NovaBridge Biosciences - H1 2023

Transcript

Tyler Ehler (Senior Director of Investor Relations)

Morning, everyone, thank you for joining us this morning and for standing by. I'd like to take this opportunity to welcome you all to the I-Mab Biopharma Mid-Year 2023 Financial Results and Business Update Conference Call. My name is Tyler Ehler, I'm 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 will conduct a Q&A session, instructions will follow at that time. Earlier today, we issued a press release providing a review of our financial results for the midyear ended June 30th, 2023, 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 I-Mab. Joining me today on the call from I-Mab senior management team are Raj Kannan, CEO, Dr.

John Hayslip, Chief Medical Officer, Dr. Andrew Zhu, President and Head of R&D, and Richard Ye, Interim CFO and COO. Raj will provide a high-level overview of our recent achievements and upcoming milestones. John will provide an update on our R&D progress. Richard will then provide a summary of our financial results for the 6 months ended June 30th, 2023, before we turn the call over to Raj for a few final comments. Then back 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. The forward-looking statements 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, and 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 on this earnings call. 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, including, but not limited to, the Risk Factors section in I-Mab's most recent annual report on Form 20-F, as well as discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the SEC. Moreover, we operate in an evolving environment.

New risk factors emerge from time to time, and it is not possible for us to predict all risk factors, nor can we assess the impact of all factors on our business or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements. We qualify all of our forward-looking statements by these cautionary statements. You should not rely upon forward-looking statements as predictions of future events. The forward-looking statements made in today's press release and on this earnings call relate only to the events or information as of the date on which the statements are made.

Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. We'll 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 earlier today for a definition of non-GAAP financial measures and a reconciliation of GAAP to non-GAAP financial results. With that, I'll now turn the call over to our CEO, Raj Kannan. Raj, please go ahead.

Raj Kannan (CEO)

Thank you, Tyler. Good morning, everyone, and thank you for joining us. It has been an energizing few weeks for me since I came on board as CEO in June. I came to this new role with much confidence in I-Mab's innovative programs and an understanding that we have a great deal of work ahead of us. Today, I'm pleased to speak with you and set out a clear direction for I-Mab that could potentially unlock the significant inherent value that I see in this company for our shareholders. During our call, I will provide you with a high-level update on our performance in the first half of 2023. Importantly, frame our strategic direction and plan.

I will ask John Hayslip, our Chief Medical Officer, to provide you with an update on the 2 prioritized clinical assets in oncology that we plan to rapidly advance in the U.S. and globally. Finally, review the recently released positive phase 3 results from our lead program in China. Richard Ye, our Interim Chief Financial Officer, will review the financial results for the first 6 months of 2023, and then hand it back to me for closing remarks. The first 8 months of 2023 have been productive for I-Mab. We made significant progress on our innovative assets, including uliledlimab, our differentiated CD73 antibody, givastomig, our novel claudin 18.2 and 4-1BB bispecific antibody, and eftansomatropin alfa, our long-acting human growth hormone that reported out positive phase 3 results today.

As we look to building out the future for I-Mab, we plan to focus on 3 strategic pillars. First, rapidly advance our 2 promising clinical assets globally within oncology. 2, maintain our strong balance sheet. 3, focus on establishing a new operating model to become a US-based global biotech company. Taking them 1 at a time. 1, we plan to advance uliledlimab, our novel CD73 antibody, and givastomig, our differentiated claudin 18.2 and 4-1BB bispecific antibody in the US and globally. We believe that both uliledlimab and givastomig each have interesting biology, encouraging early clinical data, and differentiated characteristics that enable them to stand out from other drugs in development.

We believe that uliledlimab could be a critical value driver for IMAB, if approved, could be a unique and differentiated immuno-oncology agent, which has the potential to be the preferred adjunct to immunotherapies across a wide range of tumors. Our goal is to submit an IND in the first half of 2024 for uliledlimab in combination with chemotherapy and checkpoint inhibitors in newly diagnosed patients with advanced non-small cell lung cancer. John will further provide details on the data that we presented at ASCO and why these results give us the confidence that uliledlimab can be a differentiated entrant and a significant value driver for IMAB. We believe that Givastomig has the potential to be a differentiated agent in gastric cancer. This unique bispecific antibody was designed to target claudin 18.2 positive tumors and stimulate pro-immune 4-1BB signaling.

Givastomig was designed to selectively target 4-1BB expressing cells in the tumor microenvironment, potentially reducing the risk of systemic toxicity. Claudin 18.2 targeted therapies could represent an important new treatment option, especially for patients with gastric cancers, including tumors of the gastroesophageal junction, or GEJ, and esophageal cancer. With encouraging signs of monotherapy efficacy, including in tumors with lower levels of claudin 18.2 expression, we believe that Givastomig has the characteristics that could potentially position the program as a leading candidate in these tumors, where there remains a significant unmet medical need. Our goal is to initiate a phase 1B dose escalation study in the US, Japan, and China, in combination with standard chemotherapy and immunotherapy regimens for patients with treatment-naive gastric, GEJ, and esophageal cancer in the first half of 2024.

