evaluate a PIK3CA wild-type cohort and a PIK3CA mutant cohort. For the PIK3CA wild-type cohort, there are 2 primary endpoints that will be tested hierarchically, whereas the PIK3CA mutant patient cohort has a single primary endpoint. The primary analysis for each patient cohort is triggered upon reaching a predefined number of progression events.

VIKTORIA-1 試驗包括 2 個患者隊列，具有獨立的統計分析計劃和主要終點。VIKTORIA-1 的主要終點是透過盲法獨立中央審查評估的無惡化存活期或 PFS。該研究旨在獨立評估 PIK3CA 野生型隊列和 PIK3CA 突變型隊列。對於 PIK3CA 野生型隊列，有 2 個主要終點將按層次進行測試，而 PIK3CA 突變型患者隊列有一個主要終點。當達到預定數量的進展事件時，將觸發對每個患者群體的主要分析。

And based on the current blinded event rates, we anticipate the primary completion of the PIK3CA wild-type patient cohort will occur in June, which would allow us to announce in a press release top line data in the third quarter and to present full results from this patient cohort at a medical conference later in 2025. If positive, we expect the data will support our first new drug application and if approved, our transition to a commercial stage company. If proven effective, gedatolisib in combination with fulvestrant and palbociclib could offer a new standard of care for patients with HR-positive/HER2-negative advanced breast cancer whose disease progressed on or after treatment with a CDK4/6 inhibitor. For the PIK3CA mutant patient cohort, we anticipate reporting top line data in the fourth quarter of 2025. The current second-line treatment paradigm for HR-positive/HER2-negative patients with advanced breast cancer includes selective estrogen receptor degraders or SERDs, like fulvestrant or elacestrant as single agents or 1 of 3 approved PAM inhibitors combined with endocrine therapy.

根據目前的盲法事件發生率，我們預計 PIK3CA 野生型患者隊列的主要研究將於 6 月完成，這將使我們能夠在第三季度的新聞稿中宣布頂線數據，並在 2025 年晚些時候的醫學會議上展示該患者隊列的全部結果。如果結果呈陽性，我們預計數據將支持我們的第一個新藥申請，如果獲得批准，我們將過渡到商業階段的公司。如果證明有效，gedatolisib 與氟維司群和 palbociclib 聯合使用可以為 HR 陽性/HER2 陰性晚期乳癌患者提供新的治療標準，這些患者在使用 CDK4/6 抑制劑治療期間或治療後病情出現進展。對於 PIK3CA 突變患者群體，我們預計將在 2025 年第四季報告頂線數據。目前，針對 HR 陽性/HER2 陰性晚期乳癌患者的二線治療方案包括選擇性雌激素受體降解劑或 SERD，如氟維司群或埃拉司群作為單一藥物或 3 種獲批的 PAM 抑制劑中的 1 種與內分泌療法聯合使用。

However, each of the PAM inhibitors only targets a single PAM node, such as PI3K alpha, AKT or mTORC1, which is suboptimal because the uninhibited PAM nodes can induce compensatory resistance. In patients who've received prior treatment with the CDK4/6 inhibitor, none of these single node PAM inhibitors have demonstrated efficacy in patients who have PIK3CA wild-type tumors, while only the PIK3CA alpha and AKT inhibitor have reported benefit in patients with PIK3CA mutations. And these results are consistent with the nonclinical data that shows these single node inhibitors are 3 to 4 times less potent in breast cancer cells without PIK3CA mutations than in those with them. Of course, we recognize the foundation of gedatolisib's role in this treatment landscape will require that gedatolisib be well tolerated and report a clinically meaningful result measured in terms of the incremental improvement in both PFS and the hazard ratio relative to standard of care. Breast cancer KOLs and regulators generally consider an incremental improvement in PFS of 3 months relative to its control to be clinically meaningful.

