Nurix Therapeutics, Inc. (NRIX) Earnings Call Transcript & Summary

Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, senior analyst covering SMid-cap biotech. And 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. So Nurix is a very exciting time point. You're in the pivotal for your lead program and then also you have a platform supporting a lot of the early pipeline development well across the Oncology and I&I space. Maybe, Arthur, give us the latest about Nurix and then we can dive into the conversation.

Yes. 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 will be a significant, I think, update on bexobrutideg, our lead BTK degrader program in CLL. So in that presentation, -- and the abstracts have been published there, but 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. So we have some treatment-naive patients who will then -- 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 the first BTK therapy. And then also patients who have not received a BCL-2 inhibitor, venetoclax, for example, yet. And so these are early stage. Those would be second-line types of patients. So these cohorts of patients will be describing, so that's going to be a significant events for us. Of course, we have a lot of European investigators we're meeting with in Stockholm as well. And so 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. I'm sure you'll have some questions about that. And also our IRAK4 degrader, which is partnered with Gilead. These are all partnerships where we maintain a 50-50 opt-in structure as well. So those are progressing. And then bexobrutideg itself, we're very interested in advancing that into autoimmune indications as well. And so that will 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 without -- even without the BCL-2. So I understand you are also trying to do the combination approach to moving to the earlier line. And then where are they in the combo? And then with this, I believe it's the mono data, how this profile will support the combo and then when we're going to start to see the data?

Yes. So we're intending to start our first combination trial, Phase Ib/II program with bexobrutideg in combination with a number of agents. So venetoclax, the BCL-2 inhibitor was one of the primary combinable drugs, and that is -- would enable a frontline approach as well. What's exciting there is that people -- this would be the first degrader combined -- BTK degrader combined with venetoclax in the clinic. And investigators and I think patients are very interested in the potential for fixed duration therapy. So therapies that would last a year or 2 years, likely 2 years on the combination regimen and then have basically drug holiday or no drug period. So that's one potential. In addition, anti-CD20 antibodies are of high interest in combination. So RITUXAN being a mainstay, of course, but then obinutuzumab as well. And then there's multiple other combination potentials built into that protocol. It's a Phase Ib/II protocol. So that's poised to start midyear. Of course, data would then take a year or more after that. So that is -- that's sort of next step for a trial start. But at the same time, we're starting our big Phase III program in CLL monotherapy. So that's in second line. So these are patients that have received a BTK covalent inhibitor, but have progressed. And so that trial will be starting midyear as well. That's about a 600-patient trial and is -- will be in over 20 countries. So 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. So yes, all of that is moving forward. So very busy midyear for us.

Excellent. As you mentioned, you are doing the mono pivotal as third-plus line triple exposed, I believe that's the population you are doing initially. And then we also know another BTK degrader is running a slightly different setting, but also later line. They may have data earlier, than you will have data next year. So when we see the data, what you are looking for in terms of the ORR, PFS, maybe some of the safety signal, tolerability dose? So what will be considered as a good scenario for Nurix to be able to maybe even benchmarking and then also the beating there.

So you're talking about in the later line patients, so these are third line, fourth line. We've had 6 lines -- patients with 6 lines of prior therapy, actually up to 10 lines. And so what we've seen so far in those patients is around 70% to 80% response rate. The response rates do go down the later lines of therapy that patients have had. So -- but I think if you look at fourth-line plus in general, anything between 50% to 60%, 65% is an excellent overall response rate in those really late-line patients. Now you contrast that with some of the early line patients, we're seeing 85% or greater response rates with the BTK degrader. And I think that's -- those are quite strong. But 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. And then also NHL, we're also interested in expanding in NHL indications as well. So yes, those are the data to sort of look for.

And also compare and contrast other BTK degrader, they're also in the pivotal right now. And then how do you think Bex can differentiate in the later line STAR and then early line probably a bit too early to compare.

Well, our goal is to be best-in-class in the degrader class. There really are only 2 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. I mean 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. And 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 a very -- 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. So 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, but the catalytic nature of degradation. So one drug molecule of bexobrutideg, I'll call it bexdeg for short, can degrade 10,000 BTK proteins per hour in the cell. So one drug molecule removing 10,000 drug-target proteins per hour. This is fundamentally different PK/PD compared to inhibitors where it's 1:1. You need one drug molecule for every BTK protein. So you really have to swamp the system with drug, and that's how inhibitors work. But degraders work catalytically because they harness this incredible -- incredibly efficient proteasomal machinery in the cell. That's how we work. So we're fundamentally different. We think we're going to have a fundamentally better safety profile. And the big picture is we're talking about BTK, but this technology has the potential to replace many inhibitors because of these attributes. So...

Yes. Yes, makes sense. And then one of the other discussion I've been having with investors and then also with you is the sequence of use all kinds of different BTK. We have a covalent, we have non-covalent and then now we're about to have a degrader coming to the line. So 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 result -- initial result a patient gets from a drug, the better their prognosis is overall. So 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. So that's the clinical rationale to start with the best agent up front. And that's what we've seen going on in CLL. There -- 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. So 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. So if you have the best result upfront, the patient will do better and live a longer, healthier life. So 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.

Yes, it's a cancer patient, right? Best foot forward is probably a lot of the logical choice. The only thing is people thinking about degrader is powerful, right? When you knock down the entire protein, would you develop some resistant mutation maybe no other therapy can address versus covalent -- non-covalent can address the covalent mutation and then non-covalent mutation can be addressed by the degrader. So that's the sequencing potential logic as well. So how do 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. So that sounds like a logic to start with an inhibitor and then you have a degrader in the second line. But why ever develop the resistance mutations in the first place if you don't need to and so that is why you should start with the best drug upfront that doesn't even allow for resistance or at least has -- is harder to become resistant to is what we're seeing in the clinic. So the degrader is harder to get around. Now 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? And that's why a degrader would be superior. Now 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 A42AD mutation. So 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 such -- so mutated, it does not work well. And by the way, it responds to combination agents very easily. So that mutation is not really a big threat. So anyway, I hope I've answered the sort of the rationale to start with the best drug upfront. We think that's going to be a degrader eventually.

