Tyler Ehler
大家早上好,感谢各位今天上午加入我们的电话会议。感谢各位的耐心等待。我谨借此机会欢迎各位参加天境生物2022年全年财务业绩及业务更新电话会议。我是Tyler Ehler,天境生物投资者关系高级总监。目前所有参会者均处于只听模式。本次电话会议结束后,我们将进行问答环节,届时将提供相关说明。今天早些时候,我们发布了新闻稿,回顾了截至2022年12月31日的全年财务业绩,并概述了近期公司亮点及即将到来的里程碑。该新闻稿可在我们网站投资者关系栏目ir.i-mabbiopharma.com上查阅。今天与我一同参加电话会议的天境生物高级管理团队成员包括:创始人兼董事长臧敬武博士;代理首席执行官朱秀轩博士;以及临时首席财务官兼首席运营官叶永军先生。朱秀轩博士将概述我们近期的成就和即将到来的里程碑,并提供研发进展的最新情况。叶先生随后将总结截至2022年12月31日的全年财务业绩,之后我们将把电话转交给接线员回答各位的问题。请注意,今天的讨论将包含有关公司未来业绩的前瞻性陈述,这些陈述是根据美国《1995年私人证券诉讼改革法案》的安全港条款作出的。此类陈述并非对未来业绩的保证,并受制于某些风险、不确定性、假设以及其他因素。其中一些风险超出公司的控制范围,可能导致实际结果与今天新闻稿和讨论中提及的内容存在重大差异。关于可能影响天境生物业务和财务业绩的风险因素的一般性讨论包含在公司向美国证券交易委员会提交的某些文件中。除非法律要求,公司不承担更新此前瞻性信息的义务。我们还在今天的电话会议中讨论了特定的非美国通用会计准则财务指标。这些指标的呈现并非旨在孤立考虑或替代根据美国通用会计准则编制和呈现的财务信息。请参阅今天发布的财务业绩新闻稿,了解非美国通用会计准则财务指标的定义以及美国通用会计准则与非美国通用会计准则财务业绩的调节表。现在,我将电话转交给我们的代理首席执行官朱秀轩博士。朱博士,请开始。
Tyler Ehler
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. This is Tyler Ehler here. I-Mab's Senior Director of Investor Relations. At this time, all participants are in a listen-only mode. 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. Joining me today on the call from I-Mab 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. Dr. Andrew Zhu will provide a high level overview of our recent achievements and upcoming milestones and 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. 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 US 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. A general discussion of the risk factors that could affect I-Mab's business and financial results is included in certain filings of the company with the Securities and Exchange Commission. The company does not undertake any obligation to update this forward-looking information except as required by law. We 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 US 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. And with that, I'll now turn the call over to Dr. Andrew Zhu, our Acting CEO. Dr. Zhu. Please go ahead.
Andrew Zhu
翻译中...