然而，每種 PAM 抑制劑僅針對單一 PAM 節點，例如 PI3K alpha、AKT 或 mTORC1，這並不是最理想的，因為未受抑制的 PAM 節點會引起補償性抵抗。對於接受 CDK4/6 抑制劑治療的患者，這些單節點 PAM 抑制劑均未證明對 PIK3CA 野生型腫瘤患者有效，而只有 PIK3CA alpha 和 AKT 抑制劑報告對 PIK3CA 突變患者有益。這些結果與非臨床數據一致，顯示這些單節點抑制劑在沒有 PIK3CA 突變的乳癌細胞中的效力比在有突變的乳癌細胞中的效力低 3 到 4 倍。當然，我們認識到 gedatolisib 在這種治療領域中的作用的基礎將要求 gedatolisib 具有良好的耐受性，並報告以 PFS 和相對於治療標準的風險比的增量改善來衡量的具有臨床意義的結果。乳癌 KOL 和監管機構通常認為，相對於對照組，PFS 增加 3 個月具有臨床意義。

Current MPFS or median progression-free survival benchmarks for patients pretreated with a CDK4/6 inhibitor patient population we're evaluating are modest. Only 2 non-chemo-related therapies have been evaluated in this patient population and received approval. One reported a 1.9 months incremental median PFS improvement relative to its comparator in patients with ESR1 mutations. The other did not report median progression-free survival improvement relative to current standard of care, but it did report a more favorable safety profile in patients with PIK3CA mutations. Despite the modest or no efficacy improvements on this benchmark, both of these recently approved drugs has experienced rapid market adoption and penetration.

我們正在評估的接受 CDK4/6 抑制劑預先治療的患者群體的當前 MPFS 或中位無惡化存活期基準是適中的。僅有 2 種非化療相關療法在該患者群體中進行了評估並獲得批准。其中一項研究報告稱，對於存在 ESR1 突變的患者，其 PFS 中位數相對於對照者增加了 1.9 個月。另一項研究並未報告相對於目前標準治療的中位無惡化存活期改善，但報告指出 PIK3CA 突變患者的安全性更為有利。儘管以這一基準來看，療效的改善不大甚至沒有，但這兩種最近批准的藥物都得到了迅速的市場採用和滲透。

Each drug reached revenue run rates within the first 12 months of launch estimated to be nearly $0.5 billion despite approvals that only address 30% to 40% of the eligible second-line patient population. We believe this demonstrates the significant interest amongst oncologists for new treatment options for these patients and the relatively low bar required to obtain adoption and market penetration. A potentially more important data point than incremental PFS benefit to consider in advanced breast cancer when assessing the clinical benefit of one therapeutic regimen relative to another is the hazard ratio. And this is because recent randomized studies evaluating therapies for patients with HR-positive/HER2-negative advanced breast cancer have enrolled widely heterogeneous patient populations. Since physicians make different treatment decisions for patients depending on, among other factors, how many lines of therapy, how well they respond to the prior therapy and which type of therapy they may have received, results from these studies can be hard to interpret using absolute median PFS for incremental PFS benefit alone.

儘管批准的藥物僅涵蓋了 30% 至 40% 的符合條件的二線患者群體，但每種藥物在上市後的前 12 個月內的收入運行率都達到了估計近 5 億美元。我們相信這表明腫瘤學家對這些患者的新治療方案有濃厚的興趣，並且獲得採用和市場滲透所需的門檻相對較低。在評估晚期乳癌中一種治療方案相對於另一種治療方案的臨床益處時，需要考慮的一個潛在比增量 PFS 益處更重要的數據點是風險比。這是因為最近針對 HR 陽性/HER2 陰性晚期乳癌患者治療方法的隨機研究招募了廣泛異質的患者群體。由於醫生會根據患者的治療方案數、患者對先前治療的反應程度以及患者可能接受的治療類型等因素為患者做出不同的治療決策，因此僅使用絕對中位 PFS 來解釋增量 PFS 效益可能難以解釋這些研究的結果。

As a result, top line and PFS results from these studies don't provide sufficient clarity about the actual benefit a particular patient population may receive. The hazard ratio essentially factors out the differences in study populations and thus provides physicians with a more objective benchmark. We not only hope to report a hazard ratio that is statistically significant, but one that compares favorably to the hazard ratio reported for other therapies available for second-line patients whose disease progressed while receiving a CDK4/6 inhibitor. If gedatolisib ultimately does receive FDA approval for both the PIK3CA wild-type and mutant populations, we estimate the peak revenue potential for the second-line indication could exceed $2 billion with just 40% market penetration. I'd like now to turn to our first-line breast cancer program and our VIKTORIA-2 trial.

