Okay, great. Go ahead and kick off the last segment of the day here. Thanks to everybody for joining us here, second day of Piper Sandler's Annual Healthcare Conference. It's my real pleasure to welcome the team from I-Mab Biopharma. Joining us is their CEO, Sean Fu, as well as their CMO, Phillip Dennis. Sean and Phillip, thanks so much for joining us. Maybe, Sean, before we kick off into Q&A, I can give you the opportunity to maybe just sort of level set and give everybody an introduction in a couple of minutes to I-Mab, what you guys have been up to and what we have to look forward to. Sure. Thank you for the invitation, and great to have the opportunity here to share the I-Mab story. I joined I-Mab recently. Since July, I was the interim CEO, and in November, I was the permanent CEO. So you can say I'm sort of new, sort of old, but I think it's a sweet spot to really talk about how I think about the company going forward. I-Mab went through a lot of changes. I think the biggest one really had a strategic impact was the one that we did announce in April, is the divestiture of China assets. So in that divestiture, we split it out to the China assets and formed a separate company. And I-Mab today here with you is the U.S.-based company. In that process, the company became a lot more efficient. We went from 200 people, discovery, development, manufacturing, commercial, the whole nine yards capability, operation in both China and in the United States, to what it is today, a company of 33 full-time employees, all in America. We focus on three clinical-stage assets, all IO oncology, and all show the clinical activities. We have a team, like I said, 33, and these are 33 experienced, highly trained folks focused on clinical development. That is our strategy to bring forward, leveraging our pipeline, leveraging our strong financial position to advance these pipelines, create value for investors, also create therapeutic options for patients. Maybe on this sort of topic of now versus a couple of years ago, I think I-Mab a couple of years ago had a pretty well-defined kind of BD strategy of in-licensing late-stage assets for China and then a global portfolio where you look to find partners. Maybe on that front, as you look at your current pipeline and maybe future pipeline, how you guys think about BD opportunities and how that compares to maybe the historical approach? Yeah, we're definitely open for the right type of deals at the right times. Maybe I'll take this opportunity also to bring up a related transaction recently. Our partner in China, the TJ Bio, the company which was the result of our divesting China-based assets, they announced a deal in September with Sanofi to out-license one of our assets' greater China rights. This is UliledlIMab. We call it Uli, and this is an antibody against the CD73 for non-small cell lung cancer. So in that deal, Sanofi took over the greater China rights for that assets with the upfront about, I think it was EUR 32 million, and the total deal size is EUR 213 million. And this is just for greater China rights, right? So from that deal, obviously, we're very excited about the fact that they signed the deal. This is a validation of the asset value for us, and the deal really does more than that because as Sanofi and TJ Bio develop the asset in China, we have additional clinical readouts of the same assets, and that will help us improve and strengthen our own development program and de-risk our overall position. We are very happy and positive about that development. Now, to your BD question, we have a couple of assets you will hear hopefully later on from Dennis and others that we will develop those assets for first-line indications, and those tend to be significant late-phase clinical developments. We are obviously looking for capable, experienced partners to help us to demonstrate the value clinically for those assets in late-stage clinical development studies, and so we are, like I said, looking for the right deal with the right partner. Also, on the flip side, we are optimistic when it comes to in-licensing opportunities. Great. So I do want to, of course, get to Uli, but maybe we could start with Givastomig. Claudin 18.2, obviously a pretty competitive and active landscape, as is the TCE space, a lot of momentum there. Maybe you could talk about sort of the design of that molecule and how maybe 4-1BB going after that offers some uniqueness relative to a CD3 engaging TCE. Yeah, I think our molecule is really designed to do some really interesting things, one of which is to activate the T cells through the 4-1BB pathway, but only does it in a tumor microenvironment where Claudin 18.2 is expressed positively. And that conditional activation, we believe, is contributing to some of the efficacy profile we see in monotherapy settings for gastric cancer and what we are doing in combination therapy in a first-line setting with Nivolumab chemo against the gastric cancer. More importantly, I think it is contributing to reduce the systemic toxicity sometimes we associate with 4-1BB. And in monotherapy, we see very benign safety profiles, very well tolerated, no DLT. And that gives us the ability, really, the product profile to move this asset into a front-line setting. Right? Phillip, do you have anything? Yeah, I'd like to, first, it's a pleasure to be here. I will say that we refer to it as Giva. Givastomig is referred to as Giva. I think it threads the needle in terms of efficacy and toxicity. What do I mean by