Cogent Biosciences, Inc. (COGT) 2019 Q2 法說會逐字稿

Good afternoon, and welcome to the Unum Therapeutics quarterly investor conference call. Today, we'll be showing updates on our company's progress and our financial results for the second quarter of 2019.

下午好，歡迎參加 Unum Therapeutics 季度投資者電話會議。今天，我們將展示公司最新進展以及2019年第二季的財務表現。

With me on our call today are Chuck Wilson, CEO; Jessica Sachs, CMO; Seth Ettenberg, CSO; and Matt Osborne, CFO. Following our prepared remarks, we'll open the line for questions. Before we begin our prepared remarks, I'll remind you that the estimates and forward-looking statements included in this call represent the company's view as of today, August 12, 2019. Unum Therapeutics disclaims any obligation to update these statements to reflect the future events or circumstances. Please refer to today's press release as well as Unum's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements. Please note that the call is simultaneously webcast online. With that, I'll turn the call over to Chuck Wilson, Unum's CEO. Chuck?

今天和我一起參加電話會議的有：執行長 Chuck Wilson；行銷長 Jessica Sachs；首席策略長 Seth Ettenberg；以及財務長 Matt Osborne。在我們發表完準備好的演講後，我們將開放提問環節。在我們開始正式發言之前，我要提醒各位，本次電話會議中包含的估計和前瞻性陳述代表了公司截至 2019 年 8 月 12 日的觀點。Unum Therapeutics 聲明沒有義務更新這些聲明以反映未來的事件或情況。請參考今天的新聞稿以及 Unum 向美國證券交易委員會提交的文件，以了解可能導致實際結果與此類聲明中明示或暗示的結果有重大差異的風險因素。請注意，本次通話將同時進行網路直播。接下來，我將把電話交給 Unum 的執行長 Chuck Wilson。查克？

Thank you, and good afternoon. I'm pleased to report the progress we've made during the quarter across our preclinical and pipeline programs based on our ACTR and BOXR platforms. On this call, Jessica will discuss the updated results presented today from our ACTR707 trial in non-Hodgkin lymphoma, our activities with ACTR087 targeting BCMA in multiple myeloma, and our progress with ACTR707 in combination with trastuzumab targeting solid tumors. Seth will describe BOXR1030, the first product candidate to emerge from our BOXR platform; and Matt will review the financials.

謝謝，下午好。我很高興地向大家匯報，本季我們在基於 ACTR 和 BOXR 平台的臨床前和在研項目方面取得了進展。在本次電話會議上，Jessica 將討論我們今天發表的 ACTR707 在非何杰金氏淋巴瘤試驗中的最新結果，我們針對 BCMA 治療多發性骨髓瘤的 ACTR087 的研究進展，以及 ACTR707 與曲妥珠單抗聯合治療實體瘤的進展。Seth 將介紹 BOXR1030，這是我們 BOXR 平台誕生的第一個候選產品；Matt 將審查財務狀況。

Before turning it over to Jessica, I want to take a moment to highlight from a broader level the approach with both ACTR and BOXR, and the ability of these technologies to service platforms for Unum. With ACTR, we can use the same ACTR T cell product in potentially many different types of cancer. This is because the extracellular portion of ACTR derived from CD16, an immune cell receptor, targets the T cell [to] the tumor in a directed way, only in the presence of a monoclonal antibody. We can then combine this ACTR T cell with a range of different monoclonal antibodies to target tumor antigens. We don't need to reengineer the T cell each time we want to target a different tumor antigen. We're currently testing this approach with rituximab and anti-BCMA antibody in hematologic malignancies and with trastuzumab and HER2+ solid tumors to drive tumor cell killing. The second potential key benefit of ACTR is the ability to control or tune the level of its activity. This ability to control T cell activity doesn't exist with current generation T cell therapy. We're currently exploring the impact of antibody dose on ACTR T cell activity in multiple dose escalating Phase I trials.

在將發言權交給傑西卡之前，我想花點時間從更廣泛的層面上重點介紹 ACTR 和 BOXR 的方法，以及這些技術為 Unum 平台提供服務的能力。透過 ACTR，我們可以將同一種 ACTR T 細胞產品用於治療多種不同類型的癌症。這是因為源自 CD16（一種免疫細胞受體）的 ACTR 的細胞外部分，只有在單株抗體存在的情況下，才能以定向的方式將 T 細胞靶向腫瘤。然後，我們可以將這種 ACTR T 細胞與一系列不同的單株抗體結合，以靶向腫瘤抗原。我們不需要每次想要靶向不同的腫瘤抗原時都對 T 細胞進行重新設計。我們目前正在使用利妥昔單抗和抗BCMA抗體治療血液系統惡性腫瘤，以及使用曲妥珠單抗和HER2+實體瘤測試此方法，以促進腫瘤細胞死亡。ACTR 的第二個潛在關鍵優勢是能夠控製或調節其活動量。目前這一代T細胞療法還不具備控制T細胞活性的能力。我們目前正在透過多劑量遞增的 I 期試驗，探索抗體劑量對 ACTR T 細胞活性的影響。