因此，這些研究的頂線和 PFS 結果並不能充分清楚地說明特定患者群體可能獲得的實際益處。風險比基本上排除了研究人群的差異，從而為醫生提供了更客觀的基準。我們不僅希望報告具有統計意義的風險比，而且希望報告的風險比與接受 CDK4/6 抑制劑治療期間病情出現進展的二線患者可用的其他療法的風險比相比具有優勢。如果 gedatolisib 最終獲得 FDA 對 PIK3CA 野生型和突變型人群的批准，我們估計二線適應症的峰值收入潛力可能超過 20 億美元，而市場滲透率僅為 40%。現在我想談談我們的第一線乳癌計畫和 VIKTORIA-2 試驗。

The VIKTORIA-2 study is a global Phase III open-label randomized clinical trial, evaluating the efficacy and safety of gedatolisib in combination with fulvestrant plus investigator's choice of either ribociclib or palbociclib as a first-line treatment for patients with HR-positive, HER2-negative advanced breast cancer, and these patients are endocrine therapy resistant. Approximately 638 subjects will be assigned to a cohort based on their PIK3CA mutation status. The primary PFS endpoint for each of the cohorts will be evaluated independently. Prior to initiation of the Phase III portion of the trial, a safety run-in study will be conducted in 12 to 36 participants to assess the safety profile of gedatolisib in combination with ribociclib and fulvestrant. And during the first quarter, we completed our site qualification activities, and we're now focused on activating the nearly 200 sites we've qualified across North America, Europe, Latin America and Asia Pacific.

VIKTORIA-2 研究是一項全球 III 期開放標籤隨機臨床試驗，評估 gedatolisib 聯合氟維司群加上研究者選擇的 ribociclib 或 palbociclib 作為 HR 陽性、HER2 陰性晚期乳腺癌患者一線治療的療效和安全性，並且這些患者對內分泌治療有抵抗力。大約 638 名受試者將根據其 PIK3CA 突變狀態被分配到一個隊列。將獨立評估每個隊列的主要 PFS 終點。在開始此試驗的 III 期階段之前，將對 12 至 36 名參與者進行安全性試運行研究，以評估 gedatolisib 與 ribociclib 和氟維司群聯合使用的安全性。在第一季度，我們完成了站點資格認證活動，現在我們專注於啟動我們在北美、歐洲、拉丁美洲和亞太地區已認證的近 200 個站點。

We've also begun screening patients and expect to dose our first patient during the second quarter. Current standard of care first-line treatment for most endocrine therapy-resistant patients includes any of the 3 approved CDK4/6 inhibitors combined with fulvestrant. Results from a recent trial suggest that the median PFS period for patients receiving 1 of these 3 regimens is only 7 to 8 months. And these results compare poorly to the median PFS of 25 to 27 months reported for patients who are sensitive to endocrine therapy and who receive a similar regimen, highlighting the significant need for more effective therapies for patients with advanced breast cancer that are resistant to endocrine therapy. Now I'd like to turn to our Phase Ib/II trial that's evaluating the safety and efficacy of gedatolisib in combination with darolutamide in patients with metastatic castration-resistant prostate cancer whose disease progressed while receiving a next-generation androgen receptor inhibitor.

