Iteos Therapeutics Inc (ITOS) 2021 Q3 法說會逐字稿

Good afternoon and welcome to the iTeos Therapeutics third-quarter 2021 financial results conference call. At this time, all participants are in listen-only mode. Following the formal remarks, we will open the call up for you for questions. Please be advised that this call is being recorded at the company's request.

下午好，歡迎來到 iTeos Therapeutics 2021 年第三季度財務業績電話會議。此時，所有參與者都處於只聽模式。在正式發言之後，我們將開始為您提問。請注意，此次通話是應公司要求進行錄音的。

At this time, I'd like to turn it over to Ryan Baker, Head of Investor Relations for Iteos. Ryan, please proceed.

在這個時候，我想把它交給 Iteos 投資者關係主管 Ryan Baker。瑞安，請繼續。

Thank you, operator, and thank you, everyone, on the call for joining us today. Joining me from Iteos with prepared remarks are Michel Detheux, President and Chief Executive Officer; Jo Lager, Chief Medical Officer; and Matthew Gall, Chief Financial Officer.

謝謝你，接線員，也謝謝大家今天加入我們的電話會議。來自 Iteos 的總裁兼首席執行官 Michel Detheux 和我一起發表了準備好的講話； Jo Lager，首席醫療官；和首席財務官 Matthew Gall。

Before we begin, the team will be making forward-looking statements in the prepared remarks and during the Q&A session. Any statements made during this call that are not statements of historical or current facts are intended to be forward-looking statements pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. We want to emphasize that such forward-looking statements reflect our current expectations and assumptions regarding timing, progress, and success of our clinical trials, therapeutic potential thereof, expected milestones, our financial condition, including cash runway, our business operation, development efforts, and the potential benefits of our collaboration and are neither predictions nor guarantees of future events or performance.

在我們開始之前，團隊將在準備好的評論中和問答環節中做出前瞻性陳述。根據 1995 年《私人證券訴訟改革法案》的安全港條款，本次電話會議期間作出的任何不屬於歷史或當前事實陳述的陳述均屬於前瞻性陳述。我們要強調的是，此類前瞻性陳述反映了我們目前對臨床試驗的時間、進展和成功、治療潛力、預期里程碑、我們的財務狀況（包括現金跑道）、我們的業務運營、開發努力以及我們合作的潛在好處的預期和假設，都不是預測也不保證未來事件或性能。

Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business, including those under the heading entitled Risk Factors in our quarterly report on Form 10-Q for the quarter ended September 30, 2021, which was filed with the SEC as well as in subsequent reports, including our current reports on Form 8-K. The company disclaims any obligation to update or revise any forward-looking statements except as required by law.

由於與我們業務相關的風險和不確定性，包括我們截至 9 月 30 日季度的 10-Q 表季度報告中題為“風險因素”標題下的風險和不確定性，實際結果可能與這些前瞻性陳述中明示或暗示的結果存在重大差異， 2021，已提交給美國證券交易委員會以及隨後的報告，包括我們目前關於 8-K 表格的報告。除非法律要求，否則公司不承擔任何更新或修改任何前瞻性陳述的義務。

Michel will start today's call by sharing with you the significant progress our team here at iTeos has made in the past quarter. He'll recap our corporate strategy and provide an overview of our robust clinical development plans for our pipeline programs. And then our Chief Medical Officer, Jo Lager, will provide a more detailed update on our clinical programs. We'll wrap up our comments with our CFO, Matthew Gall, who will provide an update on our financial status, followed by Michel's closing remarks. We'll then open the lines for the Q&A session.

Michel 將通過與您分享我們在 iTeos 的團隊在過去一個季度取得的重大進展來開始今天的電話會議。他將回顧我們的企業戰略，並概述我們針對管道項目的強大臨床開發計劃。然後我們的首席醫療官 Jo Lager 將提供有關我們臨床計劃的更詳細更新。我們將與我們的首席財務官 Matthew Gall 結束我們的評論，他將提供我們財務狀況的最新信息，然後是米歇爾的結束語。然後我們將打開問答環節。

With that, I will hand it over to Michel.

有了這個，我會把它交給米歇爾。

Thank you, Ryan. Hello, everyone. Thanks for joining us for our third-quarter 2021 earnings call.

謝謝你，瑞安。大家好。感謝您加入我們的 2021 年第三季度財報電話會議。

At iTeos, our team is dedicated to understanding the biology of the tumor microenvironment. We use that deep understanding to design what we believe are best-in-class assets to harness the immune system to help patients with cancer live longer and better lives. We are continuing to progress our preclinical programs EOS-448, an anti-TIGIT antibody, which we partner with GlaxoSmithKline to jointly develop and commercialize; and inupadenant, our wholly owned selective A2A inhibitor.

