Lantern Pharma Inc (LTRN) 2022 Q4 法說會逐字稿

Good afternoon, everyone. I'm Nicole Leber with Investor Relations here at Lantern Pharma, and welcome to our fourth-quarter and full-year 2022 earnings call. I will be your host for today's call.

大家下午好。我是 Lantern Pharma 投資者關係部的 Nicole Leber，歡迎參加我們的 2022 年第四季度和全年財報電話會議。我將擔任今天電話會議的主持人。

As a reminder, this call is being recorded and all attendees are in a listen-only mode. We will open up the call for questions and answers after management's presentation. A webcast replay of today's conference call will be available on our website at lanternpharma.com after the call.

提醒一下，此通話正在錄音，所有與會者均處於僅聽模式。在管理層演講後，我們將開放問答徵集。電話會議結束後，我們將在我們的網站 Lanternpharma.com 上提供今天電話會議的網絡直播重播。

We issued a press release after market close today summarizing our financial results and progress across the company for the fourth quarter and full year of 2022. A copy of this release is available through our website at lanternpharma.com, where you will also find a link to the slides that management will be referencing on today's call.

今天收盤後，我們發布了一份新聞稿，總結了 2022 年第四季度和全年的財務業績和整個公司的進展。此新聞稿的副本可通過我們的網站 Lanternpharma.com 獲取，您還可以在其中找到鏈接管理層將在今天的電話會議上參考的幻燈片。

I 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 the impact of the COVID-19 pandemic, results of clinical trials, and the impact of competition.

我想提醒大家，有關未來預期、業績、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 警告說，這些前瞻性陳述受到可能導致實際結果與預期結果存在重大差異的風險和不確定性。許多因素可能導致實際結果與前瞻性陳述所示的結果存在重大差異，包括 COVID-19 大流行的影響、臨床試驗的結果以及競爭的影響。

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, 2022, which is on file with the SEC and available on our website.

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 2022 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。

Forward-looking statements made on this conference call are as of today, Monday, March 20, 2023, 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. The webcast replay of the conference call and webinar will be available on Lantern's website.

本次電話會議中做出的前瞻性陳述截至今天，即 2023 年 3 月 20 日星期一，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。電話會議和網絡研討會的網絡直播重播將在 Lantern 網站上提供。

On today's webcast, we have Lantern Pharma CEO, Panna Sharma; CFO, David Margrave; and CSO, Kishor Bhatia. Panna will start things off with an overview of Lantern's strategy and business model and highlight recent achievements in our operations. After which, David will discuss our financial results, which will be followed by Dr. Bhatia, who will provide a brief update on our development programs and upcoming webinars. This will be followed by some concluding comments from Panna, and then we'll open up the call for Q&A.

在今天的網絡廣播中，我們有 Lantern Pharma 首席執行官 Panna Sharma；首席財務官大衛·馬格雷夫；首席戰略官 Kishor Bhatia。 Panna 將首先概述 Lantern 的戰略和商業模式，並重點介紹我們最近在運營中取得的成就。之後，大衛將討論我們的財務業績，隨後巴蒂亞博士將簡要介紹我們的發展計劃和即將舉行的網絡研討會的最新情況。接下來是 Panna 的一些總結性評論，然後我們將開始問答環節。

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 總裁兼首席執行官 Panna Sharma。潘娜，請繼續。

Thank you, Nicole. Good afternoon, everyone, and welcome to our fourth-quarter 2022 earnings call and company update. Thank you for joining us this afternoon to hear about our fourth quarter and year-end results and also our corporate progress of Lantern Pharma.

謝謝你，妮可。大家下午好，歡迎參加我們的 2022 年第四季度財報電話會議和公司最新動態。感謝您今天下午加入我們，了解我們第四季度和年終的業績以及藍騰醫藥的企業進展。

Lantern Pharma is at the leading edge of leveraging artificial intelligence, machine learning algorithms, biomarker, clinical, genomic, and drug response data to transform the costs, compress the timelines, and derisk oncology drug discovery and development. During 2022, our team was extremely focused on taking these insights and driving them to meaningful clinical programs that will be launched this year with our new first in-human clinical -- with our first in-human drug candidates, LP-184 and LP-284.

Lantern Pharma 在利用人工智能、機器學習算法、生物標誌物、臨床、基因組和藥物反應數據來降低成本、壓縮時間並降低腫瘤藥物發現和開發風險方面處於領先地位。 2022 年，我們的團隊非常專注於獲取這些見解，並將其推動到有意義的臨床項目中，這些項目將於今年推出，我們將推出新的首個人體臨床試驗——我們的第一個人體候選藥物 LP-184 和 LP- 284.

We've done this at a fraction of the time of traditional drug development approaches. This is really also the future of drug development, specifically in cancer where there's so much data available and that data can be used to accelerate programs, derisk the identification of patients who will respond to the drug or diseases that will best benefit from the therapy, and progress those potentially life-changing medicines with reduced cost and reduced time.

我們只用了傳統藥物開發方法的一小部分時間就完成了這一任務。這實際上也是藥物開發的未來，特別是在癌症領域，有大量可用數據，這些數據可用於加速項目，避免識別對藥物有反應的患者或最能從治療中受益的疾病，並以降低成本和縮短時間來開發那些可能改變生命的藥物。

Our model both works for transforming early-stage discovery and development, where we've been able to develop many new indications in a fraction of the time, literally less than two years for many indications, most of those in parallel. And it also helps with sharpening later-stage clinical trials where we believe by focusing on fewer more select patients, those patients that are more likely to respond, we can significantly save time and money in later-stage trials. Our platform is focused on being able to accomplish both.

我們的模型既適用於改變早期發現和開發，我們已經能夠在很短的時間內開發出許多新的適應症，對於許多適應症來說，實際上不到兩年，其中大多數是並行的。它還有助於加強後期臨床試驗，我們相信，通過關注更少的更多精選患者，那些更有可能做出反應的患者，我們可以在後期試驗中顯著節省時間和金錢。我們的平台致力於實現這兩點。

At the same time, our team has been advancing the clinical foundation and infrastructure for our Phase 2 Harmonic clinical trial for never smokers with non-small cell lung cancer. And this has been a very important endeavor and we strengthened our clinical operations team with some select and highly experienced colleagues that have joined us to help scale up the program. We now have activated over five clinical trial sites across 12 different locations and centers in the US, including Ohio, Illinois, New York, Texas, and California.

與此同時，我們的團隊一直在推進針對患有非小細胞肺癌的從不吸煙者的 2 期 Harmonic 臨床試驗的臨床基礎和基礎設施。這是一項非常重要的努力，我們通過一些精選的、經驗豐富的同事加強了我們的臨床運營團隊，他們加入我們，幫助擴大該項目的規模。目前，我們已在美國 12 個不同地點和中心啟動了超過 5 個臨床試驗中心，包括俄亥俄州、伊利諾伊州、紐約州、德克薩斯州和加利福尼亞州。

Across the five clinical trial sites, there's already one consented patient that is anticipated to be dosed later this month and also 14 additional patients -- potential patients that are being pre-screened and are being monitored for possible enrollment. Multiple additional trial sites across the US are expected to be activated in the first half of 2023 and will bolster patient recruitment and enrollment.