John will review our early results and explain why we believe our program could potentially be a valuable treatment option for patients. Lastly, we're pleased to report hot-off-the-press, positive phase 3 data from eftansomatropin alfa, our long-acting human growth hormone candidate being developed for the market in China. This represents a significant milestone for the company as it is the first completed phase 3 data that we have reported. The new eftansomatropin alfa data met the primary endpoint and achieved non-inferiority compared to Novo Nordisk's Norditropin. These results and the compound's weekly delivery formulation should position eftansomatropin alfa to be a key player in the human growth hormone market in China, which is a market currently dominated by once-daily injectables. This multi-billion dollar market in China is expected to grow over the next five to eight years, with long-acting growth hormones estimated to significantly build market share.

As you may know, we have an agreement in place with Jumpcan to commercialize eftansomatropin alfa in China. We have two other clinical assets specifically being developed for the China market. felzartamab, our CD38 antibody, and Lemzoparlimab, our CD47 antibody. John will review the clinical results to date and provide an overview of next steps for these programs being developed for the China market. Moving on to our second strategic pillar, continue to maintain a strong balance sheet. IMAB's $414 million cash balance adequately supports the execution of the company's strategic plan. We've begun streamlining our spend for the second half of this year to support our key global assets in oncology and rationalizing our spend in other areas.

In addition, we will continue monetizing non-global core assets and make the difficult choices where needed in our pipeline to earmark cash for the most promising programs, including exploring external opportunities. Now the third strategic pillar. We're focused on establishing a new operating model as a U.S.-based global biotech company. This will position us to unlock the inherent value in the single largest pharmaceutical market in the world, and the area in particular, where our stakeholders expect to derive the most value from our innovative assets. We embark on this change by building on a company's strong foundation from a core set of differentiated oncology assets, a strong balance sheet, and a skilled R&D organization in China. I just noted, we also remain open to bringing in new assets that we view as value-driving to complement our existing pipeline.

We recognize that to make this company into a truly U.S.-based global biotech, it'll involve significant changes ranging from governance, stock market listing, culture, to talent management. It is important to emphasize that the full I-Mab board and I are in full alignment with regard to the future direction of the company. I look forward to providing you with those updates on our progress on this strategic pillar in early 2024. Now, before I hand the call over to John, I would like to recognize the leadership of Dr. Andrew Zhu during his time as interim CEO. Also, I'm grateful for the dedication and hard work shown by the entire I-Mab team. With that overview, I'd like to hand it over to John to provide clinical details on our key global assets and the novel programs being developed specifically for the China market. John?

John Hayslip (Chief Medical Officer)

Thank you, Raj, and good day to everyone on the call. My name is John Hayslip, and I'm pleased to provide you with a clinical overview. First, I'd like to provide updates about uliledlimab, our CD73 targeting antibody, designed to block a key pathway that tumor cells may use to evade the immune system, adenosine production. As previously reported, uliledlimab is differentiated by design to avoid hook effect biology, which is a potential liability of other competitor drugs in development. Simply put, the hook effect may prevent other drugs from achieving complete inhibition of enzyme function, though uliledlimab is designed to allow up to 100% inhibition due to its unique functionality.

At the American Society of Clinical Oncology meeting in June of this year, we shared encouraging clinical and translational findings from a phase 1B/2 study, indicating patients with advanced non-small cell lung cancer receiving uliledlimab and PD-1 inhibitor toripalimab. Uliledlimab was well tolerated, using an every 3-week dosing regimen in combination with toripalimab. Most treatment-related adverse events were grade 1 or 2 in severity. In the 67 efficacy evaluable patients, the objective response rate, or ORR, was 31%, regardless of CD73 or PD-L1 expression. Notably, patients whose tumors had high levels of CD73 expression experienced a higher response rate than those with lower CD73 expression.

The response rate increased to 63% in patients who had both high levels of CD73 expression and a PD-L1 Tumor Proportion Score, or TPS, of greater or equal to 1%, whereas patients with low CD73 expression had an ORR of 20%. We are excited by these preliminary findings of a correlation between higher CD73 expression and an increased response rate. With this chemotherapy-free uliledlimab and checkpoint inhibitor combination. Data from other studies have suggested that chemotherapy may increase CD73 expression in cancer cells, and we are eager to begin combination studies of uliledlimab with chemotherapy in the near future. At the time of the data cutoff, with a median follow-up of 10.4 months, 18 of the 21 patients whose tumors had achieved an objective response remained on treatment, and the median duration of response was not yet reached.

Progression-free survival and overall survival data will be analyzed when the data are fully mature. We continue to enroll patients with previously treated ovarian cancer to the combination regimen of uliledlimab and toripalimab, and expect to report preliminary results in 2024 for this phase 2 cohort of patients. Building upon these encouraging clinical findings and other non-clinical investigations, we plan to file a new IND with the FDA to expand the uliledlimab program and combine with chemotherapy and checkpoint inhibitors for patients with newly diagnosed advanced non-small cell lung cancer. Owing to the potential effect of chemotherapy to upregulate CD73 in tumors, we hope this combination may benefit an even broader group of patients, potentially regardless of pretreatment CD73 expression. I'd like to emphasize this important point.