在 iTeos，我們的團隊致力於了解腫瘤微環境的生物學。我們利用這種深刻理解來設計我們認為是一流的資產，以利用免疫系統幫助癌症患者活得更長、生活得更好。我們正在繼續推進我們的臨床前項目 EOS-448，這是一種抗 TIGIT 抗體，我們與葛蘭素史克合作共同開發和商業化； inupadenant，我們全資擁有的選擇性 A2A 抑製劑。

Both of these therapies have demonstrated single-agent efficacy and excellent safety profile, and both targets are simply being de-risked through our own data as well as external randomized data. We are really excited by these programs, and their potential to significantly impact patients' lives. This is what drives us here at iTeos every day.

這兩種療法都證明了單藥療效和出色的安全性，並且通過我們自己的數據和外部隨機數據，這兩個目標都被簡單地降低了風險。我們對這些計劃及其對患者生活產生重大影響的潛力感到非常興奮。這就是驅使我們每天來到 iTeos 的原因。

Let's start by discussing our strategic collaboration with GlaxoSmithKline on our anti-TIGIT antibody, EOS-448. This collaboration is an opportunity to accelerate and expand the development plan of EOS-448. In the third quarter of 2021, we closed the co-development and co-commercialization collaboration agreement and received $625 million upfront payment. Beyond the upfront payment, we are eligible to receive up to $1.45 billion in additional development and commercial milestones payments should the program achieve certain milestones.

讓我們首先討論我們與葛蘭素史克在我們的抗 TIGIT 抗體 EOS-448 上的戰略合作。此次合作是加速和擴展 EOS-448 開發計劃的機會。 2021 年第三季度，我們完成了聯合開發和聯合商業化合作協議，並收到了 6.25 億美元的預付款。除了預付款外，如果該計劃達到某些里程碑，我們還有資格獲得高達 14.5 億美元的額外開發和商業里程碑付款。

This partnership validates our view that TIGIT is the most promising new target in the coming generation of new IO therapies, and that EOS-448 has significant potential to be differentiated relative to the other asset in their class.

這種夥伴關係證實了我們的觀點，即 TIGIT 是下一代新 IO 療法中最有前途的新目標，並且 EOS-448 相對於同類中的其他資產具有巨大的差異化潛力。

The GSK partnership has brought enormous value to iTeos in many ways. To highlight a couple, this partnership brings together the best-in-class expertise, capability, and portfolio of the two companies and enables us together to pursue our combination into the culmination in the TIGIT-CD226 axis in ways no other companies can.

GSK 的合作夥伴關係在許多方面為 iTeos 帶來了巨大的價值。值得一提的是，這種合作夥伴關係匯集了兩家公司一流的專業知識、能力和產品組合，使我們能夠以其他公司無法做到的方式共同追求 TIGIT-CD226 軸的結合。

As an example, we will be evaluating the combination of GSK-approved anti-PD-1 Jemperli or dostarlimab with those of our highly differentiated clinical-stage candidates, EOS-448 and inupadenant. This is just one of the many unique combination we are available to explore.

例如，我們將評估 GSK 批准的抗 PD-1 Jemperli 或 dostarlimab 與我們高度分化的臨床階段候選藥物 EOS-448 和 inupadenant 的組合。這只是我們可以探索的眾多獨特組合之一。

Also, the structure of this partnership provides strategic flexibility as we aim to become an industry leader in the immuno-oncology space through (inaudible) cash, 60-40 sharing of the development cost, and a 50-50 profit share and co-commercialization rights in the US.

此外，這種夥伴關係的結構提供了戰略靈活性，因為我們的目標是通過（聽不清）現金、60-40 的開發成本分攤以及 50-50 的利潤分享和共同商業化成為免疫腫瘤學領域的行業領導者在美國的權利。

Now turning to inupadenant, our clinical-stage program targeting adenosine-driven immunosuppression. We work with interest and differentiated data that are suited to the reported, [as I mentioned], CD73 therapeutic. The data continued to validate our antigen for this pathway and target. Based on our unique understanding of this specific condition, which is the tumor microenvironment, iTeos [hinted] thoughtfully designed inupadenant, restoratively and potently inhibit the A2A receptor in the specific conditions of the tumor microenvironment.

現在轉向 inupadenant，這是我們針對腺苷驅動的免疫抑制的臨床階段計劃。我們使用適合報告的興趣和差異化數據，[正如我提到的那樣]，CD73 治療。數據繼續驗證我們針對該途徑和目標的抗原。基於我們對這種特定條件（即腫瘤微環境）的獨特理解，iTeos [暗示] 精心設計了在腫瘤微環境的特定條件下抑制、恢復和有效抑制 A2A 受體的方法。

These two programs are just the beginning of what we are working on at iTeos. Our scientists continue to innovate, and we have a range of diverse and exciting programs for queues on further harnessing the power of the immune system to detect cancer. As previously guided, we've nominated an additional targeted candidate, targeting [immuno-oncology] in the adenosine pathway for IND-enabling studies. This is a first-in-class program against a new target identified by our in-house scientific team demonstrating our capabilities in higher discoveries. And we continue to capitalize on our demonstrated track record of success in building a differentiated immuno-oncology pipeline.