BOXR was specifically developed by Unum to improve engineered T cell functionality by identifying and incorporating a bolt-on transgene to overcome resistance by the solid tumor microenvironment to T cell attack. Solid tumors are very good at making a hostile environment to T cells. They do this in part by creating competition for metabolic resources by suppressing immune cells and by exhausting T cells due to chronic stimulation. BOXR is designed to identify transgenes to potentially overcome these mechanisms and incorporate them into different types of T cells. As Seth will describe, we expect to advance BOXR1030 towards clinical trials to treat liver and lung cancers. We're excited by the ability of ACTR and BOXR to generate novel product candidates. We've been able to create 3 unique constructs and drive them forward in 4 separate clinical trials, while applying best-in-class manufacturing, clinical development and regulatory capabilities.

BOXR 是 Unum 公司專門開發的，旨在透過識別和整合外接轉基因來提高工程化 T 細胞的功能，從而克服實體瘤微環境對 T 細胞攻擊的抵抗力。實體瘤非常擅長為T細胞創造不利環境。它們透過抑制免疫細胞和透過慢性刺激耗盡 T 細胞，從而造成代謝資源的競爭，部分原因就在於此。BOXR 旨在識別能夠克服這些機制的轉基因，並將其整合到不同類型的 T 細胞中。正如 Seth 將要描述的那樣，我們希望推進 BOXR1030 進入臨床試驗階段，用於治療肝癌和肺癌。我們對 ACTR 和 BOXR 產生新型候選產品的能力感到興奮。我們利用一流的生產、臨床開發和監管能力，成功創造了 3 種獨特的結構，並在 4 項獨立的臨床試驗中推進了這些結構的發展。

I also want to take a moment to highlight the new addition to Unum's leadership team, 2 of whom are joining us on today's call. Jessica Sachs was recently appointed to her new role as Chief Medical Officer, having joined Unum in 2017. Jessica has been a core member of the team in setting clinical development strategy and providing medical and translational oversight of the Unum portfolio. She brings deep experience in oncology and pediatrics and a decade in industry, including a decade in Millennium where she led multiple clinical programs in oncology and transplantation, and at Genzyme Corporation where she was responsible for postmarketing, safety surveillance and risk management activities for a variety of oncology products.

我還想藉此機會重點介紹一下 Unum 領導團隊的新成員，其中兩位今天將與我們一起參加電話會議。傑西卡·薩克斯 (Jessica Sachs) 於 2017 年加入 Unum 公司，最近被任命為首席醫療官。Jessica 一直是團隊的核心成員，負責制定臨床開發策略，並對 Unum 產品組合進行醫學和轉化方面的監督。她在腫瘤學和兒科學領域擁有豐富的經驗，並在業界工作了十年，其中包括在 Millennium 公司工作十年，領導了多個腫瘤學和移植領域的臨床項目；以及在 Genzyme 公司工作十年，負責各種腫瘤產品的上市後、安全監測和風險管理活動。

Matt Osborne joined us just over a month ago as Chief Financial Officer. Many of you may know Matt from his role [in] the biotechnology industry over the past 20 years, serving as Investor Relations, Corporate Affairs and Communications lead and as a former sell-side analyst where he helped biotechnology companies grow through various stages of development.

Matt Osborne 於一個多月前加入我們，擔任財務長。你們中的許多人可能都認識 Matt，因為他在過去 20 年裡一直從事生物技術行業的工作，擔任投資者關係、企業事務和傳播主管，並且曾擔任賣方分析師，幫助生物技術公司度過各個發展階段。

And we're also pleased to have Mert Aktar join us as Head of Business and Corporate Development. Mert brings significant multinational experience in pharmaceuticals and biotechnology, including leadership roles in business development and technical operations. And he joins Unum from Shire where he most recently served as a global Head of Hematology and Immunology Business Development. We also recently announced the appointments of 2 new independent board members, Arlene Morris and Matthew Ros. Together they bring significant commercial and corporate development experience within oncology to the board.

我們也很高興Mert Aktar加入我們，擔任業務和企業發展主管。Mert 在製藥和生物技術領域擁有豐富的跨國經驗，曾在業務發展和技術營運方面擔任領導職務。他加入 Unum 之前在 Shire 擔任全球血液學和免疫學業務發展主管。我們最近也宣布任命了兩位新的獨立董事，分別是 Arlene Morris 和 Matthew Ros。他們共同為董事會帶來了腫瘤領域豐富的商業和企業發展經驗。

I'm thrilled with the additions of these members to the team and the Board. Their deep experience and their respective functions will be important to our work, building and advancing a pipeline of engineered T cell therapies. With that, I'll turn it over to Jessica to discuss updates from our clinical pipeline.

