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

You may have covered this, but this Phase III trial that is designed, it will be designed to look for a superiority standard of care or noninferiority?

So the question is whether or not the Phase III will be designed to look for superiority versus noninferiority.

It will be designed to look for superiority to the control arm, yes.

So just quickly on ASH. I know we're getting an update on the Ib/Ia dose expansion/dose escalation data. What's kind of the expectation framework that you would like to provide in terms of what we're going to see? And is there anything that you would kind of suggest to investors that they should maybe pay -- be paying some attention to?

Certainly. The -- so the abstracts published, and it was sufficiently vague in order to allow us to present the data that we want to -- we think is going to be most impactful at the time of the presentation because, of course, you submit these abstracts in August and then the presentations in December. So there's a big gap there, and there's a lot of -- there's data cuts that occur. But I think what people will be looking for is a duration of response or progression-free survival numbers. How does Bexdeg perform? How long can patients stay on the therapy, which is a critical question. So I think that will be probably number one. I think looking for justification of the dose, data that justifies the 600 versus the 200-milligram dose, I think that's a major important point. So I think those 2 things because if you combine those 2 things, if you look at those and really study the data, then I think it will predict really how the drug will perform in the DAYBreak study, the Phase II single arm, but also how it will perform against competing agents. So I think those are going to be things to really align on. We expect to have these competing agents presenting a lot of data as well. So I think it will be really interesting. We often end up on the podium together with our competitors, and it usually makes for pretty interesting sessions.

So this notion of being able to get better visibility into durability. I know at EHA, right, you presented the dose escalation data only, right? And that kind of is the segment of patients who have been on drug the longest, and that allows us to maybe better tease out what that durability might look like. The ASH abstract lumped the 2 together, dose expansion, dose escalation. Will you somehow be providing kind of another snapshot of that dose escalation cohort for us to maybe better understand durability?

Yes, that's the goal. I mean to understand durability, you really need to look at the cohorts that have been on the drug the longest and that would be the Phase Ia. Then the Ib section where we're able to look at a randomization and doses gives you this picture into the dose question, right? So -- and then you can look at -- for safety, you can look at the groups together. So I think what we're going to try to do at ASH is to really look at the different slices because they'll show you different dimensions of how the drug performs, right? So that's very important to look at those different categories. Of course, the Ia data, although you can get durability from it, you have to remember that these are patients that are on all different doses from 50 to 600 milligrams, and they're all mixed together in terms of treatment duration. So I think the duration you'll see from the Ia is not going to be -- should be less than the duration you expect from the 600-milligram cohort ultimately once they've been treated sufficiently long period of time, right? So the snapshot that you'll see from -- at ASH and the Ia in terms of duration, I think, should be an underestimate basically of what the drug can actually do.

Okay. So one of the updates you also gave here in conjunction with this overview was this selectivity data, right? And I know that you and I have been kind of qualitatively speaking to this for a little while. But I think we finally saw a snapshot of it. And I think it looks pretty interesting. Can you kind of just summarize what you think that selectivity data is telling you about Bexdeg relative to some of the other competitor BTK degraders. And do you think this now begins to explain maybe some of the differences that we've seen on the safety tolerability side?

