Good morning everyone. My name is Daina Graybosch. I'm a senior equity research analyst here at Leerink Partners. I'm happy to be hosting management from NovaBridge Biosciences, formerly I-Mab. Sean and Phillip, nice to have you both here. We were just gossiping about clinical trials that started slightly late. Maybe we'll ask about that one now that you know about it, as we go in. Let's spend most of our time on NovaBridge. I wanna start with some corporate questions, particularly, you know about your name change and the strategy. Talk about Givastomig, your claudin 18.2 4-1BB T-cell engaging agonist, and then talk about your AMD asset 'cause you had some data released this week. Mm-hmm That's ambitious for the 28 minutes we have left, so let's see what we can do. Can you talk about first, your business transformation and strategy, that accompanied the name change last year, from I-Mab to NovaBridge? Why now and, what was the motivation? Yes, thanks Daina. Good morning. Thanks for the invitation. We did a business pivot October of last year, went from a asset-based biotech company to a biotech platform companies focusing on bringing China innovations to global patients. That is the sense of the pivot. Why do we do it? It was really a conviction on two things. One is that the board look at the capability that we had as a company. In the last eight years, the company has been extremely successful and efficient when it comes to innovative asset development in the translational clinical development space, going before and after achieving clinical approval concept. That’s one capability. The other conviction is that the company realized that the China biotech ecosystem has been one of the supporting pillars in terms of global biotech innovations, value creations. If you look at the value of the in-licensing deals in the last three years, it went up from 10% to 30% to 40%, and you just cannot ignore that from business perspective. The question in front of the board was how did we leverage what we have built and what we have access to in terms of the China ecosystem, and systematically monetize the outpouring of innovations in China. That was the decision by the companies to say, "Hey, we are a strong company with strong access to China ecosystem. This is one area we differentiate from many U.S. companies and we have a strong U.S.-based operation, fully staffed business, and a business development, a clinical development teams in U.S. for eight years. This is a differentiating factor versus many China cos. Let's put two and two together and take advantage of this growth of innovation and systematically bring innovations to the global market. It's everybody knows about China and the rise of innovation, and that we're starting to translate that globally, and more companies and venture funds are taking similar approaches. What advantage does NovaBridge have over the competitors in this regard? This is a good question, and we thought about it carefully. When you look at what we bring to the table, I alluded to this earlier, is really the combination of the roots and access in China and of the operation and the presence knowhow in US. NovaBridge, formerly known as I-Mab, was founded in China over 10 years ago. Some of our important backers, investors, for example, CBC Group, was the largest healthcare focused PE firm in Asia Pacific space, with over $10.5 billion asset under management. When you combine those strengths, what you have is a consistent, robust and broad overview and an access to China ecosystem. To make it concrete, if you give me a name of the China biotech company, chances are I can talk to their CEO tomorrow if I wanted a deal, if I wanted to understand their assets. Compared to many U.S.-based cos, or funds, that wanted to access China innovation, I think that is a significant competitive advantage. Now, compared to China cos, you mentioned that many of them wanted to do this kind of deals. I think NovaBridge is uniquely positioned through its business presence, historical presence in U.S., both in terms of, like I said, fully staffed the functional business functions as well as translational clinical development capabilities. We'll hear more later on when we talk about Givastomig, when we talk about VIS-101. These data were all generated with internal teams in U.S., designed with the idea that those assets will be one day partnered, licensed out or further developed in U.S. Not for China, right? In U.S., for the bigger market opportunities in U.S., EU and Japan. That is differentiated compared to China co. If you look at some of the biggest successful China cos, they have trouble establishing U.S.-based operations. You think about the Hengrui, they tried multiple times. Innovent tried multiple times, and they retreated because it's really difficult to operate across culture, really understand how to interact with FDA, build network with U.S.