Cellectar Biosciences Inc (CLRB) 2025 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome. (Operator Instructions) Please be advised at today's conference may be recorded. I will not like to hand the conference call over to Anne Marie Fields, Managing Director at Precision AQ. Please go ahead.

女士們、先生們，謝謝你們的支持，歡迎你們。（操作員指示）請注意，今天的會議可能會被錄音。我不想將電話會議交給 Precision AQ 的董事總經理 Anne Marie Fields。請繼續。

Thank you. Thank you, operator. Good morning, and welcome to Cellectar Biosciences first quarter 2025 financial results and business update conference call. Joining us today from Cellectar are Jim Caruso, President and CEO, who will provide an overview of the company's progress before turning the call over to Chad Kolean, CFO, for a financial review of the quarter and the year. Following this, Jarrod Longcor, Chief Operating Officer, will give an update on the company's progress and plans for its promising clinical development pipeline of radiopharmaceuticals.

謝謝。謝謝您，接線生。早安，歡迎參加 Cellectar Biosciences 2025 年第一季財務業績和業務更新電話會議。今天，Cellectar 的總裁兼執行長 Jim Caruso 也將加入我們，他將概述公司的進展情況，然後將電話交給財務長 Chad Kolean，對本季和全年進行財務審查。隨後，營運長 Jarrod Longcor 將介紹公司在放射性藥物有前景的臨床開發管道方面的進展和計劃。

Cellectar issued a press release earlier this morning detailing the content of today's call. A copy can be found on the Investor page of Cellectar's corporate website. I want to remind callers that the information discussed on the call today is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. I caution listeners that management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the business.

Cellectar 今天早上發布了一份新聞稿，詳細介紹了今天電話會議的內容。您可以在 Cellectar 公司網站的投資者頁面上找到一份副本。我想提醒來電者，今天電話會議中討論的資訊屬於《私人證券訴訟改革法案》安全港條款的保護範圍。我提醒聽眾，管理階層將會做出前瞻性的陳述。由於與業務相關的風險和不確定性，實際結果可能與我們的前瞻性陳述所明示或暗示的結果有重大差異。

These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and in the company's SEC filings. The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, May 13, 2025. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call and webcast. As a reminder, this conference call and webcast are being recorded and archived. We will begin the call with prepared remarks and then open the line for your questions.

這些前瞻性陳述完全受到今天的新聞稿和公司提交給美國證券交易委員會 (SEC) 的文件中警示性聲明的限制。本次電話會議的內容包含時間敏感訊息，這些資訊僅在本次直播之日（2025 年 5 月 13 日）準確。本公司不承擔修改或更新任何前瞻性陳述以反映本次電話會議和網路廣播日期之後的事件或情況的義務。提醒一下，本次電話會議和網路廣播正在錄製和存檔。我們將以準備好的發言開始通話，然後開放熱線回答您的問題。

I will now turn the call over to Jim Caruso. Jim?

現在我將電話轉給吉姆·卡魯索。吉姆？

Thank you, Anne Marie, and thank you all for joining us this morning as we review the progress Cellectar has made throughout the first quarter of 2025. We entered 2025 with continued focus on our PDC platform, our radioconjugate pipeline and finalizing the requirements from the FDA and EMA, or European Medicines Agency, regarding iopofosine I 131 for the treatment of Waldenstrom's Macroglobulinemia, or WM.

謝謝你，安妮瑪麗，也謝謝大家今天早上加入我們，一起回顧 Cellectar 在 2025 年第一季的進展。進入 2025 年，我們將繼續專注於我們的 PDC 平台、我們的放射性結合物管道，並最終確定 FDA 和 EMA（歐洲藥品管理局）關於使用碘泊磷 I 131 治療華氏巨球蛋白血症（WM）的要求。

We rapidly scheduled and completed a productive meeting with the US Food and Drug Administration regarding the accelerated approval, regulatory path for iopofosine I131 in WM. The results from the Phase 2 CLOVER-WaM clinical trial of iopofosine I 131 as a treatment for relapsed, refractory WM demonstrated the drug's unique efficacy and safety product profile, which we believe represents a significant opportunity as a promising therapeutic candidate in a relapsed, refractory market where no approved drugs currently exist.

我們迅速安排並完成了與美國食品藥物管理局的富有成效的會議，討論了 WM 中碘泊磷 I131 的加速審批和監管途徑。氯泊磷 I 131 治療復發、難治性 WM 的 II 期 CLOVER-WaM 臨床試驗結果證明了該藥物獨特的療效和安全性產品特性，我們認為，這代表著該藥物在目前尚無獲批藥物的複發、難治性市場中，作為一種有希望的治療候選藥物，具有重大機遇。

In parallel, we are seeking guidance from the EMA on conditional approval for iopofosine I 131 as a treatment for WM based on the CLOVER-WaM Phase 2 study. We believe the compelling results from the study support the conditional marketing authorization strategy and will make available this critically needed new medicine to WM patients in Europe more rapidly.

