Puma Biotechnology Inc (PBYI) 2024 Q3 法說會逐字稿

Thank you for joining us for today's conference. Our conference will be beginning shortly. Once again, thank you for joining us today and your conference will begin shortly. Thank you.

感謝您參加我們今天的會議。我們的會議即將開始。再次感謝您今天加入我們，您的會議即將開始。謝謝。

Good afternoon. My name is Rob, and I'll be your conference call operator today. (Operator Instructions). As a reminder, this call is being recorded.

午安.我叫羅布，今天我將擔任您的電話會議接線生。（操作員說明）。提醒一下，此通話正在錄音。

I would now like to turn the conference over to Mariann Ohanesian, Senior Director of Investor Relations for Puma Biotechnology. You may begin your conference.

現在我想將會議交給 Puma Biotechnology 投資者關係高級總監 Mariann Ohanesian。您可以開始您的會議了。

Thank you, Rob. Good afternoon, and welcome to Puma's conference call to discuss our financial results for third quarter of 2024. Joining me on the call today are Alan Auerbach, Chief Executive Officer, President and Chairman of the Board of Puma Biotechnology, Maximo Nougues, Chief Financial Officer, and Jeff Ludwig, Chief Commercial Officer.

謝謝你，羅布。下午好，歡迎參加 Puma 電話會議，討論我們 2024 年第三季的財務表現。今天與我一起參加電話會議的包括 Puma Biotechnology 執行長、總裁兼董事會主席 Alan Auerbach、財務長 Maximo Nougues 和首席商務官 Jeff Ludwig。

After market closed today, Puma issued a news release detailing the earnings results for the third quarter of 2024. That news release, the slides that Jeff will refer to, and a webcast of this call are accessible via the homepage and investor sections of our website at Pumabiotechnology.com. The webcast and presentation slides will be archived on our website and available for replay for the next 90 days.

今天收盤後，彪馬發布了一份新聞稿，詳細介紹了 2024 年第三季的獲利結果。新聞稿、傑夫將參考的幻燈片以及本次電話會議的網路廣播均可透過我們網站 Pumabiotechnology.com 的主頁和投資者部分存取。網路廣播和簡報投影片將存檔在我們的網站上，並可在接下來的 90 天內重播。

Today's conference call will include statements about Puma's future expectations, plans, and prospects that constitute forward-looking statements for purposes of federal security slides. Such statements are subject to risks and uncertainties, and actual events and results may differ from those expressed in these forward-looking statements.

今天的電話會議將包括有關彪馬未來期望、計劃和前景的聲明，這些聲明構成聯邦安全幻燈片中的前瞻性聲明。此類陳述存在風險和不確定性，實際事件和結果可能與這些前瞻性陳述中表達的有所不同。

For a full discussion of these risks and uncertainties, please review our periodic and current reports filed with the SEC from time-to-time, including our annual report on Form 10-K for the year ended December 31, 2023.

如需對這些風險和不確定性進行全面討論，請查看我們不時向 SEC 提交的定期報告和當前報告，包括我們截至 2023 年 12 月 31 日的年度 10-K 表格年度報告。

You are cautioned not to place undue reliance on these forward-looking statements, which would speak only as of the date of this live conference call, November 7, 2024. Puma undertakes no obligation to revise or update any forward-looking statement to reflect the events or circumstances after the date of this call, except as required by law.

請您注意不要過度依賴這些前瞻性陳述，這些陳述僅代表截至 2024 年 11 月 7 日現場電話會議之日的情況。除非法律要求，彪馬不承擔修改或更新任何前瞻性聲明以反映本次電話會議之後發生的事件或情況的義務。

During today's call, we may refer to certain non-GAAP financial measures that involve adjustments to our GAAP figures. We believe these non-GAAP metrics may be useful to investors as a supplement to, but not as substitutes for, our GAAP financial measures. Please refer to our third quarter 2024 news release for a reconciliation of our GAAP to non-GAAP results.

在今天的電話會議中，我們可能會提及某些涉及對我們的 GAAP 數據進行調整的非 GAAP 財務指標。我們相信，這些非公認會計原則指標可能對投資者有用，作為我們公認會計原則財務指標的補充，但不能替代。請參閱我們的 2024 年第三季新聞稿，以了解我們的 GAAP 與非 GAAP 業績的調整表。

I will now turn the call over to Alan.

我現在將把電話轉給艾倫。

Thank you, Mariann, and thank you all for joining our call today. Today, Puma reported total revenue for the third quarter of 2024 of $80.5 million. Total revenue includes product revenue net, which consists entirely of NERLYNX sales, as well as royalties from our sub-licensees.

謝謝瑪麗安，也謝謝大家今天加入我們的電話會議。今天，Puma 公佈 2024 年第三季總營收為 8,050 萬美元。總收入包括產品淨收入（完全由 NERLYNX 銷售額組成）以及來自我們的分授權人的特許權使用費。

Product revenue net was $56.1 million in the third quarter of 2024, which was an increase from both the $44.4 million reported in Q2, 2024, and the $51.6 million reported in Q3, 2023. Product revenue for the third quarter of 2024 was impacted by approximately $0.6 million of inventory increase at our specialty pharmacies and specialty distributors. Royalty revenue was $24.4 million in the third quarter of 2024, compared to $2.7 million in Q2, 2024, and $4.5 million in Q3, 2023.

2024 年第三季的產品淨收入為 5,610 萬美元，較 2024 年第二季的 4,440 萬美元和 2023 年第三季的 5,160 萬美元有所增加。2024 年第三季的產品收入受到我們的專業藥局和專業經銷商約 60 萬美元庫存增加的影響。2024 年第三季的版稅收入為 2,440 萬美元，而 2024 年第二季為 270 萬美元，2023 年第三季為 450 萬美元。

Royalty revenue in the latest quarter included the expected sales to China by our offshore partner, Pierre Fabre, as we noted in our August forecast of Q3, 2024 results. We reported 2,723 bottles of NERLYNX sold in the third quarter of 2024, an increase of 208 from the 2,515 bottles sold in Q2, 2024. In Q3, 2024, we estimate that inventory increased by about 37 bottles.

正如我們在 8 月對 2024 年第三季業績的預測中指出的那樣，最近一個季度的特許權使用費收入包括我們的離岸合作夥伴皮爾法伯 (Pierre Fabre) 對中國的預期銷售額。我們報告稱，2024 年第三季 NERLYNX 銷量為 2,723 瓶，比 2024 年第二季銷量 2,515 瓶增加了 208 瓶。2024年第三季度，我們預計庫存增加約37瓶。

In Q3, 2024, new prescriptions were up 3%, compared to Q2, 2024, and total prescriptions were essentially flat compared to Q2, 2024. Jeff will provide further details in his comments and slides. I will now provide a clinical review of the quarter, and then Jeff Ludwig will address our additional color on NERLYNX's commercial activities.

與 2024 年第二季相比，2024 年第三季的新處方數量增加了 3%，總處方數與 2024 年第二季基本持平。傑夫將在他的評論和幻燈片中提供更多詳細資訊。我現在將提供本季的臨床回顧，然後 Jeff Ludwig 將討論我們對 NERLYNX 商業活動的額外看法。

Maximo Nougues will then follow with highlights of the key components of our financial statements for the third quarter of 2024. As previously discussed, Puma has an ongoing Phase 2 study of our investigational drug, alisertib, to confirm the efficacy of alisertib monotherapy in patients with small cell lung cancer with biomarkers where the aurora kinase pathway plays a role.

