Compugen Ltd (CGEN) 2023 Q2 法說會逐字稿

Ladies and gentlemen, thank you for joining us today. Welcome to Compugen's second quarter 2023 results conference call. (Operator Instructions) As a reminder, today's call is being recorded. An audio webcast of this call will be made available on the Investors section of Compugen's website, www.cgen.com. I would now like to introduce Yvonne Naughton, Head of Investor Relations and Corporate Communications. Yvonne, please go ahead.

女士們、先生們，謝謝你們今天加入我們。歡迎參加 Compugen 2023 年第二季業績電話會議。 （操作員說明）謹此提醒，今天的通話正在錄音。本次電話會議的音訊網路廣播將在 Compugen 網站 www.cgen.com 的投資者部分提供。我現在想介紹投資者關係和企業傳播主管 Yvonne Naughton。伊馮，請繼續。

Thank you, operator, and thank you all for joining us on the call today. Joining me for Compugen for the prepared remarks are Dr. Anat Cohen-Dayag, President and Chief Executive Officer; and Alberto Sessa, Chief Financial Officer. Dr. Henry Adewoye, Chief Medical Officer; and Dr. Eran Ophir, Chief Scientific Officer, will join us for the Q&A.

謝謝接線員，也謝謝大家今天加入我們的電話會議。與我一起參加 Compugen 準備發言的還有總裁兼執行長 Anat Cohen-Dayag 博士；和財務長阿爾貝托·塞薩。 Henry Adewoye 博士，首席醫療官；首席科學官 Eran Ophir 博士將與我們一起參加問答。

Before we begin, I would like to remind you that during this call, the company may make projections or forward-looking statements regarding future events, business outlook, research and development efforts, and the potential outcome, the capabilities of the company's discovery platform, anticipated progress and plans, results and timelines for its programs, financial and accounting-related matters, including projected financial information as well as statements regarding the company's future cash position and other results, and the company's future initiatives.

在我們開始之前，我想提醒您，在這次電話會議中，公司可能會對未來事件、業務前景、研發工作以及潛在結果、公司發現平台的能力做出預測或前瞻性陳述，其計劃的預期進度和計劃、結果和時間表、財務和會計相關事項，包括預計的財務資訊以及有關公司未來現金狀況和其他結果的報表，以及公司未來的舉措。

We wish to caution you that such statements reflect only the company's current beliefs, expectations, and assumptions but actual results, performance or achievements of the company may differ materially. These statements are subject to known and unknown risks and uncertainties which could cause the company's actual results to differ materially from those projected in such forward-looking statements.

我們希望提醒您，此類陳述僅反映公司當前的信念、期望和假設，但公司的實際結果、績效或成就可能存在重大差異。這些陳述受到已知和未知的風險和不確定性的影響，可能導致公司的實際結果與此類前瞻性陳述中的預測有重大差異。

And we refer you to the SEC filings for more details on these risks, including the company's most recent annual report on Form 20-F filed with the SEC on February 28, 2023. The company undertakes no obligation to update projections and forward-looking statements in the future.

我們建議您參閱 SEC 文件，以了解有關這些風險的更多詳細信息，包括該公司於 2023 年 2 月 28 日向 SEC 提交的最新 20-F 表格年度報告。該公司不承擔更新預測和前瞻性陳述的義務將來。

And now I'll turn the call over to Anat.

現在我將把電話轉給阿納特。

Thank you, Yvonne. Good morning and good afternoon, everyone, and welcome to our second quarter 2023 update. At Compugen, our goal is to transform the treatment of cancer patients who have no effective treatment options by discovering novel drug targets and developing potential first-in-class drugs.

謝謝你，伊馮。大家早安、下午好，歡迎來到我們 2023 年的第二季更新。在 Compugen，我們的目標是透過發現新的藥物標靶和開發潛在的一流藥物來改變沒有有效治療選擇的癌症患者的治療方法。

On this front, we were efficiently executing on our differentiated clinical approach to evaluate the benefit of our chemotherapy-free triple cancer immunotherapy combination of COM701, COM902, and pembrolizumab blocking three pathways of the DNAM axis, PVRIG, TIGIT and PD-1.

在這方面，我們正在有效地執行我們的差異化臨床方法，以評估我們的無化療三重癌症免疫療法組合COM701、COM902 和派姆單抗阻斷DNAM 軸（PVRIG、TIGIT 和PD-1）的三種途徑的益處。

At ASCO this year, we were excited to see the positive momentum and interest of the industry and the scientific community encouraging the DNAM-1 axis as a potential novel approach in treating cancer reflected by our own data and data presented by others, including AstraZeneca, Roche, and Arcus Gilead.

在今年的ASCO 上，我們很高興看到行業和科學界的積極勢頭和興趣，鼓勵DNAM-1 軸作為治療癌症的潛在新方法，這反映在我們自己的數據和其他人提供的數據中，包括阿斯特捷羅氏和阿克斯吉利德。

Looking at the totality of the data we have presented to date in hard-to-treat cancer patients, there was enthusiasm among those we spoke with regarding responses demonstrated with our triple combination approach in patients with microsatellite stable endometrial cancer, who had failed standard of care, including prior pembro and lenvatinib treatment. For these patients, there were no other treatment options. In nine patients, we showed an overall response rate of 22% and a disease control rate of 44%.

縱觀我們迄今為止在難治性癌症患者中提供的全部數據，我們採訪的那些人對我們的三聯療法在微衛星穩定子宮內膜癌患者中所顯示的反應充滿熱情，這些患者未達到治療標準護理，包括先前的pembro 和lenvatinib 治療。對於這些患者來說，沒有其他治療選擇。在 9 名患者中，我們的整體緩解率為 22%，疾病控制率為 44%。

The responses were durable and supported by immune activation better than what one would expect for an anti-PD-1 alone. This endometrial data is consistent with the anti-tumor activity we reported for COM701 based combinations in patients with other hard-to-treat tumor, including microsatellite stable colorectal cancer, platinum resistant ovarian cancer, and checkpoint inhibitor experienced non-small cell lung cancer patients.