在五個臨床試驗中心，已經有一名同意的患者預計將於本月晚些時候接受給藥，還有另外 14 名患者——正在接受預篩选和監測可能入組的潛在患者。美國各地的多個額外試驗地點預計將於 2023 年上半年啟動，並將促進患者招募和入組。

In the US, there are approximately 20,000 to 30,000 never smokers with non-small cell lung cancer diagnosed annually, representing an estimated annual market potential just in the US of $1.5 billion to $2 billion. This opportunity has been developed by understanding why certain molecular profiles in non-small cell lung cancer, those largely associated with never smokers, and those are very low tumor mutation burden and targeted mutations, large, and the tyrosine kinase pathways are responsive to our drug, LP-300, when used in combination with the current chemotherapy standard of care. This effort without the use of large-scale data and modeling would have really continued to stay on the shelf.

在美國，每年約有 20,000 至 30,000 名從不吸煙者被診斷出患有非小細胞肺癌，僅美國一年的市場潛力估計就達 15 億至 20 億美元。這個機會是通過了解為什麼非小細胞肺癌中的某些分子譜（這些分子譜主要與從不吸煙者相關）以及這些分子譜的腫瘤突變負擔非常低和靶向突變大而開發的，並且酪氨酸激酶途徑對我們的藥物有反應, LP-300，與當前化療標準治療聯合使用。如果不使用大規模數據和建模，這項工作實際上將繼續擱置。

We're also using this transformative data-driven approach for our proprietary RADR AI platform. Our platform uncover significant opportunities in cancer, opportunities that are either underserved, unmet, or often overlooked. We do this with tremendous accuracy. Our prediction success is 80% to 90%. And that's because not only the data points, but also because we're relying on over 200 advanced machine learning algorithms. We've used this to both advance and rescue compounds, bringing them into Phase 2 clinical trials, and also to develop entirely new drug candidates for first-in-human trials, many that will be launching in the coming months. And again, we're doing this at a fraction of the cost and timeline, and Dave will discuss some of our financials later today. Also, Kishor will talk about the progress on our exciting new molecules and how they are entering the clinic in the next few months and quarters.

我們還將這種變革性的數據驅動方法用於我們專有的 RADR AI 平台。我們的平台揭示了癌症領域的重大機會，這些機會要么服務不足、未得到滿足，要么經常被忽視。我們以極高的準確性做到這一點。我們的預測成功率為 80% 到 90%。這不僅是因為數據點，還因為我們依賴 200 多種先進的機器學習算法。我們用它來推進和​​拯救化合物，將它們帶入二期臨床試驗，並開髮用於首次人體試驗的全新候選藥物，其中許多將在未來幾個月內推出。再說一遍，我們的成本和時間表只是一小部分，戴夫將在今天晚些時候討論我們的一些財務狀況。此外，基肖爾還將談論我們令人興奮的新分子的進展以及它們如何在未來幾個月和幾個季度進入臨床。

Our unique AI platform, as I mentioned, is served by over 25 billion data points and nearly 200 algorithms that can help us understand, predict, and model questions that are fundamental to oncology drug development. Our goals for our platform this year, we expect that it will reach over 50 billion data points, and we expect it to enhance functionality in three major areas. One, better predictive model combination regimens of small molecules with certain antibody classes, anti-cancer antibodies, at least; the ability to understand and develop ADCs, antibody drug conjugates, at a fraction of the current cost; and third, develop highly specific targeted predictions of key safety features of the compound and predict blood-brain barrier permeability of those compounds. And we're already pretty far along the process of generating algorithms that we believe are not only best-in-class, but probably will be some of the best BBB algorithms out there.

正如我所提到的，我們獨特的人工智能平台由超過 250 億個數據點和近 200 種算法提供服務，可以幫助我們理解、預測和建模對於腫瘤藥物開發至關重要的問題。我們今年平台的目標是，我們預計它將達到超過 500 億個數據點，並且我們預計它將增強三個主要領域的功能。一、小分子與某些抗體類別（至少是抗癌抗體）的更好預測模型組合方案；能夠以當前成本的一小部分來理解和開發 ADC、抗體藥物偶聯物；第三，對化合物的關鍵安全特性進行高度特異性的針對性預測，並預測這些化合物的血腦屏障滲透性。我們在生成算法的過程中已經取得了很大進展，我們相信這些算法不僅是同類最佳的，而且可能會成為最好的 BBB 算法。

And talking about our new clinical trials, the first in-human trials will be with drug candidates LP-184 and LP-284. We believe that both molecules can be synthetically lethal in certain cancers, LP-184 largely in solid tumors, while LP-284 is directed at a range of blood cancers. The compression of costs and timeline that we are creating with our drug development process have allowed us to grow our portfolio from three programs about 30 months ago to 12 programs today.

說到我們的新臨床試驗，第一個人體試驗將是候選藥物 LP-184 和 LP-284。我們相信，這兩種分子在某些癌症中都具有綜合致死性，LP-184 主要針對實體瘤，而 LP-284 針對一系列血癌。我們通過藥物開發流程壓縮成本並縮短時間，使我們的產品組合從大約 30 個月前的 3 個項目增加到今天的 12 個項目。

We expect that many of these programs to create high-value opportunities for our investors and potentially life-transforming therapies for cancer patients. Several of these programs, we have brought together in a very exciting, new, wholly owned subsidiary called Starlight Therapeutics.

我們期望其中許多項目能夠為我們的投資者創造高價值的機會，並為癌症患者創造潛在的改變生命的治療方法。我們將其中的幾個項目集中在一個非常令人興奮的新全資子公司 Starlight Therapeutics 中。

The programs being developed by Starlight were born from the analysis of billions of oncology-focused data points and by using Lantern's AI platform, RADR. STAR-001 is a powerful antitumor mechanism, synthetic lethality, coupled with the collaborations that we've done with internationally recognized institutions, including Hopkins and Greehey Children's Cancer Center at UT Health, San Antonio, make it well positioned to rapidly advance these CNS-focused therapies in a targeted and efficient clinical development pathway.

Starlight 正在開發的程序是通過對數十億個腫瘤學數據點的分析並使用 Lantern 的人工智能平台 RADR 誕生的。 STAR-001 是一種強大的抗腫瘤機制，具有綜合致死性，再加上我們與國際知名機構（包括聖安東尼奧 UT Health 的霍普金斯大學和 Greehey 兒童癌症中心）的合作，使其處於有利地位，能夠快速推進這些 CNS-將治療集中在有針對性和有效的臨床開發途徑中。

Starlight intends to pursue human clinical trials for multiple CNS indications. Again, we've gone from one to now seven indications quite rapidly starting in late 2023. It will build upon the prior IND-enabling studies and the upcoming Phase 1A clinical testing that would be conducted by Lantern. The clinical development of STAR-001 in CNS cancers beyond the Phase 1A trial will be conducted exclusively by Starlight.

