Cue Biopharma Inc (CUE) 2022 Q4 法說會逐字稿

Greetings, and welcome to the Cue Biopharma Fourth Quarter and Full Year 2022 Earnings Call.

您好，歡迎參加 Cue Biopharma 2022 年第四季度和全年收益電話會議。

(Operator Instructions)

（操作員說明）

As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. Dan Passeri, Chief Executive Officer. Please go ahead.

提醒一下，本次會議正在錄製中。現在我想將會議交給東道主首席執行官 Dan Passeri 先生。請繼續。

Yes. Thank you, and good afternoon, everyone. As a reminder, this conference will be recorded and available on our website for the next 30 days. Also as a reminder, those listening in, just be aware of the webcast, you need to advance the slides as you are listening, and we'll notify you which slide we're on at a given time.

是的。謝謝大家，大家下午好。謹此提醒，本次會議將被錄製並在未來 30 天內在我們的網站上提供。另外提醒一下，那些正在收聽的人，請注意網絡廣播，您需要在收聽時推進幻燈片，我們會在給定時間通知您我們正在播放哪張幻燈片。

Joining me on today's call is Dr. Matteo Levisetti, our Chief Medical Officer; Dr. Ken Pienta, now in the role as a Clinical Advisory Cue; Dr. Anish Suri, our President and Chief Scientific Officer; and Kerri Millar, Chief Financial Officer. Also joining us briefly on today's call is Dr. Sara Pai, surgical oncologist and Director of Translational Head and Neck Cancer Research at the Mass General Hospital. She is an investigator in our ongoing trial with CUE-101. We'll provide a brief perspective of clinical observations to date. In addition to Dr. Pienta, Dr. Pai has also recently become a clinical adviser to Cue Biopharma helping to define our clinical strategies going forward.

與我一起參加今天電話會議的是我們的首席醫療官 Matteo Levisetti 博士； Ken Pienta 博士，現擔任臨床諮詢顧問；我們的總裁兼首席科學官 Anish Suri 博士；和首席財務官 Kerri Millar。參加今天電話會議的還有麻省總醫院外科腫瘤學家兼轉化頭頸癌研究主任 Sara Pai 博士。她是我們正在進行的 CUE-101 試驗的研究員。我們將提供迄今為止臨床觀察的簡要觀點。除了 Pienta 博士之外，Pai 博士最近還成為 Cue Biopharma 的臨床顧問，幫助制定我們未來的臨床策略。

As shown here on Slide 2, this presentation and overview may contain some forward-looking statements, and any forward-looking statements made during this call represents the company's views as of today, March 21, 2023. On the next slide, please. You'll see our agenda for today's call. Just want to please note that on this slide under the financial results, that's meant to read fourth quarter 2022, not third quarter. Apologies for that. We just noticed that before the call.

如幻燈片 2 所示，本演示文稿和概述可能包含一些前瞻性陳述，本次電話會議期間做出的任何前瞻性陳述均代表公司截至今天（2023 年 3 月 21 日）的觀點。請看下一張幻燈片。您將看到我們今天電話會議的議程。只是想請注意，在財務業績下方的這張幻燈片上，這意味著讀取的是 2022 年第四季度，而不是第三季度。對此表示歉意。我們在通話之前才注意到這一點。

Okay. I'll begin by providing an overview and status update of our current corporate positioning, and we'll describe our competitive advantage, which we believe places us in a differentiated strategic position of strength and opportunity despite the present challenges of the capital markets. We're also well positioned with capital into the second half of '24. And importantly, our platform has generated numerous programs at various stages of development, representing multiple partnering opportunities.

好的。首先，我將概述我們當前的公司定位和狀態更新，我們將描述我們的競爭優勢，我們相信，儘管目前資本市場面臨挑戰，但我們相信這些優勢使我們處於優勢和機遇的差異化戰略地位。我們在 24 年下半年的資本方面也處於有利地位。重要的是，我們的平台已經產生了許多處於不同發展階段的項目，代表了多種合作機會。

As a reminder, we recently entered into a strategic partnership with Ono Pharmaceuticals for the development of CUE-401, which is our bispecific regulatory T cell inducer in activator for potentially addressing a broad spectrum of autoimmune diseases. Importantly, this transaction was structured to provide us with requisite capital through program funding, thereby subsidizing the ongoing research and development costs with CUE retaining a 50% co-development option for the U.S. market. So this was obviously a very balanced transaction for the company.

提醒一下，我們最近與 Ono Pharmaceuticals 建立了戰略合作夥伴關係，開發 CUE-401，這是我們的雙特異性調節 T 細胞誘導劑激活劑，有可能解決廣泛的自身免疫性疾病。重要的是，這筆交易的目的是通過項目資金為我們提供必要的資本，從而補貼持續的研發成本，同時 CUE 保留美國市場 50% 的共同開發選擇權。因此，這對公司來說顯然是一次非常平衡的交易。

CUE-101's clinical data continues to support the clinical validation and the corresponding reduction of risk for the entire IL-2-based CUE-100 series and importantly, appears to provide us with defined options for potential registration paths.

CUE-101 的臨床數據繼續支持整個基於 IL-2 的 CUE-100 系列的臨床驗證和相應的風險降低，重要的是，它似乎為我們提供了潛在註冊路徑的明確選項。

Both CUE-101 and Q102 currently in clinical development address significant unmet medical need across multiple cancer indications. Based on the clinical data generated to date, we believe we're now well positioned with our oncology portfolio to seek partnerships and transactions similarly structured to the Ono partnership to ensure we retain involvement in upside -- optimal upside potential while addressing capital access for building out our promising pipeline of potentially breakthrough therapeutics.

目前正在進行臨床開發的 CUE-101 和 Q102 都解決了多種癌症適應症中未滿足的重大醫療需求。根據迄今為止生成的臨床數據，我們相信我們的腫瘤學投資組合現在處於有利地位，可以尋求與小野合作夥伴結構類似的合作夥伴關係和交易，以確保我們繼續參與上行業務——最佳上行潛力，同時解決建設的資本准入問題展示我們有希望的潛在突破性療法的管道。

As seen in the next slide, it's Slide #4. We believe our corporate positioning and competitive advantage are firmly established on solid foundational data and CUE-101 as an exemplary of the CUE-100 series represents a potential therapeutic breakthrough. To date, CUE-101 has demonstrated, as you see on this slide, monotherapy activity in late-stage cancer patients. What's important here is this is a single-agent activity in patients that basically are refractory to various chemotherapies but also checkpoint inhibitors. To date, we're observing significant increase, that is at least a doubling of the overall response combination with checkpoint inhibition compared with historic monotherapy with checkpoint inhibitors.

正如下一張幻燈片所示，它是幻燈片#4。我們相信，我們的企業定位和競爭優勢是建立在堅實的基礎數據之上的，而 CUE-101 作為 CUE-100 系列的典範，代表著潛在的治療突破。迄今為止，正如您在這張幻燈片上看到的那樣，CUE-101 已在晚期癌症患者中證明了單一療法的活性。這裡重要的是，這是針對基本上對各種化療和檢查點抑製劑都難治的患者的單藥活性。迄今為止，我們觀察到顯著的增加，與歷史上使用檢查點抑製劑的單一療法相比，檢查點抑制組合的總體反應至少增加了一倍。

Favorable tolerability. We've dosed greater than 70 patients to date with no evidence of vascular leak syndrome or cytokine release syndrome. Antibody-based design gives us favorable cost of goods for manufacturability, and actually, the drug to date has demonstrated astonishingly stable characteristics whereas stability has gone out to greater than 36 months, significant regulatory advantages. We have Fast Track designation and both mono as well as combination. And importantly, the FDA authorized CUE-102's, i.e., based on the safety data from CUE-101, basically viewing CUE-101 as an analog with no requirement for IND-enabling toxicology and approval to start the trial at a higher dose, saving significant time and cost. Matteo will elaborate upon these observations momentarily.

良好的耐受性。迄今為止，我們已經對超過 70 名患者進行了給藥，沒有證據表明存在血管滲漏綜合徵或細胞因子釋放綜合徵。基於抗體的設計為我們提供了有利的可製造成本，實際上，迄今為止，該藥物已表現出驚人的穩定特性，而穩定性已超過 36 個月，這是顯著的監管優勢。我們擁有快速通道稱號，既有單聲道也有組合。重要的是，FDA 批准了 CUE-102，即基於 CUE-101 的安全數據，基本上將 CUE-101 視為類似物，無需 IND 毒理學要求，並批准以更高劑量開始試驗，從而節省了成本。大量的時間和成本。馬特奧將立即詳細闡述這些觀察結果。

We view the cumulative data as supportive of our central premise, namely that the Immuno-STAT platform and more specifically, the IL-2-based CUE-100 series represents a therapeutic breakthrough by harnessing nature's specificity. That's through targeting the T cell receptor or TCR enabling the targeted delivery of cytokines such as IL-2 to disease-relevant T cells. We believe this approach enables the achievement of a therapeutic index for IL-2 and other cytokines by avoiding the deleterious side effects of nonselective indiscriminate activity, often seen with other modalities.

我們認為累積數據支持了我們的中心前提，即免疫-STAT 平台，更具體地說，基於 IL-2 的 CUE-100 系列代表了利用自然特異性的治療突破。這是通過靶向 T 細胞受體或 TCR，將 IL-2 等細胞因子靶向遞送至疾病相關 T 細胞。我們相信，這種方法可以通過避免非選擇性不加區別的活性的有害副作用（常見於其他方式）來實現 IL-2 和其他細胞因子的治療指數。

As a reminder, our platform modularity allows us also to deploy other modulatory co-stimulators beyond IL-2 based on the same principle. I'm now going to turn the call over to Matteo and then he'll be followed by Ken and Sara to generally describe the emerging clinical observations from our ongoing CUE-101 and CUE-102 trials, and Anish will then provide a brief summary for our autoimmune programs, emphasizing the recent developments, including the CUE-401 partnership with Ono. Matteo?

