All right, welcome back, everyone, to the third session of the first day of Citi's Virtual Oncology Summit. I'm Yigal Nochomovitz, a biotech analyst here at Citi. So for the third session, we have with us the head of R&D at Zai Lab, Rafael Amado. So welcome, Rafael. Thank you so much for taking the time to chat with us. As a reminder, if anyone listening has questions, just email me, yigal.nochomovitz@citi.com, and I will hopefully see it and be able to relay over to Rafael. So with that, obviously, there's a lot going on at Zai Lab in the oncology world. Of course, you don't just do oncology, but we're going to focus on oncology today. In addition to, of course, the approved drugs, there's a lot happening on the R&D. So you want to start maybe just by giving us a high-level overview of what are the key assets in the pipeline on oncology, maybe some of the key data readouts that everyone should have on their calendars for 2025. And then we can go into more detailed discussion on specific assets as desired. Absolutely, Yigal, and thank you so much for having me today. I wanted to just start by giving a brief overview about Zai for those of you that are not very familiar with the company, but we are a commercial-stage biotech. We have our own research and end-to-end R&D capabilities. We are in the market in China and in research and development, both for regional assets as well as global assets, and we are in a variety of therapeutic areas. Oncology is perhaps the most prominent, but we also are in autoimmune disorders, neurosciences, and we've developed some antibodies in collaboration with other partners as well. And we focus on first-in-class and best-in-class molecules through open innovation collaboration as well as internal discovery assets that come from our laboratories, both in Shanghai as well as San Diego. I'll highlight a few of our leading programs. Starting with oncology, we have built a diverse and differentiated pipeline across targeted therapies, antibody-drug conjugates, and immuno- oncology. And we also have a device sort of franchise with our partner, Novocure, on tumor treating fields. So for instance, our most recent sort of data presentation was on DLL3, which is called ZL-1310. And this is an antibody-drug conjugate for small cell lung cancer. This is a great example of strategic partnership work. We have global rights to this product, and perhaps we can spend some time later talking about our initial phase I study results that were presented at ENA about three months ago. Beyond ADCs, we're also advancing specific areas of immune oncologies, particularly an interest in T-cell engagers as well as ways to improve PD-1 and cytokine-type therapy. And outside of oncology, we focus on immunology discovery and development. And our lead molecule is bispecific IL-13/IL-31, which we intend to develop for atopic dermatitis and other indiications that are amenable to the blockade of the cytokines. So we have set ourselves a goal of having one or two new INDs per year. And our regional pipeline is very broad. I'll just highlight that in cancer, for instance, we have the bemarituzumab in collaboration with Amgen, which is an FGFR2b receptor inhibitor for those that are positive for this marker. Tivdak, which is a product that we're filing now in collaboration with Seagen, now Pfizer, for cervical cancer, is also an antibody-drug conjugate. Outside of oncology in the regional area, we have KarXT in collaboration with Bristol Myers Squibb for schizophrenia, as well as a variety of other indications in psychiatry. Efgartigimod, which is FcRn receptor inhibitor, which is across multiple indications in autoimmunity. And a recent addition, like povetacicept, which is in collaboration with Vertex for IgA nephropathy. All our products have potential transformational changing medical care type properties. We choose them very carefully for that with our partners on the regional side. On the global side, which is more incipient, we also are looking for big first-in-class differentiated molecules or improved molecules such as best-in-class new generation ADCs, DLL3 or 1310 being a good example of the latter. Hopefully, this gives you a broad sense of our footprint, which is both global and regional and across therapy areas that encompass oncology, autoimmunity, and neurosciences. Okay. No, that was very comprehensive, certainly. A lot to discuss. So we'll start with the oncology. So 1310, you mentioned the ADC targeting DLL3. There's a ton of interest in this target, as you know. There's several players in the space. You're one of them. You had the data recently. Can you talk about what were the key conclusions out of that data and then how you see this asset as differentiated potentially from the others in the space in terms of molecule design, be it the payload, the way you're developing the antibody, and/or the linker? Yes. This is a product that has moved very fast in our pipeline. The I&D was just December of last year, and we drove it through those escalations and those findings, both in Asia and the United States, and now more recently, we've added Europe. And we completed those