Great, we'll get started now. I'd like to welcome everybody to H.C. Wainwright's At Home series. Today we're hosting I-Mab Biopharma. My name is Andres Maldonado, I'm a senior healthcare analyst here at H.C. Wainwright and it's my pleasure to host you today. It's my pleasure to introduce I-MAB Biopharma's Chief Executive Officer Sean Fu and I-MAB's Chief Medical Officer Philip Dennis. The crux of our fireside chat will be to give you an overview of the Claudin 18.2 landscape in order to provide proper context ahead of the company's mini oral presentation that is expected at ESMO GI and scheduled for July 2nd. I'd like to take the time now to welcome Sean and Philip. Thank you for joining us today. Thank you, Andrés. It's a pleasure to be here. Great. I guess you know, to kick things off, for those who are getting up to speed on the I-MAB name, you know, could you begin with a brief overview of the company's vision and the current clinical pipeline? Absolutely. Andre, thanks for the invitation. Very happy to have the opportunity to join the H.C. W fireside here. I-MAB is a company that went through significant transformations so you can think of it as a new company if you will. Last year we went through divestiture so we split out the assets and operations and teams in China and really focus on the U.S. side of operations. As a result we have a new business model which I believe is capital focused, capital efficient compared to the old model. We have 5 full time employees, all of them in the U.S. You can see that we are a much smaller company which means we're much more focused. Focused on what our clinical pipelines. We have three clinical stage assets and the one that we're going to be talking about, spend most of the time today, is the Claudin 18.2 4-1BB bispecific and we're very excited about this asset. As Andres mentioned earlier, this asset is subject to a mini oral presentation at ESMO GI on July 2. What about this asset? This is an asset that we are actively developing as a bolt-on to the standard of care in frontline gastric cancer, which is IO chemo. Our strategy is unique compared to other competitors, is that we are adding Jiva to the standard of care without changing anything of the standard care itself. In the monotherapy studies, it's clear that Giva, which is the bispecific antibody, Giva is an active agent. We have 18% monotherapy heavily treated population ORR and the safety was very well tolerated. We liked it a lot. We bring into combination and this is the study data that we're going to share at ESMO GI. In this study we looked at the 17 patients over three doses. When we add Giva to the unadulterated nivo chemo standard of care and the ORR looks very, very exciting and the safety continues to look promising. We do not see any additional tox beyond and above small numbers, but above and beyond nivo chemo background. This is really exciting data. I also wanted to say that why are we focused on gastric cancer frontline? This is still a very devastating disease when someone is diagnosed. Unfortunately with metastatic gastric cancer, the five year survival rate is only 7%. This is significant unmet medical needs where we believe Giva can add to the overall arsenal of the treatment options for patients around the globe. Because of the unmet medical needs and the relatively large population, this gastric cancer ranked number five in terms of frequency and number four in terms of mortality. This actually translates to significant commercial opportunities. We're talking about the frontline Claudin 18.2-positive patients represent a $12 billion addressable market just in the U.S., EU, and Japan. That's where we have rights. Right. I think this is a significant unmet medical need, very exciting assets, promising data and we are full steam pushing forward with the clinical studies. Now before I hand it over to Philip to talk about the data, let me just also say that I-MAB is in a strong position when it comes to finance. We have $168 million on balance sheet as of end of the first quarter, which means we are positioned to see through some of the important financial clinical readouts in the next six to twelve months. With that I would turn it over to Philip and let's dive into the data. Great. I guess the first question I have, very interesting bispecific Giva is, and I want to start with on the basic biology of the targeting of Claudin 18.2 before we start incorporating the other arm, the 4-1BB. Maybe to start with, you know, how does claudin exposure, you know, enable you to target selective tumor types? Would be great to talk about its expressional levels, its overall importance in tumorigenesis, and any implications given, you know, where the cells that express 18.2 are, you know, given they're in a tight rich junction of the epithelial cells. Any high level thoughts there to kick off are kind of