Yes. I think that this is a real differentiating feature for Bexdeg. I think Bexdeg is the most selective drug in the category. So -- and we see the selectivity superiority based on proteomics, very in-depth proteomics. So when you're working with a degrader, you can actually do the proteomics on cell types of relevance, i.e., B cells, and we've done this head-to-head against B1 and against AbbVie's molecule. And you can see which proteins are degraded that disappear in the proteomic scan. And for us, if you go at 10x the dose level that we treat, which is way you evaluate these drugs for selectivity, the only protein degraded is BTK. So it's really -- it's a thing of beauty in terms of seeing this proteomic spectrum. If you look at the competing molecules, you see many other proteins degraded. AbbVie is actually fairly clean, although TEC kinase is degraded, which is a known off-target associated with cardiovascular disease or cardiovascular side effects, I should say. And with the B1 drug, too, not only do they hit TEC, but they hit several other kinases that we think are associated with liabilities that are significant. So this proteomic scanning is really the latest technology to show this ability. And I think before degraders and before the proteomics at this level, you couldn't tell how clean your drug was. So of course, we've been using proteomics for years. And so Bexdeg is an extremely clean selective drug, and we think that will translate to safety advantages. People are familiar with the kinome scan to look for selectivity and kinase inhibitors. This takes it to a whole another level of selectivity. And so it's pretty impressive technology. So we think we're the most selective, and we think we're going to have -- that will translate to the both safety profile, and it also has translated to enabling us to dose at the 600-milligram dose level to get efficacy, maximize efficacy.

I know you have development aspirations for this drug in I&I. Maybe you can talk a little bit about what's ongoing right now and what we should expect to learn on the I&I front for Bexdeg within the next 12 months or so?

So we're currently conducting a multiple ascending dose study in healthy volunteers with our new formulation, which is designed for an I&I indication. And so in 2026, we expect to share those data, and that will really speak to the dose and also talk about which indication we intend to pursue. So this application of BTK in I&I, I think the inhibitors have gone there already, and we think the advantage of a degrader will be just as great for I&I as it is in oncology.

Speaking of the inhibitors, I think Roche just announced last week that fenebrutinib won in a couple of different Phase III studies in various MS populations. We know the CNS penetrants of Bexdeg is pretty exquisite. So does this now -- I think this is kind of like the second confirmatory signal that we've seen from an inhibitor within the context of MS, maybe more cleaner than the first one in terms of ambiguity, but where does MS sit on the hierarchy of things that you're interested in?

Well, given Roche's results, which I think are fantastic, on top of them Sanofi's result, I think it puts MS very high in terms of the target list for indications for a degrader. So the central thesis there is that they can inhibit the microglia, BTK in the microglia of the brain, and that will shut down the neuronal-based attack on neurons basically. So what's impressive with Bexdeg is we've done all those experiments, okay, with -- in animal models. In rats, especially, we've seen near 100% degradation of BTK in microglia in the brains. And of course, we get drug levels that equal plasma levels, free drug level in the plasma is equivalent to CSF levels. In addition, in our patients currently with CLL with brain involvement as well as primary CNS lymphoma, we've had some dramatic responses to our drug in clearing tumor cells from the brain. So we have little doubt that we have activity that's profound in the brain. And we think that this can translate to a real advantage potentially in MS. So the microglia are really the target. So it's really an exciting advancement of the field. But the advantage of a degrader versus inhibitor is that one Bexdeg molecule can degrade 10,000 to 20,000 BTK target proteins per hour. This is how the degradation is catalytic, how powerful it is. So it really will be able to deliver, we think, a much greater therapeutic effect than any inhibitor in the I&I setting.

Before we jump into a couple of the other things that are I&I related, maybe real quickly on CBL-B. We just saw data at ESMO. Maybe talk about what are next steps? And are you confident that you've established proof of concept here?

We are confident that we've established mechanistic proof of concept by inhibiting CBL-B, which is an E3 ligase, we are activating the human immune system with antitumor effects, and we published that at ESMO and now again, at SITC, another dimension that we published. And the signal was the strongest in colorectal cancer and prostate cancer. So cancers are normally cold, cold tumors in terms of their response to anti-PD-1 antibodies. So we're very encouraged by that. The biggest indicator for a potential successful IO agent is to see monotherapy activity. And we think we're seeing strong signals of monotherapy activity. The next step then would be to expand that and confirm those signals. So in a Ib study to expand cohorts as monotherapy and look for monotherapy activity against the tumors.

Okay. And then maybe just on 2127, which is another version of a BTK degrader that has preserved some of the Revlimid or the IMiD-like activity of the E3 ligase itself.

