Cellectar Biosciences Inc (CLRB) 2025 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome.

女士們、先生們，謝謝你們的支持，歡迎你們。

(Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to Anne Marie Fields, Managing Director at Precision AQ. Please go ahead.

（操作員指示）請注意，今天的會議正在錄音。現在，我想將會議交給 Precision AQ 的董事總經理 Anne Marie Fields。請繼續。

Thank you, operator. Good morning, and welcome to Cellectar Biosciences Second 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. Following this, Jarrod Longcor, Chief Operating Officer, will give an update on the company's progress and plans for its promising clinical pipeline of radiopharmaceuticals.

謝謝您，接線生。早安，歡迎參加 Cellectar Biosciences 2025 年第二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 也來到我們這裡；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管線方面的進展和計劃。

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 provision of the Private Securities Litigation Reform Act.

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。

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. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's and in our SEC filings.

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。這些前瞻性陳述完全符合今天和我們向美國證券交易委員會提交的文件中所含的警告性聲明。

The content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 14, 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'll begin with prepared remarks and then open the line for your questions.

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 8 月 14 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。我們將首先發表準備好的發言，然後開放提問環節。

I'll now turn the call over to? Jim Caruso. Jim?

我現在把電話轉給？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 half of 2025. First half of 2025 has been a period of strong execution and strategic progress for Cellectar. We've made significant strides across our development pipeline, regulatory strategy corporate development initiatives and fundraising efforts, collectively positioning us for a strong conclusion to 2025.

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 年上半年的進展。2025 年上半年是 Cellectar 執行力強、策略進展順利的時期。我們在開發管道、監管策略、企業發展計畫和融資工作方面都取得了重大進展，為 2025 年取得圓滿成功奠定了基礎。

Let me begin with our lead asset, I am focusing I-131, which continues to demonstrate its potential as a first-in-class radio conjugate therapy for patients with Waldenstrom's maIcroglobulinemia or WM. As we reported in this morning's press release, we have shifted our regulatory strategy and now plan to submit a new drug application or NDA with the FDA under an accelerated approval pathway for iopofosine I 131 as a treatment for WM, subject to sufficient funding and having a confirmatory study underway.

首先介紹我們的主要資產，我關注的是 I-131，它繼續展示出作為華氏巨球蛋白血症 (WM) 患者的一流放射性結合療法的潛力。正如我們在今天早上的新聞稿中所報道的，我們已經改變了監管策略，現在計劃根據加速審批途徑向 FDA 提交碘泊磷 I 131 作為 WM 治療的新藥申請或 NDA，前提是有足夠的資金並且正在進行確認性研究。

The CLOVER-WaM study will serve as the primary basis for the demonstration of efficacy. Our confidence in this new strategy is supported by a number of key elements that we will discuss later in the call. Importantly, we also believe this new regulatory path aligns with the FDA's commitment to expediting treatments for rare diseases such as WM.

CLOVER-WaM 研究將作為證明療效的主要依據。我們對這項新策略的信心得到了一些關鍵因素的支持，我們將在稍後的電話會議中討論這些因素。重要的是，我們也相信，這一新的監管途徑符合 FDA 加快治療 WM 等罕見疾病的承諾。

In parallel, we are advancing our regulatory strategy for iopofosine I 131 in Europe, where the product candidate has been granted prime designation which is the FDA equivalent of breakthrough designation, which is designed to provide early regulatory support to accelerate the development of innovative medicines addressing unmet medical needs for patients in Europe.

同時，我們正在歐洲推進碘泊磷I 131的監管策略，該產品候選藥物已獲得主要認定，相當於美國食品藥物管理局（FDA）的突破性認定，旨在提供早期監管支持，加速開發創新藥物，滿足歐洲患者未滿足的醫療需求。

Last quarter, we submitted a filing seeking guidance from the EMA on conditional approval of iopofosine I 131 and as a treatment for WM based on the CLOVER-WaM Phase II data. We believe the results from the study should be sufficiently compelling to support the conditional marketing authorization strategy. Since then, we've entered the scientific advice process with the EMA and anticipate a response late in the third quarter or very early in the fourth quarter.

上個季度，我們提交了一份文件，尋求 EMA 的指導，以有條件批准碘泊磷 I 131 並根據 CLOVER-WaM 第二階段數據將其用於治療 WM。我們相信研究結果應該要夠令人信服，以支持有條件的行銷授權策略。從那時起，我們就進入了與 EMA 的科學諮詢流程，預計將在第三季末或第四季初得到回應。

These dual regulatory tracks reflect our commitment to bringing iopofosine to patients globally as efficiently as possible. To support our vision for iopofosine and these efforts, we are in active discussions with the potential partners, both regional and global. We would expect these partnerships, if completed, to provide nondilutive capital, additional human resources and subject matter expertise while preserving long-term value for our shareholders.

