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spk13: Good morning, everyone, and thank you for joining us this morning and for standing by. I'd like to take this opportunity to welcome you all to the IMAP Biopharma Mid-Year 2023 Financial Results and Business Update Conference Call. My name is Tyler Ehler, and I'm IMAP's Senior Director for 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 mid-year 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 ir.i-mabbiopharma.com. Joining me today on the call from IMAP senior management team are Raj Kanan, CEO, Dr. John Haislip, Chief Medical Officer, Dr. Andrew Zhu, President and Head of R&D, and Richard Yeh, Interim CFO and COO. Raj will provide a high-level overview of our recent achievements and upcoming milestones, and John will provide an update on our R&D progress. Richard will then provide a summary of our financial results for the six months ended June 30, 2023, before we turn the call over to Raj for a few final comments, and 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, and 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 IMAP'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 factor section in IMAP's most recent annual report on Form 20F, as well as discussions of potential risks, uncertainties, and other important factors in IMAP'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 affects 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. And with that, I'll now turn the call over to our CEO, Raj Kanan. Raj, please go ahead. Thank you, Tyler.
spk02: And 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 IMAP'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 IMAP 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, and importantly, frame our strategic direction and plan. I will ask John Haislett, our Chief Medical Officer, to provide you with an update on the two prioritized clinical assets in oncology that we plan to rapidly advance in the U.S. and globally. And finally, review the recently released positive phase three results from our lead program in China. Richard Yeh, our interim chief financial officer, will review the financial results for the first six months of 2023 and then hand it back to me for closing remarks. The first eight months of 2023 have been productive for IMAP. We made significant progress on our innovative assets, including Uli-Del-Lamap, our differentiated CD73 antibody, Givastomic, our novel Claudin 18.2 and 4.1 BB bispecific antibody, and F10 somatropin alpha, our long-acting human growth hormone that reported out positive phase 3 results today. As we look to building out the future for IMAP, we plan to focus on three strategic pillars. First, rapidly advance our two promising clinical assets globally within oncology. Two, maintain our strong balance sheet. And three, focus on establishing a new operating model to become a US-based global biotech company. Taking them one at a time, One, we plan to advance ulilidlamab, our novel CD73 antibody, and Givostomic, our differentiated Claudine 18.2 and 4-1-BB bispecific antibody in the U.S. and globally. We believe that both ulilidlamab and Givostomic 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 ulilidlamab could be a critical value driver for IMAP, and 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 ulilidlamab in combination with chemotherapy and checkpoint inhibitors in newly diagnosed patients with advanced non-small cell-linked cancer. John will further provide details on the data that we presented at ASCO and why these results give us the confidence that ulilidlamab can be a differentiated entrant and a significant value driver for IMAP. We believe that geostomic has the potential to be a differentiated agent in gastric cancer. This unique bispecific antibody was designed to target Claudine 18.2 positive tumors and stimulate pro-immune 4,1-BB signaling. Gevastomic was designed to selectively target 4,1-BB-expressing cells in the tumor microenvironment, potentially reducing the risk of systemic toxicity. Claudine 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 Claudine 18.2 expression, we believe that Givastomic 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 U.S., 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 three data from F10 somatropin alpha, 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 three data that we have reported. The new F10 somatropin alpha data met the primary endpoint and achieved non-inferiority compared to Novo Nordisk's Norditopin. These results and the tampon's weekly delivery formulation should position F10 somatropin alpha to be a key player in the human growth hormone market in China, which is a market currently dominated by one's 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 Jumcan to commercialize F-tansomatropin alpha in China. We have two other clinical assets specifically being developed for the China market. Pelzardimab, our CD38 antibody, and Lemzoparlimab, our CD47 antibody. We expect to commercialize these assets through partners, and John will review the clinical results to date and provide an overview of next steps with these programs being developed for the China market. Now, moving on to our second strategic pillar, continue to maintain a strong balance sheet. IMAP'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. And now the third strategic pillar, We're focused on establishing a new operating model as a US-based global biotech company, as 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. As 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 US-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 IMAP 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 IMAP 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?
