Afternoon, everyone, and thanks for bearing with us for a few minutes. My name is Gil, and I'm a Senior Biotech Analyst here at Needham and Company. It is my pleasure to have with me today Dr. Arthur Sands, who's President and CEO of Nurix. As a reminder, viewers who are watching can submit questions through the Ask a Question box. Arthur, a little belated, but some introductory comments and maybe a quick word on the company's platform and pipeline. Sure. We're very excited to be entering phase III this year with our lead agent, Bexobrutideg, which is a BTK degrader being developed for CLL. In addition, we do have ambitions for its use in I&I disease, and I'm sure we'll talk a little bit about that in autoimmune indications. All of the Bex deg success through the development so far really relates to our, I think, incredible drug discovery platform in which we have identified a whole host of novel degrader, targeted protein degrader molecules, against not only oncology targets, but also autoimmune targets, including STAT6 with our partnership with Gilead and IRAK4, I mean STAT6, sorry, with Sanofi, and then IRAK4 with Gilead, which is in the clinic now and STAT6 soon to be. We have a whole pipeline to discuss. Gil, I know you're really familiar with our story overall. We're headquartered in the Bay Area, approximately 350 employees, and again, very exciting year to enter pivotal trials, registrational trials. Maybe a good place to start is bex deg in CLL. Just a quick reminder for people how the data looks like. Yeah, we've reported, at ASH most recently, an 83% overall response rate in fourth-line+ patients, very advanced patients with CLL, a very significant ORR. We also have some of the first PFS measures, progression-free survival measures, that we've disclosed now at 22 months for our most advanced cohort of patients from the phase Ia, which compares very favorably with competing agents, again, in very advanced patients. We're very excited to initiate, as I said, the registrational trials. We're already running a potential accelerated approval trial, which is a potential pivotal trial phase II in these advanced patients, a very similar patient population to what we've treated so far. That's just highlights of the data. Of course, we get complete BTK degradation. We have great biomarkers that also all are moving in the right direction. We can talk about other aspects of the data as you wish. Have physicians shared any initial thoughts? You already have a pretty decent data set. How has this been accepted by physicians? Well, the best evidence for that is the rapid opening of our sites for these registrational trials. Lots of interest. I think that's going to go quickly through the initiation phase for the phase III, and then I would anticipate enrollment will go rapidly as well because the results are positive. Of course, physicians prefer to put their patients on a drug that has a great probability of working. I'd say very well accepted. I think the degradation mechanism of action is being increasingly accepted and well-recognized. That's been a very interesting process of education now for the past several years. There it's clear that degradation allows for addressing the resistance mutations to inhibitors. That's a very compelling molecular story that we've been able to show because, of course, we can catalog all the resistance mutations that our patients have that have been on these inhibitors, and then show that these patients are responding. That's really connected with investigators. I think the other attributes of the drug, its long durability, and now that we're getting the PFS data, durability of response is also connecting quite strongly with investigators and of course, with patients. We've had patients now on over three years on Bexobrutideg. Are you guys seeing any challenges or competition for the patients while you're enrolling these studies? You kind of alluded that it sounds like you have a good selling point. Yeah. Well, it's a competitive area, CLL. There's lots of trials going on. There's lots of combination trials. We're one of two degrader mechanisms, BeOne being the other company. There's some competition there, but that's not a lot of competition to be one of two. We're in good company. BeOne is certainly a leader in the field, and so I think that has lent a lot of credibility to the Nurix program, the BTK degradation concept in general. Of course, we think Bexobrutideg is going to distinguish itself as a best-in-class degrader overall. So far, the competition has not really been an issue because, again, we're very unique in our MOA. Yeah. Super helpful. I do want to spend a second on the confirmatory study, which is also planned in the near term. You guys changed a little bit the way that you designed it. It was best available therapy. Now it's against pirtobrutinib. Can you walk us a bit through the considerations there? Well, first off, pirtobrutinib only recently gained full approval. In terms of going against a comparator arm, it is generally best to go against something that is approved fully. That gives you the broadest base worldwide. With that, and plus looking at our own data as it had matured, that we became very convinced that we have a potential superior activity to pirtobrutinib, you know, as our data matured. We didn't really have our PFS data until late last year, so you really have to look at the data to be able to even predict the scale of your trial, power it appropriately, all of those things. Suddenly we could do that when we had all the data. It coincided with Pirto's full approval, and so it was logical to then just upgrade the trial to really go against the latest approved agents, which we think we can beat. I mean, it also helps that it is aligned with your