Plus Therapeutics Inc (PSTV) 2024 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to Plus Therapeutics fourth quarter and full-year 2024 results conference call.

女士們、先生們，午安。歡迎參加 Plus Therapeutics 2024 年第四季和全年業績電話會議。

Before we begin, we want to advise you that over the course of the call, including any question-and-answer session, forward-looking statements will be made regarding events, trends, business prospects, and financial performance, which may affect Plus Therapeutics' future operating results and financial position. All such statements are subject to risk and uncertainties, including the risk and uncertainties described under the risk factors section included in Plus Therapeutics' annual report on Form 10-K and quarterly report on Form 10-Q filed with the Securities and Exchange Commission from time to time. Plus Therapeutics advises you to review these risk factors in considering such statements.

在我們開始之前，我們想提醒您，在通話過程中，包括任何問答環節，都會對事件、趨勢、業務前景和財務業績做出前瞻性陳述，這些陳述可能會影響 Plus Therapeutics 未來的經營業績和財務狀況。所有此類聲明均受風險和不確定性的影響，包括 Plus Therapeutics 不時向美國證券交易委員會提交的 10-K 表年度報告和 10-Q 表季度報告中風險因素部分中所述的風險和不確定性。Plus Therapeutics 建議您在考慮此類聲明時審查這些風險因素。

Plus Therapeutics assumes no responsibility to update or revise any forward-looking statements to reflect events, trends or circumstances after the date they are made.

Plus Therapeutics 不承擔更新或修改任何前瞻性陳述以反映其作出之日後的事件、趨勢或情況的責任。

It is now my pleasure to turn the floor over to Dr. Marc Hedrick, Plus Therapeutics' President and Chief Executive Officer. Sir, you may begin.

現在我很高興將發言權交給 Plus Therapeutics 總裁兼執行長 Marc Hedrick 博士。先生，您可以開始了。

Thank you, Sherry. Good afternoon, everyone. Thank you once again for taking the time to join us today as we provide an overview of recent business highlights and discuss our fourth quarter and full-year 2024 financial results and go-forward guidance.

謝謝你，雪莉。大家下午好。再次感謝您今天抽出時間加入我們，我們將概述最近的業務亮點並討論我們第四季度和 2024 年全年的財務業績和未來指引。

Joining me for the call today is Mr. Andrew Sims, our Chief Financial Officer.

今天與我一起參加電話會議的是我們的財務長安德魯·西姆斯先生。

I'll begin the call by providing more detail on four important recent corporate announcements. Then I'll discuss progress in our most advanced clinical programs and then discuss progress and plans for CNSide and its commercialization. After that, I'll turn the call over to Andrew to review our financials.

我將在電話會議開始時詳細介紹公司近期發布的四項重要公告。然後我將討論我們最先進的臨床項目的進展，然後討論 CNSide 及其商業化的進展和計劃。之後，我會將電話轉給安德魯來審查我們的財務狀況。

So first of all, in early March, (technical difficulty) posted on an underwritten equity financing of $15 million in gross proceeds with new stockholders. This was preceded by a smaller financing from existing stockholders. We also received about that time $2 million in its accelerated grant proceeds from CPRIT.

首先，在 3 月初，（技術困難）向新股東公佈了 1,500 萬美元的承銷股權融資。此前，現有股東曾進行小額融資。那時我們也從 CPRIT 獲得了約 200 萬美元的加速撥款收益。

This capital, in combination with further anticipated grant funds, strengthens our balance sheet and provides funding through key milestones into mid-2026. Additionally, the financings enabled Plus to regain compliance with Nasdaq's minimum stockholders equity listing requirement. Andrew will in fact provide additional details on the transactions, future grant availability, and cash runway.

這筆資金與預期的進一步撥款相結合，增強了我們的資產負債表，並為 2026 年中期實現關鍵里程碑提供資金。此外，此次融資使 Plus 重新符合納斯達克的最低股東權益上市要求。事實上，安德魯將提供有關交易、未來補助金可用性和現金流的更多細節。

On a personal note, and on behalf of our Board of Directors and our dedicated management team, I would like to express our collective gratitude to our current and new stockholders for their support of and confidence in Plus and our mission. We're also grateful to those organizations with which we have substantial financial and grant support, specifically the US NIH, and that's the NCI, National Cancer Institute; the US Department of Defense; and the state of Texas, specifically secret.

我個人謹代表董事會和敬業的管理團隊，向現有和新股東對 Plus 和我們使命的支持和信任表示感謝。我們也要感謝那些給予我們大量資金和資助的組織，特別是美國國立衛生研究院 (NIH)，也就是美國國家癌症研究所 (NCI)；美國國防部；以及德克薩斯州，特別是秘密。

Also, moving on, we recently taken to strengthen our senior leadership team, specifically for Plus Therapeutics. Dr. Mike Rosol joined us as Chief Development Officer, responsible for leading our preclinical and clinical development activities, including clinical operations. Mike has extensive experience in oncology, radiotherapeutics, and biomarker development, all highly germane to Plus' pipeline.

此外，我們最近也採取措施加強我們的高階領導團隊，特別是針對 Plus Therapeutics。Mike Rosol 博士加入我們擔任首席開發官，負責領導我們的臨床前和臨床開發活動，包括臨床營運。Mike 在腫瘤學、放射治療學和生物標記開發方面擁有豐富的經驗，這些經驗與 Plus 的產品線密切相關。

Specifically for CNSide Diagnostics, our wholly owned subsidiary, Mr. Russ Bradley joined us as President and General Manager of CNSide. Russ is a seasoned and successful (technical difficulty) field previously holding top management positions at both major and smaller diagnostic companies as well as related Board positions. Russ has a deep knowledge of diagnostic operations, fast-growing commercial diagnostics, market access activities, and business development.

具體來說，對於我們的全資子公司 CNSide Diagnostics，Russ Bradley 先生加入我們，擔任 CNSide 總裁兼總經理。Russ 是一位經驗豐富且成功的（技術難度）領域人士，之前曾在大型和小型診斷公司擔任高階管理職位以及相關董事會職位。Russ 對診斷操作、快速成長的商業診斷、市場進入活動和業務發展有著深入的了解。

Additionally, I'm pleased to welcome Dr. Jonathan Stein to the team at CNSide as its Medical Director. Jonathan has extensive experience in all aspects of diagnostic operations, compliance, and regulatory affairs.

此外，我很高興歡迎 Jonathan Stein 博士加入 CNSide 團隊擔任醫療主任。喬納森在診斷操作、合規性和監管事務的各個方面擁有豐富的經驗。

Now I'm excited to introduce you to REYOBIQ. We now have an FDA-accepted proprietary name which is REYOBIQ, and that goes alongside the USAN adopted and INN recommended non-proprietary name or generic name, rhenium Re-186 obisbemeda. All of these are required for a future marketing application with the FDA.

現在我很高興向您介紹 REYOBIQ。我們現在有一個 FDA 認可的專有名稱，即 REYOBIQ，它與 USAN 採用的和 INN 推薦的非專有名稱或通用名稱錸 Re-186 obisbemeda 一致。所有這些都是未來向 FDA 提交行銷申請所必需的。

Working with the leader in pharmaceutical brand name creation development, we are striving to develop a powerful brand identity for REYOBIQ, and that all begins with its global name. In parallel, we will be rolling out comprehensive branding materials that will strengthen and shape the REYOBIQ brand identity. And going forward, we'll use REYOBIQ to refer to our lead drug now in mid-stage clinical trials for use in patients with glioblastoma, leptomeningeal cancer, and soon in children with pediatric brain cancer.

