All right. Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, senior analyst covers mid-cap biotech. It's my pleasure to have my next fireside chat with Nurix Therapeutics. We have CEO Arthur Sands. Welcome, Arthur. Thank you. Great to be here, Roger. Awesome. All right. Nurix is in a very exciting time frame. You're in a pivotal for your lead program, also you have a platform to supporting a lot of the early pipeline development well across the oncology and in I&I space. Maybe, Arthur, give us the latest about Nurix, we can dive in the conversation. Well, the latest is we're coming upon EHA, European Hematology Association conference, essentially next week in Stockholm. We'll have an oral presentation there. It'll be a significant, I think, update on bexobrutideg, our lead BTK degrader program in CLL. In that presentation, the abstracts have been published there, in the presentation, we'll be giving updates on some of the latest cohorts of patients, new data related to earlier lines of therapy in CLL. We have some treatment-naive patients who are now treated with bexobrutideg as their first treatment for CLL. Also, patients who have not received a BTK-targeted agent at all yet, so BTK inhibitor naive, and then they'll be getting our degrader as a first BTK therapy. Also patients who have not received a BCL2 inhibitor, venetoclax, for example, yet. These are early stage. Those would be second-line types of patients. These cohorts of patients we'll be describing, that's going to be a significant event for us. Of course, we have a lot of European investigators we're meeting with in Stockholm as well. That's coming up. I think that also people have been very interested in the progress on our other fronts in I&I, namely the status of our STAT6 degrader, which is partnered with Sanofi, and I'm sure you'll have some questions about that. Also our IRAK4 degrader, which is partnered with Gilead. These are all partnerships where we maintain a 50/50 opt-in structure as well. Those are progressing. Bexobrutideg itself, we're very interested in advancing that into autoimmune indications as well. That'll be a second-half sort of events for us. Excellent. All right. Maybe we can spend a few minutes on the CLL, the lead program for now. I think it's interesting you will start to report some earlier line of the result even without the BCL2. I understand that you are also trying to do the combination approach to moving to the early line. Where are they in the combo, with this, I believe it's a mono data, how this profile will support the combo, when we're going to start to see the data? We're intending to start our first combination trial phase I-B/II program with bexobrutideg in combination with a number of agents. Venetoclax, a BCL2 inhibitor, was one of the primary combinable drugs, that would enable a frontline approach as well. What's exciting there is that this would be the first BTK degrader combined with venetoclax in the clinic. Investigators and I think patients are very interested in the potential for fixed-duration therapy. Therapies that would last a year or two years, likely two years, on the combination regimen, have basically a drug holiday or no drug period. That's one potential. In addition, anti-CD20 antibodies are of high interest in combination. Rituxan being a mainstay, of course, obinutuzumab as well. There's multiple other combination potentials built into that protocol. It's a phase I-B/II protocol. That's poised to start mid-year. Of course, data would then take a year or more after that. That's sort of next up for a trial start. At the same time, we're starting our big phase III program in CLL monotherapy. That's in second line. These are patients that have received a BTK covalent inhibitor but have progressed. That trial will be starting mid-year as well. That's about a 600-patient trial, will be in over 20 countries. We're very busy in terms of trial initiations and trial execution. You mentioned the pivotal trial is running. That's a phase II trial, about 100 patients. That's in a later-line CLL patient population. Yeah, all of that is moving forward, so very busy mid-year for us. Excellent. As you mentioned, you are doing the mono pivotal as the third plus line, triple-exposed, I believe that's the population you are doing initially. We also know another BTK degrader is running, slightly different setting, but also later line. They may have data earlier, then you will have data next year. When we see the data, what you are looking for in terms of the ORR, PFS, maybe some of the safety signal, tolerability, those. What will be considered as a good scenario for Nurix to be able to maybe even benchmarking and then also the beating there? You're talking about in the later-line patients? Yeah. Yeah. Later-line first, yeah. These are third- line, fourth-l ine. We've had patients with six lines of prior therapy, actually up to 10 lines. What we've seen so far in those patients is around a 70%-80% response rate. The response rates do go down the later lines of therapy that patients have had. I think if you look at fourth- line plus in general, anything between 50%-60%, 65% is an excellent overall response rate in those fairly late-line patients. You contrast that with some of the early line patients, we're seeing 85% or greater response rates with the BTK degrader. I think those are quite strong. As you go across the lines of therapy, obviously we want to position bexobrutideg to be able to serve patients at every line of therapy, wherever they are in their CLL journey. Then also NHL, we're also interested in expanding in NHL indications