Starlight 打算針對多種中樞神經系統適應症進行人體臨床試驗。同樣，從 2023 年底開始，我們很快就從一個適應症發展到了現在的七個適應症。它將建立在之前的 IND 啟用研究和即將由 Lantern 進行的 1A 期臨床測試的基礎上。 1A 期試驗之後的 STAR-001 在 CNS 癌症中的臨床開發將由 Starlight 獨家進行。

Following the launch of Starlight, Lantern will continue to advance LP-184 in clinical development for non-CNS indications. Indications such as pancreatic where we've partnered with Fox Chase Cancer Center, bladder cancer, triple-negative breast cancer, and other solid tumors that have DDR deficiencies. We'll also continue to provide AI bioinformatic and computational biology support to Starlight.

繼 Starlight 上市後，Lantern 將繼續推進 LP-184 的非 CNS 適應症臨床開發。我們與 Fox Chase 癌症中心合作的適應症包括胰腺癌、膀胱癌、三陰性乳腺癌以及其他具有 DDR 缺陷的實體瘤。我們還將繼續為星光提供人工智能生物信息和計算生物學支持。

The formation of Starlight as a wholly-owned subsidiary allows Lantern to sharpen the focus on advancing STAR-001 through targeted clinical trials and dedicate increased time, resources, and personnel to progress what we think is one of the most promising drug candidates for CNS cancer patients in decades. We believe that by focusing our efforts via Starlight Therapeutics, we can accelerate and deepen our commitment to the CNS cancer patient community, while also creating the potential for meaningful additional upside for our investors. We'll always be looking for additional opportunities with the development, needs, and unique focus of certain programs or assets can be separated and developed in a focused manner.

Starlight 作為全資子公司的成立使 Lantern 能夠更加專注於通過有針對性的臨床試驗推進 STAR-001，並投入更多的時間、資源和人員來開發我們認為最有前途的中樞神經系統癌症候選藥物之一幾十年來的病人。我們相信，通過星光療法的集中努力，我們可以加速和深化我們對中樞神經系統癌症患者社區的承諾，同時也為我們的投資者創造有意義的額外收益的潛力。我們將始終尋找額外的機會，某些項目或資產的開發、需求和獨特重點可以分開並以集中的方式開發。

Our collaborative portfolio also continues to grow. In addition to our work with Actuate, we started a collaboration earlier this year with TTC Oncology. They're an emerging biotech focused on breast cancer. They have a best-in-class management team and they have a really exciting drug called TTC-352 that's focused on certain unmet needs in ER-positive breast cancer patients. And as we develop our collaboration, we may have the ability to get an exclusive right to license the drug and a collaborative intellectual property to then develop it. This is a real case of where the platform is the currency, and you'll hear more about this program and this collaboration in the coming quarters as it develops.

我們的合作組合也在不斷增長。除了與 Actuate 的合作外，我們還在今年早些時候開始與 TTC Oncology 合作。它們是一種專注於乳腺癌的新興生物技術。他們擁有一流的管理團隊，並且擁有一種名為 TTC-352 的真正令人興奮的藥物，該藥物專注於 ER 陽性乳腺癌患者的某些未滿足的需求。隨著我們開展合作，我們可能有能力獲得該藥物的獨家許可權和合作知識產權，然後進行開發。這是一個以平台為貨幣的真實案例，隨著該計劃的發展，您將在未來幾個季度聽到更多有關該計劃和合作的信息。

Lantern Pharma has entered now in a major period of transformation itself. As we evolve and mature, many of our initial AI-driven insights advanced them to drug candidates into human clinical trials. We're continuing to make significant meaningful progress in terms of the observations and insights generated by our platform, validated in the labs, into advancements for cancer patients and potentially breakthrough high-value clinical programs.

元宵藥業目前已進入重大轉型時期。隨著我們的發展和成熟，我們許多最初的人工智能驅動的見解將它們推進到候選藥物進入人體臨床試驗。我們將繼續在我們的平台產生的觀察和見解方面取得重大、有意義的進展，並在實驗室中得到驗證，從而為癌症患者帶來進步，並可能實現突破性的高價值臨床項目。

Our programs both at Lantern and Starlight span in multiple highly attractive indications and have been developed at a level of cash burn and resourcing that is almost unheard of in this space that has been driven by our growing AI platform. We expect many of these programs, we partner with larger biopharma companies as they develop.

我們在 Lantern 和 Starlight 的項目涵蓋了多個極具吸引力的適應症，並且開發的現金消耗和資源水平在這個由我們不斷發展的人工智能平台驅動的領域幾乎是聞所未聞的。我們預計會有許多這樣的項目，我們會與較大的生物製藥公司合作開發它們。

And continuing our focus on providing insight, transparency, and also educating the market through webinars, we'll be hosting a KOL webinar on synthetic lethality, key mechanism of Lantern's drug candidates, LP-100, -184, and -284. That webinar will be tomorrow, Tuesday. The webinar will feature an internationally recognized expert in synthetic lethality, Zoltan Szallasi. He's an MD, who serves joint appointments both as a principal investigator at the Danish Cancer Research Center, which is one of our collaborative sites, and as an Assistant Professor of Pediatrics at Boston Children's Hospital, a Harvard Medical School affiliate. Additional details with the KOL webinar can be found on our website and a link has also been provided in our earnings release and slides.

我們將繼續專注於提供洞察力、透明度，並通過網絡研討會教育市場，我們將舉辦一場關於合成致死性、Lantern 候選藥物 LP-100、-184 和 -284 的關鍵機制的 KOL 網絡研討會。該網絡研討會將於明天星期二舉行。該網絡研討會將邀請國際公認的合成殺傷專家 Zoltan Szallasi 出席。他是一名醫學博士，同時擔任丹麥癌症研究中心（我們的合作地點之一）的首席研究員，以及哈佛醫學院附屬機構波士頓兒童醫院的兒科助理教授。有關 KOL 網絡研討會的更多詳細信息，請訪問我們的網站，我們的收益發布和幻燈片中也提供了鏈接。

We expect to follow up on this webinar with another additional webinar and synthetic lethality, specifically in terms of what the programs are for 184 and the implications for both mono and combination therapy. This will be led by our own Dr. Kishor Bathia, our Chief Scientific Officer, in late April.

我們希望在本次網絡研討會之後再舉辦另一場關於綜合致死性的網絡研討會，特別是針對 184 的計劃以及對單一療法和聯合療法的影響。該工作將於 4 月底由我們的首席科學官 Kishor Bathia 博士領導。

With that overview, I'll now turn the call over to our CFO, David Margrave, to provide overview of our fourth-quarter and year-end results, and also walk you through some basic housekeeping items. David?