We plan to evaluate uliledlimab with chemotherapy and checkpoint inhibitors in patients, regardless of the CD73 expression, before initiating treatment. non-small cell lung cancer is one of the most common and deadly cancer diagnoses globally, and we believe that uliledlimab has the potential to improve upon currently available care. We plan to discuss further details regarding the plan studies in the first half of 2024, after we have had initial discussions and alignment with regulatory agencies. Next, I'd like to provide an update on Givastomig, our claudin 18.2 by 4-1BB bispecific antibody, a program that has made significant clinical progress. As you may know, other groups have attempted to develop 4-1BB engaging drugs in the past because 4-1BB is a strong stimulant to the immune system.

Unfortunately, earlier attempts to develop 4-1BB drugs caused severe toxicities because the widespread effects of 4-1BB stimulation could not be tolerated by patients. Therefore, we developed a unique approach of this bispecific antibody in that it first binds to tumor cells expressing the claudin 18.2 protein, and then the 4-1BB arm can stimulate immune cells in the immediate environment of the tumor. More specifically, Givastomig was designed to do two important things. First, to become conditionally active only upon tumor engagement, while remaining silent elsewhere to avoid or minimize liver toxicity and systemic immunotoxicity, commonly seen with 4-1BB antibodies as a drug class. Second, to effectively maintain strong tumor binding and anti-tumor activity attributable to a synergistic effect of the bispecific claudin 18.2 antibody and 4-1BB antibodies.

We believe Givastomig has achieved our design goals for this molecule based on early clinical data. This July, the Journal for ImmunoTherapy of Cancer, or JITC, published a paper detailing the significant potential of Givastomig in treating gastric cancer and its unique molecular design and properties. Looking forward, I am happy to report that the first clinical abstract for Givastomig has been accepted for a presentation at the European Society for Medical Oncology, or ESMO, in October of this year. While the specifics of the study results are embargoed until the meeting, I'm happy to report that in the dose escalation phase 1 study, objective responses have been observed with single agent Givastomig amongst patients who have received multiple previous treatments for their cancer, including chemotherapy and checkpoint inhibitors.

A dose expansion cohort in this phase one study continues to enroll patients with previously treated claudin 18.2-positive gastric, gastroesophageal junction or GEJ, and esophageal cancer with Givastomig monotherapy, and interim results for these patients are anticipated in the first half of 2024. Additionally, based upon these encouraging observations and recent non-clinical studies indicating a positive benefit for the combination, we plan to launch new investigations of the combination of Givastomig with standard chemotherapy and immunotherapy regimens for patients with treatment-naive gastric, GEJ, and esophageal cancer. We anticipate enrollment to begin by the first half of 2024 and plan to provide further details once we finalize the trial design. Speaking of our clinical bispecific programs, TJ-L14B was designed to treat PD-1 or PD-L1 antibody-resistant tumors.

Like Givastomig, the antibody acts by inducing conditional activation of 4-1BB when it binds to its target, in this case, PD-L1. A phase 1 dose escalation study is underway in patients with progressive, locally advanced or metastatic solid tumors that have relapsed or are refractory following prior lines of treatment. A preliminary efficacy signal has been observed, and a maximal tolerated dose has not yet been reached. The dose expansion portion of the phase 1 study is underway in the U.S. and South Korea. The program is being developed in collaboration with ABL Bio. Today, we reported the first positive phase 3 results from an I-Mab-sponsored program with the successful trial of eftansomatropin alfa with weekly dosing for children with human growth hormone deficiency.

The results we are sharing today highlight that the phase 3 study met its primary endpoint of annualized height velocity, or AHV, at week 52, and demonstrated that eftansomatropin alfa was non-inferior to Novo Nordisk's Norditropin. As a reminder, eftansomatropin alfa was given as a weekly injection, while Norditropin was given as a daily injection in this study. The mean AHV was 10.76 centimeters per year for eftansomatropin alfa versus 10.28 centimeters per year for Norditropin, with a non-inferiority P value of less than 0.0001. Eftansomatropin alfa was well tolerated, and no drug discontinuations were reported due to treatment-emergent adverse events. We believe the safety profile of eftansomatropin alfa appears comparable to Norditropin in this study.

These data create a strong clinical database supporting the potential clinical utility of I-Mab's long-acting human growth hormone candidate. We plan to submit a BLA in China in 2024. Next, I'd like to turn to Felzartamab, a fully human monoclonal antibody directed against CD38 in development for the treatment of multiple myeloma. We have successfully completed the first trial with registration potential in China for Felzartamab as a third-line treatment for multiple myeloma. Our study confirmed the efficacy of Felzartamab, with additional benefits such as a shorter infusion time and lower infusion-related reaction rate than reported for daratumumab in its IV form. These product attributes may allow Felzartamab to be used in an outpatient clinic setting and together create a potentially differentiated product profile. We are evaluating our regulatory strategy and plan to provide an update following further discussions with the China CDE.

We plan to share additional clinical data after those discussions are completed. In terms of the phase 3 randomized study of Felzartamab in combination with lenalidomide for patients who have received one prior line of treatment, enrollment was completed in September of 2021. The primary endpoint for this study is progression-free survival, and we expect the study to read out in 2024, followed by a planned BLA submission.

