Plus Therapeutics Inc (PSTV) 2023 Q2 法說會逐字稿

Good afternoon, ladies and gentlemen. Welcome to the Plus Therapeutics Second Quarter 2023 Results Conference Call.

女士們、先生們，下午好。歡迎參加 Plus Therapeutics 2023 年第二季度業績電話會議。

Before we begin, we want to advise you that over the course of the call and 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 risks and uncertainties, including the risks and uncertainties described under the Risk Factors section included in Plus Therapeutics' annual report on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission from time to time.

在我們開始之前，我們想提醒您，在電話會議和問答環節中，我們將做出有關事件、趨勢、業務前景和財務業績的前瞻性陳述，這可能會影響 Plus Therapeutics 的未來運營業績和財務狀況。所有此類陳述均受到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 表季度報告中的風險因素部分所述的風險和不確定性到時間了。

Plus Therapeutics advises you to review these risk factors in considering such statements. 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 建議您在考慮此類聲明時審查這些風險因素。 Plus Therapeutics 不承擔更新或修改任何前瞻性陳述以反映其發布後的事件、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 總裁兼首席執行官 Marc Hedrick 博士。先生，您可以開始了。

Thank you, Abigail. Good afternoon, everyone, and thank you once again for taking the time to join us today as we provide an overview of recent business highlights and discuss our 2023 second quarter financial results.

謝謝你，阿比蓋爾。大家下午好，再次感謝您今天抽出寶貴時間加入我們，我們將概述近期業務亮點並討論我們 2023 年第二季度的財務業績。

Joining me for the call today is Dr. Norman LaFrance, our Chief Medical Officer; and Mr. Andrew Sims, our Chief Financial Officer. I'll begin the call by reviewing our recent clinical and regulatory progress with a focus on the second quarter and then turn the call over to Andrew to review our financials, and Norman will then be joining us for Q&A.

今天和我一起參加電話會議的是我們的首席醫療官 Norman LaFrance 博士；以及我們的首席財務官安德魯·西姆斯先生。我將首先回顧我們最近的臨床和監管進展，重點關注第二季度，然後將電話轉交給安德魯，以審查我們的財務狀況，然後諾曼將加入我們進行問答。

I'll begin with updates on our 2 lead CNS cancer programs. First, an update on our ReSPECT-LM trial for patients with leptomeningeal metastases or LM. In Q2, we completed enrollment in the Phase I Part A that's cohorts 1 through 3. And as is called for in the protocol, we reviewed the safety data with the FDA and they approved us to continue the Part B of the Phase I, specifically dose escalation from cohorts 4 and beyond until a DLT is observed.

我將首先介紹我們兩個主要中樞神經系統癌症項目的最新情況。首先，我們針對軟腦膜轉移瘤或 LM 患者進行的 ReSPECT-LM 試驗的最新情況。在第二季度，我們完成了第一階段 A 部分的入組，即隊列 1 至 3。按照方案的要求，我們與 FDA 審查了安全數據，他們批准我們繼續第一階段的 B 部分，特別是從第4 組及之後的組開始劑量遞增，直到觀察到DLT。

At the SNO/ASCO CNS Cancer Conference last week in San Francisco, we reported the results from our ReSPECT-LM Phase I Part A trial. Recall that we've treated 10 patients with a single administration, except for 1 patient that received a second treatment off trial under compassionate use. And as mentioned, that was in 3 dose escalation cohorts. Thus far, we found that Rhenium Obisbemeda circulated fully in the CSF space within minutes of injection and remain concentrated in the CSF space for at least 7 days following administration. Critical organs outside the central nervous system, including blood, spleen and liver showed de minimis absorbed radiation doses well below critical safety levels.

上週在舊金山舉行的 SNO/ASCO CNS 癌症會議上，我們報告了 ReSPECT-LM I 期 A 部分試驗的結果。回想一下，我們已經用單次給藥治療了 10 名患者，除了 1 名患者在富有同情心的使用下接受了試驗外的第二次治療。如前所述，這是在 3 個劑量遞增隊列中進行的。到目前為止，我們發現錸 Obisbemeda 在註射後幾分鐘內在腦脊液空間中完全循環，並在給藥後至少 7 天內在腦脊液空間中保持濃縮。中樞神經系統以外的重要器官，包括血液、脾臟和肝臟，吸收的輻射劑量遠低於臨界安全水平。

In contrast, target organs in the arachnoid spinal CSF showed linear increases in absorbed dose that correlated with administered dose. In Part A, we dosed from 6.6 millicuries up to 26.4 millicuries, and we achieved absorbed doses of up to 102 gray to the ventricles and cranial subarachnoid space.

相反，蛛網膜脊髓腦脊液中的靶器官顯示吸收劑量線性增加，與給藥劑量相關。在 A 部分中，我們的劑量從 6.6 毫居里到 26.4 毫居里，腦室和顱腦蛛網膜下腔的吸收劑量高達 102 戈瑞。

So to summarize the dosing or dosimetry findings, the radiation is clearly getting to the target organs and the off-target effects thus far are minimal through Cohort 3. In terms of safety, consistent with the low off-target absorbed doses, no dose-limiting toxicities have been observed. Furthermore, the overall safety profile was favorable -- approximately 83% of adverse events were mild or moderate, and the majority were not related to treatment. The favorable safety profile provided the basis for moving forward into Part B of Phase I. However, we've also assessed whether there were target disease target effects by measuring tumor cell counts, survival and symptomatic improvement.

