Celcuity Inc (CELC) 2024 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the Celcuity Second Quarter 2024 financial results conference call. (Operator Instructions) This call is being recorded today, August 14, 2024.

女士們、先生們，下午好，歡迎參加 Celcuity 2024 年第二季財務業績電話會議。（操作員說明）此通話將於今天（2024 年 8 月 14 日）錄音。

I would now like to turn the conference over to Maria Yonkoski with ICR Westwicke. Please go ahead.

現在我想將會議交給 ICR Westwicke 的 Maria Yonkoski。請繼續。

Thank you, operator, and good afternoon to everyone on the call. Thank you for joining us to review so Celcuity's Second Quarter 2024 financial results and business update. Earlier today, Celcuity released financial results for the quarter ending June 30, 2024 the press release can be found on the Investors section of the website.

謝謝接線員，祝所有通話的人下午好。感謝您與我們一起回顧 Celcuity 2024 年第二季的財務表現和業務更新。今天早些時候，Celcuity 發布了截至 2024 年 6 月 30 日的季度財務業績，該新聞稿可在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.

今天和我一起參加電話會議的還有 Celcuity 執行長兼聯合創始人 Brian Sullivan； Vicky Hahne，財務長；以及首席醫療官伊戈爾·戈爾巴切夫斯基 (Igor Gorbatchevsky)，他將在問答環節出席。

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 and actual events or results may differ materially from those projected in the forward-looking statements.

在開始之前，我想提醒聽眾，我們今天的評論將包括一些前瞻性陳述。這些聲明涉及今天的新聞稿、我們的報告以及向美國證券交易委員會提交的文件中概述的許多風險和不確定性，實際事件或結果可能與前瞻性聲明中的預測有重大差異。

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. 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.

此類前瞻性陳述及其影響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。在這次電話會議上，我們也將提及非公認會計準則財務指標。管理階層使用這些非公認會計原則衡量標準來制定策略決策、預測未來績效並評估公司目前績效。

Management believes 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.

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, Maria, and good afternoon, everyone. We appreciate your interest and Celcuity. We made significant strides advancing the clinical development of gedatolisib this quarter. Overall enrollment and Victoria one, our Phase 3 study evaluating data to listen plus fulvestrant within without palbociclib as second line treatment for patients with HR-positive HER2-negative advanced breast cancer remains robust and on track.

謝謝瑪麗亞，大家下午好。我們感謝您的興趣和 Celcuity。本季我們在推進 gedatolisib 的臨床開發方面取得了重大進展。整體入組情況和維多利亞一期，我們的3 期研究評估了在不使用哌柏西利的情況下聽加氟維司群作為HR 陽性HER2 陰性晚期乳腺癌患者二線治療的數據，該研究仍然穩健且步入正軌。

Our Phase 1b 2 trial evaluating patients with metastatic castration resistant prostate cancer is also enrolling on schedule, and we further expanded the patient population eligible for gedatolisib when we initiated efforts to launch Victoria, two, a Phase 3 study designed to evaluate gedatolisib as a first-line treatment option for patients with HR-positive HER2-negative advanced breast cancer in our view, each of these three programs has the potential to generate blockbuster levels of revenue.

我們評估轉移性去勢抵抗性前列腺癌患者的1b 2 期試驗也在按計劃入組，當我們開始努力啟動維多利亞二號時，我們進一步擴大了符合gedatolisib 資格的患者群體，這是一項旨在評估gedatolisib 的第一個3 期研究我們認為，這三個項目都有可能產生巨額收入。

The Phase 3 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. We first announced our plans to conduct a Victoria one study over two years ago in May 2022.

第三階段計劃最終獲得監管部門的批准。我們估計全球近 20 萬名晚期癌症患者有資格接受 gedatolisib 治療。兩年多前，在 2022 年 5 月，我們首次宣布計劃進行一項 Victoria One 研究。

At that time, we estimated that 65% of the patients enrolled would lack detectable [PiC] three CA mutations and would thus be assigned to the study's picture. You see a wild type cohort, and this assumption was used to estimate enrollment by cohort and in turn the timing of events for primary analysis, we estimated that the threshold number of events required to trigger the primary analysis for this picture, you see a wild type cohort of patients would be reached in the second half of 2024.

