Great. Welcome back, everyone. Welcome to the 2025 RBC Global Healthcare Conference. My name is Greg Renza, one of the biotech equity research analysts here at RBC, and we're very pleased to have Nurix Therapeutics, a team and a company we know well. Joining us from the company is the Chief Business Officer, Jason Cantor, as well as Chief Financial Officer, Hans Van Houte. Guys, it's great to see you. Always a lot of activity and interest in Nurix, and we're in an interesting time with the company, with data unveiling, with maturity of, obviously, your oncology platform, but also emergence into I&I. Maybe for those who aren't familiar with Nurix, just have you give a brief overview of the company along with targeted protein degradation.
Sure. Maybe I'll start. Nurix is in the field of targeted protein degradation. Instead of a small molecule inhibiting a protein of interest, we actually have small molecules that will degrade the protein of interest using the ubiquitous proteasome system. We've built a fairly large and robust research platform in order to do this. We call it DEL-AI, and it involves large DNA-encoded libraries to get kind of chemical matter and basically be able to screen pretty much any protein target of interest against that DNA-encoded library. It has manifested itself through wholly owned programs, including Bexobrutideg, which is our BTK degrader, and that will be moving into phase two, phase three studies in the second half of the year.
This is a big year for Nurix Therapeutics in terms of moving from a phase one company, which we have been for the past three years, into phase two, phase three. That's a big step forward for Nurix. In addition, we have a number of collaborations, notably with Gilead Sciences and Sanofi and Pfizer, who have, I think, picked out our platform as being the industry leader for building degraders, in the case of Pfizer, degrader antibody conjugates. That also helps contribute revenue milestones and license payments to the company to help offset expense. We're moving forward with a good cash position, good runway to kind of prosecute on our programs and moving forward with our partners also as an integral part of our pipeline.
That's great. As you, the company, Bexo in the space, frankly, are seemingly wedded to twice a year data updates, this is a good time to talk about the EHA abstracts that have since been released, and we're getting an update on Bexo on 5948. Maybe just walk us through some of the data points in focus in terms of that response rate, the duration that you've seen, just that new data cut, and what we should be focusing on when it comes to EHA coming up.
You want to take that, Jason?
Yeah, sure. First of all, thank you, Greg, and thanks to the RBC team for having us here. It's a great conference. Yeah, as Hans mentioned, our lead program, Bexobrutideg, is a BTK degrader. It's an oral brain-penetrant degrader. It's in development for CLL, which is the lead indication, but also across B-cell malignancies, including an indication called Waldenström macroglobulinemia. We'll be having, we'll call that WM. We'll be having data in both CLL and WM at EHA in June. The abstracts came out last week, and the data continues to track fantastically. The overall response rate remains quite high in the CLL setting. This is patients with a median number of prior therapies of four who are very heavily pretreated, including patients who have failed the latest BTK inhibitors, patients with mutations in BTK and other high-risk mutations. We're reporting an 80% ORR.
The data that we'll be presenting that's in the abstract is from January 2, the data cut. We'll be updating that with an additional approximately three-month more follow-up. The goal of this presentation is to really track the phase one A patients to get to a better answer around what the durability of those responses are. I think we've clearly shown that the drug has a high response rate, and the biggest question people have for us is, how durable are those responses? We're taking this discrete cohort, the phase one A, and looking at that over time to get to it. We haven't reached the median duration of response in the abstract, and we will continue to track that. Importantly, we're not seeing any new safety signals, and the safety looks very good.
Some of the things that people watch for in the BTK space, things like AFib, hypertension, not seeing that. The amylase and lipase, which is something that's come up, we're not seeing that. The safety data looks very good.
That's great. At this stage, Jason, what do you think constitutes a competitive profile for a BTK degrader, maybe relative to the inhibitors at this stage? Meaning, as you prioritize what to look at with the recent data cut and the ones you frankly have disclosed, what should we see as the profile that suggests this differentiation and this competitiveness?
Yeah, and I think it's already showing it. It's showing it for our drug. There are other drugs in the class that are showing similar levels of efficacy. What we can really say is that there is incredible enthusiasm in the investigator community for BTK degradation as a new modality to go after a target that's very well understood. It's a great target in Hem-Onc because it's one of those few targets where patients who are treated with one drug for that will subsequently get treated with another drug against the same target. To come at it from the degrader perspective after patients have failed inhibitors is very attractive. This comes from the fact that the degraders address all of the clinically relevant resistance mutations that arise when patients are treated chronically with BTK inhibitors.
The safety looks very clean, as I said, and the efficacy is higher than the most recently approved BTK inhibitors in the space. It is a very exciting time for 5948 or Bexobrutideg.
How are you and the team thinking about sequencing? I'm certainly a healthy discussion with not just with sponsors, but with the investigator community. Comments that the sequencing is so key, but maybe some watchouts when we think about moving into earlier treatment settings. Just walk us through sort of the larger strategy, moving into earlier lines, and maybe what you're thinking about when it comes to mechanism resistance of using degraders earlier, maybe precluding other treatment options. What's the Nurix view on this?
