Harpoon Therapeutics Inc (HARP) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by. And welcome to the Harpoon Therapeutics 4Q 2020 financial results and corporate update conference call. At this time, all participants are in a listen-only mode. Please be advised that today's conference may be recorded. (Operator Instructions)

女士們先生們，感謝你們的支持。歡迎參加 Harpoon Therapeutics 2020 年第四季度財務業績和公司更新電話會議。此時，所有參與者都處於只聽模式。請注意，今天的會議可能會被錄製。 （操作員說明）

On the call today from Harpoon are Jerry McMahon, President and Chief Executive Officer; Georgia Erbez, Chief Financial Officer; Natalie Sacks, our Chief Medical Officer; and Holger Wesche, our Chief Scientific Officer. Following management's prepared remarks, we will be conducting a Q&A session. (Operator Instructions) I will now turn the call over to Georgia Erbez.

今天，魚叉公司總裁兼首席執行官傑里·麥克馬洪 (Jerry McMahon) 接聽了電話； Georgia Erbez，首席財務官；娜塔莉·薩克斯 (Natalie Sacks)，我們的首席醫療官；以及我們的首席科學官 Holger Wesche。在管理層準備好發言後，我們將舉行問答會議。 （接線員指示）我現在將電話轉給 Georgia Erbez。

Thank you, operator. Good afternoon, and welcome to Harpoon Therapeutics webcast and conference call for discussion of the company's fourth quarter and full Year 2020 financial results and a corporate update.

謝謝你，接線員。下午好，歡迎收看 Harpoon Therapeutics 網絡廣播和電話會議，討論該公司第四季度和 2020 年全年財務業績以及公司最新情況。

Before I turn the call over to Dr. McMahon, I would like to remind you that today's call will include forward-looking statements. These forward-looking statements are based on Harpoon's expectations and assumptions as of the date of this call. Each of these forward-looking statements involves risks and uncertainties that could cause Harpoon's clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements.

在我將電話轉給麥克馬洪博士之前，我想提醒您，今天的電話會議將包含前瞻性陳述。這些前瞻性陳述基於 Harpoon 截至本次電話會議之日的預期和假設。這些前瞻性陳述均涉及風險和不確定性，可能導致 Harpoon 的臨床開發計劃、未來結果或業績與前瞻性陳述所明示或暗示的結果或業績存在顯著差異。

Please refer to Harpoon's filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2020, which was filed today, and which are available on Harpoon's website for information concerning factors that could cause Harpoon's actual results to differ from those expressed or implied in the forward-looking statements discussed on this call. Except as required by law, Harpoon assumes no obligation to update any forward-looking statements discussed on this call to reflect any change in expectations even as new information becomes available.

請參閱 Harpoon 向 SEC 提交的文件，包括今天提交的截至 2020 年 12 月 31 日的 10-K 表格年度報告，該報告可在 Harpoon 網站上獲取，了解可能導致 Harpoon 實際結果發生變化的因素的信息。與本次電話會議中討論的前瞻性陳述中明示或暗示的內容不同。除法律要求外，即使有新信息，Harpoon 也不承擔更新本次電話會議中討論的任何前瞻性陳述以反映預期變化的義務。

I will now turn the call over to Dr. Jerry McMahon, President and CEO of Harpoon Therapeutics.

我現在將把電話轉給 Harpoon Therapeutics 總裁兼首席執行官傑里·麥克馬洪 (Jerry McMahon) 博士。

Thank you, Georgia. And thank you all for joining us on this call this afternoon. I am very pleased with Harpoon's achievement of significant clinical, scientific, and operational milestones during the past year. At the time of our IPO in February 2019, our goal was to have four programs in clinical development by the end of 2020.

謝謝你，格魯吉亞。感謝大家今天下午參加我們的電話會議。我對 Harpoon 在過去一年中取得的重大臨床、科學和運營里程碑感到非常高興。在 2019 年 2 月首次公開募股時，我們的目標是到 2020 年底有四個項目進入臨床開發。

Harpoon achieved that goal, including starting two new clinical trials in 2020. We maintain our commitment to driving multiple products forward for the potential treatment of cancers and the benefit they could provide to many cancer patients who have limited treatment options.

Harpoon 實現了這一目標，包括在 2020 年啟動兩項新的臨床試驗。我們繼續致力於推動多種產品的潛在治療癌症，並為許多治療選擇有限的癌症患者帶來益處。

Some of the key accomplishments for Harpoon in 2020 included the progress of our lead product candidate, HPN424, which is continuing in the dose escalation portion of the Phase 1/2a clinical trial in patients with metastatic castration resistant prostate cancer. We also advanced our other three TriTAC clinical programs, including HPN536 for the potential treatment of mesothelin expressing tumors, with a focus on ovarian and now including pancreatic and mesothelioma cancers.

Harpoon 在 2020 年取得的一些關鍵成就包括我們的主要候選產品 HPN424 的進展，該產品正在轉移性去勢抵抗性前列腺癌患者中繼續進行 1/2a 期臨床試驗的劑量遞增部分。我們還推進了其他三個 TriTAC 臨床項目，包括 HPN536，用於潛在治療表達間皮素的腫瘤，重點是卵巢癌，現在包括胰腺癌和間皮瘤。

Our third product candidate, HPN217, entered the clinic in April of last year with initiation of a Phase 1/2 clinical trial for multiple myeloma. And finally, in the second half of 2020, we submitted an IND and initiated a Phase 1/2 trial for our fourth program, HPN-328 targeting DLL3 for small cell lung cancer and other DLL3 expressing tumors. We also made significant progress with our proprietary ProTriTAC T cell engager pro-drug platform designed to remain inert systemically until its activation in the tumor.

我們的第三個候選產品 HPN217 於去年 4 月進入臨床，啟動了針對多發性骨髓瘤的 1/2 期臨床試驗。最後，在2020 年下半年，我們提交了IND 並啟動了我們的第四個項目HPN-328 的1/2 期試驗，HPN-328 靶向DLL3，用於治療小細胞肺癌和其他表達DLL3 的腫瘤。我們還通過專有的 ProTriTAC T 細胞接合前藥平台取得了重大進展，該平台旨在保持系統惰性，直到在腫瘤中激活。

We believe this platform can enable the safe targeting of more broadly expressed tumor antigens. HPN601 has been nominated as a clinical candidate and becomes our first conditionally active T cell engager program. It targets the tumor antigen, epithelial cell adhesion molecule, or EpCAM, which is broadly expressed on a wide variety of solid tumors. It is currently undergoing additional preclinical and IND-enabling investigations. We will keep you updated on our progress for this exciting program.

我們相信該平台可以安全地靶向更廣泛表達的腫瘤抗原。 HPN601已被提名為臨床候選藥物，並成為我們的第一個有條件活性T細胞接合計劃。它針對腫瘤抗原、上皮細胞粘附分子或 EpCAM，廣泛表達於多種實體瘤中。目前正在進行額外的臨床前和 IND 驗證研究。我們將隨時向您通報這一令人興奮的計劃的最新進展。

Recently, Harpoon strengthened its financial position significantly with our successful follow-on offering in January 2021 that raised approximately $108 million of net cash. The financial resources from this transaction, along with our existing cash, cash equivalents and marketable securities, that are on the balance sheet of $150 million as of the end of December, gives us a pro forma cash balance of approximately $258 million. These resources are being deployed to further support and advance each of our clinical development and research programs to multiple potential value-creating milestones for our shareholders.

最近，Harpoon 在 2021 年 1 月成功進行後續發行，籌集了約 1.08 億美元的淨現金，顯著增強了其財務狀況。截至 12 月底，此次交易的財務資源加上我們資產負債表上的現有現金、現金等價物和有價證券為 1.5 億美元，預計現金餘額約為 2.58 億美元。這些資源正在被部署以進一步支持和推進我們的每個臨床開發和研究項目，為我們的股東實現多個潛在的價值創造里程碑。

Now let me review some key aspects of our TriTAC technology. And after that, I will update you on our clinical development programs. Harpoon's TriTAC technology platform is a novel and proprietary approach to engage T cells, the most potent killer cells of the immune system.

現在讓我回顧一下我們 TriTAC 技術的一些關鍵方面。之後，我將向您介紹我們的臨床開發計劃的最新情況。 Harpoon 的 TriTAC 技術平台是一種新穎的專有方法，用於吸引 T 細胞（免疫系統中最有效的殺傷細胞）。

T cell engagers are engineered proteins that physically connect a patient's own T cells to target cells that express specific proteins or surface markers. This result in the activation of T cells unleashing the natural power to kill the target cell by releasing potent cytokines and other factors. Our current pipeline of product candidates is focused on oncology indications, but other uses would also be possible.