當時，我們估計 65% 的入組患者缺乏可檢測的 [PiC] 三種 CA 突變，因此將被分配到該研究的圖片中。您看到一個野生型隊列，這個假設用於估計隊列的入組情況，進而估計主要分析的事件時間，我們估計觸發此圖片的主要分析所需的事件閾值數量，您看到一個野生型隊列類型的患者群組將於2024 年下半年達到。

And while the study's overall enrollment remains on track and robust relative to the estimate we made over two years ago. Total proportion of patients enrolled who have picked to say wild type tumors has recently shifted lower. We now project that 60% of the patients enrolled in the study will be enrolled in the picture. You see a wild-type cohort rather than the 65% originally estimated and this proportion was lower than our original estimate. It's within the range reported in other studies.

儘管該研究的總體入組人數與我們兩年多前的估計仍然正常且強勁。最近，選擇說野生型腫瘤的入組患者總比例下降。我們現在預計參加研究的患者中有 60% 會參加該圖片。您看到的是野生型隊列，而不是最初估計的 65%，而這個比例低於我們最初的估計。它在其他研究報告的範圍內。

And thus, we don't believe the shift to study related, but simply result of normal sample variation within a population despite the lower proportion of fixed, we see a wild type patients completed enrollment for the picture, we see a wild-type cohort is over 80% complete, we expect to reach the enrollment target for the picture. You see a wild type cohort during the fourth quarter rather than the end of the third quarter.

因此，我們不相信向研究的轉變相關，而只是群體內正常樣本變異的結果，儘管固定比例較低，我們看到野生型患者完成了圖片登記，我們看到野生型隊列已完成80%以上，預計能達到圖片的招生目標。你會在第四季而不是第三季末看到野生型群體。

As we originally forecast, we now expect the primary analysis event threshold trigger for the picture. You see a wild-type cohort will be reached sometime between late Q4 '24 and the end of Q1 2025. Our guidance regarding the fixed ratio mutant patient subgroup remains unchanged, and we expect primary analysis for this cohort to be triggered during the first half of 2025.

正如我們最初預測的那樣，我們現在期望圖片的主要分析事件閾值觸發。您會看到野生型隊列將在 24 年第 4 季末到 2025 年第 1 季末之間的某個時間達到。我們關於固定比率突變患者亞組的指導保持不變，我們預計該隊列的初步分析將在 2025 年上半年觸發。

Turning now to our Victoria two study, we announced our plans to initiate this Phase 3 clinical trial. This past May study will evaluate gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first line treatment for patients with HR-positive HER2-negative advanced breast cancer, whose disease recurs while receiving or within 12 months of completing adjuvant endocrine therapy.

現在轉向我們的維多利亞兩項研究，我們宣布計劃啟動這項 3 期臨床試驗。今年5 月的研究將評估gedatolisib 加CDK4/6 抑制劑和氟維司群作為HR 陽性HER2 陰性晚期乳癌患者的第一線治療，這些患者在接受輔助內分泌治療期間或完成輔助內分泌治療後12 個月內疾病復發。

While these patients are considered to have endocrine therapy resistant disease may have a significantly poorer prognosis than endocrine therapy sensitive patients whose disease recurs more than 12 months after completing their adjuvant endocrine therapy. Current standard of care first-line treatment for endocrine therapy resistant patients includes any of the three approved CDK4/6 inhibitors combined with fulvestrant, the limited efficacy.

雖然這些患者被認為患有內分泌治療抗藥性疾病，但與內分泌治療敏感患者相比，其預後可能明顯較差，後者在完成輔助內分泌治療後 12 個月以上疾病復發。目前內分泌治療抗藥性患者的第一線治療標準包括三種已批准的 CDK4/6 抑制劑中的任何一種與氟維司群聯合使用，但療效有限。

These regimens offer endocrine therapy resistant patients. So was not well understood until the end of [120] study Phase 3 clinical trial for the [pic 3 CPI 3 alpha] inhibitor and have listened reported results last December. As part of this trial, the efficacy of standard of care, palbociclib and fulvestrant was evaluated as first-line treatment in patients who were resistant to endocrine therapy.

這些方案為內分泌治療抗藥性的患者提供了治療方案。因此，直到 [120] 研究 [pic 3 CPI 3 α] 抑制劑的 3 期臨床試驗結束並聽取了去年 12 月報告的結果後，才得到很好的理解。作為該試驗的一部分，評估了標準護理、哌柏西利和氟維司群作為第一線治療對內分泌治療抗藥性的患者的療效。

And for these patients median PFS was only 7.3 months. And for those patients whose disease relapsed within the first two years of their regimen endocrine therapy, the median PFS was only 3.7 months. And these results compare poorly to the median PFS of 27 months reported for patients who are sensitive to endocrine therapy and have received the same regimen highlighting a significant need for more effective therapies for patients with advanced breast cancer that are resistant to endocrine therapy.

