Lantern Pharma Inc (LTRN) 2024 Q3 法說會逐字稿

Good afternoon, and welcome to our third-quarter 2024 earnings call. As a reminder, this call is being recorded.

下午好，歡迎參加我們的 2024 年第三季財報電話會議。提醒一下，此通話正在錄音。

(Operator Instructions)

（操作員說明）

A webcast replay of today's conference call will be available on our website at lanternpharma.com.

今天電話會議的網路廣播重播將在我們的網站 Lanternpharma.com 上提供。

Shortly after the call, we issued a press release after market close today summarizing our financial results and progress across the company for the third quarter ended September 30, 2024. A copy of this release is available through our website at lanternpharma.com where you will also find a link to the slides management will be referencing on today's call.

電話會議後不久，我們在今天收盤後發布了一份新聞稿，總結了截至 2024 年 9 月 30 日的第三季度的財務業績和整個公司的進展。新聞稿的副本可透過我們的網站 Lanternpharma.com 取得，您還可以在其中找到指向今天電話會議中將引用的幻燈片管理層的連結。

We would like to remind everyone that remarks about future expectations, performance, estimates and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Lantern Pharma cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated. A number of factors could cause actual results to differ materially from those indicated by forward-looking statements, including results of clinical trials and the impact of competition. Additional information concerning factors that could cause actual results to differ materially from those in the forward-looking statements can be found in our annual report on Form 10-K for the year ended December 31, 2023, which is on file with the SEC and available on our website. Forward-looking statements made on this conference call are as of today, November 7, 2024, and Lantern Pharma does not intend to update any of these forward-looking statements to reflect events from circumstances that occur after today, unless required by law.

我們想提醒大家，有關未來預期、績效、估計和前景的言論構成前瞻性陳述，以符合 1995 年《私人證券訴訟改革法案》中的安全港條款。Lantern Pharma 警告稱，這些前瞻性聲明存在風險和不確定性，可能導致實際結果與預期有重大差異。許多因素可能導致實際結果與前瞻性陳述所示的結果有重大差異，包括臨床試驗結果和競爭的影響。有關可能導致實際結果與前瞻性陳述中的結果存在重大差異的因素的更多信息，請參閱我們截至 2023 年 12 月 31 日的 10-K 表格年度報告，該報告已向 SEC 備案並可供查閱在我們的網站上。本次電話會議中所做的前瞻性陳述截至今天，即 2024 年 11 月 7 日，除非法律要求，否則 Lantern Pharma 不打算更新任何這些前瞻性陳述以反映今天之後發生的事件。

The webcast replay of the conference call and webinar will be available on Lantern's website. On today's webcast, we have Lantern Pharma's CEO, Panna Sharma and members of management. Panna will start things off with introductions and an overview of Lantern's strategy and business model and highlight recent achievements in our operations, followed by discussions of our financial results and our R&D efforts.

電話會議和網路研討會的網路直播重播將在 Lantern 網站上提供。在今天的網路廣播中，我們有 Lantern Pharma 執行長 Panna Sharma 和管理層成員。Panna 將首先介紹和概述 Lantern 的策略和商業模式，並重點介紹我們最近在營運中的成就，然後討論我們的財務表現和研發工作。

I'd now like to turn the call over to Panna Sharma, President and CEO of Lantern Pharma. Panna, please go ahead.

我現在想將電話轉給 Lantern Pharma 總裁兼執行長 Panna Sharma。潘娜，請繼續。

Good afternoon, and thank you for joining Lantern Pharma's Third Quarter 2024 Earnings Call. Today, I'll share our continued progress in advancing our AI-guided clinical programs and discuss our financial results. The pharmaceutical industry is experiencing a fundamental transformation. AI and computational approaches are no longer optional tools, they have become essential drivers of innovation across the entire drug development spectrum. For molecular design to patient selection, for manufacturing to clinical trial execution, AI is revolutionizing how we develop life-changing therapies.

下午好，感謝您參加 Lantern Pharma 的 2024 年第三季財報電話會議。今天，我將分享我們在推動人工智慧引導臨床專案方面的持續進展，並討論我們的財務表現。製藥業正在經歷根本性變革。人工智慧和計算方法不再是可選工具，它們已成為整個藥物開發領域創新的重要驅動力。從分子設計到患者選擇，從製造到臨床試驗執行，人工智慧正在徹底改變我們開發改變生活的療法的方式。

Lantern has been at the forefront of this transformation. Since our IPO in 2020, our RADR AI platform has enabled us to generate and advance 14 drug programs at a fraction of the cost of traditional drug development. More importantly, we've demonstrated the ability to consistently progress these AI-guided candidates into actual patient trials, something very few other AI companies have done, including our ongoing Phase 2 HARMONIC trial and our Phase 1 programs for both LP-184 and LP-284. This quarter validates our AI-driven approach with significant clinical progress across multiple programs, including encouraging early data from our HARMONIC trial and the recent FDA Fast Track designation for LP-184 in glioblastoma. These achievements underscore how our technology-first approach is accelerating the development of precision cancer therapies while maintaining capital efficiency.

Lantern 一直處於這一轉變的最前線。自 2020 年 IPO 以來，我們的 RADR AI 平台使我們能夠以傳統藥物開發成本的一小部分來產生和推進 14 個藥物專案。更重要的是，我們已經證明了能夠持續將這些人工智慧引導的候選藥物推進到實際的患者試驗中，這是其他人工智慧公司很少做到的，包括我們正在進行的2 期HARMONIC 試驗以及我們針對LP-184 和LP 的1 期項目-284。本季度驗證了我們的人工智慧驅動方法，在多個項目中取得了重大臨床進展，包括來自我們的HARMONIC 試驗的令人鼓舞的早期數據以及最近FDA 對LP-184 膠質母細胞瘤的快速通道指定。這些成就凸顯了我們的技術優先方法如何在維持資本效率的同時加速精準癌症療法的開發。

Our dedicated teams remain laser-focused on our mission to transform cancer patients' lives while dramatically reducing the time and cost of oncology drug development, a commitment that drives every aspect of our work and is reflected in the momentum we're building across our pipeline. Our company's leadership and the innovative use of AI and machine learning to transform costs and time lines in the development of precision oncology therapies should yield significant returns for investors and patients as our industry matures and adopts an AI-centric and data-first approach to drug development.

我們的專業團隊始終專注於我們的使命，即改變癌症患者的生活，同時大幅減少腫瘤藥物開發的時間和成本，這項承諾推動我們工作的各個方面，並反映在我們在整個管道中建立的勢頭中。隨著我們行業的成熟並採用以人工智慧為中心和數據優先的藥物方法，我們公司的領導地位以及創新地利用人工智慧和機器學習來改變精準腫瘤治療開發的成本和時間線，應該會為投資者和患者帶來可觀的回報發展。

Let me start with a high-level view of our clinical progress. We currently have three precision oncology drug candidates advancing through clinical trials, all guided by our RADR AI platform. These include both Phase 1 and Phase 2 programs and alongside these clinical programs, we're evaluating several promising ADC candidates in preclinical development, many of which have come from our AI-driven ADC module. I'm particularly excited to share updates on our HARMONIC trial, which is testing LP-300. The initial data has been very encouraging, and we detailed that in our last earnings call. In our first seven patients, we saw an 86% clinical benefit rate. To put this in perspective, these are never smoker patients with non-small cell lung cancer who have limited treatment options. So these early signals are particularly meaningful, especially since they cover a wide range of prior kinase mutations.

讓我先對我們的臨床進展進行高層次的概述。目前，我們有三種精準腫瘤候選藥物正在通過臨床試驗，全部由我們的 RADR AI 平台指導。其中包括 1 期和 2 期項目，除了這些臨床項目外，我們還在臨床前開發中評估幾種有前途的 ADC 候選藥物，其中許多來自我們的人工智慧驅動的 ADC 模組。我特別高興能分享我們正在測試 LP-300 的 HARMONIC 試驗的最新情況。最初的數據非常令人鼓舞，我們在上次財報電話會議中詳細介紹了這一點。在我們的前七名患者中，我們看到了 86% 的臨床受益率。從長遠來看，這些非小細胞肺癌患者從不吸煙，治療選擇有限。因此，這些早期訊號特別有意義，特別是因為它們涵蓋了廣泛的先前激酶突變。

We continue to enroll additional patients across our U.S. sites but also we've made significant strides in expanding our HARMONIC trial into Asia, specifically Japan and Taiwan. This expansion is strategically important because in these countries, [never smoker] lung cancer represents a much larger portion of all lung cancer cases, about 1/3 of new cases compared to what we see in Western countries, which is about 15% to 20%. We're establishing a total of 10 sites across Japan and Taiwan, five in each country, we've actually already begun onboarding the sites, and we expect patients to enroll this quarter. This expansion not only accelerates our enrollment in the trial overall but also positions LP-300 in regions where the medical need is particularly high.