我非常高興這些成員加入團隊和董事會。他們豐富的經驗和各自的職能對我們建立和推進工程化 T 細胞療法產品線的工作至關重要。接下來，我將把發言權交給傑西卡，讓她來介紹我們臨床試驗計畫的最新進展。

Thanks, Chuck. Today, we provide preliminary results from the 5 patients treated with ACTR707 and cohort 3 of the ATTCK-20-03 trial. 20-03 trial is a Phase I dose-escalating multicenter trial evaluating ACTR707 in combination with rituximab in patients with relapsed or refractory B cell non-Hodgkin lymphoma. Patients who have enrolled in this trial have had advanced lymphoma, which has proven refractory or resistant to prior treatment. The majority of patients treated today have required alternative therapy following 3 or more prior lines of treatment. We continue to be very encouraged by the preliminary data on the trial to date. Complete responses have been achieved in 5 of the 14 patients treated in the first 3 cohorts, and the overall response rate in the first 2 cohorts combined is more than 50%. This preliminary antitumor activity is particularly encouraging in the context of the observed safety data, specifically no adverse events of cytokine release syndrome or severe neurotoxicity that have been reported with other autologous T cell [product] have been reported in the first 3 cohorts of the trial as of the data cutoff in May of this year. As an update of preliminary data provided today, from the 5 patients treated in cohort 3 after 707 administered in combination with rituximab, following a lymphodepletion regimen, generated a complete response in 1 of 5 patients and an overall response in 4 of 5 patients.

謝謝你，查克。今天，我們提供了 5 名接受 ACTR707 治療的患者以及 ATTCK-20-03 試驗第 3 組患者的初步結果。20-03 試驗是一項 I 期劑量遞增多中心試驗，旨在評估 ACTR707 與利妥昔單抗合併治療復發或難治性 B 細胞非何杰金氏淋巴瘤患者的療效。參加這項試驗的患者均患有晚期淋巴瘤，且已證明對先前的治療無效或抗藥性。目前接受治療的大多數患者都是在接受過 3 種或更多種先前的治療後才需要替代療法。我們對迄今為止的試驗初步數據感到非常鼓舞。在前 3 個隊列中接受治療的 14 名患者中，有 5 名患者達到了完全緩解，前 2 個隊列的總緩解率超過 50%。就觀察到的安全性數據而言，這種初步的抗腫瘤活性尤其令人鼓舞，特別是截至今年 5 月數據截止時，試驗的前 3 個隊列中沒有報告其他自體 T 細胞 [產品] 曾報告的細胞因子釋放綜合徵或嚴重神經毒性等不良事件。根據今天提供的初步數據更新，在淋巴清除方案之後，接受 707 與利妥昔單抗聯合治療的 3 組 5 名患者中，1 名患者達到完全緩解，4 名患者達到整體緩解。

There was also evidence of deepening responses after the first clinical assessment at day 42, where 2 patients with stable disease following the first response assessment subsequently improved to a partial response and a complete response, as of the last data cutoff, which was in May of this year. Overall, we're encouraged with the overall response rate, including complete responses with no adverse events of cytokine release syndrome or severe neurotoxicity in cohorts 1 through 3. We're looking forward to analyzing all of the results, including the results from cohort 4 later this year, to continue to build our understanding of the relationship of cell dose to antitumor activity and safety before determining the recommended dose for further study.

在第 42 天的首次臨床評估之後，也有證據顯示療效加深，其中 2 名在首次療效評估後病情穩定的患者，截至今年 5 月的最後一次數據截止日，分別改善為部分緩解和完全緩解。整體而言，我們對整體緩解率感到鼓舞，包括第 1 至 3 組患者均達到完全緩解，且未出現細胞激素釋放症候群或嚴重神經毒性等不良事件。我們期待分析所有結果，包括今年稍後公佈的第 4 組結果，以便在確定進一步研究的建議劑量之前，繼續深入了解細胞劑量與抗腫瘤活性和安全性之間的關係。

Turning to our ACTR087 Phase I trials in multiple myeloma and non-Hodgkin lymphoma. Dose escalations continued during the quarter in the ATTCK-17-01 Phase I trial, a trial that we're conducting in collaboration with Seattle Genetics, to develop a BCMA targeted therapy for multiple myeloma. Enrollment and dosing of patients in cohorts 4 and 5 of this study is complete, and we expect to report data from this trial in the second half of 2019. As we previously announced, our ATTCK-20-2 Phase I trial, which is a study of ACTR087 in combination with rituximab in patients with relapsed or refractory non-Hodgkin lymphoma, was placed on clinical hold by the FDA in July of 2019 due to serious adverse events, including severe neurotoxicity experienced by a patient on this trial. As an update to this case, this patient subsequently experienced septic shock that was ultimately fatal and reported by the investigator as related to ACTR087.