提醒一下，我們的平台模塊化允許我們基於相同的原理部署 IL-2 之外的其他調節共刺激器。我現在將把電話轉給 Matteo，然後 Ken 和 Sara 將概括地描述我們正在進行的 CUE-101 和 CUE-102 試驗中出現的臨床觀察結果，然後 Anish 將提供簡短的總結對於我們的自身免疫項目，強調了最近的進展，包括與 Ono 的 CUE-401 合作夥伴關係。馬特奧？

Thanks, Dan. The clinical data from the ongoing CUE-101 trial continues to demonstrate robust metrics of clinical benefit for heavily pretreated recurrent metastatic HPV positive head and neck squamous cell carcinoma patients treated with monotherapy and for newly diagnosed patients with recurrent metastatic HPV positive head and neck cancer treated in combination with pembrolizumab.

謝謝，丹。正在進行的 CUE-101 試驗的臨床數據繼續證明，對於經過大量預處理的複發性轉移性 HPV 陽性頭頸鱗狀細胞癌單藥治療患者以及新診斷的複發性轉移性 HPV 陽性頭頸癌患者而言，臨床獲益的可靠指標與派姆單抗聯合使用。

As shown on Slide 5, data from the ongoing clinical trials with CUE-101 as monotherapy and in combination with pembrolizumab have provided clinical proof-of-concept in derisking of our Immuno-STAT platform. The latest data generated to date in 2023 and continues to support prior observations and further enhances our confidence in CUE-101 as a potential therapeutic for patients battling HPV-positive head and neck squamous cell carcinoma.

如幻燈片 5 所示，正在進行的 CUE-101 作為單一療法以及與派姆單抗聯合使用的臨床試驗數據為我們的免疫 STAT 平台消除風險提供了臨床概念驗證。 2023 年迄今為止生成的最新數據繼續支持之前的觀察結果，並進一步增強了我們對 CUE-101 作為治療 HPV 陽性頭頸鱗狀細胞癌患者的潛在療法的信心。

As previously and consistently stated, we believe CUE-101's mechanism of action, as evidenced by the ongoing data generated to date, provides effective and tolerated dose levels, enabling selective expansion of targeted tumor-specific T cells directly in the patient's body. Recurrent metastatic HPV positive head and neck cancer is a tough incurable disease. The data we have observed throughout the monotherapy trial bolsters our position and enhances our confidence that CUE-101 is in fact stimulating the targeted cancer-specific T cells within a subset of these patients, resulting in demonstrable antitumor effect. Furthermore, and importantly, we continue to observe an evolving pattern of enhanced survival in the monotherapy trial. We believe this enhanced survival is due to the persistent expansion of tumor-specific T cells given CUE-101's mechanism of action.

正如之前一貫指出的，我們相信 CUE-101 的作用機制（迄今為止生成的持續數據所證明的）提供了有效且耐受的劑量水平，能夠直接在患者體內選擇性擴增靶向腫瘤特異性 T 細胞。復發性轉移性 HPV 陽性頭頸癌是一種棘手的不治之症。我們在整個單一療法試驗中觀察到的數據支持了我們的立場，並增強了我們的信心，即 CUE-101 實際上是在這些患者的子集中刺激目標癌症特異性 T 細胞，從而產生明顯的抗腫瘤效果。此外，重要的是，我們繼續觀察單一療法試驗中生存率提高的演變模式。我們認為，鑑於 CUE-101 的作用機制，這種生存率的提高是由於腫瘤特異性 T 細胞的持續擴增。

As shown on Slide 6, CUE-101 demonstrates well-behaved pharmacokinetics with low inter-patient variability at the recommended Phase II dose of 4 milligrams per kilogram. The exposure pattern is consistent throughout multiple cycles of treatment without any attenuation of PK parameters, supporting the premise that there is no evidence of clinically relevant immunogenicity. Regarding its pharmacodynamic or PD profile, CUE-101 treatment also results in a consistently observed sustained increase in natural killer cells or NK cells a positive attribute associated with an antitumor response as NK cells are known to assist in tumor killing.

如幻燈片 6 所示，CUE-101 在建議的 II 期劑量 4 毫克/公斤下表現出良好的藥代動力學，患者間變異性較低。在多個治療週期中，暴露模式是一致的，PK參數沒有任何減弱，支持了沒有臨床相關免疫原性證據的前提。就其藥效學或 PD 特徵而言，CUE-101 治療還導致持續觀察到的自然殺傷細胞或 NK 細胞持續增加，這是與抗腫瘤反應相關的積極屬性，因為已知 NK 細胞有助於殺死腫瘤。

Importantly, we observed only a modest and transient increase in regulatory T cells. Regarding the intended PD effect, i.e., activation of targeted tumor-specific T cells, we have observed, as shown in the middle panel, robust expansion of tumor-specific E7 reactive T cells in their peripheral blood of patients as early as 1 week after administration of CUE-101, paired and post-treatment biopsies demonstrate an increase in tumor infiltrating T cells and associated tumor necrosis. In addition to the favorable PK and PD just described in patients with advanced HPV-positive head and neck cancer are experiencing intriguing patterns of clinical benefit.

重要的是，我們觀察到調節性 T 細胞僅出現適度且短暫的增加。關於預期的 PD 效應，即激活靶向腫瘤特異性 T 細胞，如中圖所示，我們觀察到，早在術後 1 週，患者外周血中腫瘤特異性 E7 反應性 T 細胞就出現強勁擴增。給予 CUE-101、配對和治療後活檢表明腫瘤浸潤 T 細胞和相關腫瘤壞死增加。除了剛剛描述的晚期 HPV 陽性頭頸癌患者的良好 PK 和 PD 之外，還經歷了有趣的臨床獲益模式。

Three examples are shown on Slide 7. Patient A experienced a durable partial response with an approximate 60% reduction in tumor burden evident at 6 weeks after 2 cycles of CUE-101. This response lasted close to 1 year. This patient demonstrated a significant reduction in HPV cell-free DNA that coincided with the initiation of the partial response and the HPV cell-free DNA was undetectable for most of the time on treatment. Patient B, who remains on treatment at the present time for approximately 1.5 years has had stable disease with tumor burden reduction of approximately 20% observed at week 48 and maintained to the present time at greater than 75 weeks.

幻燈片 7 中顯示了三個例子。患者 A 經歷了持久的部分緩解，在 2 個週期的 CUE-101 治療後 6 週時，腫瘤負荷明顯減少了約 60%。這種反應持續了近1年。該患者表現出 HPV 無細胞 DNA 顯著減少，這與部分反應的開始同時發生，並且在治療的大部分時間裡檢測不到 HPV 無細胞 DNA。目前仍在接受治療約 1.5 年的患者 B 病情穩定，在第 48 週時觀察到腫瘤負荷減少了約 20%，並且一直維持到目前超過 75 週。

Notably, this patient has also had complete disappearance of HPV cell-free DNA in the blood since week 6. And the undetectable HPV cell-free DNA, which is an increasingly recognized biomarker of disease activity is suggestive of a pathologic complete response, i.e., a potential cure in this patient who we expect may have surgical resection of the lesion for histopathological analysis.

值得注意的是，自第 6 週起，該患者血液中的 HPV 無細胞 DNA 也完全消失。而檢測不到的 HPV 無細胞 DNA，這是一種越來越被認可的疾病活動生物標誌物，提示病理完全緩解，即，該患者的潛在治愈可能是通過手術切除病變進行組織病理學分析。

Patient C has experienced tumor reduction after a prolonged period on drug where no resist based objective response was initially observed by imaging. In this patient treated with CUE-101 at 2 milligrams per kilogram, we can see that the first several months appear to demonstrate gradual tumor growth even beyond the 20% threshold used by RECIST criteria. However, based upon the overall clinical status, the patient continued treatment. After approximately 6 months, the tumor began to shrink and the patient remained on therapy for greater than 18 months after starting treatment with CUE-101. This observation consistent with observations made by others, demonstrates that kinetics of T cell antitumor activity may manifest over a long period of time.

患者C在長期用藥後經歷了腫瘤縮小，但最初通過成像未觀察到基於抗藥性的客觀反應。在這名接受 2 毫克/公斤 CUE-101 治療的患者中，我們可以看到，前幾個月似乎顯示出腫瘤逐漸生長，甚至超過了 RECIST 標準使用的 20% 閾值。然而，根據總體臨床狀況，患者繼續接受治療。大約 6 個月後，腫瘤開始縮小，患者在開始使用 CUE-101 治療後繼續接受治療超過 18 個月。這一觀察結果與其他人的觀察結果一致，表明 T 細胞抗腫瘤活性的動力學可能會在很長一段時間內顯現出來。

The next slide, Slide 8, conveys our ongoing survival swimmer plot for the 20 patients dosed the recommended Phase II dose of 4 milligrams per kilogram. The swimmer plot for the 20 patients dosed at the RP2D of 4 mgs per kg demonstrates a trend of increased survival of approximately 12 months median overall survival compared to the historic reported survival of approximately 8 months observed in patients treated in the second line in the KEYNOTE-040 trial of pembrolizumab. As any experience oncologist understands the survival with third-line treatment is expected to be less as the disease has further developed and become more unstable.

下一張幻燈片，即幻燈片 8，展示了我們對 20 名接受 II 期推薦劑量（每公斤 4 毫克）的患者進行的生存游泳者圖。 RP2D 劑量為 4 mg/kg 的 20 名患者的游泳者圖表明，與在主題演講中觀察到的二線治療患者中觀察到的歷史報導的約 8 個月的生存期相比，中位總生存期的生存期增加了約 12 個月的趨勢-040 派姆單抗試驗。任何經驗豐富的腫瘤學家都知道，隨著疾病進一步發展並變得更加不穩定，三線治療的生存率預計會降低。

Our evolving data continues to support the premise that treatment with CUE-101 stimulates the patient's immune system and results in what appears to be a meaningful increase in survival for patients with advanced recurrent metastatic HPV positive head and neck cancer. This monotherapy data has encouraged our principal investigators and offers a potential path forward to a registrational trial.

