Cellectar Biosciences Inc (CLRB) 2024 Q2 法說會逐字稿

Good morning, and welcome to Cellectar Biosciences second quarter 2024 financial results call. Today's call is being recorded.

早安，歡迎參加 Cellectar Biosciences 2024 年第二季財務業績電話會議。今天的通話正在錄音。

Before we begin, I would like to remind everyone that statements made during this call relating to Cellectar's expected future performance, future business prospects or future events or plans are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995.

在我們開始之前，我想提醒大家，在本次電話會議中所做的有關Cellectar 預期未來業績、未來業務前景或未來事件或計劃的陳述屬於1995 年《私人證券訴訟改革法案》所定義的前瞻性陳述。

Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions, actual outcomes and results are subject to risks and uncertainties that could differ materially from those forecast due to the impact of many factors beyond the control of Cellectar. The company assumes no obligation to update or supplement any forward-looking statements, whether as a result of new information, future events, or otherwise.

儘管該公司認為此類前瞻性聲明中反映的預期是基於合理的假設，但實際結果和結果會受到風險和不確定性的影響，由於許多Cellectar 無法控制的因素的影響，這些風險和不確定性可能與預測有重大差異。本公司不承擔更新或補充任何前瞻性陳述的義務，無論是由於新資訊、未來事件或其他原因。

Participants are directed to the cautionary notes set forth in today's press release which is available on the Investor Relations portion of the company's website as well as the risk factors set forth in Cellectar's annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward-looking statements.

參與者請參閱今天新聞稿中列出的警告說明（可在公司網站的投資者關係部分獲取）以及 Cellectar 向 SEC 提交的年度報告中列出的風險因素，以了解可能導致實際結果不同的因素與前瞻性陳述中的預期有重大差異。

At this time, I would like to turn the call over to Jim Caruso, President and Chief Executive Officer of Cellectar. Mr. Caruso, please go ahead.

現在，我想將電話轉給 Cellectar 總裁兼執行長 Jim Caruso。卡魯索先生，請繼續。

Thank you, operator, and good morning, everyone. It is my pleasure to be here with you to provide a corporate update for our second quarter of 2024. With me today are Dr. Andrei Shustov, Senior Vice President, Medical; Jarrod Longcor, Chief Operating Officer; Shane Lea, Chief Commercial Officer; and Chad Kolean, Chief Financial Officer.

謝謝接線員，大家早安。我很高興與您一起提供 2024 年第二季的公司最新情況。今天與我在一起的有醫療高級副總裁安德烈·舒斯托夫 (Andrei Shustov) 博士； Jarrod Longcor，營運長； Shane Lea，首席商務官；和財務長查德‧科林 (Chad Kolean)。

I will begin today with a brief recap of our progress over the past quarter and discuss anticipated near-term milestones.

今天，我將首先簡要回顧我們過去一個季度的進展，並討論預期的近期里程碑。

I will then ask Chad to provide an update on our financials. Andrei will follow with additional insights regarding our CLOVER WaM pivotal study, followed by Jarrod, who will provide an operations update on the regulatory front and manufacturing. Finally, Shane will review our commercial progress. We will then open the call for Q&A.

然後我將要求乍得提供我們財務狀況的最新資訊。Andrei 將提供有關 CLOVER WaM 關鍵研究的更多見解，隨後 Jarrod 將提供監管方面和製造方面的營運最新資訊。最後，Shane 將回顧我們的商業進展。然後我們將開始問答環節。

As you are likely aware, on July 23, we announced our full data results from our pivotal trial in WM, which are truly impressive and maintain the potential to meaningfully improve upon the current standard of care in WM.

您可能知道，7 月 23 日，我們公佈了 WM 關鍵試驗的完整數據結果，這些結果確實令人印象深刻，並且有可能顯著改善 WM 當前的護理標準。

Andrei will talk to the quality of the data in an extremely challenging patient population. However, I'd like to emphasize to everyone that the patients in the clinical trial were by far the most refractory ever studied in this indication with iopofosine I-131 representing the fifth medium line treatment. It is, therefore, impressive to observe comparable results obtained in CLOVER WaM to those reported in first and second line with other treatments. Of course, our near-term organizational focus remains lock on iopofosine's WM regulatory and commercial objectives.

安德烈 (Andrei) 將討論極具挑戰性的患者群體中的數據品質。然而，我想向大家強調的是，臨床試驗中的患者是迄今為止該適應症研究中最難治的患者，碘泊福辛 I-131 代表了第五種中線治療。因此，令人印象深刻的是，在 CLOVER WaM 中觀察到的結果與第一線和二線其他治療方法所報告的結果相當。當然，我們近期的組織重點仍然鎖定碘泊福辛的 WM 監管和商業目標。

Iopofosine has also demonstrated utility in other hematologic indications such as relapsed/refractory multiple myeloma and DLBCL. And clinical development is ongoing in our Phase 1b for pediatric high-grade gliomas.

碘磷辛也被證明可用於其他血液學適應症，例如復發/難治性多發性骨髓瘤和 DLBCL。我們針對兒童高級別膠質瘤的 1b 期臨床開發正在進行中。

As you may recall, we initiated and enrolled the first patient in this Phase 1b study earlier this year. With iopofosine's ability to cross the blood-brain barrier, we remain excited about the potential it may provide in this high unmet medical need treatment setting. We plan to provide a study update in the second half of this year.

您可能還記得，我們​​在今年稍早發起並招募了第一位患者參加這項 1b 期研究。由於碘泊福辛具有穿過血腦屏障的能力，我們對其在這種高度未滿足的醫療需求治療環境中可能提供的潛力感到興奮。我們計劃在今年下半年提供研究更新。

Beyond iopofosine, our PDC platform continues to serve as the backbone to our radiotherapeutic franchise. We have now successfully conjugated nearly all available isotopes with our platform, including beta, OG, and alpha emitters, and have completed extensive preclinical proof of concept work in each area.

除了碘泊磷之外，我們的 PDC 平台仍然是我們放射治療專營權的支柱。現在，我們已經成功地將幾乎所有可用的同位素與我們的平台結合，包括 β、OG 和 α 發射體，並在每個領域完成了廣泛的臨床前概念驗證工作。

We are currently advancing one of our actinium-based conjugates through IND-enabling studies in preparation for a Phase 1 in solid tumors. We continue to focus on completing the work for our NDA filing with plans to submit our filing to the FDA in the fourth quarter. Assuming we are granted priority review associated with our fast track designation, we expect a six-month review.

我們目前正在透過 IND 支持研究來推進我們的一種基於錒的綴合物，為實體瘤的一期臨床試驗做準備。我們繼續專注於完成 NDA 備案工作，並計劃在第四季度向 FDA 提交備案。假設我們獲得與快速通道指定相關的優先審查，我們預計審查時間為六個月。

Finally, prior to turning the call to Chad for greater detail, I would like to emphasize that the 8-K filed this past Friday, indicating that we are in process of restating our recent historical financial statements, although unfortunate, does not impact cash or cash burn and the changes to historical earnings will all be non-operating and non-cash. Chad?

最後，在致電乍得以了解更多細節之前，我想強調上週五提交的 8-K，表明我們正在重述我們最近的歷史財務報表，儘管不幸的是，但這並不影響現金或現金消耗和歷史收益的變動都將是非經營性和非現金的。查德?

Thank you, Jim. Our cash and cash equivalents balance as of June 30, 2024, was $25.9 million compared to $9.6 million as of December 31, 2023. To note that at the end of the first quarter, we had a cash balance of $40 million, resulting in the net cash used in operating activities during the second quarter being approximately $14.1 million.

謝謝你，吉姆。截至 2024 年 6 月 30 日，我們的現金及現金等價物餘額為 2,590 萬美元，而截至 2023 年 12 月 31 日為 960 萬美元。需要注意的是，第一季末，我們的現金餘額為 4,000 萬美元，導致第二季經營活動使用的淨現金約為 1,410 萬美元。

In addition to the cash on hand at the end of June, in July, nearly all of the investors from the September 2023 financing exercised their Tranche B warrants at a reduced as-converted common stock price of $2.52 per share. Those investors who exercised their Tranche B warrants also received new warrants as part of the transaction, which generated gross upward proceeds of approximately $19.4 million before customary expenses and fees.

除了 6 月底手頭上的現金之外，7 月份，幾乎所有 2023 年 9 月融資的投資者都以每股 2.52 美元的轉換普通股價格行使其了 B 部分認股權證。作為交易的一部分，行使 B 部分認股權證的投資者還收到了新的認股權證，在扣除常規費用和費用之前，該交易產生了約 1,940 萬美元的總收益。

The company believes its cash on hand, inclusive of the July warrant exercise proceeds, it's adequate to fund budgeted operations into the second quarter for 2025.