同時，我們正在尋求 EMA 的指導，以 CLOVER-WaM 第 2 階段研究為基礎，有條件批准碘泊磷 I 131 用於治療 WM。我們相信，該研究的令人信服的結果支持有條件的上市授權策略，並將更快地為歐洲的 WM 患者提供這種急需的新藥。

In addition to our iopofosine program in WM, we continue to progress our solid tumor-focused radioisotope programs, which include our alpha emitter for pancreatic cancer and the Auger emitter for evaluation in triple-negative breast cancer, both of which highlight the novel utility of our delivery platform. Jarrod will speak further to these programs later in the call. As we explore strategic alternatives for the company, we have engaged Oppenheimer as an exclusive financial adviser to assist us. These alternatives may include, but are not limited to, mergers, acquisitions, partnerships, joint ventures, licensing arrangements or other non-dilutive transactions.

除了針對華氏巨球蛋白血症 (WM) 的碘泊磷項目外，我們還在繼續推進針對實體瘤的放射性同位素項目，其中包括用於治療胰腺癌的 α 發射體和用於評估三陰性乳腺癌的俄歇發射體，這兩項項目都凸顯了我們遞送平台的新穎性。賈羅德稍後將在電話會議中進一步討論這些計劃。當我們探索公司的策略替代方案時，我們聘請了奧本海默作為獨家財務顧問來協助我們。這些替代方案可能包括但不限於合併、收購、合作、合資、授權安排或其他非稀釋性交易。

Now, let me turn the call over to Chad for a review of our financial results. Chad?

現在，讓我將電話轉給查德，讓他回顧我們的財務結果。查德?

Thank you, Jim, and good morning, everyone. I will address our financial results for the period ended March 31, 2025. We ended the quarter with cash and cash equivalents of $13.9 million. This compared to $23.3 million as of December 31, 2024. We expect the cash on hand is adequate to fund budgeted operations into the fourth quarter of 2025.

謝謝你，吉姆，大家早安。我將介紹截至 2025 年 3 月 31 日的財務表現。本季末我們的現金和現金等價物為 1,390 萬美元。相比之下，截至 2024 年 12 月 31 日，這一數字為 2,330 萬美元。我們預計庫存現金足以支持 2025 年第四季的預算營運。

As Jim stated, we have engaged Oppenheimer & Company to serve as our exclusive financial adviser as we seek to explore strategic alternatives available to Cellectar that will allow us to maximize shareholder value moving forward.

正如吉姆所說，我們已聘請奧本海默公司 (Oppenheimer & Company) 擔任我們的獨家財務顧問，尋求探索 Cellectar 可用的戰略替代方案，以使我們能夠最大限度地提高股東價值。

Regarding our results from operations, research and development expenses for the three months ended March 31, 2025, were approximately $3.4 million compared to approximately $7.1 million for the three months ended March 31, 2024. The overall decrease in research and development was largely driven by the reduction in patient follow-up activities for our CLOVER-WaM Phase 2 clinical study in WM and a reduction in personnel costs.

關於我們的營運業績，截至 2025 年 3 月 31 日的三個月的研發費用約為 340 萬美元，而截至 2024 年 3 月 31 日的三個月的研發費用約為 710 萬美元。研發費用的整體下降主要是由於我們在 WM 領域進行的 CLOVER-WaM 第 2 期臨床研究的患者追蹤活動的減少以及人員成本的降低。

General and administrative expenses for the three months ended March 31, 2025, were $3.0 million compared to $4.9 million for the same period in 2024. The decrease in G&A was primarily driven by a reduction in pre-commercialization and personnel costs. Net loss for the three months ended March 31, 2025, was $6.6 million, or $0.14 per share, compared to $26.6 million, or $0.91 per share, during the three months ended March 31, 2024.

截至 2025 年 3 月 31 日的三個月的一般及行政費用為 300 萬美元，而 2024 年同期為 490 萬美元。一般及行政費用的減少主要是由於商業化前期成本和人員成本的減少。截至 2025 年 3 月 31 日的三個月的淨虧損為 660 萬美元，即每股 0.14 美元，而截至 2024 年 3 月 31 日的三個月的淨虧損為 2660 萬美元，即每股 0.91 美元。

Now, I will turn the call over to Jarrod for an operational update, including plans for our promising pipeline of radiopharmaceuticals.