competitor as well, apples to apples and that kind of thing. Yeah. It's apples to apples. Certainly, we're going to go toe to toe. I'm sure we can talk about differentiation later, but I think it's important. Also things are competitive, as you mentioned earlier, so you really have to design a competitive, attractive trial where the control arm is the most recently approved agent. Your trial is relevant, and will be relevant three years from now as well. A lot of things go into the trial design, obviously. Just as a clarification, are there any issues with this ex-U.S., specifically? I'm sorry, could you? Ex-US Repeat that? Any issues ex-U.S.? Yeah. No. We don't see any. It's been a very popular agent. I think it's going to be attractive. We do have to make sure it's available in all these different countries since it is recently approved. There's a few logistical things, but this is going to be mainly a U.S. and European trial, right? Pirtobrutinib's going to have wide distribution availability there too. Right. Let's spend some time on the competition, maybe starting with how you guys view yourselves as differentiated from BeOne. Well, we've shown some of the data of how we're differentiated at a preclinical level, where we can actually compare compounds head-to-head in human cells, B cells, et cetera. There we are 10-fold more potent on a cellular basis when looking head-to-head. We also see greater selectivity. We've measured off-targets very carefully through global proteomics, and the only thing we hit is BTK, and with the BeOne compound, we see many off-targets lighting up on the proteomics scan, indicating that they are hitting those in some way. I think that in addition to potency, which generally translates to efficacy, I think we're more selective. We've got, which translates generally to safety, I mean, just speaking in broad terms. I think that will ultimately lend itself to a best-in-class profile. Yeah. It's a very important point, I think worth emphasizing, considering how long patients stay on inhibitors of BTK as it relates to any safety differential would eventually show up if you wait long enough. That's a major consideration. That is certainly true. Also, of course, it increases the longevity of the drug in general, drug use in general, which of course translates to sales, et cetera. There's another dimension, Gil, which is it also affects dose. The safer you are, the higher you can dose. We're dosing at our maximum dose tested at 600 mg, which we went through the randomization cohorts under Project Optimus of the FDA and submitted, and they agreed with us that 600 was a safe dose to go forward to. Optimus is all about safety, really, for targeted therapies. That gives us more coverage of mutations in our view too. All kinds of mutations, not just BTK mutations, but certainly all BTK mutations. I think safety can also affect efficacy because you can not only dose for longer periods of time chronically, as you pointed out, but also you can dose at a higher level to cover bulky disease, genomic disease of all kinds in these patients. It's really important. It all translates to efficacy in the end, superior efficacy in the end. Another important point is this a winner-takes-all kind of market? Is this a market where you feel more than one competitor can live side by side? It tends to be a side-by-side market, unless there's a distinct advantage, usually around safety, as you pointed, because of the chronic use. That's why you see zanubrutinib and acalabrutinib. Yeah Quite well. There's probably room for Pirtobrutinib. This market is growing, forecast to grow to, I think, $12 billion a year or more in the next couple of years. I think there's room. Again, if you do get an edge somehow, either safety being the most likely, then you can really become just the primary winner actually. Okay. I do want to spend some time also on the earlier lines. Sure That's the larger portion. You guys are doing several forays here, combinations, et cetera. Just given length of therapy on earlier lines, is it feasible for you guys to continue development in that setting? It is. You have to be very smart about how you design the trials so that you have endpoints that are reachable in our lifetime, right, which is our goal. We don't want to be waiting forever for results. We're looking at these different approaches very carefully, trial design, et cetera. I'm not really prepared to talk about a second-line or a front-line combo trial yet. Of course, the pirtobrutinib head-to-head is a second-line. There, these patients advance more rapidly, unfortunately, so the time frames are reasonable. In front line, whether it be combo or mono, we really have not outlined that design yet, but we're going to work very hard to make it a smart design, so we get meaningful readouts in a meaningful period of time. Any thoughts about another selective study, let's say, CNS involvement? You guys do penetrate the blood-brain barrier. So we do have a cohort open for patients with CNS disease. And I do think, eventually, one way or another, that should make it onto our label, although we'd have to see exactly how that happens. It is such a unique, and relatively rare set of patients, but it's medically important for patients that don't have CNS disease also. Because what it means is you're providing coverage of the brain so that the brain does not become a sanctuary organ, which is what happens with chronic therapy. You can actually get, then the cells eventually are selected for that are in the brain. So obviously, nobody wants that to happen. So I think it becomes a medically important distinguishing feature, and we've had some dramatic results for patients who've had terrible CNS disease, actually, coming into the trial. Because we uniquely