encapsulating the biology of Claudin 18.2. Oh, Philip, I think you're muted. Sorry about that. Thanks, Andres. The 18.2 is a very good example of precision oncology. What do I mean by that? It alludes to what you just mentioned, which is we're looking for ways to maximize the therapeutic index to target cancer cells and not harm normal cells that lead to toxicities that patients experience. Claudin 18.2 is a component of tight junctions between gastric epithelial cells and it die epithelial cells. What happens with the transformation of a gastric epithelial cell is that the polarity is lost. The polarity that normally means that the Claudin 18.2 is tethered very tightly and junctions literally mean that that liquid can't get through. It is a tight junction impermeable to really anything other than ions. Even water is too big. The idea here is that with transformation, the polarity is lost. The Claudin 18.2 is expressed on the cell surface where it can be identified by antibody-based approaches such as bispecifics, ADCs, anything that uses an antibody to target Claudin 18.2. Now, even though, and because it's selectively expressed in tumor versus normal, again, in normal, it's hidden. If you look at cell membranous staining of 18.2, you don't find it in normal cells. There are a couple interesting features. In spite of the fact that it is selective for tumor versus normal, it's not an oncogenic driver. It doesn't change the biology of the tumor cells. It's simply a homing address for the therapeutics that we develop. I will also say we're referring and we're focused on frontline gastric cancer, but the expression of Claudin 18.2 is very high in other GI malignancies as well, such as pancreatic adenocarcinoma and biliary tract cancer, where the majority of those tumor types also have high levels of Claudin expression. It is a feature of GI malignancies. The polarity is lost with transformation, allowing claudin directed assets and medicines to get to the tumor. Great. Now, very helpful. You know, on one side of Givastomig we have the Claudin 18.2 arm, and on the other side, oncology investors are very familiar with the 4-1BB arm, you know, after a host of other utilizations of that target. I guess the question becomes, you know, how does the conditional activation of 4-1BB via tumor localized Claudin 18.2 binding, you know, really overcome the limitations that we have seen previously with 4-1BB agonists and particularly in avoiding those off-tumor, you know, hepatotoxicity that the class has previously seen. Yeah, this is a really. Jiva is differentiated structurally in terms of its mechanism of action. The first word I'm going to, I'm going to use is conditional activation of 4-1BB, being conditional activation of T cells. That's through the binding to Claudin 18.2. The binding to Claudin 18.2 is highly avid, the KD log lower for Jiva than it is for Zolbetuximab. It's very avid binding. What's also critical is the Fc effector function is eliminated through a mutation that we introduced. This allows two important things to not happen. To eliminate, one is the induction of processes such as antibody-dependent cellular cytotoxicity and CDC as well that have been associated with the toxicity of other assets due to the fact that ADCC and CDC are directed against normal gastric mucosal cells. The first thing is we lose ADCC and CDC, which is a good thing because it's associated with toxicity. The second thing is that because we lose that Fc receptor function, we can no longer get imprecise clustering of 4-1BB via the Fc receptors. Basically what we end up with is a precise targeting of 18.2 without getting ADCC or CDC and we activate T cells in the microenvironment only through 4-1BB. We've shown this preclinically in our preclinical data. We show in circulation that Jiva by itself, if Jiva encounters a T cell in circulation, it does not activate 4-1BB because the Fc moiety again is silenced and there's no clustering of 4-1BB. The clustering of 4-1BB, the activation of T cells only occurs in the tumor microenvironment. You can say, you know, this is a scientific hypothesis, it's mouse data, blah blah blah. I think that our clinical data, the toxicity profile of Giva as monotherapy, which showed single digit grade three and above nausea and vomiting, which showed minimal hepatic toxicity, says to us that Giva in fact is acting in patients the way we show animals and the way we think it should act. This is all being borne out in our combination study that will be presented in just a few days at LGI. Very helpful. You did touch upon a little bit this next question. I kind of want to drill down to really bring some clarity here. You know, with the role of the co-stimulation of 4-1BB, you know, in terms of T cell exhaustion and memory differentiation, which you were just touching upon, how does this differ from, how should