Nurix Therapeutics, Inc. (NRIX) September 2026 Conference Transcript

All right. Great. Good morning, everybody. Thanks for joining us. I'm Terrence Flynn, Morgan Stanley's U.S. Biopharma Analyst. I'm very pleased to be hosting Nurex this morning. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com backslash research disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Joining us from the company this morning is Arthur Sands, the company's president and CEO. Thanks so much, Arthur, for taking the time. Really appreciate it. Thank you, Terrence. Bright and early in the middle of Times Square. Yes, it is early. Well, I thought, you know, maybe to kick us off, we'd talk about the Roche collaboration. Now that that's closed, congratulations there. Maybe just talk to us a little bit about the strategic rationale for partnering Bexteg, which is your lead pipeline asset.

Yeah, so that deal we announced in June. It did just close in August. It's a landmark deal, I think, for the field of targeted protein degradation. And in B-cell malignancies and autoimmune disease, two therapeutic area deal, that's number one. So that was one of the strategic considerations as we were embarking on a partnership process, which was a competitive process. we wanted a partner that really could span both oncology and immunology because those are the two major areas for Neurix in terms of creating drugs and value. And Roche was really perfect for that. They have, of course, I think the preeminent drug portfolio in B-cell malignancies, CLL and NHL, and then also in autoimmune disease with their multiple sclerosis expertise. and, of course, their Zolaire franchise. And so these are areas of great importance to us for Bexteg. And so this deal really maximizes the clinical development program for Bexteg and thereby maximizes the market potential of the drug and also gives us a global footprint, of course, with Roche. So those are some of the strategic considerations. Plus, they're great people to work with and terrific scientists. Great.

Maybe talk about the milestone structure in terms of any more clarity you can provide there in terms of some of the maybe near-term milestones and then how to think about some of those. But, again, I think it's about $2.3 billion all in.

Yeah, in total cash payments, most significantly the upfront payment of $700 million, which I think signifies the level of importance of this deal and, again, the breadth of the clinical development plan. and then an additional $1.6 billion in clinical development, regulatory, and sales milestones pretty much evenly distributed among those three categories. So this is very accessible future cash, the $1.6 for the company. In addition, I think, and probably most importantly long-term, it's a 50-50 cost-profit share, co-development, co-commercialization in the United States. Roche will commercialize ex-US, for which we receive significant milestones and royalties. So it really, again, maximizes the global footprint, play to each other's strengths as two companies, and it's a terrific deal.

And then how do you think about capital deployment in terms of what that upfront can do for the rest of your portfolio now in terms of maybe additional investments or other areas that you could potentially accelerate as a result of that up front? I'm sure it gives you some more flexibility now.

Well, the main area for acceleration right away is the autoimmune opportunity for Bexteg because within the deal and defined in the clinical development plan up front is a CSU trial, so chronic spontaneous urticaria, which we're in the midst of planning with Roche, and their Zolaire team, you know, which they've got such expertise in this whole allergy area, and then also MS. So right away we get an acceleration, you know, there. Of course, the funding, you know, we can use, we are using that for our share. Now the cost portion is 40%, Nurek 60% Roush, so the offsets in the cost are significant. So if you look at all of the cash financials of this deal, really it is essentially a self-funding deal, you know, if you look at it that way within oncology and the current clinical development plan. Now, it can expand beyond that clinical development plan. Both parties would need to agree to such future expansions. I think there will be expansions because next day can go so far, very farther in autoimmune disease. There are so many indications. We are covering essentially the waterfront of CLL and NHL, so I think that's already fully baked.

We'll talk about NHL, CLL in a bit, but what's the time frame for that indication expansion on the immunology side? Are we talking months or are we talking quarters?

We're talking months. Our goal is to file the IND for CSU this year, which would put us right into a Phase II trial, basically. We've already completed over 200 healthy volunteer studies with our new formulation designed with certain different profile improvements for autoimmune disease currently, and so that's all ready to go. And then MS would be next year.

And would MS be gated by CSU initial data, or are they kind of separate development paths?

They're very separate development paths. No, there's no gating. We'll go right into the planning for that. The planning's already started. And, yeah, MS, big opportunity, as you know. The whole BTK hypothesis, very exciting. Recent announcements from Novartis with remebrutinib. I think the playbook for remebrutinib is quite intriguing and appears to be very successful so far. So we see, you know, we think degrading BTK is superior in oncology, and it'll be a superior approach in autoimmune disease. Great.

Maybe we'll just go into the, you know, lead indication, CLL. So you've already enrolled the first patient in the Phase 3, 306 trial. This is versus Lilly's Chapurka. Maybe just walk us through the design here and how to think about, you know, your confidence in showing superiority.

