Conference Transcript - NRIX 2026-06-03

Roger Song, Analyst — Jefferies

Welcome, everyone, to Jeffrey's 2026 Global Healthcare Conference. My name is Roger Song, senior and this covers SMIC at Biotech. And it's my pleasure to have my next fireside chat with Nurex Therapeutics. We have CEO Arthur Thent. Welcome.

Speaker 2

Thank you. Great to be here, Roger.

Roger Song, Analyst — Jefferies

Awesome. All right, so Nurex is in a very exciting time frame. You're in a pivotal for your lead program, and then also you have a platform to support a lot of the early pipeline development as well across oncology and in the I&I space. Maybe, Arthur, give us the latest about Nurex, and then we can dive in the conversation.

Speaker 2

Yeah, well, the latest is we're coming upon EHA, European Hematology Association, conference, essentially next week in Stockholm. We'll have an oral presentation there. It'll be a significant, I think, update on Vexabrutadeg, our lead BTK degrader program in CLL. So in that presentation, and the abstracts have been published there, but in the presentation, we'll be giving updates on some of the latest cohorts of patients, new data related to earlier lines of therapy in CLL. So, we have some treatment-naive patients who will then or are now treated on with Bexabrutideg as their first treatment for CLL. Also, patients who have not received a BTK-targeted agent at all yet, so BTK-inhibitor-naive, and then they'll be getting R-degrader as a first BTK therapy. And then also patients who have not received a BCL-2 inhibitor, venetoclax, for example, yet. And so these are early stage. Those would be second-line types of patients. So these cohorts of patients we'll be describing. So that's going to be a significant event for us. Of course, we have a lot of European investigators we're meeting with in Stockholm as well. And so that's coming up. I think that also people have been very interested in the progress on our other fronts in INI, namely the status of our STAT-6 degrader, which is partnered with Sanofi, and I'm sure you'll have some questions about that, and also our IRAC-4 degrader, which is partnered with Gilea. These are all partnerships where we maintain a 50-50 opt-in structure as well. So those are progressing. And then Bexbrutadeg itself, we're very interested in advancing that into autoimmune indications as well. And so that will be a second half sort of events for us.

Roger Song, Analyst — Jefferies

Excellent. Maybe we can spend a few minutes on the CLL, the LE program for now. I think it's interesting you will start to report some earlier line of the result, you know, even without the BCL2. So I understand that you are also trying to do the combination, you know, approach to moving to the early line. And then where are they in the combo? And then with this, you know, I believe it's a model data, how this profile will support the combo? And then when are we going to start to see the data?

Speaker 2

Yeah. Yeah, so we're intending to start our first combination trial, Phase 1B2 program with Bexabrutideg in combination with a number of agents. So Venetoclax, a BCL2 inhibitor, was one of the primary combinable drugs, and that would enable a frontline approach as well. Well, what's exciting there is that people, this would be the first degrader combined, BTK degrader combined with venetoclax in the clinic and investigators and I think patients are very interested in the potential for fixed duration therapies. So therapies that would last a year or two years, likely two years on the combination regimen and then have basically a drug holiday or no drug period. So that's one potential. In addition, anti-CD20 antibodies are of high interest in combination, so rituxan being a mainstay, of course, but then obinutuzumab as well. And then there's multiple other combination potentials built into that protocol. It's a phase 1B2 protocol. So, that's poised to start mid-year. Of course, data would then take a year or more after that. So, that's sort of next up for a trial start. But at the same time, we're starting our big phase three program in CLL monotherapy. So, that's in second line. So, these are patients that have received a BTK covalent inhibitor but have progressed. and so that trial will be starting mid-year as well that's about a 600 patient trial and and is will be in over 20 countries so we're very busy in terms of trial initiations and trial execution you mentioned the pivotal trial is running that's a phase two trial about a hundred patients that's in a later line CLL patient population so yeah all of that is moving forward so very busy

Roger Song, Analyst — Jefferies

mid-year for us. Excellent. As you mentioned, you are doing the monopiridol as the third plus line triple exposed. I believe that's the population you are doing initially. And then we also know another BTK degrader is running, you know, slightly different setting, but also later line. And then they may have data earlier than you will have data next year. So when we see the data, what you are looking for in terms of the OR, PFS, maybe some of the safety signal, tolerability, those. So what will be considered as a good scenario for Nurex to be able to, you know, maybe even benchmarking and then also that beating there?