we be thinking about this signaling differences when it comes to Claudin 18.2 low expressors versus 18.2 high expressors? Does it expand the utilization of Giva there? Yes, so without a doubt. Our monotherapy phase one data that's been presented previously shows that we have responders with Claudin 18.2 expression as low as 11% of tumor cells being positive. We can extend the range of Claudin expression very low. You will also see in the ESMO GI presentation, patients with very low levels of Claudin, lower than 11%, also responding to the combination of Giva plus nivolu mab plus chemotherapy, the conditional activation in terms of T cell subsets and function. What we have shown preclinically in our animal studies is that Giva monotherapy induced a localized immune activation and that was shown by an increase of CD8+ to regulatory T cells, increased memory T cells, and decreased exhausted T cells in the tumor microenvironment. We also saw a long lasting memory response against tumor rechallenge as well. We're having the types of effects on the immune system that you would want to provide long lasting benefit. Again, we have this combination of a breadth of Claudin expression that we can target, targeted expression of 4-1BB activation of that costimulatory signal in T cells in the tumor microenvironment, leading to increased CD8+ T cells, a decrease in Tregs, and ultimately tumor immunity. Such that if we rechallenge—again talking about mice now—if we rechallenge mice, they actually successfully mount an immune response and do not develop new tumors with rechallenge. Great. Incredibly helpful, thanks for that, you know, giving us a good basis for the scientific context of Giva. One of the things I want to move on to now is the true differentiation of Givastomig. Obviously, you know, we spoke at ASCO, we saw many different approaches to targeting Claudin 18.2 that are up and coming and many historical ones as well. I guess, you know, broadly speaking, before we get into the nitty gritty of, you know, one-off, one-to-one comparisons, just on a modality basis, you know, can you walk us through the key differentiation points for Giva versus other types of ADCs, other CD3 bispecifics, or any type of modality that comes to mind targeting Claudin 18.2 to start. First thing I'll say as oncologist, I think this is a really exciting time for patients who have Claudin 18.2 positive tumors. I think we're seeing a lot of progress in the field in general and I think that's a great thing for patients. Giva is highly differentiated in this very crowded field. It's differentiated for several reasons. The first, and I'm going to start with the basics here, which is the fact that it targets the broadest range of Claudin positive patients. Our cutoff in all of our clinical studies is 1% of cells 1 plus or greater intensity. The next part of the differentiation is an incredibly well tolerated asset as monotherapy, but with a discernible objective response rate in highly pretreated gastric cancer patients, namely an ORR to Sean's point of 18%. If you want to develop, we know that in solid tumors, patients benefit most by getting the best therapies up front. Our strategy all along was to move Givastomig into frontline therapy. If you look across the entire 18.2 asset class, I dare say there's no better suited drug to be moved into standard of care without modifying the standard of care than Givastomig. That's again what's going to be shown at ESMO GI where we can add Giva to regular standard of care, regular doses, regular schedule of Nivolumab plus FOLFOX without modifying it. It's well tolerated and the efficacy, it's, you know, it's very notable and you'll see that. In comparison to other assets, there are other assets that will clearly have a role to play. ADCs, T cell engagers that activate T cells through CD3. You know, we just had a very interesting presentation on Claudin 18.2 CAR-T cells that are being developed in China. These assets will have a role. They have a high active response rate, but they also come burdened by a high rate of toxicity. Now, as monotherapy, you could say, okay, as an oncologist, second and third line, I'm willing to tolerate that toxicity profile. What I'm thinking about is benefiting the most patients by moving it into frontline therapy. I have to think about the existing toxicities of Nivolumab plus FOLFOX. I'm saying to myself, I don't see how this works. How can you add something that has a 50-60% grade three and above treatment-related adverse event incidence? How can you add that to standard of care without taking something away from standard of care? We know health authorities don't like that approach. Health authorities love additions to standard of care because in a study where you're comparing standard of care plus standard of care plus an experimental therapy, everyone gets standard of