該公司認為，其手頭現金（包括 7 月認股權證行權收益）足以為 2025 年第二季的預算營運提供資金。

The three warrant tranches issued last month provide potential additional funding based upon their respective expiration dates, which occur with a first tranche of approximately $17 million after we received a PDUFA date in the FDA, a second tranche of approximately $32.9 million after we receive approval of iopofosine I-131 from the FDA, and a third tranche of approximately $23.5 million after the first quarter in which we generate $10 million in revenue from iopofosine I-131. Assuming our discussions with the FDA go as planned, this funding would get Cellectar to the point where we will be cash flow positive.

上個月發行的三批認股權證根據各自的到期日期提供了潛在的額外資金，其中第一批資金約為1700 萬美元，是在我們收到FDA 的PDUFA 日期後，第二批資金約為3290 萬美元，是在我們收到批准後進行的。 -131 中獲得了1000 萬美元的收入。假設我們與 FDA 的討論按計劃進行，這筆資金將使 Cellectar 達到現金流量正值。

Turning back to the second quarter, R&D expense was approximately $8.2 million, compared to $6.3 million in the second quarter of 2023. The increase is largely driven by the timing of expenditures for our WM pivotal trial to support patients' final visits and perform the extensive analytical work necessary to complete the NDA submission. We have also continued investing substantial in our product sourcing, manufacturing and logistics infrastructure by developing multiple sources for each aspect of iopofosine production.

回到第二季度，研發費用約為 820 萬美元，而 2023 年第二季為 630 萬美元。這一增長主要是由我們的 WM 關鍵試驗的支出時間推動的，該試驗旨在支持患者的最終就診並進行完成 NDA 提交所需的廣泛分析工作。我們也透過為碘泊膦生產的各個方面開發多種來源，繼續對產品採購、製造和物流基礎設施進行大量投資。

G&A expense for the second quarter of 2024 was $6.4 million, compared to $2.0 million last year. This incremental spend is focused on the establishment of the necessary commercialization capabilities to support product sales upon our expected 2025 NDA approval.

2024 年第二季的一般管理費用為 640 萬美元，而去年為 200 萬美元。這項增量支出主要用於建立必要的商業化能力，以支持我們預計在 2025 年 NDA 獲得批准後的產品銷售。

As Jim stated earlier, we filed an 8-K with the SEC indicating that we are in the process of restating our historical financial statements for fiscal years 2022 and 2023 in the first quarter of this year. This was precipitated by a re-evaluation of the accounting for the warrants issued in October 2022. At the time they were issued, the warrants were classified as equity. This was based on our assessment, which was supported by third-party expert evaluation.

正如 Jim 之前所說，我們向 SEC 提交了 8-K，表明我們正在今年第一季重述 2022 財年和 2023 財年的歷史財務報表。這是由於對 2022 年 10 月發行的認股權證的會計重新評估而促成的。發行時，認股權證被歸類為股權。這是基於我們的評估，並得到第三方專家評估的支持。

We now believe they should be classified as liabilities, necessitating a revision in our historical reporting. While previously reported earnings will be modified, the restatement does not impact cash or cash burn and the changes to historical earnings will all be non-operating and non-cash. The work required to restate the historical results is in process and must be completed before we can file in the second quarter 10-Q, which delays the 10-Q filing. We are performing this work as rapidly as possible. And while we do not have a definite target date for completion, we expect it will take approximately six weeks.

我們現在認為它們應該被歸類為負債，因此有必要對我們的歷史報告進行修訂。雖然先前報告的收益將被修改，但重述不會影響現金或現金消耗，且歷史收益的變化將全部是非經營性和非現金的。重述歷史結果所需的工作正在進行中，必須在我們提交第二季 10-Q 報告之前完成，這會延遲 10-Q 報告。我們正在盡快進行這項工作。雖然我們沒有確定的完成目標日期，但我們預計大約需要六週。

With that, I will now turn the call over to Andrei.

現在，我將把電話轉給安德烈。

Thank you, Chad, and good morning, everyone. Recently, we provided an update on the topline results from our pivotal CLOVER WaM study that is fully enrolled with all living patients who have completed study treatment remaining in long-term follow-up.

謝謝查德，大家早安。最近，我們提供了關鍵 CLOVER WaM 研究的最新結果，該研究已完全納入所有已完成研究治療且仍處於長期追蹤的在世患者。

There are 65 patients in the safety data set defined as all patients receiving at least one dose of iopofosine I-131, and there are 55 patients who met the criteria for inclusion in the efficacy valuable set defined as all patients who have received at least 60 millicurie total administered dose and have undergone at least one response assessment. The response rates and safety data discussed today are as of May 31, 2024, data cutoff date.

安全資料集中有 65 名患者，定義為所有接受至少一劑碘泊福辛 I-131 的患者，有 55 名患者符合納入療效價值組的標準，定義為所有接受至少 60 劑的患者毫居里總給藥劑量並已接受至少一次反應評估。今天討論的回覆率和安全數據截至數據截止日期 2024 年 5 月 31 日。

As a reminder, CLOVER WaM is a global single-arm Phase 2b study examining iopofosine I-131 in relapsed and refractory patients who have received at least two prior lines of therapy, including those patients who failed or have suboptimal response to BTKi, the only FDA-approved class of treatment for this cancer.

需要提醒的是，CLOVER WaM 是一項全球單臂2b 期研究，在接受過至少兩種既往治療的複發和難治性患者中檢查碘泊福辛I-131，包括那些對BTKi 治療失敗或反應欠佳的患者，BTKi 是唯一的治療方案。

Study patients received a total of four doses of iopofosine I-131 over two cycles without maintenance or retreatment and were evaluated for response at regular protocol-defined intervals using standard IWWM criteria.

研究患者在兩個週期內總共接受了四劑碘泊福辛 I-131，無需維持或再治療，並使用標準 IWWM 標準按照方案規定的定期間隔評估療效。

As Jim stated, patients enrolled in CLOVER WaM were the most heavily pretreated and the most refractory WM patient population ever reported in clinical trials. Please allow me to review a few key patient and disease characteristics.

正如 Jim 所說，參加 CLOVER WaM 的患者是臨床試驗中報告的預處理程度最高且最難治的 WM 患者群體。請容許我回顧一下一些關鍵的患者和疾病特徵。

The median age was 70 years with August enroll patients aged 88 years. The median number of prior therapies was 4 with a range from 2 to 14. 71% of patients were previously treated with BTKi, 91% were treated with rituximab, and 84% received prior multi-agent chemotherapy.

8 月入組的患者中位數年齡為 70 歲，年齡為 88 歲。過去治療次數中位數為 4 次，範圍為 2 至 14 次。

Over 90% of patients were refractory to at least one class of drugs with refractories to BTKi reported in 67% to rituximab in 60% and to chemotherapy in 56% of patients exposed to those treatments. 40% of all patients in the efficacy set were considered dual class refractory, including BTKi and rituximab, and 27% with triple class refractory, including BTKi, rituximab, and chemotherapy.

超過 90% 的患者對至少一類藥物有抗藥性，其中 67% 的患者對 BTKi 有抗藥性，60% 的患者對利妥昔單抗抗藥性，56% 的患者對化療有抗藥性。療效集中的所有患者中有40% 被認為是雙級難治性患者，包括BTKi 和利妥昔單抗，27% 的患者被認為是三級難治性患者，包括BTKi、利妥昔單抗和化療。

Further, more than half or 55% of CLOVER WaM patients in efficacy valuable set were considered median or high risk based on IPSS WM score, which is a recognized negative prognostic factor for progression-free survival and overall survival in WM patients treated with available therapies.

此外，根據IPSS WM 評分，療效有價值組中超過一半或55% 的CLOVER WaM 患者被認為是中位或高風險，這是公認的對接受現有療法治療的WM 患者無進展生存期和總生存期的負面預後因素。

Finally, approximately 30% were found to have wild-type MYD88 gene and known genomic factor confirm resistance to BCKi therapy.

最後，大約 30% 被發現具有野生型 MYD88 基因，並且已知的基因組因素證實了對 BCKi 療法的抗藥性。

Now let me briefly review key efficacy results. Iopofosine I-131 demonstrated an impressive and clinically relevant 80% overall response rate and 98.2% clinical benefit rate. This is highly meaningful for this elderly patient population with an incurable malignancy for these patients' annual reduction in tumor burden or even disease stability brings clinical benefit, improve symptoms, and extend progression-free survival and time off treatment.