escalations, and we presented efficacy data in 19 patients and safety data on 24 patients. And the response rate was 74%. Some of them were still unconfirmed, but we thought that it was really remarkable in terms of the performance of an ADC to really start disseminating the data in the community. So out of these, there were nine unconfirmed responses at the time. It was early data: five confirmed responses. What intrigued us was not only the high response rate, but patients were responding at the very first dose, and so a relatively flat dose response. There were responses across all the doses that we tested, and they responded very quickly within the first cycle. We saw a patient respond that had failed tarlatamab. As you know, tarlatamab is a T-cell engager that binds DLL3, so it's the same target, and this patient continued to express DLL3 and had a 67% tumor reduction. So it appears that there's no cross-resistance, at least anecdotally, with this patient. And we're enrolling other patients as well, and importantly, we saw response in the brain in all the patients, six out of six patients. And this is a big problem, as you know, in small cell lung cancer, and we saw it in both lesions that were pretreated with brachytherapy as well as patients that were untreated. Then with DLL3 levels, with H- scores as low as two, we started to see activity. So a nd in terms of the product durability response, it was still immature at that time. But there are now patients, and we sort of released this at JPMorgan that have been in response for nine months and beyond. We now have confirmation data on all 25 patients. And we started dose optimization that is accruing really well. And we plan to update these results, both the totality of the dose escalation as well as the preliminary data with the dose optimization in the first half of this year. So pretty excited about this product. So far, what we're seeing aligns very well with what we presented at the triple meeting in Barcelona. And we are in regulatory discussions to see how we can expeditiously move this forward. And then I'll just say, with regards to some of the questions that you asked, it's a DAR8. So it has eight molecules of payload per antibody. And it has a very high affinity. And it has this system called TMALIN, whereby there's penetration and internalization of the ADC in cells that bear the target. There is hydrophobicity, so the payload does not get released from the cell. However, the linker is cleaved in the matrix of the tumor and the tumor microenvironment. And it can penetrate cells that are target negative through a bystander effect. So I think the combination of DAR8, the high affinity of the antibody, and this system of high bystander effect is really what's led to this high response rate that we've observed. The specific chemical entity that's the payload is which? This is a topoisomerase I inhibitor, yeah, plus C24. And in terms of the design, as you pointed out, the cleavage in the tumor microenvironment as opposed to the cleavage within the once internalized, how do you see that as an advantage potentially as far as both, I guess, on efficacy and/or safety? There is cleavage intracellularly. There also occurs, but the drug doesn't efflux the cell. The additional efficacy, I think, is related to the fact that it can be cleaved in the microenvironment and penetrate cells that don't bear the target. I think that's what really leads to us being able to see responses in patients that express very low levels of DLL3. In fact, the only patient that progressed did not express DLL3. We only saw one patient out of 25 in that series. Everybody else had some kind of decrease in tumor size. Even the ones that didn't respond had stable disease with some shrinkage. I think it's, again, a high concentration in the tumor microenvironment. When we look at the PK profile of this molecule, there's about four log difference in concentration between the intact ADC and the payload itself. The payload circulates at a very, very low level because it's highly concentrated in the TME. I think it's because of how rapidly it can penetrate cells, including those that don't bear the target. Okay, so obviously, as small cell lung cancer, you're going to go forward, and when are we going to have a sense as to the exact study of what's the next study design going to look like for small cell, and then are you looking at other neuroendocrine-type tumors? Yeah, great question. So we obtained orphan drug designation and have initiated breakthrough designation discussions and other discussions with FDA. The two drugs that are approved in second line, the most recent two drugs, were approved as accelerated approval. And in Imdelltra or T arlatamab, the most recent one is a dis engager, as I mentioned before. I think everybody recognizes that this remains an unmet medical need and there's a dearth of agents that are actually safe and effective. But importantly, because the tumor is chemosensitive, what's required also is durability of response. So we still believe that accelerated approval is a pathway. And we're discussing with FDA what is the best