care. The development path is much easier when you have an asset that can just be added. That's the situation that Giva is in because of its properties of being very well tolerated and having discernible clinical efficacy. Incredibly helpful. You know, it's a perfect lead in to my next question. Again, you touched upon this but kind of really want to drill down again. When investors, you know, are comparing, you know, whether it be the efficacy profile or the safety profile of Giva against, you know, one of the first monoclonal antibodies of Rituximab, an ADC like CMG 901 or a TCE like IBI398, you know, can you just broadly speak about some of the caveats of those cross trial comparisons and how, you know, investors might get hooked up on maybe focusing too much on ORR without taking into account the holistic safety profile. Any high level thoughts there would be helpful. Yeah, this I'm trying to. Thank you, Andres. I will try not to get in the weeds too greatly here but I will point out the differentiation of, again, Givastomig. We have the widest, broadest range of eligibility for Claudin at a 1% cut. Zolbetuximab has an indication in frontline gastric cancer in combination with chemotherapy. That indication is that it's 75% of tumor cells. That gives you a breadth of the exposure. Other assets such as, you know, AstraZeneca's ADC AZD0901, Innovent's T-cell engager, the ADC XNW that was just presented at ASCO, again variable levels of Claudin 18.2 expression were the lowest. What you see again across these asset class, especially in Zolbetuximab and their phase one data with a cut point of 50%, their objective response rate was 9% or 18%. If you look at the ADC and T-cell engager it's 25% - 30%. With this ADC presented at ASCO, the ORR was 60% or so. This is a way to compare. Again, I go through the toxicity profile for distinguishing these assets. One category that you can look at are grade three and above treatment-related adverse events. If we look at the monotherapy for all of these different assets, Givastomig has grade three and above treatment-related adverse events of 33%. For 0901, the percent was 57%. For the Innovent T-cell engagers, 58%, almost double of what we see. For the ADC presented at ASCO, XNW, it was over 60%. Again, if you have monotherapy activity, sure. But monotherapy toxicity, where grade three and above are that high, it's just going to be prohibitive. If you hone down into the toxicities, for example, ADCs almost always have bone marrow toxicity because of premature release of the warhead. No linker is perfect. Right. The minute you have grade 3 and above, neutropenia, anemia, thrombocytopenia, and you're looking at FOLFOX, which does the same thing, it's going to be very hard to combine. Right. In totality, we have these assets with different profiles. Giva is arguably best suited to be combined because the other assets, whatever they come with with activity and toxicity, are not well suited to move into frontline. If it is suited to move into frontline like Zolbetuximab, it becomes very limited because the activity of zolbetuximab is limited to tumors that really only express Claudin 18.2 in almost all tumor cells at very intense staining of 2-3+. Very helpful then just to confirm. I guess as we think about the prior kind of CRS rates observed with other CD3 bispecifics, and as we take into account the broad expressional coverage Giva affords, with an 18.2 targeting, you know, what is the strategy, I guess, in terms of, or what's the internal bar there for, you know, saying that, look, we can expand beyond, you know, the patient subset of, you know, Zolbetuximab and other competitors. What I'm really trying to hone in on is, you know, as we're looking at through the dose escalation data and as you lock in the, you know, the real, real world dosage, you know, I guess what are some of the puts and takes there? We're honing in on the patient population that benefits the most with the clean safety profile. Yeah, I've been an oncologist a long time and I will say that the data that's going to be presented is very interesting. It's very intriguing. Our primary endpoint in this dose patient was safety. So we did not hit a maximum tolerated dose. The toxicity profile, as Sean mentioned, looks very much like Nivolumab plus FOLFOX and importantly we're not seeing a large increase in, we're not really seeing no increase in immune related adverse events. Our follow up for this cohort is almost a year and one reason why we wanted to wait so long to present this data, I wanted to be assured as someone who has more than a decade experience of developing agents in pharma that I wanted to be assured that we didn't have late onset IRAEs. We're not, we don't have it. Success to me looks like a well tolerated regimen. The next point is, okay, it's tolerated. Who's benefiting? We already talked about