spk10: Thank you, Raj. And good day to everyone on the call. My name is John Haislip, and I'm pleased to provide you with a clinical overview. First, I'd like to provide updates about uvulimab, 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, uliledumab 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 uliledumab 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 1b2 study indicating patients with advanced non-small cell lung cancer receiving uleleumab and PD-1 inhibitor toripalimab. Uleleumab was well tolerated using an every three-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 uliledumab 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 uliledumab with chemotherapy in the near future. Additionally, 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. Additionally, we continue to enroll patients with previously treated ovarian cancer to the combination regimen of ululelamab and toripalamab. and expect to report preliminary results in 2024 for this phase two 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 Uli Ledlumab 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 ulileplumab 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 uleleumab has the potential to improve upon currently available care. We plan to discuss further details regarding the planned 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 Givastomic, Arcladin 18.2 by 4-1-BB bispecific antibody, a program that has made significant clinical progress. As you may know, other groups have attempted to develop 4-1-BB engaging drugs in the past because 4-1-BB is a strong stimulant to the immune system. Unfortunately, earlier attempts to develop 401BV drugs caused severe toxicities because the widespread effects of 401BV stimulation could not be tolerated by patients. Therefore, we developed the unique approach of this bispecific antibody in that it first binds to tumor cells expressing the clodin 18.2 protein, and then the 401BV arm can stimulate immune cells in the immediate environment of the tumors. More specifically, Givostomic 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 401BB antibodies as a drug class. And secondly, to effectively maintain strong tumor binding and antitumor activity attributable to a synergistic effect of the bispecific clotin-18.2 antibody and 4-1B antibodies. We believe Givostomig has achieved our design goals for this molecule based on early clinical data. This July, the Journal of Immunotherapy of Cancer, or JITC, published a paper detailing the significant potential of Givostomig in treating gastric cancer. and its unique molecular design and properties. Looking forward, I am happy to report that the first clinical abstract for Givostomic has been accepted for a presentation at the European Society of 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 one study, objective responses have been observed with single agent geovastomic 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 clot and 18.2 positive gastric, gastroesophageal junction, or GEJ, and esophageal cancer with geovastomic 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 G-vastomic with standard chemotherapy and immunotherapy regimens for patients with treatment-naive gastric, GEJ, and esophageal cancers. 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, TJL1-4B was designed to treat PD-1 or PD-L1 antibody-resistant tumors. Like Givostomic, the antibody acts by inducing conditional activation of 4-1-BB when it binds to its target, In this case, PD-L1. A phase one 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 one 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 III results from an IMAP-sponsored program with a successful trial of F-tansomatropin-alpha with weekly dosing for children with human growth hormone deficiencies. The results we are sharing today highlight that the Phase III study met its primary endpoint of annualized height velocity, or AHV, at week 52 and demonstrated that F-tansomatropin alpha was non-inferior to Novo Nordisk's Nordotropin. As a reminder, F-tansomatropin alpha was given as a weekly injection, while Nordotropin was given as a daily injection in this study. The mean AHV was 10.76 centimeters per year for F-tansomatropin alpha versus 10.28 centimeters per year for nortotropin, with a non-inferiority p-value of less than 0.0001%. F-Tansomatropin-alpha was well tolerated, and no drug discontinuations were reported due to treatment emergent adverse events. We believe the safety profile of F-Tansomatropin-alpha appears comparable to Nordotropin in this study. These data create a strong clinical database supporting the potential clinical utility of IMAP's long-acting human growth hormone candidate. We plan to submit a BLA in China in 2024. Next, I'd like to turn to felzartumab, 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 felzartumab as a third-line treatment for multiple myeloma. Our study confirmed the efficacy of filzartamab 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 filzartamab 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 III randomized study of felzartumab 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. Lastly, the development of limzoparlamab focused on China has the potential to be the first-in-class CB47 antibody for hematologic malignancies in this market. The Phase III program is evaluating limzoparlamab in combination with azacitidine, as first line treatment for patients with newly diagnosed higher risk myelodysplastic syndrome. Enrollment in the phase three trial was initiated in April of 2023. The company will continue to review follow-up data from our phase two 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.