Andrew Zhu
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 update and major progress in core asset development for the year ended December 31st, 2022. Since the start of 2022, the company faced multiple challenges, including, but not limited to geopolitical issues such as ADR delisting risks, macroeconomic factors, including interest rate hikes and COVID-19 pandemic. 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 five 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. In terms of the ADR delisting risk, on December 15th, 2022, the PCAOB issued 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 commission 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. 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 three of our key assets lemzoparlimab, uliledlimab and givastomig. Here we highlight the five key clinical assets that we have prioritized. These assets are novel, highly differentiated and among the frontrunners globally and all in China. First of all eftansomatropin alfa, a long-acting growth hormone. We completed enrollment of 168 patients for our Phase 3 trial in the first half of 2022. We expect to have a data readout in the second half of 2023, followed by subsequent BLA submission. In November 2021, we announced a commercial partnership with Jumpcan, a top 100 Chinese pharmaceutical company specialized in the pediatric space. Second, felzartamab, a differentiated CD38 antibody. In addition to the completed Phase 2 registration study, our Phase 3 study for second line multiple myeloma is on track despite the impact of COVID-19. Continue to make progress with the local manufacturing plan in preparation for BLA submission and seek a potential commercial partnership. Next, we have three key assets that I will discuss in more detail later. Lemzoparlimab, a differentiated CD47 antibody has reached the Phase 3 stage. Uliledlimab, a differentiated CD73 antibody and a global frontrunner, has demonstrated impressive antitumor activity, a non-small cell lung cancer in a Phase 2 trial. The clinical response is correlated with tumor CD73 expression. Next, givastomig, a Claudin18.2 4-1BB bispecific antibody with a favorable safety profile and single agent efficacy signal. 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. I would like to remind you that lemzoparlimab is differentiated by design to avoid binding to red blood cells while maintaining strong antitumor 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 [Technical Difficulty]. This molecular differentiation has been validated preclinically and has translated into clinical advantages that are being validated. 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. Here I want to highlight lemzoparlimab safety differentiation with clinical data. In a systemic safety data review of 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 US and China studies continue to be favourable 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 five hematological TRAE's have been reported. In the Phase 2 study in MDS, we have observed a favourable 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 three and above anemia, and 51% of the patients had grade three 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. Next, I would like to highlight the clinical efficacy results presented at ESMO 2022. Of the 53 patients enrolled as of March 31st, 2022 for patients who began treatment six 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 four months or longer, the ORR was 86.2% with a CRR of 31%. I'm happy to share that the updated results from the most recent data analysis of 62 patients have 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. 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 2 MDS trial demonstrated a consistent efficacy trend, including ORR and CRR, with 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 3 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 licensing collaboration agreement. As a result, both parties are continuing to collaborate on the global development of anti-CD47 antibody therapy. Next, I'd like to turn to uliledlimab, another 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 by an abnormal phenomena that a drug molecule paradoxically loses the effect at higher doses. 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 differentiation comes from a unique binding epitope at the C-terminals. We believe the differentiation give 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 a biomarker-guided pivotal trial in advanced non-small cell lung cancer in the second half of 2023. So on the left side of this slide is our PK study. It really demonstrated linear PK profiles at 5 mg per kg weekly or higher, indicating target saturation. A 30 mg per kg 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 one or grade two. Uliledlimab RP2D has been determined to be 30 mg per kg every three weeks in combination with toripalimab to 40 milligram every three weeks. This slide highlights the clinical experience of our US Phase 1 study of uliledlimab in combination with atezolizumab in patients with refractory solid tumors. About 13 efficacy evaluable patients, three responses were seen, including 1 PR with an overall response rate at 23% and the disease control rate at 46%. More importantly, shown on the right, all three 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. As of December 2022, 70 patients had been enrolled in the Phase 2 study of uliledlimab in combination with toripalimab, a PD-1 antibody in Stage 4 non-small cell lung cancer patients. As a high level 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 of 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%. 