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

All right, everyone, I think we'll get started here with our next fireside discussion. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells. I'm very excited to have with us Nurex Therapeutics. From the company, we have Jason Cantor, Chief Business Officer. Jason, good to see you.

Good to see you, Derek. Thank you so much for having us.

Yeah, I mean, maybe just to start off, a lot of things going on at Nurex. You guys announced a big deal on Bexteg and other things. So maybe give us kind of the state of the business first, and then we can kind of get into more specific questions.

Sure, terrific. So for those who don't know Nurex well, we are a multi-product, multi-therapeutic area, biopharma focused on targeted protein degradation. Our lead asset is a degrader of BTK, which is a central node in B-cell signaling as well as other immune cells. It's in pivotal studies for CLL and is moving into phase two for chronic spontaneous urticaria. CSU and also multiple sclerosis MS. We've got partnerships with Roche as you mentioned for Bexteg but also discovery partnerships with Gilead, Sanofi and Pfizer. We've got our lead programs in those collaborations include a stat 6th grader with Sanofi and an IRAC 4th grader with Gilead and I'm very happy to be here. Thank you very much.

Yeah so maybe to start off just on kind of backstay and what kind of underpinned the deal with Roche in terms of the strength of the data in CLL and kind of the promise in some of these I&I indications?

Yeah, it's a great question. What I'll say is last year as we were thinking about our strategy around this product, one of the things that was really clear was in order to achieve the right kind of value inflection for the program, we wanted to, one, establish the efficacy, two, establish long-term durability. So on the efficacy side, we had 83% response rate in heavily refractory patients. We had 22.1 month median PFS. We wanted to be able to have an established dose to take into Pivotal, and we did a randomized study for Project Optimist. So having the data package in place and being on the cusp of phase three, doing the deal at this point is ideal for us because not only does it de-risk us financially in terms of our ability to execute, but it expands the indication space we can go into, which increases the total addressable market. And that includes not only the malignant heme, but also INI and neuro. And Roche is the ideal partner for us in this respect.

So in terms of just kind of the CLL opportunity, so you guys had already started kind of the late line trial, and then obviously the Roche partnership opens up, you know, kind of early line, but how do you kind of think about the competitive dynamics with, you know, kind of the next-gen BTK inhibitors versus kind of a BTK degrader, and then within that kind of class, you know, how do you guys feel like you're differentiated versus kind of the Beijing or B1 molecule?

Yeah, a fantastic question. I mean, the BTK inhibitor space, you know, obviously started with a Brutinib and then a Calabrutinib, Xanabrutinib, and then the non-covalence like Pertibrutinib. And so with each of those, it's been, you know, the goal of getting better selectivity, better safety, and then ultimately to increase the therapeutic footprint into INI. Degraders bring an entirely new modality to a target that's proven. So in CLL, you know, or the BTK space right now is 13 billion dollars annually. It's growing at close to 15 percent and the indication space keeps growing. We are the only, you know, the BTK degraders are really the first to try to cross both oncology and INI so the inhibitors have tend to be do one or the other but the B2K degraders such as Bex and Brutadeg have the advantage of removing the protein doing it catalytically and being able to address mutations as well as wild type and so the data has been I think remarkable and And we're full steam ahead on all of that. In terms of differentiation versus our closest competitor, B1, it's hard to say. Right now, they're both showing fantastic efficacy in the 80% range, which is remarkable. And I think ultimately, probably where we'll see the differentiation is on the safety side. We think we have a safer molecule. We think we have a more selective molecule. and we'll just have to see that play out over time.

So I guess when you think about the Roche deal in terms of the economics to you guys and ultimately the development plans too in terms of the costs, can you just walk us through stepwise how you go from where we are today and then building out the overall set of CLL opportunities?