spk08: Thank you, John. Now, I will review our first half 2023 financial results. About June 30, 2023, the company had cash equivalents, restricted cash, and short-term investment of $3 billion in R&D. or $414.6 million in U.S. dollars, compared with $489 million U.S. dollars as of December 31st, 2022. IMAP'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 the stock literature program of up to $40 million U.S. dollars to attach a long-term credit holder value of the company. Total revenue for the first six months of 2023 were 2.7 million U.S. dollars compared with the 7.7 million U.S. dollars for the same period in 2022. Revenue consists of revenues recognized in connection with the strategic collaboration with the ABBV and the revenues generated from the supply of Investigational Products to Abavit and Human Immunobiosciences or Hibio. Now let me turn to the R&D expenses. Research and development expenses for the first six months of 2023 were 61.6 million US dollars compared with the 67.6 million US dollars 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 U.S. dollars, compared with 51.3 million U.S. dollars 54.1 million US dollars 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 the professional services. Non-GAAP adjusted net loss, which exclude the share-based compensation expenses for the first six months of 2023 was 87.5 million US dollars, compared with 116.9 million US dollars for the comparable period in 2022, as of June 30th, 2023, IMAP has approximately 190 million shares outstanding. I would like to reiterate strong cash position of 414.6 million US dollars as of June 30th, 2023, which allow us to execute our strategic plan. Lastly, please note that the conversion of certain RMB amounts into US dollars for historical period presented in this column 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.
spk02: Thank you, Richard. To conclude, I'm even more convinced than before that I made the right choice to join IMAP and that we're on the right track with the strategic plan. Looking ahead, we intend to advance our two lead oncology assets, Ulidellimab and Gevastomic, rapidly into additional studies in the US 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 and we intend to focus on a new operating model to establish a US-based global biotech company with the full support of the board. We're excited about IMAP'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. Thank you, Raj.
spk13: 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 Shea. Kelly, please go ahead.
spk01: 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 weakly injected growth hormone from phase three trial? and in comparison to other competitor weekly programs? And also, could you let us know the projected timeline for regulatory approval and also commercial launch? And I also have a follow-up. Thanks.
spk02: Kelly, thank you for that question. We are quite excited about the potential of F10 somatropin alpha 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 multibillion 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?
spk10: Thank you, Raj. Thank you, Kelly, for the question. As Raj mentioned, this trial is a randomized head-to-head trial against Novonordisc's Nordotropin. And 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 nortotropin. In addition, I think we're pleased with how the safety profile of this drug looks compared to other drugs in the field. And 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.
spk14: Andrew, are you on?
spk11: Yes. Can you hear me?
spk14: Yeah, we can hear you.
spk11: Yeah. Kelly, thank you for the question. As you know, we just actually released the results. All the secondary endpoints, including safety and also various variables of the clinical data, are being actively analyzed. And right now, we can definitely say the safety profile compare very, very comparable to the weekly injection. And 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. Definitely we think with the phase three data, this provide 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.
spk02: Yep. Andrew, I just wanted to make one clarification. I think the safety profile compared very favorably to the ones daily injection.
spk13: Yes. Correct. Thank you for your question, Kelly. With that, I would like to direct the next question to Joe Cananzaro. Joe, please go ahead.
spk03: Hey, guys. Hopefully you can hear me okay. I guess I had two questions. Maybe first one on gibbastomig, and particularly as it relates to clotting expression levels. Wondering with the potential approval of zolbatuximab, I guess, next year, whether, you know, based on what you've seen thus far, whether there's opportunity to maybe capture a broader clotting expression range with gibbastomig. Thanks, and I have a follow-up.