現在讓我簡單回顧一下主要功效結果。碘磷辛 I-131 表現出令人印象深刻的臨床相關性：80% 的整體緩解率和 98.2% 的臨床受益率。這對於患有無法治癒的惡性腫瘤的老年患者群體來說非常有意義，因為這些患者每年腫瘤負擔的減少甚至疾病的穩定帶來了臨床獲益，改善症狀，並延長無進展生存期和停藥時間。

The major response rate defined as partial response or better was 56.4%, significantly exceeding the protocol-defined primary endpoint statistical hurdle of 20%. We are also excited to report that in line with our previous observation and reported trends in late responses after iopofosine therapy an additional partial response was registered after the latest data cut off, effectively bringing the MRR to 58.2%.

定義為部分緩解或更好的主要緩解率為 56.4%，顯著超過方案定義的主要終點統計門檻 20%。我們也很高興地報告，根據我們先前的觀察和報告的碘泊膦治療後晚期反應趨勢，在最新數據截止後記錄了額外的部分反應，有效地將 MRR 提高到 58.2%。

As follow-up of study patients continues, we might expect further improvement in major response rate due to delayed responses. Further, the data showed a 7.3% complete response or very good partial response rate in a patient population in which CRs have not been previously observed or reported.

隨著對研究患者的追蹤繼續進行，我們可能會預期由於延遲反應而導致主要反應率進一步提高。此外，數據顯示，在先前未觀察到或報告 CR 的患者群體中，有 7.3% 的完全緩解率或非常好的部分緩解率。

I would also like to highlight the observed high response rate to iopofosine in highly refractory and challenging to treat patient subpopulations. First, among patients with MYD88 wild-type tumors that are inherently resistant to BTKi therapy. The overall response rate was 81%. And among those previously treated with BTKi, the overall response rate was 72%.

我還想強調在高度難治性和難以治療的患者亞群中觀察到的對碘泊膦的高反應率。首先，在患有 MYD88 野生型腫瘤且對 BTKi 治療固有抗藥性的患者中。整體回應率為81%。在先前接受過 BTKi 治療的患者中，整體緩解率為 72%。

In patients with tumors refractory to both BTKi and rituximab or dual refractory, the overall response rate was 65%. And in those with tumors refractory to BTKi, rituximab and multiple chemotherapy agents or triple refractory, which are the patients with no available treatment options, the overall response rate was 54%.

對於 BTKi 和利妥昔單抗均難治或雙重難治的腫瘤患者，整體緩解率為 65%。而在那些對BTKi、利妥昔單抗和多種化療藥物具有抗藥性或三重抗藥性的腫瘤（即沒有可用治療選擇的患者）中，整體緩解率為54%。

Seeing these rate of responses in highly refractory patient population is very impressive and we believe it positions iopofosine as the standard of care for relapsed/refractory patients and for development in earlier lines of therapy. The duration of clinical benefit is critical for elderly patients with WM. The treatment-free survival enabled by iopofosine I-131 fixed course of therapy is in sharp contrast with continuous or maintenance therapy approach is currently utilized with FDA-approved agents and significantly improves patients' quality of life.

在高度難治性患者群體中看到這些反應率非常令人印象深刻，我們相信它將碘泊膦定位為復發/難治性患者的護理標準以及早期治療方案的發展。臨床獲益的持續時間對於老年 WM 患者至關重要。碘泊福辛 I-131 固定療程實現的無治療生存期與目前 FDA 批准的藥物使用的連續或維持治療方法形成鮮明對比，並顯著改善患者的生活品質。

Durability of responses in CLOVER WaM were assessed on 41 overall responders and 26 major responders at the data cutoff date on March 7, 2024, with a median follow-up of 8.8 months that did not include four additional overall responses, and five additional major responses reported at the latest cutoff date of May 31, 2024.

截至2024 年3 月7 日數據截止日期，CLOVER WaM 中的反應持久性對41 名總體反應者和26 名主要反應者進行了評估，中位隨訪時間為8.8 個月，其中不包括4 名額外的總體反應和5 名額外的主要反應報告截止日期為2024年5月31日。

The median duration of response and median progression-free survival were not reached with an estimated 72% of patients with overall response and 78% of patients with major response remaining progression-free at 18 months. This is in sharp contrast with our findings using data extracted from community-based oncology providers indicating the demand dose of approximately 10% responders in third class line of therapy.

中位緩解持續時間和中位無惡化存活期尚未達到，估計有 72% 的整體緩解患者和 78% 的主要緩解患者在 18 個月時保持無進展。這與我們使用從社區腫瘤學提供者提取的數據得出的結果形成鮮明對比，該數據顯示大約 10% 的反應者在三線治療中的需求劑量。

The duration of response is expected to be around six months. We anticipate that as our data matures, the durability enabled by both the 80% overall response and a 58% major response rate will continue to improve and position iopofosine as an attractive option in WM treatment landscape, assuming FDA approval.

預計回應持續時間約為六個月。我們預計，隨著我們數據的成熟，假設獲得FDA 批准，80% 的整體緩解率和58% 的主要緩解率所帶來的持久性將繼續改善，並使碘泊福辛成為WM 治療領域中有吸引力的選擇。

To put forward WaM results into clinical practice perspective, it is our belief that while MRR is an important endpoint that satisfies the study primary objective threshold and positions iopofosine favorably for regulatory approval and the VGPR/CR our important research endpoints that supports iopofosine as disease-modifying therapy. It is the overall response rate and clinical benefit rate combined with impressive durability and time of treatment that will drive treatment decisions in favor of iopofosine and the management of this challenging patient population.

為了將WaM 結果納入臨床實踐的角度，我們相信，雖然MRR 是滿足研究主要目標閾值的重要終點，並使碘泊福辛有利於獲得監管批准，但VGPR/CR 我們的重要研究終點支持碘泊福辛作為疾病 -修改治療。整體緩解率和臨床獲益率，加上令人印象深刻的持久性和治療時間，將推動有利於碘泊膦的治療決策以及對這一具有挑戰性的患者群體的管理。

Iopofosine I-131 was well tolerated in this vulnerable elderly patient population, possessing multiple age-related comorbidities with their bone marrow compromised by cancer and multiple prior toxic therapies. The observed safety profile remains consistent with previously reported data. Grade 3 or higher treatment-emergent adverse events occurring in more than 10% of patients in the safety population with an N of 65 were thrombocytopenia, 80%; neutropenia, 69.2%; anemia, 44.6%; lymphopenia, 13%; and all infection, 12.3%. There were no reported opportunistic or invasive fungal infections observed in the study patients.

碘泊福辛 I-131 在這一脆弱的老年患者群體中具有良好的耐受性，他們患有多種與年齡相關的合併症，其骨髓因癌症和多種先前的毒性治療而受損。觀察到的安全性概況與先前報告的數據保持一致。在 N 為 65 的安全性族群中，超過 10% 的患者發生 3 級或以上治療引起的不良事件，其中血小板減少症為 80%；中性白血球減少症，69.2%；貧血，44.6%；淋巴球減少，13%；和所有感染，12.3%。在研究患者中沒有觀察到機會性或侵襲性真菌感染的報告。

In the entirety of the study, there was only one AE-related death reported in the safety set, and it was from infection. Importantly, unlike other WM therapies, iopofosine demonstrated negligible off-target effect on solid organ systems. Patients did not experience cardiovascular, pulmonary, neurologic, renal, liver toxicities, which lead to treatment discontinuation with other available therapies in a significant proportion of patients.

在整個研究中，安全組中僅報告了 1 例 AE 相關死亡，且死亡原因為感染。重要的是，與其他 WM 療法不同，碘泊膦對實體器官系統的脫靶效應可以忽略不計。患者沒有出現心血管、肺、神經、腎、肝毒性，導致很大一部分患者停止使用其他可用療法。

To put CLOVER WaM safety results into clinical practice perspective, observed cytopenias are consistent with the age-related physiologic loss of marrow function, cumulative amount of trial myelosuppressive therapies and the degree of pre-existing inflammatory marrow suppression due to high disease burden in CLOVER WaM patients.