It's a simple design, head-to-head study against perturbrutinib from Lilly. and really what we're testing the central hypothesis of degrading BTK or removing BTK, is it superior to inhibiting the kinase activity? And we think it is. Many lines of evidence have pointed us in this direction, not the least of which is the fact that our BTK degradation mechanism can overcome all the resistance mutations that are cropping up after treatment with inhibitors. and there are a number of these new mutations that have evolved with treatment with xanabrutinib or acalabrutinib. Originally with ibrutinib, the original, it was really just C481S, the covalent cysteine bomb, but there's more now, and pertubrutinib does not cover those. It was designed for C481S, and it does so effectively, but now emerging are about half the mutations are different categories. where we covered those, so we think that's a big advantage. In addition...

Are you going to have a pre-specified criteria that you're going to have a certain percentage of patients that are going to have these mutations, or is it just an all-comers straight?

It's all-comers second line, so they do have to have been treated with a covalent inhibitor, which we'll select for these, but that's just the natural process. We're not going to select from an enrollment standpoint. The other major advantage we see is that we remove what's called the scaffolding function of BTK. So that's a structural signaling function for BTK, and it's actually quite substantial. So it's really interesting. If you really look at this mutational spectrum of these patients, about half, really about 40%, have some type of BTK mutation driving resistance to inhibitors, but 60% are wild-type. And so that means the wild-type BTK is not responding to an inhibitor. So what's going on here? We think it's that signaling function through the scaffold. The structural function of BTK can go through another kinase mechanism that's part of the physical scaffold. So we remove that via degradation in the proteasome system. So that's actually a very important feature that's, I think, sometimes kind of overlooked. Okay, great.

And I think the co-primary endpoints, ORR and PFS, have you guys talked at all about what kind of effect size you'd like to see for the trial to be successful?

They're dual primary endpoints. And, well, of course, we've scaled the trial according to certain statistical assumptions of superiority. We've not shared what those are. But it brings us to a patient number around 600, 620, is, I think, the target number. But it's an event-driven trial, so there's opportunities to evaluate earlier based on events. And, yeah, we think the trial will enroll very rapidly. It'll be, you know, we're going against the latest agent, so it's very attractive for patients to have two really actually excellent drugs to choose from. Well, they don't choose. It's randomization.

So the interim is, It sounds like there's an interim based on PFS events, because ORR is just ORR scan. So, again, an interim would be triggered by PFS?

There's some standard ways to look with interim results. I'm not going to go into the details of it here. But, yeah, it's a fairly typical trial design. Like I said, a very simple statistical plan, too.

Could you, if, let's say, ORR shows a benefit earlier at some landmark analysis, Could you file there, or do you need both OR and PFS to kind of file on?

So, again, I don't want to speculate at this point. You know, there's a lot of – as we get farther in, we probably provide more clarity on the more interim plans.

And you guys haven't guided the timing yet because it's contingent on enrollment and events.

Right. So what we have announced is the first patient. So let's go from there, and then as we get more, we'll give you some updates.

Fair enough. You also have a single-arm 201 study, so maybe, again, similar type of questioning here. Just remind us, kind of design there, that patient population, and then what you've said about accelerated approval pathway.

This is a third-line-plus patient population, if you will. Largely the kind of patients we've already treated in the phase one, frankly. I mean, there we were fourth and fifth line, so here we can take third-line plus, which means they need to have seen a BTK inhibitor covalent, a BCL-2 inhibitor, which is standard now, you know, would be for second line, and then a non-covalent, so likely protibrutinib. So in that patient population, this is about 100 patients for single-arm trial, potential accelerated approval. We have seen, you know, excellent results in those patients in the phase one portion, and we hope to replicate that in this single-arm registrational, you know, trial.

And just remind us what your ORR was in kind of a similar patient population from phase one, just as a benchmark.

So between 65% and 80%, depending on which, you know, category of patients you look at exactly. We have, you know, multiple cohorts there. Actually, some of the latest cohorts we just reported at EHA were more the early Lyme patients. But just to tell you about those results, they're very exciting. They're 85% and 90% response rates ORR in the earlier Lyme patients. And actually, they hadn't even been treated that long. I mean, we think they have potential to move up to 95% or 100% ORR. So we'll see. We're continuing to track those early stage patients. But the later line patients, we're in the 70%, 65% range.

And just remind us on the durability, like how much durability data do you guys have? And then, again, what's the minimum amount you need for kind of an accelerated approval from the ongoing study?