spk02: Thanks, Joe. As you can tell, we're very excited about this particular program, including our TJL14B that we're collaborating with ABL Bio. But in particular, we continue to believe that GIVA stomic is quite differentiated from the agents that are in development. I'll ask John to comment more on the specific area of clot in 18.2 that you specifically referred to. John? Yeah.
spk10: Yeah, thank you, Joe. So as I alluded to in my comments, in a non-clinical time, early in the development of Givostomig, we've seen that Givostomig can be efficacious and have biologic effect down to very low levels of clotting expression. And in addition, you'll see in our clinical data, we've seen clinical benefit in patients who have quite low levels of clotting expression. So we're optimistic. The program is early still, but we're optimistic that Gevastomig may be able to bring benefit to a broader and much broader group of patients with lower CLAWDIN 18.2 expression as well.
spk03: Great. That's helpful. And maybe my follow-up question quickly on Lemsaparlamab and the ongoing Phase 3 trial in 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 Megrelumab's enhanced trial, just wondering how you think about, you know, what ultimately we could see from that trial and, you know, how it influenced your decision with Lemzopolamab and its clinical strategy. Thanks.
spk02: 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 three 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. And then I would think our shareholders would appreciate that to make an informed decision in the first half of next year in advancing the molecule. So we'll certainly further analyze the details of the enhanced study as well as the data becomes available in the public markets.
spk03: Okay, perfect. Appreciate you taking my questions. Thanks so much.
spk13: Thanks, Joe. Thank you, Joe. I'd like to direct the next question to Louise Chen. Louise, please go ahead.
spk07: Hi, thank you for taking my question, Chair. Congratulations on the progress this quarter. So, Raj, I wanted to ask you if you could elaborate more on your vision for IMAP 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. And when you might reveal more details on your next generation CD47, or is that project on hold right now? And then I know you've mentioned the Jivastomic 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.
spk02: 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. So 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. And so I think I give myself 24 months to be able to start looking at the strategic plan and the progress that we've made. So 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 it into a U.S.-based global biotech is going to take time. But again, I think if I had to put my 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? So that was the first question, I believe, Louise. The second question is on Lemso outside of China. As you can imagine, as we've said before, right, that AbbVie had terminated the development, global development of Lemso, but we have the rights to China, so we continue the trial in China. At this time, we have no plans to initiate a study until 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, Luis, to clearly articulate as to if we're going to move forward with Lemso or the backup compound. And then the last question, Louise, was on the conferences. Yeah.
spk07: Yeah. Anything on the side from ESMO? I know you mentioned Giva Stomach from ESMO, but any other of your main compounds going to be presenting new data at conferences throughout the remainder of the year?
spk02: As far as we know, I don't think there's anything that jumped out to us for the rest of the year, but I'll let John comment on it.
spk10: John? Yeah, thank you. So as we mentioned, we plan to present the GIVA Stomach Dose Escalation Clinical Findings at the European Society of Medical Oncology in October this year. Also, 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. So we'll be reviewing those results and bringing those forward as quickly as possible. But for the remainder of 2023, no additional conferences to add at this time.
spk07: Okay, great. Thank you very much.
spk13: Thank you, Luis. Thank you, Luis. Next question, we will direct to Ethan Markowski. Ethan, please go ahead.
spk04: Hi, everyone. This is actually Gil, not Ethan. So maybe a quick one on the commercial opportunity for Aftan. Are you guys thinking of pricing it similar to the current standard of care in China? If you had any thoughts there?
spk02: Hi, Gil. I think it would be a little premature right now to comment on price, but 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, and we're excited about the growing large commercial opportunity that we have available for the human growth hormone product. So 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.
spk04: Okay. And maybe a quick biology question on give a stomach. So signaling for, for one BB usually requires trimorization 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 give a stomach or is this even an issue? Thank you.