為了將CLOVER WaM 安全性結果納入臨床實踐的角度，觀察到的血球減少症與年齡相關的骨髓功能生理性喪失、試驗性骨髓抑制治療的累積量以及CLOVER WaM 中由於高疾病負擔導致的預先存在的發炎性骨髓抑製程度一致患者。

Two mid-cycle cytopenia occurrences were transitory and well managed. The cytopenias recovered with standard supportive care in all patients within a median two to four weeks of the nadir. Further, despite the high rate and degree of thrombocytopenia, there were no clinical significant or life-threatening bleeding events in the study. Notably, the low rate of serious infections in CLOVER WaM study patients with known immunosuppressive effect of underlying malignancy and from prior therapies is encouraging in the context of severe immunocompromised patients.

兩次週期中期血球減少症的發生是暫時的並且得到了很好的處理。所有患者的血球減少症在標準支持治療後均在最低點後兩到四周內恢復。此外，儘管血小板減少症的發生率和程度很高，但該研究中沒有發生臨床顯著或危及生命的出血事件。值得注意的是，CLOVER WaM 研究中已知具有潛在惡性腫​​瘤免疫抑製作用且接受既往治療的患者嚴重感染率較低，這在嚴重免疫功能低下患者的背景下令人鼓舞。

Effective management of cytopenias and prophylaxis of infectious attest to understanding and comfort of hematologic oncologists managing these patients both in the academic setting and in the community. It is also important to point out that with continuous treatment therapies, adverse events such as cardiotoxicity of peripheral neuropathies must be managed over the entire course of treatment or until therapy is discontinued for lack of effectiveness or intolerance with other agents.

血球減少症的有效管理和感染的預防證明了血液腫瘤學家在學術環境和社區中管理這些患者的理解和安慰。同樣重要的是要指出，在連續治療中，必須在整個治療過程中控制週邊神經病變心臟毒性等不良事件，或直到因其他藥物缺乏有效性或不耐受而停止治療為止。

In summary, CLOVER WaM was the largest study in relapsed/refractory post-BTKi patients to date and the first WM study to evaluate dual refractory and old class refractory patient populations. We believe that achieving an 80% overall response rate and 58.2% major response rate updated after the latest data cutoff with the previously noted durability is nothing short of remarkable especially with a demonstrated favorable safety profile.

總之，CLOVER WaM 是迄今為止針對 BTKi 治療後復發/難治性患者最大規模的研究，也是第一個評估雙重難治性和老年難治性患者群體的 WM 研究。我們相信，在最新數據截止後達到80% 的整體回應率和58.2% 的主要回應率，以及之前提到的耐久性，這無疑是令人矚目的，尤其是在已證明良好的安全性的情況下。

The four dose truly takes duration force of treatment and prolonged treatment-free interval will provide clinically significant and meaningful benefit for elderly patients with an incurable life-long malignancy. We also anticipate that the data will continue to mature favorable.

這四種劑量真正需要持續的治療力和延長的免治療間隔將為患有無法治癒的終身惡性腫瘤的老年患者提供臨床上顯著且有意義的益處。我們也預計數據將繼續成熟有利。

To conclude, we believe that based on the demonstrated CLOVER WaM study results, iopofosine has the potential to become first-in-class and best-in-class radio therapeutic agent to address the high clinical need for WM patients.

總而言之，我們相信，基於已證實的 CLOVER WaM 研究結果，碘泊膦有潛力成為一流且一流的放射治療劑，以滿足 WM 患者的高臨床需求。

With that, I will turn the call to Jarrod.

這樣，我會將電話轉給賈羅德。

Thank you, Andrei. As Andrei described, our clinical data from the CLOVER WaM study continues to be quite impressive and improves with time. We remain actively engaged in the review, clinical cleaning, and prepping of the CLOVER WaM pivotal study data for the near-term NDA submission. As you are aware, the NDA submission process requires relentless attention to detail and is a time-consuming project.

謝謝你，安德烈。正如 Andrei 所描述的，我們從 CLOVER WaM 研究中獲得的臨床數據仍然令人印象深刻，並且隨著時間的推移而不斷改善。我們仍然積極參與 CLOVER WaM 關鍵研究數據的審查、臨床清理和準備工作，以供近期 NDA 提交。如您所知，NDA 提交過程需要對細節的不懈關注，並且是一個耗時的專案。

For your background, the thousands of patient data points collected over the course of the study must be validated and verified. This is a process called data cleaning, which also includes identifying and correcting any data entry errors. Once this process is complete, the database is locked and the final study data sets can be produced for the NDA. This information is required for the completion of the clinical study report and the clinical sections of the NDA submission.

對於您的背景，必須對研究過程中收集的數千個患者數據點進行驗證和驗證。這是一個稱為資料清理的過程，其中還包括識別和修正任何資料輸入錯誤。此過程完成後，資料庫將被鎖定，並且可以為 NDA 產生最終研究資料集。完成臨床研究報告和 NDA 提交的臨床部分需要此資訊。

We are expediting this process by performing several of these activities in parallel. For example, as a subset of the data is clean and finalized, we use this data to complete required sections in both the clinical study report and the NDA rather than waiting for the entirety of the data to be finalized. This allows us to shorten the traditional timeline of approximately six to eight months of final study results to a submission around to four to six months to that submission timeline.

我們正在透過並行執行其中多項活動來加快這一過程。例如，由於數據的子集是乾淨且最終確定的，我們使用這些數據來完成臨床研究報告和新藥申請中所需的部分，而不是等待整個數據最終確定。這使我們能夠將最終研究結果的傳統提交時間（大約六到八個月）縮短為大約四到六個月的提交時間。

In addition to these activities, we continue to work closely with the FDA to ensure our submission meets all requirements planned remaining FDA interactions prior to the final submission include the determination of the potential need for a confirmatory study. And should the FDA require one agreement on the design of the confirmatory study and the pre-NDA meeting with submission plan for Q4 2024.

除了這些活動之外，我們還繼續與 FDA 密切合作，以確保我們的提交符合最終提交之前計劃的 FDA 剩餘互動的所有要求，包括確定驗證性研究的潛在需求。FDA 是否應該要求就驗證性研究的設計和 NDA 前會議以及 2024 年第四季的提交計劃達成協議。

Shifting now to the supply chain. Our supply chain and logistics for radiopharmaceuticals have been a challenge for some organizations. There are essentially three main components to the manufacture and supply of radiopharmaceuticals. First, the isotope; second, the carrier or targeting ligand; and third, the combined finished product.

現在轉向供應鏈。我們的放射性藥物供應鏈和物流對一些組織來說是一個挑戰。放射性藥物的製造和供應基本上由三個主要組成部分組成。首先，同位素；第二，載體或標靶配體；第三，組合成品。

Due to the infrastructure and specialized facilities necessary to produce radioactive isotopes both the sites of production and supply of these isotopes are limited, whether it's iodine-131 or actinium-225 there are selected sources globally.

由於生產放射性同位素所需的基礎設施和專門設施，這些同位素的生產和供應地點都有限，無論是碘 131 還是錒 225，全球都有選定的來源。

At Cellectar, we have adopted a strategy to contract with suppliers of the isotope directly and to establish these relationships early in our drug development process. As discussed previously, for iopofosine I-131, which utilizes iodine-131 we have contracted with and validated three separate suppliers and continue to assess additional suppliers. Our current partners provide redundancy in the isotope supply to allow uninterrupted production of iopofosine I-131 either weekly or multiple times a week.

在 Cellectar，我們採取了直接與同位素供應商簽訂合約的策略，並在藥物開發過程的早期建立這些關係。如前所述，對於利用 iodine-131 的碘泊磷 I-131，我們已與三個獨立的供應商簽訂合約並對其進行了驗證，並繼續評估其他供應商。我們目前的合作夥伴提供同位素供應冗餘，以便每週或每週多次不間斷地生產碘泊膦 I-131。

The same model is being employed for our actinium program, we are partnering with both existing and future suppliers of actinium, which will provide sufficient supply of actinium throughout the drug development process and into commercialization. This approach can be employed for a variety of radioisotopes, whether they are alpha, beta, or OG-emitting. The second key component is our targeting ligand or PLE, which is the basis of our Novel platform.

我們的錒項目採用了相同的模式，我們正在與現有和未來的錒供應商合作，這將在整個藥物開發過程和商業化過程中提供充足的錒供應。這種方法可用於多種放射性同位素，無論它們是α、β或OG發射的。第二個關鍵成分是我們的標靶配體或 PLE，它是我們 Novel 平台的基礎。

Similar to the isotope sourcing strategy, we validated and secured sourcing from multiple contractors. Currently, a single targeting ligand batch produces enough of the targeting ligand to allow for greater than a three-year supply of iopofosine I-131 at maximum forecasted sales volumes and will support and would support at least one other program with the capacity to increase supply as needed.