接下來我們來看看我們在多發性骨髓瘤和非何杰金氏淋巴瘤中進行的 ACTR087 I 期試驗。本季度，ATTCK-17-01 I 期試驗的劑量遞增仍在繼續。該試驗是我們與 Seattle Genetics 合作進行的，旨在開發針對多發性骨髓瘤的 BCMA 標靶療法。本研究第 4 組和第 5 組患者的入組和給藥工作已經完成，我們預計將於 2019 年下半年公佈該試驗的數據。正如我們之前宣布的那樣，我們的 ATTCK-20-2 I 期試驗（一項研究 ACTR087 與利妥昔單抗聯合治療復發或難治性非霍奇金淋巴瘤患者的試驗）於 2019 年 7 月被 FDA 暫停臨床試驗，原因是該試驗中一名患者出現了嚴重的神經毒性等嚴重不良事件。作為該病例的最新進展，該患者隨後出現感染性休克，最終死亡，調查人員報告稱這與 ACTR087 有關。

Since our announcement of the hold, the FDA provided written comments to us clarifying that the trial was on partial clinical hold. Patients who previously received ACTR087 and have ongoing clinical responses can continue to receive rituximab infusions with continued monitoring for adverse event per protocol. Recall that late last year, Unum did deprioritize the ACTR087 lymphoma program in favor of the ACTR707 lymphoma program. We plan to report data from the ATTCK-20-2 trial at the end of 2019.

自從我們宣布暫停試驗以來，FDA 向我們提供了書面評論，澄清該試驗處於部分臨床暫停狀態。先前接受過 ACTR087 治療且有持續臨床反應的患者可以繼續接受利妥昔單抗輸注，並依照方案繼續監測不良事件。回想一下，去年年底，Unum 確實降低了 ACTR087 淋巴瘤計畫的優先級，轉而優先發展 ACTR707 淋巴瘤計畫。我們計劃在 2019 年底公佈 ATTCK-20-2 試驗的數據。

Now turning to our effort with ACTR707 in solid tumors. We're excited to pursue ACTR707 in solid tumors based on the results from our preclinical efforts, which suggest that ACTR707 can potentially overcome some of the challenges with traditional T cell therapies in the solid tumor environment. After an extensive screening campaign searching for novel active receptors, we selected the ACTR707 construct for solid tumor cancers based on its improved activity and proliferation, cytokine secretion and persistent assays against solid tumor targets.

現在讓我們來看看我們在實體腫瘤治療中使用 ACTR707 所做的努力。根據我們的臨床前研究結果，我們很高興能夠繼續在實體腫瘤領域研究 ACTR707，這些結果表明 ACTR707 有可能克服傳統 T 細胞療法在實體腫瘤環境中面臨的一些挑戰。經過廣泛的篩選活動尋找新型活性受體後，我們根據ACTR707構建體在實體瘤癌症中的活性和增殖、細胞激素分泌以及針對實體瘤靶點的持久性檢測方面的改進，選擇了該構建體。

In preclinical studies, ACTR707+ T cells administered with trastuzumab were highly selective for HER2 overexpressing tumor cells and were able to discriminate [against] cells from normal tissues known to express low levels of HER2.

在臨床前研究中，使用曲妥珠單抗治療的 ACTR707+ T 細胞對 HER2 過度表現的腫瘤細胞具有高度選擇性，並且能夠區分 [與] 已知表達低水平 HER2 的正常組織細胞。

We initiated the Phase I trial, ATTCK-34-01, with ACTR707 in HER2+ advanced solid tumor cancers earlier, this year. Clinical trials site activation, patient identification, screening and enrollment are underway in this Phase I multicenter, open-label, single-arm dose escalation trial evaluating ACTR707 in combination with trastuzumab. The adaptive design of this study allows us to escalate both the trastuzumab and ACTR707 doses to define the dose combinations that's relevant for a Phase II trial. To date, we've activated 5 clinical trial sites with more [plans] , and we plan to report patient enrollment status and preliminary safety data at the end of 2019.

今年早些時候，我們啟動了針對 HER2+ 晚期實體腫瘤癌症的 ACTR707 的 I 期試驗 ATTCK-34-01。目前，臨床試驗中心正在啟動，患者識別、篩選和入組工作正在進行中。這是一項 I 期多中心、開放標籤、單臂劑量遞增試驗，旨在評估 ACTR707 與曲妥珠單抗合併用藥的療效。本研究的適應性設計使我們能夠逐步增加曲妥珠單抗和 ACTR707 的劑量，以確定與 II 期試驗相關的劑量組合。截至目前，我們已啟動 5 個臨床試驗點，並計劃啟動更多試驗點，我們計劃在 2019 年底公佈患者入組情況和初步安全性數據。

With that, I'll turn the call over to Seth Ettenberg, our Chief Scientific Officer, who'll discuss our BOXR platform and pipeline initiatives in solid tumors.