-based KOLs, and build a network to talk to MNCs as your potential business partner. When you have an asset, you want to partner out. All of those things takes time to build, and NovaBridge has been doing that for the last 8 years successfully. I think it's really the intersection of this robust China access and a strong U.S. execution that differentiates us. Hot take. Do you need that strong U.S. execution? I mean, in the future, will you be more and more moving to a model where you can do proof of concept in China and then move to global studies? Yes, I think there's a difference in the concept here. Having the presence in U.S. gave us access to translational clinical development talents. China has 3,000-5,000, depending on who you ask, biotech companies. Many of them were founded by chemists, biologists. They were great coming up with molecules. But if you ask them to do the right translational clinical development for their molecule with an eye to subsequently license out to U.S. or European-based multinationals, I don't think that they were trained or they were ready for that. In fact, there is no global registrational pivotal study done by any China pharma up to this point, and that takes time to accumulate. To answer your question, in the near term, I think that is still very important. But we're not ruling out, right, conducting that U.S.-designed, expert-designed, like Phillip, right? People like Phillip designed the study, but with significant China patients. Still benefit from the efficiency and speed of a China market, but you generate the data that our partners, downstream partners, can actually use to design a pivotal study. We're bridging the gap. That gap in the near term, I think gonna exist, and like I said, it takes time for the China biotech to catch up in this particular area. Got it. Let's move on and talk about Givastomig. Earlier this year, you shared some updates from the combination of Givastomig with Nivolumab and chemo and frontline gastroesophageal adenocarcinoma. I wonder if you could summarize what's most encouraging about the updated outcomes. I think the most encouraging is the consistency of the data. We presented data in July of last year at ESMO GI where we had 17 patients worth of data. We now have an additional 21 patients in dose expansion at two different doses, completely consistent data with outstanding efficacy data in terms of objective response rates. We announced that we now have progression-free survival of approximately 17 months, which far exceeds any cross-trial comparison that we can find, and a tox profile that is very consistent with the standard of care of nivolumab and FOLFOX as established in CheckMate 649, with one exception of this gastritis that emerged. We now know it's in a minority of patients. There's very few high-grade events. It's manageable, and it's astonishingly associated with improved clinical outcomes. It's again, it's the consistency of the effect. It's the strong data in terms of the efficacy outcomes that there hasn't been one waiver as we continue to enroll patients. The challenge of this data, I think, is that it's single arm. Correct. I think most investors are aware that Arcus-Gilead in the same indication had a pretty promising single-arm clinical readout from EDGE-Gastric, and then they failed, totally flatlined, failed in phase 3, announced recently in the STAR-221. Why should we believe this strong survival signal with Givastomig is different? As a scientist, I'm not gonna argue against the value of a randomized trial. In fact, that's why we're doing one. I will say it is really the consistency, right? To have objective response rates in the 70%-80% range that are maintained across claudin subgroups, across PD-L1 subgroups, having a PFS of 17 months when, again, CheckMate 649 comes in at 7.7 months. SPOTLIGHT, which led to the approval of zolbetuximab, comes in at 10.5 months. ILLUSTRO, a single-arm study with zolbetuximab reported at ASCO GI in early January, came in at 14.8 months. We're in every cross-trial comparison, we're consistently better. I think this lends us to have a high belief that we have a high probability of technical success in a randomized study. You know, it's funny you said that you were encouraged by the consistency in PD-L1 and claudin 18.2. That actually worries me a little bit. Particularly on the claudin 18.2 side, because claudin 18.2 is the associated antigen for which you get your conditional activation, sort of hoping to see greater activity in claudin 18.2 higher tumors. It's great that you have it in low, but I would want to see sort of a biomarker response. Why should I not be worried about that? Why are you excited? Well, two things come to mind. The first is that the fact that we have high levels of activity does not mean that there won't be a gradation in activity, but it is not a step off a cliff in terms of activity. We are looking very closely at different subsets of claudin patients to see if there is a pattern, and it's too early to really say if there is. For us, what we really think is that we wanna target the patients that don't qualify for other 18.2 assets based on the cutoff that they're using. 