NovaBridge Biosciences (NBP) 2022 Q4 法說會逐字稿

Good morning to everyone, and thank you for joining us this morning. Thank you all for standing by, and I'd like to take this opportunity to welcome you all to the I-Mab Biopharma Full Year 2022 Financial Results and Business Update Conference Call.

大家早上好，感謝您今天早上加入我們。感謝大家的支持，我想藉此機會歡迎大家參加 I-Mab Biopharma 2022 年全年財務業績和業務更新電話會議。

This is Tyler Ehler here, I-Mab's Senior Director of Investor Relations.

我是 Tyler Ehler，天境生物的投資者關係高級總監。

(Operator Instructions) At the end of this call, we'll conduct a Q&A session and instructions will follow at that time. Earlier today, we issued a press release providing a review of our financial results for the full year ended December 31, 2022, as well as an overview of our recent corporate highlights and upcoming milestones. The press release can be accessed on the Investor Relations tab on our website at ir.i-mabbiopharma.com.

（操作員說明）在本次電話會議結束時，我們將進行問答環節，屆時將提供說明。今天早些時候，我們發布了一份新聞稿，回顧了我們截至 2022 年 12 月 31 日的全年財務業績，並概述了我們最近的公司亮點和即將到來的里程碑。可在我們網站 ir.i-mabbiopharma.com 的“投資者關係”選項卡上訪問新聞稿。

Joining me today on the call from I-Mab's senior management team are Dr. Jingwu Zang, our Founder and Chairman; Dr. Andrew Zhu, our acting CEO; and Mr. Richard Yeh, our Interim CFO and COO.

今天，我們的創始人兼董事長臧敬武博士應天境生物高級管理團隊的電話與我會面；我們的代理首席執行官Andrew Zhu博士；以及我們的臨時首席財務官兼首席運營官 Richard Yeh 先生。

To start, Dr. Andrew Zhu will provide a high-level overview of our recent achievements and upcoming milestones, also provide an update on our R&D progress. Mr. Yeh will then provide a summary of our financial results for the full year ended December 31, 2022 before we turn the call over to the operator to take your questions.

首先，Andrew Zhu 博士將對我們最近的成就和即將到來的里程碑進行高層次的概述，並提供我們研發進展的最新情況。然後，葉先生將提供我們截至 2022 年 12 月 31 日的全年財務業績摘要，然後我們將電話轉給接線員回答您的問題。

Please note that today's discussion will contain forward-looking statements relating to the company's future performance and are made under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Such statements are not guarantees of future performance and are subject to certain risks and uncertainties, assumptions as well as other factors. Some of these risks are beyond the company's control and could cause actual results to differ materially from those mentioned in today's press release and in today's discussion.

請注意，今天的討論將包含與公司未來業績相關的前瞻性陳述，這些陳述是根據 1995 年美國私人證券訴訟改革法案的安全港條款作出的。此類陳述不是對未來業績的保證，並具有一定的風險和不確定性、假設以及其他因素。其中一些風險超出了公司的控制範圍，可能導致實際結果與今天的新聞稿和今天的討論中提到的結果大相徑庭。

The general discussion of the risk factors that could affect I-Mab's business and financial results is included in certain filings of the company -- of the Securities and Exchange Commission. The company does not undertake any obligation to update this forward-looking information, except as required by law.

可能影響 I-Mab 業務和財務業績的風險因素的一般性討論包含在公司提交給美國證券交易委員會的某些文件中。除法律要求外，公司不承擔任何更新此前瞻性信息的義務。

We will also discuss specific non-GAAP financial measures during today's call, the presentation of which is not intended to be considered in isolation or as a substitute for the financial information prepared and presented in accordance with U.S. GAAP. Please see the financial results press release issued today for a definition of non-GAAP financial measures and a reconciliation of GAAP to non-GAAP financial results.

我們還將在今天的電話會議上討論具體的非 GAAP 財務措施，其介紹並非旨在孤立地考慮或替代根據美國 GAAP 準備和介紹的財務信息。請參閱今天發布的財務業績新聞稿，了解非 GAAP 財務指標的定義以及 GAAP 與非 GAAP 財務業績的對賬。

And with that, I'll now turn the call over to Dr. Andrew Zhu, our acting CEO. Dr. Zhu, please go ahead.

有了這個，我現在將把電話轉給我們的代理首席執行官 Andrew Zhu 博士。朱醫生，請繼續。

Thank you, Tyler. It's a pleasure to welcome all of you to our call today. I want to take this opportunity to discuss our key business updates and major progress in core asset development for the year ended December 31, 2022. Since the start of 2022, the company faced multiple challenges, including but not limited to geopolitical issues such as ADR delisting risk, macroeconomic factors, including interest rate hikes, and 2019 pandemic.

謝謝你，泰勒。今天很高興歡迎大家來參加我們的電話會議。我想藉此機會討論我們截至 2022 年 12 月 31 日止年度的主要業務更新和核心資產開發的主要進展。自 2022 年開始以來，公司面臨多重挑戰，包括但不限於 ADR 等地緣政治問題退市風險、加息等宏觀經濟因素、2019年疫情。

In response to these challenges, the company made several strategic efforts to reposition the overall business and prioritize its pipeline. These measures resulted in a streamlined corporate structure and workforce as well as focused development of 5 key assets, leading to a significant reduction in the cash burn rate in 2022 and beyond. These efforts have allowed us to achieve critical milestones for our prioritized pipeline and deliver near-term value.

為了應對這些挑戰，該公司做出了多項戰略努力，以重新定位整體業務並確定其管道的優先級。這些措施精簡了公司結構和員工隊伍，並重點開發了 5 項關鍵資產，從而顯著降低了 2022 年及以後的現金消耗率。這些努力使我們能夠為我們的優先管道實現關鍵里程碑並提供近期價值。

In terms of the ADR delisting risk on December 15, 2022, the PCAOB issued in a report that vacated the previous determination and removed Mainland China and Hong Kong from the list of jurisdiction where it is unable to inspect or investigate completely registered public accounting firms. For this reason, the company does not expect to be identified as a clinician identified issuer under the HFCAA, after it files the annual report on Form 20-F for the fiscal year 2022. This has removed a significant headwind the company faced in 2022.

針對2022年12月15日的ADR退市風險，PCAOB發布報告，撤銷此前的認定，將中國大陸和香港從無法對完全註冊的會計師事務所進行檢查或調查的司法管轄區名單中刪除。因此，在提交 20-F 表 2022 財年年度報告後，該公司預計不會被確定為 HFCAA 下的臨床醫生識別發行人。這消除了該公司在 2022 年面臨的重大阻力。

With the above-mentioned strategic efforts, on the pipeline development front in 2022, we achieved 13 key clinical milestones, including positive results -- including positive data readouts for 3 of our key assets, lemzoparlimab, uliledlimab and givastomig. Here, we highlight the 5 key clinical assets that we have prioritized. These assets are novel, highly differentiated and among the frontrunners globally and in China. First for all, eftansomatropin alfa, our long-acting growth hormone, we completed the enrollment of 168 patients for our Phase III trial in the first half of (inaudible). We expect to have a data readout in the half of 2023 followed by subsequent BLA submission.