這些反應是持久的，並且受到免疫活化的支持，比人們對單獨的抗 PD-1 藥物的預期效果更好。此子宮內膜數據與我們報告的基於COM701 的組合在其他難以治療的腫瘤患者中的抗腫瘤活性一致，包括微衛星穩定結直腸癌、鉑耐藥卵巢癌和患有檢查點抑製劑的非小細胞肺癌患者。

Reflecting on the totality of the data to date, in patients typically not responsive to standard of care, including immunotherapy, our data suggests that our COM701 based combinations have the potential to offer a treatment option with a favorable safety profile for hard-to-treat patients across the spectrum of PD-L1 expression levels in patients who are anti-PD-1 treatment refractory pointing to a potential COM701 mediated mechanism of action.

考慮到迄今為止的全部數據，對於通常對標準護理（包括免疫療法）沒有反應的患者，我們的數據表明，我們基於 COM701 的組合有可能為難以治療的患者提供具有良好安全性的治療選擇抗PD -1 治療難治性患者中各種PD-L1 表達水平的患者，顯示COM701 介導的潛在作用機制。

Our immediate focus is on expanding our data in two indications: platinum-resistant ovarian cancer and MSS colorectal cancer, while continuing to invest in biomarker discovery which is important in efficiently setting our development path forward. However, we believe that the therapeutic potential of COM701 as part of the DNAM-1 axis may be much broader than these two indications. As mentioned earlier, AstraZeneca presented clinical results at ASCO on rilvegostomig, a PD-1/TIGIT bispecific antibody derived from our COM902, establishing its safety and pharmacokinetic profile and showing anti-tumor activity in patients previously exposed to checkpoint inhibitors and usually not responsive to immunotherapy.

我們目前的重點是擴展兩個適應症的數據：鉑抗藥性卵巢癌和 MSS 大腸癌，同時繼續投資於生物標記發現，這對於有效設定我們的發展道路非常重要。然而，我們相信 COM701 作為 DNAM-1 軸一部分的治療潛力可能比這兩個適應症更廣泛。如前所述，阿斯特捷利康在ASCO 上展示了rilvegostomig 的臨床結果，這是一種源自我們的COM902 的PD-1/TIGIT 雙特異性抗體，確定了其安全性和藥物動力學特徵，並在先前接觸過檢查點抑制劑且通常對檢查點抑制劑無反應的患者中顯示出抗腫瘤活性。免疫療法。

AstraZeneca continues to rilvegostomig's development in multiple studies, including a Phase II trial in checkpoint inhibitor-naive non-small cell lung cancer patients and a Phase II trial in hepatobiliary cancer and previously announced plans to initiate a Phase III trial this year. We know that not all anti-PD are designed the same. And like COM902, which is an anti-PD with reduced Fc effector functions, rilvegostomig was engineered to have an inactive Fc domain to enhance antitumor activity.

阿斯特捷利康繼續在多項研究中推進rilvegostomig 的開發，包括針對未接受檢查點抑制劑的非小細胞肺癌患者的II 期試驗和肝膽癌的II 期試驗，以及此前宣布的今年啟動III 期試驗的計劃。我們知道並非所有抗 PD 藥物的設計都是相同的。與 COM902（一種 Fc 效應器功能降低的抗 PD 藥物）一樣，rilvegostomig 也被設計為具有非活性 Fc 結構域，以增強抗腫瘤活性。

Another program in this Fc inactive or reduced effector function came in Arcus' anti-TIGIT. At ASCO, Arcus-Gilead showed continued improvement in progression-free survival versus blocking PD-1 alone with a potentially better safety profile to what has been shown to date with Fc active anti-TIGIT. Another session that gained great interest at ASCO was Roche TIGIT liver cancer data. This is the third randomized trial showing the benefit of adding an anti-TIGIT to standard of care.

另一個 Fc 失活或效應器功能減弱的程序是 Arcus 的抗 TIGIT。在 ASCO 上，Arcus-Gilead 與單獨阻斷 PD-1 相比，顯示出無進展生存期的持續改善，並且與迄今為止使用 Fc 活性抗 TIGIT 所顯示的相比，其安全性可能更好。 ASCO 上另一個引起極大興趣的會議是羅氏 TIGIT 肝癌數據。這是第三項隨機試驗，顯示在標準護理中添加抗 TIGIT 藥物的益處。

Blocking TIGIT resulted in a four times greater overall response rate and a doubling the progression-free survival on top of standard of care. And Roche has initiated a Phase III trial in first-line hepatocellular cancer based on these results. We were pleased that the discussions of Roche presentation highlighted the potential significance of adding PVRIG blockade in hepatocellular cancer. This is another hard-to-treat indication which may serve as a fit for COM701 treatment.

阻斷 TIGIT 可使整體緩解率提高四倍，並且在標準護理的基礎上使無進展生存期提高一倍。羅氏根據這些結果啟動了一線肝細胞癌的 III 期試驗。我們很高興羅氏演講的討論強調了在肝細胞癌中添加 PVRIG 阻斷的潛在意義。這是另一種難以治療的適應症，可能適合 COM701 治療。

The important role of PVRIG was also called out in another ASCO session on novel approaches to checkpoint inhibitors, in which the presenter was intrigued by our data presented by Dr. Mike Overman from MD Anderson at [CC] last year showing that blocking PVRIG in combination with PD-1 led to responses in unexpected diseases like microsatellite stable colorectal cancer. It is great to see an increased awareness of PVRIG role in cancer immunotherapy. It is important to highlight Compugen's differentiated approach and how we stand out among all the players.