Yeah, sure. So we announced the deal back in early June, so it was not long ago. It was the largest single-degrader deal to date in terms of upfront. So it was a $700 million upfront payment, $2.3 billion total milestone and upfront package. The cost sharing is 40-60 on the development costs, and it's a U.S. 50-50 profit share ex-U.S. royalty. Now, people have asked, oh, is Roche taking over? And no, this is truly a collaboration. We have equal representation in all the joint governance, and we're working together on a very ambitious CDP. That CDP includes the randomized phase three study that we talked about, which is head to head versus pertubrutinib, which is the standard of care in this second line setting. And we are about to kick off a phase one B2 study in combination with the venetoclax in order to enable you know the potential for maybe fixed duration shorter course therapies that could get to very deep and durable responses you ask how we're thinking about covering the CLL landscape well Roche is the perfect partner because they have all the potential combination drugs including venetoclax CD20 antibodies and the CD19 by specifics we're also looking to expand into Waldenstrom and mantle cell and that just covers the heme space gotcha but maybe you know we're gonna get some updates I think you know later this year what should we be paying attention to for for the back stag you know kind of additional CLL data and anything else kind of in the heme space yeah so in terms of beck stag data we are also in addition to running you know having the ongoing studies in heme we are running a healthy volunteer SADMAD study with a new tablet formulation which is designed to initially go into our studies for CSU and MS and so we will have disclosures around that phase one data set this year. We're also working towards an IND in CSU as well as MS. CSU would come first, MS to follow. And then in terms of the cadence of news flow on the clinical side in CLL and NHL, we typically present data at ASH and at EHA. So that's the American Society of Hematology is in December and the European Hematology Association is in June. And we'll have updates on our phase 1B cohorts at that time.

Should we, I mean, I think we're going to look at some earlier CLL patients in that data set. So I guess what are the benchmarks should we be looking there for those patients?

Yeah, so at EL, we showed data from patients who were BTK inhibitor naive, including people who were treatment naive. We also looked at a cohort of patients who were BCL2 inhibitor naive, and the response rates were quite high. I think in one of the cohorts, the response rate got just above 90 percent. So what we'll look at going forward is, you know, do we see further deepening of responses? Do some of the stable disease convert to PR? Do any of the PRs convert to CRs over time? This is something we've seen in the later line patients. And then, you know, how does the durability overall look in those patients as well as the safety? I mean, every time we've looked at the data it continues to look very positive so you know my expectations is going to continue to look that way.

Gotcha and then maybe just to shift gears to the I&I you know side of the coin so you know we know BTK works in a variety of different indications you know Remy Bruton has approved in CSU you know there's been a variety of different MS trials so I guess you know when you think about the best kind of differentiator there is it more the efficacy play or more the safety play given that there's been kind of a checkered past even in these MS trials about safety to be fair even Remy's got some you know bleeding risk associated with it yeah these are these are great questions so the reason that people got very excited about looking at BTK outside of the hemon space is because BTK is a central signal signaling node for not

only B cells, but mast cells, basophils, microglia in the case of MS. And so disrupting the signaling has the potential to really shut down a lot of these autoimmune diseases. What was unexpected when the BTK inhibitors went into these spaces was a lot of them suffered from liver tox. And it's never really been fully explained why many of these ran into liver tox signals. Some of the possible explanations are higher doses that were needed in order to get the proper exposure in the brain in the case of MS. Certainly some sort of off-target because it's not a BTK on-target signal as far as we can tell. In our experience, we have not seen a liver tox signal. And just in general, we think we are more selective than many of the BTK inhibitors. So we are very encouraged by that, and that's led us to feel good about moving into these indications.

Now, in terms of efficacy, do you think what we've seen in CLL in somewhat translates, like full degradation of BTK will confer better efficacy in INI? That was the other part of your question. Yeah, I missed that.