that? To Sean's point, as monotherapy, we did not encounter any dose-limiting toxicity. We did not need, we did not determine a maximum tolerated dose. We chose effective doses to test subsequently. But importantly, if we look at competitors in the field, so we can look at Zolbi, right, in terms of that it has an indication in front-line gastric cancer in combination with chemotherapy, we have less nausea and vomiting than they observed in their phase I studies. We have a better ORR than they observed in their phase I studies. If we look at other competitors in the Claudin 18.2 space, such as T-cell engagers, we have no CRS, right? So if you look at, so we have a favorable toxicity profile from that. And then if you look at the ADCs that are being developed, such as CMG901, yes, they have a better objective response rate, but at the same time, they have tremendous, in my mind, they have a notable AE profile with significant, more than half the patients getting grade three or above adverse events. So I think, again, this is a sweet spot for us in terms of efficacy and tolerability, and it's allowing us to move into the front-line setting, not in any way where we have to subtract from the standard of care, but we bolt on to the existing standard of care. And that's where we're moving Giva now. I wanted to probe in on that a little bit more on Giva's tolerability, specifically the GI-related events, which are remarkably low compared to what Zolbi sees. Why do you think the molecule is seeing that? What about Giva's design, maybe is allowing it to potentially avoid maybe some Claudin 18.2 in normal sort of GI tract? Yeah, I mean, that's a great point. Again, the GI, remember, 18.2 in normal tissue is normally part of tight junctions, and it's hidden, right? So in normal tissues, it should be hidden. It's not on the cell surface as much as in between cells, not on the apical cell surface. But in gastric cancer, there's really a redistribution at 18.2 to the cell surface that makes it accessible to antibody-like approaches. But to your point, Zolbi relies on ADCC, right? So we've been engineered out ADCC. So again, we think they're just attributes that, and frankly, the clinical data speak for itself, right? Even if we can't invoke a firm mechanism of action, what we can do is look at the incidence and say it's lower and better tolerated. Yeah. I wanted to follow up maybe on efficacy and sort of your thoughts across the Claudin 18.2 landscape. You mentioned Zolbi and what we saw there. What about the ADCs? What about the other sort of CD3-based T cell engagers? How does it compare? How does it contrast? And ultimately, where you see Giva sort of fitting in? Sure. I think the easy answer for the ADCs is with an ORR that's been observed with CMG901, anywhere from 30%-40%, even if it's toxic. That's the kind of drug that you want to move into a second or third-line setting where you want a rapid response, you want a notable ORR, but at the same time, you have this toxicity. For the T cell engagers, again, with CRS, if you're adding that to a checkpoint inhibitor, I think it's going to raise questions initially and maybe during the clinical testing of that, is that going to be tolerated? And what I can tell you is that we're in the process of doing a dose escalation with Giva, Nivolumab, and chemotherapy in front-line gastric cancer. And to date, we have not encountered any dose-limiting toxicities, no CRS at all. I think that there's, again, this is an interesting Claudin 18.2 asset that has the right mix of efficacy and toxicity to be combined with an IO chemo backbone for front-line gastric. Go ahead. Just to add, I think the product profile of Giva is quite interesting in a sense that it's a combination, sweet spot combination of efficacy and tolerability. That gave us opportunity to go to front line, but not just for gastric cancer. There are other cancers, pancreatic cancer I can think of, that has a significant percentage of patients that is 18.2 positive. So you can think about the upside for Giva goes way beyond gastric cancer and into other medical needs, such as pancreatic and other few cancers. I want to come back to that, but maybe first, you know, we mentioned Zolbi a couple of times. That molecule is obviously restricted to very high Claudin 18.2 expressors. Where are your thoughts currently on where Giva stands in terms of the Claudin 18.2 cutoff that may be required for activity or maybe no cutoff required at all? So I think that the way we're designing our clinical trials, we think it's only fair because it's an antibody-based approach. We need some level of expression. But at the same time, we've seen responses in the study that I just mentioned, this dose escalation study with Nivo and FOLFOX, with patients that have a very low 1% and 1% distribution. So we think that we will understand any type of hierarchy of response based on Claudin 18.2 expression, but we're casting a wide net. In fact, we've seen responses in our monotherapy data with Claudin 18.2 expression as low as 11% with monotherapy. So we think that we're going to be able to target. I think the Zolbi indication leaves a lot of white space in terms of 18.2. And then if you think about their indication with chemo only, the standard of care for patients who have PD-L1 greater than 1% is IO chemo. So the fact is, I think we're going to be able to fill in a lot of the white space with Zolbi. And in fact, potentially given our head-to-head comparisons, we might be best