PVRIG 的重要角色在另一場關於檢查點抑制劑新方法的ASCO 會議上也得到了強調，其中演講者對我們去年在[CC] 上MD 安德森的Mike Overman 博士提出的數據很感興趣，該數據顯示聯合阻斷PVRIG PD-1 可以對意想不到的疾病（如微衛星穩定大腸直腸癌）產生反應。很高興看到人們越來越認識到 PVRIG 在癌症免疫治療中的作用。重要的是要強調 Compugen 的差異化方法以及我們如何在所有參與者中脫穎而出。

Firstly, we have always said that blocking TIGIT may not be enough and that PVRIG may be needed. Our discovery of PVRIG and the extensive research we have conducted to test the effect of unlocking its biological function as a new drug target in the context of the DNAM axis support the need to block it. This disease is consistently being reinforced as we roll out our clinical data across multiple indications.

首先，我們一直說阻止TIGIT可能還不夠，可能需要PVRIG。我們對 PVRIG 的發現以及我們為測試在 DNAM 軸背景下釋放其作為新藥物靶點的生物功能的效果而進行的廣泛研究支持了阻斷它的必要性。隨著我們跨多種適應症推出臨床數據，這種疾病不斷加強。

Secondly, we believe we have a potentially best-in-class reduced Fc effector function anti-TIGIT. The data available today suggest that Fc design of the TIGIT antibody may either not matter or it may be better to have a reduced or inactive Fc domain as we have.

其次，我們相信我們擁有潛在同類最佳的 Fc 效應功能降低的抗 TIGIT。今天獲得的數據表明，TIGIT 抗體的 Fc 設計可能並不重要，或者像我們一樣具有減少的或無活性的 Fc 結構域可能會更好。

And finally, with COM701 and COM902, our two wholly owned PVRIG and TIGIT programs, we're the leader in the unique chemotherapy-free triple combination approach of blocking three DNAM axis immune checkpoints, PVRIG, TIGIT, and PD-1 with initial clinical data to support our hypothesis.

最後，憑藉我們全資擁有的兩個PVRIG 和TIGIT 項目COM701 和COM902，我們成為獨特的無化療三重組合方法的領導者，該方法通過初始臨床阻斷三個DNAM 軸免疫檢查點PVRIG、TIGIT 和PD -1數據來支持我們的假設。

Along with a very successful ASCO, I would like to refer to additional progress we have made in the first half of the year. We're advancing patient enrollment in our two follow on proof-of-concept studies. Enrollment in the MSS-CRC study is on track to be completed by the end of the year. Enrollment is slower than planned in the platinum-resistant ovarian cancer study, but we believe, we can catch up on enrollment with a planned activation of additional sites.

除了非常成功的 ASCO 之外，我還想談談我們在今年上半年的其他進展。我們正在推進兩項後續概念驗證研究的患者入組。 MSS-CRC 研究的招募工作預計將於今年底完成。鉑類抗藥性卵巢癌研究的入組速度比計劃的要慢，但我們相信，我們可以透過計劃激活其他站點來趕上入組速度。

As a reminder, the goal of these studies is to obtain more data, help us better understand the contribution of components, and build on extensive biomarker work to identify the patients most likely to respond. We believe that this strategy provides the fastest way to efficiently set our development path forward and to potentially de-risk our lead assets, COM701 and COM902 in these two indications.

提醒一下，這些研究的目標是獲得更多數據，幫助我們更好地了解成分的貢獻，並在廣泛的生物標記工作的基礎上確定最有可能做出反應的患者。我們相信，這項策略提供了最快的方式來有效地設定我們的發展道路，並潛在地降低我們的領先資產 COM701 和 COM902 在這兩個適應症中的風險。

In May of this year, we presented data on our potential first-in-class anti IL-18 binding protein antibody, COM503, and at CIMT Conference, Europe's annual immunology conference. We believe there is excitement around our innovative approach leading to the development of this COM503 program and its potential in addressing immunotherapy resistance.

今年 5 月，我們在歐洲年度免疫學會議 CIMT 會議上展示了我們潛在的一流抗 IL-18 結合蛋白抗體 COM503 的數據。我們相信，我們的創新方法導致了 COM503 項目的開發及其在解決免疫療法抗藥性方面的潛力，這令人興奮。

Finally, on the progress in the first half of 2023, we're delighted with the favorable ruling of the European patent office to uphold the broad claims in our PVRIG patent. It's ruling of the European patent office is the win for our innovation, the discovery of PVRIG's role as a novel immune checkpoint and a drug target for cancer. As a company that excels in the discovery of new drug targets, we harnessed a broad patent strategy that takes advantage of our novel target discovery capability.

最後，關於 2023 年上半年的進展，我們很高興歐洲專利局做出了有利的裁決，維持了我們 PVRIG 專利中的廣泛權利要求。歐洲專利局的裁決是我們創新的勝利，是我們發現 PVRIG 作為新型免疫檢查點和癌症藥物標靶的作用的勝利。作為一家擅長發現新藥物標靶的公司，我們採用了廣泛的專利策略，充分利用了我們的新標靶發現能力。

Now moving on to what you should expect to see from us over the second half of the year. First, we plan to report initial findings from our ongoing proof-of-concept study by the end of the year and final data at a medical conference in 2024. Second, we're expecting to present new translational and initial biomarker data and long-term patient follow-up from our platinum-resistant ovarian cancer study presented at ESMO-IO last year, as well as additional data from our COM503 preclinical program, all by the end of the year.

現在讓我們來談談下半年您應該看到的內容。首先，我們計劃在今年年底之前報告我們正在進行的概念驗證研究的初步結果，並在2024 年的醫學會議上報告最終數據。其次，我們預計會提出新的轉化和初始生物標記數據以及長期研究結果。去年年底，我們在 ESMO-IO 上公佈了我們的鉑耐藥性卵巢癌研究的長期患者隨訪數據，以及我們 COM503 臨床前項目的其他數據，全部在今年年底完成。

We also plan to present new data from the metastatic breast cancer study of 17 patients treated with COM701 and nivolumab. Patients were enrolled into this cohort regardless of their ER, PR, and HER2 status. These patients were heavily pretreated and had exhausted all available standard treatments which could include immune checkpoint inhibitors and ADCs.