我們繼續在美國各地招募更多患者，但我們在將 HARMONIC 試驗擴展到亞洲（特別是日本和台灣）方面也取得了重大進展。這種擴張具有重要的戰略意義，因為在這些國家，[從不吸煙]肺癌在所有肺癌病例中所佔比例要大得多，約佔新發病例的1/3，而西方國家則約為15 % 至20%。我們在日本和台灣總共建立了 10 個站點，每個國家 5 個，實際上我們已經開始加入這些站點，我們預計患者將在本季度註冊。此次擴展不僅加速了我們整體試驗的入組速度，而且使 LP-300 能夠在醫療需求特別高的地區佔有一席之地。

Now let me turn to our synthetic lethal drug candidates, LP-184 and LP-284. Both are first-in-human, Phase 1a trials, and they continue to show strong progress and are enrolling across centers in the U.S. We've now dosed over 50 patients across both programs, and importantly, we haven't observed any dose limiting toxicities in any of our patient cohorts. This safety profile is particularly encouraging as we advance these programs clinically and sharpen the indications and clinical positioning of these highly potent drug candidates.

現在讓我談談我們的合成致命候選藥物 LP-184 和 LP-284。兩項都是首次人體1a 期試驗，它們繼續顯示出強勁的進展，並且正在美國各個中心進行招募。沒有觀察到任何劑量限制我們的任何患者群體中的毒性。隨著我們在臨床上推動這些計畫並加強這些高效候選藥物的適應症和臨床定位，這種安全性尤其令人鼓舞。

We also received exciting news this quarter regarding LP-184, which many of you know, will be developed at STAR-001 in CNS and brain cancer indications through our wholly owned subsidiary, Starlight Therapeutics. The FDA granted us fast track designation for glioblastoma or GBM. This designation not only demonstrates the significant unmet need in GBM, but also provides potential opportunities to expedite development and drive greater commercial value for our molecule. Speaking of GBM, we've been successfully enrolling recurrent GBM patients in our existing Phase 1a trial for LP-184 across three sites, two prestigious academic centers, including Johns Hopkins Medicine and Indiana University and one community site. The data we're gathering from these GBM patients is particularly valuable as they will inform our development for future clinical trials, including Phase 1b/2 trials which Starlight Therapeutics expects to initiate in 2025 or any investigator-led initiatives that we undertake. This represents a significant step forward in our CNS cancer program, where effective treatment options are severely limited. At the same time, investors in Lantern will potentially benefit as we look to further develop and finance Starlight Therapeutics.

本季我們也收到了有關LP-184 的令人興奮的消息，你們很多人都知道，LP-184 將透過我們的全資子公司Starlight Therapeutics 在STAR-001 中開發，用於CNS 和腦癌適應症。FDA 授予我們膠質母細胞瘤或 GBM 快速通道資格。這個頭銜不僅表明 GBM 的需求尚未得到滿足，而且還提供了加速開發並為我們的分子帶來更大商業價值的潛在機會。說到GBM，我們已經在三個中心、兩個著名學術中心（包括約翰霍普金斯大學醫學院和印第安納大學）和一個社區中心成功招募了復發性GBM 患者參加我們現有的LP-184 1a期試驗。我們從這些GBM 患者收集的數據特別有價值，因為它們將為我們未來臨床試驗的發展提供信息，包括Starlight Therapeutics 預計於2025 年啟動的1b/2 期試驗或我們開展的任何由研究者主導的舉措。這代表著我們的中樞神經系統癌症計劃向前邁出了重要一步，在該計劃中，有效的治療選擇受到嚴重限制。同時，隨著我們尋求進一步開發 Starlight Therapeutics 並為其提供融資，Lantern 的投資者將可能受益。

I'd like to highlight now some particularly exciting opportunities, developments in our biomarker program. As many of you know, PTGR1 was initially identified through our RADR AI platform as a key biomarker for LP-184 response. This discovery represents one of our platform's most significant predictive insights, demonstrating how AI can identify precise biological mechanisms that drive drug response. We've now begun analyzing PTGR1 expression using qPCR in patient samples from our first seven cohorts in the LP-184 Phase 1a trial. This analysis is crucial because it will help validate our AI-driven hypothesis that has been validated in vitro and in vivo and also through CRISPR experimentation. But now we can also validate it in human clinical trials. This data will allow us to better predict which patients are most likely to respond to treatment and perhaps even look at monitoring progress and sensitivity to our drug.

我現在想強調我們的生物標記計畫中一些特別令人興奮的機會和發展。正如你們許多人所知，PTGR1 最初是透過我們的 RADR AI 平台確定為 LP-184 反應的關鍵生物標記。這項發現代表了我們平台最重要的預測見解之一，展示了人工智慧如何識別驅動藥物反應的精確生物機制。我們現在開始使用 qPCR 分析 LP-184 1a 期試驗中前七個隊列的患者樣本中的 PTGR1 表達。這項分析至關重要，因為它將有助於驗證我們的人工智慧驅動假設，該假設已在體外和體內以及透過 CRISPR 實驗得到驗證。但現在我們也可以在人體臨床試驗中驗證它。這些數據將使我們能夠更好地預測哪些患者最有可能對治療產生反應，甚至可能監測進展和對我們藥物的敏感性。

We also received very important regulatory recognition this quarter with three new FDA rare pediatric designations for LP-184. This is in addition to the existing one for [ATRT]. The three new designations were all in ultra-rare childhood cancers. These designations are particularly significant because each one carries the potential to receive a priority review voucher or PRV upon FDA approval. For those who may not be familiar with PRVs, they are transferable assets that can be sold to other pharmaceutical companies and have historically been valued in excess of $100 million. We have four of these, each PRV allows its holder to accelerate FDA review of a future drug candidate making them highly valuable assets in the biopharma industry. The fact that LP-184 has received these designations not only underscores its potential impact in areas of high unmet need amongst children, but particularly where these treatment options are often limited or have no options. This is valuable for patients, but also potentially valuable as future value for our shareholders and our future programs.

本季我們也獲得了非常重要的監管認可，LP-184 獲得了 FDA 三個新的罕見兒科指定。這是對現有的一項的補充[ATRT]。這三個新名稱均針對極為罕見的兒童癌症。這些指定特別重要，因為每一項指定都有可能在 FDA 批准後獲得優先審查憑證或 PRV。對於可能不熟悉 PRV 的人來說，它們是可轉讓資產，可以出售給其他製藥公司，歷史上估值超過 1 億美元。我們有四個這樣的產品，每個 PRV 都允許其持有者加速 FDA 對未來候選藥物的審查，使其成為生物製藥行業非常有價值的資產。LP-184 獲得這些指定的事實不僅強調了其在兒童需求未滿足的領域的潛在影響，而且特別是在這些治療方案通常有限或沒有選擇的情況下。這對患者來說很有價值，但對於我們的股東和我們未來的專案也具有潛在的未來價值。

Our scientific team has been particularly productive this quarter with three significant publications and presentations and numerous insights about how to guide our drug into future combination trials. Our Chief Scientific Officer, Dr. Kishor Bhatia, will provide additional details around these and other areas that will be important for our future work. This past quarter, we published a peer-reviewed paper highlighting our novel AI-powered approach to ADC development using the RADR platform an area of growing interest in the oncology community. We also presented new findings about our synthetic lethal drug candidate at two major conferences: The immuno-oncology summit, where we shared exciting data about the role of LP-184 in synergy with anti-PD-1 drugs and at the Society of Hematologic Oncology, where we presented insights regarding LP-284. These presentations generated significant interest from collaborators, pharma companies and also help strengthen our AI-driven approach to drug development by giving us insights, models and new data.

我們的科學團隊本季特別富有成效，發表了三份重要的出版物和演示文稿，以及關於如何指導我們的藥物進入未來聯合試驗的大量見解。我們的首席科學官 Kishor Bhatia 博士將提供有關這些領域以及對我們未來工作非常重要的其他領域的更多詳細資訊。上個季度，我們發表了一篇同行評審論文，重點介紹了我們使用 RADR 平台進行人工智慧驅動的新型 ADC 開發方法，這是腫瘤學界越來越感興趣的領域。我們還在兩個主要會議上展示了有關我們的合成致命候選藥物的新發現：免疫腫瘤學峰會，我們在會上分享了有關LP-184 與抗PD-1 藥物協同作用的令人興奮的數據，以及在血液腫瘤學會上，其中我們提出了有關 LP-284 的見解。這些演講引起了合作者、製藥公司的極大興趣，並透過為我們提供見解、模型和新數據，幫助加強我們的人工智慧驅動的藥物開發方法。

We'll also get more details today from my colleague, David Margrave, our CFO today, on our financial position and operations. At a top level, Lantern closed the quarter with approximately $28.1 million in cash, cash equivalents and marketable securities, and we used approximately $4.5 million in operations this past third quarter.

今天我們還將從我的同事、我們的財務長 David Margrave 獲得有關我們財務狀況和營運的更多詳細資訊。從高層來看，Lantern 本季末擁有約 2,810 萬美元的現金、現金等價物和有價證券，而我們在過去第三季的營運中使用了約 450 萬美元。

So I'm going to hand this over now to David to talk in more detail about our finance and operations. David?

因此，我現在將把這個問題交給大衛，更詳細地討論我們的財務和營運情況。大衛？

Thank you, Panna, and good afternoon, everyone. I will now share some financial highlights from our third quarter ended September 30, 2024. We recorded a net loss of approximately $4.5 million for the third quarter of 2024 or $0.42 per share compared to a net loss of approximately $3.2 million or $0.29 per share for the third quarter of 2023. For the third quarter of 2024, our R&D expenses were approximately $3.7 million, up from approximately $2.2 million for the third quarter of 2023. This increase was largely driven by an increase in clinical trial activity.