我們也已經開始對患者進行篩檢，預計在第二季度為第一位患者進行給藥。目前，對於大多數內分泌治療抗性的患者，第一線治療的標準包括三種已核准的 CDK4/6 抑制劑與氟維司群的組合。最近一項試驗的結果表明，接受這 3 種方案中的 1 種方案的患者的中位 PFS 期僅為 7 至 8 個月。這些結果與對內分泌治療敏感並接受類似治療方案的患者的 25 至 27 個月的中位 PFS 相比相差甚遠，凸顯了對內分泌治療有抗藥性的晚期乳癌患者迫切需要更有效的治療方法。現在我想談談我們的 Ib/II 期試驗，該試驗評估了格達托利西布聯合達洛魯胺對轉移性去勢抵抗性前列腺癌患者（其病情在接受下一代雄激素受體抑製劑治療期間出現進展）的安全性和有效性。

The Phase Ib/II study evaluates gedatolisib in combination with darolutamide, which is an androgen receptor signaling inhibitor in patients with metastatic castration-resistant prostate cancer. We've completed enrollment of the Phase Ib dose escalation portion of the study and anticipate reporting top line data by the end of the second quarter this year. Since we're at an earlier phase in this program, our focus is optimizing the dose and schedule for this tumor type and drug combination. This data set will include approximately 36 patients, half of whom will have received a 120-milligram dose of gedatolisib, the other half a 180-milligram dose. Each are administered on a 3-week on, 1-week off schedule.

Ib/II 期研究評估了 gedatolisib 與 darolutamide 的聯合用藥效果，darolutamide 是一種用於治療轉移性去勢抵抗性前列腺癌患者的雄激素受體信號抑製劑。我們已經完成了該研究 Ib 期劑量遞增部分的招募，預計將在今年第二季末報告頂線數據。由於我們處於該計劃的早期階段，我們的重點是優化這種腫瘤類型和藥物組合的劑量和時間表。該資料集將包括約 36 名患者，其中一半將接受 120 毫克劑量的 gedatolisib，另一半將接受 180 毫克劑量的 gedatolisib。每種療法均採用 3 週治療、1 週停藥的方案。

And we're comparing both the landmark PFS at 6 months and safety profile of these 2 arms to each other and to historical control data for second-line metastatic castration-resistant prostate cancer patients who are retreated with an androgen receptor inhibitor. And finally, we're excited about the opportunity we announced today to collaborate with the Dana Farber Cancer Institute and Massachusetts General Hospital to evaluate gedatolisib in combination with abemaciclib and letrozole in patients with endometrial cancer. The rationale to initiate the study is based on compelling historical clinical data that indicates women with ER-positive or type 1 endometrial cancer may benefit from treatment with a PI3K/AKT/ mTOR inhibitor like gedatolisib in combination with endocrine therapy. Additionally, results from a prior Phase II clinical study evaluated gedatolisib as a monotherapy in patients with either type 1 or type 2 endometrial cancer, and these results were encouraging. So I'd like now to turn the call over to Vicky to review our finances.

我們正在比較這兩個方案的 6 個月 PFS 里程碑和安全性概況，並將其與使用雄激素受體抑制劑進行再治療的二線轉移性去勢抵抗性前列腺癌患者的歷史對照數據進行比較。最後，我們很高興今天宣布有機會與丹娜法伯癌症研究所和麻省總醫院合作，評估 gedatolisib 與 abemaciclib 和來曲唑聯合用於治療子宮內膜癌患者。啟動這項研究的理由是基於令人信服的歷史臨床數據，表明 ER 陽性或 1 型子宮內膜癌女性可能受益於使用 PI3K/AKT/mTOR 抑制劑（如 gedatolisib）聯合內分泌療法治療。此外，先前的 II 期臨床研究結果評估了 gedatolisib 作為 1 型或 2 型子宮內膜癌患者的單一療法的效果，這些結果令人鼓舞。所以現在我想把電話轉給 Vicky 來審查我們的財務狀況。

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the first quarter of 2025. Our first quarter net loss was $37 million or $0.86 per share compared to $21.6 million net loss or $0.6 per share for the first quarter of 2024. Our non-GAAP adjusted net loss was $34.7 million or $0.81 per share for the first quarter of 2025 compared to non-GAAP adjusted net loss of $19.9 million or $0.59 per share for the first quarter of 2024. Research and development expenses were $32.2 million for the first quarter of 2025 compared to $20.6 million for the first quarter of 2024.

