All right. Welcome, everyone, to Jefferies London Healthcare Conference 2025. My name is Roger Song, one of the senior analysts covering medical 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, 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? You just announced you will have—you announced before you will have a data, the abstract, the presentation, and then some event at ASH. Can you just give us some overview, preview, what we expect to see at ASH, and then we can drill down a little bit of details?
Sure. Yeah. We're looking forward to ASH. It's a big event for us every year. We will be reporting on bexobrutideg and 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. That's a critical factor. It'll 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 two years on therapy. I think that'll 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 mg once-a-day dose for bexobrutideg. This is a result of running our Project Optimus randomized cohorts in phaseIb, looking at 200 mg versus 600 mg. I think this is an important development for the program. We're very enthusiastic about having the 600 mg dose being selected and having FDA agreement with that selection. It enables us to maximize for efficacy, which is, of course, critical. We can do that because the safety profile was very similar to the 200 mg and any of the other doses, too. We've tested from 50 mg- 600 mg. Having a safe profile allows you 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 covalents, non-covalents. There are five or six mutations that come up, these resistance mutations. We have seen this in about 40% of our patients. Bexobrutideg can degrade all of them, which is great. You do not have to design a specific new drug for every mutation, right? This has the ability to degrade them all. 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. One thing is that your later-line CLL pivotal study is going to 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'll get from the phase Ia or phase Ib for the triple-exposed patient?
It is too early to really do a really meaningful subset analysis at this point. We simply do not have enough patients in each of the categories. 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. That is an area of high unmet medical need. There is really no therapy approved here. We are 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 is our anticipation.
Okay. Yeah, 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. How do you think about 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? 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 actually set you apart from your competitor?
Ultimately, the most important label is, of course, gaining full approval as a result of the randomized control 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. It really is not going to be the largest market, and that's not the intention of accelerated approval. We're really looking forward to the full approval for which we're designed a study in the second line. Just after covalent BTK inhibitors would be the first full approval goal. That is a very large marker where you're talking over 10,000 patients per year, likely.
Got it. 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. This may change. Some of the accelerated approval can be a moving target and is defined by the agency, really, at the time of filing. I do think that we have not only this triple-exposed population, but we have other cohorts of patients in the phase Ia and Ib that will also support, especially the safety database, of course, the ultimate filings.
Got it. Okay. Got it. Maybe circle back on the ASH. CLL, BTK degrader space, you have a couple of players there. Obviously, you will give us a very big update there. What are the other data points you are looking for? Also, you can give investors some contextualization, say, "Okay, these are the data may be meaningful for us to compare across different programs.
We have a podium presentation in that session. B1 will also be presenting, I believe. It is 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. It is really interesting to see these evolve. I think there is a lot of attention from the investigator community on the degrader modality. We will be looking to see what they present. Pertobrutinib's progress is always very important to us, as I think what will be the latest entrant into the CLL market. We also will be presenting a poster on Waldenstrom's, where we also see an 85% response rate, so very high response rate like CLL. I think we will be very interested in the other presentations on Waldenstrom'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. We will be monitoring progress in NHL, which is a very complicated field with a lot of combinations. I think we are also planning a combination trial with bexobrutideg in CLL. I think looking at all the latest combination data with the inhibitors will also be informative as we formulate that trial.
Yeah, absolutely. Okay, so the pivotal study you are started in the third-plus line triple-exposed population. This is 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? Yeah, start from there.
For the first accelerated approval, it's about 100 patients. We haven't revealed our exact statistical plan for that, but it's a fairly straightforward single-arm study. I think that'll be, again, fairly straightforward from a stats standpoint. The randomized control trial, bexobrutideg versus standards of care, plural. We currently have outlined 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 rituximab. We are studying that because in different geographies, we want to do one global trial. Different geographies have different approval status and use status for these different drugs. We are studying that very carefully. We want something that'll be the most appealing across the board. We will be in over 20 countries with that randomized control trial. Currently, that's what we've outlined in terms of control arm.
Again, we have to have conversations with all the regulatory authorities and come out to some consensus view of what single trial would play well across the globe.
Yeah. Because it is dealers' choice across different comparator arm, how are you going to manage the comparator arm performance and then when you design the study?
We have made certain assumptions about use in the control arm, but also we need to integrate regulatory feedback as we implement the phase III. There may be some regulatory considerations there in terms of what proportions of patients are required or desirable in the control arm. All that's ongoing work.