T 細胞接合器是工程蛋白質，可將患者自身的 T 細胞與表達特定蛋白質或表面標記的靶細胞物理連接。這會導致 T 細胞被激活，釋放出強效細胞因子和其他因子來殺死靶細胞的自然力量。我們目前的候選產品主要集中在腫瘤學適應症上，但其他用途也是可能的。

We believe our TriTACs have a number of features that could be advantageous when compared to other immunologic approaches to the treatment of cancer.

我們相信，與其他癌症治療免疫方法相比，我們的 TriTAC 具有許多優勢。

First, our TriTACs are modular by design and are about 75% similar to one another. They consist of three primary components that perform three different functions, T cell binding, half-life extension, and tumor cell binding.

首先，我們的 TriTAC 採用模塊化設計，彼此相似度約為 75%。它們由三個主要成分組成，執行三種不同的功能：T 細胞結合、半衰期延長和腫瘤細胞結合。

To address half-life extension, we utilize a domain that binds transiently to human serum albumin. We utilize single domain antibodies for target binding and human serum albumin binding, which makes our molecules smaller and more flexible than would be possible with larger antibody derived fragments.

為了延長半衰期，我們利用了與人血清白蛋白瞬時結合的結構域。我們利用單域抗體進行靶標結合和人血清白蛋白結合，這使得我們的分子比較大的抗體衍生片段更小、更靈活。

Furthermore, these domains are inherently very stable, contributing to a platform that potentially has very little off-target activity and is therefore expected to have a therapeutic window ideal for applications in solid tumors.

此外，這些結構域本質上非常穩定，有助於形成一個潛在具有很少脫靶活性的平台，因此預計具有適用於實體瘤的理想治療窗口。

Second, our TriTAC molecules are relatively small globular proteins that can be administered to patients by intravenous delivery in a one-hour infusion every week or two weeks. The TriTAC protein is about one-third the size of a typical antibody. And we believe the smaller size and globular shape of TriTACs allows them to diffuse more freely into tumor tissue compared to antibodies.

其次，我們的 TriTAC 分子是相對較小的球狀蛋白，可以每週或兩週通過靜脈注射一小時輸注給患者。 TriTAC 蛋白的大小約為典型抗體的三分之一。我們相信，與抗體相比，TriTAC 較小的尺寸和球形形狀使它們能夠更自由地擴散到腫瘤組織中。

And finally, our TriTACs can be manufactured [in chose] cells and use standard methods of conventional antibody-based manufacturing techniques. This completely avoids the cost and complexity of personalized or cell-based therapies such as CAR-T.

最後，我們的 TriTAC 可以在[選定的]細胞中製造，並使用基於傳統抗體的製造技術的標準方法。這完全避免了個性化或基於細胞的療法（如 CAR-T）的成本和復雜性。

Utilizing all of these unique features, our TriTACs are designed to connect with and convert a patient's own T cells to kill tumors. They are engineered to optimize the therapeutic index of T cell engagers and bring success as seen in liquid tumors to solid tumors.

利用所有這些獨特的功能，我們的 TriTAC 旨在連接並轉化患者自身的 T 細胞以殺死腫瘤。它們經過精心設計，可優化 T 細胞接合劑的治療指數，並為實體瘤帶來液體腫瘤的成功。

Now let me review where we are with our four clinical development programs. Our lead TriTAC product candidate, HPN424, targets prostate-specific membrane antigen or PSMA for the treatment of metastatic castration resistant prostate cancer and continues in dose escalation of our Phase 1/2a clinical trial. At our December 2020 data update, we reported that for the highest fixed dose tested, 160 nanogram per kilogram, seven patients had been enrolled.

現在讓我回顧一下我們的四個臨床開發項目的進展情況。我們的主要 TriTAC 候選產品 HPN424 以前列腺特異性膜抗原或 PSMA 為目標，用於治療轉移性去勢抵抗性前列腺癌，並繼續進行 1/2a 期臨床試驗的劑量遞增。在 2020 年 12 月的數據更新中，我們報告稱，對於測試的最高固定劑量（每公斤 160 納克），已有 7 名患者入組。

And one patient had achieved a confirmed partial response based on RECIST version 1.1 criteria. Three patients enrolled in this cohort had serum PSA reductions, including one with a reduction of 50% or PSA50. For this difficult-to-treat patient population, we are encouraged by these early results. We are continuing to enroll patients and to advance the dose escalation.

根據 RECIST 1.1 版標準，一名患者已達到確認的部分緩解。納入該隊列的 3 名患者血清 PSA 降低，其中一名患者降低 50% 或 PSA50。對於這一難以治療的患者群體，我們對這些早期結果感到鼓舞。我們正在繼續招募患者並推進劑量遞增。

We are also able to employ step dosing in this trial where patients are receiving a dose of 300 nanogram per kilogram. This allows for a faster advancement to much higher doses than a traditional fixed dose escalation would allow. We are planning to present data from this trial at a medical meeting later in the first half of this year, most likely at ASCO.

我們還能夠在該試驗中採用逐步給藥，患者接受的劑量為每公斤 300 納克。與傳統的固定劑量遞增相比，這可以更快地提高劑量。我們計劃在今年上半年晚些時候的一次醫學會議上（最有可能在 ASCO）展示該試驗的數據。

As a reference point to keep in mind, PSMA is present in 85% to 90% of patients with advanced metastatic prostate cancer. Market research shows that prostate cancer is the third leading cause of cancer death in the United States. There are approximately 174,000 new cases and 31,000 prostate cancer deaths in the United States each year.

請記住，85% 至 90% 的晚期轉移性前列腺癌患者中存在 PSMA。市場研究表明，前列腺癌是美國癌症死亡的第三大原因。美國每年約有 174,000 例前列腺癌新發病例和 31,000 例前列腺癌死亡。

Our second TriTAC product candidate to enter the clinic, HPN536, targets mesothelin. Initially, we began studying HPN536 in platinum refractory ovarian cancer and expanded enrollment to include metastatic pancreatic cancer patients and mesothelioma patients in this trial. Mesothelin is expressed on malignant cells of ovarian and pancreatic carcinomas, mesothelioma, non-small cell lung cancer, and breast cancer, among others.

我們進入臨床的第二個 TriTAC 候選產品 HPN536，針對間皮素。最初，我們開始研究 HPN536 在鉑類難治性卵巢癌中的應用，並將入組範圍擴大到包括轉移性胰腺癌患者和間皮瘤患者。間皮素在卵巢癌、胰腺癌、間皮瘤、非小細胞肺癌和乳腺癌等惡性細胞上表達。

While mesothelin has been the focus of some CAR-T efforts, HPN536 is the first mesothelin targeted T cell engager to enter clinical development. Patients receiving weekly infusions of HPN536, and the trial is proceeding in line with our expectations. At our clinical update in December 2020, we reported dosing 39 patients across nine fixed dose cohorts at 6 to 280 nanogram per kilogram and one step dose cohort up to 600 nanogram per kilogram.

雖然間皮素一直是一些 CAR-T 項目的重點，但 HPN536 是第一個進入臨床開發的間皮素靶向 T 細胞接合劑。患者每週接受 HPN536 輸注，試驗的進展符合我們的預期。在 2020 年 12 月的臨床更新中，我們報告了 9 個固定劑量組的 39 名患者的劑量為 6 至 280 納克每公斤，一步劑量組的劑量高達 600 納克每公斤。

Since the update, we have advanced to a 1,200 nanogram per kilogram step dosing cohort. The experience we have gained from HPN424 has been beneficial in our conduct of the 536 trial. We expect to provide interim data from the ongoing dose escalation portion of the trial by the year end 2021, possibly at ESMO or at [Citi], as well as initiation of a dose expansion cohort in the second half of 2021.

自更新以來，我們已將劑量劑量提升至每公斤 1,200 納克。我們從 HPN424 中獲得的經驗對我們進行 536 試驗是有益的。我們預計到 2021 年年底，可能在 ESMO 或 [Citi] 提供該試驗正在進行的劑量遞增部分的中期數據，並在 2021 年下半年啟動劑量擴展隊列。

Our third TriTAC product candidate, HPN217 targets B-cell maturation antigen or BCMA. We initiated a Phase 1/2 clinical trial in April 2020 in the treatment of relapsed refractory multiple myeloma and are pleased by the progress of the trial. This program is covered by a collaboration and option agreement with AbbVie. And dosing of the first patient triggered a milestone payment of $50 million, which we received in June 2020.

我們的第三個 TriTAC 候選產品 HPN217 靶向 B 細胞成熟抗原或 BCMA。我們於2020年4月啟動了治療復發難治性多發性骨髓瘤的1/2期臨床試驗，並對試驗的進展感到高興。該計劃包含在與艾伯維 (AbbVie) 的合作和期權協議中。第一位患者的給藥引發了 5000 萬美元的里程碑付款，我們於 2020 年 6 月收到了這筆付款。

In January 2021, HPN217 received orphan drug designation from the FDA. And our December clinical update, we indicated we had treated six single-patient fixed dose cohorts of 5 to 810 micrograms, reflecting a more than hundredfold increase in dose within the first eight months of the trial. A presentation of interim data is expected in 2021, possibly at ASH. And we expect to initiate a dose expansion cohort in the second half of 2021.