有了這個概述，我現在將把電話轉給我們的首席財務官 David Margrave，他會概述我們第四季度和年終的業績，並引導您完成一些基本的內務管理項目。大衛？

Thank you, Panna, and good afternoon, everyone. I will now share some financial highlights from our fourth quarter and the full year ended December 31, 2022. I'll start with a review of the fourth quarter.

謝謝潘納，大家下午好。現在，我將分享第四季度和截至 2022 年 12 月 31 日的全年的一些財務亮點。我將首先回顧第四季度。

Our R&D expenses were $2.3 million for the fourth quarter of 2022, up slightly from $2.2 million in the fourth quarter of 2021. General and administrative expenses were $1.6 million for the fourth quarter of 2022, up slightly from $1.4 million in the prior year period. We recorded a net loss of 3.4 million for the fourth quarter of 2022 or $0.31 per share compared to a net loss of $3.5 million or $0.31 per share for the fourth quarter of 2021.

2022 年第四季度我們的研發費用為 230 萬美元，略高於 2021 年第四季度的 220 萬美元。2022 年第四季度的一般和管理費用為 160 萬美元，略高於去年同期的 140 萬美元。我們的 2022 年第四季度淨虧損為 340 萬美元，即每股 0.31 美元，而 2021 年第四季度的淨虧損為 350 萬美元，即每股 0.31 美元。

For the full year of 2022, our R&D expenses were $8.6 million, up from $7.6 million for 2021. This increase was primarily attributable to increases in research studies, increases in consulting expenses, and increases in R&D payroll expenses. Specifically for the full-year 2022, our spend on research studies increased by approximately $1.5 million, consulting expenses increased approximately $0.2 million, and R&D payroll expenses were up approximately $0.1 million. These increases were partially offset by decreases in product candidate manufacturing-related expenses of approximately $0.2 million, decreases in licensing fees of approximately $0.1 million, and a net decline in payments to Allarity Therapeutics of approximately $0.5 million.

2022 年全年，我們的研發費用為 860 萬美元，高於 2021 年的 760 萬美元。這一增長主要歸因於研究的增加、諮詢費用的增加以及研發工資費用的增加。具體而言，2022 年全年，我們的研究支出增加了約 150 萬美元，諮詢費用增加了約 20 萬美元，研發工資支出增加了約 10 萬美元。這些增長被候選產品製造相關費用減少約 20 萬美元、許可費用減少約 10 萬美元以及支付給 Allarity Therapeutics 的款項淨減少約 50 萬美元所部分抵消。

During the year ended December 31, 2021, we made a one-time $1 million upfront payment to Allarity Therapeutics to take the rights to LP-100 back into our control, which we are now looking at combining with PARP inhibitors in a combination program aimed at cancers with homologous repair deficiency or HRD cancers. During the year ended December 31, 2022, we released an escrow payment of approximately $459,000 to Allarity Therapeutics.

截至 2021 年 12 月 31 日的年度，我們向 Allarity Therapeutics 一次性預付了 100 萬美元，以將 LP-100 的權利重新納入我們的控制之下，我們現在正在考慮將 LP-100 與 PARP 抑製劑結合在一項聯合計劃中，旨在具有同源修復缺陷的癌症或 HRD 癌症。截至 2022 年 12 月 31 日的年度，我們向 Allarity Therapeutics 發放了約 459,000 美元的託管付款。

Manufacturing-related expenses for the year ended December 31, 2022, were also reduced by $935,000 as a result of a payment we received in July 2022 from one of our service providers in connection with the resolution of a difference of views regarding the agreement with the service provider.

截至 2022 年 12 月 31 日止年度的製造相關費用也減少了 935,000 美元，因為我們於 2022 年 7 月從我們的一家服務提供商處收到了一筆付款，該付款與解決與服務提供者。

Our general and administrative expenses for 2022 were $5.8 million, up slightly from $5 million for 2021. The increase was primarily attributable to increases in payroll and compensation expenses of $0.5 million, increases in other professional fees of $0.4 million, increases in legal and patent-related expenses of $0.1 million, and increases in travel expenses of $0.1 million. Our R&D expenses continue to exceed our G&A expenses by a strong margin, reflecting our focus on advancing and expanding our product pipeline.

我們 2022 年的一般和管理費用為 580 萬美元，略高於 2021 年的 500 萬美元。這一增長主要歸因於工資和薪酬費用增加 50 萬美元、其他專業費用增加 40 萬美元、法律和專利費用增加。相關費用 10 萬美元，差旅費用增加 10 萬美元。我們的研發費用繼續大幅超過一般管理費用，反映出我們專注於推進和擴大我們的產品線。

The net loss for full-year 2022 was $14.3 million or $1.31 per share compared to a net loss of $12.4 million or $1.13 per share for the full-year 2021. As of December 31, 2022, we had approximately 10.86 million shares of common stock outstanding and outstanding warrants to purchase approximately 177,998 shares and outstanding options to purchase approximately 1,037,591 shares. These warrants and options, combined with our outstanding shares of common stock, give us a total fully diluted shares outstanding of 12,072,629 shares as of December 31, 2022.

2022 年全年淨虧損為 1,430 萬美元，即每股 1.31 美元，而 2021 年全年淨虧損為 1,240 萬美元，即每股 1.13 美元。截至 2022 年 12 月 31 日，我們擁有約 1,086 萬股普通股已發行和未行使的認股權證可購買約 177,998 股股份，未行使的期權可購買約 1,037,591 股。這些認股權證和期權，加上我們已發行的普通股，截至 2022 年 12 月 31 日，我們的已完全稀釋流通股總數為 12,072,629 股。

Our cash position, which includes cash equivalents and marketable securities at December 31, 2022, was $55.2 million. This balance is expected to carry us into 2025. Importantly, we believe our solid financial position will fuel continued growth and evolution of our RADR AI platform, accelerate the development of our portfolio of targeted oncology drug candidates, and allow us to introduce additional targeted products and collaboration opportunities in a capital efficient manner.

截至 2022 年 12 月 31 日，我們的現金頭寸（包括現金等價物和有價證券）為 5520 萬美元。這種平衡預計將帶領我們進入 2025 年。重要的是，我們相信我們穩健的財務狀況將推動我們 RADR AI 平台的持續增長和發展，加速我們的靶向腫瘤候選藥物組合的開發，並使我們能夠推出更多的靶向產品以資本有效的方式提供合作機會。

Our team continues to be very productive under a hybrid operating model. This hybrid model also removes geographic restrictions to our hiring initiatives, which gives us the ability to recruit extremely high-caliber team members that otherwise might not be available. We currently have 23 employees who are primarily focused on leading and advancing our research and drug development efforts. We see this number expanding slightly in coming quarters as we add additional experienced and talented individuals to help advance our mission.

我們的團隊在混合運營模式下繼續保持高效。這種混合模式還消除了我們招聘計劃的地域限制，這使我們能夠招募到否則可能無法招募到的極高素質的團隊成員。我們目前有 23 名員工，他們主要致力於領導和推進我們的研究和藥物開發工作。隨著我們增加更多經驗豐富、才華橫溢的人員來幫助推進我們的使命，我們預計這一數字在未來幾個季度將略有擴大。

I'll now turn the call over to our Chief Scientific Officer, Kishor, for an update on some of our development programs. Kishor?