Maximo Nougues 隨後將重點介紹我們 2024 年第三季財務報表的主要組成部分。如前所述，Puma 正在對我們的研究藥物 alisertib 進行 2 期研究，以確認 alisertib 單藥療法對具有極光激酶通路發揮作用的生物標誌物的小細胞肺癌患者的療效。

The goal is to correlate the efficacy in these biomarker subgroups in the ALISCA-Lung1 study to the efficacy that was previously seen in the biomarker subgroups from the randomized trial of Paclitaxel plus alisertib versus Paclitaxel plus placebo that was published in the Journal of Thoracic Oncology in 2020.

目標是將ALISCA-Lung1 研究中這些生物標記亞群的療效與先前在《胸腔腫瘤學雜誌》上發表的紫杉醇加alisertib 與紫杉醇加安慰劑隨機試驗的生物標誌物亞組中觀察到的療效相關聯。

If the efficacy and biomarker data are comparable from the two studies, the company believes it would represent a potential accelerated approval strategy and would engage FDA to discuss this further. As investors will remember, alisertib was previously tested as a monotherapy in patients with small cell lung cancer, and the results of this trial were published in Lancet Oncology in 2015. In this trial, Alisertib was administered as a monotherapy to patients with small cell lung cancer.

如果兩項研究的功效和生物標記數據具有可比性，該公司認為這將代表一種潛在的加速批准策略，並將與 FDA 進一步討論這一問題。投資者應該記得，alisertib 之前曾作為小細胞肺癌患者的單一療法進行過測試，該試驗的結果於 2015 年發表在《刺胳針腫瘤學》上。在這項試驗中，Alisertib 作為單一療法用於小細胞肺癌患者。

The safety results, from the trial, showed that 37% of the patients experienced grade 3/4 neutropenia, 7% experienced grade three-fouth drug-related febrile neutropenia, and 22% of the patients discontinued treatment due to adverse events. The efficacy results from an efficacy of valuable population of 48 patients showed that for the 36 chemotherapy-sensitive patients, the objective response rate was 19%, and the PFS was 2.6 months. And for the 12 chemotherapy-resistant or relapsed patients, the objective response rate was 25% with a PFS of 1.7 months.

此試驗的安全性結果顯示，37%的患者出現3/4級中性粒細胞減少症，7%的患者出現四分之三級藥物相關性發燒性嗜中性白血球減少症，22%的患者因不良事件而停止治療。48位有價值族群的療效結果顯示，36位化療敏感患者的客觀緩解率為19%，PFS為2.6個月。12 例化療抗藥性或復發患者的客觀緩解率為 25%，PFS 為 1.7 個月。

As investors will also remember, Alisertib was also previously tested in a randomized phase 2 trial of Paclitaxel plus Alisertib versus Paclitaxel plus placebo in patients with second-line small cell lung cancer, which was published in the Journal of Thoracic Oncology in 2020.

投資人還記得，Alisertib 先前還在二線小細胞肺癌患者中進行了紫杉醇加 Alisertib 與紫杉醇加安慰劑的隨機 2 期試驗，該試驗於 2020 年發表在《胸腔腫瘤學雜誌》上。

Alisertib was dosed at a different dose than in the monotherapy trial, with Alisertib being administered at 40 mg BID for three weeks on days one to three, eight to 10, and 15 to 17, plus Paclitaxel 60 mg intravenously on days one, eight, and 15, whereas the comparator arm received placebo plus Paclitaxel 80 mg per meter squared IV on days one, eight, and 15 in 28-day cycles. The trial also incorporated an extensive biomarker analysis with a pre-specified analysis of c-Myc expression, as well as a retrospective analysis of genetic alterations in ctDNA with clinical outcome.

Alisertib 的給藥劑量與單一療法試驗中不同，Alisertib 在第1 至3 天、第8 至10 和15 至17 天以40 mg BID 給藥，持續三週，並在第1、8、8 天靜脈注射紫杉醇60 mg 15 日和 15 日，而對照組在 28 天週期中的第一天、第八天和第 15 天接受安慰劑加紫杉醇 80 毫克/平方米靜脈注射。該試驗還結合了廣泛的生物標記分析和預先指定的 c-Myc 表達分析，以及 ctDNA 遺傳改變與臨床結果的回顧性分析。

The safety results from the combination arm of the trial showed that 40% of the patients experienced grade three or higher neutropenia, with 13% experiencing grade three or higher drug-related febrile neutropenia. 16% of the patients discontinued study treatment because of an adverse event, and 38% of the patients had a dose reduction because of an adverse event. The primary endpoint of that trial was progression-free survival, or PFS.

此試驗聯合組的安全性結果顯示，40% 的患者出現三級或以上的中性粒細胞減少症，其中 13% 的患者出現三級或以上的藥物相關性發燒性中性粒細胞減少症。 16% 的患者因不良事件而停止研究治療，38% 的患者因不良事件而減少劑量。本試驗的主要終點是無惡化存活期（PFS）。

For the ITT population, the hazard ratio for PFS was 0.77, with a p-value of 0.113. When using the corrected definition for the stratification of relapse type, the hazard ratio for PFS was 0.71, with a p-value of 0.038. For the patients with chemotherapy-resistant or refractory disease, the hazard ratio was 0.66, with a p-value of 0.037.

對於 ITT 族群，PFS 的風險比為 0.77，p 值為 0.113。當使用復發類型分層的校正定義時，PFS 的風險比為 0.71，p 值為 0.038。化療抗藥性或難治性疾病患者，風險比為0.66，p值為0.037。

With respect to the biomarkers that were studied in that trial, for the patients in the trial who were found to be IHC-positive for c-Myc expression, the hazard ratio in the trial was 0.29, with a median PFS for the paclitaxel plus Alisertib arm of 4.64 months, and a median PFS for the paclitaxel plus placebo arm of 2.27 months.

就該試驗中研究的生物標記而言，對於試驗中發現 c-Myc 表達 IHC 陽性的患者，試驗中的風險比為 0.29，紫杉醇加 Alisertib 的中位 PFS紫杉醇加安慰劑組的中位PFS 為4.64 個月，紫杉醇加安慰劑組的中位PFS 為2.27 個月。

Also, for patients with alterations in cell cycle genes, including CDK6, RBL1, RBL2, and RB1, the PFS for the paclitaxel plus Alisertib arm was 3.68 months, while the placebo plus paclitaxel arm was 1.8 months, and the hazard ratio for PFS was 0.395, with a p-value of 0.003.

此外，對於細胞週期基因（包括 CDK6、RBL1、RBL2 和 RB1）發生改變的患者，紫杉醇加 Alisertib 組的 PFS 為 3.68 個月，而安慰劑加紫杉醇組為 1.8 個月，PFS 的風險比為0.395， p 值為0.003。

The overall survival for that subgroup of patients was 7.2 months for the Alisertib arm and 4.47 months for the placebo arm, with a hazard ratio of 0.427 and a p-value of 0.00085.

Alisertib 組此亞組患者的總存活期為 7.2 個月，安慰劑組為 4.47 個月，風險比為 0.427，p 值為 0.00085。

When Puma licensed Alisertib, we stated that one of our focuses would have tried to reduce the adverse event profile of the drug, and more specifically, the grade 3/4 neutropenia, by giving prophylactic GCSF with the administration of Alisertib, and this is being instituted in the ALISCA-Lung1 trial.

當Puma 授權Alisertib 時，我們表示，我們的重點之一是嘗試透過使用Alisertib 時給予預防性GCSF 來減少該藥物的不良事件，更具體地說，減少3/4 級中性粒細胞減少症，目前正在這樣做在 ALISCA-Lung1 試驗中進行。

Currently, there are 20 patients enrolled in the ALISCA-Lung1 trial, with several in screening and prescreening. For the first 18 patients who were available for safety, there has been one patient, or 5.6%, with grade 3/4 neutropenia, and one patient, 5.6%, with febrile neutropenia. No patient has discontinued Alisertib due to adverse events, and one patient, or 5.6%, has required a dose hold.