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. The efficacy data continued to mature for ORR and PFS in 2023. Our data have 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. 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 uliledlimab/toripalimab demonstrated robust anti-tumor activity in non-small cell lung cancer with the clinical responses correlating with CD73 expression. With regard to our further development plan for uliledlimab, a data readout for the 70 patients in our Phase 2 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 and further clinical development plan is being finalized to include a biomarker-guided pivotal trial of uliledlimab in combination with PD-1 therapy in Stage 4 non-small cell lung cancer in second half of 2023 in China. And a global study of uliledlimab in combination with a PD-1 therapy and chemo regimen in advanced non-small cell lung cancer. 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. 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 Claudin18.2 and the other targeting 4-1BB through conditional or local activation. The key differentiation of givastomig is twofold. Firstly, it binds to tumors with a wide range of Claudin18.2 expression levels, including lower expression, as demonstrated on the right in pre-clinical 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 site without systemic toxicities. For example liver toxicity and systemic cytokine release, that are typically associated with 4-1BB. Here. I'd like to take a moment to highlight givastomig's unique differentiation compared to other Claudin18.2 target agents. The differentiated molecular design makes givastomig unique among Claudin18.2 target agents including ADC and zolbetuximab. Zolbetuximab, a Claudin18.2 monoclonal antibody. Givastomig has the potential to target a broader population, including those with lower Claudin18.2 expression. In contrast, the antitumor activity with zolbetuximab and AGC is rather limited to patients with higher Claudin18.2 expression in the tumor. 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 with no systemic toxicities, including hepatic toxicity and cytokine release syndrome. In addition, givastomig exhibits less gastrointestinal toxicity that that is commonly observed for other Claudin18.2 targeted therapeutics. Together. givastomig is clinically positioned to target gastric and pancreatic cancers that have lower Claudin18.2 expression and are considered not eligible for treatment by zolbetuximab clotting Claudin18.2 ADC respectively. And those with high 18.2 expression by offering a more favorable safety profile over other Claudin18.2 therapeutic modalities. Zolbetuximab 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. Here, I want to summarize the ongoing Phase 1 dose escalation trial of givastomig in patients with advanced or metastatic solid tumors. By the end of 2022, eight 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 mg per kg or above Ctrough reaches its target concentration in over 90% of the patients observed. Meanwhile, PD data indicate that T cell activation occurs only at tumor site. As mentioned, we have disclosed a PR at 5 mg per kg 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 1 data in the second half of 2023 and we continue to engage in discussions for a potential global partnership. 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 3 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 3 for felzartamab and a potential commercial partnership. The second area is on the clinical development of lemzoparlimab. We will initiate the Phase 3 clinical trial for lemzoparlimab as a first line MDS treatment. We expect our Phase 3 study in China will support a planned BLA submission with the goal of being first-to-market and first-in-class in China. Next is uliledlimab, our exciting CD73 antibody. This year, we expect an additional data readout for uliledlimab Phase 2 non-small cell lung cancer trial while planning to initiate a biomarker-guided pivotal study in Stage 4 non-small cell lung cancer in the second half of 2023. We continue to engage in discussions for a potential global partnership. Finally, we continue to be excited by the development we see in givastomig. We are currently completing our Phase 1 clinical trial and continue to engage in discussion for a potential partnership. Lastly, we expect to initiate new INDs this year. As a reminder, I have not even touched on the multiple pre-clinical stage assets we have in development. The company continues to focus on fundamentals with innovative strategies. With that, I'm happy to turn to over to Richard, who will discuss our financials. Richard?
Richard Yeh
谢谢,Andrew。现在我来回顾一下截至2022年12月31日的全年财务业绩。截至2022年12月31日,我们的现金及现金等价物和短期投资为人民币35亿元或5.14亿美元,而截至2021年12月31日为人民币43亿元或6.71亿美元。I-Mab强大的现金余额预计将为公司未来三年提供充足的资金支持其关键业务运营。2022年全年总收入为人民币-2.216亿元或3210万美元,而2021年全年为人民币8800万元。2022年净收入下降主要是由于2022年8月与艾伯维修订原始许可和合作协议后,在2022年下半年记录的一次性会计处理4800万美元。更多细节可在我们的年度财务业绩中找到。这一下降部分被来自许可和合作安排以及管线产品供应的收入人民币9260万元或3040万美元所抵消。现在让我转向研发费用。2022年全年研发费用为人民币9.049亿元或1.31亿美元,而2021年全年为人民币12亿元。这一下降主要是由于公司为2021年管线产品采购充足库存导致管线产品需求减少,以及较低的股权激励费用。2022年全年行政费用为人民币7.2亿元或1.044亿美元,而2021年全年为人民币8.99亿元。这一下降主要是由于与管理人员相关的股权激励费用降低,以及运营和行政费用的优化控制。2022年全年其他净支出为人民币1.266亿元或1840万美元,而2021年全年其他净收入为人民币8320万元。这一变化主要是由于2022年人民币兑美元汇率波动导致的未实现汇兑损失。我想重申的是——我们保持了2022年底持有的5.14亿美元的强劲现金状况。我们当前的现金状况,加上先前对外授权交易和合作可能带来的即将到来的里程碑付款,预计将进一步增强我们的现金储备。这主要是通过我们在2022年中期的重新优先排序工作,将重点放在管线中的五个关键临床资产上实现的。我们还精简了公司结构。这也包括通过人员优化来精简员工队伍,这与我们管线重新优先排序、整体运营费用减少和公司结构调整保持一致。通过这一点,我们实施了成本控制措施,我们打算继续保持承诺,因为我们决心保持运营效率和非常精简的运营预算。总体而言,这代表了2022年成本约20%的减少。我们预计2023年将进一步减少,因为我们继续专注于能为股东创造最重要价值的领域。最后,我们当前强劲的现金状况将为我们未来三年的研发活动提供充足的灵活性。说到这里,我现在想把电话交回给Tyler,开始我们的问答环节。Tyler?