Speaker 2

So you're talking about in the later line patients? Yeah, later line first, yeah. So these are third line, fourth line. We've had six lines of patients with six lines of prior therapy, actually up to 10 lines. And so what we've seen so far in those patients is around 70 to 80 percent response rate. The response rates do go down the later lines of therapy that patients have had, but I think if you look at fourth line plus in general, anything between 50 percent to 60 percent, 65% is an excellent overall response rate in those really late-line patients. Now, you contrast that with some of the early-line patients. We're seeing 85% or greater response rates with the BTK-degrader, and I think those are, you know, quite strong. But as you go across the lines of therapy, obviously, we want to position Bexabrutideg to be able to serve patients at every line of therapy, wherever they are in their CLL journey, and then also NHL. We're also interested in expanding in NHL indications as well. So, yeah, those are the data to sort of look for.

Roger Song, Analyst — Jefferies

And then also compare contrast to other BTK degrader. They're also in the pivotal right now. And then how do you think, you know, BACs can differentiate in the later line, star, and then, you know, early line probably with a bit too early to compare?

Speaker 2

Well, our goal is to be best in class in the degrader class. There really are only two degraders, really, that are up front and center now in drug development. We think we have the highest selectivity profile. We certainly have the highest potency compared to any other degrader molecule. and that should translate into higher efficacy and better safety. I mean, that's really the profile we're looking for, and that's so far what we've seen play out. We've now been in over 150 CLL patients at various lines of therapy, as we discussed, and the profile is remarkably consistent. High ORR, excellent safety profile, relatively low infection risk compared to other agents, no major bleeding risk, which is also a distinguishing feature compared to BTK inhibitors. We have a very, we have an excellent liver safety profile. We've not seen any elevation of liver enzymes. That's also been a bit of a hex on the BTK inhibitor class in general. So I think the degrader class, and specifically Bexabrutideg, has great potential to be this best-in-class profile. A lot of mechanistic reasons for that, Roger, some of which I'll just mention. I know you know them, but the catalytic nature of degradation. So one drug molecule of Bexabrutideg, I'll call it Bexdeg for short, can degrade 10,000 BTK proteins per hour in the cell. So, one drug molecule removing 10,000 drug target proteins per hour. This is fundamentally different PK-PD compared to inhibitors, where it's one-to-one. You need one drug molecule for every BTK protein. So you really have to swamp the system with drug, and that's how inhibitors work. But degraders work catalytically because they harness this incredibly efficient proteasomal machinery in the cell. That's how we work. So we're fundamentally different. We think we're going to have a fundamentally better safety profile. And, you know, the big picture is we're talking about BTK, but this technology has the potential to replace many inhibitors because of

Roger Song, Analyst — Jefferies

these attributes. So. Yeah. Yeah. Makes sense. And then one of the other discussion I've been having with the investors and then also with you is the sequence of use, all kinds of different btk we have a covalent we have non-covalent and then now we're about to have a degrader coming to the line so what's the you know biological clinical rationale to use which modality first at the first line maybe second line and then save to the later line which makes

Speaker 2

the most sense well the clinical rationale is that the better result initial result a patient gets from a drug, the better their prognosis is overall. So there's a strong rationale in cancer therapy in general to start with the best regimen, start with the best drug, get the best result, the deepest response, the longest lasting response that you can get in your initial treatment. You will live longer than your progression-free survival, overall survival, is all improved. So that's the clinical rationale to start with the best agent up front. And that's what we've seen going on in CLL. They're, you know, this whole targeted therapy started with abrutinib, which was a very great advance, but then has been displaced by acalabrutinib and xanabrutinib, better safety profile, better adherence to the drug regimen, and better prognosis. So those agents have become front line. We think that can happen with degraders, the degraders clearly superior in terms of hitting the target and we think going to be superior in terms of efficacy and ultimately safety because of some of the reasons I mentioned already. So if you have the best result up front, the patient will do better and live a longer healthier life. So that's the rationale to start with your, you know, your best foot forward, and the degrader would be the best foot forward, I think, in the future for BTK-targeted therapy.