So we reported 22.1 or so months of PFS, which is really quite remarkable. Again, these are patients that have failed all available therapies have failed the patient, I should say. And so that, we think, is if we come anywhere in that ballpark, that's really, we think, a significant benefit for patients. Obviously, that's up to the FDA in terms of their judgment calls over what constitutes accelerated approval criteria.

Okay, great. The other one, you know, on the competitive landscape is B1's 673. That's another BTK degrader. Maybe just talk about high-level, again, differentiation of BEXDAG in your view. What are some of the key features here?

So they've been presenting with us basically at every conference. You know, we're going to share the podium with them every six months or so at ASH or EHA. And the efficacy data does look similar. So I think between the two agents, and I think that's very encouraging. We have, you know, external validation, completely different company, different trial, coming up with the same results in very difficult-to-treat patients. I think, you know, I do believe our safety profile looks slightly better. You know, sort of by our interpretation of data so far, there aren't many patients to make that judgment on. But if you, I think, read between the lines, I do think there's a safety advantage. We have looked and profiled both compounds cellularly and molecularly, and we do believe we have a selectivity advantage at the cellular and molecular level. Certain targets that we see showing up on proteomics analysis with the B1 compound, we do not hit, we do not degrade. So we think we have a more selective compound.

Okay. Okay. I guess when we think about the phase one, two data we were just going through, are we going to see another update at ASH this year? Is that a fair expectation?

That would be a fair expectation. I mean, we're at ASH every year in some form or fashion. It depends on, you know, getting your abstracts accepted and where will we end up. But, yeah, we've been giving updates. Basically, the cadence has been about every six months.

Okay. I guess, you know, the other thing is just frame for us kind of how to think about the initial opportunity before you get to front line, just how to think about kind of second, third line plus in terms of numbers. I mean, I think Chaperca so far has had a, you know, fairly good ramp, but how are you guys sizing up those kind of later line opportunities?

Well, the later line opportunities are kind of difficult to really get accurate numbers on, but it's not a lot of patients. The real benefit will be in the second line and any front line opportunity where you're talking about tens of thousands of patients potentially, depending on how competitive our agent will be. So the goal is second line, I think is the focal point. But, you know, if we can start in the third and fourth line and offer benefit and get on the market, that could be an advantage. Okay, great.

Maybe talk to us just what is the frontline strategy. I know in frontline there have been a number of moving pieces. Like you said, there's been, you know, Ibrutinib was the standard of care, but now there's CalQuintz, some other drugs that are moving there. Then you also have the notion of kind of combination therapy, fixed duration. So it seems like there's a lot of different directions that you guys could go in that front-line setting. And so what's right now the current thinking in terms of kind of how you guys with Roche would approach that?

So it's an active area of discussion with Roche. What is the best strategy? And it's true that fortunately patients have a lot of options now in the front line. But they do boil down to monotherapy or some type of combination. And really I believe the majority of patients are still in the monotherapy sort of camp, and investigators, you know, if you go to academic centers and more of the tertiary care centers, they really favor the combinations, and getting a deeper response, a longer response, and even trying to find a combination that could approach a cure-like level for this chronic disease. So it's an active area of debate, and we'll just have to keep you posted on that as we evolve our thinking there.

Any rough timelines? Is that like months, quarters, when we might get an update? I think quarters, yeah.

Yeah, it's important to get going. Yeah. Okay, all right, we'll stay tuned.

The other area is just non-Hodgkin's lymphoma. So maybe just, again, similar type question, what data you have there, then how are you thinking about addressing that opportunity?

Yeah, so Waldenstrom's and then also NCL, we've presented on some of our later stage patients in Waldenstrom's with, again, about an 80% plus response rate as monotherapy. So those two areas are defined within the clinical development plan of the agreement to be initiated. that will be largely a Roche-driven trial, two trials, and largely combination approaches. So we haven't specified those yet. Beyond that, we're... And that's later lines, or that's going to go front line? Like, with any more detail there? The current discussion is around second line, but also front line. So we haven't outlined exactly the strategy there, but, again, that will be likely a combination approach. And then with regard to the other areas of NHL, that's for future exploration.

Maybe just pivoting, we talked about this a little bit at the beginning, but just, you know, immunology, neurology, again, you know, a molecule can go in a lot of different directions. So maybe just elaborate a little bit more on kind of the multiple sclerosis piece there, kind of biological rationale here, what gives you and Roche confidence to move into the MS. So we've demonstrated brain activity, number one.

