Celcuity Inc (CELC) 2023 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to Celcuity fourth-quarter and year-end financial results conference call. (Operator Instructions) I would now like to turn the conference over to Maria Yonkoski with ICR Westwicke. Please go ahead.

女士們、先生們，下午好，歡迎參加 Celcuity 第四季和年終財務業績電話會議。（操作員指示）我現在想將會議轉交給 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 Celcuity's fourth-quarter and full-year 2023 financial results and business update. Earlier today, Celcuity released financial results for the fourth quarter and full year ending December 31, 2023. 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 2023 年第四季和全年財務表現和業務更新。今天早些時候，Celcuity 發布了截至 2023 年 12 月 31 日的第四季度和全年財務業績。新聞稿可以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.

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 SEC 提交的報告和文件中進行了概述。

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.

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影響涉及已知和未知的風險、不確定性以及其他可能導致實際結果或績效與預測有重大差異的因素。

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 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、預測未來結果並評估公司當前績效。管理階層認為，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. In 2023, we made significant progress advancing development of gedatolisib while strengthening our balance sheet and adding to our leadership team. Our Phase 3 VIKTORIA-1 trial remains on track to report top line data from the PIK3CA wild-type patient subgroup in the second half of this year and top line data for the PIK3CA mutated patient subgroup in the first half of 2025.

謝謝瑪麗亞，大家下午好。2023 年，我們在推進 gedatolisib 的開發方面取得了重大進展，同時加強了我們的資產負債表並擴大了我們的領導團隊。我們的 3 期 VIKTORIA-1 試驗仍在按計劃於今年下半年報告 PIK3CA 野生型患者亞組的頂線數據，並於 2025 年上半年報告 PIK3CA 突變患者亞組的頂線數據。

We were also excited to begin development of gedatolisib for patients with metastatic castration-resistant prostate cancer this past year. Enrollment has begun in our Phase 1b/2 trial evaluating gedatolisib in combination with darolutamide, and we look forward to sharing preliminary data from this trial in the first half of 2025.

我們也很高興去年開始為轉移性去勢抵抗性前列腺癌患者開發 gedatolisib。我們的 1b/2 期試驗已開始入組，評估 gedatolisib 與 darolutamide 的組合，我們期待在 2025 年上半年分享該試驗的初步數據。

Our VIKTORIA-1 Phase 3 clinical trial is designed to evaluate gedatolisib in combination with fulvestrant with and without palbociclib in patients with advanced hormone receptor positive, HER2-negative breast cancer whose disease has progressed after treatment with a CDK4/6 inhibitor.

我們的VIKTORIA-1 3 期臨床試驗旨在評估gedatolisib 合併氟維司群聯合或不合併哌柏西利治療晚期荷爾蒙受體陽性、HER2 陰性乳癌患者，這些患者在接受CDK4/6 抑制劑治療後病情出現進展。

We're seeking to improve outcomes for this patient population, which today receives only limited benefit from current second-line standard of care therapies. We estimate that this initial potential target population represents over 100,000 breast cancer patients globally on an annual basis.

我們正在尋求改善這群患者的治療結果，目前該患者群體僅從目前的二線標準護理治療中獲得有限的益處。我們估計，這個最初的潛在目標族群代表全球每年超過 10 萬名乳癌患者。

Current standard of care for these patients includes endocrine therapies such as fulvestrant and regimens that combines fulvestrant with an mTOR specific or PI3K alpha-specific targeted therapy. These therapies only offer modest progression-free survival periods. And in the case of the approved PI3K alpha inhibitor, a very challenging safety profile.

目前這些患者的護理標準包括氟維司群等內分泌治療以及氟維司群與 mTOR 特異性或 PI3K α 特異性標靶治療相結合的治療方案。這些療法僅提供適度的無惡化存活期。對於已核准的 PI3K α 抑制劑來說，安全性非常具有挑戰性。

The significant unmet need for these breast cancer patients has led to development and subsequent investigation of a significant number of new therapies, an oral SERD for patients with an ESR1 mutation, an AKT inhibitor for patients with a PIK3CA or AKT mutation was recently approved.

這些乳癌患者的顯著未滿足需求導致了大量新療法的開發和後續研究，最近批准了針對 ESR1 突變患者的口服 SERD、針對 PIK3CA 或 AKT 突變患者的 AKT 抑制劑。

Median progression-free survival, or PFS, for these two new therapies range from 3.8 to 5.5 months, respectively, in the same patient population in our Phase 3 trial is enrolling. While the availability of new drug alternatives for patients is always good news, based on the results reported for these drugs, the unmet need for these patients will still remain.