2021年1月，HPN217獲得FDA孤兒藥資格認定。我們 12 月的臨床更新表明，我們已經治療了 6 個單患者固定劑量組，劑量為 5 至 810 微克，反映出試驗前八個月內劑量增加了一百多倍。預計將於 2021 年在 ASH 上發布中期數據。我們預計將在 2021 年下半年啟動劑量擴展隊列。

HPN328 is our fourth TriTAC product candidate. And it targets delta-like ligand 3 or DLL3, a protein highly expressed in a majority of small cell lung cancers and other DLL3 expressing tumors. We submitted an IND for HPN328 in the third quarter of 2020 and initiated the Phase 1/2 clinical trial in December, which includes step dosing as part of the protocol. We expect to present interim data from the dose escalation portion of the trial in the second half of 2021.

HPN328 是我們的第四個 TriTAC 候選產品。它的目標是 δ 樣配體 3 或 DLL3，這是一種在大多數小細胞肺癌和其他表達 DLL3 的腫瘤中高度表達的蛋白質。我們於 2020 年第三季度提交了 HPN328 的 IND，並於 12 月啟動了 1/2 期臨床試驗，其中包括階梯給藥作為方案的一部分。我們預計在 2021 年下半年提供試驗劑量遞增部分的中期數據。

Despite the challenges of this past year, it was a period of impressive pipeline advancement for Harpoon. With four programs in the clinic, we look forward to providing clinical data from all of our product candidate programs in 2021 and beyond. We have a unique off-the-shelf platform for T cell engagers that reprogram a patient's own immune cells to treat a wide variety of malignancies. Our unique pipeline is well positioned to generate exciting data and drive shareholder value.

儘管過去的一年面臨著挑戰，但 Harpoon 的產品線進展卻令人印象深刻。四個項目已進入臨床階段，我們期待在 2021 年及以後提供所有候選產品項目的臨床數據。我們擁有一個獨特的現成 T 細胞接合器平台，可以對患者自身的免疫細胞進行重新編程，以治療多種惡性腫瘤。我們獨特的渠道能夠很好地生成令人興奮的數據並推動股東價值。

With that, I will now turn the call over to Georgia for a discussion of our financial results for the fourth quarter and the full year 2020.

現在，我將把電話轉給喬治亞州，討論我們第四季度和 2020 年全年的財務業績。

Thank you, Jerry. And good afternoon, everyone. I will provide a brief overview of our financial results here on the call and invite you to review our 10-K filed today for a more detailed discussion.

謝謝你，傑瑞。大家下午好。我將在電話會議上簡要概述我們的財務業績，並邀請您查看我們今天提交的 10-K 以進行更詳細的討論。

Revenue for the fourth quarter ended December 31, 2020, was $7.5 million compared to $2.2 million for the fourth quarter ended December 31, 2019. Revenue for the year ended December 31, 2020, was $17.4 million compared to $5.8 million for the prior year. During both the three-month period and full year periods, the increase in revenue was primarily due to the revenue recognized from the development and option agreement with AbbVie signed in November of 2019.

截至2020年12月31日的第四季度收入為750萬美元，而截至2019年12月31日的第四季度收入為220萬美元。截至2020年12月31日的年度收入為1740萬美元，而上一年為580萬美元。在三個月期間和全年期間，收入的增長主要是由於2019年11月與艾伯維簽署的開發和期權協議確認的收入。

I want to remind everyone that revenue recognition is a noncash amortization of cash we have already received. Research and development expense for the fourth quarter of 2020 was $15.1 million compared to $12.7 million for the fourth quarter ended December 31, 2019. R&D expense for the year ended December 31, 2020, was $52.6 million compared to $41.6 million for the prior year.

我想提醒大家，收入確認是我們已經收到的現金的非現金攤銷。 2020年第四季度的研發費用為1510萬美元，而截至2019年12月31日的第四季度的研發費用為1270萬美元。截至2020年12月31日止年度的研發費用為5260萬美元，而上一年的研發費用為4160萬美元。

The increase for both periods was primarily due to higher clinical development and personnel-related expense, including conducting preclinical studies and continuation or initiation of clinical trials for HPN424, HPN536, HPN217, and HPN328. These higher expenses were offset by a decrease in manufacturing costs, which resulted from a scale-up of manufacturing activities in 2019 compared to 2020 to support our four TriTAC product candidates.

這兩個時期的增長主要是由於臨床開發和人員相關費用增加，包括進行臨床前研究以及繼續或啟動 HPN424、HPN536、HPN217 和 HPN328 的臨床試驗。這些較高的費用被製造成本的下降所抵消，這是由於 2019 年為支持我們的四種 TriTAC 產品候選而擴大了製造活動。

General and administrative expenses for the quarter ended December 31, 2020, were $3.9 million compared to $4.3 million for the fourth quarter of 2019. General and administrative expenses for the year ended December 31, 2020, were $16.2 million compared to $22.4 million for the prior year.

截至2020 年12 月31 日止季度的一般及行政費用為390 萬美元，而2019 年第四季度為430 萬美元。截至2020 年12 月31 日止年度的一般及行政費用為1,620 萬美元，而上一季度為2,240 萬美元。年。

The decrease was primarily attributable to lower legal expenses partially offset by an increase in personnel expenses related to a higher headcount and professional services to support our ongoing operations as a public company.

減少的主要原因是法律費用減少，但部分被與員工人數增加和專業服務相關的人員費用增加所抵消，以支持我們作為上市公司的持續運營。

The net loss for the fourth quarter ended December 31, 2020, was $11.4 million compared to $14.3 million for the fourth quarter ended December 31, 2019. Net loss for the year ended December 31, 2020, was $49.9 million compared to $55.6 million for the prior year. Harpoon Therapeutics ended 2020 with $150 million in cash and cash equivalents compared to $155.1 million as of December 31, 2019.

截至2020年12月31日止第四季度的淨虧損為1140萬美元，而截至2019年12月31日止第四季度的淨虧損為1430萬美元。截至2020年12月31日止年度的淨虧損為4990萬美元，而截至2019年12月31日止年度的淨虧損為5560萬美元。去年。 Harpoon Therapeutics 截至 2020 年末的現金和現金等價物為 1.5 億美元，而截至 2019 年 12 月 31 日為 1.551 億美元。

Net cash used in investing activities for the year ended December 31, 2020, was $63.6 million, primarily related to the purchase and maturities of marketable securities. Net cash provided by financing activities for the year ended December 31, 2020, was $4.7 million, primarily comprised of approximately $3.0 million in net proceeds from the sale of our common stock pursuant to our controlled equity offering with Cantor Fitzgerald in October and November of 2020.

截至2020年12月31日止年度，投資活動使用的現金淨額為6360萬美元，主要與有價證券的購買和到期有關。截至2020 年12 月31 日的年度融資活動提供的淨現金為470 萬美元，主要包括根據我們於2020 年10 月和11 月與Cantor Fitzgerald 進行的受控股權發行出售普通股的淨收益約300 萬美元。

Net cash used in operations for the year ended December 31, 2020, was $8.6 million. And I would like to remind you that the cash balance at the end of the year does not include the follow-on financing that closed on January 11, 2021, resulting in a net cash proceeds of approximately $108.1 million. On a pro forma basis for the offering we completed in January 2021, Harpoon's cash balance was $258 million. For 2021, we are estimating cash used in operating activities will be approximately $85 million to $95 million.

截至 2020 年 12 月 31 日止年度，運營所用現金淨額為 860 萬美元。我想提醒大家的是，年末現金餘額不包括2021年1月11日結束的後續融資，由此產生的淨現金收益約為1.081億美元。根據我們於 2021 年 1 月完成的發行預計，Harpoon 的現金餘額為 2.58 億美元。 2021 年，我們預計經營活動所用現金約為 8500 萬至 9500 萬美元。

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

這樣，我現在將把電話轉回給傑瑞。

Thank you, Georgia. I am very pleased with the tremendous progress Harpoon made during the past year. The momentum with which we have entered 2021 and the exciting potential of all of our product candidates and our proprietary TriTAC and ProTriTAC platforms. With four of our product candidates, HPN424, 536, 217, and 328, all in clinical development, we achieved the goal we stated at the time of our IPO in early 2019.