接下來，我將把電話交給我們的首席科學官塞思·埃滕伯格，他將討論我們在實體瘤領域的 BOXR 平台和研發管線計畫。

Thanks, Jessica. The BOXR technology was created at Unum and is designed to further engineer T cells to overcome the immunosuppressive mechanisms of solid tumors, including metabolic competition, immunosuppressive cells and exhaustion due to chronic stimulation. The BOXR platform does this by identifying bolt-on transgenes that offer the potential to add enhanced functionality to T cells. We've demonstrated that the bolt-on transgenes are interchangeable, and we can incorporate these transgenes into different types of therapeutic T cells, including ACTR T cells and CAR-T cells. Importantly, the new functionality added to T cells by the BOXR transgenes may not be readily achievable by traditional therapeutic approaches. For example, by inserting the gene for an enzyme into an engineered T cell, we are able to [change] it to metabolic pathways in very defined ways while avoiding direct effects on either cancer cells or normal cells, something that cannot easily be accomplished using small molecule or antibody-based drugs.

謝謝你，潔西卡。BOXR 技術由 Unum 公司研發，旨在進一步改造 T 細胞，以克服實體瘤的免疫抑制機制，包括代謝競爭、免疫抑制細胞和慢性刺激導致的耗竭。BOXR 平台透過識別可增強 T 細胞功能的額外轉基因來實現這一目標。我們已經證明，外接轉基因是可以互換的，我們可以將這些轉基因整合到不同類型的治療性 T 細胞中，包括 ACTR T 細胞和 CAR-T 細胞。重要的是，BOXR 轉基因賦予 T 細胞的新功能可能無法透過傳統治療方法輕易實現。例如，透過將酵素的基因插入工程化的 T 細胞中，我們可以以非常明確的方式將其改變為代謝途徑，同時避免對癌細胞或正常細胞產生直接影響，這是使用小分子或抗體藥物難以實現的。

BOXR1030 is our first product candidate to emerge from the platform and consists of a T cell co-expressing a CAR targeted to glypican-3 or GPC3, and an undisclosed metabolism enhancing bolt-on transgene. GPC3 is a well-known oncofetal antigen, which is selectively expressed in a variety of tumor types, including certain liver and lung cancers. We've shown that the bolt-on transgene incorporated [the] BOXR1030 acts as a central regulator of T cell metabolism, and its expression impacts several important functions of T cell biology necessary for activity in solid tumors. In preclinical studies, expression of the metabolic bolt-on transgene achieved complete tumor regressions across a range of stringent xenograft models. In the absence of the bolt-on transgene, there was little to no antitumor activity of the CAR-T in these same stringent models. IND-enabling activities, including toxicology testing and process development to support GMP manufacturing are progressing nicely. We plan to expand the capabilities of the BOXR platform to identify and further pursue new transgenes. Additionally, we plan to provide further preclinical data on BOXR1030 later this year. With that, let me turn the call over to Matt.

BOXR1030 是我們從該平台誕生的第一個候選產品，它由一個 T 細胞組成，該 T 細胞共表達靶向糖蛋白聚醣-3 或 GPC3 的 CAR，以及一個未公開的代謝增強附加轉基因。GPC3 是一種眾所周知的癌胚抗原，它選擇性地表達於多種腫瘤類型中，包括某些肝癌和肺癌。我們已經證明，插入的轉基因 BOXR1030 可作為 T 細胞代謝的中心調節因子，其表達影響 T 細胞生物學的幾個重要功能，這些功能對於實體瘤的活性至關重要。在臨床前研究中，代謝附加轉基因的表達在一系列嚴格的異種移植模型中實現了腫瘤的完全消退。在這些嚴格的模型中，如果沒有外接轉基因，CAR-T 幾乎沒有抗腫瘤活性。IND申報活動，包括毒理學測試和支持GMP生產的製程開發，進展順利。我們計劃擴展 BOXR 平台的功能，以識別和進一步研究新的轉基因。此外，我們計劃在今年稍後提供更多關於 BOXR1030 的臨床前數據。那麼，我把電話交給馬特吧。

Thank you, Seth. During the second quarter of 2019, we realized collaboration revenue of $3.1 million compared to $1.7 million for the same period of 2018. The increase reflects the recognition of a portion of the upfront payment received from Seattle Genetics under Unum's collaboration agreement as well as reimbursements of research and development costs attributed to the collaboration agreement.