enrolled, allowed enrollment of those patients. We'll have to figure out the regulatory approach there, but I do think medically it's very, very important and will be another differentiator. Let's shift gears a little bit to autoimmune with Bexobrutideg. Yeah. Yes. A little bit on the change of formulation here, what is the logic, tablets versus the oncology formulation? The logic is severalfold. First off, when you have a new agent and you generally go in with one of the more straightforward formulations to manufacture to get into the clinic and look for results, which is what we did with our crystalline formulation. It's had great results and been very rapid in terms of development and manufacturing. With a new MOA, typically one will look for better formulations to improve the pill burden, improve absorption, perhaps improve certain other parameters. These degrader molecules are actually rather large, small molecules. They do tend to have poor absorption. Okay? Let me illustrate for this. We're dosing at 600 milligrams. Our blood levels that we achieve, but we're far more potent than the inhibitors. You measure the inhibitors. Why is our dose 600 mg if we're 10x-100x or 1,000x more potent? Well, the absorption's fairly poor. You have a good window to improve upon by working on other oral formulations, and you could get a lot more drug in, perhaps enhance efficacy as well, and other attributes. The blood levels of our drug, just to compare to Pirtobrutinib, for example, to illustrate what I'm talking about. Our therapeutic blood levels are approximately 2,000-fold lower than Pirtobrutinib's therapeutic blood levels. That just shows you how dramatically different these MOAs are. You don't need much drug to get in. The more efficient you make that, probably the better results you're going to get overall. That's sort of on the PK/PD side. On the commercial side, it does allow you to brand a different drug, and very different doses are going to be needed, and very different safety profiles will be generated. With a different agent, that is a branded different agent, ultimately, you can distinguish all of those features. In autoimmune disease, there's so many different ways we can go. You guys did guide for some data later this year, specifically from this study. Any expectations we should have here? We've been talking about the healthy volunteer studies. Yeah Of the new formulation, which will help describe where we're going in autoimmune disease. They'll be very relevant at many levels to the study design, to the indication choice, and the data themselves, I think, will be important in these regards, even though it's healthy volunteers. There's so many biomarkers we can study with this approach that it becomes very graphic in terms of how you would align to the existing agents or inhibitors. We have such biomarkers given degradation mechanism. We can really align our dose and align where we think we'll be efficacy-wise, even based on healthy volunteer studies. We'll do the best we can with that. Last but not least. All right. All right. What kind of indications should we be thinking of? You have mentioned this in the past, just a reiteration. Well, there's so many choices. I see them in certain buckets. You want to consider the risk benefits, the pricing, the precedents, other drugs, competing drugs. Roughly, they can be grouped into dermatologic as one bucket, neurologic, such as MS, and then hematologic. There's the heme, a non-malignant heme, autoimmune, ITP, wAIHA, those sorts of things. In the dermatologic, there's a few categories, but in general, they're allergic-based or severe allergy-based, which could also include, when you talk about allergy, then food allergy comes into potential play. There's a number of areas we could go in, and each one, of course, is very different, will have different dosing, and has different timetables for drug development. One of our goals would be do something where we can get results fairly quickly, compared to other indications. The other, when you look at something like MS, which takes longer, that's so valuable and so unique, and we already know we have activity in the brain. That's also very attractive. All right. I'm not answering yet because we're going to. Not answering yet. Save that for the second half and show you the data that goes with it. I do want to spend some time on STAT6, specifically because this is something we get asked a lot about. Right. You have your partnership with Sanofi. Anything you can say about your progress there to date? Well, it's been quite a great drug discovery road with Sanofi. We started the program in 2019, when it was just considered an undruggable target as part of our original Sanofi drug discovery alliance. That target and then development candidate was selected just over a year ago. That triggered the IND-enabling studies by any calendar, typical calendar of drug development preclinical. We should be on the threshold of entering the clinic with Sanofi. Now, it is up to them. They take control at development candidate stage. They control timing. They control news flow. Of course, they're funding the whole thing at this point. After human proof of concept in the clinic, we then have our 50/50 opt-in option, 50/50 in the United States for a co-co. That would be a time period that I think would be very exciting. In the meantime, really, it's a Sanofi program. I can't think of anyone better to develop this. Of course, they have Dupixent, and they have strategic interests in this area, other strategic interests. I think this is going to be a very interesting program to watch this year. Speaking of competition there, how do you feel the space has changed with the data disclosures from Kymera? Well, it's gotten even more valuable. I think that