Richard Yeh
Thank you, Andrew. Let me turn to review our financial results for the full year ended December 31st, 2022. As of December 31st, 2022, our cash and cash equivalents and short-term investments were RMB3.5 billion or US$514 million compared with RMB4.3 billion or US$671 as of December 31st, 2021. I-Mab's strong cash balance is expected to provide the company with adequate funding to support its key business operations over the next three years. Total revenue for the full year of 2022 were RMB-221.6 million or US$32.1 million compared with RMB88 million for the full year of 2021. The decrease in 2022 net revenue was primarily due to a one-off accounting treatment of US$48 million recorded in the second half 2022, following the amendment to the original licensing 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 RMB92.6 million or US$30.4 million from licensing and collaboration arrangements and the supply of pipeline products. Now let me turn to the R&D expenses. Research and development expenses for the full year of 2022 were RMB904.9 million or US$131 million compared with RMB1.2 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 a lower share-based compensation expenses. Administrative expenses for the full year of 2022 were RMB720 million or US$104.4 million compared with RMB899 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 optimized control of operation and administrative expenses. Net other expenses for the full year of 2022 were RMB126.6 million or US$18.4 million compared with net other income of RMB83.2 million for the full year of 2021. The change was primarily caused by unrealized exchange losses due to fluctuation in the exchange rate of RMB against the US dollars in 2022. I would like to reiterate that -- we maintain a strong cash position of US$514 million that we held at the end of 2022. Our current cash position combined with potential upcoming milestone payments from the previous out-licensing deals and the collaborations is expected to further strengthen our cash reserves. This has been largely achieved by our move to focus on five key clinical assets in our pipeline through our reprioritization effort in mid-2022. We also streamlined our corporate structure. This has also been included in streamlining our workforce through a headcount optimization that was in line with the reprioritization 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. 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. In closing, our current strong cash position will provide us with ample flexibility to support our R&D activities in the next three years. With that, I would now like to turn the call back to Tyler and begin our Q&A sessions. Tyler?
Tyler Ehler
谢谢Richard,也谢谢朱博士今天抽出时间分享见解。接下来我们将开始问答环节。如果您有任何问题,请使用Zoom的举手功能,我们会为您解除静音以便提问。第一个问题来自Kelly Shi。Kelly,请开始提问。
Tyler Ehler
Thank you, Richard and thank you Dr. Zhu for your time and for your insights today. Next, we will begin our Q&A session. If you do have any questions please use Zoom's Raise Your Hand feature and we'll unmute you for your questions. First question we see is from Kelly Shi. Kelly, please go ahead.
Kelly Shi
谢谢Tyler,也谢谢您回答我的问题。我的第一个问题是,天境生物是否已经完全解决了退市风险?我还有一个后续问题。谢谢。
Kelly Shi
Thank you, Tyler, and thank you for taking my questions. My first question is, has I-Mab been able to resolve its delisting risks fully and also have follow-up. Thanks.