我們還計劃提供 17 名接受 COM701 和 nivolumab 治療的患者的轉移性乳癌研究的新數據。無論患者的 ER、PR 和 HER2 狀態如何，他們都被納入該隊列。這些患者接受了大量的預處理，並且已經用盡了所有可用的標準治療方法，其中包括免疫檢查點抑制劑和 ADC。

Before handing over to Alberto, I will touch briefly on our finances and then Alberto will go into the details. We have an expected cash runway for at least the end of 2024, which we believe is sufficient to support all planned operations and reach milestones to potentially de-risk our lead assets, COM701 and COM902.

在交給阿爾貝託之前，我將簡要介紹我們的財務狀況，然後阿爾貝托將詳細介紹。我們預計至少到 2024 年底就有現金跑道，我們相信這足以支持所有計劃的運營並達到里程碑，從而可能降低我們的主要資產 COM701 和 COM902 的風險。

In terms of future funding, non-dilutive funding of our pipeline assets is our priority. On this front, it is worth noting that the trend in immunotherapy is to combine and treat earlier, and we believe the profile of our lead assets, COM701 and COM902, make them ideal combination candidates to be used in earlier treatment settings.

就未來的融資而言，我們的優先事項是對我們的管道資產進行非稀釋性融資。在這方面，值得注意的是，免疫療法的趨勢是早期聯合治療，我們相信我們的主要資產 COM701 和 COM902 的概況使它們成為早期治療環境中使用的理想組合候選者。

Additionally, there is increasing excitement around the potential of IL-18 pathway modulation in immuno-oncology. And with COM503, we're happy that we have a differentiated approach to potentially harness this cytokine biology for optimal use in treating cancer. Finally, through our partnership with AstraZeneca, we may become eligible for future milestone payments.

此外，IL-18 路徑調節在免疫腫瘤學中的潛力越來越令人興奮。透過 COM503，我們很高興我們擁有一種差異化的方法來潛在地利用這種細胞因子生物學來最佳地用於治療癌症。最後，透過與阿斯特捷利康的合作，我們可能有資格獲得未來的里程碑付款。

And with that, I will hand over to Alberto for the financial update.

接下來，我將把財務最新情況交給阿爾貝托。

Thank you, Anat. I'm now to summarize our financial results. I will start with our cash balance. As of June 30, 2023, cash, cash equivalents, and cash investments were approximately $66.5 million compared with approximately $83.7 million as of December 31, 2022, affirming our focus on capital efficiency, while continuing our execution on our DNAM-1 axis hypothesis. The company has no debt.

謝謝你，阿納特。我現在總結一下我們的財務表現。我將從我們的現金餘額開始。截至2023 年6 月30 日，現金、現金等價物和現金投資約為6,650 萬美元，而截至2022 年12 月31 日約為8,370 萬美元，這證實了我們對資本效率的關注，同時繼續執行DNAM- 1 軸假設。公司沒有負債。

We recognize the importance of cash efficiency. And we are disciplined in how we deploy our cash resources, ensuring we will focus on reaching key milestones with our available cash runway through at least the end of 2024.

我們認識到現金效率的重要性。我們在如何部署現金資源方面遵守紀律，確保我們至少在 2024 年底之前專注於利用可用現金跑道實現關鍵里程碑。

Expenses for the second quarter of 2023 were in line with our plans. R&D expenses for the second quarter of 2023 were $7.8 million, up from $6.8 million in the second quarter of 2022. The increase is mainly due to the end of the amortization of deferred participation in R&D expenses on March 31, 2023, and an increase in preclinical and CMC activities associated with COM503 activities, offset by a decrease in clinical trial expenses, headcount, and currency exchange effect.

2023 年第二季的費用符合我們的計劃。 2023年第二季的研發費用為780萬美元，高於2022年第二季的680萬美元。這一增長主要是由於遞延參與研發費用攤銷於2023年3月31日結束，以及與COM503活動相關的臨床前和CMC 活動被臨床試驗費用、人員數量和貨幣兌換影響的減少所抵消。

Our G&A expenses for the second quarter of 2023 were $2.4 million compared to $2.6 million in the second quarter of 2022. For the second quarter of 2023, net loss was $9.3 million, or $0.11 for basic and diluted share compared to a net loss of $9.1 million, or $0.11 per basic and diluted share in the second quarter of 2022.

我們2023 年第二季的一般管理費用為240 萬美元，而2022 年第二季為260 萬美元。2023 年第二季的淨虧損為930 萬美元，基本股和稀釋股虧損0.11 美元，而淨虧損為9.1 美元百萬美元，即 2022 年第二季每股基本股和稀釋股 0.11 美元。

With that, I will hand back to Anat to summarize.

至此，我將交回給 Anat 進行總結。

Thank you, Alberto. To summarize, we continue to execute and deliver on our growth. With our most recent data in microsatellite stable endometrial cancer, we continue to provide evidence supporting the potential COM701 mandated clinical benefit in hard-to-treat patients who are not responding to standard of care and failed prior IO therapy.

謝謝你，阿爾貝托。總而言之，我們繼續執行並實現我們的成長。憑藉我們關於微衛星穩定子宮內膜癌的最新數據，我們繼續提供證據支持 COM701 對於對標準護理無反應且先前 IO 治療失敗的難治性患者俱有潛在的臨床益處。

We're looking forward to presenting new translational and initial biomarker data and long-term patient follow-up from COM701 combination in ovarian cancer, first data in metastatic breast cancer as well as additional data from our COM503 preclinical program, all by the end of the year.