謝謝你，布萊恩，大家下午好。我將簡要概述我們 2025 年第一季的財務表現。我們第一季的淨虧損為 3,700 萬美元，即每股 0.86 美元，而 2024 年第一季的淨虧損為 2,160 萬美元，即每股 0.6 美元。2025 年第一季度，我們的非 GAAP 調整後淨虧損為 3,470 萬美元，即每股 0.81 美元，而 2024 年第一季的非 GAAP 調整後淨虧損為 1,990 萬美元，即每股 0.59 美元。2025 年第一季的研發費用為 3,220 萬美元，而 2024 年第一季的研發費用為 2,060 萬美元。

Of the approximately $11.6 million increase in R&D expenses, $5.9 million was related to increased employee and consulting expenses and $5.7 million primarily related to activities supporting our ongoing clinical trials. General and administrative expenses were $3.9 million for the first quarter of '25 compared to $1.8 million for the first quarter of 2024. Increased employee and consulting-related expenses accounted for $1.6 million of the increase. Professional fees, expanding infrastructure and other administrative expenses accounted for the remaining increase of approximately $0.5 million. Net cash used in operating activities for the first quarter of 2025 was $35.9 million compared to $17.1 million for the first quarter of 2024.

在研發費用增加的約 1,160 萬美元中，590 萬美元與員工和諮詢費用的增加有關，570 萬美元主要與支持我們正在進行的臨床試驗的活動有關。2025 年第一季的一般及行政費用為 390 萬美元，而 2024 年第一季的一般及行政費用為 180 萬美元。員工和諮詢相關費用的增加佔增加額的 160 萬美元。專業費用、擴大基礎設施和其他管理費用佔剩餘增加額的約 50 萬美元。2025 年第一季經營活動所用淨現金為 3,590 萬美元，而 2024 年第一季為 1,710 萬美元。

We ended the quarter with approximately $205.7 million of cash, cash equivalents and short-term investments. We expect this cash, cash equivalents and short-term investments and drawdowns on our debt facility to fund current clinical development program activities through 2026. I will now hand the call back to Brian.

本季末，我們擁有約 2.057 億美元的現金、現金等價物和短期投資。我們預計這些現金、現金等價物以及短期投資和債務融資將為目前的臨床開發計畫活動提供資金，直至 2026 年。我現在將把電話交還給布萊恩。

We're now ready to turn the call over for questions.

我們現在準備將電話轉交給大家提問。

(Operator Instructions) Maury Raycroft, Jefferies.

（操作員指示）Maury Raycroft，Jefferies。

Congrats on the progress. was going to ask one on VIKTORIA-1. You're using the blinded independent central review analysis, which can take a longer amount of time to analyze versus investigator assessed. And so just wondering if you can provide more perspective on how long you think it will take to lock the data set sometime in June and then to get to the actual results in 3Q. Just wondering if you can give more perspective on the amount of time there.

祝賀取得進展。打算在 VIKTORIA-1 上問一個。您正在使用盲法獨立中央審查分析，與研究人員評估相比，這可能需要更長的分析時間。所以我只是想了解您是否可以提供更多觀點，您認為需要多長時間才能在 6 月的某個時候鎖定資料集，然後在第三季度獲得實際結果。只是想知道您是否可以提供更多關於在那裡的時間的觀點。

Sure the primary completion date essentially is referencing the data cutoff date when you stop collecting data, and that's typically done and in our case, will be done when you've achieved the prescribed event threshold. And so from there, you are engaged in the data cleaning process and ultimately, at that point, you lock the database. So we expect that in Q3, and we're -- if we achieve what we're very confident about achieving with completing the -- achieving the primary completion date, we think that Q3 is absolutely certain time when we would have the data available. And we're not going to get into more specificity in terms of month. But again, I think there's no further risk of delay at this point in the trial of being able to report these results.