在我們正在招募的 3 期試驗的相同患者群體中，這兩種新療法的中位無惡化存活期 (PFS) 分別為 3.8 至 5.5 個月。雖然為患者提供新的藥物替代品始終是個好消息，但根據這些藥物報告的結果，這些患者的未滿足的需求仍然存在。

To further elucidate the different therapeutic effects of gedatolisib versus other PI3K, AKT, mTOR, or PAM inhibitors, we performed a series of non-clinical studies using breast cancer cell lines. We presented the results of these studies during a poster session at the 2023 San Antonio Breast Cancer Symposium. In a panel of 28 breast cancer cell lines, gedatolisib was found to be more cytotoxic and at least 300-fold more potent on average compared to the single node PAM inhibitors.

為了進一步闡明 gedatolisib 與其他 PI3K、AKT、mTOR 或 PAM 抑制劑的不同治療效果，我們使用乳癌細胞系進行了一系列非臨床研究。我們在 2023 年聖安東尼奧乳癌研討會的海報會議上展示了這些研究的結果。在一組 28 種乳癌細胞系中，發現 gedatolisib 的細胞毒性更強，與單節點 PAM 抑制劑相比，平均效力至少高 300 倍。

Mechanistically, gedatolisib decreased cell survival, DNA replication, protein synthesis, glucose consumption, lactate production, and oxygen consumption, more effectively than the other PAM inhibitors. In vivo studies confirmed that PAM PI3K/mTOR inhibition by gedatolisib reduced tumor cell growth more effectively than single node inhibitors in breast cancer patient-derived xenograft models with and without PAM pathway mutations.

從機制上講，gedatolisib 比其他 PAM 抑制劑更有效地降低細胞存活、DNA 複製、蛋白質合成、葡萄糖消耗、乳酸產生和氧氣消耗。體內研究證實，在有或沒有 PAM 途徑突變的乳癌患者來源的異種移植模型中，gedatolisib 抑制 PAM PI3K/mTOR 比單節點抑制劑更有效地減少腫瘤細胞生長。

We believe gedatolisib highly differentiated mechanism of action as an equipotent PAM PI3K/mTOR inhibitor is uniquely suited to most effectively address this unmet need, especially since gedatolisib has demonstrated activity independent of the PIK3CA or ESR1 mutational status of a patient's tumor.

我們相信gedatolisib 作為等價PAM PI3K/mTOR 抑制劑的高度差異化作用機制特別適合最有效地解決這一未滿足的需求，特別是因為gedatolisib 已證明其活性獨立於患者腫瘤的PIK3CA 或ESR1 突變狀態。

The results from our Phase 1b study in patients receiving the Phase 3 dosing schedule for gedatolisib in combination with palbociclib and fulvestrant was very promising. Median PFS was 12.9 months, and the objective response rate was 63%, both of which compares very favorably to published data for current standard of care regimens.

我們對接受 gedatolisib 合併帕博西尼和氟維司群 3 期給藥方案的患者進行 1b 期研究，結果非常有希望。中位無惡化存活期 (PFS) 為 12.9 個月，客觀緩解率為 63%，這兩者都與目前標準護理方案的已發表數據相比非常有利。

Another important goal for us in 2023 was to begin development of gedatolisib in a new tumor type. In the fourth quarter, we initiated a Phase 1b/2 clinical trial to evaluate gedatolisib in combination with darolutamide, which is a potent androgen receptor signaling inhibitor, in patients with metastatic, castration-resistant prostate cancer. We enrolled our first patient in the study in February, and we expect to report preliminary data in the first half of 2025.

2023 年我們的另一個重要目標是開始開發用於新腫瘤類型的 gedatolisib。第四季度，我們啟動了一項 1b/2 期臨床試驗，以評估 gedatolisib 與 darolutamide 聯合治療轉移性去勢抵抗性前列腺癌患者的效果，darolutamide 是一種有效的雄激素受體信號抑製劑。我們在 2 月招募了第一位患者參與研究，預計在 2025 年上半年報告初步數據。

Treatment options for these patients are limited and there's an urgent need for new drugs to treat them. Numerous preclinical studies have demonstrated interaction between the androgen receptor and PAM pathways, suggesting that combining a PAM inhibitor with an androgen receptor inhibitor may induce a synergistic antitumor effect in patients with prostate cancer.

這些患者的治療選擇有限，迫切需要新藥來治療他們。大量臨床前研究已證明雄激素受體和 PAM 路徑之間的相互作用，表明 PAM 抑制劑與雄激素受體抑制劑聯合使用可能會在前列腺癌患者中誘導協同抗腫瘤作用。

There's also compelling clinical evidence with an earlier generation PAM inhibitor providing a proof of concept of our hypothesis that combining gedatolisib with an androgen receptor inhibitor may be efficacious.