因此，總結劑量或劑量測定結果，輻射顯然已到達目標器官，並且迄今為止，通過隊列 3，脫靶效應很小。在安全性方面，與低脫靶吸收劑量一致，沒有劑量-已觀察到限制性毒性。此外，總體安全性良好——大約 83% 的不良事件是輕度或中度，並且大多數與治療無關。良好的安全性為進入 I 期 B 部分提供了基礎。然而，我們還通過測量腫瘤細胞計數、存活率和症狀改善來評估是否存在目標疾病目標效應。

Recently, a highly specific and sensitive CSF tumor cell and numeration technology called CNS side assay has been approved, and we are employing it in the ReSPECT-LM trial. In our view, the technology is a significant advance in CSF tumor assessment over standard of care. In Part A, we found that tumor cell counts trended lower immediately after treatment and were sustained through day 28 post treatment.

最近，一種高度特異性和敏感性的腦脊液腫瘤細胞和計數技術（稱為 CNS 側測定）已獲得批准，我們正在 ReSPECT-LM 試驗中採用它。我們認為，該技術是腦脊液腫瘤評估相對於護理標準的重大進步。在 A 部分中，我們發現腫瘤細胞計數在治療後立即呈下降趨勢，並持續到治療後 28 天。

At 28 days, tumor cell counts were reduced on average of 53% and up to 91% over preoperative baseline. And then generally, we noted a rebound in tumor cell counts at 56 days. Our view is that effective therapies in the management of LM such as potentially Iridium Rhenium Obisbemeda can disrupt the care of LM but the addition of a reliable tumor cell and numeration technology can magnify that therapeutic and commercial impact. Current means of LM diagnosis, specifically the triad of imaging clinical symptomatology and CSF analysis of cells, we use now the old steroids of protein glucose and cytology, both lack sensitivity and specificity.

28 天時，腫瘤細胞計數比術前基線平均減少 53%，最多減少 91%。一般來說，我們注意到腫瘤細胞計數在 56 天時出現反彈。我們的觀點是，治療 LM 的有效療法（例如潛在的銥錸 Obisbemeda）可能會擾亂 LM 的治療，但添加可靠的腫瘤細胞和計數技術可以放大這種治療和商業影響。目前的LM診斷手段，特別是影像學、臨床症狀學和腦脊液細胞分析三聯徵，我們現在使用的是蛋白葡萄糖和細胞學的老類固醇，兩者都缺乏敏感性和特異性。

Specifically, tumor cell enumeration may allow earlier diagnosis, diagnosis of subclinical cases and LM is about 2 to 4x underdiagnosed and then support decisions on re-dosing patients through their treatment course. Finally, in terms of survival. As of today, 5 of the 10 treated patients in the Phase I Part A are live and the median overall survival is at 10 months. This compares favorably with the published overall survival rates of approximately 3 to 9 months observed with standard of care. As a note, as part of the SNO/ASCO meeting in San Francisco in which the Phase I data was presented, plus co-hosted a KOL roundtable with Dr. Justin Walsh, which also included 2 ReSPECT-LM investigators, Dr. Andrew J. Brenner from The University of Texas Health Sciences at San Antonio and Dr. Priya Kumthekar from the Neurology and Medicine Departments at Northwestern University's Feinberg School of Medicine.

具體來說，腫瘤細胞計數可以實現早期診斷、亞臨床病例的診斷，LM 的診斷不足率約為 2 至 4 倍，然後支持患者在整個治療過程中重新用藥的決定。最後，在生存方面。截至目前，第一階段 A 部分的 10 名接受治療的患者中有 5 名存活，中位總生存期為 10 個月。這與已公佈的標準護理觀察到的約 3 至 9 個月的總體生存率相比是有利的。需要說明的是，作為在舊金山舉行的SNO/ASCO 會議的一部分，會上展示了第一階段的數據，並與Justin Walsh 博士共同主持了一次KOL 圓桌會議，其中還包括2 位ReSPECT-LM 研究人員Andrew J 博士. 德克薩斯大學聖安東尼奧健康科學分校的 Brenner 和西北大學范伯格醫學院神經病學和醫學系的 Priya Kumthekar 博士。

This KOL roundtable is available for replay on our website (inaudible) about an hour. During the KOL roundtable, Dr. Brenner and Dr. Kumthekar provided a comprehensive discussion about the ongoing ReSPECT-LM Phase I/IIa dose escalation clinical trial with emphasis on epidemiology, diagnosis, safety and tolerability, dosing and efficacy. We urge everyone that's interested to watch the webinar for a deeper look at LM and the ReSPECT clinical trial findings thus far.

本次 KOL 圓桌會議可在我們的網站上重播（聽不清），時間約為一小時。在KOL 圓桌會議期間，Brenner 博士和Kumthekar 博士對正在進行的ReSPECT-LM I/IIa 期劑量遞增臨床試驗進行了全面討論，重點討論了流行病學、診斷、安全性和耐受性、劑量和療效。我們敦促有興趣的每個人觀看網絡研討會，以更深入地了解 LM 和迄今為止的 ReSPECT 臨床試驗結果。

In terms of next steps for LM, the clinical development plan is to continue to dose escalate to the maximum tolerated dose and in parallel, expand the Phase I dose escalation trial to explore multiple dosing. This approach is critical to enhancing the potential for the clinical benefit of Rhenium Obisbemeda in these patients, which will require further FDA discussions. As mentioned, we did treat in Part A, one patient with a second dose of Rhenium Obisbemeda outside the trial under compassionate use, and that patient continues to do quite well and is over a year out from her initial treatment.