Andrew Zhu (President and Head of R&D)

Lastly, the development of Lemzoparlimab focused on China, has the potential to be the first-in-class CD47 antibody for hematologic malignancies in this market. The phase 3 program is evaluating Lemzoparlimab in combination with azacitidine as first-line treatment for patients with newly diagnosed higher risk myelodysplastic syndrome. Enrollment in the phase 3 trial was initiated in April of 2023. The company will continue to review follow-up data from our phase 2 clinical study in higher risk MDS, while at the same time analyzing details from trials evaluating other CD47 targeted agents as they are released, to inform our decisions on the future steps for the program. I'll now hand the call over to Richard to discuss our financial results.

Richard Yeh (Interim CFO and COO)

Thank you, John. Now, I will review our first half 2023 final results. As of June 30, 2023, the company had a cash, cash equivalent, restricted cash, and short-term investment of RMB 3 billion, or $414.6 million, compared with $489 million as of December 31, 2022. I-Mab's strong cash balance is estimated to provide the company with adequate funding to support the execution of the company's strategic plan. As you may have seen today, we also announced that the board has authorized a stock repurchase program of up to $40 million to enhance the long-term shareholder value of the company.

Total revenue for the first six months of 2023 were $2.7 million, compared with the $7.7 million for the same period in 2022. Revenue consists of revenues recognized in connection with the strategic collaboration with AbbVie, and the revenues generated from the supply of investigational products to AbbVie and Human Immunology Biosciences, or HI-Bio. Now, let me turn to the R&D expenses. Research and development expenses for the first six months of 2023 were $61.6 million, compared with the $67.6 million for the same period in 2022. The decrease was primarily due to the reduced payroll expenses and the share-based compensation expenses, partially offset by a slight increase in chemistry, manufacturing, and control service fees.

Administrative expenses for the first six months of 2023 were $33.8 million, compared with $54.1 million for the same period in 2022. The decrease was primarily due to lower payroll expenses and the share-based compensation expenses in related to management personnel, and lower expenses for professional services. Non-GAAP adjusted net loss, which exclude the share-based compensation expenses for six months of 2023, was $87.5 million, compared with $116.9 million for the comparable period in 2022. As of June 30, 2023, I-Mab has approximately 190 million shares outstanding.

I would like to reiterate the strong cash position of $414.6 million as of June 30, 2023, which allow us to execute our strategic plan. Lastly, please note that the conversion of certain RMB amounting to US dollars for historical period presented in this call may not be identical to the ones that previously announced, due to the differences in particular exchange rate used by the company for this one, compared to the historical exchange rates. With that, I would like to turn the call over to Raj for the few closing remarks. Raj?

Raj Kannan (CEO)

Thank you, Richard. To conclude, I'm even more convinced than before that I made the right choice to join I-Mab, that we're on the right track with the strategic plan. Looking ahead, we intend to advance our two lead oncology assets, uliledlimab and Givastomig, rapidly into additional studies in the U.S. and beyond in the first half of 2024. We plan to maintain our strong balance sheet by continuing to streamline and rationalize our spend to advance the most promising programs. We intend to focus on a new operating model to establish a U.S.-based global biotech company with the full support of the board. We're excited about I-Mab's new strategic plan and look forward to providing you with periodic updates on our progress. Thank you all for taking the time to join us today.

I'll now turn the call over to Tyler for the Q&A session.

Tyler Ehler (Senior Director of Investor Relations)

Thank you, Raj. As we begin our Q&A session, if you do have any questions, please use Zoom's Raise Your Hand feature. It will unmute you for your questions. I would like to direct our first question to Kelly Shi. Kelly, please go ahead.

Andrew Zhu (President and Head of R&D)

Thank you, Tyler, and congrats on the great progress, and thank you for taking my questions. Firstly, could you comment on the safety profile of your weekly injected growth hormone from phase 3 trial, and in comparison to other competitor weekly programs? Also, could you let us know the projected timeline for regulatory approval and also commercial launch? I also have a follow-up. Thank you.

Raj Kannan (CEO)

... Yep. Kelly, thank you for that question. We are quite excited about the potential of eftansomatropin alfa as a weekly option for our patients, and given the strong results that we just disseminated, I believe this will be a valuable option in the China market, especially in a growing multi-billion dollar growth hormone market. I think I'll let John comment on it, and then Andrew, if you wanted to comment more on Kelly's question and how it compares to other drugs in development, that'd be great. John?

John Hayslip (Chief Medical Officer)

Yeah. Thank you, Raj. Thank you, Kelly, for the question. As Raj mentioned, this trial is a randomized head-to-head trial against Novo Nordisk's norditropin. As we review the results coming from this trial, we're quite pleased by the safety profile we've observed in this trial as compared to norditropin. In addition, I think we're pleased with how the safety profile of this drug looks compared to other drugs in the field. We'll look forward to disclosing those more completely in the future as we disclose the full data set. I'd like to ask Andrew if you'd like to add any additional comments.

Raj Kannan (CEO)

Andrew, are you on?

Andrew Zhu (President and Head of R&D)

Yes. Can you hear me?