in class. We have opportunities for that. Maybe I want to come back to PD-L1 cutoff. There was just the recent FDA discussion in gastric cancer on chemo PD-1 combos and what the appropriate PD-L1 cutoff is there. I'm wondering how, and I think the FDA has yet to give an answer on where they stand, how that decision potentially impacts or maybe doesn't impact how you think about Giva in combination with chemo PD-1 and front-line gastric. Again, so it's a consideration in that the recommendation from the ODAC meeting was to restrict the label to 1% or greater. You're absolutely right. We don't know if the FDA will agree with the ODAC recommendation or not. But the patients that are PD-L1 negative are only 10%-20% of all patients. And then if you're looking at the 75% Claudin 18.2 of that, again, it's a very, very low percent. So for our development point of view at this point, we want to bolt it on to IO plus chemo, which is going to cover the majority of the PD-L1 status. And then we can drop the Claudin 18.2 to 1% with a 1% distribution with 1% staining. Just to highlight the opportunity for Giva, you know, when we compare to Zolbi, with the limitation of Claudin being greater than 75% and in terms of combination is only with chemo, which means there's less than 1% of the PD-L1 expression, they are doing quite well financially. In Japan, we just saw the data that for the full year 2024, they are projected to sell just for Japan, $24 million. That really highlights, if you think about the entire canvas of opportunity for Giva, this is a very significant drug. And the Zolbi sales is just for the gastric cancers, right, what we are approved for. And we're thinking about other indications. This is a really exciting opportunity for us. So, I want to go to the front-line trial that you're running now. Maybe you could just sort of give us an update on where things stand, and I guess more specifically for 2025, you know, the type of data set maybe you anticipate having and what you might be able to say about the program in combination with chemo PD-1. We are running those escalation studies. Like Phillip said, it's with Nivo and chemo. And we completed enrollment for that study. And we're considering accelerated development options into an expansion study to achieve proof of concept in a broader database to substantiate the value proposition we believe Giva has. And in 2025, we see the escalation data to be shared sometime second half of 2025 in scientific meetings. So we're looking forward to that. I guess maybe when we think about, you know, the safety tolerability of Giva, which we just spoke about and what we've seen with chemo PD-1 and potential or there or not of overlapping toxicity, is there anything there like top of mind or are the safety profiles largely mutually exclusive? My take on this without data would be that because you're activating T cells via 4-1BB, are you going to exacerbate immune-related adverse events? That would be my number one concern going in. I can tell you we've gone through, again, three dose levels. We've completed enrollment. We've gone through, we're having the safety review committee at the last dose level, but it's an open label study. We've had no dose-limiting toxicities. We have no IRAEs that are of note above that of Nivo plus chemo alone. But we're also realistic that we've, the dose level one was recruited early, so that has the longest follow-up. So we are being very judicious in terms of the maturity of data and when we're presenting it. So even though we've completed enrollment, we probably won't present the data until later next year to ensure that what we're observing early, which is no increase in immune-related adverse events, plays out over time. Yeah. So Sean, I want to come back to something you said in terms of additional opportunities. So we have seen some interesting claudin 18.2 data in pancreatic cancer, which I think you mentioned. Maybe just speak to that a little bit more at one point. At what point do you sort of take that step and start to look a little bit further of Giva's opportunities outside of gastric cancer? Yeah, definitely. I think that the opportunity for us is wide open. We're considering some various cancer indications where Claudin 18.2 plays a role where Giva can contribute. But the first thing first, I think for us, the strategy remains very clear is to have a clear demonstration of proof of concept in gastric settings. Then we can think about programs that could potentially expand that benefit to other indications. And we will see what data comes out from the escalation and the expansion study final and when the data matures. Then we have plans to quickly pivot into other indications if the data supports. Yeah. And if I could just add to that, the other GI tumors that come to mind in addition to pancreatic is cholangiocarcinoma and small bowel adenocarcinoma. And the interesting thing about small bowel adenocarcinoma is treated with a FOLFOX-based regimen, right? So I think the proof of concept that we generate in gastric with that signal, it's natural and logical to expand to these other tumor types. So maybe with that, I can move to UliledlIMab, your CD73 antibody. You know, the adenosine pathway has been of interest for a little while and there's been a number of different attempts to go after it. Maybe just speak to UliledlIMab, its design and what maybe makes it a differentiated way of going after adenosine. Yeah, I think Uli is unique in several areas. One is