way to achieve this. Obviously, one way is to continue under Project Optimus finding a dose and extending that dose and file as a single arm. And that's what Tarlatamab did. The other way to obtain accelerated approval is to launch a randomized trial and do an indirect analysis for response, obtain accelerated approval that way, and then confirm the approval with overall survival. So I think we will sort of sharpen the strategy as we go forward. And we are doing combinations now in front line as well to start dose optimization in front line and do registration trials in first line under, you know, FDA guidance to move these products early on. You mentioned neuroendocrine tumor. Neuroendocrine carcinomas express at a very high level. And this is really a disease without really any effective therapy. And so there's been a great interest in the field on this molecule. And we just, a few weeks ago, received a May Proceed letter for an IND in this disease. And we have really good centers that are going to start in the next month enrolling patients. And there are recent papers that you may have seen as well as DLL3 being expressed in other tumor types, like certain pediatric CNS tumors, certain subtypes of non-small cell lung cancer, melanoma, and also neuroendocrine tumors that are not carcinomas, but they're slower-growing tumors. So I think our plan is to try to extract as much potential value for patients with this product. But our first I&Dication, obviously, as you mentioned, would be second line and beyond in small cell lung cancer and very rapidly move it into front line and at the same time will obtain data in neuroendocrine carcinoma. So of the two strategies you mentioned, talking to the FDA using Project Optimus versus doing a randomized study, as you pointed out, with the accelerated approval, which of those is the one that seems to be more favored or likely, or that's all up for discussions? You still have to have the data that's just being generated now, obviously. Yeah. I mean, Project Optimus is required anyway. In either strategy, we have to have a dose and agree with FDA on what is the optimal dose. As you know, traditionally, ADCs have had a narrow therapeutic index. So obviously, the agency will, in discussions with us as a sponsor, we will come up with a dose that achieves the right balance of benefit-risk. I think more recently, the agency has advocated for randomized trials, even in the setting of accelerated approval based on surrogate endpoints like response, because it's easier for them and for anybody, really, to ascertain safety. And so that may be a way to go. It will save us having to do a confirmatory trial in second line. And it'll be a single study. Potentially, there could be a speedier registration if we were to do a single-arm study. But as I said, I think it's a bit premature. These discussions with FDA are taking place almost as we speak. So I think we're going to know very quickly where we stand with the agency. And we're also going to start discussions in first-line as well. And there is also the possibility of doing accelerated approval in second-line with a single-arm and confirmatory trials in first-line. So this is also an option that others have pursued. So what is clear, I think, is that in drugs that are effective and safe and have activity that is durable, particularly in the setting of greater unmet need, the agency rapidly becomes a partner with the sponsor in trying to find a way to get the drug to patients as soon as possible. And that's our objective. Okay. So just to summarize on the second line, what is the next data set we're going to get from you? Is what? Just an update and a further maturity on the current 25 patients and then some information about the regulatory strategy, I would think, later this year. Is that fair? What we will present is, as you say, all 25 patients in the dose discussion study with the possibility of confirmatory assessments for response. So all these patients that had unconfirmed response, we will know what the actual confirmed response rate is in each one of the cohorts, as well as the durability. It is possible that we may not have reached the median duration. So we may need to represent this in some other way. But for instance, even in the lowest dose, as I said, we have patients now 10 months and beyond. So we will see how much follow-up we have. But in terms of response, the response rate will be mature. The other cohort that we will present will be the randomization between two doses to arrive at a randomized phase II dose. And so that randomization started a couple of months ago, and we've enrolled really fast. And we should have data both confirmed and unconfirmed on an additional 30 patients or so. So I think in total, there would be 50 patients plus, including both dose escalation as well as dose optimization. Obviously, the latter will have a shorter follow-up than the former. But we will begin to see really at least landmark analysis in terms of what is the proportion of patients that remain on response at a given time point by dose in the dose escalation phase and then by the two doses that