目前，有 20 名患者參加了 ALISCA-Lung1 試驗，其中幾名患者正在篩選和預篩選中。在前 18 名可安全接受治療的患者中，有 1 名患者（5.6%）患有 3/4 級中性粒細胞減少症，1 名患者（5.6%）患有發燒性中性粒細胞減少症。沒有患者因不良事件而停用 Alisertib，且有 1 名患者（即 5.6%）需要暫停劑量。

Based on the preliminary improved neutropenia and tolerability that is being seen in the trial, and assuming this continues to be seen, the company is considering the potential to increase the dose of Alisertib monotherapy in the trial.

基於試驗中發現的中性粒細胞減少症和耐受性的初步改善，並假設這種情況繼續出現，該公司正在考慮增加試驗中 Alisertib 單藥治療劑量的可能性。

Also, assuming this improved neutropenia and tolerability continues to be seen when Alisertib is combined with paclitaxel, the company believes that it may result in better efficacy of the combination of paclitaxel with Alisertib, and that the company may be able to increase the dose of Alisertib that is able to be given with paclitaxel.

此外，假設當Alisertib 與紫杉醇聯合使用時，繼續看到中性粒細胞減少症和耐受性的改善，該公司認為，這可能會導致紫杉醇與Alisertib 聯合用藥的療效更好，並且該公司可能能夠增加Alisertib 的劑量這可以與紫杉醇一起給予。

Of the 18 patients dosed with Alisertib, 16 have had a post-baseline tumor assessment. Of these, seven had chemotherapy-sensitive disease, which is defined as a relapse more than 90 days, but less than 180 days, after primary treatment, and nine had chemotherapy-resistant or refractory disease, defined as relapse less than 90 days after primary treatment.

在接受 Alisertib 治療的 18 名患者中，有 16 名患者接受了基線後腫瘤評估。其中，7 例患有化療敏感疾病，定義為初次治療後超過 90 天但不到 180 天的復發，9 例患有化療抗藥性或難治性疾病，定義為初次治療後 90 天以內復發治療。

In the chemotherapy-sensitive patients, one patient, or 14%, has shown stable disease, and the median PFS has been 1.2 months. In the patients with chemotherapy-resistant or refractory disease, there have been 2 patients, or 22%, with a partial response, and 1 patient, or 11%, with stable disease, and the median PFS has been 1.4 months.

在化療敏感患者中，1 名患者（即 14%）病情穩定，中位 PFS 為 1.2 個月。在化療抗藥性或難治性疾病患者中，有 2 名患者（即 22%）獲得部分緩解，1 名患者（即 11%）疾病穩定，中位 PFS 為 1.4 個月。

As previously mentioned, we are conducting an extensive analysis of the biomarkers that are known to be involved with the aurora kinase pathway activation to see if it correlates with clinical outcome. The two refractory or resistant patients with partial responses did have biomarkers that correlate with the aurora kinase pathway activation, including RB1 mutations and MYC gains.

如前所述，我們正在對已知與極光激酶途徑活化有關的生物標記進行廣泛的分析，以了解其是否與臨床結果相關。兩名獲得部分緩解的難治性或抗藥性患者確實具有與極光激酶路徑活化相關的生物標記物，包括 RB1 突變和 MYC 增益。

We caution that this is very early data, and we do not have tissue on all the patients enrolled, so the number of patients with biomarker data is too small to be able to draw definitive conclusions on the associations between biomarkers and Alisertib activity.

我們警告說，這是非常早期的數據，我們沒有所有入組患者的組織，因此具有生物標記數據的患者數量太少，無法就生物標記與 Alisertib 活性之間的關聯得出明確的結論。

The company believes that the preliminary data from the ALISCA-1 trial is providing a preliminary indication of potentially better activity in patients with chemotherapy-resistant or refractory disease, which is similar to what was seen in the trials published in the Lancet Oncology and the randomized trial that was published in the Journal of Thoracic Oncology.

該公司認為，ALISCA-1 試驗的初步數據初步表明，對於化療抗藥性或難治性疾病患者可能具有更好的活性，這與《柳葉刀腫瘤學》和隨機研究中發表的試驗相似。發表在《胸腔腫瘤學雜誌》。

The company plans to continue enrollment in the ALISCA-1 trial and anticipates additional data will be presented at Medical Conferences in 2025.

該公司計劃繼續參加 ALISCA-1 試驗，並預計在 2025 年的醫學會議上公佈更多數據。

The company also plans to meet with its steering committee for the trial in order to determine the next steps for the drug and the treatment of small cell lung cancer patients. The company will keep investors updated on this as it progresses.

該公司還計劃與其試驗指導委員會會面，以確定該藥物和小細胞肺癌患者治療的後續步驟。隨著進展，該公司將向投資者通報最新情況。

Investors will also remember that the company plans to test Alisertib in the ALISCA-1 trial, a Phase II trial of Alisertib in combination with endocrine treatment in patients with chemotherapy-naive, HER2-negative, hormone receptor-positive metastatic breast cancer.

投資人還會記得，該公司計劃在ALISCA-1 試驗中測試Alisertib，這是Alisertib 與內分泌治療相結合的II 期試驗，用於治療未接受過化療、HER2 陰性、激素受體陽性的轉移性乳腺癌患者。

Currently, there are three sites that have been activated for the trial, and we anticipate the initiation of the trial in the fourth quarter of 2024. The company will keep investors updated on this as it progresses.

目前，共有三個站點已啟動試驗，我們預計試驗將於 2024 年第四季啟動。隨著進展，該公司將向投資者通報最新情況。

As mentioned on prior earnings calls and in response to investor questions, Puma continues to evaluate several drugs to potentially end license that will allow the company to diversify itself and leverage Puma's existing R&D, regulatory, and commercial infrastructure. The company will keep investors updated on this as it progresses.

正如先前的財報電話會議和回答投資者問題時提到的，Puma 繼續評估幾種可能終止許可的藥物，這將使公司能夠實現多元化，並利用 Puma 現有的研發、監管和商業基礎設施。隨著進展，該公司將向投資者通報最新情況。

I will now turn the call over to Jeff Ludwig, Puma's Chief Commercial Officer, for a review of our commercial performance during the quarter.

我現在將把電話轉給彪馬商務長傑夫路德維希（Jeff Ludwig），以回顧我們本季的商業表現。

Thanks, Alan. I appreciate it, and thanks to everyone for joining our third quarter earnings call. Before I move into the commercial review, just a reminder that I will be making forward-looking statements.

謝謝，艾倫。我對此表示感謝，並感謝大家參加我們的第三季財報電話會議。在進行商業評論之前，請提醒我，我將做出前瞻性陳述。

The commercial team is focused on increasing the utilization of NERLYNXs with an emphasis on HER2-positive early-stage breast cancer patients, who are deemed to have a higher risk of reoccurrence.

商業團隊致力於提高 NERLYNX 的使用率，並專注於 HER2 陽性早期乳癌患者，這些患者被認為具有較高的復發風險。

A significant portion of these patients are treated in the community setting and are being seen by a large number of community oncologists. Given this broad distribution of patients, it's very important to look for opportunities to increase share of voice through personal and or non-personal promotion with a focus on trying to engage physicians at the proper time when they are making treatment decisions related to the extended adjuvant setting.