Roger Song, Analyst — Jefferies

Yeah, it's a cancer patient, right, best foot forward is probably a lot of the logical choice. The only thing is, you know, people thinking about, because degrader is powerful, right, when you knock down the entire protein, would you develop some resistant mutation, maybe no other therapy you can address versus covalent, non-covalent, non-covalent can address the covalent mutation, and then non-covalent mutation can address by the degrader. So that's a sequencing potential logic as well. So how do you respond to that?

Speaker 2

Well, what we know so far is that the BTK inhibitors basically select for resistance mutations that are coming up in now over 50% of patients. Once you have a resistance mutation, you then have to try to overcome it with another therapy, either combination or in the case of degraders, we can overcome all of those resistance mutations. So that sounds like a logic to start with an inhibitor and then you have a degrader in the second line. But why ever develop the resistance mutations in the first place if you don't need to? And so that is why you should start with the best drug up front that doesn't even can allow for resistance, or at least is harder to become resistant to, is what we're seeing in the clinic. So the degrader is harder to get around. Now, cancer can always get around, you know, drugs, and so there will be resistance mutations that will occur, but you want that to be a low-frequency event, right? And that's why a degrader would be superior. Now, in terms of what are the mechanisms of resistance to degraders, well, there's one mutation that's been identified. It happens to be also a mutation that inhibitors don't work on, and that is the A42AD mutation. So basically, none of the BTK-targeted agents work against that. It's a very rare mutation. Fortunately, it is also what's called an unfit mutation. the cells actually don't even grow very well because the BTK is so mutated it does not work well. And, by the way, it responds to combination agents very easily. So that mutation is not really a big threat. So anyway, I hope I've answered the, you know, sort of the rationale to start with the best drug up front. We think that's going to be the greater eventually. Yeah. And

Roger Song, Analyst — Jefferies

then you do have a solution as a combination, you know, go beyond the BTK if you develop for something not necessarily addressed by the BTK approach, right?

Speaker 2

Yeah, I think with venetoclax and a BTK degrader, you're basically going to take out anything. So, yeah, and we're focused on BTK, but there are a lot of other mutations that take place in these patients, unfortunately, P53 and other really bad actor mutations. So, those all need to be dealt with as well. So, combination, that's why combination agents will be necessary.

Roger Song, Analyst — Jefferies

Yeah. I think Neurix is well capitalized to run, you know, the ongoing phase two at the monotherapy and then also fund the phase three for the monotherapy in the second plus line. How do you think about the earlier line strategy at the corporate level? You want to, you know, do this standalone or you think it's better to find a partnership?

Speaker 2

You know, I think the frontline strategy, you know, partnership makes a lot of sense. Number one, you're going to be combining with an agent. Again, our lead choice would be a venetoclax. These are agents that, you know, are expensive to run in combination trials, so great to have a clinical trial partner of some type. There's also all the antibody agents, bispecifics. There's a lot of combinations. It almost becomes kind of an endless opportunity, and to do that solo is, you know, is challenging. So, yeah, we do favor a partnership model in general. We've done several very successful partnerships with Sanofi, Gilead, Pfizer currently. All of them involve options for Nurex to go 50-50 in the United States and COCOs, so we'd like those kinds of structures. But there's a lot of opportunity for partnership in the CLL space, and that's not even to bring up yet the autoimmune area, where that's another huge market opportunity. Yeah, we'll talk about the INI in a minute.