我們期待在 2019 年底之前提供 COM701 組合治療卵巢癌的新的轉化和初始生物標記數據以及長期患者隨訪、轉移性乳腺癌的首個數據以及來自我們的 COM503 臨床前項目的其他數據。那一年。

We also plan to share initial findings from our two ongoing study in microsatellite stable colorectal cancer and platinum-resistant ovarian cancer evaluating our leading triple combination blockade of PVRIG, TIGIT, and PD-1 with COM701, COM902, and pembrolizumab by the end of the year.

我們也計劃在2018 年底分享我們正在進行的兩項關於微衛星穩定結直腸癌和鉑金抗藥性卵巢癌研究的初步結果，評估我們領先的PVRIG、TIGIT 和PD-1 與COM701、COM902 和pembrolizumab 的三聯療法阻斷作用。年。

The opportunity we have to positively impact the lives of so many motivates every single employee within Compugen every day. With that, I return the call over for questions. Operator?

我們有機會積極影響許多人的生活，這每天都激勵著 Compugen 的每位員工。說完，我回電話詢問問題。操作員？

(Operator Instructions) Stephen Willey, Stifel.

（操作員說明）Stephen Willey，Stifel。

Good morning. Thanks for taking the questions. I guess just with respect to the Phase 2 platinum-resistant ovarian cancer study, you talked about enrollment, I guess, going a little bit slower than expected.

早安.感謝您提出問題。我想就 2 期鉑耐藥卵巢癌研究而言，您談到了入組，我想，進展比預期要慢一些。

Are you -- is that just a function of the kinetics of site activation? Or do you now need to bring more sites than originally planned online in order to meet the target enrollment goal, which I believe was about 50% before the end of this year?

這只是位點激活動力學的函數嗎？或者，您現在需要提供比原計劃更多的網站，才能實現目標註冊目標（我認為今年年底前大約為 50%）？

Henry, would you like to address this question?

亨利，你願意回答這個問題嗎？

Yes, Anat. Thank you very much, Stephen. So first, let me say that there's a strong interest by the sites and investigators to participate on this study.

是的，阿納特。非常感謝你，史蒂芬。首先，我要說的是，網站和研究人員對參與這項研究表現出濃厚的興趣。

There's a strong belief in the hypotheses in activity in the DNAM-1 axis with a triple combination of pembrolizumab, COM701, and COM902 at least based on the results we previously disclosed with the triplet that consisted of COM701, the BMS TIGIT antibody, and nivolumab, 20% response rate as we presented at ESMO-IO.

至少基於我們先前揭露的由 COM701、BMS TIGIT 抗體和 nivolumab 組成的三聯體的結果，人們強烈相信派姆單抗、COM701 和 COM902 三聯體在 DNAM-1 軸中具有活性的假設，正如我們在ESMO- IO 上展示的那樣，回應率為20%。

What we've observed is that there is a delay as a result of restricted resources at the sites, resources meaning personnel mainly, change in timing of IRB and FX coming to review cycles, and a few competing studies in the platinum-resistant ovarian population also. We are in close contact to the sites and several additional sites are being considered who are more likely to recruit platinum-resistant ovarian cancer patients, and they're very pleased to opening now, which should get us back on track.

What we've observed is that there is a delay as a result of restricted resources at the sites, resources meaning personnel mainly, change in timing of IRB and FX coming to review cycles, and a few competing studies in the platinum-resistant ovarian population也.我們正在與這些站點保持密切聯繫，並正在考慮另外幾個站點，這些站點更有可能招募鉑類抗藥性卵巢癌患者，他們很高興現在開放，這應該會讓我們重回正軌。

Okay. And I guess when you think about the year-end update, is there some threshold, the number of patients specifically in ovarian that you want to have enrolled before you tried to communicate something incremental?

好的。我想當你考慮年終更新時，在你嘗試傳達一些增量訊息之前，是否有一些閾值，即你想要登記的卵巢患者的具體數量？

So maybe I'll take this one. So in general, we're still guiding to the same guidance that we shared that we hope to enroll up to 20 patients by the end of the year. And that's what Henry is saying that we believe we can catch up to that is that what we need.

所以也許我會選擇這個。因此，總的來說，我們仍然遵循我們分享的相同指導方針，即我們希望在今年年底前招募最多 20 名患者。這就是亨利所說的，我們相信我們能夠趕上，這就是我們所需要的。

So we cannot at this point in time estimate any deviation from the guidance. But obviously, if there will be any, obviously, we will share that and we believe that we will be able to share data as planned by the end of the year.

因此，我們目前無法估計與指導意見的任何偏差。但顯然，如果有的話，我們顯然會分享，而且我們相信我們將能夠在年底前按計劃分享數據。

I just want to remind that in any case, we indicated that for the two studies this will be initial data from this study and that as we enroll additional patients in the ovarian study in 2024, we'll share the full data disclosure.

我只是想提醒一下，無論如何，我們表示，對於這兩項研究，這將是這項研究的初始數據，當我們在 2024 年招募更多患者參加卵巢研究時，我們將分享完整的數據披露。

Okay. And then maybe just lastly, I guess, you've talked about having, I guess, these two datasets to present at a medical conference in '24. And just kind of wondering internally, is the goal at this point to be able to make some kind of registrational go-forward decision before the end of 2024 on the basis of these two studies? I'm just trying to think about what's kind of the next step here once we get the proof-of-concept data. Thanks.

好的。我想，也許最後，你已經談到了在 24 年的一次醫學會議上展示這兩個資料集。只是內部想知道，目前的目標是能夠在 2024 年底之前根據這兩項研究做出某種註冊前進決定嗎？我只是想考慮一下，一旦我們獲得了概念驗證數據，下一步該做什麼。謝謝。

Yeah. So maybe I start and Henry, if you would like to add to chime in. But basically the goal of the study from the get-go for these two studies was to add more data to the data that we already have in these two indications, which seems promising to us, and to assess some of the contribution of components and to build a path towards building a study that will take us to eventually to build the registration path. So that's the goal we have.