這些患者中有很大一部分在社區環境中接受治療，並由大量社區腫瘤學家就診。鑑於患者分佈廣泛，尋找機會透過個人和/或非個人推廣來增加話語權非常重要，重點是在醫生做出與延長輔助治療相關的治療決策時在適當的時間讓他們參與環境。

HCP call activity increased about 11% quarter-over-quarter and about 17% year over year. Consistent with the last several quarters, the majority of our calls continue to be live interactions, but the team does look for opportunities to leverage virtual calls depending on the situation. In Q3, greater than 80% of our calls were live interactions, which is very similar to what we reported in Q2 of this year.

HCP 通話活動較上季成長約 11%，較去年同期成長約 17%。與過去幾季一樣，我們的大部分通話仍然是即時互動，但團隊確實會根據情況尋找利用虛擬通話的機會。在第三季度，我們超過 80% 的通話都是即時互動，這與我們今年第二季度的報告非常相似。

The commercial team is committed to finding ways to utilize our resources more efficiently and effectively. We are evaluating new partners, new data, and new approaches with the goal of improving our impact and ultimately increasing the utilization of NURLINX.

商業團隊致力於尋找更有效率、更有效地利用我們資源的方法。我們正在評估新合作夥伴、新數據和新方法，目標是提高我們的影響力並最終提高 NURLINX 的利用率。

Let me now transition to some of the commercial slides, where I will provide some additional specifics around performance. Once I have finished, I will turn the call over to Maximo for a more detailed review of our financial results.

現在讓我轉向一些商業幻燈片，其中我將提供一些有關性能的其他細節。完成後，我會將電話轉給 Maximo，以便對我們的財務表現進行更詳細的審查。

Looking at slide 3, slide 3 is an overview of our distribution model, which is broken out into the specialty pharmacy channel and the specialty distributor or in-office dispensing channel. We do see quarterly fluctuations, but the majority of our business continues to flow through the specialty pharmacy channel. In Q3, about 74% of our business passed through the specialty pharmacy channel, which is similar to the 72% we reported during our Q2 earnings call.

檢視投影片 3，投影片 3 概述了我們的分銷模式，該模式分為專業藥房通路和專業經銷商或辦公室內配藥通路。我們確實看到季度波動，但我們的大部分業務繼續透過專業藥局管道流動。第三季度，我們約 74% 的業務透過專業藥局管道，這與我們在第二季財報電話會議上報告的 72% 相似。

Moving to slide 4. NURLINX net revenue in Q3 of 2024 was $56.1 million, which represents an increase of $11.7 million from the $44.4 million we reported in Q2 of 2024 and a $4.5 million increase from the $51.6 million we reported in Q3 of 2023. The significant change in quarterly net revenue was primarily driven by four factors. Number one, inventory changes.

轉到投影片 4。NURLINX 2024 年第三季的淨收入為5,610 萬美元，比我們報告的2024 年第二季的4,440 萬美元增加了1,170 萬美元，比我們報告的2023 年第三季的5,160 萬美元增加了450 萬美元。季度淨收入的重大變動主要由四個因素驅動。第一，庫存變化。

Number two, higher US ex-factory sales. Number three, increased product supply revenue to our global partners. And four, a lower gross to net adjustment. I will provide some more details around inventory changes and Maximo will provide some additional specifics during his update.

第二，美國出廠銷量增加。第三，增加了我們全球合作夥伴的產品供應收入。第四，毛淨調整幅度較低。我將提供有關庫存變化的更多詳細信息，Maximo 將在更新期間提供一些其他細節。

In regards to inventory, we estimate that inventory increased by about $600,000 in Q3 of 2024. As a comparison, we estimate that inventory decreased by about $2.3 million in Q2 of 2024 and increased by about $600,000 in Q3 of 2023.

在庫存方面，我們估計 2024 年第三季庫存增加約 60 萬美元。作為比較，我們估計 2024 年第二季庫存減少約 230 萬美元，2023 年第三季庫存增加約 60 萬美元。

Slide 5 shows Q3 2024 ex-factory bottle sales and also provides both a year-over-year and a quarter-over-quarter comparison. In Q3 of 2024, NERLYNX's ex-factory bottle sales were 2,723, which represents an approximate 8% quarter-over-quarter increase and a 5% year-over-year decrease.

幻燈片 5 顯示了 2024 年第三季出廠瓶銷量，並提供了同比和環比比較。2024年第三季度，NERLYNX的出廠瓶銷售量為2,723瓶，較上季成長約8%，較去年同期下降5%。

In regards to inventory impact, we estimate that inventory increased by about 37 bottles in Q3 of 2024. As a comparison, we estimate that inventory decreased by about 132 bottles in Q2 of 2024 and increased by about 32 bottles in Q3 of 2023.

關於庫存影響，我們估計 2024 年第三季庫存增加約 37 瓶。作為比較，我們估計2024年第二季庫存減少約132瓶，2023年第三季庫存增加約32瓶。

Now let me take just a moment to provide some additional metrics and insights into our third quarter performance. In Q3, we saw new patient starts, or NRX, increased by about 3% quarter-over-quarter and about 8% year-over-year. Total prescriptions, or TRX, were flat quarter-over-quarter and down about 8% year-over-year.

現在，讓我花點時間提供一些有關我們第三季業績的額外指標和見解。在第三季度，我們看到新患者開始數 (NRX) 環比增長約 3%，同比增長約 8%。總處方量 (TRX) 環比持平，年減約 8%。

Overall demand increased by about 1.5% quarter-over-quarter but was down about 5% year-over-year. Enrollments and SD demand are also important factors in looking at our performance. Enrollments are an important leading indicator, as we have discussed previously. As a reminder, enrollments turn into new patient starts. New patient starts turn into refills, which impact demand in subsequent quarters. In Q3, enrollments were down just under 1% quarter-over-quarter and were up approximately 10% year-over-year.

整體需求較上季成長約1.5%，但年減約5%。入學率和 SD 需求也是衡量我們績效的重要因素。正如我們之前所討論的，入學率是一個重要的領先指標。提醒一下，登記會變成新病患開始。新患者的開始轉為補充，這會影響隨後幾季的需求。第三季度，入學人數較上季下降近 1%，但年增約 10%。

As a reminder, and as we mentioned during our Q3 2023 earnings call last year, we did see some enrollment softness last year that largely occurred in the first part of Q3 of 2023. That softness is contributing to this positive year-over-year comparison.

提醒一下，正如我們在去年的 2023 年第三季財報電話會議中提到的那樣，我們去年確實看到了一些入學人數的疲軟，這主要發生在 2023 年第三季的上半年。這種疲軟促成了這種積極的同比比較。

SD demand is also an important performance indicator, as there are patients that are treated solely in the SD channel, which means we will never capture an enrollment from this group. SD demand increased 5% quarter-over-quarter and 13% year-over-year.

SD 需求也是一個重要的績效指標，因為有些患者僅在 SD 管道中接受治療，這意味著我們永遠不會從該群體中獲取入組人數。SD 需求較上季成長 5%，較去年同期成長 13%。

Turning to slide 6, slide 6 highlights the quarterly adoption of dose escalation since NERLYNX's launch. In Q3, approximately 65% of patients started NERLYNX's at a reduced dose. This is similar to the 66% that was reported in Q2 of this year.

轉向幻燈片 6，幻燈片 6 重點介紹了自 NERLYNX 推出以來每季採用劑量遞增的情況。在第三季度，大約 65% 的患者開始減少劑量的 NERLYNX。這與今年第二季報告的 66% 相似。

The benefits of dose escalation to initiate therapy with NERLYNX's continues to be an important part of our commercial messaging. The control trial showed a significant reduction in grade three diarrhea and showed improved persistence and compliance when patients were started at a lower dose.