Raj Kannan (CEO)

Yeah, we can hear you.

Andrew Zhu (President and Head of R&D)

can definitely say the safety profile compare very, very comparable to the weekly injection, and, you know, definitely we will share the data very, very soon. With regard to the second part of the question, we are actively pursuing the BLA submission. You know, definitely, we think, you know, with the phase 3 data, this provide, you know, the solid foundation for us to engage this process. And obviously, we're starting the engagement with regulatory agency, so hopefully we will have additional timeline to report soon. Thank you. </transcript

Raj Kannan (CEO)

Yep. Andrew, I just wanted to make one clarification. I think the safety profile compared very favorably to the once daily injection, Norditropin.

Andrew Zhu (President and Head of R&D)

Yes.

Raj Kannan (CEO)

Perfect.

Operator (participant)

Thank you for your question, Kelly. With that, I would like to direct the next question to Joe Catanzaro. Joe, please go ahead.

Joe Catanzaro (Senior Research Analyst)

Hey, guys. hopefully you can hear me okay. I guess I had 2 questions, maybe, first one on Givastomig, and particularly as it relates to claudin expression levels. wondering with the, you know, potential approval of zolbetuximab, I guess, next year, whether, you know, based on what you've seen thus far, whether there's opportunity to maybe capture a broader claudin expression range, with Givastomig. Thanks. I have a follow-up.

Raj Kannan (CEO)

Yep. Thanks, Joe. As you can tell, we're very excited about this particular program, including our TJ-L14B, that we're collaborating with ABL Bio. In particular, we continue to believe that Givastomig is quite differentiated from the agents that are in development. I'll ask John to comment more on the specific area of claudin 18.2 that you specifically referred to. John?

John Hayslip (Chief Medical Officer)

Yeah. Thank you, Joe. As, as I alluded to in my comments, in a non-clinical time, you know, early in the development of Givastomig, we've seen that Givastomig can be efficacious and, and have, have biological effect down to very low levels of claudin expression. In addition, you'll see in our clinical data, we've seen clinical benefit in patients who have quite low levels of claudin expression. We're optimistic. The program is early still, but we're optimistic that Givastomig may be able to bring benefit to a, a broader, a much broader group of patients with lower claudin 18.2 expression as well.

Joe Catanzaro (Senior Research Analyst)

Great. That's, that's helpful.

John Hayslip (Chief Medical Officer)

Thank you, Joe.

Joe Catanzaro (Senior Research Analyst)

Maybe my follow-up question quickly on Lemzoparlimab and the ongoing phase 3 trial on MDS in China. I guess it sounds like there's a lot of considerations there, and the maybe situation is fluid, but I guess now knowing the outcome of mogamulizumab's MAVORIC trial, just wondering how you think about, you know, what ultimately we could see from that trial and, you know, how it influence your decision with Lemzoparlimab and its clinical strategy. Thanks.

Raj Kannan (CEO)

Thanks, Joe, for that question. I think this was an intense discussion as well within the company, as you can imagine, with the recent results from the other CD47 targeting agents. I think it would be premature for us to make a decision on our molecule. We continue to believe that our molecule is differentiated, and we continue to enroll in our ongoing phase 3 study in China. We do plan to review interim data early next year and complete an advisory panel to review all of the class data as it becomes available and to compare what we have. Then I, I would think our shareholders would appreciate that to make an informed decision in the first half of next year in advancing the molecule.

We'll certainly further analyze the details of the enhanced study as well, as the data becomes available in the public market.

Joe Catanzaro (Senior Research Analyst)

Okay, perfect. Appreciate you taking my questions. Thanks so much.

Operator (participant)

Thanks, Joe. Thank you, Joe. I'd like to direct the next question to Louise Chen. Louise, please go ahead.

Andrew Zhu (President and Head of R&D)

Hi, thank you for taking my question, sir, and congratulations on the progress this quarter. Raj, I wanted to ask you if you could elaborate more on your vision for I-Mab and how long it'll take you to reach your objectives. Secondly, on CD47, again, just curious where you stand with your outside of China opportunity with AbbVie here?

Louise Chen (Senior Research Analyst and Managing Director)

... When you might reveal more details on your next generation CD47, or is that project on hold right now? I know you've mentioned the Givastomig ESMO presentation, but are there any other important data presentations throughout the end of the year at healthcare conferences that should be on our radar? Thank you.

Raj Kannan (CEO)

Yep. Thank you, Louise, for all those questions. I'm going to remember every one of them, as much as possible, and if I do forget, please reiterate it. We were frantically writing those questions down. The first one is, what's the timeline that I expect to deliver on the strategic objectives or the plan that I laid out? I think, as you will see, in the next couple of years, there's quite a few catalysts that are going to become available to our stakeholders. I think I give myself 24 months to be able to start looking at the strategic plan and the progress that we've made.

That would be an important timeline for investors to understand that this is not going to happen overnight, but the shift in the focus and how we're thinking about making into a U.S.-based global biotech is going to take time. Again, I think if I had to put pen to paper and think about a timeline that should be important, it should be by the end of 2025, second half of 2025, we should be in a good position to look back and say, you know, "How is our strategy working and how is it enhancing the value for our shareholders?" That was the first question, I believe, Louise. The second question is on lemzop outside of China. As you can imagine.