謝謝你，塞思。2019 年第二季度，我們的合作收入為 310 萬美元，而 2018 年同期為 170 萬美元。此次成長反映了根據 Unum 與 Seattle Genetics 的合作協議收到的部分預付款的確認，以及與該合作協議相關的研發成本的補償。

R&D expenses of $10.6 million for the second quarter ended June 30, 2019, compared to $9.1 million for the same period of 2018. The increase primarily reflects higher clinical trial costs for the active Phase I trials as well as increased personnel-related costs to support these trials. G&A expenses of $3.1 million for the quarter ended June 30 compared to $2 million for the same period of 2018. The increase primarily related to higher personnel-related costs due to increased headcount and increased expenses related to operating as a public company. Unum's net loss of $10.5 million for the second quarter of 2019 compared to a net loss of $9 million for the same period of 2018. As of the end of Q2, Unum had cash and cash equivalents of $55.9 million, an amount that we believe will fund operating expenses and capital expenditure requirements into early 2021.

截至 2019 年 6 月 30 日的第二季度，研發費用為 1,060 萬美元，而 2018 年同期為 910 萬美元。此次成長主要反映了正在進行的 I 期臨床試驗成本的增加，以及支持這些試驗的人員相關成本的增加。截至 6 月 30 日的季度，一般及行政費用為 310 萬美元，而 2018 年同期為 200 萬美元。成長主要與人員增加導致的人員相關成本上升以及作為上市公司營運相關費用增加有關。Unum 2019 年第二季淨虧損 1,050 萬美元，而 2018 年同期淨虧損 900 萬美元。截至第二季末，Unum 擁有現金及現金等價物 5,590 萬美元，我們認為這筆款項足以支付營運費用和資本支出需求，直至 2021 年初。

With that, I'll turn it over to Chuck.

這樣，我就把麥克風交給查克了。

Thank you, Matt. We're excited with the progress during the quarter with our ACTR and BOXR platforms, with the data emerging from ACTR707 and relapsed/refractory non-Hodgkin lymphoma and with the progress within this construct in solid tumors. With BOXR1030, our first program to emerge from the BOXR platform, we're excited to advance this towards the clinic to potentially improve T cell functionality and the tumor microenvironment. We look forward to reporting on the progress of these programs over the next 6 to 12 months. With that, I'll be ready to take questions.

謝謝你，馬特。我們對本季 ACTR 和 BOXR 平台的進展感到興奮，ACTR707 和復發/難治性非何杰金氏淋巴瘤的數據以及該平台在實體瘤方面的進展都令人振奮。BOXR1030 是我們基於 BOXR 平台推出的第一個項目，我們很高興能夠將其推進到臨床階段，以期改善 T 細胞功能和腫瘤微環境。我們期待在未來 6 至 12 個月內報告這些項目的進展。這樣，我就可以開始回答問題了。

(Operator Instructions) And our first question will come from the line of Matthew Harrison of Morgan Stanley.

（操作員說明）我們的第一個問題將來自摩根士丹利的馬修·哈里森。

This is Vikram on for Matthew. So 2 questions on the DLBCL data presented today for the cohort 3 data. So for the partial responses you saw, would you expect them to turn into complete responses over time? And overall, why do you think you're seeing lower CR rates as you go up in dose? And then separately, beyond the cohort 3 data, on the HER2 study, you mentioned you'll have data by year end '19. We just wanted to get a sense of how much data you think you'll be able to present them in terms of status? How many patients that you enrolled yet, if enrollment has started?

這裡是Vikram為Matthew報道。所以，關於今天公佈的 DLBCL 數據（第三組數據），有兩個問題。那麼，對於你看到的這些部分回答，你認為它們會隨著時間的推移變成完整的回答嗎？總的來說，你認為隨著劑量增加，完全緩解率反而降低的原因是什麼？另外，除了隊列 3 的數據之外，關於 HER2 研究，您提到您將在 2019 年底之前獲得數據。我們只是想了解一下，您認為您能夠向他們展示多少數據，包括現狀方面的資訊？如果已經開始招募患者，目前已經招募了多少名患者？

Vikram, thanks for calling in and thanks for the questions. Starting with the questions on the DLCBL program. So I think -- I don't think we want to necessarily predict the future course of the partial responses. We do note, as Jessica indicated, that we have seen in this cohort deepening responses over time, and obviously we'll continue to monitor patients and update their status as we continue the program.