透過劑量增加來啟動 NERLYNX 治療的好處仍然是我們商業資訊的重要組成部分。對照試驗顯示，當患者開始服用較低劑量時，三級腹瀉顯著減少，且持久性和依從性得到改善。

We track multiple cohorts of patients and continue to see improved persistence when patients are started at a lower dose. The commercial team continues to explore additional opportunities to better support patients throughout their NERLYNX's therapy.

我們追蹤了多個患者隊列，並繼續看到當患者以較低劑量開始時，持久性有所改善。商業團隊繼續探索更多機會，在患者的整個 NERLYNX 治療過程中更好地支持患者。

Slide 7 highlights the strategic collaborations we have formed across the globe. In Q3, NERLYNX's received regulatory approval in Algeria in the extended adjuvant setting. In addition, NERLYNX's was launched in both South Africa and the United Arab Emirates, also in the extended adjuvant setting. We really appreciate the excellent work being done by our partners around the globe and look forward to supporting their continued success moving forward.

投影片 7 重點介紹了我們在全球範圍內形成的策略合作。第三季度，NERLYNX 的擴展佐劑治療方案在阿爾及利亞獲得了監管部門的批准。此外，NERLYNX 在南非和阿拉伯聯合大公國也以延長佐劑的形式上市。我們非常感謝全球合作夥伴所做的出色工作，並期待支持他們繼續取得成功。

I'd like to wrap up by thanking my Puma colleagues for their unwavering commitment. The team is passionate about making a difference in the lives of patients and their families battling cancer. The commercial team remains focused on finding ways to be more efficient and effective with their resources and also fully committed to balancing the short-term and long-term priorities of Puma and its shareholders.

最後，我要感謝我的彪馬同事們堅定不移的承諾。團隊熱衷於改變與癌症作鬥爭的患者及其家人的生活。商業團隊仍專注於尋找更有效利用其資源的方法，並全力致力於平衡彪馬及其股東的短期和長期優先事項。

I will now turn the call over to Maximo Nougues for a review of our financial results. Maximo?

我現在將把電話轉給 Maximo Nougues，以審查我們的財務表現。馬克西莫？

Thanks, Jeff. I will begin with a brief summary of our financial results for the third quarter of 2024. Please note that I will make comparisons to Q2 2024, which we believe is a better indication of our progress as a commercial company and year-over-year comparison.

謝謝，傑夫。我將首先簡要概述我們 2024 年第三季的財務表現。請注意，我將與 2024 年第二季度進行比較，我們認為這更好地表明了我們作為一家商業公司的進展以及同比比較。

For more information, I recommend that you refer to our Q3 thank you, which will be filed today and includes our consolidated financial statements. For the third quarter of 2024, we reported net income based on GAAP of $20.3 million, or $0.41 per share.

如需了解更多信息，我建議您參閱我們的第三季度致謝函，該致謝函將於今天提交，其中包括我們的合併財務報表。2024 年第三季度，我們報告的基於 GAAP 的淨利潤為 2,030 萬美元，即每股 0.41 美元。

This compares to net loss in Q2 2024, or $4.5 million, or $0.09 per share. On a non-GAAP basis, which is adjusted to remove the impact of stock-based compensation expense, we reported net income of $22.4 million, or $0.45 per diluted share, for the third quarter of 2024. Gross revenue from NERLYNX was $67.7 million in Q3 2024 and $55.8 million in Q2 2024. Alan mentioned it.

相比之下，2024 年第二季的淨虧損為 450 萬美元，即每股 0.09 美元。根據非公認會計原則（為了消除股票薪酬費用的影響而進行調整），我們報告的 2024 年第三季淨利潤為 2,240 萬美元，即稀釋後每股收益 0.45 美元。NERLYNX 2024 年第三季的總營收為 6,770 萬美元，2024 年第二季為 5,580 萬美元。艾倫提到過。

Net product revenue from NERLYNX was $56.1 million, an improvement from the $44.4 million reported in Q2 2024. Higher product sales to our global partners of about $7.4 million, higher US demand, and lower gross-to-net adjustment dropped the higher sales versus Q2 2024. Inventory increased by our distributor was approximately $0.6 million in Q3 versus approximately $2.3 million of drawdown in Q2 2024. Loyalty revenue totaled $24.4 million in the third quarter of 2024 compared to $2.7 million in Q2 2024.

NERLYNX 的產品淨收入為 5,610 萬美元，比 2024 年第二季報告的 4,440 萬美元有所改善。與 2024 年第二季相比，我們向全球合作夥伴的產品銷售額增加了約 740 萬美元，美國需求增加以及毛淨調整降低，導致銷售額增加。我們的經銷商在第三季增加的庫存約為 60 萬美元，而 2024 年第二季的庫存減少約為 230 萬美元。2024 年第三季的忠誠度收入總計 2,440 萬美元，而 2024 年第二季為 270 萬美元。

Our gross-to-net adjustment in Q3 2024 was about 17.1%, compared to the 20.4% gross-to-net adjustment reported in Q2 2024. Cost of sales for Q3 2024 increased to $29.1 million, reflecting the sales of NERLYNX to our China partner and includes $2.4 million for the amortization of intangible assets related to our NERLYNX license.

我們 2024 年第三季的毛淨調整約為 17.1%，而 2024 年第二季報告的毛淨調整為 20.4%。2024 年第三季的銷售成本增加至 2,910 萬美元，反映了 NERLYNX 向我們中國合作夥伴的銷售，其中包括與我們的 NERLYNX 許可相關的無形資產攤提 240 萬美元。

Cost of sales for Q2 2024 was $10.7 million. Going forward, we will continue to recognize amortization of the milestones to the license short, about $2.4 million per quarter as cost of sales. For fiscal year 2024, Puma anticipates that net product revenue for NERLYNX will be in the range of $187 million to $290 million.

2024 年第二季的銷售成本為 1,070 萬美元。展望未來，我們將繼續確認許可證短期里程碑的攤銷，即每季約 240 萬美元的銷售成本。對於 2024 財年，Puma 預計 NERLYNX 的淨產品收入將介於 1.87 億美元至 2.9 億美元之間。

We also anticipate that our gross-to-net adjustment for the full year 2024 will be between 20.5% and 21.5%, higher than 2023 due to the impact of the Inflation Reduction Act unexpected Medicaid rebates. In addition, for fiscal year 2024, we anticipate receiving royalties from our partners around the world in the range of $34 to $36 million. We expect license revenue in 2024 in the range of $1 million to $2 million.

我們也預計，由於《通貨膨脹削減法案》意外的醫療補助回扣的影響，2024 年全年的毛淨調整將在 20.5% 至 21.5% 之間，高於 2023 年。此外，在 2024 財年，我們預計將從世界各地的合作夥伴處獲得 3,400 至 3,600 萬美元的特許權使用費。我們預計 2024 年的授權收入將在 100 萬美元至 200 萬美元之間。

We also expect that net income for the full year will be in the range of $15 million to $17 million. We anticipate that for Q4 2024, NERLYNX net product revenue will be in the range of $46 million to $48 million. We expect Q4 royalties revenues will be in the range of $3.5 million to $5 million, and we anticipate $1 million to $2 million of license revenue. We further estimate that the gross-to-net adjustment in Q4 2024 will be approximately 21% to 22%, and Puma anticipates Q4 net income between $4 million and $6 million.