as well. Yeah, those are the data to look for. Also compare and contrast the other BTK degrader. They're also in the pivotal right now. How you think bex can differentiate in the later line star and then early line probably will be a bit too early to compare? Well, our goal is to be best in class in the degrader class. There really are only two degraders really that are up front and center now in drug development. We think we have the highest selectivity profile. We certainly have the highest potency compared to any other degrader molecule, and that should translate into higher efficacy and better safety. That's really the profile we're looking for, and that's so far what we've seen play out. We've now been in over 150 CLL patients at various lines of therapy, as we discussed. The profile is remarkably consistent. High ORR, excellent safety profile, relatively low infection risk compared to other agents, no major bleeding risk, which is also a distinguishing feature compared to BTK inhibitors. We have an excellent liver safety profile. We've not seen any elevation of liver enzymes. That's also been a bit of a hex on the BTK inhibitor class in general. I think the degrader class, and specifically bexobrutideg, has great potential to be this best-in-class profile. A lot of mechanistic reasons for that, Roger, some of which I'll just mention. I know you know them, the catalytic nature of degradation. One drug molecule of bexobrutideg, I'll call it bex-deg for short, can degrade 10,000 BTK proteins per hour in the cell. One drug molecule removing 10,000 drug target proteins per hour. This is fundamentally different PK/PD compared to inhibitors, where it's one to one. You need one drug molecule for every BTK protein. You really have to swamp the system with drug, and that's how inhibitors work. Degraders work catalytically because they harness this incredibly efficient proteasomal machinery in the cell. That's how we work. We're fundamentally different. We think we're going to have a fundamentally better safety profile. The big picture is we're talking about BTK, but this technology has the potential to replace many inhibitors because of these attributes. Yep. Makes sense. One of the other discussion I've been having with the investors and then also with you is the sequence of use all kinds of different BTK. We have a covalent, we have a non-covalent, and then now we're about to have a degrader coming to the line. What's the biological or clinical rationale to use which modality first at the first line, maybe second line, and then save to the later line? Which makes the most sense? Well, the clinical rationale is that the better initial result a patient gets from a drug, the better their prognosis is overall. There's a strong rationale in cancer therapy in general to start with the best regimen, start with the best drug, get the best result, the deepest response, the longest lasting response that you can get in your initial treatment. You will live longer than your progression-free survival. Overall survival is all improved. That's the clinical rationale to start with the best agent up front. That's what we've seen going on in CLL. This whole targeted therapy started with ibrutinib, which was a very great advance, but then has been displaced by acalabrutinib and zanubrutinib. Better safety profile, better adherence to the drug regimen, and better prognosis. Those agents have become frontline. We think that can happen with degraders. Degrader is clearly superior in terms of hitting the target, and we think going to be superior in terms of efficacy and ultimately safety because of some of the reasons I mentioned already. If you have the best result up front, the patient will do better and live a longer, healthier life. That's the rationale to start with your best foot forward, and the degrader would be the best foot forward, I think, in the future for BTK-targeted therapy. Yeah, it's a cancer patient, right? Best for forward is probably not the logical choice. The only thing is, degrader is powerful, right? When you knock down the entire protein, would you develop some resistant mutation? Maybe no other therapy you can address versus covalent, non-covalent. A non-covalent can address a covalent mutation, non-covalent mutation can address by the degrader. That's a sequencing potential logic as well. How you respond to that? Well, what we know so far is that the BTK inhibitors basically select for resistance mutations that are coming up in now over 50% of patients. Once you have a resistance mutation, you then have to try to overcome it with another therapy, either combination or in the case of degraders, we can overcome all of those resistance mutations. That sounds like a logic to start with an inhibitor, and then you have a degrader in the second line. Yeah. Why ever develop the resistance mutations in the first place if you don't need to? Yeah. That is why you should start with the best drug up front that doesn't even allow for resistance. Or at least is harder to become resistant to, is what we're seeing in the clinic. The degrader is harder to get around. Cancer can always get around drugs, and so there will be resistance mutations that will occur, but you want that to be a low-frequency event, right? That's why a degrader would be superior. In terms of what are the mechanisms of resistance to degraders, well, there's one mutation that's been identified. It happens to be also a mutation that inhibitors don't work on, and that is the A428D mutation. Basically, none of the BTK-targeted agents work against that. It's a very rare