Yes. And then you do have a solution at the combination called beyond the BTK if you develop something not necessarily addressed by the BTK approach, right?

Yes. I think with venetoclax and a BTK degrader, you're basically going to take out anything. So yes, and we're focused on BTK, but there are a lot of other mutations that take place in these patients, unfortunately, p53 and other really bad-actor mutations. So those all need to be dealt with as well. So combination -- that's why combination agents will be necessary.

Yes. 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 or mono in the second plus line. How do you think about the earlier line strategy at the corporate level, you want to do this stand-alone 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 that almost becomes kind of an endless opportunity. And to do that solo is challenging. So yes, 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. So we'd like those kind of structures. But 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.

Yes. We'll talk about the I&I. So 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. So -- but you plan to release some data this year? And how should we -- what should we kind of expect from the NHL cohort?

Yes. So our data release periodicity tends to be every 6 months, so EHA and ASH. We are talking about potentially NHL cohort data at ASH. We haven't settled on what we'll submit, but 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, marginal cell lymphoma and Waldenström's, where we have shown some data. There, again, seeing this 85% response rate. So yes, 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.

Yes. Okay. Good. I&I is a very interesting thought thinking about the degrader approach because the scaffold function, et cetera. So I think recently, CSU, some of the early data by other degrader and then you're also thinking about developing into different indications. And then right now, what's the thought about the indication selection? What's the area you want to go first and then proof of concept for the degrader?

Yes. So I think that the advantage of a degrader in I&I is actually somewhat similar to what we've seen in Oncology. And 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. So there's another whole signaling pathway going on with BTK that kinase inhibitors don't touch, and that's operating in autoimmune disease also. And so we're excited by what we can do there from a theoretical standpoint. And so what we've done so far is conduct a very significant healthy volunteer study with our new formulation designed for autoimmune disease. And we did have a little bit of data come out at our -- at an oral presentation in Chicago at the dermatologic meeting recently, where we show complete degradation of BTK in the skin of healthy volunteers at low doses, and this is once-a-day dosing. So 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 look 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. So again, we think we can improve on that.

Yes. Awesome. So it seems that skin makes a lot of sense. And any other therapeutic 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 Bexdeg quite well, which is quite remarkable. And we know our CSF levels are basically equivalent to our serum levels. And so 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. And we've seen some preliminary positive results, not so preliminary actually Phase III results from fenebrutinib with Roche, which look quite encouraging. So I think MS is another area for Nurix to consider.

Got it. And then you did mention earlier line of CLL makes a lot of sense for partnership. And then also I&I is a big area if you want to pursue multiple indications later on the NHL. So how do you think about those different therapeutic area for Bexdeg in terms of the overall corporate strategy for the partnership?

So we see this Bexdeg as a foundational therapy. So 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? I mean, so 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. So in terms of corporate strategy, then it really lends itself to partnership as well. But it would have to be a very unique partnership really that has the vision of this broad vision for Bexdeg being a foundational therapy across indications. So 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. But 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. And I think we can definitely initiate the I&I platform as well. So we're in a great position.

Yes. So as you said, you also have a tablet formulation maybe better for the I&I already. So it's a different product. But overall, it's a degrader, but you can have a different presentation for the pipeline.

Yes. So we have the tablet formulation. It's new. This has been now in over 200 healthy volunteers as we've developed it ready for the autoimmune indications. So it will definitely be different presentation, different doses, and 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. So this is -- it's all kind of a green light for us right now.

Awesome. All right. Maybe last couple of minutes, talk about the partnership with Sanofi and Gilead. STAT6 got a lot of the airtime within the I&I space. So I know preclinically, you show comparable, if not better than the current degrader. And then what should we expect to see? And then the more interesting thing, you do have the opt-in option and then potential co-co decision later. So what will make you to make that decision opt-in? And then if you make that decision, how are you going to fund those program if you move forward?

Right. So STAT6 is a transcription factor. It's a very exciting transcription factor. Clearly is a small molecule target basically competitive with DUPIXENT is the ultimate goal there. So 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. And then if on schedule, should start Phase I. And Sanofi is 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 United States. And this is a high-priority project for us. So I mean, this would clearly be something that we would be very interested in exercising our option on. So that program is, 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 a little bit ahead of time, ahead of STAT6 and we may have some data this year. Is that still the expectation?

IRAK4 should -- degrader should be completing Phase I this year. And that is a similar structure as the Sanofi deal, but with Gilead. Gilead then 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 number -- a couple of others have fallen away. So we're out in front with this degrader program. I think we've got a great partner. And yes, hopefully, they'll disclose data this year, and we'll see that march into Phase II at some point.

Awesome. Alright. Okay. Just the last minute or 2. Anything else from the pipeline? We do have the IO program and then maybe some of the other earlier you want to tell people.

Yes. So NX-1607, our immuno-oncology program is an inhibitor of CBL-B ligase that could be transitioning into Phase Ib in the second half. So I think we'll get the data and make some decisions there. And then new programs. So we do have new programs in our pipeline. We haven't disclosed anything yet. Hopefully, in the second half, we'll be able to do something in that regard. And then also the DAC program with Seagen and 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 DAC. So 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. So 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 that -- with you in the future.

Excellent. Okay. Thank you, Arthur. Thank you, everyone.

Thank you.