As, as we've said before, right, that AbbVie had terminated the development, global development of Lemzop, but we had the rights to China, so we continued the trial in China. At this time, we have no plans to initiate a study till we see the interim data, we analyze the class data of the other CD47 targeting agents, and we meet with an expert panel to be able to understand if our molecule is truly differentiated from the other CD47s, and we can come back at that time, Louise, to clearly articulate as to, you know, if we're going to move forward with Lemzop or the backup compound. Then the last question, Louise, was on the, sorry.

Louise Chen (Senior Research Analyst and Managing Director)

Conferences?

Raj Kannan (CEO)

You could-

Louise Chen (Senior Research Analyst and Managing Director)

Anything-

Raj Kannan (CEO)

Yeah.

Louise Chen (Senior Research Analyst and Managing Director)

Anything Aside from ESMO, I know you mentioned Givastomig from ESMO, but any other of your main compounds going to be presenting new data at conferences throughout the remainder of the year?

Raj Kannan (CEO)

As far as we know, I don't think there, there's anything that jumped out to us for the rest of the year, but I'll let John comment on it. John?

John Hayslip (Chief Medical Officer)

Yeah, thank you. As we mentioned, we plan to present the Givastomig dose escalation, clinical findings at the European Society for Medical Oncology in October this year. As I mentioned, we anticipate the dose expansion cohort, the continued enrollment of patients with gastric, GEJ, and esophageal cancer. We expect to have interim results early next year from that cohort of patients. We'll be, you know, reviewing those results and bringing those forward as quickly as possible. For the remainder of 2023, no additional conferences to add at this time.

Louise Chen (Senior Research Analyst and Managing Director)

Okay, great. Thank you very much.

Raj Kannan (CEO)

Thank you, Louise.

Operator (participant)

Thank you, Louise. The next question we will direct to Ethan Markowski. Ethan, please go ahead.

Speaker 12

Hi, everyone. This is actually Gil, not Ethan. Maybe, maybe a quick one on the commercial opportunity for Eftan. Are you guys thinking of pricing it similar to, you know, the current standard of care in China? If you have any thoughts there.

Raj Kannan (CEO)

Hi, Gil. I think it would be a little premature right now to comment on price. I do know that we're excited about the profile of the compound itself in terms of the benefit that it could bring to patients. We're excited about the growing large commercial opportunity that we have available for the human growth hormone product. I think we're going to price it competitively. I can definitely assure you that, but I think it's a little too early for us to actually comment on price publicly before we've even filed the product.

Speaker 12

Okay. Maybe a quick biology question on, on Givastomig. So signaling for 4-1BB usually requires trimerization of, of the ligand, which, you know, leads to these weird-looking bell curves, a little bit like the hook effect. I'm just wondering, have you seen that in preclinical studies with Givastomig, or is this even an issue? Thank you.

Raj Kannan (CEO)

John, do you want to take that?

John Hayslip (Chief Medical Officer)

Sure. Yeah, thanks, Gil. Good to, good to hear from you. This has not been a non-clinical, was not a preclinical issue for Givastomig. Further, in the early clinical findings, we continue to see the systemic pharmacodynamic effect of soluble 4-1BB, in a predicted manner. We've been quite confident by what we've observed to date, with Givastomig regarding the PD effect.

Speaker 12

Thank you.

Raj Kannan (CEO)

Thank you, Gil.

Operator (participant)

Thank you, Gil. Next up, I would like to direct the next question to Andres Maldonado. Andres, please go ahead.

Andres Maldonado (Equity Analyst)

Hi, thank you, very much for taking my questions. Congrats on the progress. Just one quick one, maybe for Raj from us. Could you elaborate on where do any initiatives for finding commercial pipeline, commercial partnerships for the pipeline fall with your new vision for the company? Obviously, prior to you joining, there was a lot of talk on partnering uliledlimab. I'm curious on your thoughts on the potential for partnerships outside of uliledlimab, and how they align with your new vision. Thank you.

Raj Kannan (CEO)

Yep. Thank you for that question. I think as I look within the company and talk with my colleagues in R&D and in business development, we're very excited about our assets. We think they have interesting biology. They have produced early, encouraging clinical data. I think we have a very healthy balance sheet to be able to take them forward on our own at this time. I think it would be, my estimation, premature to start talking about partnering till we actually produce mature data, either proof of concept or the ability to actually have a higher probability of success in taking these to market.

I think at that time would be ideal, to, to talk about if, appropriate, depending on what else do we have in terms of opportunities, to be able to talk about, you know, do we need a partner and, and why? I will say also as a note, you know, we continue to get incoming inquiries of interest on, on, on, these assets, and we continue to engage with these outside partners. That doesn't mean that we're keen on partnering until it makes strategic sense, and we believe that that option produces the highest value for our shareholders, in the near to mid-term.

Operator (participant)

Thank you for your question, Andres.

Raj Kannan (CEO)

Does that answer your question, Andres?

Andres Maldonado (Equity Analyst)

Yes. Thank you very much.

Raj Kannan (CEO)

Thank you.

