My name's Peter Lawson. I'm one of the biotech analysts at Barclays, a covered mid-cap, predominantly oncology-focused companies, but it's also interesting to see many oncology companies pivoting and moving a little bit to other areas and other indications. Up on stage with me, I've got Nurix's management team. We've got Arthur Sands, President, CEO, and Hans van Houte, CFO. I'll be moderating this, but if you have questions, do email me, peter.lawson@barclays.com. With that, first questions I've been asking a series of companies, and they're mostly no impact kind of questions, but supply chain disruptions. Anything you're kind of thinking through and worried about just with tariffs, or are you kind of prepped from COVID in a sense? Our supply chain is based in the U.S. and Europe primarily, and it really has to do with starting materials and production of the drug. We do not really have issues that we can foresee at this point with that. We have carefully moved things out of Asia in terms of starting materials, etc. Production of our clinical trial drugs looks fine. I mean, there are no issues. Yeah. Okay, perfect. FDA, I know it's kind of early days and fear of cuts there. Are you seeing any change in the speed of communication with the FDA, or do you anticipate? We've seen no change. Of course, we're in the oncology division. I don't think there's going to be a lot of changes there, but no, things have been moving along really at a good clip, actually. Okay, perfect. Thank you. I guess a longer-term impact, very likely on innovation, would of course be NIH budgetary cuts. Whether you share that view and do you see if there's kind of near-term or mid-term impacts around that? As a drug discovery company ourselves, I mean, we really are pretty much independent of NIH and considerations there. We do not really see that impacting us in the near term. In the long term, perhaps, but that is the long term. On your pipeline, the CLL study, your BTK inhibitor. I guess the first question is, what we've seen so far, and what are we going to get from the next update, which I presume is probably kind of an ASH timeframe, year-end-ish kind of timeframe for the updates, or? Yeah, our lead candidate is NX-5948, which is a BTK degrader. It removes the protein from the cells, a small molecule, once-a-day drug that is currently completing our dose expansion study in phase Ib. We've been on a cadence of every six months having updates on the program. We target our European colleagues and audience at EHA and other conferences in Europe mid-year, and also ASH at the end of the year. They're, again, providing updates on the trial as it progresses and the data. We've had terrific data, I think, as we've gone forward from ASH 2024, where we're looking at a 70%-80% overall response rate with NX-5948 in very advanced CLL patients. We expect that to continue. Of course, we're wholly focused on starting our pivotal trial this year, as well as a randomized control trial to go with that. That is kind of the pace we're on. It is a very vigorous pace for 2025. Gotcha. What should we look at for the next update? I guess mid-2025, EHA-ish kind of timeframe. Our data continue to be solid. I think we'll give a data update, but I think most people will be interested in our regulatory approach for the pivotal trials. It will really be an update about how do we progress this from a regulatory perspective towards registration. We hope to have clarity mid-year on that and be able to share that. What are the things, what are the outcomes we should be thinking about as you think about the regulatory strategy and path? Yeah, so in CLL, in third line plus, so post-BTK inhibitor therapy, post-BCL2 inhibitor therapy, this is a fast track status population that we have been granted from the FDA. We have PRIME status from the EMA now, which was excellent. The question really is, what is the, is there an accelerated approval pathway, and what is that pathway? What is the trial design for accelerated approval, and what would the confirmatory trial be, and what is that design? That really is the key, I think, the key questions for us in the next six months. Would that confirmatory trial kind of move you into an earlier line, or how do you think about that? Do you think about it as kind of additive potentially to the label, or just confirming that label? We think of trying to move it to an earlier line. From third line for the accelerated approval study to a second line setting for the confirmatory trial, that would be essentially a label expansion from the third line setting to the second line. We have designs also for first line trials, but those are more in the future. Right now, 2025, it is the accelerated approval pathway for 5948, and then the confirmatory trial. Gotcha. Thank you. For that second line setting, would that be monotherapy, or is it better to combine, or how do we think about that? Definitely monotherapy is prioritized. We're seeing, again, great results with monotherapy, and it's the most rapid pathway. It continues to be the largest market segment with a once-a-day medication for CLL. Combination would be more of a first line setting. Okay. As we think about that first line setting, what would be good combination agents? Are there things that are off the list or on the list that it can combine with or can't? You know, there's several options. The main one would be BCL2 inhibitor, most likely venetoclax, which is part of the standard of care in the second line at this point and also in the front line. Combination with venetoclax, which would combine then the BTK degradation, our drug 5948, with blocking BCL2 pathway, which are two of the major growth signaling pathways in B cells. I think that would be a very exciting combination, actually. There's been great results with inhibitors Plus BCL2 inhibitors, but to combine it with a degrader, I think will be really more powerful. It actually could be a very exciting study. Yeah. I guess one triangulation point, it's probably going to be difficult to ask, but like the VenaSys data set where they kind of didn't show it functioning in the broader group, but it works well in the ESR1 population. Are there any fears? I guess fundamentally, some investors we were, some KOLs were thinking, well, it's a different mechanism of