謝謝潘納，大家下午好。我現在將分享截至 2024 年 9 月 30 日的第三季的一些財務亮點。我們的 2024 年第三季淨虧損約為 450 萬美元，即每股 0.42 美元，而 2023 年第三季的淨虧損約為 320 萬美元，即每股 0.29 美元。2024 年第三季度，我們的研發費用約為 370 萬美元，高於 2023 年第三季的約 220 萬美元。這一增長主要是由臨床試驗活動的增加所推動的。

Our general and administrative expenses for the third quarter of 2024 were approximately $1.5 million up slightly from approximately $1.3 million for the third quarter of 2023. The increase was primarily attributable to increases in professional fees and increased patent and legal fees. Our R&D expenses continue to exceed our G&A expenses by a strong margin reflecting our focus on advancing our product candidates and pipeline. Our loss from operations in the third quarter of 2024 was partially offset by interest income and other income net totaling approximately $674,000 as compared to a loss offset from interest income and other income net of approximately $362,000 for the third quarter of 2023. Our cash position, which includes cash equivalents and marketable securities was approximately $28.1 million as of September 30, 2024. We anticipate this balance will provide us with a cash runway into at least late 2025. Importantly, we believe our solid financial position will fuel continued growth and evolution of our [RADR AI] platform, continue the development of our portfolio of targeted oncology drug candidates and allow us to introduce additional targeted programs and collaboration opportunities efficiently and effectively.

我們 2024 年第三季的一般和管理費用約為 150 萬美元，略高於 2023 年第三季的約 130 萬美元。這一增長主要歸因於專業費用以及專利和法律費用的增加。我們的研發費用持續大幅超過一般管理費用，反映出我們專注於推進我們的產品候選人和管道。我們 2024 年第三季的營運虧損被總計約 674,000 美元的利息收入和其他收入淨額部分抵消，而 2023 年第三季的利息收入和其他收入淨額抵消的虧損約為 362,000 美元。截至 2024 年 9 月 30 日，我們的現金部位（包括現金等價物和有價證券）約為 2,810 萬美元。我們預計這一餘額將為我們提供至少到 2025 年末的現金跑道。重要的是，我們相信我們穩健的財務狀況將推動我們的[RADR AI] 平台的持續增長和發展，繼續開發我們的靶向腫瘤候選藥物組合，並使我們能夠高效、有效地引入更多的有針對性的專案和合作機會。

As of September 30, 2024, we had 10,784,725 shares of common stock outstanding, outstanding warrants to purchase 70,000 shares and outstanding options to purchase 1,274,546 shares. These warrants and options, combined with our outstanding shares of common stock, give us a total fully diluted shares outstanding of approximately 12.1 million shares as of September 30, 2024.

截至 2024 年 9 月 30 日，我們擁有 10,784,725 股已發行普通股、已發行認股權證（可購買 70,000 股）以及已發行選擇權（可購買 1,274,546 股）。這些認股權證和選擇權，加上我們已發行的普通股，截至 2024 年 9 月 30 日，我們的完全稀釋後已發行股票總數約為 1,210 萬股。

Our team at Lantern continues to be very productive under a hybrid operating model. We currently have approximately 24 employees and four FTE consultants focused primarily on leading and advancing our research and drug development efforts. Many of the initial observations made with the help of RADR are now being brought forth into the clinic, as you can see in our portfolio slide that's being presented. As many of you know, RADR has guided the rapid and efficient development of three AI-guided drug candidates into ongoing clinical trials. As these clinical trials mature and continue to enroll patients, we expect to leverage our internal clinical operations capabilities across these trials and functions, making efficient use of our capital, while lowering dependency on external higher-cost providers. Additionally, we believe having more direct internal ownership, not only reduces our overall financial expenditures, but also gives our team greater ownership, control and access to current information, sites and day-to-day activity in the hospitals and cancer centers relating to our trials. This, we believe, will strengthen our company and allow us to capitalize on observations and decrease our external costs. We are fortunate to have developed a dedicated, highly motivated clinical operations team with alignment around our core values to help us in the efficient management and maturation of these clinical trials across LP-300, both in the U.S, and Asia and our first in-human drug candidates, LP-184 and LP-284.

我們 Lantern 的團隊在混合營運模式下持續保持高效率。我們目前擁有約 24 名員工和 4 名 FTE 顧問，主要致力於領導和推進我們的研究和藥物開發工作。正如您在我們正在展示的投資組合幻燈片中所看到的，在 RADR 的幫助下進行的許多初步觀察現在已被帶入臨床。眾所周知，RADR 已指導三種人工智慧引導的候選藥物快速且有效率地開發到正在進行的臨床試驗中。隨著這些臨床試驗的成熟並繼續招募患者，我們希望在這些試驗和職能中利用我們的內部臨床營運能力，有效利用我們的資本，同時減少對外部高成本提供者的依賴。此外，我們相信，擁有更直接的內部所有權，不僅可以減少我們的整體財務支出，而且還可以讓我們的團隊對與我們相關的醫院和癌症中心的當前資訊、網站和日常活動擁有更大的所有權、控制權和存取權。我們相信，這將增強我們公司的實力，並使我們能夠利用觀察結果並降低外部成本。我們很幸運地建立了一支專注、積極主動的臨床營運團隊，與我們的核心價值保持一致，幫助我們有效管理和成熟LP-300 的這些臨床試驗，無論是在美國還是亞洲，以及我們的第一個 -人類候選藥物 LP-184 和 LP-284。

I'll now turn the call back to Panna for an update on Starlight and its focus on CNS and brain cancers. Panna?

現在我將把電話轉回 Panna，了解 Starlight 的最新情況及其對中樞神經系統和腦癌的關注。潘納？

Thanks, David. We also continue to make significant progress on the launch of our clinical stage CNS and brain cancer-focused subsidiary, Starlight Therapeutics. This is a company that has been largely developed as a result of big data and AI. The methods and computational approaches to uncover the indications and optimize the use of LP-184 for brain and CNS cancers. Notably, we have started initiating site selection for the upcoming Phase 1b and Phase 2 trials, especially in recurrent [IDH] wild type [hydrate gliomas] like GBM and are also in discussions for the use of the drug in potentially -- settings. If you have not reviewed our webinar in webinar Wednesdays regarding Starlight, I would definitely urge you all to listen to the webinars. They provide details on the timing and focus of the trials and also provide insights from Dr. Mark Chamberlain about how we expect to advance this both in adult and pediatric brain cancers.

謝謝，大衛。我們也在推出專注於中樞神經系統和腦癌臨床階段的子公司 Starlight Therapeutics 方面繼續取得重大進展。這是一家很大程度上依靠大數據和人工智慧而發展起來的公司。揭示 LP-184 治療腦癌和中樞神經系統癌症的適應症並優化其使用的方法和計算方法。值得注意的是，我們已經開始為即將到來的1b 期和2 期試驗開始選址，特別是在復發性[IDH] 野生型[水合神經膠質瘤] 如GBM 中，並且還在討論該藥物在潛在環境中的使用。如果您還沒有在周三的網路研討會上觀看有關星光的網路研討會，我強烈建議大家收聽網路研討會。他們提供了有關試驗的時間和重點的詳細信息，並提供了 Mark Chamberlain 博士關於我們期望如何在成人和兒童腦癌方面推進這一進展的見解。

I'd like to take a moment to emphasize two significant recent developments that further validate our CNS cancer program. First, the FDA's Fast Track designation for LP-184 in glioblastoma represents a crucial milestone. This designation is particularly meaningful because it recognizes both the serious nature of GBM and the significant unmet medical need. We have a new effective single-agent therapy approved for GBM in nearly 20 years. Fast Track status provides us several important advantages, including more frequent interactions with the FDA, the potential for rolling review of our future NDA and if criteria are met, could lead to accelerated approval and priority review. These benefits could potentially shave years off our development time line in GBM and make the asset significantly more valuable in the hands of a larger biopharma partner.