我們與醫藥品牌名稱創建開發領域的領導者合作，致力於為 REYOBIQ 打造強大的品牌形象，而這一切都始於其全球名稱。同時，我們將推出全面的品牌材料，以加強和塑造 REYOBIQ 品牌形象。展望未來，我們將使用 REYOBIQ 來指稱我們目前處於中期臨床試驗階段的領先藥物，用於治療膠質母細胞瘤、軟腦膜癌患者，並且很快將用於治療兒童腦癌患者。

Finally, we recently received approval by the US FDA on our application for orphan designation for the use of REYOBIQ in patients with LM due to lung cancer. This adds to our previously received orphan designation for LM due to breast cancer and our fast track designation for REYOBIQ. This is reflective of our strategy to focus on the top two causes of LM, specifically breast and lung cancer, which represents two-thirds of the LM market.

最後，我們最近獲得了美國 FDA 的批准，批准我們申請 REYOBIQ 治療肺癌 LM 患者的孤兒藥資格認定。這補充了我們之前因乳癌而獲得的 LM 孤兒藥資格以及 REYOBIQ 的快速通道資格。這反映了我們的策略重點：關注 LM 的兩大原因，即乳癌和肺癌，這兩大病因佔 LM 市場的三分之二。

Now, I'd like to switch gears and focus on our leptomeningeal metastasis clinical development program in which we are investigating our lead radiotherapeutic REYOBIQ in the respect LM trials, which are substantially funded by the state of Texas. We recently announced the completion of the ReSPECT-LM Phase 1 trial single administration dose escalation trial. In that trial, we have determined a recommended Phase 2 dose of 44 millicuries as well as the maximum feasible dose of 75 millicuries.

現在，我想轉換主題，重點介紹我們的軟腦膜轉移臨床開發計劃，該計劃正在研究我們的主要放射治療藥物 REYOBIQ 在相關 LM 試驗中的應用，這些試驗主要由德克薩斯州資助。我們最近宣布完成 ReSPECT-LM 第一階段試驗單次給藥劑量遞增試驗。在該試驗中，我們確定了第 2 階段的建議劑量為 44 毫居里，以及最大可行劑量為 75 毫居里。

Based on these determinations and promising clinical safety and efficacy data, which I'll highlight in a moment, we have expanded our integrated clinical development plan for REYOBIQ as follows. First, because a single dose of REYOBIQ at the recommended Phase 2 dose was deemed safe, well-tolerated, and exhibited a promising efficacy signal in terms of clinical response and overall survival, we intend to move forward on a dose expansion trial at 44 millicuries to gather additional safety and efficacy data for REYOBIQ.

根據這些決定以及有希望的臨床安全性和有效性數據（我稍後會重點介紹），我們擴展了 REYOBIQ 的綜合臨床開發計劃，如下所示。首先，由於 REYOBIQ 在建議的 2 期劑量下單劑量服用被認為是安全的、耐受性良好的，並且在臨床反應和總體生存方面表現出有希望的療效信號，我們打算在 44 毫居里進行劑量擴展試驗，以收集 REYOBIQ 的更多安全性和有效性數據。

In terms of next steps, once the final clinical study report is complete, we plan to conduct an end of Phase 1 meeting with the FDA to align on an optimal path to approval for REYOBIQ and tailor the next clinical development steps. As there are no approved drugs for LM and a substantial clinical need, we intend to leverage promising clinical data for REYOBIQ , our orphan drug designations as mentioned, fast track designation, to identify the most expedited path to market for patients that are in desperate need for options.

就下一步而言，一旦最終的臨床研究報告完成，我們計劃與 FDA 進行第一階段結束會議，以確定 REYOBIQ 批准的最佳途徑並自訂下一步的臨床開發步驟。由於目前尚無核准的 LM 藥物，但臨床需求龐大，我們打算利用 REYOBIQ 的有希望的臨床數據（如上所述，我們的孤兒藥稱號、快速通道稱號）為急需治療選擇的患者找到最快的上市途徑。

We think given the promising Phase 1 data, a single dose of 44 millicuries warrants further evaluation for FDA approval for LM related to breast cancer.

我們認為，鑑於有希望的第 1 階段數據，單劑量 44 毫居里值得進一步評估，以獲得 FDA 批准用於治療乳癌相關的 LM。

In parallel, the ReSPECT-LM multiple dose escalation trial of REYOBIQ will begin enrollment soon for the purpose of dose optimization. Key details for the trial are as follows. The single dose at the recommended Phase 2 dose of 44 millicuries will be fractionated into three doses of approximately 13 millicuries.

同時，REYOBIQ 的 ReSPECT-LM 多劑量遞增試驗很快就會開始招募患者，以優化劑量。試驗的關鍵細節如下。建議的第 2 階段劑量為 44 毫居里的單劑量將分成三劑，每劑約 13 毫居里。

Based on the PK and PD data derived from the Phase 1 single-dose trial, three doses will be given at diminishing intervals, or first, every two months, then every month, and then every 15 days. There are options to expand the size of the treatment cohorts and extend the number of treatments beyond three to six doses total.

根據第 1 階段單劑量試驗得出的 PK 和 PD 數據，將以遞減的間隔給予三劑，或先每兩個月給予一次，然後每月給予一次，然後每 15 天給予一次。可以選擇擴大治療組的規模並將治療次數延長至總共三至六劑以上。

Besides the pharmacokinetic and pharmacodynamic data and dose optimization, the trial will assess safety and efficacy. The trial will be a basket trial initially and has been approved previously by the FDA and site startup is ongoing.

除了藥物動力學和藥效動力學數據以及劑量優化外，試驗還將評估安全性和有效性。該試驗最初將是一項籃子試驗，之前已獲得 FDA 批准，並且現場啟動正在進行中。

The plan to pursue both single and multiple doses in an accelerated clinical development approach is based on the positive clinical data specifically presented at the end of last year at the Society for Neuron Oncology Annual Meeting and the San Antonio Breast Cancer Symposium in December, as well as data that has been obtained subsequently. Those conference presentations include important new data on PK/PD safety, clinical response and survival.

計畫以加速臨床開發方式進行單劑量和多劑量治療，是基於去年年底在神經元腫瘤學會年會和 12 月聖安東尼奧乳癌研討會上特別提出的積極臨床數據，以及隨後獲得的數據。這些會議報告包括有關 PK/PD 安全性、臨床反應和存活的重要新數據。

Key highlights of the conference presentations and some of the more recent data that we will present in detail at upcoming conferences include 29 patients with LM who received a single intraventricular dose of REYOBIQ between 6.6 and 75 millicuries.

會議報告的主要亮點以及我們將在即將召開的會議上詳細介紹的一些最新數據包括 29 名 LM 患者，他們接受了單次腦室內劑量 6.6 至 75 毫居里的 REYOBIQ。

In terms of safety data, there was one DLT, which is a grade 4 platelet count reduction that was observed at the Cohort 5 dose of 66.14 millicuries, and two DLTs were observed in one patient in Cohort 6. That was a grade 4 platelet and neutrophil count reductions, indicating at least some bone marrow exposure consistent with the PK analysis data.

在安全性資料方面，在第 5 組劑量 66.14 毫居里時觀察到一次 DLT，即 4 級血小板計數減少，在第 6 組一名患者中觀察到兩次 DLT。這是 4 級血小板和中性粒細胞計數減少，顯示至少有一些骨髓暴露與 PK 分析數據一致。

Notably, there were no SAEs that occurred in Cohort 4 patients and what is determined to be the RP2D. PK and PD analysis showed target to off-target radiation-absorbed dose ratios of greater than 100 to 1. To put that in perspective, such ratios are impressive because they mean the dose is much more effectively delivered to the area of interest, the tumor in this case, than to the other areas of the body where one desires to keep the doses as low as possible. In other words, our drug design and formulation strategy works.

值得注意的是，第 4 組患者中沒有發生 SAE，並且被確定為 RP2D。PK 和 PD 分析表明，目標與脫靶輻射吸收劑量比大於 100:1。從這個角度來看，這樣的比例令人印象深刻，因為它們意味著劑量更有效地輸送到感興趣的區域（在本例中是腫瘤），而不是輸送到人們希望將劑量保持在盡可能低的身體其他部位。換句話說，我們的藥物設計和配方策略是有效的。

Clinical response to a single dose of REYOBIQ was assessed through 4 months or 112 days post-treatment to deliberately exclude the effect on patients receiving (technical difficulty) under a compassionate use protocol who survived well beyond the published median overall survival. Specifically, in these patients, we assessed change in CSF tumor cells via our CNSide tumor cell enumeration assay, which is the best measure of tumor cell bulk or prevalence. Also, we looked at radiographic response, and survival benefit was also assessed.