So it is a combination drug in one pill, in one molecule. It does deliver Revlimid-like activity along with BTK degradation. So that tees it up for really use in non-Hodgkin's lymphomas, diffuse large B-cell and mantle cell, where we've seen some dramatic, again, complete responses. So that is currently in dose escalation. We want to finish that in 2026 and then determine the next steps for that molecule.

Okay. Your I&I collaborations with Gilead and Sanofi, I know you're kind of limited as to what you can say about each of these things. But maybe you can just qualitatively speak to how you view the opportunity for competitive differentiation kind of relative to some of the first-gen molecules that we've seen out there thus far, right? So maybe the first-gen 1.0 version of an IRAK4 degrader from Kymera, now kind of the STAT6 degrader from Kymera. Where do you think there's opportunity to differentiate? And I guess in the case of STAT6, just given the magnitude of the opportunity, does that differentiation matter?

Well, starting with STAT6, it probably doesn't matter. There will be room for more than one successful molecule in the type 2 inflammation space, which is, of course, the Dupixent market, but probably greater than the Dupixent market given that these are oral. So I think there's going to be more than one winner in the STAT6 space. It's a fantastic target. Having said that, you're talking about really having to create a highly, highly selective compound that's very clean. The risk-benefit equation in type 2 inflammation is different than in cancer. And so really, you have very low tolerability for any safety issues. That's what happened to the first IRAK4 degrader ran into some types of safety issues, which was then canceled by -- with Sanofi and Kymera. Ours is in MAD studies right now, healthy volunteers with Gilead. And we think that we have a very clean molecule, our IRAK4 degrader, we think will proceed nicely into the clinic. We work extremely hard to make that exquisitely selective and safe, and it looks quite good. We apply the same standards to our STAT6 degrader, which, again, you have to set an incredibly high bar for selectivity. This is where this proteomics analysis comes in again. And we really throw the book of these molecules, making sure that we find the cleanest molecule that degrades just one protein. STAT6, it's clearly the sole protein we degrade. So I think that we're in a good position there. Sanofi has taken that molecule, which is NX-3911 into IND-enabling studies. And in 2026, we should see it go into healthy volunteers.

Okay. And then what are you expecting from the IRAK4 degrader that Gilead currently has in clinical development? And I guess, do you have any freedom to communicate around progress that is made with that drug under the umbrella of that collaboration? Or is that just something that will go through healthy volunteers, Phase I SAD, MAD and we'll never see anything?

I don't know. I suspect we will see data from the healthy volunteer data. I mean it's in Gilead's interest, too, because you need to cultivate interest with investigators to get enrollment and to show that these agents are safe and they hit the target. So they've been very good to collaborate with in terms of publication. And they published, too. They presented this fall, September, they did a whole poster on GS-6791 is the Gilead number now. And then also, we were allowed to show some data recently in our investor meetings with regard to our penetrance of keratinocytes of our IRAK4 degrader getting into keratinocytes and degrading IRAK4. And they're interested in atopic dermatitis, of course, and other -- there's, of course, a whole host. So yes, I think we'll be seeing data from -- I certainly hope so from the IRAK4 degrader.

Okay. Last question, unless there's any more from the room. Maybe just talk a little bit about the balance sheet. I know that you guys just strengthened it, cash runway and just what that now allows you to achieve.

Yes. So we have over $650 million in cash currently. This gives us runway through the end of 2027 into 2028. And this was strengthened recently. We're very fortunate to have a great investor base, with an offering we did of $250 million recently, and that put us in a really strong position to launch our pivotal programs, which is the primary use of proceeds, but also move our entire pipeline forward, including, of course, our participation with STAT6 and IRAK4. So we're in strong financial shape, and we're going to have a lot of data readouts over the next several months here. Starting with ASH in the next...

Starting with ASH in the next week or next month. Sunny Orlando. You can meet at Applebee's for beer.

Yes, that will be great to go to Disney World.

Thank you, Arthur. I always appreciate that.

Thanks, Steve.