這些雙重監管軌道反映了我們致力於盡可能高效地為全球患者提供碘泊磷的承諾。為了支持我們對碘泊磷的願景和這些努力，我們正在與區域和全球的潛在合作夥伴進行積極討論。我們期望這些合作關係一旦完成，將提供非稀釋性資本、額外的人力資源和專業知識，同時為我們的股東保留長期價值。

With robust clinical data and a well-understood safety profile, potential expedited program designations in both the US and Europe and a compelling commercial market potential. We believe iopofosine I 131 represents an attractive candidate for potential partners seeking impactful innovation and accelerated development pathways.

憑藉強大的臨床數據和充分了解的安全性，在美國和歐洲都有可能獲得快速的專案指定，並具有引人注目的商業市場潛力。我們相信，對於尋求有影響力的創新和加速發展途徑的潛在合作夥伴來說，iopofosine I 131 是一個有吸引力的候選藥物。

Beyond iopofosine, we are equally excited about the progress in our next-generation radiopharmaceutical pipeline. We remain on track to initiate a Phase I trial for CLR 125 in late 2025 or early 2026. CLR 125, our iodine-125 Auger-emitting agent is advancing towards clinical evaluation in triple-negative breast cancer, and we've already submitted the Phase I protocol to the FDA.

除了碘泊磷之外，我們對下一代放射性藥物管道的進展同樣感到興奮。我們仍有望在 2025 年底或 2026 年初啟動 CLR 125 的第一階段試驗。我們的碘-125俄歇發射劑 CLR 125 正在推進三陰性乳癌的臨床評估，我們已經向 FDA 提交了 I 期方案。

Meanwhile, we are prepared to advance CLR 225, our actinium radio conjugate into a Phase I study as a potential solid tumor treatment, such as pancreatic cancer, of course, contingent upon sufficient company funding. Jarrod will provide further detail on both of these promising programs.

同時，我們準備將我們的錒系放射性結合物 CLR 225 推進到 I 期研究階段，作為潛在的實體瘤治療方法，例如胰腺癌，當然，這取決於公司是否有足夠的資金。賈羅德將提供有關這兩個有前景的項目的更多細節。

Operationally, we've strengthened our foundation with a long-term isotope supply agreement and raised nearly $10 million in recent financings. These funds will support our clinical programs and regulatory milestones while enabling continued progress on strategic initiatives.

在營運方面，我們透過長期同位素供應協議加強了基礎，並在最近的融資中籌集了近 1000 萬美元。這些資金將支持我們的臨床項目和監管里程碑，同時推動戰略計劃的持續進展。

In summary, Cellectar is entering the second half of 2025 with positive momentum a potentially streamlined regulatory path for iopofosine and a series of interesting and novel Phase I ready as well as early-stage assets. We are energized by the opportunities ahead and remain deeply committed to delivering innovative, life-extending therapies to patients with cancer.

總而言之，Cellectar 正以積極的勢頭進入 2025 年下半年，其碘泊磷的監管路徑可能得到簡化，並且擁有一系列有趣且新穎的 I 期準備資產和早期資產。我們對未來的機會充滿信心，並將繼續致力於為癌症患者提供創新的、延長生命的治療方法。

Thank you for your continued support. I'll now turn the call over to Chad Kolean, our CFO, for a review of our financials. Chad?

感謝您一直以來的支持。現在我將把電話轉給我們的財務長 Chad Kolean，讓他審查我們的財務狀況。查德?

Thank you, Jim, and good morning, everyone. I will address our financial results for the quarter ended June 30, 2025, beginning with our cash position. We ended the quarter with cash and cash equivalents of $11 million which includes $2.3 million in net funds raised from the June financing, compares to $23.3 million as of December 31, 2024. Right after the close of the second quarter, we completed a financing that raised an additional $5.8 million net and expect that our cash on hand is adequate to fund budgeted operations into the second quarter of 2026.

謝謝你，吉姆，大家早安。我將從現金狀況開始介紹我們截至 2025 年 6 月 30 日的季度財務表現。本季末，我們的現金和現金等價物為 1,100 萬美元，其中包括 6 月份融資籌集的 230 萬美元淨資金，而截至 2024 年 12 月 31 日為 2,330 萬美元。第二季結束後，我們立即完成了一項融資，額外籌集了 580 萬美元的淨資金，預計我們手頭上的現金足以為 2026 年第二季的預算運營提供資金。

Turning to our results from operations. Research and development expenses for the three months ended June 30, 2025, and were approximately $2.4 million compared to approximately $7.3 million for the three months ended June 30, 2024. The overall decrease in research and development was largely the result of our having concluded both patient enrollment and a significant portion of the necessary follow-up for our CLOVER-WaM Phase II clinical study in WM and a reduction in personnel costs.