在治療後 4 個月或 112 天內對單劑量 REYOBIQ 的臨床反應進行評估，以刻意排除接受同情用藥方案治療（技術難度）的患者的影響，這些患者的生存期遠遠超過已公佈的中位總生存期。具體來說，在這些患者中，我們透過 CNSide 腫瘤細胞計數分析評估了 CSF 腫瘤細胞的變化，這是測量腫瘤細胞數量或流行程度的最佳方法。此外，我們也觀察了放射學反應，並評估了存活益處。

Through Cohort 5 and at the time of data cutoff for the conference presentations, data was available for 16 patients. 5 or 31% of those patients showed a radiographic response based on investigator (technical difficulty). We also used clinical benefit rate, or CBR, as an outcome measure in this very fragile patient population as it encompasses complete response, partial response, and stable disease outcomes.

透過第 5 組以及會議報告的數據截止時間，共有 16 名患者的數據可用。 5 或 31% 的患者根據研究者的研究結果表現出放射學反應（技術難度）。我們也使用臨床受益率（CBR）作為這個非常脆弱的患者群體的結果衡量標準，因為它涵蓋完全緩解、部分緩解和穩定的疾病結果。

An additional 7 of the 16 patients I just mentioned showed stable disease through four months for a rated graphically determined clinical benefit rate when combining the five I just mentioned before of 75%. So 75% CBR related to imaging analysis.

在我剛才提到的 16 名患者中，另外 7 名患者在四個月內病情穩定，將我剛才提到的五名患者結合起來，其額定圖形確定的臨床受益率為 75%。因此 75% 的 CBR 與成像分析有關。

Additionally, in terms of clinical responses, a decrease in disease symptoms was noticed in 2 of 14 evaluable patients, or 14%, with 10 showing stable symptoms through four months for a clinical benefit rate of 86%.

此外，在臨床反應方面，14 名可評估患者中，有 2 名（14%）出現疾病症狀減輕，其中 10 名患者在四個月內症狀穩定，臨床受益率為 86%。

Lastly, when looking at the cerebrospinal fluid, or the CSF tumor cell enumeration assay, again, our CNSide assay, which is the most sensitive measure we have for assessing tumor volume, which has also been shown to correlate with survival, this decreased up to 100% by day 28 following REYOBIQ treatment, with 4 of the 15 evaluable patients showing a response translating to a clinical benefit rate of 93%.

最後，當觀察腦脊髓液或 CSF 腫瘤細胞計數試驗時，同樣，我們的 CNSide 試驗是我們評估腫瘤體積最敏感的指標，也已被證明與生存率相關，在 REYOBIQ 治療後第 28 天，腫瘤體積下降了 100%，15 名可評估患者中有 4 名出現反應，臨床受益率為 93%。

In terms of survival, median overall survival was nine months, which compares favorably to the historically reported consensus in the literature of about four months, supporting the potential efficacy of REYOBIQ for LM. The full presentations from SNO and San Antonio Breast Cancer Meetings are available on our website for further review.

在存活方面，中位總存活期為 9 個月，與文獻中歷史報導的約 4 個月的共識相比更為有利，支持了 REYOBIQ 對 LM 的潛在療效。SNO 和聖安東尼奧乳癌會議的完整簡報可在我們的網站上查閱，以供進一步查看。

In terms of guidance for our integrated development plan for LM, we anticipate an FDA meeting, likely a Type B end of Phase 1 meeting as soon as possible to align on the following. First, a path to a registrational trial for a single dose of REYOBIQ in patients with LM resulting from breast cancer primaries. That includes a single-dose expansion trial that would provide an expeditious path to registration. Key issues to resolve in this meeting, if possible, are things like endpoints, comparators, tumor subtypes that we'll study, and so forth.

就我們對 LM 的綜合開發計劃的指導而言，我們預計 FDA 將盡快召開一次會議，很可能是第 1 階段 B 類結束會議，以就以下內容達成一致。首先，對因乳癌原發性 LM 患者進行單劑量 REYOBIQ 的註冊試驗。其中包括單劑量擴展試驗，這將提供快速的註冊途徑。如果可能的話，本次會議要解決的關鍵問題是終點、比較器、我們將要研究的腫瘤亞型等等。

Second, we seek to align on the integration of a future multiple-dose strategy given the promising data we have seen with compassionate use treatment in the single dose Phase 1 and anticipated data expected later this year in the formal multiple-dose escalation trial.

其次，鑑於我們在單劑量第一階段的同情用藥治療中看到的有希望的數據以及預計在今年晚些時候正式的多劑量遞增試驗中得到的數據，我們尋求在未來的多劑量策略整合方面達成一致。

In the second half of 2025, we anticipate completion of the first and longest duration of the multiple-dose expansion cohorts. By then, we anticipate having FDA alignment, a definitive clinical plan for a single-dose expansion trial, and site onboarding should be ongoing.

我們預計在 2025 年下半年完成多劑量擴展隊列的第一次也是持續時間最長的一次。到那時，我們預計將獲得 FDA 的批准，單劑量擴展試驗的明確臨床計劃，並且現場入職培訓也將持續進行。

Furthermore, on May 9, 2025, Plus will be presenting response data from the ReSPECT single-dose LM trial, essentially the full Phase 1 data set as it exists at that time, at the Nuclear Medicine and Neuroncology Symposium in Vienna, Austria. Other data presentations are anticipated throughout the remainder of 2025, and we'll update on acceptance and agreement to participate.

此外，2025 年 5 月 9 日，Plus 將在奧地利維也納舉行的核子醫學和神經腫瘤學研討會上展示 ReSPECT 單劑量 LM 試驗的反應數據，基本上是當時存在的完整第 1 階段數據集。預計在 2025 年剩餘時間內將有其他數據展示，我們將更新接受和參與協議的資訊。

Now switching gears a bit to glioblastoma. In terms of ReSPECT, GBM, and dose trials. The Phase 1 trial results were recently published in Nature Communications, a prestigious high-impact journal. We have made that publication open access and is now available on Plus' website or directly through Nature. The results show a strong safety and efficacy signal that has been further confirmed through the first half of the Phase 2 trial as previously reported.

現在稍微轉換一下主題，來談談膠質母細胞瘤。就 ReSPECT、GBM 和劑量試驗而言。第一階段試驗結果最近發表在著名的高影響力期刊《自然通訊》。我們已將該出版物開放，現在可以在 Plus 網站上或直接透過《Nature》取得。結果顯示出強大的安全性和有效性訊號，正如先前報導的那樣，這已通過第二階段試驗的前半部分得到進一步證實。

For the program as a whole, a total of 52 patients have been enrolled through both both Phase 1 and 2, and we anticipate Phase 2 completion in 2025. And the ReSPECT trial continues to benefit from a grant from the NCI.

就整個計畫而言，第 1 階段和第 2 階段共有 52 名患者入組，我們預計第 2 階段將於 2025 年完成。ReSPECT 試驗繼續受益於 NCI 的資助。

An offshoot of the adult glioblastoma trial is our pediatric brain cancer program. We previously announced that we have received a US Department of Defense award of a $3 million grant to substantially support a Phase 1 trial for children with pediatric high-grade glioma and ependymoma. Approximately a $900,000 payment was received in September 2024 as part of this award, and we anticipate an additional $1.1 million payment in 2025.