我們不斷發展的數據繼續支持這一前提，即 CUE-101 治療可刺激患者的免疫系統，並導致晚期復發性轉移性 HPV 陽性頭頸癌患者的生存率顯著增加。這一單一療法數據鼓舞了我們的主要研究人員，並為註冊試驗提供了潛在的途徑。

As shown on Slide 9, CUE-101 and checkpoint inhibition have complementary mechanisms of action and preclinical studies have demonstrated enhanced response and survival when both are given in combination. In this aggressive HPV-positive mirroring tumor model shown in the right panel, the survival curves demonstrated survival of 90% for mice treated with combination of CUE-101 in anti-PD-1 compared to the 0% and 20% and end-of-study survival for anti-PD-1 and CUE-101 monotherapy, respectively. The demonstration of monotherapy activity in patients bolsters our beliefs that we should have observed complementary mechanistic effects in combination with pembrolizumab.

如幻燈片 9 所示，CUE-101 和檢查點抑制具有互補的作用機制，臨床前研究表明，當兩者聯合使用時，可增強反應和生存。在右圖所示的侵襲性 HPV 陽性鏡像腫瘤模型中，生存曲線顯示，與抗 PD-1 中的 CUE-101 組合治療的小鼠相比，使用 CUE-101 和抗 PD-1 治療的小鼠的生存率分別為 0% 和 20%，最終的生存率為 90%。 -分別研究抗 PD-1 和 CUE-101 單一療法的生存率。患者中單藥治療活性的證明增強了我們的信念，即我們應該觀察到與派姆單抗聯合使用的互補機制效應。

As a reminder, the data from patients treated in the CUE-101 monotherapy trial. Clearly, this approach supports the 2101 increases the number of tumor-specific T cells in the patient's body. In the combination study with pembrolizumab, it appears that these activated T cells have greater capacity to kill cancer cells when coupled with the inhibition of the PD-1 pathway, a major mechanism used by cancer cells to prevent immune-mediated killing. As reported at SITC in November of last year and as shown on the waterfall plot on Slide 10.

提醒一下，這些數據來自 CUE-101 單藥治療試驗中接受治療的患者。顯然，這種方法支持2101增加患者體內腫瘤特異性T細胞的數量。在與 pembrolizumab 的聯合研究中，這些活化的 T 細胞在與 PD-1 途徑的抑制相結合時，似乎具有更強的殺死癌細胞的能力，PD-1 途徑是癌細胞用來防止免疫介導殺傷的主要機制。正如去年 11 月 SITC 的報導以及幻燈片 10 的瀑布圖所示。

Four of the first 10 evaluable patients treated at the recommended Phase II combination dose of CUE-101 at 4 milligrams per kilogram plus pembrolizumab have experienced partial responses, i.e., at least 2 consecutive scans demonstrating a cumulative reduction of tumor burden of minus 30% or greater. Notably, 3 of the 4 partial responses have been observed in tumors with low PD-L1 expression as evidenced by CPS scores of 20 or less. -- as has been indicated by other studies, tumors that had CPS scores greater than 20 have been more responsive to PD-1 blockade and exhibit higher objective response rates compared to tumors with CPS scores less than 20.

前 10 名可評估患者中，有 4 名接受推薦的 II 期 CUE-101 聯合劑量（4 毫克每公斤）加派姆單抗治療，已出現部分緩解，即至少 2 次連續掃描顯示腫瘤負荷累計減少負 30% 或更大。值得注意的是，在 PD-L1 表達低的腫瘤中觀察到了 4 種部分緩解中的 3 種，CPS 評分為 20 或更低即可證明。 ——正如其他研究表明的那樣，與 CPS 分數低於 20 的腫瘤相比，CPS 分數大於 20 的腫瘤對 PD-1 阻斷的反應更靈敏，並且表現出更高的客觀緩解率。

The overall response rate of greater than 40% observed with CUE-101 in combination with pembrolizumab to date compares favorably to the historical objective response rate of 19% and observed with pembrolizumab monotherapy in the KEYNOTE-048 study.

迄今為止，CUE-101 聯合派姆單抗聯合治療觀察到的總體緩解率超過 40%，優於 KEYNOTE-048 研究中派姆單抗單藥治療觀察到的歷史客觀緩解率 19%。

The follow-up data on these first 10 patients as well as new emerging data on additional patients treated with combination therapy continues to strengthen, and we look forward to providing an update on the cumulative data at an upcoming oncology meeting. Key observations in patients treated with CUE-101 monotherapy in the third line and beyond include as detailed on Slide 11 demonstration of single-agent antitumor efficacy evidenced by RECIST based partial response and durable stable disease in third line and beyond recurrent metastatic head and neck cancer patients and a median overall survival benefit emerging from survival follow-up in the RP2D cohort.

關於前 10 名患者的隨訪數據以及關於接受聯合治療的其他患者的新出現的數據繼續加強，我們期待在即將召開的腫瘤學會議上提供累積數據的更新。在第三線及以後接受 CUE-101 單藥治療的患者中的關鍵觀察結果包括幻燈片 11 中詳細說明的單藥抗腫瘤功效的證明，由基於 RECIST 的部分緩解和三線及以後復發性轉移性頭頸癌的持久穩定疾病證明RP2D 隊列的生存隨訪中出現的患者和中位總生存獲益。

As previously announced, the robust data on CUE-101's activity in monotherapy and in combination with pembrolizumab enabled the granting of Fast Track designation for the treatment of patients in both the first and third line setting. The cumulative data from these ongoing trials with CUE-101 have provided us with clear evidence of targeted expansion of HPV E7-specific T cells with antitumor activity as a single agent and as a complementary mechanism with checkpoint inhibition for what we believe will broaden patient reach and enhance efficacy of checkpoint blockade therapy.

正如之前宣布的那樣，CUE-101 在單一療法以及與 pembrolizumab 聯合治療中的活性的可靠數據使得能夠授予一線和三線患者治療的快速通道資格。這些正在進行的 CUE-101 試驗的累積數據為我們提供了明確的證據，證明 HPV E7 特異性 T 細胞的靶向擴增具有抗腫瘤活性，作為單藥和檢查點抑制的補充機制，我們相信這將擴大患者覆蓋範圍並增強檢查點阻斷治療的療效。

As such, we believe CUE-101 as our first biologic therapeutic from our CUE-100 series represents a potential therapeutic breakthrough for patients, and we look forward to providing you with updated additional data at an upcoming oncology conference. Furthermore, we believe the data from CUE-101 has provided a derisking and mechanistic validation for additional biologics from the CUE-100 series beginning with CUE-102 as shown on Slide 12.

因此，我們相信 CUE-101 作為 CUE-100 系列中的第一個生物治療藥物代表了患者的潛在治療突破，我們期待在即將召開的腫瘤學會議上為您提供最新的附加數據。此外，我們相信 CUE-101 的數據為從 CUE-102 開始的 CUE-100 系列其他生物製劑提供了去風險和機制驗證，如幻燈片 12 所示。

Regarding our progress update pertaining to CUE-102, which targets Wilms Tumor 1, positive tumors in a trial that is enrolling patients with advanced colorectal, gastric, pancreatic and ovarian cancers. We anticipate completing the dose escalation portion of the trial by midyear -- the treatment has been well tolerated with no DLTs observed to date. We plan to present preliminary data from the dose escalation portion of this trial at an upcoming oncology conference.

關於 CUE-102 的進展更新，該藥物針對腎母細胞瘤 1，這是一項招募晚期結直腸癌、胃癌、胰腺癌和卵巢癌患者的試驗中的陽性腫瘤。我們預計在年中完成試驗的劑量遞增部分——該治療的耐受性良好，迄今為止尚未觀察到 DLT。我們計劃在即將召開的腫瘤學會議上提供該試驗劑量遞增部分的初步數據。

As a reminder, CUE-102 and CUE-101 tiered 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of CUE-102 as we were not required by the FDA to repeat IND-enabling toxicology studies for CUE-102, and we were also able to initiate the Phase I dose escalation study at 1 milligram per kilogram a dose at which we observed clear signs of biologic activity with CUE-101.

提醒一下，CUE-102 和 CUE-101 的氨基酸序列同一性為 99%。這使我們能夠顯著減少 CUE-102 的開發時間和成本，因為 FDA 不要求我們重複 CUE-102 的 IND 毒理學研究，而且我們還能夠在 1 時啟動 I 期劑量遞增研究。毫克每公斤的劑量，我們觀察到 CUE-101 生物活性的明顯跡象。

As Slide 13 shows, we are conducting the CUE-102 dose escalation study in colon, gastric, pancreatic and ovarian cancers. This design offers us the ability to perform monotherapy expansion studies any or all of the indications being evaluated in the dose escalation phase of the trial. This trial is actively accruing and will be open at 15 sites throughout the United States. We plan to present additional data at an upcoming oncology conference and look forward to presenting the corresponding data.

如幻燈片 13 所示，我們正在進行結腸癌、胃癌、胰腺癌和卵巢癌的 CUE-102 劑量遞增研究。這種設計使我們能夠對試驗劑量遞增階段正在評估的任何或所有適應症進行單一療法擴展研究。該試驗正在積極積累中，並將在美國 15 個地點開放。我們計劃在即將召開的腫瘤學會議上提供更多數據，並期待提供相應的數據。

I will now turn the call over to Ken. Ken?

我現在將把電話轉給肯。肯？

Thanks, Matteo. The evolving and maturing data from these programs is so extremely gratifying for me to see early on as an adviser to Cue, I recommend the potential promise of the platform for engineering biologics that could target cancer-specific T cells and could potentially deliver clinically meaningful levels of IL-2 to patients without the well-known toxicities associated with IL-2 that we all are aware of, such as vascular leak syndrome and cytokine release syndrome observed with Aldesleukin.