So we have run a lot of preclinical studies looking at B-cell activation, mast cell, basophil activation, and our B2K degrader is much more potent than all of the inhibitors. So there's a potency. Now potency could just relate to dose, too, so you get away with a smaller dose. But what we've also seen, especially in the B-cell assay, is a deeper suppression, and we think that that is likely scaffolding-driven. So that you actually can get more out of the suppression of the target than you can by simply inhibiting it. So there is work to be done there to prove the sort of scaffolding function in the I&I setting. But, you know, biologically, it makes sense. And we think we can get to a deeper suppression, specifically in CSU. I mean, Remy kind of sets the bar. They have shown biologic-like activity. So activity similar to Dupi or to Zolaire, the activity is actually quicker, it's more rapid, but it's a twice-a-day drug, and there is some rebound of symptoms between doses, even on a twice-a-day drug. We think with a degrader, with Bexteg, we can dose once a day. We think we can have coverage throughout the treatment window, and we think that we could potentially drive that efficacy better. About half the patients are well-controlled on each one of those therapies. So that leaves half the patients who aren't. And we think we can probably push the BTK mechanism a little harder than Remy does.

I mean, is there any insights? So I know, you know, B1, you know, had a trial there in China. You know, they're degraded in CSU. And, you know, any insight to, like, how that performed? And it does sound like they want to move that forward. So, you know, what do you think, you know, I guess, like, what would your internal benchmark BE TO MOVE SOMETHING FORWARD WITH KIND OF AN INCUMBENT BTK, HOW MUCH BETTER WOULD YOU NEED TO BE AND WHAT DIFFERENTIATION WOULD YOU WANT TO SEE TO MOVE THAT FORWARD INTO A GLOBAL REGISTRATION PHASE 3 TRIAL?

I THINK REMI DOES SET A BAR AND I THINK WE WOULD LOOK TO AT LEAST MEET THAT BAR. I THINK THERE ARE ADVANTAGES POTENTIALLY JUST BEING ONCE A DAY VERSUS TWICE A DAY, BUT But we think we can probably do better than that. But I think that bar is pretty well established now in terms of the composite endpoints on itching and hives and swelling that's associated with the disease.

Is there any specific part of the disease, whether it be itching or hives or anything like that, that is more directly driven by the scaffolding function? Or is that just too nuanced and we don't really know?

It's very nuanced and we probably don't have all the right information and I'm probably not the right person to be able to answer that. What I can say is the place preclinically where we've seen, you know, or in vitro where we've seen the most differentiation is on the B cell side. So the disease involves both the B cells in terms of the autoantibodies that are involved But then also the mast cells and basophils, which are, you know, releasing the compounds that are causing the itching and swelling. So, you know, BTK is impacting the disease in three different cell types. And, you know, we think that certainly at the B cell side, at least from the data I've seen, we do have good evidence of a deeper suppression of the pathway than we do with Remy. Gotcha.

And then just on the other side in terms of MS. So, you know, MS is quite a mature market. and fairly crowded, but I guess, where do you think BTK should play? Is it more relapse and remitting or progressive, given some of the data sets that we've seen with prior BTKs, where do you want to establish the beachhead?

Yeah, it's a crowded market, but it's a big market, and it's a market with still high unmet medical need and a market where new therapies are adopted, New oral therapies are needed. The place where the biggest unmet medical need remains is in for drugs that can slow disability progression. I think that's the hope for BTK-targeted therapy, particularly if you can get access to the microglia. So the microglia are immune cells that are resident in the brain. They're believed to be involved in some of the demyelination. that's critical for the progression of the disease. So I think mechanistically, a B2K degrader should work across all of the forms of the disease. But I think, you know, commercially and clinically, the place where we'd want to see the benefit would be in disability progression.

How do you think about generating, you know, proof of concept with Bexteg there?