與同位素採購策略類似，我們驗證並確保了多個承包商的採購。目前，單一標靶配體批次生產的標靶配體足以以最大預測銷售量提供超過三年的碘泊福辛 I-131 供應，並將支援並將支援至少一項有能力增加供應的其他計劃根據需要。

Finally, we are also multi-sourcing iopofosine I-131 as the fully finished ready-to-use product. We currently have two production sites in North America that can supply approximately 200 patient doses per week at current capacity with the capability to scale to nearly 1,000 weekly doses. In addition to supplying our finished product requirements, our outsourcing model provides additional benefits.

最後，我們也多採購碘泊磷 I-131 作為完全成品的即用型產品。目前，我們在北美擁有兩個生產基地，以目前產能，每周可供應約 200 劑患者劑量，並可擴展到每週近 1,000 劑。除了滿足我們的成品需求外，我們的外包模式還提供了額外的好處。

One, we have significantly reduced the capital expenditure and future maintenance costs associated with an internal manufacturing capability. Second, we have demonstrated the ability to complete the iopofosine I-131 technology transfer in timely and efficient process to multiple sites, which allows for the rapid transition into another organization's manufacturing facility as needed. In addition to addressing potential production constraints unique to radiopharmaceuticals, we have taken a similar approach to addressing potential issues with logistics.

第一，我們大幅減少了與內部製造能力相關的資本支出和未來維護成本。其次，我們展示了及時有效地將碘泊膦 I-131 技術轉移到多個地點的能力，從而可以根據需要快速過渡到另一個組織的生產設施。除了解決放射性藥物特有的潛在生產限制之外，我們還採取了類似的方法來解決物流的潛在問題。

We have developed a novel formulation for iopofosine I-131 that provides a 17-day shelf life once produced. This unique advantage by iopofosine I-131 provides physicians and patients with greater treatment schedule, flexibility and a likely reduction in drug waste, resulting in a lower total cost of treatment to the healthcare system. Additionally, like our approach with sourcing of manufacturing materials, we have partnered with multiple logistics and shipping organizations to ensure global delivery to the treatment sites within 48 to 72 hours of production, ensuring a minimum of 14 days and a maximum of 16 days to dose a patient.

我們開發了一種新型碘泊福辛 I-131 配方，生產後保質期為 17 天。碘泊磷 I-131 的這一獨特優勢為醫生和患者提供了更大的治療方案、靈活性，並可能減少藥物浪費，從而降低醫療保健系統的總治療成本。此外，與我們採購製造材料的方法一樣，我們與多個物流和運輸組織合作，確保在生產後48 至72 小時內將貨物運送到全球治療地點，確保最短14 天、最長16 天的給藥時間一個病人。

As described, we have built a robust and redundant supply chain that allows us to meet the finished product requirements for iopofosine I-131 today and into the future. Additionally, this modular outsourced model is being replicated for our other radio therapeutic programs like our actinium program to ensure clinical research and commercialization supply as needed.

如上所述，我們已經建立了一個強大且冗餘的供應鏈，使我們能夠滿足當今和未來對碘泊福辛 I-131 的成品要求。此外，這種模組化外包模式正在複製到我們的其他放射治療項目（例如錒專案），以確保根據需要進行臨床研究和商業化供應。

I will now turn the call to Shane for the commercial update. Shane?

我現在將致電肖恩以獲取商業更新。謝恩？

Thank you, Jarrod. Good morning, everyone.

謝謝你，賈羅德。大家早安。

I'm excited to share our commercial planning progress regarding the product launch of iopofosine, Waldenstrom's macroglobulinemia or WM. We continue to make significant advances in our commercial capabilities and understanding of the WM market dynamics, which along with the highly scalable nature of the market will allow our team to capture the WM opportunity with a focused and efficient commercialization model.

我很高興與大家分享我們關於碘泊福辛、華氏巨球蛋白血症或 WM 產品上市的商業規劃進展。我們在商業能力和對 WM 市場動態的理解方面不斷取得重大進步，再加上市場的高度可擴展性，將使我們的團隊能夠透過專注且高效的商業化模式抓住 WM 機會。

As previously noted, WM is a rare type of non-Hodgkin's lymphoma with a prevalence of approximately 26,000 patients in the US. Of these, about 80% are currently receiving active treatment. The market is highly concentrated with 80% of the opportunity located in just 15 states. We plan to pursue a relapse or refractory indication, which has an estimated population of approximately 11,500 patients. We have also built conservative plans with a base case indication assumption for the third line plus setting which represents an addressable population of 5,700 patients who could benefit from iopofosine therapy.

如前所述，WM 是一種罕見的非何杰金氏淋巴瘤，在美國約有 26,000 名患者患病。其中，約80%目前正在接受積極治療。市場高度集中，80% 的機會集中在 15 個州。我們計劃尋求復發或難治性適應症，估計患者人數約為 11,500 名。我們還制定了保守計劃，其中包含針對三線+設置的基本案例適應症假設，該計劃代表了 5,700 名可從碘泊福辛治療中受益的可尋址人群。

Of these, approximately 4,700 patients are currently receiving third line plus therapy and approximately 1,000 patients have exhausted all treatment options, leaving them an acute need for new therapy. Additionally, there are approximately 2,200 new third line plus patients each year, which means that 2,200 additional patients advanced into the third line plus treatment setting annually. Our base case assumption provides a significant iopofosine market opportunity in terms of the total addressable population in the likelihood of orphan drug pricing.

其中，約 4,700 名患者目前正在接受第三線聯合治療，約 1,000 名患者已用盡所有治療選擇，因此迫切需要新的治療。此外，每年約有 2,200 名新的三線以上患者，這意味著每年有 2,200 名額外的患者進入三線以上治療環境。就孤兒藥定價的可能性而言，我們的基本案例假設提供了重要的碘泊膦市場機會。

Importantly, there is a significant unmet need in the third line plus setting, with only approximately 10% of third line plus patients achieving a major response and the duration of response for these one in 10 patients is approximately six months. Moreover, 60% of the drugs utilized in this setting are non-FDA approved, which means limited competitive promotional activity and a low share of voice. It is also notable that as a result of limited treatment options, approximately 50% of patients are treated with a therapy they received in earlier line.

重要的是，三線+治療領域存在顯著的未滿足需求，只有大約 10% 的三線+患者實現了主要緩解，而這些患者中十分之一的緩解持續時間約為六個月。此外，這種情況下使用的藥物中有 60% 未經 FDA 批准，這意味著競爭性促銷活動有限且話語權較低。另外值得注意的是，由於治療選擇有限，大約 50% 的患者接受了早期接受的治療。

We recently completed additional third-party research evaluating the profile of iopofosine and WM. The key findings from this research demonstrated that WM treaters acknowledged the urgent need for more effective treatments, new mechanisms of action. The WM treaters also emphasized the importance of achieving durable responses and maintaining a high quality of life for patients with the primary treatment goal of reducing IgM levels. We also observed an interesting finding that there was a lack of consistency and treatment goals amongst hematologists because of the heterogenicity of disease.

我們最近完成了額外的第三方研究，評估了碘磷辛和 WM 的概況。這項研究的主要發現表明，西粒細胞治療者認識到迫切需要更有效的治療方法和新的作用機制。WM 治療人員也強調了患者獲得持久緩解和維持高品質生活的重要性，其主要治療目標是降低 IgM 水平。我們也觀察到一個有趣的發現，由於疾病的異質性，血液學家之間缺乏一致性和治療目標。

In other words, most therapies are limited in clinical benefit based on patient characteristics. Therefore, this created lack of consistency with treatment approach and outcome based on the limitations of existing therapies. The same hematologists participants also reviewed the iopofosine product profile and provided a highly positive rating, acknowledging that iopofosine addresses key treatment goals and existing unmet needs while highlighting the fixed course of therapy. Hematologists were very encouraged by iopofosine's results in such a difficult patient population, noting its potential to treat the broad WM patient population, which contrasts with existing therapies.

換句話說，根據患者特徵，大多數療法的臨床益處有限。因此，由於現有療法的局限性，這導致治療方法和結果缺乏一致性。這些血液學家參與者也審查了碘泊福辛產品概況，並提供了高度正面的評價，承認碘泊福辛解決了關鍵治療目標和現有未滿足的需求，同時強調了固定療程。血液學家對碘泊膦在如此困難的患者群體中取得的結果感到非常鼓舞，並指出其治療廣泛的 WM 患者群體的潛力，這與現有療法形成鮮明對比。

Iopofosine's efficacy and unique mechanism of action were highlighted as key differentiators for its use in WM. We were encouraged by this research supporting our belief that iopofosine will be highly differentiated to address the clear unmet need in WM providing durable, meaningful responses regardless of patient characteristics with a fixed course of therapy, thereby simplifying the treatment process for providers and patients.