我想花點時間強調最近的兩項重大進展，進一步驗證了我們的中樞神經系統癌症計劃。首先，FDA 對 LP-184 治療膠質母細胞瘤的快速通道指定是一個重要的里程碑。這個頭銜特別有意義，因為它認識到 GBM 的嚴重性和未滿足的重大醫療需求。近 20 年來，我們有一種新的有效單藥療法被批准用於治療 GBM。快速通道狀態為我們提供了幾個重要的優勢，包括與 FDA 更頻繁的互動、對我們未來 NDA 進行滾動審查的潛力，以及如果滿足標準，可能會導致加速批准和優先審查。這些好處可能會縮短我們 GBM 的開發時間，並使該資產在更大的生物製藥合作夥伴手中變得更有價值。

Equally exciting is the formation of Starlight Therapeutics Scientific Advisory Board, which brings together some of the most respected minds in neuro-oncology. Let me share with you the distinguished members who have joined us. Dr. Mitchel Berger from UCSF, who chairs their Department of Neurosurgery and directs both their brain tumor center and center for neurological injury and repair. Dr. Berger is internationally recognized for his expertise in brain mapping during tumor surgery; Dr. Lisa DeAngelis, who serves as Chief Physician Executive at [Memorial Sloan Kettering] Cancer Center, where she oversees all clinical operations across their network of sites, She's an internationally recognized expert in brain cancer and help establish Memorial Sloan Kettering's Brain tumor Center; Dr. Stuart Grossman from Johns Hopkins and [Sydney Kimmel] Cancer Center, who co-leads their brand cancer program and brings over 22 years of experience directing NCI-funded brain tumor consortia; and lastly, but definitely not least -- in the least, Dr. John Laterra, also from Johns Hopkins, who co-directs their brain cancer program and is internationally recognized for his work on mechanisms of brain tumor malignancy. Dr. Laterra has been an early supporter and has encouraged us to pursue this indication and has helped our research efforts and continues to help guide combination regimen ideas that we think will be significant in the clinical setting. My colleague, Dr. Kishor Bhatia will discuss those later today in our webinar.

同樣令人興奮的是星光療法科學諮詢委員會的成立，該委員會匯集了神經腫瘤學領域一些最受尊敬的人士。讓我跟大家分享一下加入我們的尊貴會員。加州大學舊金山分校的 Mitchel Berger 博士擔任神經外科系主任，並指導腦腫瘤中心和神經損傷與修復中心。伯傑博士因其在腫瘤手術期間腦部繪圖方面的專業知識而受到國際認可。 Lisa DeAngelis 博士是[紀念斯隆·凱特琳]癌症中心的首席醫師執行官，負責監督整個中心網絡的所有臨床操作。腦腫瘤中心；來自約翰霍普金斯大學和 [Sydney Kimmel] 癌症中心的 Stuart Grossman 博士共同領導了他們的品牌癌症項目，並擁有超過 22 年指導 NCI 資助的腦腫瘤聯盟的經驗；最後，但絕對不是最不重要的——同樣來自約翰霍普金斯大學的John Laterra 博士，他共同指導了他們的腦癌項目，並因其在腦腫瘤惡性腫瘤機制方面的工作而受到國際認可。Laterra 博士是早期的支持者，鼓勵我們追求這種適應症，幫助我們的研究工作，並繼續幫助指導我們認為在臨床環境中具有重要意義的聯合治療方案想法。我的同事 Kishor Bhatia 博士將在今天稍後的網路研討會上討論這些問題。

The Starlight Advisory Board, which includes two recipients of the Society for Neuro-Oncology's Lifetime Achievement Award brings unprecedented expertise to guide our CNS cancer programs. Their willingness to join our advisory board speaks volumes about the potential they see in our approach to treating these devastating cancers.

星光顧問委員會包括兩名神經腫瘤學會終身成就獎得主，他們帶來了前所未有的專業知識來指導我們的中樞神經系統癌症計畫。他們願意加入我們的諮詢委員會，充分說明了他們在我們治療這些毀滅性癌症的方法中所看到的潛力。

Let me walk you through some of our progress now with the synthetic lethal drug candidates, LP-184 and LP-284. The Phase 1a basket trial for LP-184 we've now completed nine cohorts with escalating doses. We haven't seen any dose-limiting toxicities. We're actively enrolling patients across multiple solid tumor types including those that have high PTGR1 like triple-negative, GBM and pancreatic cancer, and now we're zeroed in on tumors that have DNA damage response deficiency. Based on our pharmacokinetic analysis, we're approaching an exciting milestone. Our upcoming cohort should reach dosage levels where we expect to see therapeutic concentrations of our drug candidate LP-184, and hopefully, impact on the cancers. We anticipate completing enrollment by year-end or in January with initial safety and molecular correlation data expected either late this year or during early 2025.

讓我向您介紹我們目前在合成致命候選藥物 LP-184 和 LP-284 方面取得的一些進展。我們現已完成 LP-184 的 1a 期籃子試驗，並逐步增加劑量。我們尚未發現任何劑量限制性毒性。我們正在積極招募多種實體瘤類型的患者，包括那些具有高 PTGR1 的患者，如三陰性、GBM 和胰腺癌，現在我們將注意力集中在 DNA 損傷反應缺陷的腫瘤上。根據我們的藥物動力學分析，我們正在接近一個令人興奮的里程碑。我們即將推出的隊列應該達到我們期望看到候選藥物 LP-184 的治療濃度的劑量水平，並希望對癌症產生影響。我們預計在年底或 1 月完成註冊，並預計在今年年底或 2025 年初獲得初步安全性和分子相關性數據。

I'm particularly excited about our progress in developing a companion diagnostic for LP-184, we're advancing a quantitative PCR-based test that could help us identify the patients most likely to respond to treatment, ones that have PTGR1 above a certain threshold, which is a key aspect of our precision medicine approach. We're currently validating this assay using patient samples, but also now using them in the first seven cohorts in the Phase 1 trial. These molecular correlations that will be invaluable in designing our future trials and helping us select patients. The combination of clinical progress and diagnostic development exemplifies our comprehensive approach to drug development. We're not just advancing a therapeutic candidate, but also developing the tools to identify the right patients for treatment.

我對我們在開發LP-184 伴隨診斷方面取得的進展感到特別興奮，我們正在推進基於定量PCR 的測試，該測試可以幫助我們識別最有可能對治療產生反應的患者，即PTGR1 高於特定閾值的患者，這是我們精準醫療方法的關鍵面向。我們目前正在使用患者樣本驗證該測定，但現在也在第一階段試驗的前七個隊列中使用它們。這些分子相關性對於設計我們未來的試驗和幫助我們選擇患者將具有無價的價值。臨床進展和診斷開發的結合體現了我們全面的藥物開發方法。我們不僅在開發候選治療藥物，還在開發工具來識別合適的治療患者。

Turning to our LP-284 program, which targets hematologic cancers, we're making equally exciting progress. We're currently dosing our fourth cohort, again, in escalating doses in the Phase 1a trial, and like LP-184, we're seeing favorable safety profile with no dose-limiting toxicities. Let me highlight why we're excited about LP-284, remarkable potency in the [nanomolar] range for multiple blood cancer types, but specifically in mantle cell and double-hit lymphomas both very aggressive NHL subtypes, particularly those that have ATM mutations. To put this opportunity in perspective, we're targeting an area of significant -- nearly all [mantle cell in double lymphoma] patients and in general hybrid B-cell lymphomas. Again, we received two orphan designations for this drug eventually relapse after current standard treatments. The market opportunity is substantial in the U.S, and Europe alone, about 16,000 to 20,000 new patients annually about a market exceeding somewhere in the range of $2.8 billion to $3 billion just in U.S, and Europe alone.

談到我們針對血液癌症的 LP-284 項目，我們正在取得同樣令人興奮的進展。我們目前正在對第四組進行給藥，在 1a 期試驗中劑量不斷增加，與 LP-184 一樣，我們看到了良好的安全性，沒有劑量限制性毒性。讓我強調為什麼我們對LP-284 感到興奮，LP-284 在[納摩爾] 範圍內對多種血癌類型具有顯著功效，特別是對套細胞和雙重打擊淋巴瘤這兩種非常具有侵襲性的NHL 亞型，特別是那些具有ATM 突變的亞型。為了正確看待這個機會，我們的目標是一個重要的領域—幾乎所有[雙淋巴瘤中的套細胞]患者和一般的混合 B 細胞淋巴瘤。同樣，我們再次獲得了該藥物的兩個孤兒藥資格，在目前的標準治療後最終復發。光是在美國和歐洲，市場機會就很大，每年約有 16,000 至 20,000 名新患者，光是在美國和歐洲，市場規模就超過 28 億至 30 億美元。

We're now in the process of expanding our trial to additional hematology focused sites, which we expect will accelerate our enrollment through the end of this year. Based on our current trajectory, we believe we could advance to Phase 1b or future phases like Phase 2 by early to mid-2025. When we look at both LP-184 and LP-284 together, these are sister molecules. We're seeing consistent patterns that validate our synthetic lethal approach, strong safety profiles, encouraging signs of biological activity and the potential to address significant unmet cancers where oftentimes, there is no here in the later-stage setting. So these are very exciting. This kind of excitement has helped us do one very important thing which is secure 11 FDA designations, fast track designations, orphan drug designations and rare pediatric disease designations. This is a strong testament to our data-driven rapid and focused drug development initiatives. We believe this will aid in more frequent guidance and interaction with the FDA and also strengthen our commercial value in talks with partners and clinicians during adoption. With our HARMONIC trial, LP-300, the data has been very encouraging, and more importantly, this is for patients where there is no real treatment options today. After they fail [kinase] therapy, there are very limited treatment options. So these early signals, though in a small group, are particularly meaningful. We also see a diverse set of patients in the U.S. with a varying range of [kinase] mutations and also with low to intermediate tumor mutation burden, we should have some interesting implications for biomarker-based selection or monitoring as we mature the drug candidate.