這些患者的中位 PFS 僅為 7.3 個月。對於那些在內分泌治療的頭兩年內疾病復發的患者，中位無惡化存活期僅為 3.7 個月。這些結果與對內分泌治療敏感且接受相同治療方案的患者報告的 27 個月的中位 PFS 相比較差，這凸顯了對內分泌治療抗藥性的晚期乳癌患者迫切需要更有效的治療。

We reported last year the preliminary clinical data from our Phase 1b trial for gedatolisib as first-line treatment in patients with advanced recurrent breast cancer. As you may recall, the median progression-free survival in endocrine sensitive patients were treatment-naive and were treated with gedatolisib in combination with palbociclib and letrozole was 48.6 months and the objective response rate of 79%. And these results compare very favorably to the results reported for palbociclib plus letrozole in this population.

去年，我們報告了 gedatolisib 作為晚期復發性乳癌患者第一線治療的 1b 期試驗的初步臨床數據。您可能還記得，內分泌敏感患者未接受過治療且接受 gedatolisib 合併 Palbociclib 和來曲唑治療的中位無惡化存活期為 48.6 個月，客觀緩解率為 79%。這些結果與針對該族群報告的哌柏西利加來曲唑的結果非常有利。

Additionally, the end of 120 study that evaluated and have listed combined with palbociclib and for restaurant in the endocrine resistant patients reported positive data on how these patients had tumors with Pixar's, the mutations and the patients were not prediabetic or diabetic subgroup only represents about 20% of the total endocrine resistant patient population. However, the results reported were positive relative to the control, providing further evidence of the critical role.

此外，評估並列出了120 項研究的結尾，該研究列出了與palbociclib 聯用和用於內分泌抵抗患者的餐廳報告的陽性數據，這些患者如何與皮克斯的腫瘤、突變和患者不是糖尿病前期或糖尿病亞組僅代表約20佔內分泌抗性患者總數的百分比。然而，報告的結果相對於對照組是正面的，進一步證明了其關鍵作用。

The picture you see a pathway plays as a driver of disease and treatment naive patients in Victoria to study for the CDK4/6 inhibitor. Investigators may choose either ribociclib or palbociclib safety profile of gedatolisib combined with fulvestrant and palbociclib as well described. But the investigational combination of get us listed with ribociclib has not yet been clinically tested and therefore, the safety run-in of approximately 12 to 36 patients will evaluate the safety profile of gedatolisib combined with ribociclib, fulvestrant safety run-in will be completed.

您看到的圖片中的一條通路是維多利亞州未接受治療的疾病和治療患者研究 CDK4/6 抑制劑的驅動因素。研究人員可以選擇 ribociclib 或 palbociclib 的 gedatolisib 與氟維司群和 palbociclib 組合的安全性（如上文所述）。但 get us list 與 ribociclib 的研究組合尚未經過臨床測試，因此，大約 12 至 36 名患者的安全磨合將評估 gedatolisib 與 ribociclib 組合的安全性，氟維司群安全磨合將完成。

I got to tell us about Phase 3 dose with ribociclib confirmed before enrolling patients in the Phase 3 portion of the study for the study, approximately 638 subjects will be assigned to a cohort based on their picks. We see a mutation status after the investigator selects the CDK4/6 inhibitor for us subject will then be randomly assigned on a one-to-one basis to either be treated with gedatolisib fulvestrant and either ribociclib and palbociclib or be assigned to an arm that treats patients with fulvestrant in either rival or palbo.

在將患者納入研究的第 3 階段部分之前，我必須告訴我們有關 ribociclib 的第 3 階段劑量已確認，大約 638 名受試者將根據他們的選擇分配到一個隊列。在研究者為我們選擇 CDK4/6 抑制劑後，我們看到了突變狀態，然後受試者將被一對一地隨機分配到要么接受 gedatolisib 氟維司群以及 ribociclib 和 palbociclib 治療，要么分配到治療組服用氟維司群的患者無論是競爭對手或帕博。

The clinical trial, primary endpoints are progression-free survival per resist one criteria as assessed by blinded independent central review and the primary PFS endpoint for each of the two cohorts will be evaluated independently. Study design was reviewed and discussed with US, FDA during the Type C meeting first quarter. And then we've also just recently received feedback from the FDA on the study protocol as part of the Type C meeting.