碘泊福辛的功效和獨特的作用機制被強調為其在 WM 中使用的關鍵區別因素。這項研究讓我們感到鼓舞，它支持了我們的信念，即碘泊膦將具有高度差異性，可滿足WM 中明顯未滿足的需求，無論患者特徵如何，透過固定療程提供持久、有意義的反應，從而簡化提供者和患者的治療過程。

In conclusion, our commercialization efforts are advancing steadily to support the potential US launch of iopofosine and WM. The research findings underscore a significant unmet need and the potential impact of iopofosine for the treatment of WM. We are confident that iopofosine's unique profile and demonstrated efficacy will address the critical needs of WM patients and provide a much-needed new treatment option with a potential FDA approval.

總之，我們的商業化工作正在穩步推進，以支持碘泊福辛和西藥在美國的潛在上市。研究結果強調了碘泊福辛治療 WM 的巨大未滿足需求和潛在影響。我們相信，碘泊膦獨特的特性和已證實的療效將滿足 WM 患者的關鍵需求，並提供急需的新治療選擇，並可能獲得 FDA 批准。

I will now turn the call back over to Jim Caruso for closing remarks.

現在，我將把電話轉回給吉姆·卡魯索，讓其致閉幕詞。

Thank you, Shane. It certainly remains an exciting time for us at Cellectar with a potential approval for iopofosine I-131 on the horizon, coupled with our unique delivery platform providing differentiated radioisotope offerings. We are confident in our market position and excited about our future. We look forward to our meaningful milestones in the second half of this year, positioning us for further advancements and real growth as a company.

謝謝你，謝恩。對於 Cellectar 來說，這無疑是一個激動人心的時刻，碘泊磷 I-131 即將獲得批准，再加上我們獨特的交付平台提供差異化的放射性同位素產品。我們對我們的市場地位充滿信心，並對我們的未來感到興奮。我們期待在今年下半年實現有意義的里程碑，為我們作為一家公司取得進一步的進步和真正的成長做好準備。

With that, I would now like to open the call for Q&A. Operator?

現在，我想開始問答環節。操作員？

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session.

謝謝。女士們、先生們，我們現在開始問答環節。

Jonathan Aschoff, ROTH.

喬納森·阿肖夫，羅斯。

Thank you. Good morning, guys. I think I might have missed a couple of numbers you were throwing out there. Do you have a new major response rate of 58 point something?

謝謝。早安，夥計們。我想我可能錯過了你拋出的幾個數字。有沒有新的專業回覆率達到58點的東西？

That is correct, Jonathan. With the latest data cut it's now 58.2%. And I think Andrei can talk to one of the reasons why we see consistent improvement over time with iopofosine for these patients.

這是正確的，喬納森。根據最新數據削減，現在為 58.2%。我認為安德烈（Andrei）可以談談為什麼我們看到這些患者隨著時間的推移碘泊福辛持續改善的原因之一。

(multiple speakers)

（多個發言者）

And that's based on what? Jim, or you can say that it's based on what end?

這是基於什麼？吉姆，或者你可以說這是基於什麼目的？

Yeah, the patient end.

是的，病人結束了。

Jonathan, good morning, Andrei here. So we have 55 patients in the efficacy evaluable set, and as Jim pointed out, after the most recent data cutoff, we just registered another late response effectively brings the MRR rate to 58.2%. We also expect that we might see additional major responses based on our prior observations that we demonstrated or reported in January that responses can occur as late as six months after receiving therapy. So we will not be surprised, and we actually anticipate that if I have additional major responses as follow-up continues.

喬納森，早安，安德烈在這裡。因此，我們的療效評估組中有 55 名患者，正如 Jim 指出的那樣，在最近的數據截止之後，我們剛剛登記了另一個延遲反應，有效地將 MRR 率提高到了 58.2%。我們也預計，根據我們先前的觀察結果，我們可能會看到更多的主要反應，我們在一月份證明或報告，反應可能會在接受治療後六個月內出現。因此，我們不會感到驚訝，而且我們實際上預計，隨著後續行動的繼續，我是否會做出其他重大回應。

Okay. That's very helpful. Chad, can you help us out a little closer on even if it's just the bottom result for the quarter, meaning the net income? And can you help us out on a share count and whether that's a time point or a weighted average?

好的。這非常有幫助。查德，你能幫助我們更接近一點嗎，即使這只是本季的最低結果，即淨利潤？您能幫我們計算一下份額數嗎？

So I can't provide a net income at this point, Jonathan, because the restatement has to be brought all the way forward, the evaluation needs to be done on a quarter-by-quarter basis to do that. That's why we didn't provide it in the comments, unfortunately. We simply need to work through that before we can essentially publish that information; so my apologies there. We did obviously provide operating expenses, but the non-operating components need to be further definitized.

所以我現在無法提供淨收入，喬納森，因為重述必須一路推進，需要逐季進行評估才能做到這一點。不幸的是，這就是為什麼我們沒有在評論中提供它。我們只需要解決這個問題，然後才能發布該資訊；所以我很抱歉。顯然我們確實提供了營運費用，但非營運部分需要進一步明確。

And how about the share count?

那麼股份數量又如何呢？

So on the share front, I think the expectation is we're going to get an 8-K published on that because I want to essentially publish the entire cap table. And so that is forthcoming. You should have that in the very near future.

因此，在股票方面，我認為我們的預期是我們將發布一份 8-K 股票，因為我想基本上發布整個股權結構表。這即將到來。你應該在不久的將來擁有它。

Okay. That's helpful. This is also something I may have missed. But when will your HGG data come out your next data set for that? And how is about starting the timing for Phase 1 for the alpha-emitter actinium?

好的。這很有幫助。這也是我可能錯過的。但是您的 HGG 資料什麼時候會出現您的下一個資料集呢？α發射體錒的第一階段的開始時間如何？

Sure. I'll have Andrei talk to the pediatric high grade glioma study, and then Jarrod can address our work with our actinium-based program.

當然。我會讓安德烈（Andrei）談論兒科高級神經膠質瘤研究，然後賈羅德（Jarrod）可以透過我們基於錒的專案來解決我們的工作。

Thanks again, Jonathan. We started enrollment in the HGG study at the very beginning of this year with patients already enrolled in the study and a few patients being screened as we anticipate that will provide initial look initial results from that study by the end of the year.

再次感謝，喬納森。我們在今年年初開始參加 HGG 研究，患者已經參加了該研究，並且一些患者正在接受篩選，因為我們預計將在年底前提供該研究的初步結果。

Okay. And starting Phase 1.

好的。並開始第一階段。

Yes. Great question, Jonathan. So real fast, what I'd say is we sit in a unique advantage in that our phospholipid ether delivery targeting mode is validated based on the iopofosine data as a validated targeting ligand. And we have a unique advantage in that that allows us to accelerate our timelines into clinical trials and completion of IND-enabling studies. I think as we mentioned before, we expect to complete the IND-enabling studies here in the fourth quarter of this year and either late this year or early next year, initiate that Phase I study with the actinium program.

是的。好問題，喬納森。如此之快，我想說的是，我們擁有獨特的優勢，因為我們的磷脂醚遞送靶向模式是根據碘泊膦數據作為經過驗證的靶向配體進行驗證的。我們擁有獨特的優勢，這使我們能夠加快臨床試驗和完成 IND 支持研究的時間表。我認為正如我們之前提到的，我們預計將在今年第四季完成 IND 啟用研究，並在今年年底或明年初啟動錒專案的 I 期研究。

And Jarrod, we haven't talked about it very much, but could you share a little bit about the OG program and --

Jarrod，我們還沒有談論太多，但你能分享一些關於 OG 計劃的資訊嗎？--

Yes, absolutely. So obviously, as Jim just alluded to, Jonathan, we've got -- as we've talked about, we've validated with a number of different isotopes or different emitting isotopes. And as Jim just said, we also have the advantage of being able to use OG emitting isostopes quite readily. And we do have a program that has been in the background for a little while that we're moving forward with that we would expect that we could quickly initiate Phase 1 study in that arena as well shortly on the heels of the actinium spending capital.