spk10: John, do you want to take that? Sure. Yeah, thanks, Gil. Good to hear from you. So this has not been a non-clinical. It was not a preclinical issue for geovastomic. And further, in the early clinical findings, we continue to see the systemic pharmacodynamic effect of soluble 401BV in a predicted manner. So we've been quite confident by what we've observed to date with geovastomic regarding the PD effect.
spk13: Thank you, Gil.
spk14: Thank you, Gil.
spk13: Next up, I would like to direct the next question to Andres Maldonado. Andres, please go ahead.
spk09: Hi, thank you very much for taking my questions and 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 Ululelamab. I'm curious on your thoughts on the potential for partnerships outside of Ululelamab and how they align with your new vision. Thank you.
spk02: 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. And we think they have interesting biology. They have produced early encouraging clinical data. And 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 in 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. And I think at that time would be ideal to talk about if appropriate, depending on what else do we have in terms of opportunities to be able to talk about, do we need a partner and why? But I will say also as a note, you know, we continue to get incoming inquiries of interest on these assets. And we continue to engage with these outside partners. But that doesn't mean that we are keen on partnering until it makes strategic sense. And we believe that that option produces the highest value for shareholders in the near to midterm.
spk14: Thank you for your question, Andres. Does that answer your question, Andres?
spk09: Yes, thank you very much.
spk13: Thank you. I'd like to direct the next question to Chu Xiaoyi. Xiaoyi, please go ahead.
spk00: Hi, this is Xiaoyu from CICC, and thanks for taking my question. I have a quick one on the CD73 antibody. So we see very encouraging results of this antibody in first-line non-small cell lung cancer. And in the phase two trial, about 16 out of 60-ish patients that has both high CD73 and PD-L1 expression. And the ORR reaches really high for this population. Do you predict similar percentage of target patient population in the real world? Or what's the target population average for this both double positive expressing patient population in the real world? And also for the pivotal trial, I just want to ask about the design for this trial, because I see like for the patients that with really low TPS expression, you see like the response is minimal. And 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?
spk02: in the response to city 73. yeah that's very good questions on on on uli 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 uh especially in advancing that program in the settings that john articulated in his prepared remarks So 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 want to comment more on that and the second question that she had?
spk10: Yeah, I would just add that we've been working with WUSHI Diagnostics throughout the development program regarding the CD73 status. biomarker assay. And so 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. So CD73 expression to the broader group, that was not an entry criterion. So we would believe within the setting of a modest size clinical trial, the rates that we observed may be consistent with what we would generally observe in future studies. Though, of course, the precision around that, we need larger studies to increase our confidence. So I think that the rates are I think that's what we know about the rates of the double high population. But as Raj said, importantly, 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. But when you combine checkpoint inhibitors with chemotherapy, then the benefit of checkpoint inhibitors expands to really the broad population of newly diagnosed patients with lung cancer. And so we're optimistic that as we move forward in combinations with chemotherapy, 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.
spk13: Thank you for your question, Xiaoyi. I'd like to direct the next question to Bing Zhao. Bing, please go ahead.
spk12: Thank you for taking my questions. This is Bing Zhao from China Renaissance. I'm still interested about the Clotting 18.2 and 4MB-B bispecific antibody, because I realized that the STELUS Clotting 18.2 antibodies is going to be listed in US probably second half of this year. And also STELUS is looking for listing in China mainland as well. So I'm wondering if... their products being commercialized, will this affect our future clinical plan? And also, I realize that for clouding a biospecies antibody, there are many combinations on the market. Let's say, for example, clouding 18.2 with CD3 or clouding with PD-L1. But I'm interested to know more biologics behind why we choose the clouding and the 4-1-B-B instead of the other targets. Thank you.
spk02: Thank you for your question, Dingxiao. I think as you're talking about, the positive is there is a lot of interest in the cloud in 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 GivaStomach has, as we articulated in our prepared remarks. John, do you want to specifically address some of the differences that geostomic has to what Big Jiao brought up in his question?