是的。所以也許我可以開始，亨利，如果你想補充的話。但基本上，這兩項研究從一開始的目標就是在這兩個適應症中已有的數據中添加更多數據，這對我們來說似乎很有希望，並評估組件的一些貢獻，並建立一條建立研究的道路，最終將引導我們建立註冊路徑。這就是我們的目標。

And we need to see as we go with these studies or is that data how it looks at things. And as we said, previously, it's more than the over response rate. It is the additional parameters that were evaluating the durability and the safety profile, et cetera. This will allow us to gain the understanding of how we move forward. Henry, anything to add on this front?

當我們進行這些研究時，我們需要看看這些數據是如何看待事物的。正如我們之前所說，這不僅僅是過度回應率。這是評估耐用性和安全性等的額外參數。這將使我們能夠了解如何前進。亨利，在這方面還有什麼要補充的嗎？

No, thank you, Anat. You have covered it all.

不，謝謝你，阿納特。你已經涵蓋了這一切。

Okay, thanks.

好的謝謝。

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene，Truist 證券公司。

Yes, good morning. Thanks for taking my questions. I'm going to build on the questions that Stephen asked here.

是的，早安。感謝您回答我的問題。我將以史蒂芬在這裡提出的問題為基礎。

So for the update that we're getting for in platinum-resistant ovarian cancer by year end, I know the expectation is that initial data. Can you just clarify what kind of efficacy data will we see in that presentation? And is it still right to assume that this is going to be perhaps more as an investor update and not a medical meeting update for the presentation of this year?

因此，對於我們在年底前獲得的鉑耐藥性卵巢癌的最新情況，我知道我們的期望是初始數據。您能否澄清一下我們將在該演示中看到什麼樣的功效數據？假設這可能更多是投資者更新而不是今年的醫學會議更新，這仍然是正確的嗎？

It will be an investor update and not a medical conference update from the two new proof-of-concept studies that we do, yes. We tend to present data in medical conferences from studies that are more completed where we have more insights, yes.

是的，這將是投資者更新，而不是我們所做的兩項新概念驗證研究的醫學會議更新。是的，我們傾向於在醫學會議上展示來自更完整的研究的數據，我們有更多的見解。

Okay. And then there's a question about what efficacy data will be in these two updates? Just wanted to try and see that if you can -- if there's any confirmed scan or is it just a proliferate scan or should we set different expectations?

好的。那麼問題來了，這兩次更新會有哪些功效數據呢？只是想嘗試看看是否可以 - 是否有任何確認的掃描，或者只是激增的掃描，還是我們應該設定不同的期望？

Henry, would you like to address this?

亨利，你想解決這個問題嗎？

Oh, yes, Anat. Thank you. The earliest readout one can get for this patient population will be response rates. We obviously would be interested also in looking at other important clinical endpoints such as duration of response or possibly a progression-free survival.

哦，是的，阿納特。謝謝。對於這群患者，最早可獲得的讀數將是緩解率。我們顯然也有興趣研究其他重要的臨床終點，例如反應持續時間或可能的無惡化存活期。

Now all that being said, this will depend on enrollment and our ability to catch up like we think we will be able to -- we project we'll be able to do. But those are the key endpoints, the most important being response rates.

話雖這麼說，這將取決於入學率和我們趕上的能力，就像我們認為我們能夠做到的那樣——我們預計我們將能夠做到。但這些是關鍵終點，其中最重要的是回應率。

Got it. And then on the issue with the delays, I totally appreciate that there's some personnel restrictions and this intense IRBs, et cetera happening. I'm just wondering, is there any impact of the ADC launch in platinum-resistant ovarian cancer is also maybe causing any delays here? And then related to that, have you seen any delays in recruitments for the colorectal study?

知道了。然後，關於延誤的問題，我完全理解存在一些人員限制和如此嚴格的 IRB 等情況。我只是想知道，ADC 在鉑類抗藥性卵巢癌中的推出是否有任何影響也可能導致任何延遲？與此相關的是，您是否發現結直腸研究的招募有任何延遲？

Henry?

亨利？

Thank you, Asthika. In speaking with the investigators and all the sites that we have, we haven't observed, though they haven't reported back to us, that the ADCs have contributed meaningfully to the delay that we've just highlighted. Now as you recall, Asthika, the ADC that we're talking about here is mirvetuximab, which is -- which has accelerated approval in platinum-resistant ovarian cancer that has not been the communication we'll receive back.

謝謝你，阿斯提卡。在與調查人員和我們擁有的所有站點交談時，我們沒有觀察到 ADC 對我們剛才強調的延遲做出了有意義的貢獻，儘管他們沒有向我們報告。現在，Asthika，您還記得嗎，我們在這裡討論的 ADC 是 mirvetuximab，它加速了鉑類抗藥性卵巢癌的批准，但這並不是我們將收到的資訊。

And that accelerated approval is also in the restricted biomarker limited populations folate receptor alpha-positive patient population. So that has not been a part of the reason for the minimal delay that we've discussed.

加速核准也適用於受限制的生物標記有限人群葉酸受體α陽性患者群體。因此，這並不是我們所討論的最小延遲的原因之一。

Got it. And so -- and just wanted to double check. There's been no delays on the colorectal side, right? And obviously, there's no competing products there, but is that recruiting well as well guys?

知道了。所以——只是想仔細檢查一下。結直腸方面沒有延遲，對吧？顯然，那裡沒有競爭產品，但是這招募得好嗎？

The studies that we have, it fits well with colorectal cancer. As you know, the patient populations with microsatellite stable colorectal cancer is a very underserved one. There are lots of patients unfortunately, that there's need of new therapies for microsatellite stable colorectal cancer. And we haven't experienced that much of a significant delay with that population.