早期 PAM 抑制劑也有令人信服的臨床證據，為我們的假設提供了概念證明，即 gedatolisib 與雄激素受體抑制劑聯合使用可能有效。

And finally, as we get closer to having data for the PIK3CA wild-type patients in our Phase 3 breast cancer study, we need to begin laying the commercial and marketing groundwork necessary to bring gedatolisib to the clinic. To head up our commercialization efforts, Eldon Mayer joined our management team as our Chief Commercial Officer in February.

最後，隨著我們在 3 期乳癌研究中越來越接近獲得 PIK3CA 野生型患者的數據，我們需要開始奠定將 gedatolisib 推向臨床所需的商業和行銷基礎。為了領導我們的商業化工作，埃爾登·梅耶爾 (Eldon Mayer) 於二月加入我們的管理團隊，擔任首席商務官。

Eldon has over 30 years of biopharma commercial experience in companies ranging from early-stage biotechs to full-scale pharmaceutical companies across many therapeutic areas, including oncology. Eldon is an exceptional leader with a proven track record of building commercial organizations from the ground up to support the launch of a biotech company's first drug.

Eldon 擁有 30 多年的生物製藥商業經驗，其服務範圍從早期生物技術公司到大型製藥公司，涉及許多治療領域，包括腫瘤學。埃爾登是一位傑出的領導者，在從頭開始建立商業組織以支持生物技術公司第一種藥物的推出方面擁有良好的記錄。

And with that, I'll turn the call over now to Vicky Hahne, our Chief Commercial Officer (sic - Chief Financial Officer); to review our financial results.

現在，我將把電話轉給我們的首席商務官（原文如此，財務長）Vicky Hahne；審查我們的財務業績。

Thank you, Brian, and good afternoon, everyone. I'll provide a brief overview of our financial results for the fourth quarter and full year '23, and I invite you to review our 10-K, which will be filed later today for a more detailed discussion. Our fourth quarter net loss was $18.8 million or $0.65 per share compared to $11.6 million net loss or $0.69 per share for the fourth quarter of '22.

謝謝你，布萊恩，大家下午好。我將簡要概述我們 23 年第四季和全年的財務業績，並邀請您查看我們的 10-K 報表，該報表將於今天晚些時候提交以進行更詳細的討論。我們第四季的淨虧損為 1,880 萬美元，即每股 0.65 美元，而 2022 年第四季的淨虧損為 1,160 萬美元，即每股 0.69 美元。

Net loss for the full year of 2023 was $63.8 million or $2.69 per share compared to $40.4 million net loss or $2.64 per share for the same period in 2022. Because these quarterly and full-year net losses include significant non-cash items, including stock-based compensation and non-cash interest, we also include in our press release non-GAAP adjusted net loss for the quarter and full year ending December 31, 2023.

2023 年全年淨虧損為 6,380 萬美元，即每股 2.69 美元，而 2022 年同期淨虧損為 4,040 萬美元，即每股 2.64 美元。由於這些季度和全年淨虧損包括重大非現金項目，包括基於股票的薪酬和非現金利息，因此我們還在新聞稿中納入了截至 12 月 31 日的季度和全年非 GAAP 調整後淨虧損， 2023 年。

Our non-GAAP adjusted net loss was $17.6 million or $0.61 per share for the fourth quarter of '23 compared to non-GAAP adjusted net loss of $10.3 million or $0.61 per share for the fourth quarter of '22. Non-GAAP adjusted net loss for the full year 2023 was $57.8 million or $2.44 per share compared to non-GAAP adjusted net loss of $35 million or $2.27 per share for the full year 2022.

2023 年第四季非 GAAP 調整後淨虧損為 1,760 萬美元，即每股 0.61 美元，而 22 年第四季非 GAAP 調整後淨虧損為 1,030 萬美元，即每股 0.61 美元。2023 年全年非 GAAP 調整後淨虧損為 5,780 萬美元，即每股 2.44 美元，而 2022 年全年非 GAAP 調整後淨虧損為 3,500 萬美元，即每股 2.27 美元。

Research and development expenses were $18.1 million for the fourth quarter of '23 compared to $10.6 million for the fourth quarter of '22. R&D expenses for the full year '23 were $60.6 million compared to $35.3 million for the prior year.

23 年第四季的研發費用為 1,810 萬美元，而 22 年第四季的研發費用為 1,060 萬美元。23 年全年的研發費用為 6,060 萬美元，而前一年為 3,530 萬美元。

Of the approximately $25.3 million increase in R&D expenses year over year, $22.9 million was related to activities supporting the VIKTORIA-1 Phase 3 trial and the initiation of the Phase 1b/2 clinical trial. The remaining $2.4 million increase in R&D expense is related to increased employee and consulting expenses.