現在，我將把電話轉給賈羅德，讓他報告營運最新情況，包括我們有前景的放射性藥物管道計劃。

Thank you, Chad, and good morning, everyone. I will now review the regulatory and clinical status of iopofosine and two of our exciting earlier-stage radioconjugates. The first is our alpha-emitting actinium-based compound CLR 121225. And the second is CLR 121125, our lead auger-emitting radiotherapeutic. The path to achieve conditional approval of iopofosine I 131 is based on major response rate, or MRR, and to obtain full approval based on progression-free survival, or PFS.

謝謝你，查德，大家早安。我現在將回顧一下碘泊磷和我們兩種令人興奮的早期放射性結合物的監管和臨床狀況。第一個是我們的發射α射線的錒化合物 CLR 121225。第二個是 CLR 121125，我們的領先螺旋發射放射治療藥物。獲得碘泊磷I 131有條件批准的途徑是基於主要反應率（MRR），而獲得完全批准則基於無進展生存期（PFS）。

In a randomized controlled Phase 3 study evaluating the activity of iopofosine I 131 versus an investigator's choice comparator arm, which will provide the study investigators a choice between one of two NCCN approved treatment options. The primary endpoint for accelerated conditional approval is superiority based upon the MRR, progression-free survival from the same patients will be used to receive full approval. This trial is expected to enroll approximately 100 patients per arm. Since there is no data available for efficacy of any comparator in this patient population, Cellectar is working with the FDA to utilize claims data demonstrating the current utilization patterns by physicians to select the two NCCN guideline listed drugs for the comparator arm.

在一項隨機對照的 3 期研究中，評估了碘泊磷 I 131 與研究者選擇的比較組的活性，這將為研究人員提供兩種 NCCN 批准的治療方案之一的選擇。加速有條件批准的主要終點是基於 MRR 的優越性，來自同一患者的無惡化存活期將用於獲得完全批准。預計該試驗每組將招募約 100 名患者。由於沒有任何對照藥物在該患者群體中的療效數據，Cellectar 正在與 FDA 合作，利用展示醫生目前使用模式的索賠數據來選擇 NCCN 指南列出的兩種藥物作為對照藥物。

As our earlier-stage pipeline -- as for our earlier stage pipeline, CLR 121225 is our lead alpha-emitting radioconjugate product candidate. To date, it has shown excellent biodistribution and uptake into solid tumors with demonstrated activity across multiple solid tumor animal models, including challenging to treat pancreatic and refractory colorectal cancers.

作為我們早期階段的管道—就我們早期階段的管道而言，CLR 121225 是我們的主要 α 發射放射性共軛產品候選物。迄今為止，它已表現出優異的生物分佈和在實體瘤中的吸收，並在多種實體瘤動物模型中表現出活性，包括治療胰腺癌和難治性結直腸癌的挑戰性。

CLR 121225 has been observed to be well tolerated in these experiments. The Phase 1 trial for CLR 121225 is designed to comprehensively evaluate the compound's biodistribution, safety and tolerability in patients with pancreatic adenocarcinoma. The study will commence with the dosimetry phase aimed at determining the absorbed dose in both normal and tumor tissues. This initial assessment will provide valuable insights into the compounds biodistribution and potential therapeutic window, laying the foundation for subsequent phases of the trial and future development.

在這些實驗中觀察到 CLR 121225 具有良好的耐受性。CLR 121225 的 1 期試驗旨在全面評估該化合物在胰腺腺癌患者中的生物分佈、安全性和耐受性。研究將從劑量測定階段開始，旨在確定正常組織和腫瘤組織中的吸收劑量。初步評估將為化合物的生物分佈和潛在治療窗口提供寶貴的見解，為試驗的後續階段和未來的發展奠定基礎。

Following dosimetry, the study will progress to a dose escalation phase, systematically evaluating increasing doses of CLR 121225 to establish the maximum tolerated dose. This approach offers an opportunity to demonstrate proof of concept for our innovative combination of phospholipid ether, or POE, technology with alpha emitters, potentially showcasing this radioconjugates unique ability to safely treat large bulky solid tumors.

劑量測定之後，研究將進入劑量遞增階段，系統地評估 CLR 121225 的增加劑量以確定最大耐受劑量。這種方法為我們將磷脂醚（POE）技術與α發射體進行創新組合的概念驗證提供了機會，有可能展示這種放射性結合物安全治療大型實體腫瘤的獨特能力。

Our auger-emitting radioconjugates product candidate, CLR 121125, represents the peak of precision in targeted radiotherapy with its emissions traveling only a few nanometers. With our delivery mechanism providing the necessary targeting to the tumor, entry into the cell and transport to the nucleus as validated through preclinical studies, we have seen CLR 121125 demonstrate significant tumor uptake and activity with enhanced tolerability across multiple challenging animal models, including triple-negative breast cancer and metastatic breast cancer.