我們的研究表明，它與大腸直腸癌非常吻合。如您所知，患有微衛星穩定結直腸癌的患者群體是一個服務水平非常低的群體。不幸的是，有許多患者需要針對微衛星穩定大腸直腸癌的新療法。而且我們並沒有經歷過對這些人口的嚴重延遲。

Nice one. Thanks so much for taking my questions, guys. I'll jump back in queue.

好一個。非常感謝你們回答我的問題，夥伴們。我會插回隊列。

Daina Graybosch, Leerink Partners.

戴娜‧格雷博斯 (Daina Graybosch)，Leerink 合夥人。

Hi, this is Jeff La Rosa for Daina. Thanks for taking our questions. I guess the first is what do you hope to show the breast cancer update that'll be supportive of your plans and strategy in ovarian cancer and MSS-CRC?

大家好，我是戴娜的傑夫·拉羅莎。感謝您回答我們的問題。我想第一個問題是您希望展示哪些乳癌最新進展，以支持您在卵巢癌和 MSS-CRC 方面的計劃和策略？

And for the initial, I mean, the updated translational initial biomarker data in proc with Bristol's TIGIT, how comparable is this dataset to your own study with your TIGIT? Any differences there you could point to?

對於初始的，我的意思是，在布里斯托爾的 TIGIT 中更新的翻譯初始生物標記數據，這個數據集與您自己使用 TIGIT 進行的研究有何可比性？您可以指出其中的任何差異嗎？

And regarding the ASCO data, in HCC, was that a tumor type that you sort of predicted would be amenable to PVRIG blockade and what's your interest in that indication? Thank you.

關於 HCC 中的 ASCO 數據，您預測這種腫瘤類型是否適合 PVRIG 阻斷，您對該適應症有何興趣？謝謝。

So, Henry, you'll start with the breast, and then Eran will take the biomarker and HCC expression.

所以，Henry，您將從乳房開始，然後 Eran 將獲取生物標記和 HCC 表達。

Yes. Thank you for the question. With regards to the breast cancer data, all I can see at this point is that the patient population that we've enrolled, a patient population that's heterogenous with respect to whether the ER/PR positive or ER/PR negative or HER2 in negative.

是的。感謝你的提問。關於乳癌數據，我目前所能看到的是我們已入組的患者群體，無論是 ER/PR 陽性、ER/PR 陰性還是 HER2 陰性，患者群體都是異質的。

This is a patient population that have exhausted all available standard-of-care therapies, including therapies that are approved such as Trodelvy.

這個患者群體已經用盡了所有可用的標準護理療法，包括 Trodelvy 等已批准的療法。

Now the important thing that we're looking for in this patient population is to see a signal of antitumor activity, and that will confirm to us that there is activity with the combination that we're pursuing with COM701 plus nivolumab. So that's what would be of interest to us, especially in these hard-to-treat patient population that have possibly received several lines of therapy.

現在，我們在這個患者群體中尋找的重要事情是看到抗腫瘤活性的信號，這將向我們證實我們正在尋求的 COM701 加納武單抗的組合具有活性。這就是我們感興趣的，特別是在這些可能接受過多種治療的難治性患者群體中。

Yes. Then for the questions about the biomarker. So yes, we anticipate that the same biomarkers that would inform -- that we learned form in the study of using the BMS TIGIT should be relevant also for the other studies that we are doing, both BMS TIGIT and our own COM902 are seen nonactive, and in general, that was a study of blocking triple blockade of TIGIT, PD-1 and PVRIG.

是的。然後是關於生物標誌物的問題。所以，是的，我們預計，我們在使用 BMS TIGIT 的研究中學到的相同生物標記也應該與我們正在進行的其他研究相關，BMS TIGIT 和我們自己的 COM902 都被認為是非活躍的，總的來說，這是一項阻斷TIGIT、PD-1 和PVRIG 三重阻斷的研究。

So biologically, it should be very similar to the study that we are currently conducting and if you will identify some new translational or potential predictive biomarkers in that study, we definitely think it could be and should be relevant also to the follow-up study that we're currently doing. Now about the HCC. So we identified ovarian endometrial as one of the top indications in dominance of the pathway. And that's why we went to these indications also breast.

因此，從生物學角度來看，它應該與我們目前正在進行的研究非常相似，如果您在該研究中發現了一些新的轉化或潛在的預測生物標記物，我們絕對認為它可能而且應該與後續研究相關我們目前正在做。現在關於 HCC。因此，我們將卵巢子宮內膜確定為該途徑的主要適應症之一。這就是為什麼我們也要去研究這些乳房適應症。

But HCC is definitely one of the top expressers of the pathway. We couldn't start with all of them. And PVRL2 is quite broadly expressed in many indications. So HCC is definitely an indication in which the pathway is dominant in it's a target indication that we definitely see a potential in.

但 HCC 絕對是該路徑的最高表現者之一。我們無法從所有這些開始。 PVRL2 在許多適應症中的表現相當廣泛。因此，HCC 絕對是該途徑占主導地位的跡象，因為它是我們肯定看到潛力的目標跡象。

And just in terms of whether we're going to test the indication to your specific question, I see that it is being shown by now that the PVRIG blockade potential, the COM701 therapeutic potential is much broader than the two indications that we're focusing right now. We took to focus on these two indications where we have data and where we believe that additional data that we will expand with these studies may allow us to better design the path forward.

至於我們是否要測試您的特定問題的適應症，我發現現在已經表明 PVRIG 阻斷潛力、COM701 治療潛力比我們關注的兩個適應症要廣泛得多現在。我們將重點放在這兩個跡像上，我們擁有數據，我們相信我們將透過這些研究擴展的額外數據可能使我們能夠更好地設計前進的道路。

But I want to stress that again and again, the therapeutic potential of COM701 is much beyond these two indications. And it include endometrial cancer and non-small cell lung cancer and HCC. And as we said, we would present data in breast towards the end of the year. That's very encouraging to us.