談談我們的營運結果。截至 2025 年 6 月 30 日的三個月的研發費用約為 240 萬美元，而截至 2024 年 6 月 30 日的三個月的研發費用約為 730 萬美元。研發費用的整體減少主要是因為我們已完成 WM 的 CLOVER-WaM II 期臨床研究的患者招募和必要的後續工作的很大一部分，以及人員成本的降低。

General and administrative expenses for the three months ended June 30, 2025, were $3.6 million compared to $6.4 million for the same period in 2024. The decrease in general and administrative was primarily driven by a reduction in pre-commercialization efforts and personnel costs.

截至 2025 年 6 月 30 日的三個月的一般及行政費用為 360 萬美元，而 2024 年同期為 640 萬美元。一般及行政開支的減少主要是由於商業化前期工作和人員成本的減少。

Other income and expense for the quarter was a gain of approximately $0.6 million for the quarter as compared to $12.8 million in the same period in the prior year. Most of this activity in other income is noncash in nature and relates to either the issuance exercise or changes in the valuation of warrants. These noncash changes are having a significant impact on earnings, nonoperating only, but do not impact cash burn or runway.

本季其他收入和支出收益約為 60 萬美元，而去年同期為 1,280 萬美元。其他收入中的大部分活動本質上是非現金的，並且與發行活動或認股權證估值的變化有關。這些非現金變動僅對非營業收益產生重大影響，但不會影響現金消耗或跑道。

Net loss for the three months ended June 30, 2025, was $5.4 million or $3.39 per basic and diluted share, compared with $0.9 million or $0.77 per basic and $5.43 per diluted share during the three months ended June 30, 2024. As I just mentioned, the significant differences in the net loss and earnings per share are the result of the noncash impact of warrant activity.

截至 2025 年 6 月 30 日的三個月的淨虧損為 540 萬美元，即每股基本虧損和稀釋虧損均為 3.39 美元，而截至 2024 年 6 月 30 日的三個月的淨虧損為 90 萬美元，即每股基本虧損 0.77 美元，每股稀釋虧損 5.55.55 美元。正如我剛才提到的，淨虧損和每股盈餘的顯著差異是認股權證活動的非現金影響的結果。

With that financial overview, let me turn the call over to Jarrod for an operational update, including plans for our pipeline of radiopharmaceuticals.

在了解了財務概況後，我將把電話轉給賈羅德，讓他介紹營運最新情況，包括我們的放射性藥物管道計劃。

Thank you, Chad, and good morning, everyone. Earlier this year, iopofosine I 131 was granted FDA breakthrough therapy designation for the treatment of WM. I will now focus on the FDA strategy for iopofosine based on these outcomes. Following the breakthrough designation and an analysis of data from the Phase IIb CLOVER-WaM study, including a subset analysis of patients being treated with iopofosine immediately following treatment with a Bruton Tyrosine Kinase inhibitor or BTKi treatment failures and the completion of a minimum of 12-month follow-up on all patients as requested by the FDA.

謝謝你，查德，大家早安。今年早些時候，碘泊磷I 131被FDA授予治療WM的突破性療法認定。我現在將根據這些結果重點介紹 FDA 針對碘泊磷的策略。在獲得突破性認定並對 IIb 期 CLOVER-WaM 研究的數據進行分析後，包括對接受布魯頓酪氨酸激酶抑製劑治療或 BTKi 治療失敗後立即接受碘泊磷治療的患者進行子集分析，並根據 FDA 的要求對所有患者完成至少 12 個月的隨訪。

Cellectar has decided to shift our regulatory strategy to pursue accelerated approval for iopofosine I 131 using the CLOVER-WaM study data. During our discussions with the FDA late last year, it was clear that if we wanted to pursue an accelerated approval using the CLOVER-WaM study data, we would need to move to an earlier line of treatment for confirmatory study and would also need to include a minimum of 12 months of follow-up from time of response for all patients in our NDA package.

Cellectar 已決定改變我們的監管策略，利用 CLOVER-WaM 研究數據尋求對碘泊磷 I 131 的加速批准。在去年年底與 FDA 的討論中，我們明確表示，如果我們想利用 CLOVER-WaM 研究數據尋求加速批准，我們需要轉向更早的治療線進行確認性研究，並且還需要對我們 NDA 包中的所有患者從出現反應之日起進行至少 12 個月的隨訪。

The subset analysis that has been conducted demonstrates the potential for iopofosine to be highly effective in an earlier line of therapy, i.e., post-BTKi failure, which is now commonly used in the first-line setting. This, combined with the now minimum of 12 months of data on all patients allow us to advance this regulatory strategy contingent upon sufficient funding and a confirmatory study being underway at the time of regulatory action, which would be expected approximately eight months post submission or six months post filing given the breakthrough designation.