我們也預計全年淨利潤將在 1500 萬美元至 1700 萬美元之間。我們預計 2024 年第四季度，NERLYNX 產品淨收入將在 4,600 萬美元至 4,800 萬美元之間。我們預計第四季度的版稅收入將在 350 萬美元至 500 萬美元之間，我們預計許可證收入將在 100 萬美元至 200 萬美元之間。我們進一步估計，2024 年第四季的毛淨調整約為 21% 至 22%，Puma 預計第四季淨利潤在 400 萬美元至 600 萬美元之間。

SG&A expenses were $16.8 million in the third quarter of 2024, compared to $25 million for the second quarter of 2024. SG&A expenses included non-cash charges for stock-based compensation of $1.5 million for Q3 2024, up from $1.4 million in Q2 2024.

2024 年第三季的銷售、行政管理費用為 1,680 萬美元，而 2024 年第二季為 2,500 萬美元。SG&A 費用包括 2024 年第三季基於股票的薪酬的非現金費用為 150 萬美元，高於 2024 年第二季的 140 萬美元。

Research and development expenses were $12.5 million in the third quarter of 2024, down from $13.6 million in the second quarter of 2024. R&D expenses included non-cash charges for stock-based compensation of $0.6 million in the third quarter of 2024, unchanged from the second quarter of 2024. On the expense side, Puma anticipates flat to slightly lower operating expenses in 2024 compared to 2023.

2024 年第三季的研發費用為 1,250 萬美元，低於 2024 年第二季的 1,360 萬美元。2024 年第三季研發費用包括 60 萬美元的股票薪酬非現金費用，與 2024 年第二季持平。在費用方面，Puma 預計 2024 年的營運費用將與 2023 年持平或略有下降。

More specifically, we anticipate SG&A expenses to decrease by 10% to 12% and R&D expenses to increase 11% to 14% year-over-year. In the third quarter of 2024, Puma reported cash burn of approximately $0.1 million. This compares to cash burn of approximately $10.3 million in Q2 2024.

更具體地說，我們預計 SG&A 費用將年減 10% 至 12%，研發費用將年增 11% 至 14%。2024 年第三季度，Puma 報告現金消耗約 10 萬美元。相比之下，2024 年第二季的現金消耗約為 1,030 萬美元。

Please note that during Q3, we made our second principal loan payment of $11.1 million related to our obligation with Ethereum. As a result of this, our outstanding principal debt balance decreased to approximately $78.1 million. On September 30, 2024, we had approximately $97 million in cash, cash equivalents, and marketable securities versus about $96 million at year-end in 2023.

請注意，在第三季度，我們支付了與以太坊義務相關的第二筆本金貸款 1,110 萬美元。因此，我們的未償本金債務餘額減少至約 7,810 萬美元。截至 2024 年 9 月 30 日，我們擁有約 9,700 萬美元的現金、現金等價物和有價證券，而 2023 年底約為 9,600 萬美元。

Our accounts receivable balance was $54.6 million. Our accounts receivable terms ranged between 10 days and 68 days, but our sales outstandings are about 48 days. We estimate that as of September 30, 2024, our distribution network maintained approximately three weeks of inventory. Overall, we continue to deploy our financial resources focused on the commercialization of NERLYNX, the development of our services, and controlling our expenses.

我們的應收帳款餘額為 5,460 萬美元。我們的應收帳款期限在10天到68天之間，但我們的銷售欠款期限約為48天。我們估計，截至 2024 年 9 月 30 日，我們的分銷網絡維持約三週的庫存。總體而言，我們將繼續部署財務資源，重點關注 NERLYNX 的商業化、服務的開發以及費用的控制。

Thanks, Maximo. Puma's Senior Management, in cooperation with the Board of Directors, continues to remain focused on NERLYNX sales trends in 2024 and beyond, and recognizes its fiscal responsibility to shareholders to continue to maintain a positive net income. In the fourth quarter of 2021, we implemented a reduction in expenses with the goal of reducing expenses in order to maximize operational cash flows.

謝謝，馬克西莫。Puma 的高階管理層與董事會合作，繼續關注 2024 年及以後的 NERLYNX 銷售趨勢，並認識到其對股東的財務責任，以繼續保持正的淨利潤。2021年第四季度，我們實施了費用削減，目標是減少開支，以實現營運現金流最大化。

We believe that the positive net income that was seen in 2023 resulted from these expense reductions. The expense reductions that we have previously performed and continue to perform are also a major contributor to the positive net income that the company achieved in Q3 of 2024 and that the company is guiding for full year 2024. The company remains committed to continuing to achieve this positive net income and will continue to reduce expenses, if needed, to achieve this.

我們認為 2023 年淨利為正值是這些費用削減的結果。我們先前實施並繼續實施的費用削減也是公司在 2024 年第三季實現正淨利潤以及公司對 2024 年全年的指導的主要貢獻者。該公司仍然致力於繼續實現這一正淨利潤，並將在需要時繼續減少開支以實現這一目標。

We look forward to updating investors on this in the future. There continues to remain a significant unmet need for patients battling breast cancer, lung cancer, and other solid tumors. We at Puma are committed and passionate about finding more effective ways of helping these patients during their journey, and we will continue to strive to achieve that goal.

我們期待未來向投資者通報最新情況。對於與乳癌、肺癌和其他實體腫瘤作鬥爭的患者來說，仍然存在巨大的未滿足的需求。Puma 致力於並熱衷於尋找更有效的方法來幫助這些患者度過他們的旅程，我們將繼續努力實現這一目標。

This concludes today's presentation. We will now turn the floor back to the operator for Q&A. Operator?

今天的演講到此結束。我們現在將把發言權轉回接線生進行問答。操作員？

(Operator Instructions)

（操作員說明）

Ed White with H.C. Wainwright.

懷特 (Ed White) 與 H.C.溫賴特。

Good afternoon. Thanks for taking my questions, and congratulations on the quarter. Alan and Jeff, I just wanted to get your thoughts on the sales, exceeding expectations. What are you attributing that to when you dig down into it?

午安.感謝您回答我的問題，並祝賀本季。艾倫和傑夫，我只是想聽聽你們對超出預期的銷售的看法。當你深入研究它時，你將其歸因於什麼呢？

And then also, how does persistence play into that? As you keep saying that as patients are using the lower doses, they remain on drugs longer. So I just wanted to get your thoughts on how that's playing through in the revenue numbers?

還有，堅持是如何發揮作用的？正如您一直所說，隨著患者使用較低劑量，他們服藥的時間會更長。所以我只是想聽聽您對收入數字的看法？

Yeah, Ed, thanks. I appreciate the questions. I would say a couple things in terms of demand numbers. One, as we state over and over, we believe this drug is very promotionally sensitive, and so trying to get the field force in front of more customers on a regular basis continues to be a very key priority for us.

是的，艾德，謝謝。我很欣賞這些問題。我想就需求數字說幾件事。第一，正如我們一再聲明的那樣，我們相信這種藥物的促銷非常敏感，因此定期讓現場人員在更多客戶面前仍然是我們的一個非常重要的優先事項。

And not only is it getting in front of them, but trying to get in front of these customers at the time they're making decisions is also a huge priority for us. And some of the things we're trying to do to make that happen are leveraging claims data to find out what doctors have patients now, looking at NPP when folks are engaging with their NPP, learning more about NERLYNXs.

不僅是它擺在他們面前，而且在這些客戶做出決定時嘗試擺在他們面前也是我們的首要任務。為了實現這一目標，我們正在努力做的一些事情是利用索賠數據來了解醫生現在有哪些患者，在人們參與 NPP 時查看 NPP，以了解有關 NERLYNX 的更多資訊。

That's obviously a signal to us that they're making decisions. So we're trying to get much better with the data to drive the location of our sales force. I would say, we're also seeing a very nice conversion from enrollments to new patient starts, to commercial new patient starts. The team is following up on any pending or delayed cases, and that is also a big priority for us.