謝謝，馬特奧。這些項目不斷發展和成熟的數據讓我在作為 Cue 顧問的早期就看到了這一點，我非常高興，我推薦該平台在工程生物製劑方面的潛在前景，它可以靶向癌症特異性 T 細胞，並有可能提供具有臨床意義的水平IL-2 治療患者沒有我們都知道的與 IL-2 相關的眾所周知的毒性，例如用 Aldesleukin 觀察到的血管滲漏綜合徵和細胞因子釋放綜合徵。

I subsequently took on the role of acting CMO, to establish the initial clinical trials that would affect the behavior and therapeutic activity. And I'm so proud to have Shepherd 101 and 102 to those initial clinical trials and very pleased to have handed the CMO role over to you, Matteo, as you've taken on the role to bring these maturing and promising programs forward. Now once again, in the role of clinical advisers of the company, I look forward to continuing to help develop the CUE-101, 102 and future assets for the benefits of patients.

隨後，我擔任代理 CMO，以建立影響行為和治療活動的初步臨床試驗。我很自豪 Shepherd 101 和 102 能夠參與這些初步臨床試驗，並且很高興將 CMO 職位交給您，Matteo，因為您承擔了推動這些成熟且有前途的項目向前發展的角色。現在，我再次以公司臨床顧問的身份，期待繼續幫助開發 CUE-101、102 和未來的資產，以造福患者。

At this time, I'd like to take this opportunity to introduce Sara Pai, MD PhD who has served as our lead investigator for the CUE-101 program and has now joined me as a clinical adviser to the company. Dr. Pai is 1 of the world's foremost experts not only in HPV-driven head and neck cancer, but all head and neck cancer and has deep expertise as a surgeon, scientist, taking care of patients with this disease as well as running a lab studying this disease as well as the development of clinical trials for testing agents in the treatment of cancer. Sara, welcome.

這次，我想藉此機會介紹醫學博士 Sara Pai，她曾擔任我們 CUE-101 項目的首席研究員，現在加入我擔任公司的臨床顧問。 Pai 博士是世界上最重要的專家之一，不僅在 HPV 驅動的頭頸癌方面，而且在所有頭頸癌方面都具有深厚的專業知識，作為外科醫生、科學家、照顧患有這種疾病的患者以及運營實驗室，他擁有深厚的專業知識研究這種疾病以及開發癌症治療測試藥物的臨床試驗。薩拉，歡迎。

Thank you, Ken. Well, it's exciting for me personally to help designed the original CUE-101 studies and to take part as an investigator on the trials. It is important to emphasize that recurrent and/or metastatic HPV-associated head and neck cancer patients need new and promising therapies that have antitumor activity while also maintaining a good quality of life without the debilitating side effects of cancer treatment.

謝謝你，肯。嗯，對我個人來說，能夠幫助設計最初的 CUE-101 研究並作為研究人員參與試驗，我感到很興奮。需要強調的是，復發性和/或轉移性 HPV 相關頭頸癌患者需要新的、有前景的療法，這些療法具有抗腫瘤活性，同時還能保持良好的生活質量，且沒有癌症治療帶來的使人衰弱的副作用。

What we have consistently observed with CUE-101 is activity as a monotherapy. And furthermore, what appears to be synergistic activity in combination with KEYTRUDA even in those patients with a low PD-L1 biomarker score and these patients are often the most difficult to treat with immunotherapy. Therefore, CUE-101 is certainly hitting the mark by addressing this unmet clinical need.

我們一直觀察到 CUE-101 作為單一療法的活性。此外，即使在那些 PD-L1 生物標誌物評分較低的患者中，與 KEYTRUDA 聯合使用似乎也具有協同活性，而這些患者通常是最難用免疫療法治療的患者。因此，CUE-101 通過解決這一未滿足的臨床需求無疑達到了目標。

Importantly, we have observed that CUE-101 is well tolerated at clinically active doses without many of the side effects associated with IL-2 when given systemically. This attribute of CUE-101 is key since it creates a therapeutic index for IL-2, which historically has been a significant challenge and has limited the assessment of the full potential of this important cytokine for effective cancer immunotherapy.

重要的是，我們觀察到 CUE-101 在臨床活性劑量下具有良好的耐受性，在全身給藥時不會出現與 IL-2 相關的許多副作用。 CUE-101 的這一屬性非常關鍵，因為它為 IL-2 創建了治療指數，而這在歷史上一直是一個重大挑戰，並且限制了對這種重要細胞因子用於有效癌症免疫治療的全部潛力的評估。

To have some cancer patients on an immunotherapy agent for over a year with readily manageable side effects underscores the potential importance of CUE-101 or Immuno-STATs. This observation is highly relevant in the setting of an increasingly aging cancer patient population in which the median age is now 66. I'm really looking forward to seeing the continued results of the trials.

一些癌症患者接受免疫治療藥物一年多，且副作用易於控制，這凸顯了 CUE-101 或免疫 STAT 的潛在重要性。這一觀察結果與癌症患者群體日益老齡化的背景高度相關，目前癌症患者的中位年齡為 66 歲。我真的很期待看到試驗的持續結果。

I will now hand the call back to Ken.

我現在將把電話交還給肯。

Thanks, Sara. And again, I want to thank you for your thoughtful offer to be available for a brief comment today and giving us your thoughts We really appreciate your participation and benefit from your advise device and guidance throughout this process. And we continue to want to do that as we march forward to help these patients afflicted with this off of disease. We'll talk again soon. I'll now turn the call over to Anish who will discuss some recent developments in the autoimmune applications of the CUE platform along with the collaboration with Ono Pharmaceuticals for the development of CUE-401. Anish?

謝謝，薩拉。再次，我要感謝您深思熟慮的提議，讓我們今天可以發表簡短的評論，並向我們提供您的想法。我們非常感謝您的參與，並在整個過程中從您的建議設備和指導中受益。當我們繼續前進以幫助這些患有這種疾病的患者時，我們仍然希望這樣做。我們很快就會再談。現在我將把電話轉給 Anish，他將討論 CUE 平台自身免疫應用的一些最新進展，以及與 Ono Pharmaceuticals 合作開發 CUE-401。安尼什？

Thanks, Ken, and welcome to all joining this call. Let me begin by providing a perspective on the significant opportunities for resetting immune balance or functional tolerance within the broad spectrum of autoimmune diseases with our platform assets.

謝謝肯，並歡迎大家加入這次電話會議。首先，我將介紹利用我們的平台資產在廣泛的自身免疫性疾病中重置免疫平衡或功能耐受性的重要機會。

As shown here on Slide 14, we have developed an overarching strategy for addressing autoimmune and inflammatory disorders by focusing on 3 key approaches. The first approach is the selective induction and expansion of regulatory T cells, which are the natural guardians for controlling pathogenic inflammatory immune responses. To that end, we have developed a unique bispecific biologic composed of an IL-2 variant and a variant of TGF-beta termed CUE-401 that has the potential to convert pathogenic T cells into regulatory T cells as well as expand the natural recurring regulatory T cells. We recently announced our collaboration with Ono Pharmaceuticals that supports the development of CUE-401 through defined milestones.

如幻燈片 14 所示，我們通過重點關注 3 個關鍵方法，制定了解決自身免疫性和炎症性疾病的總體策略。第一種方法是選擇性誘導和擴增調節性 T 細胞，調節性 T 細胞是控制致病性炎症免疫反應的天然守護者。為此，我們開發了一種獨特的雙特異性生物製劑，由 IL-2 變體和 TGF-β 變體組成，稱為 CUE-401，它有可能將致病性 T 細胞轉化為調節性 T 細胞，並擴展自然重複的調節性 T 細胞。 T細胞。我們最近宣布與 Ono Pharmaceuticals 合作，通過明確的里程碑支持 CUE-401 的開發。

The second approach is a selective dampening and control of autoreactive T cells via our Immuno-STAT platform. This approach applies to those diseases with strong HLA association and known dominant driver autoantigens. We have previously shared the proof-of-concept data for this approach in type 1 diabetes, we have selective inhibition of insulin reactive T cells.

第二種方法是通過我們的免疫-STAT 平台選擇性抑制和控制自身反應性 T 細胞。這種方法適用於那些與 HLA 相關性強且已知顯性驅動自身抗原的疾病。我們之前分享過這種方法在 1 型糖尿病中的概念驗證數據，我們可以選擇性抑制胰島素反應性 T 細胞。

And the third approach is the generation of bispecific molecules that incorporate the nonclassical HLA-G molecule, which has been implicated in activation of tolerogenic dendritic cells expansion of regulatory T cells and suppression of autoreactive T cells. Incidentally, HLA-G is also recognized as an important checkpoint for cancer immunotherapy, where in tumors up-regulated HLA-G to escape immune detection.

第三種方法是生成包含非經典 HLA-G 分子的雙特異性分子，該分子與耐受性樹突狀細胞的激活、調節性 T 細胞的擴增和自身反應性 T 細胞的抑制有關。順便說一句，HLA-G 也被認為是癌症免疫治療的重要檢查點，在腫瘤中，HLA-G 上調以逃避免疫檢測。

For the remainder of this section, I will focus and highlight the significant differentiation and competitive position of CUE-401 in the induction of regulatory T cells, representing a significant potential value driver. As shown in the next slide, CUE-401 is a highly differentiated approach from all other IL-2 mutein teams being pursued for expansion of regulatory T cells. CUE-401 builds upon a wealth of knowledge gained within the immunology community over the past 2 decades, describing the fact that IL-2 and TGF-beta signals can convert peripheral CD4-positive T cells into regulatory T cells also known as induced Tregs or iTregs.