就LM的下一步而言，臨床開發計劃是繼續劑量升級至最大耐受劑量，同時擴大I期劑量升級試驗以探索多重給藥。這種方法對於增強錸 Obisbemeda 對這些患者的臨床獲益潛力至關重要，這需要 FDA 進一步討論。如前所述，我們在A 部分中確實對一名患者進行了試驗外的第二劑錸Obisbemeda 治療，該患者在富有同情心的情況下接受了第二劑錸Obisbemeda 治療，該患者的情況仍然很好，距離初次治療已經過去一年多了。

Now with respect to our clinical trial called ReSPECT-GBM for patients with recurrent glioblastoma or GBM, we continue to enroll both our active Phase I and Phase II trials. Our Phase I now has enrolled 4 patients in cohort 8 with tumor sizes being treated in that with greater than 20 milliliters. And they were treated with an administered radiation dose of 41.5 millicuries in a treatment volume of 16.4 milliliters. We have now successfully used up to 5 catheters per treatment in multiple patients and no DLTs have thus far been observed. We plan to treat 6 total patients in this cohort in case it's the last cohort but we will also assess whether to continue dose escalation or make other dosing changes with an eye toward any potential amendments we might deem to make in the Phase II protocol.

現在，關於我們針對複發性膠質母細胞瘤或 GBM 患者的名為 ReSPECT-GBM 的臨床試驗，我們繼續招募活躍的 I 期和 II 期試驗。我們的第一階段現已在第 8 組中招募了 4 名接受治療的腫瘤大小大於 20 毫升的患者。他們接受的放射劑量為 41.5 毫居里，治療體積為 16.4 毫升。現在，我們已成功地在多名患者的每次治療中使用了多達 5 個導管，並且迄今為止尚未觀察到 DLT。我們計劃治療該隊列中的總共6 名患者，以防這是最後一個隊列，但我們還將評估是否繼續劑量遞增或進行其他劑量變化，並著眼於我們可能認為在II 期方案中進行的任何潛在修改。

Our Phase II continues to enroll patients with tumor sizes of 20 ccs or less using an administered radiation dose of 22.3 millicuries in a treatment volume of 18.8 milliliters -- excuse me, 8.8 milliliters. We remain on track to complete Phase II enrollment by the end of 2024.

我們的第二階段繼續招募腫瘤大小為 20 cc 或更小的患者，使用 22.3 毫居里的放射劑量，治療體積為 18.8 毫升（對不起，8.8 毫升）。我們仍有望在 2024 年底前完成第二階段的註冊。

In order to continue to meet our clinical trial enrollment goals, we have expanded our internal clinical team, including adding a VP of Clinical Operations and also adding additional select CROs to support the trials. The impact of these decisions are already being felt and will become increasingly more apparent as we end 2023 and go into 2024 and beyond.

為了繼續實現我們的臨床試驗入組目標，我們擴大了內部臨床團隊，包括增加一名臨床運營副總裁，並增加額外的精選 CRO 來支持試驗。這些決定的影響已經顯現，並且隨著 2023 年結束、2024 年及以後的到來，影響將變得越來越明顯。

As the ReSPECT-GBM trials are open-label trials, we are analyzing the data in an ongoing manner in our (inaudible) the GBM data readouts going forward. First, we intend to publish the Phase I data of equal to 21 patients in peer-reviewed literature, and that's in process. Second, we continue to evaluate the feasibility, safety and efficacy in the ongoing Phase I trial. The extended Phase I trial is evaluating the safety at these higher dosages and volumes, as mentioned and the impact of these higher doses and volumes on RNL distribution and tumor coverage. And then also finally, on the effects on large tumors.

由於 ReSPECT-GBM 試驗是開放標籤試驗，我們將在未來的（聽不清）GBM 數據讀出中持續分析數據。首先，我們打算在同行評審文獻中發布 21 名患者的 I 期數據，目前正在進行中。其次，我們繼續評估正在進行的一期試驗的可行性、安全性和有效性。如上所述，擴展的 I 期試驗正在評估這些更高劑量和體積的安全性，以及這些更高劑量和體積對 RNL 分佈和腫瘤覆蓋範圍的影響。最後，關於對大腫瘤的影響。

And I think it should be obvious from some of the data I mentioned before in terms of volume and administered dose that we're really pushing the limits in terms of what's achievable in convection-enhanced delivery in the brain in terms of targeted radiation and volume. And that data will be presented at Society for Neuro-Oncology Meeting in November. Third, we continue to periodically assess the actively enrolling Phase II alone and in a pooled fashion with representative data from the Phase I, and that data will also be presented at the SNO meeting in November.

我認為從我之前提到的關於體積和給藥劑量的一些數據中應該可以明顯看出，我們確實在目標輻射和體積方面突破了大腦對流增強傳遞所能實現的極限。該數據將於 11 月在神經腫瘤學會會議上公佈。第三，我們繼續定期單獨評估積極入組的第二階段，並以第一階段代表性數據的匯總方式進行評估，這些數據也將在 11 月的 SNO 會議上公佈。

Fourth, we have recently reported top line data from a propensity matched real-world data analysis of recurrent GBM patients receiving either bevacizumab or convection-enhanced delivery. That data will be used as a real-world control comparator arm for the Phase I and Phase II trials and also for regulatory purposes, including as it relates to potential pivotal trial design. More detailed data will be presented on the real-world propensity match trial at SNO in 2023 as well. I think we have 5 posters or presentations at SNO this year.