這兩個項目只是我們在 iTeos 所做工作的開始。我們的科學家不斷創新，我們有一系列多樣化和令人興奮的計劃，以進一步利用免疫系統的力量來檢測癌症。正如之前的指導，我們已經提名了一個額外的目標候選人，針對腺苷通路中的 [免疫腫瘤學] 進行 IND 支持研究。這是針對我們內部科學團隊確定的新目標的一流計劃，展示了我們在更高發現方面的能力。我們繼續利用我們在建立差異化免疫腫瘤管道方面的成功記錄。

In summary, our progress through 2021 has laid the groundwork for our robust interdependent plan. With expansion on the way for both our internal program, we have demonstrated our ability to conflate scientific innovation into clinical programs with the potential to improve outcomes for people who have cancer. We have leveraged our deep understanding of cancer immunology and immunosuppressive pathway to build our pipeline and attract a partnership that will provide us with additional opportunities.

總之，我們在 2021 年取得的進展為我們強有力的相互依存計劃奠定了基礎。隨著我們內部計劃的擴展，我們已經展示了我們將科學創新融入臨床計劃的能力，並有可能改善癌症患者的預後。我們利用我們對癌症免疫學和免疫抑制途徑的深刻理解來建立我們的管道並吸引合作夥伴，這將為我們提供更多機會。

We are now focused on the execution of our clinical trials, delivering on the promise we have made for our patients with advanced cancer. With that, I will hand it over to Jo Lager, our Chief Medical Officer, to provide further details on the significant progress that we have made and where we are with these exciting programs.

我們現在專注於臨床試驗的執行，兌現我們為晚期癌症患者做出的承諾。有了這個，我將把它交給我們的首席醫療官 Jo Lager，以提供有關我們取得的重大進展以及我們在這些令人興奮的計劃中取得的進展的更多詳細信息。

Thanks, Michel. I'll begin with key updates on our anti-TIGIT antibody, EOS-448. EOS-448 has the potential to achieve significant anti-tumor immune response through a multifaceted mechanism.

謝謝，米歇爾。我將從我們的抗 TIGIT 抗體 EOS-448 的關鍵更新開始。 EOS-448 有可能通過多方面的機制實現顯著的抗腫瘤免疫反應。

The antibody blocks the binding of TIGIT to its ligand, resulting in the immune-mediated killing of tumor cells by T cells and NK cells. It also engages the FC gamma receptor, further promoting anti-tumor immune response through the release of pro-inflammatory cytokine and chemokine and the activation of antigen-presenting cells. Also, the antibody causes depletion of immunosuppressive Tregs and exhausted T cells, cells that are known to dampen the immune response.

該抗體可阻斷 TIGIT 與其配體的結合，從而導致 T 細胞和 NK 細胞對腫瘤細胞進行免疫介導的殺傷。它還與 FC γ 受體結合，通過釋放促炎細胞因子和趨化因子以及激活抗原呈遞細胞進一步促進抗腫瘤免疫反應。此外，該抗體會導致免疫抑制性 Tregs 耗盡和耗盡的 T 細胞，這些細胞已知會抑制免疫反應。

We are pursuing a clinical development plan based on this multifaceted mechanism of action of EOS-448, which is focused on the indications and combinations where we see the greatest potential to benefit patients. Given the encouraging monotherapy data we presented earlier this year, we are progressing the next set of trials for this program. We are pleased to share that we have initiated dosing and two combination cohorts in patients with solid tumors in our Phase 1/2 clinical trial of EOS-448.

我們正在根據 EOS-448 的這種多方面作用機制制定臨床開發計劃，重點關注我們認為最有可能使患者受益的適應症和組合。鑑於我們今年早些時候提供的令人鼓舞的單藥治療數據，我們正在推進該項目的下一組試驗。我們很高興地與大家分享，我們已經在 EOS-448 的 1/2 期臨床試驗中開始對實體瘤患者進行給藥和兩個聯合隊列。

The first, in combination with pembrolizumab; and the second, in combination with inupadenant. As a reminder, we had planned to initiate this combination study with pembrolizumab prior to entering into the collaboration with GSK, and both parties agreed that it made sense to generate data on this combination. This will inform our clinical strategy with dostarlimab.

第一種，與 pembrolizumab 聯合使用；第二，結合inupadenant。提醒一下，在與葛蘭素史克合作之前，我們曾計劃啟動與 pembrolizumab 的聯合研究，並且雙方都同意生成有關該組合的數據是有意義的。這將為我們使用 dostarlimab 的臨床策略提供信息。

Over the next several months, we will indicate additional studies exploring the safety and efficacy of EOS-448. This will include the combination with GSK's approved anti-PD-1 dostarlimab. We will also evaluate EOS-448 in monotherapy and in combination with Bristol Myers Squibb's iberdomide in multiple myeloma. We look forward to providing updates on the clinical development plan for EOS-448 as we progress.