是的，絕對是。顯然，正如吉姆剛才提到的那樣，喬納森，我們已經討論過，我們已經用許多不同的同位素或不同的發射同位素進行了驗證。正如吉姆剛才所說，我們也具有能夠輕鬆使用 OG 發射同位素的優勢。我們確實有一個項目已經在後台進行了一段時間，我們正在推進該項目，我們預計我們可以在錒支出資本之後很快啟動該領域的第一階段研究。

Jeff Jones, Oppenheimer.

傑夫瓊斯，奧本海默。

Hi, guys and thanks for taking the question. A couple from me. Andrei, you gave a really long and really detailed update on the data, and obviously, key update there was the increase in the MRR. Were there any other changes that I might have missed from the prior data set that was described in July?

大家好，感謝您提問。我的一對。Andrei，您對數據進行了非常長且非常詳細的更新，顯然，關鍵更新是 MRR 的增加。從 7 月描述的先前資料集中，我是否可能遺漏了任何其他變更？

Thank you, Jeff. I don't think you missed anything. This is the single most impactful update even though it's just one additional response, it brings us closer to our previously reported number within margin of error. So the current MRR effectively is 58.2%. And we expect that we might have in the next few months additional responses converting from minor to major responses as we model at the beginning of the year. But where we sit now is 58.2% and that's the most impactful update from a month ago.

謝謝你，傑夫。我不認為你錯過了什麼。這是最有影響力的更新，儘管它只是一個額外的回應，但它使我們在誤差範圍內更接近先前報告的數字。因此目前的 MRR 有效值為 58.2%。我們預計，在接下來的幾個月裡，我們可能會得到更多的反應，從次要反應轉變為主要反應，正如我們在年初建模的那樣。但我們現在的支持率為 58.2%，這是一個月前最具影響力的更新。

Great. Thank you. In terms of the NDA filing, one of the major reasons folks have been getting refusal to files or rejections have been on the CMC side. So you talked about a lot about the importance of supply chain and how you build redundancy in your supply chain. But can you speak to the level of confidence in the NDA filing in the CMC section, perhaps what you've done in terms of quality audits and preparations for FDA inspections?

偉大的。謝謝。就 NDA 備案而言，人們拒絕提交或拒絕備案的主要原因之一是 CMC 方面。您談到了很多關於供應鏈的重要性以及如何在供應鏈中建立冗餘的問題。但您能否談談對 CMC 部分 NDA 備案的信心程度，也許您在品質審核和 FDA 檢查準備方面所做的工作？

Yeah, absolutely. So that's a great question, Jeff. And there's a lot to unpack in that. So I'll try to unpack as much as I can in a little bit of time here. But -- so as it comes to our confidence, we are highly confident for a number of reasons, not least of which we've done -- we've been producing iopofosine at these facilities for a while now, particularly one of those facilities we've been producing and have not missed a single batch in over three years. As I exemplified, we've replicated that process, and the second facility have produced multiple batches now, a number of batches at that facility without any hitches as well.

是的，絕對是。所以這是一個很好的問題，傑夫。其中有很多東西需要解開。所以我會嘗試用一點時間在這裡盡可能地解開包裝。但是，說到我們的信心，我們非常有信心，原因有很多，尤其是我們已經完成的原因，我們在這些設施生產碘泊膦已經有一段時間了，特別是其中一個設施三年多來，我們一直在生產，沒有錯過任何一個批次。正如我所舉的例子，我們已經複製了這個過程，第二個工廠現在已經生產了多個批次，該工廠也生產了多個批次，沒有任何問題。

So we're very confident in the robustness of the ability to do the tech transfer and of both manufacturing facilities to actually produce the material as defined and with inside the criteria as necessary for release. In addition to that, again, we've done that from the beginning to the end of sort of things. And like anything, we use a design sort of approach with our manufacturing that allows us to get controlled by design sort of -- quality by design sort of approach. So we're always looking to optimize and enhance that a little by little. So that's part of it.

因此，我們對技術轉移能力的穩健性以及實際生產所定義材料並符合發布所需標準的製造設施的穩健性非常有信心。除此之外，我們從頭到尾都這麼做了。就像任何事情一樣，我們在製造中使用設計類方法，這使我們能夠透過設計類方法進行控制——品質由設計類方法控制。因此，我們一直在尋求一點一點地優化和增強。這就是其中的一部分。

The other piece that I think we've done is when we started this process, we actually -- and I'm going to get in a little bit too much detail probably, but we took this outside of our hands and we actually had an outside group come in and do a gap analysis on our entire manufacturing process from beginning to end to identify any potential gaps in any historical areas that we would need to backfill for questions we might want to answer to make sure our submission was as robust as possible and we did that.

我認為我們已經完成的另一件事是，當我們開始這個過程時，我們實際上 - 我可能會講得太多細節，但我們把這件事放在我們的手中，我們實際上有一個外部小組進來，對我們的整個製造流程從頭到尾進行差距分析，以確定我們需要回填我們可能想要回答的問題的任何歷史領域中的任何潛在差距，以確保我們提交的內容盡可能穩健我們做到了。

One of those folks was actually a gentleman who used to work at the FDA and had actually established a lot of their radiopharmaceutical manufacturing criteria. So we were taking a very robust look at that, and we've gone through that, and we continue to sort of reassess it.

其中一個實際上是一位曾經在 FDA 工作的紳士，實際上已經制定了許多放射性藥物的製造標準。因此，我們對此進行了非常深入的研究，我們已經經歷過這一點，並且我們將繼續重新評估它。

Now as you enunciated, the last piece is the audits, as I'll call them, whether that be pre-FDA audits or regular audits. We do our own regular audits, both by our team and by external teams every couple of years with all of the sites. So we've done that. And right now, we've done it with everybody leading into the FDA submission.

現在，正如您所闡明的，最後一部分是審計，正如我所說的那樣，無論是 FDA 前審計還是定期審計。我們自己的團隊和外部團隊每隔幾年就會對所有站點進行定期審核。所以我們已經做到了。現在，我們已經與所有向 FDA 提交申請的人一起完成了這項工作。

To your point, we are -- with every one of our manufacturers right now, we do have on the books, the plan to do pre-FDA, pre-NDA evaluations. So that when they do get audited, we will have already gone through there again just to make sure and tighten the screw so that everything is above board and appropriate, so to speak.

就你的觀點而言，我們現在與我們的每一家製造商一起，確實有 FDA 前、 NDA 前評估的計劃。因此，當他們接受審核時，我們已經再次經過那裡，以確保並擰緊螺絲，以便一切都光明正大且適當，可以這麼說。

Perfect. Thank you very much for that, Jarrod. And then one very quick clarification. For the actinium-based program in solid tumors, the carrier there is the same as iopofosine, correct? Or is it a modification?

完美的。非常感謝你，賈羅德。然後是一個非常快速的澄清。對於基於錒的實體腫瘤方案，那裡的載體與碘泊膦相同，對嗎？或者說是一種修改？

There is a modification, but what I would say is that it's about 90-ish percent, 95%, depending on what chemists you asked, the same. There are slight tweaks.

有一個修改，但我想說的是，大約 90% 左右，95%，取決於你問的化學家，是一樣的。有一些細微的調整。

Okay. So in essence, the targeting agent is the same.

好的。所以本質上，靶向劑是相同的。

Exactly.

確切地。

Got it. Great. Thanks, guys.

知道了。偉大的。謝謝，夥計們。

All right. Thank you, Jeff. We appreciate your questions and obviously your continued interest and support of the company. Thank you.

好的。謝謝你，傑夫。我們感謝您的提問，當然也感謝您對公司的持續關注與支持。謝謝。

Ahu Demir, Ladenburg Thalmann.

阿胡·德米爾，拉登堡·塔爾曼。

Hi, good morning. This is Chungs for Ahu Demir. Thank you for taking our questions. We also have a question regarding the NDA applications. So for the application, what population are you targeting? Will be three line clients and patients treated with the BTK inhibitor before it will be double or triple refractory patients? And are there any additional analysis that the company plans to do prior to the submission? Thank you.

嗨，早安。我是阿胡‧德米爾 (Ahu Demir) 的鐘 (Chung)。感謝您接受我們的提問。我們還有一個關於 NDA 申請的問題。那麼對於該應用程序，您的目標人群是哪些？在成為雙重或三重難治性患者之前，是否會出現三線客戶和接受 BTK 抑制劑治療的患者？公司計劃在提交之前進行任何其他分析嗎？謝謝。

Okay. I think prior to handing it over to Jarrod and Andrei for their perspective and optics here, as we originally designed the study, it was for a third line or greater originally post-BTKi based on the patient population and roll that supported that, it's essentially a relapsed/refractory patient population. And so, it is our belief that we have an opportunity as we continue to engage with the FDA that our data package would be supportive of a relapsed/refractory indication or essentially second line and beyond.