were randomized in the optimization. Did you disclose which those two doses are that are getting randomized? We haven't disclosed them, and obviously, they will be disclosed at the time of the presentation. Okay. I guess we can make our guesses as to which ones you decided not to pursue. But okay, we'll wait on that. Now, as far as the front line, so what's the strategy going to be there? You're doing some combo work, correct? So what is the combo? What are you combining with? So the idea is to try to spare chemotherapy in front line. We will retain the checkpoint inhibitor. In our case, we have started combinations with the Atezolizumab. With that and Durva are both approved in small cell lung cancer. And then we're moving rapidly to combine the triplet with the lowest dose of 13. 1310, a nd the third drug would be carboplatin. So our goal is to try to avoid Etoposide, which is very malosuppressive and I think limits the length of treatment that these patients can withstand. So once we have a dose with that doublet of Atezo/Carbo, we will initiate discussions with regards to this phase III study. And it will obviously be compared with the current standard of care, which is Etoposide, Carboplatin, and either Durva or Atezo So, you know, like what's seen with other ADCs, they combine well with checkpoint inhibitors, and t hey, in some cases, have supplanted chemotherapy like that, for instance, in GU. So you're trying to do chemo sparing, but you're not going to get rid of the carbo altogether. Could you try that? We could try that. I think it is premature to say that we could do without carboplatin at this point. And unless we generate more efficacy data, it will be difficult to start a study with just Ateo and 1310. I wouldn't quite rule it out because, I mean, the response rate in second line plus is, you know, in the 70-plus percentage range. That's what the current regimen gives. And so removing those two agents and adding 1310 plus Atezoliumab, you know, resulting similar or superior. A nd the durability may be better just because, you know, patients tend to either become refractory to platinum or become intolerant, you know, after a medium of four or five doses. S o it is possible that we may be able to remove Carbo, but we would have to have some efficacy data first. Okay. That makes sense. And what are the timelines for front line then? You started one already, right? Yeah. We've been in those escalation modes. So we have safety data with atezolizumab. We didn't expect you know, that there would be any issues with tolerability given that the toxicities are different. So we're now starting the carbo combination at the lowest dose of ZL-1310. And we will move pretty quickly to the next dose of 1310 and try to ascertain a dose. And most likely, as many sponsors have done, but again, this requires regulatory discussions. We may choose two doses of 1310 in an initial randomized phase of a phase III study. These doses, are they going to be synchronous with the monotherapy doses? I mean, of the two-year, is it going to be one of the two-year randomizing in the monotherapy, or it could be something else? So in general, I mean, this is not just a question for our asset. It's you know, common question that arises in drug development with active drugs is, do you need to do Project Optimus with different lines of therapies and different combinations? Or is it those different in monotherapy than it is in combination? And in general, the agency encourages sponsors to do dose fI&Ding, particularly if the combining partner agents are different. So in our case, obviously, one is monotherapy, and the other could be a tesla or a tesla cargo. So we will need to do some dose optimization in front line, b ut it is possible that the dose may be the same. It just depends on what the data tells us. Okay. So that's the development plan. And then, as you said, you're going to have the other neuroendocrine tumors. You've listed a whole bunch of those, which starting this year. Yeah. So the second line pivotal trial, we hope to start it this year. We will discuss the best approach in front line. We hope to finish the dose escalation in front line in combination with carbo and then choose which one to move forward with, whether it's a triplet or the doublet. And then we're starting pretty quickly to enroll the first patient in neuroendocrine carcinoma first. And then other I&Dications may follow, but we're concentrating on these three for the moment. But there's a lot of interest in moving this, as I said, particularly in CNS disease, CNS tumors. Okay, then more of a bigger picture question, which is more, I guess, a strategy question, but you're developing a lot of value here, presumably, so what are your thoughts as far as how long you would take this asset forward yourself versus determine it's better suited with a global partner, for an example, to even further accelerate? Yeah. Well, we are exploring all options. Obviously, we're doing all this work ourselves for now. And we want to generate as much data as possible. But we are considering potential partnership or out-licensing, whether it's