75% for zolbetuximab, 25% for AstraZeneca's ADC. Our cutoff is 1%, and we have great activity between 1%-49%, 50%-74%, 75%-100%. We really have strong activity across the board. The beauty of 18.2 is that the gastritis is a really interesting example because this bispecific antibody, which is one end interacts with 18.2, the other is a 4-1BB agonist. We don't have indiscriminate immune activation, irAEs that are really toxic. If you look at our irAE profile, it looks identical to CheckMate 649. There's no exacerbation except for gastritis, which we think is an on target, off tumor, but on organ, right? If you think about it's in an organ, right? We're not actually seeing any other 18.2. We're not seeing pancreatitis. Claudin 18.2 is expressed in pancreatic tissue. We don't see pancreatitis. We see the gastritis occur in stomach, in only stomach tissue that expresses claudin 18.2. What we now know is that the gastritis occurs typically 2-3 months after a response occurs. Mm. Our hypothesis now is that as tumors regress, as patients respond, and again, 75%-80% of patients have a confirmed objective response, a subset of them with a tumor regression, we hypothesize have exposure of normal tissue that does express claudin 18.2 on the cell surface and in fact, we induce such a strong antitumor response against 18.2 with T cell activation that those T cells now become active against normal gastric tissue, and that's what we have to manage subsequently. I think it's a really. It's a very interesting biologic process. The reason you don't see pancreatitis, claudin 18.2 is expressed on tight junctions, so in that healthy pancreas. Mm You're just not causing the tissue disruption to expose it? I think yes. Again, I think it's related to the fact that in the gastric tissue I mean, the hypothesis in that 18.2 should exist in tight junctions in normal gastric mucosa as well, but what we're seeing is with the tumor regression, I think that there's some disordered expression in normal tissue. Again, I'm surprised frankly that we don't see pancreatitis, but we do not, so yes. How are you gonna use claudin 18.2 and PD-L1 in future to either stratify or enrich? We plan in our continued development to enroll patients that are 1% of cells, one+ or greater. That's consistent in our entire clinical development in both gastric cancer, and now we have two cohorts open in frontline pancreatic cancer and frontline biliary tract cancer in our phase I study. Same cutoff for claudin 18.2. Looking forward to a registrational study with Givastomig in combination with frontline standard of care nivolumab and FOLFOX, our cutoff will be 1% or greater of CPS, which is the label restriction in the United States. Got it. Are you looking, when you enroll that phase III, to have a cap on the claudin 18.2 low expressers? I imagine you'll just have more demand naturally given zolbetuximab is approved for the high. Two comments. One is that what we've heard from our investigators and from investigators that really we talk to at every meeting, the zolbetuximab chemo combination is not as attractive. I will be the first to say that the ILUSTRO data shows that it looks like it can be combined. They're getting tolerable safety profile. I think right now the standard of care is zolbetuximab chemo, which is not very desirable. People wanna have IO chemo. They wanna have IO with their chemotherapy. We will ensure in the execution of this study that we have a normal distribution of claudin 18.2 patients. We know that. This is important for health authorities, right? They wanna know that your patient population is representative, so we will ensure. Again, if you look at the data that's available, approximately half of patients are 75%-100%, and half are the proportion that are 75%-100% is equivalent to the proportion that are 1-74. We will ensure that those proportions are maintained in a registrational study. Got it. Gastric cancer is increasingly competitive. You have mAbs. You talked about zolbetuximab adding onto Nivolumab chemo. Prior to this, looks like AstraZeneca's starting a phase III study in frontline gastric with over 2,000 patients with their claudin 18.2 ADC and various configurations with their TIGIT and other molecules, but you also have T-cell engagers. You have a CAR T. What gives you confidence that Givastomig is the best approach and that especially for frontline? I think what I start with is the profile of Givastomig as a monotherapy. What led us to combine it with frontline standard of care? It had clinical activity with an objective response rate of 18% in third-line patients and beyond, so we clearly have activity as monotherapy. But if we look at the toxicity profile, we had 33% grade three or greater treatment-related adverse events, which is about half that of any ADC or a T-cell engager that activates via CD3. A priority when you're looking at these assets, even though the ADC and the T-cell engagers that activate via CD3 have greater single-agent activity, when you think about frontline therapy, combining it with nivo chemo, which is tolerated, but let's face it's IO chemo. It is not a walk in the park for patients. We think we have an advantage because we can combine effectively, and that's now we're up