此臨床試驗的主要終點是透過盲法獨立中心審查評估的符合一項標準的無惡化存活期，並且將獨立評估兩個隊列中每一個隊列的主要 PFS 終點。在第一季的 C 類會議上，研究設計與美國 FDA 進行了審查和討論。最近，作為 C 類會議的一部分，我們也剛收到 FDA 對研究方案的回饋。

So we can now focus on our feasibility and site selection activities. We expect to activate roughly 200 clinical sites across North America, Europe, Latin America and Asia. And we expect to enroll the first patient in the second quarter of 2025. We estimate that 15,000 to 20,000 patients with endocrine therapy resistant advanced breast cancer are diagnosed each year in the United States alone.

因此，我們現在可以專注於可行性和選址活動。我們預計在北美、歐洲、拉丁美洲和亞洲啟動約 200 個臨床中心。我們預計在 2025 年第二季招募第一位患者。我們估計，光在美國每年就有 15,000 至 20,000 名內分泌治療抗藥性的晚期乳癌患者被診斷出來。

Since this population does not overlap with the patient population we are evaluating in our Victoria one study and approval to treat these patients would increase the size of the addressable US market potential for gedatolisib by up to $3 billion.

由於這一人群與我們在維多利亞州進行的一項研究中評估的患者人群並不重疊，如果批准治療這些患者，將使 gedatolisib 在美國的潛在市場規模增加高達 30 億美元。

Given the importance of developing a more efficacious therapeutic regimen for these patients and the scale of the financial opportunity, we decided it was important to proceed as quickly as possible to initiate a Phase 3 study for this patient population.

考慮到為這些患者開發更有效的治療方案的重要性以及財務機會的規模，我們認為盡快針對該患者群體啟動 3 期研究非常重要。

To accomplish this, we needed to strengthen our balance sheet, which we did this quarter when we raised $129 million gross proceeds from equity and debt offerings by initiating this trial now 12 months earlier than we would have been able to do so without this financing, we estimate we added over $1 billion to the net present value of the potential revenue stream from this indication.

為了實現這一目標，我們需要加強我們的資產負債表，我們在本季度就做到了這一點，當時我們透過啟動這項試驗，從股票和債務發行中籌集了1.29 億美元的總收益，比沒有在這項融資的情況下我們能夠做到的提前了12 個月，我們估計，這一跡象為潛在收入流的淨現值增加了超過 10 億美元。

I'd like to turn now to our Phase 1b 2 trial that's evaluating the safety and efficacy of debt at the close of in combination with darolutamide, an androgen receptor inhibitor in patients with metastatic castration resistant prostate cancer study dosed its first patient in February of this year and enrollment's on track. We continue to expect to report preliminary data in the first half of 2025.

我現在想談談我們的1b 2 期試驗，該試驗正在評估債務與darolutamide 聯合治療的安全性和有效性，darolutamide 是一種雄激素受體抑製劑，用於治療轉移性去勢抵抗性前列腺癌患者，該研究於2017 年2 月對第一位患者進行了給藥。我們繼續預計在 2025 年上半年報告初步數據。

We're also pleased that our non-clinical research describing got its illicit activity in different tumor types was recently published in two leading journals. In June, Nature breast cancer published results from various in vitro and in vivo studies, we conducted that compared get unsolicited activity in several approved single node, [PSVK, AKTM, PAM] inhibitors in various breast cancer models.

我們也很高興我們的非臨床研究描述了其在不同腫瘤類型中的非法活性，最近在兩家領先期刊上發表。6 月，《自然乳癌》發表了各種體外和體內研究的結果，我們在各種乳癌模型中比較了幾種已批准的單節點 [PSVK、AKTM、PAM] 抑制劑的主動活性。

And in August, Molecular Oncology published results of similar studies in prostate cancer models. Both sets of studies demonstrated that gedatolisib exhibited more potent and cytotoxic effects compared to the single node PAM inhibitors, regardless of the PAM pathway mutation mutational status of the cell lines.

八月，《分子腫瘤學》發表了前列腺癌模型的類似研究結果。兩組研究均表明，與單節點 PAM 抑制劑相比，gedatolisib 表現出更有效的細胞毒性作用，無論細胞系的 PAM 途徑突變狀態如何。

And these results indicate that inhibition of multiple PAM pathway nodes by [PAMP, KMTOR] inhibitor, like gedatolisib was more effective at inducing antitumor activity and single node PAM inhibitors in vitro and in animal models, overall was a very busy and productive quarter. I'm very pleased of the progress we made. I'd like now to turn the call over to Vicky, who will review our financials.