已進行的子集分析表明，碘泊磷在早期治療（即 BTKi 治療失敗後）中具有很高的療效，目前常用於一線治療。結合目前所有患者至少 12 個月的數據，我們可以推進這項監管策略，但前提是有足夠的資金和在監管行動時正在進行的確認性研究，預計這將在提交申請後約八個月或申請後六個月完成，因為獲得了突破性的認定。

I will now provide an update on our two exciting Phase I-ready radio conjugates. The first is CLR 121125 or CLR 125, our lead Auger-emitting compound. Our second and alpha-emitting actinium-based compound, CLR 121225 or referred to as CLR 225. Our Auger-emitting radio conjugate product candidate, CLR 125, potentially represents the highest level of precision in targeted radiotherapy with its emissions traveling only a few nanometers.

我現在將提供有關我們兩個令人興奮的、已進入第一階段的放射性共軛的最新資訊。第一個是 CLR 121125 或 CLR 125，我們的領先俄歇發射化合物。我們的第二種會發射α射線的錒基化合物是 CLR 121225，或稱為 CLR 225。我們的俄歇發射放射性共軛候選產品 CLR 125 可能代表了標靶放射治療的最高精度水平，其發射距離僅為幾奈米。

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 CLR125 demonstrate significant tumor uptake and activity with enhanced tolerability across multiple challenging animal models, including triple-negative breast cancer or TNBC and metastatic breast cancer.

我們的遞送機制提供了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 CLR125 在多種具有挑戰性的動物模型中表現出顯著的腫瘤攝取和活性，並增強了耐受性，包括三陰性乳腺癌或 TNBC 和轉移性乳腺癌。

Building on these promising preclinical results with CLR 125, we have submitted a Phase Ib dose-finding study protocol to the FDA for the treatment of triple-negative breast cancer, including metastatic disease and are now able to initiate the study pending Institutional Review Board or IRB sign-off.

基於 CLR 125 的這些有希望的臨床前結果，我們已向 FDA 提交了用於治療三陰性乳癌（包括轉移性疾病）的 Ib 期劑量探索研究方案，現在可以啟動該研究，等待機構審查委員會或 IRB 簽字批准。

The proposed Phase Ib dose-finding study in relapsed TNBC will utilize dosimetry to determine tumor versus normal tissue uptake and evaluate the activity of 3 distinct doses of CLR125, 32.75 millicuries per dose for four cycles versus 62.5 millicuries per dose for 3 cycles and 95 millicuries per dose for two cycles with four doses per cycle in 15 patients per arm with a planned expansion arm.

建議的針對複發性 TNBC 的 Ib 期劑量探索研究將利用劑量測定法來確定腫瘤與正常組織的攝取情況，並評估 3 種不同劑量 CLR125 的活性，其中 4 個週期每劑 32.75 毫居里、3 個週期每劑 62.5 毫居里和 2 個週期每劑 95 名患者計劃 5 名患者 5 名

The primary endpoint of the study will be to determine the recommended Phase II dose and dosing regimen and will also evaluate safety and tolerability as well as initial response assessments per RECIST as well as progression-free survival in patients. Our confidence in CLR 125 is grounded in its molecular similarity to iopofosine I-131, designed to provide targeted delivery of iodine radioisotopes for which we have evidence supporting proof of concept and tolerability from the CLOVER-WaM Phase IIb clinical trial.

研究的主要終點是確定建議的 II 期劑量和給藥方案，並將評估安全性和耐受性以及根據 RECIST 的初步反應評估以及患者的無惡化存活期。我們對 CLR 125 的信心源於其與碘泊磷 I-131 的分子相似性，旨在提供碘放射性同位素的靶向輸送，我們有證據支持 CLOVER-WaM IIb 期臨床試驗的概念驗證和耐受性。

Leveraging dosimetry imaging to measure drug delivered directly to the tumors is expected to provide CLR 125 proof of concept of the therapeutic window and appropriate dosing. Initiating this Phase Ib study in late 2025 or early 2026 will mark a significant milestone and an important step towards evaluating the safety and optimal dosing of CLR 125 in patients, ultimately providing a potential new treatment option for those patients afflicted by this challenging disease.

利用劑量影像來測量直接輸送到腫瘤的藥物有望為 CLR 125 治療窗口和適當劑量的概念證明提供基礎。2025 年末或 2026 年初啟動這項 Ib 期研究將標誌著一個重要的里程碑，也是評估 CLR 125 在患者中的安全性和最佳劑量的重要一步，最終為受這種棘手疾病折磨的患者提供一種潛在的新治療選擇。

Looking now to CLR 225, our lead alpha-emitting radio conjugate product candidate. To date, it has shown excellent biodistribution and uptake into solid tumors and demonstrated activity across multiple solid tumor animal models, including four distinct refractory pancreatic cancer models. CLR 225 has been observed to be well tolerated in these experiments. The Phase I trial for CLR 225 is designed to comprehensively evaluate the compound's biodistribution, safety and tolerability in patients with pancreatic adenocarcinoma.