their data is excellent, and I think that it shows that I do personally believe an oral will open up the market, as they have said quite a bit. I think there's a lot of room for more than one agent. It's going to be bigger than the Dupixent market. That I think could be quite substantial. What else? It's not a lot to differentiate on so far. We get that question a lot ourselves. How are you different? I think that all I can say is that we optimize this with Sanofi kind of in lockstep with their standards. I believe that we've got a highly efficacious agent and exquisitely selective. I think that we'll just have to see ultimately. Efficacy and safety, the whole name of the game. Now with atopic dermatitis, safety is even more important, right? Yeah. Even way more important than even CLL, right? I think what people are going to watch next in small molecule development in this area is going to be safety. I think you're going to see efficacy, but then how safe is it? Because Dupixent is very safe. These biologics are very safe. Your small molecule's got to be absolutely clean as a whistle. I do want to spend also a second on IRAK4. Let's not forget that that's a program you guys are also running and actually may have nearer-term information. Any guidance there? No. It should on its schedule with Gilead, of course, it's similar structure to Sanofi. So they're running the phase Is, and hopefully we should see phase I data this year. They've been in healthy volunteers, I think, for over a year. So that should be important, and then we'll see where it's going to go from there. So I think that's another great example of building a molecule that's exquisitely selective and safe and also shows efficacy. It's not lost on anybody that the first IRAK4 degrader fell out of bed because of safety going into autoimmune disease. So this just illustrates that you really got to emphasize selectivity with these kinds of indications. Not forgetting NX-2127, what's the status here? How do you guys view this program at this point? I know we're waiting on some non-Hodgkin's lymphoma updates. Yeah. That's been walking through phase Ia dose escalation with the chirally controlled compound. Hopefully we'll have data in the second half for NX-2127. Don't forget NX-1607 either. That's next on my list. Next on your list. Yeah, we've had a couple programs that have, shall we say, taken their time in phase Ia because of dosing and figuring out just about every detail one possibly can, and a few twists and turns. Now, I think with NX-1607, we're at the stage of really getting to phase Ib. I think NX-1607 is ahead of NX-2127 in that decision-making tree. I hope also in the second half to have updates on NX-1607. Okay, there were some challenges around formulating the correct dosing. It seems you have worked through those. I think we've overcome them. There was some simple, actually, GI tolerability challenges. In terms of once we learn how to dose and navigate that, patients tolerate out that. That seems to disappear in a large fraction of patients. You have to give their bodies a chance to adjust to the dosing regimen. It is definitely turning on the immune system. We've published that. We see the biomarkers moving in the right directions. We see some early signals of activity, which are really intriguing as a monotherapy. We're poised to be very excited about that program. We just have to get to the end of this I-A journey. Maybe at the risk of sounding silly, but that one always felt like the combination story is probably where it's at, in the sense that it's immunological activation. You usually need more oomph than that. Yeah. Definitely we set a high bar. We want to see some monotherapy activity. I think that then you have at least a much better chance of seeing the combo. Yes. I think some other agents went in with basically no monotherapy signal. There's going to be a miracle, a combo miracle, and then it's going to work. I don't think that that's really the way it goes. I think that NX-1607 is a strong agent. You're not going to take it forward as a monotherapy, is your point, ultimately. Yeah. You want to see some signal that is believable. Yeah, no, I agree 100%. Yeah. All right. Not giving short shrift to the rest of the platform, you guys are going to have quite a lot of presentations at AACR. Any one of these you'd like to highlight? I think there are four of them, so I'm not going to show any bias because I love them all like my children. In terms of where the next big wave of technology platform productivity is, the DACs, the degrader antibody conjugates, I think that's a really exciting area. We have not published a lot since signing up with Seagen, now Pfizer, of course. That's an area that I would watch, just as the technology itself, not only Nurix programs, but others. Right, a little brass tacks, cash position, and kind of operational runway. Yeah, I think our last disclosure, what? $650 million in cash. I have to admit, I don't memorize every number. That's approximately it, about two years of runway into 2027, so toward the second half. I think we're in good shape cash-wise. We're certainly well-funded to get the phase III's running. I think it's going to be an exciting second half. We've really had our nose to the grindstone for the first half, I have to say. We've been a little bit quiet, but we've been working on getting all these trials up and going. Excellent. We're pretty much at time. Yes. If you have any other item you'd like to highlight. I think that we're going to have a great second half. That's all I can say. We'll have a lot more news flow, and I think data flow. Like I said, this half has been really logistical and execution-based. Great. That's fair. Right. Thank you, Arthur. All right. Thank you. Thanks, Gil.