研發費用年增約 2,530 萬美元，其中 2,290 萬美元與支持 VIKTORIA-1 3 期試驗和啟動 1b/2 期臨床試驗的活動有關。其餘 240 萬美元的研發費用增加與員工和諮詢費用的增加有關。

General and administrative expenses were $1.6 million for the fourth quarter of '23 compared to $1 million for the same period in '22. G&A expenses for the full year of '23 were $5.6 million compared to $4.1 million for the prior year.

2023 年第四季的一般和管理費用為 160 萬美元，而 22 年同期為 100 萬美元。2023 年全年的一般管理費用為 560 萬美元，而前一年為 410 萬美元。

Of the approximately $1.5 million increase in G&A expenses, $1.1 million was related to increased employee-related expenses and $0.4 million related to professional fees and other expenses associated with compliance-related activities that support financing and clinical operations.

在約 150 萬美元的一般管理費用增加中，110 萬美元與員工相關費用增加有關，40 萬美元與專業費用以及與支持融資和臨床運營的合規相關活動相關的其他費用有關。

Net cash used in operating activities for the fourth quarter of '23 was $18.5 million compared to $9.5 million for the fourth quarter of '22. This was a result of non-GAAP adjusted net loss of $17.6 million, plus approximately $900,000 of working capital changes.

23 年第四季經營活動使用的現金淨額為 1,850 萬美元，而 22 年第四季為 950 萬美元。這是由於非 GAAP 調整後淨虧損 1,760 萬美元，加上約 90 萬美元的營運資本變動所致。

Net cash used in operating activities for the full year '23 was $53.8 million compared to $36 million for the full year '22. This was a result of non-GAAP adjusted net loss of approximately $57.8 million, offset by working capital changes of approximately $3.9 million.

'23 全年營業活動使用的現金淨額為 5,380 萬美元，而 '22 全年為 3,600 萬美元。這是由於非 GAAP 調整後淨虧損約 5,780 萬美元，被約 390 萬美元的營運資本變動所抵銷。

We ended the year with approximately $180.6 million of cash, cash equivalents, and short-term investments compared to $168.6 million on December 31, 2022. The increase in cash year over year is the result of two financing activities that occurred in the fourth quarter of '23 and yielded gross proceeds of $65 million, which was offset by cash used in operating activities of $53.8 million in '23.

截至年底，我們的現金、現金等價物和短期投資約為 1.806 億美元，而 2022 年 12 月 31 日為 1.686 億美元。現金年增是由於 2023 年第四季發生的兩項融資活動產生的總收益為 6,500 萬美元，但被 2023 年經營活動使用的現金 5,380 萬美元所抵銷。

The first financing activity included a private placement offering through a prefunded warrant arrangement, which generated $50 million in gross proceeds. The second financing activity generated gross proceeds of $15 million by accessing our at-the-market offering. We expect cash, cash equivalents and investments, and available funds under our debt facility to provide adequate capital to fund current operational activities into the first half of 2026.

第一項融資活動包括透過預融資認股權證安排進行私募發行，產生了 5,000 萬美元的總收益。第二次融資活動透過我們的市場發行產生了 1500 萬美元的總收益。我們預計現金、現金等價物和投資以及債務融資下的可用資金將為 2026 年上半年的當前營運活動提供充足的資金。

I will now hand the call back to Brian.

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，維琪。接線員，可以打開電話提問嗎？

(Operator Instructions) Tara Bancroft, TD Cowen.

（操作員說明）Tara Bancroft，TD Cowen。

Hi. Good afternoon. I was wondering if you could tell us more about the overlap of ESR1 and PIK3A mutations. And if the FDA still considers Arm C or fulvestrant alone, the best comparator for Arms A and B, now a year into the launch of elacestrant. So I'm just basically trying to gauge level of confidence in Arm B versus C endpoint or even the chances that you might go for an ESR1 wild-type labeling for that subset or what. Thanks.

你好。午安.我想知道您是否可以告訴我們更多有關 ESR1 和 PIK3A 突變重疊的資訊。如果 FDA 仍然單獨考慮 Arm C 或氟維司群，那麼 A 臂和 B 臂的最佳比較器現在已經推出一年了。因此，我基本上只是想衡量 Arm B 與 C 端點的置信度，甚至是您可能會對該子集或其他內容進行 ESR1 野生型標記的可能性。謝謝。

Thanks for the question, Tara. We have not seen any variation in outcomes for patients associated with ESR1 mutation, with the combination of therapy that we're evaluating in this study. And so we don't anticipate a challenge on that front.

謝謝你的提問，塔拉。對於我們在本研究中評估的聯合療法，我們尚未發現與 ESR1 突變相關的患者的結果有任何變化。因此，我們預計這方面不會遇到挑戰。

We closely collaborated with the FDA when we were developing the design of our study. We've reviewed the study with them on an ongoing basis through a series of type B meetings where we are collaborating with them and in close contact to review not only the clinical development but also work associated with what we hope is a future NDA.