在本節的其餘部分中，我將重點關注並強調 CUE-401 在誘導調節性 T 細胞方面的顯著差異化和競爭地位，代表著重要的潛在價值驅動因素。如下一張幻燈片所示，CUE-401 是一種與所有其他用於擴增調節性 T 細胞的 IL-2 突變蛋白團隊高度不同的方法。 CUE-401建立在過去20年免疫學界獲得的豐富知識的基礎上，描述了IL-2和TGF-β信號可以將外周CD4陽性T細胞轉化為調節性T細胞（也稱為誘導Tregs或iTreg。

And in contrast to all other IL-2 mutein approaches that simply focus on the preexisting small fraction of natural Tregs or Tregs, CUE-401 generates new populations of induced Tregs and can also expand the pre-existing natural Tregs. Importantly, and as we have demonstrated, CUE-401 can convert pathogenic autoreactive T cells into regulatory T cells, hence providing a very attractive opportunity to reset immune tolerance. This significant differentiation is highlighted in the table shown on the bottom of the slide comparing CUE-401 to other CD25 biased IL-2 mutein approach. An example of CUE-401's activity is shown on the next slide, Slide 16.

與僅關注預先存在的一小部分天然 Tregs 或 Tregs 的所有其他 IL-2 突變蛋白方法相比，CUE-401 生成新的誘導性 Tregs 群體，並且還可以擴展預先存在的天然 Tregs。重要的是，正如我們所證明的，CUE-401 可以將致病性自身反應性 T 細胞轉化為調節性 T 細胞，從而為重置免疫耐受提供了一個非常有吸引力的機會。比較 CUE-401 與其他 CD25 偏向 IL-2 突變蛋白方法的幻燈片底部顯示的表格突出顯示了這種顯著差異。下一張幻燈片（幻燈片 16）顯示了 CUE-401 活動的示例。

In this in vitro assays, CD4 positive T cells from patients suffering from inflammatory bowel disease or rheumatoid arthritis were treated with CUE-401 and then followed for the induction of FOXP3 as shown on the y-axis of the graph.

在此體外測定中，使用 CUE-401 處理來自患有炎症性腸病或類風濕性關節炎的患者的 CD4 陽性 T 細胞，然後誘導 FOXP3，如圖中 y 軸所示。

FOXP3 is the master transcription factor expressed by regulatory T cells and is obligatory for the lineage differentiation of T cells into regulatory T cells. As noted here, treatment with CUE-401 resulted in significant induction and expansion of regulatory T cells. The base level of natural Tregs is around 2% to 5% of the CD4-positive T cells upon treatment with CUE-401 up to 50% or greater of the CD4 positive T cells differentiated into the Treg phenotype.

FOXP3 是調節性 T 細胞表達的主要轉錄因子，對於 T 細胞譜系分化為調節性 T 細胞是必需的。如本文所述，CUE-401 治療導致調節性 T 細胞顯著誘導和擴增。在用 CUE-401 處理後，天然 Tregs 的基礎水平約為 CD4 陽性 T 細胞的 2% 至 5%，高達 50% 或更多的 CD4 陽性 T 細胞分化為 Treg 表型。

We have extensively characterized the Tregs induced and expanded by CUE-401. The phenotype and genotype of these T cells are stable and robust and they demonstrate functional suppression in cell-based assays. In a collaboration with Dr. Richard DiPaolo's laboratory at the St. Louis University, we've also demonstrated in vivo conversion of Tregs and the functionality in murine models of autoimmunity. An example is shown on the next slide, Slide 17. In this model of T cell-mediated autoimmune gastritis mice were treated with only 2 doses of CUE-401 at day 1 and day 14, and the disease assessments were performed post 60 days.

我們對 CUE-401 誘導和擴增的 Tregs 進行了廣泛的表徵。這些 T 細胞的表型和基因型穩定且強大，並且在基於細胞的檢測中表現出功能抑制。在與聖路易斯大學 Richard DiPaolo 博士實驗室的合作中，我們還展示了 Tregs 的體內轉化及其在小鼠自身免疫模型中的功能。下一張幻燈片（幻燈片 17）顯示了一個例子。在這個 T 細胞介導的自身免疫性胃炎模型中，小鼠在第 1 天和第 14 天僅接受 2 劑 CUE-401 治療，並在 60 天后進行疾病評估。

As shown here, the histological analysis of the stomach tissues showed extensive pathology and destruction in the mice treated with PBS, which is a controlled middle panel. In contrast, the mice treated with CUE-401 demonstrated protection from autoimmune destruction and their stomach tissue histology look more similar to the healthy controlled mice. The graph on the right measures various metrics to generate a composite gastritis score. In this blinded assessment of histology sections, the Q401-treated mice exhibited significant reduction in the gastritis scores compared to the PBS-treated disease mice. The.

如圖所示，胃組織的組織學分析顯示用 PBS 處理的小鼠存在廣泛的病理學和破壞，這是一個受控的中間組。相比之下，用 CUE-401 治療的小鼠表現出免受自身免疫破壞的保護，並且它們的胃組織組織學看起來與健康對照小鼠更相似。右圖測量了各種指標以生成綜合胃炎評分。在組織學切片的盲法評估中，與 PBS 治療的疾病小鼠相比，Q401 治療的小鼠表現出胃炎評分顯著降低。這。

next slide highlights the vast therapeutic opportunities with CUE-401. These indications span from the well-known autoimmune diseases such as lupus, IBD, rheumatoid, arthritis, type 1 diabetes, et cetera. to opportunities in neuro inflammatory disorders such as multiple sclerosis, ALS, Alzheimer's, to pulmonary and metabolic diseases and sod and open transplantation NGVHD. We are most excited about developing CUE-401 to address many of the indications noted here.

下一張幻燈片重點介紹了 CUE-401 的巨大治療機會。這些適應症涵蓋了眾所周知的自身免疫性疾病，如狼瘡、炎症性腸病、類風濕、關節炎、1 型糖尿病等。神經炎症性疾病（如多發性硬化症、肌萎縮側索硬化症、阿爾茨海默氏症）、肺部和代謝疾病以及開放移植 NGVHD 的機會​​。我們對開發 CUE-401 來解決此處提到的許多適應症感到非常興奮。

The recently announced partnership with Ono Pharmaceuticals provides us with resource support as well as a series of defined milestone payments to support the further development of CUE-401 towards IND filing and clinical development. Importantly, we have retained an option for 50% interest in the U.S. market, providing significant commercial potential to CUE if the drug is successfully developed and approved.

最近宣布的與小野製藥的合作夥伴關係為我們提供了資源支持以及一系列明確的里程碑付款，以支持 CUE-401 向 IND 申請和臨床開發的進一步開發。重要的是，我們保留了美國市場 50% 權益的選擇權，如果該藥物成功開發並獲得批准，將為 CUE 提供巨大的商業潛力。

With that, I'll now turn the call over to Kerri to give us a brief financial update. Kerri?

現在，我將把電話轉給 Kerri，向我們提供簡短的財務最新情況。凱里？

Thanks, Anish. Turning now to Slide 19. I'd like to provide a brief update on our financial results for the year ended December 31, 2022. The company reported collaboration revenue of approximately $0.15 million and $8.3 million for the 3 months ended December 31, 2022 and 2021, respectively. The decrease was primarily due to the completion of the research phase of the LGC collaboration in the first quarter of 2022. Research and development expenses were $11.3 million and $11.5 million for the 3 months ended December 31, 2022 and 2021, respectively.

謝謝，安尼什。現在轉向幻燈片 19。我想提供有關截至 2022 年 12 月 31 日的年度財務業績的簡要更新。該公司報告截至 2022 年 12 月 31 日的 3 個月的合作收入約為 15 萬美元和 830 萬美元，分別為2021年。減少的主要原因是 LGC 合作的研究階段於 2022 年第一季度完成。截至 2022 年 12 月 31 日和 2021 年 3 個月的研發費用分別為 1,130 萬美元和 1,150 萬美元。

The decrease was due to the completion of enrollment in the Phase I monotherapy clinical trial of CUE-101 in recurrent or metastatic head and neck squamous cell cacinoma in the beginning of 2022. We General and administrative expenses were $3.7 million and $4.7 million for the 3 months ended December 31, 2022 and 2021, respectively. The decrease was primarily due to lower stock-based compensation expense recorded during the first quarter of 2022 as compared to the same period in 2021.

減少的原因是 CUE-101 治療復發性或轉移性頭頸鱗狀細胞癌的 I 期單藥臨床試驗的入組工作於 2022 年初完成。我們的一般和管理費用分別為 370 萬美元和 470 萬美元。分別截至2022年12月31日和2021年12月31日。減少的主要原因是 2022 年第一季度記錄的股票薪酬費用低於 2021 年同期。

The company reported collaboration revenue of approximately $1.2 million and $14.9 million for the years ended December 31, 2022 and 2021, respectively. The decrease was primarily due to the completion of the research phase of the LGC collaboration in the first quarter of 2022. Research and development expenses for the year were $38.6 million and $41.3 million for december 31, 2022 and 2021, respectively, and the decrease was due to a decrease in costs related to clinical trial activity for the CUE-101 monotherapy and combination clinical trials and lower manufacturing costs related to the CUE-101 and CUE-102 clinical material.

該公司報告截至2022年12月31日和2021年12月31日的年度合作收入分別約為120萬美元和1490萬美元。減少的主要原因是LGC合作的研究階段於2022年第一季度完成。2022年12月31日和2021年12月31日的年度研發費用分別為3860萬美元和4130萬美元，減少額為由於與 CUE-101 單一療法和聯合臨床試驗的臨床試驗活動相關的成本下降，以及與 CUE-101 和 CUE-102 臨床材料相關的製造成本降低。

General and administrative expenses were $16.2 million and $17.3 million for the years ended December 31, 2022 and 2021, respectively. The decrease in general and administrative expenses was due primarily to lower professional and consulting fees, stock-based compensation and rent in 2022. As of December 31, 2020, the company had approximately $76.3 million in cash, cash equivalents and marketable securities as compared to $64.4 million as of December 31, 2021. Our current cash equivalents and marketable securities will fund operations into the second half of 2024.

