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

All right. Welcome, everyone, to Jefferies London Healthcare Conference 2025. My name is Roger Song, one of the senior analysts cover SMid-cap biotech in the U.S. It is my pleasure to have the fireside chat with our next company, Nurix Therapeutics, CEO, Arthur Sands.

Thanks for having us, Roger.

Absolutely. Great. Okay. So I think we have quite a few things to cover today. Why don't we start with the most near-term event that you will have at ASH, right? So you just announced you will have -- you announced before you will have data, the abstract presentation and then some event at ASH. Can you just give us an overview, preview what we expect to see at ASH? And then we can drill down a bit of details.

Sure. Yes. So we're looking forward to ASH. It's a big event for us every year. So we will be reporting on bexobrutideg NX-5948 follow-up data, longer-term data from the Phase Ia as well as data from the Phase Ib. I think the most relevant disclosures will involve the duration of therapy, duration of response, where now in the Phase Ia, these are the patients that have been on the drug the longest, so we can start to actually measure and look at PFS and duration of response, and so that's a critical factor. It will be the first time, I think, that we'll have enough time gone by on therapy to be able to measure this because we've had patients now over 2 years on therapy. So I think that will be one important component. The other will be looking at the dose selection for the pivotal trial, which I'm talking about in CLL, which is our primary indication. That is we've selected the 600-milligram once-a-day dose for bexobrutideg. This is a result of running our Project Optimus randomized cohorts in Phase Ib, looking at 200 versus 600. And so this is, I think, an important development for the program. We're very enthusiastic about having the 600-milligram dose being selected and having FDA agreement with that selection. It enables us to maximize for efficacy, which is, of course, critical. And we can do that because the safety profile was very similar to the 200 and any of the other doses, too. We've tested from 50 to 600. So having a safe profile allows you to test to proceed with your maximum dose to really push the efficacy envelope and maximize efficacy. This becomes important to address, we can degrade all of the BTK protein in the cell, even those proteins that have gained mutations as patients have become resistant to the current BTK inhibitors, including all the covalent, non-covalent. There's 5 or 6 mutations that come up, these resistance mutations. And we've seen this in about 40% of our patients. So bexobrutideg can degrade all of them, which is great. You don't have to design a specific -- a new drug for every mutation, right? This is -- has the ability to degrade them all. So dose and duration therapy.

Excellent. Okay. Great. That's the beauty of the degrader for the well-validated target. Another thing is that you recently -- we're going to talk about the pivotal design and then what's the recent alignment with the FDA. But one thing is that your -- the later line CLL pivotal study, specifically in the triple exposed patient population. Will we be able to see some of those data? I mean maybe specific kind of sub cohort we will get from the Phase I or Phase Ia or Phase Ib for the triple exposed patient?

So it's too early to really do a really meaningful subset analysis at this point. We simply don't have enough patients in each of the categories. And so I think that will be a future disclosure. We have focused our first pivotal study, which is a single-arm study in the triple exposed population because we do see excellent activity there, and that's an area of high unmet medical need. So there's really no therapy approved here. We're anticipating that pirtobrutinib, the non-covalent inhibitor from Eli Lilly will gain full approval and that, therefore, that accelerated approval potential shifts to this triple exposed population, at least that's our anticipation.

Okay. Yes. Maybe stay on this pivotal plan, assuming you will do the study in the triple exposed patient and then you get approval and the accelerated approval path. And how do you think about the -- when you launch the drug and then using the population versus you have a competitor and it seems they are not specific for the triple exposed. And you say you're assuming -- you're expecting this product will become a standard of care at least in the U.S. How about U.S. versus ex U.S.? How do you think about this launch will -- your label will actually set you apart from your competitor?

Well, ultimately, the most important label is, of course, gaining full approval as a result of the randomized controlled study. I think the accelerated approval really allows physicians to start to work with the drug early to use the drug in certain populations and to really start to get into the market. But it really is not going to be the largest market, and that's not the intention of accelerated approval. So we're really looking forward to the full approval for -- which we designed a study in the second line. So just after covalent BTK inhibitors would be the first full approval goal. And that is a very large market. We're talking of over 10,000 patients per year likely.

Got it. So the accelerated approval path is really fast to the market and then the most high unmet need, that's the intention for the initial population?

