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

preparing with us for a few minutes. My name is Gil, and I'm a senior biotech analyst here at Needham Company. It is my pleasure to have with me today Dr. Arthur Sands, who's president and CEO of Nurex. And as a reminder, viewers who are watching can submit questions for the ask the question box. So, Arthur, a little belated, but some introductory comments and maybe a quick word on the company's platform relates.

Sure. So, we're very excited to be entering phase three this year for with our new uh our our lead agent bexabrutideg which is a uh btk degrader being developed for cll um in addition uh we do have ambitions for uh its use in ini disease and i'm sure we'll talk a little bit about that so autoimmune indications um but all of the bexdeg success through the development so far really relates to our, I think, incredible drug discovery platform in which we have identified a whole host of novel degrader, targeted protein degrader molecules against not only oncology targets, but also autoimmune targets, including STAT6 with our partnership with gilead and iraq four i mean stat six sorry with sanofi um and then iraq four with gilead uh which are uh which is in the clinic now and uh stat six soon to be uh so we have a whole pipeline to discuss gill i know you're really familiar with our story overall uh we're we're headquartered in the bay area approximately 350 employees and again very exciting year to to enter pivotal trials, registrational trials.

So maybe a good place to start is SpexDeg in CLL. Just a quick reminder for people kind of how the data looks like.

Yeah, so we've reported at ASH most recently an 83% overall response rate in fourth line plus patients. So very advanced patients with CLL. So a very significant ORR. We also have some of the first PFS measures, progression-free survival measures that we've disclosed now at 22 months for our most advanced cohort of patients from the Phase Ia, which compares very favorably with competing agents, again, and very advanced patients. So we're very excited to initiate, as I said, the registrational trials. We're already running a potential accelerated approval trial, which is a potential pivotal trial phase two in these advanced patients, very similar patient population to what we've treated so far. So that's just highlights of the data. Of course, we get complete BTK degradation. We have great biomarkers that also all are moving in the right direction. and we can talk about other aspects of the data as you wish.

Have physicians shared any initial thoughts? I mean, we already have a pretty decent data set. How has this been accepted by physicians?

Well, the best evidence for that is the rapid opening of our sites for these trials, for these registrational trials, lots of interest. I think that's going to go quickly through the initiation phase for the phase three. And then I would anticipate enrollment will go rapidly as well because the results are positive. Of course, physicians prefer to put their patients on a drug that has a great probability of working. So I'd say very, very well accepted. I think the degradation mechanism of action is being increasingly accepted and well recognized. That's been a very interesting process of education now for the past several years. And there it's clear that degradation allows for addressing the resistance mutations to inhibitors. And so that's a very compelling molecular story that we've been able to show because, of course, we can catalog all the resistance mutations that our patients have that have been on these inhibitors and then show that these patients are responding so that's been that's really connected uh with with investigators and i think the other attributes of the drug it's it's long durability uh and now that we're getting the pfs data durability of response it's also connecting uh quite strongly with investigators and of course with patients we've had patients now on over three years on Bex and Brutadag.

Are you guys seeing any challenges or competition for the patients while you're in these studies? I mean, you kind of alluded to it sounds like you have a good selling point.

Yeah, well, it's a competitive area of CLL. There's lots of trials going on. There's lots of combination trials. We're one of two to greater mechanisms, so B1 being the other company. There's some competition there, but that's not a lot of competition to be one of two. And we're in good company. B1 is certainly a leader in the field. And so I think that has lent a lot of credibility to the Nurex program, the BTK degradation concept in general. Of course, we think Bexut Brutadeg is going to distinguish itself as a best-in-class degrader overall. But so far, you know, the competition has not really been an issue because again, we're very unique in our MOA.

Yeah, super helpful. So I do want to spend a second on the confirmatory study, which is also planned in the near term. You guys changed a little bit the way that you designed it. It was best available therapy. Now it's against PERTO.

Can you walk us a bit through the considerations there well so first off purdo only recently gained full approval so in terms of going against a comparator arm it is you know generally best to go against something that is approved fully uh so that gives you the broadest base worldwide um and so with that um And plus, looking at our own data as it matured, that we became very convinced that we have a potential superior activity to protobrutinib, you know, as our data matured. We didn't really have our PFS data until late last year, so you really have to look at the data to be able to even predict the scale of your trial, power it appropriately, all of those things. Suddenly, we could do that when we had all the data. It coincided with PROTO's full approval. And so it was logical to then just upgrade the trial to really go against the latest approved agents, which we think we can beat.

I mean, it also helps that it is aligned with your competitor as well. Apples to apples.