當然，主要完成日期本質上是指您停止收集資料的資料截止日期，這通常是在您達到規定的事件閾值時完成的，在我們的案例中也是如此。從那時起，您就開始參與資料清理過程，並最終在那時鎖定資料庫。因此，我們預計在第三季度，如果我們實現了我們非常有信心實現的目標——實現初步完成日期，我們認為第三季度是我們絕對可以獲得數據的時間。我們不會就月份進行更具體的說明。但我再次認為，在試驗的這個階段，報告這些結果不會再有延遲的風險。

Understood. But I guess for that amount of time from locking the database to reporting the data, any general estimate on how long that could take?

明白了。但我猜從鎖定資料庫到報告資料這段時間，有沒有大概的估計需要多久？

I mean, typically, you would see no more than 3 months and typically less than that.

我的意思是，通常情況下，你會看到的時間不會超過 3 個月，而且通常少於 3 個月。

Got it. Okay. And then understanding that overall survival might not be fully mature at the top line, do you think you would be able to provide some sort of an update on just the directionality of survival trend that you're seeing between the 3 arms at the data readout?

知道了。好的。然後了解到總體生存率可能還沒有完全成熟，您是否認為您能夠提供一些關於您在數據讀數中看到的 3 個組之間的生存趨勢方向性的更新？

The data readout that we expect to make in a press release will only include the median PFS and the hazard ratios for the 2 primary analyses. The subsequent data will be analyzed rather presented at the medical conference later in the year.

我們預計在新聞稿中發布的數據將僅包括 2 個主要分析的中位數 PFS 和風險比。後續數據將進行分析，並在今年稍後的醫學會議上展示。

Andrew Berens, Leerink.

安德魯貝倫斯（Andrew Berens），Leerink。

This is [Elison] on for Andy. I wanted to get your thoughts on the potential impact of SERENA-6 on the second-line setting for HR-positive patients. Just curious what could broad adoption from this need for GEA in the wild-type population? And also kind of a similar question, what could the potential impact be to GA in the mutant patient population as well?

我是 [Elison]，為 Andy 表演。我想了解您對 SERENA-6 對 HR 陽性患者二線治療的潛在影響的看法。只是好奇野生型族群對 GEA 的這種需求能被廣泛採用嗎？還有一個類似的問題，這對突變患者群體中的 GA 可能產生什麼潛在影響？

Sure. Well, we don't think that would affect us at all. These are still essentially first-line CDK4/6 patients. It's actually current practice amongst many doctors, depending on the profile of their patients to transition them off letrozole to fulvestrant depending on how they believe their patients are progressing. So this trial essentially identified a more precise way of determining the timing and what appears to be a very effective way of doing that.

當然。嗯，我們認為這根本不會對我們產生影響。這些基本上仍是第一線 CDK4/6 患者。實際上，目前許多醫生的做法是，根據患者的病情，根據他們認為患者的病情進展情況，將患者從來曲唑轉為氟維司群。因此，這次試驗基本上確定了一種更精確的確定時間的方法，而且似乎是一種非常有效的方法。

But the patients in our trial are essentially consistent with the patients that this trial evaluated, which are patients who received CDK4/6 and eventually progressed. And so if our data is favorable, we would expect physicians to then seek to continue treatment with the CDK4/6 inhibitor with one that includes gedatolisib. And I don't think the practice will vary between those patients who lack PIK3CA mutations versus those who do have PIK3CA mutations. I think the primary effect may be on how other CDK4/6 plus oral SERD combinations get used.