這些結果表明，[PAMP、KMTOR] 抑制劑（如gedatolisib）對多個PAM 路徑節點的抑制在誘導抗腫瘤活性方面更有效，而單節點PAM 抑制劑在體外和動物模型中總體上是一個非常繁忙和富有成效的季度。我對我們所取得的進展感到非常高興。我現在想把電話轉給 Vicky，她將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 second quarter 2024. Our second quarter net loss was $23.7 million or $0.62 per share compared to $14.6 million net loss or $0.66 per share for the second quarter of '23. Because these quarterly net loss losses included significant noncash items, including stock-based compensation and interest.

謝謝你，布萊恩，大家下午好。我將簡要概述 2024 年第二季的財務表現。我們第二季的淨虧損為 2,370 萬美元，即每股 0.62 美元，而 2023 年第二季的淨虧損為 1,460 萬美元，即每股 0.66 美元。因為這些季度淨虧損包括大量非現金項目，包括基於股票的薪酬和利息。

We also included in our press release, non-GAAP adjusted net loss for the quarter ending June 30, 2024, our non-GAAP adjusted net loss was $22.2 million or $0.58 per share for the second quarter of '24 compared to non-GAAP adjusted net loss of $11.1 million or $0.51 per share for the second quarter of '23.

我們也在新聞稿中納入了截至2024 年6 月30 日的季度非GAAP 調整後淨虧損，與非GAAP 調整後相比，2024 年第二季非GAAP 調整後淨虧損為2,220 萬美元，即每股0.58 美元2023 年第二季淨虧損 1,110 萬美元，即每股虧損 0.51 美元。

Research and development expenses were $22.5 million for the second quarter of '24 compared to $13.8 million for the same period in 2023. Of the approximately $8.7 million increase in R&D expenses, $6.6 million, primarily related to activities supporting the Victoria one Phase 3 trials and the initiation of the Phase 1b 2 prostate trial and $2.1 million was related to increased employee and consulting expenses. General and administrative expenses were $1.8 million for the second quarter of '24 compared to $1.3 million for the second quarter of '23.

2024 年第二季的研發費用為 2,250 萬美元，而 2023 年同期為 1,380 萬美元。研發費用增加約 870 萬美元，其中 660 萬美元主要與支持 Victoria one 第 3 期試驗和啟動 1b 2 期前列腺試驗的活動有關，210 萬美元與員工和諮詢費用的增加有關。2024 年第二季的一般和管理費用為 180 萬美元，而 2023 年第二季的一般和管理費用為 130 萬美元。

Employee and consulting related expenses accounted for $0.3 million of the increase, professional fees and other administrative expenses accounted for the remaining increase of approximately $0.2 million. Net cash used in operating activities for the second quarter of '24 was $18.1 million compared to $9.7 million for the second quarter of '23. We ended the quarter with approximately $283.1 million in cash, cash equivalents and short-term investments compared to $180.6 million at December 31, 2023. The increase of approximately $102 million in cash and cash equivalents and short-term investments was the result of several financing activities that occurred in the first half of 2024 and yielded net proceeds of $137.5 million.

員工和諮詢相關費用佔成長的 30 萬美元，專業費用和其他管理費用佔剩餘成長的約 20 萬美元。2024 年第二季經營活動使用的現金淨額為 1,810 萬美元，而 2023 年第二季為 970 萬美元。截至本季末，我們的現金、現金等價物和短期投資約為 2.831 億美元，而截至 2023 年 12 月 31 日為 1.806 億美元。現金及現金等價物和短期投資增加約 1.02 億美元，是 2024 年上半年發生的多項融資活動的結果，產生的淨收益為 1.375 億美元。

We closed on two financing activities in May, resulting in gross proceeds of $122 million and net proceeds of $115.5 million. First, activity was an equity financing resulting in $60 million of gross proceeds with net proceeds of $56.3 million. Second, activity was a debt offering resulting in gross proceeds of $61.7 million with net proceeds of $59.2 million additional financing activities in the first half of the year resulted from warrant exercises of $14.2 million, accessing our at-the-market offering of $7.3 million and stock option exercises. Employee stock purchases of $0.5 million to $137.5 million was offset by year to date operating cash used of $35.1 million. I will now hand the call back to Brian.