第四，我們最近報告了接受貝伐單抗或對流增強遞送的複發性 GBM 患者的傾向匹配現實世界數據分析的頂線數據。這些數據將用作第一階段和第二階段試驗的真實控制比較器，也可用於監管目的，包括與潛在的關鍵試驗設計相關的數據。 2023 年 SNO 的現實世界傾向匹配試驗也將提供更詳細的數據。我想今年我們在 SNO 上有 5 張海報或演示文稿。

In terms of the GBM program in general, we continue to demonstrate feasibility and safety without dose-limiting toxicities and promising efficacy signals as we presented before. One thing I just wanted to highlight beyond the safety profile is what we've observed relating to the dose response data, specifically the correlation between overall survival and both increasing radiation absorbed dose to the tumor and increasing percent coverage of the tumor volume.

總體而言，就 GBM 計劃而言，我們繼續證明可行性和安全性，沒有劑量限制性毒性和我們之前提出的有希望的療效信號。除了安全性之外，我想強調的一件事是我們觀察到的與劑量反應數據相關的內容，特別是總體生存率與腫瘤輻射吸收劑量增加和腫瘤體積覆蓋百分比增加之間的相關性。

In summary, we have learned that for each 100 gray increase in total dose and distribution volume, the risk of death decreases by 45.6%. And for each 10% increase in the ratio of treated to total tumor volume, the risk of death decreases by 66.9%, with neither a threshold for either. Both have very low p values, and this provides us with gathering confidence that there is indeed a meaningful treatment effect.

綜上所述，我們了解到，總劑量和分佈體積每增加100格雷，死亡風險就會降低45.6%。治療體積與總腫瘤體積的比例每增加 10%，死亡風險就會降低 66.9%，兩者都沒有閾值。兩者的 p 值都非常低，這讓我們更有信心相信確實存在有意義的治療效果。

Now in terms of our planned pediatric brain cancer trial, we have formally responded to the FDA request for additional safety data from adults. And assuming no new request, we anticipate IND approval and then moving forward with our pediatric brain cancer trial in the second half of 2023. As mentioned in the past, management's practice is to rely heavily on grants or other third-party funding through Phase II for each active program. We currently have a number of grant submissions in excess of $1 million under review, including 2 specifically dedicated brain cancer program.

現在，就我們計劃的兒童腦癌試驗而言，我們已正式回應 FDA 要求提供成人額外安全數據的要求。假設沒有新的請求，我們預計IND 會獲得批准，然後在2023 年下半年推進我們的兒科腦癌試驗。正如過去提到的，管理層的做法是在第二階段嚴重依賴贈款或其他第三方資金對於每個活動程序。目前，我們正在審查多項超過 100 萬美元的撥款申請，其中包括 2 個專門針對腦癌的項目。

Our second radio therapeutic drug is making steady regulatory and development programs. We recently received feedback from the FDA on our pre request for designation. The question is whether that drug will be deemed a device, a drug or a combination product. Specifically, the FDA notified us that the BAM radio-embolic product will be regulated as a device, primarily by CDRH. This is consistent with the 2 generation 1 products that are now on the market that collectively share a market opportunity of about $1.3 billion. Obviously, the benefits of this device-based approach would be that there are established regulatory reimbursement pathways already out there and potential speed to market.

我們的第二種放射治療藥物正在製定穩定的監管和開發計劃。我們最近收到了 FDA 對我們預先指定申請的反饋。問題是該藥物是否會被視為器械、藥物或組合產品。具體來說，FDA 通知我們，BAM 放射栓塞產品將作為一種器械進行監管，主要由 CDRH 監管。這與目前市場上的第 2 代第 1 代產品一致，它們共同分享約 13 億美元的市場機會。顯然，這種基於設備的方法的好處是已經建立了監管報銷途徑，並且可以加快上市速度。

In terms of drug production and manufacturing, we continue to expand and shore up existing supply agreements and work to build in supply chain redundancy, including as it relates to isotope availability, for example, we recently contracted with Piramal Pharma Solutions that produce additional cGMP liposome intermediate products to meet the forecasted increase in demand for Rhenium 186 Obisbemeda for an ongoing and planned clinical trials. Our view is that we are where we should be today in terms of our supply chain, and we are executing on a longer-term plan to stay ahead of the curve as we move our radiotherapeutic products closer to market.

在藥品生產和製造方面，我們繼續擴大和鞏固現有供應協議，並努力建立供應鏈冗餘，包括與同位素可用性相關的供應鏈冗餘，例如，我們最近與Piramal Pharma Solutions 簽訂了合同，生產額外的cGMP 脂質體中間產品，以滿足正在進行和計劃的臨床試驗中對錸 186 Obisbemeda 的需求的預測增長。我們的觀點是，就供應鏈而言，我們已經達到了今天應該達到的水平，並且我們正在執行一項長期計劃，以便在我們將放射治療產品推向市場的同時保持領先地位。

With that summary on our clinical development programs and other important company updates, I'll turn the floor over to our Chief Financial Officer, Andrew Sims, who will review the financials. Andrew?