在接下來的幾個月裡，我們將提出更多探索 EOS-448 安全性和有效性的研究。這將包括與 GSK 批准的抗 PD-1 dostarlimab 的組合。我們還將評估 EOS-448 的單一療法以及與 Bristol Myers Squibb 的 iberdomide 聯合治療多發性骨髓瘤的療效。隨著我們的進展，我們期待提供 EOS-448 臨床開發計劃的最新信息。

Turning to inupadenant, we have a unique drug candidate in three ways: first, unlike the other adenosine receptor antagonist, inupadenant was designed to inhibit the A2A receptor in the high concentrations of adenosine found within tumors; second, inupadenant was designed to be highly selected for the A2A receptor, which plays a key role in regulating adenosine immuno-suppressive effects within the tumor; and third, inupadenant does not penetrate the central nervous system, reducing the potential for off-target safety effects and improving its therapeutic index.

談到 inupadenant，我們在三個方面擁有獨特的候選藥物：首先，與其他腺苷受體拮抗劑不同，inupadenant 旨在抑制腫瘤內發現的高濃度腺苷中的 A2A 受體；其次，inupadenant 被設計為高度選擇 A2A 受體，該受體在調節腫瘤內的腺苷免疫抑製作用中起著關鍵作用；第三，inupadenant 不穿透中樞神經系統，降低了脫靶安全效應的可能性並提高了其治療指數。

We continue to make significant progress in our clinical developments and have several updates to share. We have completed enrollment in the initial evaluation of inupadenant in combination with chemotherapy and with pembrolizumab, and it found a profile that supports future development. We have also completed enrollment in the cohort exploring inupadenant and monotherapy in castrate-resistant prostate cancer and have initiated an expansion of the combination of inupadenant with pembrolizumab in PD-1-resistant melanoma.

我們繼續在臨床開發方面取得重大進展，並有幾項更新可以分享。我們已經完成了對 inupadenant 聯合化療和 pembrolizumab 的初步評估的註冊，它發現了支持未來發展的概況。我們還完成了在去勢抵抗性前列腺癌中探索 inupadenant 和單一療法的隊列的註冊，並開始擴大 inupadenant 與 pembrolizumab 聯合治療 PD-1 抵抗性黑色素瘤。

Finally, as we mentioned earlier, while discussing the updates on the EOS-448, we have initiated the evaluation of the combination of inupadenant with EOS-448, and we'll also be evaluating the triple combination of EOS-448 with inupadenant and GSK's dostarlimab. In addition, we are building on the identification of potential patient selection biomarkers identified in our monotherapy study and plan to open a new cohort in our ongoing Phase 1/2A trial in patients with high biomarker expression.

最後，正如我們之前提到的，在討論 EOS-448 的更新時，我們已經開始評估 inupadenant 與 EOS-448 的組合，我們還將評估 EOS-448 與 inupadenant 和 GSK 的三重組合dostarlimab。此外，我們正在確定我們的單一療法研究中確定的潛在患者選擇生物標誌物，併計劃在我們正在進行的具有高生物標誌物表達的患者的 1/2A 期試驗中開設一個新隊列。

Our initial trial is a rich source of translational data that we continue to use to optimize the inupadenant clinical development programs to evaluate inupadenant in the patient and tumor types most likely to benefit from treatment. With the data we already have in hand and that we are generating on ongoing studies and validation from other approaches in the adenosine pathway, we are initiating the next phase of development. We will have data in several indications and combinations that we expect will provide many attractive options as we move into the randomized controlled setting.

我們的初始試驗是一個豐富的轉化數據來源，我們將繼續使用這些數據來優化 inupadenant 臨床開發計劃，以評估 inupadenant 在患者和最有可能從治療中獲益的腫瘤類型。有了我們手頭已有的數據，以及我們正在從腺苷途徑中的其他方法進行的持續研究和驗證中產生的數據，我們正在啟動下一階段的開發。我們將擁有多種適應症和組合的數據，我們預計隨著我們進入隨機對照環境，它們將提供許多有吸引力的選擇。

I will now hand the call over to Matthew Gall, our Chief Financial Officer.

我現在將電話轉交給我們的首席財務官 Matthew Gall。

Thanks, Jo. I'd like to provide an update on our financial results for the third quarter of 2021. The company's cash and cash equivalent position was $899.8 million as of September 30, 2021, as compared to $340 million as of September 30, 2020. iTeos is well capitalized to support the programs we just detailed.

謝謝，喬。我想提供我們 2021 年第三季度財務業績的最新情況。截至 2021 年 9 月 30 日，公司的現金和現金等價物頭寸為 8.998 億美元，而截至 2020 年 9 月 30 日為 3.4 億美元。iTeos 是充足的資本來支持我們剛剛詳述的項目。

Following receipt of the upfront payment from GSK pursuant to our collaboration and license agreements in August 2021, we believe that our existing cash and cash equivalents would enable us to fund our operating expenses and capital expenditure requirements into 2026. Revenues, nearly all of which were associated with the recognition of a portion of the upfront payment received from GSK, were $104.3 million for the quarter, while we recorded no revenue in the third quarter of 2020.