謝謝你，格魯吉亞。我對 Harpoon 在過去一年取得的巨大進步感到非常高興。我們進入 2021 年的動力以及我們所有候選產品和我們專有的 TriTAC 和 ProTriTAC 平台的令人興奮的潛力。我們的四個候選產品 HPN424、536、217 和 328 均處於臨床開發階段，我們實現了 2019 年初 IPO 時提出的目標。

We expect 2021 to be an exciting year for Harpoon. We plan to initiate expansion cohorts in three of our four clinical programs and plan to provide data updates to our shareholders throughout the year. Our financial position is strong. And we have the resources in place to continue advancing our pipeline.

我們預計 2021 年對於 Harpoon 來說將是激動人心的一年。我們計劃在四個臨床項目中的三個中啟動擴展隊列，併計劃全年向股東提供數據更新。我們的財務狀況強勁。我們擁有適當的資源來繼續推進我們的管道。

Before we jump into Q&A, let me quickly review our anticipated near-term milestones, which includes interim data updates for each of our four clinical programs.

在我們開始問答之前，讓我快速回顧一下我們預期的近期里程碑，其中包括我們四個臨床項目中每一個的中期數據更新。

For 424, the dose escalation part of the Phase 1/2a clinical trial is ongoing. We're planning to present interim data and initiate a dose expansion cohort in the first half of this year. We anticipate a second data update from the expansion cohort by the end of 2021.

對於 424，1/2a 期臨床試驗的劑量遞增部分正在進行中。我們計劃在今年上半年提供中期數據並啟動劑量擴展隊列。我們預計到 2021 年底，擴展隊列將進行第二次數據更新。

For HPN536, the Phase 1/2a clinical trial is continuing to enroll patients in the dose escalation part of the trial. We are planning to present interim data from this trial by the end of the year 2021 and initiate a dose expansion cohort in the second half of 2021.

對於 HPN536，1/2a 期臨床試驗正在繼續招募患者參加試驗的劑量遞增部分。我們計劃在 2021 年底之前提供該試驗的中期數據，並在 2021 年下半年啟動劑量擴展隊列。

For HPN217, we expect to present interim data from the dose escalation part of the Phase 1/2 trial in 2021 and initiate the expansion cohort in the second half of 2021.

對於 HPN217，我們預計將在 2021 年提供 1/2 期試驗劑量遞增部分的中期數據，並在 2021 年下半年啟動擴展隊列。

For HPN328, we're planning to present interim data from the dose escalation part of our Phase 1/2 clinical trial in the second half of 2021.

對於 HPN328，我們計劃在 2021 年下半年提供 1/2 期臨床試驗劑量遞增部分的中期數據。

So, with that, operator, we are now ready for questions.

那麼，接線員，我們現在準備好回答問題了。

Thank you. (Operator Instructions) Jonathan Chang, SVB Leerink.

謝謝。 （操作員說明）Jonathan Chang，SVB Leerink。

Hi, guys. Thanks for taking my questions. First question on HPN424. Can you confirm whether or not an abstract has been submitted to ASCO. And can you help set investor expectations as the interim data update?

嗨，大家好。感謝您回答我的問題。關於 HPN424 的第一個問題。您能否確認摘要是否已提交給 ASCO？您能否在中期數據更新時幫助設定投資者預期？

Yeah. What I can say -- Hi, Jonathan -- is that we have submitted an abstract for ASCO. Obviously, our hope is that this would be accepted, and we could present some data from the ongoing trial there. The dataset will be comparable to what we presented at ASCO. in June of last year, which is a very broad and comprehensive look at all the features of the clinical trial.

是的。我能說的是——嗨，喬納森——我們已經向 ASCO 提交了一份摘要。顯然，我們希望這一點能夠被接受，並且我們可以提供正在進行的試驗的一些數據。該數據集將與我們在 ASCO 上展示的數據集相當。去年六月，這是對臨床試驗所有特徵的非常廣泛和全面的審視。

Let me turn it over to Natalie to give a little bit more detail on that.

讓我把它交給娜塔莉，讓她提供更多細節。

Sure. Thanks for the question, Jonathan. This is Natalie. So again, we'd like to give as comprehensive as possible update on the escalation portion of the trial. Remember, the objectives of the first part of the trial are to characterize safety activity, pharmacokinetics, markers of T cell engagement, markers of target engagement such as CTC, so a rich pharmacokinetic and pharmacodynamic dataset. So, all of the objectives of the trial I mentioned, we want to summarize the data and learnings to date.

當然。謝謝你的提問，喬納森。這是娜塔莉。因此，我們想再次提供有關試驗升級部分的盡可能全面的最新信息。請記住，試驗第一部分的目標是表徵安全活性、藥代動力學、T 細胞參與標記、CTC 等靶點參與標記，從而獲得豐富的藥代動力學和藥效數據集。因此，對於我提到的試驗的所有目標，我們希望總結迄今為止的數據和經驗教訓。

Got it. Second question, how should investors be thinking about the potential implications on HPN424 from the Novartis VISION study readout also expected in the first half of the year?

知道了。第二個問題，投資者應該如何考慮諾華 VISION 研究結果對 HPN424 的潛在影響，該研究結果預計也會在今年上半年公佈？

So Jonathan, it's Jerry. So obviously, we're paying close attention to that trial. It's an interesting trial with a small molecule PSMA-targeted agent, a radio conjugate. And it is conducting in a late-stage cancer population, prostate cancer population, with progression and survival as potential endpoints for the trial.

喬納森，是傑瑞。顯然，我們正在密切關注該試驗。這是一項針對小分子 PSMA 靶向藥物（放射性結合物）的有趣試驗。它正在晚期癌症人群、前列腺癌人群中進行，進展和生存作為試驗的潛在終點。

So, we really want to learn from a trial like that because in concept this could be a patient population of interest for us as we think about how to bring 424 to patients. So, it's a trial that we have a lot of interest in, but of course, it is a different modality, although it's the same target. So, we have to be cautious in how much to read through into the data, but we're still interested in those particular endpoints for the trial.

所以，我們真的很想從這樣的試驗中學習，因為從概念上講，當我們考慮如何將 424 帶給患者時，這可能是我們感興趣的患者群體。所以，這是一個我們非常感興趣的試驗，但當然，這是一種不同的模式，儘管它是相同的目標。因此，我們必須謹慎對待要閱讀多少數據，但我們仍然對試驗的那些特定終點感興趣。

Understood. And just last question here. With the Takeda acquisition of Maverick, can you refresh our memories on the latest development and legal status for ProTriTAC? And discuss what, if any, impact the acquisition has on your ProTriTAC strategy? Thank you.

明白了。最後一個問題。隨著武田收購 Maverick，您能否讓我們回憶一下 ProTriTAC 的最新發展和法律地位？並討論此次收購對您的 ProTriTAC 戰略有何影響（如果有）？謝謝。

Well, I will defer the question related to ProTriTAC to Holger. But as it relates to the litigation matter with that's ongoing around this, we can't comment on that. And we will not be able to comment on that today. But maybe Holger, we can talk a little bit about our platform and where we're focused.

好吧，我將把與 ProTriTAC 相關的問題交給 Holger。但由於它涉及正在進行的訴訟事宜，我們無法對此發表評論。今天我們無法對此發表評論。但也許霍爾格，我們可以談談我們的平台和我們的重點領域。

Yeah. I mean so -- our platform, as you know, the ProTriTAC platform aims at bringing the TriTAC advantage of increased stability and presumably fewer side effects to more tumor targets, less safe targets, enabling us to dose an inactive ProTriTAC prodrug and then it gets activated in the patient's tumor, hence, increasing the therapeutic index [there and] allow us to go after targets and indications we weren't able to go after before.

是的。我的意思是這樣的——我們的平台，如你所知，ProTriTAC 平台旨在為更多的腫瘤靶點、不太安全的靶點帶來TriTAC 的穩定性增強和副作用更少的優勢，使我們能夠劑量非活性的ProTriTAC 前藥，然後它得到在患者的腫瘤中被激活，因此增加了治療指數，使我們能夠追求以前無法追求的目標和適應症。

Jonathan, any concrete question from me regarding the platform.

喬納森，我有任何關於該平台的具體問題。

I guess I was curious to know if there were any implications from that acquisition on your strategy for developing the platform?

我想我很想知道這次收購是否會對你們開發平台的策略產生任何影響？

Yeah, I mean, this is a developing story. As of today, I'm not aware of any such impact. But I would say, I have the exact same information about this acquisition as you do. And I think we have to wait a little bit to learn more what this really means in detail.

是的，我的意思是，這是一個正在發展的故事。截至今天，我還沒有意識到任何此類影響。但我想說，關於此次收購，我所掌握的信息與您完全相同。我認為我們需要等待一段時間才能詳細了解這真正意味著什麼。

Got it. Thank you.

知道了。謝謝。

Tara Bancroft, Piper Sandler.