Operator (participant)

I'd like to direct the next question to Xiaoyi Lei. Xiaoyi, please go ahead.

Xiaoyi Lei (Analyst)

Hi, this is Xiaoyi from CICC. Thanks for taking my question. I have a quick one on the CD73 antibody. We see very encouraging results of this and antibody in first-line non-small cell lung cancer. In the 1B phase 2 trial, there are about 16 out of 60-ish patients that has both high CD73 and PD-L1 expression. The OR reaches really high for this population. Do you predict similar % of target patient population in the real world? Like, what, what's the target population, like, what in average for this both, like, double positive expressing patient population in the real world?

and also for, the people who try, I just want to ask about the design for this trial, 'cause, I see, like, for the patients that, with really low, TPS expression, you see, like, the response is minimal. By adding the chemo on top of the immune checkpoint inhibitors, do you see any evidence preclinically or clinically that adding chemo can boost the sensitivity of these PD-L1 active patients in the response to CD73?

Raj Kannan (CEO)

Yep. Xu, that's very good questions on Ulee. Let me just take the first comment, and then I'll pass it on to John. I think all of the results that we've generated in the program to date, give us the confidence, especially in advancing that program in the settings that John articulated in his prepared remarks. I, I think our intent would be to go to a broader group of patients, while we will continue to assess the PD-L1 status and CD73 status, but that's just a subset of what we would be focused on. John, do you wanna comment more on that and the second question that she had?

John Hayslip (Chief Medical Officer)

Yeah, I would just add that we've been working with WuXi Diagnostics throughout the development program regarding the CD73 biomarker assay. The, the trial that we reported, we allowed patients to enroll who had newly diagnosed non-small cell lung cancer, who were not eligible or who refused to receive chemotherapy. In other words, the patients were allowed to enroll before they even knew their CD73 expression. CD73 expression to the broader group, but that, that was not an entry criterion. We would believe within the setting of a modest-sized clinical trial, the, the, the rates that we observed may be consistent with what we would generally observe in future studies. Though, of course, the precision around that, you know, we need larger studies to, to increase our confidence.

I think the, the rates are... I, I think that's what we know about the, the rates of the double-high population. As Raj said, you know, importantly, as, as we move the program forward, we do see, as you mentioned, with checkpoint inhibitors, which themselves are not so efficacious as monotherapy for patients with lower PD-L1 expression. When you combine checkpoint inhibitors with chemotherapy, then the benefit of chemo, checkpoint inhibitors expands to the, really the broad population of newly diagnosed patients with lung cancer. We're optimistic that as we move forward in combinations with chemotherapy, that, that similar rate, that rates of benefit like that may extend to the broader patient population and not just those who were elevated prior to the initiation of treatment.

Operator (participant)

Thank you for your question, Shayi. I'd like to direct the next question to Bing Zhao. Bing, please go ahead.

Bing Zhao (Chief Healthcare Analyst)

Yeah, thank you for taking my questions. This is Bing Zhao from China Renaissance. I'm still interesting about the Claudin 18.2 and 4-1BB bispecific antibody. Because I realized that Status Claudin 18.2 antibodies is going to be listed in US, probably second half of this year, and also Status is looking for listing in China mainland as well. So I'm wondering if their products being commercialized, what is affecting our future clinical plan? I realized that for Claudin anti-bispecific antibody, there are many combination on the market. Let's say, for example, Claudin 18.2 with with CD3 or Claudin with PD-L1.

I'm interested to know more biologics behind why we choose the claudin and 4-1BB instead of the other targets. Thank you.

Raj Kannan (CEO)

Thank you for your question, Bing Zhao. I, I, I think as we, as you're talking about, the positive is there's a lot of interest in the claudin 18.2 space itself. It's a highly relevant, tumor antigen, and as you said, there's a lot of work going on, and we're excited about the differentiation that givosomig has, as we articulated in our prepared remarks. John, do you want to specifically address some of the differences that givosomig has to what Bing Zhao brought up in his question?

John Hayslip (Chief Medical Officer)

Yeah. Thank you. Maybe first I'll just touch upon. We are aware of a lot of the work being done in the field, and I'll just first touch on CAR T-cell therapies, which may hold significant potential. The cost and tolerability may relegate that approach to patients who have received previous treatments in the past. Similarly, we have seen some early reports from ADC-type therapies and some of those with encouraging results. Really, we think it's too early to know about those drugs if they'll eventually get to the market or not. In the past, for example, ADC-type drugs have not always combined well with established treatments, and therefore, are sometimes used after established treatments have been exhausted.

Maybe just finally, to touch on the monoclonal antibodies in development, which you mentioned, and which may commercialize in the next year or so. You know, this, this, these results are indeed important, but as I mentioned earlier, we, we look for Givastomig. We're about to begin in combination studies. We intend to study with chemotherapy and with checkpoint inhibitors. As I mentioned also, we've, we've seen benefit in even monotherapy in patients across a wide range of claudin expression, including patients with quite low expression, have received monotherapy benefit. We're, we're quite encouraged by what we've seen to date with Givastomig and the ability that Givastomig could help address the unmet needs for a wide range of patients, and look forward to initiating those studies to combine with current standard frontline treatments.