在 2021 年 8 月根據我們的合作和許可協議收到葛蘭素史克的預付款後，我們相信我們現有的現金和現金等價物將使我們能夠為 2026 年的運營費用和資本支出需求提供資金。收入，幾乎所有收入都是本季度與確認從葛蘭素史克收到的部分預付款相關的收入為 1.043 億美元，而我們在 2020 年第三季度沒有收入。

We expect to recognize the full upfront payment through revenue over the next few years. Additional information regarding revenue recognition related to the collaboration agreement will be included in our Form 10-Q for the quarter ended September 30, 2021.

我們希望在未來幾年通過收入確認全部預付款。有關與合作協議相關的收入確認的更多信息將包含在我們截至 2021 年 9 月 30 日的季度的 10-Q 表格中。

Research and development expenses were $16.1 million for the quarter ended September 30, 2021, as compared to $8.7 million for the third quarter of 2020. This increase was primarily due to an increase in activities related to clinical trials for EOS-448 and inupadenant, our preclinical pipeline, and the expansion of our team.

截至 2021 年 9 月 30 日止季度的研發費用為 1610 萬美元，而 2020 年第三季度為 870 萬美元。這一增長主要是由於與 EOS-448 和 inupadenant 臨床試驗相關的活動增加，我們的臨床前管道，以及我們團隊的擴大。

General and administrative expenses were $8.8 million for the quarter ended September 30, 2021, as compared to $4.8 million for the third quarter of 2020. This increase was primarily due to more hires, professional fees, and other costs associated with becoming a public company. The net income attributable to common shareholders was $69.6 million, or a net income of $1.98 per basic share, and $1.86 per diluted share for the quarter ended September 30, 2021, as compared to a net loss of $11.6 million, or a net loss of $0.48 per basic and diluted share for the third quarter of 2020.

截至 2021 年 9 月 30 日的季度，一般和行政費用為 880 萬美元，而 2020 年第三季度為 480 萬美元。這一增長主要是由於更多的招聘、專業費用以及與成為上市公司相關的其他成本。截至 2021 年 9 月 30 日止季度，歸屬於普通股股東的淨收入為 6960 萬美元，即基本股每股淨收入 1.98 美元，稀釋後每股淨收入 1.86 美元，而淨虧損為 1160 萬美元，淨虧損為2020 年第三季度每股基本股和稀釋股 0.48 美元。

I'll now turn the call back over to Michel for closing remarks.

我現在將電話轉回 Michel 以作結束語。

Thank you, Matt. As we have shared on this call, we are executing on our accelerated clinical development plans for both of our highly differentiated immunotherapy: our potent, high-affinity anti-TIGIT antibody, EOS-448; and inupadenant, our A2A receptor antagonist, that has been optimized for the tumor microenvironment.

謝謝你，馬特。正如我們在本次電話會議上分享的那樣，我們正在執行我們兩種高度差異化免疫療法的加速臨床開發計劃：我們的強效、高親和力抗 TIGIT 抗體 EOS-448； inupadenant，我們的 A2A 受體拮抗劑，已針對腫瘤微環境進行了優化。

We remain focused on scientific innovation to improve clinical outcomes for patients. With our deep understanding of tumor immunology, we will continue to advance our current pipeline and accelerate our R&D efforts to discover new targets and strategies to advance cancer immunotherapies. In our current terms, resources pipeline and the team we have assembled, we are in a better position than ever to be among the frontrunners to develop this new generation of IO therapy, and we remain focused on our ambition to be a leader in bringing the therapy to patients.

我們仍然專注於科學創新，以改善患者的臨床結果。憑藉我們對腫瘤免疫學的深刻理解，我們將繼續推進我們目前的產品線並加速我們的研發工作，以發現新的目標和策略來推進癌症免疫療法。就我們目前的條件、資源管道和我們組建的團隊而言，我們比以往任何時候都更有能力成為開發新一代 IO 療法的領跑者，我們仍然專注於成為領導者的雄心壯志對患者進行治療。

Thank you very much for joining today's call. I'd like to now turn the call back to the operator to open up the line for questions.

非常感謝您參加今天的電話會議。我現在想將電話轉回給接線員以打開問題熱線。

Thank you. (Operator Instructions) Daina Graybosch, SVB Leerink.

謝謝。 （操作員說明）Daina Graybosch，SVB Leerink。

Thank you. Maybe two for Jo.

謝謝。也許兩個給喬。

Jo, you talked about completing enrollments for the inupadenant combination of chemo and pembro. Two questions on that. One, I think you said there is a profile supportive of further development. Can you better, more fully characterize what you mean by profile supportive? And then you also mentioned expansion in melanoma PD-1 pre-treated. Have you made a go-no-go decision on expanding in prostate and [CMBCS]?

喬，你談到完成化療和 pembro 的魯莽組合的註冊。有兩個問題。第一，我想你說過有一個支持進一步發展的配置文件。你能更好、更全面地描述你所說的個人資料支持的意思嗎？然後你還提到了黑色素瘤 PD-1 預處理的擴展。您是否已做出關於擴大前列腺和 [CMBCS] 的決定？

Yeah. Thanks, Daina. So in terms of the first question, yes, for inupadenant, we've completed the safety evaluation or the dose evaluation for the combination with both pembrolizumab and with chemotherapy.