我們的螺旋發射放射性結合物候選產品 CLR 121125 代表了標靶放射治療的精度峰值，其發射距離僅為幾奈米。我們的遞送機制能夠提供對腫瘤的必要靶向性，進入細胞並運輸到細胞核，這已通過臨床前研究得到驗證，我們已經看到 CLR 121125 在多種具有挑戰性的動物模型（包括三陰性乳腺癌和轉移性乳腺癌）中表現出顯著的腫瘤攝取和活性，並具有增強的耐受性。

We are preparing CLR 121125 for a Phase 1b study in triple-negative breast cancer. This trial will evaluate three distinct doses and dosing regimens and the primary objective of identifying the optimal recommended Phase 2 dose. The study will include an imaging component to further elucidate the biodistribution of CLR 121125, providing crucial insights into its targeting and potential efficacy. It is important to note that the initiation and timing of these trials is dependent on the company obtaining the necessary funding.

我們正在為三陰性乳癌的 1b 期研究準備 CLR 121125。該試驗將評估三種不同的劑量和給藥方案，主要目標是確定最佳建議的 2 期劑量。該研究將包括成像部分，以進一步闡明 CLR 121125 的生物分佈，為其靶向性和潛在功效提供關鍵見解。值得注意的是，這些試驗的啟動和時間取決於公司是否獲得必要的資金。

With that, let me turn the call back to Jim for closing remarks. Jim?

說完這些，請允許我把電話轉回給吉姆，請他做最後發言。吉姆？

Thank you, Chad and Jarrod. Before opening the call to questions, I would like to thank our dedicated and talented Cellectar team who continue to work with tremendous determination to move these important programs and our company forward. We remain committed to the WM community and sincerely appreciate the abundance of support and continued encouragement to advance iopofosine I 131 to market.

謝謝你，查德和賈羅德。在開始提問之前，我想感謝我們敬業且才華橫溢的 Cellectar 團隊，他們繼續以極大的決心努力推動這些重要項目和我們公司向前發展。我們始終致力於 WM 社區，並真誠感謝大家的大力支持和持續鼓勵，以推動碘泊磷 I 131 推向市場。

Operator, we are ready to open the call for questions.

接線員，我們已準備好開始回答問題。

(Operator Instructions)

（操作員指示）

Aydin Huseynov, Ladenburg.

拉登堡的艾登‧胡賽諾夫 (Aydin Huseynov)。

Good morning everyone. Thank you for taking the questions and I appreciate the updates this morning regarding the application for conditional approval in Europe. So I want to ask a question regarding a hypothetical match of 131, iopofosine 131 against rituximab in earlier lines. So since you're going to run the Phase 3 trial anyways and going to take more than perhaps two years to read this out, would it make sense to run against rituximab in earlier lines of therapy just to get the bigger market? And what do you think about the hypothetical efficacy against rituximab in earlier lines? Thank you.

大家早安。感謝您回答這些問題，我很感謝今天上午有關歐洲有條件批准申請的最新消息。所以我想問一個關於 131、碘泊磷 131 與早期利妥昔單抗的假設匹配的問題。因此，既然您無論如何都要進行第 3 階段試驗，並且可能要花兩年多的時間才能讀出這個結果，那麼，為了獲得更大的市場，在早期的治療中與利妥昔單抗競爭是否有意義？您如何看待早期利妥昔單抗的假設療效？謝謝。

Yeah, thank you, Aydin. I appreciate your participation today and certainly the question. As you would imagine, we've evaluated a number of different study designs and opportunities for iopofosine, not only in the relapsed refractory setting, which would be our initial to market play. But, obviously, in earlier lines of therapy, there could be a real benefit for patients that either do not tolerate BTKis. BTKis are not effective.

是的，謝謝你，艾丁。我感謝您今天的參與以及提出的問題。正如您所想的，我們已經評估了碘泊磷的多種不同研究設計和機會，而不僅僅是在復發難治性環境中，這將是我們首次進入市場。但顯然，在早期的治療方法中，對於無法耐受 BTKis 的患者來說，可能會有真正的好處。BTK 無效。

And in your particular case, rituximab or rituximab combinations as well. I will say that for the US FDA, the team has done a really nice job based on our November discussion to very rapidly secure an additional meeting with the FDA that occurred in March. And as part of that, we have -- we believe, very clear line of sight on what a pivotal study would look like, certainly in the US with -- based on the FDA's guidance.

在您的特定情況下，也可以使用利妥昔單抗或利妥昔單抗組合。我想說的是，對於美國 FDA 來說，根據我們 11 月的討論，該團隊做得非常出色，能夠非常迅速地確保在 3 月與 FDA 舉行額外的會議。作為其中的一部分，我們相信，基於 FDA 的指導，我們對關鍵研究的樣子有非常清晰的認識，當然在美國。

And one of those comparator arms in the relapsed refractory setting will most likely be rituximab. Based on data there in these later lines of therapy, rituximab, certainly in third line or greater is in this kind of 10% to 20% range based on the data that we can -- we have observed using data and claims in the US. In earlier lines of therapy, there are clinical studies available, and I'll have Jarrod speak to our thinking around that.