截至2022年12月31日和2021年12月31日止年度的一般和行政費用分別為1,620萬美元和1,730萬美元。一般和管理費用的減少主要是由於 2022 年專業和諮詢費用、股票薪酬和租金的下降。截至 2020 年 12 月 31 日，公司擁有約 7630 萬美元的現金、現金等價物和有價證券截至 2021 年 12 月 31 日為 6,440 萬美元。我們當前的現金等價物和有價證券將為 2024 年下半年的運營提供資金。

I'll now turn the call back over to Dan, who will -- for his closing remarks. Dan?

現在我將把電話轉回丹，他將作結束語。擔？

Yes. Thanks, Kerri. I can go to the next slide. And look, in summary, we believe we are well positioned to achieve our stated objectives. With CUE-101 exemplary of the IL-2-based CUE-100 series, demonstrating clear evidence of single-agent clinical activity and what appears to be at least a doubling of overall response in combination with KEYTRUDA and frontline patients. We believe we're beginning to observe what may prove to be a therapeutic breakthrough.

是的。謝謝，凱里。我可以轉到下一張幻燈片。總而言之，我們相信我們有能力實現既定目標。 CUE-101 是基於 IL-2 的 CUE-100 系列的典範，顯示出單藥臨床活性的明確證據，並且與 KEYTRUDA 和一線患者聯合使用時，總體反應似乎至少翻倍。我們相信我們正在開始觀察可能被證明是治療突破的情況。

Importantly, CUE-101 has demonstrated clinical activity in combination with KEYTRUDA in patients having a low CPS score, that is in patients whose tumors appear to be immunologically inactive or less active, where a checkpoint inhibitor is thought to be less likely to provide benefit. We believe our drug is mechanistically complementing checkpoint inhibition by activating and expanding targeted cancer-specific T cells in a well-tolerated manner, thereby broadening the patient reach and enhancing therapeutic outcome. We're focused on the following core initiatives and milestones intended to further strengthen our competitive positioning.

重要的是，CUE-101 已證明與 KEYTRUDA 聯合治療 CPS 評分較低的患者俱有臨床活性，即腫瘤似乎免疫不活躍或活性較低的患者，而檢查點抑製劑被認為不太可能提供益處。我們相信，我們的藥物通過以良好耐受的方式激活和擴增靶向癌症特異性 T 細胞，從機制上補充檢查點抑制，從而擴大患者範圍並增強治療效果。我們專注於以下核心舉措和里程碑，旨在進一步加強我們的競爭地位。

The emerging survival data in the CUE-101 monotherapy expansion cohort in the third line refractory metastatic HPV positive head and neck cancer patients. is approaching a median overall survival of 12 months and beyond, which represents substantial benefit when compared to the historical median survival of 8 months observed in second line with checkpoint inhibitors. The strength of this data provides us with the opportunity of conducting a potential Registrational trial in patients that have progressed on prior chemotherapy and checkpoint inhibitor therapy. CUE-101 plus pembrolizumab or KEYTRUDA combination in the expansion cohort is expected to complete enrollment of the full 20 patients midyear with a potential registrational trial being defined by the end of the year.

三線難治性轉移性 HPV 陽性頭頸癌患者的 CUE-101 單藥治療擴展隊列中新出現的生存數據。中位總生存期已接近 12 個月及以上，與二線檢查點抑製劑觀察到的歷史中位生存期 8 個月相比，這代表著巨大的益處。這些數據的強度為我們提供了對先前化療和檢查點抑製劑治療取得進展的患者進行潛在註冊試驗的機會。擴展隊列中的 CUE-101 加 pembrolizumab 或 KEYTRUDA 組合預計將在年中完成全部 20 名患者的入組，並在年底確定潛在的註冊試驗。

As reported, we continue to be highly encouraged by the data presented at SITC on the first 10 patients enrolled to date, follow-up analysis of these initial 10 patients as well as additional patients dosed and evaluated to date continue to hold or enhance what appears to be a doubling of the ORR compared to the checkpoint inhibition alone based on historical data as reported. Our observations from the ongoing clinical trials appears to support the premise that CUE-101 and by implication, the entire CUE-100 series mechanistically complements checkpoint inhibition. And as such, we believe our platform and growing pipeline, expands patient reach and therapeutic benefit of checkpoints.

據報導，SITC 上公佈的關於迄今為止入組的前 10 名患者的數據繼續令我們深受鼓舞，對這些最初 10 名患者以及迄今為止接受給藥和評估的其他患者的後續分析繼續保持或增強了出現的情況根據報告的歷史數據，與單獨的檢查點抑制相比，ORR 加倍。我們對正在進行的臨床試驗的觀察結果似乎支持這樣的前提：CUE-101 以及整個 CUE-100 系列在機制上補充了檢查點抑制。因此，我們相信我們的平台和不斷增長的管道可以擴大檢查點的患者範圍和治療效益。

Turning to CUE-102, the monotherapy dose escalation trial is going quite well. CUE-102 target Wilms tumor 1. Just to remind you that WT1 expressing cancers represents a very broad opportunity. We believe that evidence of clinical activity would be a significant catalyst for further validation and value enhancement of our platform. And we expect data from the dose-escalation trial to report in the second half of the year with significant potential market opportunities, as I stated, in WT1 positive cancer indications. With that, we look forward to providing you with ongoing updates in the coming months, and we'd like to thank those listening in very much for your attention and interest in Cue Biopharma, and I'd like to turn the call back to the operator for questions. Operator?

至於 CUE-102，單一療法劑量遞增試驗進展順利。 CUE-102 靶向腎母細胞瘤 1。只是提醒您，表達 WT1 的癌症代表著非常廣闊的機會。我們相信，臨床活動的證據將成為進一步驗證和提升我們平台價值的重要催化劑。我們預計劑量遞增試驗的數據將在今年下半年報告，正如我所說，WT1 陽性癌症適應症具有巨大的潛在市場機會。因此，我們期待在未來幾個月為您提供持續更新，我們非常感謝那些收聽的人對 Cue Biopharma 的關注和興趣，我想將電話轉回給操作員提問。操作員？

(Operator Instructions)

（操作員說明）

Our first question comes from the line of Ted Tenthoff with Piper Sandler.

我們的第一個問題來自特德·滕托夫和派珀·桑德勒的對話。

looking like it's picking up to be a really exciting year for you guys. I wanted to get a sense for what else we should be expecting from 101 in terms of data? And what else do you guys expect to learn in terms of helping define or design, sorry, the registrational trial?

看來今年對你們來說將是非常激動人心的一年。我想了解一下 101 數據方面我們還應該期待什麼？在幫助定義或設計註冊試驗方面，你們還希望學到什麼？

Sure. So thanks, Ted. Good to hear from you. I'll take that generically, and then I'll turn that over to Matteo and Ken. So right now, we're still in the dose -- the patient expansion phase of the combination. We are going to be filling that out, let's say, by midyear -- and as we've stated, that data continues to be followed and looks promising. We're clearly looking at overall response rate, and we're very encouraged by what we're seeing. We're also looking at biomarker metrics such as the self circulating HPV DNA as a proxy of response. Anish's group evaluates the PK/PD of these patients. So we're following those metrics accordingly.

當然。所以謝謝，特德。很高興聽到你的消息。我會籠統地接受這個問題，然後將其交給 Matteo 和 Ken。所以現在，我們仍處於劑量——組合的患者擴展階段。比方說，我們將在年中之前填寫該數據，正如我們所說，這些數據將繼續得到跟踪，並且看起來很有希望。我們顯然正在關注總體響應率，我們對所看到的情況感到非常鼓舞。我們還在研究生物標誌物指標，例如作為反應指標的自循環 HPV DNA。 Anish 的小組評估了這些患者的 PK/PD。因此，我們正在相應地遵循這些指標。

And obviously, progression-free survival is being monitored as well as overall survival. All of these metrics are currently looking very supportive and promising. So that's what we intend to be gathering and reporting, say, second half of the year, and all of that will go into the -- our corresponding registration strategy. Regarding strategy going forward, we have potential registration path for the monotherapy, principally based on median overall survival, but a lot of supporting metrics going into that. and we have the registration trial potential with the combination.

顯然，我們正在監測無進展生存期以及總生存期。所有這些指標目前看起來都非常有支持性且充滿希望。這就是我們打算在今年下半年收集和報告的內容，所有這些都將納入我們相應的註冊策略。關於未來的策略，我們有單一療法的潛在註冊路徑，主要基於中位總生存期，但有很多支持指標。我們有結合該組合進行註冊試驗的潛力。

What we're doing is just looking -- we feel fortunate that we have options there. Just based on the current capital markets and limited resources, we need to be very prudent on what we prioritize and focus upon, and we're going to have discussions with the FDA and obviously, discussions with potential partners to determining which approach we're going to take the actual design of the trial we're working out in discussion with our participating investigators, et cetera. I'm going to stop there, turn it over to Matteo and Ken if they want to add something in further more detail.

我們所做的只是尋找——我們很幸運，因為我們在那裡有選擇。僅基於當前的資本市場和有限的資源，我們需要非常謹慎地確定我們的優先事項和重點，我們將與 FDA 進行討論，顯然，還會與潛在合作夥伴進行討論，以確定我們要採用哪種方法我們將與參與的研究人員等討論我們正在製定的試驗的實際設計。我就到此為止，如果 Matteo 和 Ken 想要添加更詳細的內容，請將其轉交給他們。

Thanks, Dan. No, I think you've covered it quite well. I would just reemphasize that it's really the strength of the data as it's evolving and maturing that really provides options from a regulatory registrational point of view, for development, both as a monotherapy in laddered lines is really late line patients, so patients that have progressed on prior chemo and checkpoint inhibitor that's really an area that represents an unmet need where there's really no standard of care.