mutation. Fortunately, it is also what's called an unfit mutation. The cells actually don't even grow very well because the BTK is so mutated it does not work well. By the way, it responds to combination agents very easily. That mutation is not really a big threat. Anyway, I hope I've answered the rationale to start with the best drug up front. We think that's going to be a degrader eventually. Yeah. Then you do have a solution as a combination go beyond the BTK if you develop something not necessarily addressed by the BTK approach, right? Yeah. I think with venetoclax and a BTK degrader, you're basically going to take out anything. Yeah. We're focused on BTK, but there are a lot of other mutations that take place in these patients, unfortunately. Yep. P53 and other really bad actor mutations. Those all need to be dealt with as well. That's why combination agents will be necessary. I think Nurix is well-capitalized to run the ongoing phase II as the monotherapy and then also fund the phase III for the mono, also mono in the second-plus line. How do you think about the earlier line strategy at the company level? You want to do this standalone, or you think it's better to find a partnership? I think the frontline strategy, partnership makes a lot of sense. Number one, you're going to be combining with an agent. Again, our lead choice would be venetoclax. These are agents that are expensive to run in combination trials, so great to have a clinical trial partner of some type. There's also all the antibody agents, bispecifics. There's a lot of combinations. It almost becomes kind of an endless opportunity. To do that solo is challenging. Yeah. Yeah, we do favor partnership model in general. We've done several very successful partnerships with Sanofi, Gilead, Pfizer. Currently, all of them involve options for Nurix to go 50/50 in the United States, and co-co. We like those kinds of structures. There's a lot of opportunity for partnership in the CLL space, and that's not even to bring up yet the autoimmune area, where that's another huge market opportunity. Yeah. We'll talk about the I&I in a minute. Yeah. Before that is, I think you've been running the trial in NHL for a while, and then we haven't seen much data from there. You plan to release some data this year, and what should we kind of expect from the NHL cohort? Our data release periodicity tends to be every six months, EHA and ASH. We are talking about potentially NHL cohort data at ASH. We haven't settled on what we'll submit. We have seen some really dramatic responses in every category of NHL. We've seen some complete responses in every category. We've included patients with primary CNS lymphoma. We're talking about DLBCL, and MCL, mantle cell lymphoma, and Waldenstrom's, where we have shown some data. There again, seeing this 85% response rate. I do think NHL will be an area for us in the future to have more disclosure, more publication. It's also another area for combination therapies too. Yeah. Okay, good. I&I is a very interesting thinking about the degrader approach because the scaffold function, et cetera. I think recently, CSU, some of the early data by other degrader, you're also thinking about developing into different indications. Right now, what's the thought about the indication selection? What's the area you want to go first and then proof concept for the degrader? I think that the advantage of a degrader in I&I is actually somewhat similar to what we've seen in oncology. You hit on it, which is that we're addressing both the kinase function of BTK in this case, but also the scaffolding function or the structural signaling function. There's another whole signaling pathway going on with BTK that kinase inhibitors don't touch, and that's operating in autoimmune disease also. We're excited by what we can do there from a theoretical standpoint. What we've done so far is conduct a very significant healthy volunteer study with our new formulation designed for autoimmune disease. We did have a little bit of data come out at an oral presentation in Chicago at the dermatologic meeting recently. Yep. Where we show complete degradation of BTK in the skin of healthy volunteers at low doses, and this is once-a-day dosing. I think we'd like to see the rest of the data from our healthy volunteer data set, and then our goal is to file an IND in the second half of this year. I think CSU is a very logical place to start. It has proven successful for Novartis, with remibrutinib. Data looked quite good, and I think the uptake has been very positive for that drug. That's a twice-a-day drug, I think, and also an inhibitor class drug. Again, we think we can improve on that. Yeah. Awesome. It seems the scheme makes a lot of sense. Any other therapy area for I&I potential? Well, the other one that we're very interested in is multiple sclerosis, so MS. We have activity in the brain. We know this from our patients with CLL and primary CNS lymphoma who have responded to bex-deg quite well, which is quite remarkable. We know our CSF levels are basically equivalent to our serum levels. We know the drug has brain activity. We know we can hit BTK in the resident microglia cells, which is really where the next, I think, frontier for getting really great responses in MS are, is to hit the microglia. We've seen some preliminary positive results. Well, not so preliminary, actually. phase III results from fenebrutinib with Roche, which look quite encouraging. I think MS is another area for Nurix to consider. Got it. You did mention earlier line of CLL makes a lot of sense for partnership, then also I&I is a big area if you