復發難治性治療中的對照組之一很可能是利妥昔單抗。根據這些後期治療方案中的數據，利妥昔單抗在第三線或更高線的應用肯定在 10% 到 20% 的範圍內，這是基於我們在美國觀察到的數據和聲明。在早期的治療方法中，有可用的臨床研究，我會讓賈羅德談談我們對此的想法。

Yeah. As Jim said, Aydin, we did look at going to an early line. The challenge with going to an earlier line is the size of the study becomes much larger. As you might imagine, looking at differentials in major response rate or progression-free survival in earlier lines with going against rituximab, where there is a relatively higher rate of responses as opposed to the 20% -- approximate 20% that Jim just quoted for major response rate in later lines, it jumps up to 60%, 70% or 80% depending on exactly what line you're looking at.

是的。正如吉姆所說，艾登，我們確實考慮過早排隊。進入更早的研究路線的挑戰在於研究規模變得更大。您可能想像得到，對比早期治療中與利妥昔單抗相比主要緩解率或無進展生存期的差異，早期治療中的緩解率相對較高，而 Jim 剛才提到的後期治療中主要緩解率約為 20%，根據您具體觀察的治療線，後期治療中的緩解率可能會躍升至 60%、70% 或 80%。

That then alters your patient population sizing, so the number of patients required to execute that study goes up pretty quickly and pretty significantly, making the cost of the study considerably more than what we're looking at right now. So we've hesitated on that.

這會改變患者群體規模，因此執行研究所需的患者數量會迅速且顯著地增加，使研究成本遠高於我們現在所看到的。所以我們對此猶豫不決。

Yeah. Makes sense. And regarding the Phase 3 trial design, the investigator choice out of the all possible sort of NCCN recommended choices, what is the weakest essentially comparator -- hypothetical comparator arm you would choose or sort of compel physicians to choose in order to improve the chances of 131 in this Phase 3 trial? And are there any eligibility criteria where 131 would be the best suitable option versus other potential options that NCCN recommends?

是的。有道理。關於第 3 階段試驗設計，在 NCCN 推薦的所有可能選擇中，研究者會選擇最弱的本質上的比較器 - 假設的比較器組，或者強制醫生選擇以提高 131 在本次第 3 階段試驗中的機會？是否存在任何資格標準，使得 131 成為與 NCCN 推薦的其他潛在選項相比最合適的選項？

Yeah. That's a great question. And before I hand this off to Jarrod, as you think about this, there's little to no data available relative to most of those treatments that are identified in NCCN guidelines. They're there because they're treating other hematologic malignancies. And oftentimes in WM, in second line, you can already be in a salvage therapy mode in some form of a combination, chemotherapeutic soup, et cetera.

是的。這是一個很好的問題。在我把這個問題交給賈羅德之前，請您思考一下，對於 NCCN 指南中確定的大多數治療方法，幾乎沒有可用的數據。他們在那裡是因為他們正在治療其他血液系統惡性腫瘤。在 WM 中，很多時候，在二線治療中，您已經可以採用某種形式的聯合治療、化療湯等進行挽救治療。

Keeping in mind, this is a much older patient population that may already be -- have been treated with multiple lines of therapy prior from a adverse event perspective, it could be a challenge for these patients. And so, there's clearly, to your point, a dearth of information relative to the performance of these drugs, certainly in second line and beyond and clearly in a relapsed refractory setting.

請記住，這是一個年齡較大的患者群體，他們可能已經接受過多種治療，從不良事件的角度來看，這對這些患者來說可能是一個挑戰。因此，正如您所說，關於這些藥物的作用機制的資訊顯然很缺乏，尤其是在二線及以上治療領域，以及復發難治性治療領域。

So there's high unmet medical need there based on the data claims and utilizing information from third-party community-based integrated oncology delivery networks, you typically see in third line or greater this kind of 10% to 15% response rate based on the data that we're able to garner.

因此，根據數據聲明並利用來自第三方社區綜合腫瘤學交付網絡的信息，那裡存在很高的未滿足醫療需求，根據我們能夠收集的數據，您通常會看到第三線或更高的這種 10% 到 15% 的響應率。

Yeah. And Aydin, if I may follow up a little bit. So the interesting piece, and I'll put it back into the hypothetical. The interesting piece of your question is the hypothetical piece is, can you identify essentially the weakest drug to go against to ensure success. And I'll come to why we don't really care in a moment. I think it will make a lot more sense. But at the end of the day, what -- no matter what drug you pick or pair of drugs you pick, whatever you pick as the investigator choice, you obviously have the FDA to approve those choices. And the FDA wants to stick to what is the most common treatment paradigm that is ongoing right now.