塔拉·班克羅夫特，派珀·桑德勒。

Hi, guys. Thanks for taking the questions. I guess I'll stay on that topic. I'm kind of curious if you consider other prodrug technologies like those [in mechanics] or Amunix. How would you compare your proTriTAC platform? And are you developing additional aspects of this platform that address other masking technologies, for instance?

嗨，大家好。感謝您提出問題。我想我會繼續討論這個話題。我很好奇您是否考慮其他前藥技術，例如 [機械] 或 Amunix。您如何比較您的 proTriTAC 平台？例如，您是否正在開發該平台的其他方面來解決其他屏蔽技術？

Well, let me start to just say that we're obviously -- there are many companies now pursuing ways to bring T cell engagers into the tumor microenvironment. And you referenced some companies doing that. And from the very beginning, we wanted to do something with our platform that would be a logical extension of the advantages we saw on TriTAC. So, I'm going to turn it over to Holger now to give you more detail about that.

好吧，我首先要說的是，很明顯，現在有許多公司正在尋求將 T 細胞參與者帶入腫瘤微環境的方法。您提到了一些公司正在這樣做。從一開始，我們就希望利用我們的平台做一些事情，這將是我們在 TriTAC 上看到的優勢的邏輯延伸。所以，我現在將把它交給 Holger，為您提供更多相關細節。

Thanks, Jerry. Yeah, so to your question, I mean, you're not going to be overly surprised to hear that, we, of course, think our platform is superior to the competitors. And after looking at the landscape, we think there's reason for that.

謝謝，傑瑞。是的，所以對於你的問題，我的意思是，聽到這個消息你不會感到太驚訝，我們當然認為我們的平台優於競爭對手。在觀察了情況之後，我們認為這是有原因的。

Just to point out a few things. Our modality is not Fc base, so the ProTriTAC carries on the TriTAC advantage of not having liabilities like Fc receptor binding and so on and so forth that most of our competitors have. What I personally think are two outstanding attributes of our platform as we have disclosed in the past, one of them is that our platform couples half-life to activation.

只是指出幾件事。我們的模式不是 Fc 基礎，因此 ProTriTAC 繼承了 TriTAC 的優勢，即不具有大多數競爭對手所具有的 Fc 受體結合等缺點。我個人認為，正如我們過去所披露的那樣，我們的平台有兩個突出的屬性，其中之一是我們的平台將半衰期與激活結合起來。

And that means when the drug gets active, it uses its half-life, which is additional safety switch, meaning we can be a little bit more lenient in terms of when and where our drug is getting cleaved because it can't accumulate after activation. That we think raises the possibility of an increased efficacy compared to competitors that don't do that. It's just one example of how we think we are superior to that.

這意味著當藥物變得活躍時，它會使用其半衰期，這是額外的安全開關，這意味著我們可以在藥物裂解的時間和地點方面更加寬鬆一些，因為它在活化後不會積累。我們認為，與不這樣做的競爭對手相比，這提高了效率的可能性。這只是我們認為自己比這更優越的一個例子。

But through to the competition, basically, summary, we maintain the TriTAC advantage, we avoid the Fc-based related issues. And we have some special tricks [and otherwise], it's like the coupling of half-life to activation, in our expectation [leading] potentially to an increased therapeutic index. That was the first part of your question. I think there was a second part, if I recall correctly.

但通過比賽，基本上總結一下，我們保持了TriTAC的優勢，我們避免了基於Fc的相關問題。我們有一些特殊的技巧[和其他]，就像半衰期與激活的耦合一樣，我們期望[導致]潛在的治療指數增加。這是你問題的第一部分。如果我沒記錯的話，我想還有第二部分。

Yeah, I guess maybe just a little bit more information on if you're developing any other kind of masking technology.

是的，我想如果您正在開發任何其他類型的掩蔽技術，可能會提供更多信息。

Right. Thank you. So, yes, I would say innovation at Harpoon never stops. We are constantly working on all our platforms. And yes, we have other aspects we're looking at and evaluating. However, we have not publicly disclosed that. [It's a little bit] too early for that, but as other approaches reach maturity throughout the year, we will continue updating you.

正確的。謝謝。所以，是的，我想說 Harpoon 的創新永遠不會停止。我們在所有平台上不斷努力。是的，我們正在研究和評估其他方面。不過，我們尚未公開披露這一點。 [現在有點]為時過早，但隨著其他方法在全年中趨於成熟，我們將繼續為您提供最新信息。

Thanks so much.

非常感謝。

Yigal Nochomovitz, Citigroup.

伊格爾·諾霍莫維茨，花旗集團。

All right. Great. Thanks for taking the questions. I just had one on HPN328. Is the plan to screen for expression of DLL3 in small cell lung cancer or the expectation that the expression of that target is high, and that tumor C won't need to screen? And additionally, what other tumor types would you go after that have high DLL3 expression?

好的。偉大的。感謝您提出問題。我剛剛在 HPN328 上買了一張。是計劃在小細胞肺癌中篩選 DLL3 的表達，還是期望該靶標的表達很高，並且腫瘤 C 不需要篩選？此外，您還想尋找哪些其他具有高 DLL3 表達的腫瘤類型？

Yes, I'll start the answer. This is Jerry, and I'll turn it over to Natalie. So, we don't believe we need to select for patients for DLL3. The prevalence and expression of this target is actually quite unique and quite profound in many ways.

是的，我要開始回答了。這是傑瑞，我會把它交給娜塔莉。因此，我們認為不需要為 DLL3 選擇患者。這個目標的流行和表達實際上在很多方面都是相當獨特和深刻的。

It does track to the neuro endocrine features of small cell lung cancer compared to typical ad known squamous cell carcinomas of the lung. So, it's pretty unique in that regard. And, from that viewpoint, we also know that the data that emerged from Amgen last year related to targeting DLL3 for T cell engagers was quite encouraging in treating patients broadly who have small cell lung cancer. So, we don't have any requirement to do that in this initial trial.

與典型的已知肺鱗狀細胞癌相比，它確實追踪了小細胞肺癌的神經內分泌特徵。所以，它在這方面非常獨特。而且，從這個角度來看，我們還知道去年安進公司發布的有關 T 細胞接合者靶向 DLL3 的數據對於廣泛治療小細胞肺癌患者來說是相當令人鼓舞的。因此，在這個初步試驗中我們沒有任何要求這樣做。

Natalie, a question related to other tumor types.

娜塔莉，一個與其他腫瘤類型相關的問題。

Sure. So, we're doing both in response to your two-part question. As Jerry mentioned for small cell lung cancer, we do not regard patient selection as required. A hallmark of the TriTAC platform is that cell killing can be achieved with extremely low target antigen density.

當然。因此，我們這樣做是為了回答您的兩部分問題。正如傑里（Jerry）提到的，對於小細胞肺癌，我們不認為患者選擇是必需的。 TriTAC 平台的一個特點是可以以極低的靶抗原密度實現細胞殺傷。

So, in fact, for all four ongoing clinical trials, we take all comers during escalation and we do examine retrospectively the expression of the target to enhance our learnings. But again, given the potency of the molecule or the approach, we could not persuade ourselves that there was a level of expression which was too low. However, for the other tumor types, which don't necessarily have a reasonable chance of DLL3 expression, we are relying on pathology, and we'll accept any tumor type with evidence in pathology that's suggestive of DLL3 expression.

因此，事實上，對於所有四項正在進行的臨床試驗，我們在升級過程中吸收了所有參與者，並且我們確實回顧性地檢查了目標的表達，以增強我們的學習。但同樣，考慮到分子或方法的效力，我們無法說服自己相信表達水平太低。然而，對於其他腫瘤類型，它們不一定具有合理的 DLL3 表達機會，我們依賴於病理學，並且我們將接受任何具有提示 DLL3 表達的病理學證據的腫瘤類型。

So, there's a number of pathologic features which meet that criteria. So, the short answer is any tumor type with some evidence pathologically of DLL3 expression. We're particularly interested in prostate cancer or the so-called neuro endocrine phenotype of prostate cancer, which is increasing in incidence, I think in part because of the selective pressure of the novel androgen targeting medicines.

因此，有許多病理特徵符合該標準。因此，簡短的答案是任何具有 DLL3 表達病理學證據的腫瘤類型。我們對前列腺癌或所謂的前列腺癌神經內分泌表型特別感興趣，這種癌症的發病率正在增加，我認為部分原因是新型雄激素靶向藥物的選擇性壓力。

And there's a strong interest in the field right now to find medicines that are effective for those patients and where very few options exist. So, prostate with neuro endocrine features is important and will be [enrolling knows]. And then in addition, any other patient tumor types with our characteristics of DLL3 expression.

目前，人們對尋找對這些患者有效且選擇很少的藥物有濃厚的興趣。所以，具有神經內分泌特徵的前列腺很重要，並且會[報名就知道]。此外，任何其他具有我們 DLL3 表達特徵的患者腫瘤類型。

Thank you. Just one housekeeping question regarding the dose expansion plans for 536 and 217. Have you determined what dose you will be expanding at for those two studies?