Yeah, so it's apples to apples. Certainly, we're going to go toe to toe. I'm sure we can talk about differentiation later, but I think it's important. And also, you know, things are competitive, as you mentioned earlier. So you really have to design a competitive, attractive trial where the control arm is the most recently approved agent. Your trial is relevant, you know, and will be relevant three years from now as well. So a lot of things go into the trial design, obviously.

Just as a clarification, are there any issues with this XUS specifically?

I'm sorry, could you repeat that? any issues ex-US yeah uh no i we don't see any uh you know it's been a very popular agent so there's a lot of i think it's going to be attractive um we do have to you know make sure it's available in all these different countries since it is recently approved so there's a few logistical things but i mean this is going to be mainly a u.s and european trial right these are and and perdo is going to have wide distribution availability there too all right let's spend some time in the competition um maybe starting with how you guys view yourselves as differentiated from from b1 well we uh we've shown some of the data of how we're differentiated at a pre-clinical level uh where we can actually compare compounds head to head in human cells, B cells, etc. And there we are tenfold more potent on a cellular basis when looking head to head. We also see greater selectivity. We've measured off targets very carefully through global proteomics. And the only thing we hit is BTK. And with the B1 compound, We see many off targets lighting up on the proteomics scan, indicating that they are hitting those in some way. So I think that in addition to potency, which generally translates to efficacy, I think we're more selective. So we've got, which translates generally to safety. I mean, just speaking in broad terms. So I think that that will ultimately lend itself to the best in class profile. Yeah, it's a very important point, I think, worth emphasizing, you know, considering how long patients stay on inhibitors of BTK as it relates to any safety differential would eventually show up if you wait long enough. that's a major consideration that that is certainly true and then also uh of course it increases the you know longevity of the drug in general drug use in general which of course translates to sales etc um but then there's another dimension uh gill which is it also affects dose so the safer you are the higher you can dose and we we're dosing at our our maximum maximum dose tested at 600 milligrams which we went through the randomization cohorts under project optimus of the fda and um submitted and they agreed with us that 600 uh was a safe dose to go forward to you know optimus is all about safety really uh for targeted therapies and so that gives us more coverage of mutations in our view too so that all all kinds of mutations mutations not just btk mutations but certainly all btk mutations so i think it can also safety can also affect efficacy because you can not only dose for longer periods of time chronically as you point as you pointed out but also you can dose at a higher level to cover you know bulky disease genomic disease of all kinds in these patients it's really important it all translates to efficacy in the end superior efficacy in the end and another important point is is this a winner takes all kind of market is this a market where you feel more than welcome better can live side by side you know it tends to be a side by side market uh unless there's a distinct advantage usually around safety as you point out because of the chronic use um and that's why you see you know zanabrutinib and acalabrutinib doing you know quite well um you know there's probably room for protobrutinib this market is growing forecast to grow to i think 12 billion dollars a year or more in the next couple years so i think there's room but again if you do get an edge somehow either safe safety being the most likely um then then you can really become just the primary winner actually okay um i do want to spend some time also on earlier lines that's the sure that's a larger portion you guys are doing several forays here combinations etc just given length of therapy on earlier lines is it feasible for you guys to like continue development in that state in that setting it is i mean you have to be very smart about how you design the trials so that You have endpoints that are, you know, reachable in our lifetime, right? I mean, which is our goal. We don't want to be waiting forever for results. So we're looking at these different approaches very carefully, trial design, et cetera. I'm not really prepared to talk about, you know, a second line or a frontline combo trial yet. Of course, the PERDO head-to-head is a second line. um and but there you know these patients advance more more rapidly unfortunately so the time frames are reasonable um in front line whether it be combo or mono you really we really have not outlined that design yet but we're going to work very hard to make it a smart design so we get meaningful readouts in a meaningful period of time any thoughts about another selective study, let's say, CNS involvement?

You guys do penetrate the blood-brain barrier.