Would you do kind of phase two, you know, kind of MRI, or do you want to go into kind of a longer trial? what's what's kind of the design that you guys would like to do and and now with the kind of the backing of Roche you know and help there you can fund kind of any trial that you'd actually like yeah I mean one of the great advantages of working with Roche is is is having that collaborative team now that's working on finalizing the trial design for the phase two I mean there's no group out there that has more knowledge of for example biomarkers in the space and they've just run a full program for femtobrutinib, and so they are fully aware of how best to run the study. I think you always, in early trials, want to look at MRI-type endpoints, things that are quantitative, but ultimately you need to show data on relapse rates or disability progression but your ability to measure that in smaller studies you know you really have to look at both circuits as well as clinical endpoints so we should think you know more of a standard proof of concept you know MRI you know imaging based endpoint study first for kind of going all in on a phase three our thought around just our general thought and I'm not going to speak specifically to the trial designs at this point but our general thought both for CSU and for MS is to run registration-enabling trials that will enable a registrational study. So something that will provide, we're not looking for a quick proof of concept, we're looking for a full understanding of the right dose and the right patient population in order to enable a positive registration study to follow.

How do you think about dosing across these I&I indications relative to what you guys have seen in CLL? I mean, you'll have to do some exploration, and I don't know if there's some differences in the tablet, but maybe you can kind of give us a view of, like, should we be expecting multiple doses, and what sort of PD effect do you need to show to maybe drive efficacy?

Yeah, so this is a great question, and it's part of the reason that we've run such a robust phase one program. So not only do we have, you know, this big CLL and NHL patient experience to rely on, but we have very, you know, well-run phase one SADMAD studies, which includes PKPD, and that's really going to form the basis of our dose selection for not only the new formulation, but just to be specific for each of these indications. So we've shown a little bit of data on the activity of the drug in the skin. We see very robust BTK degradation in the skin. We're also looking at PK levels in the CNS, which is going to be very important for the MS indication. And so we'll show some of that data later this year, and that should support our dose selection. We will be looking at lower doses than we are looking in oncology.

I mean, do you think that's probably a fair assumption that ultimately you probably need lower doses in autoimmune, or we just don't know yet?

Yeah. I mean, when we are dosing in oncology, we are really looking at trying to get to as high a dose as possible within the context of Project Optimus. We're dosing at 600 milligrams once a day. And part of the reason for that is we really want to make sure we're adequately covering all the mutations. That's not really an issue in terms of what you see in I&I and in neuro. In I&I and neuro, it's really more about what is your coverage in the right tissue. So in the skin, how well are you covering BTK? In the CSF, how well are you covering BTK? And the good news is, again, we're working catalytically. We work at very, very low plasma concentrations. So you only need very little of this drug in its active form to degrade. We've measured the rate of degradation. A single molecule of our drug can degrade 10,000 BTK proteins an hour. And then that has to be resynthesized to come back. So the target coverage is phenomenal and is very, very different than sort of one-to-one inhibition that you see with an inhibitor and it's it's why we think we can get away with lower doses why we can dose once a day and why we think we can get better target coverage gotcha and I know it sounds like the near-term priorities on the INI side are CSU and MS but you know where else could you go you know with with kind of BTK and INI and I guess when would that happen would it happen more about the time we get proof of concept for these two and then you know kind of start to expand or could that even happen sooner yeah so some of the areas that people have shown good data for for BTK inhibitors include you know food allergy is one that a lot of people talk about I mean their safety is it's really paramount so I think showing showing good safety in and I and I indication may be may be important before embarking on that but there are a lot of there's a long list of I and I indications including some you know rarer but higher value higher or higher morbidity diseases that we could consider going after as well terms of when the governance around the collaboration with Roche has us and Roche really equally represented and it's really whether the the you know each therapeutic area team feels is best so we are excited to understand where Roche would like to take the drug we have ideas right now we have a lot on our plate you know just in terms of executing on what we set out but it's possible that we would add additional indications got it maybe switching gears to the stat six you guys have a program that your partner with sanofi and you know your your peer out there chimera will have data you know hopefully to de-risk you know this this target and this class of drugs so maybe just talk about your program the partnership with Sanofi and it's just I think entered the clinic so yeah you're hoping to get some maybe data you know maybe sometime next year but maybe you'll give us a little bit of background and where we are in development yeah great so the program with Sanofi stems from a 2019 five target discovery deal that we did stat six was one of the initial targets that was put into that collaboration we generated a degrader to it we licensed it to them last year at the, you know, just development candidate stage. And just this past month, we announced that they've initiated the phase one study for that program. We've shown some preclinical data. It's very potent, subnanomolar potent. It's probably the most selective degrader that we've made it's incredibly selective we think it's a fantastic drug and Sanofi has disclosed her in phase one that study is a sad mad healthy volunteer with at least they're also treating patients in that study that study should inform our option decision so when that data is when that trial is complete we have an option to um to go 50 50 uh co-development co-promotion profit share with them in the u.s um and uh yeah so the chimera data we're eager to see the you know how that pans out so far they've shown biologic like activity uh with a relatively clean safety profile as far as we know and um you know the more de-risk this target gets i think the more value that will accrete to to our program so as you think so you kind of talked about so this phase one program will include a cohort of patients is that so should we think about this is a similar type of program that chimera ran but theirs with like a near like phase one b you know kind of small cohort uncontrolled or um is it more robust than that yeah i mean unfortunately i can't say more about it than that uh san sanofi has limited disclosures and we're only uh able to speak to what's in the public domain there is a listing on the european clinical trials site which states that it includes healthy volunteers and patients it doesn't denote what type of patients those are or how that cohort is designed um but uh you know i look to what chimera did and it was similar could have been described similarly so um so yeah that's uh that's really all i can say about it got it And I guess when you think about STAT6 degradation versus STAT6 inhibitors, you know, there's a few other out there like Rekludix and whatnot, also exploring that, Pfizer.

