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

Welcome to the UBS call. Mr. David Dai, you may begin.

Thank you so much, operator. Well, welcome to the UBS Targeted Protein Degradation Day. I'm David Dai, I'm one of the biotech analyst here at UBS. It's our great pleasure to welcome Nurix Therapeutics today. With us today, we have Arthur Sands, President and CEO. Arthur, welcome.

Thanks, David. Great to be here.

Great. So Nurix is a quite interesting story. You're definitely one of the leading players in the protein degradation space and have programs in both oncology and I&I. So to start things off, could you just give us an overview of Nurix. Maybe introduce your Target Protein Degradation technology to our audience here? And what are some key differentiations compared to other protein degradation companies out there?

Certainly. So let me start off by introducing our pipeline, and that will help me describe our technology. And can you see my pipeline slide right now, David?

Yes. Perfect.

Okay. Great. So yes, we have a very large oncology portfolio, which is at the top of the slide here. And then we have our I&I portfolio at the bottom. Now all of these compounds that are in development are developed by Nurix at Nurix. And we have centered our technology around the E3 ligase system, which is the cellular system that triggers protein degradation. So we began with Targeted Protein Degradation studying BTK. And that's why 5948 is at the top of our pipeline and also a second BTK degrader, which is a dual degrader, BTK and Ikaros and Aiolos. So it has immunomodulatory activity combined. That's NX-2127. And so I'll talk a little bit about that. So those are targeted protein degraders. But we also have our 1607 compound, which is an inhibitor of an E3 ligase. So Nurix started out as an E3 ligase centric company with science from Berkeley and UCSF around E3 ligase, biochemistry and structure and biologic activity. And so we then embarked on harnessing ligases for targeted protein degradation as shown here with BTK and then also our -- we have an ability to inhibit them as the CBL inhibitor that we're developing. So this also allowed us to form multiple partnerships. And if we look at -- back to our pipeline slide, we have deals in place with Gilead, Sanofi and Pfizer. The Gilead and Sanofi deals are focused on targeted protein degradation in oncology and then also autoimmune disease. And with Pfizer, which was formerly Seagen, we originally did the deal with is focused on using our degrader molecules as payloads on ADCs. So a very broad portfolio now and very versatile. So these degraders are extremely potent and very versatile. So I'll pause there. That's my overview of Nurix and we can dive into any one of these in much greater detail.

Yes. Sure. Sounds good, Arthur. Maybe before we dive in, just help us understand what are some of the key updates we should be expecting over the next 12 months?

So most attention is focused on 5948, and we have -- and future data disclosures. We've guided to having a next day -- disclosure in the second half. So within 6 months with 5948, focused on CLL and NHL which is where the trials are enrolling at the current time. I believe that we'll have other disclosures we've guided to around 1607 and we provide periodic updates with our partners on the partnership programs. Those occur in collaboration with the partners, we have lost control the timing of those. But historically, there's been a certain periodicity to partnership updates as well. But really, I think most attention is moving Nurix to pivotal trials in 2025. That's really a major goal for NX-5948. So that's certainly -- we'd like that to be within the next 12 months that will take us into mid-2025. Our goal -- and what we stated is that 2025 is going to be a big year for starting pivotal trials for Nurix.

That's excellent. Let's -- so talk about the lead program, 5948, your BTK degrader targeting multiple myeloma and lymphoma. So you recently presented some data at EHA this year. Can you just walk us through the summary of the key data points and where you are currently with this program?

Sure. So this shows you the trial design. We're actually -- we're focused on chronic lymphocytic leukemia, CLL. I think you may have mentioned multiple myeloma. We're actually focused on CLL with this. And also NHL, which covers many different lymphoma categories. But the EHA data was all about CLL primarily. We shared the patient demographics and then the initial response rates, which are quite high. But just a word about the patients enrolled in the trial, heavily pretreated, so four prior lines of therapy on average, you can see some of those therapies broken down under the previous therapy section here. And then also heavily genetically mutated disease burden in these patients. So over half had -- well, approximately half had TP53 mutations of tumor suppressor gene, about another half had BTK resistance mutations. These are mutations that render patients resistant to the current inhibitors. And -- so heavily pretreated patient population. We've presented data demonstrating the drug was very well tolerated. This is the AE table. You can see really quite an excellent safety profile overall. And then I think most importantly, we're looking here at lymph node reductions. You can see across the board, the vast majority of patients show lymph node shrinkage and reduction, which is, of course, one of the key elements of clinical response we're looking for. The green arrows indicate those patients that have remained on study. This is indicative of how well tolerated the drug is. So we have great compliance. We've had patients with CNS disease, these two hatch marks here, who have also shown excellent responses. We do know our drug gets -- it crosses the blood brain barrier, and we've seen effects there. And this translates to approximately a 70% objective response rate in this advanced patient population. So this is some of the data that we shared that I think has been very intriguing and encouraging for our investors and our patients and our investigators. This is a swim lane plot showing the different dose levels we've gone through from 50 to 600. We're finishing up the dose escalation at 600 currently, David. And again, the green triangles indicate clinical responses here, here and here, you can see them all over. And the green arrows show the ongoing -- patients ongoing on the trial. So I'll pause there, and then we have more data. Of course, we can discuss about how we overcome resistance mutations. We also presented data on that as well as some really interesting patient case studies that really demonstrate how well our drug can work.