但我想一再強調，COM701的治療潛力遠遠超出了這兩個適應症。它包括子宮內膜癌、非小細胞肺癌和肝癌。正如我們所說，我們將在年底前提供乳房數據。這對我們來說非常鼓舞人心。

Yeah, I think one of the other questions you had asked was if there was any substantive difference between the triplets that we're currently exploring in the ovarian cancer space, which is the triplet I'm referring to now is COM902 plus COM701 plus pembrolizumab versus the earlier triplets which is the triplet with BMS TIGIT antibody BMS-986207, and nivolumab. We did -- as a reminder, we did have a press release where we enrolled the first patients into the current triplet of COM902, COM701, and pembrolizumab. And as part of what's going to be what we said was that we did not -- this is one of the investigators on that study.

是的，我認為您問的其他問題之一是我們目前在卵巢癌領域探索的三聯體之間是否存在任何實質性差異，我現在指的三聯體是 COM902 加 COM701 加派姆單抗與早期的三聯體相比，即使用BMS TIGIT 抗體BMS-986207 和納武單抗的三聯體。我們確實這樣做了——提醒一下，我們確實發布了一份新聞稿，其中我們將第一批患者納入當前的 COM902、COM701 和 pembrolizumab 三聯體。作為我們將要說的一部分，我們沒有——這是該研究的研究人員之一。

The initial observation is that this combination, which is the pembrolizumab continuing a triplet of COM902,COM701, and pembro. It's very well tolerated as observed, at least in the patient population with microsatellite semi-colorectal cancer in the initial study that we enrolled. So there are no differences observed so far.

最初的觀察結果是，這種組合是派姆單抗（pembrolizumab），延續了 COM902、COM701 和派姆布羅（pembro）的三聯體。據觀察，它的耐受性非常好，至少在我們招募的最初研究中的微衛星半結直腸癌患者群體中是如此。所以到目前為止沒有觀察到差異。

And this is earlier on as we enrolled a colorectal patients -- microsatellite colorectal cancer patients. We do not expect there to be any substantive differences in terms of safety and tolerability. I hope that answers your question.

這是早期我們招募的一位大腸直腸患者—微衛星大腸癌患者。我們預計在安全性和耐受性方面不會有任何實質差異。我希望這能回答你的問題。

It does. Thank you, all.

確實如此。謝謝你們。

Tony Butler, EF Hutton.

東尼·巴特勒，EF·赫頓。

Good morning. I would like to go back to this notion of PVRL2 dominance at least over PVR, which seems to be a recurring theme in some of the cohorts in which you're attempting to move forward with the triple combination and in particular, of course, 701. And that's back to ASCO where you had some really good data in endometrial cancer.

早安.我想回到 PVRL2 至少在 PVR 上占主導地位的概念，這似乎是一些你試圖推進三重組合的隊列中反復出現的主題，當然，特別是 701 . 回到ASCO，那裡有一些關於子宮內膜癌的非常好的數據。

The cutoff that I recall was in April, the two responses and then two patients who had stable disease. And I wondered if there was any additional information on follow-up that is, were patients actually able to show an additional reduction in tumour size of those responses and/or of those patients who had stable disease? Thank you.

我記得的截止日期是四月份，當時有兩次緩解，然後兩名患者病情穩定。我想知道是否有任何關於隨訪的額外信息，即患者是否真的能夠表現出這些反應和/或疾病穩定的患者的腫瘤大小進一步減小？謝謝。

Eran, would you like to address the PVRL2 portion?

Eran，您想談談 PVRL2 部分嗎？

So the PVRL2 portion, I think that is not only PVRL2. I mean, in general, it's the PVRG pathway dominant. PVRL2, obviously, is important part of it. And this is, again, a measure that we looked at in both endometrial, we have a dominant and also another indication as mentioned before.

所以PVRL2部分，我認為不只是PVRL2。我的意思是，總的來說，PVRG 途徑占主導地位。顯然，PVRL2 是其中的重要組成部分。這也是我們在子宮內膜中觀察的指標，我們有一個顯性的指標，還有先前提到的另一個指標。

Henry anything you want to add?

亨利你還有什麼要補充的嗎？

Nothing more to add to what Eran had mentioned.

埃蘭提到的內容沒什麼好補充的了。

But anything more on the patients for additional follow-up that were presented at that time?

但當時對患者的額外追蹤還有什麼更多資訊嗎？

So we are going to present a follow-up data on these patients. Remember that when we shared the data in December at ESMO-IO on December 22, we had patients that were still on study treatment, responsive patients and some of them had durability of more than nine months. We are going to present data by year-end, a follow-up data for these patients.

因此，我們將提供這些患者的後續數據。請記住，當我們在 12 月 22 日在 ESMO-IO 上分享 12 月的數據時，我們有仍在接受研究治療的患者、有反應的患者，其中一些患者的持續時間超過 9 個月。我們將在年底前提供這些患者的後續數據。

So I get that you'd have answers to some of your questions then.

所以我知道你的一些問題將會得到答案。

And that will -- I just want to be sure that will include the endometrial patients? That's what I'm focusing on.

我只是想確定這將包括子宮內膜患者？這就是我關注的重點。

No, it will relate today to the ovarian. Sorry, I misheard your question. It will relate to the ovarian. No, we didn't plan yet to have any follow up on the ovarian cancer -- on the endometrial cancer patients.

不，今天它與卵巢有關。抱歉，我聽錯你的問題了。和卵巢有關係。不，我們還沒有計劃對卵巢癌——子宮內膜癌患者進行任何追蹤。

Okay. Thank you.

好的。謝謝。

This concludes the Q&A session and Compugen's investor conference call. Thank you for your participation. You may go ahead and disconnect.

問答環節和 Compugen 投資者電話會議到此結束。感謝您的參與。您可以繼續並斷開連線。