our Claudin cutoff being threshold possible. We're also seeing, we also know that the responses Nivolumab and two other checkpoint inhibitors that have indications in frontline gastric cancer are limited now in the U.S. to PD-L1 1% or above. That says that there's a gradation of response to the standard of care. Nivolumab plus FOLFOX based on PD-L1. In our cohort we have patients that are low PD-L1, we have low Claudin 18.2, and we have a small number that are actually low for both. We have the majority of responders in that select group low for both. We're observing objective responses. That to me says that is, it's a small number of patients. We don't want to make too much of it, which is why we're doing a dose expansion that's ongoing as we speak. This is very intriguing data. The other intriguing data that we want to look for, that everyone wants, is duration of response. This is IO. We all want duration of response. The good and bad news is that the data is immature. We've had very few events, so you're going to see little in terms of progression, median PFS. We do make an effort to look at PFS and present data that we think is appropriate given the immaturity of it. The immaturity is a good thing. If you don't have events, you can't have a median. Right. This is a really, it's kind of a, it's a very impressive, intriguing data set and it has the attributes and the unique features that I just described. No, absolutely, you know, really interesting strategy. You know, kind of continuing on the strategy portion of the clinical strategy of Giva. Obviously, you know, the strategy was a bolt on to frontline, but given the safety profile, and these are early days, so context is key here. Given the safety profile so far, you know, is the door, you know, are you excited to maybe explore alternative chemotherapy backbones and if you decided to, you know, where would that kind of steer the Jiva ship, whether it would be further within, you know, GI cancers or maybe even outside there? We're committed to develop Giva in frontline metastatic gastric cancer. That is our mission, to get an indication there to have the greatest benefit for the greatest number of patients. That's what we're focused on. We are laser like focused on frontline metastatic gastric cancer. Having said that, we know that with any good drug, we want to make a good drug available to as many patients as we can. Where might we test Giva next? I think there's some kind of obvious places both within gastric cancer and outside gastric cancer. What do I mean within gastric cancer? We just heard presentation of the MATTERHORN data from AstraZeneca. Combining Durvalumab with FLOT is a different, arguably more toxic chemotherapy regimen that is used for locally advanced resectable gastric cancer and gastroesophageal junction cancer. We saw positive data there. It's likely they will get an indication there. If we establish proof of concept with Giva plus a checkpoint inhibitor plus chemotherapy in metastatic, why not move into locally advanced? That's an obvious place to look. As I mentioned, two other tumor types, pancreatic cancer and biliary tract or cholangiocarcinoma, also have high prevalent levels of Claudin 18.2. The standard of care for frontline pancreatic cancer is the chemotherapy doublet. Why not test Giva in that setting, having established POC in frontline metastatic gastric? The same could be said for biliary tract cancer, where the standard of care is again a checkpoint inhibitor plus chemotherapy. There is a tremendous upside to Giva. We are laser-like focused on the development of frontline metastatic. That's what we want to drive home. We want to add Giva as a standard of care to IO plus chemo. Great. No, very helpful for giving us that prospective context, but I guess in a, in a current state context would be great. You know, ahead of the ESMO GI presentation on July 2, that we will all be tuning into. Would be great to just, you know, touch base with you on walking us through the dose escalation logic of this study, you know, and what you're evaluating pharmacodynamic wise and, you know, as a guide to, you know, really honing in on that RP2D selection. Correct? Yes. Our design of the combination with the standard of care of biochemo was based on our monotherapy analyses. In our monotherapy dose escalation study, we know the doses where responses occur. We know that the pharmacokinetics for exposure are dose dependent. We also know something very interesting, which is if we look at a pharmacodynamic marker, namely release of soluble 4-1BB by T cells that are stimulated through Giva, what we find is that there's actually, even though there's linear PK, a plateau of the pharmacodynamic number above 5 mg per kg in the monotherapy study. The doses that we chose that we will reveal at ESMO GI were based on that PK and PD data that we saw