Where do you think, whether the issues or the challenges lies with inhibitors relative to degraders and, you know, what gets you confident that degradation is the best approach?

Yeah, so I have two thoughts on that. The first is that the knockout for STAT6 looks really clean and the degrader mechanism is the closest thing we have to a knockout phenotype. And, you know, all the preclinical data supports that. And, you know, our experience with BTK and other targets suggests that this is, you know, a very safe and effective way of really maximally addressing a target. Now, when we talk about comparing, so this is the second point, we talk about comparing degraders to inhibitors. Classically, you think of an inhibitor as being the less risky modality. You know, we have inhibitors of BTK, we have inhibitors of lots of things, but there has never been, you know, an inhibitor of a STAT-6 because it's not a catalytic enzyme, it's a transcription factor. So the novelty around inhibitors is actually quite high as it relates to transcription factors and some of the ways that they're trying to do it, whether it's SH2 blockers or other types of blockers, there's a lot of novelty and a lot that's not known about selectivity and off targets and things like that. So, and target coverage, it's, you know, it's not as easy to measure, I think, as an enzyme. So, you know, our view is you want to hit the target, degrade it. Gotcha.

And so trials ongoing, and as you said, you'll get a decision point at some point where, you know, you will see the data. I mean, should we understand that, like, because it's a phase one trial, and Santa Fe's probably not going to report out results, but at some point you'll kind of just pop up and be like, you know, we've decided to move forward with, you know, the co-development plan, or like, how would that disclosure end up happening? And I'm sure there's some sort of period where you will sit with the data, review it, and then come to that decision, but what are, I guess, maybe high level, what are kind of the mechanics of the decision-making process?

Yeah, so our option is triggered by results of a trial that were designed to assess safety, dose, and efficacy. So given that last piece, efficacy, that would require at least a pilot phase 1B in a disease setting. And so it's our assumption that the trial that they're running should be sufficient for that. And we would, yes, we would get a data package, which we would then have a period of time to make a decision. In the meantime, we're paying zero dollars for the development. And then if we opt in, we would just pay our share going forward. There's no catch-up payment or nothing like that. in terms of their disclosure you know we're we're you know we're eager to have them say more I should say but that's really going to be up to them seemingly an important program for them yes and then I guess one of the things I'd love to get your take on so you know we cover chimera and you know I think there's differing views and like where the efficacy needs to be first at sixth to greater relative to DUPI.