通過上述戰略努力，在 2022 年的管道開發方面，我們實現了 13 個關鍵的臨床里程碑，包括積極的結果——包括我們的 3 項關鍵資產，lemzoparlimab、uliledlimab 和 givastomig 的積極數據讀出。在這裡，我們重點介紹了我們優先考慮的 5 項關鍵臨床資產。這些資產新穎、差異化程度高，在全球和中國均處於領先地位。首先，對於我們的長效生長激素 eftansomatropin alfa，我們在上半年（聽不清）完成了 168 名患者的 III 期試驗登記。我們預計將在 2023 年下半年讀取數據，隨後提交 BLA。

In November 2021, we announced a commercial partnership with Jumpcan, a top 100 Chinese pharmaceutical company specialized in the pediatric space.

2021 年 11 月，我們宣布與專注於兒科領域的中國百強製藥公司 Jumpcan 建立商業合作夥伴關係。

Second, felzartamab, a differentiated CD38 antibody. In addition to the completed Phase II registration study, our Phase III study for second-line multiple myeloma is on track despite the impact of COVID-19. We continued to make progress with the local manufacturing plant in preparation for BLA submission and seek a potential commercial partnership.

其次，felzartamab，一種分化的 CD38 抗體。除了已完成的 II 期註冊研究外，儘管受到 COVID-19 的影響，我們針對二線多發性骨髓瘤的 III 期研究仍在進行中。我們繼續與當地製造工廠取得進展，為 BLA 提交做準備，並尋求潛在的商業合作夥伴關係。

Next, we have 3 key assets that I will discuss in more detail later. Lemzoparlimab, a differentiated CD47 antibody has reached the Phase III stage. Uliledlimab, a differentiated CD73 antibody and a global frontrunner has demonstrated impressive antitumor activity in a non-small cell lung cancer in a Phase II trial. The clinical response is correlated with tumor CD73 expiration.

接下來，我們有 3 個關鍵資產，稍後我將詳細討論。 Lemzoparlimab 是一種分化的 CD47 抗體，已進入 III 期階段。 Uliledlimab 是一種分化的 CD73 抗體和全球領先者，在 II 期試驗中已證明其在非小細胞肺癌中具有令人印象深刻的抗腫瘤活性。臨床反應與腫瘤 CD73 過期相關。

Next, givastomig, a Claudin 18.2 4-1BB bispecific antibody with a fair safety profile and single-agent efficacy signal.

接下來是 givastomig，一種 Claudin 18.2 4-1BB 雙特異性抗體，具有良好的安全性和單藥療效信號。

I would like to start by highlighting our highly differentiated CD47 antibody lemzoparlimab, which has certainly attracted so much attention in the immuno-oncology field, because of its leading position to be among the first CD47 antibody drugs potentially approved for hematological malignancies.

我想首先強調我們高度分化的 CD47 抗體 lemzoparlimab，它在免疫腫瘤學領域肯定引起瞭如此多的關注，因為它是首批可能被批准用於血液惡性腫瘤的 CD47 抗體藥物之一。

I would like to remind you that lemzoparlimab is differentiated by design to avoid binding to red blood cells while maintaining strong anti-tumor activity. This differentiation includes the expected favorable safety profile with no priming dose required, less RBC mediated sink effect and compelling antitumor activity across several (inaudible). This molecular differentiation has been validated preclinically and has translated into clinical advantages that are being validated.

我想提醒您，lemzoparlimab 通過設計進行區分，以避免與紅細胞結合，同時保持強大的抗腫瘤活性。這種差異化包括預期的有利安全性，無需啟動劑量，較少的 RBC 介導的匯效應和令人信服的跨多個（聽不清）的抗腫瘤活性。這種分子分化已在臨床前得到驗證，並已轉化為正在驗證的臨床優勢。

I should also add in September 2022, AbbVie and I-Mab entered into an amendment to the original license and collaboration agreement. As a result, both parties are continuing to collaborate on the global development of anti-CD47 antibody therapy.

我還應該補充一點，2022 年 9 月，AbbVie 和 I-Mab 對原始許可和合作協議進行了修訂。因此，雙方將繼續就抗 CD47 抗體療法的全球開發展開合作。

Here, I want to highlight lemzoparlimab safety differentiation with clinical data. In a systemic safety data review for approximately 200 patients who are treated with lemzoparlimab, either as monotherapy or in various combinations, we have seen a compelling safety profile today. Overall, the safety data from both the U.S. and China studies continue to be favorable when administered without a priming dose regimen. MTD was not reached in any dose regimen, mild TRAE in solid tumor and NHL and we have seen a good safety profile in combination with azacitidine in AML and MDS, and no Grade 5 [hematological TRAEs] have been reported.

在這裡，我想用臨床數據強調 lemzoparlimab 的安全差異。在對大約 200 名接受 lemzoparlimab 單藥治療或多種聯合治療的患者進行的系統安全性數據審查中，我們今天看到了令人信服的安全性概況。總的來說，在沒有啟動劑量方案的情況下，來自美國和中國研究的安全數據仍然是有利的。任何劑量方案均未達到 MTD，實體瘤和 NHL 中的輕度 TRAE，我們已經看到在 AML 和 MDS 中與阿扎胞苷聯合使用具有良好的安全性，並且沒有報告 5 級 [血液學 TRAE]。

In the Phase II study in MDS, we have observed a favorable safety profile shown on the right. Of note, this study enrolled more patients with worse baseline conditions than the comparable clinical trials conducted in Western countries due to the underlying disease that is heavily influenced by clinical practice in China. In this group, 74% of patients had grade 3 and above anemia and 51% of the patients had grade 3 and above thrombocytopenia at baseline. The overall safety results showed that lemzoparlimab, even without the priming dose, was well tolerated in combination with azacitidine, and the safety profile was comparable with that of azacitidine monotherapy.

在 MDS 的 II 期研究中，我們觀察到右側顯示的良好安全性。值得注意的是，由於基礎疾病受中國臨床實踐的嚴重影響，與在西方國家進行的可比臨床試驗相比，本研究招募了更多基線狀況更差的患者。在該組中，基線時 74% 的患者有 3 級及以上的貧血，51% 的患者有 3 級及以上的血小板減少症。總體安全性結果表明，lemzoparlimab，即使沒有啟動劑量，與阿扎胞苷聯合使用也具有良好的耐受性，安全性與阿扎胞苷單藥療法相當。

Next, I would like to highlight the clinical efficacy results presented at ESMO 2022. Of the 53 patients enrolled as of March 31, 2022, for patients who begin treatment 6 months or longer prior to the analysis, the overall response rate and complete response rate were 86.7% and 40%, respectively. For those who began treatment 4 months or longer, the ORR was 86.2% with CRR of 31%.