So we do have a cohort open for patients with CNS disease. And I do think, you know, eventually, one way or another, that should make it onto our label, although we'd have to see exactly how that happens. It is such a unique and, you know, relatively rare set of patients, but it's medically important for patients that don't have CNS disease also, because what it means is you're providing coverage of the brain so that the brain does not become a sanctuary you know organ where which is what happens with chronic therapy you can actually get then the cells eventually are selected for that are in the brain so you don't want you know obviously nobody wants that to happen so i think it becomes a medically important distinguishing feature and we've had some dramatic results with patient for patients who had terrible cns disease actually um coming into the trial because we we uniquely enrolled allowed enrollment of those patients so we'll have to figure out the regulatory approach there but i do think medically it's very very important and will be another differentiator um let's shift gears a little bit to autoimmune with that so deb yes um a little bit on the change of formulation here um kind of what is the logic i mean uh tablets versus the the oncology formulation so the the logic is several fold so uh first off when you have a new agent and you you generally go in with one of the more most straightforward uh formulations to manufacture to get into the clinic and look for results which is what we did with our crystalline formulation and and it's had great results and been very rapid in terms of development and manufacturing and then you know with a new moa typically one will look for better formulations to improve improve the pill burden improve absorption perhaps improve other certain other parameters and these degrader molecules are actually rather large small molecules so they do tend to have poor absorption okay so let me illustrate for this so we're dosing at 600 milligrams but we're our blood levels that we achieve but we're we're far more potent than the inhibitors you measure the inhibitors you know so why is our dose 600 milligrams if we're 10 to 100 times or a thousand times more potent well not the absorption is fairly poor so you you have a good window uh to improve upon by working on other oral formulations and you could get a lot more drug in, perhaps enhanced efficacy as well and other attributes. The blood levels of our drug, just to compare to perturbrutinib, for example, to illustrate what I'm talking about, our therapeutic blood levels are approximately 2,000 fold lower than perturbrutinib's therapeutic blood levels. So that just shows you how dramatically different these moas are so you don't need much drug to get in and the more efficient you make that probably the better uh the better results you're going to get overall that's that's sort of on the pkpd side then on the on the commercial side you know it does allow you to brand a different drug and very different doses are going to be needed and very different safety profiles will be generated so with a different agent that is a branded different agent, ultimately, you can distinguish all of those features. And in autoimmune disease, there's so many different ways we can go.

You guys did guide for some data later this year, especially from specifically from the study. Any expectations we should have here?

So we've been talking about the healthy volunteer studies of the new formulation, which will help describe where we're going in autoimmune disease. So they'll be very relevant at many levels to the study design, to the indication choice, and the data themselves, I think, will be important in these regards, even though it's healthy volunteers. So there's so many biomarkers we can study with this approach that it becomes very graphic in terms of how you would align to the existing agents of inhibitors. So we have such biomarkers given degradation mechanism. We can really align our dose and align where we think will be efficacy-wise, even based on healthy volunteer studies. So we'll do the best we can with that.

And last but not least, what kind of indications should we be thinking of? You have mentioned this in the past.

Just a reiteration. well there's so many choices um i i see them in certain buckets um and you want to consider the risk benefits the the pricing uh the precedents other drugs competing drugs but roughly they can be grouped into uh dermatologic as one bucket um neurologic like such as ms um and then hematologic there's the heme um a non-malignant heme auto i mean itp uh weha those sorts of things in the dermatologic there's a few categories but in general they're they're allergic based or severe allergy based which could also include when you talk about allergy then food allergy comes into potential play so there's a number of areas uh we could go in and each one of course is very different we'll have different dosing and has different timetables for drug development so one of our goals would be do something where we can get results fairly quickly you know compared to other other indications um but then the other when you look at something like ms which takes longer that's so valuable and so unique and we already know we have activity in the brain. That's also very attractive. I'm not answering yet because we're going to save that for the second half and show you the data that goes with it.

I do want to spend some time on StatsX specifically because this is something we get asked a lot about. Do you have your partnership with Sanofi? Anything you can say about your progress there to date?

Well, it's been quite a great drug discovery road with Santa Fe. You know, we started the program in 2019 when it was just considered an undruggable target as part of our original Santa Fe Drug Discovery Alliance. And that target and then development candidate was selected just over a year ago. So that triggered the IND enabling studies by any calendar, the typical calendar of drug development preclinical and so we should be on the threshold of you know entering the clinic with saniby now it is up to them they have they take control at development candidate stage they control timing they control news flow and of course they're funding the whole thing at this point and then um and then after human proof of concept In the clinic, we then have our 50-50 opt-in option, 50-50 in the United States, for a COCO. So that would be a time period that I think would be very exciting. But in the meantime, really, it's a Sanofi program. I can't think of anyone better to develop this. Of course, they have Dupixent, and they have strategic interests in this area, other strategic interests. So I think this is going to be a very interesting program to watch this year.

So speaking of competition there, I mean, how do you feel the space has changed with the data disclosures from Primera?