當我們開發研究設計時，我們與 FDA 密切合作。我們透過一系列 B 型會議與他們一起持續審查該研究，在會議上我們與他們合作並密切聯繫，不僅審查臨床開發，還審查與我們希望未來的 NDA 相關的工作。

As far as changing the control, there's no discussion or consideration of that. Drug was recently approved capivasertib that used fulvestrant as a control just this past few months. And so we'll certainly have data available to us to report potential outcomes in patients according to their mutational status, but we don't anticipate, as I said earlier, to find any differences -- or clinically meaningful differences.

至於改變控制，沒有討論或考慮。最近幾個月，該藥物被批准為 capivasertib，該藥物使用氟維司群作為對照。因此，我們當然會有可用的數據來根據患者的突變狀態報告潛在的結果，但正如我之前所說，我們預計不會發現任何差異或有臨床意義的差異。

Great. Thanks. Have you said which HR you're powering to for the B versus the endpoint? You commented on that.

偉大的。謝謝。您是否說過您為 B 與終點提供哪一個 HR 動力？你對此發表了評論。

We haven't commented on that.

我們還沒有對此發表評論。

Okay.

好的。

But again, we're powering the study sufficiently to support regulatory approval.

但我們再次強調，我們正在為這項研究提供足夠的支持，以支持監管部門的批准。

Okay. Thanks so much.

好的。非常感謝。

Thank you.

謝謝。

Maury Raycroft, Jefferies.

莫里‧雷克羅夫特，傑弗里斯。

Hi. Thanks for taking my questions. It seems like the data timing is intact and on track. Is there anything else you're saying about enrollment rate? I think at one point, you mentioned you aim to enroll 50% of the wild-type patients by the end of the first quarter. Wondering if you've achieved that milestone. And is that something that you could announce for the wild-type cohort?

你好。感謝您回答我的問題。資料時序似乎完好無損且步入正軌。關於入學率，您還有什麼想說的嗎？我想您曾經提到您的目標是在第一季末招募 50% 的野生型患者。想知道您是否已經實現了這一里程碑。您可以為野生型隊列宣布這一點嗎？

That milestone is associated with one of the terms of our debt facility, and we did achieve that milestone during this quarter. And so we remain on track that is consistent with the guidance we provided about having data in the second half of this year.

這一里程碑與我們的債務融資條款之一相關，我們在本季確實實現了這一里程碑。因此，我們仍處於與我們提供的有關今年下半年數據的指導一致的軌道上。

Okay. Great. And for the Phase 3 readout, can you provide an estimate for how much follow-up you think you will have by the time of the data readout?

好的。偉大的。對於第三階段的讀出，您能否估計在資料讀出時您將有多少後續行動？

That's not a number that we'll disclose at this point. We anticipate obviously reporting the top line data and the data readout is -- will be triggered by achieving sufficient events and that factors in follow-up period necessary to get a fulsome mature set of data.

我們目前不會透露這個數字。我們預計顯然會報告頂線數據，並且數據讀出將透過實現足夠的事件以及獲得一組完整的成熟數據所需的後續時間因素來觸發。

Okay. Yeah, it makes sense. And lastly, another question on mutations. When you analyze the Phase 1b data, you reported similar efficacy in patients with or without PI3K mutations. But can you remind me if you looked at other mutations in the pathway, including AKT, mTOR, and PTEN loss. And for the Phase 3, have you had discussions with FDA on how you would evaluate patients with other non-PI3K mutations?

好的。是的，這是有道理的。最後，另一個關於突變的問題。當您分析 1b 期數據時，您報告了在有或沒有 PI3K 突變的患者中具有相似的療效。但您能否提醒我，您是否觀察過該路徑中的其他突變，包括 AKT、mTOR 和 PTEN 缺失。對於第 3 階段，您是否與 FDA 討論過如何評估其他非 PI3K 突變的患者？

We've done an analysis of patients with these other mutations, but the numbers are small. And so we didn't feel that reporting those results would be scientifically rigorous enough to really discuss, but we have evaluated them and based on at least our interpretation of the small sample sizes, we haven't seen anything that is concerning or were inconsistent with the comparable results we saw with wild-type PIK3CA versus mutated PIK3CA.

我們對患有這些其他突變的患者進行了分析，但數量很少。因此，我們認為報告這些結果在科學上不夠嚴格，無法真正進行討論，但我們已經對其進行了評估，並且至少基於我們對小樣本量的解釋，我們沒有看到任何令人擔憂或不一致的內容我們在野生型PIK3CA 與突變型PIK3CA 中看到的結果相當。

And as far as other mutations and how that might interact with the FDA, essentially when you design a clinical trial, Phase 3 clinical trial, you have a very detailed protocol with statistical analysis that's well prescribed. And you essentially interact with the agency quite a bit, or at least we did, to get their feedback and to ensure that our assumptions and the statistical analysis plan would be satisfactory, subject to review to support an NDA, and nothing on that front has changed.