from the monotherapy data. We also have observed very similar data in combinations. We observe linear pharmacokinetics in terms of exposure, but we also observe a plateau of the pharmacodynamic marker, suggesting that the three doses we chose were really well chosen because we have a low, a middle, and a high dose. We felt as though that is perfectly adequate because again, based on the monotherapy data, with the plateauing of the pharmacodynamic marker, dose level three is probably as high as we want to go. We have a very, we're in a very good position now to choose the dose moving forward in terms of the recommended phase two dose. We're going to be able to make a much more informed decision after the completion of our dose expansion data. Again, we're going to be enrolling 20 patients each in each of the top two doses. This will allow us to validate the objective response rates we've seen in escalation, which again are very notable, very notable, very much above the phase III ORRs that were reported for CheckMate649 as well as SPOTLIGHT, leading to approvals of Nivolumab or Zolbetuximab, respectively. We want to validate what we saw in escalation. We'll have a total of anywhere from 25-30 patients at each of the two doses that we're testing in expansion and will be able to make a choice, we think, after that. We'll also obviously be able to have more patients in those defined subsets. Right, so it's a question, does dose matter if you have really low levels of Claudin? Right? We don't know that. We don't, you know, that's one of the things that we're trying to figure out. The dose expansion for us is very important, but we're well suited to choose a dose and we also have great confidence based on some consultations we've had, that the approach we've had for dose expansion will satisfy Project Optimus. We haven't spoken to the FDA. I don't want to overstate it, but I think the experts that we talked to have experience with Optimus, I have experience with Optimus as well, in prior positions. This will satisfy Project Optimus. I think we're in a very good position to be choosing a dose to move forward. Very helpful. So then, you know, ahead of the ESMO data, you know, probably, you know, as investors are trying to formulate what they view as successful dose escalation data, could you talk about not so much the internal bars for success, because I think you've covered them, you know, and what we need to see. Could you speak more to some of the cross trial, you know, comparison caveats, you know, that are, that may be over interpreted here. If you can speak to any, maybe internal safety thresholds that you guys have, you know, that could help frame, you know, the, you know, a more stringent and real world kind of assumptions of what to expect as just defined as good data. I do think that we've laid some of this out. I would say that when looking at the data, if I'm looking at this as an investor or as an attendee at ESMO GI, if I'm looking at the safety, I want to know, is there a dose limiting toxicity? There's not. I want to know, does the toxicity profile look different than the standard of care of Nivolumab plus chemotherapy? It looks very similar. I'd like to know, is there a sign that because of activation of T cells through 4-1BB, you're exacerbating what is already known about Nivolumab in this regimen and we're not seeing any notable increment above that. I think those are the things that I would look for, I would look for in the escalation. Again, I think that what we have and what you'll see are confirmed responses in everyone. You will have a sense if you keep in mind CheckMate 649 and SPOTLIGHT. The objective response rates, the fact that Zolbetuximab doesn't increase objective response rate, but improves PFS and OS, I think you'd want to look at our ORR and think about the data from those two phase III studies and say, how does this. Is this a small increment of improvement or is it a very large incremental improvement? I think you'd want to know, does it look like patients are staying on study? Those are the parameters I think that we would, I would certainly look at as an oncologist and I'm sure investors will be doing the same thing. I will say that with the objective response rates that you will see, and we present this for the whole cohort and then we will also present data on the upper two doses that we are moving forward in expansion. What I'll simply say is when the objective response rate is so high and it's so high using an IO agent, not a small molecule, this is not a tyrosine kinase inhibitor where you might get a deep response and the tumor evolves and develops resistance. That certainly happens with IO, but it doesn't happen rapidly. I would be surprised as a clinician that if our objective response rate that will be reported doesn't translate into improved PFS. Again, it's not a