接下來，我想重點介紹在 2022 年 ESMO 上公佈的臨床療效結果。在截至 2022 年 3 月 31 日入組的 53 名患者中，對於在分析前 6 個月或更長時間開始治療的患者，總體緩解率和完全緩解率分別為 86.7% 和 40%。對於開始治療 4 個月或更長時間的患者，ORR 為 86.2%，CRR 為 31%。

I'm happy to share that the updated results from the most recent data analysis of 62 patients has demonstrated consistent clinical efficacy including ORR and CRR, with no new safety signals identified. We are planning to present the updated data at a major scientific meeting in the second half in 2023.

我很高興與大家分享，對 62 名患者的最新數據分析的更新結果已經證明了一致的臨床療效，包括 ORR 和 CRR，沒有發現新的安全信號。我們計劃在 2023 年下半年的一次重要科學會議上展示更新後的數據。

Here, I would like to summarize the key progress on lemzoparlimab. We have observed consistent and favorable safety profiles in more than 200 patients with hematologic and solid tumors treated with lemzoparlimab. Our Phase II MDS trial demonstrated a consistent efficacy trend, including ORR and CRR, with a longer follow-up time since the ESMO data presentation in September 2022. Lemzoparlimab, in combination with azacitidine, has obtained approval from the CDE to initiate a Phase III registrational trial for the first-line treatment for patients with newly diagnosed higher-risk MDS. Importantly, AbbVie and I-Mab entered into an amendment to the original license and collaboration agreement. As a result, both parties are continuing to collaborate on the global development of anti-CD47 antibody therapy.

在這裡，我想總結一下lemzoparlimab的關鍵進展。我們在 200 多名接受 lemzoparlimab 治療的血液腫瘤和實體瘤患者中觀察到一致且良好的安全性。自 2022 年 9 月 ESMO 數據發布以來，我們的 II 期 MDS 試驗顯示了一致的療效趨勢，包括 ORR 和 CRR，且隨訪時間更長。Lemzoparlimab 與阿扎胞苷聯合使用，已獲得 CDE 批准啟動 III 期新診斷高危 MDS 患者一線治療的註冊試驗。重要的是，艾伯維和 I-Mab 對原始許可和合作協議進行了修訂。因此，雙方將繼續就抗 CD47 抗體療法的全球開發展開合作。

Next, I'd like to turn to uliledlimab, another the global frontrunner that we are developing with a focus on non-small cell lung cancer. As previously reported, uliledlimab is differentiated by design to avoid the hook effect. So what is the hook effect? Simply put, the hook effect is characterized an abnormal phenomenon that a drug molecule paradoxically loses the effect at higher dosage. As shown in the figure on the right side, uliledlimab achieved complete enzymatic inhibition without the hook effect. In contrast, oleclumab could only achieve partial inhibition with hook effect with higher concentrations. Uliledlimab has differentiation comes from a unique binding epitope as the C terminals. We believe the differentiation, if uliledlimab the potential to be best-in-class with an improved therapeutic window and more flexibility when combined with other antitumor drugs. We have observed robust efficacy data in stage 4 non-small cell lung cancer with high CD73 expression, and we are currently conducting focusing our efforts on the biomarker-guided clinical trial in advanced non-small cell lung cancer in the second half of 2023.

接下來，我想談談 uliledlimab，這是我們正在開發的另一個全球領先者，專注於非小細胞肺癌。正如之前報導的那樣，uliledlimab 通過設計進行區分，以避免鉤子效應。那麼什麼是鉤子效應呢？簡單地說，鉤子效應是一種藥物分子在較高劑量時反常地失去作用的異常現象。如右圖所示，uliledlimab實現了完全的酶促抑制，沒有鉤狀效應。相比之下，oleclumab 只能通過更高濃度的鉤狀效應實現部分抑制。 Uliledlimab 的分化來自於作為 C 末端的獨特結合表位。我們相信，如果 uliledlimab 與其他抗腫瘤藥物聯合使用時，有可能成為同類最佳藥物，具有改進的治療窗口和更大的靈活性。我們已經在 CD73 高表達的 4 期非小細胞肺癌中觀察到穩健的療效數據，我們目前正在集中精力於 2023 年下半年的晚期非小細胞肺癌的生物標誌物指導的臨床試驗。

So on the left side of this slide is our PK study. It really demonstrated linear PK profiles at 5-milligram per kilogram weekly or higher, indicating target saturation. At 30-milligram per kilogram, saturation and complete inhibition of CD73 activity were observed in human tumor biopsy samples. Studies of uliledlimab, in combination with an anti-PD-1 or PD-L1, have shown treatment is safe and well tolerated with no dose-limiting toxicities observed. Most treatment-related adverse events were either grade 1 or grade 2. Uliledlimab RP2D has been determined to be 30-milligram per kilogram every 3 weeks, in combination with toripalimab at 240-milligrams every 3 weeks.

所以這張幻燈片的左側是我們的 PK 研究。它確實展示了每週每公斤 5 毫克或更高的線性 PK 曲線，表明目標飽和度。在 30 毫克/千克時，在人類腫瘤活檢樣本中觀察到 CD73 活性飽和和完全抑制。 uliledlimab 聯合抗 PD-1 或 PD-L1 藥物的研究表明，治療是安全且耐受性良好的，未觀察到劑量限制性毒性。大多數與治療相關的不良事件為 1 級或 2 級。Uliledlimab RP2D 已確定為每 3 週 30 毫克/公斤，與每 3 週 240 毫克的特瑞普利單抗聯合使用。

This slide highlights the clinical experience of our U.S. Phase I study of uliledlimab in combination with atezolizumab in patients with refractory solid tumors. About 13 efficacy evaluable patients, 3 responses were seen, including 1 PR with an overall response rate at 23% and the disease control rate at 46%.

這張幻燈片重點介紹了我們在美國 uliledlimab 聯合 atezolizumab 治療難治性實體瘤患者的 I 期研究的臨床經驗。約13例可評價療效的患者，3例緩解，其中1例PR，總緩解率為23%，疾病控制率為46%。

More importantly, shown on the right, all 3 responders were identified to exhibit higher expression of tumor 73 -- CD73 as compared to non-responders. This provides the initial indication that high CD73 expression may correlate with the clinical activity of uliledlimab. Here, I want to highlight the latest clinical development update on uliledlimab.

更重要的是，如右圖所示，與無反應者相比，所有 3 名反應者都表現出更高的腫瘤 73 -- CD73 表達。這初步表明，高 CD73 表達可能與 uliledlimab 的臨床活性相關。在這裡，我想強調 uliledlimab 的最新臨床開發更新。

As of December 2022, 70 patients have been enrolled in the Phase II study of uliledlimab in combination with toripalimab, a PD-1 antibody, in stage 4 non-small cell lung cancer patients. As a high level of summary, at the time of the first data cut off in March 2022, ORR was 26% and the DCR was 74% for the first 19 evaluable patients. Remarkably, in patients with high CD73 expression, defined at least 35% expression level in tumor cells or immune cells, a much higher ORR was observed with a 57% ORR and DCR at 100%.