在總結了我們的臨床開發計劃和其他重要的公司最新情況後，我將把發言權交給我們的首席財務官安德魯·西姆斯（Andrew Sims），他將審查財務狀況。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 2023 second quarter ended June 30, 2023. First, regarding the balance sheet. As of June 30, 2023, cash and cash equivalents were $10.9 million compared to $18.1 million as of December 31, 2022.

謝謝你，馬克。大家下午好。請參閱我們今天早些時候發布的新聞稿，了解我們截至 2023 年 6 月 30 日的 2023 年第二季度財務業績摘要。首先，關於資產負債表。截至 2023 年 6 月 30 日，現金及現金等價物為 1,090 萬美元，而截至 2022 年 12 月 31 日為 1,810 萬美元。

In addition, this month, we were notified that CPRIT released approximately $1.9 million in additional cash anticipated to flow to the company's balance sheet in August. As a reminder, the company benefits from both a 3 million NIH award for the ReSPECT-GBM clinical trial through Phase II and a $17.6 million award from CPRIT for the ReSPECT-LM trial through Phase II.

此外，本月，我們獲悉 CPRIT 釋放了約 190 萬美元的額外現金，預計將在 8 月份流入該公司的資產負債表。需要提醒的是，該公司受益於 NIH 為 ReSPECT-GBM 臨床試驗第二階段提供的 300 萬美元獎勵，以及 CPRIT 為 ReSPECT-LM 試驗第二階段提供的 1760 萬美元獎勵。

Going forward in years 2 and 3, grant funding is forecast to be $6.7 million and $7.1 million, respectively, likely split into 2 or more advanced payments each year. Furthermore, the company has discretionary or stockholder-approved access to capital from its ATM and equity line of credit of at least $49 million. Now on the income statement, the company recognized $1.9 million of grant revenue in the second quarter of 2023, which represents secret share of costs incurred to fund a portion of our LM clinical program. Total operating expenses for the second quarter of 2023 was $3.3 million compared to total operating expenses of $5.1 million for the same period the prior year.

展望未來的第 2 年和第 3 年，贈款資金預計分別為 670 萬美元和 710 萬美元，每年可能分為 2 筆或更多筆預付款。此外，該公司可以自行決定或經股東批准從其 ATM 和至少 4900 萬美元的股權信貸額度中獲取資本。現在在損益表上，該公司在 2023 年第二季度確認了 190 萬美元的撥款收入，這代表了為我們的部分 LM 臨床項目提供資金所產生的秘密份額。 2023 年第二季度的總運營費用為 330 萬美元，而上年同期的總運營費用為 510 萬美元。

The decrease is due primarily to the company completing one-off investments in the GMP development of the company's lead drug Rhenium 186 Obisbemeda in Q3 2022. In addition, we incurred lower legal and professional fees in 2023 versus the prior year. Interest expense decreased from $181,000 for the second quarter of 2022 to $112,000 for the second quarter of 2023. This decrease reflects the continued principal paydown on the company's Oxford debt. Net loss for the quarter of 2023 was $1.5 million or $0.59 per share compared to a net loss of $5.3 million or $3.56 per share for the same period of the prior year.

減少的主要原因是公司於 2022 年第三季度完成了對公司主導藥物錸 186 Obisbemeda 的 GMP 開發的一次性投資。此外，我們在 2023 年的法律和專業費用比上一年有所減少。利息支出從 2022 年第二季度的 181,000 美元下降至 2023 年第二季度的 112,000 美元。這一下降反映了該公司牛津債務本金的持續償還。 2023 年季度的淨虧損為 150 萬美元，即每股 0.59 美元，而上年同期的淨虧損為 530 萬美元，即每股 3.56 美元。

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

現在我會把它轉回給你，馬克。

Thank you, Andrew. Before we move on to Q&A, let me provide some guidance on anticipated milestones through the remainder of the year. We are on track to initiate the Phase I Part B of the ReSPECT-LM trial in the second half of this year, and we plan to expand dosing to multiple doses for each patient. More to come on that. We also published the ReSPECT-GBM Phase I data and provide a comprehensive trial update at the Society for Neuro-Oncology Meeting in November 2023.

謝謝你，安德魯。在我們進行問答之前，讓我就今年剩餘時間內的預期里程碑提供一些指導。我們有望在今年下半年啟動 ReSPECT-LM 試驗的 I 期 B 部分，並且我們計劃將劑量擴大到每位患者的多次劑量。未來還會有更多內容。我們還發布了 ReSPECT-GBM I 期數據，並在 2023 年 11 月舉行的神經腫瘤學會會議上提供了全面的試驗更新。

We are on track to initiate the Phase I RESPECT pediatric brain cancer trial for pediatric patients with ependymoma and high-grade glioma in the second half of 2023. We intend to finalize the device designation for our BAM product and expand our activities accordingly.

我們有望於2023 年下半年針對患有室管膜瘤和高級別神經膠質瘤的兒科患者啟動I 期RESPECT 兒科腦癌試驗。我們打算最終確定我們的BAM 產品的設備名稱，並相應地擴大我們的活動。

Finally, in general, management has internal targets around portfolio and business development opportunities and additional nondilutive grant funding, both are progressing, and we will update on those when appropriate to do so.

最後，總的來說，管理層圍繞投資組合和業務發展機會以及額外的非稀釋性贈款資金制定了內部目標，兩者都在取得進展，我們將在適當的時候更新這些目標。

At this point, Abigail, I'll now turn the call back over to you for Q&A.