我們現在正在將試驗擴展到更多以血液學為重點的站點，我們預計這將在今年年底之前加快我們的入組速度。根據我們目前的發展軌跡，我們相信我們可以在 2025 年初至中期推進到 1b 階段或第 2 階段等未來階段。當我們同時觀察 LP-184 和 LP-284 時，它們是姐妹分子。我們看到了一致的模式，這些模式驗證了我們的合成致死方法、強大的安全性、令人鼓舞的生物活性跡像以及解決重大未滿足癌症的潛力，而這些癌症通常在後期環境中是沒有的。所以這些都是非常令人興奮的。這種興奮幫助我們做了一件非常重要的事情，即獲得 11 項 FDA 指定、快速通道指定、孤兒藥指定和罕見兒科疾病指定。這有力地證明了我們數據驅動的快速且專注的藥物開發計劃。我們相信，這將有助於與 FDA 進行更頻繁的指導和互動，並在採用過程中增強我們與合作夥伴和臨床醫生談判的商業價值。透過我們的 HARMONIC 試驗 LP-300，數據非常令人鼓舞，更重要的是，這適用於目前沒有真正治療選擇的患者。當[激酶]治療失敗後，治療選擇非常有限。因此，這些早期訊號雖然是在一個小群體中，但卻特別有意義。我們也看到美國的不同患者群體具有不同範圍的[激酶]突變，並且具有低至中等的腫瘤突變負擔，隨著我們成熟的候選藥物，我們應該對基於生物標誌物的選擇或監測產生一些有趣的影響。

We continue to enroll patients across our U.S. sites and are also expanding into Asia and Japan and Taiwan, as I've stated earlier. In East Asia, including Taiwan, Japan and South Korea, nearly 40% of new cases now in non-small cell lung cancer or amongst ever smokers. This is a remarkable percentage and underscores our commitment to expand the HARMONIC trial to where it's needed in these countries. We're opening up 10 sites in Asia, five in Japan, five in Taiwan, and very importantly, working close to the top KOLs in each country. Dr. [Goa], the National Cancer Center Japan and Tokyo and Dr. [Lee] at the National [Cheng Kong] University Hospital located in Tainan City in Taiwan.

正如我之前所說，我們繼續在美國網站招募患者，並擴展到亞洲、日本和台灣。在東亞，包括台灣、日本和韓國，目前有近 40% 的新病例為非小細胞肺癌或曾經吸菸者。這是一個了不起的百分比，突顯了我們將 HARMONIC 試驗擴大到這些國家需要的地方的承諾。我們將在亞洲開設 10 個站點，其中 5 個在日本，5 個在台灣，而且非常重要的是，我們將與每個國家的頂級 KOL 密切合作。日本國立癌症中心和東京的[果阿]博士以及台灣台南市國立[長江]大學醫院的[李]博士。

In the majority of East Asia EGFR mutations comprise a significant an overwhelming percentage of the targetable kinase mutations among ever smokers. We've already seen some early signs of efficacy in our initial cohort. Now this is important because we think this represents an important opportunity in Asia, where we've now begun discussions regarding partnering, licensing or co-development of this asset in that geography.

在大多數東亞地區，EGFR 突變在曾經吸菸者的標靶激酶突變中佔據了壓倒性的比例。我們已經在最初的隊列中看到了一些功效的早期跡象。現在這很重要，因為我們認為這代表了亞洲的一個重要機會，我們現在已經開始討論在該地區合作、許可或共同開發該資產。

Now I'll turn the call over to our Chief Scientific Officer, Kishor Bhatia, who will provide an overview of our R&D updates and speak specifically to a number of highly promising combination regimens for LP-184. Ones that have been shaped and informed and guided by RADR, but now ill help shape future clinical trials that will be very meaningful. Kishor?

現在我將把電話轉給我們的首席科學官 Kishor Bhatia，他將概述我們的研發更新，並具體介紹一些非常有前途的 LP-184 組合方案。那些由 RADR 塑造、告知和指導的項目，現在將有助於塑造未來非常有意義的臨床試驗。基肖爾？

Thank you, Panna. As we accrue clinical data and define the [MTD] in our Phase 1 clinical trial, we are actively pursuing additional areas of R&D that contribute to further successes of LP-184. A general consensus that has emerged from collective experiences in oncology has been that successful treatments are most likely to be based about combination therapeutics rather than monotherapy. With this in mind, we are studying the optimal selection of potential agents to combine with LP-184, which enhance the efficacy of treatment have little, if any, overlapping toxicity as well as expand indications.

謝謝你，潘娜。當我們在 1 期臨床試驗中累積臨床數據並定義 [MTD] 時，我們正在積極尋求其他研發領域，以促進 LP-184 的進一步成功。從腫瘤學的集體經驗中得出的普遍共識是，成功的治療最有可能基於聯合治療而不是單一治療。考慮到這一點，我們正在研究與 LP-184 聯合使用的潛在藥物的最佳選擇，這些藥物可增強治療效果，幾乎沒有（如果有的話）重疊毒性，並擴大適應症。

For the past year, our RADR translation and clinical teams have addressed these immediate needs. Towards fulfilling these rapidly, we have also engaged with several expert collaborators that are shown in this slide that is being displayed, and these include scientists from MD Anderson, UNICEF Massachusetts, Boston, Johns Hopkins and the industry of Texas and (inaudible). Today, I'm going to talk about three distinct LP-184 combinations. Two of which are in accelerated protocol development by the clinical team. I won't have time to show data, but I can mention here that new unique combinations for LP-184 are emerging from both RADR and [bench] studies, the latter including [ISPA] analysis studies.

在過去的一年裡，我們的 RADR 翻譯和臨床團隊已經解決了這些緊迫的需求。為了快速實現這些目標，我們還與幾位專家合作者進行了合作，如這張幻燈片所示，其中包括來自MD 安德森、聯合國兒童基金會馬薩諸塞州、波士頓、約翰霍普金斯大學以及德克薩斯州和德克薩斯州工業界的科學家。（聽不清楚）。今天，我將討論三種不同的 LP-184 組合。其中兩個正在由臨床團隊加速方案開發。我沒有時間展示數據，但我可以在這裡提到，RADR 和 [bench] 研究正在出現 LP-184 的新獨特組合，後者包括 [ISPA] 分析研究。

So a significant aspect of (inaudible) that results from tumor-specific PTGR1 in expression for which now we have a [biosite], which causes a [bioactivation] of LP-184 in tumor cells is that it ends up in the formation of double-strand breaks. When threatened with LP-184, cancer cells, therefore, need to engage multiple repair factors and pathways beyond transcription coupled [necrotide] exceeding repair. (inaudible) Clearly requires the attention of homologous recombination repair pathways. It was, therefore, expected that LP-184 demonstrated synthetic lethality in tumors deficient in such pathways including mutations affecting BRCA1 and BRCA2. Such synthetic lethality of LP-184 extends beyond the classical BRCA-mutated tumors and also includes tumors with [BRCA-ness] such as those with mutations in additional genes involved in the homologous combination pathway. What has been surprising has been the evidence that LP-184 synergizes with PARP inhibitors both in HRD, but also in those HRD tumors that have become PARP inhibitor resistant. This slide shows that (inaudible) lower doses of LP-184 are sufficient to achieve 3 to 14 fold greater regulation compared to Olaparib alone in tumors mutated either in BRCA1 or BRCA2.

因此，（聽不清楚）腫瘤特異性 PTGR1 表達的一個重要方面是，它最終形成了雙鏈斷裂。因此，當受到 LP-184 威脅時，癌細胞需要利用多種修復因子和途徑，超越轉錄偶聯[壞死性物質]的修復。（聽不清楚）顯然需要注意同源重組修復途徑。因此，預計 LP-184 在缺乏此類途徑（包括影響 BRCA1 和 BRCA2 的突變）的腫瘤中表現出合成致死性。LP-184 的這種合成致死性超出了經典的 BRCA 突變腫瘤，還包括具有 [BRCA 性] 的腫瘤，例如在同源組合途徑中涉及的其他基因中具有突變的腫瘤。令人驚訝的是，有證據表明 LP-184 與 PARP 抑制劑在 HRD 以及那些已對 PARP 抑制劑產生抗藥性的 HRD 腫瘤中具有協同作用。這張幻燈片顯示，與單獨使用奧拉帕尼相比，（聽不清楚）較低劑量的 LP-184 足以在 BRCA1 或 BRCA2 突變的腫瘤中實現 3 至 14 倍的調節作用。

I would particularly like to draw your attention to the synergies seen in both tumors with low doses of LP-184, but if you look at the tumor on the right which, as you can see, is resistant to all our (inaudible), it is wiped out by LP-184 at 2 milligrams per kg, and when you combine Olaparib with less than 1/4 of this LP-184 grows, this tumor now loses its refractoriness to PARP inhibitors. The likely success of this potential is further supported by similar data generated by our independent collaborators at [UNICEF] Massachusetts Boston, who also have suggested additional mechanisms involving depletion of RPA as one of the drivers of this synergy. A combination with PARP inhibitors that can make (inaudible) resistant tumors sensitive is, therefore, a significant advantage for LP-184. We are particularly only excited by the potential of such a combination and have developed a protocol to actively test this in our Phase 1b clinical trial arm.