Yeah, it's a great question. Let me just level set. As Hans said, our plan is to initiate pivotal studies this year. What we've guided to is a single-arm, single-agent accelerated approval strategy in the third-line plus setting, which is post-BTKI, post-BCL2. Those are two standard of cares in the first and second-line setting. We will also be initiating a randomized controlled confirmatory study in what we're calling the second-line plus setting, which would be post-BTKI. That's really, when you think, where does a degrader fit in? I think the easiest place to think about a degrader, at least initially, is once patients have failed any BTK inhibitor, there really is going to be no reason to go on to another BTK inhibitor. We think there's going to be too much resistance that's occurring, even at a very low level.
We think that bringing on a degrader like Bexobrutideg immediately after a BTK inhibitor will be the way to go.
Avoiding the concept of a re-challenge with an inhibitor.
Exactly. Exactly. Now, ultimately, we do think that the BTK degraders, Bexobrutideg, could be a first-line therapy. Those are obviously much longer trials to run. Right now, our focus is on launching the two trials that we mentioned.
Excellent. Maybe just talk a bit about the timelines for those trials. As you mentioned, you're launching these pivotals, second-line plus first-line CLL. Where should investors be focusing on sort of the time points for the trial when we think about control arms and comparators? Maybe walk us through some of those going in details.
Yeah, we have guided to starting both of those studies this year. That is the plan. We have not been more granular than that. In terms of the specific phase three comparator arm, what we said is that we will provide an update on our thinking around that in the mid-year timeframe. We have not communicated exactly what the control arm would be. I mean, there are a lot of studies out there that you can look at. There are very specific choices that we have. We are working through that, and we will communicate that in the mid-year.
Even today during the conference and over the last couple of days, lots of discussions about strategic partnerships and entering mid-cap biotech, participating in large markets, running large trials. Certainly with the BTK space and CLL, large markets globally. Maybe just talk about your going in position about independently running the trials and how you can, in a singular way, just maximize the value of Bexobrutideg.
Yeah, sure. First of all, we do want to maximize the value of the program for patients, first and foremost, but also for our investors. I think that means hanging on to the asset, the value of the asset as long as possible. We think there is a significant value inflection from a partnering perspective for checking several of the key boxes that we're in the middle of checking right now. One of those is understanding the duration of response better, which we will be reporting on at EHA. The other is determining the dose for the phase three program. We are doing a randomized phase 1b, which is fully enrolled to satisfy Project Optimus. That is also something that pharma companies would be very interested in and just having full alignment with FDA on the design of those studies.
We think making the transition from a phase one AB company to a pivotal and phase three company is an important value for the program. We look to retain US marketing rights either wholly or in a 50/50 type of arrangement. We do want to be a Hem-Onc company fully integrated. We are moving in that direction.
That's great. When it comes to Bexo, just the concept and the rationale of exploring indications beyond oncology in the immunized space, how do you break that down, of course, related to optimizing the value, but also as far as the upside for the molecule?
Yeah, BTK is one of those great targets. It's very clean. It's involved in B cell biology. We know it's important in CLL. We know it's important across B cell malignancies. We also know that it's important in many B cell-driven autoimmune indications. There's a whole group of BTK inhibitors that are moving forward in a variety of these indications. We also are interested in advancing Bexobrutideg in autoimmunity. At ASH, we outlined a strategy, which is to start in the autoimmune hemolytic anemia space, specifically to open a cohort in our CLL study, which is for CLL patients who have autoimmune hemolytic anemia. Ultimately, the goal would be a broader ionized strategy, which could include non-malignant heme, could include derm indications, as well as neuro indications like multiple sclerosis.
Our drug, as I mentioned, is brain penetrant, and that is an important factor for that indication. Capital markets are tough. We can't fund all of that. We are moving cautiously with everything that's outside of our critical path for getting this drug to market.
Okay. Great. Maybe a good segue on talking about the ionized programs and just that continued enhancing dimension of the story. Hans, just remind us and the audience about the partnerships that you've laid out. Certainly want to talk STAT6 as a development candidate and the play there to move the assets and the programs forward.
Yeah, I think our collaborations, which the Gilead and Sanofi collaborations were started in the middle of 2019, the end of 2019, have really progressed very well. They started out as skeptics about degradation to being full-blown believers about targeted protein degradation. I think that manifested itself in the IRAK4 program with Gilead, which they just recently had an IND accepted. They're moving into clinical studies. With STAT6 with Sanofi, which we've guided towards them basically taking the development candidate and optioning it to move it forward on their own nickel from development candidate to presumably IND in a 12 months-ish timeframe and then into the clinic. High-value programs, which we developed on behalf of our partners, very productive partnerships. Both of those programs are moving forward with them spending the money to take it from development candidate to IND to phase one.
We have the ability to look at the data post phase one or post kind of clinical proof of concept, depending on the collaboration, and opt in 50/50 for co-development, co-promotion in the U.S. High-value targets, high-value collaborations with substantial rights. The nice thing is we do not have to spend any money on it right now as we focus on Bexobrutideg, moving that forward.