現在來看看 CLR 225，我們的主要 α 發射放射性共軛產品候選物。迄今為止，它已顯示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，包括四種不同的難治性胰腺癌模型。在這些實驗中觀察到 CLR 225 具有良好的耐受性。CLR 225 的 I 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。

The study will commence with a dosimetry phase aimed at determining the absorbed dose in both normal and tumor tissues. The initial assessment will provide valuable insights into the compound's biodistribution and potential therapeutic window, laying the foundation for subsequent phases of the trial and future development.

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。初步評估將為該化合物的生物分佈和潛在治療窗口提供寶貴的見解，為後續試驗階段和未來發展奠定基礎。

Following dosimetry, the study will progress to a dose escalation phase systematically evaluating increasing doses of CLR 225 to establish the maximum tolerated dose. This approach offers an opportunity to demonstrate proof of concept for our innovative combination of phospholipid ether or PLE technology with alpha emitters, potentially showcasing its radio conjugates 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 225 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或 PLE 技術與 α 發射體進行創新組合提供了概念驗證的機會，有可能展示其放射性結合物安全治療大型實體腫瘤的獨特能力。

It is important to note that the initiation of this trial is dependent on the company obtaining the necessary funding. With that overview, let me turn the call back to Jim for closing remarks. Jim?

值得注意的是，這項試驗的啟動取決於公司是否獲得必要的資金。概述完畢後，請容許我將電話轉回給吉姆，請他作最後發言。吉姆？

Thanks, Jarrod. As we reflect on the first half of 2025, I'm incredibly proud of the progress our team has made across every dimension of our business from clinical development and regulatory strategy to operational excellence. We've laid a strong foundation for what we believe will be an important growth opportunity for Cellectar.

謝謝，賈羅德。回顧 2025 年上半年，我為我們的團隊在從臨床開發和監管策略到卓越營運等業務各個方面取得的進步感到無比自豪。我們已經為 Cellectar 的重要成長機會奠定了堅實的基礎。

With breakthrough therapy and prime designations in hand for iopofosine and what we believe is compelling clinical data, we have defined a clear regulatory strategy for accelerated approval in the US and remain engaged with the EMA regarding advice on a conditional marketing authorization approval in Europe, for which we anticipate a decision late in the third or early in the fourth quarter of 2025.

憑藉碘泊磷的突破性療法和主要指定以及我們認為令人信服的臨床數據，我們已經制定了在美國加速批准的明確監管策略，並繼續與 EMA 就歐洲有條件上市許可批准提供建議，我們預計將在 2025 年第三季度末或第四季度初做出決定。

At the same time, our next-generation pipeline assets are advancing rapidly. CLR 125 and CLR 225 represent exciting opportunities to expand our impact into solid tumors. As we look ahead, our focus remains clear to deliver transformative radiopharmaceutical therapies to patients with cancer efficiently globally and with purpose. We are grateful for the continued support of our investors, our collaborators and most importantly, the patients and families who inspire our work every day.

同時，我們的下一代管道資產正在快速推進。CLR 125 和 CLR 225 代表著將我們的影響力擴展到實體腫瘤領域的令人興奮的機會。展望未來，我們的重點依然是在全球範圍內有目的地為癌症患者提供變革性的放射性藥物療法。我們感謝投資人、合作者的持續支持，最重要的是感謝每天激勵我們工作的病人和家屬。

Thank you again for joining us this morning. We look forward to sharing more updates as we continue to execute on our mission and advance toward key milestones in the months ahead.

再次感謝您今天早上加入我們。我們期待在未來幾個月繼續執行我們的使命並朝著關鍵里程碑邁進的過程中分享更多更新。

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

接線員，我們已準備好開始問答環節。

(Operator Instructions) Fanyi Zhong, Oppenheimer.

（操作員指令）鐘凡一，奧本海默。

This is Fanyi on for Jeff. A couple of questions. First, for WM program, where do you stand with the EU on the path to approval? And then for 125 programs, for the preclinical biodistribution data on these molecules, what are the off-target sites of the greatest concern with that platform?

這是 Fanyi 為 Jeff 表演的。有幾個問題。首先，對於WM計劃，您與歐盟在批准道路上的立場如何？那麼對於 125 個項目，對於這些分子的臨床前生物分佈數據，該平台最擔心的脫靶位點是什麼？

Thank you, Fanyi. So let me see if I captured the first question correctly. feel free to correct me or guide me if I don't answer it fully. But iopofosine I 131, as we look to the approval pathway, and I'll say for the FDA, obviously, we have continuing discussions for conditional market authorization in the coming weeks with the EMA.