want to pursue multiple indication later on the NHL. How you think about those different therapy area for bex-deg in terms of the overall corporate strategy for the partnership? We see this bex-deg as a foundational therapy. I think it could have the potential to be like an anti-CD20, like a rituxan. Lots of applications. Now, with the degrader capability, one can actually take advantage. It's more versatile than an antibody, right? We've developed different formulations, different doses. Really, we'll have different products that actually are developed ultimately across not only CLL and NHL, but also the autoimmune indications. In terms of corporate strategy, it really lends itself to partnership as well. It would have to be a very unique partnership, really, that has the vision of this broad vision for bex-deg being a foundational therapy across indications. Multi-indication drug development program, with a global partner that has the kind of capabilities that would be required. That's sort of the corporate strategy standpoint. We're well positioned to move this forward ourselves. We're well-funded, as you said. We have a great investor base. We're moving forward into phase III, full on with CLL. I think we can definitely initiate the I&I platform as well. We're in great position. Yeah. As you said, you also have a tablet formulation, maybe better for the I&I already. It's a different product, but overall, it's a degrader, but you can have a different presentation for the pipeline. Yeah. We have the tablet formulation that's new. This has been now in over 200 healthy volunteers as we've developed it, ready for the autoimmune indications. It will definitely be different presentation, different doses. It's well-positioned for that. The CLL current tablet capsule formulation is moving forward, of course, into phase III, so that's all good. We have the manufacturing all down. We're really in good shape there. It's all kind of a green light for us right now. Awesome. All right. Maybe last couple minutes, talk about the partnership with Sanofi and Akidea. STAT6 got a lot of The air time within the I&I space. I know preclinically, you show comparable, if not better, than the current degrader. What should we expect to see? The more interesting thing is you do have the opt-in option, and then the potential co-co decision later. What will make you to make that decision opt-in? If you make that decision, how are you going to fund those program if you move forward? Right. STAT6 is a transcription factor, it's very exciting. Transcription factor clearly is a small molecule target, basically competitive with DUPIXENT is the ultimate goal there. It's a very large opportunity in autoimmune disease. We have been developing a degrader to STAT6 with Sanofi since 2019, so this is quite a mature project. This is something that scientific teams have been working on together for many years. Sanofi exercised their option to take that forward into clinical development about a little over a year ago. They initiated the IND-enabling studies, which should be coming to completion this year. If on schedule, should start phase I, and Sanofi's responsible for that clinical development period up through human proof of concept. At which point, Nurix has this opt-in that you referred to, so we could opt-in 50/50 in a co-co in the U.S. This is a high priority project for us, so this would clearly be something that we would be very interested in exercising our option on. That program's, I think, a high visibility program, and the next steps would be in Sanofi's court in order to move this program forward. Okay. Similar thing for IRAK. I think IRAK is little bit ahead of time, ahead of STAT6, and we may have some data this year that still the interpretation. IRAK4 degrader should be completing phase I this year, and that is a similar structure as the Sanofi deal, but with Gilead. Gilead will control the disclosures around that and the next steps. It's a great program. I think it's probably now the leading IRAK4 degrader program. A couple of others have fallen away. We're out in front with this degrader program. I think we've got a great partner. Hopefully they'll disclose data this year, and we'll see that march into phase II at some point. Awesome. All righty. It's the last minute or two. Anything else from the pipeline? You do have the IO program and then maybe some of the other earlier you want to tell people. Yeah. NX-1607, our immuno-oncology program, is an inhibitor of Cbl-b ligase that could be transitioning into phase I-B in the second half. I think we'll get the phase I-A data, make some decisions there. New programs, we do have new programs in our pipeline. Hopefully, in the second half we'll be able to do something in that regard. Also the DAC program with Seagen Pfizer. This is a degrader antibody conjugate program, where these payloads that we engineer, teaming up with a great ADC team in Seattle to create the degrader antibody conjugates, or DACs. That's another whole area. That's actually progressed quite well. I think we're the leaders there between Pfizer and Nurix teaming up together. I think some others are really going to try to move into that space. I do think it's the next generation of ADCs, because you're bringing this incredibly powerful, targeted payload into the tumor cell, and you don't have the toxicities of the toxin payloads. This is a very exciting area. Some of the results there look quite good with our partner, and I hope to be able to share information with you in the future. Excellent. Okay. Thank you, Arthur. Thank you, everyone. Thank you.