我們 5 月完成了兩項融資活動，總收益為 1.22 億美元，淨收益為 1.155 億美元。首先，活動為股權融資，總收益為 6,000 萬美元，淨收益為 5,630 萬美元。其次，債務發行活動產生的總收益為 6,170 萬美元，淨收益為 5,920 萬美元，上半年的額外融資活動來自 1,420 萬美元的認股權證行使，我們的市場發行額為 730 萬美元，股票選擇權行使。員工股票購買額為 50 萬至 1.375 億美元，被年初至今使用的 3,510 萬美元營運現金所抵銷。我現在將把電話轉回給布萊恩。

Thank you, Vicky. Operator, could you please open the call for questions.

謝謝你，維姬。接線員，可以打開電話提問嗎？

Thank you. (Operator Instructions) Maury Raycroft, Jefferies.

謝謝。（操作員說明）Maury Raycroft，Jefferies。

Hi. Thanks for taking my question. I'm just checking on the enrollment. I appreciate that the time line is moving a little bit based on the shift in proportion of wild-type and mutant populations. Is it possible that wild-type and mutant readouts could happen at the same time? Or are you confident that the wild type and mutant readouts will be staggered? And secondly, is it fair to assume you'll do another update on enrollment in fourth quarter and provide more specifics on the plan for the readout at that point.

你好。感謝您提出我的問題。我只是查一下報名狀況。我很欣賞，根據野生型和突變體族群比例的變化，時間線發生了一些變化。野生型和突變型讀數是否有可能同時發生？或者您有信心野生型和突變體讀數會交錯嗎？其次，假設您將在第四季度再次更新註冊情況，並提供有關當時讀出計劃的更多細節，是否公平？

Yeah. Thanks, Maurice. And thanks for your question. As far as the timing of announcement of results for mutated were maintaining our guidance that we would expect to have those results available sometime in the first half. We're rolling the same number of patients in each cohort of the study is the wild-type versus mutant and 40% of the patients are mutated.

是的。謝謝，莫里斯。謝謝你的提問。就突變結果公佈的時間而言，我們維持了我們的指導，我們預計將在上半年的某個時候公佈這些結果。我們在每個研究群組中滾動了相同數量的野生型患者與突變型患者，其中 40% 的患者發生突變。

So that enrollment period will take longer to complete, albeit a little bit sooner than we originally planned because of the higher proportion of mutated patients, but we're not changing our guidance at this time. And as far as updating enrollment, we'll continue to update the guidance as we have every quarter on when we expect to report top line results.

因此，由於突變患者的比例較高，登記期將需要更長的時間才能完成，儘管比我們最初計劃的要早一些，但我們目前不會改變我們的指導。至於更新註冊情況，我們將繼續更新每季的指南，以了解我們預計何時報告頂線結果。

Okay, makes sense. And then for Victoria two in the frontline setting, can you talk more about the safety run-in with the 12 to 36 patients. Why is there a range of patients that you could enroll and down? Are you sensing any variations with what dosing strategy and how long we have to treat these patients?

好吧，有道理。然後，對於前線環境中的維多利亞二號，您能多談談與 12 至 36 名患者的安全磨合嗎？為什麼您可以招募和拒絕一系列患者？您是否感覺到劑量策略以及我們必須治療這些患者的時間有任何變化？

I'll give you an initial high-level summary and then Igor could maybe fill in the blanks. Essentially, the study is designed to evaluate if needed various dose levels of gedatolisib defined the Phase 3 dose of it. We don't need to reduce the dose of gedatolisib in the first cohort of patients that we're evaluating and we'll be able to proceed with the data from that group of 12 patients.

我會給你一個初步的高級總結，然後伊戈爾也許可以填補空白。本質上，該研究旨在評估是否需要不同劑量等級的 gedatolisib 定義的 3 期劑量。我們不需要減少我們正在評估的第一組患者的 gedatolisib 劑量，我們將能夠繼續使用該組 12 名患者的數據。

And then subsequently, if we find that we need to dose reduce data, we would enroll another 12 patients and we'll do the same thing again, if we had to enroll another 12 patients. So essentially, you're depending on what the results and the outcome of that of each cohort or one cohort will or may or may not lead you to enroll additional patients as far as the thresholds. I mean, it's a standard safety run-in design. Igor maybe you could provide a little bit more color on that question.