Vikram，感謝你的來電和提問。首先是關於DLCBL計畫的問題。所以我認為——我們不一定想預測部分響應的未來方向。正如傑西卡所指出的，我們注意到，隨著時間的推移，這群患者的反應越來越深入，顯然，我們將繼續監測患者，並在計畫繼續進行的過程中更新他們的狀況。

In terms of changes in response rates across cohorts, I do think it is obviously worth making the point that these are relatively small cohorts. It's hard to infer any sort of statistical significance based on differences from one cohort to the next. I do think the important aspect from our perspective is that, as we continue to advance this trial starting initially with cohorts 1 and 2, data presented last year, now with cohort 3, a very consistent picture is emerging of potent anti-tumor activity, but with what looks like a very differentiated safety profile. And so simply expanding out that data set, I think, gives us a lot of encouragement. Maybe, I'll just pause here and ask Jessica if there's anything to add.

就不同群體間應答率的變化而言，我認為顯然有必要指出，這些群體規模相對較小。很難根據不同群體之間的差異推斷出任何統計意義。我認為從我們的角度來看，重要的一點是，隨著我們繼續推進這項試驗，從最初的第一組和第二組（去年公佈了數據）到現在的第三組，一個非常一致的畫面正在浮現，那就是強大的抗腫瘤活性，但安全性似乎卻截然不同。因此，我認為，僅僅是擴大數據集就給了我們很大的鼓舞。或許，我應該先停一下，問問傑西卡還有什麼要補充的。

Thank you, Jeff. No, I don't have anything to add. That sounds all right.

謝謝你，傑夫。不，我沒有什麼要補充的。聽起來不錯。

Great. And then moving on to your question about ATTCK-34-01. So again, just as a quick reminder, this design is an adaptive Bayesian design, dose escalation, where we have the ability to escalate both ACTR T cells and the antibody dose. We're running this as a multisensor study. Today, we've activated 5 sites, and we're continuing to enroll and treat patients in the first cohort. So our expectation at this point is, by the end of the year to be in a position to report updates both in terms of enrollment status and initial safety data, our expectation is for meaningful efficacy data to report it sometime in 2020 and provide more specifics in terms of the timing around that later in the year.

偉大的。接下來回答你關於 ATTCK-34-01 的問題。所以再次快速提醒一下，這個設計是一種自適應貝葉斯設計，劑量遞增，我們可以同時遞增 ACTR T 細胞和抗體劑量。我們正在進行一項多感測器研究。今天，我們已經啟用了 5 個治療點，並且正在繼續招募和治療第一批患者。因此，我們目前的預期是，到今年年底，我們將能夠報告入組情況和初步安全性數據方面的最新進展；我們預計，在 2020 年的某個時候，我們將報告有意義的療效數據，並在今年晚些時候提供更多關於時間安排的具體信息。

And our next question will come from the line of Peter Lawson with SunTrust Robinson.

接下來，我們將向 SunTrust Robinson 的 Peter Lawson 提問。

Just -- as we think about, I guess, durability. Is there anything you can comment around the cohort 1, 2 or 3 around the durability you have been seeing?

就像——當我們思考耐用性的時候。關於您觀察到的第一批、第二批或第三批人群的持久性，您有什麼想說的嗎？

It's a great question. I think, obviously, from our perspective, response rates are important, as is durability. We presented really just high-level data at this update. We'll be repeating -- reporting more complete data on aspects of the data of the trial, including durability as well as more details in terms of efficacy and safety aspects at the appropriate venue later this year.

這是一個很好的問題。我認為，顯然從我們的角度來看，響應率很重要，耐用性也很重要。本次更新我們僅展示了一些高層次的數據。我們將在今年稍後在合適的場合再次報告試驗數據的更完整數據，包括持久性以及療效和安全性方面的更多細節。

Do you get any sense that as you go up in dose, the durability would increase?

你覺得隨著劑量增加，藥效持續時間會延長嗎？

I think it's -- that's speculation -- again, obviously we're continuing dose escalation. We're expecting to report data later this year from cohort 4. And obviously, we'll be continuing to look at how does the efficacy profile, both in terms of response rate and durability change as we continue dose escalation as well as looking at what happens with the safety profile.

我認為這只是猜測——顯然，我們正在繼續增加劑量。我們預計將於今年稍後公佈第四組的數據。顯然，我們將繼續觀察隨著劑量遞增，療效（包括反應率和持久性）的變化情況，以及安全性方面的變化。

And you mentioned deepening responses in answer to one of the questions. How -- have you seen PRs go to CRs or is it kind of -- has it not been that extreme?

你在回答其中一個問題時提到了要深入思考。你看過公關稿變成正式稿嗎？還是說這種情況沒有那麼極端？

We have and just for clarity, I think we've also seen this, as we reported earlier, I think in the ATTCK-20-2 study. And again, we're seeing a handful of deepening responses in the most recent cohort in ATTCK-20-03 study, including going from stable disease to partial response to complete response.

我們已經看到了這一點，為了更清楚地說明，我認為我們也看到了這一點，正如我們之前報道的那樣，我認為是在 ATTCK-20-2 研究中。此外，在 ATTCK-20-03 研究的最新隊列中，我們看到一些病情加深的病例，包括從病情穩定到部分緩解再到完全緩解。

Got you. And then you may have mentioned in the prepared comments, I apologize if I missed it. The IND for BOXR1030. When could we see that?