截至 2022 年 12 月，已有 70 名患者參加了 uliledlimab 聯合 PD-1 抗體特瑞普利單抗治療 4 期非小細胞肺癌患者的 II 期研究。作為一個高度總結，在 2022 年 3 月第一次數據截止時，前 19 名可評估患者的 ORR 為 26%，DCR 為 74%。值得注意的是，在 CD73 高表達（定義為腫瘤細胞或免疫細胞中至少 35% 的表達水平）的患者中，觀察到更高的 ORR，ORR 為 57%，DCR 為 100%。

Similar efficacy data in relation to CD73 expression were obtained in August 2022, with 32 evaluable patients and December 2022 with 45 evaluable patients, showing a consistent trend of efficacy signal with an overall ORR greater than 30% in all patients and an ORR approximately 50% in CD73 high-expression patients as compared to approximately 10% to 15% for those with CD73 low expression.

2022 年 8 月 32 名可評估患者和 2022 年 12 月 45 名可評估患者獲得了與 CD73 表達相關的類似療效數據，顯示療效信號趨勢一致，所有患者的總體 ORR 均大於 30%，ORR 約為 50%在 CD73 高表達患者中，與 CD73 低表達患者的大約 10% 至 15% 相比。

The efficacy data continue to mature for ORR and PFS in 2023. Our data has demonstrated that higher clinical response of uliledlimab and PD-1 combination therapy correlated with high tumor CD73 expression in patients with advanced non-small cell lung cancer.

2023 年 ORR 和 PFS 的療效數據繼續成熟。我們的數據表明，uliledlimab 和 PD-1 聯合治療的更高臨床反應與晚期非小細胞肺癌患者的高腫瘤 CD73 表達相關。

I want to summarize the key development of uliledlimab on this slide. Uliledlimab is a differentiated CD73 antibody with best-in-class potential. It can achieve complete CD73 inhibition without the hook effect. Uliledlimab has a favorable safety profile and the combination of toripalimab demonstrated robust anti-tumor activity in non-small cell lung cancer with the clinical responses correlating with CD73 expression.

我想在這張幻燈片上總結 uliledlimab 的關鍵發展。 Uliledlimab 是一種分化的 CD73 抗體，具有同類最佳的潛力。可實現完全抑制CD73，無鉤效應。 Uliledlimab 具有良好的安全性，與 toripalimab 的組合在非小細胞肺癌中顯示出強大的抗腫瘤活性，臨床反應與 CD73 表達相關。

With regard to our further development plan uliledlimab, a data readout for the 70 patients in our Phase II study is expected for ORR in the first half of 2023 and for PFS in the second half of 2023. The company plans to present the data at a major scientific venue in 2023.

關於我們的進一步開發計劃 uliledlimab，我們 II 期研究中的 70 名患者的數據讀數預計在 2023 年上半年的 ORR 和 PFS 在 2023 年下半年。公司計劃在2023 年的主要科學場所。

A further clinical development plan is being finalized to include a biomarker-guided people to trial of uliledlimab, in combination with PD-1 therapy, in Stage IV non-small cell lung cancer in second half of 2023 in China. And a global study of uliledlimab in combination with the PD-1 therapy and chemo regimen in advanced non-small cell lung cancer.

一項進一步的臨床開發計劃正在最終確定中，其中包括一項生物標誌物指導的人們於 2023 年下半年在中國試驗 uliledlimab 聯合 PD-1療法治療 IV 期非小細胞肺癌。以及 uliledlimab 聯合 PD-1 療法和化療方案治療晚期非小細胞肺癌的全球研究。

In parallel, a companion diagnostic kit is being developed with WuXi Diagnostics and is on track for the planned studies. With the new data, the company has been actively engaging in a potential global partnership in sync with the planned global study.

與此同時，藥明康德正在開發一種伴隨診斷試劑盒，並正在按計劃進行研究。有了新數據，該公司一直在積極參與與計劃中的全球研究同步的潛在全球合作夥伴關係。

The last asset I'd like to touch on today is givastomig, our novel Claudin18.2 4-1BB bispecific antibody that has also made significant clinical progress. Givastomig is a novel bispecific antibody with one arm targeting Claudin 18.2 and the other targeting 4-1BB through conditional or local activation. The key differentiation of givastomig is twofold. Firstly, it binds the tumor with a wide range of Claudin18.2 expression levels, including lower expression, as demonstrated on the right in preclinical models. Secondly, the 4-1BB arm of givastomig is designed to function upon local tumor engagement as a mechanism of conditional activation. This feature makes givastomig a unique T-cell activator, only localized at the tumor side without systemic toxicities. For example, liver toxicity and systemic cytokine release that are typically associated with 4-1BB.

我今天要談的最後一項資產是 givastomig，我們的新型 Claudin18.2 4-1BB 雙特異性抗體也取得了重大臨床進展。 Givastomig 是一種新型雙特異性抗體，其一隻臂靶向 Claudin 18.2，另一隻臂通過條件或局部激活靶向 4-1BB。 givastomig 的關鍵區別是雙重的。首先，它以廣泛的 Claudin18.2 表達水平（包括較低表達）結合腫瘤，如臨床前模型右側所示。其次，givastomig 的 4-1BB 臂被設計為在局部腫瘤參與時作為條件激活機制發揮作用。這一特性使 givastomig 成為一種獨特的 T 細胞激活劑，僅局限於腫瘤一側而無全身毒性。例如，通常與 4-1BB 相關的肝毒性和全身細胞因子釋放。

Here, I'd like to take a moment to highlight givastomig unique differentiation compared to other Claudin18.2 target agents. The differentiated molecular design makes givastomig unique among Claudin 18.2 target agents, including ADC and zolbetuximab. Zolbetuximab, a Claudin 18.2 monoclonal antibody. Givastomig has the potential to target a broader population, including those with lower Claudin 18.2 expression. In contrast, the antitumor activity with zolbe and ADC is rather limited to patients with higher Claudin 18.2 expression in the tumor. Secondly, the 4-1BB arm of givastomig is designed to function upon local tumor engagement at the mechanism of conditional activation. This feature makes givastomig a unique T-cell activator with no systemic toxicities, including hepatic toxicity and cytokine release syndrome.

在這裡，我想花點時間強調一下 givastomig 與其他 Claudin18.2 目標藥物相比的獨特差異。差異化的分子設計使 givastomig 在 Claudin 18.2 目標藥物中獨一無二，包括 ADC 和 zolbetuximab。 Zolbetuximab，一種 Claudin 18.2 單克隆抗體。 Givastomig 有可能針對更廣泛的人群，包括 Claudin 18.2 表達較低的人群。相反，zolbe 和 ADC 的抗腫瘤活性相當限於腫瘤中 Claudin 18.2 表達較高的患者。其次，givastomig 的 4-1BB 臂設計用於在局部腫瘤參與條件激活機制時發揮作用。這一特性使 givastomig 成為一種獨特的 T 細胞激活劑，沒有全身毒性，包括肝毒性和細胞因子釋放綜合徵。

In addition, givastomig exhibits less gastrointestinal toxicity than that is commonly observed for other Claudin 18.2 targeted therapeutics. Together, givastomig is clinically positioned to target gastric and pancreatic cancers that have lower Claudin 18.2 expression and are considered not eligible for treatment by zolbe or Claudin ADC, respectively. And those with high 18.2 expression by offering a more favorable safety profile over other Claudin 18.2 therapeutic modalities. Zolbe has the potential to be combined with first-line standard chemo PD-1 therapy in gastric cancer and also in several other tumor types. The preliminary clinical data are consistent with the differentiation of givastomig.