成人膠質母細胞瘤試驗的一個分支是我們的兒童腦癌計畫。我們先前宣布，我們已獲得美國國防部 300 萬美元的資助，以大力支持兒童高級別膠質瘤和室管膜瘤的 1 期試驗。作為該獎項的一部分，我們在 2024 年 9 月收到了約 90 萬美元的付款，預計 2025 年還將收到 110 萬美元的付款。

Interactions with the FDA are ongoing towards final IND approval. We anticipate obtaining that approval in 2025 with Lurie Children's Hospital associated with Northwestern and Chicago serving as the initial clinical trial site.

目前正與 FDA 進行溝通以獲得最終的 IND 批准。我們預計將於 2025 年獲得該批准，西北大學和芝加哥的 Lurie 兒童醫院將作為初始臨床試驗地點。

Now, regarding REYOBIQ radiotherapeutic drug production and supply chain management, this remains an important and active focus (technical difficulty) ongoing behind the scenes. Recently, we announced partnerships with SpectronRx, IsoTherapeutics, RadioMedix, and ABx, the details of which can be found in previous press releases and earning earnings calls.

現在，關於REYOBIQ放射治療藥物的生產和供應鏈管理，這仍然是幕後正在進行的一個重要且活躍的焦點（技術困難）。最近，我們宣布與 SpectronRx、IsoTherapeutics、RadioMedix 和 ABx 建立合作夥伴關係，詳情可在先前的新聞稿和收益電話會議中找到。

Furthermore, to ensure our ability to meet the demands of expedited or accelerated late-stage clinical trials, as I mentioned before, and future commercial production requirements for REYOBIQ, we continue to expand key partnerships in 2025 as we have in previous years, but now with the focus geared more towards supply chain redundancy and backup supply.

此外，正如我之前提到的，為了確保我們能夠滿足加快或加速後期臨床試驗的需求，以及 REYOBIQ 未來的商業生產要求，我們將像往年一樣在 2025 年繼續擴大關鍵合作夥伴關係，但現在的重點更多地放在供應鏈冗餘和備用供應上。

Now, fundamentally switching gears, I'd like to update you on our CNSide business. But I think it's important to give a brief background on CNSide for those of you that may not be as familiar with it. And frankly, we haven't talked much about it over the over the last (technical difficulty).

現在，從根本上轉換主題，我想向您介紹我們的 CNSide 業務。但我認為，對於那些可能不太熟悉 CNSide 的人來說，簡單介紹一下 CNSide 的背景是很重要的。坦白說，過去我們並沒有談論太多（技術難度）。

CNSide is a CNS cancer testing platform we have been utilizing in our ReSPECT-LM clinical development programs as a biomarker and exploratory endpoint since 2022. Since then and over that time, extremely high conviction of the value of CNSide for REYOBIQ's future commercial success, and specifically I mean increasing the total addressable market by 2 to 4 times for REYOBIQ.

CNSide 是一個中樞神經系統癌症檢測平台，自 2022 年以來，我們一直在 ReSPECT-LM 臨床開發計畫中將其用作生物標記和探索性終點。從那時起，我一直堅信 CNSide 對 REYOBIQ 未來商業成功的價值，具體來說，我的意思是將 REYOBIQ 的總目標市場擴大 2 到 4 倍。

The immense value also for hundreds of thousands of cancer patients at risk for LM but are in a diagnostic quandary. And then finally, the substantial value of CNSide is a commercial diagnostic platform in and of itself.

對於數十萬面臨 LM 風險但診斷困難的癌症患者來說，這也具有巨大的價值。最後，CNSide 的實質價值在於其本身就是一個商業診斷平台。

Given this, we seized on the opportunity last year to acquire it outright. Since then, we have been investing thoughtfully in the people, the means, and the materials to bring CNSide back to market in a manner that can unlock its full value for patients, providers, and stockholders.

有鑑於此，我們去年抓住機會直接收購了它。自那時起，我們一直在對人才、方法和材料進行精心投資，以便將 CNSide 重新推向市場，為患者、供應商和股東釋放其全部價值。

What is CNSide? What does it do? CNSide, in a brief way, brief description, is it's a cerebrospinal fluid, or CSF assay platform, that accomplishes three core things.

CNSide 是什麼？它起什麼作用？簡而言之，CNSide 是一個腦脊髓液或 CSF 檢測平台，可完成三個核心任務。

First, diagnosis. Specifically, it can confirm, more importantly, reject the clinical suspicion doctors may have that a patient with almost any type of solid tissue cancer may have LM. It does so at a much higher sensitivity, or said differently, a true positive or true negative rate that's much better that can be done with existing technology, which is essentially cytology.

首先，診斷。具體來說，它可以證實，更重要的是，可以駁斥醫生的臨床懷疑，即幾乎任何類型的實體組織癌患者都可能患有 LM。它具有更高的靈敏度，或者換句話說，其真實陽性率或真實陰性率比現有技術（本質上是細胞學）好得多。

It also accomplishes treatment monitoring. In patients with LM, monitoring of CSF tumor cells has been shown to correlate with survival and is now recommended in the NCCN clinical guidelines, i.e., one can address whether a patient is responding to treatment. Do they need a different therapy or therapeutic of choice, or perhaps can therapy be paused potentially? Perhaps they may have safety issues related to their current course of therapy.

它還可以完成治療監測。對於 LM 患者，腦脊髓液腫瘤細胞監測已被證實與存活率相關，目前 NCCN 臨床指引已建議進行此類監測，即可以確定患者是否對治療有反應。他們是否需要選擇不同的療法或治療方法，或者是否可以暫停治療？也許他們目前的治療過程有安全問題。

And then finally, as a treatment selection tool, LM cancers often exhibit a drift in biomolecular signal that may influence treatment approaches and drug selection decisions in the future once drugs are approved by the FDA. Clinical data has shown that CNSide can be important in this clinical decision making process.

最後，作為一種治療選擇工具，LM 癌症通常會表現出生物分子訊號的漂移，一旦藥物獲得 FDA 批准，這可能會影響未來的治療方法和藥物選擇決策。臨床數據顯示 CNSide 在這項臨床決策過程中發揮重要作用。

Users of CNSide are neuroncologists, neuroimmunologists, and medical oncologists or other practitioners caring for patients with common cancers such as breast and lung cancers, as well as melanoma and others. It's not strictly limited to patients that have LM or highly suspected suspected of having LM.

CNSide 的使用者是神經腫瘤學家、神經免疫學家、腫瘤內科醫生或其他護理乳腺癌、肺癌以及黑色素瘤等常見癌症患者的從業者。它並不嚴格限於患有 LM 或高度懷疑患有 LM 的患者。

Now let me talk about the status of the business in brief. As mentioned, we have hired a seasoned core team to both launch and manage the business day to day, specifically Mr. Bradley and Dr. Stein, who I mentioned previously. But other key hires have been made and onboarded in the past 12 months.

現在我簡單介紹一下業務狀況。如上所述，我們聘請了一支經驗豐富的核心團隊來啟動和管理日常業務，特別是我之前提到的布拉德利先生和史丹博士。但在過去 12 個月中，其他關鍵員工也已入職。

We have also established a clear registered centralized laboratory for test operations in Houston, Texas. That is actively testing patient samples from our clinical trial and ongoing pre-commercial pilot testing. Key market access activities have been ongoing for nine months in the areas of medical affairs and reimbursement. This includes negotiations with commercial payers, as well as seeking expanded coding approvals and NCCN CNS cancer change requests for LM diagnosis.

我們還在德克薩斯州休斯頓建立了一個明確註冊的集中實驗室，用於測試操作。我們正在積極測試來自臨床試驗和正在進行的商業化前試點測試的患者樣本。在醫療事務和報銷領域，關鍵的市場准入活動已經持續了九個月。這包括與商業付款人的談判，以及尋求擴大編碼批准和 NCCN CNS 癌症對 LM 診斷的變更請求。

Furthermore, key marketing, corporate product branding, and sales planning activities have been completed.

此外，關鍵的行銷、企業產品品牌和銷售計畫活動已經完成。

In terms of guidance. First of all, the company will be exhibiting CNSide at key medical conferences in 2025 and plan to submit abstracts and publications as we move forward this year.