geographically or we are open to discussions. Clearly, there's potentially a lot of patients that could benefit from this drug. And we wouldn't want to leave any value for patients on the table. And we would like to maximize the potential for this drug. So we will continue to execute on what I related to you. But there's been discussions, and there will continue to be discussions. And I think the decision will come depending on the type of partner, the fit, the complementarity, and you know, whether it's by geography or indication or out-licensing or so on. I mean, those are still discussions that we haven't finalized. Where w e've been open to having dis interactions, but I think it's still early to say, you know, where we'll land. Okay. By the way, I also wanted to get your thoughts because you had some data in, well, you had activity in brain Mets. Is there something specific about this molecule that you believe is driving that activity in brain Mets that may be different from others? First of all, we were very pleased to see it because, as you know, it's so common in small cell lung cancer. Up to 70% of patients have it. And, I think it was really gratifying to see, w e know that there's disruption of the blood-brain barrier in these lesions. But I think the high level of activity probably has to do with its picomolar affinity and also its high DAR as well as this bystander effect. So it readily penetrates, metastatic lesions and you know, w hether they're target lesions or they're not target lesions you know, we've seen actually really important responses that have been very persistent. My sense is that it probably has to do mostly with the system with this TMALIN system again the high affinity but also the half-life. This is an ADC that has a half-life of about a week six to seven days, whereas others that have not seen a lot of activity in the brain have a very short half-life. So you know, I think dwelling time in the metastatic deposit may also influence the ability to elicit responses in the brain. Okay. And then there are other ADCs hitting other targets, right? So for example, like a B7-H3 or B7-H4, for example, and there's some other ones. What do you believe is different with the DLL3? Is it just the expression level or something else about the tumor biology that makes it possibly a better way to deliver the chemo? Well B7-H3, if you look at the molecules that the ADCs that are out there, the responses have been in the 30s, 40s, except for YL201, which is a Medi Link B7-H3 ADC, which also shares this TMALIN system as well, where they've seen responses in the 60s. I think, and what we hear from our investigators and other opinion leaders is that, you know, there is no gross resistance between these targets. And so, you know, it's good that there's another agent out there that has activity. Expression of B7-H3 is at least 10% lower in most series than DLL3. DLL3 is almost universally expressed. There are some differentiations between YL201. I mean, again, the half-life is shorter. The affinity of the antibody is lower. Whether that translates into differential activity and durability, I think it remains to be seen because we need more maturity of our data. But at least numerically and from what we are observing, we think this is probably the best-in-class ADC that exists for small cell lung cancer. S o, and of course, there's other modalities, as you know, a nd we talked about tarlatamab, but that's a different mechanism of action and different level of activity. So yeah, I guess the main point I would make is that although B7-H3 is present in small cell lung cancer, most of the molecules that are out there in development are not achieving response rates in the 60s and 70s, except for the MediLink molecule. Right. Okay. All right, l et's see. Let's move on a little bit since we've spent a lot of time on DLL3. All right, So for BEMA, that's the FGFR, can you just tell us that data is coming up quite soon, no? And what do you need to show for a phase III study in front line gastric cancer to be successful? That's the one obviously partnered with Amgen, used to be the Five P rime drug. That's right. This was a Five P rime drug. S o there are two studies in this program, both in FGFR2B expressors. One is with NIVO and the other is without NIVO. So the first study, which is 101, which is the one that's going to read out first, is 446 plus minus Bemarituzumab. We expect the data in the Q1 of this year, so soon. A s you know, the phase II data was extremely promising. I mean, the control arm in the phase II study was pretty much in sync with what you would expect, less than a year with placebo and about 25 months with Bemarituzumab. So obviously, that was a phase II study. It was again, doubling of survival with a ratio of 0.5. So that really, you know, sort of gives us a lot of hope and enthusiasm that we are going to see positive data, but we will have to see it once the data is uncovered. And we plan to file this year in front line. Then the second line and the front line with Nivolumab, which is 102, there will be an interim analysis, but the final readout is still to be