to about 70 patients in our phase I study and it is very well-tolerated. I'll point out if we take this step by step, the ADCs, every ADC including AZD0901 has a lot of bone marrow toxicity. We don't have a lot of bone marrow toxicity. If you take an ADC and you combine it with FOLFOX or part of FOLFOX, you can pick the 5-FU component or oxaliplatin, and I admit I don't know the details of the design and which chemo. My guess is having worked at AZ previously, that they're taking something away from FOLFOX because they know the bone marrow toxicity could be insurmountable. Okay. Now let's move on to the CD3. We know that there is cytokine release syndrome even though, for example, with an anti-CD3 based bispecific, most of it was low grade. It's 60% low grade that all those patients are admitted, right? Now you're gonna add that to nivo. You're gonna add a CD3 based T-cell activator with a checkpoint inhibitor. I think that that's. I think if you had to look at what one would expect from adding our bispecific that activates via 4-1BB, a bispecific for CD3, and ADC, we're just very well suited to be combined as an add-on without modifying any component or schedule of the IO chemo. I also wanna add, I think you talk about the competitions. I think that's a good thing because then, it's validating our, confidence in the commercial opportunities in the frontline gastric cancer space. We recently had an interaction with FDA, and, FDA was very engaging, gave us very positive and, consistent, substantive guidance how to develop, Givastomig. We will share more once, we have a more detailed plan. I think the message here is that we wanted to position Givastomig based on the clinical data and now regulatory strategy, not only as a best-in-class potential molecule, and we want it to be very competitive in the space of frontline gastric cancer and position it in the front of the pack, fighting to get to approval line and in combination with IO chemo. Got it. One thing we haven't talked about here, and we would have, let's say, three years ago, is liver tox. Mm-hmm. I think what's been remarkable, if you follow the 4-1BB agonist, is that making its activity conditional on claudin 18.2 or tumor-associated antigen has really given you a therapeutic window that traditionally the 4-1BB agonists have really struggled with. I wonder if you've thought about expanding this platform. Like, you know, claudin 18.2 is only expressed in certain places. Are you looking at going after some other tumor-associated antigens, particularly those that work with CD3 engagement and making 4-1BBs there? This is one of the advantages of our business model, right? Which is we can look for novel assets, and we've actually have begun, and this began a while ago, looking at novel agents, bispecifics, tri-specifics, bispecific ADCs with different types of payloads. We absolutely, that this is a, as a proof of concept, this tells us what's possible with this bispecific. But we know the realm of creativity with early-stage high-quality assets coming out of China is really remarkable. This is one advantage of our business model, is we can scour the landscape and say, "What can we do to make Jeva, what can-- what's the, what's, you know, version two of Jeva look like? What could we add to it to enhance its activity? What would be complementary to Jeva? I think it's something that we are looking at, and it's again it fits beautifully within our business model. Let's move on and talk about VIS-101. You had some data, a data update on Monday. Maybe you could quickly give us what was most exciting. Sure from your updated data there. Yeah, we for the first time disclosed the clinical data for VIS-101. At a high level, this is a molecule that I think we call it purposely designed to target VEGF-A and Ang2 as a bispecific biologics. In the clinical study, we saw favorable safety profiles. More interestingly, we saw a quick onset of response, robust response, and importantly, durable responses. We saw the vision improvement of 10 or more letters, and we observed reduction in the CST, the thickness, by anywhere between 100- 150 micrometers. The durability, it's really, I think it's the highlight of the readout, if you will. Two-thirds of the patients on our phase IIa study remain treatment-free, no need to rescue by four months. About half of the patients remain retreatment-free by six months. In comparison, again, cross-study, Vabysmo is about 16 weeks, so four months, half of the patients. We are much better in the durability space. If you look at the marketplace in the past, there is an established conviction that the durability primarily drives the market share. I think from that perspective, given the safety and the strong efficacy, overall, especially in the durability space, VIS-101 is positioned to be a potential best-in-class molecule. What'd you say Vabysmo was in terms of retreatment? You said. 47% of the patients up to 16 weeks. Anywhere between eight- 16 16 weeks, and you're at six months. Yes. We have about half of the patients retreatment-free by six months, and at 16 weeks, we have two