現在，我將把電話轉給我們的首席科學官 Kishor，了解我們一些開發計劃的最新情況。基肖爾？

Thank you, David. During the last quarter, we provided you with updates to our drug programs, LP-184 and LP-284. These programs included developing LP-184 for two main classes of cancers: solid tumors such as genetically defined pancreatic and bladder cancers; and also the central nervous system cancers, including glioblastoma and brain mets.

謝謝你，大衛。在上個季度，我們向您提供了我們的藥物計劃 LP-184 和 LP-284 的更新。這些項目包括開髮用於治療兩類主要癌症的 LP-184：實體瘤，如基因定義的胰腺癌和膀胱癌；還有中樞神經系統癌症，包括膠質母細胞瘤和腦轉移瘤。

The second program was developing LP-284 for lymphoma and the focus on mantle cell and diffuse large B-cell lymphomas, and among the data, particularly double-hit and triple-hit lymphomas. At that time, we had apprise you of our plans to launch Phase 1 clinical trials for LP-184 in early 2023. I'm pleased now to provide you with updates on these plans, along with insights from our completed IND-enabling studies.

第二個項目是開髮用於淋巴瘤的 LP-284，重點關注套細胞和瀰漫性大 B 細胞淋巴瘤，以及數據，特別是雙重打擊和三重打擊淋巴瘤。當時，我們已告知您我們計劃於 2023 年初啟動 LP-184 的 1 期臨床試驗。現在我很高興向您提供這些計劃的最新信息，以及我們已完成的 IND 支持研究的見解。

Following a recent filing of pre-IND application with the FDA and completion of essentially all the pharmacology toxicology studies required to file the IND, we are pleased to report that the necessary documents and results for the IND submission are nearly complete, and we are anticipating the IND submission to occur in early April 2023, with a steady start-up in later of quarter two. We expect the first patient to be dosed in summer of 2023. We anticipate to have all currently targeted clinical sites activated in the third and fourth quarter of 2023.

繼最近向 FDA 提交 IND 前申請並完成提交 IND 所需的基本上所有藥理學毒理學研究後，我們很高興地報告， IND 提交所需的文件和結果已接近完成，我們預計IND 提交將於 2023 年 4 月上旬進行，並在第二季度末穩步啟動。我們預計第一位患者將於 2023 年夏季接受給藥。我們預計將在 2023 年第三和第四季度啟動所有當前目標臨床中心。

Besides that, this clinical trial will be conducted within two top-tier comprehensive cancer centers such as the Fox Chase Cancer Center and Johns Hopkins. These and other similar trial sites routinely assess tumor genome sequencing and characterization, a resource that is critical to our approach for identifying the most sensitive tumors.

此外，這項臨床試驗將在福克斯蔡斯癌症中心和約翰霍普金斯大學等兩個頂級綜合癌症中心進行。這些和其他類似的試驗中心定期評估腫瘤基因組測序和表徵，這是我們識別最敏感腫瘤的方法至關重要的資源。

Additionally, the protocol for Phase 1 trial has been finalized after discussions with our leading KOLs. The Phase 1 design is depicted in this slide that you see. The trial design is a Bayesian optimal interval design, and this was chosen because it allows us to balance the risk of inadvertently arriving at a lower dose while maintaining safety to reach an effective dose.

此外，在與我們的主要 KOL 討論後，第一階段試驗的方案已經最終確定。您看到的這張幻燈片描述了第一階段的設計。試驗設計是貝葉斯最佳間隔設計，選擇這種設計是因為它使我們能夠平衡無意中達到較低劑量的風險，同時保持達到有效劑量的安全性。

Following the escalation phase and as recommended by FDA, we'll have two cohorts of 10 patients each at two dose levels, which will provide us with the related dose response or RDR for the Phase 2 trial. Based upon the dose range finding study in dogs from the completed IND-enabling studies, we will begin the first in-human studies with a starting dose of 0.015 milligrams per kg.

在升級階段之後，按照 FDA 的建議，我們將分為兩組，每組 10 名患者，採用兩種劑量水平，這將為我們提供 2 期試驗的相關劑量反應或 RDR。根據已完成的 IND 啟用研究中對狗的劑量範圍發現研究，我們將開始首次人體研究，起始劑量為每公斤 0.015 毫克。

Now LP-184, of course, has the potential as a potent monotherapy agent, but also has the potential to be used in combination with other FDA-approved therapies. These combination choices, to us, are dictated and guided by clues based upon the mechanism of action of LP-184, as well as the interrogation of the interactive part base using our in silico assessment on the RADR platform.

當然，現在 LP-184 具有作為有效單一療法藥物的潛力，但也有可能與 FDA 批准的其他療法聯合使用。對我們來說，這些組合選擇是由基於 LP-184 作用機制的線索決定和指導的，以及使用我們在 RADR 平台上的計算機評估對交互式部件庫的詢問。

The transcription-coupled nucleotide excision repair or TC-NER pathway, which is critical in the repair of DNA damage caused by LP-184, provides it with a synthetic lethal properties in tumors that are deficient in this pathway. The mechanism of action of LP-184 can be leveraged further, therefore, by combination of molecules that would diminish the activity of the TC-NER pathway.

轉錄偶聯的核苷酸切除修復或 TC-NER 途徑對於修復 LP-184 引起的 DNA 損傷至關重要，它為缺乏該途徑的腫瘤提供了合成致死特性。因此，可以通過組合降低 TC-NER 途徑活性的分子來進一步利用 LP-184 的作用機制。

Such molecules, as you can envisage, will also help broaden the tumor indications that we got hypersensitive to LP-184, as well as provide the potential for widening the therapy index of LP-184. In this regard, one molecule that we have been investigating and for which we now have a substantial positive in silico, in vitro, as well as in vivo data is spironolactone. This is an FDA-approved drug for hypertension and other non-oncological indications.

正如您可以想像的那樣，此類分子還將有助於擴大我們對 LP-184 過敏的腫瘤適應症，並提供擴大 LP-184 治療指數的潛力。在這方面，我們一直在研究的一種分子是螺內酯，我們現在在計算機、體外和體內數據中都獲得了實質性的陽性結果。這是 FDA 批准的治療高血壓和其他非腫瘤適應症的藥物。

In continuing our focus on providing insight and transparency about our research through webinars, we are hosting a KOL webinar on synthetic lethality, as Panna mentioned, tomorrow, March 21, at noon, Easter. This webinar will feature an internationally recognized expert in synthetic lethality, Dr. Zoltan Szallasi, who serves joined appointments as Principal Investigator at the Danish Cancer Center, with whom we collaborate, and Assistant Professor of Pediatrics at Boston Children's Hospital, a Harvard Medical School affiliate. Later on, in quarter -- in the second quarter, we will have an in-depth second webinar on how Lantern is leveraging the synthetic lethal properties are LP-184 and LP-284 for multiple solid tumors.