that it completely blocks CD73 activity. And that's very important that it's going in. And also it does not suffer from what we call the hook effect where you have a decrease in activity as you increase concentration. And that obviously could complicate your dosing regimen going into the clinical settings. We do not have that. So that is another thing going for us. Thirdly, we have a very strong clinical proof of concept where we observed response rate in lung cancer patients that goes hand in hand with the CD73 levels. So those are strong indications about activity and about the mode of actions. And Uli as a molecule has the potential to be best in class. Now what we are doing right now is working with our partners and they are running studies in China, same asset, a randomized study of Uli plus Tori, which is a PD-L1 agent, and in that study, we'll compare against the Pembro and Tori, so that data will come out second half of next year, and we are also internally, we're running a phase II data, we expect it first in human first half of next year, which looked at CD73 Uli in two different doses, and this will give us indication, this will give us information about what's the best dose to carry forward in a phase II study, and combined with the TJ Bio data, this will really inform the project going into a phase III study. So I want to sort of get to your maybe shift in strategic strategy. So the company historically had looked at Uli plus PD-1 in a frontline population. You've sort of made that pivot to chemo PD-1 plus Uli. What sort of drove that? What was the sort of major sort of driving factor to make that sort of slight switch to where you said? I think we always wanted to do the phase frontline in combination with PD-1 and the chemo. The reason why we look at the combination of Uli and PD-1 is for signal finding. We wanted to make sure that in combination with checkpoint inhibitors, we see an incremental benefit contributed from Uli. And it's really not a strategic shift as much as an expansion, right? So more patients arguably are treated with, you know, checkpoint inhibitor plus chemo than checkpoint inhibitor alone, right? Even PD-L1 high patients are treated commonly with, you know, the Pembro plus the Keynote-189 regimen. But I will say that there's also a rationale for this in that chemotherapy induces CD73 expression, right? So the idea here is that, you know, you could argue that the reason why you add chemo to frontline. I'm just going to use Pembro as an example. The reason why you add chemo to Pembro is to keep the tumor in check while Pembro can activate the immune system because we know there are all these early progressors if you don't have chemo on board. I would argue that the addition of Uli to such a regimen will basically unmask the full potential of Pembro because if chemo induces CD73, which makes adenosine, which dampens the response to Pembro by having Uli on board, you'll unleash the full potential of the entire regimen. For us, I think it's a natural progression of monotherapy IO because it's a clean signal, right? It's basically the combination versus single agent. That's the data we're waiting for to come from our collaborator, which is a randomized study to confirm what was observed in the non-randomized study in a CD73 selected population. I'll mention one thing. There was a poster at SITC from Arcus showing that in their pancreatic study, they selected for CD73 positive patients. Guess what? Their small molecule worked better in that population as well. I think our strategy to select patients based on CD73 will pay off in the long run. Yeah. So actually, I want to connect a couple of dots on the CD73 expression as a biomarker. I recall in the sort of original PD-1 Uli data set, there was that correlation between responders and CD73 expression. And then Phillip, you just sort of mentioned that chemo induces CD73 expression. So in the chemo PD-1 combo trial that you're going to kick off, what is the strategy on CD73 selection? So that's a great point. So what we're taking, our approach is we know that we're going to test retrospectively. So in other words, we are enrolling all comers in this study. However, we'll be testing retrospectively to confirm the cutoff that's been generated by our collaborators because we want to ensure because of this regulation of CD73 by chemotherapy potentially, we just want to validate the cutoff. And so we're going to do so retrospectively. In this last minute, maybe I'll give you the opportunity to give any updates on Ragistomig, the 4-1BB, PD-L1 bispecific, anything to say there? Phillip? Yeah. So I think we have Ragi is a clinically active drug with a notable, you know, ORR of 26% that has great monotherapy potential. Our line of sight for this drug is to be able to combine it with other drugs. To be able to combine it, we want to decrease the rate of liver adverse events. A similar approach has been taken by Genmab with their bispecific. And they've shown by decreasing the dosing frequency and/or the dose, you can minimize T cell exhaustion, increase the number of memory T cells. And so we're taking a very similar approach to see if less might be more with Ragistomig. So we're actually testing Ragi in different dosing cohorts as we speak. Great. Well, with that, we're on time here. So Sean, Phillip, thanks so much for your time and thoughts. Thanks everybody for tuning in. Take care and enjoy the rest of your day here. Thank you. Thank you. Thanks so much. Thank you.