但我們試驗中的患者與本次試驗評估的患者基本一致，都是接受CDK4/6治療並最終出現進展的患者。因此，如果我們的數據是有利的，我們預計醫生會尋求繼續使用 CDK4/6 抑制劑治療，其中包括 gedatolisib。我認為缺乏 PIK3CA 突變的患者和有 PIK3CA 突變的患者之間的治療不會有差異。我認為主要影響可能在於其他 CDK4/6 加口服 SERD 組合的使用方式。

Operator?

操作員？

Tara Bancroft, TD Cowen.

塔拉·班克羅夫特（Tara Bancroft），TD Cowen。

So I was wondering if you could provide any updated thoughts on what minimum HR you would consider to be good data in the wild-type update, not just for hitting stats, but in relation to other data sets and indication like SERENA-6 that was just mentioned and other marketed products? And what do KOLs want to see in order to use it?

所以我想知道您是否可以提供任何更新的想法，即您認為在野生型更新中什麼樣的最低 HR 是好數據，不僅僅是為了達到統計數據，還與其他數據集和指示（如剛才提到的 SERENA-6 和其他市場產品）相關？那麼 KOL 想要看到什麼才能使用它呢？

No, I appreciate the question. At this time, with the data fairly imminent, we're not going to comment specificity about those types of projections. We've commented because the analysis is easier to do that an incremental 3 months would be considered clinically meaningful. Certainly, any statistically significant hazard ratio that's consistent with 3 months would also be considered clinically meaningful. How the regimen and the results specifically stack up against other regimens will just be a function of how those 2 sets of data compare.

不，我很感謝你提出這個問題。目前，由於數據即將公佈，我們不會對這些類型的預測做出具體評論。我們之所以評論說，是因為分析更容易進行，所以增量的 3 個月將被認為具有臨床意義。當然，任何與 3 個月一致的具有統計意義的風險比也將被認為具有臨床意義。此療法及其結果與其他療法相比如何，僅取決於這兩組數據的比較情況。

(Operator Instructions) Gil Blum, Needham & Company.

（操作員指示）Gil Blum，Needham & Company。

So just to fully clarify this, what exactly drove the slight change in timing for the wild-type readout? And should we expect to see no change in the PIK3CA time line? And as a follow-on, what investment, if any, would you need to do to support the endometrial cancer collaboration?

因此，為了完全澄清這一點，究竟是什麼導致了野生型讀數時間的輕微變化？我們是否應該預期 PIK3CA 時間線不會改變？作為後續行動，您需要進行哪些投資（如果有的話）來支持子宮內膜癌合作？

Sure. As far as what drove it, again, I think we've indicated on prior calls that because this is a 3-arm trial and the primary analysis is driven by reaching an event threshold in each of 2 different analyses, it's imprecise for us to estimate the timing. I think there's this variance in how those results are distributed within the aggregate total of events for all 3 arms. And we're now at a point where the potential for variability is de minimis. And so that's why we have confidence about being able to establish a data cutoff in June.

當然。至於推動因素，我想我們在先前的電話會議上已經指出，因為這是三組試驗，主要分析是透過在兩種不同的分析中分別達到事件閾值來驅動的，所以我們無法準確地估計時間。我認為這些結果在所有 3 個分支的事件總數中的分佈方式存在差異。我們現在處於一個變化可能性極小的階段。這就是為什麼我們有信心在六月確定資料截止日期。

And as far as Q4 for the PIK3CA mutant, we're confident about that. It's a less complicated tracking of event threshold because even though the 3 arms, the third arm comprises only about 15% of the total. So the primary analysis event threshold is much more closely aligned to the aggregate of the 3 arms. And as far as the endometrial study that we announced, we are supplying drug product and providing clinical support to that study. So we don't think we'll have any incremental financial effect on the company.

至於 PIK3CA 突變體的 Q4，我們對此很有信心。這是一個不太複雜的事件閾值跟踪，因為儘管有 3 個臂，但第三個臂僅佔總數的 15% 左右。因此，主要分析事件閾值與 3 個分支的總和更加緊密相關。就我們宣布的子宮內膜研究而言，我們正在為該研究提供藥物和臨床支持。因此我們認為我們不會對公司產生任何增量財務影響。

Operator?