Jingwu Zang
是的。嘿,Kelly,谢谢你的问题。我认为大部分退市风险已经通过我们与现任审计师根据PCAOB新规的合作得到了缓解。所以去年我们的退市风险已经基本得到缓解。
Jingwu Zang
Yeah. Hey, Kelly, thank you for your question. I think most of the delisting risk has been mitigated by our -- working with our current auditor through the PCAOB new rules. So our delisting risk has been largely mitigated throughout last year.
Kelly Shi
谢谢。另外关于CD73抗体在IV期非小细胞肺癌的二期试验。您更新了截至去年底已入组70名患者的信息。我想了解,能否分享更多关于患者基线特征的信息,特别是PD-L1表达水平以及既往PD-1治疗情况?他们是PD-1或其他PD-1药物难治性或复发的患者吗?谢谢。
Kelly Shi
Thanks. And also regarding the Phase 2 trial of CD73 antibody in Stage 4 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 PD-L1 expression level and also prior PD-1 treatment? Are they like refractory or relapsed from any PD-1 other PD-1 agents? Thank you.
Andrew Zhu
好的,我来回答这个问题。Kelly,正如我在演示中提到的,我展示的数据中,那个70名患者的队列专门针对初治的IV期非小细胞肺癌患者。所以他们肯定对所有治疗都是初治的,包括PD-1。所以我们的数据,是的。
Andrew Zhu
Yeah, let me take that question. So, Kelly, as I indicated in my presentation, the data that I presented, the one with 70 patient cohort that's specifically targeting the treatment naive Stage 4 non-small cell lung cancer. So they are definitely naive to all the treatments, including PD-1. And so our date, yeah.
Kelly Shi
抱歉。请继续。
Kelly Shi
Sorry. Go ahead.
Andrew Zhu
您有后续问题吗?
Andrew Zhu
You have a follow-up question?
Kelly Shi
没有,抱歉。请继续。我对这个回答满意。
Kelly Shi
No, sorry. Go ahead. I'm okay with that.
Andrew Zhu
是的。基本上,我认为我们的研究专门针对这一特定人群,考察我们二期试验中的活性和耐受性。
Andrew Zhu
Yeah. So basically, I think, you know, our study exclusively look at that particular population, you know, for our activity and also tolerability in our Phase 2 trial.
Kelly Shi
好的。谢谢。
Kelly Shi
Okay. Thank you.
Tyler Ehler
谢谢,Kelly。我看到Joe Catanzaro在线。Joe,请开始。
Tyler Ehler
Thank you, Kelly. And I'm showing Joe Catanzaro. Joe, please go ahead.
Joseph Catanzaro
大家好。希望你们能听清楚我的声音。关于givastomig,我可能只有一个简短的问题。我知道你们在准备好的发言中已经提到了一些,但Claudin18.2领域显然已经变得竞争非常激烈。所以可能围绕这个有两个问题。首先,你们如何看待我们看到的zolbetuximab数据以及这对Claudin18.2作为靶点意味着什么?其次,考虑到多种不同治疗方式的竞争,你们认为givastomig在这里的定位如何?谢谢。
Joseph Catanzaro
Hey, guys. Hopefully you can hear me okay. Maybe just one quick one from me on givastomig. I know you touched on this a bit in the prepared remarks, but the Claudin18.2 space is obviously become highly competitive. So maybe for two questions around this. First, how do you think about the data that we've seen for zolbetuximab and the implications around Claudin18.2 as a target? And then second, given the competitiveness with a lot of different modalities, how do you think givastomig is positioned here? Thanks.