阿比蓋爾，現在我會將電話轉回給您進行問答。

(Operator Instructions) Our first question comes from Justin Walsh with JonesTrading.

（操作員說明）我們的第一個問題來自 JonesTrading 的 Justin Walsh。

Congrats on the progress. My first question, I'm wondering about your current thoughts about potential -- potentially approvable endpoints for LM in the context of the data you presented. Overall survival obviously could make sense, particularly given the 10-month median overall survival you saw in the first 10 patients but wondering if there are others you're thinking about.

祝賀取得的進展。我的第一個問題，我想知道您目前對在您提供的數據背景下潛在的、可能可批准的 LM 端點的想法。總生存期顯然是有意義的，特別是考慮到您在前 10 名患者中看到的 10 個月中位總生存期，但想知道您是否正在考慮其他患者。

And in particular, I'm kind of just thinking about like potential for using symptomatic changes given that we know some of the earlier radiopharmaceuticals were approved for bone pain palliation and prostate cancer.

特別是，我只是在考慮使用症狀改變的潛力，因為我們知道一些早期的放射性藥物已被批准用於緩解骨痛和前列腺癌。

Justin, it's Marc. I think at this point, it's a bit -- it's a bit too early to say definitively as you sort of hinted in your question. But beyond the gold standard of overall survival, I do think quality of life or symptomatic improvement are potentially approvable endpoints. We'll be implementing and expanding a QOL metric in the trial, and there are some that are out there that would be appropriate. Relative response rate is difficult because imaging can be difficult. And -- however, I think there might be an opportunity in terms of reducing CNS tumor cell count with the -- as I mentioned before. So I think that's less likely. But I do think that, as you mentioned, QOL or symptomatic improvement are also possible endpoints. It certainly not primary endpoints, it would be secondary endpoints.

賈斯汀，我是馬克。我認為在這一點上，正如你在問題中所暗示的那樣，現在下結論還為時過早。但除了總體生存的黃金標準之外，我確實認為生活質量或症狀改善是潛在的可批准的終點。我們將在試驗中實施和擴展生活質量指標，並且有一些合適的指標。相對響應率很困難，因為成像可能很困難。然而，我認為在減少中樞神經系統腫瘤細胞計數方面可能存在機會，正如我之前提到的。所以我認為這種可能性較小。但我確實認為，正如您提到的，生活質量或症狀改善也是可能的終點。它當然不是主要終點，而是次要終點。

Got it. And then one more question. I'm just sort of wondering if you can comment on just some more broad thoughts on why LM is so underdiagnosed. And I guess, how much of that comes from the challenges of having effective diagnostics for it? And how many come from maybe the fact that there may be is not a lot out there that can currently be used to specifically treat LM. So just some thoughts on that. Maybe a little bit of a chicken and the egg thing that hopefully is being resolved with your work and some of the diagnostic stuff that's going on. But just curious for your perspectives on that.

知道了。然後還有一個問題。我只是想知道您是否可以就為什麼 LM 診斷不足的問題發表一些更廣泛的想法。我猜，其中有多少來自對其進行有效診斷的挑戰？其中有多少可能是因為目前可用於專門治療 LM 的藥物並不多。所以只是對此的一些想法。也許有點先有雞還是先有蛋的問題，希望通過你的工作和正在進行的一些診斷工作得到解決。但只是好奇你對此的看法。

Yes, it's a good question. The mortality is high. Patients that are nontreated live 4 to 6 weeks in just a few months with treatment. So with better treatment, it's likely the incidence will be higher. Patients will live longer and also with better primary tumor treatment, patients that can live longer as well. The 2 to 4x increased incidence is based on autopsy study. So I think there are a lot of subclinical infections that are out there.

是的，這是一個好問題。死亡率很高。未經治療的患者在接受治療後的短短幾個月內可以存活 4 至 6 週。因此，如果治療效果更好，發病率可能會更高。患者會活得更久，而且如果原發腫瘤得到更好的治療，患者也能活得更久。發病率增加 2 至 4 倍是基於屍檢研究。所以我認為存在很多亞臨床感染。

Patients may die of their primary disease, but they die their primary disease with CNS meds or some -- oftentimes, the imaging is poor, the CSF analysis is indeterminant and the symptoms are -- symptomatic pattern is not really clear. So they may have it. They may actually be symptomatic, but it's very difficult to nail down the diagnosis, so they may have other issues. So that's why I think -- are we likely to have a near-term significant improvement in our ability to sort out the symptoms? Probably not. Are we likely to be -- see kind of a near-term improvement in our ability to image these patients? Not so sure, doubtful.

患者可能死於原發疾病，但他們死於中樞神經系統藥物或其他藥物的原發疾病——通常，成像效果很差，腦脊液分析不確定，而且症狀——症狀模式並不真正清楚。所以他們可能擁有它。他們實際上可能有症狀，但很難確定診斷，因此他們可能還有其他問題。所以這就是為什麼我認為——短期內我們解決症狀的能力是否可能有顯著改善？可能不會。我們是否有可能在短期內看到我們對這些患者進行成像的能力有所改善？不太確定，值得懷疑。

But I do think there's a real possibility with a highly sensitive and specific CSF assay to evaluate patients that may be asymptomatic but that are at risk, triple-negative breast cancer patients that are asymptomatic with normal imaging and so forth and pick it up early. And then there's an opportunity for us if we have a treatment on the market to treat them early and then potentially substantially prolonged survival in these patients. So that's how I think about it. And that's why I think the importance of tumor cell enumeration assay could be really valuable potentially in terms of a companion diagnostic too as well at some point.