determined. It depends on, you know what, whether the study is positive and the DMC makes a recommendation this year. Now, this is one of those situations where Zai contributed to the global study. Is that right? Yeah, that's very true. How much did you contribute? Did you talk about that? Well we contributed particularly in the 101 study because it's a study that was very difficult to do in the West because of the advent of NIVO. Even though NIVO only added a little less than two months to survival, it was very difficult to accrue to a non-CPI arm study. So that wasn't really so much of a problem for us in China where gastric cancer is very prevalent. So we went above and beyond what was required for us to be able to submit to CDE. And this was for the sake of the program and accelerating the program. I mean, then the numbers were in the 150-plus patients and so on. On the 102 study, we've been able to bring that study about five months forward just by adding more patients from China. I think Zai has been really instrumental in the Bemarituzumab program, and it's been a wonderful partnership with Amgen to be able to hopefully bring this drug a lot sooner working together. But you're going to, if you hit on front line gastric in the first study, then you file right away, and then the NIVO one comes later? That is a discussion that's being had. It depends, and I'm not sure what Amgen has announced yet, but certainly our desire will be to file IND first. Okay. All right. Let's try to hit a few of the other earlier programs. So you have another ADC. This is targeting LRRC15. First of all, can you tell us a little more about that target? That's not one that's super familiar to most people, and I get the sense it's probably less competitive than DLL3, but maybe there are a lot of early preclinical ones out there that are under the radar. Yeah, it is a target that's expressed in fibroblasts in the tumor microenvironment. And so the initial idea was, can we disrupt the tumor microenvironment and cause shrinkage of tumors? And also because of this bystander effect, because this has the same, even though the antibody was discovered at Zai, the cross-linking is with the TMALIN system. By having the tumor microenvironment cleave the linker, then target cancer cells that don't express LRRC15. So I think that question has never been asked with an ADC, and it's one that I think deserves to be answered. But in addition to that, there are tumors that express LRRC15 in their own right, particularly sarcomas. Osteosarcoma almost universally does, and then about half of the soft tissue sarcomas do as well. So they are both in the fibroblasts as well as in the cancer cells themselves. And there was a molecule called ABBV-085. I think, a DAR 2, but still encountered some toxicity. We believe that this being a next-generation molecule will behave similarly to DLS3 with regards to the toxicity profile and potentially the doses could be similar. And I think being able to understand this idea of using the fibroblasts as targets and then the bystander effect on cancer cells for the non-expressing tumors and also the target itself in tumors such as sarcomas, we've seen it in certain subtypes of breast cancer, I think has a lot of merit. And we are pretty excited about having this IND open this year and start enrolling patients. Okay. There are a few others we can just very briefly touch on, and then we can maybe ask a bit about autoimmune. So there's a ROR1 ADC, and then you have a CCR8, which is not an ADC. How do those fit into the prioritization of resources and level of investment? Yeah. So briefly, ROR1 could be our next product IND. We licensed that and we have global rights. We licensed it from BAPIA. A nd ROR1, as you know, has been shown to be validated in lymphoma. It is expressing solid tumors, and we've done extensive studies across multiple solid tumors, endometrial ovarian triple-negative breast and others. And we plan to go to solid tumors first with this product. So that's ROR1. CCR8, it's an antibody that essentially blocks the cytokine, which is critical for migration and the population of Tregs in the tumor microenvironment. A phase I study continues. We haven't said very much, but we are testing it primarily in tumors that are not susceptible to checkpoint inhibition, perhaps because of the inhibitory effects of Tregs. And so far, we are pleased with what we're seeing. And we are still in dose escalation and scheduled escalation as well to see because the dynamics of repopulation of Tregs vary in different organs. And so the studies still continue in the dose and schedule setting. But we are actually pleased with what we have seen so far with this product. So we will make a decision on it as to whether to move it to the next stage by the middle of this year. Okay. Let's try to sneak in a few non-oncology questions. Even though this is technically the virtual oncology summit, I think we'll give you a pass since we have a lot of interesting things. So tell us quickly, you have an IL-13, IL-31 bispecific, which is an interesting combo. What's the design rationale for that, and how is it going to