好的。我認為，在將其交給Jarrod 和Andrei 之前，因為他們的觀點和觀點，正如我們最初設計的這項研究一樣，它是針對第三線或更多的最初的BTKi 後基於患者群體和支持這一點的滾動，它本質上是復發/難治性患者群體。因此，我們相信，隨著我們繼續與 FDA 合作，我們有機會相信我們的資料包將支援復發/難治性適應症或基本上二線及以上。

And so I can have Jarrod and/or Andrei provide both the regulatory and some of our clinical thinking around that.

因此，我可以讓賈羅德和/或安德烈提供監管和我們對此的一些臨床思考。

Yeah. I think from a regulatory perspective, if you look at the patient population, as Jim said and as Andrei defined or described to you in the -- when you look at base characteristics, you can clearly see that this is a highly relapsed/refractory patient population, whether you want to cut it from post BTKi, which essentially is BTKis are predominantly being used to refine these days kind of element to whether you just want to say, let's just look at the refractory.

是的。我認為從監管的角度來看，如果你觀察患者群體，正如吉姆所說和安德烈在中向你定義或描述的那樣——當你觀察基本特徵時，你可以清楚地看到這是一位元高度復發/難治的患者人口，無論你是否想從後BTKi中削減它，本質上BTKs主要用於精煉當今的某種元素，無論你是否只想說，讓我們看看耐火材料。

I think the key element there is, as Andrei stated, the data shows that irrespective of the patient population, the drug works consistently and robustly in all of these patients. And because of that, when the agency or any agency evaluates the drug based off of that and they start to do subanalysis, what you see is there's really no change in the patient population or the response rates. And that means that you're likely to get a broader label and a label like what Jim just described in relapsed/refractory.

我認為關鍵因素是，正如安德烈所說，數據顯示，無論患者群體如何，該藥物對所有這些患者都一致且穩健地發揮作用。正因為如此，當該機構或任何機構據此評估藥物並開始進行亞分析時，您會看到患者群體或反應率實際上沒有變化。這意味著您可能會獲得更廣泛的標籤和吉姆剛剛在復發/難治性中描述的標籤。

I'll turn it over to Andrei for any other thoughts.

如果有其他想法，我會將其轉交給安德烈。

Thank you, Jarrod. I would thank you for this question. It's a very important question that we are discussing internally, and I'm completely aligned from a clinical perspective with my colleagues that our data is supportive of broad applicability in clinic iopofosine in WM patients, as described in our call, population in CLOVER WaM contained patients post chemo, post-BTKi, post-ritux exposed to couples of those classes, all of those classes, different genomic profiles.

謝謝你，賈羅德。我要感謝你提出這個問題。這是我們正在內部討論的一個非常重要的問題，我從臨床角度與我的同事完全一致，我們的數據支持碘泊膦在WM 患者臨床中的廣泛適用性，如我們的電話中所述，CLOVER WaM 中的族群包含化療後、BTKi 後、ritux 後的患者暴露於這些類別的夫婦，所有這些類別，不同的基因組圖譜。

So the data is highly applicable clinically to entire WM population and clinically, again, supports the proposed label that Jarrod discussed, and more importantly, applicability once and if iopofosine is approved, applicability to a broad variety of patients with relapsed/refractory WM.

因此，這些數據在臨床上高度適用於整個WM 人群，並且在臨床上再次支持Jarrod 討論的擬議標籤，更重要的是，一旦碘泊膦獲得批准，就適用於各種復發/難治性WM 患者。

Ted Tenthoff, Piper Sandler.

特德·滕索夫，派珀·桑德勒。

Great. Thank you very much and thanks for the update. Following up on some of the questions with respect to the NDA, I'm curious, what are the major segments that still need to be done? You've got into some good detail on the CMC portion is clinical and everything else all ready to go. Just giving a sense for what still needs to be done. Thank you.

偉大的。非常感謝您並感謝您的更新。跟進有關 NDA 的一些問題，我很好奇，仍然需要完成哪些主要部分？您已經了解了 CMC 部分的一些詳細信息，這是臨床的，其他一切都已準備就緒。只是讓大家了解還需要做什麼。謝謝。

Absolutely, Ted. And this is -- yes, essentially, all modules are nearly complete. And when I say that, so CMC is complete, preclinical is complete, I think module two is essentially complete. Module one will be finished when we have the full sort of -- well, sort of table contents completed based off of the clinical piece. So right now, where we sit is really wrapping up the final pieces of the clinical. And when I say that, what I mean is all of the other clinical components have been -- are essentially there and done. It's really just the addition of the final data reports and essentially the CSR out of the CLOVER WaM study.

當然，泰德。這是——是的，基本上，所有模組都已接近完成。當我這麼說時，CMC 已經完成，臨床前已經完成，我認為模組二基本上已經完成。當我們根據臨床部分完成完整的表格內容時，模組一將完成。所以現在，我們所坐的位置實際上正在完成臨床的最後部分。當我這麼說時，我的意思是所有其他臨床組成部分基本上都已經存在並完成了。這實際上只是最終數據報告的添加，本質上是 CLOVER WaM 研究中的企業社會責任。

So as that data comes in and gets put into the NDA, that essentially will wrap it up. And that's exactly -- as I tried to describe in the conversation earlier, that's where that detail comes in that process of going from final -- going from having the data to finalizing the data and having a locked database and all the analytics completed.

因此，當這些數據進入並被納入 NDA 時，基本上就會結束它。這正是——正如我之前在談話中試圖描述的那樣，這就是從最終到最終確定數據、鎖定資料庫和完成所有分析的過程中的細節。

Sure. And then would you guys anticipate having a panel for this. I know it will probably take some time. But what are your thoughts on that? Thank you.

當然。然後你們會期待為此設立一個小組嗎？我知道這可能需要一些時間。但你對此有何看法？謝謝。

And when you -- Ted, just so that I understand, when you mean a panel, are you thinking of an ODAC?

當您 - Ted，請讓我理解，當您指的是面板時，您是否在考慮 ODAC？

Yes, advisory committee, correct.

是的，顧問委員會，正確。

Yes. So obviously, that's something we will come to. Eventually, I wouldn't be surprised if there is an ODAC request or a desire by the agency to have an ODAC as you may be aware, many of the radiopharmaceuticals have not actually had an ODAC. They've gone through without that. However, we're not -- we're flexible with that. I don't know, Andrei, if there's anything else you'd like to add?

是的。顯然，這就是我們將會討論的問題。最終，如果有 ODAC 請求或機構希望擁有 ODAC，我不會感到驚訝，因為您可能知道，許多放射性藥物實際上並沒有 ODAC。他們已經經歷了沒有那樣的事情。然而，我們不是——我們對此很靈活。我不知道，安德烈，您還有什麼要補充的嗎？

Yeah. Thank you, Jarrod, and thank you, Ted. A great question, and we, again, keep discussing this continuously internally our efficacy data looks from our perspective, really impressive and great tolerability and safety data is also impressive.

是的。謝謝你，賈羅德，謝謝你，特德。這是一個很好的問題，我們再次在內部不斷討論這個問題，從我們的角度來看，我們的療效數據確實令人印象深刻，出色的耐受性和安全性數據也令人印象深刻。

Having said that, it depends on the composition of FDA panel that reviews it and how comfortable they are experienced with disease they're looking at, whether they need additional advice from the panel. I think it's a tossup at this point from a clinical perspective. We will continue to prepare for it. We are putting groundwork assuming that it might be necessary to go through, we will be ready.

話雖如此，這取決於 FDA 審查小組的組成以及他們對正在研究的疾病的感受程度，以及他們是否需要小組的額外建議。我認為從臨床角度來看，目前這是一個折騰。我們將繼續為此做好準備。我們正在做基礎工作，假設可能有必要進行，我們會做好準備。

Thank you. And at this time, there are no further questions in the queue. I will now turn the call over to Jim Caruso for closing remarks.

謝謝。而此時，隊列中已經沒有其他問題了。現在，我將把電話轉交給吉姆·卡魯索，讓其致閉幕詞。

All right. Thank you, operator. I would like to thank certainly our analysts and everyone for joining us today. We look forward to speaking with you, hopefully, in the near term. Thank you.

好的。謝謝你，接線生。我當然要感謝我們的分析師和今天加入我們的所有人。我們期待在短期內與您交談。謝謝。

Thank you, everyone. This concludes today's conference call. You may now disconnect.

謝謝大家。今天的電話會議到此結束。您現在可以斷開連線。