是的。謝謝，黛娜。因此，就第一個問題而言，是的，對於 inupadenant，我們已經完成了與 pembrolizumab 和化療聯合使用的安全性評估或劑量評估。

For pembrolizumab, we have a dose where -- what are our criteria for saying that that profile is suitable for moving forward? We have a dose that is safe. We have PK as expected for the drug. And we have initial evidence of efficacy in that cohort that makes us interested in moving forward with. And as we said, we are moving forward with the pembrolizumab combo in melanoma. The same is true for chemotherapy, that we have selected a dose where we have good safety, and we have preliminary evidence of activity.

對於 pembrolizumab，我們有一個劑量——我們說該配置文件適合向前推進的標準是什麼？我們有一個安全的劑量。我們對藥物進行了預期的 PK。我們在那個隊列中有初步的療效證據，這讓我們有興趣繼續前進。正如我們所說，我們正在推進黑色素瘤中的 pembrolizumab 組合。化療也是如此，我們選擇了安全性良好的劑量，並且我們有初步的活性證據。

And in terms of the other cohorts, for prostate cancer, we have completed the monotherapy evaluation in prostate cancer, and we have decided not at this time to open the cohort in prostate cancer in combination with pembrolizumab. We think that there are better options for development of the drug at this time.

就其他隊列而言，對於前列腺癌，我們已經完成了前列腺癌的單藥治療評估，我們決定此時不開放前列腺癌聯合 pembrolizumab 的隊列。我們認為目前有更好的藥物開發選擇。

And in terms of the combination with chemotherapy, we are moving that forward. We have evaluated with different indications including triple negative breast cancer and have chosen the indication to move forward. And we will be giving an update on that as that study began ready to start.

就與化療的結合而言，我們正在向前推進。我們評估了不同的適應症，包括三陰性乳腺癌，並選擇了向前推進的適應症。我們將在研究開始準備開始時提供最新情況。

Great. Thank you very much.

偉大的。非常感謝。

Thank you.

謝謝。

Chris, your line is open. Please ensure you're unmuted locally.

克里斯，你的線路是開放的。請確保您在本地未靜音。

Oops, sorry. Can you guys hear me? Hello?

哎呀，對不起。你們能聽到我說話嗎？你好？

Yes -- please go ahead.

是的——請繼續。

Can you guys hear me? Oh, great. Thank you. Thanks, guys, for taking the question. Just to -- I'm sorry, a strategic question here on inupadenant. Yeah, I know you're taking the first agent, the first-generation agent here into randomized trials, and you talked about this next generation.

你們能聽到我說話嗎？哦，太好了。謝謝。謝謝，伙計們，提出這個問題。只是 - 對不起，這是一個關於 inupadenant 的戰略問題。是的，我知道你正在把這裡的第一代代理人帶到隨機試驗中，你談到了下一代。

I think you've addressed this before, but maybe just remind us, how do these two agents coexist? What's the strategy there in terms of bringing both of them forward? And then I also -- I don't think I heard you, guys, before talk about this triplet combo of 448, the GSK PD-1, and inupadenant. Can you maybe talk a little bit about what led you to begin that trial and what data prompted that? Thanks.

我想你之前已經解決過這個問題，但也許只是提醒我們，這兩種代理是如何共存的？將兩者都向前推進的策略是什麼？然後我也——我想我沒有聽到你們，伙計們，在談論 448、GSK PD-1 和 inupadenant 的三重組合之前。您能否談談是什麼促使您開始該試驗以及是什麼數據促使您這樣做？謝謝。

Yeah, Chris. So on your first question about our drugs targeting the adenosine pathway, inupadenant is our lead there. It is the A2A receptor antagonist that we think is optimized for use in the tumor microenvironment to really optimize the anti-tumor response of the immune system.

是的，克里斯。因此，關於您關於我們針對腺苷途徑的藥物的第一個問題，inupadenant 是我們的領導者。我們認為它是 A2A 受體拮抗劑，經過優化，可用於腫瘤微環境，真正優化免疫系統的抗腫瘤反應。

And as you mentioned, we have selected a candidate for a new mechanism of action that is also in the adenosine pathway. Our preclinical data has shown that these two targets are both effective ways to restore the immune system and also may work well together. So that is why, both -- they should work independently and should also work well together, so that's why we're progressing both of these drugs. So inupadenant, which is in clinic, and the new drug candidate that we've recently selected.