在指導方面。首先，該公司將在 2025 年的主要醫學會議上展示 CNSide，並計劃在今年提交摘要和出版物。

Commercially, the CNSide tumor cell enumeration test is on track to launch fully this year, beginning in a geographically limited manner, expanding over the course of the year as market access activities such as state licensures, key payer agreements, and medical system contracts are expanded. Specific financial guidance will be forthcoming later this year as visibility improves.

從商業角度來看，CNSide 腫瘤細胞計數測試預計將在今年全面推出，首先以地域限制的方式開始，隨著國家許可、關鍵付款人協議和醫療系統合約等市場准入活動的擴大，測試將在一年內逐漸擴展。隨著知名度的提高，具體的財務指引將於今年稍後公佈。

And finally, CNSide product offerings will also evolve in 2025, and more on that over the next few quarters.

最後，CNSide 產品也將在 2025 年持續發展，並在接下來的幾季中推出更多產品。

And with that, I'll now turn the call over to our Chief Financial Officer, Andrew Sims. Andrew?

現在，我將把電話轉給我們的財務長安德魯·西姆斯 (Andrew Sims)。安德魯？

Thank you, Marc. Good afternoon, everyone. Please refer to our press release issued earlier today for a summary of our financial results for the fourth quarter and full year ended December 2024.

謝謝你，馬克。大家下午好。請參閱我們今天稍早發布的新聞稿，以了解我們截至 2024 年 12 月的第四季度和全年財務業績摘要。

The cash and investments balance was $3.6 million at December 31, 2024, compared to $8.6 million at December 31, 2023. The company recognized $5.8 million in grant revenue in 2024, compared to $4.9 million in 2023. This represents CPRIT's share of the costs incurred for our REYOBIQ development for the treatment of patients with LM.

截至 2024 年 12 月 31 日的現金和投資餘額為 360 萬美元，而 2023 年 12 月 31 日為 860 萬美元。該公司 2024 年的贈款收入為 580 萬美元，而 2023 年為 490 萬美元。這代表了 CPRIT 在我們開發 REYOBIQ 用於治療 LM 患者時所產生的成本份額。

We expect 2025 grant revenue to be in the range of $6 million to $8 million, of which we've already received (technical difficulty). The total operating loss in 2024 was $14.7 million compared to $13.3 million for the full year 2023. The increase is primarily due to increased spend relating to the ReSPECT-LM trial.

我們預計 2025 年的贈款收入將在 600 萬美元至 800 萬美元之間，其中我們已經收到了（技術難度）。2024 年總營運虧損為 1,470 萬美元，而 2023 年全年為 1,330 萬美元。成長的主要原因是與 ReSPECT-LM 試驗相關的支出增加。

Net loss in 2024 was $13 million, or $1.95 per share, compared to a net loss of $13.3 million, or $4.24 per share for full year 2023.

2024 年淨虧損為 1,300 萬美元，即每股 1.95 美元，而 2023 年全年淨虧損為 1,330 萬美元，即每股 4.24 美元。

I would also like to provide an update on our runway based on the previously announced private placement and provide guidance on our grant funding for 2025. There are two additional sources of cash to which Plus has access beyond the balance disclosed in cash on hand and liquid investments on a Q4 2024 balance sheet.

我還想根據先前宣布的私募情況提供我們的最新進展，並為我們 2025 年的贈款資金提供指導。除了 2024 年第四季資產負債表上揭露的現金餘額和流動投資外，Plus 還可以獲得另外兩個現金來源。

The first source is the cash from the recently announced private placement closed on March 4 with gross proceeds of $15 million. The second source of cash remains our continued funding through three grants.

第一個來源是最近宣布的私募資金，該私募於 3 月 4 日完成，總收益為 1500 萬美元。第二個現金來源仍然是我們透過三項撥款持續提供的資金。

Firstly, the CPRIT grant to support the ReSPECT-LM trial. Coming into 2025, we have $7.2 million remaining to be received on the grants, of which we received $2 million in Q1 2025 and are on track to receive $1.6 million in Q2, with the balance to be received in late Q3 or early Q4 2025.

首先，CPRIT 撥款支持 ReSPECT-LM 試驗。到 2025 年，我們還有 720 萬美元的贈款待收，其中我們在 2025 年第一季收到了 200 萬美元，並預計在第二季度收到 160 萬美元，餘額將在 2025 年第三季末或第四季初收到。

Plus also has just over $2 million remaining of grant proceeds from an award from the United States Department of Defense for $3 million in total to support the upcoming ReSPECT pediatric brain cancer trial. The first advance was received in 2024 for just under $900,000. Plus, it also continues to benefit from the NIH grant to support the ReSPECT-GBM Phase 1/2 trial.

此外，該公司還從美國國防部獲得了總計 300 萬美元的資助，剩餘的 200 多萬美元將用於支持即將進行的 ReSPECT 兒童腦癌試驗。第一筆預付款於 2024 年收到，金額略低於 90 萬美元。此外，它還繼續受益於 NIH 的資助，以支持 ReSPECT-GBM 第 1/2 階段試驗。

Although expected to be completed in 2025, it currently covers approximately 90% of the overall trial costs. We also continue to source other non-dilutive sources of capital.

儘管預計要到 2025 年才能完成，但目前它已涵蓋了整個試驗成本的約 90%。我們也將繼續尋找其他非稀釋性資本來源。

We will continue to only report on individual grants when they are awarded. In addition, in Q1 2025, we consolidated our operations into our CNSide facility in Houston, streamlining operations and reducing costs. Taken in total, the cash runway is well into (technical difficulty) Marc laid out being fully funded.

我們將繼續僅在個別贈款獲得時進行報告。此外，2025 年第一季度，我們將業務整合至位於休士頓的 CNSide 工廠，從而簡化營運並降低成本。整體而言，現金流已經完全進入馬克所規劃的（技術難度）全額資助階段。

And now I'll turn it back to you, Marc.

現在我把話題轉回給你，馬克。

Thank you, Andrew. Before we move on to the Q&A, I'll take a moment to provide a summary of guidance on anticipated key events and milestones for the remainder of the year.

謝謝你，安德魯。在我們進入問答環節之前，我將花一點時間來總結今年剩餘時間預計發生的關鍵事件和里程碑的指導。

First of all, in terms of data and related presentations, specifically at the Nuclear Medicine and Neuro Oncology Symposium in May, we'll provide a comprehensive ReSPECT-LM data review of the single-dose Phase 1 trial, including new key safety and efficacy data. In terms of other targeted meetings for the remainder of the year, we plan to contribute abstracts and presentations along the way at a minimum to our core constituencies in oncology, specifically at the Society for Neuro-Oncology, American Society of Clinical Oncology Joint Meeting in August and the Society for Neuro-Oncology Annual Conference in November.

首先，在數據和相關展示方面，特別是在 5 月的核醫和神經腫瘤學研討會上，我們將對單劑量 1 期試驗的 ReSPECT-LM 數據進行全面的審查，包括新的關鍵安全性和有效性數據。就今年剩餘時間的其他目標會議而言，我們計劃至少向腫瘤學領域的核心支持者貢獻摘要和演示文稿，特別是在 8 月份的神經腫瘤學會、美國臨床腫瘤學會聯合會議和 11 月份的神經腫瘤學會年會上。

In addition, besides the submitted abstracts, the company plans to host an educational seminar at SNO/ASCO featuring KOL presentations on both REYOBIQ and CNSide and potentially at the SNO Annual Meeting.

此外，除了提交的摘要外，該公司還計劃在 SNO/ASCO 舉辦一場教育研討會，其中將包括關於 REYOBIQ 和 CNSide 的 KOL 演講，並可能在 SNO 年會上進行演講。

More on that to come later. In terms of clinical and regulatory milestones this year, we are on track to initiate the ReSPECT-LM Phase 1 multiple dose escalation trial and complete the first cohort of multiple doses at the two-month intervals. We're also on track to meet with the FDA this year following completion of the ReSPECT Phase 1 clinical study report, which is in process to seek agreement with the FDA on a few things. First, the broad issues around the clinical development of REYOBIQ through approval, first for breast cancer and other cancers.