是的。還有艾登，我可以稍微跟進一下嗎？所以這是一個有趣的部分，我將把它放回假設中。你的問題有趣的部分是假設部分，你能否確定本質上最弱的藥物來確保成功。我稍後會解釋為什麼我們並不真正在乎。我認為這會更有意義。但最終，無論您選擇哪種藥物或哪種藥物組合，無論您選擇哪種研究者選擇，顯然都需要 FDA 批准這些選擇。FDA 希望堅持目前最常見的治療模式。

Obviously, physicians aren't likely to be prescribing drugs that they know are failing rapidly. That said, one of the things that I think leads to this is, when you get into the second line and the third line, like Jim said, and you're in this sort of already coming into a salvage therapy, frequently, what you actually see is, physicians are just satisfied with patients not having a major response, but achieving stable disease or suppression of the sequelae associated with the disease, so peripheral neuropathy, maybe reduction in their fatigue, what have.

顯然，醫生不太可能開出他們知道很快就會失效的藥物。話雖如此，我認為導致這種情況的原因之一是，當你進入二線和三線治療時，就像吉姆所說的那樣，你已經進入了這種挽救治療階段，通常，你實際上看到的是，醫生對患者沒有出現重大反應感到滿意，但實現了病情穩定或抑制了與疾病相關的後遺症，因此周圍神經病變可能會減輕他們的疲勞，等等。

And that's what they're really trying to do. They're not actually trying to alter the disease course. They're just trying to ameliorate symptoms and signs of the disease essentially. What's interesting is, what does that mean? That means, as Jim said, most of these other drugs, at least from what we're seeing, have a very -- have very low major response rates and very short progression-free survival.

這正是他們真正想要做的事情。他們其實並沒有試圖改變疾病的進展。他們只是試圖從本質上改善疾病的症狀和徵兆。有趣的是，這意味著什麼？這意味著，正如吉姆所說，至少從我們所看到的情況來看，大多數其他藥物的主要反應率非常低，無惡化存活期非常短。

So as we said, rituximab or even some of the rituximab combinations range in and around this 10% to 30% maximum major response rate and sub six months of progression-free survival. And so, we feel very confident that with our near 60% major response rate, which I think was at the 58.2% in the overall patient population that we will easily be able to demonstrate with major response rate, the potential of iopofosine here. And then when you look at the PFS, again, if you're looking at sub-six months and you look at what our ongoing PFS was in the study, the last time we reported, which was north of 11 months.

正如我們所說，利妥昔單抗或甚至一些利妥昔單抗組合的最大主要緩解率和六個月以下的無進展生存期都在 10% 到 30% 左右。因此，我們非常有信心，我們的主要反應率接近 60%，我認為在整體患者群體中佔 58.2%，我們能夠輕鬆證明碘泊磷的潛力。然後，當您再次查看 PFS 時，如果您查看的是六個月以下的時間，並且查看我們研究中正在進行的 PFS，上次我們報告的時間是 11 個月以上。

Again, we think we have a very strong compelling position as it relates to any comparator that we will select. And we do think with the discussions with the agency, the selection here is really about a fixed course therapy that compares with our fixed course therapy. And so, that means you're basically rituximab and rituximab combinations only as your alternative.

再次，我們認為，與我們將選擇的任何比較器相比，我們具有非常強大的競爭力。我們確實認為，透過與機構的討論，這裡的選擇實際上是關於與我們的固定療程療法進行比較的固定療程療法。所以，這意味著基本上利妥昔單抗和利妥昔單抗組合只能作為您的替代方案。

I think on the other piece, when you think about eligibility, you asked the question about, is there a way to enhance the eligibility to ensure, again, better patient population for iopofosine. And we think we've done that. Fundamentally, this post-BTKi patient population that we're pursuing, keeping in mind that now with ibrutinib approved in the first line, you're seeing a lot more utilization of BTKi in combination with rituximab in that first line setting. What does that mean?

我認為，另一方面，當您考慮資格時，您問的問題是，是否有辦法提高資格，以再次確保更好的碘泊磷患者群體。我們認為我們已經做到了。從根本上來說，我們所追求的這個 BTKi 後患者群體，請記住，現在隨著依魯替尼在第一線獲得批准，您會看到 BTKi 與利妥昔單抗在第一線環境中的聯合使用得到更多的利用。這意味著什麼？

And why is that important? What we've seen through, both anecdotally and then also through the claims data that Jim referred to, what you see is that patients who've had a BTKi tend to fail almost every subsequent treatment after that. However, as you will note from our study and in our press release, I think, this morning, when we look at the post-BTKi population with iopofosine, you're looking at a 15.9% or essentially a 60% or 59% -- sorry, a 59% major response rate in that patient population. So again, we don't see a change. And we think that just select that patient population enriches a true separation and really identifies the need for iopofosine.