謝謝，丹。不，我認為你已經講得很好了。我想再次強調的是，隨著數據的不斷發展和成熟，數據的力量確實為開發提供了從監管註冊角度來看的選擇，無論是梯形線中的單一療法還是晚期線患者，因此已經取得進展的患者對於之前的化療和檢查點抑製劑來說，這實際上是一個未滿足需求的領域，實際上沒有護理標準。

And so one could really, I think, envision considering a very efficient randomized trial, looking at the monotherapy versus an investigator's choice of regimens. With regards to the combination, you'd ask about the data sets really by the end of the year, we should have rather mature data on the response rates for the 20 patients to be enrolled in Part D. And really, the efficacy that we're observing to date, if that's maintained and strengthened positions that to enable a trial really that could have a proximal endpoint of PFS or objective response rate in the context of a confirmatory enrolled patient trial that could potentially support an earlier approval. So just a couple of additional thoughts. It's really the strength of the data in both lines as it evolves, I think, that gives us many options to consider.

因此，我認為，人們確實可以設想考慮一項非常有效的隨機試驗，比較單一療法與研究者選擇的治療方案。關於組合，你會在今年年底詢問數據集，我們應該有關於 D 部分中 20 名患者的反應率的相當成熟的數據。實際上，我們的療效迄今為止，我們正在觀察，如果這一立場得以維持和加強，那麼在確認性入組患者試驗的背景下，試驗真正可以達到 PFS 的近端終點或客觀緩解率，這可能支持早期批准。所以還有一些額外的想法。我認為，這實際上是兩條線路中數據的強度隨著它的發展而給我們提供了許多可供考慮的選擇。

Our next question comes from the line of Ren Benjamin with JMP Securities.

我們的下一個問題來自 JMP 證券的任本傑明 (Ren Benjamin)。

Congratulations on the progress. I guess I'd like to just kind of start off, start off. You mentioned patient A, patient B and patient C I'd love to just kind of get your thoughts maybe from Ken or Sara if she's on as to 1 reasons for potential relapse, is there any work or anything that you might be able to gather from interacting with the patient or any of the biomarker studies that might give you some clues as to that?

祝賀取得的進展。我想我想開始，開始。您提到了患者 A、患者 B 和患者 C，我很想從 Ken 或 Sara 那裡了解您的想法，如果她對潛在復發的 1 個原因有了解，是否有任何工作或您可以收集的任何信息通過與患者的互動或任何可能為您提供一些線索的生物標誌物研究？

And then the other kind of related to it, more on the combo side is you have these objective responses like the PRs, but have you observed, I think you did in the monotherapy portion of the study, a deepening of response where SDs are becoming PRs and what is driving those kinds of responses? And then I have a follow-up.

然後與之相關的另一種，更多的是在組合方面，你有這些客觀的反應，比如 PR，但是你有沒有觀察到，我認為你在研究的單一治療部分中觀察到了，SD 正在變得更加深入的反應公關以及是什麼推動了這些反應？然後我有一個後續行動。

So this is Ken. Sara had a drop off a few go to see a patient. But basically, patients fail primary therapy because tumor cells are left behind. And currently, an activated immune system is not in place to wipe out any remaining microscopic nests of cells that we just don't see. So with radiation or surgery, we just have left a cell behind and our own immune systems don't clean them up. I mean -- so we're very interested, for example, in the neoadjuvant study we have going on to see if we can activate T cells by using CUE-101 to try and get those last cells cleaned up. And that's what we're seeing over and over in all of cancer, including head and neck cancer, that it's these unseeable few cancer cells that are left behind that we have to figure out how to get cleaned up by activating the immune system. So I'll stop there and see if that answered your question or if you need further -- need more.

這就是肯。薩拉有幾次下車去看病人。但基本上，患者的主要治療失敗是因為腫瘤細胞被遺留下來。目前，激活的免疫系統還無法消滅任何我們看不到的殘留的微觀細胞巢。因此，通過放射或手術，我們只是留下了一個細胞，而我們自己的免疫系統無法清理它們。我的意思是 - 所以我們非常感興趣，例如，在新輔助研究中，我們正在進行，看看我們是否可以通過使用 CUE-101 來激活 T 細胞，嘗試清理最後的細胞。這就是我們在所有癌症（包括頭頸癌）中反复看到的情況，正是這些看不見的少數癌細胞被留下，我們必須弄清楚如何通過激活免疫系統來清除它們。所以我會停在那裡，看看這是否回答了你的問題，或者你是否需要進一步 - 需要更多。

Yes. So you mentioned the neoadjuvant study and as I was kind of quickly stepping out the milestones for this year, I might have missed when we might see something regarding the neoadjuvant study. Can you just give us an update as to how that's progressing and when we might see some initial results from that study? .

是的。所以你提到了新輔助研究，由於我很快就邁出了今年的里程碑，我可能錯過了我們可能看到有關新輔助研究的一些內容。您能否向我們介紹一下進展情況以及我們何時可以看到該研究的一些初步結果？ 。

I'll give that 1 to Matteo since.

從那以後我會把這個1給Matteo。

The neoadjuvant trial is going well. The first cohort of patients in schema 1 have been fully enrolled. And the preliminary data looks very, very intriguing, whereby we've seen evidence of expansion of V7 reactive T cells and increases in NK cells. So -- the study now is currently recruiting and enrolling Schedule B, which is 2 doses prior to surgery or definitive treatment. And we'd anticipate completing enrollment into that cohort by the end of the year.

新輔助試驗進展順利。方案 1 中的第一批患者已全部入組。初步數據看起來非常非常有趣，我們已經看到了 V7 反應性 T 細胞擴增和 NK 細胞增加的證據。因此，該研究目前正在招募和登記 Schedule B，即手術或最終治療前 2 劑。我們預計在今年年底前完成該群體的註冊。

Got it. Okay. And then just as we think about the registrational potential registrational studies, I guess then, if we take out the potential for a partner. Let's just say that's a discussion that winds up taking too long. Can you just maybe take us through the steps that would, I guess, help you decide like which trial to go ahead and start like I would think that the refractory monotherapy study is the way to go. But I don't know what are the other factors that you might be thinking about as you decide to commit to one or the other?

知道了。好的。然後，正如我們考慮註冊潛力註冊研究一樣，我想，如果我們排除合作夥伴的潛力。我們只能說這個討論花費的時間太長了。您能否帶領我們完成一些步驟，我想，這些步驟可以幫助您決定進行哪項試驗，並像我認為難治性單一療法研究是正確的那樣開始。但我不知道當您決定致力於其中之一時，您可能會考慮哪些其他因素？

Yes. And so it's a really important question, Ren. And it's 1 that we obviously are looking at very seriously and dynamically in the various factors we have to consider. So for instance, you just mentioned monotherapy, maybe the more attractive ones since it is monotherapy direct path forward. It's primary readout is the -- is basically median overall survival. We have to follow patients. Also bear in mind, it's a smaller market. And so part of countering that is in the front line, which is further upstream broader market of patients, we're seeing these very promising results. So by essence of the promise of those results, we would be potentially shrinking that downstream market even further.

是的。所以這是一個非常重要的問題，Ren。顯然，我們正在非常認真、動態地考慮我們必須考慮的各種因素。例如，您剛才提到單一療法，也許更有吸引力，因為它是單一療法的直接前進道路。它的主要讀數是——基本上是中位總生存期。我們必須跟踪患者。另請記住，這是一個較小的市場。因此，應對這種情況的一部分是在前線，即更上游的更廣泛的患者市場，我們看到了這些非常有希望的結果。因此，從本質上講，從這些結果的承諾來看，我們可能會進一步縮小下游市場。

So -- and what we'd be measuring there is you probably would be overall response rate, clearly, we'd be following median overall survival, but it's a broader market. And we're also looking at moving even more upstream there with the neoadjuvant adjuvant setting, for instance. So these are kind of the various factors we have to consider. And it also has to do with the capital access that we have, whether it is through a partnership, if we're doing it ourselves, we have to think about the size of the study and the duration of that study.

因此，我們要衡量的可能是整體反應率，顯然，我們會遵循中位整體生存率，但這是一個更廣闊的市場。例如，我們還在考慮通過新輔助輔助設置向上游邁進。所以這些是我們必須考慮的各種因素。它還與我們擁有的資本渠道有關，無論是通過合作夥伴關係，還是我們自己做，我們都必須考慮研究的規模和研究的持續時間。

So all of those variables are being considered. I think the important take home for us right now at this point in time is we have the prospect of more than 1 potential registration path to choose from.

因此，所有這些變量都在考慮之中。我認為目前對我們來說最重要的收穫是我們有超過 1 種潛在的註冊路徑可供選擇。

Our next question call comes from the line of Mark Breidenbach with Oppenheimer.

我們的下一個問題電話來自馬克·布雷登巴赫和奧本海默的電話。

Just some timing questions for me to make sure I heard you guys correctly. we should be expecting the next data both from the CUE-101 combination study in the second half of this year as well as the initial data from CUE-102 -- so first of all, is that correct? And second, what should we expect in the CUE-102 data? Is it just be safety and PK data initially? Or should we kind of expect a more complete analysis of the dose escalation cohorts from that? And I have a follow-up.

只是向我提出一些時間問題，以確保我正確地聽到了你們的聲音。我們應該期待今年下半年 CUE-101 組合研究的下一個數據以及 CUE-102 的初始數據——所以首先，這是正確的嗎？其次，我們應該對 CUE-102 數據有何期待？最初只是安全性和PK數據嗎？或者我們是否應該期待對劑量遞增隊列進行更完整的分析？我有一個後續行動。

Sure. All right. Thanks, Mark. Appreciate it. So the first question, just to clarify, when we said the second half of the year, that's the sort of completed analysis or the analysis of the completed 20 patient expansion. The next update we'll be providing is at an upcoming oncology conference. So that could be midyear. We're not going to wait until second half of the year to release an update. So what we're referring to the second half is that's all 20 patients completed surveyed, et cetera, a more deeper analysis.