此外，與其他 Claudin 18.2 靶向治療藥物通常觀察到的相比，givastomig 表現出更少的胃腸道毒性。總之，givastomig 在臨床上定位於靶向 Claudin 18.2 表達較低且被認為不符合 zolbe 或 Claudin ADC 治療條件的胃癌和胰腺癌。那些具有高 18.2 表達的人通過提供比其他 Claudin 18.2 治療方式更有利的安全性。 Zolbe 有可能與胃癌和其他幾種腫瘤類型的一線標準化療 PD-1 療法聯合使用。初步臨床數據與givastomig的分化一致。

Here, I want to summarize the ongoing Phase I dose escalation trial of givastomig in patients with advanced or metastatic solid tumors. By the end of 2022, 8 dose cohorts have been completed up to 15 mg per kg without encountering dose-limiting toxicity. Most treatment-related adverse events are Grade 1 or Grade 2. There is a dose-dependent increase of drug exposure and soluble 4-1BB in serum, suggestive of a favorable PK/PD profile and potentially a longer dosing interval with durable T-cell activation. A 5-milligram per kilogram or above, C-12 reaches its target concentration in over 90% of the patients observed. Meanwhile, PD data indicate that T-cell activation occurs only at tumor site.

在這裡，我想總結一下正在進行的 givastomig 在晚期或轉移性實體瘤患者中的 I 期劑量遞增試驗。到 2022 年底，已經完成了 8 個劑量組，最高劑量為 15 mg/kg，沒有遇到劑量限制性毒性。大多數與治療相關的不良事件是 1 級或 2 級。藥物暴露量和血清中可溶性 4-1BB 呈劑量依賴性增加，這表明具有良好的 PK/PD 特徵，並且持久性 T 細胞的給藥間隔可能更長激活。每公斤 5 毫克或以上，C-12 在超過 90% 的觀察患者中達到其目標濃度。同時，PD 數據表明 T 細胞激活僅發生在腫瘤部位。

As mentioned, we have disclosed a PR at 5 mg per kilo last July, and we have since seen additional single-agent efficacy signal, including PR and stable disease in different cohorts as well. We expect to share the Phase I data in the second half of 2023, and we continue to engage in discussions for a potential global partnership.

如前所述，我們在去年 7 月披露了 5 mg/kg 的 PR，此後我們看到了更多的單藥療效信號，包括不同隊列中的 PR 和疾病穩定。我們預計將在 2023 年下半年共享 I 期數據，並且我們將繼續就潛在的全球合作夥伴關係進行討論。

Finally, I would like to highlight the expected catalysts in the near future. The first area is really to deliver our pre-BLA assets. We expect a Phase III data readout on eftansomatropin in the second half of 2023, followed by subsequent BLA submission. We are particularly excited about this asset and the market opportunity that exists in China. We're also on track with Phase III felzartamab and a potential commercial partnership.

最後，我想強調一下在不久的將來預期的催化劑。第一個領域實際上是交付我們的 BLA 前資產。我們預計將在 2023 年下半年讀出關於 eftansomatropin 的 III 期數據，隨後將提交 BLA。我們對這項資產和中國存在的市場機會感到特別興奮。我們還在進行 III 期 felzartamab 和潛在的商業合作夥伴關係。

The second area is on the clinical development of lemzoparlimab. We will initiate the Phase III clinical trial for lemzoparlimab as a first-line MDS treatment. We expect our Phase III study in China will support a planned BLA submission with the goal of being first to market and first in class in China.

第二個領域是lemzoparlimab的臨床開發。我們將啟動 lemzoparlimab 作為一線 MDS 治療的 III 期臨床試驗。我們預計我們在中國的 III 期研究將支持計劃中的 BLA 提交，目標是在中國率先上市和一流。

Next is uliledlimab, our exciting CD73 antibody. This year, we expect an additional data readout for uliledlimab Phase II non-small cell lung cancer trial, while planning to initiate a biomarker-guided pivotal study in Stage IV non-small cell lung cancer in the second half of 2023. We continue to engage in discussions for a potential global partnership.

接下來是 uliledlimab，我們令人興奮的 CD73 抗體。今年，我們預計 uliledlimab II 期非小細胞肺癌試驗將有更多數據讀出，同時計劃在 2023 年下半年啟動一項針對 IV 期非小細胞肺癌的生物標誌物指導的關鍵研究。我們將繼續參與有關潛在全球夥伴關係的討論。

Finally, we continue to be excited by the development we see in givastomig. We are currently completing our Phase I clinical trial and continue to engage in discussion for a potential partnership.

最後，我們繼續對我們在 givastomig 中看到的發展感到興奮。我們目前正在完成 I 期臨床試驗，並繼續就潛在的合作夥伴關係進行討論。

Lastly, we expect to initiate new INDs this year. As a reminder, I have not even touched on the multiple preclinical stage assets we have in development. The company continues to focus on fundamentals with innovative strategies.

最後，我們預計今年將啟動新的 IND。提醒一下，我什至沒有談到我們正在開發的多個臨床前階段資產。公司繼續通過創新戰略專注於基本面。

With that, I'm happy to turn over to Richard, who will discuss our financials. Richard?

有了這個，我很高興轉向理查德，他將討論我們的財務狀況。理查德？

Thank you, Andrew. Let me turn to review our financial results for the full year ended December 31, 2022. As of December 31, 2022, our cash and cash equivalents and the short-term investments were RMB 3.5 billion, or USD 514 million, compared with RMB 4.3 billion, or USD 671 of December 31, 2021.

謝謝你，安德魯。讓我回顧一下我們截至 2022 年 12 月 31 日的全年財務業績。截至 2022 年 12 月 31 日，我們的現金和現金等價物以及短期投資為 35 億元人民幣或 5.14 億美元，而 4.3 元人民幣十億美元，或 2021 年 12 月 31 日的 671 美元。

I-Mab's strong cash balance is expected to provide the company with adequate funding to support key business operations over the next 3 years. Total revenue for the full year of 2022 were RMB minus 221.6 million, or USD 32.1 million (sic) [minus USD 32.1 million], compared with RMB 88 million for the full year of 2021. The decrease in 2022 net revenue was primarily due to a one-off accounting treatment of USD 48 million recorded in second half 2022 following the amendment to the original license and collaboration agreement with AbbVie in August 2022. Further details can be found in our annual financial results. The decrease was partially offset by the revenue of RMB 92.6 million, or for USD 13.4 million from license and collaboration arrangements and the supply of pipeline products.