Roger Song, Analyst — Jefferies

So before that, I think you've been running the trial in NHL for a while, and then we haven't seen much data from there. But you plan to release some data this year, and what should we kind of expect from the NHL cohort?

Speaker 2

Yeah, so our data release periodicity tends to be every six months, so EHA and ASH. We are talking about potentially NHL cohort data at ASH. We haven't settled on what we'll submit. But we have seen some really dramatic responses in every category of NHL. We've seen some complete responses in every category. We've included patients with primary CNS lymphoma. We're talking about DLBCL and MCL, marginal cell lymphoma, and Waldenstrom's, where we have shown some data there, again, seeing this 85 percent response rate. So yeah, I do think NHL will be an area for us in the future to have more disclosure, more publication. It's also another area for combination therapies, too.

Roger Song, Analyst — Jefferies

I and I is very interesting, you know, thinking about the degrader approach because the scaffold function, et cetera. So I think recently CSU, some of the early data by other degrader, and then you're also thinking about developing into different indications. And then right now, what's the thoughts about the indication selection? What's the area you want to go first and then proof concept for the degrader?

Speaker 2

Yeah, so I think that the advantage of a degrader in INI is actually somewhat similar to what we've seen in oncology. And you hit on it, which is that we're addressing both the kinase function of BTK in this case, but also the scaffolding function or the structural signaling function. So there's another whole signaling pathway going on with BTK that kinase inhibitors don't touch, and that's operating in autoimmune disease also. And so we're excited by what we can do there from a theoretical standpoint. And so what we've done so far is conduct a very significant healthy volunteer study with our new formulation designed for autoimmune disease. And we did have a little bit of data come out at an oral presentation in Chicago at the dermatologic meeting recently where we show complete degradation of BTK in the skin of healthy volunteers at low doses, and this is once-a-day dosing. So I think we'd like to see the rest of the data from our healthy volunteer data set. And then our goal is to file an IND in the second half of this year. I think CSU is a very logical place to start. It has proven successful for Novartis with remebrutinib. Data looked quite good, and I think the uptake has been very positive for that drug. That's a twice-a-day drug, you know, I think, and also an inhibitor-class drug. So, again, we think we can improve on that.

Roger Song, Analyst — Jefferies

Yeah, awesome. So it seems that skin makes a lot of sense. And any other therapeutic area for INI potential?

Speaker 2

Well, the other one that we're very interested in is multiple sclerosis, so MS. We have activity in the brain. We know this from our patients with CLL and primary CNS lymphoma who have responded to Bexteg quite well, which is quite remarkable. And we know our CSF levels are basically equivalent to our serum levels. And so we know the drug has brain activity. we know we can hit BTK in the resident microglia cells, which is really where the next, I think, frontier for getting really great responses in MS are, is to hit the microglia. And we've seen some preliminary positive results, not so preliminary, actually, phase three results from phenobrutinib with Roche, which look quite encouraging. So I think MS is another area for

Roger Song, Analyst — Jefferies

Nurx to consider. Got it. And then you did mention earlier line of CLL makes a lot of sense for partnership, and then also INI is a big area if you want to pursue multiple indication, let alone the NHL. So how do you think about those different areas for Bexodag in terms of the overall corporate strategy for the partnership?

Speaker 2

So we see this, you know, Bexodag as a foundational therapy, so So I think it could have the potential to be like an anti-CD20, like a Rituxan. Lots of applications. Now with the degrader capability, one can actually take advantage. It's more versatile than an antibody, right? I mean, so we've developed different formulations, different doses. Really we'll have different products that actually are developed ultimately across not not only CLL and NHL, but also the autoimmune indications. So in terms of corporate strategy then, it really lends itself to partnership as well. But it would have to be a very unique, you know, partnership really that has the vision of this broad vision for Bexteg being a foundational therapy across indications. So multi-indication drug development program with, you know, a global partner that has the kind of capabilities that would be required. That's sort of the corporate strategy standpoint. But we're well positioned to move this forward ourselves. You know, we're well funded, as you said. We have a great investor base. We're moving forward into phase three, you know, full on with CLL. And I think we can definitely initiate the INI platform as well. So we're in a great position.