為什麼這很重要？我們從軼事和 Jim 提到的索賠數據中看到，接受過 BTKi 治療的患者幾乎在每次後續治療中都會失敗。但是，正如您從我們的研究和新聞稿中註意到的那樣，我認為，今天早上，當我們觀察使用碘泊磷的 BTKi 後人群時，您會看到 15.9% 或基本上 60% 或 59% - 抱歉，該患者群體的主要反應率為 59%。因此，我們再次沒有看到變化。我們認為，只需選擇該患者群體就能實現真正的分離，並真正確定對碘泊磷的需求。

The only other thing -- that was very comprehensive, Jarrod. Thank you. The only other thought that I would provide to Aydin is, this concept of rechallenging, where what you typically see is rituximab or some rituximab combination being used in multiple lines of therapy. Hypothetically, if it was used in first, you may see it in third and fourth. And it's in this kind of, I think, 30% to 40% range for treatments used in the second, third, fourth, fifth lines of therapy.

唯一的另一件事——那非常全面，賈羅德。謝謝。我要向艾丁提供的唯一另一個想法是，這種重新挑戰的概念，你通常會看到利妥昔單抗或某種利妥昔單抗組合用於多種療法。假設，如果它在第一個中使用，那麼您可能會在第三個和第四個中看到它。我認為，第二、第三、第四、第五線治療的成功率在 30% 到 40% 之間。

And that's really -- and each time it's used, typically, it becomes less and less effective by line of therapy as you use it to rechallenge patients. And as a result of that, it just really talks to the high unmet medical need that exist here in this patient population.

事實確實如此——通常，每次使用它來重新治療患者時，它的療效就會越來越差。因此，這實際上說明了該患者群體中存在大量未滿足的醫療需求。

Yeah, makes a lot of sense. One additional question I have regarding the conditional marketing application in Europe. So this is -- I think there's a 10-year report from EMA that says 6 out of 10 drugs that were submitted, got approved conditional first and some of them actually got full approval after that. But how do you assess the commercial opportunity in Europe after you will hear back from EMA, I think you mentioned third quarter 2026? So how do you assess the commercial opportunity given the pricing environment there, given the market size environment there? Just curious your thoughts on -- to hear your thoughts on this.

是的，很有道理。我還有一個關於歐洲有條件上市申請的問題。所以這是——我認為 EMA 有一份 10 年報告，其中指出提交的 10 種藥物中有 6 種首先獲得有條件批准，其中一些實際上在那之後獲得了完全批准。但是，在您收到 EMA 的回覆後，您如何評估歐洲的商業機會，我想您已經提到了 2026 年第三季？那麼，考慮到那裡的定價環境和市場規模環境，您如何評估商業機會？只要好奇您的想法——想聽聽您對此的看法。

Sure. I think first, perhaps an update in terms of where we sit with the EU in terms of potential for conditional approval there and how we're thinking about the regulatory pathway. And we also aid and view that market as a very rich one as well.

當然。我認為首先，也許我們需要更新我們與歐盟在獲得有條件批准的可能性方面的進展，以及我們對監管途徑的看法。我們也為該市場提供協助，並將該市場視為非常豐富的市場。

Yeah. So, Aydin, to your point, 6 out of 10 drugs that seek conditional approval in Europe received it, which is a nice percentage. 60% of the time, you're going to get it. We think that our possibilities there may be enhanced because we have the prime designation and the data set that we have is so strong. We did have a meeting -- a scientific advice meeting with the EMA previously. During that meeting, it was commented by them about the study design sort of separate from the US, they were much more focused on a single trial design approach for the drug, and they were very impressed with the data they were looking at, at that point from the CLOVER-WaM study. They did not have all of the data. So they are looking forward to receiving that.

是的。所以，Aydin，正如您所說，在歐洲尋求有條件批准的藥物中，有十分之六都獲得了批准，這是一個不錯的比例。 60% 的情況下，您都會獲得批准。我們認為，我們的可能性可能會增強，因為我們擁有主要稱號，而且我們擁有的資料集非常強大。我們之前確實與 EMA 舉行過一次科學諮詢會議。在那次會議上，他們評論說，該研究設計與美國有所不同，他們更注重藥物的單一試驗設計方法，並且他們對當時從 CLOVER-WaM 研究中看到的數據印象深刻。他們並沒有掌握全部數據。所以他們期待收到它。

So we expect, as you sort of said, that we will have the meeting with them to discuss the pathway and to basically ensure that we are eligible and that we should seek the approval on that study. We also think because -- where we sit right now is with the new Phase 3 study design that we come with the FDA, we'll be sharing that with EMA as essentially the confirmatory study for full approval in Europe.