當然。好的。謝謝，馬克。欣賞它。所以第一個問題，只是為了澄清，當我們說下半年時，這是那種已完成的分析或已完成的 20 名患者擴展的分析。我們將在即將召開的腫瘤學會議上提供下一次更新。所以那可能是年中。我們不會等到下半年才發布更新。所以我們指的是下半年，所有 20 名患者都完成了調查，等等，更深入的分析。

So I hope that's helpful. We're looking at an update probably midyear at a cancer conference -- and then regarding the metrics on 102, I think the way you couched the question that's actually the answer is we'll be doing the dose escalation, completing that by midyear, and we'll be providing the corresponding metrics that we've been measuring along the way, which, in fact, has to do with PK/PD, a possibility, obviously, of some clinical activity as well. and that's going to be midyear, second half of the year.

所以我希望這有幫助。我們正在研究可能在年中的癌症會議上進行的更新，然後關於 102 的指標，我認為您提出問題的方式實際上是答案，我們將進行劑量升級，在年中之前完成，我們將提供我們一直在測量的相應指標，事實上，這與 PK/PD 有關，顯然，這也與某些臨床活動有關。那將是年中、下半年。

Matteo, I don't know if you want to add anything to that? If not, that's fine.

Matteo，我不知道你是否想補充什麼？如果沒有，那也沒關係。

No, that's fine. Nothing to add.

不，沒關係。沒什麼可補充的。

Okay. That's super helpful. And then just maybe 1 for Anish on CUE-401. I'm just wondering if you have any plans to present head-to-head preclinical comparisons versus some of the other IL-2 muteins that are out there? Is that something that's on the agenda for 2023?

好的。這非常有幫助。然後 CUE-401 上的 Anish 可能只有 1。我只是想知道您是否有計劃與其他一些 IL-2 突變蛋白進行頭對頭的臨床前比較？這是 2023 年議程上的事情嗎？

Yes, Mark, we've actually, in previous meetings, and there's an upcoming Treg meeting in May, where we're talking. But in a meeting in Paris last year, we presented on this where we compare this to CD25-biL-2-muten where we show clear induction by CUE-401 where the IL-2 mutein as expected, did not convert. And that's not surprising. It is the anticipated immunological outcome. We're continuing to build on that data and in vivo models as well, and we'll be discussing that in the future. But so far, the biology strongly supports the induction and generation of new populations of Tregs which 401 can do but obviously a CD25 biased IL mutine cannot.

是的，馬克，實際上，我們在之前的會議中已經討論過，並且我們正在討論 5 月份即將召開的 Treg 會議。但在去年巴黎的一次會議上，我們對此進行了介紹，我們將其與 CD25-biL-2-muten 進行了比較，其中我們顯示了 CUE-401 的明顯誘導作用，其中 IL-2 突變蛋白如預期的那樣沒有轉化。這並不奇怪。這是預期的免疫學結果。我們將繼續以這些數據和體內模型為基礎，我們將在未來討論這一點。但到目前為止，生物學強烈支持新的 Tregs 群體的誘導和產生，401 可以做到這一點，但顯然偏向 CD25 的 IL 突變體不能做到。

(Operator Instructions)

（操作員說明）

And our next question comes from the line of Stephen Willey with Stifel.

我們的下一個問題來自斯蒂芬·威利和斯蒂菲爾的對話。

Congrats on progress. So on CUE-102, I know you're talking about monotherapy dose escalation initiating dose expansion monotherapy. But are there plans to initiate dose escalation with CUE-102 in combination with the checkpoint inhibitor? And I guess, is that something that you would expect to start in parallel with monotherapy dose escalation?

祝賀進步。因此，在 CUE-102 上，我知道您正在談論單一療法劑量遞增啟動劑量擴展單一療法。但是否有計劃啟動 CUE-102 與檢查點抑製劑聯合用藥的劑量遞增？我想，您是否希望與單藥治療劑量遞增同時開始？

Very good question. And the answer is yes. I mean, obviously, it's very similar to 101. We expect same general pattern. We are -- just to remind everyone, our first trial is with pembrolizumab, but we expect that our drugs in platform will work with any checkpoint. So we're looking at various options and alternatives presently, but that is our intent to also survey in combination it's first to show the monotherapy tolerability profile, which we expect to, in essence, mirror what we've seen with 101. But obviously, having that data will be important. And then as you have stated, that's the natural next step.

非常好的問題。答案是肯定的。我的意思是，顯然，它與 101 非常相似。我們期望有相同的一般模式。我們只是提醒大家，我們的第一個試驗是使用 pembrolizumab，但我們希望我們平台上的藥物能夠與任何檢查點一起使用。因此，我們目前正在考慮各種選擇和替代方案，但我們的目的也是進行聯合調查，首先顯示單一療法的耐受性概況，我們希望在本質上反映我們在 101 中看到的情況。但顯然，擁有這些數據很重要。然後正如您所說，這是自然的下一步。

Okay. And would you be prespecifying tumors to be WT1 positive with the combination as well? And then I guess, does the monotherapy dose expansion then maybe inform select tumor types for expansion with combo?

好的。您是否會通過該組合預先指定腫瘤為 WT1 陽性？然後我猜想，單一療法劑量擴展是否可能會通知選擇的腫瘤類型以進行組合擴展？

So the answer is yes to both of those questions. Yes, we will be stratifying patients based on WT1 expression and then also in terms of the type of cancers. And the 101 -- I'm sorry, the 102 monotherapy will certainly guide our thinking of tumors that are more responsive. So that's absolutely spot on both questions.

所以這兩個問題的答案都是肯定的。是的，我們將根據 WT1 表達以及癌症類型對患者進行分層。 101——我很抱歉，102單一療法肯定會指導我們對反應性更強的腫瘤的思考。所以這兩個問題都完全正確。

Okay. And I guess, there appears to be a bit more discussion just around the pursuit of partnering opportunities. And I guess just philosophically, curious if you think that the more proximal opportunities for you are also autoimmune focus, maybe with the CUE-300 series? Or do you think that there's an opportunity here with either the 2 CUE-100 programs we know about, maybe some more that we don't know about that could be kind of put out to bid?

好的。我想，圍繞尋求合作機會似乎有更多的討論。我想只是從哲學角度來說，好奇您是否認為對您來說更接近的機會也是自身免疫焦點，也許是 CUE-300 系列？或者您認為我們知道的 2 個 CUE-100 項目是否有機會，也許還有一些我們不知道的項目可以進行競標？

Yes. So Steve, it's a really important question, complicated question because there are a lot of different perspectives on that and variables we have to consider. I think what we're trying to emphasize is this partnership we just announced with Ono. It's not a -- it's sort of classic license for some money. We're actively involved. They're a collaborator. They're supporting the preclinical development work. We have an option to codevelop.

是的。所以史蒂夫，這是一個非常重要的問題，也是一個複雜的問題，因為對此有很多不同的觀點，我們必須考慮變量。我認為我們想要強調的是我們剛剛宣布與小野的合作關係。這不是一個——它是某種金錢的經典許可證。我們正在積極參與。他們是合作者。他們正在支持臨床前開發工作。我們可以選擇共同開發。

They pay milestones along the way. Those milestone payments go a long way to subsidizing our portion if we decide to co-develop and that allows us to basically retain a significant upside. And what we're trying to basically state here is we have no intention of partnering assets where we're doing preclinical work and then licensing the upside so that we're just monetizing assets. We want to be involved, but the key is to have leverage through the power of the data that we're generating. And we think with the 101 and hopefully 102 following behind data sets that we're developing.

他們一路上支付里程碑費用。如果我們決定共同開發，這些里程碑式的付款對補貼我們的份額大有幫助，這使我們基本上能夠保留顯著的優勢。我們在這裡試圖基本上聲明的是，我們無意與正在進行臨床前工作的資產進行合作，然後許可優勢，以便我們只是將資產貨幣化。我們希望參與其中，但關鍵是要利用我們生成的數據的力量來發揮影響力。我們認為，我們正在開發的數據集後面有 101 個，希望還有 102 個。

This basically validates the whole 100 Series. And what we'd like to be in a position of leverage in terms of structuring partnerships that allow us to subsidize some of the costs, i.e., capitalization risk but retain significant upside. We also would benefit from the depth of clinical development capabilities from various partners in the checkpoint space. So we're not adverse to partnering 101 and 102, but we're certainly not going to hand over the upside of the asset to somebody and just do preclinical work.

這基本上驗證了整個100系列。我們希望在構建合作夥伴關係方面處於有利地位，使我們能夠補貼一些成本，即資本化風險，但保留顯著的上行空間。我們還將受益於檢查點領域各個合作夥伴的深度臨床開發能力。因此，我們並不反對 101 和 102 合作，但我們當然不會將資產的優勢交給某人，而只做臨床前工作。

So we intend to be involved. So we have retained interest and involvement and commercialization rates hopefully in co-development. But also what you stated, the 300 series is also a natural point for partnering as well. We have a very attractive data set there.

所以我們打算參與其中。因此，我們希望在共同開發中保留興趣、參與度和商業化率。但正如您所說，300 系列也是自然的合作點。我們那裡有一個非常有吸引力的數據集。

Thank you. There are no further questions at this time. I'd like to turn the call back to Dan Passeri for closing remarks.

謝謝。目前沒有其他問題。我想將電話轉回丹·帕塞里（Dan Passeri），讓其致閉幕詞。

Yes. Thank you. Again, I just want to thank everyone for your time and attention during these trying times in the market and really appreciate your time, and we look forward to providing you with ongoing updates particularly midyear, right. Thank you very much. Bye-bye.

是的。謝謝。再次，我想感謝大家在市場艱難時期所付出的時間和關注，並非常感謝您的時間，我們期待為您提供持續的更新，特別是年中，對吧。非常感謝。再見。

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation, and have a great day.

今天的會議到此結束。此時您可以斷開線路。感謝您的參與，祝您有美好的一天。