我特別想提請您注意低劑量LP-184 在兩種腫瘤中所見的協同作用，但如果您觀察右側的腫瘤，正如您所看到的，它對我們所有的（聽不清）有抵抗力，它LP-184 以每公斤2 毫克的劑量將其消滅，當您將奧拉帕尼與不到1/4 的LP-184 生長量結合使用時，該腫瘤現在失去了對PARP 抑製劑的抗藥性。我們在馬薩諸塞州波士頓的獨立合作者產生的類似數據進一步支持了這種潛力可能取得的成功，他們也提出了涉及 RPA 耗盡的其他機制，作為這種協同作用的驅動因素之一。因此，與 PARP 抑制劑組合可以使（聽不清楚）抗藥性腫瘤變得敏感，這是 LP-184 的一個顯著優勢。我們對這種組合的潛力感到特別興奮，並製定了一項協議，在我們的 1b 期臨床試驗部門中積極測試這一點。

There are several reasons why LP-184 might be an exceptional combinatorial agent for power inhibitors, which comes from understanding the PARP inhibitor resistant factors. This next slide identifies factors that have been dispersed to be associated with the resistance to power inhibitors. If you specifically look at [road 3], much of our data suggests that LP-184 effectively combats these factors even in the presence of gene conversion, LP-184 has been effective. loss of (inaudible) complex that allows tumors to become resistant to PARP inhibitors actually makes tumor sensitive to LP-184. Additional insights have been the agnostic feature of LP-184 to (inaudible) loss of (inaudible) impairs prolonged (inaudible) arrest upon PARP perimeter exposure, thereby using resistance. But (inaudible) level loss does not affect sensitivity to LP-184, what this means in practical terms is that when using combination with PARP inhibitors, LP-184 is highly indicative, not only for synergy but also for reducing the resistance to PARP inhibitors.

LP-184 可能成為強力抑制劑的特殊組合藥物有多種原因，這源於對 PARP 抑制劑抗藥性因素的了解。下一張投影片確定了與功率抑制劑抵抗力相關的分散因素。如果您專門查看[道路 3]，我們的大部分數據表明，即使存在基因轉換，LP-184 也能有效對抗這些因素，LP-184 一直有效。失去（聽不清楚）複合物使腫瘤對 PARP 抑制劑產生抗藥性，實際上使腫瘤對 LP-184 敏感。額外的見解是 LP-184 的不可知特徵，對（聽不清楚）損失（聽不清楚）損害了 PARP 週邊暴露後的長時間（聽不清楚）逮捕，從而使用阻力。但（聽不清楚）水平下降並不影響對LP-184 的敏感性，這實際上意味著當與PARP 抑制劑聯合使用時，LP-184 具有很強的指示性，不僅可以發揮協同作用，還可以降低對PARP 抑制劑的抗藥性。

The other molecule that we are proposing to the clinic as a combinatorial partner of LP-184 is a drug that has extensive clinical experience, albeit from non-oncology indications. This drug, spironolactone, is an FDA-approved drug used for various indications, including hypertension and acne. What (inaudible) specifically to this drug were multiple observations of which the most important was the serendipitous discovery the spiral electron targets ERCC3 to degrade it. The scientific rationale and reasoning of combining LP-184 with spironolactone, was fully justified by a battery of preclinical studies (inaudible) collaborators conducted. In this slide, in the box A, you can see that spironolactone increases sensitivity of GBM cell lines to LP-184 3 to sixfold. What this specifically means is that even in settings where there is lower bioavailability of LP-184, the combination can result in sustained DNA damage, as you can see in [Panel D] and that these effects correlate with a significant reduction in the repair protein ERCC3 shown in Panel C. Not surprising, therefore, the combination resulted in excellent responses in in vivo glioblastoma models with most cures, only one of five tumors show recurrence to the combination.

我們向臨床建議作為 LP-184 組合夥伴的另一種分子是一種具有豐富臨床經驗的藥物，儘管來自非腫瘤學適應症。這種藥物螺內酯是 FDA 批准的藥物，用於多種適應症，包括高血壓和痤瘡。這種藥物特有的（聽不清楚）是多次觀察，其中最重要的是偶然發現螺旋電子靶向 ERCC3 來降解它。合作者進行的一系列臨床前研究（聽不清楚）充分證明了將 LP-184 與螺內酯結合的科學原理和推理。在這張投影片的 A 框中，您可以看到螺內酯將 GBM 細胞係對 LP-184 的敏感度提高了 3 至 6 倍。這具體意味著，即使在LP-184 生物利用度較低的環境中，該組合也可能導致持續的DNA 損傷，正如您在[圖D]中所看到的，並且這些影響與修復蛋白的顯著減少相關C 組顯示了 ERCC3。

In order to use this combination clinically, we need to better understand the time window where LP-184 should be administered, following spironolactone treatment. So we carried out several [time code] studies. In this slide, we demonstrate that ERCC3 is at its lowest level in both orthotopic and subcutaneous glioblastoma xenograft at eight hours after spironolactone administration dosed as human equivalent of 200 milligrams per [KD]. In addition to glioblastoma, the combination of spironolactone enhances the activity of LP-184 in other select tumor types, including ATRT, pancreatic cancer and renal cancers. Even the rare pediatric orphan disease designation and the lack of any approved therapy for ATRT, we are particularly enthusiastic of the clinical studies in ATRT and are in active discussions with several pediatric neuro-oncology groups, including poetic and children's oncology Group.

為了在臨床上使用這種組合，我們需要更好地了解螺內酯治療後應該施用 LP-184 的時間窗口。因此我們進行了多項[時間碼]研究。在這張幻燈片中，我們證明了在給予相當於人體劑量 200 毫克螺內酯後 8 小時，原位和皮下膠質母細胞瘤異種移植物中 ERCC3 處於最低水平。[KD]。除了膠質母細胞瘤之外，螺內酯的組合還可以增強 LP-184 在其他選定腫瘤類型中的活性，包括 ATRT、胰腺癌和腎癌。即使是罕見的兒科孤兒病指定以及 ATRT 缺乏任何批准的治療方法，我們仍然對 ATRT 的臨床研究特別熱情，並正在與幾個兒科神經腫瘤學小組進行積極的討論，包括詩意和兒童腫瘤學小組。

I will now shift to the third combination we are exploring, which is combining LP-184 with immune checkpoint inhibitors. We have previously observed during our [steady up] DNA strand breaks the accumulation of cytogenic DNA in tumor cells following LP-184 treatment. This feature would suggest LP-184 as an immune activating molecule as well to test the potential of LP-184 combined with checkpoint inhibitors. We've developed a collaboration with [Dr. Lin] at MD Anderson, who has previously shown that the involvement of replication stress detect correlates with immune responsing tumors. (inaudible) could be pharmacologically induced this replication stress response defect and, therefore, extend the benefits of immune checkpoint inhibitors for a wider patient population. We have (inaudible), therefore, that LP-184 treatment might escalate replication stress levels, particularly in [TNBC] and induce replication stress response (inaudible). As you can see in the slide, when LP-184 cells were assessed for induction of replication stress defend compared to a similar effect induced by what would be expected from a [cell cycle] checkpoint inhibitor, the results show a 60% of relative [defect] increase by LP-184 compared to 75% with (inaudible) at equimolar doses. We then tested the effects of a combination of anti-PD-1 antibody in combination with LP-184 in a murine synthetic TNBC model. The results shown in this slide evidence enhancement of tumor growth inhibition from 51% in LP-184 alone detect tumors to 72% in the combination. Additional steady indicate that LP-184 might actually modulate both the pure microenvironment as well as T cell function. Uniquely, it appeared that LP-184 reduces (inaudible).

我現在將轉向我們正在探索的第三種組合，將 LP-184 與免疫檢查點抑制劑結合。我們先前曾觀察到，在 LP-184 治療後，我們的 [穩定] DNA 鏈斷裂，腫瘤細胞中細胞源性 DNA 的累積。這項特徵表明 LP-184 也可以作為免疫活化分子，並測試 LP-184 與檢查點抑制劑聯合的潛力。我們已經與[Dr. MD Anderson 的 Lin] 先前已證明複製壓力檢測的參與與免疫反應腫瘤相關。 （聽不清楚）可以透過藥理學誘導這種複製壓力反應缺陷，因此可以將免疫檢查點抑制劑的益處擴展到更廣泛的患者群體。因此，我們（聽不清楚）認為 LP-184 治療可能會升高複製壓力水平，特別是在 [TNBC] 中，並誘導複製壓力反應（聽不清楚）。正如您在幻燈片中所看到的，當評估 LP-184 細胞複製壓力防禦的誘導與[細胞週期]檢查點抑制劑預期誘導的類似效果相比時，結果顯示 60% 的相對 [與等摩爾劑量（聽不清楚）的75% 相比，LP-184 增加了缺陷]。然後，我們在小鼠合成 TNBC 模型中測試了抗 PD-1 抗體與 LP-184 組合的效果。此投影片中顯示的結果證明，腫瘤生長抑制率從 LP-184 單獨檢測腫瘤時的 51% 增強到組合檢測的 72%。額外的穩定表明 LP-184 實際上可能調節純微環境以及 T 細胞功能。獨特的是，LP-184 似乎減少了（聽不清楚）。

Based upon these results, we are now in discussion with various clinical investigators towards development of a clinical study in TNBC cold tumors. Many other rationally designed combinatorial partners are emerging from our RADR and CRISPR based analysis such as inhibitors of (inaudible) but also include molecules that are outside the (inaudible) and repair pathways, once that pathway and (inaudible) particularly like to mention, which is demand is important, is the (inaudible) pathway, and we hope to share with you in the near future some exciting data business combinations.