至於其他突變以及它們如何與 FDA 相互作用，基本上，當您設計臨床試驗（第 3 期臨床試驗）時，您有一個非常詳細的方案，其中包含詳細規定的統計分析。你基本上與該機構進行了相當多的互動，或者至少我們這樣做了，以獲得他們的反饋並確保我們的假設和統計分析計劃令人滿意，並接受審查以支持NDA，而這方面沒有任何進展。改變了。

And the primary biomarker that we're using is primarily to assign patients to a study that's focusing on PIK3CA mutated patients and the study that's associated with or randomizing patients who lack PIK3CA mutation. And we're using what the PIK3CA mutations that have supported approval of PIK3CA alpha inhibitor. So again, we're relying on an approved PIK3CA test and have confidence that, that test will support subject to review by the FDA and NDA submission.

我們使用的主要生物標記主要是將患者分配到專注於 PIK3CA 突變患者的研究以及與缺乏 PIK3CA 突變的患者相關或隨機分組的研究。我們正在使用支持 PIK3CA α 抑制劑批准的 PIK3CA 突變。因此，我們再次依賴已批准的 PIK3CA 測試，並相信該測試將支持 FDA 審查和 NDA 提交。

Got it. That's helpful. Thanks for taking my question.

知道了。這很有幫助。感謝您提出我的問題。

You're welcome.

不客氣。

Gil Blum, Needham.

吉爾布魯姆，李約瑟。

Gil, I think that was for you.

吉爾，我想那是給你的。

I think my name was butchered pretty severely there. Sorry. So okay, a quick question on the prostate cancer. So just to understand, I mean you're now with a first patient little far from this. What kind of signs of early efficacy would the company be looking for in that study? I mean having responses here or PSA activity.

我認為我的名字在那裡被嚴重屠殺了。對不起。好吧，這是一個關於前列腺癌的快速問題。所以為了理解，我的意思是你現在遇到的第一個病人離這裡還很遠。公司將在該研究中尋找什麼樣的早期療效跡象？我的意思是在這裡做出回應或公益廣告活動。

Sure. While the study is a primary endpoint is PFS, the PFS rate at -- after six months of treatment and then there are a number of secondary endpoints, which include PFS at nine and 12 months as well as evaluating PSA change. We think the most important milestone or rather end point is related to radiographic progressive-free survival since that's the regulatory endpoint that we would use for evaluation in a registrational study.

當然。雖然研究的主要終點是 PFS，但治療 6 個月後的 PFS 率，還有許多次要終點，其中包括 9 個月和 12 個月的 PFS 以及評估 PSA 變化。我們認為最重要的里程碑或更確切地說終點與放射學無惡化存活期相關，因為這是我們在註冊研究中用於評估的監管終點。

And so we will be I think consistently reporting that number. And as that number matures with the number of patients who've achieved that -- whether six-month milestone, nine months or 12-month milestone, that will conduct -- or that will be a rhythm that we'll have for reporting data.

因此，我認為我們將持續報告這個數字。隨著這個數字隨著實現這一目標的患者數量的增加而成熟——無論是六個月里程碑、九個月還是 12 個月里程碑，這都會進行——或者這將成為我們報告數據的節奏。

That's very helpful. Maybe another detail on the enrollment here. So it sounds like the wild-type cohort is enrolling well. Any thoughts on the mutant cohort? Thank you.

這非常有幫助。也許有關註冊的另一個細節在這裡。所以聽起來野生型隊列的招募情況很好。對變種人群體有什麼想法嗎？謝謝。

They enroll in tandem. Essentially, we're enrolling and screening patients who have had prior CDK4/6. If they meet criteria, screening criteria that includes assessment of their PIK3CA status, they then get randomized. So essentially, the enrollment of wild-type and mutant are occurring concurrently. And so if our wild type is on track, then our mutant population is on track, just because of the way the trial enrollment is designed.

他們同時報名。本質上，我們正​​在招募和篩選先前接受過 CDK4/6 的患者。如果他們符合篩選標準（包括評估其 PIK3CA 狀態），那麼他們就會被隨機分配。因此本質上，野生型和突變體的招募是同時發生的。因此，如果我們的野生型步入正軌，那麼我們的突變體群體也步入正軌，這只是因為試驗招募的設計方式。

Thank you. That's very helpful clarification. Thanks for taking our questions.

謝謝。這是非常有幫助的澄清。感謝您回答我們的問題。

You're welcome.