Yes, that's excellent. I apologize. I misspoke on the indication, it should CLL, not myeloma. My apologies. On that front, there looks about 70% ORR, looks very interesting. Just help us understand what will be considered reasonable benchmark for this particular line of CLL patients?

Well, I think the most closely compared drug for us is pirtobrutinib. So that -- in this patient population, which is this post-BCL2, post-BTK inhibitor. So where patients -- where two drugs have failed the patient. Then that's a category where I think they reported approximately 70% response rate. Now within -- so we're in a similar way of fast-track designation in that same patient population, by the way. So again, that's probably the best competitor. Now within this study, however, we have about 20% of patients that have also failed pirtobrutinib that -- where we have seen responses in such patients as well. So we think we're doing a lot more than your typical inhibitor. And our goal is to show that by removing the BTK protein, by degrading it, you can actually get better efficacy, hopefully improved durability and you can address the resistance mutations as well.

Got it. That's really helpful. And so then just on the CNS front, you've seen some quite interesting data, especially from that case study where one patient had some CNS benefits. Could you maybe just elaborate on the CNS penetration activities for your drug?

Yes. So here is the patient you're referring to, the patient journey I'm showing on the screen now. And let me just walk you through this. So first off, yes, CNS involvement, you see the malignant cells in the CSF. So this patient really presented with central nervous system findings, very, very sick. You can see the number of prior treatments in the upper right-hand corner here, substantial prior treatments, very challenging mutational profile. And actually developed a CNS involvement while on acalabrutinib. So on our trial, what you're looking at here to the right is the absolute lymphocyte count or ALC which when a response is happening, the first thing you tend to see is lymphocytosis or elevated absolute lymphocyte counts, which we're seeing here. And then these counts start to come down. And with the decrease in counts, you begin to see the lymph node reduction, which I showed you the waterfall plots before, reduction in spleen size, normalization of some of the cytopenias, platelet counts going back to normal, hemoglobin resolving anemia. And then by week 24, you see this malignant cells in CSF being unknown. So there were no cells found in the CSF. This patient has done very well over six months. And we know and we've confirmed because of multiple patients with CNS involvement now, that our drug levels are -- in the CSF are comparable to the free drug levels in the plasma. So we're -- we know drug is there, we're getting biologic effect, and we're seeing clinical response. So it all adds up as a very encouraging profile.

Got it. So could this be considered one of the key differentiator of this drug versus other BTK inhibitors?

I certainly think it could be. The concept is there -- what percentage of patients have CNS involvement, well, depending on how you look, it's either 5% or less. But I think it's a broader distinguishing feature than just that subpopulation because as we saw with this patient, is, if you have a drug that can keep your CNS compartment protected, so it's not to get to CNS involvement, we think that's a very desirable feature. And we think that we do cover and can protect the brain from that kind of involvement of disease. And we intend to continue to pursue that and allow -- and have enrollment of patients with CNS disease. They're typically -- such patients are typically excluded from these early phase trials but we've included them, and we're seeing some good results.

Got it. And that's really helpful. And then just on the next phase, which is going to be your development plan for monotherapy and combo pivotal trials. Any thoughts on your trial design and what's the regulatory path so far?

So we have just some basic strategic thoughts, which I'm showing here now which is let's capitalize on the fact we have fast-track designation. That's in that same population that pirtobrutinib received accelerated approval recently. And so that definitely will be something that we would like to pursue as a single-arm trial. Then also simultaneously begins the randomized control trials or the confirmatory trials. These can sometimes be earlier lines of therapy. We find that to be attractive. That's a much larger market opportunity, that second line and then potentially first line. And then the third category would be the fixed duration combination trials. And what we're looking at there is venetoclax, obinutuzumab and potentially rituximab. These are a few agents that are commonly used in earlier lines of therapy, which can allow for a fixed duration of therapy. So this is sort of the big picture of how we're moving towards pivotal trials. And again, our target is next year.

Got it. That's really interesting. So on the -- moving on to the lymphoma opportunity, so we should be seeing some additional data in NHL patients in the second half of this year. Could you perhaps just set some expectations for data readout? Or what would be sort of like consider clinically meaningful benchmark, which should be expected here?