Andrew Zhu
是的。Joe,这个问题问得很好。我认为,基于SPOTLIGHT和GLOW这两项一线转移性胃癌领域的III期临床试验数据,在标准化疗基础上联合zolbetuximab,两项研究都令人信服地证明了改善的疗效获益。我认为,我们显然已经验证了Claudin是胃癌中一个相关的治疗靶点。所以这部分,我个人认为,这绝对没有争议。我认为抗Claudin18.2抗体有其作用。这无疑将使转移性胃癌患者受益。但你也知道,这两项试验都是基于Claudin18.2表达来选择患者的。他们使用的标准实际上是2+和3+表达至少达到75%。所以你可以想象,如果仔细研究这个人群,这可能适用于大约30%的高Claudin18.2表达患者。所以我的感觉是,zolbetuximab将在特定患者群体中发挥作用,特别是对于那些PD-L1低表达的患者。这可能成为与化疗联合的主要靶向疗法。但话虽如此,我们也坚信givastomig在Claudin18.2治疗靶点领域,在胃癌以及可能在其他肿瘤类型中,具有非常独特的地位。因为其独特的分子设计确实使这种分子能够覆盖更广泛的人群,包括不同水平的Claudin18.2表达,特别是较低的Claudin18.2表达。我们在临床前模型中已经证明了这一点,与其他Claudin18.2靶向抗体相比,它表现出更有利的抗肿瘤活性。我们正在进行的I期试验也给了我们初步的信心,我们确实在Claudin18.2低表达患者中观察到了抗肿瘤活性。我们的试验实际上仍在进行中,这只是一项I期研究,但尽管如此,早期的疗效信号令我们感到鼓舞。另一方面是其安全性特征,得益于我们独特的模块化设计。正如我在演示中提到的,我们的分子只有在与肿瘤相关抗原(在这种情况下是Claudin18.2阳性肿瘤细胞)结合时才会被激活。在这种情况下,4-1BB将被激活。因此,这种方式实际上避免了全身毒性,包括肝毒性和细胞因子释放综合征。这在其他T细胞衔接器模式(包括基于4-1BB的)中很常见。所以我们认为,即使对于高Claudin18.2人群,我们的分子也具有额外的优势,因为它可能具有与标准一线疗法(例如基于FOLFOX/PD-1的联合疗法)以及其他肿瘤类型联合使用的潜力。我们绝对有潜力探索我们的药物与其他肿瘤类型中其他联合化疗方案的组合。最后,正如你所知,Claudin18.2靶向药物实际上存在所谓的类别特异性副作用,因为胃肠道毒性非常显著。恶心、呕吐很常见,其中一些可能极具挑战性。而在我们的试验中,我们只观察到非常轻微的胃肠道毒性,特别是恶心、呕吐,我们认为这提供了更好的耐受性优势,对胃癌患者来说尤其如此。所以我们肯定希望进一步探索givastomig的开发,无论是作为单药(正如我们现在所做的),还是未来进行联合治疗。谢谢你,Joe。
Andrew Zhu
Yeah. So, Joe, great question. I think with the data from SPOTLIGHT and GLOW, you know, two Phase 3 trials in the first line metastatic gastric cancer space. With the addition of zolbetuximab to the standard chemo backbone both studies, you know, convincingly demonstrated the improved benefit. And I think, you know, clearly we have validated Claudin being a relevant therapeutic target in gastric cancer. So I think that part, you know, I personally feel that, you know, there's absolutely no argument. I think anti- Claudin18.2 antibody has a role. This will definitely benefit patients with metastatic gastric cancer. But also, as you know, both trials select patients based on Claudin18.2 expression. And the criteria they use is actually two plus, plus three plus of at least 75%. So you can imagine, I think, if you look at this population very carefully, this probably will be applicable for about 30% of the patients with high Claudin18.2 expression. So my feeling is that, you know, I think zolbetuximab 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, you know, we also feel strongly that givastomig has a very, very unique position in a very Claudin, you know, Claudin18.2 therapeutic target space in gastric and potentially maybe in other tumor types. Because, you know, the unique molecular design really allow this molecule to cover a wider population with different levels of Claudin18.2 expression. In particular the lower Claudin18.2 expression. And we demonstrated that in preclinical models, you know, clearly it behaves favorably with more robust antitumor activity in comparison with other Claudin18.2 target antibody. Our ongoing Phase 1 trial also gives us the initial confidence that, you know, we definitely have seen antitumor activity in Claudin18.2 low expression patients are granted. Our trial is still actually just ongoing. It's a Phase 1 study, but nevertheless, we are encouraged by the early efficacy signal. On the other side of the spectrum