正如你提到的，我們已經選擇了一種新的作用機制的候選藥物，它也存在於腺苷途徑中。我們的臨床前數據表明，這兩個靶標都是恢復免疫系統的有效方法，並且可以很好地協同工作。所以這就是為什麼，它們都應該獨立工作，也應該很好地協同工作，所以這就是為什麼我們正在開發這兩種藥物。所以 inupadenant，它在臨床上，以及我們最近選擇的新候選藥物。

In terms of your second question around the triplet of PD-1 plus TIGIT plus A2A, this is something we've been interested in for a while. As we've previously disclosed, we were moving forward with the doublet of TIGIT and inupadenant. And it makes sense to also evaluate the triplet, the combination of PD-1 plus TIGIT plus inupadenant.

關於你關於 PD-1 加 TIGIT 加 A2A 三聯體的第二個問題，這是我們一段時間以來一直感興趣的問題。正如我們之前披露的那樣，我們正在推進 TIGIT 和 inupadenant 的組合。評估三聯體，即 PD-1 加 TIGIT 加 inupadenant 的組合也是有意義的。

There also has been some recent data, or not data, but some information from the ongoing Arcus trial in non-small cell lung cancer, where they have suggested that they have interesting data on a triplet, including a PD-1, TIGIT, and adenosine receptor antagonists. And that also increased our interest in moving forward with that combination.

還有一些最近的數據，或者不是數據，但是來自正在進行的非小細胞肺癌 Arcus 試驗的一些信息，他們建議他們有關於三聯體的有趣數據，包括 PD-1、TIGIT 和腺苷受體拮抗劑。這也增加了我們推進該組合的興趣。

Okay. And I'm sorry, I want to make sure that I understand that -- the answer that you had to the first question. Did I hear you say that you're not taking 854 in prostate cancer? Is that correct? Or did I mishear that?

好的。很抱歉，我想確保我理解你對第一個問題的回答。我有沒有聽到你說你不服用 854 治療前列腺癌？那是對的嗎？還是我聽錯了？

That is correct. We're not moving forward in prostate cancer into the company. We are not going to evaluate the combination with pembrolizumab in prostate cancer at the time. We have decided to prioritize other developments of that drug.

那是對的。我們不會在前列腺癌方面取得進展。我們當時不打算評估與 pembrolizumab 聯合治療前列腺癌。我們決定優先考慮該藥物的其他開發。

Okay. Thank you.

好的。謝謝。

Anupam Rama, JP Morgan.

摩根大通的 Anupam Rama。

Hey, guys. Hope you're all well, and thanks so much for taking the question. On EOS-448, so what do you -- along with lines of some of the prior questions, what are you trying to learn specifically from the pembro combination study that you might be able to apply to your dostarlimab combination study? Thanks so much.

大家好。希望你一切都好，非常感謝你提出這個問題。在 EOS-448 上，除了前面的一些問題之外，你想從 pembro 組合研究中具體學到什麼，你可以將它們應用到你的 dostarlimab 組合研究中？非常感謝。

Thanks, Anupam. So we had plans, had started initiating that trial of EOS-448 with pembrolizumab prior to entering into the partnership with GSK. And when we looked at the timelines, we realized that we could initiate that study sooner than we could initiate the study with dostarlimab.

謝謝，阿努帕姆。所以我們有計劃，在與葛蘭素史克建立合作夥伴關係之前，我們已經開始使用 pembrolizumab 啟動 EOS-448 試驗。當我們查看時間表時，我們意識到我們可以比使用 dostarlimab 啟動研究更快地啟動該研究。

We think having the data from that study in combination with pembrolizumab will help us as we are initiating the combination trial with dostarlimab to select the dose and perhaps move a bit faster in that combination based on having data already with anti-PD-1. So it mainly was about speed. I think, as we move forward, we also think it could be valuable to have data on how the drug performs with different anti-PD-1 partners.

我們認為，將該研究的數據與 pembrolizumab 結合使用將對我們有所幫助，因為我們正在啟動與 dostarlimab 的聯合試驗來選擇劑量，並且根據已有的抗 PD-1 數據，可能在該組合中移動得更快一些。所以它主要是關於速度。我認為，隨著我們的前進，我們還認為獲得有關該藥物如何與不同的抗 PD-1 合作夥伴一起發揮作用的數據可能很有價值。

Thanks so much for taking our questions.

非常感謝您回答我們的問題。

Thanks, Anupam.

謝謝，阿努帕姆。

David Nierengarten, Wedbush Securities.

David Nierengarten，Wedbush 證券。

Thanks for taking my questions. First, regarding the combination with pembro and GSK's work with the dostarlimab.

感謝您回答我的問題。首先，關於與 pembro 的結合以及葛蘭素史克與 dostarlimab 的合作。

I'm assuming, but correct me if I'm wrong, that there's no gating mechanism. So they're not going to wait for data from your pembro study in order to begin the combination studies with dostarlimab. And then the second question that I had was, do you plan or is there a plan for incorporating the adenosine assay that you have been working on from the monotherapy study into the combination studies and maybe trying to look at having an arm or two where you stratify according to expression effects?