基於這些結果，我們現在正在與各個臨床研究人員討論進行 TNBC 冷腫瘤的臨床研究。許多其他合理設計的組合夥伴正在從我們基於RADR 和CRISPR 的分析中出現，例如（聽不清楚）的抑制劑，但也包括（聽不清楚）和修復途徑之外的分子，一旦該途徑和（聽不清楚）特別喜歡提及，其中需求很重要，（聽不清楚）途徑很重要，我們希望在不久的將來與您分享一些令人興奮的數據業務組合。

And now I'll turn it back to Panna.

現在我會把它轉回給潘納。

Sure. Thank you very much. As you can see, we're already turning our attention now to the next phases of clinical development and pathway for our exciting drug LP-184. We know that many of these combinations are with drugs that are a part of the meaningful arsenal in cancer, especially PD-1, anti-PD-1 and [part] and we expect there to be a lot of excitement in the clinical community as there has been so far in the research community, but also very importantly, in the biopharma community, given the number of [PARPS] and their limited range of extended use in some of these tumors and also the same with PD-1. When you have a drug like LP-184 that can widen the therapeutic window and potentially open up new avenues there should be a lot of excitement and potential for partnering opportunity.

當然。非常感謝。正如您所看到的，我們現在已經將注意力轉向令人興奮的藥物 LP-184 的下一階段臨床開發和途徑。我們知道，這些組合中的許多藥物都是癌症治療中有意義的武器庫的一部分，特別是 PD-1、抗 PD-1 和 [部分]，我們預計臨床界會感到非常興奮，因為迄今為止，在研究界，但在生物製藥界也非常重要，因為[PARPS] 的數量及其在某些腫瘤中的擴展使用範圍有限，PD-1 也是如此。當您擁有像 LP-184 這樣的藥物，可以擴大治療窗口並有可能開闢新途徑時，應該會產生許多令人興奮的合作機會和潛力。

Let's now talk a little bit about Webinar Wednesday. We've had a lot of exciting webinars about one a month. For those that have not listened in on the backdrop of these webinars are the details. Our last webinar Wednesday for the year will be held on December 11, not the last Wednesday of November and not the last Wednesday of December, but we know it's a challenging time. So we try to pick right at the middle of the month. That webinar will focus on the power of AI in drug development, specifically around the use of molecular features to predict blood-brain barrier permeability, with RADR. The webinar will discuss also future development plans we have and the potential commercialization and commercial availability of this radar platform module, which leverages extensive molecular feature analysis enrich the proprietary models and proprietary data.

現在我們來談談週三的網路研討會。我們舉辦了很多令人興奮的網路研討會，大約每月一次。對於那些沒有聽過這些網路研討會背景的人來說，可以了解詳細資訊。我們今年最後一次網路研討會星期三將於 12 月 11 日舉行，不是 11 月的最後一個星期三，也不是 12 月的最後一個星期三，但我們知道這是一個充滿挑戰的時刻。所以我們盡量在月中旬挑選。這場網路研討會將重點關注人工智慧在藥物開發中的力量，特別是圍繞使用分子特徵透過 RADR 預測血腦屏障滲透性。這場網路研討會還將討論我們未來的發展計畫以及此雷達平台模組的潛在商業化和商業可用性，該模組利用廣泛的分子特徵分析豐富了專有模型和專有數據。

According to the therapeutic data comments, a coordinated initiative to access and evaluate artificial intelligence capability across therapeutic modalities and across stages of discovery, Lantern's BBB algorithms are five of the top 10 performing algorithms on the leaderboard. So that's very exciting, and that was some of our early algorithms. In fact, they continue to mature and get refined and have actually matured significantly in some of their future discrimination. So we're pretty excited to talk about that on December 11 with one of our data scientists who's been working on those models.

根據治療數據評論（一項旨在跨治療方式和跨發現階段存取和評估人工智慧能力的協調計劃），Lantern 的 BBB 演算法是排行榜上表現最好的 10 種演算法中的 5 個。所以這非常令人興奮，這就是我們早期的一些演算法。事實上，他們在不斷成熟和完善，並且在未來的一些歧視方面實際上已經顯著成熟。因此，我們非常高興能在 12 月 11 日與一位一直致力於這些模型研究的資料科學家討論這個問題。

As you know, 2024 has been a year of progress, accelerated progress where our insights are impacting patients in their journey to fight cancer and also influencing the development decisions and progress -- actually of other cancer companies. Our collective efforts and dedication have fostered a transformational shift for our company, setting us on an exciting trajectory towards the future, where we are improving the lives of cancer patients with affected and affordable treatment options. As you can see, the work being done by Kishor and his team and also our clinical operations team is focused on meticulous execution, but constantly with one hand on the wheel of innovation. During the fourth quarter and into next year, we will have several clinical readouts and milestones to share with our investors as we advance our pipeline and company.

如您所知，2024 年是進步的一年，進步加速，我們的見解不僅影響患者對抗癌症的旅程，也影響其他癌症公司的開發決策和進展。我們的集體努力和奉獻精神促進了我們公司的轉型轉變，使我們走上了通往未來的令人興奮的軌道，我們正在透過受影響且負擔得起的治療方案來改善癌症患者的生活。正如您所看到的，Kishor 和他的團隊以及我們的臨床營運團隊所做的工作專注於一絲不苟的執行，但不斷地用一隻手推動創新。在第四季度和明年，隨著我們推進我們的產品線和公司，我們將有幾個臨床數據和里程碑與我們的投資者分享。

As I've said before, the golden age of AI in medicine is just beginning and it is being powered by large-scale, highly available computing power, massive data storage, massive data collaborations and it is being said by health care patients and cancer data, which is more widely available and at increasing levels of quality much more so than ever before. Companies that harness these capabilities in the biotech and biopharma arena, will be long-term leaders in this biotech are really now becoming more tech bio industry, and we think these are companies that are well poised to create massive value for patients long term and ultimately for investors in our industry.

正如我之前所說，醫學人工智慧的黃金時代才剛剛開始，它的動力來自於大規模、高可用的計算能力、海量數據存儲、海量數據協作，醫療保健患者和癌症患者都在這麼說。的可用性比以往任何時候都更加廣泛，而且品質水準也不斷提高。在生物技術和生物製藥領域利用這些能力的公司將成為該生物技術領域的長期領導者，現在確實正在變得更加科技化的生物行業，我們認為這些公司已經準備好為患者長期並最終創造巨大的價值對於我們行業的投資者來說。

I'd like to take a moment right now to personally thank our team for helping to prepare us for these calls, to prepare the materials, gather the data, provide insight and to their amazing dedication. If it wasn't for them, we probably would have a very handicap call.

我現在想花點時間親自感謝我們的團隊幫助我們為這些電話會議做好準備、準備材料、收集數據、提供見解以及他們驚人的奉獻精神。如果沒有他們，我們可能會遇到一個非常困難的情況。

So with that, I'd like to now open the call to any questions or clarifications.

因此，我現在想打開電話詢問任何問題或澄清。

(Instructions)

（指示）

Yes. I'll go ahead and answer the first question. The first question asked is, one, do we expect additional data regarding our HARMONIC and LP-300 trial?

是的。我繼續回答第一個問題。第一個問題是，我們是否期望獲得更多有關 HARMONIC 和 LP-300 試驗的數據？

As we just opened up the sites in Asia, our goal is to gather another 14 to 28 patients actively, and for HARMONIC, we'll know a lot more once we see the impact of the trial expansion in Asia and also the data from the planned interim analysis, which will take place at 31 patients. So those two events will really guide us in terms of the next big clinical readout regarding the HARMONIC trial, and we expect that around mid of next year, if not earlier, but middle of next year is when we're expecting it.

由於我們剛剛在亞洲開設了站點，我們的目標是積極收集另外 14 至 28 名患者，對於 HARMONIC 來說，一旦我們看到亞洲試驗擴展的影響以及來自亞洲的數據，我們就會了解更多。對31 名患者進行中期分析。因此，這兩件事將真正指導我們關於 HARMONIC 試驗的下一個大型臨床結果，我們預計會在明年中旬左右（如果不是更早的話），但明年中旬就是我們所期待的。

Next question. Any updates on how RADR is growing and collaboration efforts?

下一個問題。有關 RADR 如何發展和合作的最新消息？

As you know, we announced last quarter our collaboration with Oregon Therapeutics, which is going very well. We expect the first phase of that collaboration to finalize some time during the next month probably before the end of the year where we will be able to answer several questions and set the framework for some good joint IP in regards to indications and perhaps biomarker signatures that correlate to response for their drug -- for their PDI inhibitor. We are looking at additional collaborations. As you know, we've had three very important ones with emerging biopharma companies. We're now focused on larger biotech companies. I would say, more mid-market and more -- ones with much more diverse portfolio. So our attention now is increasing to larger companies given that the platform has matured quite a bit over the last 1.5 years.