因此，正如您所說，我們期望與他們舉行會議，討論途徑，並從根本上確保我們有資格，並且我們應該尋求對該研究的批准。我們也認為，因為我們目前所處的位置是與 FDA 一起進行的新的 3 期研究設計，我們將與 EMA 分享該設計，作為在歐洲獲得全面批准的確認性研究。

And we think that, that study, as it is designed, will ensure that they are more amenable to the conditional approval because, obviously, it does then address several of their traditionally desired things, a comparator-controlled trial, a comparator that is widely used throughout Europe, one that you can then use from a pricing perspective as well. So all of these things will help them to be in a position to grant a conditional approval.

我們認為，按照該研究的設計，它將確保他們更容易獲得有條件的批准，因為顯然，它確實解決了他們傳統上期望的幾個問題，即對照試驗，一種在整個歐洲廣泛使用的對照試驗，你也可以從定價的角度使用它。因此，所有這些都將有助於他們獲得有條件的批准。

And then I think as you asked the question on the commercial side, yes, pricing is different in Europe. And yes, it is significantly lower than here in the US. However, one of the new regulations and new approaches there is, you have to do a comparator-controlled trial so that you can get appropriate pricing and justify.

然後我想，正如你從商業方面提出的問題一樣，是的，歐洲的定價是不同的。是的，它比美國低得多。然而，根據新規定和新方法，您必須進行對照試驗，以便獲得適當的定價和證明。

In a rare disease like this, you get some benefit. Keeping in mind that this disease is predominantly a disease of older Northern European descendants. It is more common or equally as common in Europe, even though the population size is a bit lower, it is relatively common. And I would say that the other key component there is, we do believe that rituximab will be one of the comparator arms as that is much more highly utilized in Europe than it is here in the US. I think as Jim quoted a little bit ago, rituximab generally in the US, irrespective line of therapy is being given at 30%-ish, 40%-ish of the time. And Europe is almost double that.

對於這種罕見疾病，您會獲得一些益處。請記住，這種疾病主要是北歐老年人後裔的疾病。它在歐洲更為常見或同樣常見，儘管人口規模略低，但它相對常見。我想說的是，另一個關鍵因素是，我們確實相信利妥昔單抗將成為比較組之一，因為它在歐洲的使用率比在美國高得多。我認為，正如 Jim 剛才提到的那樣，在美國，利妥昔單抗的治療比例一般在 30% 到 40% 左右，無論採用哪種療法。而歐洲的數字幾乎是這個數字的兩倍。

So now you're taking out one of the leading utilized drugs across Europe. And if you're demonstrating that you can beat it with a superiority study, you should be instantly placed in front of it as utilization across Europe. While the pricing might be different, you actually will likely see an increase in total volume offsetting that price differential.

所以現在您正在服用歐洲最常用的藥物之一。如果你證明你可以透過優勢研究擊敗它，那麼你應該立即在歐洲範圍內利用它。雖然定價可能不同，但實際上您可能會看到總量的增加抵消了價格差異。

And Jarrod, for clarity relative to the conditional approval time line, we will know from our friends at the EMA in the third quarter of this year as to whether or not a conditional regulatory pathway with conditional approval would be acceptable.

賈羅德，為了明確有條件批准的時間表，我們將在今年第三季從 EMA 的朋友那裡了解有條件批准的有條件監管途徑是否可以接受。

Correct. And then it would -- essentially from there, it's approximately -- the filing would go in and then it's 12 months from the filing generally for EMA.

正確的。然後 — — 基本上從那時開始，大約 — — 申請就會提交，然後從提交申請到 EMA 通常需要 12 個月的時間。

Right. All right. Okay. Thank you. Thanks so much for taking the questions, and I appreciate the discussion.

正確的。好的。好的。謝謝。非常感謝您回答這些問題，我很欣賞這次討論。

Of course. Thank you, Aydin.

當然。謝謝你，艾登。

Thank you.

謝謝。

(Operator Instructions) There are no further questions at this time. I will now turn the call over to the Cellectar team for closing remarks. Please go ahead.

（操作員指示）目前沒有其他問題。現在我將把電話交給 Cellectar 團隊來做結束語。請繼續。

Well, operator, thank you for facilitating the call, and also thank you to everyone participating today. This does conclude our call, and you may disconnect. Thank you.

好的，接線生，感謝您主持這通通話，也感謝今天參與的所有人。我們的通話到此結束，您可以掛斷電話了。謝謝。

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

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。