Andrew Zhu (President and Head of R&D)

Hey, Raj, could I add one point to John's comment?

Operator (participant)

Sure, sure, Andrew. Sure.

Andrew Zhu (President and Head of R&D)

Yeah. Bing, you know, you're obviously touching a very, very critical point. We are fully aware of the competitive landscape in the claudin targeting area. However, as John pointed out, I think definitely our drug can actually cover a broad range of claudin expression level. The second attractive feature is really the safety profile. As, as you know, you know, for zolbetuximab and all the claudin-targeted naked antibodies, they have the claudin specific toxicity profile. In particular, the GI side effects is actually quite challenging for the clinicians to manage. Our data so far really highlight the favorable safety profile of Givastomig.

I think, you know, combined with these two features, I think even in the first line setting, even with the pending zolbetuximab approval, we still think, you know, we can actually position our drug, you know, very broadly in the first line gastric esophageal space, just because of the broader coverage with claudin expression as well as the favorable safety profile. Just want to clarify that point.

Raj Kannan (CEO)

Thank you. just, just one other thing I just wanted to say is, right, you, we will have more details of the data presented at ESMO, which will be interesting as well for you to take note of.

Andrew Zhu (President and Head of R&D)

Yep. Thanks.

Operator (participant)

Yeah. Thank you, Bing. Next question, I'd like to direct it to Juesheng Jiang. Juesheng , please go ahead.

Bing Zhao (Chief Healthcare Analyst)

Okay. Thank you very much for this chance. My question is about our early-stage pipeline development. Could you elaborate more about the pipelines that are going to enter the IND stage? Thank you.

Raj Kannan (CEO)

Great question. I think the the early pipeline in China has been the the the China specifically the talent in China, has been a complete foundation and a core driver for innovation in how I-Mab has progressed to date. That being said, I think if as you look hear the prepared remarks that we have today and the shift in the focus and the strategy, is to really focus on those drugs that are in the clinic today, to be able to accelerate the development and bring it to market. I think that is a huge shift. While we will continue to look assets in the earlier stage.

Right now, in terms of shareholders and value inflection, we're looking at the next two to five years in terms of how we can maximize the value of the company for our shareholders, who have been with us for these years, right? You'll see more information as we progress the late-stage compounds. We feel comfortable on the likelihood and the success of those compounds getting to market and participating in the market. You'll see more data on how we start focusing on preclinical and early-stage compounds. Does that answer your question?

Andrew Zhu (President and Head of R&D)

Yeah. Yes, thank you.

Operator (participant)

Thank you, Juesheng . We'll take one last quick question. We have 3 minutes left. I would like to direct the last question to Wang Ming . Wang Ming, please go ahead.

Ming Wang (Analyst)

Hello, everyone. This is Wang Ming from CICC Research, thank you for taking my question. I have 2 small questions. One, the first one is about the CD47 project, we know that Gilead Sciences and Axoncology have just terminated their project due to the limited efficacy. Could you give us more color on the efficacy gap between the phase 2 and the phase 3 trial? As we know, the primary endpoint for our phase 3 trial is overall survival. Can you comment more about the improvement, the improvement in the ORR to the benefit of the OS?

Yeah, this is the first question, and the second follow on the D73 project. For our coming pivotal study, where the regulatory open green light, open green light for single arm, single arm pivotal study, or it should be head-to-head phase 3 study? Thank you.

Raj Kannan (CEO)

Thank you for, for, for the question on Lemzo and then uliledlimab as well. Let me just reiterate on the Lemzo one, right? We have seen the announcements from the CD47 targeting companies recently, and as we said, this was obviously great interest to us in terms of the announcement itself and how that impacts our program. As we said before, I think it's a little premature for us to think about a decision whether we should continue or stop the molecule development. I think we continue to enroll our ongoing phase 3 study in China. We continue to believe that our molecule is differentiated. As we said, we're also going to review the interim data.

We're going to look at the full data from these CD47s that have announced their, their trial termination fully, and then meet with experts to be able to make an informed decision on CD47. That, that, I think, is the crux of how we're thinking about our program. As we said, this is only in China. We are not progressing with Lemzo anywhere else outside of China till we get that information in our hand. On the uliledlimab question, let me pass it on to John to address that question in particular.

John Hayslip (Chief Medical Officer)

Thank you, Raj. I'd just add regarding Uliledlimab and the potential development pathways. We have the utmost respect for the regulatory agencies. Certainly they have a, you know, a challenging task and, and regulatory guidance changes from time to time. At this point, we would not comment further regarding the specific regulatory pathway for Uliledlimab until after we've reached alignment with the regulators, and then we'd speak further about it after that time.

Raj Kannan (CEO)

Does that answer your question?

Ming Wang (Analyst)

Yes. Thank you.

Raj Kannan (CEO)

Thank you.

Operator (participant)

Thank you, Wang Ming. With that, we're running a little over time, we will conclude today's call. If there are any follow-up questions, please feel free to reach out to your local IR representative, and we'll get back to you as quickly as possible. Thank you, everyone. Have a great day.

Raj Kannan (CEO)

Thank you.