稍後我們將對此進行更詳細的介紹。就今年的臨床和監管里程碑而言，我們預計將啟動 ReSPECT-LM 第 1 階段多劑量遞增試驗，並以兩個月的間隔完成第一批多劑量試驗。在完成 ReSPECT 第一階段臨床研究報告後，我們也計劃今年與 FDA 會面，並正在就一些事項尋求與 FDA 達成協議。首先，REYOBIQ 透過審批的臨床開發面臨的廣泛問題，首先是針對乳癌和其他癌症。

Also, we intend for these meetings to provide us with substantial agreement on key issues such that we can optimally design a Phase 2/3 registrational trial for both a single dose of REYOBIQ for breast cancer and later to integrate dosing optimization thereafter as additional multiple dose data becomes available.

此外，我們希望這些會議能為我們就關鍵問題達成實質共識，以便我們能夠最佳地設計針對乳癌的單劑量 REYOBIQ 的 2/3 期註冊試驗，並在之後獲得更多多劑量數據時整合劑量優化。

And then, finally, as a result of these meetings, we will be better able to design a single-dose expansion trial in agreement with the FDA and be in start-up mode in the second half of 2025. Also, we intend to complete enrollment of the final patients in the ReSPECT-GBM Phase 2 trial by the end of the year.

最後，透過這些會議，我們將能夠更好地設計與 FDA 達成一致的單劑量擴展試驗，並在 2025 年下半年進入啟動模式。此外，我們計劃在今年年底前完成 ReSPECT-GBM 第 2 期試驗的最終患者的招募。

We also plan to obtain IND approval for the ReSPECT-PBC Phase 1 trial of REYOBIQ for pediatric brain cancer. We'll also push to get enrollment started there as well this year at Lurie Children's Hospital. Regarding CNSide, this will be a very important year for Plus, with many commercially oriented milestones planned.

我們也計劃獲得 REYOBIQ 針對兒童腦癌的 ReSPECT-PBC 第一階段試驗的 IND 批准。我們也將推動今年在 Lurie 兒童醫院開始招生。對於 CNSide 而言，今年對 Plus 來說將是非常重要的一年，並計劃實現許多商業化的里程碑。

Specifically, CNSide is on track to launch fully this year. This is beginning with a geographically limited introduction now, but with building steam, over the course of the year as CNSide is an assay platform, initial tumor cell enumeration or tumor cell number counting is to be followed with additional testing capabilities thereafter. Market access activities are ongoing, and state hospital and bellwether medical system contracts will be announced as completed.

具體來說，CNSide 預計在今年全面推出。目前，這項服務僅在有限的地理範圍內開展，但隨著 CNSide 成為一種檢測平台，在未來一年內，該服務將逐漸發展壯大，初始腫瘤細胞計數或腫瘤細胞數量計數之後還將增加額外的測試能力。市場准入活動正在進行中，州立醫院和龍頭醫療系統合約即將宣布完成。

Geographically, since lab testing is centralized, market expansion will be driven as market access objectives are met. Most importantly, commercially related financial guidance is planned to begin later in this year as key milestones are achieved and visibility is improved. Additionally, the company will be exhibiting CNSide at key medical conferences and plans to submit a variety of abstracts and publications as we move forward this year.

從地理位置來看，由於實驗室測試是集中的，因此隨著市場准入目標的實現，市場擴張將得到推動。最重要的是，隨著關鍵里程碑的實現和知名度的提高，與商業相關的財務指導計劃於今年稍後開始。此外，該公司將在主要的醫學會議上展示 CNSide，並計劃在今年提交各種摘要和出版物。

So with that, Sherry, I'll turn it back over to you for Q&A.

因此，雪莉，我將把時間交還給你進行問答。

(Operator Instructions) Edward Woo, Ascendiant Capital.

（操作員指示）Edward Woo，Ascendiant Capital。

Congratulations on all the progress that you're making. On the CNside, do you anticipate building up a major sales force? Or will you look for partners to commercialize this?

恭喜你所取得的所有進步。在 CNside，您是否預計會建立一支主要的銷售團隊？或者您會尋找合作夥伴來實現這項商業化？

Thanks for the question. Appreciate it. So, it's not a major sales force, and let me clarify that. This is a niche opportunity. So in one sense, we're beginning the sales process with academic neuro-oncologists at major oncology centers, call it, the 30 NCI-designated cancer centers. That's a relatively small group.

謝謝你的提問。非常感謝。所以，這不是一支主要的銷售隊伍，讓我澄清一下。這是一個利基機會。因此從某種意義上說，我們正在與主要腫瘤中心（即 30 個 NCI 指定的癌症中心）的學術神經腫瘤學家開始銷售流程。這是一個相對較小的群體。

There are only about 300 neuro-oncologists in the country. There are a lot more medical oncologists, and there are a lot more emergency room doctors who could use it. But that will come later. The key thing is to launch this into this narrow group of thought leaders at major institutions, which probably gets you 80% of the market and then, over time, expand it out to the broader medical oncology market and perhaps even, as mentioned, the ER docs.

全國只有大約300名神經腫瘤學家。現在有更多的腫瘤內科醫生和更多的急診室醫生可以使用它。但那將是以後的事。關鍵在於將其推向主要機構中這一小群思想領袖，這可能會讓你佔據 80% 的市場份額，然後隨著時間的推移，將其擴展到更廣泛的腫瘤醫學市場，甚至可能像前面提到的那樣，擴展到急診室醫生市場。

That's well within our capability to execute and finance. And I don't think it makes sense at this point to partner, although at some point, partnering in the US and/or outside the US will be something that we're going to look at very closely and be predisposed to do.

這完全在我們的執行和融資能力範圍內。我認為現在進行合作是沒有意義的，儘管在某些時候，我們會非常仔細地考慮並傾向於在美國和/或美國以外合作。

(Operator Instructions) Jason Kolbert, D. Boral Capital.

（操作員說明）Jason Kolbert，D. Boral Capital。

Hi, Dr. Hedrickt. This is [Lindsey] on for Jason. First off, I just want to say congratulations on the financing. We just have a few questions for you. The first question is the recurrent GBM trial is the most advanced. Are you able to lay out what must happen to meet the goal of data this year?

你好，Hedrickt 博士。我是 [Lindsey]，為 Jason 主持。首先，我只想對融資表示祝賀。我們只想問您幾個問題。第一個問題是復發性GBM試驗是最先進的。您能否詳細說明為了實現今年的數據目標必須採取哪些措施？

Hi, Lindsey. Yes, in a way, it's most advanced, although if you truly look at the integrated development plans for both, it's very likely that LM could get approved before. But superficially, yes, GBM is in sort of late-stage Phase 2. So as I mentioned, we've enrolled over 50 patients, including completing Phase 1, completing the dose escalation over halfway through the Phase 2.

你好，林賽。是的，從某種程度上來說，它是最先進的，但如果你真正看一下兩者的綜合發展計劃，LM 很有可能更早獲得批准。但從表面上看，GBM 確實處於第 2 階段的後期階段。正如我所提到的，我們已經招募了 50 多名患者，包括完成第 1 階段的患者，並在第 2 階段中期完成了劑量遞增。

The key thing has been adding new sites. We've got a flood of new sites that are interested on the heels of the Nature Communications publication. We really don't need more new sites. We now have five sites that are enrolling, now a New York site and an upper Midwest site. So we've got sort of Chicago area and Upper Midwest covered as well as the Northeast.

關鍵是增加新站點。在《自然通訊》發表之後，我們收到了大量對此感興趣的新網站。我們確實不需要更多的新站點。我們現在有五個招生點，一個位於紐約，另一個位於中西部北部。因此，我們的業務範圍涵蓋芝加哥地區、中西部北部地區以及東北部地區。

So we're really talking about 11 patients to complete that. And so that will be a focus over the next year. I think that's going to be achievable.