I-Mab 強勁的現金餘額有望為公司提供充足的資金，以支持未來 3 年的關鍵業務運營。 2022 年全年總收入為人民幣減 2.216 億元，或 3210 萬美元（原文如此）[減去 3210 萬美元]，而 2021 年全年為人民幣 8800 萬元。2022 年淨收入減少的主要原因是在 2022 年 8 月修訂與 AbbVie 的原始許可和合作協議後，在 2022 年下半年記錄了 4800 萬美元的一次性會計處理。更多詳細信息可以在我們的年度財務業績中找到。該減少部分被許可和合作安排以及管道產品供應的收入 9260 萬元人民幣或 1340 萬美元所抵消。

Now let me turn to R&D expenses. Research and development expenses for the full year of 2022 were RMB 904.9 million, or USD 131 million, compared with RMB 1.2 billion for the full year of 2021. The decrease was primarily due to the reduced demand for pipeline products as the company prepared to procure the sufficient stock for the pipeline products in 2021 and lower share-based compensation expenses.

現在讓我談談研發費用。 2022 年全年研發費用為人民幣 9.049 億元（合 1.31 億美元），而 2021 年全年為人民幣 12 億元。減少的主要原因是公司準備採購對管道產品的需求減少2021年在研產品庫存充足，股權激勵費用較低。

Administrative expenses for the full year of 2022 were RMB 720 million, or USD 104.4 million, compared with RMB 899 million for the full year of 2021. The decrease was primarily due to lower share-based compensation expenses in relation to the management personnel and an optimized control of operation and administrative expenses.

2022 年全年行政費用為 7.2 億元人民幣（1.044 億美元），而 2021 年全年為 8.99 億元人民幣。減少的主要原因是與管理人員相關的股權補償費用減少以及優化運營管理費用控制。

Net other expenses for the full year of 2022 were RMB 126.6 million, or USD 18.4 million, compared with net other income of RMB 83.2 million for the full year of 2021. The change was primarily caused by unrealized exchange losses due to fluctuation in exchange rate of RMB against U.S. dollars in 2022. I would like to reiterate that we maintain a strong cash position USD 514 million that we held at the end of 2022. Our current cash position, combined with potential upcoming milestone payments from the previous all licensing deals and the collaborations is expected to further strengthen our cash reserves. This has been largely achieved by our move to focus on 5 key clinical assets in our pipeline through our reprioritization effort in mid-2022.

2022 年全年其他費用淨額為 1.266 億元人民幣（1840 萬美元），而 2021 年全年其他收入淨額為 8320 萬元人民幣。變化主要是由於匯率波動導致的未實現匯兌損失2022 年人民幣兌美元匯率。我想重申，我們在 2022 年底持有 5.14 億美元的強勁現金頭寸。我們目前的現金頭寸，加上之前所有許可交易可能即將到來的里程碑付款和預計這些合作將進一步加強我們的現金儲備。這在很大程度上是通過我們在 2022 年年中通過重新確定優先級的努力將重點放在我們管道中的 5 個關鍵臨床資產上來實現的。

We also streamlined our corporate structure. This has also been included in streamlining our workforce through headcount optimization that was in line with the re-prioritization of our pipeline reduction in our overall operating expenses and corporate structure. With this, we have implemented cost initiatives that we intend to maintain committed as we were determined to maintain operational efficiency and a very lean operational budget.

我們還精簡了公司結構。這也包括在通過優化員工人數來精簡我們的員工隊伍中，這與我們在整體運營費用和公司結構中減少管道的重新優先順序一致。有了這個，我們已經實施了我們打算保持承諾的成本計劃，因為我們決心保持運營效率和非常精簡的運營預算。

Overall, this represents about a 20% reduction in cost in 2022. We expected to further reduce in 2023 as we continue to focus on where we can deliver the most important value to our shareholders.

總體而言，這意味著到 2022 年成本將降低約 20%。我們預計 2023 年將進一步降低成本，因為我們將繼續關注可以為股東提供最重要價值的領域。

In closing, our current strong cash position will provide us with ample flexibility to support our R&D activities in the next 3 years.

最後，我們目前強勁的現金狀況將為我們提供足夠的靈活性來支持我們未來 3 年的研發活動。

With that, I would now like to turn the call back to Tyler and begin our Q&A session. Tyler?

有了這個，我現在想把電話轉回泰勒並開始我們的問答環節。泰勒？

Thank you, Richard, and thank you, Dr. Zhu for your time and for your insights today.

謝謝你，理查德，也謝謝你，朱博士今天抽出時間來分享你的見解。

(Operator Instructions) First question, we see is from Kelly Shi.

（操作員說明）第一個問題，我們看到來自 Kelly Shi。

My first question is, has I-Mab been able to resolve its delisting risks fully? And I also have a follow-up.

我的第一個問題是，天境生物能否全面化解退市風險？我也有跟進。

Kelly, thank you for your question. I think most of the delisting risk has been mitigated by our working with our current auditor [through] PCOAB new rules. So our delisting risk has been largely mitigated throughout last year.

凱利，謝謝你的問題。我認為，通過 PCOAB 新規則，我們與現任審計師合作，大部分退市風險已經得到緩解。因此，我們的退市風險在去年已大大降低。

And also regarding the Phase II trial of CD73 antibody in stage IV non-small cell lung cancer, you updated 70 patients has been enrolled by the end of last year. I'm curious, could you share more information regarding the patient baseline characteristics regarding [PL-1] expression level and also prior PD-1 treatment? Are they like refractory or relapsed from any PD-1 -- either PD-1 agents?

還有關於CD73抗體在IV期非小細胞肺癌的II期臨床試驗，你們更新說去年底已經入組了70名患者。我很好奇，您能否分享更多關於 [PL-1] 表達水平和之前 PD-1 治療的患者基線特徵的信息？它們是否像任何 PD-1 的難治性或複發一樣——無論是 PD-1 代理？

Let me take that question. So Kelly, as I indicated in my presentation, the data that I presented, the one with 70 patients cohort, that specifically targeting the treatment-naive stage IV non-small cell lung cancer. So they are definitely naive to all the treatments, including PD-1. And so our data...

讓我來回答這個問題。所以凱利，正如我在我的演講中指出的那樣，我展示的數據是 70 名患者隊列，專門針對未經治療的 IV 期非小細胞肺癌。所以他們肯定對所有的治療都是幼稚的，包括PD-1。所以我們的數據...

Sorry, go ahead.

對不起，繼續。

If you have a follow-up question?

如果您有後續問題？

No, sorry, go ahead.

不，對不起，繼續。

So basically, I think our study exclusively look at that particular population for our activity and also tolerability in our Phase II trial.

所以基本上，我認為我們的研究專門針對特定人群的活動以及我們 II 期試驗的耐受性。

And I'm showing Joe Catanzaro.