Yeah. On the Gilead partnership, I guess it's 6791 now, GS-6791. You mentioned the IND clearance and opt-in potentials. How do you communicate sort of those benchmarks for ethics and safety on phase one results that would meet Nurix's bar to opt in for co-development and potentially co-detail?
That's a great question. I mean, I think we'll know it when we see it. Those programs, we don't have a lot of influence in the direction of those programs because they're our partners. We're also gated somewhat in terms of what we can disclose on those programs because we're subject to confidentiality and have to come to agreement with our partners on what we can disclose, what we can't disclose. As those programs continue to build value, we presume that there'll be some data that we can, that we'll be able to look at and potentially be able to share in terms of our decision process.
Certainly with STAT6, increasing competition, I think it translates, frankly, to increasing interest. When you think about your partner, Sanofi, and the plans to accelerate development once past DC, just talk about the levels of differentiation that your platform brings in this area.
You want to tackle that one, Jason?
Yeah, sure. This is STAT6. It is a transcription factor. It is classically undruggable, so it does not have a classic active site for an inhibitor. This was, I think, one of the toughest but most exciting targets that came into the collaboration. We used our DEL technology to discover novel binders to this transcription factor and developed a very potent degrader. Again, that is subject to potential license by Sanofi in this collaboration. We cannot really talk too much about how we think our molecule may differentiate. In all of our programs, including IRAK4 and including BTK, we have a line of sight into what we think is a best-in-class profile. In the case of IRAK4 and STAT6, there are molecules that are ahead of us. We can at least internally consider our benchmarking against those.
We have a personal view that our drugs are going to be superior.
Fantastic. Maybe we can just close with talking a little bit about the other aspects of the pipeline. Just your latest, Jason, on 2127 and how this fits into the degrader strategy, certainly, as you think about the more aggressive lymphomas and you talk about the sequencing and the landscape that you want to serve. What's the latest on 2127?
Yeah, so NX-2127 is another oral BTK degrader in our pipeline. It's in a phase one AB trial. It is a unique molecule in that it retains, through the cerebellum binding region, immunomodulatory activity similar to what Revlimid has. So it's a dual degrader of BTK and a transcription factor called IKZF1 and 3. We've put this into patients, CLL patients and NHL patients. What we saw, which we thought was really remarkable, is very rapid and long-lasting complete responses. Specifically, the two that we've highlighted, one was a DLBCL patient who was CR at week eight and remained in CR for almost three years at the last update, which was at ASH. This is a remarkable finding for this patient.
We had a mantle cell patient who was on therapy in CR for 17 cycles, so 17 months of therapy, came off the drug, just didn't want to be on the drug anymore for whatever reason, and remained in CR for 12 months. That was at the last update. That patient was still in CR. We're seeing some very remarkable activity. We think it's because both activities bring in anti-tumor activity. The imid-like activity also brings in T cell activation. We think in certain aggressive tumors, this combination approach is going to be advantaged. We would like to see that program advance in these aggressive malignancies. We're planning to complete the phase one A portion of the study this year.
Excellent. Excellent. There is always more to talk about with the Nurix team. When we think about the degrader antibody conjugate platform, the collaboration with Pfizer, it always comes down to your appetite and folks wanting to know the bandwidth to establish additional collaborations. To that end, when we think of some of the really interesting preclinical programs that we are seeing, maybe as recently as a CR, and maybe talk about some of those potential programs, was 4972, the Aurora A degrader, and as well as 0305, the pan-BRAF degrader. How interesting are these targets? Maybe use this as an illustration of the productive pipeline and the platform.
Yeah, so there was a lot in that question. Yeah, we continue to be open for business in terms of additional collaborations on the discovery side. I think Hans mentioned we built this very robust and productive engine. There are more targets that we could go after than we can ultimately prosecute on our own. We still do entertain discovery collaborations. We do look at additional DAC collaborations, so degrader antibody conjugates. We did this deal with CGen. We were one of the first major collaborations linking a degrader to an antibody, two very exciting modalities to combine. That collaboration is going very well. We are also doing that internally on our own with a focus on INI. We would welcome additional collaborations in that space. In terms of the preclinical assets that you mentioned, I'll just highlight our pan-mutant BRAF degrader.
People are familiar with BRAF inhibitors. They only address the class one mutations. There are class two and three mutations. The degrader addresses all three of those. It also addresses mutational resistance that arises when patients are treated with BRAF inhibitors. This is a drug class that could be relevant for melanoma, colorectal cancer, lung cancer, thyroid cancer, for a genetically defined subset, which is always attractive when you're developing something in solid tumors. It also combines extremely well preclinically with the MEK inhibitors, and the data there is quite impressive.
Excellent. Just in the last moment, I just want to open it up to the audience here in New York. Any questions for the Nurix team before we part? All right. Hans, Jason, great to see you. Congratulations.
Thank you very much. Yeah.
Thank you, Greg.
It's going to be a great year.
All right.
Thank you.
Thanks, everybody.