為了繼續致力於通過網絡研討會提供有關我們研究的見解和透明度，正如 Panna 提到的那樣，我們將於明天（3 月 21 日）復活節中午舉辦一場有關合成殺傷力的 KOL 網絡研討會。本次網絡研討會將邀請國際公認的合成致死專家 Zoltan Szallasi 博士擔任嘉賓，他是我們合作的丹麥癌症中心的首席研究員，也是哈佛醫學院附屬機構波士頓兒童醫院的兒科助理教授。稍後，在第二季度，我們將舉辦第二次深入的網絡研討會，介紹 Lantern 如何利用 LP-184 和 LP-284 的合成致死特性治療多種實體瘤。

Now, in addition to updating you on LP-184's clinical trial plans, we also have updates for LP-284 clinical development plans. As I had mentioned before, Lantern is developing LP-284 for multiple B-cell non-Hodgkin's lymphomas where LP-284 has some nanomolar potency across multiple in vitro and in vivo studies, and lymphomas where there is a demonstrated clinical need. NHL indications for LP-284 are targeted at this time to include mantle cell lymphomas and double-hit lymphomas and a few other NHL cancer subtypes.

現在，除了向您更新 LP-184 的臨床試驗計劃外，我們還更新了 LP-284 的臨床開發計劃。正如我之前提到的，Lantern 正在開發 LP-284，用於治療多種 B 細胞非霍奇金淋巴瘤，其中 LP-284 在多項體外和體內研究中具有一定的納摩爾效力，並且對於有臨床需求的淋巴瘤。目前，LP-284 的 NHL 適應症包括套細胞淋巴瘤和雙重打擊淋巴瘤以及其他一些 NHL 癌症亞型。

There is a significant clinical need for additional late-stage therapeutic options for these patients, as nearly all patients relapse from the current standard-of-care therapy, such as bortezomib and ibrutinib. We are therefore equally excited about building the clinical trials with LP-284. The IND-enabling studies and IND submission are slated to be completed second quarter of 2023. We have already received interest from multiple major cancer centers to serve as LP-284 trial sites when launched.

這些患者非常需要額外的晚期治療方案，因為幾乎所有患者都會從當前的標準治療（例如硼替佐米和依魯替尼）中復發。因此，我們對利用 LP-284 進行臨床試驗同樣感到興奮。支持 IND 的研究和 IND 提交預計將於 2023 年第二季度完成。我們已經收到多個主要癌症中心的興趣，希望在 LP-284 啟動時作為試驗地點。

Our confidence in the molecule is grounded on several exciting results, such as those that we presented at the 2020 ASH annual meeting. There we showed that mantle cell lymphomas are highly sensitive to LP-284. And as you can see in this slide, the tumors that actually become nonresponsive to standard-of-care agents, ibrutinib and bortezomib, which is shown on panel B in the slide, continue to retain responsiveness to LP-284. This is critically important from a patient perspective as nearly all patients relapse from these agents.

我們對該分子的信心基於一些令人興奮的結果，例如我們在 2020 年 ASH 年會上展示的結果。我們發現套細胞淋巴瘤對 LP-284 高度敏感。正如您在這張幻燈片中所看到的，實際上對標準護理藥物伊布替尼和硼替佐米無反應的腫瘤（如幻燈片 B 部分所示）繼續保留對 LP-284 的反應。從患者的角度來看，這一點至關重要，因為幾乎所有患者都會因這些藥物而復發。

Later this year, we will also look forward to sharing with you additional data from our preclinical clinical ADC development program, and also from our rapidly progressing pediatric studies for both LP-184 and LP-284. Most importantly, we'll also share with you clinical data from our upcoming and ongoing clinical trials.

今年晚些時候，我們還將期待與您分享來自我們的臨床前臨床 ADC 開發計劃以及我們快速進展的 LP-184 和 LP-284 兒科研究的更多數據。最重要的是，我們還將與您分享我們即將進行和正在進行的臨床試驗的臨床數據。

I'll now turn the call back to Panna.

我現在將電話轉回給潘納。

Thank you, Kishor. As Kishor pointed out, we are accelerating the pace at which we're developing and validating insights, and these insights are meaningful and ready to be deployed now in the clinic. We're also very well positioned to efficiently develop our assets and partner them out with larger biopharma companies.

謝謝你，基肖爾。正如 Kishor 指出的那樣，我們正在加快開發和驗證見解的步伐，這些見解很有意義，現在就可以在診所中部署。我們也非常有能力有效地開發我們的資產並與更大的生物製藥公司合作。

At the same time, David pointed out in his review our very efficient use of capital in developing multiple programs and multiple indications and also launching clinical trials, completing our manufacturing campaigns. And so our strong cash position is being carefully utilize to make meaningful progress in a disciplined manner.

與此同時，大衛在他的評論中指出，我們非常有效地利用資本來開發多個項目和多個適應症，並啟動臨床試驗，完成我們的生產活動。因此，我們正在謹慎利用強大的現金狀況，以有紀律的方式取得有意義的進展。

With that, I'd like to now open the call up to any questions.

至此，我現在想開始通話，回答任何問題。

Thank you, Panna. (Conference Instructions)

謝謝你，潘娜。 （會議須知）

We already have some questions coming in here. First, I see John Vandermosten's hand up.

我們已經收到一些問題。首先，我看到約翰·范德莫斯坦舉起了手。

John, you should be able to talk.

約翰，你應該能說話。

All right. Thank you, Nicole. Thought I'd start with kind of a bigger picture question. We saw a recent bid for Seagen. Does that indicate in your mind a shift in interest to ADCs and does that affect how you might develop your own portfolio given that positive indication?

好的。謝謝你，妮可。我想我應該從一個更大的問題開始。我們最近看到了對 Seagen 的收購。這是否表明您對 ADC 的興趣發生了轉變？考慮到這一積極跡象，這是否會影響您開發自己的投資組合的方式？

John, that's a great question. Thank you for asking that. We're very excited about the Pfizer's buying up of Seagen or Seattle Genetics for their ADC program. As you know, I started looking at ADC and developing that in their pipeline a year ago.

約翰，這是一個很好的問題。謝謝你這麼問。我們對輝瑞公司收購 Seagen 或 Seattle Genetics 的 ADC 項目感到非常興奮。如您所知，我一年前開始研究 ADC 並在他們的管道中開發它。

But we've been, I would say, more focused on launching it into the clinic because that's kind of what we heard analysts and investors, that they really wanted to see the clinical progress for 184 and 284. So we really shifted to that majority of last year as opposed to balancing both ADC and 184. And with the long-term kind of, I would say, challenges in the biotech market, we're really focused also on cash preservation. And so with the ADCs, we're kind of on the -- moving more of the back burner.