is really the safety profile with our unique modular design. As I indicated in my presentation, our molecule will only become active when the molecule is engaged with the tumor-associated antigen, in this case, Claudin18.2 positive tumor cells. In this case, the 4-1BB will get activated. So in this way it's actually spares the systemic toxicity, including hepatic and also cytokine release syndrome. And this is actually commonly seen with other T cell engager modalities including 4-1BB based. So we think our molecule also has the added advantage even for those with high Claudin18.2 population, because it may potentially have the potential to be combined with a standard first line. For example FOLFOX/PD-1 based combo and also for other tumor types. We definitely have the potential to explore the combination of our drug with other combination chemotherapy in other tumor types. And lastly, as you know, there is actually the so-called class specific side effects associated with Claudin18.2 target agents because the GI toxicity is actually very remarkable. You know, nausea, vomiting is commonly observed, and some of them could be actually incredibly challenging to manage. And in our trial, we only observed very mild gastrointestinal toxicity, in particular, nausea, vomiting, which we think, you know, offers the advantage to be better tolerated, you know, in gastric cancer patients. So we definitely would like to further explore, you know, givastomig development, either as a single agent, as we're doing right now, but also in combination down the road. Thank you, Joe.
Tyler Ehler
谢谢朱博士,也谢谢乔的提问。接下来,我们有请路易丝·陈。路易丝?
Tyler Ehler
Thank you, Dr. Zhu and thank you, Joe, for that question. Next, we'll have Louise Chen. Louise?
Louise Chen
你好。谢谢。大家好,感谢回答我的问题。关于4-1BB激动剂的毒性问题,你们是否有任何担忧?这些特性在过去的研究项目中阻碍了高靶点参与度。那么,我们能否期待从这项剂量递增研究中获得更多结果?谢谢。
Louise Chen
Hi. Thank you. Hi. Thanks for taking my question. So do you have any concerns regarding the toxicity of 4-1BB agonists? These features have prevented high target engagement in past programs. So can we expect more results from this dose escalation study? Thank you.
Andrew Zhu
是的。路易丝,我来回答你的问题。这确实是一个非常非常重要的问题,涉及到任何双特异性抗体,特别是T细胞衔接器模式的耐受性和安全性。正如我之前回答乔的问题时提到的,我们的双特异性设计独特之处在于,只有在肿瘤部位与Claudin18.2结合时才能诱导4-1BB激活。因此,我们实际上避免了通常与4-1BB以及其他激动剂治疗相关的全身毒性。从这个意义上说,与其他4-1BB抗体或其他T细胞衔接器(包括基于CD3的)相关的毒性担忧,我们实际上在我们的1期临床试验中显示出非常有利的安全性特征。因为我们没有观察到全身毒性,包括肝毒性和细胞因子释放综合征,而且我们双特异性抗体的额外优势是胃肠道毒性也相对较轻。
Andrew Zhu
Yeah. 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 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 Claudin18.2 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. 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 1 ongoing Phase 1 trial. Because, you know, we're not actually seeing the systemic toxicity, including hepatic toxicity, cytokine release syndrome and also the added bonus for our bispecific is that our GI toxicity also is on the mild side.
Tyler Ehler
谢谢朱博士。谢谢路易丝的提问。由于时间有点超时,我们再回答最后一个问题。有请安德烈斯·马尔多纳多。安德烈斯,请提问。
Tyler Ehler
Thank you, Dr. Zhu. Thank you, Louise for that question. We'll take one last one since we're a bit over time. Andres Maldonado. Andres, please go ahead.