這顯然向我們發出了一個信號，表明他們正在做出決定。因此，我們正在努力更好地利用數據來確定我們銷售人員的位置。我想說，我們也看到從註冊到新患者開始，再到商業新患者開始的非常好的轉變。團隊正在跟進任何未決或延遲的案件，這也是我們的首要任務。

You asked lastly about persistence, and we continue to see at any stage along the persistence curve, whether it's first refill, second, third, or fourth, we see about 5% to 10% of more patients on drug at any given time if they started with low dose as opposed to starting at full dose.

您最後問到關於持久性的問題，我們繼續看到在持久性曲線上的任何階段，無論是第一次補充、第二次、第三次還是第四次，我們看到在任何給定時間服用藥物的患者大約有5% 到10% 如果他們從低劑量開始，而不是從全劑量開始。

So that continues to be a big priority for us, and that does drive better overall bottles per patient. Let me know if that's helpful, if you have more questions.

因此，這仍然是我們的首要任務，這確實可以提高每位患者的整體瓶數。如果您還有其他問題，請告訴我這是否有幫助。

No, that's great. Thank you. And, Alan, thanks for the update on Alisertib. You had mentioned about still looking at other business development opportunities.

不，那太好了。謝謝。Alan，感謝您對 Alisertib 的更新。您曾提到仍在尋找其他業務發展機會。

How should we be thinking about what you're looking at? Are you looking at something, that you can leverage your current sales force and also perhaps use in concert with Alisertib, or how should we be thinking about what you look for?

我們該如何思考您所看到的內容？您是否正在尋找一些可以利用您目前的銷售隊伍，也可以與 Alisertib 配合使用的東西，或者我們應該如何考慮您正在尋找的東西？

Yeah, Ed, thanks for the question. Yeah, in terms of looking at assets, we always are ongoing looking at additional assets to bring in. Are we interested in commercial assets that we could leverage our existing sales force and could put us in a position to kind of have that channel teed up, if you will, for Alisertib?

是的，艾德，謝謝你的提問。是的，就資產而言，我們一直在尋找額外的資產來引入。我們是否對商業資產感興趣，我們可以利用這些資產來利用我們現有的銷售隊伍，並使我們能夠為 Alisertib 建立該管道（如果您願意的話）？

Absolutely, that would be something of interest to us. So we're looking across the span, if you will, and there's no question bringing in additional commercial assets we think would make a lot of sense, especially if they could put us in a position to kind of lay the groundwork for Alisertib.

當然，這會是我們感興趣的事。因此，如果你願意的話，我們正在放眼整個跨度，毫無疑問地引入我們認為很有意義的額外商業資產，特別是如果它們能讓我們為 Alisertib 奠定基礎的話。

Okay, thanks, Alan, for taking my questions. And if I could just follow-up on one question, as far as China goes when you have that bolus of patients, is that the way we should be thinking of sales into China in 2025 too, that it's going to be lumpy like that?

好的，謝謝艾倫回答我的問題。如果我能跟進一個問題，就中國而言，當你有這麼多病人時，我們是否也應該這樣考慮 2025 年在中國的銷售，它會像這樣不穩定嗎？

Yes, Ed, if you look historically at our sales to China, it's always been lumpy, and the reason for that is that we kind of have a sale into the distribution channel, kind of in those kind of lumpy boluses, if you will. So it's always been like that quarterly, and I would anticipate it would probably change. I would anticipate it would not change in 2025.

是的，艾德，如果你回顧我們對中國的銷售歷史，你會發現它總是不穩定的，原因是我們在分銷管道中進行了銷售，如果你願意的話，可以說是那種不穩定的丸劑。所以每季都是這樣，我預計它可能會改變。我預計到 2025 年它不會改變。

Okay. Thanks. For taking my questions.

好的。謝謝。回答我的問題。

Divya Rao with TD Cowen.

Divya Rao 和 TD Cowen。

Hi, guys. Thanks for taking my question. I'll add my congrats on the initial data in lung cancer. Just a couple questions on that. Are the two patients that had a PR still on the trial as of the data cut? And then just in terms of expanding the dose or expanding the dose range potentially, do you have to meet with the FDA before looking at increased doses of Alisertib?

嗨，大家好。感謝您提出我的問題。我將對肺癌的初步數據表示祝賀。對此只有幾個問題。截至數據截斷時，兩名獲得 PR 的患者是否仍在試驗中？然後就擴大劑量或潛在擴大劑量範圍而言，在考慮增加 Alisertib 劑量之前是否必須與 FDA 會面？

And then how are you thinking about maybe how many doses you're planning on exploring? Is it just one or are you trying to go or are you trying to do like a sequential dose escalation to figure out kind of where you can get the most efficacy? Thank you.

然後您如何考慮您計劃探索多少劑量？這只是其中之一還是您正在嘗試這樣做，或者您是否正在嘗試按順序增加劑量以找出可以獲得最大功效的地方？謝謝。

Yep. Thanks for the questions, Divya. In terms of the two patients who are with the PRs, I apologize I don't have the data in front of me, so I don't know the answer to that question.

是的。謝謝你的提問，迪維亞。就兩位 PR 患者而言，我很抱歉我沒有數據，所以我不知道這個問題的答案。

With regard to the dose, you'll remember that we licensed this drug from Takeda, and they had previously done monotherapy dose escalation at much higher doses. We're currently dosing at 50 milligrams BID for days 1 to 7, and on that schedule, I think they went as high as like 100, if I remember correctly, somewhere in that ballpark.

關於劑量，您會記得我們從武田獲得了這種藥物的許可，並且他們之前以更高的劑量進行了單藥治療劑量遞增。目前，我們在第1 天到第7 天的每日每日服藥劑量為50 毫克，按照那個時間表，如果我沒記錯的話，我認為劑量會高達100 毫克，大概在這個範圍內的某個地方。

So, we've got quite a ways to go that the drug has already been tested, so I don't anticipate, we would certainly inform FDA of our decision to do that, but we wouldn't need kind of a separate meeting or like to schedule a type C meeting or something like that for that. I apologize, your last question?

因此，我們還有很長的路要走，該藥物已經經過測試，所以我預計，我們肯定會通知 FDA 我們這樣做的決定，但我們不需要單獨的會議或例如為此安排一次C 型會議或類似的會議。抱歉，你的最後一個問題？

Just in terms of like how many doses you're thinking about exploring and how are you thinking about the data evolving as you figure out how many doses to explore?

就像您正在考慮探索多少劑量，以及當您計算出要探索多少劑量時，您如何考慮數據的演變？

Yeah, so remember that, where we saw the initial efficacy in terms of these subgroups, the biomarker subgroups, was in the randomized trial, which was the Paclitaxel-Alisertib against Paclitaxel-plus placebo. We continue to think that, you know, that is the approvable randomized study design. So one issue becomes what do we do as a monotherapy.

是的，所以請記住，我們在這些亞組、生物標記亞組方面看到的初步療效是在隨機試驗中，即紫杉醇-Alisertib 與紫杉醇加安慰劑的對比。我們仍然認為，這是可批准的隨機研究設計。因此，一個問題是我們應該採取什麼單一療法。

The other becomes, you know, what do you do in combination with Paclitaxel because again, I'm forecasting forward here, but let's just say for the sake of argument we do indeed decide that there's an accelerated approval pathway available here as a monotherapy. You'd have to have that trial. The FDA rule is you have to have that trial up and running and I believe they want it almost enrolled, so we kind of have to work on both of those.