如您所知，我們上季度宣布了與 Oregon Therapeutics 的合作，進展非常順利。我們預計該合作的第一階段將在下個月的某個時間（可能是今年年底之前）完成，屆時我們將能夠回答幾個問題，並為一些良好的聯合知識產權制定框架，涉及適應症和生物標誌物簽名，與他們的藥物（PDI 抑制劑）的反應相關。我們正在考慮更多的合作。如您所知，我們與新興生物製藥公司達成了三個非常重要的協議。我們現在專注於更大的生物技術公司。我想說的是，更多的中端市場以及更多的產品組合更加多樣化。因此，鑑於該平台在過去 1.5 年中已經相當成熟，我們現在越來越關注大公司。

I'll take the next question coming in the Q&A panel. Can we speak to any partnership interest?

我將回答問答面板中的下一個問題。我們可以談談任何合作夥伴利益嗎？

Although it's probably too early to speak to partnership interest for the never smoker trial. We have gotten some conversation started. Obviously, this is, as I mentioned, from a epidemiological basis, never smokers account for 33% to 40-plus percent of non-small cell lung cancer cases in East Asia, again, primarily Japan, Taiwan and South Korea, many of the major regions in China are similar. But so you can expect that we're in discussions with larger pharma companies in Japan now. So that's very early, but we are receiving interest given the focus and given the prevalence of the disease there.

儘管現在談論合作夥伴對從不吸煙者試驗的興趣可能還為時過早。我們已經開始了一些對話。顯然，正如我所提到的，從流行病學的角度來看，東亞非小細胞肺癌病例中從不吸煙者佔 33% 至 40% 以上，同樣，主要是日本、台灣和韓國，許多國家中國的主要地區都是相似的。但你可以預料到我們現在正在與日本較大的製藥公司進行討論。所以現在還為時過早，但考慮到人們的關注焦點以及該地區疾病的流行情況，我們正在引起人們的興趣。

The other thing that I'd like to add is, obviously, we did hint at a biomarker signature correlating to lower intermediate tumor mutation burden. Now we're obviously chasing that down clinically. We've had very good initial data. We're looking to support this data as more patients get enrolled and we understand the tumor mutation burden status of those patients, and that also could mark a very important turning point in terms of interest with all the companies that are going after high tumor mutation burden, whereas this is for lower human mutation burden.

我想補充的另一件事是，顯然，我們確實暗示了與較低的中間腫瘤突變負擔相關的生物標記特徵。現在我們顯然正在臨床上追尋這一點。我們已經有了非常好的初始數據。隨著越來越多的患者入組，我們希望支持這一數據，並且我們了解這些患者的腫瘤突變負擔狀態，這也可能標誌著所有追求高腫瘤突變的公司的興趣的一個非常重要的轉折點負擔，而這是為了降低人類突變負擔。

Next question is on Starlight Therapeutics and the scientific advisory board members.

下一個問題是關於星光療法和科學顧問委員會成員的。

We're quite thrilled about the decisions for Dr. DeAngelis, Berger, Laterra and Grossman to join the Scientific and Clinical Advisory Board, and these guys are among the most preeminent in their field, and for them to be interested in the drug and the indications, again, speaks volumes. [If we] think of the potential for this very novel site-activated alkylating agent to potentially transform the lives of both pediatric and adult brain cancer patients.

我們對 DeAngelis 博士、Berger、Laterra 和 Grossman 博士加入科學和臨床諮詢委員會的決定感到非常興奮，這些人是他們領域中最傑出的人之一，他們對藥物和藥物感興趣跡象再次說明了一切。 [如果我們]想到這種非常新穎的位點活化烷化劑有可能改變兒童和成人腦癌患者的生活。

In my personal feeling, and this is very important, is that we're making progress each quarter. We're opening up sites, we're enrolling patients, we think the biotech market is fundamentally getting stronger. I think there'll be a lot of interest we've had in both private and public financing, and we'll find the best route to capitalize Starlight independently, so it can grow and develop its own trials. We believe that the trials for IB and II or for some other unique trials should be launched sometime in early 2025 for Starlight. But in the meantime, we try to maintain a lot of fiscal discipline, and again, those are planned trials. We'll see how the financing events go, and we try to use a lot of the existing lantern infrastructure and people to advance Starlight in parallel. So there's a lot of work for our team, and again, this work creates a lot of value for our investors long term. But we think this could be one of several planned spinouts from Lantern where the portfolio is more focused. The portfolio is in a certain modality and is aimed at a certain group of cancers or in a certain population.

以我個人的感覺，這一點非常重要，那就是我們每季都在進步。我們正在開放網站，我們正在招募患者，我們認為生物技術市場正在從根本上變得更加強大。我認為我們對私人和公共融資都會有很大的興趣，我們會找到獨立利用星光的最佳途徑，這樣它就可以發展和發展自己的試驗。我們認為，IB 和 II 的試驗或其他一些獨特的試驗應該在 2025 年初的某個時候針對 Starlight 啟動。但同時，我們努力維持大量的財務紀律，而且這些都是有計畫的試驗。我們將看看融資活動進展如何，我們將嘗試利用大量現有的彩燈基礎設施和人員來並行推進星光計畫。因此，我們的團隊有很多工作要做，而且這項工作為我們的投資者長期創造了很多價值。但我們認為這可能是 Lantern 計劃中的幾個分拆項目之一，其投資組合更加集中。該產品組合採用某種形式，針對特定的癌症組或特定人群。

Well with that, we're coming up against about an hour, 50 minutes into the call, long call today, but I want to thank everyone. We got a good overview of what's next in the combination trials. Again, we're very far into the Phase 1a for LP-184, where we expect to get to an MTD in the next two cohorts, and that should correlate with what we believe is going to be something we can go into future plan to Phase 1b and Phase 2 planned trials with as well, and we continue to make very solid progress with our AI platform, both with our collaborators and internally with new functionality, and we now will be expanding rapidly into Asia with our LP-300 trial.

好吧，今天的通話時間長達一小時 50 分鐘，時間很長，但我要感謝大家。我們對聯合試驗的下一步進行了很好的了解。同樣，我們已經進入 LP-184 的 1a 階段，我們預計在接下來的兩個隊列中達到 MTD，這應該與我們認為可以納入未來計劃的內容相關。 AI 平台將繼續與我們的合作者以及內部新功能取得非常紮實的進展，現在我們將透過LP-300 試驗迅速擴展到亞洲。

Very importantly, as David pointed out, we continue to be very meticulous about execution and cost conscious. We do think that our existing capital and balance sheet allows us to take us through significant events, but we're watching the markets carefully if there's opportunities to partner our assets out or to access the capital markets will do so if it makes sense, but we're also very prepared to continue executing, and at the same time, we do think the markets will probably improve. But more importantly, we'll have opportunities to partner our assets and leverage our capabilities.

非常重要的是，正如大衛指出的那樣，我們在執行和成本意識方面仍然非常細緻。我們確實認為我們現有的資本和資產負債表使我們能夠帶領我們度過重大事件，但我們正在仔細觀察市場，如果有機會與我們的資產合作或進入資本市場，如果有意義的話，我們會這樣做做，但是我們也非常準備繼續執行，同時我們確實認為市場可能會改善。但更重要的是，我們將有機會合作我們的資產並利用我們的能力。

Internally, operationally, which is very important, we've begun to slowly bring in but vary step-by-step, aspects of clinical operations to try to build really a world-class [Ninja] team in clinical operations that we can use across our trials and [across] the various functions, and we think that gives us a lot of synergy, reduces our external spend. But as David pointed out, brings us closer in contact with our patients, our clinical sites and our data. So again, I think we're doing the right things operationally and are very focused on maintaining kind of the burn rate in the same range that we have historically.

在內部，在營運上，這一點非常重要，我們已經開始慢慢引入但逐步改變臨床操作的各個方面，以嘗試在臨床操作中建立真正世界一流的[忍者]團隊，我們可以在各個方面使用它我們的試驗和[跨]各個職能，我們認為這為我們帶來了很多協同作用，減少了我們的外部支出。但正如 David 指出的那樣，這讓我們與患者、臨床站點和數據的連結更加緊密。再說一次，我認為我們在營運上做了正確的事情，並且非常注重將燃燒率維持在我們歷史上的同一範圍內。

So with that, I'd like to thank everyone for their time today, and I want to express my deep gratitude to our team, for our partners and our stakeholders for their support, and also to realize that together, we are really trying to light the way for a brighter, more scalable future in oncology care and oncology drug development. So thank you very much for joining us at the forefront of a new era for drug discovery and joining our -- listening to our team that we believe is bringing us to that [new] era. Thank you.

因此，我要感謝大家今天抽出時間，對我們的團隊、我們的合作夥伴和利益相關者的支持表示深深的感謝，同時也讓我們認識到，我們真的在共同努力為腫瘤治療和腫瘤藥物開發創造更光明、更可擴展的未來指明道路。因此，非常感謝您加入我們，走在藥物發現新時代的最前沿，並加入我們的團隊——聆聽我們的團隊的聲音，我們相信他們正在將我們帶入那個[新]時代。謝謝。

Thank you.

謝謝。