spk10: Thank you. So 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. But really, we think it's too early to know about those drugs if they'll eventually get to the market or not. And 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. These results are indeed important. But as I mentioned earlier, we look for Givostomig. We're about to begin in combination studies. We intend to study with chemotherapy and with checkpoint inhibitors. And as I mentioned also, we've seen benefit in even monotherapy in patients across a wide range of clot and expression, including patients with quite low expression have received monotherapy benefit. So we're quite encouraged by what we've seen to date with G-vastomig and the ability that G-vastomig 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.
spk11: Hey, Roger, can I add one point to John's comment? Sure. Yeah. So being, you know, you're obviously touching a very, very critical point. We are fully aware of the competitive landscape in the clouding targeting area. However, as John pointed out, I think definitely our drug can actually cover a broad range of clouding expression levels. And the second attractive feature is really the safety profile. As you know, for zobitoximab and all the clotting-targeted naked antibodies, they have the clot-specific toxicity profile. In particular, the GI side effects is actually quite challenging for the clinicians to manage. So our data so far really highlight the favorable safety profile of gibbostomic. So I think, you know, combined with these two features, I think even in the first-line setting, even with the pending Zobitoxin MAP 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 clotting expression as well as the favorable safety profile. Just want to clarify that point.
spk02: And I think just one other thing I just wanted to say is, right, we will have more details of the data presented at ESMO, which will be interesting as well for you to take note of.
spk13: Thank you, Bing. Next question, I'd like to direct it to Zhusheng Jiang. Zhusheng, please go ahead.
spk05: Okay, so thank you very much for this chance. And my question is about our early stage pipeline development. So Could you elaborate more about the pipelines that are going to enter the IND stage? Thank you.
spk02: Yeah, so great question. I think the early pipeline and China has been, specifically the talent in China, has been a complete foundation and a core driver for innovation in how IMAP has progressed to date. That being said, I think as you 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 at 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? So 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?
spk05: Yes, thank you.
spk13: Thank you, Jiuquan. We'll take one last quick question. We have three minutes left. I would like to direct the last question to Wangbin Zhou. Wangbin, please go ahead.
spk06: Hello, everyone. This is Wangbin from CT Research, and thank you for taking my question. And I have two small questions. The first one is about the CD47. the CD47 project. And we know that the Gilead and AirX oncology have just terminated their project due to the limited efficacy. So could you give us more color on the efficacy gap between the phase two and the phase 3 trial and as we know the primary endpoint for our phase 3 trial is overall survival and can you comment more about the improvement in the OI rate to the benefit of the OS. And yeah, this is the first question. And the second is the D73 project. And for our coming pivotal study, where the repertory open green light for a single arm single pivotal study or it should be head to head phase three step.
spk02: Thank you. So thank you for the question on LEMSO and then Uli as well. So let me just reiterate on the LEMSO one, right? So 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 – to think about a decision whether we should continue or stop the molecule development. I think we continue to enroll our ongoing phase three study in China. We continue to believe that our molecule is differentiated. But as we said, we are also going to review the interim data. We're going to look at the full data from these studies. CD47s that have announced their trial termination fully, and then meet with experts to be able to make an informed decision on CD47. So 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 LEMSO anywhere else outside of China until we get that information in our hand. On the ULI question, let me pass it on to John to address that question in particular.
spk10: Thank you, Raj. So I just add regarding ULILAMAB and the potential development pathways, we have the utmost respect for the regulatory agencies. Certainly they have a challenging task and regulatory issues. guidance changes from time to time. So at this point, we would not comment further regarding the specific regulatory pathway for Uli Ledlumab until after we've reached alignment with the regulators, and then we'd speak further about it after that time.
spk14: Does that answer your question?
spk06: Yes, thank you.
spk13: Thank you. Thank you, Wan-Bing. And with that, we're running a little over time, so 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. Thank you.
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