謝謝你，凡妮。所以讓我看看我是否正確地回答了第一個問題。如果我沒有完全回答，請隨時糾正我或指導我。但是，當我們考慮碘泊磷 I 131 的批准途徑時，我想對 FDA 說，顯然，我們將在未來幾週與 EMA 繼續討論有條件的市場授權。

But for the FDA, where we sit now is finalization of a protocol for an accelerated approval confirmatory study and where we sit with regard to the submission for the NDA. I think as we've referred to in the past, we have largely completed most of the NDA package.

但對於 FDA 來說，我們現在所處的位置是最終確定加速批准確認研究的方案，以及提交 NDA 的相關事宜。我認為，正如我們過去提到的，我們已經基本完成了大部分保密協議。

We now -- now that we have the 12-month follow-up data that we're referring to and independent review committee's review of the data, confirming the response rates and durability of those responses, we are now finalizing the clinical portion of the data package with the idea that pending sufficient capital, we'd be in a position to submit later this year or at the latest early next year.

現在，我們已經獲得了所指的 12 個月的追蹤數據以及獨立審查委員會對數據的審查，確認了回應率和回應的持久性，我們現在正在最終確定數據包的臨床部分，並認為，只要有足夠的資金，我們就可以在今年晚些時候或最遲明年年初提交。

The only other thing I'll add to that, Jarrod's thorough response is as we thought about the shift in regulatory strategy here with our friends at the FDA, it was important to note, and as Jarrod highlighted in his overview a few moments ago, was that we now have 12 months of follow-up on all patients that we were required to for this study, which was a prerequisite to apply for this more, let's call it, a traditional accelerated approval pathway.

我要補充的另一件事是，賈羅德的全面回應是，當我們與 FDA 的朋友們一起思考監管策略的轉變時，值得注意的是，正如賈羅德剛才在他的概述中強調的那樣，我們現在對本研究所需的所有患者進行了 12 個月的跟踪，這是申請此項研究的先決條件，我們稱之為傳統的加速審批途徑。

And then additionally, with that traditional accelerated approval pathway, the company was obligated to advance iopofosine up into earlier lines of therapy. And at that point in time, we did not have data to support that transition to earlier lines of therapy. Based on an analysis of the data that we currently have, the company remains highly confident that post BTKi failures regardless of line of therapy that this drug would perform very, very well.

此外，透過傳統的加速審批途徑，該公司有義務將碘泊磷推進到早期治療領域。而在那個時候，我們還沒有數據支持轉向早期治療方法。根據我們目前掌握的數據的分析，公司仍然非常有信心，無論 BTKi 治療失敗後，這種藥物都會表現得非常非常好。

So that gives us now confidence to advance further upstream into second line. And as you're likely aware, there's been a significant transition to the utilization of a combination with ibrutinib and a BTKI, let's say, ibrutinib in the first line of therapy. And as that number continues to increase, that second line now becomes available for post BTK treatment such as iopofosine.

因此，這讓我們有信心進一步向上游推進至第二線。您可能已經知道，目前已發生了重大轉變，開始使用依魯替尼和 BTKI 的組合療法，例如將依魯替尼作為一線療法。隨著這一數字不斷增加，現在可以採用第二線藥物進行 BTK 後治療，例如碘泊磷。

I think I will also mention that we did receive breakthrough designation from the FDA in late May, which is also factored into this as well. So we have -- we go into this with an approach with a higher degree of confidence based on the data that we have from the Phase II CLOVER-WaM study.

我想我也會提到，我們確實在 5 月底獲得了 FDA 的突破性認定，這也是其中的一個因素。因此，我們根據從第二階段 CLOVER-WaM 研究中獲得的數據，以更高程度的信心來處理這個問題。

And then Fanyi, and I think your second question then was on the biodistribution of CLR 125?

然後是范毅，我認為您的第二個問題是關於 CLR 125 的生物分佈？

Yeah.

是的。

Yeah. So I'll summarize because it takes too long to go through all of it, but let me just say this. Fundamentally, what we see is approximately 25% to 30% of the infused drug when you look -- when you evaluate it into the tumor. When you look across all other tissues, off-target tissues, so to speak, what we see is approximately less than -- and I'll say approximately less than 5% of the activity in any single tissue. As one might expect, probably the most common tissue that you tend to see accumulation in is the liver. But again, it's well below 5% or around 5%, I should say, for that, so well below a concerning level.