謝謝。只是一個關於 536 和 217 劑量擴展計劃的內務問題。您是否確定了這兩項研究的擴展劑量？

Natalie, you answered that initially. So, they're all ongoing escalations. And of course, we don't have any precision to the doses that will drive the expansions or any of our trials before we do the work. And so, a lot of this will be driven by the data we see that emerges at the various doses.

娜塔莉，你一開始就回答了這個問題。所以，它們都在不斷升級。當然，在我們開展工作之前，我們對推動擴張或任何試驗的劑量沒有任何精確度。因此，這在很大程度上將由我們看到的不同劑量下出現的數據驅動。

Obviously, if one achieves a maximum tolerated dose, then of course, you have a limit, but at this point, we have not achieved an MTD on our two lead programs. And we continue to explore doses to see which doses, warrant expansion moving forward. In the case of 536, that expansion will probably be a tumor-specific expansion. Again, this is a trial that is enrolling three tumor types.

顯然，如果達到了最大耐受劑量，那麼當然會有一個限制，但目前，我們的兩個主導項目尚未實現 MTD。我們繼續探索劑量，看看哪些劑量可以保證繼續擴大。就 536 而言，這種擴展可能是腫瘤特異性的擴展。同樣，這是一項招募三種腫瘤類型的試驗。

So, expansion will most probably involve the treatment of a particular tumor type moving forward. Natalie, anything else you want to add on this question?

因此，擴展很可能涉及對特定腫瘤類型的治療。娜塔莉，你對這個問題還有什麼要補充的嗎？

No, we look forward to giving data updates throughout the year on that data question. Sure. Nothing else to add.

不，我們期待全年提供有關該數據問題的數據更新。當然。沒什麼可補充的了。

Thank you, Jerry, and thank you, Natalie.

謝謝你，傑瑞，謝謝你，娜塔莉。

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene，Truist 證券公司。

Okay. Good to speak to you all, and thanks for taking my questions. Jerry, you've already answered what I just had about MTD. So, let's really focus on 424. What comes after the 300 nanogram dose? Are you going to go into 600? Or given that you have some data in hand with 536, would you feel comfortable jumping to the 1,200 nanogram step dose? And I got to follow-up after that.

好的。很高興與大家交談，感謝您提出我的問題。 Jerry，你已經回答了我剛才關於 MTD 的問題。那麼，讓我們真正關注 424。300 納克劑量之後會發生什麼？你打算進600嗎？或者考慮到您手頭有 536 的一些數據，您是否願意跳至 1,200 納克步進劑量？之後我就得跟進。

Yeah, Natalie can get into more of the nuance here. The determination of any dose, whether it's a step dose or a fixed dose, is determined based on an analysis, of course, of various factors. And although we have increased the dose, threefold threefold in many cases and step dose, we obviously have a lot of discretion as to the actual increment as well as we want to do multiple steps. And all those are are under consideration. So, it's not formulaic in that regard. And let me turn it over to Natalie to add more color to that.

是的，娜塔莉可以在這裡了解更多細微差別。當然，任何劑量的確定，無論是階梯劑量還是固定劑量，都是基於對各種因素的分析來確定的。儘管我們增加了劑量，在許多情況下增加了三倍，並且增加了步驟劑量，但我們顯然對實際增量有很大的自由裁量權，並且我們想要進行多個步驟。所有這些都在考慮之中。因此，在這方面它不是公式化的。讓我把它交給娜塔莉來添加更多的色彩。

Sure. If I understand the question, I just want to clarify that the doses across the trials don't behave in the same way. Although these are all TriTACs, they don't have the exact same potency for various reasons. So, 600 nanograms of one is not the same as 600 nanograms of, say the other. So, learnings from one dose on one trial don't necessarily influence the absolute dose on another trial, if that's what you are asking.

當然。如果我理解這個問題，我只是想澄清一下，試驗中的劑量並不以相同的方式表現。儘管這些都是 TriTAC，但由於各種原因它們並不具有完全相同的效力。因此，一種物質的 600 納克與另一種物質的 600 納克不同。因此，如果您想問的話，從一次試驗中的一個劑量中獲得的經驗並不一定會影響另一次試驗中的絕對劑量。

So, as we mentioned in the December data release, we're exploring step dosing across the trials. We're looking -- at that time, we said, we're looking at 300 in HPN424, and up to 1,200 in HPN536. And we don't have further updates today about dosing, but of course, we'll be sharing more data throughout the year.

因此，正如我們在 12 月發布的數據中提到的，我們正在探索試驗中的分步給藥。我們當時說，我們正在尋找 HPN424 中的 300 個，以及 HPN536 中的 1,200 個。今天我們沒有有關劑量的進一步更新，但當然，我們將在全年分享更多數據。

Okay, great. That actually answers my next question I had. So thanks a lot, guys. Appreciate it.

好的，太好了。這實際上回答了我的下一個問題。非常感謝，伙計們。欣賞它。

Zegbeh Jallah, ROTH Capital Partners.

Zegbeh Jallah，羅仕資本合夥人。

Hi, guys. Just had couple of different questions for you. I think the first is I really like the flow of data that we're going to see this year, particularly from your first two programs. So just kind of want to get a sense of how concrete the data is going to be because I think the early data was just kind of looking at safety, the use of dexamethasone and things like that. And so, are we really going to have data that we can draw comparisons from?

嗨，大家好。只是有幾個不同的問題要問你。我認為第一是我真的很喜歡今年我們將看到的數據流，特別是來自前兩個項目的數據流。所以我只是想了解一下數據的具體程度，因為我認為早期的數據只是關注安全性、地塞米鬆的使用等等。那麼，我們真的會有可以進行比較的數據嗎？

And then the second one here is just, you'll be doing dose expansion this year, at what point are you going to start considering probably some combos, like IO combos. And then third is that DLL3 is exciting, glad you're in the clinic with that, and are we likely to see you expanding into other tumor types looking at that for the mesothelin program? And then the last one, I think this one is probably for Holger or actually Jerry can answer this one as well.

第二個問題是，今年你將進行劑量擴展，你什麼時候會開始考慮一些組合，比如 IO 組合。第三，DLL3 令人興奮，很高興您在臨床中使用它，我們是否有可能看到您擴展到其他腫瘤類型，尋找間皮素項目？然後最後一個，我想這個可能是給霍爾格的，或者實際上傑瑞也可以回答這個。

Just wondering as you continue to expand your pipeline beyond these programs that we have, are you going to just focus more on the ProTriTAC or you got to expand more with your TriTAC? And I'm just wondering, does the ProTriTAC leave some efficacy on the table? It is just more costly that if you don't need it, why use it? Or is it just better and you're just going to continue with that moving forward?

只是想知道，當您繼續將您的管道擴展到我們現有的這些計劃之外時，您是否會更多地關注 ProTriTAC，還是必須通過 TriTAC 進行更多擴展？我只是想知道，ProTriTAC 是否還有一些功效？只是成本更高，如果不需要，為什麼要使用它？或者只是更好，而您只是要繼續前進？

So let me start and hand it over to Holger. And I will start with your last question first, because I'm not sure I completely remember the first two questions at this point. But the last question, ProTriTAC was invented for those targets in which if you were to have a TriTAC that was completely active from the moment of infusion, tt might limit the utility of the drug because of T cell activation against normal tissues. And so the intent of our first development program, HPN601, is to explore a target that has broad potential utility and for which previously there's been shown some evidence of tissue toxicity. So, that is really the goal of our first program. But Holger can address that as well as future products that we're focusing on in the company currently.

那麼，讓我開始並將其交給 Holger。我首先從你的最後一個問題開始，因為我不確定我現在是否完全記得前兩個問題。但最後一個問題，ProTriTAC 是為那些目標而發明的，在這些目標中，如果您要擁有從輸注那一刻起就完全活躍的TriTAC，由於T 細胞針對正常組織的激活，可能會限製藥物的效用。因此，我們第一個開發計劃 HPN601 的目的是探索一個具有廣泛潛在效用的靶標，並且之前已顯示出一些組織毒性的證據。所以，這確實是我們第一個計劃的目標。但霍爾​​格可以解決這個問題以及我們目前在公司重點關注的未來產品。

Yeah, so as Jerry pointed out, so on one level, there are certain targets. Let me take a step back. We developed ProTriTAC to be able to go after targets we can't go after with TriTAC for safety reasons. As Jerry pointed out, and there's one answer to your question, use ProTriTAC for things that we can't use TriTAC like targeting EpCAM.