Okay. So maybe some range of the population or the percentage of the patient population need to use certain comparator arm, the dealer's choice.
Yeah, 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 feel that they will gain an important therapy by being in the trial regardless of where they're randomized. There are still some items that we need to calculate.
Got it. Okay. You mentioned you will have a combination as an option moving forward. This is also very important to move into a real first and second-line CLL population. I believe you are starting or you already started the combination phase I study. When are we going to start to see those combo data and how is the moving to the pivotal stage?
Yeah, so to be clear, we have not started that study yet, but it's in planning stages. I think combination of bexobrutideg BTK degrader with venetoclax is something I think everyone would like to see rapidly, so the BCL-2 inhibitor. That'll 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. I think venetoclax will be one. We're looking at anti-CD20 as well, potential rituximab or obinutuzumab. Obinutuzumab would be more of a front-line combination. Rituximab would be in the second line. 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 or bringing the T-cell into the equation with bexobrutideg. That's another potential combination. Again, stay tuned for that. We have not actually implemented that trial. We're actively working on planning.
Okay, great. Okay, this is your CLL part of the story, but given you are a degrader platform company, you are having other angles. Maybe start with just still the BTK degrader, you also potentially can do the INI indication. Remind us where you are for the INI. I believe you start from the CLL cohort and then move into non-malignant INI population.
Yeah, so BTK inhibitors have made a lot of progress in many indications where they've been tried. People are seeing success across several companies. The advantage we would have with a degrader, however, is really, we think, significant because the inhibitors are really only addressing the kinase function. As in CLL, we're addressing both the kinase function of BTK and the scaffolding function. We've discovered through our CLL work, the scaffolding function or structural function of BTK, by virtue of the protein simply being there located at a node in the cytoplasm, B-cell receptor signaling goes through that structural function. It's not just the kinase function. It's actually quite a significant and powerful signaling function coming through that. We think we can bring the same improved efficacy to autoimmune disease as we're seeing in CLL.
We have a mechanistic rationale to have BTK degradation be an advantage in autoimmune disease. We are and have developed a new formulation for bexobrutideg, which we think would distinguish its product profile. We have not revealed what those attributes are yet. We are currently in multiple ascending dose studies in healthy volunteers in preparation for potential IND in 2026.
Got it. I believe your bexo is also starting to get some data from the INI population within the CLL patients. Where they are and then do we expect to see any clinical data near?
Yeah, we were able to fairly rapidly. We've opened a cohort in CLL for patients that have autoimmune disease also. There is a layer of warm autoimmune hemolytic anemia in certain CLL patients. We do have a separate cohort there. That cohort is not enrolled yet. We have not forecast when we'll have data from that. I should also mention, we also have our CNS involvement cohort. That's another distinguishing feature of bexobrutideg is the activity in the CNS. We enroll patients with CNS lymphoma. Again, on the IND front, it's the AIHA group of patients.
Okay, you have not yet enrolled patients?
We have enrolled patients. We haven't completed enrollment, and we don't have enough patients to really report on yet. But we have enrolled patients, yes.
Got it. Got it. In terms of non-malignant autoimmune disease, what are the indications? Because BTK approved in multiple indications, including multiple sclerosis and then CSU. What are the indications most interest you? How's the feedback you hear that men need to address on top of the beyond the inhibitor, the indication you can address?
I think I mentioned the CNS activity because I think in MS, it is probably really one of the most interesting areas potentially given Roche's recent results with their BTK inhibitor in MS. I think we're encouraging based on their press release. I think Sanofi's results have also been very encouraging. They had two major publications in the New England Journal of Medicine. The central thesis there in terms of why it's advantageous as compared to the anti-CD20 antibodies in MS, which currently dominate really the MS market, is that you're blocking the actual microglia in the brain that are thought to be responsible for the neuronal, the degradation of neurons. For the ultimate neuronal damage is driven by that brain-resident inflammatory process. Rather than just depleting the B cells, you actually need a molecule that can block the microglia activity.
That's the central thesis of, and you'll really modify the disease progression then. That is really the hope, and I think it's the most exciting thing in MS right now. Data we have, we know we cross the blood-brain barrier, number one, from our CLL patients. We know we have responses with inpatients that have CNS disease, quite dramatic responses. We have clinical activity. Our drug levels in the cerebral spinal fluid, CSF, are basically equivalent to the free drug plasma levels. We get a one-to-one. We're getting good exposure in the brain. Some of our recent data in animal models, especially the rat, we see basically 97%+ degradation of BTK, so removal of BTK from the microglia cells. We have a direct measure of hitting this microglia hypothesis. Of course, the microglia are thought to be responsible.