be differentiated potentially from Dupixent? Yeah. We're actually pretty excited about this molecule. You know, these are proven targets. As you obviously know, Dupixent is IL-4. We think IL-13 may be safer, and there's perhaps some evidence that there may be less conjunctivitis and better tolerability. But because it's linked to 31, so 13 blocks the ligand, 31 blocks the receptor, it involves an itch-scratch inflammation cycle that is seen in atopic dermatitis. And that's key contribution to increasing the speed to resolution of these lesions as well as the durability. We presented some data showing that it is effective in animals and that in non-human primates. And we're seeing, interestingly enough, a long half-life that I think would allow a long interval of self-administration that would make this a more convenient, more active, potentially less toxic product. So definitely one that we want to put a lot of resources on to take to phase I-B or prepare as phase II-B. But you know, the development in atopic dermatitis and other pruritic disorders, including also other disorders like asthma, et cetera, I mean, these are formidable sets of studies that are required. So we want to demonstrate proof of concept that this is actually a superior molecule and hopefully be able to partner with the best possible partner to develop it in AD and other disorders. But so far, everything that we've seen preclinically and in GLP tox has been pretty positive. Okay. And then the other one was the, which this one's a little bit more advanced, but still in phase II is the topical IL-17 for plaque psoriasis. How's that coming along? Yeah, that study is accruing. It's accruing pretty well, actually. It has multiple arms that it's testing different strengths and different schedules, and it's against placebo, and we're coming up to an interim analysis in the second quarter, and we will, that will determine namely activity and then a number of other translational markers as well, but we will get a recommendation from the IDMC as to what the next steps are, but we're pleased that the accrual has been brisk, and we will have a preliminary answer in an interim pretty soon. Then the last one on autoimmune is the deal you mentioned, I think you did with Vertex of Povetacicept. So that's for IgA nephropathy, which is an interesting market in China. What are the plans there? And I assume you're going to need to do some kind of local study similar conceptually to what you did with KarXT to get the bridge data. It may be a little different. There are some Chinese patients that are already being enrolled. And so having patients already in the pivotal trial coming from China is always more desirable than doing a specific bridging study, as you know. So we're very pleased that the stage of the drug was such that we can just accelerate enrollment in that study. So it's a very prevalent disease in China and one in need for therapies. There are other molecules, but we think this is best in class, and we're pretty excited with this collaboration and putting resources to expedite enrollment in the global study. Okay. And then last big picture question going back to oncology. Obviously, you're a pretty heavy footprint in ADCs as well as just classical antibodies. What about other areas like radio pharma? It's getting more interesting. There's lots going on there. Or any next-generation immuno-oncology targets? There's a long list there. Are those areas you're focusing on for future BD? Yeah. So internally, we have molecules that are aimed to enhancing PD-1 activity like others. And I think this stems from the success of the PD-1 blockade. But there's a lot of data suggesting that there are cytokines that in a bispecific manner with the right stoichiometry, you could deliver those cytokines that otherwise would be too toxic in combination with PD-1 and obtain better activity. So those were made in-house, and we plan to move those into IND enabling studies. And the other aspect that is immuno-oncology is T-cell engagers. And we think that these are orthogonal approaches to ADCs. They obviously work very differently. But there are some really unique and interesting targets that could be approached with one or another type of modality. We are obviously right now have more ADCs, and we just named some that are recently acquired. So you may see us this year starting to penetrate the T-cell engaging field. And we have some potential partners with whom we may start first in autoimmune disease and then move into oncology. Okay, so did I hear you correctly that you do have a VEGF PD-1 or PD-L1? No, no, no. Our combinations are bispecific with specific cytokine, not VEGF. Not VEGF. Okay. But a PD-1 on one arm or a PD-L1 on one arm. Correct. But it sounds like you haven't talked much about that yet. No, we haven't talked very much about it yet, and we will in the future as we develop more data. Okay. Awesome. All right. Well, thanks again. Appreciate it. A lot going on, no doubt. We're looking forward to seeing everything evolve. Thanks, Rafael. Thank you so much, Yigal, for your interest. You're welcome. Pleasure. All right. Bye-bye.