隨後，如果我們發現需要減少數據劑量，我們將再招募 12 名患者，如果我們必須再招募 12 名患者，我們將再次做同樣的事情。因此，從本質上講，您取決於每個隊列或一個隊列的結果和結果將或可能或可能不會導致您在閾值範圍內招募更多患者。我的意思是，這是標準的安全磨合設計。伊戈爾也許你可以就這個問題提供更多的資訊。

Thank you, Brian. And as Brian pointed out, it's a very straightforward safety run-in. Three dose level will be tested 12 subjects per each dose level and DLT will be assessed after one cycle of treatment is completed. It's a very safe and straightforward design that has been discussed with the regulators and agreed upon. And to Brian's point, the decision about initiation of a randomized Phase 3 study could be done as early as completion of initial cohort 12 subject.

謝謝你，布萊恩。正如布萊恩所指出的，這是一次非常簡單​​的安全磨合。將測試三個劑量水平，每個劑量水平有 12 名受試者，並將在一個治療週期完成後評估 DLT。這是一種非常安全且簡單的設計，已經與監管機構討論並達成一致。Brian 認為，啟動隨機 3 期研究的決定最早可以在初始第 12 組受試者完成後做出。

Got it. Okay. Thanks for taking my questions.

知道了。好的。感謝您回答我的問題。

You're welcome.

不客氣。

Tara Bancroft, TD Cowan.

塔拉·班克羅夫特，TD·考恩。

Hi, good afternoon. I was hoping you could tell us exactly what you're seeing now for the percentage of the split of wild-type versus mutant that you think you're observing now versus what your previous expectations were? And also just a point of clarification by target enrollment, you mean completion, right?

嗨，下午好。我希望你能準確地告訴我們你現在看到的野生型與突變型的分裂百分比，你認為你現在觀察到的與你之前的期望是什麼？另外，透過目標招生來澄清一點，你的意思是完成，對吧？

Right. Right. There's always variation. You may have patients in screening at the end of a period and enroll additional patients just because you can't not enroll patients that you've potentially already approved screening once you hit that target, but but completed, enrollment is correct. So we were at 65% at the end of '23 and so over the course of '23, you'd see fluctuations month to month, which is kind of expected fluctuations from normal.

正確的。正確的。總是有變化。您可能在一段時間結束時讓患者接受篩檢，並招募更多患者，只是因為一旦您達到該目標，您就不能不招募那些您可能已經批准篩檢的患者，但完成後，招募是正確的。因此，我們在 23 年末處於 65%，因此在 23 年期間，您會看到逐月波動，這是正常情況下的預期波動。

So you again, we were cautious in interpreting variation, but because we ended the year at the target number we had set in May '22. Now it's now 18 months prior. We thought that that estimate was solid and we would continue. And once we hit 80% enrollment, which we did recently the wild-type cohort and we were at 60%, we just decided that we should update our forecast for the current ratio of cumulative ratio, which is 60%.

再說一次，我們在解釋變化時持謹慎態度，但因為我們以 22 年 5 月設定的目標數字結束了這一年。現在已經是 18 個月前了。我們認為這個估計是可靠的，我們將繼續下去。一旦我們的入學率達到 80%（我們最近對野生型隊列進行了測試，我們的入學率達到了 60%），我們就決定應該更新對當前累積比率的預測，即 60%。

Okay. Great. And then so I guess late Q4 for potentially meeting the event time line that would potentially fit into the San Antonio conference time line. Is this still maybe what you're primarily hoping for? I know that in the abstract deadline, it passed early too early to mid July and so to do that? Did you submit an abstract or plan on presenting now?

好的。偉大的。然後我猜想第四季末可能會滿足聖安東尼奧會議時間線的活動時間線。這仍然是您主要希望的嗎？我知道在抽象的截止日期中，它過早地過早到了七月中旬，所以要這樣做嗎？您現在提交了摘要或計劃嗎？

So we haven't yeah -- we are going to until we get have an announcement to make about the data. We are really going to go into details about what venue will be reporting that data, and it's going to be very situational depending on the timing and relative to the next most relevant meeting. And so once the data is available, we'll report the top line as soon as we have it. And then we'll provide guidance on when we would go into it more detail at a meeting or go into some detail in the announcement press release.

所以我們還沒有——我們會這樣做，直到我們發布有關數據的公告。我們確實將詳細討論在哪個地點報告這些數據，這將根據具體情況而定，具體取決於時間表以及與下一次最相關的會議的相關性。因此，一旦獲得數據，我們將立即報告第一行。然後我們將提供指導，說明何時在會議上更詳細地討論該問題或在公告新聞稿中討論一些細節。

Okay, great. Thanks so much for taking the question.

好的，太好了。非常感謝您提出問題。

You're welcome.

不客氣。

(Operator Instructions) Brad Canino, Stifel.