MS is the largest, but any neuroinflammatory type of disease. I think that's a very exciting pathway. You're right. In skin, CSU, and others, others have shown activity. There's a lot of excitement in the field. I think bringing a degrader into that realm could be quite interesting.
Excellent. Okay. We spent most of our time on the BTK, as expected. As we mentioned, you have a platform, and you also have some partnership, right? Some of the high-interest, high-value targets, including STAT6 and IRAK4. Maybe one is, where is the status of those, kind of the early partnership pipeline? Also, how do you think about the research from the industry, from other companies? You think, compare your program with theirs, and then once they get data, how do you think about the research?
Yeah, so the first one, IRAK4 degrader, with Gilead GS-6791, is in a multiple ascending dose study currently. They are conducting the phase I program. That has been a discovery program with Gilead for the past six years. We are very happy that it is in phase I. We hope that we will see data from that in 2026. That program has an excellent profile. It obviously has sailed through all the safety studies. We have not seen any QT signal there, which is one of the signals that derailed another molecule in the space, not our molecule, but a competing molecule. We are very happy with the profile of GS-6791. The second one is in IND enabling studies, it is our STAT6 degrader, NX-3911. It is with Sanofi, who is prosecuting the IND enabling studies.
We expect it to get a very long Sanofi number eventually, but NX-3911 is easy to remember. It is a great profile drug. We were allowed to show certain data, preclinical data for both of those recently. NX-3911, the STAT6 degrader, is extremely potent. It is picomolar level degradation of STAT6, very clean safety profile. We showed the proteomic profile where the only protein degraded is STAT6. It is very, very significant and clean. That, I think, has gotten a lot of attention. We know that chimera will have data shortly. I think that is the program you are referring to, their STAT6 program. That looked quite good in phase I. We look forward to their atopic dermatitis data. The big goal is to have a dupixent in a pill as the goal for this in terms of therapeutic profile, so very large market opportunity.
Yeah, sure. You do have the co-development and then co-commercialization, right? Right now, they control the early development, but you do have that. Remind us where you are and how you're going to make that decision to opt in to become the co?
Yeah, thanks for bringing that up. Yeah, we have a very valuable opt-in right after human proof of concept for our STAT6 degrader with Sanofi. That option would trigger a 50-50 co-development in the United States, co-commercialization. We get to see human data before we make that decision. Obviously, the data is what is the most important in terms of deciding factor. If the data from the human studies, the patients look anything like they do in the animals, which are fantastic atopic dermatitis results, asthma results we've seen in these animal models with Sanofi, that would be a great option to exercise. IRAK4, similarly, we are able to see phase I data. We get to see the human data package from phase I with Gilead and then make a decision about the option there.
With the Gilead option, they do have one veto right. We have options on several programs across our partnerships. We actually have six options across three partnerships. A number of these options will be starting to hit in the 2026, 2027, 2028 timeframe. We are going to have a lot of decisions to make, a lot of data to consider, and a lot of very valuable options. Sanofi does not have that veto right. We were able to not have that in that agreement. There is no veto right there, but.
That's interesting. Okay, good.
Yeah, it's a little bit of poker.
Yeah, okay. Push and pull. Okay. Lastly, you have a lead program in a very late stage and potentially moving towards the pivotal. You also have an earlier pipeline and the partnership. How's your balance sheet look like? Any other early pipeline you want to highlight to us for the last minute?
Yeah, so we were very fortunate to have a great group of investors participate in a recent round, raised $250 million, I think, about a month ago. Counting that, it brings us to over $650 million in the banks. We're in a very strong position runway through the beginning of 2028. That allows us to get our CLL program fully underway. Also we expect during that time horizon, we'll have some of these options we talked about that'll come to fruition. Fortunately, those don't cost us anything when we act on them. There's no option fee, but then we would be responsible for go forward funding in the United States.
Yeah. Obviously, if your data is positive, you've made the decision to opt in, probably the investor community will appreciate the opportunity and then you can.
Oh, yeah, that'll be part of the equation.
Yeah. Got it. All righty. Thank you, Arthur, for this morning. Thank you, everyone.
Yeah, thank you, Roger.