Yes. Currently, yes. And this may change. So some of the accelerated approval is -- can be a moving target and is defined by the agency really at the time of filing. And I do think that we have not only the triple exposed population, but we have other cohorts of patients in the Phase Ia and b that will also support, especially the safety database, of course, the ultimate filings.

Got it. Okay. Got it. And then maybe circle back on the ASH. So CLL, BTK degrader space, you have a couple of players there. And obviously, you will give us a very big update there. And what are the other data points you are looking for? And then also you can give investors some contextualization and say, okay, these are the data may be meaningful for us to compare across different programs.

Well, in our -- we have a podium presentation in that session, BeOne will also be presenting, I believe. And it's always kind of interesting to see this competing degrader. These molecules are kind of neck and neck, tend to share the same session at every international meeting. So it is really interesting to see these evolve. I think there's a lot of attention from the investigator community on the degrader modality. So we'll be looking to see what they present. But also pirtobrutinib's progress is always very important to us as I think the latest -- what will be the latest entrant into the CLL market. We also are very -- we'll be presenting a poster on Waldenström, where we also see an 85% response rate, so very high response rate like CLL. And I think we'll be very interested in the other presentations on Waldenström's and other NHL programs. We have yet to present any of our NHL data, but we have over 100 patients in each of those across the NHL indication. So we'll be monitoring progress in NHL, which is a very complicated field with a lot of combinations. So I think we're also planning a combination trial with bexobrutideg in CLL. And so I think looking at all the latest combination data with the inhibitors will also be informative as we formulate that trial.

Yes, absolutely. Okay. So the pivotal study, you started in the third plus line triple exposed population in the -- it's a single arm and then also the confirmatory study, the second plus line for the comparator. Just remind us what's the statistical assumption you designed the study? Yes, we'll start on there.

So it's -- for the first accelerated approval, it's about 100 patients. And we haven't revealed our exact statistical plan for that, but it's a fairly straightforward single-arm study. And so I think that will be, again, fairly straightforward from a stat standpoint. The randomized controlled trial of bexobrutideg versus standards of care, plural, we currently have outlined an investigator choice control arm, which we believe will include bendamustine and rituximab as one option, also pirtobrutinib as another option. Another option could be idelalisib and RITUXAN. But we are studying that because in different geographies, we want to do one global trial, different geographies have different approval status for -- or end use status for these different drugs. So we're studying that very carefully. We want something that will be the most appealing across the board, and we'll be in over 20 countries with that randomized controlled trial. But currently, that's what we've outlined in terms of control arm. But again, we have to have conversations with all the regulatory authorities and come out to some consensus view of what trial -- what single trial would play well across the globe.

Yes. So because it is dealers choice across different comparator arm, how are you going to manage the comparator arm performance in the way you designed the study?

So we have made certain assumptions about use in the comparative -- in the control arm, but also we need to integrate regulatory feedback as we implement the Phase III. So there may be some regulatory considerations there in terms of what proportions of patients are required or desirable in the control arm. So all that's ongoing work.

Okay. So certain -- maybe some range of the population or the percentage of the patient population need to use certain comparator arm within those trials?

Yes. I think we'll have to study that. We haven't settled on what the breakdown would be. We want it to be, again, an attractive trial. We want patients to be -- to feel that they will gain an important therapy by being in the trial regardless of where they're randomized. So there's still some items that we need to calculate.

Got it. Okay. And then you mentioned you will have a combination as option moving forward. And this is also very important to move into a real first and second-line CLL population. So I believe you are starting or you already started the combination Phase I study. So when are we going to start to see those combo data? And then how is the moving to the pivotal stage?

Yes. So to be clear, we have not started that study yet, but it's in planning stages. I think combination of bexobrutideg, a BTK degrader with venetoclax is something I think everyone would like to see rapidly, so the BCL2 inhibitor. So that will be an important combination to get going and to decide on the dose. Again, since we have a safe profile, we feel very confident about our ability to combine. We have to prove that again that the safety is there. And so I think venetoclax will be one. We're looking at anti-CD20 as well, potential rituximab or obinutuzumab. Obinutuzumab will be more of a front-line combination. Rituximab will be in the second-line. And then we have other -- we could combine also with bispecific antibodies. I think there's a lot of interest in looking at some type of T cell engager, bringing the T cell into the equation with bexobrutideg. So that's another potential combination. So again, stay tuned for that. We have not actually implemented that trial. We're actively working on planning.