不客氣。

Brad Canino, Stifel.

布拉德·卡尼諾，斯蒂菲爾。

Hi. Good afternoon. I want to ask, is there any way you've been able to track adherence with the prophylactic mouthwash for stomatitis mitigation in VIKTORIA-1?

你好。午安.我想問，有什麼方法可以追蹤 VIKTORIA-1 中預防性漱口水緩解口腔炎的依從性嗎？

Well, we do. One of the primary advantages we have in managing that and monitoring compliance is when the patients come in for their three week on one week off infusion. And so the treating physicians or the associated nurses are evaluating, including compliance with that prophylactic and standard questionnaire. And so we have a high degree of confidence based on that, that if patients aren't compliant, we'll find out, but also we reinforce the value of that prophylaxis.

嗯，我們願意。我們在管理這一點和監測依從性方面的主要優勢之一是，患者在停輸一週後三週內就診。因此，治療醫生或相關護理師正在進行評估，包括遵守預防性和標準問卷的情況。因此，我們對此充滿信心，如果患者不配合，我們會發現，而且我們也會加強這種預防的價值。

And just as a reminder, that prophylaxis is only used and prescribed for the first two cycles of treatment. The data is fairly clear that for patients who may be prone to development of mucositis, it's in almost all cases, likely to occur in the first two cycles of treatment. And so that if you are able to provide that prophylaxis for that first two cycles that the manifestation of mucositis is much, much lower after that period. So it's not a requirement then for patients to remain on that prophylaxis beyond those first two cycles.

提醒一下，預防措施僅在前兩個治療週期中使用和規定。數據相當清楚，對於可能容易發生黏膜炎的患者，幾乎在所有情況下，都可能發生在治療的前兩個週期。因此，如果您能夠在前兩個週期中提供預防措施，那麼該週期之後粘膜炎的表現就會大大降低。因此，在前兩個週期之後，患者不需要繼續進行預防治療。

Okay. And then I'll try to ask another enrollment question maybe in a slightly different way because I think the continued reiteration of top line guidance for VIKTORIA-1 is going to be important for investors. I think based on the enrollment pace you see, is there anything you can share about a time point that could be passed this year where you would reach that sufficient enrollment to fully secure the second half guidance for the wild type using the rate assumptions you've got for events?

好的。然後我會嘗試以稍微不同的方式提出另一個註冊問題，因為我認為繼續重申 VIKTORIA-1 的頂線指導對投資者來說非常重要。我認為，根據您看到的註冊速度，您是否可以分享關於今年可以通過的時間點，在該時間點您將達到足夠的註冊量，以使用您的比率假設完全確保野生型的下半年指導有活動嗎？

I think, again, we provided the guidance for the second half of this year. Obviously, as we get closer to that, we can get more granular. And I think we'll update that each quarter. And so the closer we get, I think the more descriptive we can be. But so far, again, we monitor enrollment. We're monitoring the event rate. And you make certain assumptions about the event rate, and we're tracking to what our assumptions are so far.

我認為，我們再次提供了今年下半年的指導。顯然，隨著我們越來越接近這個目標，我們可以變得更細化。我想我們每季都會更新一次。因此，我們越接近，我認為我們就越能描述。但到目前為止，我們再次監控入學情況。我們正在監控事件發生率。您對事件發生率做出某些假設，我們正在追蹤迄今為止的假設。

Thanks for the question.

謝謝你的提問。

You're welcome.

不客氣。

Swayampakula Ramakanth, H.C. Wainwright.

拉瑪坎特 (Swayampakula Ramakanth)，H.C.溫賴特。

Thank you. This is RK from H.C. Wainwright. Good afternoon, Brian.

謝謝。我是 H.C. 的 RK。溫賴特。下午好，布萊恩。

Good afternoon.

午安.

Quick question. Most of my questions have been answered. So when the data -- when you're ready to publish the data from the wild type in the second half, would that -- I'm just trying to figure out how would you disseminate that information? Would that be a medical meeting or do a press release and then follow up with a medical meeting at the appropriate time?

快問。我的大部分問題都得到了解答。因此，當數據——當你準備好在下半年發布來自野生型的數據時——我只是想弄清楚你將如何傳播這些訊息？是召開醫療會議還是發布新聞稿，然後在適當的時間召開醫療會議？

It's somewhat situational depending on the timing of meetings and when the data will be cleaned and able to be released publicly. And so when the event threshold is triggered, we'll understand whether -- what the gross -- not gross but what the data is telling us and we would finish up data cleaning at that point.