另一個問題是，你知道，與紫杉醇聯合使用會做什麼，因為我再次在這裡進行預測，但為了爭論，我們確實決定這裡有一個加速批准途徑作為單一療法。你必須接受那個審判。FDA 的規則是你必須啟動並運行該試驗，我相信他們希望它幾乎註冊，所以我們必須在這兩個方面開展工作。

So I think that we're looking at potentially increasing monotherapy dose, but also in, as I mentioned, in the randomized trial that was done, the Paclitaxel plus Alisertib , they only went up to, if I remember correctly, 30 milligrams or 40 milligrams of Alisertib . We would also be looking whether or not you could increase that as well because again, what we really want to do here is get as great of an efficacy signal as we can and no question, if we can in a randomized trial position ourselves such that not only do we see that, but significant survival benefits, that would be to our advantage as well.

因此，我認為我們正在考慮增加單藥治療劑量的可能性，但正如我所提到的，在進行的隨機試驗中，紫杉醇加Alisertib ，如果我沒記錯的話，它們只增加到30 毫克或40 毫克。。我們也會考慮是否可以增加這一點，因為我們真正想做的是盡可能獲得有效信號，毫無疑問，如果我們能夠在隨機試驗中定位自己，這樣我們不僅看到了這一點，而且還看到了顯著的生存效益，這也對我們有利。

So, I think we want to kind of look at both the monotherapy dose and the combination with Paclitaxel as well.

因此，我認為我們想要研究單一療法的劑量以及與紫杉醇的組合。

That's helpful. Thank you.

這很有幫助。謝謝。

Gina Wong with Barclays.

巴克萊銀行的吉娜黃。

Hi. Thank you for taking our questions. So this is Jenny for Gina. So we have a question about ALISCA-Breast 1 cancers interim readout. So could you provide more color about the timeline? I mean, you mentioned, like, in a medical meeting, and then we wonder, like, how many number of patients data you would report. I think last quarter, it got the readout, it's like a fourth quarter of 2024, but why it is postponed to 2025? Also, like, what is the kind of the benchmark for this, like, activity? Thank you.

你好。感謝您接受我們的提問。這是吉娜的珍妮。我們對 ALISCA-Breast 1 癌症臨時讀數有疑問。那麼您能否提供更多有關時間軸的資訊？我的意思是，您在一次醫學會議上提到過，然後我們想知道您會報告多少患者數據。我想上個季度，它得到了讀數，就像 2024 年第四季一樣，但為什麼要推遲到 2025 年？另外，這項活動的基準是什麼？謝謝。

Okay. So in terms of ALISCA-Breast breast, we haven't started enrolling that trial yet. So once we get enrollment for that we'll have a much better -- a better view of when we'll be able to present data. So obviously, there's two ways of presenting data. One is to do it on a call like this. The other is at a medical meeting.

好的。因此，就 ALISCA-Breast 乳房而言，我們還沒有開始招募該試驗。因此，一旦我們獲得註冊，我們將能夠更好地了解何時能夠提供數據。顯然，有兩種呈現數據的方式。一種是在這樣的通話中執行此操作。另一個正在參加醫學會議。

In terms of your second question, we originally said we were going to provide interim data on the ALISCA-Lung trial, sometime in Q4 of 2024. That's what today's update was. Now, in terms of full presentation at a medical meeting, that will be sometime next year. That's we have a steering committee. They will make that decision. In terms of what the benchmark is, again, we're taking a biomarker-driven approach to the development of Alisertib.

關於你的第二個問題，我們最初表示我們將在 2024 年第四季的某個時間點提供 ALISCA-Lung 試驗的中期數據。這就是今天的更新內容。現在，就醫學會議上的完整演示而言，那將是明年的某個時候。這就是我們有一個指導委員會。他們將做出這個決定。就基準而言，我們再次採用生物標記驅動的方法來開發 Alisertib。

In the previous monotherapy trial, they didn't do a biomarker analysis, so it's hard to do a comparative view. In the randomized trial, that's where they did do the biomarker analysis, and that's where the signals popped up of having PFS benefits and potentially, I believe, OS benefits in the patients with the c-Myc gains and the RB1 mutations. In terms of our current trial, again, I don't have the data in front of me, but if I remember correctly, there were more patients in the resistant refractory group that had biomarkers that were associated with a raw kinase activity than in the chemotherapy-sensitive group.

在先前的單一療法試驗中，他們沒有進行生物標記分析，因此很難進行比較。在隨機試驗中，他們確實進行了生物標記分析，並且出現了信號，顯示 c-Myc 增加和 RB1 突變的患者俱有 PFS 益處，並且我相信，潛在的 OS 益處也存在。就我們目前的試驗而言，我面前沒有數據，但如果我沒記錯的話，抗藥性難治組中有更多的患者俱有與原始激酶活性相關的生物標誌物，而不是在難治性組中。

So I'm hypothesizing that that's why we're seeing that difference in activity. We had previously seen with Alisertib much better activity in the chemotherapy-resistant refractory, and that was both in the monotherapy trial that was done and published in the Lancet Oncology and in the randomized trial in the journal Thoracic Oncology.

所以我假設這就是我們看到活動差異的原因。我們之前曾在《刺胳針腫瘤學》雜誌上進行並發表的單藥治療試驗和《胸腔腫瘤學》雜誌上的隨機試驗中看到 Alisertib 對化療抗藥性難治性藥物具有更好的活性。

Again, I don't have the data in front of me, but if I remember this correctly, in the chemotherapy-resistant refractory group in ALISCA-Lung, I believe there was five patients that had RB1 mutations and c-Myc gain, whereas in the chemotherapy-sensitive group, I believe it was only one. Again, I don't have the data in front of me. That's kind of top of my head. So, again, if what we're seeing is two responders out of five that had those biomarkers, I think that puts us in a decent position.

再說一次，我面前沒有數據，但如果我沒記錯的話，在 ALISCA-Lung 的化療抗藥性難治性組中，我相信有 5 名患者出現 RB1 突變和 c-Myc 增益，而在化療敏感組中，我相信只有一個。再說一次，我面前沒有數據。這就是我的想法。因此，如果我們看到五分之二的響應者俱有這些生物標誌物，我認為這使我們處於一個不錯的位置。

But, again, I'm just speculating on that. Obviously, there's no -- they didn't do that in the previous studies. There's nothing to compare to. And to my knowledge, no one has developed a drug looking at the aurora kinase pathway in these biomarkers.

但話又說回來，我只是猜測而已。顯然，沒有——他們在先前的研究中沒有這樣做。沒有什麼好比較的。據我所知，沒有人開發出一種針對這些生物標記物中的極光激酶途徑的藥物。

No one has, you know, developed a drug looking at the aurora count pathway in these biomarkers.

你知道，沒有人開發出一種藥物來觀察這些生物標記中的極光計數途徑。

Thank you.

謝謝。

Thank you. This concludes our question-and-answer session. I would like to turn the conference back to Mariann for closing remarks.

謝謝。我們的問答環節到此結束。我想請瑪麗安來結束會議。

Thank you for joining us today. As a reminder, this call may be accessed via replay at Pumabiotechnology.com beginning later today. Have a good evening.

感謝您今天加入我們。謹此提醒，從今天稍晚開始，您可以透過 Pumabiotechnology.com 重播本次電話會議。祝你晚上愉快。

Ladies and gentlemen, thank you for participating in today's conference call. This concludes our program. Everyone have a great day. You may now disconnect.

女士們、先生們，感謝你們參加今天的電話會議。我們的計劃到此結束。每個人都度過了愉快的一天。您現在可以斷開連線。