（操作員說明）Brad Canino，Stifel。

Thanks for taking the question, Brian, I'm just wondering, can you talk about how the potential forthcoming approval of Roche's intervals that factors into your clinical and regulatory strategy for frontline, at least for the proportion who will have the mutations? And also how important is the ultimate label outcome around the metabolic parameter eligibility as you think about this? Thank you.

感謝您提出問題，布萊恩，我只是想知道，您能否談談羅氏的間隔即將獲得批准如何影響您的一線臨床和監管策略，至少對於將有突變的比例？當您考慮這一點時，圍繞代謝參數資格的最終標籤結果有多重要？謝謝。

And I'm not sure I understand your question regarding (inaudible) have as it relates to us or are you asking a question about how that might affect our first line study?

我不確定我是否理解您關於（聽不清楚）的問題，因為它與我們有關，或者您是否在問這可能會如何影響我們的第一線研究？

Yeah.

是的。

Brad, we don't think it will because they're only evaluated patients who have had the pictures a mutation. But B, we're didn't have we're not pre-diabetic or diabetic depending on the estimates. You can narrow that indication down to 50% of mutated population. So it really is not a drug that could fully treat the indicated population, which is women who have endocrine resistant disease.

布拉德，我們認為不會，因為他們只評估了照片發生突變的患者。但是 B，根據估計，我們沒有處於糖尿病前期或糖尿病狀態。您可以將該指示範圍縮小到突變群體的 50%。因此，它確實不是一種可以完全治療指定人群（即患有內分泌抵抗性疾病的女性）的藥物。

And as a result we're when we've reviewed this information and with the FDA in several settings. So we're confident in our design, and that's what we'll be evaluating. So we don't think that data will affect us. It provides, we think validation of what we're doing. They showed in that population that the pathways involved and inhibition of that pathway can induce a meaningful treatment benefit as far as what's on the label.

因此，我們在多個環境下與 FDA 審查了這些資訊。所以我們對我們的設計充滿信心，這就是我們將要評估的。所以我們認為數據不會影響我們。我們認為它驗證了我們正在做的事情。他們在該族群中表明，所涉及的途徑和對該途徑的抑制可以產生有意義的治療益處，正如標籤上所顯示的那樣。

The drug had been tested in patients without district limitations used in this most recent study, the Innova 120. I think the eligibility criteria were informed by the results in that study. And if I recall correctly from from data, they reported, I think in 2021 where patients may have had a cutoff of A1c similar to alpelisib. I think in one of the cohorts, they treated roughly 40% grade three hyperglycemia.

該藥物已在最新研究 Innova 120 中使用的不受地區限制的患者中進行了測試。我認為資格標準是根據該研究的結果確定的。他們報告說，如果我沒記錯數據的話，我認為在 2021 年，患者的 A1c 水平可能會出現類似於 alpelisib 的情況。我認為在其中一個隊列中，他們治療了大約 40% 的三級高血糖。

So I think the it would be unlikely that the label wouldn't address on the hypoglycemia risk and the fact that the drug has not been evaluated in patients who are pre-diabetic or diabetic, and to the extent doctors decide they want to ignore that based on the results at least were reported on a preliminary basis in this other studies that it would seem that the likelihood of inducing [Grade three] hyperglycemia would be pretty significant.

因此，我認為該標籤不太可能不涉及低血糖風險，而且該藥物尚未在糖尿病前期或糖尿病患者中進行評估，並且在某種程度上醫生決定忽略這一點至少根據其他研究中初步報告的結果，似乎誘發[三級]高血糖的可能性相當大。

So I think that drug is still a similar profile in some ways as uplifts and they just narrow their patient population as a way to avoid inducing high levels of [growth three] hypoglycemia.

因此，我認為該藥物在某些方面仍然與升壓藥物相似，它們只是縮小患者群體，以避免誘發高水平的[增長三]低血糖。

Appreciate it. Thank you.

欣賞它。謝謝。

You're welcome.

不客氣。

There are no further questions at this time. I would now like to turn the call over to Brian Sullivan, CEO of Celcuity for closing remarks.

目前沒有其他問題。我現在想將電話轉給 Celcuity 執行長 Brian Sullivan 致閉幕詞。

Thank you very much for attending our call. We appreciate your interest in our company, and I look forward to reporting to you next quarter. Good evening.

非常感謝您參加我們的電話會議。我們感謝您對我們公司的興趣，我期待下個季度向您報告。晚安.

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

女士們、先生們，今天的會議到此結束。非常感謝您的參與。您現在可以斷開連線。