randomized study, but the fact is I think that our patients are going to do quite well long term. That is what I'd be looking for as well. Great. As the data set continues to mature at ESMO and beyond ESMO, you know, I guess what kind of evidence should we be looking for to really confirm that activity of Givastomig 4-1BB in delivering localized post stimulation. You know, can you point us to what PKPD signatures or immune signatures you're really honing in to confirm that there's a true—I don't know if synergistic is the right word, but a true kind of additive effect there, you know, that goes beyond just trying to suppress the caveats of some of the older safety signals that some of those strategies have had. We will not be presenting biomarker data in the escalation study other than, in other words, biomarkers for T cell activation. We will have data forthcoming subsequently on that, and we will be presenting the dose expansion data. We have recruited quite well into those dose expansion cohorts, and we anticipate being able to present that data early next year. What I will say is what to look for would be, I think, you know, the clinical surrogate of T cell activation precise in the tumor microenvironment versus imprecise in circulation. Our cytokine release syndrome would be hepatic toxicity. That is commonly observed with 4-1BB. You will see very, very low incidence. We have no CRS, and you will see a very low incidence of hepatic toxicity. That is the kind of thing that we would look for, what we know, and one reason we were not lazy or kind of confident about not doing biomarkers. What I will say is we are doing them. We showed preclinically that in mouse studies, the only changes in T cell subsets were in the microenvironment of the tumor once the tumor was excised and digested. If we look in the periphery of the circulation in the mice treated with Giva, we saw no changes. It is really, we do not expect to see changes in humans, but we are looking, but we will not be presenting this data in a few days at ESMO GI. Great. Now that was very helpful context. Obviously the biomarker strategy takes a long time and always chomping at the bit for more and more data here. I guess the next logical question is, you know, given the, you know, the very positive data package you have presented for Giva thus far and you've touched upon kind of, you know, Giva's potential maybe outside of GI or other, you know, in other tumor types. So kind of wanted to hone in on your opinion on across tissue types. You know, how much does the experience of Giva in gastrointestinal cancers really set a threshold for what other tumor types you can target? Let's say for pancreatic cancer, does the threshold hold up for the threshold of Claudin expression and do you expect a similar activity? If you can give any high level macro view there on the translatability of this data set to potentially inform activity in other tumor types, it would be very helpful. A great question. I love thinking more broadly about this. I will say that if you look at databases that have looked at Claudin 18.2 expression, the three tumor types that have the highest levels of expression are indeed gastric, pancreatic, and biliary tract. There are other rare tumor types that have subsets that are very positive for Claudin 18.2 expression. Right now, we're not pursuing a tumor agnostic indication. I think if Giva were incredibly successful, it would be very much a life cycle management project to actually look at other tumor types agnostically to look for Claudin 18.2. I do think that the focus again is on gastric. The obvious places would be the solid tumors that I've mentioned. The challenge is, for the bar for success for Giva, again, I'm a pretty cautious oncologist. One of the things about pancreatic cancer is, IO doesn't work in pancreatic cancer, right. If we establish a proof of concept, combining Giva with a traditional checkpoint inhibitor and a chemotherapy regimen, one of those drugs doesn't work well in pancreatic cancer. The question is, one of the things we would want to understand is, does Giva have activity absent the checkpoint inhibitor, right. That's something that I think is a very important question that we're considering. The next question, if you're thinking about biliary tract cancer, could we apply the lesson learned in gastric to biliary tract cancer. The first thing you want to think about is biliary tract cancer is in the liver, right. Whatever we've seen with gastric cancer, even though it's very well tolerated in gastric, one of the things we need to think about very carefully is would the toxicity profile be very different, adding Giva to IO and a chemotherapy regimen in biliary cancer? I think these are all opportunities. They all make sense to explore, but I think each of them, the lessons learned in gastric are important, but they