So we've demonstrated our drug crosses the blood-brain barrier. We can measure it in the CSF free drug levels compared to the plasma level to CSF roughly one-to-one. So we know we're at effective concentrations. And most importantly, we have patients with CNS disease in the oncology setting that have responded to the drug, some quite dramatically. So we have biologic proof of activity in a disease setting. And in addition, we have all the animal model data for MS where we have really very potent activity, including demonstration of degradation of BTK in the microglia of the brain. So this is central to the whole microglial hypothesis as being the resident immune cells embedded within the neuronal structures that are responsible for the debilitating aspects of MS. And so if you can shut that down, which the CD20 antibodies don't really do, then you could block this debilitating progression. That's central to the hypothesis, and we've demonstrated that in animal models. So I think that this is a very exciting new dimension to explore. Our degraders have a unique, I think, advantage here because the drug levels required are low to achieve basically complete removal of BTK. And I think that gives us a safety advantage. The other advantage is taking out that scaffolding function because that's every bit as important in autoimmune disease as it is in cancer. And so the inhibitors don't do that. So I think they're leaving some efficacy on the table, and I think it'll be very interesting to explore this.

What are you predicting from a dose level versus, you know, CLL, for example? You mentioned, you know, the potency in CNS. But, again, are you going to need potentially a lower dose or are you going to need to push the dose because of the blood-brain barrier? Like, how do you think about dose selection relative to CLL?

You know, that's an excellent question. The devil's in the details with dosing and determining what levels are required for that particular pathology. So the current thinking is it'll either be a similar dose to the oncology setting or it'll be less. It won't be more, we don't think, basically.

So you don't need to do any more additional animal talks to explore higher dose. You have all that stuff covered, so it's just a matter of...

Yeah, no, in terms of we won't go up. So, yeah, we've covered in terms of dose levels. It could be as low as one-third or one-fourth the amount, but we'll model the best we can, probably test two doses. Really, you just have to go with the empirical study in a phase two.

And you said that's next year? That's next year.

We hope to initiate it next year, yeah.

Okay, got it. And just remind me, because, again, I haven't looked at these MS studies in a while, that's just usually like an MRI imaging type phase two study? That's the typical approach. Like lesion, something like that?

Yeah, lesion measurement, 12-week, 13-week, that's what's been done. That will definitely be part of the picture. We may do more, but that will be determined when we get to the IND level.

Okay, great. You mentioned CSU. Obviously, Roche, a lot of experience here with Zolaire. There have been some other targets that have been successful now. So just remind us kind of the paradigm in CSU and then where you think, you know, Bexteg would slot into that current paradigm.

So there's antihistamines, and a lot of patients will progress with serious CSU, which is triggered by this mass cell degranulation, so significant allergic response and, you know, quite debilitating. so BTK is a driver in mast cells it's clearly a driver in the allergic response in multiple cell types which we hit including basophils and we can measure in healthy volunteers so I think mechanistically we're spot on, of course remibrutinib has demonstrated it clinically is launching quite well in this area so we anticipate similar rapid onset of therapeutic activity which would be an advantage Zolaire is a slower onset, although they do get a very deep response. It is the leading drug, I think, in the area. So I think it would be an important addition to that franchise for Roche, and it would be of course a new expansion for us. But it's clearly a great place to start. It's a rapid initial proof-of-concept trial, so that's attractive. MS is longer. And again, Remy Brutenev has and Novartis, you know, charted a very, very nice, successful course.

And where is that, where is Remy used mainly? Is this post-Zolair or is it used pre-Zolair?

You know, I don't know how it's actively being prescribed, but, I mean, they were post-histamine. And then I'm not sure about the post-Zolair or not. Okay, got it.

All right, well, maybe just in the last few minutes here, because, again, you might be able to answer some of these, you might not, because they're partner programs. But, you know, Sanofi, you guys received a $10 million milestone payment for, you know, the stat six moving into phase one. So maybe just anything more you can say on that and, you know, how, I guess, big picture, what a lot of investors are looking to is this upcoming Chimera data as well as like a kind of lateral. So first just talk about this phase one trial and then maybe your profile and differentiation versus the Chimera approach?