我正在展示 Joe Catanzaro。

Maybe just one quick one from me on givastomig. I know you touched on this a bit in the prepared remarks, but the Claudin 18.2 space has obviously become highly competitive. So maybe 2 questions around this. First, how do you think about the data that we've seen for zolbetuximab and the implications around Claudin 18.2 as a target? And then second, given the competitiveness with a lot of different modalities, how do you think givastomig is positioned here?

也許只是我在 givastomig 上的一個快速的。我知道你在準備好的評論中稍微提到了這一點，但 Claudin 18.2 空間顯然已經變得非常具有競爭力。所以也許有兩個問題。首先，您如何看待我們看到的關於 zolbetuximab 的數據以及圍繞 Claudin 18.2 作為目標的影響？其次，考慮到許多不同模式的競爭力，您認為 givastomig 在這方面的定位如何？

Yes. So Joe, great question. I think with the data from SPOTLIGHT and GLOW 2 Phase III trials in the first-line metastatic gastric cancer space, with the addition of zolbe to the standard chemo backbone, both studies convincingly demonstrated the improved benefit. And I think clearly, we have validated Claudin being a relevant therapeutic target in gastric cancer. So I think that part, I personally feel that there's actually no argument. I think anti-Claudin 18.2 antibody has a role. This will definitely benefit patients with metastatic gastric cancer. But also, as you know, both trials select patients based on Claudin 18.2 expression and the criteria they use is actually 2-plus [plus] 3-plus of at least 75%.

是的。喬，好問題。我認為，根據 SPOTLIGHT 和 GLOW 2 III 期一線轉移性胃癌試驗的數據，將 zolbe 添加到標準化療骨幹中，這兩項研究都令人信服地證明了療效的改善。而且我清楚地認為，我們已經證實 Claudin 是胃癌的相關治療靶點。所以我認為那部分，我個人覺得實際上沒有爭論。我認為抗 Claudin 18.2 抗體有作用。這必將使轉移性胃癌患者受益。但是，正如您所知，這兩項試驗都根據 Claudin 18.2 表達來選擇患者，他們使用的標準實際上是至少 75% 的 2+ [plus] 3+。

So you can imagine, I think if you look at this population very carefully, this probably will be applicable for about 30% of the patient with Claudin expression -- Claudin 18.2 expression. So my feeling is that I think zolbe will define -- will have the role in certain patients. And also, for those who have low PD-L1 expression, this may become the major target therapy in combination with chemo. But having said that, we also feel strongly that givastomig has a very, very unique position in a very crowded Claudin 18.2 therapeutic target space, in gastric and potentially maybe in other tumor types because the unique molecular design really allow this molecule to cover a wider population with different levels of Claudin 18.2 expression, and in particular, the lower 18.2 expression.

所以你可以想像，我認為如果你非常仔細地觀察這個人群，這可能適用於大約 30% 的 Claudin 表達患者——Claudin 18.2 表達。所以我的感覺是我認為 zolbe 將定義 - 將在某些患者中發揮作用。而且，對於PD-L1表達低的患者，這可能成為與化療聯合的主要靶向治療。但話雖如此，我們也強烈認為 givastomig 在非常擁擠的 Claudin 18.2 治療目標空間中具有非常非常獨特的地位，在胃和可能在其他腫瘤類型中，因為獨特的分子設計確實允許這種分子覆蓋更廣泛的範圍具有不同水平 Claudin 18.2 表達的人群，特別是較低的 18.2 表達。

And we demonstrated that in preclinical models. Clearly, it behaves favorably with more robust anti-tumor activity in comparison with the other Claudin 18.2 target antibody. Our ongoing Phase I trial also give us the initial confidence that we definitely have seen anti-tumor activity in Claudin 18.2 low expression patients are granted (inaudible) is still actually just ongoing it's a Phase I study. But nevertheless, we are encouraged by the early efficacy signal.

我們在臨床前模型中證明了這一點。顯然，與其他 Claudin 18.2 目標抗體相比，它具有更強大的抗腫瘤活性。我們正在進行的 I 期試驗也給了我們初步的信心，我們肯定已經看到 Claudin 18.2 低表達患者的抗腫瘤活性被授予（聽不清）實際上仍在進行中，這是一項 I 期研究。儘管如此，我們對早期療效信號感到鼓舞。

On the other side of the spectrum, it's really the safety profile with our unique molecular design. As I indicated in my presentation, our molecule will only become active when the molecule is engaged with the tumor-associated [entity] in this case, Claudin 18.2 positive tumor cells. In this case, the 4-1BB will get activated. So in this way, it actually spares the systemic toxicity, including hepatic and also cytokine release syndrome and this is actually commonly seen with other T-cell inhibitor modalities, including 4-1BB (inaudible).

另一方面，我們獨特的分子設計確實具有安全性。正如我在演講中指出的那樣，我們的分子只有在與腫瘤相關 [實體] 結合時才會變得活躍，在這種情況下，Claudin 18.2 陽性腫瘤細胞。在這種情況下，4-1BB 將被激活。因此，通過這種方式，它實際上避免了全身毒性，包括肝臟和細胞因子釋放綜合徵，這在其他 T 細胞抑製劑形式中很常見，包括 4-1BB（聽不清）。

So we think our molecule also has the added advantage even for those with high Claudin 18.2 population because it may potentially have the potential to be combined with the standard first line, for example, (inaudible) PD-1 based combo and also for other tumor types, we definitely have the potential to explore the combination of our drug without a combination chemotherapy in other tumor types.

因此，我們認為我們的分子即使對於那些具有高 Claudin 18.2 人群的人也具有額外的優勢，因為它可能有可能與標準一線相結合，例如，（聽不清）基於 PD-1 的組合以及其他腫瘤類型，我們絕對有可能在其他腫瘤類型中探索我們的藥物組合而無需聯合化療。

And lastly, as you know, there is actually the so-called class-specific side effects associated with Claudin 18.2 target agents because the GI toxicity is actually very remarkable, nausea, vomiting is commonly observed some of them could be actually incredibly challenging to manage. And in our trial, we only observed a very mild gastrointestinal toxicity in particular nausea and vomiting, which we think offers the advantage to be better tolerated in gastric cancer patients. So we definitely would like to further explore givastomig development either as a single agent as we're doing right now but also in combination down the road.

最後，如您所知，實際上存在與 Claudin 18.2 目標藥物相關的所謂類別特異性副作用，因為胃腸道毒性實際上非常顯著，通常會觀察到噁心、嘔吐，其中一些實際上可能難以控制.在我們的試驗中，我們只觀察到非常輕微的胃腸道毒性，尤其是噁心和嘔吐，我們認為這有助於胃癌患者更好地耐受。因此，我們絕對希望進一步探索 givastomig 的開發，既可以像我們現在正在做的那樣作為單一代理，也可以在未來結合使用。

Next, we'll have Louise Chen. Louise?

接下來，我們將請 Louise Chen 發言。路易絲？

So do you have any concerns regarding the toxicity of 4-1BB agonist. These features have prevented high target engagement in past programs. So can we expect more results from this dose escalation study?