Well, it's gotten even more valuable. I think that their data is excellent. And I think that it shows that I do personally believe an oral will open up the market, as they have said quite a bit. So I think there's a lot of room for more than one agent. So it's going to be bigger than the Dupixen market. And so that, you know, I think it'd be quite substantial. And what else? I mean, it's not a lot to differentiate on so far. You know, we get that question a lot ourselves. How are you different? So I think that all I can say is that we optimize this with Sanofi kind of in lockstep with their standards. i believe that we've got highly highly efficacious agent and exquisitely selective so i think that you know we'll just have to see ultimately efficacy and safety the whole name of the game you know but now with atopic dermatitis i mean safety is even more important right even way more important than even cll right so i think what people are going to watch next in small molecule development in this area is going to be safety there you know i think you're going to see efficacy but then how safe is it because you know depiction is very safe i mean

these biologics are very safe so your your small molecule has got to be absolutely clean as a whistle i do want to spend also a second on irac 4 uh let's not forget that's a program you guys that are also running and actually may have nearer term information. Any guidance there?

No, it should, you know, on its schedule with Gilead, of course, it's similar structure to Santa Fe. So they're running the phase ones. And, you know, hopefully we should see phase one data this year. They've been in healthy volunteers, I think, for over a year. So that should be important. And then we'll see where it's going to go from there. So I think that's another great example of, you know, building a molecule that's exquisitely selective and safe and also shows efficacy. I mean, it's, you know, not lost on anybody that the first IRAC 4-degrader fell out of bed because of safety going into autoimmune disease. So this just illustrates that you really got to emphasize selectivity with these kinds of indications.

I'm not forgetting 21-27. What's the status here? How do you guys view this program at this point? I know we're waiting on some non-Hodgkin's lymphoma updates.

Yeah, so that's been walking through phase 1A dose escalation with the chirally controlled compounds so hopefully we'll update it in the second half for two and two seven don't forget 1607 either that's also um that wasn't that's next on my list next on your list um yeah we've had a couple programs that have shall we say taken their time in phase 1a um because of dosing and figuring out just about every detail one you know possibly can and a few twists and turns But now I think with 1607, we're at the stage of really getting to phase 1b. I think 1607 is ahead of 2127 in that decision-making tree. And so I think, I hope also in the second half to have updates on 1607.

I mean, yeah, there were some challenges around formulating the correct dosing, yet. But it seems you have worked through those.

I think we've overcome them. There was some simple, actually, GI tolerability challenges. It was, you know, in terms of once we learn how to dose and navigate that, patients tolerate out that. That seems to disappear in a large fraction of patients. But you have to give their body's chance to adjust to the dosing regimen. And it is definitely turning on the immune system. So, I mean, we've shown, we've published that, we see the biomarkers moving in the right directions. We see some early signals of activity, which are really intriguing as a monotherapy. And so, you know, we're poised to be very excited about that program. We just have to get to the end of this 1A journey. I mean, maybe the risk of sounding silly, but that one always felt like the combination story is probably where it's at in the sense that you know it's immunological activation you need usually need more oomph than that yeah so definitely we set a high bar we want to see some monotherapy activity i think that that you know then it then you have at least a much better chance of seeing the combo i think some other agents went in with basically no monotherapy signal and then you know then there's going to be a miracle a combo miracle and then it's going to work and i don't think that that's really the way it goes so i you know i i think that uh 1607 is a strong agent i i do think we're going to see you're not going to take it forward as a monotherapy is your point ultimately but you want to see some signal that is believable Yeah, no, I agree.

I'm 100% agree. Not giving short shrift to the rest of the platform, you guys are going to have quite a lot of presentations at AACR. Any one of these you'd like to highlight?

I think there are four of them. So, you know, I'm not going to show any bias because I love them all, like my children. But, you know, in terms of where the next big wave of technology platform productivity is, you know, the DAX, the degrader antibody conjugates. I think that's a really exciting area. We have not published a lot since signing up with CGen, now Pfizer, of course, but that's an area that I would watch just as a technology itself, not only Nurex programs, but others.

All right.

A little brass stacks, cash position, and kind of operational runway. yeah i think our what our last disclosure uh what 650 million in cash uh you probably you know i have to admit i don't memorize every number but um that's approximately it uh about two years of runway you know into 20 um 27 so toward second half so i think you know we're in good shape cash wise um you know we're certainly well funded to get the phase threes running um and uh i think it's going to be an exciting second half i mean we really had our nose to the grindstone for the

first half i have to say we've been a little bit quiet but we've been working on getting all these trials up and going excellent um we're pretty much at time so if you have any other item you'd like to highlight?

I think that we're going to have a great second half. That's all I can say. We'll have a lot more news flow and, I think, data flow. Like I said, this half has been really logistical and execution-based.

That's fair. Thank you, Arthur.

All right, thank you. Thanks, Gil.