Do you believe that it needs to kind of mirror the efficacy or, you know, it can still be, you know, 70 to 80% of the efficacy of DUPI and still be successful because it's an oral, like where do you kind of come down on that in terms of like where you think it needs to be benchmarked? I think you wrote a giant report. I did. Yeah, I read it on the plane.

It was, that's fantastic. If you haven't read it, you should read it. You know, I heard the, you know, the doctors that you interviewed had expressed that you could have a drug that's even you know a notch down versus the biologics and efficacy and would still be a huge opportunity and you know the example of course is a tesla which is not a great drug and it does a lot because you know people want to step through an oral um and that the the the biggest opportunity is not to for example replace dupy but to expand the market there's tons of patients who suffer for a long time either before going on dupy or never go on dupy or something similar so i think a safe and effective

oral truly expands the market and um and so yeah i think there's a lot of room for for this drug class to be to be a mega blockbuster yeah great and maybe with the last couple of minutes you know just we were just talking about it before we went live here but you're kind of the the other components to your collaborations and you know what the overall nurix platform is like capable of so we were talking about you know the you know the dax and you know other things that you guys have kind of done deals on but i guess you know what what is kind of exciting to you guys that you know you've got a lot of collaborations but internal pipeline that you

guys want to start to develop because now you've got a big cash infusion you can kind of you know kind of go in any direction you want with the early stage pipeline so what what are you guys thinking in terms of new targets is it more oncology more ini or other areas like where where do you want to take it yeah it's a great question so first of all you know we think we have one of the greatest uh to greater platforms out there it's been very very productive since Since our IPO in 2020, we've put six drugs in the clinic, including two in the last two years, STAT6 and IRAC4. We have more coming. In terms of where those programs are going to be, we are primarily focused in oncology and immunology, and I think that's where you're going to see the most interest in In terms of our late preclinical, our most advanced preclinical is a pan mutant wild types bearing BRAF degrader, which has the potential to be a mutant selective genetically defined drug in lung, colon, or melanoma. It's very much best in class potential and something that we could take forward on our we also have INI programs that we haven't disclosed importantly you know you mentioned the DAX that was a deal we did with CJEN now part of Pfizer that's moving along very well we haven't disclosed much from it but we do have options for 50 50 co-promote profit share on two programs we have options for two programs out of the Sanofi and we have options for two programs out of the Gilead collaboration so our our pipeline is not only generating non dilutive capital from our partners but also generating product rights and and and ultimately drugs for our own portfolio I mean do you think the directions that would be more focused on looking at targets that maybe you're just not appropriately drug with inhibitors and kind of validated but you know sub-optimal or are you guys ready to take you know even more you know kind of risk around kind of targets on yourself like a very internal it's a great question I mean originally we went with BTK as a very de-risked easy to monitor target we saved some of the more difficult targets like SAT 6 to be under our collaboration with Sanofi going forward we are disease agnostic to a certain extent and we're looking at targets that are high value across the proteome so um you know there's stay tuned there's there's a lot a lot under the hood gotcha and then so maybe just sketch out for us with the last question like 12 to 18 months you know what should we expect you know from you guys um in terms of updates and you know internal and external partnerships as well yeah it's going to be it's going to be a busy it's been a busy year it's going to be a busy you know next year through through through the end of the year This year, we're looking at data from the Phase I Healthy Volunteer Study, which is going to enable the IND for CSU and MS. We'll have an update, a clinical update at ASH. Going into next year, we're looking at opt-in for IRAC IV and potentially some visibility on that data. we'll be looking at additional clinical updates at EHA and ASH will be making sort of go-no-go decisions for next steps for 1607 which is our civil B inhibitor as well as zelabrutamide which is our dual BTK-IKZF degrader and ultimately if you kind of think where we'll be next year end of the year we will have visibility on pivotal readouts from our CLL program will be, you know, deep into our combination studies as well as phase two studies for CSU and MS. Got it.

Well, Jason, I think we'll leave it there. Thank you so much. Terrific.