是的。所以我來總結一下，因為講完所有內容需要很長時間，但我只想說這一點。從根本上來說，當您觀察腫瘤時，我們會看到大約 25% 到 30% 的注射藥物。當你觀察所有其他組織，也就是非目標組織時，我們看到的大約不到——我想說大約不到任何單一組織中活動的 5%。正如人們所預料的那樣，最常見的積聚組織可能是肝臟。但同樣，我應該說，它遠低於 5% 或 5% 左右，因此遠低於令人擔憂的水平。

And post this call, based on the news that we've released this morning, we'll be updating our corporate presentation on the website. And there is a significant amount of new data relative to our preclinical work with a series of radioisotopes, which includes CLR 125 and the Auger-emitting work.

發布此電話後，根據我們今天早上發布的新聞，我們將在網站上更新我們的公司介紹。並且，關於我們對一系列放射性同位素進行的臨床前工作（包括 CLR 125 和俄歇發射工作）有大量新數據。

(Operator Instructions) Edward Tenthoff, Piper Sandler.

（操作員指示）Edward Tenthoff，Piper Sandler。

Congratulations. This is a really meaningful update this series of events from breakthrough designation to the 12-month data and then the commitment and decision to move into the second-line confirmatory trial, all positioning for an NDA for accelerated approval, really exciting stuff. When it comes down to the timing, when do you think you would submit this NDA? And you mentioned the need to have the confirmatory trial underway by decision, which I assume means potential approval. So how much has it cost to kind of submit and get iopofosine I 131 approved?

恭喜。這是一個非常有意義的更新，這一系列事件從突破性進展到 12 個月的數據，再到進入二線確認試驗的承諾和決定，所有這些都是為了加速批准 NDA，這真的令人興奮。說到時間，您認為您什麼時候會提交這份保密協議？您提到需要透過決定進行確認試驗，我認為這意味著潛在的批准。那麼提交並獲得碘泊磷 I 131 批准需要花費多少錢？

That's a great question, Ted. I'll open with some of the financials related to this, and then we could have Jarrod walk us through some of the nuance associated with the accelerated approval pathway. It's similar to what you just described.

泰德，這個問題問得真好。我將首先介紹一些與此相關的財務情況，然後讓賈羅德向我們介紹與加速審批途徑相關的一些細微差別。這和你剛才描述的很像。

But our estimate on the study is approximately $40 million to $45 million. And I believe we're in this kind of $20 million to $25 million range for full enrollment and to secure the necessary data and then back-ended beyond full enrollment and initial data is the follow-up costs associated with the follow-up of the study.

但我們對這項研究的估計約為 4,000 萬至 4,500 萬美元。我相信，我們需要花費 2000 萬到 2500 萬美元來完成全面招生和確保必要的數據，而除了全面招生和初始數據之外，還需要花費與研究後續相關的後續成本。

So as you think about it, we would require approximately $20 million, $25 million to complete study enrollment, get it up rolling, finalize enrollment and see some early top line data. And then the remainder of that $40 million, $45 million would be a function of follow-up.

所以，正如您所想，我們需要大約 2000 萬美元、2500 萬美元來完成研究招生、啟動研究、完成招生並查看一些早期的頂線數據。然後剩下的 4000 萬美元、4500 萬美元將用於後續工作。

Yeah. So Ted, I'll add to that with regard to some of the extra details. And one of them would be, as we think about it, and I think this links to your question, the timing, right? So the requirement by the guidance and by the FDA is that at the time of submission, the study needs to be initiated. Now the definition of initiated is not defined. I know -- as industry, we generally think of that as first patient enrolled. But for the FDA, they have made it clear that they don't have necessarily the exact same definition.

是的。所以泰德，我會補充一些額外的細節。其中之一就是，當我們思考這個問題時，我認為這與您的問題有關，即時機，對嗎？因此，指南和 FDA 的要求是，在提交時需要啟動研究。現在，發起的定義尚未明確。我知道——作為一個行業，我們通常認為這是第一位患者的入組。但對 FDA 來說，他們已經明確表示，他們的定義不一定完全相同。

To your point, then by the time of regulatory action, which is assumed to be an approval timing point, would be that, that would -- at that point, you would have enrollment ongoing, as they call it. And again, there is not a specific number of patients that would need to be enrolled by that time point.

就您的觀點而言，那麼到採取監管行動時，也就是假定批准的時間點，那將是 — — 那時，您將會進行持續的註冊，正如他們所說的那樣。再次強調，到那時並沒有規定需要招募的具體患者人數。

Our interpretation and based on what the guidance -- what the FDA has said to us and going back to your portion of your question, in order to initiate the study, you can think that somewhere between, as Jim laid out, the total cost, somewhere between 25% to 30% of the money needs to be utilized is actually spent with the CRO at the time of initiation, so somewhere in the $10 million to $12 million-ish range to get the study up and operating.