Andres Maldonado
大家好。感谢回答我的问题。我有一个简短的问题。能否提供更多关于我们应该如何看待你们2023年预期现金消耗率的详细信息?另外,一个快速的后续问题是,显然你们一直在关注准备发言中强调的四个项目。从时间和财务角度来看,你们预计何时会感到有足够的信心将更多资产引入临床研究?谢谢。
Andres Maldonado
Hi, guys. Thanks for taking my question. Quick one from 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 four highlighted programs from your prepared remarks. So just curious from a timing wise and a financial perspective, where do you expect to feel comfortable and bringing in additional assets to the clinic in the future? Thank you.
Richard Yeh
好的。感谢你的提问,乔。我先回答财务消耗率的问题,然后安德鲁会回答管线相关的问题。关于这一点,正如我们提到的,在2022年,我们花了大量时间优化成本结构。首先,我们专注于五个关键资产;其次,真正优化组织结构。今年我们将进一步降低总体成本,正如我们在电话会议中提到的,我们预计2023年的当前净消耗率将在1.3亿至1.4亿美元之间。这将进一步优化我们的运营结构,使我们的现金状况能够支持至少三年或更长时间的现金运营。考虑到我们还有其他管线产品需要安德鲁讨论开发,我们确实专注于我们的关键资产。
Richard Yeh
Yeah. Let me thank you for your question, Joe. 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 is mostly. So first of all, we actually focus on the five key assets and second, really optimizing the organizational structure. So this year we further going to reduce the overall cost as we just mentioned in the call that our expected current net burn rate for 2023 is expected to be in the range of US$130 million to US$140 million. This will further optimize our operational structure, so that our cash position can retain us at least for an additional three 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.
Andrew Zhu
是的。我认为安德烈斯,这对研发运营来说是一个非常非常重要的问题。我想分享几点看法。正如您所知,I-Mab实际上拥有一个非常非常创新的发现引擎。我们内部确实产生了相当多的创新资产,但出于我们今天讨论的原因,我们实际上一直在努力专注于那些能够创造更多价值的关键资产,您知道,更快地将项目推进到下一阶段,同时也希望更早地实现这些资产的价值,这样公司、股东,更重要的是患者都能从这一战略中受益。但话虽如此,我们从未停止关注外部的创新资产。只是,您知道,在当前情况下,我们的门槛更高了。我们肯定会对来自外部的授权机会采取更审慎的态度。但这,您知道,这是一个动态的过程。显然,我们也希望通过我们的业务发展交易产生额外的现金流。所以我认为,显然,随着我们进入2023年新的一年,我们将重新评估这一战略。但目前,您知道,我们肯定希望确保专注于内部资产。但毫无疑问,我们也会更审慎地审视那些可能具有价值、也有潜在市场的关键资产。这是我们目前的立场。
Andrew Zhu
Yeah. So I think Andres it's 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 quite 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, you know, move the program to the next level faster, but also realize the value of these assets hopefully earlier so that, you know, the company will benefit, the shareholders will benefit, or more importantly, patients will benefit from this strategy. But having said that, we never stop looking at innovative assets from outside. It's just, you know, right now with the current situation, our bar is higher. You know, we definitely want to take a more critical look when it comes to, you know, the licensing efforts from outside. But this, you know, this is a dynamic process. Clearly we are aiming to also generate additional cash flow with our BD deal. So I think clearly, you know, we will reassess the strategy as we proceed with the new year in 2023. But right now, you know, we definitely want to make sure we focus on the internal assets. But definitely we will actually look at the key assets that potentially have value and also have potential market more critically. This is our current position.
Tyler Ehler
谢谢朱博士,谢谢理查德。至此,我们将结束今天的电话会议。感谢大家拨入今天的财务业绩和业务更新电话会议。感谢各位的参与。您现在可以断开连接了。
Tyler Ehler
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 into today's Financial Results and Business Update Conference Call. Thanks, everyone, for joining in. You may now disconnect.