但我想說，我們一直更專注於將其推向臨床，因為這就是我們從分析師和投資者那裡聽到的，他們真的希望看到 184 和 284 的臨床進展。所以我們真的轉向了大多數去年，我們沒有平衡 ADC 和 184。我想說的是，由於生物技術市場面臨長期挑戰，我們也真正關注現金保存。因此，對於 ADC，我們有點將其放在次要位置。

But we've got some really good progress now on our ADCs. We'll have some data out later this year, probably very shortly about what we're doing in the ADC. It's a very exciting category. We've also fine-tuned RADR now to do more work and being able to predict and help us model both ADCs and antibody drug -- antibody small molecule regimens.

但現在我們的 ADC 已經取得了一些非常好的進展。我們將在今年晚些時候發布一些關於我們在 ADC 中所做工作的數據，可能很快就會發布。這是一個非常令人興奮的類別。我們現在還對 RADR 進行了微調，以完成更多工作，能夠預測並幫助我們對 ADC 和抗體藥物（抗體小分子方案）進行建模。

So I think -- yes, I think ADCs will be a big focus going forward. But I think everyone wants to see patients dosed with 184, 284, and 300. So that continues to be the primary focus, but ADC is definitely in the next chapter for us.

所以我認為——是的，我認為 ADC 將成為未來的一大焦點。但我認為每個人都希望看到患者服用 184、284 和 300。因此這仍然是主要焦點，但 ADC 肯定是我們的下一章。

Great. And another question on -- you know, you've got about a dozen indications, dozen of programs going on, and some of them are some smaller niche areas. Should we expect to see grant subsidies or some other support to help some of those programs as we move along? (multiple speakers)

偉大的。另一個問題是——你知道，你有大約十幾個適應症，十幾個正在進行的項目，其中一些是一些較小的利基領域。隨著我們的進展，我們是否應該期望看到贈款補貼或其他一些支持來幫助其中一些項目？ （多個發言者）

Yeah. We are looking at grants and also collaborations. And so yes, that's a -- I would say that's a valid question. And a lot of these are very ultra-rare cancers. There definitely are ways to look at grant dollars to help accelerate those.

是的。我們正在尋求資助和合作。所以，是的，這是一個——我想說這是一個有效的問題。其中很多都是非常罕見的癌症。肯定有一些方法可以利用撥款來幫助加速這些進程。

Okay, great. And let's see, I guess, a kind of a modeling question. You know now that Harmonic is in full swing, should -- what should we think about in terms of R&D for 2023 as we start adding the patients and seeing that kind of tick-off?

好的，太好了。我想，讓我們看看一個建模問題。您現在知道，Harmonic 正在如火如荼地進行，當我們開始增加患者並看到這種情況時，我們應該在 2023 年的研發方面考慮什麼？

Sure. We'll let David kind of give you some guidance for the year, but we're pretty disciplined and have modeled kind of a scale-up of Harmonic over the next four to six quarters. David?

當然。我們會讓 David 為您提供今年的一些指導，但我們非常自律，並且在接下來的四到六個季度中模擬了 Harmonic 的規模擴大。大衛？

Sure. Hi, John. We see our cash burn rate in our expenses increasing modestly as we move into clinical trials with LP-184 and LP-284, but in a disciplined way. And then as the enrollment increases for LP-300 as well, we will see our cash increased some of that, but fairly controlled from where we are now.

當然。你好，約翰。隨著我們進入 LP-184 和 LP-284 的臨床試驗，我們看到支出中的現金消耗率略有增加，但方式是有紀律的。然後，隨著 LP-300 註冊人數的增加，我們將看到我們的現金增加了一些，但與現在相比，我們的現金受到了相當程度的控制。

Great. Thank you, David. Appreciate it.

偉大的。謝謝你，大衛。欣賞它。

Okay. I see that Michael King's hand is also raised. Michael, you should now be able to speak as well. You may have to unmute yourself.

好的。我看到邁克爾·金也舉起了手。邁克爾，你現在應該也能說話了。您可能必須自行取消靜音。

Sorry. Took me a second to -- core hand-eye coordination to unmute the line. Can you guys hear me all right now?

對不起。我花了一秒鐘的時間來——核心手眼協調能力來取消線路靜音。你們現在能聽到我說話嗎？

Yes, Michael. I can hear you.

是的，邁克爾。我可以聽見你。

All right. So a couple of questions. I just would love to get a little more clarity on how you guys are thinking about the algorithm of both combination therapy as well as a patient enrichment. So for example, are you -- in the case of LP-300, are you doing any genetic selection upfront? Or is that going to await a recommended Phase 2 dose?

好的。有幾個問題。我只是想更清楚地了解你們如何思考聯合治療和患者豐富的算法。例如，就 LP-300 而言，您是否預先進行了任何基因選擇？還是要等待推薦的二期劑量？

And then when you think about combining things like PARP inhibitors, spironolactone, et cetera, as the studies mature, how should we think about the way you guys are going to layer those things in as well?

然後，當你考慮結合 PARP 抑製劑、螺內酯等藥物時，隨著研究的成熟，我們應該如何考慮你們將這些藥物分層的方式？

Sure. I'll take a first crack at that. So in regards to the LP-300, we will not be doing any genomic-based selection because that's kind of already been done in many ways. Because these patients will have relapsed or stop responding to TKI therapies. So they are kind of self-selected already for that as never smokers.

當然。我會先嘗試一下。因此，對於 LP-300，我們不會進行任何基於基因組的選擇，因為這已經在很多方面完成了。因為這些患者會復發或對 TKI 療法不再有反應。因此，作為從不吸煙者，他們已經是自我選擇的了。

We will be taking liquid biopsy for these 90 patients. And those liquid biopsy results might give us some idea about potential surrogate markers of response or potentially some interesting signatures that correlate to improved response in certain types of patients, but we won't know until we collect that. But that data will be very useful in future studies, potentially Phase 3 or to license the drug out. But for the current trial and the beauties of the trial is that we already have patients that have been genomically stratified because these are going to be TKI failures largely.

我們將為這 90 名患者進行液體活檢。這些液體活檢結果可能會讓我們了解潛在的替代反應標誌物或可能與某些類型患者的反應改善相關的一些有趣的特徵，但在我們收集這些信息之前我們不會知道。但這些數據在未來的研究中非常有用，可能是第三階段或藥物許可。但就目前的試驗而言，該試驗的優點在於我們已經對患者進行了基因組分層，因為這些患者很大程度上將是 TKI 失敗的患者。

In terms of the additional combinations like the spironolactone or the PARP inhibitors, we definitely think that spironolactone seems to be a significant enhancement in the potency of 184 and perhaps 284, but definitely 184. And we could see ourselves using that as an additional arm in certain cancers where we may want to see an uptick in the potency or maybe we may see in certain patient types a less-than-ideal therapeutic window or safety profile.

就螺內酯或 PARP 抑製劑等其他組合而言，我們絕對認為螺內酯似乎顯著增強了 184 和也許 284 的效力，但絕對是 184。我們可以看到自己將其用作對於某些癌症，我們可能希望看到效力的上升，或者我們可能會在某些患者類型中看到不太理想的治療窗或安全性。

So if we wanted to give less drug but get a heightened response and the same response at the tolerated dose, then that's where we can use spironolactone. But we see that as being introduced as an additional arm in the trial.