action, so it's going to function differently from the other oral SERDs. Are there any worries that as you get into broader populations or earlier populations that it doesn't work as well? Just trying to make a tenuous link between two degraders. Yeah, valid question. In our trial currently, we have patients with wild type BTK, and we get a tremendous response rate in wild type BTK. We also see the same response rate basically in mutant BTK. In this setting with BTK, which of course every target is different, they're working on estrogen receptor. With BTK, we see our degrader works on wild type as well as any mutant form and any of the resistant mutant forms resistant to current inhibitors. We see a very broad activity spectrum already in the current trial. I think there's every reason to believe that would translate to second line and front line, because wild type is wild type and we're seeing responses. I'm very confident that the degrader mechanism in this setting will translate to earlier lines of therapy. Perfect. Thank you so much. Kind of as we think about that update, would you, I guess, break out efficacy with the lower dose, like the 200 milligram versus the 600 milligram, kind of, what should we be thinking about how that data is broken out at EHA, whether it's EHA or mid-2025? Yeah, I think with regard to the 1B study where we're looking at 200 randomized and 600 to satisfy Project Optimus that has taken an early look at the optimal dose, we see no difference so far in safety profile. That's number one. It's really about the safety profile. That's the goal for Project Optimus. Do you see any safety signals differing between the doses? So far, we don't see any difference. At the higher dose, we do think that will provide potentially superior coverage, but that has to be, we have to look at that when we get the results from the randomized study, which is ongoing. Those results will likely be towards the end of the year from the randomized study in terms of reporting. Gotcha. Okay. What's the appropriate bar? I guess the other BTK inhibitors out there, again, to PFSs of like 14 months or so. Is that a sensible bar to get to? Yeah. So the PFS is with pirtobrutinib, you're talking about the non-covalent? Exactly, yeah. Yeah. They seem to be around 14 months. I think that is one bar. Right now, our overall response rate is in the 70%-80% range, which is trending above what non-covalents have achieved. We would hope to trend above in PFS also. Do you see a correlation of those response rates and PFS numbers in CLL? Does that kind of add to confidence around moving the PFS number out? Yeah, I think it does. Now, degraders are new, and we think that the durability will be superior to inhibitors, but that's what we're measuring right now. It is just obviously going to take time. The enrollment's going well. It's still a relatively young trial in terms of the number of patients that have enrolled recently. We have to see that duration of therapy and that duration of response. That's really, I think, probably the next major data point to look at. Gotcha. How do you think your, I guess, the comparison between you and BeiGene or B1 Medicines, how those BTK inhibitors are kind of shaken out? Is it more similar than dissimilar, or? Right now, both agents look fairly similar in terms of efficacy. I'd say that that's confirmatory that this new MOA really is working, and it's working in two companies' hands. That's very encouraging. I think it's been, again, a confirmatory sort of situation with both compounds and high efficacy rates, again, so far. The question, I think, will not be differential based on efficacy, but is there differential based on safety? That's usually the way compounds end up becoming differentiated. Okay. At what point do you think that pans out? Or I guess we've already seen a little bit of that in prior data sets. Yeah. I mean, our goal is to be best in class, which means both efficacy and safety-wise. You're going to have to see hundreds of patients' worth of data to really see if, because basically the mechanisms appear fairly safe already. You need hundreds of patients to see if there's any differential. Gotcha. Is there a difference in CNS activity? I know you showed some. Is that a differentiation point compared to B1? Yeah, very good point. We have activity in the CNS. We enroll patients with CNS lymphoma and leukemia, which is a very severe state of disease. We have had some dramatic responses with those patients. I think that is a point of differentiation. Typically, those patients are excluded from studies, which has been, I think, the case with the BeiGene study to date. We are seeing good CNS activity. We also opened a cohort in CLL for patients that have autoimmune hemolytic anemia, so an autoimmune manifestation of the disease. That is about 10%-20% of patients. That is a new cohort. We see very broad activity against most of the severe disease situations. Gotcha. Before, we definitely want to touch upon the autoimmune side of things, but trial start dates for the pivotal, is that this year? How long was, what are the gating factors to start? We definitely, our goal is to start the trial this year, our pivotal study, as well as the randomized control study, the confirmatory study. That is definitely on deck. The gating factor is really finalizing the clinical trial design plans in discussion with regulatory agencies, both U.S. and Europe. That is ongoing. That will be a big step forward. It will make Nurix a late-stage company to actually go towards approval. Also gating would be selecting the dose to take forward. That is in front of us too. It is all on track to happen, I would say, mid-year. Perfect. Thank you. As we think about the autoimmune information kind of programs, kind of what are the key milestones we should be thinking about for 2025? As I said, we're opening a cohort with autoimmune hemolytic anemia in CLL. We're also in process to evaluate filing an IND in the non-oncology hemolytic anemia setting. Those would be, I think, two key milestones: seeing data from the CLL cohort and also then moving forward with the IND in the non-oncology setting. The beauty of studying the hemolytic anemia indication is that we have very rapid readouts there, which of course we're looking for elevation of hemoglobin