我們的解釋以及基於指導意見——FDA 對我們說的話，回到您問題的部分，為了啟動這項研究，您可以認為，正如 Jim 所述，總成本中，需要使用的資金的 25% 到 30% 實際上是在啟動時花在 CRO 上的，所以要啟動和運行這項研究，大約需要 1000 萬美元到 1200 萬美元左右。

That said, we've already prepped for all this. As you might imagine, we've already have a CRO prepared to initiate. We have the quote, we have the contracts. So we've sort of outlined all of this ahead of time. So we're ready to run either if we were funded or with a partner to execute this in a rapid fire sort of method.

也就是說，我們已經為這一切做好了準備。正如您可能想像的那樣，我們已經有一位 CRO 準備啟動。我們有報價，我們有合約。因此，我們提前概述了所有這些內容。因此，如果我們獲得資金或與合作夥伴一起以快速的方式執行此操作，我們就準備好運作了。

Which is why when you asked the question about our exact timing, it might be later this year or early next year because we didn't want to have that study initiated prior to the submission, just we probably check a little extra box just so that we have time in a rare disease setting like this to have enough sufficient enrollment by the time that 6-month window based off the fast track and breakthrough designation, which gives us that accelerated review time line.

這就是為什麼當您詢問我們確切的時間安排時，可能是在今年晚些時候或明年年初，因為我們不想在提交之前啟動這項研究，我們可能會勾選一些額外的選項，這樣我們就有時間在這種罕見疾病環境中，根據快速通道和突破性指定的 6 個月窗口期，獲得足夠的註冊人數，這為我們提供了加速審查的時間表。

I would also add, Ted, thank you, Jarrod. I would also add that we would anticipate study enrollment to be very rapid based on the availability of our Phase II CLOVER-WaM data out in the public domain, the WM patient population is highly communicative among each other. They're very aware of the data.

我還要補充一點，泰德，謝謝你，賈羅德。我還要補充一點，根據我們第二階段 CLOVER-WaM 數據在公共領域的可用性，我們預計研究招募將會非常迅速，WM 患者群體之間溝通非常密切。他們非常了解這些數據。

And we would anticipate that as a result of that and the outstanding performance of our drug, both from a response perspective as well as durability just based on the four single infusions over approximately 70 days is going to be very, very attractive for these patients and we've already received significant feedback.

我們預計，由於這一點以及我們藥物的出色表現，無論是從反應角度還是基於大約 70 天內四次單次輸注的持久性來看，這些藥物對這些患者來說都非常有吸引力，而且我們已經收到了大量反饋。

I think the other element here that's important from a rapid enrollment perspective is the thought leadership is very aware of this drug. And most of the sites that we used, especially those that enrolled very quickly and in large numbers have already expressed interest in participating in the confirmatory trial. Jarrod, anything else to add about that?

我認為從快速招募的角度來看，另一個重要的因素是思想領導階層非常了解這種藥物。我們使用的大多數站點，特別是那些招募速度非常快且人數眾多的站點，已經表示有興趣參與確認性試驗。賈羅德，還有什麼要補充的嗎？

Yeah. Thank you, Jim. I would add the one piece I would add to what Jim has outlined there for rapid enrollment is also the concept, as you also noted, Ted, which is moving to an earlier line of treatment. Jim sort of outlined before, this post-BTKi patient population with so many, nearly 50% and growing of patients receiving rituximab and ibrutinib in the first-line setting or BTKi in that first-line setting, it offers a significantly larger patient population to pull from to enroll into the study. And that as well, we believe will add to the speed and quickness of the study getting completed. So we do think that the overall time line for completion and getting to the primary endpoint of the study will be much more -- much quicker.

是的。謝謝你，吉姆。我想補充一點，吉姆所概述的快速招生概念，正如泰德所說，它正在轉向更早期的治療。Jim 之前曾概述過，BTKi 後患者群體如此之多​​，幾乎有 50% 的患者在一線環境中接受利妥昔單抗和依魯替尼治療，或者在一線環境中接受 BTKi 治療，並且這一比例還在不斷增長，這為從中招募更大的患者群體來參與研究提供了可能。我們也相信這將加快研究完成的速度。因此，我們確實認為，完成研究並達到主要終點的整體時間將會快得多。

(Operator Instructions) No further questions that came through. I'll now turn the call over back to James Caruso for closing remarks. Please go ahead, sir.

（操作員指示）沒有其他問題。現在我將把電話轉回給詹姆斯卡魯索，請他做最後發言。先生，請繼續。

Thank you, operator, and thanks again for joining us this morning. We certainly look forward to sharing more updates as we continue to execute on our mission and advance towards these key milestones that we discussed this morning in the months ahead.

謝謝接線員，再次感謝您今天早上加入我們。我們當然期待在未來幾個月繼續執行我們的使命並朝著我們今天上午討論的這些關鍵里程碑邁進時分享更多更新。

Thank you. This concludes our conference call for today. Thank you all for participating. You may now disconnect.

謝謝。今天的電話會議到此結束。感謝大家的參與。您現在可以斷開連線。