Roger Song, Analyst — Jefferies

Yeah, so as you said, you also have a tablet formulation, maybe better for the INI already, so it's a different product. But overall, it's a degrader, but you can have a different presentation for the pipeline.

Speaker 2

Yes, so we have the tablet formulation. It's new. This has been now in over 200 healthy volunteers as we've developed it ready for the autoimmune indications. So, it will definitely be different presentation, different doses, and it's well positioned for that. The CLL current tablet capsule formulation is moving forward, of course, into phase three, so that's all good. We have the manufacturing all down. We're really in good shape there. So this is, you know, it's all kind of a green light for us right now.

Roger Song, Analyst — Jefferies

Awesome. Maybe last a couple of minutes, talk about the partnership with Sanofi and Gilead. You know, STAT-6 got a lot of the airtime within the ionized space. So, you know, I know pre-clinically you show, you know, comparable, if not better, than the current degrader. And then what should we expect to see? And then the more interesting thing is you do have the opt-in option and then the potential cold-cold decision later. So what will make you to make that decision, opt-in? And then if you make that decision, how are you going to fund those programs if you move forward?

Speaker 2

Right. So STAT6 is a transcription factor. It's a very exciting transcription factor. clearly is a small molecule target, basically competitive with Dupixent is the ultimate goal there. So it's a very large opportunity in autoimmune disease. We have been developing a degrader to STAT6 with Sanofi since 2019. So this is quite a mature project. This is something that scientific teams have been working on together for many years. Sanofi exercised their option to take that forward into clinical development about a little over a year ago. They initiated the IND-enabling studies, which should be coming to completion this year. And then, if on schedule, should start phase one. And Sanofi is responsible for that clinical development period up through human proof of concept, at which point Nurex has this opt-in that you referred to. So we could opt in 50-50 in a COCO in the United States, and this is a high-priority project for us. So, I mean, this would clearly be something that we would be very interested in exercising our option on. So that program's, I think, a high-visibility program. And the next steps would be in Sanofi's court in order to move this program forward.

Roger Song, Analyst — Jefferies

Okay. Similar thing for IRAC. I think IRAC is a little bit ahead of time, ahead of STASICs, and we may have some data this year that's still the expectation.

Speaker 2

IRAC for degraders should be completing phase one this year, and that is a similar structure as the Sanofi deal, but with Gilead. Gilead then will control the disclosures around that and the next steps it's a great program i think it's probably now the leading uh iraq forward to greater program a number a couple of others have fallen away um so we're uh out in front with this degrader program i think we've got a great partner and uh yeah hopefully they'll uh disclose data this year and uh we'll see that march into phase two at some point awesome all righty uh

Roger Song, Analyst — Jefferies

Okay, just last minute or two, anything else from the pipeline? You do have the I.O. program, and then maybe some of the other earlier you want to, you know, tell people.

Speaker 2

Dr. Yeah, so NX1607, our immuno-oncology program, is an inhibitor of Sybil B ligase that could be transitioning into phase 1B in the second half. So I think we'll get the 1A data and make some decisions there. And then new programs. So, we do have new programs in our pipeline. We haven't disclosed anything yet. Hopefully, in the second half, we'll be able to do something in that regard. And then also, the DAC program with Cgen-Pfizer. This is a degrader antibody conjugate program where these payloads that we engineer teaming up with a great ADC team in Seattle to create the degrader antibody conjugates, or DACs. So that's another whole area. That's actually progressed quite well. I think we're the leaders there between Pfizer and Nurex teaming up together. I think some others are really going to try to move into that space. I do think it's the next generation of ADCs because you're bringing this incredibly powerful targeted payload into the tumor cell. and you you don't have the toxicities of the toxin payloads so this is a very exciting area some of the results there look quite good with our partner and I hope to be able to share information with that with you in the future excellent okay thank you sir thank you everyone thank you