我假設沒有門控機制，但如果我錯了請糾正我。因此，他們不會等待您的 pembro 研究的數據來開始與 dostarlimab 的聯合研究。然後我的第二個問題是，你是否計劃或是否有計劃將你一直在從單一療法研究中進行的腺苷測定納入聯合研究，並可能試圖看看有一個或兩個手臂根據表達效果分層？

Thanks, David. So yes, on the combination with pembrolizumab and combination with dostarlimab that we are doing with EOS-448, we are going full speed ahead with initiating the combination with dostarlimab. And the initial data from the combination with pembrolizumab will not be gating.

謝謝，大衛。所以，是的，在我們與 EOS-448 進行的與 pembrolizumab 的組合和與 dostarlimab 的組合中，我們正在全速推進與 dostarlimab 的組合。與 pembrolizumab 聯合使用的初始數據不會設門控。

And on the second question on the assay that we've identified, that may help to predict the patients that benefit from inupadenant. We are incorporating that in our future studies. So we are planning to do cohorts with monotherapy to enroll patients who are biomarker high to better define the benefit that we see in that population. And we are including those assays in our study in melanoma, and we'll also include it in the planned randomized trial for next year.

關於我們已經確定的檢測的第二個問題，這可能有助於預測受益於 inupadenant 的患者。我們正在將其納入我們未來的研究中。因此，我們計劃對單一療法進行隊列研究，以招募生物標誌物高的患者，以更好地定義我們在該人群中看到的益處。我們將這些分析納入我們的黑色素瘤研究中，我們還將把它納入明年計劃的隨機試驗中。

Okay. Cool. Thank you.

好的。涼爽的。謝謝。

(Operator Instructions) Swayampakula Ramakanth, H.C. Wainwright.

（操作員說明）Swayampakula Ramakanth, H.C.溫賴特。

Thank you. Thanks for taking my questions. I'm just trying to understand the rationale behind combining 448 with Bristol's iberdomide for multiple myeloma. If you could please comment on it.

謝謝。感謝您回答我的問題。我只是想了解將 448 與 Bristol 的 iberdomide 聯合治療多發性骨髓瘤的基本原理。如果可以，請對此發表評論。

Yeah. So we are planning to do a study of EOS-448 as monotherapy and in combination with iberdomide in relapsed/refractory multiple myeloma. We have had a collaboration with Geoff Hill at Fred Hutch in Seattle, where we've demonstrated that there does seem to be a significant benefit of the combination of EOS-448 or FC-engaging TIGIT antibody with an image.

是的。因此，我們計劃對 EOS-448 作為單一療法以及與伊比度胺聯合治療復發/難治性多發性骨髓瘤進行研究。我們與西雅圖 Fred Hutch 的 Geoff Hill 進行了合作，在那裡我們證明了將 EOS-448 或 FC-engaging TIGIT 抗體與圖像相結合似乎確實具有顯著優勢。

And iberdomide is a potent drug. It has data in relapsed/refractory myeloma that serves as a useful historic control. And it's an attractive study to do, because it's giving patients an image that they haven't already seen before in that late-line setting where regulatory agencies require to start the development in myeloma.

iberdomide 是一種強效藥物。它有復發/難治性骨髓瘤的數據，可作為有用的歷史對照。這是一項很有吸引力的研究，因為它為患者提供了他們以前在監管機構要求啟動骨髓瘤發展的後期設置中從未見過的圖像。

Thank you. And then regarding the biomarkers that you're looking for, specifically in the inupadenant studies, what sort of biomarkers are you looking for?

謝謝。然後關於你正在尋找的生物標誌物，特別是在無節制的研究中，你在尋找什麼樣的生物標誌物？

So we disclosed at ASCO, the data that we had from our initial study in monotherapy, where we found that the adenosine receptor, A2A receptor itself, those levels of that, the expression -- the number of cells expressing A2A are in the tumor was correlated with clinical benefits in the patients in that study. That is the IHC markers. We have also looked at other markers both by IHC and by NanoString, looking at mRNA markers. And so we have identified other markers that also potentially identify the patients that benefits using those methods as well.

所以我們在 ASCO 上披露了我們從單一療法的初步研究中獲得的數據，我們發現腺苷受體，A2A 受體本身，那些水平，表達 - 腫瘤中表達 A2A 的細胞數量是與該研究中患者的臨床獲益相關。那就是 IHC 標記。我們還通過 IHC 和 NanoString 查看了其他標記，查看 mRNA 標記。因此，我們已經確定了其他標記物，這些標記物也可能識別出使用這些方法受益的患者。

Thank you. (multiple speakers)

謝謝。 （多個揚聲器）

But at this point, we are not -- thank you.

但在這一點上，我們不是——謝謝。

(Operator Instructions) I can confirm we have no further questions currently registered, so I'll hand it back to the team for any closing remarks. Thank you.

（操作員說明）我可以確認我們目前沒有其他問題，所以我會把它交還給團隊以徵求任何結束語。謝謝。

Thank you very much, everyone. Have a great evening.

非常感謝大家。祝你有個愉快的夜晚。

This now concludes today's call. Thank you all for joining. You may now disconnect your lines.

今天的電話會議到此結束。謝謝大家的加入。您現在可以斷開線路。