操作員？

Oliver McCammon, LifeSci Capital.

奧利佛·麥卡蒙（Oliver McCammon），LifeSci Capital。

Maybe we'll take a break from VIKTORIA-1 for a moment. I'm curious if you can just remind us on some of the prior proof-of-concept data for targeting the PI3K/AKT/MO4 pathway in prostate cancer. And more specifically, what you think the potential is for multi-node inhibition versus single node inhibitors like capivasertib. And then I'm also curious if you plan to share PSA data at the time of the update late in the second quarter.

也許我們應該暫時離開 VIKTORIA-1。我很好奇您是否可以提醒我們一些針對前列腺癌中 PI3K/AKT/MO4 路徑的先前概念驗證資料。更具體地說，您認為多節點抑制與單節點抑制劑（如 capivasertib）的潛力如何。然後我還想知道您是否計劃在第二季末更新時分享 PSA 數據。

Sure. And so the data that's been reported with either in particular, AKT inhibitors, those have been the inhibitors from this general class of drugs that have been evaluated in patients with metastatic castration-resistant prostate cancer. Now capivasertib reported positive data with patients who have hormone-sensitive prostate cancer that was favorable in patients who have P10 mutations, and so a subgroup of the total population. The nonclinical data that we've reported and published indicate the GE is equally active independent of the status of P10, which is the primary mutation in prostate cancer. And capivasertib hasn't demonstrated activity or it's significantly less active in tumor cells, prostate tumor cells that lack P10 mutations.

當然。因此，關於 AKT 抑制劑的具體報告數據，這些是這類藥物中的抑制劑，已在轉移性去勢抵抗性前列腺癌患者中進行了評估。目前，capivasertib 報告了針對激素敏感性前列腺癌患者的積極數據，這對於具有 P10 突變的患者（即總人口的一個亞群）來說是有利的。我們報告和發表的非臨床數據表明，GE 同樣活躍，與 P10（前列腺癌的主要突變）的狀態無關。且 capivasertib 尚未表現出活性，或在腫瘤細胞、缺乏 P10 突變的前列腺腫瘤細胞中的活性明顯較低。

And so we think that data is encouraging because it demonstrates the role the pathway plays. And similar to breast cancer, gedatolisib in nonclinical models has shown to be significantly more potent and cytotoxic than, let's say, an AKT inhibitor like capivasertib or the other drugs that have been approved that address the PAM pathway. And so that was a major part of the rationale for evaluating GEA in this setting that, a, the pathway has been demonstrated to be approved; and b, the drugs that have demonstrated activity are at least nonclinically, less active than GEA, which we think creates a very strong rationale for the trial. As far as the update, the update will really just focus on the primary analysis and safety data. And then the rest of the data, we would expect to report at a medical meeting in 2025.

因此我們認為數據令人鼓舞，因為它證明了該途徑所發揮的作用。與乳癌類似，在非臨床模型中，gedatolisib 已被證明比 AKT 抑制劑（如 capivasertib）或其他已獲批准的針對 PAM 路徑的藥物更有效、更具細胞毒性。因此，這是在這種情況下評估 GEA 的主要理由：a，該途徑已被證明是獲得批准的；b，已證明有活性的藥物至少在非臨床上活性低於 GEA，我們認為這為試驗提供了非常有力的理由。就更新而言，更新實際上只專注於主要分析和安全資料。我們預計將在 2025 年的醫學會議上報告其餘數據。

There are no further questions at this time. Please continue, Mr. Brian Sullivan.

目前沒有其他問題。請繼續，布萊恩·沙利文先生。

Well, thank you. We appreciate your interest in Celcuity, and we'll be attending and presenting at several investor conferences over the next few weeks. So I look forward to seeing some of you there. Goodbye.

好的，謝謝你。感謝您對 Celcuity 的關注，我們將在接下來的幾週內參加幾場投資者會議並發表演講。所以我期待在那裡見到你們。再見。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，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。