抓到你了。然後您可能在準備好的評論中提到過，如果我錯過了，我深表歉意。BOXR1030 的 IND。我們什麼時候能看到呢？

Yes. So again we're on track for completing the work, that will allow us to file the IND, but we haven't committed to a specific time before IND filing.

是的。所以，我們再次按計劃完成了工作，這將使我們能夠提交IND申請，但我們還沒有承諾在提交IND申請之前的具體時間。

And our next question will come from the line of Yaron Werber with Cowen.

接下來，我們將提出 Yaron Werber 與 Cowen 的合作問題。

This is [Leo] on for Yaron. Congrats on the good quarter. I just have couple questions regarding the program ATTCK-17-01. Do you guys see any signal in terms of [FT] in the expanded cohorts? And also, you mentioned that this trial design -- this adaptive design. I guess, the other trial, the ATTCK-34-01, is also adaptive design. So I'm just wondering if this adaptive design is helping you guys in terms of the dose [winding] and avoiding the [FTs]. Please give us a little bit of color on that?

這是[Leo]替補 Yaron 上場。恭喜你們本季業績出色。關於 ATTCK-17-01 程序，我有幾個問題。你們在擴大的隊列中，從[FT]方面觀察到任何訊號嗎？而且，您也提到了這種試驗設計—這種適應性設計。我猜想，另一項試驗 ATTCK-34-01 也是自適應設計。所以我想知道這種自適應設計是否對你們在劑量[纏繞]和避免[FTs]方面有所幫助。請您詳細說說這件事吧？

Sure. Just a couple of quick points. So it's obviously -- this program, the 17-01 program, where we're using SEA-BCMA -- in combination with ACTR707s to target relapsed/refractory multiple myeloma this is a partnered program with Seattle Genetics. And so I think we can provide high-level operational details on the study, but anything beyond that requires essentially a joint communication. So just also to clarify, in terms of the study design it is like really all of our trials at this point, an adaptive design, which gives us the flexibility in terms of adjusting cohort size as well as some flexibility as we sort of think about the process for dose escalation. With both the BCMA study and the 34-01 study with trastuzumab, in particular what it allows us to do is to make decisions in terms of escalating either antibody dose or ACTR T cell dose separately and separate cohorts in a way to allow us to really efficiently sort of map out parameter space around the dosing of those 2 components to really drive efficacy and safety. So in terms of the 17-01 study, just again from an operational update perspective, we've completed enrollment and treatment in cohorts 4 and 5. Cohorts 1 through 3, we presented at the end of last year, we're expecting to present data from the cohorts 4 and 5 later this year.

當然。簡單提幾點。所以很明顯，這個項目，17-01 項目，我們正在使用 SEA-BCMA 與 ACTR707s 聯合治療復發/難治性多發性骨髓瘤，這是一個與 Seattle Genetics 合作的項目。因此，我認為我們可以提供該研究的高級操作細節，但除此之外的任何事情基本上都需要雙方共同溝通。所以，為了澄清一下，就研究設計而言，它和我們目前所有的試驗一樣，是一種適應性設計，這使我們在調整隊列規模方面具有靈活性，並且在考慮劑量遞增過程時也具有一定的靈活性。BCMA 研究和曲妥珠單抗 34-01 研究特別使我們能夠分別針對不同的隊列，決定是否增加抗體劑量或 ACTR T 細胞劑量，從而有效地規劃這兩個成分的劑量參數空間，以真正提高療效和安全性。就 17-01 研究而言，從營運更新的角度來看，我們已經完成了第 4 組和第 5 組的入組和治療。第 1 組到第 3 組的數據我們在去年年底公佈了，我們預計將在今年稍後公佈第 4 組和第 5 組的數據。

And I'm showing no further questions in the queue. So now it's my pleasure to hand the conference back over to Dr. Chuck Wilson, President and Chief Executive Officer, for closing comments or remarks.

隊列中不再顯示其他問題。現在，我很高興將會議交還給總裁兼執行長查克威爾森博士，請他作閉幕致詞。

Great. Well, thank you very much everyone for joining us today, and we look forward to providing you with the updates on all of our programs throughout the rest of the year. Thank you, and goodbye.

偉大的。非常感謝各位今天蒞臨，我們期待在今年餘下的時間裡繼續為大家帶來我們所有項目的最新進展。謝謝，再見。

Ladies and gentlemen, thank you for your participation on today's conference. This does conclude our program, and you may all disconnect. Everybody, have a wonderful day.

女士們、先生們，感謝各位參加今天的會議。我們的節目到此結束，大家可以斷開連結了。祝大家今天過得愉快。