那麼您對4-1BB激動劑的毒性有任何顧慮嗎？這些功能阻止了過去計劃中的高目標參與度。那麼我們可以期待從這項劑量遞增研究中獲得更多結果嗎？

Yes. I think, Louise, I'll take your question. Again, it's a very, very important question when it comes to the tolerability, the safety of any bispecific antibody, particularly when it comes to the T-cell engager modality. I think as I was trying to answer to Joe's question earlier, I did mention that our bispecific design is unique in a sense that we can only induce 4-1BB activation upon Claudin 18.2 engagement at the tumor site. So for this reason, we actually spare the systemic toxicity commonly associated with 4-1BB and also other agonist treatment.

是的。我想，路易絲，我會回答你的問題。同樣，當涉及到任何雙特異性抗體的耐受性和安全性時，這是一個非常非常重要的問題，特別是當涉及到 T 細胞接合器模式時。我想當我之前試圖回答 Joe 的問題時，我確實提到了我們的雙特異性設計在某種意義上是獨一無二的，因為我們只能在 Claudin 18.2 與腫瘤部位結合時誘導 4-1BB 激活。因此，出於這個原因，我們實際上避免了通常與 4-1BB 和其他激動劑治療相關的全身毒性。

So in that sense, the toxicity concern associated with other 4-1BB antibody or actually other T-cell engager, including CD3-based definitely, we actually have a very favorable safety profile as shown in our Phase I -- ongoing Phase I trial. Because we're not actually seeing the systemic toxicity, including hepatotoxicity, cytokine release syndrome. And also the added bonus for our bispecific is that our GI toxicity also is on the mild side.

因此，從這個意義上說，與其他 4-1BB 抗體或實際上其他 T 細胞接合器相關的毒性問題，包括基於 CD3 的肯定，我們實際上有一個非常有利的安全概況，如我們的第一階段 - 正在進行的第一階段試驗所示。因為我們實際上並沒有看到全身毒性，包括肝毒性、細胞因子釋放綜合徵。我們的雙特異性藥物的額外好處是我們的 GI 毒性也很輕微。

We will take one last question since we're a bit over time. Andres Maldonado.

我們將回答最後一個問題，因為我們已經超時了。安德烈斯·馬爾多納多。

Quick one for me. Could you provide additional color on how we should be thinking about your expected cash burn rate in 2023? And a quick follow-up to that is, obviously, you've been focusing on the 4 highlighted programs from your prepared remarks. So I'm just curious from a timing wise and a financial perspective, would you expect to feel comfortable in bringing additional assets to the clinic in the future?

對我來說快點。您能否就我們應該如何考慮您在 2023 年的預期現金消耗率提供更多顏色？對此的快速跟進顯然是，您一直在關注您準備好的發言中突出顯示的 4 個程序。所以我很好奇，從時間安排和財務角度來看，您是否希望將來為診所帶來更多資產感到自在？

Let me -- thank you for the question, Joe (sic) [Andres]. And let me start with the financial -- the burn rate question, and Andrew can answer the pipeline question. So with this regard, as we have mentioned, that in 2022, we actually spent a lot of time actually optimizing our cost structure. It's mostly -- so first of all, we actually focused on the 5 key assets; and second, really optimizing the organizational structure. So this year, we're further going to reduce the overall cost, as we just mentioned in the call that are expected -- the current net burn rate for 2023 is expected to be in the range of USD 130 million to USD 140 million. This will further optimize our operational structure so that our cash position can retain us at least for additional 3 years or more years of cash operations. So given that we have other pipeline products that Andrew will discuss to develop, and we really focus [on] our key assets.

讓我——謝謝你提出這個問題，喬（原文如此）[安德烈斯]。讓我從財務——燃燒率問題開始，Andrew 可以回答管道問題。所以在這方面，正如我們提到的，在 2022 年，我們實際上花了很多時間來優化我們的成本結構。主要是 - 所以首先，我們實際上專注於 5 個關鍵資產；二是真正優化組織結構。所以今年，我們將進一步降低總體成本，正如我們剛剛在預期的電話會議中提到的那樣——目前 2023 年的淨消耗率預計在 1.3 億美元至 1.4 億美元之間。這將進一步優化我們的運營結構，使我們的現金狀況至少可以保留我們額外 3 年或更長時間的現金運營。因此，鑑於我們有安德魯將討論開發的其他管道產品，我們真正關注 [on] 我們的關鍵資產。

Yes. So I think Andres, this is a very, very important question for the R&D operation. I think a few things that I would like to share with you. As you know, that I-Mab actually has a very, very innovative discovery engine. We actually produce a lot of innovative assets internally. But also for reasons that we discussed today, we've been actually really trying to focus on the key assets that we can actually generate more value, move the program to the next level faster, but also realize the value of these assets, hopefully earlier, so that the company will benefit, the shareholders will benefit and more importantly, patients will benefit from this strategy.

是的。所以我認為安德烈斯，這對研發運營來說是一個非常非常重要的問題。我想有幾點想和大家分享。如您所知，天境生物實際上有一個非常非常創新的發現引擎。我們實際上在內部產生了很多創新資產。但也出於我們今天討論的原因，我們實際上一直在努力專注於我們實際上可以產生更多價值的關鍵資產，將計劃更快地推進到一個新的水平，同時也希望更早地實現這些資產的價值，這樣公司將受益，股東將從中受益，更重要的是，患者將從這一戰略中受益。

But having said that, we never stopped looking at innovative assets from outside. It's just right now, we cut the current situation, our bar is higher. We definitely want to take a more critical look when it comes to the licensing efforts from outside. But this is a dynamic process. Clearly, we are aiming to also generate additional cash flow without (inaudible). So I think, clearly, we will reassess the strategy as we proceed with the new year in 2023. But right now, we definitely want to make sure we focus on the internal assets. But definitely, we will actively look at the key assets that potentially have value and also have potential market more critically. This is our current position.

但話雖如此，我們從未停止從外部尋找創新資產。就在現在，我們削減了當前的情況，我們的門檻更高了。當涉及到來自外部的許可工作時，我們絕對希望採取更嚴格的審視。但這是一個動態的過程。顯然，我們的目標是在沒有（聽不清）的情況下產生額外的現金流。所以我認為，很明顯，我們將在 2023 年新的一年開始時重新評估該戰略。但現在，我們絕對希望確保我們專注於內部資產。但可以肯定的是，我們會更加批判性地積極看待具有潛在價值和潛在市場的關鍵資產。這是我們目前的立場。

Thank you, Dr. Zhu, and thank you, Richard. With that, we will conclude today's call. I'd like to thank you all for dialing in to today's financial results and business update conference call. Yes. Thanks, everyone, for joining me. You may now disconnect.

謝謝朱醫生，也謝謝理查德。至此，我們將結束今天的電話會議。感謝大家撥通今天的財務業績和業務更新電話會議。是的。謝謝大家加入我。您現在可以斷開連接。