是的，正如傑里指出的那樣，在某種程度上，有某些目標。讓我退後一步。我們開發 ProTriTAC 是為了能夠實現出於安全原因而使用 TriTAC 無法實現的目標。正如 Jerry 所指出的，您的問題只有一個答案，即使用 ProTriTAC 來完成我們無法使用 TriTAC 的任務，例如針對 EpCAM。

Now your question is and then implied in my answer is that there are targets when you can't use TriTAC. And your question is are we going to switch from TriTAC to ProTriTAC for those targets. And everything else being equal, my answer would be likely no, because in principle, when we can keep things simple, we will keep things simple. So ProTriTAC is more complicated than TriTAC, which from my very scientific point of view, is an added liability, just due to complexity, if I can avoid that, I will.

現在你的問題是，然後在我的回答中暗示的是，當你不能使用 TriTAC 時，有一些目標。您的問題是，針對這些目標，我們是否要從 TriTAC 切換到 ProTriTAC。在其他條件相同的情況下，我的答案可能是否定的，因為原則上，當我們能夠使事情變得簡單時，我們就會使事情變得簡單。所以 ProTriTAC 比 TriTAC 更複雜，從我非常科學的角度來看，這是一個額外的責任，只是由於復雜性，如果我能避免這種情況，我會的。

But as you know, these compounds are in the clinic, both TriTACs and -- TriTACs are in the clinics, ProTriTACs are hopefully going to be in the clinic soon or at some point in the future. And as we get this data, we're going to adjust our position there. But as of today, I look at them as optimal for different kinds of targets and hence different indications. So, I see them next to each other. But again, this is going to be driven by data over the next few years.

但正如您所知，這些化合物已經進入臨床，TriTAC 和 TriTAC 都已經進入臨床，ProTriTAC 希望很快或在未來的某個時候進入臨床。當我們獲得這些數據時，我們將調整我們的立場。但截至今天，我認為它們對於不同類型的目標以及因此不同的適應症都是最佳的。所以，我看到他們彼此相鄰。但同樣，這將由未來幾年的數據驅動。

Okay. Zegbah, your question on DLL3, I think that was your third question. What was that one again?

好的。 Zegbah，您關於 DLL3 的問題，我認為這是您的第三個問題。那又是什麼？

Yeah, I was just saying it's a very interesting target, and I was just wondering if you're going to expand to other tumor types, like you've kind of done with your mesothelin program in terms of expanding to other tumors?

是的，我只是說這是一個非常有趣的目標，我只是想知道你是否會擴展到其他腫瘤類型，就像你在擴展到其他腫瘤方面對間皮素項目所做的那樣？

Yes. Anyway, Natalie, just gave an answer to that and we have that plan. In fact, we are including other tumor types in our Phase 1 dose escalation. Natalie, do you want to briefly indicate that again, maybe?

是的。不管怎樣，娜塔莉，剛剛給出了答案，我們已經有了那個計劃。事實上，我們在第一階段劑量遞增中也包括了其他腫瘤類型。娜塔莉，你想再次簡短地指出這一點嗎？

Sure. And hi, Zegbeh. So, the comparison to 536, it's a slightly different strategy. So, it's a good question. So, HPN536, the mesothelin targeting TriTAC, we decided to enroll patients that we believe have tumors that are known to express mesothelin. And we limited that to ovarian cancer patients, pancreatic cancer patients, and mesothelioma patients.

當然。你好，澤格貝。所以，與 536 相比，它的策略略有不同。所以，這是一個好問題。因此，對於 HPN536（靶向 TriTAC 的間皮素），我們決定招募我們認為患有已知表達間皮素的腫瘤的患者。我們僅限於卵巢癌患者、胰腺癌患者和間皮瘤患者。

So, all three of those, mesothelioma in particular, are well characterized as tumor types that express mesothelin. They're all included in escalation, and we have the opportunity to do expansion cohorts for any and all of those. So that's in contrast to DLL3, like you said, where you have one tumor type that expresses DLL3 quite well, small cells, but we're also including in escalation other tumors that show that they have DLL3 expression, right?

因此，所有這三種腫瘤，尤其是間皮瘤，都被明確描述為表達間皮素的腫瘤類型。它們都包含在升級中，我們有機會針對所有這些進行擴展隊列。所以這與 DLL3 形成鮮明對比，就像你說的，其中一種腫瘤類型很好地表達 DLL3，即小細胞，但我們也在升級中包括其他顯示它們具有 DLL3 表達的腫瘤，對嗎？

So that data that could be anything. It could be some neutropenia or neuroendocrine tumors or prostate cancer. So, they're coming in not by the type of cancer they have, but that they're showing that they have DLL3 expression. So, it's a bit of a different tactic, but both of them take different tumor types.

所以這些數據可以是任何東西。它可能是一些中性粒細胞減少症或神經內分泌腫瘤或前列腺癌。因此，他們並不是根據所患癌症的類型來判斷的，而是根據他們表現出的 DLL3 表達情況來判斷的。所以，這是一種有點不同的策略，但它們都採用不同的腫瘤類型。

And then for DLL3 to HPN328, based on what we learn, we can start different expansion cohorts. You could do a basket to again, tumor-agnostic just making sure you have DLL3 expression, you can do small cell because you know they express DLL3 without checking. So, I hope that addresses your question. They both capture different tumors, but kind of in a different way, if that makes sense. One is by indication, and one is by target expression. (Multiple speakers)

然後對於DLL3到HPN328，根據我們學到的知識，我們可以開始不同的擴展隊列。你可以再次做一個籃子，與腫瘤無關，只需確保你有 DLL3 表達，你可以做小細胞，因為你知道它們表達 DLL3 而無需檢查。所以，我希望這能解決你的問題。它們都捕獲不同的腫瘤，但以不同的方式捕獲，如果這有意義的話。一種是通過指示，一種是通過目標表達。 （多位發言者）

And then Zegbeh, you had a question around combinations. And probably, it's easiest to answer that in the context of the prostate trial where we know there are various standard of care products out there where we could consider combining it in late-stage disease. And those are under active consideration as we think about different expansion cohorts for the program. Natalie, any comments around that?

然後 Zegbeh，你有一個關於組合的問題。也許最容易回答的是，在前列腺試驗的背景下，我們知道有各種標準的護理產品，我們可以考慮將其結合到晚期疾病中。當我們考慮該計劃的不同擴展群體時，這些都正在積極考慮中。娜塔莉，對此有何評論？

Sure, real brief. Just building on what you said. For oncology, it's a paradigm of combination regimens, obviously, to sort of maximize efficacy against hard-to-treat diseases. And there's two approaches, or at least, I think I have a simple way in my mind to keep it simple. Either there's a mechanistic or scientific rationale for a combination or there's a standard of care combination that makes sense, or you need to understand how your drug works with the existing standard of care.

當然，非常簡短。只是以你所說的為基礎。對於腫瘤學來說，顯然，這是一種聯合治療方案的範例，可以最大限度地提高針對難以治療的疾病的療效。有兩種方法，或者至少，我認為我心中有一種簡單的方法來保持簡單。要么有一個組合的機械或科學原理，要么有一個有意義的護理組合標準，或者您需要了解您的藥物如何與現有的護理標準一起發揮作用。

So those two buckets provide a lot of options for us. Obviously, we can consider IO combinations. There's a rationale for combination with PD, PD-L1 inhibition. You know, with T cell therapies, there's rationale in some tumor types to combine with standard of care, such as PARP inhibitors, which apply to a number of different tumor types with chemotherapy is actually a reasonable thing to do with hormone blockade and prostate cancer.

所以這兩個桶為我們提供了很多選擇。顯然，我們可以考慮IO組合。與 PD、PD-L1 抑制聯合使用是有道理的。您知道，對於T 細胞療法，某些腫瘤類型與標準護理相結合是有道理的，例如PARP 抑製劑，它適用於許多不同的腫瘤類型，而化療實際上對於激素阻斷和前列腺癌來說是合理的。

So, the answer is sort of yes, yes, and yes. We're thinking carefully about rational combination strategies for each program based on the tumor type. And our protocols and approach allow us to pursue that in expansion. Of course, we anticipate monotherapy activity for all of our compounds, and we strive to demonstrate that. But at the same time, we're already doing preclinical work and giving some thought to what combinations makes sense.

所以，答案是肯定的，是的，是的。我們正在根據腫瘤類型仔細思考每個方案的合理組合策略。我們的協議和方法使我們能夠在擴張中追求這一目標。當然，我們預計所有化合物都具有單一療法活性，並且我們努力證明這一點。但與此同時，我們已經在進行臨床前工作，並思考什麼組合才是有意義的。

Perfect. Very helpful. Thanks for all the updates and looking forward to the data readouts.

完美的。很有幫助。感謝您的所有更新並期待數據讀出。

Arlinda Lee, Canaccord.

阿琳達·李，Canaccord。

Arlinda, can you hear us?

阿琳達，你能聽到我們說話嗎？

Hi, guys. Thanks for taking my questions and congratulations and we're looking forward to all the data that's coming out this year.