as we block the destruction of red blood cells. Those tend to be at 12weeks-24 weeks, we can see rapid readouts. Those would be some of the data we hope to see. Gotcha. Okay. Sorry, the timing around the IND, is that kind of a second half? Yeah, I would say second half. We haven't specified beyond that. Okay. And then the. Oh, go ahead. I'll make it a long question. The scaffolding function of BTK, how important is that in autoimmunity versus oncology? Is that a key factor? Yeah. We have published at the American College of Rheumatology meeting in November, we had a poster demonstrating how the scaffolding function creates a much more potent suppression of B cell signaling in wild type cells. In normal cells, which of course in the non-oncology setting of autoimmune disease, the cells are genetically normal, but we are seeing a 10-100 fold greater suppression of B cell signaling compared to BTK inhibitors, which just block the kinase function. When we take out the whole protein, we are definitely seeing an increased blockade of B cell signaling. We think that is going to translate to potentially increased efficacy in the autoimmune setting. That is a really distinguishing factor. We do think that is going to be very important. The BTK inhibitors have shown signals of efficacy in autoimmune disease of a variety of sorts. There's been a number of trials done. We think there's definitely room for improvement by removing the protein, by degrading it. Gotcha. Okay. Maybe kind of a higher level question. How do you think about entering these marketplaces? Is that something you partner? Is just the process you think about it and how it kind of impacts cash burn? Turn to Hans. Yeah, sure. I mean, we ended the year with a very robust cash balance of guidance in the first half of 2027. I think as we look at aggressively pursuing 5948, our posture right now is we're doing that as a standalone entity and looking at opportunities for partnering as they arise. It would have to be on the economic terms that we and our investors would be happy with. Right now, we have the wherewithal to drive these programs, especially 5948, through the clinic, starting the pivotal trial, starting the randomized confirmatory trial, and moving that along. We plan on doing it globally. We plan on basically starting both trials with a global footprint. The ability to do potentially a regional partnership, ex-U.S., is one thing that we've thought about in terms of retaining the U.S., at least in the short term. If there is significant partner interest at economic terms that are viable for Nurix, where it gets to keep a great percentage of the rights and basically has still a great amount of control over the program, which is the other thing that we're thinking about with potential partners, we would look at that very closely. For an ex-U.S. partner, would you go for one that would kind of cover oncology and autoimmunity or is anything all up for grabs kind of thing? It probably would be difficult to find one partner that would cover both indications. We have to see how it evolves. I mean, it is early for the program in terms of autoimmune indications. I think the more control we can keep, as Hans said, the better, and maximize the value of the asset before any kind of partnership. Gotcha. Thank you. And then just using a degrader in autoimmunity, are there any risks of complete removing BTK versus oncology? That is where we are very encouraged by the genetics. There are, of course, patients, humans lacking the BTK gene completely, which is how it was discovered originally. They have a suppressed immune system, but otherwise a very safe profile, target profile. We already know genetically removing the protein is safe and it will suppress the immune system. There are precedents genetically that give us great confidence that this is a very safe mechanism and a very potent mechanism. The BTK inhibitors are clinically validated as well. Yeah, so. How would the BTK inhibitor kind of fit in with hemolytic anemia? Are there other BTKs already in there? Is it displacement? The combinations you'd have to be working with? There currently is no approved therapy for the warm autoimmune hemolytic anemia. Steroids are given. It has kind of become a standard of care, if you will, but not desirable because of the issues and side effects of steroids. I think that a BTK degrader, well, it would be the first in the space. There are inhibitors that have been tried in a variety of autoimmune indications. There, again, are hints of efficacy. ITP and other cytopenia BTK inhibitors have shown some efficacy. There are definitely reasons to believe that blocking BTK will be of therapeutic value. Again, room for improvement over the inhibitors. We think degraders can supply that. Gotcha. Thank you. Before we finish, I'd love to touch upon your partnership, so IRAK4, STAT6. What should we be expecting this year? I know it's kind of always hard when you've got Gilead and Sanofi as a partner and how much you can disclose. Yeah, so these are two very important programs, IRAK4 and STAT6, where Nurix has the option to opt in 50/50 in the U.S. ultimately after human proof of concept. What we expect in the first half is Gilead is in charge of filing the IND for the IRAK4 degrader. I think that would be a very important milestone if that's achieved. Second, we are supplying a development candidate package to Sanofi in the first half. These are both targets that are very important autoimmune targets. Sanofi has the option to take that forward into IND enabling studies and the clinic. Those are both first half events. Perfect. I guess just maybe final question of the starting dose for your BTK degrader in autoimmunity versus oncology. What's the delta that we should be thinking about? Yeah. We have a wide spectrum of dosing capabilities. We do think that the different autoimmune diseases will need different doses. We are currently using the same formulation for oncology in the autoimmune hemolytic anemia settings and starting with the same dose, which would be 200 or 600. In the future, we're going to do a dose ranging study. We'll have to determine what the dose really should be. Perfect. Thank you so much. Okay. Thank you, Peter. Thanks, Peter. Always a pleasure talking. Thank you. Yeah. Thanks. Yeah. Thanks.