所以我們實際上談論的是 11 名患者來完成這項工作。因此這將是明年的重點。我認為這是可以實現的。

And just a follow-up question. Can you remind me of the powering assumptions behind the trial? 80% powered for what delta? And then what would be exciting data for that?

這只是一個後續問題。你能提醒我這次試驗背後的主要假設嗎？80% 的動力適用於哪個三角洲？那麼，哪些數據會令人興奮呢？

So in Phase 2, its comparator is essentially the standard of care. We've actually conducted two real-world control arms that we funded through our partner, Medidata, and we have looked at two different comparator arms. One is patients that have been treated with monotherapy with the only approved drug for recurrent GBM, that's bevacizumab. And those patients live under eight months. And that's a relatively large trial.

因此，在第 2 階段，其比較器基本上是護理標準。實際上，我們已經進行了兩個由我們的合作夥伴 Medidata 資助的真實世界對照組，並且我們已經研究了兩個不同的比較組。一類是已經使用唯一獲準用於治療復發性膠質母細胞瘤的藥物貝伐單抗進行單一療法治療的患者。這些病人的存活時間不到八個月。這是一次相對較大的試驗。

That also compares with publications as well in terms of meta-analysis on recurrent GBM. At the behest of the FDA, who wanted to control for the effects of convection-enhanced delivery. We also looked at patients who received CED but were also demographically mapped to our trial. Again, the median overall survival is about eight months. So kind of any way you cut it, recurrent GBM patients, no matter what you do, live on average about eight months.

這也與復發性 GBM 的薈萃分析的出版物進行了比較。在 FDA 的要求下，他們想要控制對流增強輸送的效果。我們也研究了接受 CED 治療但在人口統計學上也與我們試驗相關的患者。再次，總存活期中位數約為八個月。所以無論如何，復發性 GBM 患者無論採取什麼措施，平均存活期都只有 8 個月左右。

So that's our clinical hurdle rate. In terms of powering assumptions, I'll kind of cut to the chase here. You kind of look at 80% powering, and you look at that as the comparator. And really, I don't think it matters as your comparator, as all roads lead to eight months. It seems that you're really talking about a trial of somewhere in the neighborhood of 100 to 150 patients.

這就是我們的臨床障礙率。就支持假設而言，我在這裡就開門見山了。您可以觀察 80% 的功率，並將其作為比較器。而實際上，我認為這作為比較來說並不重要，因為所有的道路都通往八個月。看起來您實際上談論的是針對大約 100 到 150 名患者的試驗。

We've had discussions with the FDA about using real-world control data. Actually, a real-world control Phase 3 design has been approved by the FDA. And if we're able to do that, that will mean the active patients are going to be much closer to maybe 100 patients to get that same level of powering such that we would have a randomization scheme that sort of looks like this.

我們已經與 FDA 討論了使用真實世界控制數據的問題。實際上，真實世界控制第 3 階段設計已獲得 FDA 批准。如果我們能夠做到這一點，那就意味著活躍的患者數量將更接近 100 名，以獲得相同水平的功率，這樣我們就會有一個類似這樣的隨機化方案。

You would treat three active patients and compare them to three control patients. And of those three control patients, two would be demographically matched real-world control patients and would be a true comparator prospectively taken and that would likely be either a comparator to bevacizumab or radiation or standard of care, which is essentially the physician's choice. Does that answer your question?

您將治療三名活躍患者，並將他們與三名對照患者進行比較。在這三名對照患者中，有兩名是人口統計學上匹配的真實世界對照患者，並且將是前瞻性的真正比較對象，並且可能是貝伐單抗或放射或護理標準的比較對象，這基本上是醫生的選擇。這回答了你的問題嗎？

Yes, it does. And I just want to say congratulations on the progress in the quarter.

是的。我只想對本季的進展表示祝賀。

Sean Lee, H.C. Wainwright.

肖恩李，H.C.溫賴特。

My first one is on the LM study. So you proposed a dose expansion at the 44-millicurie dose. I was just wondering if that is going to be an additional cohort to the Phase 2 study. Or are you mentioning that as part of the Phase 2 study that you're planning?

我的第一個是關於 LM 研究的。因此您建議將劑量擴大至 44 毫居里劑量。我只是想知道這是否會成為第二階段研究的額外群體。或者您提到這是您正在計劃的第二階段研究的一部分？

Sean, thanks for the question. So let me tell you what my aspiration with that is, and it is subject to discussion with the FDA. And it's subjected to their desire to move this program quickly.

肖恩，謝謝你的提問。所以讓我告訴你我的願望是什麼，這取決於與 FDA 的討論。這取決於他們想要快速推進該計劃的願望。

I think the ideal path here would be for the FDA to sign off on a Phase 2 trial focused on breast cancer, likely HER2-positive, HER2-negative patients it equals 15 of each at the 44 millicurie. So the Phase 1 dose is a basket trial, includes lung patients and breast patients, gastrointestinal cancer patients, and so forth.

我認為理想的途徑是 FDA 批准一項針對乳癌的 2 期試驗，可能是 HER2 陽性患者，HER2 陰性患者，相當於 44 毫居里各 15 名患者。因此，第一階段的劑量是一個籃子試驗，包括肺癌患者和乳癌患者、胃腸道癌症患者等等。

So the key in segmenting the patients by molecular subtype is to the degree that overall survival is in the endpoint mix, there likely will be a differential survival depending on what kinds of patients one selects based on survival data that's been reported in patients with OM. So I think we want to sort that out. But from a statistical evaluation, this discussion with the FDA, I think, will elicit the proper endpoints.

因此，按分子亞型對患者進行細分的關鍵在於總體生存率在終點組合中的程度，根據已報告的 OM 患者生存數據，選擇哪種類型的患者可能會存在差異生存率。所以我認為我們想解決這個問題。但從統計評估來看，我認為與 FDA 的討論將會得出適當的結論。

Our belief is that while overall survival is important in the ultimate goal, because these patients have essentially two cancers, a primary cancer in the breast and a metastatic cancer, that confounds the interpretation of overall survival data. Our view is that actually CNSide is the best measure of response and correlates with survival and that it could be an important primary endpoint, co-primary endpoint, or secondary endpoint, and that would change the trial design dramatically.

我們認為，雖然整體存活率對於最終目標來說很重要，但由於這些患者基本上患有兩種癌症，即乳癌原發性癌症和轉移性癌症，因此這混淆了整體存活率數據的解釋。我們的觀點是，實際上 CNSide 是衡量反應的最佳指標，並且與生存率相關，它可能是一個重要的主要終點、共同主要終點或次要終點，並且會極大地改變試驗設計。

So my anticipation is if that's the way we go with the Phase 2 with 30 patients, 15 of each hormonal subtype, we could analyze those individually and also collectively that could provide enough patients ideally, and we can build this in upfront to roll directly into an approval trial. So that would be ideal. That will take a little bit more negotiation with the FDA and likely a bit more time to get up and running.

因此，我的預期是，如果我們按照這種方式進行第 2 階段研究，有 30 名患者，每種激素亞型 15 名，我們就可以對這些患者進行單獨分析，也可以對他們進行集體分析，理想情況下可以提供足夠的患者，我們可以提前建立這個機制，直接進入審批試驗。那就太理想了。這需要與 FDA 進行更多的談判，並且可能需要更多的時間才能啟動和運行。

We could also do a Phase 1b, which is essentially a direct dose expansion. That would be quicker, but it likely would not expedite the regulatory approval process as much as going directly into a Phase 2 or a Phase 2/3 pivotal design.

我們也可以進行 1b 階段，本質上是直接劑量擴展。這會更快，但可能不會像直接進入第 2 階段或第 2/3 階段關鍵設計那樣加快監管審批流程。

With regards to the multi-dose study then, would you wait for the first data to come out from that study before you initiate a Phase 2, or would you try to build that into a Phase 2, or would that, for example, need a second study afterward?