但我確實認為，確實有可能通過高度敏感和特異性的腦脊液檢測來評估可能無症狀但有風險的患者、無症狀且影像學正常的三陰性乳腺癌患者等，並儘早發現。如果我們市場上有一種治療方法可以儘早治療他們，然後可能大大延長這些患者的生存期，那麼我們就有機會。這就是我的想法。這就是為什麼我認為腫瘤細胞計數測定的重要性在某些時候在伴隨診斷方面也可能非常有價值。

Got it. And maybe just a follow-up on that. The -- that assay, it requires a lumbar puncture, right? Just wondering how much of a concern there is that, that might, I don't know, limit patients wanting to get on board with that? Or do you think that by the time they get to the point where they have systematic LM that it's -- it could be pretty reasonable to get outpatient compliance there?

知道了。也許只是後續行動。那個檢測，需要腰椎穿刺，對吧？只是想知道有多少擔憂，我不知道，這可能會限制想要參與其中的患者嗎？或者您是否認為，當他們達到系統化LM的地步時，讓門診患者依從性可能相當合理？

Yes. Good point. So for patients that are suspected or have been diagnosed with LM, almost all of them have what's called an Ommaya reservoir, which is a small subcutaneous port with a little pigtail coming off of it that goes into the ventricle that allows the physician real-time access, which is how our LM treatment is actually infused in the patient.

是的。好點子。因此，對於疑似或已診斷患有 LM 的患者，幾乎所有人都有所謂的 Ommaya 儲庫，這是一個小型皮下端口，有一根小辮子從其中脫落，進入心室，使醫生可以實時了解訪問，這就是我們的LM 治療實際上註入患者體內的方式。

But literally any point in time during the patient's course, CSF could be sampled and tumor cell enumeration performed. So once they have that in, it's really a nonissue. In patients that are at risk, but haven't received a diagnosis, lumbar puncture will generally be required because there's no other way to get the -- the CSF out. So -- but it's still -- it's a common part of the workup. But CSF analysis, lumbar puncture is part of working up little kids with fevers oftentimes or patients that come in with neck stiffness and photophobia. So in these patients that have oncologic primaries, who are at risk potentially of LM, a lumbar puncture is a very reasonable procedure to do those. And they're frankly, very well tolerated.

但實際上，在患者病程中的任何時間點，都可以對腦脊液進行採樣並進行腫瘤細胞計數。所以一旦他們把它放進去，這真的不是問題。對於有風險但尚未得到診斷的患者，通常需要進行腰椎穿刺，因為沒有其他方法可以取出腦脊液。所以——但它仍然是——這是檢查的一個常見部分。但腦脊液分析顯示，腰椎穿刺是治療經常發燒的小孩或出現頸部僵硬和畏光的患者的一部分。因此，對於這些患有腫瘤原發性疾病且有潛在 LM 風險的患者，腰椎穿刺是一種非常合理的手術。坦率地說，他們的容忍度非常好。

Our next question comes from Sean Lee with H.C. Wainwright.

我們的下一個問題來自 Sean Lee 和 H.C.溫賴特。

My first question is on the recent LM results. I was wondering because you guys saw a linear trend with the administered dose to the absorb dose. I was wondering any relationships you've seen so far between the absorbed dose and the decreases in tumor cell counts or relative survival.

我的第一個問題是關於最近的 LM 結果。我想知道因為你們看到了給藥劑量與吸收劑量之間的線性趨勢。我想知道到目前為止您所看到的吸收劑量與腫瘤細胞計數或相對存活率下降之間的關係。

No. We haven't. I think it's still early. That's something we'll look as we get to the later cohorts. But I think we may, because the -- there's a nice linear relationship between administered and absorbed dose. So I think that's definitely something we're going to look for.

不，我們沒有。我覺得現在還早。這是我們在進入後續隊列時會看到的內容。但我認為我們可能會這樣做，因為給藥劑量和吸收劑量之間存在良好的線性關係。所以我認為這絕對是我們要尋找的東西。

Great. My second question is also on that study. You mentioned that you're going to be looking at repeat dosing for some of these patients. Would that be done under the context of a different study? Or would you be looking to expand this study protocol to include a separate repeat dosing cohort?

偉大的。我的第二個問題也與這項研究有關。您提到您將考慮對其中一些患者進行重複給藥。這會在另一項研究的背景下完成嗎？或者您是否希望擴展該研究方案以包括單獨的重複給藥隊列？

I think that will be a pending decision, be pending discussion with the FDA. Our preference would be to incorporate the current protocol. I think that's just simpler and more straightforward. I think based on what we're seeing now with a single administration and look at the overall survival signal, even at low doses -- but when you incorporate the safety profile and the reduction of tumor cell counts that we've seen, I think that it makes complete sense to continue to dose escalate to a maximum tolerated dose, but then add additional doses.

我認為這將是一個懸而未決的決定，有待與 FDA 討論。我們的首選是納入當前的協議。我認為這更簡單、更直接。我認為，根據我們現在所看到的單次給藥並觀察整體生存信號，即使是在低劑量下 - 但當你將安全性和我們所看到的腫瘤細胞計數的減少結合起來時，我認為繼續將劑量增加到最大耐受劑量，然後增加額外劑量是完全有意義的。

And we're working on that right now. So my guess is it will be part of the current trial, not a separate protocol.