嗨，大家好。感謝您提出問題並表示祝賀，我們期待今年發布的所有數據。

I had maybe a broader question about your appetite for additional collaboration. Are you planning on taking all of these forward yourself? I mean, except for 217, I guess, which has the AbbVie collaboration there. And can you remind us on the AbbVie side, at what point is the handoff happening after your Phase 1/2, but at how much -- are you going to hand over just expansion data or is dose escalation data sufficient? Thank you very much.

我可能有一個更廣泛的問題，關於您對更多合作的興趣。您打算親自推進所有這些工作嗎？我的意思是，我猜除了 217 之外，它與艾伯維 (AbbVie) 合作。您能否提醒我們艾伯維方面，在第 1/2 階段之後什麼時候進行交接，但交接的程度是多少——您打算僅交接擴展數據還是劑量遞增數據就足夠了？非常感謝。

Yeah. So, I'll answer AbbVie is the second. So, on the case of the trials, obviously, these are Phase 1/2a or Phase 1/2 trial. So having data from those trials, it's important to us. Before we even think about whether we want to work with other companies, I think we feel good about the targets and the programs, and we want to see that we have the capital to see that data. So, there's no real reason for us to enter into anything specifically around the programs until we generate those data sets.

是的。所以，我會回答艾伯維是第二個。因此，就試驗而言，顯然這些是 1/2a 期或 1/2 期試驗。因此，獲得這些試驗的數據對我們來說很重要。在我們考慮是否要與其他公司合作之前，我認為我們對目標和計劃感覺良好，並且我們希望看到我們有資本查看這些數據。因此，在生成這些數據集之前，我們沒有真正的理由專門參與有關程序的任何事情。

In the case of the AbbVie collaboration, that was an option deal or is an option deal that was started when the program was built preclinical. And the goal there was to have a potential late-stage development commercial partner for us. And so, we're generating hopefully Phase 2 data that would allow them to make a decision on whether or not to license the asset for the $200 million plus milestones and royalties. So, the option agreement really gives us an opportunity to work with them at the appropriate time. So that's the way that deal is structured. Hopefully that answers your question.

就艾伯維合作而言，這是一項期權交易，或者是在項目臨床前構建時開始的期權交易。我們的目標是為我們找到一個潛在的後期開發商業合作夥伴。因此，我們希望生成第二階段的數據，使他們能夠決定是否以 2 億美元加上里程碑和特許權使用費來許可該資產。所以，期權協議確實讓我們有機會在適當的時候與他們合作。這就是交易的結構方式。希望這能回答你的問題。

Thank you.

謝謝。

Colleen Kusy, Baird.

科琳·庫西，貝爾德。

Hi, good afternoon. Thanks for taking our question. So, on HPN536, and the last update was largely focused on ovarian. Will the next update later this year include additional tumor types? Or would we expect that to be likely focused on ovarian as well?

嗨，下午好。感謝您提出我們的問題。所以，在 HPN536 上，最後一次更新主要集中在卵巢上。今年晚些時候的下一次更新會包括其他腫瘤類型嗎？或者我們是否期望這也可能集中在卵巢上？

Yes, no, the medical conference update will be a comprehensive look at the trial, including all of the patients that have been enrolled from the three tumor types that we mentioned.

是的，不，醫學會議更新將全面審視該試驗，包括我們提到的三種腫瘤類型的所有入組患者。

In December, we just thought it was interesting to highlight a couple of patients in the ovarian part of this study that showed possibly some evidence of early antitumor effect that albeit lower doses than what we're pursuing right now. But the goal at the medical conference in the second half of the year would be to have a broad, comprehensive look at the trial in the same way that we're going to be presenting a broad data set for the 424 trial, hopefully at ASCO. Okay?

12 月，我們只是認為在這項研究的卵巢部分中強調幾位患者很有趣，這些患者可能顯示出一些早期抗腫瘤作用的證據，儘管劑量低於我們現在正在追求的劑量。但今年下半年醫學會議的目標是對這項試驗進行廣泛、全面的審視，就像我們將在 ASCO 上展示 424 試驗的廣泛數據集一樣。好的？

Yeah, great. Thank you. And then a quick follow-up. So, for HPN601, it's still in early stages, but any lead indications that look the most interesting to you at this stage?

很好。謝謝。然後快速跟進。那麼，對於 HPN601，它仍處於早期階段，但現階段您認為有哪些先導跡像是您最感興趣的嗎？

Well, we've mentioned the gastrointestinal tumors are particularly interesting, EpCAM is broadly expressed on many tumors. But from a portfolio point of view, we don't have a product focus in that area. And that would, I think, complement the rest of the portfolio to have some tumor types that are not represented by our other programs.

嗯，我們已經提到胃腸道腫瘤特別有趣，EpCAM 在許多腫瘤中廣泛表達。但從產品組合的角度來看，我們在該領域沒有產品重點。我認為，這將補充產品組合的其餘部分，以提供我們其他項目未代表的一些腫瘤類型。

Great, thank you.

太好了謝謝。

Robert Driscoll, Wedbush Securities.

羅伯特·德里斯科爾，韋德布什證券公司。

Thanks. Good afternoon, guys. Just just one quick question from me. I'm just thinking about the various dose regimens being evaluated for HPN424. Could you see some flexibility being built into any kind of selected regimen for the expansion cohort? And maybe going forward how you might think about continuing to refine that dose? Thanks.

謝謝。下午好，伙計們。我只想問一個簡單的問題。我只是在考慮正在評估 HPN424 的各種劑量方案。您是否認為擴展隊列的任何選定方案都具有一定的靈活性？也許未來您會如何考慮繼續改進該劑量？謝謝。

Yeah, no it's a very good question because this is something that is quite dynamic. And we are pursuing many ways to advance dose escalation. Natalie comments around that?

是的，不，這是一個非常好的問題，因為這是一個非常動態的問題。我們正在尋求多種方法來推進劑量遞增。娜塔莉對此有何評論？

Yeah, I agree. And if what you mean is, can we on one hand, explore a particular dose and expansion to get a little better characterization of its activity and safety profile and also escalate, at the same time, it is similar or in different patients? yes, we have the flexibility to do that.

是的，我同意。如果你的意思是，我們是否可以一方面探索特定的劑量和擴展，以更好地表徵其活性和安全性，同時升級，它是相似的或在不同的患者中？是的，我們可以靈活地做到這一點。

Got it. Thanks, guys.

知道了。多謝你們。

Sean Kang, H.C. Wainwright.

肖恩·康，H.C.溫賴特。

Hi, thank you for taking my question. Actually, so all my questions have been already answered, but just a quick one. With multiple expansion cohort initiating in second half '21, what would be the impact on the R&D expenses on second half '21 and maybe '22?

你好，謝謝你回答我的問題。事實上，我所有的問題都已經得到解答，但只是一個簡短的回答。隨著 21 年下半年啟動多個擴展隊列，對 21 年下半年甚至 22 年下半年的研發費用有何影響？

Yes. Well, let me just clarify. So, the current protocols that we have are Phase 1/2a or Phase 1/2 trials. So, the expansions, as we've described them, have already been -- we can model those expenses appropriately. Obviously, these are not -- we're not talking about new protocols. New protocols, of course, would be incremental. But maybe I'll turn it over to Georgia to answer that question.

是的。好吧，讓我澄清一下。因此，我們目前的方案是 1/2a 期或 1/2 期試驗。因此，正如我們所描述的那樣，擴張已經——我們可以適當地對這些費用進行建模。顯然，這些不是——我們不是在談論新協議。當然，新協議將是漸進的。但也許我會把它交給喬治亞州來回答這個問題。

So, the guidance that we gave does include everything that we've been talking about today in terms of expansion cohorts and clinical plans for 2021. And we have not given guidance for 2022 as of this time.

因此，我們給出的指導確實包括我們今天在 2021 年擴展隊列和臨床計劃方面討論的所有內容。截至目前，我們尚未給出 2022 年的指導。

Okay. Sounds good. Thank you.

好的。聽起來不錯。謝謝。

Okay. Well, thanks -- no, go ahead.

好的。好吧，謝謝——不，繼續吧。

I'm not showing any further questions at this time. I'd now like to turn the call back over to Jerry McMahon for any further remarks.

我目前不會提出任何進一步的問題。我現在想將電話轉回傑里·麥克馬洪以徵求進一步意見。

Yes, just briefly, thank you all once again for joining the call today. If you have any additional questions, please feel free to contact us. Have a good evening, everybody.

是的，簡單地說，再次感謝大家參加今天的電話會議。如果您還有任何其他問題，請隨時與我們聯繫。祝大家晚上好。

Thank you, ladies and gentlemen. And this concludes today's conference call. Thank you for participating. You may now disconnect.

謝謝你們，女士們、先生們。今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。