那麼，關於多劑量研究，您是否會等待該研究得出第一批數據後再啟動第 2 階段研究，或者您是否會嘗試將其納入第 2 階段研究，或者，例如，是否需要隨後進行第二項研究？

No, I think we're going to move forward directly into Phase 2 or Phase 1b. That data will be important no matter what we do in terms of increasing the performance data. On the proper endpoints in the trial, powering assumptions and expanding the PK/PD data. So, no matter what we do with multiple doses, that's going to be important data to drive the overall program. I think the Phase 1 data is very promising.

不，我認為我們將直接進入第 2 階段或第 1b 階段。無論我們採取什麼措施來提高效能數據，這些數據都很重要。在試驗中的適當終點，支持假設並擴展 PK/PD 數據。因此，無論我們如何對待多劑量，這都將是推動整個計劃的重要數據。我認為第一階段的數據非常有希望。

We've had multiple multi-year survivors, which is essentially unheard of. If you look at the survival Kaplan-Meier curve for median overall survival, you see a lot of long-tail survival, which is unheard of in the disease, which is a very positive thing.

我們已經有多個存活多年的患者，基本上是聞所未聞的。如果您查看中位總體生存期的 Kaplan-Meier 生存曲線，您會看到大量的長尾生存期，這在該疾病中是聞所未聞的，這是一件非常積極的事情。

So I do believe, based on the data, that proceeding with a single-dose approval is very promising and possible, and I think we should pursue it as quickly as we can. Either way, we win with that dataset and the multiple-dose data. I think we already know that multiple doses work.

因此，根據數據，我確實相信，進行單劑量批准是非常有希望和可能的，我認為我們應該盡快進行批准。無論哪種方式，我們都可以透過該數據集和多劑量數據獲得勝利。我想我們已經知道多次服用是有效的。

We've treated patients in the Phase 1, as you know, Sean, with multiple doses under compassionate use. We know on a small number of patients that we could do that safely at very high doses, and patients seem to live longer. Dose optimization can take a while.

正如肖恩您所知，我們已對處於第一階段的患者進行了多劑量的同情用藥治療。我們知道，對於少數患者，我們可以安全地以非常高的劑量進行治療，而且患者似乎可以活得更長。劑量優化可能需要一段時間。

So we think it's very important to get this into the market to patients, to doctors as quickly as we can. We think that pathway really goes through a single dose first, and then we'll layer on dose optimization as the data comes back and then play read and react to the data in consultation with the FDA.

因此我們認為盡快將其推向市場並提供給患者和醫生非常重要。我們認為該途徑實際上首先要經歷單劑量，然後我們將根據數據返回進行劑量優化，然後在與 FDA 協商後對數據進行讀取和反應。

My final question is on the CNside. I was wondering if you could provide a bit of color on the market opportunity and where do you think you'll be in the next 12 months or so?

我的最後一個問題是關於 CNside 的問題。我想知道您是否可以提供一些有關市場機會的信息，以及您認為未來 12 個月左右您會處於什麼位置？

It's a great question. In my view, the market opportunity in kind of the best reasonable case is 0.5 million tests a year in the US and that leverages ruling in the diagnosis, ruling out the diagnosis in patients that might have breast cancer and suspicious neurological symptoms, but indeed don't have LM and then the treatment monitoring data increasingly looks to be very promising. So you add up all those markets, and you look at the publications that are increasingly coming out showing there's an epidemic in LM that really drives that market number. So it's a very sizable market opportunity in our view.

這是一個很好的問題。在我看來，最佳合理情況下的市場機會是美國每年進行 50 萬次測試，這有利於做出診斷裁決，排除可能患有乳癌和可疑神經系統症狀但確實沒有 LM 的患者的診斷，然後治療監測數據看起來越來越有希望。因此，你把所有這些市場加起來，然後你會看到越來越多的出版物表明 LM 的流行確實推動了這個市場數字。因此，我們認為這是一個非常大的市場機會。

The prior company's commercial data over 2.5 years really support the physician acceptance of that. About half the major cancer centers in the US were using the test during that timeframe. So I think it's a very sizable market opportunity.

該公司之前兩年半的商業數據確實支持醫生對此的接受。在此期間，美國大約一半的主要癌症中心都在使用該測試。所以我認為這是一個非常大的市場機會。

Where do I think we'll be a year from now? I think that the tumor cell enumeration test will be commercial. It will roll out on a geographic scale as we get state licenses and get major payers on board, as well as Medicare. We've actually made great progress in the last nine months on those, and we'll be able to talk about that more, but we want to talk about those on a success basis, not on a forward-looking basis.

我認為一年後我們會在哪裡？我認為腫瘤細胞計數測試將會商業化。隨著我們獲得州政府許可、主要付款方以及醫療保險的加入，它將在地理範圍內推廣。事實上，我們在過去的九個月裡在這些方面取得了很大進展，我們可以更多地談論這些，但我們希望在成功的基礎上談論這些，而不是在前瞻性的基礎上。

So I think we have the ability to scale up operationally in Houston really to infinite tests. So the number I mentioned before, 0.5 million tests, we can do that in our Houston facility.

所以我認為我們有能力在休士頓擴大營運規模，真正進行無限次測試。因此，我之前提到的數字，即 50 萬次測試，我們可以在休士頓的工廠完成。

Scale-up is really a matter of extra headcount and extra capital equipment. The devices involved in the test, we actually make in Houston, so we control our destiny there. So, I think a year from now, the TCE test we'll be expanding throughout the US. We'll be adding insitu hybridization, immunocytochemistry, and NGS along with that, we'll be rolling out later in the year and we'll be building out a sales team that will be focused, as I addressed Ed's question before, on those major cancer centers and those physicians that are key opinion-leading doctors.

擴大規模其實就是增加員工和增加資本設備的問題。參與測試的設備實際上是我們在休士頓製造的，所以我們在那裡掌控著我們的命運。所以，我認為從現在起一年後，TCE 測試將會擴展到整個美國。我們將添加原位雜交、免疫細胞化學和 NGS，並將在今年稍後推出，我們將建立一個銷售團隊，正如我之前回答 Ed 的問題一樣，該團隊將專注於那些主要的癌症中心和那些作為關鍵意見領袖的醫生。

And I failed to mention Russ Bradley. Russ has been there and done this multiple times throughout a 25-, 30-year career in diagnostics, including a long stint at Abbott. knows how to scale diagnostics and has key relationships in the market and can do this operationally and commercially. So we'll really be integrating him more and more in that business over that same timeframe.

我忘了提到拉斯布拉德利。拉斯在診斷領域的 25 至 30 年職業生涯中曾多次擔任這一職務，其中包括在雅培公司的長期任職。知道如何擴大診斷規模，在市場上擁有關鍵關係，並且能夠在營運和商業上做到這一點。因此，在同一時間段內，我們確實會讓他越來越多地融入該業務。

I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Dr. Marc Hedrick for any closing remarks.

目前隊列中沒有其他問題。現在我想將電話轉回給馬克·赫德里克博士，請他做最後發言。

Thank you, Sherry. Thanks to everybody who joined us on the call or listened on the call on the recorded version. I'd just like to say on behalf of the Board that I'd like to thank our employees, our team members, the physicians that we work with, and the key opinion-leading doctors that are in this area that really appreciate their input.

謝謝你，雪莉。感謝所有參加電話會議或收聽錄音版本的人。我只想代表董事會感謝我們的員工、團隊成員、與我們合作的醫生以及該領域的關鍵意見領袖醫生，我們非常感謝他們的意見。

And then, most of all, the patients that trust us, a number of which I've talked to and interfaced with them as they've been involved in our trial. Thank you very much for your participation on the call, and have a good evening. Goodbye.

然後，最重要的是信任我們的患者，當他們參與我們的試驗時，我曾與許多患者交談過並與他們交流過。非常感謝您參加電話會議，祝您晚上愉快。再見。

This concludes today's program. Thank you all for participating. You may now disconnect.

今天的節目到此結束。感謝大家的參與。您現在可以斷開連線。