need to be applied to the specificity of each of these other tumors that we're thinking about. Great. Very helpful. I guess a subsequent question to that. You know, would it be fair to say that one of the most differentiated features of Giva, if we look beyond, you know, combinations with IO or chemo, do you think, given the safety so far, do you see potential other combinations with maybe other small molecule targets really being really adding to Giva's defensive position, specifically against, let's say, CAR-Ts, other ADCs, or other bispecifics? Yes. One of the other opportunities I didn't mention is that, again, focusing on gastric cancer, the Claudin 18.2 positive tumors we're targeting are all HER2 negative. Right. If you're thinking about other combinations. For HER2 positive gastric cancer, the standard of care is typically a HER2 agent combined with chemo plus or minus a checkpoint inhibitor. I think that is something that is worthwhile to think about, to consider. Right. In HER2 positive, we know that there's an FGFR2 antibody being developed that is currently in phase III studies in frontline, either in combination with chemo or IO chemo. I will say that we have data that suggests that the Claudin 18.2 expression is very similar in the FGFR2 positive tumors versus all gastric cancers. Could we in fact combine with other assets such as an FGFR2 antibody? I think we'll need to see what the toxicity profile looks like. I think the phase two data from that antibody suggests there's a high rate of discontinuation, a high rate of ocular toxicity that we need to think about. If I think about what other combinations, I'm not thinking as much about small molecules. I'm thinking about positioning Giva into additional sectors within gastric cancer. The HER2 positive, the FGFR2 positive, and then, you know, we'll have to see. There's so much excitement about the PD1VE bispecifics. We know that there's a lot of excitement in lung cancer, but the fact is that VEGF is a validated target in gastric cancer in second line with Ramucirumab. The fact is that could these bispecifics ever move into gastric cancer? Would they move into front line, second line? And knowing that, are you enhancing the IO response? A natural question would be, could Giva be potentially combined there? I think we need to let that mature. We need to see where those bispecifics end up going. Very helpful. Great. You know, we've heard from Sean and Philip about, you know, the biology of Claudin 18.2 and 4-1BB, the clinical landscape of 18.2, the clinical strategy, and the future strategy for Giva. At this time, I think it would be great to maybe, you know, wrap it all together for our audience here in terms of, you know, if you want to just give a brief summary overview of what Giva has done, what to expect at ESMO, and kind of a quick flipnote summary of wrapping all of our very specific deep dive questions together. I'll leave it to you, Sean and Philip, to divvy that up as you see fit. Yeah, I think that the way I look at the Giva's data flip in ESMO GI, I think it's the beginning of a series of important and exciting data readouts in the next six to twelve months. We went through a lot of the biology and clinical data in the last 40 minutes. Also with Philip. I think those are the things that we've been thinking about day in and day out that the more we look at it, the more we like the profile of Jiva. It's highly differentiated, very promising early data, but very promising, very exciting. Our execution on our clinical development strategy is robust, our recruitment is strong and we're looking forward to seeing through some of those important data flips and be able to benefit patients across the world. Very good. Philip, if you wanted to add. Any closing remarks? I'll just say Giva has properties that are truly differentiated. The phase one data show that it has clinical activity in heavily pretreated patients with a very impressive, very safe profile, successful in being able to add it to the standard of care. Nivolumab and dose escalation. You're going to see much more data to Sean's point next year with the dose expansion data. We really think that it plays out. This has great potential to help patients with Claudin 18.2 tumor first in gastric cancer and potentially later in other tumor types. It's a very exciting time. Absolutely. And just as a reminder for the investors that join later on, I-MAB will be presenting a mini oral presentation at ESMO GI scheduled for July 2, 2025. So stay tuned. That's all our questions. We're going to wrap this up on behalf of the entire HC Wainwright family. You know, we would like to thank I-MAB CEO Sean Fu and their CMO Philip Dennis for joining us today and we look forward for the data card flip. We're really excited about this new target and thank you so much for your time. Thanks, Andres. A pleasure.