這在一定程度上取決於會議的時間以及數據何時被清理並能夠公開發布。因此，當事件閾值被觸發時，我們將了解資料是否告訴我們什麼——到底是什麼——不嚴重，而是資料告訴我們什麼，我們將在那時完成資料清理。

Obviously, that's going on, on an ongoing basis. But it would be our expectation that we would announce the top line results, meaning whether or not we met statistical significance, whether this trial was positive and probably characterize how clinically relevant those results are.

顯然，這種情況正在持續發生。但我們期望我們能夠公佈最重要的結果，這意味著我們是否達到統計顯著性，這項試驗是否積極，並可能描述這些結果的臨床相關性。

But I think it's typical that you present these results of a Phase 3 study at a medical meeting. That is our -- would be our current desire. But again, depending on the timing of when the data is available, we may reconsider.

但我認為，在醫學會議上展示第三階段研究的這些結果是很典型的。這是我們目前的願望。但同樣，根據數據可用的時間，我們可能會重新考慮。

But we'll follow, I think, practice that's been used with other drugs. But I think it's fairly typical that if a major meeting isn't scheduled coincident with the availability of data that people will provide that top line and then wait until a medical meeting to provide the more fulsome description of the results.

但我認為，我們將遵循其他藥物的做法。但我認為，相當典型的是，如果一次重大會議沒有安排在數據可用的同時，人們就會提供最重要的信息，然後等到醫學會議提供對結果更全面的描述。

Thank you. Thanks for taking my question.

謝謝。感謝您提出我的問題。

You're welcome.

不客氣。

(Operator Instructions) Alex Nowak, Craig-Hallum Capital.

（操作員說明）Alex Nowak，Craig-Hallum Capital。

Hey. Great. Good afternoon, everyone. As we're getting close to the first VIKTORIA-1 readout here, you brought on a new Chief Commercial Officer, that's great. Just what are other additional investment in the commercial talent, commercial resources do you need to plan for here over this year?

嘿。偉大的。大家下午好。當我們即將在這裡發布第一個 VIKTORIA-1 讀數時，你們任命了一位新的首席商務官，這太棒了。今年您還需要在商業人才、商業資源上規劃哪些額外投資？

Sure. You start to build out the team underneath Eldon which I think typically includes a person who would head up your market access, a person who will head up your marketing, and a person who would head up commercial operations. And with that team, you can do the planning that's necessary to lay the groundwork for obviously a lot more significant efforts once the data reads out and you're really marching towards a specific date for launch.

當然。你開始在埃爾登的領導下建立團隊，我認為通常包括一個負責你的市場准入的人，一個負責你的營銷的人，以及一個負責商業運營的人。與該團隊一起，您可以製定必要的計劃，以便在數據讀出並且您確實正在朝著特定的發布日期邁進時，為明顯更重要的工作奠定基礎。

And so we factored that into the assumptions in our budget for this year. We've incorporated that in our forecast of cash requirements. And they're not extraordinary, they're appropriate relative to what needs to be done and when.

因此，我們將這一點納入今年預算的假設中。我們已將其納入現金需求預測。它們並不特殊，它們相對於需要做什麼和何時做來說是適當的。

Okay. Makes sense. And then can you remind us the IP position of geda within breast cancer? And then the potential to expand that length within breast or potentially other cancer indications?

好的。說得通。那麼能否提醒我們geda在乳癌領域的IP地位？那麼是否有可能在乳癌或其他潛在的癌症適應症中擴大該長度？

Right. So we have 11 different patents that have been approved for geda. We have several that are pending. The active pharmaceutical ingredient patent would provide an exclusivity period through December '34.

正確的。因此，我們有 11 項不同的專利已被批准用於 geda。我們有幾個待處理。活性藥物成分專利將提供截至 34 年 12 月的獨佔期。

But because geda is formulated and because the formulation actually is critical to being able to deliver the drug, administer the drug, we think that patent will be very relevant. And that patent would have an expiration date at December '39. And so we think we'll have an extended exclusive period that would potentially carry for more than 15 years post launch is -- that's our plan.

但由於 geda 是配製而成的，而且該配方實際上對於能夠輸送藥物、管理藥物至關重要，因此我們認為專利將非常重要。該專利將於 39 年 12 月到期。因此，我們認為我們將有一個延長的獨佔期，可能會在發布後持續超過 15 年——這就是我們的計劃。

Excellent. I appreciate the update. Thank you.

出色的。我很欣賞這個更新。謝謝。

You're welcome.

不客氣。

Thank you. There are no further questions at this time. Please proceed.

謝謝。目前沒有其他問題。請繼續。

Well, we appreciate your attendance on the call, and we look forward to updating you in the future.

好的，我們感謝您參加電話會議，並期待將來為您提供最新消息。

Thank you. Ladies and gentlemen, the conference has now ended. Thank you all for joining. You may all disconnect.

謝謝。女士們、先生們，會議現已結束。感謝大家的加入。你們都可以斷開連線。