我們現在正在努力解決這個問題。所以我的猜測是這將是當前試驗的一部分，而不是一個單獨的方案。

I see. I see. Then moving on to the GBM side. In the prepared remarks, you mentioned that the FDA has moved it to be a device and not a drug. So would you be looking at 510(k) be noble pathway for regulatory approval? Or would you be -- is it going to be -- what's it all PMA path?

我懂了。我懂了。然後轉到 GBM 方面。在準備好的發言中，您提到 FDA 已將其轉變為設備而不是藥物。那麼您是否認為 510(k) 是獲得監管部門批准的高貴途徑？或者你會 - 會是 - PMA 路徑是什麼？

Yes, it's a great question. Right now, it's hard to say. I think a 510(k) pathway is possible. But I can't say it's likely. I think we just -- this is going to be a new information. So we'll need a bit more time to do our evaluation with our regulatory team Obviously, if it's a 510(k), that's a pretty quick path to market. PMA would be a bit longer. But either way, it is going to be a faster path than a drug-related pathway. So we're parallel paths right now. Number one is to just the process now with the FDA is to do a pre RFD evaluation and then submit your final RFD, which we're in the process of doing that.

是的，這是一個很好的問題。現在還很難說。我認為 510(k) 途徑是可能的。但我不能說這有可能。我認為我們只是——這將是一個新信息。因此，我們需要更多時間與監管團隊一起進行評估。顯然，如果是 510(k)，那麼這是一條相當快速的上市途徑。 PMA 會更長一些。但無論哪種方式，這都將是比藥物相關途徑更快的途徑。所以我們現在是平行的道路。第一個是 FDA 目前的流程是進行 RFD 前評估，然後提交最終的 RFD，我們正在這樣做。

And then in parallel we're looking at the device-based regulatory opportunities, including 510(k) and PMA in parallel. And then once we have the final designation, then we'll be ready to move.

與此同時，我們正在研究基於設備的監管機會，包括並行的 510(k) 和 PMA。一旦我們得到最終的指定，我們就準備好行動。

(Operator Instructions) We have a question from the line of Edward Woo with Ascendiant Capital.

（操作員說明） 我們有來自 Ascendiant Capital 的 Edward Woo 的提問。

My question is on the grants that you guys are working on. Is it only with CPRIT? Or are you guys doing stuff with NIH? And also because you guys already got a major contract from CPRIT. Does it make it easier for you to get future grants?

我的問題是關於你們正在開展的贈款活動。只能用CPRIT嗎？或者你們正在與 NIH 合作嗎？而且還因為你們已經從 CPRIT 獲得了一份重要合同。這會讓您更容易獲得未來的資助嗎？

Ed, thanks for the question. There's no prevention for us going back to CPRIT for additional grants. We know of one company that has 3 CPRIT awards. So in some ways now that we understand the process, there are a little bit of economies of scale in terms of how to formulate these grants and go through the process and so forth. So it's going to be both. We're going back to CPRIT for additional grant opportunities. But we're also going to the NIH and other sources of funding here in the U.S.

艾德，謝謝你的提問。我們沒有辦法回到 CPRIT 尋求額外資助。據我們所知，有一家公司獲得了 3 項 CPRIT 獎項。因此，在某種程度上，現在我們了解了這個過程，在如何制定這些贈款和完成這個過程等方面存在一些規模經濟。所以兩者都會。我們將返回 CPRIT 尋求更多資助機會。但我們也會向美國國立衛生研究院和美國的其他資金來源尋求資助。

So taking a broad approach, but following our internal mantra, I guess, which is we want to -- before we start a new program, we want to have the funding to pay for it through Phase II in hand or nearly in hand. And so we think that there are opportunities for each new thing we bring forward, whether it's the BAM program, (inaudible) to put funding in place so that once we have the asset, we're ready to invest in it clinically or in some cases, preclinically, we have the capital to do so. So it will be a mixture of both, and that definitely includes CPRIT.

因此，採取廣泛的方法，但我想，遵循我們的內部口號，這就是我們想要的——在我們開始一個新項目之前，我們希望有資金來支付第二階段的費用。因此，我們認為，我們提出的每一項新事物，無論是BAM 計劃（聽不清），都有機會提供資金，以便一旦我們擁有資產，我們就準備好對其進行臨床投資或某些領域的投資。在臨床前的病例中，我們有資本這樣做。所以它將是兩者的混合體，其中肯定包括 CPRIT。

Thank you. That concludes the question-and-answer session. At this time, I would like to turn it back to Dr. Marc Hedrick for closing remarks.

謝謝。問答環節到此結束。現在，我想請 Marc Hedrick 博士做總結髮言。

Thank you, Abigail. Thank you to everyone that is tuned in, and we appreciate your interest in the company, and thank you for the questions. And please be sure to refer to our website, take a look at our KOL webinar that has been uploaded, and feel free to reach out to management if you have any questions. In the meantime, have a nice evening. Thank you.

謝謝你，阿比蓋爾。感謝所有收聽的人，我們感謝您對公司的興趣，並感謝您提出的問題。請務必訪問我們的網站，查看我們已上傳的 KOL 網絡研討會，如果您有任何疑問，請隨時與管理層聯繫。與此同時，祝您度過一個愉快的夜晚。謝謝。

Thank you all for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝大家參加今天的會議。這確實結束了該程序。您現在可以斷開連接。