thirds of the patients. Interesting. Yeah. You share some binding targets with Vabysmo, so what's differentiating you from that, sort of the biological plausibility for this durability signal? Yeah. Do you wanna comment about the molecules? Sure. It's both the binding affinity and the inhibitory effect are. There's a twofold improvement in VEGF-A, and then about a 17-fold improvement in Angiopoietin-2. It's really, at a molecular basis, it has attributes over Vabysmo. It's just more potent. Correct. I- it- potent and better binding. What's the dose difference that you're giving versus? We're similar. We're six milligram. The data I mentioned were observed at the six milligram dose. For the upcoming phase IIb study, we will explore a nine milligram arm that will reduce the volume and potentially increase dose. That's part of the design for phase IIb, but even at the six milligram, I think the data is very strong. It's a very crowded market with AMD with drugs that are largely been approved on non-inferiority to anti-VEGF. You showed activity in treatment-naive and pretreated patients. What are you thinking about going forward? Is this a salvage therapy, or are you aiming to go frontline standard of care? I think we're gonna design a study that will support a strong label. What we think about the phase IIb will give you an idea about what the phase III and the label might look like. In the phase IIb, I talked about the dose selection. Once we pick the dose, what we will do is a study design that will evaluate two variables, both the efficacy as well as the durability, right? It's a study, it's not too different from the one that the Vabysmo uses to get its phase III approval. You're right. I think in this space, most of the drugs will go in with a non-inferiority design. That's probably what we're gonna do, and we will have a reference active reference arm in that study design. It is a competitive space. When you look at our responses in both naive and the treatment, prior treated patients, we see robust responses. We are very excited about this molecule. That's great. Sorry. We have about a minute left. Sorry. Maybe one question on corporate strategy to finish off. Mm-hmm Maybe I'll come back with one more on AMD. You announced with the transition from I-Mab to NovaBridge that you were going to do a Hong Kong IPO. I think we've talked to many investors who were interested, let's say, in the data that you brought earlier in January for Jeva. We're sort of waiting for that IPO, and I wonder if you could help us understand that process. Yeah. There has been an adjustment of our Hong Kong IPO plan, mostly driven by the additional requirement of the documents from CSRC or China Securities Regulatory Commission. As we speak, we are preparing those documents, and so there is an adjustment related to that. Another thing I will say that I think our stock is not reflecting our true value based on the strengths of the data and in our pipeline, so we wanted to give a window for our stock price to reflect the inherent value of our pipeline, and with the data that's gonna read out into the near term, I think we'll get there. At the current level, I'll say it's far from the level that I'm willing to pull the trigger to go for an IPO. Maybe one last question. I was looking 'cause we. Sorry. On AMD. We're a little bit over. Mm-hmm. Mm-hmm. Let me see. I think, correct me if I'm wrong, that you presented efficacy, the durability in retreatment free, and I, we were wondering what the outcomes look like for the patients who were retreated. Do you see the durability or anything, there? In this particular study, the patients who were retreated are exited from the study, so we don't have data for the retreated patients, what they do, but we do have data for the patients who stay on without the need to be retreated. That's the percentage that I was mentioning, right? Two-thirds by four months, half by six months, and there is half the patients who do not need to be retreated. I understand. They're retreated with your drug, or they're retreated with another drug in that study? We don't have that information. Once they need to be retreated, they're outside of the scope. They're outside the- They come off study. Yeah. That's typically how the studies are done? Yes, for phase IIa. Why not treat them with your drug and continue following? That, that'll happen in phase IIb. Okay. Yes. The second portion of the phase IIb when we evaluate the durability, that's part of the design. Okay, one more. You had a case of intraocular inflammation. Mm-hmm. Can you tell us more about that patient, and how it was managed and if you're worried about that for the phase IIb? It is a mild to moderate case. It was asymptomatic. The patient's uveitis was discovered during an eye exam, a scheduled eye exam, and asymptomatic. It wasn't something that we felt it's out of ordinary. I would point you to the fact that most of the VEGF, if not all, clinical trials would report occasional uveitis. Okay. Great. Thank you for allowing me to sneak those in. Thank you everybody for your attention. Thanks. Thank you.