So first off, STAT-6 is a terrific target for type 2 inflammation broadly. Transcription factor, largely undruggable to date. We started the program in 2019 with Sanity. It was one of our original drug discovery programs under that alliance. So we've been working side by side with them for quite some time, quarterly joint research committee meetings, really a highly evolved program that has yielded a terrific molecule. Our number was NX3911. It has started phase one. And so in terms of its profile, it's exquisitely selective for STAT6, and we've shown that with global proteomics. Highly active in animal models of atopic dermatitis as well as asthma. and there's multiple more animal models that we haven't shown. So it really fits the bill. I think that Chimera is leading the way and has done a great job. I think their characterization of, you know, depiction in a pill is, you know, really the goal. I do believe that they're, as they described, it could open up the market quite substantially. There probably will be significant read-through. I think from, you know, looking at their data, their phase one data looks so good already, and their initial patient data. So we look forward to their data, too. And I think it would be, I anticipate it will be very positive for the STAT-6 field. So I think it's important. It's a huge market. There's room, you know, it's not a zero-sum game. There's room for many drugs here. Likely they'll have different profiles. There are inhibitors being pursued. Resludix and Pfizer probably had different profiles as well with different MOA. But we do prefer the degrader mechanism. We think that's going to be a leading mechanism based on the genetics. The removal of STAT6 gives you a great phenotype. So we're going to reproduce that.

What should we watch just in terms of STAT6 pathway? What should be top of mind in terms of the safety side for this pathway, if anything?

Well, for safety, we look at the genetics. And if you look at the mouse knockout of STAT6, they really don't have any phenotype other than blockade of IL-4, IL-13. It's incredibly clean. It's actually cleaner than BPK genetic phenotype. So from a MOA mechanism on target standpoint, it should be quite safe. Then if you look at human genetics, too, there's allelic variation. Patients with some allelic variation in STAT-6 have decreased immune, autoimmune, you know, symptomology. So really, it should be good. So the issue then is off-target. And so that's a molecule-by-molecule, you know, analysis. And if you clear all the IND, you know, enabling the GLP-TOC studies, which we have, and Sanofi has run, by the way. They've been in charge of those, and now they're in charge of the phase one. And our option, it comes in after that. But if you run all those, it looks quite safe in animal models. And then, really, it's the patients.

And this is, first, you're, I'm assuming, SAD. This is SAD phase one? Single ascending dose, this phase one?

Yeah, standard SAD-MAD type of approach is our understanding. We really haven't disclosed the design of that yet, nor is Sanofi. but that would be a standard approach.

And then, so again, typical industry timelines. I'm assuming this would wrap up sometime next year, so then the next step would be like a phase two?

Yeah, we would anticipate, you know, direct to phase two. So selection.

And then you guys would get a milestone payment and then just remind us what the size of that would be and then what economics you'd get downstream if this were approved.

Well, there are milestones along the way. We haven't disclosed the size of those, but I think the important thing is the option exercise, which would be after C, we will get a report, a clinical report, data report, on the phase one, which will also include some patient data. So we'll be able to look at an initial cohort of patients as well as the healthy volunteers, and that would trigger our option period. then we'd make a judgment based on the data of whether or not to opt into that 50-50 in the United States. And then there are milestones along the way, like I said, but the really important value creation would be the option.

So you will, the phase one will include some atopic derm patients, ultimately, like when you refer to patients that you'll get to review?

Well, so under the agreement, our option is triggered by that. We must see patient data. We anticipate that that would represent a smaller cohort, not a full phase two. But, again, Sanofi has not disclosed the design of the study yet.

But it's more than healthy volunteer data.

It will be more than healthy volunteer data. Okay, got it.

I guess the last one I had is just, you know, the IRAC-4 degrader. You know, Gilead, I think, has, you know, talked a little bit about this. Not too much, but, again, maybe just what can you say about the profile there? Kind of similar type question. Remind us of your economics.

Well, so it's a similar structure from a deal structure standpoint. IRAC 4, they should be finishing Phase 1 this year, so we anticipate a Phase 2 transition there. So we've got our Phase 1 with STAT 6, hopefully Phase 2 transition with IRAC 4, and, of course, our own Phase 3 program. So our pipeline is kind of well-timed out for, I think, value creation at many levels. The profile, it's a great molecule, again, developed side-by-side with Gilead. They had an IRAC-4 inhibitor team, which worked on the degrader with us since 2019 also. So very clean, high activity in the skin, very safe profile. We think it's going to have, you know, we're in the lead now. You know, there were two other degrader programs that have fallen away, one from Chimera, one from B1. So we will be the leading degrader there. Scaffolding function is very important for IREC4. That's why the inhibitors haven't, I think, been as exciting. And some people have gotten a little disappointed with the target, but that's not true. It's really how you hit the target, and you have to have the right molecule. The biology is fantastic. Again, the genetics is fantastic. And I guess we'll see data from Gilead's inhibitor phase two, I think, later this year, maybe, right? I would certainly hope so. They've been very diligent about appropriate publication and timing in international congresses. We've worked with them on certain posters, preclinical. So hopefully, yeah, there'll be future disclosures here. All right, Arthur. Well, that was great. Thank you so much for the time this morning. Appreciate it. Terrence, thank you very much.