因此，如果我們想減少藥物用量，但在耐受劑量下獲得增強的反應和相同的反應，那麼我們可以使用螺內酯。但我們認為這是作為試驗中的一個額外手段而引入的。

In terms of PARP, we're early on. But we think that we could actually mount some trials directly with PARP and compare it head to head against PARP alone. Because, as you know, PARP has got a couple of billion dollars in sales in certain indications. And we think in many of those indications, we can significantly improve the outcome.

就 PARP 而言，我們還處於早期階段。但我們認為我們實際上可以直接使用 PARP 進行一些試驗，並將其與單獨的 PARP 進行正面比較。因為，如您所知，PARP 在某些適應症上的銷售額已達到數十億美元。我們認為，在許多跡像中，我們可以顯著改善結果。

And I think, Kishor, you had some data on PARP on the approval and you want to share some of that with Michael?

我想，Kishor，您有一些有關 PARP 批准的數據，您想與 Michael 分享其中的一些數據嗎？

Yes. So there's PARP inhibitors that have been approved for, for example, prostate cancer, clearly focused on those prostate cancers that have mutations in BRCA or ATM. But after some time, several of these patients do develop resistance. So one part also is that, a, the combination might delay this resistance. But in addition, if they become refractory, then perhaps LP-184 will still work on those. And there are toxicities associated with, of course, both LP-184 and PARP. And using a combination in a more strategic way to diminish those toxicities is another path that we have.

是的。例如，PARP 抑製劑已被批准用於治療前列腺癌，顯然主要針對那些 BRCA 或 ATM 突變的前列腺癌。但一段時間後，其中一些患者確實產生了耐藥性。因此，一方面，這種組合可能會延遲這種抵抗。但此外，如果它們變得難治，那麼 LP-184 或許仍能發揮作用。當然，LP-184 和 PARP 都有相關的毒性。以更具戰略性的方式使用組合來減少這些毒性是我們的另一條途徑。

Okay. But if I can maybe summarize what I've heard. Is it fair to say that you'll need to get single agent PK/PD for your -- and maybe a recommended Phase 2 dose before you start putting or adding things like spironolactone or adding to PARP, is that --

好的。但如果我可以總結一下我所聽到的。公平地說，在您開始添加或添加螺內酯等藥物或添加到 PARP 之前，您需要獲得單藥 PK/PD 治療，也許還需要推薦的第 2 階段劑量，是這樣嗎？

Yes. At this time, there's the PARP, that's correct.

是的。這時候就有了PARP，沒錯。

So the question that I have, spironolactone, I can understand PARP, you can probably refer to data that's in the public domain as far as what single agent activity should be from a PARP before you add 184 on top. But I'm just wondering, in the case of spironolactone where it's not thought of as, you know, antineoplastic, how does one -- because when you do combination studies, the FDA is always interested in what does the agent add as a single agent. You have to do some studies showing that spironolactone has no effect on tumors.

所以我的問題是，螺內酯，我可以理解 PARP，在您在頂部添加 184 之前，您可能可以參考公共領域的數據，了解 PARP 中的單一代理活動應該是什麼。但我只是想知道，就螺內酯而言，它並不被認為是抗腫瘤藥物，但它是如何發揮作用的——因為當你進行組合研究時，FDA 總是對這種藥物作為單一藥物添加的內容感興趣代理人。你必須做一些研究來證明螺內酯對腫瘤沒有作用。

Yes. So I mean, spironolactone has been -- is an FDA-approved drug. So the safety profile and other things are known about it, so as are the pharmacokinetics. We have already gathered data in vivo in animal models that the combination of works and is more effective in certain -- context of certain tumors more effective than LP-184. So we believe that the data we have is sufficient for us to go to the FDA and design a study to use this combination.

是的。所以我的意思是，螺內酯是 FDA 批准的藥物。因此，其安全性和其他方面以及藥代動力學都是已知的。我們已經在動物模型中收集了體內數據，表明該組合在某些特定腫瘤背景下比 LP-184 更有效，並且更有效。因此，我們相信我們擁有的數據足以讓我們去 FDA 設計一項研究來使用這種組合。

But also in those studies, we did start spironolactone alone and it showed no effect in the tumor.

但在這些研究中，我們確實開始單獨使用螺內酯，但它對腫瘤沒有效果。

Yeah, spironolactone alone did not show any effect. That's right.

是的，單獨使用螺內酯沒有任何效果。這是正確的。

Okay. And just wondering if you have to show maybe even a small number of patients, but I'll leave that for now.

好的。只是想知道是否必須展示甚至一小部分患者，但我現在先不考慮這個。

And then just on Starlight, what is -- is there some gating items, maybe just sort of the documentation for the Phase 1 trial that would have you somewhat behind the studies of LP-184? If I read your slide correctly, it showed that Starlight IND would be a little bit later this year behind, the anticipated one for 184.

然後就在星光號上，有沒有一些門控項目，也許只是第一階段試驗的文件，可以讓你在某種程度上支持 LP-184 的研究？如果我正確地閱讀了你的幻燈片，它表明 Starlight IND 今年將落後一點，即預期的 184。

No, no. The Starlight, we'll just picked up after the 1A. So Starlight, we would -- that would pick up in Phase 1B or 2A. So the 1A is going to be multi-tumor. And once we have an MTD and the MTD minus one, then we'll probably, in that Phase 1A, have certain CNS cancer patients.

不，不。星光號，我們將在 1A 後剛剛接載。所以星光，我們會——這將在 1B 或 2A 階段開始。所以1A將是多腫瘤的。一旦我們有了 MTD 並且 MTD 減一，那麼我們可能會在 1A 階段出現某些中樞神經系統癌症患者。

Okay.

好的。

And as we've established that MTD, then we can enrich -- (multiple speakers)

當我們建立了 MTD 後，我們就可以豐富——（多位發言者）

-- over to Starlight; I got it. Okay. All right. Thanks, guys.

——前往星光；我得到了它。好的。好的。多謝你們。

No problem.

沒問題。

Do we have one more question?

我們還有一個問題嗎？

Yes. Thank you, Michael. One more question we had is -- or does the expected increased cash burn rate factor into our projection through 2025?

是的。謝謝你，邁克爾。我們還有一個問題是——或者預期的現金消耗率增加是否會影響到我們對 2025 年的預測？

Yes, we're taking that into account when we're -- we're stating that our current financial position carries us into 2025.

是的，當我們聲明我們當前的財務狀況可以讓我們進入 2025 年時，我們就會考慮到這一點。

Okay. And with that, that will conclude our webcast for today. Thank you all for joining, and we hope to see you over at our KOL webinar tomorrow. Thank you, everyone.

好的。我們今天的網絡廣播就到此結束。感謝大家的加入，我們希望明天在我們的 KOL 網絡研討會上見到您。謝謝大家。